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[A man with fatal Lassa fever following a stay in Sierra Leone].

A 48-year-old-man returned to the Netherlands from Sierra Leone and was admitted with nausea, crampy abdominal pain, myalgia, arthralgia, headache and watery diarrhoea. This was the first case of Lassa fever diagnosed in the Netherlands since 1980. Despite treatment with ribavirin, the patient died on the 16th day of illness. Prompt diagnosis of Lassa fever is critical for the timely administration of ribavirin which improves diagnosis considerably, and for the timely implementation of isolation measures. Recently, a reverse transcriptase polymerase chain reaction (RT-PCR) has become available for the rapid diagnosis of acute Lassa fever, which was implemented to diagnose this patient.

Antiviral Agents↗

Enhanced treatment of Lassa fever by immune plasma combined with ribavirin in cynomolgus monkeys.

Lassa virus-infected cynomolgus monkeys were treated with Lassa virus-immune monkey serum containing a high concentration of neutralizing antibody, the antiviral drug ribavirin, or a combination of ribavirin plus immune serum at various times after infection. When treatment was initiated early (day 0 or 4), either ribavirin (30 mg/kg of body weight per day) or immune serum alone protected monkeys. However, when the initial treatment was delayed until day 7, only four of eight ribavirin-treated and only one of six serum-treated monkeys survived. Treatment with ribavirin combined with immune serum was more successful; all infected monkeys given combination treatment survived, including six treated initially on day 10. Increased doses of ribavirin given alone were toxic. The empirical observation that combined treatment with ribavirin plus serum results in enhanced survival in experimentally infected monkeys suggests that combined treatment might benefit human patients with Lassa fever as well.

Animals↗

Exchange transfusion of a patient with fulminant Lassa fever.

We report a patient with fulminant Lassa fever who responded dramatically to a 2.5-litre exchange transfusion of whole blood. On admission he was semicomatose with facial oedema and oral haemorrhage; his platelets showed markedly depressed aggregation to ADP; and his plasma inhibited the aggregation responses of normal platelets in vitro. Exchange transfusion resulted in rapid clinical improvement, recovery of platelet function, and disappearance of platelet-inhibitory activity in plasma. The patient died 2 weeks later from an acute encephalopathy. His initial response was sufficiently impressive to suggest that further evaluation of this therapeutic approach is justified in selected patients with overwhelming Lassa virus infection.

Adult↗

Lassa fever: review of epidemiology and epizootiology.

The basic ecology of Lassa fever appears to involve enzootic transmission of virus in commensal populations of a single murine species, Mastomys natalensis. Virus may spill over from the rodent cycle to man by various routes. Secondary spread between humans may occur within domiciliary groups, and persons infected within the community who develop clinical disease may introduce the virus into hospital and begin a cycle of nosocomial infection.Between 1969, when Lassa fever was first described, and June 1975, the disease was recognized on 9 discrete occasions, affecting 114 persons. Over one-third of these infections were acquired by person-to-person spread within hospitals. In only one outbreak (in Sierra Leone) were the majority of cases acquired in the community. Recent observations have indicated hyperendemic disease in eastern Sierra Leone. Cases have occurred in Nigeria, Sierra Leone, and Liberia, and serological evidence exists for activity of the virus elsewhere in West and Central Africa. Seasonal factors appear to play a role in the appearance of human cases. Attack rates have been higher in adults than in children. The source of infection and potential routes of virus transmission in the various epidemics are discussed, and perspectives for future epidemiological research are presented.

Adolescent↗

Historical Lassa fever reports and 30-year clinical update.

Five cases of Lassa fever have been imported from West Africa to the United States since 1969. We report symptoms of the patient with the second imported case and the symptoms and long-term follow-up on the patient with the third case. Vertigo in this patient has persisted for 30 years.

Adult↗

Endemic Lassa fever in Liberia. VI. Village serological surveys for evidence of Lassa virus activity in Lofa County, Liberia.

Six villages in Lofa County, north-west Liberia, and one near the coast were surveyed for the presence of indirect fluorescent antibodies (IFA) to Lassa virus (LV). Prevalences were similar among males and females, and among various age groups. The prevalence of IFA positive sera, 6.4%, in two roadside villages was significantly higher than in two matched villages "in the bush", 1.9%. It was also higher in Gbanwei, a roadside village which did not maintain traditional sanitary measures, than in Zuwulo, similarly located but with maintenance of clean-swept areas without shrubbery or rubble between the houses. In another pair of villages, the one adjacent to a Mission Clinic with a very high prevalence of IFA positive staff members had significantly higher prevalence, 14.1%, than did the other, a roadside village with 5.1% seropositives. LV antibodies were also found in 4.3% of the inhabitants of a small coastal village near Robertsfield International Airport. Though LV infections are more common in villages in which traditional practices have been modified, they are present even in villages which are relatively unchanged. In the former they appear to be continuous while sporadic in the latter. The prevalences of IFA in the villages with the highest rates are about one third of what is found in personnel of hospitals near them, suggesting that hospital staff members acquire infections from patients as well as from the communities in which they live.

Adolescent↗

[Experimental Lassa fever in hamadryas baboons].

Intramuscular or aerogenic inoculation of baboons with Lassa virus reproduced a severe form of the disease which clinically, pathoanatomically and virologically resembles the severe form of human Lassa fever reported in the literature. The severity of monkey infection is demonstrated by rapid development of symptoms of general toxicity in the presence of fever, manifestations of hemorrhagic diathesis, high level of viremia and isolation of the causative agent from nasopharyngeal washings.

Animals↗

Endemic Lassa fever in Liberia. IV. Selection of optimally effective plasma for treatment by passive immunization.

The efficacy of passive immunization for treatment of Lassa Fever (LF) is believed to depend on the titre of the neutralizing antibody infused. For the purpose of identifying optimal donors of LV-immune plasma, a population of LF-convalescent patients in Liberia was tested for prevalence of neutralizing antibody. Minimally protective titres, expressed as a log10 neutralization index, (LNI), were established in animal models as LNI greater than 2. LNI titres for 26 donors, tested eight or more months after illness, were modest: 16 titred 1 less than LNI less than 2, 4 titred 2 greater than LNI less than 3, and only 4 titred LNI greater than 3. Sequentially obtained plasma from six donors indicated that the LNI response was delayed relative to the indirect fluorescent antibody (IFA) response, that high titres (LNI greater than 3) occurred only after seven months and in only two of six patients. Most of the unselected LV-immune plasma will require concentration to therapeutically useful LNI titres. In a passive immunization experiment, guinea-pigs were protected by a late convalescent plasma (LNI = 4.8, IFA = 320) but not by an early plasma, (LNI = 0.6, IFA = 640), thus supporting the selection of immune plasma on the basis of the LNI. Cross serological testing with LV strains and convalescent plasma from patients in Sierra Leone, Liberia and Nigeria suggested that these LV strains were indistinguishable by cross-IFA, but were readily distinguishable by cross neutralization tests. Geographical matching of LV and plasma origins may thus be a factor in selection of optimal plasma for passive immunization of Lassa fever.

Animals↗

Clinical features of Lassa fever in Liberia.

Two hundred thirteen cases of Lassa fever (LF) were diagnosed by virus isolation and seroconversion at Curran Lutheran Hospital in Zorzor, Liberia, between July 1980 and April 1986. An additional 40 cases of probable and presumptive LF were diagnosed on the basis of single serum samples. Of the 246 assessable patients, 23 (9%) died; no data were available for seven patients. Five (16%) of 32 pregnant women and three (43%) of seven immediately postpartum women died. Four (26%) of 15 children less than 12 years died. Case-fatality rates among 125 nonpregnant women and 67 men were approximately 6%. Among 150 patients studied in detail, the case-fatality rate was also 9%. Seventeen (11%) of these patients had abnormal bleeding; of these, six (35%) died. Most platelet counts were at low normal to mildly depressed levels. However, serial counts in seven patients suggested a decrease on about days 10-12 of illness. The symptoms of LF in Liberia are those of a viral syndrome. Edema, sometimes marked, is noted in seriously ill patients. A great variation in mortality and incidence of abnormal bleeding is recorded in reported series of LF; it appears that hemorrhage is a marker for cases with a high mortality. The incidence and severity of hearing defects in LF outbreaks vary. Elucidation of a number of clinical problems in LF requires more information on how strain differences affect the pattern of illness.

Diagnosis, Differential↗

Acute sensorineural deafness in Lassa fever.

A prospective audiometric evaluation of 69 hospitalized febrile patients in Sierra Leone, West Africa, revealed a sensorineural hearing deficit (SNHD) in 14 (29%) of 49 confirmed cases of Lassa fever and in 0 of 20 febrile controls. An SNHD was present in nine (17.6%) of 51 people who had evidence of previous Lassa virus infection. Twenty-six of 32 local residents who had previously sustained a sudden deafness had antibody titers to Lassa virus of 16 or greater, compared with six of 32 matched controls. Lassa fever is associated with an incidence of SNHD, which considerably exceeds that previously reported with any other postnatally acquired infection, and accounts for a prevalence of virus-related hearing impairment in the eastern province of Sierra Leone that is greater than that reported from anywhere else in the world.

Acute Disease↗

Management of Lassa fever in European countries.

The UK Public Health Laboratory Service hosted a meeting in London during November 2000 to discuss the management of Lassa fever following the four cases which had occurred in 1999/2000. Participants were invited because they had recent clinical or laboratory experience of managing cases of Lassa fever or had been involved in public health aspects of a case of this infection. The meeting was closed to enable free and frank discussion of confidential matters. This is a report of the general issues and recommendations which arose from the discussion.

Communicable Disease Control↗

Use of the complement fixation (CF) test in Lassa fever surveillance. Evidence for persistent CF antibodies.

A survey to detect individuals with antibodies to Lassa virus was undertaken among hospital personnel in the eastern and southern provinces of Sierra Leone late in 1974. Sera were evaluated by the complement fixation test. The data obtained showed that some contacts of Lassa fever patients in the 1972 epidemic had developed antibodies to the virus; individuals who had never reported being sick also showed evidence of infection, with significant CF antibody titres in their sera. Surviving Lassa fever patients from the 1972 epidemic still had easily measurable levels of persisting CF antibodies. The significance of these data is discussed; in addition it is recommended that the CF test should continue to be the method of choice in mass surveys for this virus disease until other tests can be developed.

Adolescent↗

Antibodies to Lassa virus Z protein and nucleoprotein co-occur in human sera from Lassa fever endemic regions.

It is not known whether the small 11-kDa Z protein of Lassa virus is immunogenic during human Lassa virus infection. To obtain evidence for the existence of an antibody response and to test the suitability of these antibodies for serosurveys, sera from Lassa fever endemic regions (Guinea and Nigeria, n = 75) were tested for co-reactivity to Z protein and nucleoprotein (NP). Sera from a non-endemic region (Uganda, n = 50) served as a specificity control. Z protein and NP were expressed in Escherichia coli, affinity-purified, and used as antigen in Western blot. Indirect immunofluorescence (IIF) with Lassa virus-infected cells was performed for comparison. Due to high unspecific reactivity of the African sera, Western blot testing was performed with a 1:1,000 serum dilution. Under these conditions, none of the control sera but 12% of the sera from endemic regions co-reacted with both Z protein and NP. Reactivity to Z protein was significantly associated with NP reactivity (P < 10(-6)). NP and Z protein-specific antibodies were co-detected in 33% of the IIF-positive sera and in 5% of the IIF-negative sera (P = 0.001). These data provide evidence for appearance of antibodies to Z protein and NP following Lassa virus infection. A recombinant blot for detection of both antibody specificities seems to be specific but less sensitive than IIF.

Antibodies, Viral↗

Clinical observations in 42 patients with Lassa fever.

Under continuous observation of several months, 42 patients from the eastern province of Sierra Leone, Liberia (Lofa County), and neighbouring Guinea were identified as Lassa fever cases by indirect immunofluorescent antibody technique, indicating that the disease is endemic in these areas. The clinical course varied from mild disease to severe illness with haemorrhagic disorders. The fatality rate was 14%. The occurrence of only two possible secondary cases suggests that person-to-person spread of the disease is unimportant epidemiologically. There was a wide range of patients' ages, tribes, and occupations, including a 2 months old baby and a white US citizen. Clinical, laboratory, and histopathological investigations demonstrated the panorganotropism of Lassa virus. Haematological tests in few selected haemorrhagic cases with Lassa fever did not support coagulation disorders or thrombocytopenia as causing the bleeding tendency. The histopathologic changes bear resemblance to those observed in Argentinian and Bolivian haemorrhagic fever, both being caused by viruses of the Arena group. However, Lassa virus hepatitis may be differentiated from liver lesions occurring in yellow fever, Marburg virus disease, and Ebola (Maridi) haemorrhagic fever.

Adolescent↗

Lassa fever, Marburg and Ebola virus diseases and other exotic diseases: is there a risk to Canada?

There are seven exotic diseases of concern; three of these, the most unpredictable and least understood, are Lassa fever, Marburg virus disease and Ebola virus disease. In this article the epidemiologic aspects of these diseases are discussed, with particular emphasis on exportation from their indigenous areas in Africa and on the occurrence of secondary cases. Any of these conditions could be brought into Canada either by aeromedical evacuation or inadvertently. Between 1972 and 1978 there were seven occasions when Canada could have been involved with handling cases of Lassa fever. The Government of Canada has purchased several containment bed and transit isolators. These units, with filtered air under negative pressure, accommodate infectious patients being transported and cared for without contaminating medical attendants or the environment.

Adult↗

[Use of guinea pigs for assessing the efficacy of vaccines against Lassa fever].

The use of guinea pigs as a laboratory model was proven to be appropriate in investigating the vaccines developed against Lassa fever at the preclinical study stage. An adapted variant of Lassa virus was cultivated, which caused death of guinea pigs with respect for an agent's dose. Finally, it was shown to be possible to investigate the immunogenic and protective properties of the inactivated antigen of Lassa virus in experiments with guinea pigs.

Animals↗

Endemic Lassa fever in Liberia. II. Serological and virological findings in hospital patients.

Patients admitted with fever to four Liberian hospitals were tested for Lassa fever (LF) by means of the indirect fluorescent antibody technique and by virus isolation. The incidence of LF and presumptive LF among consecutive febrile adult patients was 14% and 17% in two hospitals located in the interior; no cases of LF were found among 24 consecutive patients in a hospital near the coast. In the three inland hospitals the incidence of confirmed or presumptive LF among the patients in whom the diagnosis was seriously considered varied from 13% to 36%. Lassa virus was isolated from 17 patients out of the 59 cases found in this survey. LF is a common cause of fever in northern Liberia. The diagnosis depends upon the readiness of the staff to consider the diagnosis, the collection of blood specimens at appropriate times, and the preservation of sera at sub-freezing temperatures to permit survival of active virus and its subsequent recovery in an appropriate laboratory.

Adolescent↗