Lassa fever overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Lassa fever is an acute viral hemorrhagic fever first described in 1969 in the town of Lassa, Nigeria, located in the Yedseram river valley.[1] The virus, a member of the virus family Arenaviridae, is a single-stranded RNA virus and is zoonotic, or animal-borne. Clinical cases of the disease had been known for over a decade earlier but not connected with this viral pathogen. The infection is endemic in West African countries, and causes 300-500,000 cases annually with ~5,000 deaths.[2] Outbreaks of the disease have been observed in Nigeria, Liberia, Sierra Leone, Guinea, and the, Central African Republic, but it is believed that human infections also exist in Democratic Republic of the Congo, Mali, and Senegal. Lassa fever is also the most common hemorrhagic fever that is exported beyond its endemic area to countries like the United States, the United Kingdom of Great Britain and Northern Ireland, the Netherlands, Japan, and Israel. While Lassa fever is mild or has no observable symptoms in about 80% of people infected with the virus, the remaining 20% have a severe multisystem disease. Lassa fever is also associated with occasional epidemics, during which the case fatality rate can reach 50%.
Historical Perspective
The illness was discovered in 1969 when two missionary nurses died in Nigeria, West Africa. The cause of the illness was found to be Lassa virus, named after the town in Nigeria where the first cases originated.
Pathophysiology
Lassa virus is zoonotic (transmitted from animals). The reservoir, or host, of Lassa virus is a rodent known as the "multimammate rat" of the genus Mastomys. It is not certain which species of Mastomys are associated with Lassa; however, at least two species carry the virus in Sierra Leone. Mastomys rodents breed very frequently, produce large numbers of offspring, and are numerous in the savannas and forests of West, Central, and East Africa. In addition, Mastomys generally readily colonize human homes. All these factors together contribute to the relatively efficient spread of Lassa virus from infected rodents to humans.
Causes
Lassa fever is caused by the Lassa virus, a member of the Arenaviridae family; it is an enveloped, single-stranded, bisegmented RNA virus. Replication for Lassa virus is very rapid, while also demonstrating temporal control in replication. There are two genome segments. The first step involved is making mRNA copies of the negative-sense genome. This ensures that there are adequate proteins, which are required for replication. The N and L proteins are made from the mRNA produced. The -ve sense genome then makes vcRNA (viral circular RNA) copies of itself which are positive-sense. The vcRNA is a template for producing -ve sense progeny but mRNA is also synthesized from it. The mRNA synthesized from vcRNA translates the G (spike) proteins and Z proteins. Thus, with this temporal control, the spike proteins are produced last, making the infection further undetected by the host immune system.
Differentiating Lassa fever from other Diseases
Clinically, Lassa fever infections are difficult to distinguish from other viral hemorrhagic fevers such as Ebola and Marburg, and from more common febrile illnesses such as malaria.
Risk Factors
Individuals at risk are those who live or visit areas with a high population of Mastomys rodents infected with Lassa virus or are exposed to infected humans. Hospital staff are not at great risk for infection as long as protective measures are taken.
Natural History, Complications and Prognosis
The most common complication of Lassa fever is deafness. Various degrees of deafness occur in approximately one-third of cases, and in many cases hearing loss is permanent. Spontaneous abortion is another serious complication. Approximately 15%-20% of patients hospitalized for Lassa fever die from the illness. However, overall only about 1% of infections with Lassa virus result in death. The death rates are particularly high for women (greater than 80%) in the third trimester of pregnancy, and for fetuses, about 95% of which die in the uterus of infected pregnant mothers.
Diagnosis
History and Symptoms
Lassa fever after an incubation period of six to twenty-one days, an acute illness with multiorgan involvement develops gastrointestinal, neurological and pulmonary symptoms.
Physical Examination
Lassa fever is commonly associated with fever on physical examination at admission. At advanced stages of the disease, physical examination findings are more pertinent and often include unstable vital signs, such as tachycardia or relative bradycardia, hypotension, and tachypnea. Physical examination may also be remarkable for abdominal tenderness and distension and neurological impairment.
Laboratory Findings
There is a range of laboratory investigations that are performed to diagnose the disease and assess its course and complications. ELISA test for antigen and IgM antibodies gives 88% sensitivity and 90% specificity for the presence of the infection. Other laboratory findings in Lassa fever include lymphopenia (low white blood cell counts), thrombocytopenia (low platelets), and elevated aspartate aminotransferase (AST) levels in the blood. Lassa fever can also be found in cerebrospinal fluid. The virus itself may be cultured in 7 to 10 days. Immunohistochemistry performed on tissue specimens can be used to make a post mortem diagnosis. The virus can also be detected by reverse transcriptase polymerase chain reaction (RT-PCR); however, this method is primarily a research tool.[3] 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. [4] Research has been done in the last few year, by a team of specialists, in order to diagnose the Lassa fever on a molecular level.[5]
Treatment
Medical Therapy
Ribavirin, an antiviral drug, has been used with success in Lassa fever patients. It has been shown to be most effective when given early in the course of the illness. Patients should also receive supportive care consisting of maintenance of appropriate fluid and electrolyte balance, oxygenation and blood pressure, as well as treatment of any other complicating infections.
Primary Prevention
Primary transmission of the Lassa virus from its host to humans can be prevented by avoiding contact with Mastomys rodents, especially in the geographic regions where outbreaks occur. When caring for patients with Lassa fever, further transmission of the disease through person-to-person contact or nosocomial routes can be avoided by taking preventive precautions against contact with patient secretions and educating people comes under primary prevention.
Future or Investigational Therapies
Researchers at the USAMRIID facility, where military biologists study infectious diseases, have a promising vaccine candidate. 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.[6] Siga Technologies is developing an antiviral drug that has been shown effective in treating experimentally infected guinea pigs. In a study conducted at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), treatment with ST-193 once a day for 14 days resulted in significant reduction in mortality (71% of the animals survived at the low dose), whereas all untreated animals and those treated with ribavirin died within 20 days of the infection.[7]
References
- ↑ Frame JD, Baldwin JM, Gocke DJ, Troup JM (1970). "Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological findings". Am. J. Trop. Med. Hyg. 19 (4): 670–6. PMID 4246571.
- ↑ 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 Encephalopathy: Lassa Virus in Cerebrospinal Fluid but Not in Serum Stephan Günther, Boye Weisner, Andreas Roth, Thomas Grewing, Marcel Asper, Christian Drosten, Petra Emmerich, Jochen Petersen, Martin Wilczek and Herbert Schmitz The Journal of Infectious Diseases , Vol. 184, No. 3 (Aug. 1, 2001), pp. 345-349
- ↑ Mojeed, Momoh (14 Nov. 2012.). "Molecular Diagnostics For Lassa Fever At Irrua Specialist Teaching Hospital, Nigeria: Lessons Learnt From Two Years Of Laboratory Operation". Plos Neglected Tropical Diseases. Check date values in:
|date=(help);|access-date=requires|url=(help) - ↑ Ehichioya, Deborah U.; Asogun, Danny A.; Ehimuan, Jacqueline; Okokhere, Peter O.; Pahlmann, Meike; Ölschläger, Stephan; Becker-Ziaja, Beate; Günther, Stephan; Omilabu, Sunday A. Tropical Medicine & International Health. Aug2012, Vol. 17 Issue 8, p1001-1004. 4p. DOI: 10.1111/j.1365-3156.2012.03010.x.
- ↑ 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. PMID 15971954.
- ↑ "SIGA Passes First Hurdle with Lassa Fever Antiviral ST-193" (Press release).