Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever.

Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis.

Two Cases of Lassa Fever Successfully Treated with Ribavirin and Adjunct Dexamethasone for Concomitant Infections.

Lassa fever is a viral hemorrhagic fever treated with supportive care and the broad-spectrum antiviral drug ribavirin. The pathophysiology, especially the role of hyperinflammation, of this disease is unknown. We report successful remission of complicated Lassa fever in 2 patients in Nigeria who received the antiinflammatory agent dexamethasone and standard ribavirin.

Clinical characteristics, treatment modalities and outcome of coronavirus disease 2019 patients treated at thisday dome isolation and treatment centre, federal capital territory Abuja, Nigeria.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), a highly transmissible viral infection has spread worldwide causing exponential increase in morbidity and mortality. But so far, there is limited information available to describe the presenting characteristics, outcomes and treatment modalities of COVID-19 patients in Nigeria. This study aimed to describe the demographic and clinical characteristics, underlying comorbidities, treatment modalities and outcomes of patients isolated and treated in a repurposed COVID-19 isolation and treatment centre in Abuja, Nigeria. MATERIALS AND METHODS: A retrospective study which reviewed the medical records of 300 confirmed COVID-19 patients isolated and treated according to the World Health Organisation and Nigeria Centre for Disease Control guidelines between 22nd July and 26th October, 2020 in ThisDay Dome Isolation and Treatment Centre. Data collected from the medical records include demographics, clinical features, treatment measures and outcomes. RESULTS: Out of 300 patients studied, 61.0% were male. The mean age of the participants was 38.2 ± 14.7. Less than half of the patients (40.3%) had one or more underlying comorbidities with hypertension the most common co-morbidity. Majority (62%) of patients were mildly symptomatic, 33% were asymptomatic while only 2% were severely symptomatic. The most common presenting symptoms include cough 34.0%, fever 30.3%, anosmia 28.7% and dysgeusia 22.7%. Older age (P < 0.001), tertiary education and the presence of underlying comorbidity (P < 0.001) were significantly associated with symptomatic presentation of COVID-19. The median duration of time between positive laboratory testing and presentation for treatment was 5 days (0-29). All patients were treated with a combination of Ivermectin, Azithromycin, Zinc and Vitamin C with no recorded death. The median length of stay at facility was 9 days. CONCLUSION: Close attention should be given to patients with co-morbidities as an inefficient management of such co-morbidities could lead to mortalities which may not be directly attributable to COVID-19.

Lassa Fever 2016 Outbreak in Plateau State, Nigeria-The Changing Epidemiology and Clinical Presentation.

Lassa fever (LF) outbreaks in Nigeria mostly occur in rural areas and during the dry season, peaking between December through February. Fever is a cardinal presenting feature among the myriad manifestations of LF. Thirty four patients with clinical diagnosis of LF were analyzed. However, only 11 (32%) LASV infections were confirmed by RT-PCR. The 2016 LF outbreak showed a preferential urban occurrence and a high case fatality. Fever (≥38°C) was not detected in over a fourth of the patients at the time of examination. Bleeding diathesis was the most common presentation while abdominal pain and headache were present in more than half of the confirmed cases. Changes in the geographical distribution and clinical presentation may have implications for disease control efforts and the risk of transmission, both locally and internationally. In order to guide interventions, public health authorities should be aware that the epidemic patterns may be changing.

Postexposure prophylaxis for Lassa fever: Experience from a recent outbreak in Nigeria.

BACKGROUND: Secondary transmission of Lassa fever (LF) occurs in the community and in health-care facilities, and is associated with high fatality in Nigeria. We investigated the role of oral ribavirin postexposure prophylaxis (orPEP) in preventing LF among the primary contacts of confirmed cases from December 2015 to March 2016. MATERIALS AND METHODS: Epidemiological and clinical data of LF contacts were prospectively collected. However, information regarding ribavirin adverse effects (AEs) were collected retrospectively through a telephone interview. High-risk contacts were clinically monitored ΁ orPEP. RESULTS: Thirty-five (94.6%) out of the 37 individuals enrolled in the study were contacts of confirmed LF cases, and friends and family members (54%) constituted the largest group. However, only 29 (83%) individuals were classified as high-risk contacts. Twenty-one (60%) of contacts were prescribed ribavirin with 6 (28.6%) of them reporting AEs. Body weakness (33%) was the most frequent AE, but there was no incidence of treatment discontinuation due to AE. Furthermore, there were no reported cases of LF among all respondents (0%), whether they had orPEP or not. CONCLUSION: Secondary transmission of LF seems uncommon and the benefit of orPEP is uncertain. Although AEs of ribavirin may not be uncommon, they are rarely serious enough to cause treatment interruption. More emphasis should be on supporting persons looking after LF cases adopt measures that minimize the risks of exposure.