Lassa fever

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Lassa fever
Synonyms Lassa hemorrhagic fever
LassaBoy.png
Community education material for Lassa fever
Specialty Infectious disease
Symptoms Fever, headaches, bleeding[1]
Complications Deafness[1]
Usual onset 1–3 weeks following exposure[1]
Causes Lassa virus[1]
Risk factors Exposure to rodents in West Africa[1]
Diagnostic method Laboratory testing[1]
Differential diagnosis Ebola, malaria, typhoid fever[1]
Treatment Supportive, ribavirin[1]
Prognosis ~1% risk of death[1]
Frequency ~400,000 cases per year[2]
Deaths ~5,000 deaths per year[2]

Lassa fever, also known as Lassa hemorrhagic fever (LHF), is a type of viral hemorrhagic fever caused by the Lassa virus.[1] Many of those infected by the virus do not develop symptoms.[1] When symptoms occur they typically include fever, weakness, headaches, vomiting, and muscle pains.[1] Less commonly there may be bleeding from the mouth or gastrointestinal tract.[1] The risk of death once infected is about one percent and frequently occurs within two weeks of the onset of symptoms.[1] Among those who survive about a quarter have hearing loss, which improves over time in about half.[1]

The disease is usually initially spread to people via contact with the urine or feces of an infected multimammate rat.[1] Spread can then occur via direct contact between people.[1] Diagnosis based on symptoms is difficult.[1] Confirmation is by laboratory testing to detect the virus's RNA, antibodies for the virus, or the virus itself in cell culture.[1] Other conditions that may present similarly include Ebola, malaria, typhoid fever, and yellow fever.[1] The Lassa virus is a member of the Arenaviridae family of viruses.[1]

There is no vaccine.[3] Prevention requires isolating those who are infected and decreasing contact with the rats.[1] Other efforts to control the spread of disease include having a cat to hunt vermin, and storing food in sealed containers.[1] Treatment is directed at addressing dehydration and improving symptoms.[1] The antiviral medication, ribavirin may be useful when given early.[1] These measures improve outcomes.[1]

Descriptions of the disease date from the 1950s.[1] The virus was first described in 1969 from a case in the town of Lassa, in Borno State, Nigeria.[1][4] Lassa fever is relatively common in West Africa including the countries of Nigeria, Liberia, Sierra Leone, Guinea, and Ghana.[1][2] There are about 300,000 to 500,000 cases which result in 5,000 deaths a year.[2]

Signs and symptoms[edit]

In 80% of cases, the disease is asymptomatic, but in the remaining 20%, it takes a complicated course. The virus is estimated to be responsible for about 5,000 deaths annually. The fever accounts for up to one-third of deaths in hospitals within the affected regions and 10 to 16% of total cases.[5]

After an incubation period of six to 21 days, an acute illness with multiorgan involvement develops. Nonspecific symptoms include fever, facial swelling, and muscle fatigue, as well as conjunctivitis and mucosal bleeding. The other symptoms arising from the affected organs are:

Clinically, Lassa fever infections are difficult to distinguish from other viral hemorrhagic fevers such as Ebola and Marburg virus disease, and from more common febrile illnesses such as malaria.

High risk groups include pregnant women and newborns. The latter may have an 87% fatality rate. The "Swollen baby syndrome" occurs in newborns, infants and toddlers with pitting edema, abdominal distension and hemorrhage.[6]

Cause[edit]

Mastomys natalensis, the natural reservoir of the Lassa fever virus

Virology[edit]

Lassa virus is a member of the Arenavirida family of viruses.[7] Specifically it is an old world arenavirus, which is enveloped, single-stranded, and bi-segmented RNA. This virus has a both a large and a small genome section, with four lineages identified to date: Josiah (Sierra Leone), GA391 (Nigeria), LP (Nigeria) and strain AV.[8]

Spread[edit]

Lassa virus commonly spreads to humans from other animals, specifically the natal multimammate rat or African rat, also called the natal multimammate mouse (Mastomys natalensis).[9] This is probably the most common mouse in equatorial Africa, common in human households and eaten as a delicacy in some areas.[9][10]

The multimammate rat can quickly produce a large number of offspring, tends to colonize human settlements increasing the risk of rodent-human contact, and is found throughout the west, central and eastern parts of the African continent.[11] Once the rat has become a carrier, it will excrete the virus throughout the rest of its lifetime through feces and urine creating ample opportunity for exposure.[11] The virus is probably transmitted by contact with the feces or urine of animals accessing grain stores in residences.[10]

Individuals who are at a higher risk of contracting the infection are those who live in rural areas where Mastromys are discovered, and where sanitation isn't prevalent. Infection typically occurs by direct or indirect exposure to animal excrement through the respiratory or gastrointestinal tracts. Inhalation of tiny particles of infectious material (aerosol) is believed to be the most significant means of exposure. It is possible to acquire the infection through broken skin or mucous membranes that are directly exposed to infectious material. Transmission from person to person has been established, presenting a disease risk for healthcare workers. The virus is present in urine for between three and nine weeks after infection, and it can be transmitted in semen for up to three months after becoming infected.[12][13]

No study has proven presence in breast milk, but the high level of viremia suggests it may be possible.[6]

Diagnosis[edit]

A range of laboratory investigations are performed, where possible, to diagnose the disease and assess its course and complications. The confidence of a diagnosis can be compromised if laboratory tests are not available. One comprising factor is the number of febrile illnesses present in Africa, such as malaria or typhoid fever that could potentially exhibit similar symptoms, particularly for non-specific manifestations of Lassa fever.[7] In cases with abdominal pain, in countries where Lassa is common, Lassa fever is often misdiagnosed as appendicitis and intussusception which delays treatment with the antiviral ribavirin.[14] In West Africa, where Lassa is most prevalent, it is difficult for doctors to diagnose due to the absence of proper equipment to perform tests.[15]

The FDA has yet to approve a widely validated laboratory test for Lassa, but there are tests that have been able to provide definitive proof of the presence of the LASV virus.[7] These tests include cell cultures, PCR, ELISA antigen assays, plaque neutralization assays, and immunofluorescence essays. However, immunofluorescence essays provide less definitive proof of Lassa infection.[7] An ELISA test for antigen and Immunoglobulin M antibodies give 88% sensitivity and 90% specificity for the presence of the infection. Other laboratory findings in Lassa fever include lymphocytopenia (low white blood cell count), thrombocytopenia (low platelets), and elevated aspartate transaminase levels in the blood. Lassa fever virus can also be found in cerebrospinal fluid.[16]

Prevention[edit]

Community education material for Lassa fever

Control of the Mastomys rodent population is impractical, so measures focus on keeping rodents out of homes and food supplies, encouraging effective personal hygiene, storing grain and other foodstuffs in rodent-proof containers, and disposing of garbage far from the home to help sustain clean households. Gloves, masks, laboratory coats, and goggles are advised while in contact with an infected person, to avoid contact with blood and body fluids. These issues in many countries are monitored by a department of public health. In less developed countries, these types of organizations may not have the necessary means to effectively control outbreaks.

Researchers at the United States Army Medical Research Institute of Infectious Diseases facility, where military biologists study infectious diseases, have a promising vaccine candidate.[17] They have developed a replication-competent vaccine against Lassa virus based on recombinant vesicular stomatitis virus vectors expressing the Lassa virus glycoprotein. After a single intramuscular injection, test primates have survived lethal challenge, while showing no clinical symptoms.[18]

Treatment[edit]

All persons suspected of Lassa fever infection should be admitted to isolation facilities and their body fluids and excreta properly disposed of.

Early and aggressive treatment using ribavirin was pioneered by Joe McCormick in 1979. After extensive testing, early administration was determined to be critical to success. Additionally, ribavirin is almost twice as effective when given intravenously as when taken by mouth.[19] Ribavirin is a prodrug which appears to interfere with viral replication by inhibiting RNA-dependent nucleic acid synthesis, although the precise mechanism of action is disputed.[20] The drug is relatively inexpensive, but the cost of the drug is still very high for many of those in West African states. Fluid replacement, blood transfusion, and fighting hypotension are usually required. Intravenous interferon therapy has also been used.[citation needed]

When Lassa fever infects pregnant women late in their third trimester, inducing delivery is necessary for the mother to have a good chance of survival.[21] This is because the virus has an affinity for the placenta and other highly vascular tissues. The fetus has only a one in ten chance of survival no matter what course of action is taken; hence, the focus is always on saving the life of the mother.[22] Following delivery, women should receive the same treatment as other Lassa fever patients.

Work on a vaccine is continuing, with multiple approaches showing positive results in animal trials.[23]

Prognosis[edit]

About 15–20% of hospitalized Lassa fever patients will die from the illness. The overall mortality rate is estimated to be 1%, but during epidemics, mortality can climb as high as 50%. The mortality rate is greater than 80% when it occurs in pregnant women during their third trimester; fetal death also occurs in nearly all those cases. Abortion decreases the risk of death to the mother.[24] Some survivors experience lasting effects of the disease,[25] and can include partial or complete deafness.[1]

Because of treatment with ribavirin, fatality rates are continuing to decline.[26][27]

Epidemiology[edit]

The study of the epidemiology of Lassa fever is complicated by a lengthy incubation period, which may be up to three weeks.[7] Incubation periods as long as Lassa fever may affect spatial clustering of the disease by limiting the understanding of the incidence and distribution of the disease. The spatial clustering for this disease is still in development as a lack of easy-available diagnosis, limited public health surveillance infrastructure, and high clustering of incidence near high intensity sampling make for an incomplete look at the impact of Lassa in this region.[7]

The number of people infected by Lassa range from 100,000 to three million a year, with up to 5,000 deaths per year in West Africa alone.[11][28]

Geography[edit]

Lassa high risk areas are near the western and eastern extremes of West Africa. As of 2018, the Lassa belt includes Guinea, Nigeria, Sierra Leone and Liberia.[6] As of 2003, 10-16% of people in Sierra Leone and Liberia admitted to hospital had the virus.[9] The case fatality rate for those who are hospitalized for the disease is about 15-20%. Research in showed a twofold increase risk of infection for those living in close proximity to someone with infection symptoms within the last year.

The high risk areas areas cannot be well defined by any known biogeographical or environmental breaks except for the multimammate rat, particularly Guinea (Kindia, Faranah and Nzerekore regions), Liberia (mostly in Lofa, Bong, and Nimba counties), Nigeria (everywhere) and Sierra Leone (typically from Kenema and Kailahun districts). It is less common in the Central African Republic, Mali, Senegal and other nearby countries, and less common yet in Ghana and the Democratic Republic of the Congo. Benin had its first confirmed cases in 2014, and Togo had its first confirmed cases in 2016.[12]

As of 2013, the spread of Lassa outside of West Africa had been very limited. Twenty to thirty cases had been described in Europe, as being caused by importation through infected individuals.[11] These cases found outside of West Africa were found to have a high fatality risk because of the delay of diagnosis and treatment due to being unaware of the risk associated with the symptoms.[11] Imported cases have not manifested in larger epidemics outside of Africa due to a lack of human to human transmission in hospital settings. An exception had occurred in 2003 when a healthcare worker became infected before the patient showed clear symptoms.[11]

2018 Outbreak[edit]

An outbreak of Lassa fever occurred in Nigeria during 2018 and spread to 18 of the country's states; it was the largest outbreak of Lassa recorded.[29][30][31] As of February 25, 2018, there were 1081 suspected cases and 90 reported deaths; 317 of the cases and 72 deaths were confirmed as Lassa.[32]

Research[edit]

The Lassa virus is one of several viruses identified by WHO as a likely cause of a future epidemic. They therefore list it for urgent research and development to develop new diagnostic tests, vaccines, and medicines.[33][34]

See also[edit]

References[edit]

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad "Lassa fever". WHO. March 2016. Archived from the original on 1 November 2016. Retrieved 2 November 2016. 
  2. ^ a b c d Ogbu O, Ajuluchukwu E, Uneke CJ (2007). "Lassa fever in West African sub-region: an overview". Journal of vector borne diseases. 44 (1): 1–11. PMID 17378212. Lassa fever is endemic in West Africa 
  3. ^ Yun, N. E.; Walker, D. H. (2012). "Pathogenesis of Lassa Fever". Viruses. 4 (12): 2031–2048. doi:10.3390/v4102031. PMC 3497040Freely accessible. PMID 23202452. 
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  5. ^ Centers for Disease Control and Prevention, "Lassa Fever" Archived 23 September 2016 at the Wayback Machine.
  6. ^ a b c d David Greenky, Barbara Knust, Eric J. DziubanWhat Pediatricians Should Know About Lassa Virus. JAMA Pediatr. 2018;172(5):407-408. doi:10.1001/jamapediatrics.2017.5223
  7. ^ a b c d e f Peterson, A. Townsend; Moses, Lina M.; Bausch, Daniel G. (2014-08-08). "Mapping Transmission Risk of Lassa Fever in West Africa: The Importance of Quality Control, Sampling Bias, and Error Weighting". PLOS One. 9 (8): e100711. doi:10.1371/journal.pone.0100711. ISSN 1932-6203. PMC 4126660Freely accessible. PMID 25105746. 
  8. ^ Goeijenbier, Marco; Wagenaar, Jiri; Goris, Marga; Martina, Byron; Henttonen, Heikki; Vaheri, Antti; Reusken, Chantal; Hartskeerl, Rudy; Osterhaus, Albert (2013-02-01). "Rodent-borne hemorrhagic fevers: under-recognized, widely spread and preventable – epidemiology, diagnostics and treatment". Critical Reviews in Microbiology. 39 (1): 26–42. doi:10.3109/1040841X.2012.686481. ISSN 1040-841X. 
  9. ^ a b c Richmond, J. K.; Baglole, D. J. (2003). "Lassa fever: Epidemiology, clinical features, and social consequences". BMJ. 327 (7426): 1271–1275. doi:10.1136/bmj.327.7426.1271. PMC 286250Freely accessible. PMID 14644972. 
  10. ^ a b Werner, Dietrich, editor (2004). Biological Resources and Migration. Springer. p. 363. ISBN 978-3-540-21470-0. 
  11. ^ a b c d e f Go, AS; Bauman, M; King, SM; Fonarow, GC; Lawrence, W; Williams, KA; Sanchez, E (15 November 2013). "An Effective Approach to High Blood Pressure Control: A Science Advisory From the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention". Hypertension. 63 (4): 878–85. doi:10.1161/HYP.0000000000000003. PMID 24243703. Archived from the original on 20 November 2013. 
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  14. ^ Dongo, A. E.; Kesieme, E. B.; Iyamu, C. E.; Okokhere, P. O.; Akhuemokhan, O. C.; Akpede, G. O. (2013). "Lassa fever presenting as acute abdomen: a case series". Virology Journal. 10: 124. doi:10.1186/1743-422X-10-123. PMC 3639802Freely accessible. PMID 23597024. Archived from the original on 10 May 2013. 
  15. ^ Asogun, D. A.; Adomeh, D. I.; Ehimuan, J.; Odia, I.; Hass, M.; Gabriel, M.; Olschläger, S.; Becker-Ziaja, B.; Folarin, O.; Phelan, E.; Ehiane, P. E.; Ifeh, V. E.; Uyigue, E. A.; Oladapo, Y. T.; Muoebonam, E. B.; Osunde, O.; Dongo, A.; Okokhere, P. O.; Okogbenin, S. A.; Momoh, M.; Alikah, S. O.; Akhuemokhan, O. C.; Imomeh, P.; Odike, M. A.; Gire, S.; Andersen, K.; Sabeti, P. C.; Happi, C. T.; Akpede, G. O.; Günther, S. (2012). Bausch, Daniel G, ed. "Molecular Diagnostics for Lassa Fever at Irrua Specialist Teaching Hospital, Nigeria: Lessons Learnt from Two Years of Laboratory Operation". PLoS Neglected Tropical Diseases. 6 (9): e1839. doi:10.1371/journal.pntd.0001839. PMC 3459880Freely accessible. PMID 23029594. 
  16. ^ Günther, S.; Weisner, B.; Roth, A.; Grewing, T.; Asper, M.; Drosten, C.; Emmerich, P.; Petersen, J.; Wilczek, M.; Schmitz, H. (2001). "Lassa Fever Encephalopathy: Lassa Virus in Cerebrospinal Fluid but Not in Serum". The Journal of Infectious Diseases. 184 (3): 345–349. doi:10.1086/322033. PMID 11443561. 
  17. ^ Preston, Richard (2002). The demon in the freezer: a true story. New York: Random House. ISBN 0-375-50856-2. 
  18. ^ Geisbert TW, Jones S, Fritz EA, et al. (2005). "Development of a New Vaccine for the Prevention of Lassa Fever". PLoS Med. 2 (6): e183. doi:10.1371/journal.pmed.0020183. PMC 1160587Freely accessible. PMID 15971954. 
  19. ^ Fisher-Hoch SP, McCormick JB (2004). "Lassa fever vaccine". Expert review of vaccines. 3 (2): 189–97. doi:10.1586/14760584.3.4.S189. PMID 15056044. 
  20. ^ Crotty S, Cameron C, Andino R (2002). "Ribavirin's antiviral mechanism of action: lethal mutagenesis?". J. Mol. Med. 80 (2): 86–95. doi:10.1007/s00109-001-0308-0. PMID 11907645. 
  21. ^ Price ME, Fisher-Hoch SP, Craven RB, McCormick JB (September 1988). "A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy". BMJ. 297 (6648): 584–7. doi:10.1136/bmj.297.6648.584. PMC 1834487Freely accessible. PMID 3139220. 
  22. ^ Samuel, Daso. "Lassa fever... What you need to know" (PDF). Archived (PDF) from the original on 25 June 2017. Retrieved 1 February 2017. 
  23. ^ "WHO Target Product Profiles for Lassa virus Vaccine" (PDF). World Health Organization. April 2017. Retrieved 11 September 2017. 
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  25. ^ Emond, R. T.; Bannister, B.; Lloyd, G.; Southee, T. J.; Bowen, E. T. (1982). "A case of Lassa fever: Clinical and virological findings". British Medical Journal (Clinical research ed.). 285 (6347): 1001–1002. doi:10.1136/bmj.285.6347.1001. PMC 1500383Freely accessible. PMID 6812716. 
  26. ^ "Lassa fever". World Health Organization. Retrieved 2017-09-11. 
  27. ^ McCormick, J. B.; King, I. J.; Webb, P. A.; Scribner, C. L.; Craven, R. B.; Johnson, K. M.; Elliott, L. H.; Belmont-Williams, R. (1986-01-02). "Lassa fever. Effective therapy with ribavirin". The New England Journal of Medicine. 314 (1): 20–26. doi:10.1056/NEJM198601023140104. ISSN 0028-4793. PMID 3940312. 
  28. ^ Viral Hemorrhagic Fever Consortium Lassa fever Archived 4 April 2015 at the Wayback Machine. Page accessed April 6, 2016
  29. ^ Maxmen, Amy (15 March 2018). "Deadly Lassa-fever outbreak tests Nigeria's revamped health agency". Nature. doi:10.1038/d41586-018-03171-y. 
  30. ^ "On the frontlines of the fight against Lassa fever in Nigeria". World Health Organization. March 2018. 
  31. ^ Beaubien, Jason (March 19, 2018). "Nigeria Faces Mystifying Spike In Deadly Lassa Fever". NPR. 
  32. ^ "Lassa Fever – Nigeria". World Health Organization. 1 March 2018. 
  33. ^ Kieny, Marie-Paule. "After Ebola, a Blueprint Emerges to Jump-Start R&D". Scientific American Blog Network. Archived from the original on 20 December 2016. Retrieved 13 December 2016. 
  34. ^ "LIST OF PATHOGENS". World Health Organization. Archived from the original on 20 December 2016. Retrieved 13 December 2016. 

Further reading[edit]

  • Echioya, Deborah U.; Hass, Meike; Olshlager, Stephan; Becker-Ziaja, Beate; Chukwu, Christian O. Onyebuchi; Coker, Jide; Nasidi, Abdulsalam; Ogugua, Osi-Ogdu; Gunther, Stephan; Omilabu, Sunday A. (2010). "Lassa Fever, Nigeria, 2005-2008". Emerging Infectious Diseases. 6. 16: 1040–41. doi:10.3201/eid1606.100080. 
  • Branco, Luis M.; Grove, Jessica N.; Boisen, Matt L.; Shaffer, Jeffrey G.; Goba, Augustine; Fullah, Mohammed; Momoh, Mambu; Grant, Donald S.; Garry, Robert F. (October 4, 2011). "Emerging Trends in Lassa Fever: Redefining the Role of Immunoglobulin M and Inflammation in Diagnosing Acute Infection". Virology Journal. 8: 478. doi:10.1186/1743-422x-8-478. 
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