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Since late 2019, the coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, has rapidly evolved to become a global pandemic. Each country was affected but with a varying number of infected cases and mortality rates. Africa was hit late by the pandemic but the number of cases rose sharply. In this study, we investigated 224 SARS-CoV-2 genome sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) in the early part of the outbreak, of which 69 were from Africa. We analyzed a total of 550 mutations by comparing them with the reference SARS-CoV-2 sequence from Wuhan. We classified the mutations observed based on country and region, and afterwards analyzed common and unique mutations on the African continent as a whole. Correlation analyses showed that the duo variants ORF1ab/RdRp 4715L and S protein 614G variants, which are strongly linked to fatality rate, were not significantly and positively correlated with fatality rates (r = -0.03757, P = 0.5331 and r = -0.2876, P = 0.6389, respectively), although increased number of cases correlated with number of deaths (r = 0.997, P = 0.0002). Furthermore, most cases in Africa were mainly imported from American and European countries, except one isolate with no mutation and was similar to the original isolate from Wuhan. Moreover, unique mutations specific to countries were identified in the early phase of the outbreak but these mutations were not regional-specific. There were common mutations in all isolates across the continent as well as similar isolate-specific mutations in different regions. Our findings suggest that mutation is rapid in SARS-CoV-2 in Africa and although these mutations spread across the continent, the duo variants could not possibly be the sole cause of COVID-19 deaths in Africa in the early phase of the outbreak. Author summary: Mutations frequently occur in SARS-CoV-2 and the mutant variants, ORF1ab/RdRp 4715L and S protein 614G have been strongly linked to increased infectivity and fatality in other countries. Although increased number of cases in Africa correlated positively with increased deaths, such deaths did not correlate positively with the duo variants, ORF1ab 4715L and S protein 614G in the early part of the outbreak. This could possibly be due to the younger aged population, lower comorbidity and divergent genetic factors. [ABSTRACT FROM AUTHOR]

We describe a novel virus, designated Ntepes virus (NPV), isolated from sand flies in Kenya. NPV has the characteristic phlebovirus trisegmented genome architecture and is related to, but distinct from, Gabek Forest phlebovirus. Diverse cell cultures derived from wildlife, livestock, and humans were susceptible to NPV, with pronounced permissiveness in swine and rodent cells. NPV infection of newborn mice caused rapid and fatal illness. Permissiveness for NPV replication in sand fly cells, but not mosquito cells, suggests a vector-specific adaptation. Specific neutralizing antibodies were found in 13.9% (26/187) of human serum samples taken at the site of isolation of NPV as well as a disparate site in northeastern Kenya, suggesting a wide distribution. We identify a novel human-infecting arbovirus and highlight the importance of rural areas in tropical Africa for arbovirus surveillance as well as extending arbovirus surveillance to include hematophagous arthropods other than mosquitoes. [ABSTRACT FROM AUTHOR]

Dromedaries in Africa and elsewhere carry the Middle East respiratory syndrome coronavirus (MERS-CoV). To search for evidence of autochthonous MERS-CoV infection in humans, we tested archived serum from livestock handlers in Kenya for MERS-CoV antibodies. Serologic evidence of infection was confirmed for 2 persons sampled in 2013 and 2014. [ABSTRACT FROM AUTHOR]

Arenaviruses are feared as agents that cause viral hemorrhagic fevers. We report the identification, isolation, and genetic characterization of 2 novel arenaviruses from Namaqua rock mice in Namibia. These findings extend knowledge of the distribution and diversity of arenaviruses in Africa. [ABSTRACT FROM AUTHOR]

Active surveillance in health care centers in Gabon during 2009-2011 detected 72 clinical cases of pandemic (H1N1) 2009 (pH1N1). We found that pH1N1 virus was introduced in mid-2009 but spread throughout the country in 2010. Thus, Gabon was also affected by pH1N1. [ABSTRACT FROM AUTHOR]

Background: Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne disease well recognized through Europe and Asia where diagnostic tests and medical surveillance are available. However, it is largely neglected in Africa, especially in the tropical rainforest of Central Africa where only sporadic human cases have been reported and date back to more than 30 years. We describe here an isolated human case that occurred in the Democratic Republic of the Congo in 2008 and performed phylogenetic analysis to investigate whether it resulted from a regional re-emergence or from the introduction of a novel virus in the area. Methods and Findings: Near complete segment S and partial segment M sequences were characterized. Bayesian phylogenetic analysis and datation were performed to investigate the relationship between this new strain and viral strains from Africa, Europe and Asia. The new strain is phylogenetically close to the previously described regional genotype (II) that appears to be specific to Central Africa. Phylogenetic discrepancy between segment S and M suggested genetic exchange among local sublineages, which was dated back to 130–590 years before present. Conclusions: The phylogenetic analyses presented here suggest ongoing CCHF virus circulation in Central Africa for a long time despite the absence of reported human cases. Many infections have most probably been overlooked, due to the weakness of healthcare structures and the absence of available diagnostic procedure. However, despite the lack of accurate ecological data, the sporadic reporting of human cases could also be partly associated with a specific sylvatic cycle in Central Africa where deforestation may raise the risks of re-emergence. For these reasons, together with the high risk of nosocomial transmission, public health authorities' attention should be drawn to this etiological agent. Author Summary: Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted to humans through tick-bite or contact with infected blood or tissues from livestock, the main vertebrate hosts in a peri-domestic natural cycle. With numerous outbreaks, a high case fatality rate (3%–30%) and a high risk for nosocomial transmission, CCHFV became a public health concern in Europe and Asia. However virus surveillance in Africa is difficult due to the limited sanitary facilities. Especially, CCHFV occurrence in Central Africa is very poorly described and seems highly in contrast with the temperate to dry environments to which the virus is usually associated with. We described a single human infection that occurred in Democratic Republic of the Congo after nearly 50 years of absence. The phylogenetic analysis suggests that CCHFV enzootic circulation in the area is still ongoing despite the absence of notification, and thus reinforces the need for the medical workers and authorities to be aware of the outbreak risk. The source of infection seemed associated with a forest environment while no link with the usual agro-pastoral risk factors could be identified. More accurate ecological data about CCHFV enzootic cycle are required to assess the risk of emergence in developing countries subjected to deforestation. [ABSTRACT FROM AUTHOR]

Background: Henipaviruses (Hendra and Nipah virus) are highly pathogenic members of the family Paramyxoviridae. Fruiteating bats of the Pteropus genus have been suggested as their natural reservoir. Human Henipavirus infections have been reported in a region extending from Australia via Malaysia into Bangladesh, compatible with the geographic range of Pteropus. These bats do not occur in continental Africa, but a whole range of other fruit bats is encountered. One of the most abundant is Eidolon helvum, the African Straw-coloured fruit bat. Methodology/Principal Findings: Feces from E. helvum roosting in an urban setting in Kumasi/Ghana were tested for Henipavirus RNA. Sequences of three novel viruses in phylogenetic relationship to known Henipaviruses were detected. Virus RNA concentrations in feces were low. Conclusions/Significance: The finding of novel putative Henipaviruses outside Australia and Asia contributes a significant extension of the region of potential endemicity of one of the most pathogenic virus genera known in humans. [ABSTRACT FROM AUTHOR]

Asian bats have been identified as potential reservoir hosts of coronaviruses associated with severe acute respiratory syndrome (SARS-CoV). We detected antibody reactive with SARS-CoV antigen in 47 (6.7%) of 705 bat serum specimens comprising 26 species collected in Africa; thus, African bats may harbor agents related to putative group 4 CoV. [ABSTRACT FROM AUTHOR]

Until recently, hantaviruses (family Bunyaviridae) were believed to originate from rodent reservoirs. However, genetically distinct hantaviruses were lately found in shrews and moles, as well as in bats from Africa and Asia. Bats (order Chiroptera ) are considered important reservoir hosts for emerging human pathogens. Here, we report on the identification of a novel hantavirus, provisionally named Makokou virus (MAKV), in Noack's Roundleaf Bat ( Hipposideros ruber ) in Gabon, Central Africa. Phylogenetic analysis of the genomic l -segment showed that MAKV was the most closely related to other bat-borne hantaviruses and shared a most recent common ancestor with the Asian hantaviruses Xuan Son and Laibin. Breakdown of the virus load in a bat animal showed that MAKV resembles rodent-borne hantaviruses in its organ distribution in that it predominantly occurred in the spleen and kidney; this provides a first insight into the infection pattern of bat-borne hantaviruses. Ancestral state reconstruction based on a tree of l gene sequences of all relevant hantavirus lineages was combined with phylogenetic fossil host hypothesis testing, leading to a statistically significant rejection of the mammalian superorder Euarchontoglires (including rodents) but not the superorder Laurasiatheria (including shrews, moles, and bats) as potential hosts of ancestral hantaviruses at most basal tree nodes. Our data supports the emerging concept of bats as previously overlooked hantavirus reservoir hosts. [ABSTRACT FROM AUTHOR]

Objective: The objective of this scoping review was to map the current situation and available evidence and gaps on rabies morbidity, mortality, integrated rabies surveillance programmes, and existing prevention and control strategies in Africa., Methods: We conducted a systematic scoping review following the Joanna Briggs methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews checklist. Medline, Embase, CINAHL (EBSCOHost), Scopus, Web of Science and rabies web conferences were used to search for peer-reviewed publications between January 1946 and May 2020. Two researchers reviewed the studies and extracted data based on author (year) and region, study design and data collection duration, participants/comparators, interventions, control conditions/exposures and outcomes (rabies mortality and morbidity) and key findings/gaps/challenges. The results were reported narratively using Arksey and O'Malley's methodological framework., Results: Electronic search yielded 2775 records, of which 43 studies were included. A total of 543 714 bite victims were censored through the included studies. Most of the victims were less than 15 years of age. The studies included rabies morbidity (21) and mortality (15) fluctuating in space and time across Africa depending on countries' rabies prevention and control practices (16). Others were surveillance (nine studies); surveillance and prevention (five studies); management and control (seven studies); and surveillance, prevention and control (six studies). We found challenges in rabies reporting, existing dog vaccination programmes and post-exposure prophylaxis availability or compliance., Conclusion: This study found challenges for dog rabies control and elimination in Africa and the need for a policy to drive the goal of zero dog-transmitted rabies to humans by 2030.This is an open-access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build on this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated and the use is non-commercial (see http://creativecommons.org/licenses/by-nc/4.0/)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen endemic to the Arabian Peninsula. Dromedary camels are a likely source of infection and the virus probably originated in Africa. We studied the genetic diversity, geographical structure, infection prevalence, and age-associated prevalence among camels at the largest entry port of camels from Africa into the Arabian Peninsula., Methods: In this prospective genomic study, we took nasal samples from camels imported from Sudan and Djibouti into the Port of Jeddah in Jeddah, Saudi Arabia, over an almost 2-year period and local Arabian camels over 2 months in the year after surveillance of the port. We determined the prevalence of MERS-CoV infection, age-associated patterns of infection, and undertook phylogeographical and migration analyses to determine intercountry virus transmission after local lineage establishment. We compared all virological characteristics between the local and imported cohorts. We compared major gene deletions between African and Arabian strains of the virus. Reproductive numbers were inferred with Bayesian birth death skyline analyses., Findings: Between Aug 10, 2016, and May 3, 2018, we collected samples from 1196 imported camels, of which 868 originated from Sudan and 328 from Djibouti, and between May 1, and June 25, 2018, we collected samples from 472 local camels, of which 189 were from Riyadh and 283 were from Jeddah, Saudi Arabia. Virus prevalence was higher in local camels than in imported camels (224 [47·5%] of 472 vs 157 [13·1%] of 1196; p<0·0001). Infection prevalence peaked among camels older than 1 year and aged up to 2 years in both groups, with 255 (66·9%) of 381 positive cases in this age group. Although the overall geographical distribution of the virus corresponded with the phylogenetic tree topology, some virus exchange was observed between countries corresponding with trade routes in the region. East and west African strains of the virus appear to be geographically separated, with an origin of west African strains in east Africa. African strains of the virus were not re-sampled in Saudi Arabia despite sampling approximately 1 year after importation from Africa. All local Arabian samples contained strains of the virus that belong to a novel recombinant clade (NRC) first detected in 2014 in Saudi Arabia. Reproduction number estimates informed by the sequences suggest sustained endemicity of NRC, with a mean R e of 1·16., Interpretation: Despite frequent imports of MERS-CoV with camels from Africa, African lineages of MERS-CoV do not establish themselves in Saudi Arabia. Arabian strains of the virus should be tested for changes in virulence and transmissibility., Funding: German Ministry of Research and Education, EU Horizon 2020, and Emerging Diseases Clinical Trials Partnership., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Chikungunya virus (CHIKV) is an Aedes-borne alphavirus, historically found in Africa and Asia, where it caused sporadic outbreaks. In 2004, CHIKV reemerged in East Africa and spread globally to cause epidemics, including, for the first time, autochthonous transmission in Europe, the Middle East, and Oceania. The epidemic strains were of the East/Central/South African genotype. Strains of the Asian genotype of CHIKV continued to cause outbreaks in Asia and spread to Oceania and, in 2013, to the Americas. Acute disease, mainly comprising fever, rash, and arthralgia, was previously regarded as self-limiting; however, there is growing evidence of severe but rare manifestations, such as neurological disease. Furthermore, CHIKV appears to cause a significant burden of long-term morbidity due to persistent arthralgia. Diagnostic assays have advanced greatly in recent years, although there remains a need for simple, accurate, and affordable tests for the developing countries where CHIKV is most prevalent. This review focuses on recent important work on the epidemiology, clinical disease and diagnostics of CHIKV.

The rising incidence of emerging infectious diseases (EID) is mostly linked to biodiversity loss, changes in habitat use and increasing habitat fragmentation. Bats are linked to a growing number of EID but few studies have explored the factors of viral richness in bats. These may have implications for role of bats as potential reservoirs. We investigated the determinants of viral richness in 15 species of African bats (8 Pteropodidae and 7 microchiroptera) in Central and West Africa for which we provide new information on virus infection and bat phylogeny. We performed the first comparative analysis testing the correlation of the fragmented geographical distribution (defined as the perimeter to area ratio) with viral richness in bats. Because of their potential effect, sampling effort, host body weight, ecological and behavioural traits such as roosting behaviour, migration and geographical range, were included into the analysis as variables. The results showed that the geographical distribution size, shape and host body weight have significant effects on viral richness in bats. Viral richness was higher in large-bodied bats which had larger and more fragmented distribution areas. Accumulation of viruses may be related to the historical expansion and contraction of bat species distribution range, with potentially strong effects of distribution edges on virus transmission. Two potential explanations may explain these results. A positive distribution edge effect on the abundance or distribution of some bat species could have facilitated host switches. Alternatively, parasitism could play a direct role in shaping the distribution range of hosts through host local extinction by virulent parasites. This study highlights the importance of considering the fragmentation of bat species geographical distribution in order to understand their role in the circulation of viruses in Africa.

In recent years, novel henipavirus-related sequences have been identified in bats in Africa. To evaluate the potential of African bat henipaviruses to spread in non-bat mammalian cells, we compared the biological functions of the surface glycoproteins G and F of the prototype African henipavirus GH-M74a with those of the glycoproteins of Nipah virus (NiV), a well-characterized pathogenic member of the henipavirus genus. Glycoproteins are central determinants for virus tropism, as efficient binding of henipavirus G proteins to cellular ephrin receptors and functional expression of fusion-competent F proteins are indispensable prerequisites for virus entry and cell-to-cell spread. In this study, we analysed the ability of the GH-M74a G and F proteins to cause cell-to-cell fusion in mammalian cell types readily permissive to NiV or Hendra virus infections. Except for limited syncytium formation in a bat cell line derived from Hypsignathus monstrosus, HypNi/1.1 cells, we did not observe any fusion. The highly restricted fusion activity was predominantly due to the F protein. Whilst GH-M74a G protein was found to interact with the main henipavirus receptor ephrin-B2 and induced syncytia upon co-expression with heterotypic NiV F protein, GH-M74a F protein did not cause evident fusion in the presence of heterotypic NiV G protein. Pulse-chase and surface biotinylation analyses revealed delayed F cleavage kinetics with a reduced expression of cleaved and fusion-active GH-M74a F protein on the cell surface. Thus, the F protein of GH-M74a showed a functional defect that is most likely caused by impaired trafficking leading to less efficient proteolytic activation and surface expression.

In 2002/2003, a novel coronavirus (CoV) caused a pandemic, infecting more than 8000 people, of whom nearly 10% died. This virus, termed severe acute respiratory syndrome-CoV was linked to a zoonotic origin from rhinolophid bats in 2005. Since then, numerous studies have described novel bat CoVs, including close relatives of the newly emerging Middle East respiratory syndrome (MERS)-CoV. In this paper we discuss CoV genomic properties and compare different taxonomic approaches in light of the technical difficulties of obtaining full genomic sequences directly from bat specimens. We first present an overview of the available studies on bat CoVs, with details on their chiropteran hosts, then comparatively analyze the increase in bat CoV studies and novel genomic sequences obtained since the SARS pandemic. We then conduct a comprehensive phylogenetic analysis of the genera Alpha- and Betacoronavirus, to show that bats harbour more CoV diversity than other mammalian hosts and are widely represented in most, but not all parts of the tree of mammalian CoVs. We next discuss preliminary evidence for phylogenetic co-segregation of CoVs and bat hosts encompassing the Betacoronavirus clades b and d, with an emphasis on the sampling bias that exists among bat species and other mammals, then present examples of CoVs infecting different hosts on the one hand and viruses apparently confined to host genera on the other. We also demonstrate a geographic bias within available studies on bat CoVs, and identify a critical lack of information from biodiversity hotspots in Africa, Asia and Latin America. We then present evidence for a zoonotic origin of four of the six known human CoVs (HCoV), three of which likely involved bats, namely SARS-CoV, MERS-CoV and HCoV-229E; compare the available data on CoV pathogenesis in bats to that in other mammalian hosts; and discuss hypotheses on the putative insect origins of CoV ancestors. Finally, we suggest caution with conclusions on the zoonotic potential of bat viruses, based only on genomic sequence data, and emphasize the need to preserve these ecologically highly relevant animals. This paper forms part of a symposium in Antiviral Research on "from SARS to MERS: 10years of research on highly pathogenic human coronaviruses"., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Serological screening and detection of genomic RNA indicates that members of the genus Henipavirus are present not only in Southeast Asia but also in African fruit bats. We demonstrate that the surface glycoproteins F and G of an African henipavirus (M74) induce syncytium formation in a kidney cell line derived from an African fruit bat, Hypsignathus monstrosus. Despite a less broad cell tropism, the M74 glycoproteins show functional similarities to glycoproteins of Nipah virus.

Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis in tropical and temperate climates. Tropical genotypes 1 and 2 are associated with food-borne and waterborne transmission. Zoonotic reservoirs (mainly pigs, wild boar, and deer) are considered for genotypes 3 and 4, which exist in temperate climates. In view of the association of several zoonotic viruses with bats, we analyzed 3,869 bat specimens from 85 different species and from five continents for hepevirus RNA. HEVs were detected in African, Central American, and European bats, forming a novel phylogenetic clade in the family Hepeviridae. Bat hepeviruses were highly diversified and comparable to human HEV in sequence variation. No evidence for the transmission of bat hepeviruses to humans was found in over 90,000 human blood donations and individual patient sera. Full-genome analysis of one representative virus confirmed formal classification within the family Hepeviridae. Sequence- and distance-based taxonomic evaluations suggested that bat hepeviruses constitute a distinct genus within the family Hepeviridae and that at least three other genera comprising human, rodent, and avian hepeviruses can be designated. This may imply that hepeviruses invaded mammalian hosts nonrecently and underwent speciation according to their host restrictions. Human HEV-related viruses in farmed and peridomestic animals might represent secondary acquisitions of human viruses, rather than animal precursors causally involved in the evolution of human HEV.

Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. helvum). Immortalized cell lines were generated; their potential to induce and react on IFN was confirmed, and biological assays were adapted to application in bat cell cultures, enabling comparison of landmark IFN properties with that of common mammalian cell lines. E. helvum cells were fully capable of reacting to viral and artificial IFN stimuli. E. helvum cells showed highest IFN mRNA induction, highly productive IFN protein secretion, and evidence of efficient IFN stimulated gene induction. In an Alphavirus infection model, O'nyong-nyong virus exhibited strong IFN induction but evaded the IFN response by translational rather than transcriptional shutoff, similar to other Alphavirus infections. These novel IFN-competent cell lines will allow comparative research on zoonotic, bat-borne viruses in order to model mechanisms of viral maintenance and emergence in bat reservoirs.

Background: Anti-Lassa antibodies are detected by indirect immunofluorescence assay (IFA) or by enzyme-immunoassay (ELISA). Both methods have problems to detect low amounts of specific antibodies., Objectives: We report here highly sensitive and specific reverse ELISAs to detect Lassa virus IgG and IgM antibodies. Due to the reverse techniques, serum samples could be applied at dilutions of 1:10 without increasing non-specific background reactions., Study Design: For IgM antibody detection microtiter plates were coated with anti-IgM antibodies and for IgG antibody detection with rheumatoid factor (RF) (Sachers M, Emmerich P, Mohr H, Schmitz H. Simple detection of antibodies to different viruses using rheumatoid factor and enzyme-labelled antigen (ELA). J Virol Methods 1985;10:99-110). In both assays a tissue culture antigen was used in combination with a labeled anti-Lassa monoclonal antibody (Hufert FT, Ludke W, Schmitz H. Epitope mapping of the Lassa virus nucleoprotein using monoclonal anti-nucleocapsid antibodies. Arch Virol 1989;106(3-4):201-12)., Results: The reverse ELISA turned out to detect virus-specific IgG and IgM antibody in all 20 samples of West African patients collected 2-8 weeks after onset of Lassa fever. Moreover, both IFA and reverse ELISA found IgG antibodies in 53 out of 643 samples of healthy West Africans (sensitivity of 100%). Six of the 643 samples were positive by reverse IgG ELISA only. Thus, the specificity compared to IIF was 99.0%, but it may be even higher, because compared to IFA the IgG ELISA was clearly more sensitive in detecting low antibody titers., Conclusions: In Ghana 3% seropositives were found by IFA, but 4% by the reverse ELISA. The reverse ELISAs can be performed with high sensitivity and specificity under field conditions in Africa.

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.