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Concept: Sierra Leone

278

Background Ebola virus has been detected in the semen of men after their recovery from Ebola virus disease (EVD), but little information is available about its prevalence or the duration of its persistence. We report the initial findings of a pilot study involving survivors of EVD in Sierra Leone. Methods We enrolled a convenience sample of 100 male survivors of EVD in Sierra Leone, at different times after their recovery from EVD, and recorded self-reported information about sociodemographic characteristics, the EVD episode, and health status. Semen specimens obtained at baseline were tested by means of a quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay with the use of the target-gene sequences of NP and VP40. Results A total of 93 participants provided an initial semen specimen for analysis, of whom 46 (49%) had positive results on quantitative RT-PCR. Ebola virus RNA was detected in the semen of all 9 men who had a specimen obtained 2 to 3 months after the onset of EVD, in the semen of 26 of 40 (65%) who had a specimen obtained 4 to 6 months after onset, and in the semen of 11 of 43 (26%) who had a specimen obtained 7 to 9 months after onset; the results for 1 participant who had a specimen obtained at 10 months were indeterminate. The median cycle-threshold values (for which higher values indicate lower RNA levels) were 32.0 with the NP gene target and 31.1 with the VP40 gene target for specimens obtained at 2 to 3 months, 34.5 and 32.3, respectively, for specimens obtained at 4 to 6 months, and 37.0 and 35.6, respectively, for specimens obtained at 7 to 9 months. Conclusions These data showed the persistence of Ebola virus RNA in semen and declining persistence with increasing months since the onset of EVD. We do not yet have data on the extent to which positivity on RT-PCR is associated with virus infectivity. Although cases of suspected sexual transmission of Ebola have been reported, they are rare; hence the risk of sexual transmission of the Ebola virus is being investigated. (Funded by the World Health Organization and others.).

Concepts: DNA, Microbiology, Genome, RNA, Biological warfare, Ebola, Viral hemorrhagic fever, Sierra Leone

273

Perhaps the only good news from the tragic Ebola epidemic in Guinea, Sierra Leone, and Liberia is that it may serve as a wake-up call: we must prepare for future epidemics of diseases that may spread more effectively than Ebola. There is a significant chance that an epidemic of a substantially more infectious disease will occur sometime in the next 20 years; after all, we saw major epidemics during the 20th century, including the Spanish influenza epidemic of 1918-1919 and the ongoing pandemic of human immunodeficiency virus. In fact, of all the things that could kill more than 10 million . . .

Concepts: Epidemiology, Infectious disease, Infection, Influenza, Pandemic, Liberia, Sierra Leone, Guinea

233

Background Data from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease (EVD). Methods Beginning in March 2015, we conducted a randomized, controlled trial of ZMapp plus the current standard of care as compared with the current standard of care alone in patients with EVD that was diagnosed in West Africa by polymerase-chain-reaction (PCR) assay. Eligible patients of any age were randomly assigned in a 1:1 ratio to receive either the current standard of care or the current standard of care plus three intravenous infusions of ZMapp (50 mg per kilogram of body weight, administered every third day). Patients were stratified according to baseline PCR cycle-threshold value for the virus (≤22 vs. >22) and country of enrollment. Oral favipiravir was part of the current standard of care in Guinea. The primary end point was mortality at 28 days. Results A total of 72 patients were enrolled at sites in Liberia, Sierra Leone, Guinea, and the United States. Of the 71 patients who could be evaluated, 21 died, representing an overall case fatality rate of 30%. Death occurred in 13 of 35 patients (37%) who received the current standard of care alone and in 8 of 36 patients (22%) who received the current standard of care plus ZMapp. The observed posterior probability that ZMapp plus the current standard of care was superior to the current standard of care alone was 91.2%, falling short of the prespecified threshold of 97.5%. Frequentist analyses yielded similar results (absolute difference in mortality with ZMapp, -15 percentage points; 95% confidence interval, -36 to 7). Baseline viral load was strongly predictive of both mortality and duration of hospitalization in all age groups. Conclusions In this randomized, controlled trial of a putative therapeutic agent for EVD, although the estimated effect of ZMapp appeared to be beneficial, the result did not meet the prespecified statistical threshold for efficacy. (Funded by the National Institute of Allergy and Infectious Diseases and others; PREVAIL II ClinicalTrials.gov number, NCT02363322 .).

Concepts: Microbiology, Prediction interval, Ebola, Viral hemorrhagic fever, Malaise, Crab-eating Macaque, Sierra Leone, Western Red Colobus

175

Poor quality housing is an infringement on the rights of all humans to a standard of living adequate for health. Among the many vulnerabilities of those without adequate shelter is the risk of disease spread by rodents and other pests. One such disease is Lassa fever, an acute and sometimes severe viral hemorrhagic illness endemic in West Africa. Lassa virus is maintained in the rodent Mastomys natalensis, commonly known as the “multimammate rat,” which frequently invades the domestic environment, putting humans at risk of Lassa fever. The highest reported incidence of Lassa fever in the world is consistently in the Kenema District of Sierra Leone, a region that was at the center of Sierra Leone’s civil war in which tens of thousands of lives were lost and hundreds of thousands of dwellings destroyed. Despite the end of the war in 2002, most of Kenema’s population still lives in inadequate housing that puts them at risk of rodent invasion and Lassa fever. Furthermore, despite years of health education and village hygiene campaigns, the incidence of Lassa fever in Kenema District appears to be increasing. We focus on Lassa fever as a matter of human rights, proposing a strategy to improve housing quality, and discuss how housing equity has the potential to improve health equity and ultimately economic productivity in Sierra Leone. The manuscript is designed to spur discussion and action towards provision of housing and prevention of disease in one of the world’s most vulnerable populations.

Concepts: Epidemiology, Viral hemorrhagic fever, Lassa fever, Sierra Leone, Freetown, Kenema, Eastern Province, Sierra Leone, Kenema District

153

Lassa virus (LASV) is endemic to parts of West Africa and causes highly fatal hemorrhagic fever. The multimammate rat (Mastomys natalensis) is the only known reservoir of LASV. Most human infections result from zoonotic transmission. The very diverse LASV genome has 4 major lineages associated with different geographic locations. We used reverse transcription PCR and resequencing microarrays to detect LASV in 41 of 214 samples from rodents captured at 8 locations in Sierra Leone. Phylogenetic analysis of partial sequences of nucleoprotein (NP), glycoprotein precursor (GPC), and polymerase (L) genes showed 5 separate clades within lineage IV of LASV in this country. The sequence diversity was higher than previously observed; mean diversity was 7.01% for nucleoprotein gene at the nucleotide level. These results may have major implications for designing diagnostic tests and therapeutic agents for LASV infections in Sierra Leone.

Concepts: DNA, Gene, Virus, RNA, Viral hemorrhagic fever, Lassa fever, Liberia, Sierra Leone

152

Kambia District is located in northwestern Sierra Leone along the international border with Guinea. The district is dominated by forest and swamp habitat and has a population of approximately 270,000 persons (approximately 5% of the nation’s population) who live in rural villages and predominantly subsist on farming and trading. During 2014-2015, the remoteness of the area, a highly porous border with Guinea, and strong traditional beliefs about health care and sickness led to unique challenges in controlling the Ebola Virus Disease (Ebola) outbreak within the district.

Concepts: Sierra Leone, Temne people, Northern Province, Sierra Leone, Port Loko District, Districts of Sierra Leone, Bombali District, Kambia District, Susu people

146

In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.

Concepts: DNA, Genetics, Nigeria, West Africa, Liberia, Sierra Leone, Economic Community of West African States, Guinea

120

As Sierra Leone celebrates the end of the Ebola Virus Disease (EVD) outbreak, we can begin to fully grasp its impact on already weak health systems. The EVD outbreak in West Africa forced many hospitals to close down or reduce their activity, either to prevent nosocomial transmission or because of staff shortages. The aim of this study is to assess the potential impact of EVD on nationwide access to obstetric care in Sierra Leone.

Concepts: Medicine, West Africa, Ghana, Ebola, Viral hemorrhagic fever, Liberia, Atlantic slave trade, Sierra Leone

108

During December 2014-February 2015, an Ebola outbreak in a village in Kono district, Sierra Leone, began following unsafe funeral practices after the death of a person later confirmed to be infected with Ebola virus. In response, disease surveillance officers and community health workers, in collaboration with local leadership and international partners, conducted 1 day of active surveillance and health education for all households in the village followed by ongoing outreach. This study investigated the impact of these interventions on the outbreak.

Concepts: Ebola, Sierra Leone, Eastern Province, Sierra Leone, Districts of Sierra Leone, Kono District, Samuel Sam-Sumana, Kono people, Johnny Paul Koroma

95

Future infectious disease epidemics are likely to disproportionately affect countries with weak health systems, exacerbating global vulnerability. To decrease the severity of epidemics in these settings, lessons can be drawn from the Ebola outbreak in West Africa. There is a dearth of literature on public perceptions of the public health response system that required citizens to report and treat Ebola cases. Epidemiological reports suggested that there were delays in diagnosis and treatment. The purpose of our study was to explore the barriers preventing Sierra Leoneans from trusting and using the Ebola response system during the height of the outbreak.

Concepts: Epidemiology, Infectious disease, West Africa, Ghana, Liberia, Atlantic slave trade, Sierra Leone, Guinea