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PubMed1987

A case-control study of the clinical diagnosis and course of Lassa fever.

A prospective case-control study of Lassa fever was established in Sierra Leone to measure the frequency and case-fatality ratio of Lassa fever among febrile hospital admissions and to better delineate the clinical diagnosis and course of this disease. Lassa fever was responsible for 10%-16% of all adult medical admissions and for approximately 30% of adult deaths in the two hospitals studied. The case-fatality ratio for 441 hospitalized patients was 16.5%. We found the best predictor of Lassa fever to be the combination of fever, pharyngitis, retrosternal pain, and proteinuria (predictive value together, .81); of outcome, the best predictor was the combination of fever, sore throat, and vomiting (relative risk of death, 5.5). Complications included mucosal bleeding (17%), bilateral or unilateral eighth-nerve deafness (4%), and pleural (3%) or pericardial (2%) effusion. Lassa fever is endemic in this area and is a more-common cause of hospital admission and death than has previously been described; this disease must be considered when diagnosing febrile illness in West Africa.

Adolescent↗

PubMed1984

The use of Lassa fever convalescent plasma in Nigeria.

Lassa fever convalescent plasma (LFCP) has been administered to 27 patients in hospitals at Jos and Vom, Nigeria. Among serologically or virologically confirmed cases of Lassa fever (LF) given plasma on or before the 10th day, all eight survived, as did two of three possible LF cases. Of eight patients given LFCP after the 10th day, five died, as did all three possible LF cases. LFCP was also administered to five patients subsequently shown not to have LF, and to a suspected case contact; all survived without complications of therapy. There were 15 cases of LF during this time who did not receive plasma; 11 survived. Most cases of LF who received plasma and survived showed a rapid response to therapy, in contrast with the gradual recovery in those who did not receive LFCP.

Adolescent↗

PubMed1989

A plasma inhibitor of platelet aggregation in patients with Lassa fever.

Previous studies have shown that haemorrhage in Lassa fever is associated with abnormal in vitro platelet aggregation and a high mortality. In Sierra Leone we studied platelet aggregation in healthy local subjects, patients with laboratory-confirmed Lassa fever and febrile patients in whom Lassa virus infection was excluded. There were no significant differences in the mean platelet counts of these groups. Patients with fulminant Lassa virus infection showed a gross depression of in-vitro platelet responsiveness to 1 and 5 microM ADP and 4 micrograms/ml collagen compared to other groups (P = 0.0004-0.0008 when compared to healthy controls, P = 0.002-0.0008 when compared to mild Lassa fever patients). When plasma samples from five of these patients were mixed 1:1 with control platelet-rich plasma, a marked inhibition of ADP-induced aggregation was observed. No inhibitory activity was detected in plasma obtained from healthy subjects or febrile control patients. The presence of inhibitor was strongly associated with the occurrence of haemorrhage (P = 0.03), depression of platelet aggregation (P = 0.004) and severity of Lassa fever (P = 0.007).

Adenosine Diphosphate↗

PubMed1989

Protection of rhesus monkeys from fatal Lassa fever by vaccination with a recombinant vaccinia virus containing the Lassa virus glycoprotein gene.

Lassa fever is an acute febrile disease of West Africa, where there are as many as 300,000 infections a year and an estimated 3000 deaths. As control of the rodent host is impracticable at present, the best immediate prospect is vaccination. We tested as potential vaccines in rhesus monkeys a closely related virus, Mopeia virus (two monkeys), and a recombinant vaccinia virus containing the Lassa virus glycoprotein gene, V-LSGPC (four monkeys). Two monkeys vaccinated with the New York Board of Health strain of vaccinia virus as controls died after challenge with Lassa virus. The two monkeys vaccinated with Mopeia virus developed antibodies measurable by radioimmunoprecipitation prior to challenge, and they survived challenge by Lassa virus with minimal physical or physiologic disturbances. However, both showed a transient, low-titer Lassa viremia. Two of the four animals vaccinated with V-LSGPC had antibodies to both Lassa glycoproteins, as determined by radioimmunoprecipitation. All four animals survived a challenge of Lassa virus but experienced a transient febrile illness and moderate physiologic changes following challenge. Virus was recoverable from each of these animals, but at low titer and only during a brief period, as observed for the Mopeia-protected animals. We conclude that V-LSGPC can protect rhesus monkeys against death from Lassa fever.

Animals↗

PubMedDate not supplied

Imported lassa fever in Germany: molecular characterization of a new lassa virus strain.

We describe the isolation and characterization of a new Lassa virus strain imported into Germany by a traveler who had visited Ghana, Côte D'Ivoire, and Burkina Faso. This strain, designated "AV," originated from a region in West Africa where Lassa fever has not been reported. Viral S RNA isolated from the patient's serum was amplified and sequenced. A long-range reverse transcription polymerase chain reaction allowed amplification of the full-length (3.4 kb) S RNA. The coding sequences of strain AV differed from those of all known Lassa prototype strains (Josiah, Nigeria, and LP) by approximately 20%, mainly at third codon positions. Phylogenetically, strain AV appears to be most closely related to strain Josiah from Sierra Leone. Lassa viruses comprise a group of genetically highly diverse strains, which has implications for vaccine development. The new method for full-length S RNA amplification may facilitate identification and molecular analysis of new arenaviruses or arenavirus strains.

Adult↗

PubMed2002

Monitoring of clinical and laboratory data in two cases of imported Lassa fever.

During 2000, four cases of fatal Lassa fever were imported from Africa to Europe. In two patients, consecutive serum samples were available for monitoring of virus load and cytokine levels in addition to standard laboratory data. Both patients had non-specific early clinical symptoms including high fever. Patient 1 developed multi-organ failure and died of hemorrhagic shock on day 15 of illness, while patient 2 died of respiratory failure due to aspiration without hemorrhage on day 16. Ribavirin was administered to both patients beginning only on day 11. High serum aspartate aminotransferase and lactate dehydrogenase (LDH) levels were remarkable in both patients. Patient 1 had an initial virus load of 10(6) S RNA copies/ml as measured by real-time RT-PCR. Viremia increased steadily and reached a plateau of approximately 10(8)-10(9) copies/ml 4 days before death, while IFN-gamma and TNF-alpha rose to extremely high levels only shortly before death. In contrast, in patient 2 the virus load decreased from 10(7) to 10(6) copies/ml during the late stage of illness which was paralleled by a decrease in the IFN-gamma and TNF-alpha levels. The IL-10 level increased when specific IgM and IgG appeared. These data suggest that a high virus load and high levels of pro-inflammatory cytokines in the late stage of Lassa fever play an important role in the pathogenesis of hemorrhage, multi-organ failure, and shock in Lassa fever.

Adult↗

PubMed2001

Lassa fever in Guinea: II. Distribution and prevalence of Lassa virus infection in small mammals.

Rodents of the genus Mastomys form the reservoir for Lassa virus (LV), an arenavirus that causes a potentially severe hemorrhagic illness, Lassa fever (LF). Although Mastomys rodents exist throughout sub-Saharan Africa, areas of human LF appear to be quite focal. The distribution of small mammals and LV-infected Mastomys has been assessed in only a few countries. We conducted a survey of small mammals in selected regions of Guinea to assess the degree to which LV poses a public health risk in that country. A total of 1,616 small mammals, including 956 (59%) Mastomys, were captured from 444 households and seven bush sites. Mastomys made up > 90% of the captured animals in the savannah, savannah-forest transition, and forest regions of Guinea, while Mus musculus dominated in coastal and urban sites. Animals were analyzed via enzyme-linked immunosorbent assay (ELISA) for LV-specific antigen (blood and spleen homogenate) and IgG antibody (blood only). Virus isolation from spleen homogenates was also performed on a subset of animals. Lassa antibody and antigen were found in 96 (11%) and 46 (5%), respectively, of 884 tested Mastomys. Antibody and antigen were essentially mutually exclusive and showed profiles consistent with vertical transmission of both LV and antibody. LV was isolated only from Mastomys. ELISA antigen constituted an acceptable surrogate for virus isolation, with a sensitivity and specificity when performed on blood of 78% (95% confidence interval: 68-83%) and 98% (95-99%), respectively. The proportion of LV-infected Mastomys per region ranged from 0 to 9% and was highest in the savannah and forest zones. The proportion of infected animals per village varied considerably, even between villages in close proximity. Infected animals tended to cluster in relatively few houses, suggesting the existence of focal "hot spots" of LV-infected Mastomys that may account for the observed heterogeneous distribution of LF.

Animals↗

PubMed1986

Lassa fever in children in Sierra Leone, West Africa.

A systematic study of Lassa fever in febrile children was undertaken over a four-year period, from August 1977 to August 1981, in the Eastern Province of Sierra Leone, West Africa. 479 patients were studied; of these, 245 had adequate specimens to confirm or exclude the laboratory diagnosis of Lassa fever. 51 cases of Lassa fever were identified (21% of patients from whom diagnosis was possible). Virus was isolated from 23 patients. All children had fever; cough and vomiting were present in over 60% of cases studied. The five to nine-year age group had the highest prevalence rate (41% of cases). Seasonal clustering occurred in April, May, and August. A significantly higher proportion of females than males had Lassa fever, a finding which remains to be explained. It is concluded that Lassa fever is a disease of significant concern in the paediatric age group.

Adolescent↗

PubMed1984

Endemic Lassa fever in Liberia. V. Distribution of Lassa virus activity in Liberia: hospital staff surveys.

Serological testing of hospital personnel by the indirect fluorescent antibody (IFA) technique was used to indicate the distribution of Lassa virus (LV) activity in Liberia. Determination of the places of origin of the staff members as well as the sites of the hospitals indicated that LV is active in throughout Liberia. Prevalences of IFA varied from 3.8% at the J. J. Dossen Hospital on the coast in the south-east to 22.3, 23.5 and 40.4% in Lofa County hospitals inland in the north-west. Rises in LV antibody prevalences, high prevalences and relatively high IFA titres in hospital personnel suggest the LV activity is particularly high in Lofa, Grand Cape Mount and Nimba Counties.

Antigens, Viral↗

PubMed1985

Endemic Lassa fever in Liberia. III. Characterization of Lassa virus isolates.

Sixty-three virus isolates were obtained by inoculation of Vero cells with sera from 50 hospital in-patients in Liberia with acute febrile illnesses. 57 of the isolates were presumptively identified as Lassa virus (LV) by direct fluorescent antibody (DFA) staining of inoculated Vero cells. These, and six additional isolates obtained only by titration of supernatant fluids from inoculated Vero cells, were definitively identified as LV in a neutralization test. Two additional LV isolates were obtained from a patient's sera from Nigeria. By cross-neutralization tests, the Nigerian LV strains were serologically identical to the prototype Nigerian LV strain (PP) but were distinct from both a reference LV strain from Sierra Leone (SL), and from the Liberian (LIB) strains isolated in this study. The LIB and SL strains were closely related to each other, but not to the Nigerian LV strains. LIB LV strains were tested for virulence in strain 2 and 13 guinea-pigs, and a spectrum of virulence was observed which correlated only approximately with disease severity for human patients. Two human-lethal isolates killed all inoculated strain 2 and 13 guinea-pigs, whereas nine isolates from mildly ill patients were benign for guinea-pigs. Yet some LV isolates from severely ill or lethally infected patients, especially those from pregnant women and infants, were totally benign for guinea-pigs. These data suggest that antigenically distinct LV strains exist in nature, and that antigenically indistinguishable LV isolates may differ in virulence potential for various hosts.

Animals↗

PubMed2001

Low levels of interleukin-8 and interferon-inducible protein-10 in serum are associated with fatal infections in acute Lassa fever.

To investigate the role of inflammatory mediators in the pathogenesis of Lassa fever, the levels of a number of pro- and anti-inflammatory cytokines and chemokines in serum samples collected from hospitalized patients with fatal and nonfatal acute Lassa fever were compared with those from 2 control groups: patients with other febrile illnesses and uninfected individuals. Serum interleukin (IL)-8 and interferon (IFN)-inducible protein (IP)-10 levels were significantly higher in patients with acute nonfatal Lassa fever than in control subjects. In striking contrast, levels of these chemokines were low or undetectable in patients with fatal Lassa fever. IFN-gamma, IL-12, IL-6, and RANTES levels were elevated in all the febrile study groups. Tumor necrosis factor-alpha levels were not elevated in patients with fatal or nonfatal Lassa fever. These data indicate that acute nonfatal Lassa fever is associated with high levels of circulating IL-8 and IP-10 and that low levels or absence of these mediators correlates with a poor outcome.

Acute Disease↗

PubMed2026

Nosocomial Outbreak of Lassa Fever in Conakry, Guinea, 2022.

BACKGROUND: Lassa fever is endemic in Guinea, with high seroprevalence in the forest region. However, clinical cases have been only anecdotally reported. In August 2022, a nosocomial outbreak occurred at a private clinic in the capital, Conakry, an area previously considered low risk. METHODS: Suspected cases were confirmed by real-time reverse-transcription polymerase chain reaction within 24 hours. Viremia was monitored during hospitalization, and whole-genome sequencing was performed in-country within 13 days of outbreak detection. Outbreak investigation involved rodent testing in the home village of the suspected primary case. RESULTS: Six cases were laboratory-confirmed, 5 of which were healthcare workers of the clinic. The case fatality rate was 16.7%. Viral RNA remained detectable in blood of survivors for a median of 26 days (interquartile range, 24-41 days) post-disease onset. Epidemiological investigations identified a suspected primary case, who had died of a febrile disease compatible with Lassa fever, had contact with all secondary cases, and had a travel history from Kissidougou area. Three near-complete and 1 partial Lassa virus genomes were recovered from the secondary cases, which phylogenetically clustered with genomes from central Guinea. Consistent with a common transmission source, the 4 genomes were almost identical. Rodent testing revealed a new reservoir area in eastern-central Guinea. CONCLUSIONS: This outbreak highlights the vulnerability of healthcare settings in low-prevalence areas of West Africa to nosocomial Lassa virus transmission due to human mobility. Facilitated by capacity-building programs for viral hemorrhagic fevers, rapid diagnosis, genomic analysis, and ecological assessment enabled an efficient outbreak response and control.

Lassa Fever↗

PubMed1988

A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy.

Several viral infections have been reported to result in more severe disease in pregnant than non-pregnant women, but the relative risks have not been well characterised. This has now been done for Lassa fever in a prospective study of 68 pregnant and 79 non-pregnant women who were admitted to hospital in Sierra Leone with confirmed Lassa fever. Lassa fever was the main cause of maternal mortality in the hospital, accounting for 25% of maternal deaths. Twelve of 40 patients in the third trimester died, compared with two of 28 in the first two trimesters and 10 of 79 non-pregnant women. The odds ratio for death in the third trimester compared with the first two trimesters was 5.57 (95% confidence intervals 1.02 to 30.26). The condition of the mother improved rapidly after evacuation of the uterus, whether by spontaneous abortion, evacuation of retained products of conception, or normal delivery; 10 of 26 women without uterine evacuation died, but only four of 39 women with evacuation died (p = 0.0016). The odds ratio for death with pregnancy intact was 5.47 (95% confidence interval 1.35 to 22.16). Fetal and neonatal loss was 87%. The risk of death from Lassa fever in the third trimester is significantly higher than that in the first two trimesters and higher than that for non-pregnant women, but evacuation of the uterus can significantly improve the mother's chance of survival.

Acute Disease↗

PubMed1986

Lassa fever. Effective therapy with ribavirin.

In a study of Lassa fever in Sierra Leone, West Africa, we identified two variables associated with a high risk of death, and we evaluated the efficacy of ribavirin and Lassa virus-convalescent plasma for the treatment of Lassa fever. A serum aspartate aminotransferase level greater than or equal to 150 IU per liter at the time of hospital admission was associated with a case-fatality rate of 55 percent (33 of 60). Patients with the same risk factor who were treated for 10 days with intravenous ribavirin, begun within the first 6 days after the onset of fever, had a case-fatality rate of 5 percent (1 of 20) (P = 0.0002 by Fisher's exact test). Patients whose treatment began seven or more days after the onset of fever had a case-fatality rate of 26 percent (11 of 43) (P = 0.01). Viremia with levels greater than or equal to 10(3.6) TCID50 per milliliter on admission was associated with a case-fatality rate of 76 percent (35 of 46). Patients with this risk factor who were treated with intravenous ribavirin within the first six days after onset of fever had a case-fatality rate of 9 percent (1 of 11) (P = 0.006), whereas those treated after seven days or more of illness had a fatality rate of 47 percent (9 of 19) (P = 0.035). Oral ribavirin was also effective in patients at high risk of death. Lassa-convalescent plasma did not significantly reduce mortality in any of the high-risk groups. We conclude that ribavirin is effective in the treatment of Lassa fever and that it should be used at any point in the illness, as well as for postexposure prophylaxis.

Administration, Oral↗

PubMed1987

Pediatric Lassa fever: a review of 33 Liberian cases.

Thirty-three cases of pediatric Lassa fever were identified at Curran Lutheran Hospital and Phebe Hospital in Liberia between January 1980 and March 1984. All 18 fetal cases died and the case-fatality rate for 15 childhood cases was 27%. We identified four clinical presentations according to age, including a case of congenital Lassa fever, a condition not reported previously. Two cases of Lassa fever were found serologically during a one-month survey of all pediatric admissions at Curran Lutheran Hospital, 2.4% of those children who had serum pairs collected. We also identified a "swollen baby syndrome" consisting of widespread edema, abdominal distention, and bleeding. This distinctive clinical presentation of Lassa fever ended in death in three of four cases and was present in three of the four childhood deaths in this series. Its absence seems to be a good prognostic indicator in children.

Adult↗

PubMed1982

Pathologic and virologic study of fatal Lassa fever in man.

Postmortem examination of 21 virologically documented cases of Lassa fever, including 6 complete autopsies, was performed as part of a field study of community-acquired Lassa fever in Sierra Leone. The most consistently observed lesions were hepatocellular, adrenal, and splenic necrosis and adrenal cytoplasmic inclusions. Neither these lesions, nor other milder and less constantly observed lesions such as myocarditis, renal tubular injury, and interstitial pneumonia, appeared severe enough to explain the cause of death in Lassa fever. The central nervous system (CNS) contained no specific lesions. Viral titrations demonstrated high viral content in liver, lung, spleen, kidney, heart, placenta, and mammary gland. Clinical laboratory data included elevation of hepatic enzymes, creatine phosphokinase (CPK), and blood urea nitrogen (BUN). Because of the paucity of pathologic lesions in spite of widely disseminated viral infection, further investigation of humoral inflammatory mechanisms is indicated.

Adult↗

PubMed1989

Electrocardiographic abnormalities in patients with Lassa fever.

Electrocardiograms from 32 patients with acute Lassa fever were abnormal in over 70% of cases. The changes noted included non-specific ST-segment and T-wave abnormalities, ST-segment elevation, generalized low-voltage complexes, and changes reflecting electrolyte disturbance. None of the abnormalities correlated with clinical severity of infection, serum transaminase levels, or eventual outcome. ECG changes are common in Lassa fever, but usually unassociated with clinical manifestations of myocarditis.

Adolescent↗

PubMed2003

Imported Lassa fever in Germany: surveillance and management of contact persons.

This study sought to assess the risk of secondary transmission after import of Lassa fever into Europe. A total of 232 persons exposed to a case of Lassa fever imported into Germany were identified. The level of exposure was determined for 157 persons (68%), and 149 (64%) were tested serologically. High-risk or close contact was reported by 30 (19%) of 157 persons. No symptomatic secondary infections were observed. However, Lassa virus-specific immunoglobulin G antibodies were detected in a serum sample obtained from a physician who examined the index patient on day 9 of illness. The physician received ribavirin prophylaxis and did not develop symptoms of Lassa fever. On the basis of these data, the contact was classified as having a probable secondary infection. The study indicates a low risk of transmission during the initial phase of symptomatic Lassa fever, even with high-risk exposures. The risk may increase with progression of disease and increasing virus load.

Animals↗