MEDICIN

2023
TROPICAL
E

Rasheed Mohammed

TROPICAL | Medicine 1
 Title No.

Malaria
Schistosomiasis
Amebiasis
Bacillary dysentery
Visceral leishmaniasis
Brucellosis
Tuberculosis

TROPICAL | Medicine 2
 MALARIA
• Microbiology
- It is one of the ten most deadly diseases
- Caused by sporozoite of genus Plasmodium
o P. falciparum: malignant tertiary malaria
o P. vivax and ovale: benign tertiary malaria
o P. malarie: Quartan malaria

• Mode of transmission:
1. Transmission through bite of infected female anopheles mosquito
2. Congenital
3. Blood transfusion

• Life cycle
- Sexual cycle in mosquito
- Asexual cycle in human (the intermediate host)
- Sporozoites enter the liver to form schizonts full of merozoites (pre-erythrocytic schizogony)
- Rupture of schizonts releases merozoites in blood
- Merozoites enters RBCs (erythrocytic schizogony).
- Here the duration taking the RBCs to rupture and release merozoites is the definer of the type of
malaria (48 hrs = tertiary, 72 hrs = quartan)
- Fate of merozoites: either the asexual cycle continues → infect another RBCs OR
- they change into male and female gametocytes which are then ingested by the mosquito
- In P. vivax and P. ovale some of the schizonts will give hypnozoites (dormant stage)
- Sporozoites are the infective stage for human
- Infective stage for mosquito is gametocytes

• Natural Resistance to malaria:

- Sickle cell trait AS (not disease)
- Thalassemia
- G6PD deficiency
- Duffy coat antigen negative (resistance for vivax as this Ag is the receptor for vivax)

• Endemicity of malaria
- Measured by rate of splenic enlargement in children
a. Hypoendemic ≤ 10%
b. Mesoendemic 11-50%
c. Hyperendemic 51-75 %
d. Holoendemic ≥ 75%

• Type of infection in malaria

1. Recurrence or reinfection: sporozoites infect erythrocytes, separate from previous infection
2. Relapse: reactivation of hypnozoites form of a parasite in liver. occurs in P.vivax and P.ovale.
3. Recrudescence: exacerbation of persistent undetectable parasitemia, due to survival of erythrocytic
form. mainly P.falciparum and P.vivax

TROPICAL | Medicine 3
 • Pathogenesis of malaria
• Fever:
* Initiated by the process of RBC rupture that leads to the liberation of a new generation of
merozoites (sporulation).
* The fever might result from the release of IL-1 or TNF from macrophages involved in the
ingestion of parasitic or erythrocytic debris.
• Circulatory Changes:
* The high fever results in significant vasodilatation.
* vasodilatation leads to a decrease in the effective circulating blood volume and hypotension,
which may be aggravated by other changes in the small vessels and capillaries
• Anemia
* RBCs destruction during sporulation
* BM depression
* Sequestration of RBCs within the enlarging spleen
* Accelerated clearance of non-parasitized RBCs.
• Thrombocytopenia
* Shortened platelet lifespan by direct parasitic invasion or immune mechanisms (antibodies
mediate platelet destruction)
* Splenic pooling
• Hypoglycemia:
* Failure of hepatic gluconeogenesis
* Increased consumption of glucose by host & parasite
* Quinine stimulates β islets to secrete insulin
• Lactic acidosis:
* Increase anaerobic glycolysis
* Lactate production by the parasite
* Failure of hepatic lactate clearance
• Nephritis
* Deposition of immune complexes in the glomeruli.
• The most dangerous malaria is that of falciparum because
* Heavy parasitemia (increased number of merozoites)
* Infect RBCs of different ages. (Vivax and ovale infect young RBCs (reticulocytes), malarie infect
Old RBCs)
* Cytoadherence (attachment if the RBCs to the endothelium), rosetting (attachment of infected
RBCs to non-infected RBCs) and clumping (attachment of infected RBCs to other infected RBCs).
* Early hemolysis and endotoxin release

• Classical malaria attack

1. Cold stage: vasoconstriction, pale and increased BP and weak thready pulse
2. Hot stage: vasodilation, hot and flushed, drop in BP and full volume pulse
3. Sweating stage: Temp falls to normal, Pulse normal, Patient passes into sleep
- They don't really occur in real practice.

• Clinical feature of Uncomplicated malaria:

- I.P: about 1-3 weeks
- C/P: Abrupt onset of fever and chills, accompanied by headache, myalgias, arthralgias, Mild diarrhea
- O/E: Pallor, Jaundice, Respiratory distress, Hepatosplenomegaly, mental status change

TROPICAL | Medicine 4
 • Criteria of severe malaria:
A. Clinical:
▪ Hyperpyrexia
▪ CNS: Frustration, Multiple convulsions, Coma
▪ Eyes: clinical jaundice.
▪ Mouth and nose: abnormal spontaneous bleeding
▪ Lungs: Dyspnea, ARDS, pulmonary edema by CXR
▪ CVS: Hypotension: systolic less than 70 mmHg.
▪ Kidneys: Oliguria.
B. Laboratory:
▪ Heavy parasitemia:
a. more than 5% of RBCs are infected
b. 10% of infected RBCs contain more than one parasite
c. schizont present in the peripheral blood
▪ Hypoglycemia: glucose less than 50 mg/dL
▪ Metabolic acidosis: bicarbonate less than 15 or lactic acid more than 5.
▪ Anemia: Hb < 5 g/dL, HCT <15%
▪ Macroscopic hemoglobinuria.
▪ Creatinine more than 3 mg/dl

• Forms of severe falciparum malaria

A. Cerebral malaria
• It is a diffuse symmetrical encephalopathy (i.e. Focal neurological deficit is rare).
• C/P:
▪ Frustration; severe weakness pt. unable to stand
▪ Decreased level of consciousness
▪ Multiple convulsions more than 2 in 24 hrs. (generalized tonic clonic)
▪ Unarousable coma
• O/E:
▪ Absent superficial abdominal and Cremasteric reflexes.
▪ Tone, Reflexes and Plantar response are variable Increased or decreased
▪ There are no signs of meningism

B. GI malaria:
• Bilious remittent fever: remittent fever, nausea and coffee ground or bile strained vomiting
Hepatomegaly & jaundice [DDx: is Yellow Fever]
• Dysenteric malaria: Fever, epigastric pain, nausea and vomiting, and bloody diarrhea (red
currant jelly stool)
• Choleric malaria: fever, epigastric pain, nausea and vomiting, and profuse watery diarrhea /
dehydration.

C. Algid malaria:
• Malaria with Sudden onset hypotension (systolic less than 70 mmHg)
• Most probable cause is gram -ve septicemia associated with malaria or spontaneous.
• Usually occurs during mild attack of malaria.
• DDx is Acute adrenal insufficiency

TROPICAL | Medicine 5
 D. Pulmonary edema:
• Represent 80% of the cause of sever malaria
• Due to increase capillary permeability
• C/P: dyspnea, cough, hypoxia
• Mortality rate is 80%

E. Black water fever:

• Hemoglobinuria due to severe intravascular hemolysis or due to quinine therapy (especially
with G6PD deficiency).
• C/P: fever, pallor, jaundice, dark urine, acute kidney injuries (Cr > 3 mg/dl)

• Chronic complications of malaria:

1. Hyperreactive malarial splenomegaly syndrome (HRMSS)
▪ Major criteria
1. Resident of endemic area
2. Massive splenomegaly: more than 10 cm or reaching umbilicus)
3. Elevated serum IgM 2 SD above the local mean
4. High antibodies levels against malaria
5. Clinical and immunological response to antimalarial therapy
▪ Minor criteria
1. Hepatic sinusoidal lymphocytosis
2. Hypersplenism
3. Pancytopenia due to massive spleen
4. Negative blood film.
5. Occurrence within family or tribe
▪ Treatment:
1. Antimalarial for life.
2. Splenectomy if medical failed or severe hypersplenism
3. Death due to overwhelming sepsis.
2. Quartan malaria nephrotic syndrome:
▪ Repeated infection by plasmodium malariae
▪ Soluble immune complexes → Glomerular injury
▪ Cause proteinuria → Nephrotic syndrome
▪ Renal biopsy: Focal segmental glomerulonephritis (FSGS)
▪ Poor response to anti-malarial & steroids

• Diagnosis:
A. General:
1. CBC: normocytic normochromic anemia, Leukopenia with relative lymphocytosis, PL reduced
2. CRP, ESR: increased
3. LFT, coagulation profile, RFT

B. Specific:
1. Blood film for malaria
▪ Thick blood film: to see whether there is a parasite or not
▪ Thin blood film: to see species of the parasite and parasites count.
▪ Falciparum: more than one ring trophozoite per RBC and banana shaped gametocytes.
▪ BF –ve and still suspicious = repeat up to 3 times, if still do BM biopsy
2. Rapid test: ICT for Ag detection (usually done for screening)

TROPICAL | Medicine 6
 • Treatment:
1. Uncomplicated malaria:
A. First line: Artemether + Lumifantrine (AL) (quartum)
▪ Adult dose >35 Kg is 480 mg (= 4 tabs/dose, one tabs contain 120mg)
▪ 6 doses over 3 days
▪ Single initial dose, then again after 8 hours then every 12 hours for 2 days

B. Second line: Dihydroartemisinin + piperaquine (DHAP)

▪ Adult dose (one tab = 40mg/320mg)
o >36 and <75: 3 tabs/ dose
o > 75: 4 tabs/dose
▪ 3 doses over 3 days once daily
C. Third line: Oral Quinine
▪ One tab = 300 mg
▪ 50 kg: 10 mg/kg 3 times daily at 8-hour intervals for 7 days
▪ Adult ≥ 50 kg: 600 mg 3 times daily at 8-hour intervals for 7 days

D. In P.vivax and P.oval we add Primaquine 15 mg/daily for 14 days

2. Sever malaria
A. First line: IV Artesunate 2.4mg/Kg 3 does during over 24 hours (0, 12, 24) then shift to oral AL up
to 7 days if needed
B. Second line: IV Quinine infusion 10mg/Kg in %5 glucose 8 hourly over 4-hour duration (slow
infusion) for at least 2 days then shift to oral Quinine as soon as the pt. can tolerate oral
medication to complete the 7 days

3. Special condition:
A. Pregnancy:
▪ Uncomplicated:
• 1st trimester: oral quinine (Avoid aretemisinin & mefloquine.)
• 2nd and 3rd: similar to the usual regimen.
▪ Complicated: IV Artesunate is safe during all trimesters

B. Mefloquine: used as prophylaxis in sickle cell anemia pts. Doesn't have interactions in G6PD pts
(unlike most other antimalarials).

- Drug which acts on hypnozoites: primaquine

- Drug which acts on gametocytes: primaquine

• Bad or poor prognostic features

1. Coma (20% mortality)
2. Pulmonary edema (80% mortality)
3. High WBC ≥ 12000
4. Lactic acidosis
5. Presence of schizont in peripheral blood

TROPICAL | Medicine 7
 • Side effects of drugs:
- Quinine:
o Hypoglycemia (due to induction of insulin)
o Cinchonism (deafness or tinnitus, disturbed vision, nausea and vomiting)
o Cardiac toxicity (can cause long QT syndrome)
o Black water fever (in pts with G6PD deficiency).

- Chloroquine: pruritus, corneal & retinal deposits. Used in SLE, RA, ALA.
- Mefloquine is cardiotoxic

• Massive splenomegaly DDx: HRMSS, kalazar, myeloproliferative disorders (CML), myelofibrosis,

portal HTN. Brucellosis

TROPICAL | Medicine 8
 SCHISTOSOMIASIS

• Epidemiology of Schistosomiasis
- In Sudan: the prevalence ranges (32%-54%).
- >70% of the population is exposed.
- >5 million infected and require treatment. Most of them < 20 years old

• Life cycle:
- Egg → miracidium → enters snail → cercariae (infective stage) → penetration skin
- Veins, Rt heart, lungs, left heart, portal circulation (maturation to adult worm)
- Paired adult worms migrate against the portal flow to
o Mansoni to → mesenteric veins = produce eggs
o Hematobium to venous plexus around the bladder = produce eggs
- Eggs → intense granulomatous response → migrate through the bladder/bowel wall and are shed
in the stool/urine.
- Eggs not shed remain in tissues and swept back to the portal circulation or to the pulmonary
circulation
- Rarely eggs may settle in other organs: genital, pelvic organs, eyes, adrenals, muscle, skin, CNS
• Adult worm doesn’t multiply in body (eggs needs suitable condition to hatch)
• Snails:
o Sch. Mansoni: Biomphalaria
o Sch. Hematobium: bulinus

• Clinical Stage:
1. Stage 1 (invasion): Swimmer’s itch [Cercerial Dermatitis]:
o 1-2 days after penetration, more marked with non-human species.
o More marked in non-immune.

2. Stage 2 (migration): Acute Toxemic Schistosomiasis (Katayama fever):

o Occurs after 2-6 weeks.
o Usually occurs in visitors to endemic area
o common in S. Japonicum. rare in Hematobium.
o C/P: Fever, rigors, urticaria, cough, wheeze, diarrhea, lymphadenopathy and
hepatosplenomegaly
o Test: Blood: eosinophila. Negative stool [no eggs in stool/urine/tissues] but high antibodies.

3. Stage 3: Established infection

o 10 – 12 weeks after infection
o Mature warms start to produce eggs
o Sch. Mansoni: intestine, gallbladder, liver, lung
o Sch. Hematobium: bladder wall
o Granulomatous reaction =ulcers/polyps

4. Stage 4: complications
o Liver: Periportal fibrosis, Portal HTN, hepatosplenomegaly
o Intestine: egg deposition=polyps, ulcer-bleeding
o Urinary bladder: calcification, polyps, ulcers, uretheral fibrosis
o Lungs: pulmonary HTN, cor pulmonale.

TROPICAL | Medicine 9
 • Sch. Mansoni:
• Intestinal Schistosomiasis:
▪ C/P: low-grade fever, fatigability, bloody diarrhea, abdominal cramps
▪ Examination: abdominal tenderness
▪ DD: bacillary or amoebic dysentery /can occur concomitantly.
▪ Complication: colonic polys, Bilharzial colitis, Bilharzioma (granulomatous mass) causing
intestinal obstruction, bowel perforation

• Hepatosplenic schistosomiasis;
▪ Etiology: Portal hypertension
▪ C/P: Hematemesis from varices, Melena or anemia [Chronic Blood loss or Hypersplenism]
▪ Examination: enlarged left lobe of the liver, splenomegaly, venous hump and caput medusa,
ascites
▪ N.B. Liver function test is normal in Schistosomiasis. If abnormal either
1. Co-infection HCV infection
2. Malnutrition
3. Necrosis of hepatocytes due to ischemia (from shock).

• Cardio-pulmonary schistosomiasis
▪ Etiology: Pulmonary hypertension. Occurs after opening of the Portosystemic shunts and
spreading of the ova to systemic circulation. SO pulmonary hypertension always occurs after
portal hypertension
▪ C/P: dyspnea
▪ Examination: Palpable P2, Left Parasternal Heave, distended JVP, LL edema, Hepatomegaly
▪ CXR: lung nodules resampling TB, fibrosis

• Other complication:
▪ Malnutrition
▪ Schisto-salmonillosis: Prolonged fever in schistosoma
▪ Septicemia.
▪ Co-infection with HIV/HCV
▪ Gallbladder cancer

• Diagnosis:
▪ CBC: eosinophilia in acute stage, Anemia in chronic stage
▪ Stool microscopy:
▪ Eggs with lateral spina
▪ Egg quantification is important to determine the intensity of the disease
▪ Egg viable ova by hatching test to assess respond to treatment
▪ Serology: for Abs/Ag using FAST or ELISA
▪ LFT: usually normal
▪ RFT: as baseline and to assess renal complication
▪ Abdominal US: portal vein diameter (enlarged), fibrosis and its grading, splenomegaly
▪ Upper GI endoscopy: for varices
▪ Colonoscopy: for polyps.
▪ ECG, CXR: For pulmonary hypertension

TROPICAL | Medicine 10
 • Sch. Hematobium:
• Clinical presentation:
▪ Terminal hematuria; Bladder ulcer, polyps
▪ Abdominal pain
▪ Dysuria, urgency, frequency
▪ Pyelonephritis
• Complication:
▪ Calcification of ureter: hydroureter or hydronephrosis (AKI)
▪ Contraction and calcification of bladder (Thimble bladder)
▪ Bladder Stone formation
▪ Squamous cell carcinoma of bladder (chronic irritation)
▪ Infertility
• Diagnosis:
▪ CBC: eosinophilia in acute stage, Anemia in chronic stage
▪ Urine microscopy:
▪ Gross and microscopic hematuria
▪ Proteinuria
▪ Eggs with terminal spina)
▪ Serology: for Abs/Ang using FAST or ELISA
▪ RFT: as baseline and to assess renal complication
▪ X-ray KUB or CT-KUB: hydroureter, hydronephrosis, Stone
▪ Cystoscopy: calcification in bladder (sandy patches)
• Renal involvement in schistosomiasis
- Glomerulonephritis due to immune-complex deposition
- Nephrotic syndrome
- Amyloidosis
• Neurological involvement in Schistosomiasis
- More common with S. Japonicum
- Can occur with both S. Mansoni & S. Hematobium
- Brain: eggs-granuloma= nodular enhancing Lesions → Convulsions
- Paraplegia due to cord compression by granuloma OR transverse myelitis due to immune
complexes.
• Treatment of schistosomiasis
▪ Anti-schistosomal:
o Mansoni: Oxamniquine.
o Hematobium: Metrophonate
o Praziquantel works for both
▪ Assessment for achievement of cure: Positive Schistosoma ova in stool examination, with negative
hatching test
▪ Treatment of complications
o Obstructive urology: anti-schistosomal medications +/- surgery.
o Intestinal polyps 90% cure with anti-schistosomal medications
o Splenectomy: an option for hypersplenism
o Katayama fever: Oxamniquine, steroids
o Schisto-salmonellosis: Praziquantel plus antibiotics against salmonella

TROPICAL | Medicine 11
 • Praziquantel
* Active against all major species
* Oral does 20 mg/kg 3 doses 4 hours apart
* Acts on adult worms paralyze the worm to be attacked by the immune system.
* Well tolerated, S/E: slight GI upset, vertigo, fever
* Used as mass therapy
* Cure rate 65-90%
• Oxamniquine (Vansil):
* Active against S. mansoni only
* Acts on schistosomules & adult worms
* Oral dose: 60 mg/kg 2-3 divided doses
* S/E: ↑ serum level of transaminase, change in urine color to orange, convulsions, transient
amnesia
* Contraindicated: pregnancy
* Cure rate 60-90%

TROPICAL | Medicine 12
 AMEBIASIS
- Caused by Entamoeba histolytica which is a commensal that becomes virulent.

• Life cycle:
- Two forms: cysts (infective stage) and trophozoites (pathological stage)
- Human: Major reservoir
- Cyst → stomach → intestine → ex-cystation into 4 trophozoites → colon → encystation → cyst in
the environment
- Ameba affects large intestine. Presents with bloody diarrhea

• Risk Group:
- Developing countries
- Institutional populations
- Travelers, immigrants
- Male homosexuals

• Why does it become invasive?

- Dose of the organism
- Host resistance
- Nutritional factors
- Genetic factors (African gets a severe form)
- Damage to the intestinal mucosa by other parasites

• Mode of transmission:
- Ingestion of food or water contaminated with human feces containing cyst of E. histolytica

• Pathogenesis
- Cysts remain viable for 13 days. Ingested releases trophozoites
- Invasion happens under favorable conditions
- Lysis and necrosis of mucosa by proteolytic enzymes
- Invade the submucosa = flask shape ulcers
- Mainly affects the cecum, transverse colon and sigmoid colon
- Appendix and small bowel Sometimes are affected
- Sometimes an amoeboma /granuloma
- Deep ulcers may perforate
- Hematogenous spread through colonic epithelium to cause extraintestinal infection (liver abscess)

• Intestinal Amebiasis
1. Asymptomatic in majority of pt.
2. Acute amebic colitis: fever, offensive bloody diarrhea and normal WBCs (milder than bacillary
dysentery)
3. Fulminant amebic colitis:
▪ severe form may have dehydration, electrolyte disturbances and shock
▪ Risk factor for fulminant colitis: steroids intake and children.
4. Chronic colitis
5. Ameboma

TROPICAL | Medicine 13
 • Complications
- Dehydration and Shock
- Perforation → Peritonitis, Abscesses in liver, spleen, psoas, brain, heart
- Bleeding per rectum from an eroded blood vessel
- Intussusception in children
- Perianal skin ulcerations may resemble squamous cell carcinoma
- Balanitis

• Differential diagnosis
- Bacillary dysentery, Acute bilharzial colitis, Tuberculous colitis
- Acute Ulcerative colitis/Crohn’s
- Colonic Diverticular disease, irritable bowel syndrome.

• Extraintestinal Amebiasis
A. Amebic liver abscess:
▪ Usually 5-6 months after intestinal disease.
▪ 50% have no history of amoebic dysentery
▪ Less than 50% have +ve stool for trophozoites on microscopy
▪ C/O: Swinging fever [high grade], RUQ pain radiating to Rt shoulder, tender hepatomegaly.
▪ O/E: Firm tender Hepatomegaly, mild jaundice in some cases, shiny intercostal spaces overlying
the liver (characteristic).
▪ DDx: Pyogenic liver abscess, infected hydatid cyst, HCC, congestion (Congestive HF)
▪ The abscess is sterile with low neutrophils (Pseudo abscess)
▪ Difference from pyogenic abscess: Sterile from bacteria, Not offensive, Anchovy-sauce color
▪ Complication (Rupture):
1. Pleura → empyema (Most common)
2. Bronchi → hepato-bronchial fistula
3. Peritoneum → peritonitis
4. Pericardium → tamponade (most dangerous)
5. Skin → fistula
B. Cerebral amebiasis: Abscess
C. Cutaneous amebiasis: Rupture of ALA → fistula or extension from rectal colitis
D. Genitourinary amebiasis: Renal & Genital Ulcers
• Diagnosis:
A. Amebic colitis:
1. CBC: Usually normal
2. Stool microscopy: looking for Trophozoites containing RBCs, pus cell, RBCs
3. Stool antigen detection by ELISA
4. Colonoscopy
B. Amebic liver abscess:
1. CBC: neutrophilia
2. LFT: normal or cholestatic (↑ALP)
3. Abdominal US: hypo echoic mass → confirm the diagnosis
4. Abdominal CT: ring enhancing mass
5. Serology: Ag & Ab detection in blood by ELISA → +ve in 95%
6. Diagnostic aspiration: anchovy paste, not used, differentiate it from pyogenic abscess
* Only less than 50% of people with ALA have positive abscess, 1/3 may got active disease

TROPICAL | Medicine 14
 • Treatment:
1. Luminal Amebicidal: Paromomycin, Iodoquinolines, Diloxanide Furate
2. Tissue Amebicidal: Metronidazole and Tinidazole

- In amebic colitis and amebic liver abscess give tissue amebicidal followed by luminal amebicidal
- In treatment of carrier is by luminal

▪ Indications of therapeutic aspiration:

1. Large cyst (more than 10cm)
2. Left lobe abscess
3. Abscess that does not respond to medical treatment (3 – 5 days)

TROPICAL | Medicine 15
 BACILLARY DYSENTERY
• Microbiology:
- Shigella: Non motile gram-negative rods, non-lactose fermenting, non-gas producing
- The genus Shigella is divided into genera: S dysenteriae, S flexneri, S boydii, S sonnei

• Pathogenesis
- No bacteremia or septicemia
- Shigella shiga causes severe disease
- Perforation is unusual

• Virulence factors
1. Endotoxins: Invasion, multiplication, resistance of Shigella to phagocytosis by tissue macrophages
2. Adherence factor: Intestinal Colonization of Shigella
3. Shiga toxin: Disrupts protein synthesis and produces endothelial damage

• Clinical manifestations
- The incubation period 36 hours in average.
- Usually, self-limiting 3-7 days
• C/O:
▪ High grade fever, Abdominal pain, tenesmus, urgency, vomiting
▪ Bloody diarrhea preceded by watery diarrhea
▪ Muscular cramps /oliguria
▪ Dehydration, Lethargy, Convulsions
• O/E:
▪ ill, toxic, Signs of dehydration: delayed skin pinch , Dry mouth, tongue, sunken eyes
▪ Abdominal tenderness, Increased bowel sounds

• Differential diagnosis
a. Amoebic dysentery, Food poisoning due to staph, Dysenteric malaria, Cholera
b. Acute bilharzial colitis, Tuberculous colitis
c. Ulcerative colitis/Crohn’s
d. Colonic Diverticular disease

• Complications of bacillary dysentery

• Local:
o Intestinal hemorrhage.
o Intestinal obstruction
o Perforation. (rare), Peritonitis
o Rectal prolapse/ intussusception in children
o Bacteremia in malnourished children

• Systematic
o HUS: microangiopathic hemolytic anemia, AKI and thrombocytopenia.
o Rietter’s syndrome: conjunctivitis, urethritis and arthritis
o Hyponatremia due to SIADH
o Neurological: lethargy, confusion, convulsion
o Ocular: conjunctivitis /keratitis
o Vulvo-Vaginitis
o Myocarditis

TROPICAL | Medicine 16
 • Differentiate Shigella from Ameobic

Shigella Amoebic dysentery

Abrupt onset Insidious onset
Fever No fever
Looks ill Looks well
Non offensive Offensive stools
Watery then bloody diarrhea Bloody diarrhea
Alkaline diarrhea Acidic diarrhea

• Investigations
1. CBC: hemoconcentration (due to dehydration), leukocytosis
2. Stool microscopy: Pus cells in 90%, RBC's
3. Stool culture
4. Serology not useful

• Treatment and management

• Supportive measures
a. Antipyretic: paracetamol for fever.
b. fluid and electrolytes replacement.
c. Encourage to increase fluid intake, ORS
• Antibiotics:
a. Quinolones: Ciprofloxacin
b. Cephalosporins: Ceftriaxone
c. Ampicillin /co-trimoxazole
- Susceptibility testing is essential
- Use carefully because the resistance.
- Anti- motility agents should be avoided

TROPICAL | Medicine 17
 VISCERAL LEISHMANIASIS
• Life cycle:
▪ There are two forms of the parasite
o Promastigote: in culture and vector (in environment)
o Amastigote: in the human or animal (in the host).
▪ VL is caused by Leishmania donovani (sub-species in Sudan is leishmania donovani donavan)
▪ Vector:
o Phelobotomus sand fly in old world, Lutzomia sand fly in new world
o Active at dusk and night
o Doesn't reach high altitude (so you can protect yourself by sleeping upstairs)

▪ Reservoir:
1. Wild & domestic animals, dogs, rodents (i.e. Zoonotic)
2. Humans in India [where there is a large parasitemia, it can be human to human, can be
diagnosed by blood film]

▪ Mode of transmission:
1. Bite of infected sand fly inoculating promastigote
2. Rarely: congenital; blood transfusion; sexual, IVD abusers

▪ Sand Fly → body → promastigote → enter macrophage → amastigote → taken by Sand fly
▪ Macrophages disseminate through the lymphatic & vascular system → Bone marrow → failure.
Lymph node → generalized lymphadenopathy. Liver → hepatomegaly. Spleen → Splenomegaly.
▪ Immunity is cell mediated (mainly Th-1 cells)

• Pathogenies:
▪ Anemia due to:
1. Bone marrow suppression & infiltration by the parasite
2. Chronic diseases (due to IL-1, IL-6, TNF)
3. Hypersplenism (destruct RBCs, platelets)
▪ Leukopenia and thrombocytopenia due to
1. Bone marrow suppression
2. Hypersplenism
▪ Edema in kalazar pts is usually due
1. Malnutrition (decreases protein)
2. Protein losing enteropathy.
▪ Hypergammaglobulinemia: B-cell respond to different amastigotes in different macrophages by
proliferation & polyclonal Abs formation

• Clinical picture:
▪ I.P. 2-6 months ranges from 10d to yrs
▪ Symptoms:
o Onset usually gradual rarely acute (ATK)
o Fever intermittent with double or triple rise (100% of pts have fever)
o Weight loss despite good appetite
o Symptoms of anemia: Headaches, Fatigue, dyspnea with exertion
o Epistaxis and gum bleed
o Diarrhea due to ulceration of digestive mucosa (watery & lately became blood stained)

TROPICAL | Medicine 18
 ▪ Signs:
o Splenomegaly: early & almost invariable, Firm, painless, increases with time
o Hepatomegaly: less frequent occurs late
o Jaundice: rarely, associated with poor prognosis
o Lymphadenopathy: painless mobile (epitrochlear LN enlargement is characteristic for kalazar)
o Lately ascites, edema & Pulmonary effusion
o Renal involvement: proteinuria
o The tongue is clean in kalazar

• Evolution:
- Curable with early treatment
- Fatal in 90% if not treated due to intercurrent infection and bleeding
- Relapses due to resistant parasites & immunosuppression

• Post kalazar dermal Leishmaniasis (PKDL)

o Hypopigmented macules, papules or nodules in the face, Upper limbs or the whole body
o Contains numerous parasites and parasite dissemination
o 20% in India, 56% in Sudan
o In India occurs 1 year after treatment but in Sudan during or immediately after treatment
o May be self-cured within 6/12 months in India, Lasts for years in Sudan
o Significance of PKDL is that it may act as a source of transmission of the infection.
o DDx is lepromatous leprosy and neurofibromatosis
o Treatment: as the specific treatment of VL

• Complications of kalazar:
1. Secondary bacterial Infection:
o Chest: TB/Lobar pneumonia
o GI: Amebic /bacillary dysentery
o Cancerum oris in children
o Blood: septicemia
2. Uncontrolled bleeding or Epistaxis
3. Severe malnutrition, Anemia
4. PKDL

• Diagnosis:
1. CBC: pancytopenia, WBCs<4000 in 90%, ↑WBCs is due 2ndry infections
2. ESR: 3 figures ESR (DDx pulmonary TB, CTD (SLE, RA), multiple myeloma and nephrotic syndrome)
3. CRP: increased
4. Formal gel test: Hypergammaglobulinemia
5. Demonstration of Parasite:
a. Biopsy
▪ LN Biopsy: 65%. BM: 80%
▪ Splenic: >95% (but there is a high risk of rupture)
▪ The practical one & done in Sudan is the epi-trochlear LN biopsy.
b. Microscopy (Giemsa stain): Leishman Donovan bodies or amastigotes.
c. Culture in NNN media
d. Serology: RK39 detection test (best field test).
6. Leishmanin test: –ve

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 • Treatment:
• Supportive:
1. Antipyretic: paracetamol
2. Antibiotics for secondary infection via
3. Blood transfusion
4. Nutritional support

• Specific
▪ 1st line: IV Pentostam + Paromomycin
* Dose: 20 mg/Kg/day for 17 days (up to 28 days)
* Side Effects:
1. Fever, Shivering, arthralgia, myalgia, skin rash
2. Renal toxicity; Anaphylaxis like reaction
3. Toxic effect at end of treatment:
▪ Cardiotoxicity (T, ST & Qt changes)
▪ Hepatotoxicity: increase liver enzymes
▪ Pancreatitis
4. Sudden death with big doses

▪ 2nd line: Liposomal amphotericin B

* Dose: 3 mg/kg/day for 10 days
* Indication: age > 45, pregnancy, HIV, Cardia, renal or hepatic impairment
* Side effect:

▪ Other drugs:
* Miltefusine:
o The only oral drug
o Cytotoxic drug used for Breast Ca deposits in skin
o Not used in females of child bearing age
* Pentamidine

• Response to treatment:
- Fever subsides in 5-7 days.
- Hematological indices return to normal in 1-2 months.
- Normalization of albumin globulin ratio in 3-6 months.
- Leishmanin test becomes positive in 3-6 months.

• Failure of response:
1. Resistance organism
2. HIV co-infection
3. Other diseasess

TROPICAL | Medicine 20
 BRUCELLOSIS
(Malta Fever/Indulent Fever)
• Bacteriology
- Brucellae are aerobic Gram-negative bacilli or coccobacilli which are nonmotile and non-spore
forming
- Has may subtypes:
1. B. abortus → cattle
2. B. Miletensis → goats, sheep, camels
3. B. suis → pigs

• Transmission:
1. Ingestion of raw or unpasteurized milk: Increased risk in those taking antiacids H2 blockers and PPI
2. Direct contact with infected animal or Aerosol inhalation
3. Cut wounds and abrasions
4. Sexual transmission, Organ transplantation, Congenital and breast feeding

• Disruption:
- More in Africa, Middle East and KSA
- Occupational risk shepherds, vet, butchers, Lab infection
- Both sexes, All age groups can be affected.

• Pathogenesis:
The organisms localize in the RES, namely, the lymph nodes, liver, spleen, and bone marrow.
Many organisms are killed by macrophages, but some survive within these cells, where they are
protected from antibody. The host response is granulomatous, which can progress to form focal
abscesses.

• Clinical Picture:
A. I.P. 2-4 weeks
B. Acute form: Initially nonspecific
▪ Fever, fatigue, anorexia and night sweats
▪ Fever waxes and wanes in cycles 2-4 weeks
▪ Splenomegaly; hepatomegaly; Lymphadenopathy, pneumonia
C. Chronic form: complication
▪ Skeletal involvement:
* Osteomyelitis
* Arthritis of wight bearing joints
* Sacroiliatis, Sciatica
* Vertebral destruction and psoas abscess
▪ Neurological:
* Meningitis, cerebritis, CN palsy (2,6,8)
* Cord compression: neuro brucellosis
* Depression and suicidal tendency (no solid evidence)
▪ Genital: Epididymo-orchitis, Infertility
▪ Heart: Endocarditis usually fatal

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 • Investigation:
A. General:
1. CBC: N.N anemia, normal WBC count with relative lymphocytosis
2. LFT: ↑ ALP, Slight ↑ in transaminases; Low alb. and high globulin

B. Specific:
1. Isolation of the organism in Castaneda medium
▪ Needs 12 days to 6 weeks
▪ Blood culture +ve in 50%, -ve with use of antibiotics
▪ BM +ve in 90% not affected by Rx
2. Serological test
▪ Widal Test: (IgM agglutination), maybe –ve due to prozone phenomenon
▪ antibody detection using ICT
▪ PCR
3. X-rays or CT:
▪ Vertebral changes in chronic infection
▪ Hepatosplenic calcification: characteristic for Brucella
▪ Snow flock calcification in spleen “Pathognomonic”

• Treatment:
1. BEST according to WHO: Streptomycin 1gm + Doxycycline 200mg for 6 weeks (1st 3 weeks
combination, 2nd 3 weeks doxy. Alone)
2. if Neuro. or Skeletal manifestation same combination for 12 weeks
3. If Endocarditis: we add 3rd Generation cephalosporin +/- valve replacement
4. Children: Rifampicin + Cotrimoxazole for 6 weeks
5. Pregnancy:
▪ 1st trimester: Rifampicin alone for 6 weeks
▪ 2nd and 3rd: Rifampicin + Cotrimoxazole for 6 weeks
6. Surgical drainage of abscesses

- Streptomycin is IM; painful

- Doxycycline is oral, after food with ↑water i.e.; irritant
- Treatment can cause Jarisch-Herixheimer Reaction; treated by steroids.

• Prevention:
1. Pasteurization and boiling of milk
2. Animal vaccination
3. No human vaccine available yet

TROPICAL | Medicine 22
 TUBERCULOSIS
• Importance:
- 1/3 of the world population are infected, meaning that they have latent infection and not
necessarily manifesting the disease
- Every year:
o 30 million will be infected.
o 9 million will develop the disease.
o 3 million will die.
▪ TB is the number one killer of all infections
▪ TB kills more adults each year than AIDS + Malaria + other tropical diseases.

• Transmission:
1. Inhalation of respiratory droplets from patients with sputum positive Pulmonary TB.
2. Ingestion of infected milk (uncommon)

- One patient will infect 10 -15 people /year.

- 10% of them develop the disease

• Primary TB:
▪ Pathogenesis:
o Bacteria is inhaled to the sub-pleural alveoli of the lung in 85 % [rarely in tonsils or intestine
from ingestion of contaminated milk]
o Attacked by alveolar macrophages and T cells causing granuloma (Ghon focus)
o Then it reaches the hailer lymph node (Ghon complex)
o It spreads hematogenously in all cases and passes asymptomatic in majority of cases
o Tuberculin +ve at 6 – 8 weeks.

▪ Clinical course of primary TB:

1. Asymptomatic in majority of cases
2. Brief febrile illness at the time of tuberculin conversion.
3. Symptomatic with allergic manifestations: fever, erythema nodosum, phlectinular
conjunctivitis and pleural effusion
4. Progressive primary TB: either:
o TB spread by bronchi causing bronchopneumonia.
o Spread to hilar lymph nodes causing enlarged LNs obstructing the bronchi partially
causing wheeze or completely causing atelectasis
o Spread to the pleura causing pleural effusion

▪ Fate of primary TB:

1. Healing by fibrosis calcification [most common outcome]
2. Becoming dormant (latent TB)
3. Progress to post-primary in case of low immunity

▪ Diagnosis of primary TB:

1. CXR: usually normal but you can find the Ghon complex [subpleural area + hilar
lymphadenopathy]
2. Sputum: absent or –ve because asymptomatic
3. Tuberculin test: +ve after 6-8 weeks.
o So, need high index of suspicion

TROPICAL | Medicine 23
 • Post Primary TB:
▪ Causes:
1. Reactivation of dormant bacilli (most common; in countries where TB is not common)
2. Reinfection from an exogenous source (in endemic area like Sudan)
3. Progression of primary lesion (rarely).
▪ Pathogenesis:
o Immunity /hypersensitivity leads to localized lesions in upper lobes, necrosis and cavitation.
o The necrosis and cavitation seen are due to host immune defenses rather than the bacilli
eating out the lung tissue
o In histopathology you find caseating granuloma.
▪ Risk factors that determine progression of disease from latent to active
1. Poor housing and overcrowding.
2. Malnutrition.
3. Immunosuppression (either congenital or acquired)
4. Alcohol, Smoking.
5. Silicosis
a. Affecting the upper lobes leading to fibrosis and cavitation (similar to TB)
b. it also decreases local defense mechanisms, enhancing the development of TB
▪ Characteristics of post primary TB:
o Onset: insidious.
o Age: young adult.
o Site: upper lobes.
▪ Types
o Pulmonary TB
o Extrapulmonary: Pott’s disease, meningitis, adrenalitis, skin, LNs, miliary TB.

• Pulmonary TB
▪ Symptoms:
o Asymptomatic: discovered accidentally in X-rays done for other reason
o General: Low grade fever, Night sweating, Wt. loss, Loss of appetite, Tiredness
o Respiratory symptoms:
a. Cough: usually chronic, persistent, might be dry or productive
b. Hemoptysis.
c. Chest pain: usually dull aching pain but may be pleuritic if the pleural get involved
d. SOB: In extensive disease
e. Wheeze: in case of endobronchial TB or TB of the lymph node that leads to
narrowing of the passage
▪ Sign:
o No sign, or
o Wasting and pallor (due to anemia of chronic illness)
o Clubbing; due to empyema or bronchiectasis
▪ Chest examination:
o Crackles (post-tussive)
o Wheeze.
o Features of Consolidation.
o Features of Fibrosis.

TROPICAL | Medicine 24
 ▪ Diagnosis:
o Must be considered in patients with:
1. PUO (pyrexia of unknown origin).
2. Unexplained chronic ill health.
3. Persistent cough more than 3 weeks.
4. Non resolving pneumonia.
5. Hemoptysis.
6. Abnormal chest x-ray in asymptomatic pts.

▪ Investigation:
1. CBC: nonspecific findings, anemia of chronic illness
2. ESR: may be high but not specific, can be used for follow up.
3. CXR:
o Cavitation, consolidation, collapse, enlarged LN. or plu. effusion → Active disease.
o Fibrosis and calcification → old TB
4. Sputum examination:
o Microscopy by ZN stain or better by Auramine /Rhodamine stain
o Culture by Lowenstein Jensen media (needs 4-6 weeks) or in radioactive BACTEC media
which takes 2 weeks.
5. Gene x-pert MTB/RIF test (PCR)
o Test mycobacterium TB and rifampicin sensitivity as well
o Rapid diagnosis and detection of resistance (less than 2 hrs.).

6. Tuberculin test:
o Done by intradermal injection of PPD and measuring the induration not the erythema
after 48 – 72 hrs.:
1. +ve if more than 10 cm.
2. –ve if less than 5 cm.
3. Intermediate if 5-10 cm. (repeat the test)
4. In immunocompromised pts. 5 cm is considered +ve.
o Limitation of the test
1. Doesn’t differentiate between active and latent TB
2. false +ve test: BCG vaccination, non-mycobacterial TB infections, pt. with history of
well treated active TB infection
3. false -ve test: immunocompromising pt. (HIV, malnutrition, steroids), early disease <
6weeks from infection
7. IGRA (Interferon Gamma Release Assay):
o It is a simple blood test but like manteaux test
o Advantage: Not +ve in BCG vaccination or non-mycobacterial TB infections
o Limitation: Doesn’t differentiate between active and latent TB, so used as good tool for
screening of latent infection rather than diagnosis.

TROPICAL | Medicine 25
 • Extrapulmonary TB:
- TB can affect any part of the body.
1. Scrofula: TB of the skin of neck + underlying lymph nodes (MCC. manifestation of extrapul. TB)
2. Lymph node tuberculosis
3. TB pericarditis: result in massive pericardial effusion
4. Oropharyngeal Tuberculosis
5. GIT Tuberculosis: most common site of involvement is the ileo-cecal valve.
6. Renal tuberculosis.
7. TB meningitis.
8. Tuberculous osteomyelitis: osteomyelitis of vertebral bodies (Potts’s disease of spine)
• Miliary TB
- Disseminated TB is the most severe form, mainly affect the lung.
- Has two types:
1. Classical Miliary TB:
▪ Clinically
- Mainly occur in children.
- Classical symptoms of TB, however usually cough is not present
- Headache due to meningism
- Neck rigidity.
- Hepatosplenomegaly and lymphadenopathy
- Choroid tubercles in fundal examination in 90% of children.
▪ Diagnosis:
- Sputum: usually not helpful as there is no cough.
- Liver or bone marrow biopsy to isolate the organism then microscopy + culture
- CXR: miliary shadows
- Tuberculin test: negative
- Fundal examination: Choroid tubercles

2. Cryptic Miliary TB (elderly):

▪ Clinically:
- Mainly in elderly
- Classical symptoms of TB but There are no chest symptoms
- No choroid tubercles
▪ Diagnosis:
- Liver or bone marrow biopsy to isolate the organism then microscopy + culture
- CXR is normal (no miliary shadow)
- Tuberculin test is negative
- Fundal examination: Normal
- CBC: pancytopenia, agranulocytosis, thrombocytopenia
- ESR: is persistently high.
- LFTs: elevated transaminases.
▪ Outcome:
- 100% fatal (if untreated).
- Associated with Complications in: Lung (ARDS), Kidneys: (glomerulonephritis and renal
failure).

TROPICAL | Medicine 26
 Management of TB
• Anti-TB drugs:
- First line drugs: INH (Isoniazid), Rifampin (R), pyrazinamide (Z) and ethambutol (E)
- Second line drugs: Levofloxacin, cycloserine, amikacin, ethionamide, streptomycin

• Mode of action of anti-TB drugs:

- We divide the mycobacteria Tb in site of infection into 4 groups:
1. Major group (90%): active dividing bacteria that easily killed by Isoniazid.
2. Subgroup killed only by the acidity of pyrazinamide.
3. Subgroup remain dormant for long period of time and wake for few times, these are killed by
Rifampin
4. Small group of calcified dormant bacilli do not need treatment

- The best bactericidal drug is isoniazid.

- The best resistance preventer is isoniazid. so it is involved in all TB regimens unless significant
resistant
- The sterilizing drugs are rifampicin and pyrazinamide.
- The bacteriostatic drug is ethambutol.

• Case definition of TB:

- Depends on:
a. Site of TB disease.
b. Bacteriology (result of sputum smear).
c. Severity of TB disease.
d. History of previous treatment of TB: very important

- Pulmonary TB: divided into smear positive and smear negative.

- Extrapulmonary TB: divided into those with extensive diseases and those who don't have extensive
disease.
- Relapse: occurrence of the disease after adequate treatment.
- Defaulters: started treatment but stopped.
- Treatment failure: no response to treatment.

- MDR: resistance to isoniazid and rifampicin or resistance to three drugs.

- XDR: resistant to isoniazid, rifampicin, quinolones + one of the injectable second line drugs
(e.g., Amikacin).

- Treatment is given by direct observational therapy (DOT) is effective throughout the

treatment period or at least in the first 2 months.

TROPICAL | Medicine 27
 • Categories of TB:

Category 1: The severe Category 2: who encountered the treatment before

1. Smear positive pulmonary TB 1. Relapse

2. Extensive smear negative pulmonary TB 2. Defaulters
3. Extensive extrapulmonary TB 3. Treatment failure
4. HIV pts with T

Category 3: The mild Category 4: drug resistant

1. Mild smear negative pulmonary TB 1. Multidrug resistant (MDR).

2. Non-extensive extrapulmonary TB 2. Extensive drug resistant (XDR)

• Recommended treatment regimens:

Category 1 & Category 3

o (4x2) + (2x4)
o Total is 6 months
o Initiation phase INH, Rifampicin, Pyrazinamide and Ethambutol for 2 months.
o Continuation phase by INH & Rifampicin for 4 months.

Category 2
o (5x2) + (4x1) + (3x5)
o Total is 8 months.
o INH, rifampicin, pyrazinamide, ethambutol and streptomycin for 2 months.
o Then withdraw streptomycin (nephrotoxic) and continue with the four drugs for 1
month.
o Then withdraw pyrazinamide and continue with INH, rifampicin and ethambutol for 5
months

Category 4

o Treatment is individualized

• Monitoring:
- By sputum examination at end of initiation phase (2 months), after 5 months and after end
of treatment.
o If pt. was smear positive in 2 months and again smear positive in 5 months this is
treatment failure.
o If the pt. was smear negative and changed smear positive at any stage (2 or 5 months)
this is also treatment failure.
o If the pt. took treatment and completed the 6 months but didn't come after the 6
months for sputum examination, this is called "received successful treatment" but you
can't say "cured" as you didn't do the last sputum examination

TROPICAL | Medicine 28
 • Special problems in treatment:
▪ Pregnancy:
o Avoid streptomycin because it crosses the placental barrier and cause fetal ototoxicity
▪ Renal failure:
o Avoid Streptomycin
o Ethambutol is either given in adjusted small dose or used with regular monitoring
▪ Hepatotoxicity:
o Stop all drugs until there is no jaundice, bilirubin normal and enzymes normal
o Then you either introduce all drugs at full dose or introduce one by one.
▪ Liver disease (Decompensated liver cirrhosis)
o we should decrease the number of hepatotoxic drugs
o If severe avoid Z
o 2 SHER / 6 HE or 2 SHE / 10 HE.
▪ Hypersensitivity reactions of the drugs:
o It is a spectrum: erythema multiforme, Steven Johnson (worse) or toxic epidermal
necrolysis TEN (the worst).
o Mild reaction does not need stopping drugs
o Moderate to severe:
▪ stop all drugs until the pt. is normal
▪ Then introduce one by one gradually to see which one is causing the
hypersensitivity (don't introduce them all together)
▪ TB and HIV:
o Affect each other in negative way:
▪ TB is a febrile illness. Fever increases replication of the virus and make the disease
worse.
▪ HIV reduces immunity and cause severe TB and extrapulmonary disease as the
immunity is reduced.
o Treatment:
▪ Category A
▪ Adverse Side effects are more.
▪ Response is excellent
▪ Interactions between antitubercular and antiretroviral drugs
• Start ant-TB drugs then add the ARVT after few weeks to prevent IRIS
• Antiretroviral shouldn’t be delayed for long time)

• Indications of steroids in TB
- Definitive indication is replacement therapy in pts with TB adrenalitis
- Non definitive:
o TB laryngitis: to prevent edema and upper airway obstruction
o Serosal membranes: pericarditis and pleural effusion
o Genitourinary TB: to prevent healing by fibrosis and loss of fertility
o TB lymphadenitis, TB meningitis
o Hypersensitivity reactions.

TROPICAL | Medicine 29
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TROPICAL | Medicine 30