From: Subject: Lassa fever: epidemiology, clinical features, and social consequences -- Richmond and Baglole 327 (7426): 1271 -- BMJ Date: Tue, 7 Sep 2004 20:24:31 +0300 MIME-Version: 1.0 Content-Type: multipart/related; boundary="----=_NextPart_000_0000_01C49518.AEC4BFE0"; type="text/html" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2800.1441 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C49518.AEC4BFE0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://bmj.bmjjournals.com/cgi/content/full/327/7426/1271?eaf Lassa fever: epidemiology, clinical features, and = social consequences -- Richmond and Baglole 327 (7426): 1271 -- = BMJ
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BMJ  2003;327:1271-1275 (29 November),=20 doi:10.1136/bmj.327.7426.1271
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Clinical=20 review

Lassa fever: epidemiology, clinical features, and social = consequences=20

J Kay Richmond, freelance=20 consultant1, Deborah J=20 Baglole, health = adviser2=20

1 24 Llantrisant Rise, Llandaff, = Cardiff CF5=20 2PG, 2 Merlin, Borough, London SE1 1DB

Correspondence to: J K Richmond Kayrichmondf4h{at}btinternet.com

Lassa = fever is=20 endemic in west Africa, where it probably kills several = thousand people each year. With access to the region = improving,=20 the opportunity, and the need, to improve our understanding = of=20 this disease are increasing


   Introduction =
Top
Introduction
Method of review
Epidemiology
Clinical course
Community perspectives
Research needs
References
 
L= assa=20 fever is a viral haemorrhagic fever transmitted by rats. = It has=20 been known since the 1950s, but the virus was not identified=20 until 1969, when two missionary nurses died from it in the = town=20 of Lassa in Nigeria. Found predominantly in west = Africa,1=20 it has the potential to cause tens of thousands of = deaths.=20 Even after recovery, the virus remains in body fluids,=20 including semen.1=20 The years of civil unrest in Sierra Leone (1991-2002) = halted=20 the investigation (through international collaboration) = of=20 Lassa fever at a specialist unit in Kenema. Increasing = international=20 travel and the possibility of use of the Lassa virus as a=20 biological weapon escalate the potential for harm = beyond the=20 local level. Access to the country is improving, so = renewed=20 efforts to understand it are feasible.


   Method of review =
Top
Introduction
Method of = review
Epidemiology
Clinical course
Community perspectives
Research needs
References
 
T= he=20 information presented comes from a strategic document = produced=20 in 2002 for Merlin (Medical Emergency Relief = International,=20 a London based nongovernmental aid organisation which = manages=20 the Lassa unit in Kenema (http://www.merlin.org.uk/)). This = document, `Licking' Lassa fever,2=20 was created through collaboration with experts in = infectious=20 disease, community development, clinical management of = viral=20 haemorrhagic diseases, and qualitative research. The = sources of=20 information were a literature review using Ovid and = PubMed=20 (search term "Lassa fever"), case analysis and surveys=20 undertaken in the field, and relevant websites (such as = those=20 of the World Health Organization, Centers for Disease = Control=20 and Prevention).


   Epidemiology =
Top
Introduction
Method of review
Epidemiology
Clinical course
Community perspectives
Research needs
References
 
L= assa=20 fever is caused by a single stranded RNA virus and is a = disseminated systemic primary viral infection.3=20 4=20 The main feature of fatal illness is impaired or = delayed=20 cellular immunity leading to fulminant viraemia.5=20 The prevalence of antibodies to the virus in the = population is=20 8-52% in Sierra Leone,6=20 4-55% in Guinea,7=20 and 21% in Nigeria.8=20 Seropositivity has also been found in the Central = African=20 Republic, Democratic Republic of the Congo, Mali, and = Senegal=20 (see figure).1=20 Staff from the UK Department for International = Development, the=20 International Committee of the Red Cross, and the = United=20 Nations Mission in Sierra Leone have succumbed. = Sporadic cases=20 have occurred in travellers returning to Britain, the=20 Netherlands, and Germany.


<= IMG=20 height=3D135 alt=3D" " hspace=3D10=20 = src=3D"http://bmj.bmjjournals.com/content/vol327/issue7426/images/small/r= icj70094.f1.gif"=20 width=3D200 vspace=3D5 border=3D2>
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  = 		Distribution of Lassa = fever in west=20 Africa. Outbreaks have occurred in the Central African = Republic, Guinea, Liberia, Nigeria, and Sierra Leone;=20 serological evidence of human infection has been found = in the=20 Democratic Republic of the Congo, Mali, and Senegal =

 = ;


Summary=20 points

Lassa fever, a viral haemorrhagic fever = transmitted=20 by rats, is endemic in west Africa and may kill = tens of=20 thousands of people each year

Peak incidence was thought to be in the = dry=20 season (January to March), but data collected in = Sierra=20 Leone shows peaks in the overlap with the wet = season=20 (May to November)

Many infections are subclinical; a high index = of=20 suspicion, given the difficulties of clinical = diagnosis,=20 is needed when travellers from west Africa = present=20 with a fever of unknown origin, with = symptoms=20 appearing up to 21 days after leaving the = endemic=20 area

The virus is excreted in semen for three = months=20 after infection; we do not know how frequently = it=20 may be transmitted through sexual intercourse

Attempts are being made to produce a = vaccine=20 using the yellow fever virus as a vehicle

The possibility that Lassa virus could be used = as a biological weapon has raised the profile of = the=20 need for greater understanding of Lassa = fever and=20 for more effective control and treatment = programmes =

The vector
The natural hosts for the virus = are=20 multimammate rats (Mastomys natalensis), which = breed=20 frequently and are distributed widely throughout west, = central,=20 and east Africa.3=20 They are probably the most common rodent in tropical = Africa and=20 are found predominantly in rural areas, and in = dwellings more=20 often than in surrounding countryside.6=20 Members of the genus are infected persistently and shed = the=20 virus in their excreta. Humans are infected by contact = with the=20 rats or by eating them (they are considered a delicacy = and are=20 eaten by up to 90% of people in some areas). Rats found = in=20 houses of infected people are seropositive for the = virus 10=20 times more often than those in control houses.9=20 Virus antibodies occur after a febrile illness in twice as = many=20 people who eat rats as in those who do not, and deafness = (an=20 effect of Lassa fever) occurs four times more = frequently.10=20

Morbidity and mortality
Presentation of = cases used=20 to be highest during the dry season (January to March) = and=20 lowest during the wet season (May to November). = However, recent=20 data from Kenema (1999-2002) show that admissions were = highest=20 during the change from the dry to the wet season (see = fig A on=20 bmj.com). This change might be related partly to = population=20 movements during the civil unrest in Sierra Leone (see = fig B on=20 bmj.com)11=20 and overcrowding among refugees. Travel becomes = increasingly=20 difficult as the wet season progresses and may help to = account=20 for the decrease in numbers of cases later in the = season. All=20 the cases reported were diagnosed clinically. Until = 1998=20 laboratory confirmation of diagnosis was available=20 retrospectively and 60-70% of cases were confirmed,12=20 but in 2000 over half of a series of 22 cases were wrongly=20 diagnosed. Thus, these recent apparent changes in = infection=20 patterns must be interpreted with caution.

People of all ages are susceptible. The disease is mild or = has=20 no observable symptoms in about 80% of people infected, = but=20 20% have a severe multisystem disease. The incubation = period=20 is 6-21 days. The virus is excreted in urine for three to = nine=20 weeks from infection and in semen for three months.1=20 The extent of sexual transmission is unknown. =

Sensorineural hearing deficit is a feature of the disease: = it=20 was found in 29% of confirmed cases compared with none of=20 febrile controls in hospital inpatients.13=20 In the general population, 81% of those who experienced = sudden=20 deafness had antibodies to Lassa virus versus 19% of = matched=20 controls. There is no apparent relation between the = severity of=20 viral illness, initial hearing loss, or subsequent=20 recovery.14=20

Lassa fever was responsible for 10-16% of all adult = medical=20 admissions in 1987 in two hospitals studied in Sierra = Leone=20 and for about 30% of adult deaths.15=20 The case fatality rate in Kenema varied from 12% to 23% = for the=20 period 1997-2002. A recent case series showed low = admission=20 rates and high case fatality rates for people aged less = than 18=20 years (who make up 51% of the total population (United = Nations=20 Development Programme)) compared with older people (see = table A=20 on bmj.com). During pregnancy, high rates of maternal = death=20 (29%) and fetal and neonatal loss (87%) have been = recorded=20 (uterine evacuation improves outcome significantly), = with 25%=20 of all maternal deaths in Sierra Leone being due to = Lassa=20 fever.16=20 An estimate of the case fatality rate in the general = population=20 is 1-2%, much lower than in hospitalised cases, = possibly as a=20 consequence of differences in severity.

Using the figures for rural populations (available from = the=20 United Nations Development Programme) and the epidemiology = of=20 the disease, we estimate that the "at risk" seronegative=20 population (in Sierra Leone, Guinea, and Nigeria) may = be as=20 high as 59 million, with an annual incidence of illness = of=20 three million, fatalities up to 67 000, and up to three = million=20 reinfections (table=20 1). Until a complete picture of Lassa fever is known, = these=20 are rough estimates. Comparable data are unavailable for = the=20 other countries where seropositivity has been recorded. =


View this=20 table:
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  = 		Table 1 Estimates = of=20 seropositivity and mortality from Lassa fever in = Guinea,=20 Nigeria, and Sierra Leone (values are numbers of = people unless=20 stated otherwise) =

 = ;

Peace keepers within Sierra Leone have been affected by = Lassa=20 fever.17=20 Case records in Kenema for July-September 2002 show 11=20 admissions from the Sierra Leone army and 10 from the United=20 Nations mission in Sierra Leone, with one death in each = group.=20


   Clinical course =
Top
Introduction
Method of review
Epidemiology
Clinical = course
Community perspectives
Research needs
References
 
L= assa=20 fever presents with symptoms and signs indistinguishable = from=20 those of febrile illnesses such as malaria and other viral=20 haemorrhagic fevers such as Ebola. It is difficult to = diagnose=20 clinically but should be suspected in patients with fever = (=3D" src=3D"http://bmj.bmjjournals.com/math/ge.gif" = border=3D0>38=B0C) not=20 responding adequately to antimalarial and antibiotic = drugs (table=20 2). The most useful clinical predictors of Lassa = fever are=20 fever, pharyngitis, retrosternal pain, and proteinuria = for=20 diagnosis; and fever, sore throat, and vomiting for=20 outcome.15=20


View this=20 table:
[= in=20 this window]
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  = 		Table 2 Clinical = stages of=20 Lassa fever (adapted from McCarthy 200218) =

 = ;

Complications include mucosal bleeding (17%), = sensorineural=20 hearing deficit (4%), pleural effusion (3%), and = pericardial=20 effusion (2%).15=20 The outcome is related to the degree of viraemia, not = the=20 antibody response, and is worse with high levels of = aspartate=20 aminotransferase.4=20

On the basis of a case series of 140 men and 128 women = admitted=20 in Kenema during 2001, the duration of illness can vary=20 considerably (table B on bmj.com). The commonest = interval=20 between onset of symptoms and discharge was 17 days = (half of=20 the patients were in hospital for 10 days) and between = onset=20 and death was five days (half died within two days of=20 admission). Delays between onset and admission resulted = in most=20 patients not receiving ribavirin within the critical = first six=20 days. These data add to the uncertainty surrounding = diagnosis=20 and lethality.

Laboratory investigation
At hospital = admission,=20 most patients have antibodies to the virus (53% with = IgG and=20 67% with IgM).4=20 Together, enzyme linked immunosorbent assays (ELISAs) = for Lassa=20 virus antigen and for virus IgM are 88% sensitive and = 90%=20 specific for acute infection.19=20 Other effects of illness include lymphocytopenia and a = moderate=20 thrombocytopenia, which are maximal 10-11 days after the = onset=20 of symptoms.20=20 The thrombocytopenia is associated with a serum = inhibitor and=20 with the occurrence of haemorrhage, depression of = platelet=20 aggregation, and the severity of Lassa fever.21=20 With reverse transcription polymerase chain reaction, = Lassa=20 fever can be diagnosed in all patients by the third day of=20 illness, but immunoflourescence identifies only 52% of = the=20 patients.22=20

Clinical management
All suspected cases = should be=20 admitted to isolation facilities. Hospital transmission = occurs=20 through inadequate infection control measures.23=20 Strict isolation of cases and procedures for handling = body=20 fluids and excreta must be maintained.2=20

Treatment
Ribavirin and general support are = needed.24=20 Ribavirin is almost twice as effective when given = intravenously=20 as when taken orally, and if given within six days of = the start=20 of illness it may reduce deaths by 90%. Dehydration, = oedema,=20 hypotension, and poor renal function are common; fluid=20 replacement or the use of blood transfusion requires = careful=20 monitoring.

Surveillance and disease = control
Surveillance=20 should identify all close contacts of the patients for = three=20 weeks after the start of illness, and a search initiated = for=20 unreported or undiagnosed cases.1=20 Two areas of concern are, firstly, the treatment of = undiagnosed=20 cases in hospitals where overcrowding and poor hygiene = can=20 spread the disease to other patients, staff, or = visitors; and,=20 secondly, traditional burial ceremonies for infected = corpses,=20 with the possible risk of spread to many people. =

Vaccine
Production of a combined, single = dose=20 vaccine against yellow fever and Lassa fever has been=20 proposed.25=20 The cost and logistical problems of delivering it would = be=20 huge, particularly since fewer than 20% of districts in = the=20 countries studied achieve 80% uptake of childhood=20 vaccination.2=20 Use for visitors from the United Nations, = non-governmental=20 organisations, and business communities might make it=20 financially viable, even though it is the most = expensive of the=20 possible control strategies.


   Community perspectives=20
Top
Introduction
Method of review
Epidemiology
Clinical course
Community = perspectives
Research needs
References
 
C= ivil=20 unrest severs supply and trading links, and people want = for=20 basic commodities. Migration disrupts agricultural cycles,=20 reduces farming activities, and encourages looting, = killing=20 of livestock, and destruction of property. People are = forced=20 into overcrowded camps and public buildings, and spread of=20 communicable diseases is facilitated.

Adverse influences of Lassa fever on socioeconomic = wellbeing=20 are mediated through the inability of patients to care for=20 themselves and their dependants, the high death rate in = hospital, nosocomial transmission to staff and the = subsequent=20 loss of service, and the occurrence of hearing loss = through=20 clinical and subclinical infection.

Knowledge, attitude, and practice = survey
During=20 2001, a knowledge, attitude, and practice survey was = undertaken=20 in Kenema among 813 men and 867 women in four camps for = internally displaced people and eight primary health units. = The=20 survey revealed a reasonable knowledge of Lassa fever, its = mode=20 of transmission, control measures, and the seriousness = of the=20 disease. However, there were some worrying gaps in = application=20 of this knowledge, such as inappropriate actions after = killing=20 rats (see fig C on bmj.com). This was demonstrated by the=20 occurrence of an outbreak of 823 cases, including 153 = deaths=20 (case fatality rate 19%), from January 1996 to April = 1997,=20 after an extensive outreach programme.1=20 The need for greater understanding of the perceptions = and=20 beliefs of the local population became apparent.

Qualitative study
A small pilot study (of = 23=20 people) was undertaken through focus groups and = interviews in=20 2002. The major concerns related to

  • Effective rodent control ("We have a rat which happens to = be=20 the sweetest meat, and you tell that person not to eat = that=20 meat because it creates Lassa fever")
  • People understood that Lassa fever can be = contracted=20 through contact with an affected = person=97this leads=20 to patients and their families being = isolated and=20 stigmatised ("When my wife was admitted to Lassa = ward, well, it was not only an economic = depression, it=20 also created social embarrassment, because my=20 children no longer go to other houses, to their = relatives")
  • Early diagnosis is impeded by the absence of a = diagnostic=20 test for use in the community and = difficulties=20 reaching health facilities ("No, no, what are = you=20 trying to tell me? I don't want you to be guessing in = Lassa.... As far as Lassa is concerned, you have = to be very much more serious, you don't have to = be=20 hypothetical, you have to correct in your=20 diagnosis when you are treating Lassa fever... we = need=20 a lab." "In the rainy seasons, the river runs, = there is=20 no means of transportation. Others, the location = of the health facility is so far away, there is = no=20 ambulance service to transport the = sick")=20
  • Many people are unlikely to seek medical care if they=20 suspect they have Lassa fever: treatment is = expensive=20 and can usually be afforded only by = sacrificing=20 necessities such as food and school fees = ("There=20 will be lots of gossiping, because there = is no=20 money at home and no food at home, you have to go to=20 friends to get you some food, so you can help the=20 children, or to take to the = hospital")=20
  • Belief in traditional remedies and mistrust of = treatment=20 offered at the hospital were described = ("There are=20 certain people in the community we live in, they = believe in herbs, in going to the bush to get = some tea=20 herbs... they think herbs can mend them" = "People=20 don't go to medical facilities... especially = when=20 they say they have Lassa fever, they will be = given=20 injections to kill them")
  • Miscarriage is blamed on the woman, is often = attributed=20 to witchcraft, and commonly leads to = divorce=20 ("People class you as a witch because you = have=20 aborted")
  • Deafness was described as a social embarrassment = and as=20 having a catastrophic effect on family = relationships=20 ("She is now like someone who is crazy, stupid, = because=20 she has lost her hearing sense").=20

Many of these factors lead to social exclusion.


   Research needs =
Top
Introduction
Method of review
Epidemiology
Clinical course
Community perspectives
Research needs
References
 
T= he=20 epidemiology of both rat and human populations requires = urgent=20 investigation if we are to understand this disease fully. = It=20 could be done through developing

  • International collaboration over research
  • A map of the complete epidemiological and = clinical=20 story
  • Involvement of the communities affected =
  • Effective and affordable diagnostic kits and treatment=20
  • Efficient and effective specialist treatment centres =
  • An effective and affordable vaccine to control = the=20 infection in its natural habitat, protect=20 international visitors, and deter the use = of the=20 virus as an agent of biological warfare.=20

The terrorist attack in New York on 11 September 2001 and = the=20 subsequent anthrax attacks served to alert governments to = the=20 potential of biological agents as weapons. A special = report=20 in the Lancet signposts increased funding for the = National=20 Institute for Allergy and Infectious Disease and its = blueprint=20 for research, including Lassa fever.18=20 Thus, the need for a greater understanding of Lassa = fever and=20 for more effective control and treatment programmes has = assumed=20 a higher profile. The time is ripe for a concerted=20 international effort to achieve these ends.


Additional=20 educational resources

Merlin. Lassa fever publications=97www.merlin.o= rg.uk/template7.asp?PageID=3D178

WHO Information. Fact sheets: Lassa = fever=97www.who.int/inf-fs/en/= fact179.html

WHO Communicable Disease Surveillance = and=20 Response (CSR). Lassa fever=97www.who.int/csr/di= sease/lassafever/en/

WHO Communicable Disease Surveillance = and=20 Response (CSR). Disease outbreaks: Lassa = fever=97www.w= ho.int/disease-outbreak-news/disease/A96.2.htm

CDC. Infectious disease information: = viral=20 hemorrhagic fever=97www.cdc.g= ov/ncidod/diseases/virlfvr/virlfvr.htm

Health Protection Agency. Viral = haemorrhagic=20 fever (VHF)=97www.hpa.= org.uk/infections/topics_az/VHF/menu.htm

National Institute of Allergy and = Infectious=20 Diseases. NIAID biodefense research = agenda for=20 CDC category A agents. Bethesda, MD: US=20 Department of Health and Human Services, = National=20 Institutes of Health, 2002 (www.niaid.nih.gov/biodefense/research/biotresearchagenda.pdf). =


Figs A-C and tables A and B on = bmj.com=20 provide details about Lassa fever in Sierra Leone =

This article is based on the = Merlin=20 document `Licking' Lassa fever. We are grateful = for=20 comments on drafts from Dr Edward Coyle, director of = Wales=20 Centre for Health, Cardiff, and Professor T Cullinan, = TB health=20 adviser for Merlin, London.

Funding: `Licking' Lassa = fever was=20 produced under a grant from the Rockefeller = Foundation.=20

Competing interests: JKR was = employed by=20 Merlin in 2002 as country medical coordinator in Sierra = Leone=20 and as main author and collator of the paper = `Licking' Lassa=20 fever. DJB is employed by Merlin as a health = adviser with=20 responsibility for Sierra Leone.


   References =
Top
Introduction
Method of review
Epidemiology
Clinical course
Community perspectives
Research needs
References
&nb= sp;

  1. World Health Organization. WHO Lassa = fever=20 fact sheet No 179. Geneva:WHO, 2000.=20
  2. Merlin. `Licking' Lassa fever: a = strategic=20 review. London: Merlin, 2002. (www.merlin.org.uk/uploads/files/pr/Lassa%20Fever%20Strategy%20= 2.pdf)=20
  3. Healing T, Gopal R. Report on an = assessment=20 visit to Sierra Leone, April 12th-30th 2001. London: Merlin, = 2001.=20
  4. Johnson KM, McCormick JB, Webb PA, = Smith ES,=20 Elliott LH, King IJ. Clinical virology of Lassa fever in = hospitalized=20 patients. J Infect Dis 1987;155: 456-64.[ISI][Medline]=20
  5. Chen JP, Cosgriff TM. Hemorrhagic fever = virus-induced changes in hemostasis and vascular biology. = Blood=20 Coagul Fibrinolysis 2000;11: 461-83.[CrossRef][ISI][Medline]=20
  6. McCormick JB, Webb PA, Krebs JW, = Johnson KM,=20 Smith ES. A prospective study of the epidemiology and ecology of = Lassa=20 fever. J Infect Dis 1987;155: 437-44.[ISI][Medline]=20
  7. Lukashevich LS, Clegg JC, Sidibe K. = Lassa virus=20 activity in Guinea: distribution of human antiviral antibody = defined=20 using enzyme-linked immunosorbent assay with recombinant = antigen. J=20 Med Virol 1993;40: 210-7.[ISI][Medline]=20
  8. Tomori O, Fabiyi A, Sorungbe A, Smith = A,=20 McCormick JB. Viral hemorrhagic fever antibodies in Nigerian=20 populations. Am J Trop Med Hyg 1988;38: 407-10.[ISI][Medline]=20
  9. Keenlyside RA, McCormick JB, Webb PA, = Smith E,=20 Elliott L, Johnson KM. Case-control study of Mastomys natalensis = and=20 humans in Lassa virus-infected households in Sierra Leone. Am = J Trop=20 Med Hyg 1983;32: 829-37.[ISI][Medline]=20
  10. Ter Meulen J, Lukashevich I, Sidibe K, = Inapogui=20 A, Marx M, Dorlemann A, et al. Hunting of peridomestic rodents = and=20 consumption of their meat as possible risk factors for = rodent-to-human=20 transmission of Lassa virus in the Republic of Guinea. Am J = Trop Med=20 Hyg 1996;55; 661-6.[ISI][Medline]=20
  11. Wilson M. Infectious diseases: an = ecological=20 perspective BMJ 1995;311: 1681-4.[Free=20 Full Text]
  12. Bausch D. Lassa fever in Sierra = Leone.=20 London:Merlin, 2000.=20
  13. Cummins D, McCormick JB, Bennett D, = Samba JA,=20 Farrar B, Machin SJ, et al. Acute sensorineural deafness in = Lassa fever.=20 JAMA 1990;264: 2093-6.[Abstract]=20
  14. Liao BS, Byl FM, Adour KK. Audiometric = comparison of Lassa fever hearing loss and idiopathic sudden = hearing=20 loss: evidence for viral cause. Otolaryngol Head Neck = Surg=20 1992;106: 226-9.[ISI][Medline]=20
  15. McCormick JB, King IJ, Webb PA, = Johnson KM,=20 O'Sullivan R, Smith ES, et al. A case-control study of the = clinical=20 diagnosis and course of Lassa fever. J Infect Dis = 1987;155:=20 445-55.[ISI][Medline]=20
  16. Price ME, Fisher-Hoch SP, Craven RB, = McCormick=20 JB. A prospective study of maternal and fetal outcome in acute = Lassa=20 fever infection during pregnancy. BMJ 1988;297: = 584-7.[ISI][Medline]=20
  17. Ter Meulen J, Lenz O, Koivogui L, = Magassouba N,=20 Kaushik SK, Lewis R, et al. Short communication: Lassa fever in = Sierra=20 Leone: UN peacekeepers are at risk. Trop Med Int Health = 2001;6:=20 83-4.[CrossRef][ISI][Medline]=20
  18. McCarthy M. USA moves quickly to push = biodefence=20 research. Lancet 2002;360: 732.[CrossRef][ISI][Medline]=20
  19. Bausch DG, Rollin PE, Demby AH, = Coulibaly M,=20 Kanu J, Conteh AS, et al. Diagnosis and clinical virology of = Lassa fever=20 as evaluated by enzyme-linked immunosorbent assay, indirect=20 fluorescent-antibody test, and virus isolation. J Clin = Microbiol=20 2000;38: 2670-7.[Abstract/Free=20 Full Text]
  20. Fisher-Hoch S, McCormick JB, Sasso D, = Craven RB.=20 Hematologic dysfunction in Lassa fever. J Med Virol = 1988;26:=20 127-35.[ISI][Medline]=20
  21. Cummins D, Fisher-Hoch SP, Walshe KJ, = Mackie IJ,=20 McCormick JB, Bennett D, et al. A plasma inhibitor of platelet=20 aggregation in patients with Lassa fever. Br J Haematol = 1989;72:=20 543-8.[ISI][Medline]=20
  22. Demby AH, Chamberlain J, Brown DW, = Clegg CS.=20 Early diagnosis of Lassa fever by reverse transcription-PCR. = J Clin=20 Microbiol 1994:32;=20 2898-903.[Abstract] =
  23. Fisher-Hoch SP, Tomori O, Nasidi A, = Perez-Oronoz=20 GI, Fakile Y, Hutwagner L, et al. Review of cases of nosocomial = Lassa=20 fever in Nigeria: the high price of poor medical practice. = BMJ=20 1995;311: 857-9.[Abstract/Free=20 Full Text]
  24. McCormick JB, King IJ, Webb PA, = Scribner CL,=20 Craven RB, Johnson KM, et al. Lassa fever. Effective therapy = with=20 ribavirin. N Engl J Med 1986;314: 20-6.[Abstract]=20
  25. Fisher-Hoch SP, McCormick JB. Towards = a human=20 Lassa fever vaccine. Rev Med Virol 2001;11: 331-41.[CrossRef][ISI][Medline]=20



Rapid Responses:

Read = all Rapid=20 Responses=20

Nigeria is the best place to study Lassa = fever=20
Dr. Ahmed Ahidjo=20
bmj.com, 30 Nov 2003 [Ful= l=20 text]=20
Fever! The Hunt for a Killer Virus=20
Colin D Butler=20
bmj.com, 8 Dec 2003 [Ful= l=20 text]=20
Rat eating, sexual transmission and the burden of = Lassa=20 fever disease=20
Babafemi A Oshin=20
bmj.com, 9 Dec 2003 [Ful= l=20 text]=20
More information on Lassa fever=20
Dr Haruna Yusuph=20
bmj.com, 9 Dec 2003 [Ful= l=20 text]

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