[Show abstract][Hide abstract] ABSTRACT: HCV genotype 4 is prevalent in many African countries, yet little is known about the genotype׳s epidemic history on the continent. We present a comprehensive study of the molecular epidemiology of genotype 4. To address the deficit of data from the Democratic Republic of the Congo (DRC) we PCR amplified 60 new HCV isolates from the DRC, resulting in 33 core- and 48 NS5B-region sequences. Our data, together with genotype 4 database sequences, were analysed using Bayesian phylogenetic approaches. We find three well-supported intra-genotypic lineages and estimate that the genotype 4 common ancestor existed around 1733 (1650–1805). We show that genotype 4 originated in central Africa and that multiple lineages have been exported to north Africa since ~1850, including subtype 4a which dominates the epidemic in Egypt. We speculate on the causes of the historical intra-continental spread of genotype 4, including population movements during World War 2.
[Show abstract][Hide abstract] ABSTRACT: Foamy viruses (FVs) are a unique subfamily of retroviruses that are widely distributed in mammals. Owing to the availability of sequences from diverse mammals coupled with their pattern of codivergence with their hosts, FVs have one of the best-understood viral evolutionary histories ever documented, estimated to have an ancient origin. Nonetheless, our knowledge of some parts of FV evolution, notably that of prosimian and afrotherian FVs, is far from complete due to the lack of sequence data.
[Show abstract][Hide abstract] ABSTRACT: Non-primate hepacivirus (NPHV), equine pegivirus (EPgV) and Theiler's disease associated virus (TDAV) are newly discovered members of two genera in the Flaviviridae family, Hepacivirus and Pegivirus respectively, that include human hepatitis C virus (HCV) and human pegivirus (HPgV). To investigate their epidemiology, persistence and clinical features of infection, large cohorts of horses and other mammalian species were screened for NPHV, EPgV and TDAV viraemia and for past exposure through serological assays for NPHV and EPgV-specific antibodies. NPHV antibodies were detected in 43% of 328 horses screened for antibodies to NS3 and core antibodies, of which three were viraemic by PCR. All five horses that were stablemates of a viraemic horse were seropositive, as was a dog on the same farm. With this single exception, all other species were negative for NPHV antibodies and viraemia (donkeys (n=100), dogs (n=112), cats (n=131), non-human primates (n=164) and humans (n=362). EPgV antibodies to NS3 were detected in 66.5% of horses, including 11 of the 12 horses that had EPgV viraemia. All donkey samples were negative for EPgV antibody and RNA. All horse and donkey samples were negative for TDAV RNA. By comparing viraemia frequencies in horses with and without liver disease, no evidence was obtained that supported an association between active NPHV and EPgV infections with hepatopathy. The study demonstrates that NPHV and EPgV infections are widespread and enzootic in the study horse population and confirms that NPHV and potentially EPgV have higher frequencies of viral clearance than HCV and HPgV infections in humans.
Journal of General Virology 05/2014; · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Plasmodium vivax is the leading cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its receptor, the Duffy antigen, on human erythrocytes. The emergence of this protective allele is not understood because P. vivax is believed to have originated in Asia. Here we show, using a non-invasive approach, that wild chimpanzees and gorillas throughout central Africa are endemically infected with parasites that are closely related to human P. vivax. Sequence analyses reveal that ape parasites lack host specificity and are much more diverse than human parasites, which form a monophyletic lineage within the ape parasite radiation. These findings indicate that human P. vivax is of African origin and likely selected for the Duffy-negative mutation. All extant human P. vivax parasites are derived from a single ancestor that escaped out of Africa.
[Show abstract][Hide abstract] ABSTRACT: Monkeypox virus is a zoonotic virus endemic to Central Africa. Although active disease surveillance has assessed monkeypox disease prevalence and geographic range, information about virus diversity is lacking. We therefore assessed genome diversity of viruses in 60 samples obtained from humans with primary and secondary cases of infection from 2005 through 2007. We detected 4 distinct lineages and a deletion that resulted in gene loss in 10 (16.7%) samples and that seemed to correlate with human-to-human transmission (p = 0.0544). The data suggest a high frequency of spillover events from the pool of viruses in nonhuman animals, active selection through genomic destabilization and gene loss, and increased disease transmissibility and severity. The potential for accelerated adaptation to humans should be monitored through improved surveillance.
[Show abstract][Hide abstract] ABSTRACT: Of the seven known species of human retroviruses only one, human T-cell lymphotropic virus type 4 (HTLV-4), lacks a known animal reservoir. We report the largest screening for simian T-cell lymphotropic virus (STLV-4) to date in a wide range of captive and wild non-human primate (NHP) species from Cameroon. Among the 681 wild and 426 captive NHPs examined, we detected STLV-4 infection only among gorillas by using HTLV-4-specific quantitative polymerase chain reaction. The large number of samples analyzed, the diversity of NHP species examined, the geographic distribution of infected animals relative to the known HTLV-4 case, as well as detailed phylogenetic analyses on partial and full genomes, indicate that STLV-4 is endemic to gorillas, and that rather than being an ancient virus among humans, HTLV-4 emerged from a gorilla reservoir, likely through the hunting and butchering of wild gorillas. Our findings shed further light on the importance of gorillas as keystone reservoirs for the evolution and emergence of human infectious diseases and provide a clear course for preventing HTLV-4 emergence through management of human contact with wild gorillas, the development of improved assays for HTLV-4/STLV-4 detection and the ongoing monitoring of STLV-4 among gorillas and for HTLV-4 zoonosis among individuals exposed to gorilla populations.
[Show abstract][Hide abstract] ABSTRACT: The prevalence and genetic diversity of hepatitis C virus (HCV) and human pegivirus (HPgV) in many regions of sub-Saharan Africa is poorly characterized, including in the Democratic Republic of Congo - the largest country in the region and one of the most populous. To address this situation we conducted a molecular epidemiological survey of HCV and HPgV (previously named GB Virus C or hepatitis G virus) in samples collected in 2007 from 299 males from the DRC, whose ages ranged from 21 to 71years old. Samples were tested for the presence of HCV antibodies by ELISA reactive samples were subsequently tested for HCV RNA using RT-PCR in which both the HCV Core and NS5B genome regions were amplified. Remaining samples were tested for HPgV RNA and the HPgV NS3 genome region of positive samples was amplified. For HCV, 13.7% of the samples were seropositive (41/299) but only 3.7% were viremic (11/299). HPgV RNA was found in 12.7% (33/259) of samples. HCV viremia was strongly associated with age; the percentage of samples that contained detectable HCV RNA was ∼0.5% in those younger than 50 and 13% in those older than 50. Our study represents the first systematic survey of HCV genetic diversity in the DRC. HCV sequences obtained belonged to diverse lineages of genotype 4, including subtypes 4c, 4k, 4l and 4r, plus one unclassified lineage that may constitute a new subtype. These data suggest that HCV in the DRC exhibits an age 'cohort effect', as has been recently reported in neighbouring countries, and are consistent with the hypothesis that HCV transmission rates were higher in the mid-twentieth century, possibly as a result of parenteral, iatrogenic, or other unidentified factors. Different HCV subtypes were associated with individuals of different ages, implying that HCV infection in the DRC may have arisen through multiple separate HCV epidemics with different causes.
Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 02/2013; · 3.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As part of a virus discovery investigation using a metagenomic approach, a highly divergent novel Human papillomavirus type was identified in pooled convenience nasal/oropharyngeal swab samples collected from patients with febrile respiratory illness. Phylogenetic analysis of the whole genome and the L1 gene reveals that the new HPV identified in this study clusters with previously described gamma papillomaviruses, sharing only 61.1% (whole genome) and 63.1% (L1) sequence identity with its closest relative in the Papillomavirus episteme (PAVE) database. This new virus was named HPV_SD2 pending official classification. The complete genome of HPV-SD2 is 7,299 bp long (36.3% G/C) and contains 7 open reading frames (L2, L1, E6, E7, E1, E2 and E4) and a non-coding long control region (LCR) between L1 and E6. The metagenomic procedures, coupled with the bioinformatic methods described herein are well suited to detect small circular genomes such as those of human papillomaviruses.
PLoS ONE 01/2013; 8(3):e58404. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Climate change is predicted to result in changes in the geographic ranges and local prevalence of infectious diseases, either through direct effects on the pathogen, or indirectly through range shifts in vector and reservoir species. To better understand the occurrence of monkeypox virus (MPXV), an emerging Orthopoxvirus in humans, under contemporary and future climate conditions, we used ecological niche modeling techniques in conjunction with climate and remote-sensing variables. We first created spatially explicit probability distributions of its candidate reservoir species in Africa's Congo Basin. Reservoir species distributions were subsequently used to model current and projected future distributions of human monkeypox (MPX). Results indicate that forest clearing and climate are significant driving factors of the transmission of MPX from wildlife to humans under current climate conditions. Models under contemporary climate conditions performed well, as indicated by high values for the area under the receiver operator curve (AUC), and tests on spatially randomly and non-randomly omitted test data. Future projections were made on IPCC 4(th) Assessment climate change scenarios for 2050 and 2080, ranging from more conservative to more aggressive, and representing the potential variation within which range shifts can be expected to occur. Future projections showed range shifts into regions where MPX has not been recorded previously. Increased suitability for MPX was predicted in eastern Democratic Republic of Congo. Models developed here are useful for identifying areas where environmental conditions may become more suitable for human MPX; targeting candidate reservoir species for future screening efforts; and prioritizing regions for future MPX surveillance efforts.
PLoS ONE 01/2013; 8(7):e66071. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Zoonotic transmission of simian retroviruses in Central Africa is ongoing and can result in pandemic human infection. While simian foamy virus (SFV) infection was reported in primate hunters in Cameroon and Gabon, little is known about the distribution of SFV in Africa and whether human-to-human transmission and disease occur. We screened 3,334 plasmas from persons living in rural villages in central Democratic Republic of Congo (DRC) using SFV-specific EIA and Western blot (WB) tests. PCR amplification of SFV polymerase sequences from DNA extracted from buffy coats was used to measure proviral loads. Phylogenetic analysis was used to define the NHP species origin of SFV. Participants completed questionnaires to capture NHP exposure information. RESULTS: Sixteen (0.5%) samples were WB-positive; 12 of 16 were from women (75%, 95% confidence limits 47.6%, 92.7%). Sequence analysis detected SFV in three women originating from Angolan colobus or red-tailed monkeys; both monkeys are hunted frequently in DRC. NHP exposure varied and infected women lived in distant villages suggesting a wide and potentially diverse distribution of SFV infections across DRC. Plasmas from 22 contacts of 8 WB-positive participants were all WB negative suggesting no secondary viral transmission. Proviral loads in the three women ranged from 14 -- 1,755 copies/105 cells. CONCLUSIONS: Our study documents SFV infection in rural DRC for the first time and identifies infections with novel SFV variants from Colobus and red-tailed monkeys. Unlike previous studies, women were not at lower risk for SFV infection in our population, providing opportunities for spread of SFV both horizontally and vertically. However, limited testing of close contacts of WB-positive persons did not identify human-to-human transmission. Combined with the broad behavioral risk and distribution of NHPs across DRC, our results suggest that SFV infection may have a wider geographic distribution within DRC. These results also reinforce the potential for an increased SFV prevalence throughout the forested regions of Africa where humans and simians co-exist. Our finding of endemic foci of SFV infection in DRC will facilitate longitudinal studies to determine the potential for person-to-person transmissibility and pathogenicity of these zoonotic retroviral infections.
[Show abstract][Hide abstract] ABSTRACT: Although the origin of hepatitis C virus (HCV) remains undetermined, a close homolog of HCV found in dogs, canine hepacivirus (CHV), provides evidence for a wider distribution of hepaciviruses in mammals in a study that determined frequencies of active infection among dogs and other mammals in the United Kingdom. Samples from dogs (46 respiratory, 99 plasma, 45 autopsy samples) were uniformly PCR negative for CHV. Wider screening of 362 samples from cats, horses, donkeys, rodents, and pigs identified 142 positive results; 3 (2%) of those were from horses. These samples were genetically divergent from CHV and nonprimate hepaciviruses (NPHVs) that horses were infected with during 2012 in New York State, United States. Investigation of infected horses demonstrated NPHV persistence, high viral loads (105–107 RNA copies/mL) in plasma, and frequently normal liver function tests, although several values were in the upper normal or mildly elevated range. Disease associations and host range of NPHVs require further investigatio
[Show abstract][Hide abstract] ABSTRACT: TO THE EDITOR: Bats are hosts for various emerging viruses, including the zoonotic paramyxoviruses Hendra virus and Nipah virus, which occur in Australia and Southeast Asia, respectively, and cause severe disease outbreaks among humans and livestock (1). Antibodies and henipavirus-related RNA have also been found in the straw-colored fruit bat, Eidolon helvum, in Ghana, West Africa (2,3). These bats are a chief protein source for humans in sub-Saharan Africa and are therefore targeted by hunters (4,5). This practice raises special concern about the risk for virus transmission from bats to humans.
[Show abstract][Hide abstract] ABSTRACT: Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of 3 human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo (DRC), Africa. The cases, presenting over a 3-week period, were characterized by abrupt disease onset, high fever, mucosal hemorrhage, and, in two patients, death within 3 days. BASV was detected in an acute serum sample from the lone survivor at a concentration of 1.09×10(6) RNA copies/mL, and 98.2% of the genome was subsequently de novo assembled from ∼140 million sequence reads. Phylogenetic analysis revealed that BASV is highly divergent and shares less than 34% amino acid identity with any other rhabdovirus. High convalescent neutralizing antibody titers of >1∶1000 were detected in the survivor and an asymptomatic nurse directly caring for him, both of whom were health care workers, suggesting the potential for human-to-human transmission of BASV. The natural animal reservoir host or arthropod vector and precise mode of transmission for the virus remain unclear. BASV is an emerging human pathogen associated with acute hemorrhagic fever in Africa.
[Show abstract][Hide abstract] ABSTRACT: Hunting and butchering of wildlife in Central Africa are known risk factors for a variety of human diseases, including HIV/AIDS. Due to the high incidence of human exposure to body fluids of non-human primates, the significant prevalence of simian immunodeficiency virus (SIV) in non-human primates, and hunting/butchering associated cross-species transmission of other retroviruses in Central Africa, it is possible that SIV is actively transmitted to humans from primate species other than mangabeys, chimpanzees, and/or gorillas. We evaluated SIV transmission to humans by screening 2,436 individuals that hunt and butcher non-human primates, a population in which simian foamy virus and simian T-lymphotropic virus were previously detected. We identified 23 individuals with high seroreactivity to SIV. Nucleic acid sequences of SIV genes could not be detected, suggesting that SIV infection in humans could occur at a lower frequency than infections with other retroviruses, including simian foamy virus and simian T-lymphotropic virus. Additional studies on human populations at risk for non-human primate zoonosis are necessary to determine whether these results are due to viral/host characteristics or are indicative of low SIV prevalence in primate species consumed as bushmeat as compared to other retroviruses in Cameroon.
[Show abstract][Hide abstract] ABSTRACT: To estimate population exposure of apes and Old World monkeys in Africa to enteroviruses (EVs), we conducted a seroepidemiologic study of serotype-specific neutralizing antibodies against 3 EV types. Detection of species A, B, and D EVs infecting wild chimpanzees demonstrates their potential widespread circulation in primates.
[Show abstract][Hide abstract] ABSTRACT: Hepatitis B virus (HBV) infections are widely distributed in humans, infecting approximately one third of the world's population. HBV variants have also been detected and genetically characterised from Old World apes; Gorilla gorilla (gorilla), Pan troglodytes (chimpanzee), Pongo pygmaeus (orang-utan), Nomascus nastusus and Hylobates pileatus (gibbons) and from the New World monkey, Lagothrix lagotricha (woolly monkey). To investigate species-specificity and potential for cross species transmission of HBV between sympatric species of apes (such as gorillas and chimpanzees in Central Africa) or between humans and chimpanzees or gorillas, variants of HBV infecting captive wild-born non-human primates were genetically characterised. 9 of 62 chimpanzees (11.3%) and two from 11 gorillas (18%) were HBV-infected (15% combined frequency), while other Old world monkey species were negative. Complete genome sequences were obtained from six of the infected chimpanzee and both gorillas; those from P. t .ellioti grouped with previously characterised variants from this subspecies. However, variants recovered from P. t. troglodytes HBV variants also grouped within this clade, indicative of transmission between sub-species, forming a paraphyletic clade. The two gorilla viruses were phylogenetically distinct from chimpanzee and human variants although one showed evidence for a recombination event with a P.t.e.-derived HBV variant in the partial X and core gene region. Both of these observations provide evidence for circulation of HBV between different species and sub-species of non-human primates, a conclusion that differs from the hypothesis if of strict host specificity of HBV genotypes.
PLoS ONE 01/2012; 7(3):e33430. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Zaire ebolavirus was responsible for 2 outbreaks in Democratic Republic of the Congo (DRC), in 1976 and 1995. The virus reemerged in DRC 12 years later, causing 2 successive outbreaks in the Luebo region, Kasai Occidental province, in 2007 and 2008.
Viruses of each outbreak were isolated and the full-length genomes were characterized. Phylogenetic analysis was then undertaken to characterize the relationships with previously described viruses.
The 2 Luebo viruses are nearly identical but are not related to lineage A viruses known in DRC or to descendants of the lineage B viruses encountered in the Gabon-Republic of the Congo area, with which they do, however, share a common ancestor.
Our findings strongly suggest that the Luebo 2007 outbreak did not result from viral spread from previously identified foci but from an independent viral emergence. The previously identified epidemiological link with migratory bat species known to carry Zaire ebolavirus RNA support the hypothesis of viral spillover from this widely dispersed reservoir. The high level of similarity between the Luebo2007 and Luebo2008 viruses suggests that local wildlife populations (most likely bats) became infected and allowed local viral persistence and reemergence from year to year.
The Journal of Infectious Diseases 11/2011; 204 Suppl 3:S776-84. · 5.85 Impact Factor