Ahidjo Ayouba

Self-reactive antibodies (natural autoantibodies) in healthy individuals

Antibodies that are present in the serum of healthy individuals in the absence of deliberate immunization with any antigen, are refered to as natural antibodies. A vast majority of natural antibodies react with one or more self antigens and are termed as natural autoantibodies. The importance of natural autoantibodies in immune regulation has long been neglected, since tolerance to self was thought to be primarily dependent on the deletion of autoreactive clones, rather than on peripheral suppressive mechanisms. Clonal deletion and energy cannot account, however, for the prevalence of natural autoreactivity among healthy individuals. It is now well established that autoreactive antibodies and B cells, and autoreactive T cells, are present in healthy individuals, and in virtually all vertebrate species. Autoreactive repertoires are predominantly selected early in ontogeny. Questions pertaining to the role of natural antibodies in the regulation of the immune response and maintenance of immune homeostasis and to the distinction between natural autoreactivity and pathological autoimmunity have not been adequately addressed. Here, we focus on the current knowledge on the physicochemical and functional properties of NAA in man, and the use of NAA for therapeutic intervention. reserved.

Low Prevalence of HIV Type 1 Drug Resistance Mutations in Untreated, Recently Infected Patients from Burkina Faso, Côte d'Ivoire, Senegal, Thailand, and Vietnam: The ANRS 12134 Study

The frequency of transmitted HIV drug resistance (HIVDR) was evaluated in the context of rapid scale-up of antiretroviral treatment in Thailand, Vietnam, Burkina Faso, Côte dIvoire, and Senegal by using an adaptation of the WHO generic protocol of the HIV Drug Resistance Threshold Survey (HIVDR-TS) for sample collection and classification. Resistance-associated mutations were interpreted using the 2009 WHO list for epidemiological surveys. We included 266 subjects from the five study sites. Of the 266 RT and PR sequences analyzed, two from Vietnam harbored virus with major drug resistance mutations (G190A in RT for one individual and M46I in PR for the second individual). Phylogenetic analysis revealed that CRF01_AE predominates (>90%) in Thailand and Vietnam. CRF02 (>65%) cocirculates with other HIV-1 variants in Senegal and Côte dIvoire. The prevalence of HIVDRM is scored as low (< or = 5%) in all the five sites for the three drug classes analyzed. A continuous population survey for HIVDRM will provide a rational basis for maintaining or changing the current first line regimen in these countries.

Low Prevalence of Drug Resistance Transmitted Virus in HIV Type 1-Infected ARV-Naive Patients in Cambodia

Abstract Between November 2006 and June 2007, HIV-1 reverse transcriptase (RT) and protease (PR) genes of 67 ARV-naive Cambodian patients were amplified and sequenced. At inclusion, the median age and duration of HIV infection were 28 and 1.1 years, respectively. The median CD4 and HIV-1 RNA were 611 cells/ml [IQR: 525-759] and 4.0 log(10) copies/ml [IQR: 3.4-4.6]. Among 67 HIV-1 strains, 95.5% were CRF 01_AE viruses (n = 64) whereas three clustered with subtype B. RT analysis indicated that only 1 patient out of 67, presenting K103N and M184V mutations, was resistant to NVP/EFV and 3TC/FTC. No primary resistance to protease inhibitors was detected in 59 amplified protease genes. The 1.49% (IC 95%: 0.04-8.04%) prevalence of transmitted drug-resistant strains in drug-naive patients was low in our study. Surveys of drug-resistant transmitted viruses should be regularly performed regarding the increasing access to HAART in Cambodia.

Novel multiplexed HIV/simian immunodeficiency virus antibody detection assay.

This assay identified new simian immunodeficiency viruses in primate bushmeat.

Specific stimulation of HIV-1 replication in human placental trophoblasts by an antigen of Plasmodium falciparum.

Epidemiological data point to an increased risk of HIV-1 mother-to-child transmission in pregnant women with malaria, by unknown mechanisms. We show here that surface binding of a recombinant Plasmodium falciparum adhesin to chondroitin sulphate A proteoglycans increases HIV-1 replication in the human placental cell line BeWo, probably by a P. falciparum adhesin-induced long-terminal repeat-driven TNF-α stimulation. This suggests that placental malaria could increase the risk of HIV-1 transmission in utero.

Multidisciplinary assessment of post-Ebola sequelae in Guinea (Postebogui): an observational cohort study

BACKGROUNDnThe high number of survivors from the 2013-16 west African outbreak of Ebola virus disease (EVD) has raised several new issues: long-term clinical complications, psychosocial consequences, risks of EVD reactivation, and secondary transmission due to viral persistence in body fluids. We aimed to assess long-term clinical, psychosocial, and viral outcomes in EVD survivors in Guinea.nnnMETHODSnIn this multidisciplinary observational cohort study, we recruited patients aged 1 year or more in four sites in Guinea (Donka National Hospital, Conakry; Macenta Prefectoral Hospital, Macenta; Nzérékoré Regional Hospital, Nzérékoré; and Forécariah Prefectoral Hospital, Forécariah) following discharge from any Ebola treatment centre in Guinea. Eligible patients had had laboratory-confirmed EVD and had then been declared clear of the virus in the blood. All consenting patients were included, with no exclusion criteria. Trained clinicians assessed patients at enrolment to the cohort, recording clinical symptoms and signs of depression. We did routine blood examinations and examined viral persistence in body fluids using RT-PCR. We did psychological evaluations using questionnaires developed for different age groups. Follow-up is planned to 2 years, and here we present findings at enrolment.nnnFINDINGSnBetween March 23, 2015, and July 11, 2016, we recruited 802 patients, of whom 360 (45%) were male, 442 (55%) were female; 158 (20%) were younger than 18 years. The median age was 28·4 years (range 1·0-79·9, IQR 19·4-39·8). The median delay after discharge was 350 days (IQR 223-491). The most frequent symptoms were general symptoms (324 [40%] patients), musculoskeletal pain (303 [38%]), headache (278 [35%]), depression (124 [17%] of 713 responses), abdominal pain (178 [22%]), and ocular disorders (142 [18%]). More adults than children had at least one clinical symptom (505 [78%] vs 101 [64%], p<0·0003), ocular complications (124 [19%] vs 18 [11%], p=0·0200), or musculoskeletal symptoms (274 [43%] vs 29 [18%], p<0·0001). A positive RT-PCR in semen was found in ten (5%) of 188 men, at a maximum of 548 days after disease onset. 204 (26%) of 793 patients reported stigmatisation. Ocular complications were more frequent at enrolment than at discharge (142 [18%] vs 61 [8%] patients).nnnINTERPRETATIONnPost-EVD symptoms can remain long after recovery and long-term viral persistence in semen is confirmed. The results justify calls for regular check-ups of survivors at least 18 months after recovery.nnnFUNDINGnINSERM/Reacting, the French Ebola Task Force, and Institut de Recherche pour le Développement.

Antiretroviral treatment outcome in HIV-1-infected patients routinely followed up in capital cities and remote areas of Senegal, Mali and Guinea-Conakry

Access to antiretroviral treatment (ART) becomes more and more effective in resource‐limited settings (RLS). However, this global effort would be even more profitable if the access to laboratory services especially in decentralized settings was strengthened. We report the virological outcome and HIV‐1 drug resistance in three West African countries using dried blood spots (DBS) samples.

Simian Immunodeficiency Viruses and the Origin of HIVs

Reconstruction of the phylogenetic relationships between the human lentiviruses responsible for the AIDS epidemic and lentiviruses from African nonhuman primates can help clarify the origin of the AIDS pandemic. These studies have several scientific—and public health—implications, although the detailed circumstances of such zoonotic events are still not fully understood. As the potential for simian-to-simian, simian-tohuman, and human-to-human transmission of lentiviruses becomes better understood, the emergence of new and/or more virulent lentiviral strains, capable of causing new epidemics, needs to be considered. Multidisciplinary field studies remain important. It also appears clear that studies of simian lentiviral infections can advance our understanding of HIV’s pathogenesis, an understanding necessary for the development of effective AIDS vaccines and therapeutics.

High Rate of Simian Immunodeficiency Virus (SIV) Infections in Wild Chimpanzees in Northeastern Gabon

The emergence of HIV-1 groups M, N, O, and P is the result of four independent cross-species transmissions between chimpanzees (cpz) and gorillas (gor) from central/south Cameroon and humans respectively. Although the first two SIVcpz were identified in wild-born captive chimpanzees in Gabon in 1989, no study has been conducted so far in wild chimpanzees in Gabon. To document the SIVcpz infection rate, genetic diversity, and routes of virus transmission, we analyzed 1458 faecal samples collected in 16 different locations across the country, and we conducted follow-up missions in two of them. We found 380 SIV antibody positive samples in 6 different locations in the north and northeast. We determined the number of individuals collected by microsatellite analysis and obtained an adjusted SIV prevalence of 39.45%. We performed parental analysis to investigate viral spread between and within communities and found that SIVs were epidemiologically linked and were transmitted by both horizontal and vertical routes. We amplified pol and gp41 fragments and obtained 57 new SIVcpzPtt strains from three sites. All strains, but one, clustered together within a specific phylogeographic clade. Given that these SIV positive samples have been collected nearby villages and that humans continue to encroach in ape’s territories, the emergence of a new HIV in this area needs to be considered.

Prevalence of HIV-1 drug resistance mutations in antiretroviral naïve pregnant women from Cambodia, Cameroon, Central African Republic and Vietnam

ss Open Acce Oral presentation Prevalence of HIV-1 drug resistance mutations in antiretroviral naive pregnant women from Cambodia, Cameroon, Central African Republic and Vietnam Ahidjo Ayouba*1, Lenaig Le Fouler2, Truong TX Lien3, Nary Ly4, Valerie Marechal5, Aurelia Vessiere1, Anfumbom Kfutwah1, Jean Marc Reynes4, Elisabeth Menu6, Eric Nerrienet1, Muriel Vray2, Herve Fleury7 and Francoise Barre-Sinoussi6