Systematic review and meta-analysis of the epidemiology of Lassa virus in humans, rodents and other mammals in sub-Saharan Africa.
ABSTRACT: Accurate data on the Lassa virus (LASV) human case fatality rate (CFR) and the prevalence of LASV in humans, rodents and other mammals are needed for better planning of actions that will ultimately reduce the burden of LASV infection in sub-Saharan Africa. In this systematic review with meta-analysis, we searched PubMed, Scopus, Africa Journal Online, and African Index Medicus from 1969 to 2020 to obtain studies that reported enough data to calculate LASV infection CFR or prevalence. Study selection, data extraction, and risk of bias assessment were conducted independently. We extracted all measures of current, recent, and past infections with LASV. Prevalence and CFR estimates were pooled using a random-effect meta-analysis. Factors associated with CFR, prevalence, and sources of between-study heterogeneity were determined using subgroup and metaregression analyses. This review was registered with PROSPERO, CRD42020166465. We initially identified 1,399 records and finally retained 109 reports that contributed to 291 prevalence records from 25 countries. The overall CFR was 29.7% (22.3-37.5) in humans. Pooled prevalence of LASV infection was 8.7% (95% confidence interval: 6.8-10.8) in humans, 3.2% (1.9-4.6) in rodents, and 0.7% (0.0-2.3) in other mammals. Subgroup and metaregression analyses revealed a substantial statistical heterogeneity explained by higher prevalence in tissue organs, in case-control, in hospital outbreak, and surveys, in retrospective studies, in urban and hospital setting, in hospitalized patients, and in West African countries. This study suggests that LASV infections is an important cause of death in humans and that LASV are common in humans, rodents and other mammals in sub-Saharan Africa. These estimates highlight disparities between sub-regions, and population risk profiles. Western Africa, and specific key populations were identified as having higher LASV CFR and prevalence, hence, deserving more attention for cost-effective preventive interventions.
Project description:Lassa fever is an acute viral illness characterized by multi-organ failure and hemorrhagic manifestations. Lassa fever is most frequently diagnosed in Nigeria, Sierra Leone, Liberia, and Guinea, although sporadic cases have been recorded in other West African countries, including Mali. The etiological agent of Lassa fever is Lassa virus (LASV), an Arenavirus which is maintained in nature and frequently transmitted to humans by Mastomys natalensis. The purpose of this study was to better define the geographic distribution of LASV-infected rodents in sub-Saharan Mali.Small mammals were live-trapped at various locations across Mali for the purpose of identifying potential zoonotic pathogens. Serological and molecular assays were employed and determined LASV infected rodents were exclusively found in the southern Mali near the border of Côte d'Ivoire. Overall, 19.4% of Mastomys natalensis sampled in this region had evidence of LASV infection, with prevalence rates for individual villages ranging from 0 to 52%. Full-length genomic sequences were determined using high throughput sequencing methodologies for LASV isolates generated from tissue samples of rodents collected in four villages and confirmed the phylogenetic clustering of Malian LASV with strain AV.The risk of human infections with LASV is greatest in villages in southern Mali. Lassa fever should be considered in the differential diagnosis for febrile individuals and appropriate diagnostic techniques need to be established to determine the incidence of infection and disease in these regions.
Project description:Lassa fever is a viral hemorrhagic illness responsible for thousands of human deaths in West Africa yearly. Rodents are known as natural reservoirs of the causative Lassa mammarenavirus (LASV) while humans are regarded as incidental, spill-over hosts. Analysis of genetic sequences continues to add to our understanding of the evolutionary history, emergence patterns, and the epidemiology of LASV. Hitherto, the source of data in such investigations has mainly comprised human clinical samples. Presently, a rise in the quantity of virus strains accessed through ecological studies over the last 15 years now allows us to explore how LASV sequences obtained from rodents might affect phylogenetic patterns. In this study, we phylogenetically compared LASV sequences obtained from both rodents and humans across West Africa, including those from two localities highly endemic for the disease: Ekpoma in Nigeria and Kenema in Sierra Leone. We performed a time-calibrated phylogeny, using a Bayesian analysis on 198 taxa, including 102 sequences from rodents and 96 from humans. Contrary to expectation, our results show that LASV strains detected in humans within these localities, even those sampled recently, are consistently ancient to those circulating in rodents in the same area. We discuss the possibilities connected to this preliminary outcome. We also propose modalities to guide more comprehensive comparisons of human and rodent data in LASV molecular epidemiological studies.
Project description:The Natal multimammate mouse (Mastomys natalensis) is the reservoir host of Lassa virus (LASV), an arenavirus that causes Lassa haemorrhagic fever in humans in West Africa. While previous studies suggest that spillover risk is focal within rural villages due to the spatial behaviour of the rodents, the level of clustering was never specifically assessed. Nevertheless, detailed information on the spatial distribution of infected rodents would be highly valuable to optimize LASV-control campaigns, which are limited to rodent control or interrupting human-rodent contact considering that a human vaccine is not available. Here, we analysed data from a four-year field experiment to investigate whether LASV-infected rodents cluster in households in six rural villages in Guinea. Our analyses were based on the infection status (antibody or PCR) and geolocation of rodents (n?=?864), and complemented with a phylogenetic analysis of LASV sequences (n?=?119). We observed that the majority of infected rodents were trapped in a few houses (20%) and most houses were rodent-free at a specific point in time (60%). We also found that LASV strains circulating in a specific village were polyphyletic with respect to neighbouring villages, although most strains grouped together at the sub-village level and persisted over time. In conclusion, our results suggest that: (i) LASV spillover risk is heterogeneously distributed within villages in Guinea; (ii) viral elimination in one particular village is unlikely if rodents are not controlled in neighbouring villages. Such spatial information should be incorporated into eco-epidemiological models that assess the cost-efficiency of LASV control strategies.
Project description:BACKGROUND:Lassa fever is a viral haemorrhagic illness responsible for disease outbreaks across West Africa. It is a zoonosis, with the primary reservoir species identified as the Natal multimammate mouse, Mastomys natalensis. The host is distributed across sub-Saharan Africa while the virus' range appears to be restricted to West Africa. The majority of infections result from interactions between the animal reservoir and human populations, although secondary transmission between humans can occur, particularly in hospital settings. METHODS:Using a species distribution model, the locations of confirmed human and animal infections with Lassa virus (LASV) were used to generate a probabilistic surface of zoonotic transmission potential across sub-Saharan Africa. RESULTS:Our results predict that 37.7 million people in 14 countries, across much of West Africa, live in areas where conditions are suitable for zoonotic transmission of LASV. Four of these countries, where at-risk populations are predicted, have yet to report any cases of Lassa fever. CONCLUSIONS:These maps act as a spatial guide for future surveillance activities to better characterise the geographical distribution of the disease and understand the anthropological, virological and zoological interactions necessary for viral transmission. Combining this zoonotic niche map with detailed patient travel histories can aid differential diagnoses of febrile illnesses, enabling a more rapid response in providing care and reducing the risk of onward transmission.
Project description:Ever since it was established that rodents serve as reservoirs of the zoonotic Lassa virus (LASV), scientists have sought to answer the questions: which populations of rodents carry the virus? How do fluctuations in LASV prevalence and rodent abundance influence Lassa fever outbreaks in humans? What does it take for the virus to adopt additional rodent hosts, proliferating what already are devastating cycles of rodent-to-human transmission? In this review, we examine key aspects of research involving the biology of rodents that affect their role as LASV reservoirs, including phylogeography, demography, virus evolution, and host switching. We discuss how this knowledge can help control Lassa fever and suggest further areas for investigation.
Project description:This study systematically reviews the literature on the occurrence, incidence and case fatality rate (CFR) of invasive nontyphoidal Salmonella (iNTS) disease in Africa from 1966 to 2014. Data on the burden of iNTS disease in Africa are sparse and generally have not been aggregated, making it difficult to describe the epidemiology that is needed to inform the development and implementation of effective prevention and control policies. This study involved a comprehensive search of PubMed and Embase databases. It documents the geographical spread of iNTS disease over time in Africa, and describes its reported incidence, risk factors and CFR. We found that Nontyphoidal Salmonella (NTS) have been reported as a cause of bacteraemia in 33 out of 54 African countries, spanning the five geographical regions of Africa, and especially in sub-Saharan Africa since 1966. Our review indicates that NTS have been responsible for up to 39% of community acquired blood stream infections in sub-Saharan Africa with an average CFR of 19%. Salmonella Typhimurium and Enteritidis are the major serovars implicated and together have been responsible for 91%% of the cases of iNTS disease, (where serotype was determined), reported in Africa. The study confirms that iNTS disease is more prevalent amongst Human Immunodeficiency Virus (HIV)-infected individuals, infants, and young children with malaria, anaemia and malnutrition. In conclusion, iNTS disease is a substantial cause of community-acquired bacteraemia in Africa. Given the high morbidity and mortality of iNTS disease in Africa, it is important to develop effective prevention and control strategies including vaccination.
Project description:Lassa virus (LASV) is endemic to several nations in West Africa. In Mali, LASV was unknown until an exported case of Lassa fever was reported in 2009. Since that time, rodent surveys have found evidence of LASV-infected Mastomys natalensis rats in several communities in southern Mali, near the border with Côte d'Ivoire. Despite increased awareness, to date only a single case of Lassa fever has been confirmed in Mali. We conducted a survey to determine the prevalence of LASV exposure among persons in 3 villages in southern Mali where the presence of infected rodents has been documented. LASV IgG seroprevalence ranged from 14.5% to 44% per village. No sex bias was noted; however, seropositivity rates increased with participant age. These findings confirm human LASV exposure in Mali and suggest that LASV infection/Lassa fever is a potential public health concern in southern Mali.
Project description:<h4>Introduction</h4>Campylobacter spp. are zoonotic bacteria that cause gastroenteritis in humans worldwide, whose main symptom is diarrhea. In certain cases, extra intestinal manifestations may occur, such as Guillain Barré syndrome. The bacteria cause severe diarrhea mostly in children and in immunocompromised individuals. This review aims to address the prevalence of Campylobacter spp. in humans in sub-Saharan Africa. It also aims to understand the impact of HIV in the prevalence, as well as to report data on antibiotic resistance and propose research priorities.<h4>Methods</h4>We followed PRISMA guidelines to find studies on the occurrence of Campylobacter spp. in humans in all countries from sub-Saharan Africa. Studies published between 2000 and 2020 were searched in PubMed, Cochrane Library, CINAHL, African Index Medicus, African Journals Online, Google Scholar and Science Direct. We have conducted a random-effect meta-analysis and calculated the proportion of resistant isolates to different antibiotics.<h4>Results and discussion</h4>We found 77 studies that described such occurrence in humans in 20 out of 53 sub-Saharan African countries. Campylobacter jejuni was the most prevalent species. Pooled prevalence was 9.9% (CI: 8.4%-11.6%). No major variations within the different sub-regions were found. Most studies reported Campylobacter spp. as the cause of diarrhea, mainly in children. Some studies reported the bacteria as a possible etiologic agent of acute flaccid paralysis and urinary tract infection. Campylobacter spp. presented a higher pooled prevalence in HIV infected patients, although not statistically significant. High proportions of resistant strains were reported for many antibiotics, including erythromycin and tetracycline.<h4>Conclusion</h4>Campylobacter spp. occur in sub-Saharan Africa, although information is scarce or inexistent for many countries. Research priorities should include investigation of the understudied species; extra intestinal manifestations; the impact of HIV infection and associated risk factors. Control strategies should be reinforced to contain the spread of this pathogen and drug resistance.
Project description:Lassa fever is an acute viral haemorrhagic illness caused by Lassa virus (LASV), which is endemic throughout much of West Africa. The virus primarily circulates in the Mastomys natalensis reservoir and is transmitted to humans through contact with infectious rodents or their secretions; human-to-human transmission is documented as well. With the exception of Dengue fever, LASV has the highest human impact of any haemorrhagic fever virus. On-going outbreaks in Nigeria have resulted in unprecedented mortality. Consequently, the World Health Organization (WHO) has listed LASV as a high priority pathogen for the development of treatments and prophylactics. Currently, there are no licensed vaccines to protect against LASV infection. Although numerous candidates have demonstrated efficacy in animal models, to date, only a single candidate has advanced to clinical trials. Lassa fever vaccine development efforts have been hindered by the high cost of biocontainment requirements, the absence of established correlates of protection, and uncertainty regarding the extent to which animal models are predictive of vaccine efficacy in humans. This review briefly discusses the epidemiology and biology of LASV infection and highlights recent progress in vaccine development.
Project description:The virulent Lassa fever virus (LASV) and the non-pathogenic Mopeia virus (MOPV) infect rodents and incidentally people in West Africa. The mechanism of LASV damage in human beings is unclear. A live-attenuated reassortant of MOPV and LASV protects rodents and primates from Lassa fever disease. Peripheral blood mononuclear cells from healthy human subjects were expose to either LASV or ML29 in order to identify early cellular responses that could be attributed to the difference in virulence between both viruses. Differential expression of interferon-related genes as well as coagulation-related genes could lead to an explanation for Lassa fever pathogenesis and lead to protective treatments for Lassa fever disease. 27 RNA sampes from Human PBMC exposed to Lassa and Mop/Las (see below): 1 uninf. PBMC 4hr, 8 hr, 24 hr 2 LASV PBMC 4hr, 8 hr, 24 hr X 3 3 ML29 PBMC 4hr, 8 hr, 24 hr There are 3 biological replicates of this experiment in that the PBMC of 3 different individuals have been used.