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Lassa fever

Lassa fever is an acute viral hemorrhagic fever first described in 1969 in the Nigerian town of Lassa in the Yedseram River valley. 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, causing many deaths. Outbreaks of the disease have been observed in the following countries: more...

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  • Nigeria
  • Liberia
  • Sierra Leone
  • Guinea
  • Central African Republic

but it is believed that human infections also exist in:

  • Democratic Republic of the Congo
  • Mali
  • Senegal

It is also the most common hemorrhagic fever that is exported beyond its endemic area to countries like the United States, United Kingdom, The Netherlands, Japan and Israel.

The virus and epidemiology

The virus belongs to Arenaviridae family; it is an enveloped, single-stranded, bisegmented RNA virus. It has been determined that the virus is zoonotic (transmitted from animals), and that it spreads to man from rodents, specifically multimammate rats (Mastomys natalensis). This is probably the most common rodent in equatorial Africa, ubiquitous in human households and eaten as a delicacy by up to 90% of people in some areas. In these rats infection is in a persistent asymptomatic state. The virus is shed in their excreta (urine and feces), which can be aerosolized.

In fatal cases Lassa fever is characterized by impaired or delayed cellular immunity leading to fulminant viraemia.

The dissemination of the infection can be assessed by prevalence of antibodies to the virus in populations of:

  • Sierra Leone 8–52%
  • Guinea 4–55%
  • Nigeria approx. 21%

Like other hemorrhagic fevers, Lassa fever can be transmitted directly from one human to another. It can be contracted by an airborne route or with direct contact with infected human blood, urine, or semen. Transmission through breast milk has also been observed.

Lassa fever is less deadly compared to ebola, though they share similar symptoms. Because Lassa is a very fast replicating and debilitating virus, the chances of a worldwide epidemic are small. Patients are far too weak to board a plane and spread it to other parts of the world.

Lassa fever is a virus that has emerged relatively recently. It has managed to appear in a relatively short span of history. Because Lassa fever has a reservoir (rodents), it is difficult to get rid of the virus.

The disease

Infection in humans typically occurs via exposure to animal excrement through the respiratory or gastrointestinal tracts. Inhalation of tiny particles of infective 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 infective material. Transmission from person to person has also been established, presenting a disease risk for healthcare workers. Frequency of transmission via sexual contact has not been established.

Read more at Wikipedia.org


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Lassa fever, Nigeria, 2003 and 2004
From Emerging Infectious Diseases, 10/1/05 by Sunday Aremu Omilabu

To the Editor: Suspected outbreaks of Lassa fever have been reported in the northern part of Edo, Nigeria, including Ekpoma, Igarra, and Ibilo, in 2001 and between November 2003 and March 2004 (1,2). To confirm Lassa fever activity in this area, serum samples were collected at the Specialist Teaching Hospital in Irrua (ISTH) from September 2003 to January 2004. Approximately 16,000 patients are seen each year at ISTH, and [approximately equal to] 80% of them have febrile illness. Serum specimens were taken from patients with febrile illness (n = 31), healthy contact persons (n = 17), and healthy hospital staff (n = 12). The samples were analyzed by Lassa virus-specific reverse-transcriptase polymerase chain reaction (RT-PCR) at the University of Lagos. Aliquots of specimens were sent to the Bernhard-Nocht Institute (BNI in Hamburg, Germany) for confirmatory PCR analysis, serologic testing, and virus isolation. The PCR used at both facilities was based on primers 80F2 and 36E2 that targeted the glycoprotein precursor (GPC) gene (3), although the protocols were slightly different. At BNI, virus RNA was purified by QIAamp viral RNA kit (Qiagen, Hilden, Germany), and RT-PCR was performed with Superscript II RT/Platinum Taq polymerase 1-step reagents (Invitrogen, Karlsruhe, Germany). This PCR assay has a 95% detection limit of 2,500 copies/mL (4). At the University of Lagos, virus RNA purification and RT-PCR were performed with diatomaceous silica and Brilliant single-step RT-PCR kit (Stratagene, Heidelberg, Germany), respectively. Serologic testing for Lassa virus-specific immunoglobulin G (IgG) and IgM was performed by indirect immunofluorescence assay (IFA) by using Vero cells infected with Lassa virus strain Josiah. Virus was isolated in the biosafety level 4 laboratory at BNI with Vero cells. Results of the tests are summarized in the Table.

Acute Lassa virus infection, as shown by a positive PCR result, was diagnosed at the University of Lagos in 1 patient. This result was independently confirmed at BNI, and 2 additional samples tested positive by PCR. The PCR signals were weak, which suggests that discrepancies between laboratories stem from higher sensitivity of the assay used at BNI. Presence of a low IgM titer in the absence of IgG in 2 of the PCR-positive samples is also consistent with an acute infection. Two of the Lassa virus-positive persons (04-02 and 04-10) had febrile illness that indicated symptomatic Lassa fever, while 1 (04-04) had been classified as an asymptomatic contact at the time of sampling. Retrospective investigation showed no evidence of illness in this person before or after sampling. Sequencing the diagnostic PCR fragments (300 nucleotides [nt] of GPC gene) from the 3 patients indicated infections by closely related strains. The sequence of patient 04-10 (GenBank accession no. DQ010031) differed by 4% from those of patients 04-02 and 04-04, while the latter sequences were identical (GenBank accession no. DQ010030). The facts that patients 04-02 and 04-04 were sisters who lived in the same house, that their samples were taken on the same day (January 28, 2004), and that the sequences were identical suggest a common source of infection or an infection chain. The detection of an asymptomatic or mild Lassa virus infection in the contact person agrees with population-based studies in Sierra Leone that show only 9%-26% of all Lassa virus infections are associated with fever (5).

In an additional 10 samples, IgM with or without IgG was detected, primarily in patients with febrile illness. IgG in the absence of IgM was detected in 1 contact and 4 healthcare workers. All serologic IFA findings were confirmed with [mu]-capture and IgG enzyme-linked immunosorbent assays developed at BNI. Virus isolation was attempted with all samples that tested positive by PCR or IgM IFA. Lassa virus was isolated from 1 PCR-positive serum (04-10). The strain was designated Nig04-010. To characterize Lassa virus circulating in north Edo, phylogenetic analysis was performed. In addition to the GPC sequences of the diagnostic PCR fragments, part of the L gene of Nig04-010 was amplified and sequenced (780 nt, GenBank accession no. AY693637). Phylogenetic analysis of these sequences showed that the virus circulating around Irrua belongs to phylogenetic lineage II, which comprises Lassa virus strains from the southeastern part of Nigeria (6). Thus, genotype and geographic origin of the viruses characterized here correspond.

These data provide evidence for Lassa fever activity in north Edo. Approximately 6% of febrile patients tested had PCR-confirmed Lassa fever, which extrapolates to hundreds of patients with Lassa fever per year, when one considers the number of patients with febrile illness seen at ISTH. As shown here and elsewhere, PCR is a useful tool to diagnose Lassa virus infection (3,7), a prerequisite for effective ribavirin treatment (8). First steps have been made to establish molecular diagnostics for Lassa virus at the University of Lagos. Further efforts are necessary to improve the laboratory infrastructure in the country.

Acknowledgments

We thank Corinna Thome for technical assistance.

The study was supported by a grant from the Bundesamt fur Wehrtechnik und Beschaffung (E/B41G/1G309/1A403 to S.G.) and grants from the Alexander von Humboldt Foundation (V-8121/NRI/ 1070140 to S.A.O.). The Bernhard-Nocht Institute is a World Health Organization Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research (DEU-000115).

References

(1.) Lassa fever--Nigeria (Edo). 2004 Feb 14 [cited 2004 Dec 8]. Available from http://www.promedmail.org, archive number 20040214.0487.

(2.) Lassa fever, suspected--Nigeria (Edo). 2001 Mar 19 [cited 2004 Dec 8]. Available from http://www.promedmail.org, archive number 20010319.0552.

(3.) Demby AH, Chamberlain J, Brown DW, Clegg CS. Early diagnosis of Lassa fever by reverse transcription PCR. J Clin Microbiol. 1994;32:2898-903.

(4.) Drosten C, Gottig S, Schilling S, Asper M, Panning M, Schmitz H, et al. Rapid detection and quantification of RNA of Ebola and Marburg viruses, Lassa virus, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, dengue virus, and yellow fever virus by real-time reverse transcription PCR. J Clin Microbiol. 2002;40:2323-30.

(5.) McCormick JB, Webb PA, Krebs JW, Johnson KM, Smith ES. A prospective study of the epidemiology and ecology of Lassa fever. J Infect Dis. 1987;155:437-44.

(6.) Bowen MD, Rollin PE, Ksiazek TG, Hustad HL, Bausch DG, Demby AH, et al. Genetic diversity among Lassa virus strains. J Virol. 2000;74:6992-7004.

(7.) Trappier SG, Conaty AL, Farrar BB, Auperin DD, McCormick JB, Fisher-Hoch SP. Evaluation of the polymerase chain reaction for diagnosis of Lassa virus infection. Am J Trop Med Hyg. 1993;49:214-21.

(8.) McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM, et al. Lassa fever. Effective therapy with ribavirin. N Engl J Med. 1986;314:20-6.

Sunday Aremu Omilabu, * Sikiru Olanrewaju Badaru, * Peter Okokhere, ([dagger]) Danny Asogun, ([dagger]) Christian Drosten, ([double dagger]) Petra Emmerich, ([double dagger]) Beate Becker-Ziaja, ([double dagger]) Herbert Schmitz, ([double dagger]) and Stephan Gunther ([double dagger])

* College of Medicine of the University of Lagos, Idi-Araba, Lagos, Nigeria; ([dagger]) Irrua Specialist Teaching Hospital, Irrua, Edo, Nigeria; and ([double dagger]) Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany

Address for correspondence: Stephan Gunther, Department of Virology, Bernhard-Nocht Institute for Tropical Medicine, Bernhard-Nocht Str 74, 20359 Hamburg, Germany; fax: 49-40-4281-8378; email: guenther@bni. Uni-hamburg.de

COPYRIGHT 2005 U.S. National Center for Infectious Diseases
COPYRIGHT 2005 Gale Group

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