Publications by authors named "Martine Peeters"

242 Publications

High prevalence of anti-SARS-CoV-2 antibodies after the first wave of COVID-19 in Kinshasa, Democratic Republic of the Congo: results of a cross-sectional household-based survey.

Clin Infect Dis 2021 Jun 5. Epub 2021 Jun 5.

Département de Virologie, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo.

Background: On October, 2020, after the first wave of COVID-19, only 8290 confirmed cases were reported in Kinshasa, Democratic Republic of the Congo, but the real prevalence remains unknown. To guide public health policies, we aimed to describe the prevalence of SARS-CoV-2 IgG antibodies in the general population in Kinshasa.

Methods: We conducted a cross-sectional, household-based serosurvey between October 22, 2020, and November 8, 2020. Participants were interviewed at home and tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins in a Luminex based assay. A positive serology was defined as a sample that reacted with both SARS-CoV-2 proteins (100% sensitivity, 99.7% specificity). The overall weighted, age-standardized prevalence was estimated and the infection-to-case ratio was calculated to determine the proportion of undiagnosed SARS-CoV-2 infections.

Results: A total of 1233 participants from 292 households were included (mean age, 32.4 years; 764 [61.2%] were women). The overall weighted, age-standardized SARS-CoV-2 seroprevalence was 16.6% (95% CI 14.0-19.5). The estimated infection-to-case ratio was 292:1. Prevalence was higher among participants ≥ 40 years than among those ˂18 years (21.2% vs 14.9%, respectively; p˂0.05). It was also higher in participants who reported hospitalization than among those who did not (29.8% vs 16.0%, respectively; p˂0.05). However, differences were not significant in the multivariate model (p=0.1).

Conclusion: The prevalence of SARS-CoV-2 is much higher than the number of COVID-19 cases reported. These results justify the organization of a sequential series of serosurveys by public health authorities to adapt response measures to the dynamics of the pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab515DOI Listing
June 2021

Investigating the Circulation of Ebola Viruses in Bats during the Ebola Virus Disease Outbreaks in the Equateur and North Kivu Provinces of the Democratic Republic of Congo from 2018.

Pathogens 2021 May 4;10(5). Epub 2021 May 4.

Institut National de Recherche Biomédicale (INRB), 1197 Kinshasa, Democratic Republic of the Congo.

With 12 of the 31 outbreaks, the Democratic Republic of Congo (DRC) is highly affected by Ebolavirus disease (EVD). To better understand the role of bats in the ecology of Ebola viruses, we conducted surveys in bats during two recent EVD outbreaks and in two areas with previous outbreaks. Dried blood spots were tested for antibodies to ebolaviruses and oral and rectal swabs were screened for the presence of filovirus using a broadly reactive semi-nested RT-PCR. Between 2018 and 2020, 892 (88.6%) frugivorous and 115 (11.4%) insectivorous bats were collected. Overall, 11/925 (1.2%) to 100/925 (10.8%) bats showed antibodies to at least one Ebolavirus antigen depending on the positivity criteria. Antibodies were detected in fruit bats from the four sites and from species previously documented to harbor Ebola antibodies or RNA. We tested for the first time a large number of bats during ongoing EVD outbreaks in DRC, but no viral RNA was detected in the 676 sampled bats. Our study illustrates the difficulty to document the role of bats as a source of Ebolaviruses as they might clear quickly the virus. Given the increasing frequency of EVD outbreaks, more studies on the animal reservoir are urgently needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens10050557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147758PMC
May 2021

Integration of genomic sequencing into the response to the Ebola virus outbreak in Nord Kivu, Democratic Republic of the Congo.

Nat Med 2021 04 12;27(4):710-716. Epub 2021 Apr 12.

Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo.

On 1 August 2018, the Democratic Republic of the Congo (DRC) declared its tenth Ebola virus disease (EVD) outbreak. To aid the epidemiologic response, the Institut National de Recherche Biomédicale (INRB) implemented an end-to-end genomic surveillance system, including sequencing, bioinformatic analysis and dissemination of genomic epidemiologic results to frontline public health workers. We report 744 new genomes sampled between 27 July 2018 and 27 April 2020 generated by this surveillance effort. Together with previously available sequence data (n = 48 genomes), these data represent almost 24% of all laboratory-confirmed Ebola virus (EBOV) infections in DRC in the period analyzed. We inferred spatiotemporal transmission dynamics from the genomic data as new sequences were generated, and disseminated the results to support epidemiologic response efforts. Here we provide an overview of how this genomic surveillance system functioned, present a full phylodynamic analysis of 792 Ebola genomes from the Nord Kivu outbreak and discuss how the genomic surveillance data informed response efforts and public health decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-021-01302-zDOI Listing
April 2021

CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses.

Proc Natl Acad Sci U S A 2021 Mar;118(13)

Lukuru Wildlife Research Foundation, Tshuapa-Lomami-Lualaba Project, BP 2012, Kinshasa, Democratic Republic of the Congo.

Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. Several identical CD4 polymorphisms, including the addition of -linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. Moreover, seven different guenons ( spp.) shared multiple distinct D1 domain variants, pointing to long-term trans-specific polymorphism. These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2025914118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020793PMC
March 2021

Understanding the long-term evolution and predictors of sequelae of Ebola virus disease survivors in Guinea: A 48-month prospective, longitudinal cohort study (PostEboGui).

Clin Infect Dis 2021 Feb 23. Epub 2021 Feb 23.

IRD/INSERM/Montpellier University, Montpellier, France.

Background: Longitudinal analyses are needed to better understand long-term Ebola virus disease (EVD) sequelae. We aimed to estimate the prevalence, incidence and duration of sequelae and identify risk factors associated with symptom occurrence among EVD survivors in Guinea.

Methods: We followed 802 EVD survivors over 48 months and recorded clinical symptoms with their start/end dates. Prevalence, incidence and duration of sequelae were calculated. Risk factors associated with symptom occurrence were assessed using an extended Cox model for recurrent events.

Results: Overall, the prevalence and incidence of all symptoms decreased significantly over time, but sequelae remained present 48 months after Ebola treatment center discharge with a prevalence of 30.68% (95% confidence interval [CI] 21.40-39.96) for abdominal, 30.55% (95% CI 20.68-40.41) for neurologic, 5.80% (95% CI 1.96-9.65) for musculoskeletal and 4.24% (95% CI 2.26-6.23) for ocular sequelae. Half of all patients (50.70%; 95% CI 47.26-54.14) complained of general symptoms 2 years' post-discharge and 25.35% (95% CI 23.63-27.07) 4 years' post-discharge. Hemorrhage (hazard ratio [HR], 2.70; P = .007), neurologic (HR 2.63; P = .021) and general symptoms (HR 0.34; P = .003) in the EVD acute phase were significantly associated with the further occurrence of ocular sequelae, whereas hemorrhage (HR 1.91; P =.046) and abdominal (HR 2.21; P = .033) symptoms were significantly associated with musculoskeletal sequelae.

Conclusion: Our findings provide new insight into the long-term clinical complications of EVD and their significant association with symptoms in the acute phase, thus reinforcing the importance of regular, long-term follow-up for EVD survivors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab168DOI Listing
February 2021

Multiplex detection of antibodies to Chikungunya, O'nyong-nyong, Zika, Dengue, West Nile and Usutu viruses in diverse non-human primate species from Cameroon and the Democratic Republic of Congo.

PLoS Negl Trop Dis 2021 01 21;15(1):e0009028. Epub 2021 Jan 21.

Recherches Translationnelles sur le VIH et Maladies Infectieuses/INSERM U1175, Institut de Recherche pour le Développement et Université de Montpellier, France.

Background: Epidemic arbovirus transmission occurs among humans by mosquito bites and the sylvatic transmission cycles involving non-human primates (NHPs) still exists. However, limited data are available on the extent in NHPs infections and their role. In this study, we have developed and validated a high-throughput serological screening tool to study the circulation of multiple arboviruses that represent a significant threat to human health, in NHPs in Central Africa.

Methodology/principal Findings: Recombinant proteins NS1, envelope domain-3 (DIII) for the dengue (DENV), yellow fever (YFV), usutu (USUV), west nile (WNV) and zika (ZIKV) and envelope 2 for the chikungunya (CHIKV) and o'nyong-nyong (ONNV) were coupled to Luminex beads to detect IgG directed against these viruses. Evaluation of test performance was made using 161 human sera of known arboviral status (66 negative and 95 positive). The sensitivity and specificity of each antigen were determined by statistical methods and ROC curves (except for ONNV and USUV). All NS1 antigens (except NS1-YFV), CHIKV-E2 and WNV-DIII had sensitivities and specificities > 95%. For the other DIII antigens, the sensitivity was low, limiting the interest of their use for seroprevalence studies. Few simultaneous reactions were observed between the CHIKV+ samples and the NS1 antigens to the non-CHIKV arboviruses. On the other hand, the DENV+ samples crossed-reacted with NS1 of all the DENV serotypes (1 to 4), as well as with ZIKV, USUV and to a lesser extent with YFV. A total of 3,518 samples of 29 species of NHPs from Cameroon and the Democratic Republic of Congo (DRC) were tested against NS1 (except YFV), E2 (CHIKV/ONNV) and DIII (WNV) antigens. In monkeys (n = 2,100), the global prevalence varied between 2 and 5% for the ten antigens tested. When we stratified by monkey's biotope, the arboreal species showed the highest reactivity. In monkeys from Cameroon, the highest IgG prevalence were observed against ONNV-E2 and DENV2-NS1 with 3.95% and 3.40% respectively and in DRC, ONNV-E2 (6.63%) and WNV-NS1 (4.42%). Overall prevalence was low in apes (n = 1,418): ranging from 0% for USUV-NS1 to 2.6% for CHIKV-E2. However, a very large disparity was observed among collection site and ape species, e.g. 18% (9/40) and 8.2% (4/49) of gorillas were reactive with CHIKV-E2 or WNV-NS1, respectively in two different sites in Cameroon.

Conclusions/significance: We have developed a serological assay based on Luminex technology, with high specificity and sensitivity for simultaneous detection of antibodies to 10 antigens from 6 different arboviruses. This is the first study that evaluated on a large scale the presence of antibodies to arboviruses in NHPs to evaluate their role in sylvatic cycles. The overall low prevalence (<5%) in more than 3,500 NHPs samples from Cameroon and the DRC does not allow us to affirm that NHP are reservoirs, but rather, intermediate hosts of these viruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0009028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853492PMC
January 2021

Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon.

Lancet HIV 2020 10;7(10):e677-e687

TransVIHMI, University of Montpellier, IRD, INSERM, 34394 Montpellier, France; Montpellier University Hospital Centre, Montpellier, France.

Background: Updated WHO guidelines recommend a dolutegravir-based regimen as the preferred first-line treatment for HIV infection and low-dose efavirenz (400 mg) as an alternative. We aimed to report the non-inferior efficacy of dolutegravir compared with efavirenz 400 mg at week 96.

Methods: We did a multicentre, randomised, open label, phase 3 trial in in three hospitals in Yaoundé, Cameroon, in HIV-1 infected antiretroviral-naive adults with an HIV RNA viral load of greater than 1000 copies per mL to compare dolutegravir 50 mg with efavirenz 400 mg (reference treatment), both combined with lamivudine and tenofovir disoproxil fumarate. The primary endpoint was the proportion with a viral load of less than 50 copies per mL at week 48 (10% non-inferiority margin). The study is registered with ClinicalTrials.gov, NCT02777229 and is ongoing.

Findings: Between July, 2016, and August, 2019, of 820 patients assessed, 613 were randomly assigned to receive at least one dose of study medication, with 310 in the dolutegravir group and 303 in the efavirenz 400 mg group. At week 96 in the intention-to-treat analysis, 229 (74%) of 310 patients receiving dolutegravir and 219 (72%) of 303 patients receiving efavirenz, achieved plasma HIV-1 RNA less than 50 copies per mL (difference 1·6%, 95% CI -5·4 to 8·6; p=0.66). Viral load suppression was reached significantly more rapidly in the dolutegravir group (p<0·001). Virological failure (>1000 copies per mL) was observed in 27 patients (eight in the dolutegravir group, among which, three women switched to efavirenz 600 mg because of the dolutegravir teratogeneicity signal, and 19 in the efavirenz 400 mg group). No acquired resistance mutations to dolutegravir were observed against 17 mutations to efavirenz with or without mutations to lamivudine and tenofovir disoproxil fumarate among the 19 efavirenz 400 mg participants with virological failure. Weight gain was greater in the dolutegravir group (median weight gain, 5·0 kg in the dolutegravir group and 3·0 kg in the efavirenz 400 mg group, p<0·001, and incidence of obesity, 22% in the dolutegravir group and 16% in the efavirenz 400 mg group, p=0·043). The incidence of new WHO HIV-related stage 3 and 4 events was similar in each group (12 [4%] in each group). The two groups had similar rates of serious adverse events (28 [9%] of 310 in the dolutegravir group and 21 [7%] of 303 in the efavirenz 400 mg group). 18 deaths were observed during the 96-week follow-up (eight in the dolutegravir group and ten in the efavirenz 400 mg group).

Interpretation: The non-inferior efficacy of the dolutegravir-based regimen and non-emergence of dolutegravir resistance at 96 weeks supports its use as a first-line regimen for antiretroviral-naive adults with HIV-1 infection. Viral load suppression was reached more quickly in the dolutegravir group and weight gain was significantly higher.

Funding: UNITAID and the French National Agency for AIDS Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3018(20)30238-1DOI Listing
October 2020

Role of Wildlife in Emergence of Ebola Virus in Kaigbono (Likati), Democratic Republic of the Congo, 2017.

Emerg Infect Dis 2020 09;26(9):2205-2209

After the 2017 Ebola virus (EBOV) outbreak in Likati, a district in northern Democratic Republic of the Congo, we sampled small mammals from the location where the primary case-patient presumably acquired the infection. None tested positive for EBOV RNA or antibodies against EBOV, highlighting the ongoing challenge in detecting animal reservoirs for EBOV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2609.191552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454093PMC
September 2020

Wide Diversity of Coronaviruses in Frugivorous and Insectivorous Bat Species: A Pilot Study in Guinea, West Africa.

Viruses 2020 08 5;12(8). Epub 2020 Aug 5.

TransVIHMI, Institut de Recherche pour le Développement, University of Montpellier, INSERM, 34394 Montpellier, France.

Zoonoses can constitute a threat for public health that can have a global importance, as seen with the current COVID-19 pandemic of severe acute respiratory syndrome coronavirus (SARS-CoV2). Bats have been recognized as an important reservoir of zoonotic coronaviruses (CoVs). In West Africa, where there is a high diversity of bat species, little is known on the circulation of CoVs in these hosts, especially at the interface with human populations. In this study, in Guinea, we tested a total of 319 bats belonging to 14 genera and six families of insectivorous and frugivorous bats across the country, for the presence of coronaviruses. We found CoVs in 35 (11%) of the tested bats-in three insectivorous bat species and five fruit bat species that were mostly captured close to human habitat. Positivity rates varied from 5.7% to 100%, depending on bat species. A wide diversity of alpha and beta coronaviruses was found across the country, including three sequences belonging to SarbeCoVs and MerbeCoVs subgenera known to harbor highly pathogenic human coronaviruses. Our findings suggest that CoVs are widely spread in West Africa and their circulation should be assessed to evaluate the risk of exposure of potential zoonotic CoVs to humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v12080855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472279PMC
August 2020

Multiplex detection and dynamics of IgG antibodies to SARS-CoV2 and the highly pathogenic human coronaviruses SARS-CoV and MERS-CoV.

J Clin Virol 2020 08 22;129:104521. Epub 2020 Jun 22.

Recherches Translationnelles sur le VIH et Maladies Infectieuses/INSERM U1175, Institut de Recherche pour le Développement et Université de Montpellier, France.

Background: Knowledge of the COVID-19 epidemic extent and the level of herd immunity is urgently needed to help manage this pandemic.

Methods: We used a panel of 167 samples (77 pre-epidemic and 90 COVID-19 seroconverters) and SARS-CoV1, SARS-CoV2 and MERS-CoV Spike and/or Nucleopcapsid (NC) proteins to develop a high throughput multiplex screening assay to detect IgG antibodies in human plasma. Assay performances were determined by ROC curves analysis. A subset of the COVID-19+ samples (n = 36) were also tested by a commercial NC-based ELISA test and the results compared with those of the novel assay.

Results: On samples collected ≥14 days after symptoms onset, the accuracy of the assay is 100 % (95 % CI: 100-100) for the Spike antigen and 99.9 % (95 % CI:99.7-100) for NC. By logistic regression, we estimated that 50 % of the patients have seroconverted at 5.7 ± 1.6; 5.7 ± 1.8 and 7.9 ± 1.0 days after symptoms onset against Spike, NC or both antigens, respectively and all have seroconverted two weeks after symptoms onset. IgG titration in a subset of samples showed that early phase samples present lower IgG titers than those from later phase. IgG to SARS-CoV2 NC cross-reacted at 100 % with SARS-CoV1 NC. Twenty-nine of the 36 (80.5 %) samples tested were positive by the commercial ELISA while 31/36 (86.1 %) were positive by the novel assay.

Conclusions: Our assay is highly sensitive and specific for the detection of IgG antibodies to SARS-CoV2 proteins, suitable for high throughput epidemiological surveys. The novel assay is more sensitive than a commercial ELISA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcv.2020.104521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308014PMC
August 2020

Detection of DNA of filariae closely related to Mansonella perstans in faecal samples from wild non-human primates from Cameroon and Gabon.

Parasit Vectors 2020 Jun 16;13(1):313. Epub 2020 Jun 16.

IRD UMI 233-INSERM U1175, University of Montpellier, Montpellier, France.

Background: The Onchocercidae is a family of filarial nematodes with several species of medical or veterinary importance. Microfilariae are found in the blood and/or the dermis and are usually diagnosed in humans by microscopy examination of a blood sample or skin biopsy. The main objectives of this study were to evaluate whether filariae DNA can be detected in faecal samples of wild non-human primates (NHPs), whether the detected parasites were closely related to those infecting humans and whether filarial DNA detection in faeces is associated with co-infections with nematodes (Oesophagostumum sp. and Necator sp.) known to cause blood loss while feeding on the host intestinal mucosa.

Methods: A total of 315 faecal samples from 6 species of NHPs from Cameroon and Gabon were analysed. PCRs targeted DNA fragments of cox1 and 12S rDNA genes, to detect the presence of filariae, and the internal transcribed spacer 2 (ITS2), to detect the presence of Oesophagostomum sp. and Necator sp. infections.

Results: Among the 315 samples analysed, 121 produced sequences with > 90% homology with Onchocercidae reference sequences. However, 63% of the 12S rDNA and 78% of the cox1 gene sequences were exploitable for phylogenetic analyses and the amplification of the 12S rDNA gene showed less discriminating power than the amplification of the cox1 fragment. Phylogenetic analyses showed that the cox1 sequences obtained from five chimpanzee DNA faecal samples from Gabon and two from Cameroon cluster together with Mansonella perstans with high bootstrap support. Most of the remaining sequences clustered together within the genus Mansonella, but the species could not be resolved. Among the NHP species investigated, a significant association between filarial DNA detection and Oesophagostomum sp. and Necator sp. infection was observed only in gorillas.

Conclusions: To our knowledge, this is the first study reporting DNA from Mansonella spp. in faecal samples. Our results raise questions about the diversity and abundance of these parasites in wildlife, their role as sylvatic reservoirs and their potential for zoonotic transmission. Future studies should focus on detecting variants circulating in both human and NHPs, and improve the molecular information to resolve or support taxonomy classification based on morphological descriptions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13071-020-04184-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298833PMC
June 2020

High HIV burden and recent transmission chains in rural forest areas in southern Cameroon, where ancestors of HIV-1 have been identified in ape populations.

Infect Genet Evol 2020 10 18;84:104358. Epub 2020 May 18.

TransVIHMI, Institut de Recherche pour le Développement (IRD), INSERM, Université de Montpellier, Montpellier, France. Electronic address:

We studied HIV prevalence and genetic diversity in rural forest areas in Cameroon, where chimpanzee and gorilla populations infected with the ancestors of the different HIV-1 groups have been identified and transmitted to humans during the 20th century. A total of 2812 individuals were studied, 924 from south-central, 1116 from south-east and 772 from south-west Cameroon. Of 208 (7.4%) samples that were confirmed for HIV-1 infection all belong to HIV-1 group M. In all sites and in all age categories, HIV-1 prevalence was higher in women (160/1599 (10.0%)) as compared to men (48/1213 (4.0%)) with the highest prevalence in women aged between 25 and 34 years (>17%). For 188/208 (92.3%) HIV-1 positive individuals, a fragment of the pol gene was successfully amplified and sequenced. Phylogenetic analysis showed predominance of CRF02_AG (58%), a large diversity of subtypes (A, D, F2 and G), nine different CRFs and more than 12% URFs. Interestingly, 35/188 (18.6%) HIV-1 strains form 12 recent transmission chains. The majority of the clusters are composed of two (n = 8) or three (n = 3) sequences but one cluster included ten HIV-1 strains from women living in four different villages on a major road for logging concessions in the south-east (60 km distance). In the three regions of Cameroon where the ancestors of the four HIV-1 groups have been transmitted to humans, we observed a high HIV prevalence, especially in the southeast where HIV-1 M originated. Many factors allowing rapid establishment in the human population and subsequent rapid spread to urban areas of a new retrovirus or other pathogens of zoonotic origin are now present. Our study shows clearly that some rural areas should also be considered as hot-spots for HIV infection. Prevention efforts together with growing access to HIV diagnosis and antiretroviral treatment are urgently needed in these remote areas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.meegid.2020.104358DOI Listing
October 2020

A 40-Month Follow-Up of Ebola Virus Disease Survivors in Guinea (PostEbogui) Reveals Long-Term Detection of Ebola Viral Ribonucleic Acid in Semen and Breast Milk.

Open Forum Infect Dis 2019 Dec 8;6(12):ofz482. Epub 2019 Nov 8.

TransVIHMI, IRD/INSERM/Monpellier University, Montpellier, France.

Background: With the increasing frequency and impact of Ebola virus disease (EVD) outbreaks illustrated by recent epidemics, a good understanding of the extent of viral persistance or ribonucleic acid (RNA) detection in body fluids from survivors is urgently needed.

Methods: Ebola viral RNA shedding was studied with molecular assays in semen (n = 1368), urine (n = 1875), cervicovaginal fluid (n = 549), saliva (n = 900), breast milk (n = 168), and feces (n = 558) from EVD survivors in Guinea (PostEbogui cohort, n = 802) at a regular base period until 40 months after inclusion.

Results: Twenty-seven of 277 (9.8%) male survivors tested positive for Ebola RNA in at least 1 semen sample. The probability of remaining positive for Ebola RNA in semen was estimated at 93.02% and 60.12% after 3 and 6 months. Viral RNA in semen was more frequent in patients with eye pain ( = .036), joint pain ( = .047), and higher antibody levels to Ebola virus antigens (nucleoprotein [ = .001], glycoprotein [ = .05], and viral protein-40 [ = .05]). Ebola RNA was only rarely detected in the following body fluids from EVD survivors: saliva (1 of 454), urine (2 of 593), breast milk (2 of 168), cervicovaginal secretions (0 of 273), and feces (0 of 330). Ribonucleic acid was detected in breast milk 1 month after delivery but 500 days after discharge of Ebola treatment unit (ETU) in 1 woman who became pregnant 7 months after discharge from the ETU.

Conclusions: The frequency and potential long-term presence of viral RNA in semen confirmed that systematic prevention measures in male survivors are required. Our observation in breast milk suggests that our knowledge on viral reservoir in immune-privileged sites and its impact are still incomplete.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofz482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047953PMC
December 2019

Reply to Zhang et al.

J Infect Dis 2020 08;222(6):1065-1066

Recherches Translationelles sur le VIH et Maladies Infectieuses/Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement, and University of Montpellier, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiaa041DOI Listing
August 2020

Challenges of scale-up to dolutegravir-based regimens in sub-Saharan Africa.

AIDS 2020 04;34(5):783-787

TransVIHMI, Institut de Recherche pour le Développement (IRD)/INSERM//University of Montpellier, Montpellier, France.

Objective: Evaluate the potential effectiveness of the implementation of dolutegravir (DTG)-based regimens in patients on failing current antiretroviral treatment (ART) given the high levels of nucleoside reverse transcriptase inhibitor (NRTI) resistance in Togo.

Design: Patients on ART attending health facilities for routine follow-up visits and for whom HIV viral load test was performed were consecutively included.

Methods: Protease, reverse transcriptase and integrase fragments were sequenced and analyzed for presence of drug resistance mutations for patients with viral load more than 1000 copies/ml.

Results: Among 1681 patients, 320 (19.04%) had viral load more than 1000 copies/ml and 200 were tested for drug resistance mutations. Reverse transcriptase gene was successfully sequenced for 181/200 (90.5%) patients; 140/181 (77.4%) were resistant to NRTIs and non-NRTIs, 4/181 (2.2%) to NRTIs only and 18/181 (9.9%) to non-NRTIs only. Many viral strains accumulated mutations predicting resistance to NRTIs recommended in first and second-line DTG-based ART regimens. ART switch to a DTG-based regimen after viral load testing (viral load >1000 copies/ml) or blind switch without prior viral load testing to a new DTG-based first line, estimated 31% and 47.6% of patients to be potentially on functional DTG monotherapy respectively.

Conclusion: Overall, our results predict that, at the scale of sub-Saharan Africa a significant proportion of patients could be on functional monotherapy. To achieve the third 90 of UNAIDS objectives, implementation of DTG-based regimens should be accompanied with an accelerated scaling up of access to viral load. Studies designed to quantify the implications of use of suboptimal DTG-based regimens are also needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0000000000002470DOI Listing
April 2020

Distinct rates and patterns of spread of the major HIV-1 subtypes in Central and East Africa.

PLoS Pathog 2019 12 6;15(12):e1007976. Epub 2019 Dec 6.

KU Leuven, Department of Microbiology and Immunology, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Leuven, Belgium.

Since the ignition of the HIV-1 group M pandemic in the beginning of the 20th century, group M lineages have spread heterogeneously throughout the world. Subtype C spread rapidly through sub-Saharan Africa and is currently the dominant HIV lineage worldwide. Yet the epidemiological and evolutionary circumstances that contributed to its epidemiological expansion remain poorly understood. Here, we analyse 346 novel pol sequences from the DRC to compare the evolutionary dynamics of the main HIV-1 lineages, subtypes A1, C and D. Our results place the origins of subtype C in the 1950s in Mbuji-Mayi, the mining city of southern DRC, while subtypes A1 and D emerged in the capital city of Kinshasa, and subtypes H and J in the less accessible port city of Matadi. Following a 15-year period of local transmission in southern DRC, we find that subtype C spread at least three-fold faster than other subtypes circulating in Central and East Africa. In conclusion, our results shed light on the origins of HIV-1 main lineages and suggest that socio-historical rather than evolutionary factors may have determined the epidemiological fate of subtype C in sub-Saharan Africa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1007976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897401PMC
December 2019

Identification of a Novel Simian Immunodeficiency Virus-Infected African Green Monkey () Confirms that Tantalus Monkeys in Cameroon Are Infected with a Mosaic SIVagm Lineage.

AIDS Res Hum Retroviruses 2020 02 30;36(2):167-170. Epub 2019 Oct 30.

Recherches Translationnelles sur le VIH et Maladies Infectieuses, Institut National de la Santé et de la Recherche Médicale 1175, Institut de Recherche pour le Développement, University of Montpellier, Montpellier, France.

In this study we report on the identification of a simian immunodeficiency virus (SIV) infecting a from Cameroon. The isolate, SIVagmTAN-CA1, was molecularly characterized by sequencing partial genome (∼4,000 bp) using the conventional Sanger method and the Oxford Nanopore Technology (ONT). In and SIVagmTAN-CA1 clusters with SIVagmSAB infecting from West Africa, whereas in it clusters with SIVagmTAN infecting from Central Africa. This mosaic structure is similar to that of a previously reported isolate infecting another tantalus monkey from Cameroon and confirms that the evolution of SIVagm is complex. Our data show that ONT sequencing gives results comparable with conventional Sanger sequencing on SIV and could help in distinguishing recombination and coinfection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/AID.2019.0216DOI Listing
February 2020

Dolutegravir-Based or Low-Dose Efavirenz-Based Regimen for the Treatment of HIV-1.

N Engl J Med 2019 08 24;381(9):816-826. Epub 2019 Jul 24.

University of Dshang, Dshang (C.K.), and Central Hospital of Yaoundé (C.K.), Military Hospital of Yaoundé (M.M.-E.), and Cité Verte Hospital (P.O.B.), Yaoundé — all in Cameroon; Recherches Translationnelles sur le VIH et les Maladies Infectieuses (TransVIHMI), University of Montpellier–L’Institut de recherche pour le développement (IRD)–INSERM (S.E.-D., S.L., M.P., E.D.), and University Hospital of Montpellier (E.D.), Montpellier, and Sesstim, Aix Marseille University–IRD–INSERM, Marseille (S.B.) — all in France; and Geneva University Hospitals, Geneva (A.C.).

Background: An efavirenz-based regimen (with a 600-mg dose of efavirenz, known as EFV600) was the World Health Organization preferred first-line treatment for human immunodeficiency virus type 1 (HIV-1) infection until June 2018. Given concerns about side effects, dolutegravir-based and low-dose efavirenz-based combinations have been considered as first-line treatments for HIV-1 in resource-limited settings.

Methods: We conducted an open-label, multicenter, randomized, phase 3 noninferiority trial in Cameroon. Adults with HIV-1 infection who had not received antiretroviral therapy and had an HIV-1 RNA level (viral load) of at least 1000 copies per milliliter were randomly assigned to receive either dolutegravir or the reference treatment of low-dose efavirenz (a 400-mg dose, known as EFV400), combined with tenofovir and lamivudine. The primary end point was the proportion of participants with a viral load of less than 50 copies per milliliter at week 48, on the basis of the Food and Drug Administration snapshot algorithm. The difference between treatment groups was calculated, and noninferiority was tested with a margin of 10 percentage points.

Results: A total of 613 participants received at least one dose of the assigned regimen. At week 48, a viral load of less than 50 copies per milliliter was observed in 231 of 310 participants (74.5%) in the dolutegravir group and in 209 of 303 participants (69.0%) in the EFV400 group, with a difference of 5.5 percentage points (95% confidence interval [CI], -1.6 to 12.7; P<0.001 for noninferiority). Among those with a baseline viral load of at least 100,000 copies per milliliter, a viral load of less than 50 copies per milliliter was observed in 137 of 207 participants (66.2%) in the dolutegravir group and in 123 of 200 participants (61.5%) in the EFV400 group, with a difference of 4.7 percentage points (95% CI, -4.6 to 14.0). Virologic failure (a viral load of >1000 copies per milliliter) was observed in 3 participants in the dolutegravir group (with none acquiring drug-resistance mutations) and in 16 participants in the EFV400 group. More weight gain was observed in the dolutegravir group than in the EFV400 group (median weight gain, 5.0 kg vs. 3.0 kg; incidence of obesity, 12.3% vs. 5.4%).

Conclusions: In HIV-1-infected adults in Cameroon, a dolutegravir-based regimen was noninferior to an EFV400-based reference regimen with regard to viral suppression at week 48. Among participants who had a viral load of at least 100,000 copies per milliliter when antiretroviral therapy was initiated, fewer participants than expected had viral suppression. (Funded by Unitaid and the French National Agency for AIDS Research; NAMSAL ANRS 12313 ClinicalTrials.gov number, NCT02777229.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa1904340DOI Listing
August 2019

2018 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation.

Lancet Infect Dis 2019 06 15;19(6):641-647. Epub 2019 Apr 15.

Illumina, San Diego, CA, USA.

Background: The 2018 Ebola virus disease (EVD) outbreak in Équateur Province, Democratic Republic of the Congo, began on May 8, and was declared over on July 24; it resulted in 54 documented cases and 33 deaths. We did a retrospective genomic characterisation of the outbreak and assessed potential therapeutic agents and vaccine (medical countermeasures).

Methods: We used target-enrichment sequencing to produce Ebola virus genomes from samples obtained in the 2018 Équateur Province outbreak. Combining these genomes with genomes associated with known outbreaks from GenBank, we constructed a maximum-likelihood phylogenetic tree. In-silico analyses were used to assess potential mismatches between the outbreak strain and the probes and primers of diagnostic assays and the antigenic sites of the experimental rVSVΔG-ZEBOV-GP vaccine and therapeutics. An in-vitro flow cytometry assay was used to assess the binding capability of the individual components of the monoclonal antibody cocktail ZMapp.

Findings: A targeted sequencing approach produced 16 near-complete genomes. Phylogenetic analysis of these genomes and 1011 genomes from GenBank revealed a distinct cluster, confirming a new Ebola virus variant, for which we propose the name "Tumba". This new variant appears to have evolved at a slower rate than other Ebola virus variants (0·69 × 10 substitutions per site per year with "Tumba" vs 1·06 × 10 substitutions per site per year without "Tumba"). We found few sequence mismatches in the assessed assay target regions and antigenic sites. We identified nine amino acid changes in the Ebola virus surface glycoprotein, of which one resulted in reduced binding of the 13C6 antibody within the ZMapp cocktail.

Interpretation: Retrospectively, we show the feasibility of using genomics to rapidly characterise a new Ebola virus variant within the timeframe of an outbreak. Phylogenetic analysis provides further indications that these variants are evolving at differing rates. Rapid in-silico analyses can direct in-vitro experiments to quickly assess medical countermeasures.

Funding: Defense Biological Product Assurance Office.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(19)30124-0DOI Listing
June 2019

Medical countermeasures during the 2018 Ebola virus disease outbreak in the North Kivu and Ituri Provinces of the Democratic Republic of the Congo: a rapid genomic assessment.

Lancet Infect Dis 2019 06 15;19(6):648-657. Epub 2019 Apr 15.

Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.

Background: The real-time generation of information about pathogen genomes has become a vital goal for transmission analysis and characterisation in rapid outbreak responses. In response to the recently established genomic capacity in the Democratic Republic of the Congo, we explored the real-time generation of genomic information at the start of the 2018 Ebola virus disease (EVD) outbreak in North Kivu Province.

Methods: We used targeted-enrichment sequencing to produce two coding-complete Ebola virus genomes 5 days after declaration of the EVD outbreak in North Kivu. Subsequent sequencing efforts yielded an additional 46 genomes. Genomic information was used to assess early transmission, medical countermeasures, and evolution of Ebola virus.

Findings: The genomic information demonstrated that the EVD outbreak in the North Kivu and Ituri Provinces was distinct from the 2018 EVD outbreak in Équateur Province of the Democratic Republic of the Congo. Primer and probe mismatches to Ebola virus were identified in silico for all deployed diagnostic PCR assays, with the exception of the Cepheid GeneXpert GP assay.

Interpretation: The first two coding-complete genomes provided actionable information in real-time for the deployment of the rVSVΔG-ZEBOV-GP Ebola virus envelope glycoprotein vaccine, available therapeutics, and sequence-based diagnostic assays. Based on the mutations identified in the Ebola virus surface glycoprotein (GP) observed in all 48 genomes, deployed monoclonal antibody therapeutics (mAb114 and ZMapp) should be efficacious against the circulating Ebola virus variant. Rapid Ebola virus genomic characterisation should be included in routine EVD outbreak response procedures to ascertain efficacy of medical countermeasures.

Funding: Defense Biological Product Assurance Office.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(19)30118-5DOI Listing
June 2019

Earlier Initiation of Antiretroviral Treatment Coincides With an Initial Control of the HIV-1 Sub-Subtype F1 Outbreak Among Men-Having-Sex-With-Men in Flanders, Belgium.

Front Microbiol 2019 26;10:613. Epub 2019 Mar 26.

Laboratory of Clinical and Epidemiological Virology, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.

Human immunodeficiency virus type 1 (HIV-1) non-B subtype infections occurred in Belgium since the 1980s, mainly amongst migrants and heterosexuals, whereas subtype B predominated in men-having-sex-with-men (MSM). In the last decade, the diagnosis of F1 sub-subtype in particular has increased substantially, which prompted us to perform a detailed reconstruction of its epidemiological history. To this purpose, the Belgian AIDS Reference Laboratories collected HIV-1 sequences from all sub-subtype F1-infected patients for whom genotypic drug resistance testing was requested as part of routine clinical follow-up. This data was complemented with HIV-1 sequences from countries with a high burden of F1 infections or a potential role in the global origin of sub-subtype F1. The molecular epidemiology of the Belgian subtype F1 epidemic was investigated using Bayesian phylogenetic inference and transmission dynamics were characterized based on birth-death models. F1 sequences were retained from 297 patients diagnosed and linked to care in Belgium between 1988 and 2015. Phylogenetic inference indicated that among the 297 Belgian F1 sequences, 191 belonged to a monophyletic group that mainly contained sequences from people likely infected in Belgium (OR 26.67, 95% CI 9.59-74.15), diagnosed in Flanders (OR 7.28, 95% CI 4.23-12.53), diagnosed at a recent stage of infection (OR 7.19, 95% CI 2.88-17.95) or declared to be MSM (OR 34.8, 95% CI 16.0-75.6). Together with a Spanish clade, this Belgian clade was embedded in the genetic diversity of Brazilian subtype F1 strains and most probably emerged after one or only a few migration events from Brazil to the European continent before 2002. The origin of the Belgian outbreak was dated back to 2002 (95% higher posterior density 2000-2004) and birth-death models suggested that its extensive growth had been controlled ( < 1) by 2012, coinciding with a time period where delay in antiretroviral treatment initiation substantially declined. In conclusion, phylogenetic reconstruction of the Belgian HIV-1 sub-subtype F1 epidemic illustrates the introduction and substantial dissemination of viral strains in a geographically restricted risk group that was most likely controlled by effective treatment as prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2019.00613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443750PMC
March 2019

Prevalence of infection among asymptomatic and paucisymptomatic contact persons exposed to Ebola virus in Guinea: a retrospective, cross-sectional observational study.

Lancet Infect Dis 2019 03 11;19(3):308-316. Epub 2019 Feb 11.

Recherches translationnelles sur le VIH et les maladies infectieuses, Institut de Recherche pour le Développement, Institut National de la Santé et de la Recherche Médicale, Université de Montpellier, Montpellier, France. Electronic address:

Background: The prevalence of Ebola virus infection among people who have been in contact with patients with Ebola virus disease remains unclear, but is essential to understand the dynamics of transmission. This study aimed to identify risk factors for seropositivity and to estimate the prevalence of Ebola virus infection in unvaccinated contact persons.

Methods: In this retrospective, cross-sectional observational study, we recruited individuals between May 12, 2016, and Sept 8, 2017, who had been in physical contact with a patient with Ebola virus disease, from four medical centres in Guinea (Conakry, Macenta, N'zérékoré, and Forécariah). Contact persons had to be 7 years or older and not diagnosed with Ebola virus disease. Participants were selected through the Postebogui survivors' cohort. We collected self-reported information on exposure and occurrence of symptoms after exposure using a questionnaire, and tested antibody response against glycoprotein, nucleoprotein, and 40-kDa viral protein of Zaire Ebola virus by taking a blood sample. The prevalence of Ebola virus infection was estimated with a latent class model.

Findings: 1721 contact persons were interviewed and given blood tests, 331 of whom reported a history of vaccination so were excluded, resulting in a study population of 1390. Symptoms were reported by 216 (16%) contact persons. The median age of participants was 26 years (range 7-88) and 682 (49%) were male. Seropositivity was identified in 18 (8·33%, 95% CI 5·01-12·80) of 216 paucisymptomatic contact persons and 39 (3·32%, 5·01-12·80) of 1174 (2-4) asymptomatic individuals (p=0·0021). Seropositivity increased with participation in burial rituals (adjusted odds ratio [aOR] 2·30, 95% CI 1·21-4·17; p=0·0079) and exposure to blood or vomit (aOR 2·15, 1·23-3·91; p=0·0090). Frequency of Ebola virus infection varied from 3·06% (95% CI 1·84-5·05) in asymptomatic contact persons who did not participate in burial rituals to 5·98% (2·81-8·18) in those who did, and from 7·17% (3·94-9·09) in paucisymptomatic contact persons who did not participate in burial rituals to 17·16% (12·42-22·31) among those who did.

Interpretation: This study provides a new assessment of the prevalence of Ebola virus infection among contact persons according to exposure, provides evidence for the occurrence of paucisymptomatic cases, and reinforces the importance of closely monitoring at-risk contact persons.

Funding: Institut National de la Santé et de la Recherche Médicale, Reacting, the French Ebola Task Force, Institut de Recherche pour le Développement, and Montpellier University Of Excellence-University of Montpellier.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(18)30649-2DOI Listing
March 2019

High level of treatment failure and drug resistance to first-line antiretroviral therapies among HIV-infected children receiving decentralized care in Senegal.

BMC Pediatr 2019 02 5;19(1):47. Epub 2019 Feb 5.

Bacteriology-Virology Laboratory, A. Le Dantec CHU, Cheikh Anta Diop University, Dakar, Senegal.

Background: In Senegal in 2015, an estimated 4800 children were living with HIV, with 1200 receiving ARV treatment, of whom half had follow-up care in decentralized sites outside Dakar. However, until now no studies have determined the efficacy of pediatric treatment in decentralized settings, even though the emergence of viral resistance, particularly among children in Africa, is a well-known phenomenon. This study aimed to assess the virological status of HIV-infected children in all decentralized facilities to help improve access to quality care.

Methods: A cross-sectional epidemiological and virological study was conducted in all of Senegal's regions, except Dakar, between March and June 2015 and sought to include all HIV-infected children and adolescents (0-19 years), treated or not with ARVs. Socio-demographic and clinical data and a blood sample on blotting paper were collected for children from treatment sites. Samples were routed on public transportation, assisted by a network of community health workers. A viral load (VL) assay was performed for each child, followed by genotyping when it exceeded 1000 copies/mL (3 log).

Results: Of the 851 identified children, 666 (78%) were enrolled in the study. Half of the children were girls, and the average age was 8 years (6 months-19 years). Most of the children (96.7%) were infected with HIV-1, and 90% were treated with ART, primarily with AZT + 3TC + NVP/EFV therapeutic regimen. The median duration of time on ART was 21 months (1-129). VL was measured for 2% of children before this study. Almost two-thirds (64%) of the children are experiencing virological failure. Among them, there was resistance to at least one drug for 86.5% of cases. Also, 25% children presented resistance to one drug and 40% to two out of three. For nearly one-third of the children presenting resistance, none of the three drugs of the treatment was active. Factors associated with virological failure were male sex, follow-up by a generalist rather than a specialist, and treatment interruptions.

Conclusions: We observed a high level of virological failure and a high percentage of viral resistance among children receiving health care in decentralized facilities in Senegal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12887-019-1420-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362577PMC
February 2019

CD4 receptor diversity in chimpanzees protects against SIV infection.

Proc Natl Acad Sci U S A 2019 02 4;116(8):3229-3238. Epub 2019 Feb 4.

Sanaga-Yong Chimpanzee Rescue Center, In Defense of Animals-Africa, Portland, OR 97204.

Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells. Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions. Testing the replication fitness of SIVcpz strains in CD4 T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts. These differences were recapitulated in CD4 transfection assays, which revealed a strong association between CD4 genotypes and SIVcpz infection phenotypes. The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles. In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition. CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan. CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep. One allele was associated with lower SIVcpz prevalence rates in the wild. These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry. Although some SIVcpz strains have adapted to utilize these variants, CD4 diversity is maintained, protecting chimpanzees against infection with SIVcpz and other SIVs to which they are exposed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1821197116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386711PMC
February 2019

Understanding Ebola virus and other zoonotic transmission risks through human-bat contacts: Exploratory study on knowledge, attitudes and practices in Southern Cameroon.

Zoonoses Public Health 2019 05 24;66(3):288-295. Epub 2019 Jan 24.

TransVIHMI, Institut de Recherche pour le Développement (IRD), University of Montpellier, INSERM, Montpellier, France.

The ecology of Ebola virus (EBV) remains largely unknown, but the previous detection of viral RNA and anti-EBV antibodies in African bats suggests that they might play a role in the EBV reservoir. Moreover, African bats also carry other potentially zoonotic agents such as Henipah-like viruses, coronaviruses and lyssaviruses. Today only little information is available on interactions between humans and bats. The objective of our exploratory study was to describe the extent and modes of contacts between humans and bats in southern Cameroon, considered as an area at risk for future EBV outbreaks. The survey was conducted in 11 villages of four distinct rural areas in southern Cameroon. A total of 135 respondents were interviewed using semi-structured questionnaires, between February and May 2017. The study showed that direct contacts between bats and humans are relatively common. Bat bushmeat appeared to be an occasional meat resource; 40% of respondents consume bats with a median annual consumption of three, and 28% of respondents hunt them. About 22% of the respondents reported children catching bats. Indirect contact also appeared to be common; 55% of hunters use caves as shelters and 67% of interviewees eat fruits previously chewed by bats. Bat consumption varied significantly between regions (from 0% to 87%) and between pygmies and bantus in the extreme south-east of Cameroon. The study revealed considerable diversity in practices among interviewees, most of them being subsistence cultivators and relying on self-hunted bushmeat. Geographical diversity of contacts and perceptions regarding bats in Cameroon emphasizes the need to adjust zoonotic pathogen surveillance and education campaigns to the specificities of the communities and their context of interaction with wildlife.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/zph.12563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165775PMC
May 2019

Extensive Serological Survey of Multiple African Nonhuman Primate Species Reveals Low Prevalence of Immunoglobulin G Antibodies to 4 Ebola Virus Species.

J Infect Dis 2019 10;220(10):1599-1608

Recherches Translationelles sur VIH et Maladies Infectieuses/Institut national de la santé et de la recherche médicale, Institut de Recherche pour le Développement and University of Montpellier, France.

Bats are considered a reservoir species for Ebola viruses, but nonhuman primates (NHPs) have represented a source of infection in several outbreaks in humans. Here we report serological screening of blood or fecal samples from monkeys (n = 2322) and apes (n = 2327). Thirty-six NHP species from Cameroon, Democratic Republic of the Congo, and Ivory Coast were tested with a sensitive and specific Luminex-based assay for immunoglobulin G antibodies to 4 Ebola virus species. Using the simultaneous presence of antibodies to nucleoproteins and glycoproteins to define positivity, we showed that specific Ebola virus antibodies are not widespread among NHPs. Only 1 mustached monkey (Cercopithecus cephus) from Cameroon was positive for Sudan ebolavirus. These observations support that NHPs are most likely intermediate hosts for Ebola viruses. With the increasing frequency of Ebola outbreaks, it is crucial to identify the animal reservoir and understand the ecology of Ebola viruses to inform disease control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiz006DOI Listing
October 2019

Noninvasive western lowland gorilla's health monitoring: A decade of simian immunodeficiency virus surveillance in southern Cameroon.

Ecol Evol 2018 Nov 25;8(22):10698-10710. Epub 2018 Oct 25.

TransVIHMI Institut de Recherche pour le Développement (IRD) Institut national de la santé et de la recherche médicale (INSERM) Université de Montpellier Montpellier France.

Simian immunodeficiency virus (SIVgor) causes persistent infection in critically endangered western lowland gorillas () from west central Africa. SIVgor is closely related to chimpanzee and human immunodeficiency viruses (SIVcpz and HIV-1, respectively). We established a noninvasive method that does not interfere with gorillas' natural behaviour to provide wildlife pathogen surveillance and health monitoring for conservation. A total of 1,665 geo-referenced fecal samples were collected at regular intervals from February 2006 to December 2014 (123 sampling days) in the Campo-Ma'an National Park (southwest Cameroon). Host genotyping was performed using microsatellite markers, SIVgor infection was identified by serology and genetic amplification was attempted on seropositive individuals. We identified at least 125 distinct gorillas, 50 were resampled (observed 3.5 times in average) and 38 were SIVgor+ (seven individuals were seroconverters). Six groups of gorillas were identified based on the overlapping occurrence of individuals with apparent high rates of gene flow. We obtained SIVgor genetic sequences from 25 of 38 seropositive genotyped gorillas and showed that the virus follows exponential growth dynamics under a strict molecular clock. Different groups shared SIVgor lineages demonstrating intergroup viral spread and recapture of positive individuals illustrated intra-host viral evolution. Relatedness and relationship genetic analysis of gorillas together with Bayesian phylogenetic inference of SIVgor provided evidence suggestive of vertical transmission. In conclusion, we provided insights into gorilla social dynamics and SIVgor evolution and emphasized the utility of noninvasive sampling to study wildlife health populations. These findings contribute to prospective planning for better monitoring and conservation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ece3.4478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262910PMC
November 2018

Prevalence of pretreatment HIV drug resistance in West African and Southeast Asian countries.

J Antimicrob Chemother 2019 02;74(2):462-467

IRD UMI-233, INSERM U1175, Université de Montpellier, Unité TransVIHMI, Montpellier, France.

Background: ART in the developing world has moved to a new era with the WHO recommendation to test and immediately treat HIV-positive individuals. A high frequency of pretreatment HIV drug resistance (PDR) can compromise ART efficacy. Our study presents updated estimates of PDR in seven countries from West Africa (Burkina Faso, Cameroon, Côte d'Ivoire, Mali and Togo) and Southeast Asia (Thailand and Vietnam).

Methods: Eligible study participants were adult ART initiators, recruited from December 2015 to November 2016 in major ART clinics in each country. HIV drug resistance (HIVDR) tests were performed for all specimens and interpretation was done using the Stanford algorithm.

Results: Overall, 1153 participants were recruited and 1020 nt sequences were generated. PDR frequency among all initiators was 15.9% (95% CI: 13.8%-18.3%) overall, ranging from 9.6% and 10.2% in Burkina Faso and Thailand, respectively, 14.7% in Vietnam, 15.4% in Mali, 16.5% in Côte d'Ivoire and 19.3% in Cameroon, to 24.6% in Togo. The prevalence of NNRTI resistance mutations was 12%; NRTI and PI PDR prevalences were 4% and 3%, respectively.

Conclusions: Our study shows that in most countries PDR exceeded 10%, warranting the conduct of nationally representative surveys to confirm this trend. In the meantime, actions to prevent drug resistance, including transition from NNRTIs to more robust drug classes should be urgently implemented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dky443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337899PMC
February 2019

Survey of Ebola Viruses in Frugivorous and Insectivorous Bats in Guinea, Cameroon, and the Democratic Republic of the Congo, 2015-2017.

Emerg Infect Dis 2018 12 17;24(12):2228-2240. Epub 2018 Dec 17.

To clarify the role of bats in the ecology of Ebola viruses, we assessed the prevalence of Ebola virus antibodies in a large-scale sample of bats collected during 2015-2017 from countries in Africa that have had previous Ebola outbreaks (Guinea, the Democratic Republic of the Congo) or are at high risk for outbreaks (Cameroon). We analyzed 4,022 blood samples of bats from >12 frugivorous and 27 insectivorous species; 2-37 (0.05%-0.92%) bats were seropositive for Zaire and 0-30 (0%-0.75%) bats for Sudan Ebola viruses. We observed Ebola virus antibodies in 1 insectivorous bat genus and 6 frugivorous bat species. Certain bat species widespread across Africa had serologic evidence of Zaire and Sudan Ebola viruses. No viral RNA was detected in the subset of samples tested (n = 665). Ongoing surveillance of bats and other potential animal reservoirs are required to predict and prepare for future outbreaks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2412.180740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256401PMC
December 2018