Case histories in infectious disease

Praveen Weeratunga

Senaka Rajapakse
Contents

Cardiovascular infection

• Infective endocarditis – unusual organisms

• Infective pericarditis – TB
• Trypanosomiasis

Respiratory infection

• PCP pneumonia
• Legionella and Mycoplasma infections
• Aspergillus infection and pulmonary nodules
• Histoplasmosis
• Non TB mycobacterial infection
• Melioidosis
• Norcardia
• Leptospirosis and pulmonary syndrome

Oropharyngeal and sinus infections

• Mucormycosis
• Lemierre’s disease
• Diptheria

Gastrointestinal infections

• Pseudomembranous colitis
• Typhoid fever – rare manifestations
• Vibrio parahemolyticus sepsis
• Campylobacter with GBS
• Giardiasis
• Amoebiasis
• Stronglyloides
• CMV
• Liver abscess
• Rare manifestations of viral hepatitis

Urinary infection

• Renal TB
• Schistosomiasis

Neurological infections

• Meningitis – Listeria
• Meningitis - Mollaret
• Meningitis – TB and fungal meningitis
 • Viral encephalitis – JE
• Rabies
• Cerebral abscess
• HIV related infective neurological disease
• HTLV – 1
• Neurosyphilis
• Clostridium infections
• Lyme disease
• Neurocysticercosis
• Cerebral malaria
• CJD

Skin and soft tissue infection

• Pyomyositis

Bone and joint infection

• TB osteomyelitis
• Poncet
• Gonococcal infection

Zoonotic infection

• Unusual manifestations of leptospirosis

• Rickettsial infection

Parasitic disease

Viral infection

• Dengue – unusual manifestations

• EBV viral infections
Chapter 1
Cardiovascular infections
Case

A 55 year old female with a past history of RA presented with a 3 week history of fever, shortness of breath
and bilateral ankle edema. Her RA was in remission at the time of presentation. Her past surgical history
was significant of aortic valve replacement 5 years ago due to aortic regurgitation. She is a housewife and
maintains a small animal farm with her husband and obtains income by supplying milk and other dairy
products to local vendors

On examination, she appeared alert and well-oriented but was weak and fatigued. She had a blood pressure
of 104/57 mmHg and was tachycardic with a pulse rate of 135 bpm. On cardiovascular exam, there was a
3/6 diastolic murmur appreciated in the left sternal area with the presence of normal S1 and S2. There was
a well-healed median sternotomy scar from her prior open heart surgery. On abdominal examination, the
spleen was palpable at 23 cm from the costal margin with tenderness to deep palpation in the left upper
quadrant

FBC – normocytic normochromic anaemia with Hb – 8.4, ESR – 110, CRP – 60, UFR – Red cells – 20-30,
protein - +1

Infective endocarditis

Identify the clinical syndrome of infective endocarditis

• IE should be considered in a patients with the following manifestations

• Fever
- Of unknown origin in a susceptible patient
- With a new or changing murmur
- With evidence of cardiac failure
- Conduction disturbances
- Vascular or immunological phenomena – Roth spots, Osler’s nodes, Janeway lesions
- Embolic phenomena
- Peripheral abscesses
• Examination – peripheral stigmata, cardiovascular system – for new or changing murmurs,
abdomen for splenomegaly, CNS for focal neurology suggestive of emboli
• Investigations – elevated inflammatory markers, UFR – proteinuria and active sediment,
glomerulonephritis (MCGN, membranous

Unusual organisms causing IE

• Brucellosis
• Coxiella burnetii
• Whipple’s disease
• HACEK
• Mycoplasma and Legionella
How to confirm a diagnosis of IE

• Echocardiogram
TTE – first line imaging modality (sensitivity 40-60%)
If inconclusive and high probability of IE consider TOE
Consider TOE even if TTE is positive – higher sensitivity (90-100%), better detection of abscesses
and vegetation size, TOE is also better at detecting prosthetic valve IE
Repeat TOE/TTE in 7-10 if initial investigations negative but clinical probability remains high
Important findings – oscillating mass – vegetations, new valvular regurgitation, abscess,
dehiscence of a prosthetic valve
• Microbiological investigations
Blood cultures – traditionally three sets within a 12 hour period, newer guidelines suggest 2 sets
within 1 hour – to prevent delay in antibiotic therapy
Negative cultures seen in patients on antibiotic therapy, HACEK organisms, Coxiella, Chlamydia,
Whipple
• Serological and other investigations indicated in patients with culture negative endocarditis

Coxiella (Q fever) endocarditis

Key points to look out for

• Look for a positive contact history. The most common route of acquisition is from farm animals
• The onset is generally a flu-like illness with non- specific symptoms. A maculopapular rash can
be present
• Pulmonary involvement is common and can cause bilateral, predominantly lower lobar
infiltrates
• Hepatic involvement is also noted ranging from a mild elevation in transaminases to a
granulomatous pattern
• Myo-pericarditis and meningitis is also noted to occur
• Endocarditis is associated with a chronic infection of Q fever and is culture negative

Other closely linked differential diagnosis

• Brucellosis can be identical in its presentation. However sacroileitis, epididymo-orchitis

commonly occurs in patients with Brucellosis. The risk factors for acquisition are similar in both
diseases

How to confirm

• Serological confirmation is necessary with estimation of IgM and IgG antibodies to Coxiella
burnetii

How to treat

• Acute infection is treated with doxycycline. Quinolones are also used

• Chronic infection is treated with combination therapy of doxycycline and HCQ
Case

A 50 year old man presented with progressive ankle edema, puffiness of face and abdominal distension for
three months, dyspnea on exertion for two months. Dry & nonproductive cough for one month. General
examination revealed generalized pitting edema, swelling of face, build & nutritional status-below average,
mildly anemic, elevated jugular venous pressure, B.P.- 100/70mmHg, pulse-100/min, Respiratory rate-
20/min, temperature-normal. Systemic examination of respiratory system revealed-movement of the chest
wall-diminished on both side, trachea is centrally placed, expansibility of chest wall-slightly diminished on
both sides, percussion note were dull over mid-axillary & infrascapular line below 5th rib, normal vesicular
breath sound on the upper zone & diminished on lower zone of both lung field, vocal resonance diminished
& bilateral basal crepitation were present. Cardiovascular system examination revealed no visible apex beat
or any other pulsation, no palpable apex beat, no parasternal heave, no palpable P2. 1st and 2nd heart
sound soft in all the areas of precordium, no added sound. Examination of abdomen reveals distended
abdomen with everted umbilicus, shifting dullness positive, bowel sound present. The liver was palpable 3
finger breadth from right costal margin in mid clavicular line. Patient had a past history of pulmonary
tuberculosis and was treated with antitubercular drugs 2 years back

Constrictive pericarditis due to TB

Key points to look out for

• The typical clinical syndrome in constrictive pericarditis is characterized by features of right

heart failure
• The patient will manifest with ascites, bilateral lower limb edema and hepatic congestion
• The JVP will be elevated with a prominent y descent. Elevation of the JVP occurs with
inspiration. A pericardial knock may occur (loud early diastolic sound at the lower left sternal
border)
• Further information may also be provided – such as difficulty in feeling the apex beat
• Look for the possible aetiology to complete your diagnosis
TB
Irradiation
Malignant infiltration of the pericardium
Metabolic – long standing uremia
Sarcoidosis

Other closely related differential diagnosis

• A history of suggestive of isolated RV failure, should prompt you to look for evidence of
pulmonary hypertension, as this is the common cause
• Carcinoid syndrome is another important differential diagnosis
• Cardiogenic cirrhosis is another entity to think of
• Constrictive pericarditis can closely resemble restrictive cardiomyopathy. The table given below
gives the important features of differentiation
 Constrictive pericarditis Restrictive cardiomyopathy
Paradoxical pulse Present in 1/3 Absent
Other Pericardial knock No pericardial knock
S3 and S4 audible
Equal right and left filling Yes Difference at least 3-5 mmHg
pressures
Respiratory variation in blood Exaggerated Normal
flow

How to confirm

• Echocardiogram is most often the most important mode of diagnosis

How to treat

• Treat the underlying cause

Case

A 56-year-old female, who immigrated to the USA from Brazil, presented with worsening shortness of breath,
orthopnea, paroxysmal nocturnal dyspnea, and decreased exercise tolerance over the previous 2 months. She
was diagnosed 1 year previously with non-ischemic dilated cardiomyopathy and non-sustained monomorphic
ventricular tachycardia. An implantable cardioverter defibrillator was placed. Cause for her dilated
cardiomyopathy was unknown at that time. She did not have a family history of similar disorders and denied
consumption of alcohol and exposure to toxins and drugs. On admission, her electrocardiogram showed low
voltage complexes, with frequent premature ventricular contractions. Transthoracic two-dimensional
echocardiogram (2D ECHO) showed severely reduced ejection fraction of 20%, severe mitral regurgitation with
left ventricular (LV) hypokinesis, and inferolateral and inferior wall akinesis. On review of her records, a
contrast 2D ECHO from the previous year revealed an aneurysm of the LV apical region. Live three-
dimensional (3D) ECHO on her present admission showed persistent LV apical aneurysm. Computed
tomography angiogram showed no atherosclerotic lesions. Autoimmune screen was negative.

Myocarditis and dilated cardiomyopathy due to infectious disease

Key points to look out for

• The causes for dilated cardiomyopathy are extensive. Infection related cardiomyopathy is
known to occur in association with the following organisms
• Viral – Coxsackie, adenovirus, HIV, Hepatitis C
• Parasitic – Trypanosoma cruzi
• Bacterial – diphtheria, Lyme, Q fever
• Fungal – systemic infections
Trypanosomiasis

Key points to look out for

• This infection is limited to Central and South America and is transmitted by the Reduviid bug. It
generally affects poor rural communities
• The acute disease presents with localized tissue swelling in association with local
lymphadenopathy. Entry of the organism can occur via the conjunctiva. This causes periorbital
edema. The acute infection generally causes non-specific clinical manifestations. Acute
myocarditis and encephalitis can occur, but is extremely rare
• Chronic infection presents with dilated cardiomyopathy and esophageal involvement.
Esophageal involvement causes dilated esophagus

How to confirm

• In acute disease Giemsa stain of peripheral blood with reveal the organism
• Chronic disease requires serological evaluation

How to treat

• Nifurtimox or benznidazole
Chapter 2
Respiratory infections
Pneumonia

Background and introduction

Pneumonia is defined as an infection of the pulmonary parenchyma.

Classification of pneumonia
Pneumonia is classified based on the clinical setting into, community acquired pneumonia, healthcare
associated pneumonia – hospital acquired and ventilator associated and pneumonia in the
immunocompromised
It is also classified based on the pathological and radiological pattern into lobar and bronchopneumonia

Case

A 55 year old female presented to the emergency department with a 2 day history of high fever (38.6°C)
shortness of breath, productive cough and diarrhoea 3 days after she had arrived from London, England
on holiday. In the emergency department, her respiratory rate was 21/min, blood pressure 88/57 mmHg,
and heart rate 116/min and regular and Arterial oxygen saturation was 77% on room air and increased to
90% on 100% oxygen via a face mask. Rales were present in one third of the lung fields bilaterally and
Percussion revealed dullness at the base of the right lung, with poor air entry in the right lower base.
Additionally, her blood gas results were her blood gas results were, pH: 7.49, PaO2: 4.9 mmHg, PaCO2:
3.8 mmHg, HCO-3: 24 mM, BE: -0.5 mM and SaO2 77%. Her CURB score surprisingly was 1, one point for
Low blood pressure

Her full blood count showed a marginal neutrophil leukocytosis with an Hb of 8.9 with MCV noted to be
120. Sodium – 118, potassium 3.8, serum creatinine 140, ESR – 40, CRP - 30

A chest radiograph showed extensive consolidation present throughout the right lung and there was also
a little patchy consolidation in the left mid and lower zones

Atypical pneumonia

Key points to look out for

Mycoplasma infection

Key points to look out for

• The clinical presentation is that of fever, cough and pulmonary infiltrates

• Diarrhoea is another common presenting symptom
• The classical X - ray appearance is peribronchial in nature with interstitial infiltration.
Consolidation and pleural effusion can also occur and does not exclude the diagnosis
• The most important clues to pick up are the extra- pulmonary manifestations of Mycoplasma
pneumoniae infection
• Skin – macular, maculo-papular, vesicular, bullous and urticarial rashes, erythema multiforme is
another important skin manifestation
• Neurological – GBS, ADEM, cerebellar ataxia, transverse myelitis
 • Hematological – hemolysis – predominantly cold agglutinin disease (high MCV), aplastic
anaemia, DIC
• Spontaneous splenic rupture can occur
• Other – Glomerular involvement, cardiac – myopericarditis

Legionella infection

Closely linked differential diagnosis

• Legionella is an important case to differentiate from mycoplasma infection. The clinical

presentation can be identical to Mycoplasma. The patient may be elderly. Diarrhoea and
neurological manifestations such as confusion and altered mental status are more common in
Legionella infection. Hyponatremia, liver function abnormalities with ALT>AST and hematuria
are also more common. Look for other laboratory clues such as elevated CPK,
hypophosphatemia and glomerular involvement
• The X - ray features of Legionella are variable with diffuse pulmonary infiltrates. Pleural effusion
is common
• Psittacosis is another grey case that has to be differentiated from Mycoplasma infection. Read
the question carefully for possible contact with birds. In addition to respiratory symptoms
hepatosplenomegaly, hepatitis, endocarditis are important clues
• Chlamydia pneumoniae infection can also be similar but does not commonly present with extra-
pulmonary manifestations
• Coxiella infection can mimic Mycoplasma. Coxiella is a zoonotic infection and may have a similar
clinical presentation. Look for risk factors for zoonotic infection. Rashes and thrombocytopenia
may occur. Granulomatous hepatitis is also known to occur
• Leptospirosis with predominant pulmonary involvement is another common grey case
differential diagnosis for Mycoplasma. Look for thrombocytopenia, liver function derangement
(AST>ALT) and elevation of the serum creatinine with red cells in the urine
• Non infective causes of interstitial pneumonitis can also mimic Mycoplasma infection. These
include eosinophilic lung disease, acute interstitial pneumonitis, COP, hypersensitivity
pneumonitis and lupus pneumonitis. Look at the eosinophil count carefully to diagnose
eosinophilic lung disease.

How to confirm

• Mycoplasma serology
• Legionella - Urinary antigen to serotype 1, antibody profiles

How to treat

• Clarithromycin
Pulmonary infections in the immunocompromised

HIV related pulmonary infection

A 40-year-old woman presents for evaluation of fever and respiratory symptoms. She was diagnosed
with HIV infection 8 years ago and has intermittently received care for her HIV disease. She was last
seen 6 weeks ago and had a CD4 count of 135 cells/mm3 and an HIV RNA of 53,120 copies/ml.
Trimethoprim-sulfamethoxazole was prescribed at that time, but she has not been taking it. She did not
return for the follow-up appointment and she now presents with a 2-week history of fever, fatigue,
non-productive cough, and dyspnea on exertion. On physical examination she is noted to have a
respiratory rate of 20. Room air resting O2 saturation was 91%, and her arterial blood gas shows a pH of
7.48, a CO2 of 29 mm Hg, and a pO2 of 68 mmHg. The chest radiograph shows bilateral opacities with
an increase in interstitial markings. She has no known drug allergies. While in the ward, the patient
becomes acutely dyspnoeic and requires IC tube insertion, due to an increasing R/S apical
pneumothorax. His investigations are as follows. FBC – WBC – 4200, Neutrophil count 4000, Hb – 10,
platelet count – 150,000

PCP pneumonia

Key points to look out for

• The question may reveal that the patient has risk factors for immunosuppression, or evidence of
high risk sexual behavior
• The patient will usually present with insidious onset, progressive shortness of breath
• The most important information will be given in the investigations. The patient will have a
hypoxaemia with carbon dioxide washout and exercise desaturation
• Also look for the classical perihilar ground glass infiltrates on the CXR/HRCT. Cavities and
pneumothoraces may also be evident
• Look for a subtle, hidden leukopenia
• This infection develops in patients with a CD4 count of less than 200
• LDH is high in most cases

Closely linked differential diagnosis

• Other infective causes of pneumonia in the immunocompromised such as disseminated TB and

CMV are important diseases to differentiate
• In patients who are obviously immunocompromised TB presents as miliary disease with a high
tendency for interstitial pulmonary involvement, meningitis and smear negative disease
• Other atypical mycobacterial infections are also noted in these patients such as MAI,
Mycobaterium Kansasii
• Pulmonary cryptococcosis and aspergillosis can also present in this manner. Cavitating nodules
are the most common pulmonary manifestation
• Upper lobe cavities can also occur in pulmonary norcardiosis
 • Lymphoid interstitial pneumonitis is an interstitial pneumonia that occurs in patients with HIV.
Lymphoid infiltrate is seen in the transbronchial lung biopsy

How to confirm

• PCR for PCP in BAL

• Silver stain

How to treat

• Co-trimoxazole therapy
 Clinical manifestations Investigations Management
PCP Most common cause of CXR Co- Trimoxazole – treatment of choice
pneumonia in HIV Initially normal
Fever, cough, loss of weight, Bilateral reticulonodular Alternatives – Clindamycin + primaquine
dyspnoea on exertion interstitial infiltrate Dapsone + TMP
Lung auscultation frequently Commonly involves perihilar Atovaquone
normal region
Diffuse alveolar shadowing in Pentamidine
severe cases
Pneumothorax Steroids in severe respiratory disease
Atypical patterns in treated cases PaO2 < 70 before or with treatment
– upper lobe
Increased LDH
Gallium scan shows increased
uptake
Hypoxaemia on exertion (PaO2)

BAL
TB Can present with respiratory CXR Anti TB – rifabutin instead of rifampicin
symptoms in early disease Upper zone infiltrates Delay HAART therapy when possible
Advanced disease – non Atypical features without MDR common
specific presentation cavitation, hilar mediastinal
lympadenopathy, interstitial
Other mycobacteria – kansaii, infiltrates in advanced disease
MAC can also cause clinically
significant disease Isolation of the organism – smear
– but culture positive
Mantoux – in advanced disease
Kaposi Associated with HHV 6 CXR Chemotherapy
sarcoma Associated with cutaneous Nodular or interstitial infiltrates – HAART
lesions and palatal lesions perihilar distribution, hilar nodes
Fever and respiratory tract
symptoms
Other malignancies – Non
Hodgkin’s lymphoma, bronchial
carcinoma
Other Pneumonia – more common
with pneumococcus and H.
influenzae
Intersitial lymphoid pneumonia
More common in children

Infections
Histoplasmosis
Coccidiomycosis
Aspergillosis
Toxoplasmosis
Norcardia

Misc – PAH, COPD

Case

A 40 year old renal transplant recipient presented with cough and shortness of breath for 1 week duration.
Chest x-ray on admission revealed a cavitary lung lesion on the right upper lobe. All other examinations
and laboratory tests were within normal limits. On further questioning, the patient revealed that he was
treated for pulmonary tuberculosis in the past. Patient denied any illicit drug use, alcohol abuse or
smoking. His total leukocyte count had increased significantly with a left shift. Repeat chest x-ray showed
new bilateral pulmonary infiltrates. Multiple broad spectrum antibiotics were started to treat ventilator-
associated pneumonia; however, the patient continued to be hypoxic, requiring a high oxygen
concentration and high positive end expiratory pressure (PEEP)

Pulmonary Aspergillus infection

Invasive Aspergillosis

Key points to look out for

• This is seen almost exclusively in patients who are immunocompromised

• Neutropenic patients are particularly at risk of developing invasive Aspergillosis
• Invasive disease manifests with tracheobronchitis and pulmonary infiltrates with cavitation
• Other forms of disseminated disease such as cerebral involvement may co-exist
• Radiological features of the disease may be non – specific in the early stages of the disease and
may demonstrate pleural base masses, nodules, pulmonary infarcts and cavities
The ‘halo’ sign and ‘air crescent’ sign are important features of note in an HRCT image

How to confirm

• The gold standard is demonstration of septate, acute, branching hyphae invading lung tissue
along with a culture positive for Aspergillus
• Other markers such as Galactomannan and beta-D Glycan are elevated in patients with invasive
Aspergillosis

How to treat

• Voriconazole or Amphotericin B
Note on ABPA

Case

A 65-year-old man from Germany entered a mine in Mexico that had been out of operation for nearly
thirty years. He and his coworkers from Mexico and Sweden noted the presence of numerous bats and
bat droppings when the doors were opened. Two weeks later, he and his colleagues were in their
respective countries when they each developed decreased appetite, dry cough, dyspnea, drenching
sweats, and fevers to 40º C. The German patient was evaluated by a physician in Berlin and
hospitalized with respiratory distress. On physical examination he was tachypneic (25 breaths per
minute), febrile to 38.5º C, and hypoxic (oxygen saturation, 90% on ambient air). Pulmonary
auscultation was significant for decreased breath sounds in bilateral bases. His laboratory
examinations were mainly notable for mild elevation of the hepatic enzymes ALT 191, AST 132, LDH
360, and GGT 98. Thoracic imaging revealed bilateral nodular infiltrates, dense consolidations, and
pleural effusions

Histoplasmosis

Key points to look out for

• Look for a possible contact history. The organism exists in moist soil and can be inhaled. Is
common in North America
• The organism is classically found in caves and old buildings
• The disease predominantly presents with a pulmonary syndrome with fever, non-productive
cough, and progressive shortness of breath
• Pulmonary infiltrates occur and cavitatory disease is seen in patients who have pre-existing lung
disease. Histoplasmosis pulmonary lesions calcify with time and this is an important feature to
look out for. Mediastinal lymphadenopathy can also occur. Progressive massive fibrosis is
another rare pulmonary manifestation
 • Histoplasmosis can also cause multiple calcifications in the liver and spleen
• Disseminated disease occurs in the immunocompromised

Other closely linked differential diagnosis

• Coccidiomycosis
This is another organism with similar properties and epidemiological characteristics to
Histoplasmosis. Skin manifestations such as erythema nodosum, erythema multiforme are
common. This organism commonly causes unilateral infiltrates, effusions and hilar adenopathy.
Disseminated disease is seen in the immunocompromised. Pulmonary lesions in contrast to
Histoplasmosis, do not calcify
• Consider sarcoidosis in the differential diagnosis

How to confirm

• Isolation of the organism in sputum microscopy and culture

• Antigen test in disseminated disease

How to treat

• Itraconazole

Case

A 49 year old woman with chronic obstructive pulmonary disease (COPD) and a history of pulmonary
tuberculosis, successfully treated with standard chemotherapy six years earlier, presented with
cough and dyspnoea. On examination she was unwell and chest radiography showed left upper lobe
consolidation and cavitation. Her sputum was smear positive for acid and alcohol fast bacilli (AAFB)
and treatment was started with category II chemotherapy

What are the possibilities to consider in this case?

Consider the possibility of MOT

• Signs and symptoms of NTM pulmonary disease are variable and nonspecific. They include
chronic cough, sputum production, and fatigue. Less commonly, malaise, dyspnea, fever,
hemoptysis, and weight loss can also occur, usually with advanced NTM disease. Evaluation is
often complicated by the symptoms caused by co-existing lung diseases. These conditions
include chronic obstructive airway disease associated with smoking, bronchiectasis, previous
mycobacterial diseases, cystic fibrosis, and pneumoconiosis.
• There are some differences in the radiographic features of NTM lung disease compared with
those produced by M. tuberculosis with regard to conventional radiographic studies.
Nontuberculous mycobacteria tend to cause thin-walled cavities with less surrounding
parenchymal infiltrate, have less bronchogenic but more contiguous spread of disease, and
produce more marked involvement of pleura over the involved areas of the lungs. Occasionally,
they may produce dense pneumonic disease or a solitary pulmonary nodule without cavitation.
 Basal pleural disease is not often found, and pleural effusion is rare. Right middle lobe
bronchiectasis is also a recognized manifestation

How to confirm

• Culture

How to treat

• Modified anti TB regimens

Lung abscess

A lung abscess is defined as necrosis and cavitation of the lung tissue following a microbial infection

Clinical features

• Patients with lung abscess typically present with fever, cough with productive sputum, fatigue
and anorexia
• Examination may reveal, clubbing, amphoric/cavernous bronchial breathing on auscultation

Case

A 62 year old, previously healthy engineer, from Kosgama, working in the Southern railway development
project was admitted with a history of fever for 10 days, pleuritic type chest pain, and shortness of breath.
He had purulent sputum associated with haemoptysis and was treated in the local hospital for lung abscess
without success, despite administration of intravenous broad spectrum antibiotics. He presented to us with
worsening symptoms. He was a non-smoker and had underlying diabetes mellitus with good glycaemic
control. Examination revealed an ill looking, febrile patient. Respiratory system examination revealed
bilateral coarse crepitations and an area of bronchial breathing. There were no pleural effusions, cardiac
murmurs or organomegaly.

Chest x-ray showed large abscesses in both lung fields. He had a raised ESR of 91mm/hr and a C-reactive
protein of 60.2mg/l. Full blood count showed a neutrophil leucocytosis (WBC 18x103 /l, neutrophils 82%).
Sputum culture grew a bacterium, initially identified as a Pseudomonas species. He was treated with
intravenous meropenem according to the antibiotic sensitivity pattern. Symptoms persisted, and fever
continued despite antibiotics and chest physiotherapy. Sputum for acid fast bacilli and the Mantoux test
were negative. Right sided infective endocarditis was excluded by an echocardiogram. The patient
deteriorated and continued to have elevated inflammatory markers. His clinical picture at this stage was
suggestive of an underlying atypical infection. Retroviral screening, antinuclear antibody (ANA) and
antinuclear cytoplasmic antibodies (ANCA) were negative

Melioidosis

Key points to look out for

• This is another common grey case

• The typical presentation is fever with multiple abscesses, most commonly involving the lung
 • Other associated manifestations are cerebral abscesses, septic arthritis, osteomyelitis, renal,
splenic and parotid abscesses
• A contact history may be apparent. This infection is common among farmers and in
communities where floods are a common and recurrent problem
• Another clue that may be given is the isolation of Pseudomonas in microbiological samples
(Burkholderia pseudomallei can morphologically mimic Pseudomonas)

Other closely linked differential diagnosis

• One has to carefully differentiate from fungal and other bacterial infections causing pulmonary
cavitation

How to confirm

• Gram stain – typical safety pin appearance

• Serology for Meliodosis

How to treat

• Antibiotics – initial phase – Meropenem and continuation with Co-trimoxazole

Case

A 35-year-old male presented with cough, dyspnea, and expectoration with episodes of hemoptysis
with purulent sputum for 2 years. He took an antitubercular treatment for six months. With
antitubercular treatment his fever had subsided but the sputum and hemoptysis had continued. Two
months ago he referred to a general physician with low grade fever associated with productive cough
and received some medication without any improvement. His condition became worsened. Chest X-
ray showed infiltrations in right upper lobe with cavity formation and computed tomography (CT)
revealed the presence of areas of consolidation with air bronchograms and cavitary lesions
containing air and infiltration beginning from the apical segment lying to anterior segment of right
lower lobe He was treated with ceftazidime and ciprofloxacin. But he did not have any improvement
in respiratory symptoms. Several sputum samples were collected and tested for the presence of acid-
fast bacilli, but all smears were negative. The patient then underwent bronchoscopy and aspirated
material was negative for tuberculosis, fungi (including Pneumocystis jirovecii), and malignancy.
FNAC was done from the right upper lung lesion. Aspirated material was negative for tuberculosis
and malignancy. Because of progressive worsening of clinical status, right upper lobectomy was
performed. On gram staining, the organism appeared as Gram-positive, thin branching filaments

Pulmonary Norcardiosis

Key points to look out for

• This infection is acquired through a soil borne organism. Immunocompromised individuals

manifest severe infection
• Pulmonary Norcardiosis is associated with pulmonary alveolar proteinosis
• The typical pulmonary disease causes cavitatory lesions, nodular lesions or diffuse parenchymal
infiltrates
 How to confirm

• Sputum examination – Gram positive filamentous organism

How to treat

• Co-trimoxazole

Case

A 40 year old farmer presented with a 3 day history of fever, cough, headache, arthralgia and myalgia

Examination revealed a dehydrated patient with cool extremities. He had subconjunctival suffusion which is
characterized by conjunctival redness especially on the palpebral conjunctiva. There was no obvious skin rash.
Vital signs recorded a blood pressure of 101/82 mmHg. He was tachycardic at 118 beats per minute with a
reduced radial pulse volume. His temperature was 38.2o C and he had an oxygen saturation of 90% on room
air. He was also jaundiced with an associated pallor. No cervical lymph nodes were palpable. Respiratory
examination revealed bilateral generalized crepitations over the lung fields. Cardiovascular, abdominal and
neurological examinations were unremarkable.

The complete blood count showed a mild anemia of 10.6 g/ dL, leukocytosis (13.9 x 109/L) with predominant
neutrophilia (absolute neutrophil count of 12.1 x 109/L) and significant thrombocytopenia (48 x 109/L). His
coagulation profile showed prolonged prothrombin time of 16.3 seconds and a normal activated partial
thromboplastin time and international normalized ratio (INR). His renal profile showed urea of 7.1 mmol/L,
high serum creatinine (197 umol/L), hypokalemia (3.09 mmol/L), and a normal sodium level. The liver function
tests showed deranged liver enzymes. The alanine transaminase (ALT) was 102 U/L and aspartate
aminotransferase (AST) was 143 U/L. The alkaline phosphatase (ALP) was 558 U/L, albumin of 34 g/L and total
bilirubin of 85.2 umol/L with unconjugated bilirubin predominating. He also had an elevated C-reactive protein
level of 15.8 mg/L and erythrocyte sedimentation rate of 97 mm/hr. Arterial blood gas exhibited features of
type 1 respiratory failure and high anion gap metabolic acidosis with pH of 7.28, pO2 58 mmHg, normal pCO2
and bicarbonate of 17 mmol/L. Urine examination was normal. Chest radiograph revealed bilateral alveolar
shadowing

Leptospirosis pulmonary syndrome

Key points to look out for

• Leptospirosis is an infection with predominant renal manifestations. However pulmonary

manifestations are also reported
• The common pulmonary manifestations of the disease are pulmonary alveolar hemorrhages and
interstitial pneumonitis
• The usual clues for leptospirosis include a positive contact history, icterus with sub-conjuctival
hemorrhages, neutrophil leukocytosis with thrombocytopenia
• Renal dysfunction is usually predominant in the severe form of the disease
• Liver functions usually show AST>ALT with high ALP and hyperbilirubinaemia

Other closely linked differential diagnosis

 • Legionella pneumonia is an important differential diagnosis. Proper epidemiological history is
essential
• Non – infectious pulmonary renal syndromes require consideration

How to confirm

• MAT for leptospirosis

• PCR

How to treat

• Antibiotics – C. Penicillin and Ceftriaxone

• Methylprednisilone has questionable benefit, with some reports of it being effective in the early
stages of the disease
Chapter 3
Oropharyngeal and sinus infection
Case

A 60–year-old man with type 2 diabetes mellitus and hypertension for 10 years complicated with non-
proliferative diabetic retinopathy and diabetic nephropathy, presented with left-sided facial paralysis of 6
hours duration. He had developed dull intermittent left-sided maxillary and temporal facial pain and
numbness associated with malaise and anorexia one month prior to presentation. There was no history
of fever, family or contact history of tuberculosis. His past glycaemic control was poor.

On examination, he was noted to have a partial 3rd nerve palsy with mild pupillary dilatation, a lower
motor neuron facial nerve palsy, and a palatal palsy on the left. Sensory loss was demonstrable in the left
trigeminal territory with involvement of the ophthalmic, maxillary and mandibular divisions. Optic fundi
showed evidence of non-proliferative diabetic retinopathy. Rest of the systems and general examination
was unremarkable. His pulse rate was regular and blood pressure was 170/90 mmHg. After admission to
hospital the patient developed 6th and 8th nerve palsies on the left while the initial 3rd, 5th and 7th
nerve palsies worsened.

His white cell count was 16,900/cumm with 80% neutrophils. Inflammatory markers were elevated with
an ESR of 136 mm/h and a CRP of 96 mg/dl. Renal and liver function tests were normal. Non-contrast
enchanced cranial computerized tomography scan was normal apart for opacities in the left ethmoid and
maxillary sinuses. Cerebrospinal fluid analysis was unremarkable

Mucormycosis

Key points to look out for

• This dreaded fungal infection is caused by the fungi Phycomycetes (order Mucorales). This
includes Rhizopus sp.
• This invasive fungal infection is more common in patients with a background of
immunosuppression
• Risk factors for infection include DM, HIV, iron overload states, steroid therapy and post –
transplant immunosuppression
• The classical presentation of the disease starts with features suggestive of chronic sinus
infection, epistaxis and purulent nasal discharge. The patient may have palatal erosions or
ulceration of the skin overlying the sinuses. Neurological manifestations with involvement of the
111-VI cranial nerves, cavernous sinus infiltration and orbital apex syndrome are also common
• Stroke is a rare manifestation of the disease

Other closely linked differential diagnosis

• Wegener’s granulomatosis, sarcoidosis, TB and Tolosa – Hunt Syndrome requires consideration

in the differential diagnosis

How to confirm

• Biopsy with demonstration of the organism

How to treat

• Amphotericin B
Case

A 27-year-old otherwise healthy male presented to the emergency department with a 10-day history of
sore throat, fever and lymphadenopathy. His condition had deteriorated to significant odynophagia,
hemoptysis, chest pain and shortness of breath. On examination his temperature was 38°C, oxygen
saturation was 93% on 2 liters of oxygen. He was jaundiced and had tender cervical lymphadenopathy and
an erythematous throat. His chest exam showed bilateral bibasilar crackles, and he had
hepatosplenomegaly. His initial investigation showed WBC 18.9×10 9 L with neutrophil count of 15.69×109 L
and a platelet count of 23/mm3. Platelets 23. A chest x-ray showed evidence of pneumonia and pleural
effusion. He was treated as presumed pneumonia with IV antibiotics, but his condition deteriorated to
respiratory failure and sepsis requiring mechanical ventilation. A CT scan showed bilateral pulmonary
empyema and thrombosed jugular veins

Lemierre’s syndrome

Key points to look out for

• Lemierre’s syndrome is a an infection by the organism Fusobaterium necrophorum

• The onset of the clinical syndrome is with pharyngitis. The hallmark of the infection is
thrombosis of the internal jugular vein
• The development of thrombophlebitis of the IJV is associated with neck pain and swelling. This
may occasionally be associated with trismus, otalgia and dysphagia
• The disease is also associated with metastatic infection. Pulmonary involvement is the most
common with pneumonia, empyema, lung abscesses and bilateral infiltrative pneumonia being
commonly reported
• Other manifestations of metastatic infection include septic arthritis, osteomyelitis, pericarditis,
hepatic abscesses and meningitis. Moreover, the spleen, skin, kidneys, brain and soft tissues
may be involved
• Full blood count usually shows a neutrophil leukocytosis. Inflammatory markers are elevated

How to confirm

• Blood culture

How to treat

• F necrophorum is usually sensitive to penicillin, clindamycin and metronidazole

Case

A 50 year old male presented a one day history of mild fever, sore throat, dysphagia, odynophagia,
difficulty in opening eyes and paresthesia of both hands and feet. He was conscious and rational but was
drooling saliva and looked very ill on admission. He had four vaccination scars on his left upper arm (a
large scar from small pox vaccination and three BCG vaccination scars). He had shotty cervical
lymphadenopathy. His sinuses were non-tender, lungs were clear, and he was maintaining his peripheral
oxygen saturation at 98% on room air with a normal hemodynamic status. His throat could not be
visualized on admission. Neurological examination revealed bilateral partial ptosis and complete
ophthalmoplegia with pupillary sparing. His full blood count on admission showed a WBC count of
7,700/mm2 with 70% neutrophils, a haemoglobin of 13.6g and a platelet count of 275,000/mm2 . His
blood picture showed a mild neutrophil leukocytosis with cytoplasmic vacuoles suggestive of a bacterial
infection. His serum sodium was 135meq/L, potassium 3.5meq/l, blood urea 21mg% and creatinine
0.7mg%. His ECG on admission showed no abnormalities. Random blood sugar on admission was 90mg%
and fasting blood sugar on the following day was 95mg%. His AST and ALT were 27 U/L and 14 U/L
respectively

Diphtheria

Key points to look out for

• The typical manifestations of the disease include sore throat as the initial manifestation. This is a
exudative pharyngitis with a pharyngeal pseudomembrane
• Neurological manifestations of the disease include complete ophthalmoplegia with pupillary
involvement
• A descending type paralysis with predominant proximal muscle weakness can also be associated
• Diphtheria can also cause myocarditis and dilated cardiomyopathy

Other closely linked differential diagnosis

• Guillain Barre syndrome and the Miller Fisher variant is the most important differential
diagnosis
• Botulism can also have similar manifestations

How to confirm

• Gram stain shows club-shaped, nonencapsulated, nonmotile bacilli found in clusters

• Toxin analysis

How to treat

• Anti-toxin
Chapter 4
Gastrointestinal infections
Acute diarrhoea

Case

A 30 year old female presented with fever, headache and diarrhea with which she had been suffering
for five days. On physical examination, she had a slight fever, with a body temperature of 38.6°C. Her
arterial blood pressure was 110/70 mm Hg and her heart rate was 60 beats/minute. The physical
examination was normal apart from a mildly enlarged spleen. Five days in to the illness the patient
developed severe hip pain and restriction of movement at the right hip joint

Laboratory analyses of the patient's blood revealed a white blood cell (WBC) count of 6200/mm3 [70%
polymorphonuclear leukocytes (PMNL), 30% mononuclear leukocytes (MNL)], hemoglobin 13g/dL,
hematocrit 38%, platelet count 103.000/mm3, erythrocyte sedimentation rate (ESR) 34 mm/hour, C-
reactive protein (CRP) 44.6 mg/L, aspartate aminotransferase (AST) 35 U/L, alanine aminotransferase
(ALT) 21 U/L, alkaline phosphatase (ALP) 148 U/L, and direct/indirect bilirubin 1.6/0.2 mg/dL. The X- ray
of the hip was reported as normal

Typhoid fever – uncommon manifestations

Key points to look out for

• Typhoid fever is caused by the organism Salmonella typhi

• The classical presentation of typhoid fever starts off with fever and muscle pain in the first week
with associated constipation. Diarrhoea ensues by the second week. The patients fever also
increases with a notable relative bradycardia. During the third week the patient may develop
intestinal perforation and encephalopathy. The encephalopathy of Typhoid is described as a
‘muttering delirium’
• A rash may be observed during the second to third week and abdominal examination reveals
splenomegaly
• The FBC generally shows a normocytic normochromic anaemia and peripheral leukopenia in
most cases or a marginal leukocytosis
• Uncommon manifestations of the disease
• Septic arthritis, vertebral osteomyelitis, infective endocarditis, pelvic and ovarian disease
• The risk of septic arthritis and vertebral osteomyelitis is exaggerated in patients with
hemoglobinopathies
• Chronic cholecystitis is a recognized long term complication of the disease

Other closely linked differential diagnosis

• Yersinia enterocolica can produce a similar clinical profile to typhoid fever

• The organism typically affects the mucosa of the terminal ileum and can cause right sided
abdominal pain

How to confirm

• Gold standard of diagnosis is demonstration of the organism in blood culture

How to treat

• Cephalosporins, ciprofloxacin

Case

A 60 year old male with a long standing history of alcoholic liver cell disease presented with an acute onset
fever, diarrhoea and increasing abdominal pain. She was admitted to the casualty unit of a local hospital and
was found to be in shock, with a blood pressure of 85/60. These symptoms had appeared approximately 24
hours after a seafood buffet in a local hotel. She did not have any past history of allergy to seafood

Vibrio parahemolyticus sepsis

Key points to look out for

• This organism thrives in salt water and is concentrated in Shellfish

• It produces an enterotoxin that causes diarrhoea. Severe infection is known to occur in patients
with pre-existing liver disease
• Consumption of shellfish is the most common risk factor for acquisition of the infection
• As this is a toxin mediated disease, symptoms commonly occur very acutely after consumption
of contaminated food

Other closely linked differential diagnosis

• Other toxin related gastroenteritis (E. coli) should be considered

How to confirm

• Blood culture will reveal a poorly staining curved gram negative bacillus

How to treat

• Cefotaxime

Case

A 63-year-old woman arrived at the Emergency Room complaining of abdominal pain, bloating and
diarrhea over three days. A week earlier she had had an upper respiratory tract infection and was
treated with oral antibiotics (amoxicillin/clavulanate). Upon physical examination there were signs of
mild dehydration and her abdomen was distended and tender on palpation in the left lower
quadrant without rebound tenderness. During the first 24 hours of hospitalization her abdominal
girth and pain increased, her mental status deteriorated and eventually she developed signs of septic
shock. A new abdominal CT showed a dilated colon (> 6cm) with air liquid levels in the ascending
colon without signs of perforation. She underwent surgery and made a complete recovery
Antibiotic associated diarrhoea – Pseudomembranous colitis

Key points to look out for

• Pseudomembranous colitis is the most severe form

• The risk factors for Clostridium difficile infection are as follows
Broad spectrum antibiotic use
Cancer chemotherapy
Other comorbidities
• The disease commonly presents with watery diarrhoea which begins 5-10 days after
commencement of antibiotic therapy. Lower abdominal pain and low grade fever are also
associated. The full blood count will demonstrate a peripheral leukocytosis. Some patients with
severe disease can present with constipation
• Toxic megacolon and intestinal perforation can occur with severe disease

How to confirm

• Stool smear generally shows blood and leukocytosis

• ELISA for C. difficile toxin A and B
• Pseudomembranes on endoscopy

How to treat

• Stop offending antibiotic

• Oral metronidazole in most cases and oral vancomycin in severe disease
• Bowel resection surgery may be required
Case

A 40 year old male presented with nausea, fever, and had suffered watery diarrhea that lasted for three
days. The diarrhea was self-limiting and he was treated only with antipyretic drugs. Ten days later, he felt
muscle weakness in both upper and lower extremities. Proximal weakness in his arms resulted in difficulty in
lifting them above his shoulders, and in his legs in difficulty climbing stairs and rising from a low chair. During
the following days weakness also appeared in his distal arm muscles, and gradually increased in his upper
and lower leg muscles until our patient became severely disabled. Three days prior to admission, our patient
complained of muscular pain in both his legs, low back and shoulders.

On admission, seven days after the first symptoms occurred, the patient's mental status was normal and
cranial nerves were not affected. Both nerves innervating the proximal and distal muscle groups were
affected in the upper and lower extremities resulting in symmetric proximal and distal muscle weakness
which ranged between 3 and 4 on the Medical Research Council (MRC) grading scale. Deep tendon reflexes
were diminished

Campylobacter gastroenteritis and complications

Key points to look out for

• Campylobacter is another common cause of gastroenteritis

• The source of infection is commonly from dairy products and shares some features with
Salmonella gastroenteritis
• Unusual complications of Camylobacter infection include GBS and reactive arthritis (Reiter
syndrome)

Other closely linked differential diagnosis

• Diarrhoea and flaccid paralysis can occur in paralytic poliomyelitis and should be considered in
regions where the infection is still reported. The typical history of paralytic poliomyelitis starts
off with a viral prodrome and progresses to severe muscle pain and headache. Muscle weakness
is generally maximal at 48 hours of disease. It is characteristically flaccid and asymmetrical.
Reflexes may be preserved in the initial stages. Transient coarse fasciculations are also
commonly noted. There is no sensory loss

How to confirm

• Blood culture

How to treat

• Ceftriaxone or ciprofloxacin
Case

A 40-year-old man presented to a tertiary care hospital with a 3-week history of weight loss, frequent
diarrhea, nausea, and vomiting, accompanied by fevers and oral candidiasis. Furthermore, the patient
reported having had flu-like symptoms without exanthema for 7 days. Clinical examination revealed
tachycardia, tachypnea, a temperature of 38.3° C, and diffuse abdominal pain, combined with massive
pain on rectal examination. Initial blood counts revealed anemia, with a hemoglobin concentration of
7.5g/dl and WBC – 3.4, normal differential, platelets – 80,000. ESR – 60, CRP -156

CMV

Key points to look out for

• CMV causes disseminated infection in patients who are immunocompromised, particularly

patients with HIV infection
• The syndrome of CMV infection in the immunocompromised includes retinitis, acute hepatitis,
pneumonitis with diffuse pulmonary infiltrates and severe colitis with multiple linear ulcers in
the gastrointestinal tract. These ulcers can be hemorrhagic and necrotic. It can also cause
esophageal disease
• The infection is also associated with cytopenia which may indicate bone marrow involvement
• In renal transplant patients graft dysfunction is part of the disseminated CMV syndrome

How to confirm

• CMV PCR
• Antibodies
• Biopsy showing ‘owl – eye’ inclusion bodies

How to treat

• Intravenous Ganciclovir or Foscarnet

Chronic infective diarrhoea

Case

A 45-year-old previously healthy male from presented with complaints of high grade fever with chills
of 15 days duration and abdominal pain in the right hypochondrium of 7 days duration. Past history
revealed a dysentery episode one month previous to the present illness which had been treated with
oral antibiotics. He was a known smoker and alcoholic.On physical examination, there was
bradycardia, bilateral pitting pedal edema and signs of dehydration. Abdomen was tense with
tenderness in right hypochondrium and epigastric region. Hepatomegaly was seen. On auscultation,
breath sounds were decreased in the right lower lung field along with presence of pleural rub.

His laboratory test results at admission were as follows: Hemoglobin - 13.4 g/dL; Hematocrit - 40.8%;
Total leukocyte count - 33,500 cells/mm3; ESR - 76 mm/hr; Total bilirubin: 5.3 mg/dL; Direct bilirubin:
3.4 mg/dL, Serum aspartate amino transferase (SGOT) - 596 U/L; Serum alanine amino transferase
(SGPT) - 296 U/L and Alkaline phosphatase: 626 IU/L. Chest X-ray showed right sided pleural effusion

Amoebic colitis and complications

Key points to look out for

• This infection has a predilection for patients who consume illicit alcohol
• The clinical manifestations generally start with a watery diarrhoea but later progresses to a
blood and mucus diarrhoea with associated tenesmus, abdominal pain and tenderness
• The organism spreads through the portal vein and causes liver abscesses. These cause reactive
pleural effusions on the right side and can rupture causing active pulmonary infections
• The stool full report generally shows mild leukocytosis when compared to other infective causes
of blood and mucus diarrhoea
• Aspirate of the abscess is generally sterile

Other closely linked differential diagnosis

• Other forms of colitis generally cause a more explosive mucoid bloody diarrhoea
• Ulcerative colitis can also cause hepatic involvement and mimic this presentation. However this
will usually be in the form of sclerosing cholangitis with elevated ALP. Acute hepatic abscesses
do not cause elevated ALP. However ALP can be elevated in chronic hepatic abscesses
• Portal pyemia in some infective diarrhoeas can cause hepatic abscesses

How to confirm

• Stool smear for the organism

• Antibodies

How to treat

• Metranidazole
 Case

A 28 year old male who resided in an urban slum area in Colombo presented with a 1 month history of loss
of appetite, loss of weight and loose stools. He had been admitted in the past with repeated episodes of
cough and shortness of breath and had been treated with prolonged courses of intravenous antibiotics. On
examination the patient was pale, had bilateral coarse crepitations on both lung fields. His abdominal
examination was unremarkable. FBC – Hb – 9.2, microcytic indices, ESR – 40, CRP – 45, serum sodium 140,
serum potassium – 3.9, calcium – 1.8, phosphate – 0.78, serum albumin 28, X ray abdomen reported as
normal. CXR – bronchiectasis. IgG 0.42mg/L, Ig A less than 0.255mg/L, Ig M less than 0.161mg/L, Ig E less
than 1.5 IU/mL. The stool smear does not show any WBCs

Giardiasis

Key points to look out for

• The infection is acquired through the faeco-oral route and is common in impoverished
communities
• It can cause a chronic malabsorption syndrome, especially in patients who have immunoglobulin
deficiency. The predominant site of involvement is the duodenal and jejunal mucosa
• Look for evidence of hypogammaglobulinaemia
• The stool smear is generally unremarkable with regard to cellular material

Other closely linked differential diagnosis

• Other small bowel malabsorption syndromes may mimic Giardiasis. These include coeliac
disease and tropical sprue
• Immunocompromised patients may present with chronic diarrhoea due to other infective
organisms such as Cryptosporidium and Isospora

How to confirm

• Repeated samples for stool smear with cysts

• ELISA
• Duodenal aspiration and biopsy in some cases

How to treat

• Oral metronidazole

Other parasitic causes of chronic diarrhoea in the immunocompromised

• This includes Cryptosporidium, Isospora belli, Microsporidium

• Diarrhoea in HIV patients is most often due to these organisms. Confirmation of these infections
is via stool examination
Gastrointestinal manifestations of HIV

Clinical manifestations Investigations Management

Oral cavity and Candidiasis Gram stain Oral imidiazoles – fluconazole
esophagus Commonest opportunistic infection in HIV
Oral thrush with whitish/yellowish plaques
Erythematous lesions, angular stomatitis

Also causes esophagitis – AIDS defining

infection

Other causes of esophagitis is HIV

CMV – longitudinal ulcers Biospsy shows inclusion bodies
HSV-1
Oral hairy leukoplakia Usually no treatment required
Associated with EBV Podophyllotoxin
Whitish lesion with an irregular border along Acyclovir
lateral part of the tongue
Bilateral
Salivary glands
Cystic hyperplasia
Intestines HIV associated diarrhea Faecal microscopy, culture
Causes – Drugs (protease inhibitors)
Regular causes of AGE
TB
Non tuberculous mycobacteria
CMV colitis
Protozoa – Cryptosporidium, Microsporidia
Lymphoma
Rectum and anus HSV
Viral warts
Tumors Kaposi sarcoma
Liver HIV/HCV coinfection Combined therapy with HAART
Coninfected patients have severe Hep C and and PEG interferon
higher viraemia

Case

A 50 year old female presented with a 5 day history of nausea, vomiting, abdominal pain and diarrhea. She
has a past history of bronchial asthma and has been treated recently with high dose steroids. Despite the
treatment she has continued wheezing episodes. On physical examination she is afebrile and predominant
rhonchi in bilateral lung fields. Her investigations revealed the following. FBC – WBC – 10,000 (N – 70%, L –
10%), Hb 10, platelet – 180,000, ESR- 60, CRP – 40. CXR – bilateral diffuse infiltrates. Due to continuing
vomiting and epigastric pain, the patient undergoes upper GI endoscopy, which reveals extensive
ulceration

Strongyloides hyperinfestation syndrome

Key points to look out for

• The manifestations involve multiple organ systems

• Look for clues for immunosuppression provided in the case history – i.e. steroid use
• Skin involvement
 • Gastrointestinal involvement can manifest with abdominal pain, diarrhea, malabsorption, and
rarely severe colitis – results in intestinal ulceration
• Pulmonary manifestations are also common – wheezing episodes
• CNS manifestations can also occur
• Eosinophilia should be actively looked for

Other closely linked differential diagnosis

• EGPA is the most important differential. The important differentiating features are the presence
of mononeuritis multiplex

How to confirm

• Repeated stool examination

• Duodenal aspiration for ova and parasites

How to treat

• Ivermectin or thiobendazole

Case

A 35 year old male presented with fever and right sided abdominal pain for 3 days duration. When he
visited the outpatient department, his body temperature was 36.5°C and he had mild right upper
abdominal tenderness without evidence of liver enlargement on vertical span. His cardiovascular system
and respiratory parameters were unremarkable. No other symptoms, such as nausea, vomiting,
diarrhea, or skin rash, were noted. His white blood cell count was 4,500/mm3 , with 65% neutrophils and
20% eosinophils. Urine and stool analyses were unremarkable. Biochemical tests for alkaline
phosphatase, gamma-glutamyltransferase, aspartate aminotransferase, and bilirubin were within normal
limits, but alanine aminotransferase was increased to 50 U/L. Tests for antihepatitis C virus antibody,
hepatitis B surface antigen (HBsAg), and anti-HBsAg antibody were negative. Plain chest X-ray
examination showed no abnormal findings. Due to the abnormal liver function test and right upper
abdominal pain, abdominal sonography was performed. A cystic mass in the right lobe of the liver was
revealed. The mass measured 6.5 × 5.5 cm, with multiple cystic components presenting a honeycombed
appearance. The abdominal X- ray demonstrated a region of calcification in the right hypochondrium.

Hydatid cyst of the liver

Key points to look out for

• Hydatid disease is a parasitic tapeworm disease caused by the larval stage of Echinococcus
granulosus or Echinococcus multilocularis
• The clinical manifestations of the disease are extremely variable. The cysts may remain
asymptomatic for a significant period of time. Jaundice is rare and is due to compression of the
biliary system. A ruptured cyst can cause severe abdominal pain and anaphylactic shock
• ALP may be elevated. Eosinophilia is also associated in most cases
 • Multiple daughter cysts may be present on imaging. CT - daughter cysts, internal septa, and
detached membranes

Other closely linked differential diagnosis

• Consider other parasitic causes of liver abscess such as amoebic liver abscess

How to confirm

• Cyst aspiration

How to treat

• Surgical management
• Mebendazole

Case

A 50 year old businessman presented with a 3 month history of myalgia, loss of appetite and low grade
fever. He was perfectly healthy previously. General examination was unremarkable apart from a blood
pressure of 160/90 mmHg in both arms. There was slight tenderness of the calves, but no evidence of
synovitis. Sensorimotor defects were evident in the distribution of several peripheral nerves, most
profoundly involving the left common peroneal nerve, but also involving the right common peroneal, both
tibial and the left median nerves. The left ankle jerk was absent.

The laboratory data showed: leucocytes 15.8×109/l, C-reactive protein (CRP) 280 mg/l, alanine
aminotransferase (ALT) 77 U/l, γ-glutamyltranspeptidase (GGT) 21 U/l, normal renal function tests and
urinary microscopy, slight proteinuria (0.13 g/l), positive hepatitis B surface antigen (HBsAg), `e' antigen
(HBeAg) and antibodies to the core antigen (anti-HBc), HBV viral load 1×107 genome equivalents (geq)/ml,
other viral serology negative, antinuclear antibodies (ANA) negative, p-ANCA borderline. The liver biopsy
showed chronic minimally active hepatitis with slight intralobular lymphocytic infiltration, occasional cell
necroses, slight periportal lymphocytic infiltration and scattered piecemeal necroses

Unusual manifestations of viral hepatitis

• The patient described above had a diagnosis of Polyartertitis nodosa

Chapter 5
Infections of the renal system
Urinary tract infection

Aetiology

• Gram – bacilli – E. coli - > 80% of UTI

Proteus, Klebsiella, Enterobacteria, Serratia, Pseudomonas (recurrent UTI, associated with
urinary manipulation, calculi, obstruction, catheter associated infections
Gram +
Staph saprophyticus – young females
Staph aureus – as a complication of bacteraemia, renal calculi, instrumentation
Staph epidermidis – catheter associated UTI
Case

A 48 year old presented with symptoms of pain in the right loin for two months and fever for one
day. The patient had not experienced coughing, hemoptysis, weight loss, night sweats or TB contact,
but did have a history of hypertension and diabetes mellitus. There was no past or family history of
TB. The patient had a temperature of 39.0°C, a blood pressure of 186/84 mmHg and tenderness of
the right loin. Laboratory results showed a white blood cell (WBC) count of 20.13×10 9/l (84.5%
neutrophils and 9.9% lymphocytes) and hemoglobin and platelet levels were normal. Urine tested
positive for WBCs, and no urinary protein or microscopic hematuria was detected. Liver and renal
functions were normal. Blood and urine cultures were negative. Other serological tests for
antinuclear antibodies, rheumatoid factor and HIV were negative. Chest X-ray and abdominal
ultrasound observations were normal. Empiric antibiotics were administered but was not successful.
Symptoms of pain in the right loin and fever remained. An abdominal CT scan was then performed,
which identified a low density focus (1.9×2.1 cm) in the lower pole of the right kidney and an
iliopsoas abscess

Renal TB

Key points to look out for

• The clinical manifestations of urinary TB are nonspecific, including back, flank and suprapubic
pain, hematuria, increased urinary frequency and nocturia, which may also indicate a
conventional bacterial urinary tract infection
• The most important clue to the diagnosis of renal TB is the presence of sterile pyuria
• Renal TB can also cause a tubulointerstitial nephritis with significant salt losing nephropathy

How to confirm

• The rates of microbiological confirmation of renal TB is poor and other evidence is usually
required to establish the diagnosis
• A low density lesion may be seen in the CT abdomen with progression to focal calcification.
Changes are unilateral in most cases
• Advanced renal TB is characterized by the presence of irregular calyces and hydronephrosis and
hydroureter. The pathognomonic lobar calcification is seen in advanced renal TB

How to treat
 • Anti TB

Case

A 37-year-old male presented with a 6 month history of intermittent, painless terminal hematuria and
irritative voiding symptoms. He does not have associated fever, anorexia or loss of weight. He has visited
mid-African countries 5 years ago for business. He stayed there for 6 months and started having symptoms
1 month after his return. He. He presented at a state hospital. His medical history was unremarkable. No
significant findings were found at physical examination.

FBC – WBC – 11,000 (neutrophils – 75%, lymphocytes 10%). The urine sediment contained 65 erythrocytes
and 8 leukocytes per field. Ultrasound revealed a solid mass with 2 cm in diameter located near the left
ureteral orifice and irregularities in the bladder wall, with nodular thickening. There were no abnormalities
noted in the kidneys

Schistosomiasis

Key points to look out for

• Schistosomiasis, or bilharzia, is a common intravascular infection caused by parasitic

Schistosoma trematode worms
• It is prevalent in Africa, the Middle East, South America, and Asia
• The clinical features are diverse but the disease commonly presents with urinary tract
involvement
• A rash occurs at the point of penetration by the cercarie of the organism
• Acute disease (Katayama fever) - fever, malaise, myalgia, fatigue, non-productive cough,
diarrhoea (with or without the presence of blood), haematuria (S haematobium), and right
upper quadrant pain. Pulmonary infiltrates can also occur. Acute schistosomiasis is seen in
people who are infected for the first time when travelling to endemic areas
• Chronic disease
Hepatic disease – granulomatous hepatitis, portal hypertension, thrombosis
GI – bowel inflammation
• Renal disease
• Haematuria, appearing 10-12 weeks after infection, is the first sign of established disease (fig 4).
Dysuria and haematuria occur in early and late disease. Late disease manifestations also include
proteinuria (often nephrotic syndrome), bladder calcification, ureteric obstruction, secondary
bacterial infection in the urinary tract, renal colic, hydronephrosis, and renal failure. Structural
abnormalities of the urinary tract may occur in children. Cystoscopy may reveal characteristic
“sandy patches,” which are areas of roughened bladder mucosa surrounding egg deposits
• GU disease
• Pulmonary involvement can also occur – pulmonary hypertension

How to confirm

• Stool/urine examination for schistosome eggs

• Full blood count: eosinophilia (>80% of patients) with acute infections; anaemia and
thrombocytopenia may be present in chronic and advanced schistosomiasis
How to treat

• Praziquantel
Chapter 6
Neurological infections
Meningitis

Definition and introduction

• Inflammation of the arachnoid, pia mater and intervening CSF

• Meningitis can be classified based on the temporal profile and progression into acute and
subacute
• Infectious aetiological agents includes bacterial, viral and fungal
• The typical clinical manifestations of meningitis includes the triad of fever, photophobia and
neck stiffness, however atypical clinical manifestations can occur

Case

A 72-year-old man was admitted to hospital complaining of a right-sided headache, fever and malaise
that had been present for one week. Four days before admission he had developed right facial
numbness, diplopia and vertigo, and he had fallen three times on the day of admission. The patient had
no past medical problems and was taking no medications

Physical examination at the time of admission revealed an alert and oriented man. His oral temperature
was 38.8°C. Mild neck stiffness was present. Funduscopic examination was normal. Examination of the
cranial nerves revealed a right sixth nerve palsy, decreased sensation in the V1 distribution of the right
trigeminal nerve and weakness in the right temporalis and masseter muscles. Cerebellar function was
impaired with nystagmus in all directions of gaze, difficulty with rapid alternating movement of the
right hand, right upper limb ataxia on finger-nose testing and an ataxic gait. Heel-shin testing was
normal bilaterally. The remainder of the neurological examination was normal

Listeria meningitis

Key points to look out for

• Listeria commonly affects patients with a sub-optimal immune response. This includes,
neonates, the geriatric population and patients on immunosuppressive medication
• Think of Listeria in pregnant patients with meningitis
• Other clues may include history of ingestion of possible contaminated food, especially dairy
products
• The typical clinical syndrome is that of meningitis associated with brainstem involvement
(Rhombencephalitis)
• The CSF examination is usually only mildly deranged and commonly shows a modest neutrophil
predominance. It can also show lymphocyte predominance, Glucose is usually normal, with
mildly elevated CSF protein
• MRI is usually non-specific with focal brainstem hyper-intense lesions, or rarely ring enhancing
lesions

Other closely linked differential diagnosis

 • Other causes of bacterial meningitis should be considered, and one should be very clear about
the risk factors of each aetiology

Streptococcus pneumoniae Most common cause in adults > 20

Risk factors
Pneumococcal pneumonia, sinusitis, otitis media,
chronic alcoholism, DM, splenectomy,
hypogammaglobulinaemia, complement
deficiency, base of skull fracture
High mortality (20%)
Neisseria meningitides Nasopharyngeal entry
Occurs in epidemics in Haj pilgrims
Risk factors – complement deficiency
Gram negative organisms Important cause in individuals with chronic illness
– DM, cirrhosis, alcoholism
Also associated with neurosurgical procedures
GBS Associated with advancing age - >50
Listeria monocytogenes Pregnancy, Age > 60, immunocompromised
individuals
Haemophillus influenzae Incidence reduced with vaccination
Staphylococcus aureus and coagulase negative Associated with neurosurgical procedures – shunt
Staphylococcus procedures for hydrocephalus

How to confirm

• The gold standard of diagnosis is demonstration is demonstration of the organism in the blood
or CSF by culture. However these are frequently negative

How to treat

• Ampicillin in combination with gentamicin is the treatment of choice. Other empirical therapies
for suspected bacterial meningitis should be continued until confirmation is achieved
 Case

A 49-year-old Indian female was admitted with a 1-day history of headache, fever and vomiting associated
with neck pain and blurring of vision. On physical examination she was febrile with a temperature of 38.5
8C and she had neck stiffness and positive Kernig’s sign. Investigations revealed a normal non-contrast
computed tomographic scan (CT) of the head. Examination of the CSF was attempted but failed. She was
treated as a case of bacterial meningitis with intravenous ceftriaxone and ampicillin. Her fever subsided
on the next day and she was discharged home in good condition after 10 days of therapy. She remained
well until 6 months later, when she presented with low-grade fever associated with chills, headache, and
vomiting. Physical examination was only remarkable for fever of 37.8 8C and neck stiffness.

Investigations revealed a normal non-contrast CT scan of the head, positive mantoux test, and negative
ELISA test for HIV (done once). CSF examination revealed: white blood cell count (WBC) 1070 cells /mm3
(lymphocytes 97%, neutrophils 2%, and monocytes 1%), protein 1.62 g/l (0.15-0.45), and glucose 2.9
mmol/dl (blood glucose – 4.8). Bacterial, fungal and mycobacterial cultures were negative in CSF. ANA was
noted to be negative

What are the possibilities to consider in this patient?

• This patient has recurrent episodes of meningitis with CSF lymphocytosis. You should consider
the following differential diagnosis
• TB meningitis
• Fungal meningitis
• Mollaret’s meningitis
• Other rare causes – NSAIDs, autoimmune disease related meningitis

Mollaret’s meningitis

Key points to look out for

• Mollaret’s meningitis is defined as benign

recurrent aseptic meningitis characterized by
3—10 episodes of fever and signs of
meningeal irritation lasting between 2 and 5
days, with spontaneous recovery. HSV-2 has
been responsible for the majority of cases,
with few cases caused by HSV-1 and Epstein—
Barr virus
• The CSF shows a lymphocytic pleocytosis with elevated protein and normal glucose
• The patient can also have genital lesions or pelvic radicular symptoms in association

Other closely linked differential diagnosis

 • TB is a major differential diagnosis, however TB would cause a more progressive meningitis with
severe neurological sequale, whereas MM is a more benign recurrent disorder. The CSF in TB
also shows more profound changes, with significant elevation of protein and low CSF glucose. A
positive mantoux test (as in this case) is non-specific and should not be used to guide therapy in
isolation
• Look for a history of NSAID use, as this can also cause recurrent meningitis
• Autoimmune disease such as sarcoid and Behcet’s can also cause recurrent lymphocytic
meningitis
• Other forms of viral meningitis are usually uniphasic and self- limiting

How to confirm

• HSV-2 serology and PCR

How to treat

• Acyclovir for acute episodes of meningitis

Case

A 48-year-old male resident of Negombo, who was a fisherman by occupation, was admitted to the
neurology department with chief complaints of high-grade fever, intermittent, moderately severe
headache lasting 25 days associated with multiple episodes of vomiting, and altered sensorium for four
days. He had no history of seizures, ear discharge or earache, nor any focal neurological deficit, head
trauma, weight loss, chronic cough, drug abuse including steroids, blood transfusion, or high-risk
behavior. No history of tuberculosis, diabetes, malignancy or any other such chronic illness was present.
On examination, the patient was febrile and unconscious, with a Glasgow coma scale of E1M5V1. Neck
rigidity and Kernig’s sign were positive. Pupillary response was bilaterally sluggish, plantars were
bilaterally extensor, and all deep tendon reflexes were diminished. A sensory and motor system
examination could not be performed.

Examination of other systems revealed no obvious abnormality. Laboratory investigations revealed

raised total leukocyte count (13,000/mm cu.) with 86% neutrophils. Serum electrolytes, renal function
tests, and liver function tests were within normal limits. A cerebrospinal fluid (CSF) examination revealed
80 cells, predominantly lymphocytes, with protein of 54.7 mg/dl and glucose of 28 mg/dl (corresponding
blood glucose was 136 mg/dl). A computerized tomography (CT) scan of the head and a chest X ray were
both normal. CSF TB culture and PCR were noted to be negative

What is the differential diagnosis you would consider in this patient?

• The salient point of this case is that the patient has a chronic meningo-encephalitis with
lymphocytic pleocytosis, elevated protein and low glucose. The differential diagnosis or this
presentation is wide but the most likely causes in this case would be TB and fungal infection
Cryptococcal meningitis

Key points to look out for

• Look for history suggestive of immunosuppression/HIV illness

• The clinical presentation is that of a subacute onset and progressive nature and has a waxing
and waning course. The most common symptoms are long standing headache with personality
changes progressing to stupor and coma
• Classical features of meningitis are usually absent
• Cranial nerve palsies can be associated – III- VIII as part of a basal meningitis syndrome
• CSF analysis reveals a lymphocytosis (20-200), elevated protein and low glucose
• MRI findings can mimic that of TB – ring enhancing lesions are known to occur. Hydrocephalus
can occur but is rare

Other closely linked differential diagnosis

• Other causes of chronic meningitis requires consideration

• TB meningitis is an important differential to consider. The clinical, laboratory and imaging profile
of TBM can be extremely difficult to differentiate from Cryptococcal meningitis. Both PCR and
culture negative for TB makes it less likely. Look for suggestive evidence of TB in other organs
Remember that early CSF can be of neutrophilic predominance in patients with TBM
• Other non-infectious aetiological agents may also be considered – sarcoid, autoimmune,
lymphoma
• Chronic eosinophilic meningitis can be due to parasitic disease

How to confirm

• The India Ink stain for the organism is only positive in 25-50% of individuals, and can be negative
if the fungal burden is low
• The Cryptococcal antigen test is more sensitive and is positive in around 90% of individuals

How to treat

• Amphotericin and Flucytosine for a minimum of 2 weeks followed by fluconazole for 3-6 months
Case

A 30 year old male from Puttlam Sri Lanka presented with fever, disturbed consciousness and seizures. The last
time when his family contacted him without any type of abnormality was two days prior to admission. His
family found him in a confused state with incoherent speech, fever, and urinary and stool incontinence. Upon
examination at the ED, his Glasgow coma scale was E4V1M4, and he had bilateral symmetric pupil size with
preserved light reflex. The admission medical officer noted some abnormal semi-purposeful movements in
both upper limbs.

Brain computed tomography (CT) showed no evidence of intracranial hemorrhage, cerebral edema or
abnormal mass effect. Neck stiffness and Kernig’s sign were detected upon physical and neurological
examination. Therefore, a lumbar puncture and cerebrospinal fluid (CSF) study was performed, revealing that
the open pressure was 17 cmCSF, with a reddish appearance. The CSF routine analysis showed a red blood cell
(RBC) count of 2600/µL and white blood cell (WBC) count of 250/uL with lymphocyte predominance (73%). The
CSF glucose level was 65 mg/ dL, and the protein level was 116.5 mg/dL. Subsequent magnetic resonance
imaging (MRI) of the brain revealed abnormal T2 hyperintense lesions in the bilateral thalami, putamina,
midbrain and pons as well as diffuse gyral swelling involving the bilateral insula, bilateral temporal lobes, and
bilateral medial frontal lobes

Viral encephalitis – JE

Key points to look out for

Identify the clinical syndrome of infective encephalitis

• The clinical syndrome of patients with viral encephalitis is usually uniform across many
infectious etiologies
• The CSF analysis also reveals a lymphocytic predominance in most cases
• The clinical presentation is usually with headache, disturbance of higher function, seizures and
progression to coma

Look for clues to the aetiology

• HSV causes predominant involvement of the temporal lobes. Due to this preferential
involvement, HSV presents with memory loss, personality alteration, prominent gustatory or
olfactory hallucinations, anosmia and hemiparesis
• JE causes predominant involvement of the basal ganglia. Therefore abnormal movements such
as chorea, athetosis and Parkinsonism are noted. Other manifestations such as hemiplegia and
cerebellar involvement are also recognized
• The MRI classically shows hyperintensities in the basal ganglia and thalami, with or without
hemorrhage

Other closely linked differential diagnosis

• HSV can mimic the presentation of JE. MRI is usually informative as it shows predominant
temporal lobe involvement in JE
 • Other causes of basal ganglia involvement include WNV, Eastern Equine encephalitis, Murray
Valley encephalitis
• Non infective causes of encephalitis can also be considered – NMDA and limbic encephalitis

How to confirm

• JE IgM and IgG in CSF

How to treat

• Conservative management

Case

A 35 year old tourist guide presented with a 4 day history of headache and fever, with progressive difficulty
in articulation and swallowing with nasal regurgitation. On the day of admission the patient had also
developed numbness of both upper limbs. He had been recently been on an expedition into the scrub
jungles in the eastern province of Sri Lanka and camped in a cave.

On examination, the patient's temperature was 38.5°C, but there was no meningism. He was lucid and
complained of increasing left-arm pain, paresthesiae in both upper limbs, and subjective difficulty in
swallowing. An erythematous area was noted on his left shoulder. His behavior was inappropriately
familiar, and he was mildly dysarthric with gaze-evoked nystagmus. His upper limbs were areflexic with
brisk reflexes in the lower limbs. Truncal, upper limb, and gait ataxia was present. Sensation was altered to
touch over the left upper limb (dysesthesia), symmetrical motor weakness was noted in both upper limbs.
On day 5 of hospitalization, the patient became acutely confused, aggressive, and agitated, and he required
sedation. The patient's score on the Glascow Coma Scale (GCS) was 6 prior to sedation. A second CT scan
(without contrast) was performed, and findings were normal. The patient's CSF protein level on this
occasion was 1091 mg/L with 20 lymphocytes per high-powered field on microscopy. Despite optimum
management the patient passed away on day 7 of illness

Rabies – encephalitis

Key points to look out for

• Rabies has a distinct presentation, with two polar forms that sometimes overlap
• Look for the classical encephalitic presentation which starts with brainstem symptoms and signs
such as dysarthria, pharyngeal muscle over activity in response to swallowing. This later
progresses to a form of encephalitis with aggressive behavior, hallucinations and hyper-
excitability
• Rabies can also present with progressive flaccid limb weakness reminiscent of GBS. The
weakness generally starts from the bitten limb
• Autonomic dysfunction and sphincter involvement is common
• CSF is generally non specific
• Look for an occupational or contact history of rabies
Other closely linked differential diagnosis

• The clinical presentation of rabies is characteristic

How to confirm

• Skin biopsy from the nape of the neck for viral antigen

How to treat

• Rabies is generally fatal in most cases

Case

A 38 year old Sri Lankan businessman from Colombo who has received his second renal transplant
presented with 1 week history of fever, headache and altered level of consciousness. His primary renal
pathology was a rapidly progressing glomerulonephritis which had evolved into ESRF despite aggressive
immunotherapy. He developed severe antibody mediated rejection, 6 months into his first transplant
which resulted in graft nephrectomy. After admission the patient developed progressive right upper and
lower limb weakness and dysphasia. The MRI brain demonstrated a ring enhancing lesion in the left
parietal lobe

Cerebral abscesses in the immunocompromised

Key points to look out for

• A cerebral abscess is a suppurative infection of the brain parenchyma

• Cerebral abscesses in the immunocompromised patient can be due to several bacterial, viral,
fungal and parasitic organisms. Important causative agents include Norcardia, Toxoplasma,
Aspergillus, Cryptococcus and Coccidioides
• The clinical manifestations are fever, headache and additional features of a space occupying
lesion with focal neurology suggestive of the anatomical localization
• MRI and CT contrast will demonstrate ring enhancing lesions. Early stages may not have ring
enhancing properties

How to confirm

• Imaging, and the above clinical profile

How to treat

• Antiobiotics – ceftriaxone, metronidazole +/- vancomycin

• Dexamethasone
Case

A 61-year-old man was referred from an ophthalmology outpatient clinic complaining of progressive visual loss,
affecting his right visual field, over the previous two to three weeks and occasional headaches, described as a
pressure sensation over the occipital region. Over the last week before presentation he has also noted gradual
and progressive right upper and lower limb weakness. He has been employed as a businessman and travels
frequently to South Africa and South East Asia for business deals.

On examination, his visual acuity was 6/36 on the right and 6/24 on the left, with a dense right-sided
hemianopia involving the macula. His optic discs were pale and pupillary responses were normal. The remainder
of the cranial nerve examination was normal. Motor examination revealed increased tone and reflexes in both
lower limbs with reduced power noted on the right side. He had sustained ankle clonus on the right and an
extensor right plantar response. Sensation was preserved. On general examination, lymphadenopathy affecting
the left supraclavicular area, both axillae and the inguinal region

What would you consider in the differential diagnosis?

• The patient has risk factors for retroviral infection

• And has features of a progressive neurological lesion in the occipito-parietal region
• Infection – PML, toxoplasmosis, cerebral tuberculoma
• Cerebral lymphoma

HIV related PML (JC virus infection)

Key points to look out for and other closely linked differential diagnosis

• Look out for risk factors for HIV infection

• The classical presentation is a progressive focal neurological deficit, commonly involving the
occipito-parietal region. Visual disturbances are a common presentation with homonymous
hemianopia noted on neurological examination
• An important differentiating factor with other infective disease and cerebral lymphoma would
be that fever, headache and features of increased intra-cranial pressure are extremely
uncommon in PML

How to confirm

• MRI T2 hyperintensities in the white matter, without surrounding cerebral edema or contrast
enhancement. This differentiates PML from most other clinically related infective and neoplastic
disease (lymphoma)
• JC virus PCR in CSF

How to treat

• HAART
HIV related neurological disease

Clinical manifestations Investigations Treatment

Cerebral Reactivation of latent Imaging Sulfadiazine +
toxoplasmosis toxoplasmosis Multiple enhancing Pyrimethamine + Folinic
Fever, confusion, focal abscesses – acid
neurological deficit corticomedullary Secondary prophylaxis
junction and basal
ganglia – Gad Prophylaxis (primary)
enhancement, CD4< 100 – TMP-SMX
marked edema

IgG antibodies +
PCR in CSF
CD4 < 200
Cryptococcal Fever, headache, CSF Intravenous
meningitis features of meningism Lymphocytosis, amphotericin B -
can be absent increased protein Fluconazole
Can be normal
CSF – India Ink stain
Antigen detection
Imaging – basal
meningeal
enhacement, masses
Progressive multifocal Due to reactivation of Imaging No specific treatment
leukoencephalopathy the JC virus Subcortical lesions HAART – initially worsens
Progressive dementia, without /edema,T2 clinical condition but
dysphasia, visual hyperintense later stabilizes
disturbances, motor PCR for JC in CSF
weakness
CMV encephalitis Usually CD4<50 Imaging Gancyclovir
Confusion, cranial nerve Diffuse T2 Foscarnet
palsies hyperintensities
Periventricular
enhancement
CSF
Primary CNS B cell origin Imaging Radiation and
lymphoma Associated with EBV Lesions with irregular chemotherapy
Confusion, headache, contrast
focal signs enhancement in
periventricular
regions

EBV PCR in CSF

Malignant cells
HAND (AIDS Present with initial CSF is non-specific HAART
dementia) apathy and depression with variable
 progressing into a increase in protein
subcortical dementia and mononuclear
with lack of executive cells
function
CMV retinitis Occurs in patients with Gancyclovir
profound Foscarnet
immunosupression
Subacute onset visual
symptoms – blurred
vision, scotomas,
flashing lights

Fundus – Exudates,
hemorrhages, vascular
sheathing

Case

A 25-year-old black male with AIDS, who had a CD4 count of 9 cells/ml and a viral load of 31 000
copies/ml, presented with a 3-month history of weakness in both lower limbs. He was unable to walk
unaided, and described ‘pins and needles’ in his legs and decreased sensation up to approximately
thoracic dermatomal level 12. He described a dull lumbo-sacral backache with no sphincter dysfunction.
He had a history of treatment for pulmonary tuberculosis in 2000. On examination, he was cachectic with
generalized lymphadenopathy and oral thrush. He was apyrexial and normotensive with a pulse rate of
86 beats/min. He was lucid and did not display any neck stiffness. Examination of the cranial nerves and
upper limbs was normal apart from proprioceptive loss in the upper limbs. The tone in his lower limbs
was increased and the power in his lower limbs was Medical Research Council scale (MRC) grade 4. The
knee reflexes were brisk but the ankle reflexes were diminished. The plantar responses were extensor
bilaterally. He had global joint position sense loss and had a thoracic dermatomal sensory level of 9 to
pinprick and light touch. Vitamin B12 and folate levels were noted to be normal

HIV related myelopathy – infection and other differential diagnosis

Key points to look out for

• The causes of myelopathy in HIV include

• HIV related vacuolar myelopathy
• HTLV-1 related myelopathy
• Infection related myelopathy – CMV, TB
• Co-existent syphilitic myelopathy
• B12 deficiency related myelopathy

Closely linked differential diagnosis

• HIV related vacuolar myelopathy is a diagnosis of exclusion. This usually occurs in the late stages
of HIV disease. Predominant posterior column involvement is noted and a sharp sensory level is
 usually not present. It has a subacute, slowly progressing temporal profile. In fact, HIV VM can
mimic vitamin B12 deficiency and subacute combined degeneration of the cord
MRI is usually normal in VM, but can also demonstrate cord atrophy or high signal intensity of
the posterior columns
• Most infection related myelopathies in HIV present with clear acute onset transverse myelitis.
CMV can also present with a cauda equina syndrome or as a lower limb radioculoplexopathy
• HTLV related myelopathy can mimic the presentation of VM. However a lymphocytic pleocytosis
is noted in HTLV – 1 disease, whereas the CSF is usually normal apart from mild protein
elevation in HIV VM
• Tabes dorsalis is a specific disorder presenting with lancinating pain of the lower limbs and
prominent posterior column signs. These patients also have Argyll Robertson pupils

How to confirm

• VM is a diagnosis of exclusion

How to treat

• No specific therapy

Case

A 55 year old intravenous drug user presented with fever and pain in the thoracic region for 4 days
duration. He was previously apparently healthy apart from COPD and is on regular inhaled corticosteroids.
After admission, the patient gradually developed bilateral lower limb weakness and urinary incontinence.
On examination the patient was febrile, with a pulse rate of 104/min and blood pressure of 110/70.
Respiratory and abdominal examination was normal. The patient had flaccid lower limbs with extensor
plantars and power 2/5 in both proximal and distal muscle groups. He had a sensory level at T7.

FBC demonstrated a neutrophil leukocytosis

Spinal epidural abscess

Key points to look out for

• Look for obvious risk factors. The most common form of spread is hematogenous
• IV drug use is one of the most common predisposing factors for epidural abscesses
• The initial symptoms are usually radicular in nature. The patient will later develop features of
cord compression
• Spinal tenderness is usually a feature
• The FBC count and inflammatory markers will usually demonstrate the profile of a bacterial
infection

How to confirm

• MRI – Can demonstrate the epidural collection

How to treat
 • Surgical decompression
• Antibiotic therapy – Ceftriaxone, metronidazole +/- vancomycin

Case

A 35 year old tourist guide presented with a 3 month history of progressing loss of memory. He has
had normal functioning up to around 2 years ago when he began to develop episodes of depression
alternating with psychotic symptoms and was treated for bipolar affective disorder. He has recently
been having hallucinations which have not responded to antipsychotic therapy. On examination the
patient has a pulse rate of 92/min, with normal respiratory and abdominal examination. His
neurological examination is normal except for an MMSE of 12/20 and bilateral small non-reactive
pupils

Neurosyphilis

Key points to look out for

• Even though this is rare in practice due to early detection and treatment of syphilis, it can
feature as a grey case
• These patients present with a multitude of manifestations. One of the important ones are with a
chronic aseptic meningitis which causes predominant basal meningeal signs and lower cranial
nerve palsies
• General paresis of the insane
This presents with progressive abnormalities including those of personality, affect (psychiatric
manifestations – mania, paranoia), hyper-reflexia, AR pupils, and altered intellect and speech
abnormalities
• Meningovascular involvement can also occur, with strokes due to thrombotic episodes
• A chronic meningoencephalitis is also recognized with dementia. An important clue is to
recognize the presence of Argyll Robertson pupils
• Tabes dorsalis presents with lancinating lower limb pain, altered proprioception and ataxia,
some patients manifest bladder incontinence
• The case may give clues of primary syphilis such as chancres and the typical rashes and
lymphadenopathy in secondary syphilis

Other closely linked differential diagnosis

• It is important to think of TBM and fungal meningitis as differential diagnoses. The CSF
examination should provide a clue. In syphilis a lymphocytic pleocytosis is noted with increased
protein and normal CSF glucose. The CSF VDRL is almost always reactive

How to confirm

• Clinical profile and CSF VDRL

How to treat

• Penicillin
 Case

A 20 year old beautician presents with progressive drooping of both eyelids, mild diplopia on lateral gaze,
and dysphagia with drooling of saliva. After admission, the patient also has noted bilateral upper limb
weakness. She does not have any past history of significant illness, but has been overly concerned about
her appearance and has been seen by a psychiatrist for possible anorexia nervosa in the past. On
examination, the patient is distressed, and has bilateral external ophthalmoplegia with flaccid upper limb
weakness and generalized hyper-reflexia. Her pupils are dilated, and poorly responsive to light. Other
systems are normal
Botulism

Botulism

Key points to look out for

• The infective organism causing botulism may be acquired from several sources. Look in the
history to identify the possible source. This may be food borne, or acquired though a
contaminated wound
• Extra-ocular muscle and bulbar involvement predominates with descending paralysis. A
important point to note is the involvement of the pupils causing pupillary dilation
• The autonomic nervous system is also involved with bowel and bladder dysfunction

Other closely linked differential diagnosis

• Botulism can closely mimic MFS. MFS does not cause weakness of the limbs, but only manifests
ophthalmoplegia, ataxia and areflexia. The pupils are also not involved
• Krait bite can also mimic the clinical presentation of botulism. It also causes external
ophthalmoplegia, with limb weakness and pupillary dilation. The circumstances should be
evaluated in the given history. Abdominal pain is also a common manifestation of krait bite
• MG should also be considered as a differential diagnosis, but MG never causes pupillary
involvement

How to confirm

• EMG
• Characteristic findings in patients with botulism include brief low-voltage compound motor-
units, small M-wave amplitudes, and overly abundant action potentials. An incremental increase
in M-wave amplitude with rapid repetitive nerve stimulation may help to localize the disorder to
the neuromuscular junction
• Demonstration of the toxin by bioassay in mice
• False positive edrophonium

How to treat

• Anti-toxin
 Case

A 55 year old farmer presented to the emergency unit with whole body spasms, trismus and dysarthria.
Two weeks earlier, he developed myalgia and had difficulty in opening his mouth. His doctor prescribed
tramadol HCl/acetaminophen, pregabalin and diazepam. However, his symptoms continued to worsen,
and he was unable to walk. He was carried to the emergency room of our hospital by an ambulance. The
patient had type 2 diabetes, which was managed with a daily self-injection of insulin and self-monitoring
of blood glucose. His family history was unremarkable. On examination, he appeared febrile, but was
lucid. His heart rate was 105/min., blood pressure was 167/ 99 mmHg, respiratory rate was 28
breaths/min, oxygen saturation was 92% and temperature was 38.9°C. On chest auscultation, his lung
sounds were clear and there was no heart murmur. His skin was sweaty, but no wounds were observed.
On neurological examination, he had severe trismus, jaw cramping, dysphagia, painful muscle spasms
involving the whole body and opisthotonos.

Initial laboratory studies showed the following: white blood cell count 14 000/mm3 , hemoglobin 16.4
g/dL, platelet count 112 9 103 , C-reactive protein 18.39 mg/dL, aspartate aminotransferase 169 IU/L,
alanine aminotransferase 94 IU/L, lactate dehydrogenase 1414 IU/L, blood urea nitrogen 116.1 mg/dL;
creatinine 5.12 mg/dL, sodium 143 mEq/L, potassium 5.1 mEq/L, chloride 105 mEq/L, serum blood
Tetanus
glucose 525 mg/dL and hemoglobin A1c 7.7%. Creatine phosphokinase was elevated to 9433 U/L.
Urinary
Key pointsmyoglobin was
to look out for890 ng/mL. Chest radiography and computed tomography showed an infiltrative
shadow in the right lower lung. The electrocardiogram was normal.
• The classical presentation of tetanus is with muscle rigidity and spasms
• Trismus, jaw cramping and a opisthotonic posture are typical clinical features
• Proximal muscles are more involved and patients usually have exaggerated reflexes and
autonomic dysfunction
• Look for a possible history of injury or skin portal of entry in the physical examination
• Look for complications of rhabdomyolysis and subsequent AKI

Other closely linked differential diagnosis

• Non infectious aetiologies should be considered in the differential diagnosis. These include
Strychinine poisoning and neuroleptic malignant syndrome

How to confirm

• Clinical diagnosis

How to treat

• ICU and respiratory care

• Antibiotics – Penicillin, metranidazole – Clindamycin in penicillin sensitive patients
• Anti toxin – HTIG – to neutralize unbound toxin in the wound and circulating toxin
• Control of muscle spasms – BDZ, therapeutic paralysis – other – baclofen, dantrolene,
magnesium
• Autonomic dysregulation- esomolol, magnesium sulphate
Case

A 28 year old who had recently returned from the USA presented with back pain. He had a history of a skin
rash while in the USA and had taken treatment for it. This pain initially developed over her right thigh and
then progressed down to her right ankle, buttocks and finally to her back. She was admitted as the pain
became excruciating and worsened on lying flat. The patient did not get any relief even after having
analgesics. The Pain gradually subsided in 14 days of post admission on treatment with analgesics and
antibiotics and was discharged. The following month she was brought to the accident and emergency
department and was diagnosed with urinary tract infection which was treated with ciprofloxacin. Two days
later she developed double vision accompanied with headache which progressed to left sided facial weakness.
Her past medical history revealed an attack of Bell’s palsy 5 years prior to this episode for which she was
treated with Acyclovir and Steroids.

On Neurological assessment her fundoscopy was normal and visual field intact. On further examination she
had bilateral 7th nerve palsy which was more prominent on right side. Both upper and lower limb examination
revealed that the tone and power were normal. But when reflexes were tested on reinforcement the triceps
showed decreased reflex activity whereas biceps exhibited an increased reflex. Similarly reflex activities were
tested on the lower limbs which exhibited decreased ankle reflex and flexor plantar response. The sensory
perception was tested using light touch, pain and prick which was found to be normal. Vibration sensation
was decreased bilaterally over both knees. Gait was normal but mildly ataxic. Romberg’s sign was negative.

Lyme’s disease – Neuroborreliosis

Key points to look out for

• Look for the cardinal temporal profile of manifestations in Lyme’s disease

• The initial manifestation is an early localized infection with the classical skin rash – erythema
chronicum migrans
• Neurological involvement develops subsequent to this initial stage. Meningitis, encephalitis,
radiculopathy and peripheral neuropathy with associated cranial nerve involvement are the
common neurological manifestations
• Cardiovascular involvement with myocarditis and conduction defects is a characteristic
presentation
• Late disease manifestations are also noted. These can persists up to several months since onset
of infection. This includes musculoskeletal involvement with joint effusions (neutrophilic
predominance), CNS involvement with a chronic encephalopathy and peripheral neuropathy
reminiscent of neurosyphilis
• Other manifestations in the late stage includes a fibromyalgia like syndrome

Other closely linked differential diagnosis

• Sarcoidosis need exclusion

 • Also think of autoimmune disease and vasculitis

How to confirm

• Serological tests are useful for the diagnosis – ELISA IgM and IgG
• Confirmatory test – Western blot

How to treat

• Doxycycline for 28 days

• Severe disease is treated with ceftriaxone

Case

A 55 year old male from an urban slum area presented with vertigo, occasional vomiting mainly in morning
and two sudden attack of seizures 11 days apart. His seizures were generalized and tonic-clonic, lasted for
about 2 minutes each time and associated with tongue bite and micturition. Historical information includes
no history of trauma, and no dental work or foreign travel. There was no history of chronic cough, chronic
diarrhoea, weight loss, decreased appetite or any past history suggestive of diabetes, hypertension and
tuberculosis.

On examination, the patient was well alert, conscious and cooperative. His cardiovascular, respiratory,
musculoskeletal and gastrointestinal systems were within normal limit. Neurological examination revealed
exaggerated all deep reflexes of upper and lower limbs with bilateral planter exterior response. His
ophthalmic examination revealed mild bilateral papilloedema. Investigations revealed a normal
hematological parameters. The erythrocyte sedimentation rate was 45 mm/h. Routine biochemical
investigations revealed normal glucose levels and renal and liver function tests. . Chest X-ray showed an
incidental solitary pulmonary nodule less than 1.5 cm in diameter in the right lung. CT brain showed
multiple calcified lesions in both cerebral hemispheres

Neurocysticercosis

Key points to look out for

• This infection is acquired by consumption of faecally contaminated food and ingestion of larvae
in undercooked pork
• Symptoms can occur many years after the actual ingestion of contaminated food
• Seizures are a common presentation. However overwhelming infection can present with
meningitis, hydrocephalus and focal neurological deficit
• Calcified lesions are the most important finding on cerebral imaging
• CSF may demonstrate eosinophilia
How to treat

• Albendazole and steroids

• Surgical resection in selected patients
Case

A 29 year old flight attendant was admitted to the National Hospital of Sri Lanka with fever for 5 days
duration. She also has associated arthralgia and myalgia as well as severe retro-orbital pain. She is
commenced on treatment for dengue, but deteriorates over the next few days with fluctuating levels of
consciousness. On examination her GCS is 12/15, no neck stiffness is noted. All reflexes are brisk with
bilateral extensor plantar response. Her PR – 120/min with blood pressure noted to be 90/60. Her
respiratory and abdominal examination is normal. Basic investigation findings are as follows. FBC – WBC
– 5000 (normal differential count), Hb 8.2 (normocytic normochromic indices), retic count – 6%,
platelets – 89,000, RBS – 50, serum sodium – 140, serum potassium – 3.8, serum creatinine – 180, AST –
90, ALT – 100, total bilirubin – 3.4, UFR – albumin +, CXR normal, CT brain – Normal

Cerebral malaria

Key points to look out for

• This is an important cause of encephalopathy to consider in an overseas travel setting. Sri Lanka
is certified to have eradicated malaria
• The encephalopathy is usually associated with multi-organ dysfunction and electrolytes
disturbances including metabolic acidosis and hypoglycaemia
• Thrombocytopenia and DIC may also occur
• Neurological manifestations are dysconjugate gaze palsies and upper motor neuron signs in the
lower limbs

Other closely linked differential diagnosis

• Flaviviral encephalopathies such as dengue can mimic cerebral malaria

How to confirm

• Thick and thin blood film

• Determination of parasitaemia

How to treat

• Intravenous artesunate
Case

A 33 year old male was referred to the neurology clinic with a 5-month history of slurred speech, clumsy upper
limbs, impaired hand writing, and progressive gait problems. He also reported worsening memory for recent
events, which he attributed to impaired concentration. A diagnosis of depression was made, and his mood
improved somewhat on selective serotonin reuptake inhibitors. He denied any visual, swallowing, or sphincter
difficulties. However, he reported uncomfortable sensations in both his lower extremities. His general health
had been good, and he had no previous history of neurologic disease. He had no family history of similar
neurologic disease. He did not smoke, he drank occasionally, and he did not use any recreational drugs.

The findings upon general examination were unremarkable, other than the patient’s flat affect. Higher-function
testing revealed

With time the patient gradually developed abnormal movements

CJD

Key points to look out for

• Sporadic CJD has a typical presentation. It manifests with progressive dementia, usually after the
age of 60 years. Other typical neurological manifestations are, myoclonus, visual or cerebellar
disturbance, pyramidal/extrapyramidal dysfunction and akinetic mutism
• The typical EEG findings are, generalized triphasic periodic complexes at approximately one per
second
• Familial forms of CJD are also recognized
• Iatrogenic CJD can occur due to prion transmission from cadaver derived pituitary hormone
• Variant CJD has a different presentation. This form of CJD occurs at a much younger mean age
and has a prominence of psychiatric and sensory signs early in the disease, with subsequent
progression to dementia and development of the classical motor signs of the disease. The EEG
also will not show the typical triphasic periodic complex pattern
• MRI findings if given usually are, cerebral atrophy and T2 hyperintensities in the basal ganglia
• A hyperintense pulvinar sign will be seen in patients with variant CJD

Other closely linked differential diagnosis

• Autoimmune encephalitis – esp. – limbic encephalitis

• JC virus – PML
• CNS lymphoma
• Dementia with Lewy bodies is a very important differential diagnosis. The classical
manifestations of DLB will be with fluctuating parkinsonism, prominent visual hallucinations and
REM sleep associated behavioral disorders
• HD dementia can also present with associated extrapyramidal movement disorders. However
chorea and athetosis are the common manifestations
• SSPE should be a differential diagnosis of variant CJD. This disorder presents in childhood with
progressive cognitive decline and worsening movement disorders including myoclonus,
 choreoathetosis, dystonia and rigidity. The EEG in SSPE synchronous bursts of high amplitude
slow wave activity. CSF has a high IG content. Confirmation is with Measles IgM in CSF

How to confirm

• Brain biopsy is the gold standard for diagnosis

• CSF 14-3-3 protein can also be performed

How to treat

• No available therapy
Chapter 7
Skin and soft tissue infection
Case

A 68-year-old man presented to the cardiovascular specialist at outpatient department with gradually
worsening pain, accompanying with progressive swelling, warm sensation, and erythematous change over
his right low leg for one week. Thrombophlebitis was impressed initially for this admission. He denied
fever, chillness, shortness of breath, chest pain, and other constitutional symptoms. He had no history of
heart disease or other medical conditions. He did not have the habit of smoking, drinking and drug abuse.
He worked at a restaurant with a history of long-term standing over 12 hours per day. Recent trauma,
heavy exercise, history of traveling, and exposure to animals were denied. On physical examination, he
appeared well nourished but felt a lot of pain over his right low leg. His right knee was held in an extension
position. He was afebrile and non-toxic with a heart rate of 82 beats per minute and a blood pressure of
127/63 mmHg. Systemic examination was normal. Local examination of his right low leg disclosed a
swollen, warm, and tense calf with overlying erythema. No evidence of fluctuance but diffuse tenderness
with a wooden consistency over the lesion was identified. Regional lymphadenopathy was absent. He
could not walk on account of the difficulty in weight bearing and knee flexion. Significant investigations
included a white cell count of 12,500/ L, with neutrophil 83.1%, lymphocyte 5.9%, monocyte 8.6%, and
eosinophil 2.4%; hemoglobin ,14.0 g/dL; platelet count, 310,000/ L; blood group B Rh positive; creatinine
phosphokinase (CK), 48 U/L; aspartate aminotransferase (AST), 30 U/L; alanine aminotransferase (ALT) 46,
U/L; blood sugar, 87 mg/dL; blood urinary nitrogen, 14 mg/dL; serum creatinine, 1.0 mg/dL; serum
albumin, 2.7 mg/dL; C-reactive protein 145.

Tropical pyomyositis

Key points to look out for

• This is a focal muscle infection, caused in most cases by Staphylococcus aureus

• Muscle groups most frequently involved are quadriceps, glutei, pectoralis major, serratus
anterior, biceps, iliopsoas, and gastrocnemius
• The infection commonly affects the immunocompromised – DM and HIV
• Clinical features are non-specific and overt features of sepsis may manifest only in the late
stages of the disease
• In the early stages of the disease, the affected area of muscle is tender, firm and has a woody
consistency. Erythema may be absent as this is a deep seated infection. By the second or third
week of illness abscesses begin to form and if left untreated, the patient develops sepsis
• Muscle enzymes are usually normal

Other closely linked differential diagnosis

• Occasionally, the stage of invasion by Cysticercus cellulosae is characterised by fever, muscle

tenderness, and eosinophilia and needs to be differentiated from tropical pyomyositis.
 • Rarely, focal or diffuse inflammatory myopathy due to trypanosomiasis or toxoplasmosis
presents as severe myalgia mimicking pyomyositis. It must also be distinguished from
spontaneous gangrenous myositis (caused by Streptococcus pyogenes) characterised by
gangrenous necrosis

How to confirm

• Aspiration of pus from the muscle or muscle biopsy with culture and tissue staining in cases of
absent macroabscesses is the gold standard for diagnosis
• Computed tomography shows areas of low attenuation with loss of muscle planes and a
surrounding rim of contrast enhancement as characteristic of pyomyositis
• MRI shows hyperintense rim on T1 weighted images with peripheral enhancement on
gadolinium

How to treat

• Surgical debridement and drainage

• Anti staphylococcal antibiotcs
Chapter 7
Bone and joint infection
Case

A 75 year old female underwent cardiac catheterization 3 months before admission. A few days after
catheterization she noted a fever that lasted for 2-3 days. Approximately 3 weeks after catheterization, she
began to experience dull pain in the lumbosacral region that progressively worsened over the next two
months. She had significant nocturnal pain and reported a 10kg weight loss.

She was febrile on examination and tachycardic with a pulse rate of 120/min. The cardiovascular
examination was significant for a systolic murmur in the left lower sternal edge. Palpation over the lower
lumbar spinal area elicited significant tenderness.

FBC – 8100 (70% neutrophils), Hb 10.4, normocytic normochromic indices, platelets – 560,000. ESR – 120,
CRP – 93.

Hematogenous osteomyelitis

Key points to look out for

• Hematogenous osteomyelitis predominantly affects the immunocompromised and patients at

extremes of age. It is also particularly common in patient who use IV drugs and in patients with
endocarditis due to septic embolization
• Long bone involvement and vertebral involvement in common. Localized tenderness with bone
pain and elevated inflammatory markers is suggestive of the diagnosis

How to confirm

• Plain X rays – periosteal elevation, areas of demineralization and loss of a sharp bony margin
with soft tissue swelling. In the late stages, areas of increased calcification or sclerosis is noted.
CT is more sensitive. CT guided tissue sampling may also be required in patients with vertebral
osteomyelitis
• Bone scan can be performed for confirmation of early disease. Gallium scan is more sensitive for
vertebral osteomyelitis
• Blood cultures

How to treat

• Antibiotics – covering Staphylococcus aureus

• Surgical debridement in some cases and decompressive surgery in patients with vertebral
osteomyelitis
Case

A 50 year old female was referred to our hospital, because of recurrent polyarthritis, recurrent erythema
nodosum on her left forearm, dry cough, and body weight loss of 4 kg over the preceding 3 months, and
slight fever for a week. She had been diagnosed with undifferentiated polyarthritis by a general practitioner.
Having been diagnosed as having bronchial asthma by a general physician, her chest X-ray was within normal
limits at the time. On clinical examination at our hospital, the patient’s elbows, wrists, knees, ankles, and
metatarsophalangeal joints were tender on palpation. There were no swollen joints on examination though
she had been suffering from recurrent polyarthritis over a course of 3 days. She had no erythema nodosum
on examination though she had recurrent painful erythema nodosum, two centimeters in diameter, for 3–5
days. She had no wheezing or crackles in her chest, or lymphadenopathy. Her body temperature was 37.0°C,
oxygen saturation by pulse oximetry (SpO2) was 98% on air, and heart rate was 71 beats per min sinus
rhythm. Laboratory findings were as follows: urinalysis: normal, white blood cells: 6,100/, hemoglobin: 10.3
g/dl, platelet count: 228,000, ESR: 15 mm/h. antinuclear antigen, rheumatoid factor and anti-cyclic
citrullinated peptide antibody (anti-CCP) were negative. CH50: 52.6 U/ml (30–45 U/ml), C3: 89 mg/dl (70–
129 mg/dl), C4: 34 mg/dl (12–36 mg/dl), CRP: 0.23 mg/dl (0–0.2 mg/dl), ferritin: 12.0 ng/ml (5–71 ng/ml).
Serum electrolytes, liver and kidney functions, total bilirubin, and serum iron: normal. Chest X-ray and
computed tomography revealed infiltration of the right upper lobe. X-rays of the hands and feet showed no
abnormalities

Poncet’s disease

Key features to look out for

• Poncet’s disease is a reactive arthritis secondary to TB

• The clinical presentation of the disease is with an oligo or polyarthritis
• Erythema nodosum may be present. Look carefully for the focus of active tuberculosis
• All other markers such as RF, ANA is negative

Other closely linked differential diagnosis

• Sarcoidosis is an important differential diagnosis to consider when a patient presents with

erythema nodosum and arthritis
• IBD should also be considered as the arthritis syndrome can precede the onset of
gastrointestinal symptoms

How to confirm

• Confirm the presence of TB and exclude other possible causes

How to treat

• This generally responds with the commencement of ATT

Case

A 25 year old male presented with high fever, sore throat and bilateral arthritis of the wrists. He had been
well until 4 days before admission, when he developed chills, fever (40℃) and sore throat. Two days
before admission, painful swelling of the right wrist and a rash appeared. He had no history of urethral
symptoms or travel abroad. Physical examination revealed a temperature of 39.4℃. The posterior wall of
the pharynx was reddened. Both tonsils were enlarged and reddened, and the crypts were covered with
white exudate. A bilateral cervical lymphadenopathy was also noted. Multiple rashes were composed of
tender erythematous papules, partly pustular, on both of the forearms and both hands. Both wrists had
painful swelling, and the right wrist had associated flexor tenosynovitis. There were no signs of meningeal,
ocular, genitourinary or rectal involvement

Disseminated Gonococcal infection

Key points to look out for

• This commonly occurs in young sexually active individuals

• Two clinical syndromes are associated with disseminated Gonococcal infection
• Tenosynovitis, dermatitis and polyarthritis syndrome – this manifests with high fever, malaise
and arthralgia. Tenosynovitis of the wrist, fingers is characteristic. Tendon sheaths of the ankles
and toes may also be involved. Pustular, pustule-vesicular and hemorrhagic skin lesions may also
be present
• The other form of the disease is with septic arthritis without obvious skin lesions

Other closely linked differential diagnosis

• Gonococcal infection and cause vasculitis and mimic IE and primary systemic vasculitis

How to confirm

• Blood cultures are the gold standard for diagnosis

How to treat

• Penicillin/Ceftriaxone
Chapter 8
Zoonotic infection
Case

A 30 year old Sri Lankan farmer presented with sudden onset of paraparesis, urinary retention, and
numbness below his upper abdomen of three weeks duration. He did not have symptoms referable to his
upper limbs and cranial nerves, seizures or loss of consciousness. On admission to our unit, he had spastic
paraparesis with grade 4 muscle power and extensor plantar responses. A sensory level with impairment of
pain, touch, temperature and joint position sense was present at the D8 segmental level. Sacral sensation
was lost. The gait was spastic, but he was able to walk with support. There were no neurological deficits in
the upper limbs. Coordination was normal. He had urinary retention, and bilateral papilloedema. Higher
cortical functions and other cranial nerves were normal. Except for a non-tender, firm enlargement of the
liver extending 3 cm below the right costal margin, the rest of physical examination was normal. Magnetic
resonance imaging (MRI) scan of the dorsal spine excluded a compressive myelopathy and demyelination. A
contrast-enhanced computed tomography (CT) of the brain excluded an intracranial spacevoccupying lesion.
The cerebrospinal fluid (CSF) was clear with 40 mg/ dl of proteins, 34/μL of lymphocytes and 4.9 mmo1/L of
glucose (Blood glucose 6.2 mmo1/L). A polymerase chain reaction test for Mycobacterium tuberculosis was
negative.

FBC – WBC – 21,000 (90% neutrophils), Hb – 9.2, platelets – 89,000, ESR – 30, Serum creatinine - 190 Serum
bilirubin – 40, AST – 340, ALT – 200, ALP – 300, UFR – protein +, field full red cells

Unusual manifestations of
leptospirosis

The table presented on the right

gives a list of the unusual
manifestations of this common
disease

Neurological manifestations are

diverse and should be taken note of

How to confirm

• MAT for leptospirosis with

analysis of serovar
• PCR for leptospirosis

How to treat

• Antibiotics – Ceftriaxone or
C. Penicillin
Case

A 38 year old tourist guide presented with symptoms of high-grade fever since 10 days followed by pedal edema
and decreased urine output since 4 days and shortness of breath after 2 days which were associated with dry
cough. There was no history of paroxysmal nocturnal dyspnea and orthopnea. History of epistaxis was present
since 1 day. He had recently visited Yala on safari and denied any unsafe sexual contact

On examination, his blood pressure was 130/80 mm Hg, pulse rate was 88/min, patient was afebrile. There were
no rashes or jaundice or pedal edema, liver, and spleen was not palpable. Cardiovascular examination revealed no
abnormality. Examination of lungs revealed bilateral crepitations, which were heard more on the left side. Blood
was sent for investigations and treatment was started with ceftriaxone. Investigations revealed hemoglobin -9.1
mg/dl, platelet count -30,000/mm 3 , blood urea -96 mg/dl, serum creatinine -1.8 mg/dl, blood sugar -71 mg/dl,
serum electrolytes: Sodium -142 mm, potassium -3.7 mm, chlorine -106 mm, bicarbonate -17 mm, X-ray chest was
suggestive of bilateral bronchopneumonia

Scrub typhus

Key points to look out for

• The clinical manifestations of typhus are diverse

• Look for risk factors suggestive of exposure to Typhus
• Typhus causes fever and a small vessel vasculitis – this can manifest with skin rash, joint pain,
renal and pulmonary involvement
• An eschar is a clinical clue to aid the diagnosis

Other closely linked differential diagnosis

• Other infections can present with a small vessel vasculitis – the most important are
leptospirosis, infective endocarditis and hepatitis B and C
• Syphilis and HIV can also present with a clinical picture suggestive of a vasculitis

How to confirm

• The Weil – Felix test is non-specific

• Antibody profiles should be evaluated

How to treat

• Doxycycline
Parasitic infection

Malaria

Introduction

• Caused by infection by the protozoan parasite plasmodium

Epidemiology

• Endemic – in Africa, South and Central America and parts of Asia

• Malaria is considered to be eradicated from Sri Lanka

Plasmodium falciparum Plasmodium vivax

Hepatic phase No hypnozoites in the liver Hypnozoites present
RBC stage Polyparasitism No polyparasitism
Multiple ring stages in RBC Single ring stage
High percentage of RBC Low percentage of RBC parasitism
parasitism
Can infect RBC at any stage Single stage mature RBCs
RBC not enlarged Enlarged RBC
Ring stages and mature All stages of development seen in
gametocytes only developmental peripheral blood
forms
Gametocyte shape - sickle Oval shaped gametocytes

Severe plasmodium malaria

Key points to look out for

• Plasmodium falciparum malaria presents with severe illness. The disease manifestations are as
follows
Cerebral malaria – reduced level of consciousness, seizures, focal neurology
Anaemia
Hepatic dysfunction
AKI
DIC and coagulopathy, hemolytic anaemia, thrombocytopenia, splenic rupture
ARDS
Metabolic complications - Lactic acidosis, hypoglycemia

How to confirm

• Thick and thin films are required for the confirmation of the diagnosis
• Rapid diagnosis

How to treat
 • This is a medical emergency and the patient should be monitored and treated for related
complications including cerebral malaria, hypoglycaemia and AKI with metabolic acidosis.
Definitive therapy is with Intravenous artesunate for a minimum of 24 hours, followed by ACT
for 3 days and a single dose of primaquine. Intravenous quinine is substituted for artesunate if
the latter is not available. All of these drugs are available only with direct request from the anti-
malaria campaign of Sri Lanka.
• The patient should be monitored clinically. The parasite load is also determined to assess the
response to treatment

Case

A 50 year old man, employed in Kenya for the 2 years presented with the patient presented with complaints
of recurrent fever with chills for six months, progressive generalized weakness for five months and loss of
appetite for one month. The patient was apparently fine seven months earlier, when he started complaining
of fever with chills on and off. He took local symptomatic treatment (paracetamol for fever and
multivitamins) for about one month but did not get any relief and gradually started developing weakness. On
abdominal examination, the liver was palpable about 2cm right below costal margin and spleen was palpable
up to 7cm below the left costal margin. Examination of the other systems was unremarkable. Routine
hematological investigations revealed pancytopenia with haemoglobin level of 7g/dl. Morphological structure
of red blood cells was normocytic hypochromic with thrombocytopenia (platelet count 63000/ml). Tuberculin
test for Tuberculosis, Widal test for enteric fever and blood culture for Brucellosis was negative

Visceral leishmaniasis

Key points to look out for

• Visceral Leishmaniasis is due to invasion of tissues of the reticulo-endothelial system by the

amastigote of the parasite L. donovani
• The epidemiological history of the disease is essential to review. The disease is seen in patients
from India, the middle east and Latin America
• The clinical manifestations of the disease include prolonged fever with loss of appetite and loss
of weight. Skin manifestations include rashes and hyperpigmentation
• Massive hepatosplenomegaly is commonly seen. The disease can occur without splenomegaly in
patients with HIV infection
• FBC commonly shows pancytopenia. A monocytosis can also be evident
• Hypergammaglobulinaemia is common. False positive autoimmune markers (RF) can also occur

Other closely linked differential diagnosis

• Lymphoma, disseminated TB
• Chronic malaria with TSS

How to confirm
 • Bone marrow examination for the amastigote

How to treat

• Amphotericin B
Chapter 9
Viral infections
Case

A 24-year-old previously healthy girl presented with a 4-day history of fever along with myalgia, headache,
and retro-orbital pain. Fever was low grade and continuous. Physical examination revealed morbilliform
rash over trunk and mild hepatosplenomegaly, but no edema or lymphadenopathy. The clinical diagnosis of
dengue fever was made, and NS1 antigen (NS1 Ag) detection for dengue virus was performed. NS1Ag was
detected. The patient started to improve with a conservative management but fever returned after 3 days.
This time the fever was high grade and intermittent with chill and rigor, and she also had developed
yellowish discoloration of eyes and urine. There was history suggestive of menorrhagia. A general survey
revealed moderate pallor and icterus and maculopapular skin rashes over the shinbone. Lymphadenopathy
was absent. Abdominal examination revealed tender hepatomegaly and moderate splenomegaly. An initial
peripheral blood picture showed pancytopenia as evidenced by a hemoglobin concentration of 6.6 g/dl and
a leukocyte count of 1.3 × 109/L with 44% neutrophils (<1 × 109/L) and platelet counts (105 × 109/L), but no
feature of hemoconcentration was found. The erythrocyte sedimentation rate was slightly raised (40
mm/h). Serum lactate dehydrogenase (LDH) was raised (2461 units/l) and serum ferritin was very high
(2161 μg/l). Fasting serum triglyceride measured 534 mg/dl (normal range < 150 mg/dl). Liver function tests
revealed hyperbilirubinemia with raised serum aminotransferases as well as alkaline phosphatase and
hypoalbuminemia. Renal parameters and electrolytes were within the normal limit. Blood and urine culture
were sterile. Chest X-ray showed no detectable abnormality. An ultrasound of abdomen revealed
hepatosplenomegaly and mild ascites

Atypical manifestations of dengue

Key points to look out for

• This demonstrates a case of HLH in dengue

fever
• Other rare clinical manifestations in
dengue are presented in the table
Case

She had had a one-week history of sore throat, non-productive cough, fever and malaise. No history of
trauma was reported. A course of oral antibiotic was prescribed by her local doctor the week prior to her ED
presentation and ceased because of a positive Monospot test. At her home, she complained of an overnight
history of chest and abdominal tenderness. In the morning, she was found lying on the floor of the toilet
after a bang heard and loss of consciousness for approximately 10 s. She had a second syncopal episode a
while later but regained consciousness quickly. Her parents called the ambulance and she was found with a
systolic blood pressure of 80 mmHg at scene and intravenous resuscitation was commenced during transfer
to the emergency department. At the hospital, she was alert and orientated. On admission, she was
haemodynamically stable with evidence of postural hypotension and mildly tachycardic. Tympanic
temperature of 38° was recorded. On examination, her abdomen was tender on palpation and left upper
quadrant was involuntarily guarded. Spleen was not palpable due to guarding and severe tenderness.
Tonsillitis was seen but no cervical lymph nodes were palpable

IMN with complications

Key points to look out for

• Fever, sore throat – phayngitis and membranous tonsilitis, lymphadenopathy – posterior

cervical group common but can be generalized
• Morbiliform/papular rash in patients treated with ampicillin/amoxicillin
• Splenomegaly
• Erythema nodosum and muliforme
• Complications
CNS (within first 2 weeks of infection) – Meningitis, encephalitis, ataxia
Also GBS, TM, cranial nerve palsy
Hematological - Coombs + cold agglutinin disease – intravascular hemolysis, cytopenia, HPS,
splenic rupture – males > females
Upper airway obstruction
Rare – hepatitis, myopericarditis, pneumonia, interstitial nephritis, genital ulcers

How to confirm

• EBV antibodies

How to treat

• Conservative management