Re: SEVERAL CASES OF FATAL ILLNESS , NOVEL ARENAVIRUS STRAIN? - SOUTH AFRICA ex ZAMBIA
<TABLE class=formlayout id=apex_layout_271110100662109808 summary=""><TBODY><TR><TD noWrap align=left>18-OCT-2008</TD></TR><TR><TD noWrap align=right>
Subject</TD><TD noWrap align=left>PRO/AH/EDR> Undiagnosed fatalities - S. Africa ex Zambia (09): arenavirus</TD></TR></TBODY></TABLE>
UNDIAGNOSED FATALITIES - SOUTH AFRICA ex ZAMBIA (09): ARENAVIRUS****************************************************************A ProMED-mail post<
http://www.promedmail.org>ProMED-mail is a program of theInternational Society for Infectious Diseases<
http://www.isid.org>Date: Thu 16 Oct 2008Source: Eurosurveillance, Volume 13, Issue 42 [edited]<
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19008>
Unknown disease in South Africa identified as arenavirus infection------------------------------------------------------------------Introduction---------------On 12 Sep 2008, a tourist guide organising safari trips, residing in Lusaka, Zambia, was evacuated in a critical condition to Johannesburg, South Africa. She was admitted to a clinic where she died on 14 Sep 2008 about 10 days after the onset of symptoms. The symptoms included a prodromal phase with fever, myalgia, vomiting, diarrhoea, followed by rash, liver dysfunction and convulsions [1]. Cerebral oedema was detected on scan examination. No laboratory specimen was available for investigation.The paramedic who had cared for the index case during her evacuation to Johannesburg developed prodromal symptoms similar to the index case. He was hospitalised on 27 Sep 2008. His condition deteriorated and he died on 2 Oct 2008. An intensive care unit nurse who cared for the index case in Johannesburg developed similar flu-like symptoms and was hospitalised on 1 Oct 2008. Her condition deteriorated on 4 Oct 2008 and she died on 5 Oct 2008 of acute respiratory distress syndrome. In both cases, the incubation period is estimated to have been about one week. On 13 Oct 2008, the World Health Organization (WHO) posted a Web site update informing about a 4th case affecting a nurse who had been in contact with the paramedic [2].On 12 Oct 2008, the National Institute for Communicable Diseases (NICD) in South Africa provided preliminary evidence that the causative agent of the disease was a virus from the family _ Arenaviridae_ [3]. Specimens were shipped to the United States Centers for Disease Control and Prevention (CDC) in Atlanta for additional investigations.Arenavirus taxonomy------------------------Arenaviruses are enveloped viruses (about 120 nm diameter) with a bi-segmented negative strand RNA genome. The typical image in electronic microscopy showing grainy ribosomal particles ("arena" in Latin) inside the virions gave the name to this family of viruses. The prototype is Lymphocytic Choriomeningitis virus (LCMV), isolated in 1933 in North America from a human case with aseptic meningitis. Cases caused by LCMV occur worldwide. Other arenaviruses causing hemorrhagic fevers were reported in South America, causing sporadic cases or limited outbreaks: Junin virus in 1958 in Argentina, Machupo virus in 1963 in Bolivia, Guanarito virus in 1990-1991 in Venezuela, Sabia virus in 1990 in Brazil and more recently Chapare virus in 2004 in Bolivia [4]. In West Africa, Lassa virus was identified in Nigeria in 1969. It causes thousands of cases each year in Sierra Leone, Liberia, Guinea and Nigeria. However, only limited data are available to assess the real incidence of Lassa fever in Africa.
Clinical symptoms of arenavirus infections, treatment and vaccine-----------------------------------------------------------------2 types of clinical presentations are described: neurological and haemorrhagic fever. However, asymptomatic arenavirus infection may be frequent. The incubation period is about 10 days (3-21 days). LCMV causes aseptic meningitis or meningoencephalitis with an overall case fatality <1 percent. Foetal infections can result in congenital abnormalities or death. Transmission of arenaviruses via organ transplantation has been documented; immunosuppressed recipient patients can develop fatal haemorrhagic fever-like disease [5,6]. The Lassa viral haemorrhagic fever usually presents as a non-specific illness with symptoms including fever, headache, dizziness, asthenia, sore throat, pharyngitis, cough, retrosternal and abdominal pain, and vomiting. In severe forms, facial oedema is associated with haemorrhagic conjunctivitis, moderate bleeding (from nose, gums, vagina, etc.) and exanthema. Neurological signs may develop and progress to confusion, convulsion, coma and death. Severe prognosis is associated with a high viraemia, elevated aspartate aminotransferase (AST) liver enzymes, bleeding, encephalitis and oedema. There is a very high risk of foetal mortality in pregnant women during the 3rd trimester of pregnancy. Case fatality rates range from 5 to 20 percent for hospitalised cases. Clinical symptoms of infection by arenaviruses in South America are similar to those described for Lassa fever in Africa.Ribavirin has been shown to be an effective treatment for Lassa fever, especially when started within the first 6 days of illness [7,8]. There is currently no vaccine for Lassa fever but several candidates are under development studies with successful trials in primates [9]. One available vaccine is licensed in Argentina for Junin virus.
Reservoir of arenavirus and transmission----------------------------------------Arenaviruses are associated with rodents, their natural hosts. Some of these viruses can be transmitted to humans by contact with faeces, urine, blood or saliva of infected rodents or with dust containing infective particles. In South America, Machupo and Junin viruses were identified in _Calomys_ sp. rodent, and Guanarito virus was found in a Sigmodon cotton rat [10]. In West Africa, _Mastomys natalensis_ (a peridomestic rodent) is the reservoir of Lassa virus. Its geographic distribution is much wider in sub-Saharan Africa that the presently known area of Lassa transmission [11]. Other arenaviruses such as Mopeia virus in Mozambique had been isolated from rodents without evidence of disease in humans [10].Fatal nosocomial and laboratory infections by arenaviruses have been reported. Contamination occurs via direct contact with body fluids or via droplets. Since the 1970s special procedures for handling these viruses (now categorised as class 4 agents) have been put in place, including the building of dedicated biosafety laboratories (BSL-4), with containment equipment for all activities involving the virus, infectious or potentially infectious body fluids or tissues.
Conclusion----------In the cluster reported here, 4 cases have been identified including an index case and 3 cases of subsequent nosocomial transmission among health workers. The clinical presentation was consistent with neurological symptoms of arenavirus infection. As the incubation period for arenaviruses is up to 3 weeks, secondary cases may still be identified as part of the follow-up of contacts established in response to this event.
The professional activities of the index case could have favoured possible exposure to rodent excreta in a rural area. This is the 1st identification of an arenavirus causing human disease in a southern African country. Further laboratory investigation will allow characterisation of the virus associated with this outbreak and its relation with the existing Lassa virus present in West Africa. Since 1969, at least 24 cases of Lassa fever are known to have been exported outside Africa, including 16 cases imported to Europe [12,13]. However, in none of these cases has secondary transmission resulted in a symptomatic disease.(Acknowledgements: We gratefully acknowledge the openness, the collaboration and the information provided by the National Institute for Communicable Diseases in South Africa, as well as the International and Tropical Department of the French Institute for Public Health Surveillance (Institut de veille sanitaire, InVS).[Reported by: H Zeller, K Leitmeyer, C Varela Santos, D Coulombier. European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden]References--------------1. National Institute for Communicable Diseases (NICD). Outbreak of an acute disease, ex-Zambia. Communicable Diseases Communique volume 7 alert 1; October 2008. Available from: <
http://www.nicd.ac.za/pubs/communique/2008/NICDSpecialCommOct_alert01.pdf>.2. WHO Web site: <
http://www.who.int/csr/don/2008_10_13/en/index.html>.3. ProMED-mail. Undiagnosed fatalities - S. Africa ex Zambia (7): arenavirus. Archive Number
20081012.3234. 12 October 2008. Available from:<
http://www.promedmail.org/pls/otn/f?p=2400:1001:::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000%2C74346>.4. Delgado S, Erickson BR, Agudo R, Blair PJ, Vallejo E, Albario CG, et al. Chapare virus, a newly discovered arenavirus isolated from a fatal hemorrhagic fever case in Bolivia. PLoS Pathog. 2008;4 (4):e1000047.5. Brief report: Lymphocytic choriomeningitis virus transmitted through solid organ transplantation - Massachusetts, 2008. MMWR Morb Mortal Wkly Rep. 2008 Jul 25;57(29):799-801.6. Palacios G, Druce J, Du L, Tran T, Birch C, Briese T, et al. A new arenavirus in a cluster of fatal transplant-associated diseases. N Engl J Med. 2008;358(10):991-998.7. 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(1):20-6.8. World Health Organization. Lassa fever - fact sheet. April 2005. Available from:<
http://www.who.int/mediacentre/factsheets/fs179/en/>9. Lukashevich IS, Carrion R Jr, Salvato MS, Mansfield K, Brasky K, Zapata J, Cairo C, Goicochea M, Hoosien GE, Ticer A, Bryant J, Davis H, Hammamieh R, Mayda M, Jett M, Patterson J. Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates. Vaccine. 2008 Sep 26;26(41):5246-54.10. Charrel RN, de Lamballerie X. Arenaviruses other than Lassa virus. Antiviral Res. 2003 Jan;57(1-2):89-100.11. Fichet-Calvet E, Lecompte E, Koivogui L, Soropogui B, DorZ A, Kourouma F, et al. Fluctuation of abundance and Lassa virus prevalence in Mastomys natalensis in Guinea, West Africa. Vector Borne Zoonotic Dis. 2007;7(2):119-128.12. Macher AM, Wolfe MS. Historical Lassa fever reports and 30-year clinical update. Emerg Infect Dis. 2006 May;12(5):835-7.13. Unit for Surveillance and Communication, Unit for Preparedness and Response, Editorial team. E-alert 24 July: Case of Lassa fever imported into Germany from Sierra Leone. Euro Surveill. 2006;11 (30)

ii=3008. Available from: <
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=3008>.--Communicated by

roMED-mail<
promed@promedmail.org>[This is a comprehensive account of the outbreak of a novel arenavirus infection in Southern Africa. Some confusion remains concerning the location of exposure of the index case and the existence of a clinical sample from the index case.With regard to the taxonomy of the arenaviruses it should be noted that the Old World arenaviruses (LCMV and the African viruses) are phylogenetically distinct from the New World arenaviruses. While similarities exist in genomic organization, structure and clinical disease caused by pathogenic Old World and New World arenaviruses these pathogens use different primary receptors. The Old World arenaviruses employ alpha-dystroglycan, a cellular receptor for proteins of the extracellular matrix, and the human pathogenic New World arenaviruses use the cellular cargo receptor transferrin receptor 1.While the New World arenavirus Junin virus enters cells via clathrin-dependent endocytosis, evidence occurred for clathrin- independent entry of the prototypic Old World arenavirus lymphocytic choriomeningitis virus. Upon internalization, arenaviruses are delivered to the endosome, where pH-dependent membrane fusion is mediated by the envelope glycoprotein (GP). While arenavirus GPs share characteristics with class I fusion GPs of other enveloped viruses, unusual mechanistic features of GP-mediated membrane fusion have recently been discovered for arenaviruses with important implications for viral entry (see: Cell entry by human pathogenic arenaviruses. Rojek JM, Kunz S. Cell Microbiol. 2008 Apr;10(4): 828-35. Epub 2007 Dec 21). - Mod.CP]:tiphat:http://www.promedmail.org/pls/otn/f?p=2400:1001:512317257793907::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,74424</PRE>