Open Forum Infectious Diseases

REVIEW ARTICLE

Sequelae of Lassa Fever: Postviral Cerebellar Ataxia

Chiomah Ezeomah,1,2 Adeyi Adoga,4 Chikwe Ihekweazu,5 Slobodan Paessler,1,2 Irma Cisneros,1,2,3 Oyewale Tomori,6 and David Walker1,7,
1
Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA, 2Galveston National Laboratory, Institute of Human Infections and Immunity, University of Texas Medical
Branch, Galveston, Texas, USA, 3Center for Addiction Research, University of Texas Medical Branch, Galveston, Texas, USA, 4Department of Otorhinolaryngology, Head and Neck Surgery, Jos
University Teaching Hospital, University of Jos, Jos, Nigeria, 5Nigerian Center for Disease Control, Federal Ministry of Health, Abuja, Nigeria 6National Lassa Fever Steering Committee, Federal
Ministry of Health, Abuja, Nigeria 7Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA

Lassa fever is a zoonotic disease endemic in some West African countries. It is exported to countries in America, Asia, and Europe.
Antivirals against Lassa fever are important to provide a cure in patients with the disease and provide protection against it. In addi-
tion, due to the potential utilization of Lassa virus as a bioterrorism agent, vaccines against the disease can be utilized as a counter-
terrorism measure. Developing antiviral compounds and vaccines against the disease requires understanding of the pathogenesis of
Lassa fever and its disease course, including the signs, symptoms, complications, and sequelae. An important sequela of Lassa fever is
ataxia. A few cases of postviral ataxia following Lassa fever have been described in the literature. This review focuses on highlighting
these cases, the gaps in scientific knowledge where further research is needed, and possible ways of diagnosing postviral ataxia after
Lassa fever in resource-limited settings.
Keywords. Lassa fever; ataxia; sequelae of Lassa fever; neurodegenerative disorder; postviral; ataxia.

Lassa fever (LF) is an acute human viral disease [1]. Its etiologic 4] and cerebrospinal fluid (CSF) [10]. LF is endemic in the West
agent is Lassa virus (LASV), an enveloped, single-stranded, African countries of Sierra Leone, Liberia, Guinea, and Nigeria
bisegmented negative-strand RNA arenavirus belonging to the and is reported in Mali, Ghana, Cote d’Ivoire, Burkina Faso,
family Arenaviridae [2, 3]. It has a lipid-containing envelope Togo, Benin, and Central African Republic. Cases have been
and is spherical, with a diameter of 70–150 µm [4]. Its nat- exported to Sweden, United Kingdom, Canada, United States,
ural reservoir is commonly Mastomys natalensis, a rodent spe- Germany, Netherlands, Japan, and Israel. Though reports esti-
cies indigenous to West Africa [5, 6]. A study involving wild mate that ~500 000 LF cases occur annually, with ~5000 fatal-
rodents trapped in Nigeria from 2011–2015 by Olayemi et al. ities, outbreaks of the disease reported between 1969 and 1972
demonstrated a higher frequency of LASV or arenavirus infec- resulted in a total of 101 cases [5]. Over 4 decades later, in 2018,
tion present in the Natal multimammate mouse—Mastomys the most significant LF outbreak in Nigeria, described as un-
natalensis—and the Guinea multimammate mouse—Mastomys precedented, occurred in 633 laboratory reverse transcription
erythroleucus—than in Praomys daltoni, Mus boaulei, Rattus quantitative polymerase chain reaction–confirmed cases out
rattus, Crocidura spp., Mus minutoides, and Praomys misonnei of 3498 suspected cases, with 171 deaths from January 1, 2018,
[7]. The first known human case of LF was reported in 1969, to December 31, 2018 [11]. LF is an important public health
when a missionary nurse stationed in the Nigerian village of concern because of its incidence, virulence, the consequences
Lassa in the state of Borno became ill. She was transferred to the of uncontrolled disease spread, and its potential as a bioter-
Evangel Hospital (now Bingham University Teaching Hospital) rorism agent. It is therefore critically important to understand
in Jos Plateau State, Nigeria, where other health care workers be- the clinical manifestations (including the signs, complications,
came infected, leading to the first recorded nosocomial spread and sequelae) and viral pathogenesis of the disease in order to
of the disease [8]. LF can also be laboratory-acquired [9] and develop effective drugs for treatment of cases and vaccines for
can spread from person to person in community settings. The the prevention and control of the disease. This review focuses
virus is isolated from serum, pleural fluid, urine, throat wash [1, on ataxia as a sequela of LF.

Received 23 October 2019; editorial decision 23 November 2019; accepted 2 December 2019. ATAXIA
Correspondence: David H. Walker, MD, University of Texas Medical Branch, 301 University
Boulevard, Galveston, Texas 77555-0609 (dwalker@utmb.edu). Ataxia is a degenerative manifestation marked by abnormalities
Open Forum Infectious Diseases ® in movement, affecting gait, coordination, and fine motor skills.
© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases It results in tremors, involuntary eye movements (nystagmus),
Society of America. This is an Open Access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ dizziness, blurred vision, slurred speech (dysarthria), and dif-
by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any ficulty swallowing (dysphagia) [12]. Some patients with ataxia
medium, provided the original work is not altered or transformed in any way, and that the work
is properly cited. For commercial re-use, please contact journals.permissions@oup.com
demonstrate a lack of proprioception. Ataxia can be identified
DOI: 10.1093/ofid/ofz512 as a nervous system degenerative disorder (nonhereditary), or it

Ataxia in Lassa Fever • ofid • 1

can be inherited or acquired due to damage to the cerebellum— 16–18]. In addition, central nervous system (CNS) involvement
the brain region that controls muscle coordination—or cer- is well documented in LF, with complications including seizures,
ebellar pathways. Damage to the cerebellum can result from labile hypotension, encephalitis, encephalopathy, aseptic men-
chronic alcoholism, stroke, tumors, malaria, typhoid fever, ingitis, vertigo, unilateral or bilateral sensorineural hearing loss,
other infectious diseases, hypothyroidism, multiple sclerosis, and ataxia (less frequently) [10, 16, 17, 19–21]. Furthermore,
head trauma, bleeding in the cerebellum, exposure to toxins, LASV was isolated from CSF in a patient whose serum had no
and deficiency of vitamin B-1, B-12, or E [13]. Moreover, cer- circulating detectable LASV [10]. This implies that LASV has
ebellar damage is also reported to be immune-mediated by the ability to infect cells of the CNS and replicate even in the
antibodies in patients with tumors, including lung, breast, absence of detected viremia.
ovarian, and gynecological cancers, digestive tract adenocar- The ability of viral agents to cross the blood–brain barrier
cinomas, malignant thymoma, and Hodgkin’s lymphoma [12, (BBB) and the blood–cerebrospinal fluid barrier (BCSFB) and
13]. Similarly, patients with insulin-dependent diabetes mel- cause damage to the CNS is well documented [22, 23], and
litus may develop antibody-mediated ataxia [12–14]. Some viruses utilize a variety of mechanisms. One mechanism in-
types of immune-mediated ataxia are associated with long-term cludes invading BBB endothelial cells and astrocytic glial cells
sequelae and poor prognoses [12]. by direct infection (either through receptor-mediated mechan-
Acute cerebellar ataxia (ACA) that accounts for ~40% of isms or endocytosis/colloidal transport) [24, 25]. In addition
ataxias in children [14, 15]. ACA in children has been exten- to direct invasion of brain endothelial cells, viral proteins can
sively reported, with the most common cause being varicella- trigger host cell signaling pathways, thereby altering the per-
zoster virus (VZV) [13]. Children are reported to make a meability of the BBB by weakening the tight junctions that hold
full recovery following ACA in most cases [14]. Although the endothelial cells together [24, 26] or they can enter through
postinfectious ataxia in adults is not reported as frequently infecting leukocytes that pass through the BBB (also known
as in children, it does occur [12]. The most common cause as the Trojan horse mechanism) [22, 24, 26, 27]. Lymphocytic
of postviral ataxia in adults is infection with Epstein-Barr choriomeningitis virus (LCMV), WNV, herpes simplex virus–1
virus (EBV) [13]. Some other viral agents linked to ataxia (HSV), coxsackievirus B3 (CVB3), measles virus, and polio-
include herpes simplex virus (HSV), enterovirus, influ- virus are reported to use this route of entry [23, 24].
enza A and B viruses, mumps virus, measles virus, hepatitis Another mechanism involves exploiting the vulnerabil-
A virus, coxsackievirus, West Nile Virus (WNV), and cyto- ities of the CNS to evade the BBB and/or BCSFB to establish
megalovirus [12, 15]. Postinfectious ataxia is described after a neuroinvasion [22, 27]. A commonly exploited area of vulner-
number of bacterial infections, such as tabetic neurosyphilis, ability in the CNS is the nerves and ganglia in the peripheral
Lyme borreliosis, and Whipple’s disease [13]. Postinfectious nervous system that connect the CNS to peripheral tissue, in-
ataxia in association with HIV infection is thought to be a re- cluding cranial nerves [27]. Viruses such as rabies virus, HSV,
sult of opportunistic infections and not to be caused by direct reovirus, enterovirus 71, Theiler’s murine encephalomyelitis
damage to the cerebellum by HIV in most cases [13]. virus, adenovirus, and Bornavirus utilize this pathway to travel
Regarding postviral ataxia, a distinction is made between cer- from peripheral tissue to the CNS, circumventing the BBB and
ebellar ataxia caused by acute viral infection, which has a more BCSFB by axoplasmic transport [23]. LASV causes damage to
favorable prognosis, and cerebellar ataxia caused by chronic the vestibulocochlear nerve, leading to hearing loss. In an in
viral infection, which can lead to progressive ataxia with a direr vivo experiment performed by Yun et al., LASV was detected in
prognosis [13]. the spiral ganglion in both signal transducer– and activator of
Ataxia is evaluated by physical examination, review of the transcription 1 (STAT1)–deficient mice and interferon alpha/
medical history, computerized tomography (CT), magnetic beta/gamma receptor (IFN α/β/γR)–deficient mice. LASV in-
resonance imaging (MRI), biochemical or molecular tests, or fection of the auditory nerve resulted in damage to the spiral
genetic testing (in cases of hereditary ataxia). Though the di- ganglion in the STAT1-deficient mice but not in the IFN α/β/
agnosis of ataxia can be challenging, Klockgether’s chart can γR–deficient mice [28]. This may indicate cranial nerve involve-
be used as a guide to accurately diagnose and classify ataxia ment in LASV neuroinvasion.
(Figure 1). Further diagnostic guidelines have been detailed by The BBB is made up of brain capillary endothelial cells,
Klockgether [13]. mural cells, the tight and adherens junctions that hold the
endothelial cells together, and the foot processes of astrocytic
glial cells [22, 27]. These form a barrier that regulates and
ATAXIA IN LASSA FEVER
protects the brain parenchyma from infiltrating substances
Multiorgan involvement is reported in LF, leading to complica- and microbes. The BCSFB is made up of epithelial–endothe-
tions including gastrointestinal symptoms, pleuritic chest pain, lial cells and tight junctions [29, 30]. The BCSFB–choroid
bleeding, acute kidney injury, convulsion, shock, and coma [10, plexus interface is prone to neuroinvasion by microorganisms

2 • ofid • Ezeomah et al
 History/clinical features

Alcoholism, Autonomic Rapid Malignant CNS Diarrhea Sensory

toxic failure progression disease infection ataxia
compound

ACD, MSA PCD, sCJD PCD HIV Whipple’s disease, Friedreich’s ataxia
toxic ataxia SREAT neurosyphilis vitamin E vitamin B12
deficiency deficiency

MRI

Suggests
Not confirmed Linear hypointensity Increased signal in Increased signal
basal ganglia in cerebellum

Superficial siderosis sCJD FXTAS

Laboratory tests

Liver enzymes, Auto-antibodies Vitamins B1, Serological 14-3-3 protein Genetic and
MCV, CDT B12, and E test and PCR in CSF biochemical tests

ACD PCD, anti-GAD Ataxia due to Whipple’s sCJD Friedreich’s

ataxia, SREAT vitamin disease, HIV, ataxia, SCAs,
deficiency neurosyphilis FXTAS

SAOA

Figure 1. Diagnostic approach to sporadic adult-onset ataxia3. History and 3clinical features3 are often highly suggestive of a specific diagnosis. Similarly, typical 3MRI3
features might suggest a particular diagnosis. If the suspected diagnosis is not confirmed by appropriate 3laboratory tests3, wider laboratory screening is required, which
will eventually lead to the final specific diagnosis. If all tests are negative, then a diagnosis of SAOA is made by exclusion. Abbreviations: ACD, alcoholic 3cerebellar de-
generation3; CDT, carbonyl-deficient 3transferrin3; FXTAS, fragile-X-associated tremor/ataxia syndrome; GAD, glutamic acid decarboxylase; MCV, mean corpuscular volume;
MSA, multiple system atrophy; PCD, paraneoplastic cerebellar degeneration; SAOA, sporadic adult-onset 3ataxia3 of unknown etiology; SCA, spinocerebellar ataxia; sCJD,
sporadic Creutzfeldt-Jakob disease; SREAT, steroid-responsive 3encephalopathy3 associated with 3autoimmune thyroiditis3 [13].

because the endothelial cells are fenestrated, unlike the endo- After viral neuroinvasion, damage to CNS structures could
thelial cells in the BBB that lack fenestration. Moreover, the result from direct viral infection, immune-mediated injury, or a
tight junctions in the BCSFB possess a lower electrical resist- combination of both [22, 28]. Though there are several possible
ance than in the BBB that makes them more vulnerable to mechanisms of damage to the CNS, the mechanism and patho-
invasion than the BBB [27, 29]. LCMV and mumps virus in- genesis of postviral ataxia, which can occur after viral infection,
vade the cerebrospinal fluid through the BCSFB [30]. Though are not completely understood [33]. Further studies are needed
the arenavirus LCMV has been shown to invade the cerebro- to elucidate the mechanisms of neuroinvasion utilized by LASV.
spinal fluid through the BCSFB, it is unclear what mechanism Clinical cases of ataxia linked to LF have been documented.
LASV utilizes to invade the CSF. Fisher-Hoch et al. reported a case of a surgical nurse and a stu-
Furthermore, viral factors (strain, receptor affinity, muta- dent nurse who washed blood-soaked materials (clothes, in-
tions) in conjunction with host factors (age, gender, genetic struments, and gloves) from a patient who died after developing
conditions, immune status) affect the neuroinvasiveness and a febrile illness during an LF outbreak driven by nosocomial
neurovirulence of different viruses [25, 31]. spread in a hospital in Imo State, Nigeria. Both the nurse and
The mechanisms of LASV neuroinvasion remain unclear, but student developed febrile illnesses within 10 days of the surgery.
Cassady and Whitley propose that LASV affects the function Their sera were positive for LASV-specific IgG and IgM anti-
of the endothelium and propose the choroid plexus as a CNS bodies. About 3 weeks after onset of febrile illness, the surgical
region that promotes viral neurotropism [25]. In the arenavirus nurse had developed deafness and was severely ataxic [34]. No
prototype LCMV, a CD8+ T-cell-dependent mechanism of BBB further follow-up of this patient was reported regarding the per-
disruption is proposed [24, 32]. sistence of the ataxia or her survival.

Ataxia in Lassa Fever • ofid • 3

 In a study involving 32 patients with LF by Solbrig et al. in CONCLUSIONS
Sierra Leone, 2 patients developed convalescent-phase ataxia. Postviral ataxia has been described in the literature following LF.
A 9-year-old febrile male patient, whose exposure to LASV To better identify and manage patients with postviral ataxia related
was confirmed by serological methods, was placed on antiviral to LF, hospitals in endemic countries might consider adopting or
ribavirin for 10 days. On day 8 of hospitalization, he developed modifying the diagnostic and classification recommendations
sudden-onset ataxia marked by difficulty sitting, truncal ataxia, proposed by Klockgether (Figure 1). In addition, hospitals might
poor tandem walk, and vertical nystagmus [35]. The second pa- consider creating and maintaining registries for patients who re-
tient, a 20-year-old female whose exposure to LASV was con- cover from LF as well as regular follow-ups with them in order to
firmed by serological methods, developed convalescent-phase document any disease conditions that arise following LF, including
ataxia while she was afebrile and hospitalized. Ataxia in this ataxia. Further research is needed to understand the mechanism,
patient was of sudden onset and was characterized by truncal prevalence, and incidence of postviral ataxia in patients who re-
and right-sided ataxia. Her CSF contained anti–Lassa virus IgG, cover from LF in endemic regions in West Africa.
demonstrated by indirect immunofluorescence antibody assay.
Acknowledgments
She still had ataxia at the time of her discharge [35]. No further
Potential conflicts of interest. All authors: no reported conflicts of in-
follow-up was reported to determine whether ataxia persisted terest. All authors have submitted the ICMJE Form for Disclosure of
in this patient. Potential Conflicts of Interest. Conflicts that the editors consider relevant to
Macher et al. reported a case of an aid worker who was in- the content of the manuscript have been disclosed.s

fected with Lassa virus in Sierra Leone in 1975. Neurological

References
examinations conducted in a US hospital in 1976 showed a
1. Johnson KM, McCormick JB, Webb PA, et al. Clinical virology of Lassa fever in
right-sided Babinski reflex, indicating possible damage to the hospitalized patients. J Infect Dis 1987; 155:456–64.
corticospinal tract that transmits motor information from the 2. Speir RW, Wood O, Liebhaber H, Buckley SM. Lassa fever, a new virus disease of
man from West Africa. IV. Electron microscopy of Vero cell cultures infected with
motor cortex to the spinal cord. The patient also had vertigo, Lassa virus. Am J Trop Med Hyg 1970; 19:692–4.
hypotension, and left-sided facial weakness. Thirty years after 3. Rowe WP, Murphy FA, Bergold GH, et al. Arenoviruses: proposed name for a
newly defined virus group. J Virol 1970; 5:651–2.
the onset of neurological manifestations, the patient still suf- 4. Buckley SM, Casals J. Lassa fever, a new virus disease of man from West Africa.
fered headache, dizziness, and staggering movements, symp- 3. Isolation and characterization of the virus. Am J Trop Med Hyg 1970; 19:680–91.
5. Monath TP, Newhouse VF, Kemp GE, et al. Lassa virus isolation from Mastomys
toms and signs of ataxia [20]. natalensis rodents during an epidemic in Sierra Leone. Science 1974; 185:263–5.
Though ataxia can be diagnosed by simple neurologic 6. Murphy F, Walker D. Arenaviruses: persistent infection and viral survival in res-
ervoir hosts. In: Kurstak E, Maramoroch K, eds. Viruses and environment. New
examination, postviral ataxia resulting from LF might be York: Academic Press; 1978:155–80.
underreported as a result of the poor health care–seeking be- 7. Olayemi A, Oyeyiola A, Obadare A, et al. Widespread arenavirus occurrence and
seroprevalence in small mammals, Nigeria. Parasit Vectors 2018; 11:416–428.
havior of patients in endemic countries in West Africa, inad- 8. Frame JD, Baldwin JM Jr, Gocke DJ, Troup JM. Lassa fever, a new virus disease
equate follow-up of patients discharged from hospitals, and of man from West Africa. I. Clinical description and pathological findings. Am J
Trop Med Hyg 1970; 19:670–6.
prohibitive cost of health care when it is available. 9. Leifer E, Gocke DJ, Bourne H. Lassa fever, a new virus disease of man from West
Africa. II. Report of a laboratory-acquired infection treated with plasma from a
person recently recovered from the disease. Am J Trop Med Hyg 1970; 19:677–9.
DIAGNOSTIC CHALLENGES OF POSTVIRAL ATAXIA
10. Günther S, Weisner B, Roth A, et al. Lassa fever encephalopathy: Lassa virus in
IN RESOURCE-LIMITED SETTINGS cerebrospinal fluid but not in serum. J Infect Dis 2001; 184:345–9.
11. NCDC. 2018 Lassa fever outbreak in Nigeria. Situation report. 2018. Available at:
Diagnosis of postviral ataxia in endemic West African countries 3Uhttps://www.ncdc.gov.ng/diseases/sitreps/?cat=5&name=An%20update%20
such as Nigeria is met with multifactorial challenges that affect of%20Lassa%20fever%20outbreak%20in%20NigeriaU3. Accessed 9 August 2019.
12. Joubert B, Rostásy K, Honnorat J. Immune-mediated ataxias. Handb Clin Neurol
the delivery of accessible and affordable health care services 2018; 155:313–32.
[36]. Some of these challenges include the absence of a system 13. Klockgether T. Sporadic ataxia with adult onset: classification and diagnostic cri-
teria. Lancet Neurol 2010; 9:94–104.
to keep track of a patient’s medical history, creating disconnec- 14. Ryan MM, Engle EC. Acute ataxia in childhood. J Child Neurol 2003; 18:309–16.
tions in a patient’s medical story. These challenges also include 15. van der Maas NA, Bondt PE, de Melker H, Kemmeren JM. Acute cerebellar ataxia
in the Netherlands: a study on the association with vaccinations and varicella
limited availability of diagnostic equipment and expensive cost zoster infection. Vaccine 2009; 27:1970–3.
of delivery for relevant health care services. The absence of ef- 16. Grahn A, Bråve A, Lagging M, et al. Imported case of Lassa fever in Sweden with
encephalopathy and sensorineural hearing deficit. Open Forum Infect Dis 2016;
fective social support systems further limits patients’ ability to 3(X):XXX–XX.
access and utilize already inadequate health care services [37, 17. Okokhere PO, Bankole IA, Iruolagbe CO, et al. Aseptic meningitis caused by
Lassa virus: case series report. Case Rep Neurol Med 2016; 2016:684–695.
38]. The health care system is further weakened by limited op- 18. Okokhere P, Colubri A, Azubike C, et al. Clinical and laboratory predictors of
eration of a national health insurance scheme [37, 39] with a Lassa fever outcome in a dedicated treatment facility in Nigeria: a retrospective,
observational cohort study. Lancet Infect Dis 2018; 18:684–95.
burdensome effect on patients in the form of out-of-pocket pay- 19. Cummins D, Bennett D, Fisher-Hoch SP, et al. Lassa fever encephalopathy: clin-
ments for health care services [40] that are prohibitive. ical and laboratory findings. J Trop Med Hyg 1992; 95:197–201.

4 • ofid • Ezeomah et al
20. Macher AM, Wolfe MS. Historical Lassa fever reports and 30-year clinical update. 30. Strazielle N, Ghersi-Egea JF. Choroid plexus in the central nervous system: bi-
Emerg Infect Dis 2006; 12:835–7. ology and physiopathology. J Neuropathol Exp Neurol 2000; 59:561–74.
21. Solbrig M. Lassa virus and central nervous system diseases. In: SMS, ed. The 31. David S. Neuroinflammation: New Insights Into Beneficial and Detrimental
Arenaviridae. Boston, MA: Springer; 1993:325–9. Functions. Hoboken, NJ: John Wiley & Sons Inc.; 2014.
22. McGavern DB, Kang SS. Illuminating viral infections in the nervous system. Nat 32. Kang SS, McGavern DB. Microbial induction of vascular pathology in the CNS. J
Rev Immunol 2011; 11:318–29. Neuroimmune Pharmacol 2010; 5:370–86.
23. Salinas S, Schiavo G, Kremer EJ. A hitchhiker’s guide to the nervous system: the 33. Abele M, Bürk K, Schöls L, et al. The aetiology of sporadic adult-onset ataxia.
complex journey of viruses and toxins. Nat Rev Microbiol 2010; 8:645–55. Brain 2002; 125:961–8.
24. Spindler KR, Hsu TH. Viral disruption of the blood-brain barrier. Trends 34. Fisher-Hoch SP, Tomori O, Nasidi A, et al. Review of cases of nosocomial Lassa
Microbiol 2012; 20:282–90. fever in Nigeria: the high price of poor medical practice. BMJ 1995; 311:857–9.
25. Cassady K, Whitley R. Pathogenesis and pathophysiology of viral infections of the 35. Solbrig M, McCormick J. Lassa fever: central nervous system manifestations. J
central nervous system. In: Scheld M, Whitley R, Marra C, eds. Infections of the Trop Geogr Neurol 1991; 1:23–30.
central nervous system. Philadelphia, PA: Lippincott Williams & Wilkins; 2014; 36. Singh P, Sachs JD. 1 million community health workers in sub-Saharan Africa by
49–64. 2015. Lancet 2013; 382:363–5.
26. Dahm T, Rudolph H, Schwerk C, et al. Neuroinvasion and inflamma- 37. Fatusi O, Akinpelu O, Amusa Y. Challenges of managing nasopharyngeal carci-
tion in viral central nervous system infections. Mediators Inflamm 2016; noma in a developing country. J Natl Med Assoc 2006; 98:758–64.
2016:1–12. 38. Adeloye D, David RA, Olaogun AA, et al. Health workforce and governance: the
27. Dando SJ, Mackay-Sim A, Norton R, et al. Pathogens penetrating the central crisis in Nigeria. Hum Resour Health 2017; 15:32–44.
nervous system: infection pathways and the cellular and molecular mechanisms 39. Adegboyega O, Abioye K. Effects of health-care services and commodities cost on
of invasion. Clin Microbiol Rev 2014; 27:691–726. the patients at the primary health facilities in Zaria Metropolis, North Western
28. Yun NE, Ronca S, Tamura A, et al. Animal model of sensorineural hearing loss Nigeria. Niger J Clin Pract 2017; 20:1027–35.
associated with Lassa virus infection. J Virol 2015; 90:2920–7. 40. Aregbeshola BS, Khan SM. Out-of-pocket payments, catastrophic health expend-
29. Wolburg H, Paulus W. Choroid plexus: biology and pathology. Acta Neuropathol iture and poverty among households in Nigeria 2010. Int J Health Policy Manag
2010; 119:75–88. 2018; 7:798–806.

Ataxia in Lassa Fever • ofid • 5