Author
Nicole Vidal
Other affiliations: University of Lomé, University of Montpellier, French Institute of Health and Medical Research ...read more
Bio: Nicole Vidal is an academic researcher from Institut de recherche pour le développement. The author has contributed to research in topics: Population & Ebola virus. The author has an hindex of 28, co-authored 71 publications receiving 2664 citations. Previous affiliations of Nicole Vidal include University of Lomé & University of Montpellier.
Topics: Population, Ebola virus, Drug resistance, Viral load, Phylogenetic tree
Papers published on a yearly basis
Papers
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TL;DR: The high number of HIV-1 subtypes cocirculating, the high intrasubtype diversity, and the high numbers of possible recombinant viruses as well as different unclassified strains are all in agreement with an old and mature epidemic in the DRC, suggesting that this region is the epicenter of HIV -1 group M.
Abstract: The purpose of this study was to document the genetic diversity of human immunodeficiency virus type 1 (HIV-1) in the Democratic Republic of Congo (DRC; formerly Zaire). A total of 247 HIV-1-positive samples, collected during an epidemiologic survey conducted in 1997 in three regions (Kinshasa [the capital], Bwamanda [in the north], and Mbuyi-Maya [in the south]), were genetically characterized in the env V3-V5 region. All known subtypes were found to cocirculate, and for 6% of the samples the subtype could not be identified. Subtype A is predominant, with prevalences decreasing from north to south (69% in the north, 53% in the capital city, and 46% in the south). Subtype C, D, G, and H prevalences range from 7 to 9%, whereas subtype F, J, K, and CRF01-AE strains represent 2 to 4% of the samples; only one subtype B strain was identified. The highest prevalence (25%) of subtype C was in the south, and CRF01-AE was seen mainly in the north. The high intersubtype variability among the V3-V5 sequences is the most probable reason for the low (45%) efficiency of subtype A-specific PCR and HMA (heteroduplex mobility assay). Eighteen (29%) of 62 samples had discordant subtype designations between env and gag. Sequence analysis of the entire envelope from 13 samples confirmed the high degree of diversity and complexity of HIV-1 strains in the DRC; 9 had a complex recombinant structure in gp160, involving fragments of known and unknown subtypes. Interestingly, the unknown fragments from the different strains did not cluster together. Overall, the high number of HIV-1 subtypes cocirculating, the high intrasubtype diversity, and the high numbers of possible recombinant viruses as well as different unclassified strains are all in agreement with an old and mature epidemic in the DRC, suggesting that this region is the epicenter of HIV-1 group M.
334 citations
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Rega Institute for Medical Research1, University of Barcelona2, Tufts University3, Stanford University4, University of Amsterdam5, World Health Organization6, Karolinska University Hospital7, University of Tartu8, University of Venda9, Public Health Agency of Canada10, Erasmus University Rotterdam11, Simon Fraser University12, Systems Research Institute13, Harvard University14, Paris Diderot University15, University College Dublin16, Grant Medical College and Sir Jamshedjee Jeejeebhoy Group of Hospitals17, Global Viral18, Johns Hopkins University School of Medicine19, University of Bordeaux20, Necker-Enfants Malades Hospital21, National Institutes of Health22, University of British Columbia23, Kanazawa University24, Mahidol University25, Walter Reed Army Institute of Research26, Chinese Academy of Sciences27, University of Malaya28, Indian Council of Medical Research29, Institut de recherche pour le développement30, University of Ljubljana31, University of California, San Francisco32, University of Edinburgh33, Chulalongkorn University34, University of California, San Diego35, Federal University of Rio de Janeiro36, Carlos III Health Institute37, University of Belgrade38, Universidade Federal de Goiás39, Centers for Disease Control and Prevention40
TL;DR: Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains.
Abstract: Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naive individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05–1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06–1.25), North America (OR = 1.19; 95% CI: 1.12–1.26), Europe (OR = 1.07; 95% CI: 1.01–1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12–1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92–1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling.Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.
206 citations
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Joris Hemelaar1, Ramyiadarsini Elangovan1, Jason Yun1, Leslie Dickson-Tetteh1 +178 more•Institutions (18)
TL;DR: The distribution of HIV-1 subtypes and recombinants changed over time in countries, regions, and globally as well as at a global level during 2005-15, where subtype B increased, subtypes A and D were stable, and subtypes C and G and CRF02_AG decreased.
Abstract: Summary Background Global genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes and recombinants during 1990–2015. Methods We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published between Jan 1, 1990, and Dec 31, 2015. We collected additional unpublished HIV-1 subtyping data through a global survey. We included prevalence studies with HIV-1 subtyping data collected during 1990–2015. We grouped countries into 14 regions and analysed data for four time periods (1990–99, 2000–04, 2005–09, and 2010–15). The distribution of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV (PLHIV) in each country to generate regional and global estimates of HIV-1 diversity in each time period. The primary outcome was the number of samples designated as HIV-1 subtypes A, B, C, D, F, G, H, J, K, CRFs, and URFs. The systematic review is registered with PROSPERO, number CRD42017067164. Findings This systematic review and global survey yielded 2203 datasets with 383 519 samples from 116 countries in 1990–2015. Globally, subtype C accounted for 46·6% (16 280 897/34 921 639 of PLHIV) of all HIV-1 infections in 2010–15. Subtype B was responsible for 12·1% (4 235 299/34 921 639) of infections, followed by subtype A (10·3%; 3 587 003/34 921 639), CRF02_AG (7·7%; 2 705 110/34 921 639), CRF01_AE (5·3%; 1 840 982/34 921 639), subtype G (4·6%; 1 591 276/34 921 639), and subtype D (2·7%; 926 255/34 921 639). Subtypes F, H, J, and K combined accounted for 0·9% (311 332/34 921 639) of infections. Other CRFs accounted for 3·7% (1 309 082/34 921 639), bringing the proportion of all CRFs to 16·7% (5 844 113/34 921 639). URFs constituted 6·1% (2 134 405/34 921 639), resulting in recombinants accounting for 22·8% (7 978 517/34 921 639) of all global HIV-1 infections. The distribution of HIV-1 subtypes and recombinants changed over time in countries, regions, and globally. At a global level during 2005–15, subtype B increased, subtypes A and D were stable, and subtypes C and G and CRF02_AG decreased. CRF01_AE, other CRFs, and URFs increased, leading to a consistent increase in the global proportion of recombinants over time. Interpretation Global and regional HIV diversity is complex and evolving, and is a major challenge to HIV vaccine development. Surveillance of the global molecular epidemiology of HIV-1 remains crucial for the design, testing, and implementation of HIV vaccines. Funding None.
189 citations
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TL;DR: It appears that the two set primers are highly specific of T. vaginalis and provide a useful tool for PCR diagnosis in asymptomatic and symptomatic patients especially among the HIV at risk individuals.
Abstract: Trichomoniasis is recognised as a major sexually transmitted disease (STD) in the world and may act as an acquired immunodeficiency syndromes (AIDS) co-factor by enhancing the transmission of human immunodeficiency virus (HIV). Diagnosis of Trichomonas vaginalis can be achieved by several methods, but sensitive detection means are still lacking. In this study a 2000-bp repeated DNA fragment of T. vaginalis was cloned. Part of a conserved region of this insert was sequenced, two primers (TVK3 and TVK4) were chosen and a highly sensitive detection by polymerase chain reaction (PCR) was then developed for T. vaginalis. All strains of T. vaginalis analysed with these primers gave the expected 350-bp fragment and a 450-bp additional fragment. Sequence analysis of these PCR amplification products revealed that the 450-bp fragment contained the 350-bp with a 100-bp insertion characterised by a TGG microsatellite. A second primer set, namely TVK3 and TVK7 (determined at the border of the insertion), yielded PCR products of expected sizes. After amplification we were able to detect a single parasite. We also detected T. vaginalis in vaginal fluids of patients with STD. There was no reaction with human DNA or other infectious agents. It appears that the two set primers are highly specific of T. vaginalis and provide a useful tool for PCR diagnosis in asymptomatic and symptomatic patients especially among the HIV at risk individuals.
138 citations
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TL;DR: The equidistance of subtype K to the other subtypes of HIV-1 suggests that this subtype existed as long as the others, the lower distance between B and D, and between F1 and F2 suggest a more recent subdivision for these latter strains.
Abstract: We recently reported a high divergence among African subtype F strains. Three well-separated groups (F1, F2, and F3) have been shown based on the phylogenetic analysis of the p24 gag and envelope sequences with genetic distances similar to those observed for known subtypes. In this study, we characterized the near-full-length genomes of two strains from epidemiological unlinked individual belonging to each of the subgroups: F1 (96FR-MP411), F2 (95CM-MP255 and 95CM-MP257), and F3 (96CM-MP535 and 97ZR-EQTB11). Phylogenetic analysis of the near-full-length sequences and for each of the genes separately showed the same three groups, supported by high bootstrap values. Diversity plotting, BLAST subtyping, and bootstrap plotting confirmed that the divergent F strains correspond to nonrecombinant viruses. The divergence between F1 and F2 is consistently lower than that seen in any other intersubtype comparison, with the exception of subtypes B and D. Based on all the different analyses, we propose to divide subt...
114 citations
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TL;DR: FastTree as mentioned in this paper uses sequence profiles of internal nodes in the tree to implement neighbor-joining and uses heuristics to quickly identify candidate joins, then uses nearest-neighbor interchanges to reduce the length of the tree.
Abstract: Gene families are growing rapidly, but standard methods for inferring phylogenies do not scale to alignments with over 10,000 sequences. We present FastTree, a method for constructing large phylogenies and for estimating their reliability. Instead of storing a distance matrix, FastTree stores sequence profiles of internal nodes in the tree. FastTree uses these profiles to implement neighbor-joining and uses heuristics to quickly identify candidate joins. FastTree then uses nearest-neighbor interchanges to reduce the length of the tree. For an alignment with N sequences, L sites, and a different characters, a distance matrix requires O(N^2) space and O(N^2 L) time, but FastTree requires just O( NLa + N sqrt(N) ) memory and O( N sqrt(N) log(N) L a ) time. To estimate the tree's reliability, FastTree uses local bootstrapping, which gives another 100-fold speedup over a distance matrix. For example, FastTree computed a tree and support values for 158,022 distinct 16S ribosomal RNAs in 17 hours and 2.4 gigabytes of memory. Just computing pairwise Jukes-Cantor distances and storing them, without inferring a tree or bootstrapping, would require 17 hours and 50 gigabytes of memory. In simulations, FastTree was slightly more accurate than neighbor joining, BIONJ, or FastME; on genuine alignments, FastTree's topologies had higher likelihoods. FastTree is available at http://microbesonline.org/fasttree.
2,436 citations
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TL;DR: Tracing the genetic changes that occurred as SIVs crossed from monkeys to apes and from apes to humans provides a new framework to examine the requirements of successful host switches and to gauge future zoonotic risk.
Abstract: Acquired Immune Deficiency Syndrome (AIDS) was first recognized as a new disease in 1981 when increasing numbers of young homosexual men succumbed to unusual opportunistic infections and rare malignancies (CDC 1981; Greene 2007). A retrovirus, now termed human immunodeficiency virus type 1 (HIV-1), was subsequently identified as the causative agent of what has since become one of the most devastating infectious diseases to have emerged in recent history (Barre-Sinoussi et al. 1983; Gallo et al. 1984; Popovic et al. 1984). HIV-1 spreads by sexual, percutaneous, and perinatal routes (Hladik and McElrath 2008; Cohen et al. 2011); however, 80% of adults acquire HIV-1 following exposure at mucosal surfaces, and AIDS is thus primarily a sexually transmitted disease (Hladik and McElrath 2008; Cohen et al. 2011). Since its first identification almost three decades ago, the pandemic form of HIV-1, also called the main (M) group, has infected at least 60 million people and caused more than 25 million deaths (Merson et al. 2008). Developing countries have experienced the greatest HIV/AIDS morbidity and mortality, with the highest prevalence rates recorded in young adults in sub-Saharan Africa (http://www.unaids.org/). Although antiretroviral treatment has reduced the toll of AIDS- related deaths, access to therapy is not universal, and the prospects of curative treatments and an effective vaccine are uncertain (Barouch 2008; Richman et al. 2009). Thus, AIDS will continue to pose a significant public health threat for decades to come.
Ever since HIV-1 was first discovered, the reasons for its sudden emergence, epidemic spread, and unique pathogenicity have been a subject of intense study. A first clue came in 1986 when a morphologically similar but antigenically distinct virus was found to cause AIDS in patients in western Africa (Clavel et al. 1986). Curiously, this new virus, termed human immunodeficiency virus type 2 (HIV-2), was only distantly related to HIV-1, but was closely related to a simian virus that caused immunodeficiency in captive macaques (Chakrabarti et al. 1987; Guyader et al. 1987). Soon thereafter, additional viruses, collectively termed simian immunodeficiency viruses (SIVs) with a suffix to denote their species of origin, were found in various different primates from sub-Saharan Africa, including African green monkeys, sooty mangabeys, mandrills, chimpanzees, and others (Fig. 1). Surprisingly, these viruses appeared to be largely nonpathogenic in their natural hosts, despite clustering together with the human and simian AIDS viruses in a single phylogenetic lineage within the radiation of lentiviruses (Fig. 2). Interestingly, close simian relatives of HIV-1 and HIV-2 were found in chimpanzees (Huet et al. 1990) and sooty mangabeys (Hirsch et al. 1989), respectively. These relationships provided the first evidence that AIDS had emerged in both humans and macaques as a consequence of cross-species infections with lentiviruses from different primate species (Sharp et al. 1994). Indeed, subsequent studies confirmed that SIVmac was not a natural pathogen of macaques (which are Asian primates), but had been generated inadvertently in US primate centers by inoculating various species of macaques with blood and/or tissues from naturally infected sooty mangabeys (Apetrei et al. 2005, 2006). Similarly, it became clear that HIV-1 and HIV-2 were the result of zoonotic transfers of viruses infecting primates in Africa (Hahn et al. 2000). In this article, we summarize what is known about the simian precursors of HIV-1 and HIV-2, and retrace the steps that led to the AIDS pandemic.
Figure 1.
Origins of human AIDS viruses. Old World monkeys are naturally infected with more than 40 different lentiviruses, termed simian immunodeficiency viruses (SIVs) with a suffix to denote their primate species of origin (e.g., SIVsmm from sooty mangabeys). ...
Figure 2.
Phylogeny of lentiviruses. The evolutionary relationships among Pol sequences (∼ 770 amino acids) derived from various mammalian lentiviruses; host species are indicated at the right. Exogenous viruses are depicted in black, with HIV-1, HIV-2, ...
1,160 citations
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TL;DR: A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival, and both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD.
Abstract: Background Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the ...
1,108 citations