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The urban mosquito species Aedes aegypti is the main vector of arboviruses worldwide. Mosquito control with insecticides is the most prevalent method for preventing transmission in the absence of effective vaccines and available treatments; however, the extensive use of insecticides has led to the development of resistance in mosquito populations throughout the world, and the number of epidemics caused by arboviruses has increased. Three mosquito lines with different resistance profiles to deltamethrin were isolated in French Guiana, including one with the I1016 knock‐down resistant allele. Significant differences were observed in the cumulative proportion of mosquitoes with a disseminated chikungunya virus infection over time across these lines. In addition, some genes related to resistance (CYP6BB2, CYP6N12, GST2, trypsin) were variably overexpressed in the midgut at 7 days after an infectious bloodmeal in these three lines. Our work shows that vector competence for chikungunya virus varied between Ae. aegypti laboratory lines with different deltamethrin resistance profiles. More accurate verification of the functional association between insecticide resistance and vector competence remains to be demonstrated. [ABSTRACT FROM AUTHOR]

Background: Hepatitis E virus (HEV), an enterically transmitted pathogen, is highly endemic in several African countries. Pregnant women are at particularly high risk for acute or severe hepatitis E. In Gabon, a central African country, the prevalence of antibodies to HEV among pregnant women is 14.1%. Recent studies have demonstrated unusual patterns of hepatitis E (chronic hepatitis, cirrhosis) among immunodeficient patients. Findings: We investigated the prevalence of antibodies to HEV among pregnant women infected with HIV-1 or HTLV-1 in Gabon. Of 243 samples collected, 183 were positive for HIV-1 and 60 for HTLV-1; 16 women (6.6%) had IgG antibodies to HEV. The seroprevalence was higher among HIV-1-infected women (7.1%) than HTLV-1-infected women (5.0%). Moreover, the HIV-1 viral load was significantly increased (p ≤ 0.02) among women with past-HEV exposure (1.3E+05 vs 5.7E+04 copies per ml), whereas no difference was found in HTLV-1 proviral load (9.0E+01 vs 1.1E+03 copies per ml). Conclusions: These data provide evidence that HIV-1-infected women are at risk for acute or severe infection if they are exposed to HEV during pregnancy, with an increased viral load. [ABSTRACT FROM AUTHOR]

Objective: The main objective of the MACOMBA (Maternity and Control of Malaria‐HIV co‐infection in Bangui) trial was to show that cotrimoxazole (CTX) is more effective than sulphadoxine–pyremethamine–IPTp (IPTp‐SP) to prevent placental malaria infection (primary end point) among HIV‐positive pregnant women with a CD4+ count ≥350 cells/mm3 in Bangui, CAR. Methods: MACOMBA is a multicentre, open‐label randomised trial conducted in four maternity hospitals in Bangui. Between 2013 and 2017, 193 women were randomised and 112 (59 and 53 in CTX and IPTp‐SP arms, respectively) were assessed for placental infection defined by microscopic parasitaemia or PCR. Results: Thirteen women had a placental infection: five in the CTX arm (one by microscopic placental parasitaemia and four by PCR) and eight by PCR in the SP‐IPTp (8.5% vs. 15.1%, p = 0.28). The percentage of newborns with low birthweight (<2500 g) did not differ statistically between the two arms. Self‐reported compliance to CTX prophylaxis was good. There was a low overall rate of adverse events in both arms. Conclusion: Although our results do not allow us to conclude that CTX is more effective, drug safety and good compliance among women with this treatment favour its widespread use among HIV‐infected pregnant women, as currently recommended by WHO. [ABSTRACT FROM AUTHOR]

Monkeypox is an emerging infectious disease, which has a clinical presentation similar to smallpox. In the two past decades, Central Africa has seen an increase in the frequency of cases, with many monkeypox virus (MPXV) isolates detected in the Democratic Republic of Congo (DRC) and the Central African Republic (CAR). To date, no complete MPXV viral genome has been published from the human cases identified in the CAR. The objective of this study was to sequence the full genome of 10 MPXV isolates collected during the CAR epidemics between 2001 and 2018 in order to determine their phylogenetic relationships among MPXV lineages previously described in Central Africa and West Africa. Our phylogenetic results indicate that the 10 CAR isolates belong to three lineages closely related to those found in DRC. The phylogenetic pattern shows that all of them emerged in the rainforest block of the Congo Basin. Since most human index cases in CAR occurred at the northern edge of western and eastern rainforests, transmissions from wild animals living in the rainforest is the most probable hypothesis. In addition, molecular dating estimates suggest that periods of intense political instability resulting in population movements within the country often associated also with increased poverty may have led to more frequent contact with host wild animals. The CAR socio-economic situation, armed conflicts and ecological disturbances will likely incite populations to interact more and more with wild animals and thus increase the risk of zoonotic spillover. [ABSTRACT FROM AUTHOR]

Background: Infection by hepatitis E virus (HEV) can cause a high burden of morbidity and mortality in countries with poor access to clean water and sanitation. Our study aimed to investigate the situation of HEV infections in the Central African Republic (CAR).Methods: A retrospective analysis of the blood samples and notification forms collected through the national yellow fever (YF) surveillance program, but for which a diagnosis of YF was discarded, was carried out using an anti-HEV IgM ELISA and a HEV-specific RT-PCR.Results: Of 2883 YF-negative samples collected between January 2008 and December 2012, 745 (~ 26%) tested positive by at least either of the 2 tests used to confirm HEV cases. The results revealed that the CAR was hit by a large HEV outbreak in 2008 and 2009. The results also showed a clear seasonal pattern with correlation between HEV incidence and rainfall in Bangui. A phylogenetic analysis showed that the circulating strains belonged to genotypes 1e and 2b.Conclusions: Overall, this study provides further evidences that HEV can be a significant cause of acute febrile jaundice, particularly among adults during rainy season or flood, in a country from Sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: Since the identification of Zika virus (ZIKV) in Brazil in May 2015, the virus has spread throughout the Americas. However, ZIKV burden in the general population in affected countries remains unknown.Methods: We conducted a general population survey in the different communities of French Guiana through individual interviews and serologic survey during June-October 2017. All serum samples were tested for anti-ZIKV immunoglobulin G antibodies using a recombinant antigen-based SGERPAxMap microsphere immunoassay, and some of them were further evaluated through anti-ZIKV microneutralization tests.Results: The overall seroprevalence was estimated at 23.3% (95% confidence interval [CI], 20.9%-25.9%) among 2697 participants, varying from 0% to 45.6% according to municipalities. ZIKV circulated in a large majority of French Guiana but not in the most isolated forest areas. The proportion of reported symptomatic Zika infection was estimated at 25.5% (95% CI, 20.3%-31.4%) in individuals who tested positive for ZIKV.Conclusions: This study described a large-scale representative ZIKV seroprevalence study in South America from the recent 2015-2016 Zika epidemic. Our findings reveal that the majority of the population remains susceptible to ZIKV, which could potentially allow future reintroductions of the virus. [ABSTRACT FROM AUTHOR]

Background: French Guiana, a French overseas department located in South America between Brazil and Surinam, is the only European territory geographically located in the Amazonian forest complex and is considered endemic for yellow fever (YF). In the context of the emergent threat of YF in Latin America, we conducted a large household cross-sectional survey from June to October 2017 to estimate vaccination coverage in the population and to determine associations with sociodemographic and geographical characteristics. Methodology/Principal findings: In total, 1,415 households and 2,697 individuals were included from the 22 municipalities of French Guiana. YF vaccination coverage was estimated at 95.0% (95% CI: 93.4–96.2) in the entire territory but was spatially heterogeneous, with the lowest levels estimated in the western part of the territory along the Surinamese cross-border region, particularly in children under 16 years who were not enrolled in school, immigrant adults and disadvantaged populations with low socioeconomic indexes. Conclusions/Significance: Despite the good vaccination coverage against YF in the general population of French Guiana resulting from the compulsory nature of YF vaccination for residents and travelers, there is an urgent need to improve vaccination coverage in vulnerable populations living in the northwestern part of the territory to limit the risk of transmission in the context of the emerging YF threat in South America. Despite the relative rarity of YF and the significant number of infectious and tropical diseases in French Guiana, clinicians should adopt a high index of suspicion for YF, particularly in vulnerable and at-risk populations. [ABSTRACT FROM AUTHOR]

HTLV-1 infection is considered as highly endemic in central Africa. Thirty years ago, a first epidemiological study was performed in Gabon, central Africa, and revealed that the prevalence varied from 5.0 to 10.5%. To evaluate current distribution of HTLVs in Gabon, 4.381 samples were collected from rural population living in 220 villages distributed within the 9 provinces of country. HTLVs prevalence was determined using two ELISA tests and positive results were confirmed by Western Blot. The overall HTLV-1 seroprevalence was of 7.3% among the rural Gabonese population; with 5.4% for men and 9.0% for women. Prevalence of HTLV-1 differed by province, ranging from 2.3% to 12.5% into the rain forest. Being a woman older than 51 years represented a high risk for HTLV-1 acquisition. Hospitalization, operation/surgery, transfusion and medical abortion or fever, arthritis and abdominal pain are also significant risk factors. In addition, 0.1% of samples were found as HTLV-2 positive, while 12.0% had an indeterminate HTLV serological pattern. HTLV-3 and HTLV-4 were not found. Phylogenetic analysis was performed on 87 samples and demonstrated that HTLV-1 present in Gabon belongs mostly to subtype B, however the rare subtype D was also found. Altogether, our results demonstrate that almost thirty years after the first epidemiological study prevention of HTLVs infection is still an issue in Gabon. [ABSTRACT FROM AUTHOR]

Molecular screening of 300 at-risk people from Central Africa identified 2 human T-lymphotropic virus (HTLV)-4-infected individuals. A zoonotic origin of infection was suggested, as both individuals reported being severely bitten by a gorilla during hunting activities. One strain was highly divergent and was designated as the HTLV-4 subtype-b prototype. [ABSTRACT FROM AUTHOR]

Non-human primates (NHPs) often live in inaccessible areas, have cryptic behaviors, and are difficult to follow in the wild. Here, we present a study on the spread of the simian T-lymphotropic Virus Type 1 (STLV-1), the simian counterpart of the human T-lymphotropic virus type 1 (HTLV-1) in a semi-captive mandrill colony. This study combines 28 years of longitudinal monitoring, including behavioral data, with a dynamic mathematical model and Bayesian inference. Three transmission modes were suspected: aggressive, sexual and familial. Our results show that among males, STLV-1 transmission occurs preferentially via aggression. Because of their impressive aggressive behavior male mandrills can easily transmit the virus during fights. On the contrary, sexual activity seems to have little effect. Thus transmission appears to occur primarily via male–male and female–female contact. In addition, for young mandrills, familial transmission appears to play an important role in virus spread. [ABSTRACT FROM AUTHOR]

The article reports on the specificity of dengue NS1 antigen in differential diagnosis of dengue and the Zika virus infection. It says that circulation of new arboviruses of the genus Flavivirus poses a major challenge for differential diagnosis. It adds that the Zika virus, a mosquito-borne virus of the family Flaviviridae, is closely linked to other arboviruses circulating in the Americas.

During January 2007-July 2012, a total of 3,220 suspected yellow fever cases were reported in the Central African Republic; 55 were confirmed and 11 case-patients died. Mean delay between onset of jaundice and case confirmation was 16.6 days. Delay between disease onset and blood collection could be reduced by increasing awareness of the population. [ABSTRACT FROM AUTHOR]

Abstract: Mandrills are naturally infected with simian T-cell leukaemia virus type 1 (STLV-1) and simian immunodeficiency virus (SIV)mnd. In humans, dual infection with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type 1 (HTLV-1) may worsen their clinical outcome. We evaluated the effect of co-infection in mandrills on viral burden, changes in T-cell subsets and clinical outcome. The SIV viral load was higher in SIV-infected mandrills than in co-infected animals, whereas the STLV-1 proviral load was higher in co-infected than in mono-infected groups. Dually infected mandrills had a statistically significantly lower CD4+ T-cell count, a lower proportion of naive CD8+ T cells and a higher proportion of central memory cells. CD4+ and CD8+ T cells from SIV-infected animals had a lower percentage of Ki67 than those from the other groups. Co-infected monkeys had higher percentages of activated CD4+ and CD8+ T cells. Two co-infected mandrills with high immune activation and clonal integration of STLV provirus showed pathological manifestations (infective dermatitis and generalised scabies) rarely encountered in nonhuman primates. [Copyright &y& Elsevier]

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

Background: The causative agent of yellow fever is an arbovirus of the Flaviviridae family transmitted by infected Aedes mosquitoes, particularly in Africa. In the Central African Republic since 2006, cases have been notified in the provinces of Ombella-Mpoko, Ouham-Pende, Basse-Kotto, Haute-Kotto and in Bangui the capital. As the presence of a vector of yellow fever virus (YFV) represents a risk for spread of the disease, we undertook entomological investigations at these sites to identify potential vectors of YFV and their abundance. Findings: Between 2006 and 2010, 5066 mosquitoes belonging to six genera and 43 species were identified. The 20 species of the Aedes genus identified included Ae. aegypti, the main vector of YFV in urban settings, and species found in tropical forests, such as Ae. africanus, Ae. simpsoni, Ae. luteocephalus, Ae. vittatus and Ae. opok. These species were not distributed uniformly in the various sites studied. Thus, the predominant Aedes species was Ae. aegypti in Bangui (90.7 %) and Basse-Kotto (42.2 %), Ae. africanus in Ombella-Mpoko (67.4 %) and Haute-Kotto (77.8 %) and Ae. vittatus in Ouham-Pende (62.2 %). Ae. albopictus was also found in Bangui. The distribution of these dominant species differed significantly according to study site (P < 0.0001). None of the pooled homogenates of Aedes mosquitoes analysed by polymerase chain reaction contained the YFV genome. Conclusion: The results indicate a wide diversity of vector species for YFV in the Central African Republic. The establishment of surveillance and vector control programs should take into account the ecological specificity of each species. [ABSTRACT FROM AUTHOR]

Background. In Gabon, several Ebolavirus outbreaks have occurred exclusively in the northeastern region. We conducted a large serosurvey to identify areas and populations at risk and potential demographic, clinical, and behavioral risk factors. Methods. Blood samples and clinical and sociodemographic data were collected from 4349 adults and 362 children in a random sample of 220 villages in the 9 provinces of Gabon. An enzyme-linked immunosorbent assay was used to detect Zaire ebolavirus (ZEBOV)-specific IgG, and thin blood smears were used to detect parasites. Logistic regression was implemented using Stata software (Stata), and a probability level of <.05 was considered to be statistically significant. Results. The prevalence of ZEBOV-specific IgG was 15.3% overall, increasing to 32.4% (P< .001) in forest areas. No sociodemographic risk factors were found, but the antibody prevalence increased linearly up to 20 years of age. Chronic arthralgia and amicrofilaremia were the only factors associated with ZEBOV seropositivity. Conclusions. These findings confirm the endemicity of ZEBOV in Gabon and its link to the ecosystem. Human antibody positivity would appear to be to the result of exposure to contaminated fruits. [ABSTRACT FROM AUTHOR]

Background Although a wide variety of non-human primates are susceptible to simian T-cell leukaemia virus type 1 (STLV-1), little is known about the virological or molecular determinants of natural STLV-1 infection. Methods We determined STLV-1 virus tropism in vivo and its relation to the immune response by evaluating cytokine production and T-cell subsets in naturally infected and uninfected mandrills. Results With real-time PCR methods, we found that STLV-1 in mandrills infects both CD4+ and CD8+ T cells; however, proviral loads were significantly higher ( P = 0.01) in CD4+ than in CD8+ cells (mean STLV-1 copies number per 100 cells (± SD) was 7.8 ± 8 in CD4+ T cells and 3.9 ± 4.5 in CD8+ T cells). After culture, STLV-1 provirus was detected in enriched CD4+ but not in enriched CD8+ T cells. After 6 months of culture, STLV-1-transformed cell lines expressing CD3+, CD4+ and HLADR+ were established, and STLV-1 proteins and tax/rex mRNA were detected. In STLV-1 infected monkeys, there was a correlation between high proviral load and elevated levels of interleukin (IL)-2, IL-6, IL-10, interferon-γ and tumour necrosis factor-α. The two monkeys with the highest STLV-1 proviral load had activated CD4+HLADR+ and CD8+HLADR+ T-cell subsets and a high percentage of CD25+ in CD4+ and CD8+ T cells. Conclusions Our study provides the first cellular, immunological and virological characterization of natural STLV-1 infection in mandrills and shows that they are an appropriate animal model for further physiopathological studies of the natural history of human T-cell leukaemia viruses. [ABSTRACT FROM AUTHOR]

Abstract: Human T-cell lymphotropic virus type 1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) has a poor prognosis owing to its intrinsic resistance to chemotherapy. Although zidovudine (AZT) and alpha interferon (IFN-α) give rise to some response and improve the prognosis of ATLL, alternative therapies are needed. Arsenic trioxide (As2O3) has been shown to synergize with IFN-α in arresting cell growth and inducing apoptosis of ATLL cells in vitro. In this study, we evaluated the toxicity and the efficacy of this combined treatment in HTLV-1-infected squirrel monkeys (Saimiri sciureus) and HTLV-1 infected cell lines derived therefrom. We first show that treatment with As2O3 and IFN-α can induce growth arrest in HTLV-1-transformed monkey T-cell lines in vitro. We then show that treatment of squirrel monkeys with As2O3 in vivo is highly toxic at 0.9 or 0.3mg/day but not at 0.14mg/day for up to 2 weeks. Although the combination of As2O3 and IFN-α did not affect significantly the HTLV-1 proviral load in infected monkeys, it reduced the absolute numbers of CD3+, CD4+ and CD8+ cells during treatment, with a significant reduction in the total number of circulating HTLV-1 flower cells in the infected monkeys with chronic ATLL-like disease. [Copyright &y& Elsevier]

Understanding cell dynamics in animal models have implications for therapeutic strategies elaborated against leukemia in human. Quantification of the cell turnover in closely related primate systems is particularly important for rare and aggressive forms of human cancers, such as adult T-cell leukemia. For this purpose, we have measured the death and proliferation rates of the CD4+ T lymphocyte population in squirrel monkeys (Saimiri sciureus) infected by human T-lymphotropic virus type 1 (HTLV-1). The kinetics of in vivo bromodeoxyuridine labeling revealed no modulation of the cell turnover in HTLV-1-infected monkeys with normal CD4 cell counts. In contrast, a substantial decrease in the proliferation rate of the CD4+ T population was observed in lymphocytic monkeys (e.g. characterized by excessive proportions of CD4+ T lymphocytes and by the presence of abnormal flower-like cells). Unexpectedly, onset of HTLV-associated leukemia thus occurs in the absence of increased CD4+ T-cell proliferation. This dynamics significantly differs from the generalized activation of the T-cell turnover induced by other primate lymphotropic viruses like HIV and SIV.Oncogene (2005) 24, 7514–7523. doi:10.1038/sj.onc.1208896; published online 8 August 2005 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about a case of hepatitis E virus in India and Central African Republic.

The article discusses research investigating the age of the simian immunodeficiency virus (SIV) in African nonhuman primates. An overview of the team's research methodology which included SIV serological tests and reverse transcription polymerase chain reaction (RT-PCR), followed by a phylogenetic analysis, of bushmeat specimens from monkeys on the isolated island of Bioko in Equatorial Guinea is presented.

During 1979-2022, Cameroon recorded 32 laboratory-confirmed mpox cases among 137 suspected mpox cases identified by the national surveillance network. The highest positivity rate occurred in 2022, indicating potential mpox re-emergence in Cameroon. Both clade I (n = 12) and clade II (n = 18) monkeypox virus (MPXV) were reported, a unique feature of mpox in Cameroon. The overall case-fatality ratio of 2.2% was associated with clade II. We found mpox occurred only in the forested southern part of the country, and MPXV phylogeographic structure revealed a clear geographic separation among concurrent circulating clades. Clade I originated from eastern regions close to neighboring mpox-endemic countries in Central Africa; clade II was prevalent in western regions close to West Africa. Our findings suggest that MPXV re-emerged after a 30-year lapse and might arise from different viral reservoirs unique to ecosystems in eastern and western rainforests of Cameroon.

Vector-borne viruses are becoming increasingly important from a public health standpoint with the emergence or reemergence of viruses and extension of the areas at risk. Here, we report the whole-genome sequences of two alphaviruses, namely, one Igbo-Ora virus and one Babanki virus, that were isolated several decades ago in Africa from human serum., (Copyright © 2019 Tricou et al.)

Tataguine virus (TATV) is an orthobunyavirus that causes febrile illnesses in Africa. Here, we report the complete genome sequences of TATV strain HB72P583, isolated in the Central African Republic in 1972. Several genetic variations were detected in the small (S), medium (M), and large (L) segments relative to a TATV strain isolated in Nigeria in 1966.

An outbreak of familial monkeypox occurred in the Central African Republic in 2015/2016 by 3 transmission modes: familial, health care-related, and transport-related. Ten people (3 children and 7 adults) were infected. Most presented with cutaneous lesions and fever, and 2 children died. The viral strain responsible was a Zaire genotype strain.

With the Zika virus outbreak in South America starting in 2015 and its potential to cause malformation of the fetus in infected women, the need for diagnostic methods became obvious. Until now, only limited data are available on the diagnostic performance of commercial kits. Here, we present data comparing the RealStar ® Zika Virus RT-PCR Kit 1.0 for detection of Zika virus from 208 serum and urine samples collected in French Guiana with a reference method. Of these, 114 samples tested positive with the RealStar ® Kit and 111 with the reference method.

Background: New sequencing technologies have opened the way to the discovery and the characterization of pathogenic viruses in clinical samples. However, the use of these new methods can require an amplification of viral RNA prior to the sequencing. Among all the available methods, the procedure based on the use of Phi29 polymerase produces a huge amount of amplified DNA. However, its major disadvantage is to generate a large number of chimeric sequences which can affect the assembly step. The pre-process method proposed in this study strongly limits the negative impact of chimeric reads in order to obtain the full-length of viral genomes., Findings: Three different assembly softwares (ABySS, Ray and SPAdes) were tested for their ability to correctly assemble the full-length of viral genomes. Although in all cases, our pre-processed method improved genome assembly, only its combination with the use of SPAdes allowed us to obtain the full-length of the viral genomes tested in one contig., Conclusions: The proposed pipeline is able to overcome drawbacks due to the generation of chimeric reads during the amplification of viral RNA which considerably improves the assembling of full-length viral genomes.

Of 78 Gabonese individuals who had received bites from nonhuman primates (NHPs) while hunting, 7 were infected with human T lymphotropic virus (HTLV-1). Five had been bitten by gorillas and were infected with subtype B strains; however, a 12-year-old girl who was severely bitten by a Cercopithecus nictitans was infected with a subtype D strain that was closely related to the simian T lymphotropic virus (STLV-1) that infects this monkey species. Her mother was infected with a subtype B strain. These data confirm that hunters in Africa can be infected by HTLV-1 that is closely related to the strains circulating among local NHP game. Our findings strongly suggest that a severe bite represent a risk factor for STLV-1 acquisition., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Understanding how pathogens spread and persist in the ecosystem is critical for deciphering the epidemiology of diseases of significance for global health and the fundamental mechanisms involved in the evolution of virulence and host resistance. Combining long-term behavioural and epidemiological data collected in a naturally infected mandrill population and a Bayesian framework, the present study investigated unknown aspects of the eco-epidemiology of simian immunodeficiency virus (SIV), the recent ancestor of HIV. Results show that, in contrast to what is expected from aggressive and sexual transmission (i.e. the two commonly accepted transmission modes for SIV), cases of SIVmnd-1 subtype were significantly correlated among related individuals (greater than 30% of the observed cases). Challenging the traditional view of SIV, this finding suggests the inheritance of genetic determinants of susceptibility to SIV and/or a role for behavioural interactions among maternal kin affecting the transmission of the virus, which would highlight the underappreciated role of sociality in the spread of infectious diseases. Outcomes of this study also provide novel insights into the role of host social structure in the evolution of pathogens.

Background: In Africa, the wide genetic diversity of HIV has resulted in emergence of new strains, rapid spread of this virus in sub-Saharan populations and therefore spread of the HIV epidemic throughout the continent., Methods: To determine the prevalence of antibodies to HIV among a high-risk population in Gabon, 1098 and 2916 samples were collected from pregnant women in 2005 and 2008, respectively. HIV genotypes were evaluated in 107 HIV-1-positive samples to determine the circulating subtypes of strains and their resistance to antiretroviral drugs (ARVs)., Results: The seroprevalences were 6.3% in 2005 and 6.0% in 2008. The main subtype was recombinant CRF02&#95;AG (46.7%), followed by the subtypes A (19.6%), G (10.3%), F (4.7%), H (1.9%) and D (0.9%) and the complex recombinants CRF06&#95;cpx (1.9%) and CRF11&#95;cpx (1.9%); 12.1% of subtypes could not be characterized. Analysis of ARVs resistance to the protease and reverse transcriptase coding regions showed mutations associated with extensive subtype polymorphism. In the present study, the HIV strains showed reduced susceptibility to ARVs (2.8%), particularly to protease inhibitors (1.9%) and nucleoside reverse transcriptase inhibitors (0.9%)., Conclusions: The evolving genetic diversity of HIV calls for continuous monitoring of its molecular epidemiology in Gabon and in other central African countries.

In South America, dengue is the arbovirus-transmitted disease with the highest incidence. Unlike other arboviruses, wild mammals have no confirmed role in the cycle of dengue in the neotropics, although serological studies have suggested a possible secondary amplification cycle involving mammals other than nonhuman primates. In French Guiana, where all four serotypes (DENV-1, DENV-2, DENV-3, DENV-4) are present, the disease is endemic with outbreak events. To determine whether wild mammals can be infected by DENV, rodents, marsupials, and bats were captured over several periods, from 2001 to 2007, at two sites. The first location is a secondary forest surrounded by an urban area where dengue is endemic. The second location is a forest edge site where the disease has not yet emerged. A total of 10,000 trap-nights were performed and 616 mammals were captured. RNAs representing the four DENV serotypes were detected at both sites by reverse-transcriptase polymerase chain reaction in the livers and/or sera of 92 mammals belonging to 14 out of 32 species distributed among all the orders investigated: Rodentia (33 positive/146 tested), Marsupialia (40/318), and Chiroptera (19/152). Sequence analyses of a portion of the capsid and premembrane junction revealed that mammal strains of DENV-1, DENV-2, DENV-3, and DENV-4 had only 92.6%, 89%, 95%, and 95.8% identity, respectively, with strains circulating in the human population during the same periods. Regarding DENV-2, strains related (99% identity) to those responsible for an epidemic event in humans in French Guiana concurrent to the capture sessions were also evidenced, suggesting that wild mammals in edge habitats can be infected by circulating human strains. Our results demonstrate, for the first time, that neotropical wild mammals can be infected with dengue virus. The question of whether mammals maintain DENV in enzootic cycles and can play a role in its reemergence in human populations remains to be answered.

Objective: To evaluate the efficacy of postexposure prophylaxis with a combination of zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV), after vaginal exposure to HIV., Design: : Experimental intravaginal exposure of female cynomolgus macaques to SIVmac251., Methods: ZDV/3TC/IDV treatment was initiated 4 h after exposure and continued for 28 days. Groups of six animals received a placebo or a combination of oral ZDV (4.5 mg/kg), 3TC (2.5 mg/kg) and IDV (20 mg/kg) twice daily or subcutaneous ZDV (4.5 mg/kg) and 3TC (2.5 mg/kg) twice daily, and a higher dose of IDV (60 mg/kg) administered orally twice daily., Results: In the placebo group, all animals were infected. Antiretroviral association protected one of the six animals if all drugs were administered orally and four of the six animals if ZDV and 3TC were administered subcutaneously and IDV was given orally at triple dose. In infected animals, viremia was significantly delayed and lowered in treated animals than in animals given placebo, and high CD4 cell counts were maintained in the treated animals, at least in the medium term. Antiretroviral dosages made in macaques receiving the same treatments showed that protection efficacy could be linked to antiretroviral plasmatic concentration., Conclusion: This study shows, for the first time in macaques, that the postexposure prophylaxis recommended for humans may be effective after vaginal exposure. Improvements in pharmacokinetic parameters significantly increased treatment efficiency.

Hepatitis E virus (HEV) is highly endemic in several African countries with high mortality rate among pregnant women. Nothing is known about the circulation of this virus in central Africa. We evaluated therefore the prevalence of anti-HEV IgG in samples collected from pregnant women living in the five main cities of Gabon, central Africa. We found that 14.1% (119/840) of pregnant women had anti-HEV IgG. The prevalence differed between regions and between age groups. In 391 newly collected samples from the region where the highest prevalence was found, a significant difference (p < 0.05) in seroprevalence was found between rural (6.4%) and urban (13.5%) areas. These data provide evidence of a high prevalence of HEV in Gabon, providing indirect evidence of past contact with this virus.

Here, we report that freshly isolated unstimulated adult T-cell leukemia (ATL) cells present high telomerase activity compared to asymptomatic carriers or normal donors. In spite of this high telomerase activity, ATL cells retained shorter telomeres compared to those of uninfected cells isolated from the same patients. Because the safeguarding of telomere length is critical to the unlimited proliferation of tumor cells, we investigated the underlying mechanism for short telomere maintenance in ATL cells. Transcriptional and posttranscriptional expression of telomere-binding proteins TRF1, TRF2, TIN2 and POT1, known to regulate telomere homeostasis and protection, were evaluated. We found that TRF1 and TRF2 are overexpressed in in vivo patient's samples from ATL but not asymptomatic carriers, while levels of POT1 expression did not specifically increase in ATL. To gain insights into the regulation of TRF genes in HTLV-I infected cells, we investigated the expression of TIN2, a regulator of these genes, and found an increase in TIN2 expression in ATL patients. Together our results underscore the importance of telomerase and telomere length regulating factors as novel markers for ATL disease progression and as potential therapeutic targets for the treatment of HTLV-I-associated malignancies.

We evaluated the presence of human herpesvirus 8 (HHV-8) infection among groups of Amerindians in French Guiana. The overall prevalence of antibodies against lytic HHV-8 antigens was 23.0% (180/781), increasing from 18.4% in children <6 years old to approximately 30% in older persons (>45 years). Seroprevalence was higher in Amerindians living in remote localities than it was in those living in the coastal region. Analysis of a 725-base pair fragment of the K1 gene amplified from DNA from a Wayampi Amerindian showed that the virus belonged to molecular subtype E, which has hitherto been found in only a few Amerindians in Brazil and Ecuador.

In immortal cells, the existence of a mechanism for the maintenance of telomere length is critical. In most cases this is achieved by the reactivation of telomerase, a cellular reverse transcriptase that prevents telomere shortening. Here we report that the telomerase gene (hTERT) promoter is up-regulated during transmission of human T-cell lymphotropic virus type-I (HTLV-I) to primary T cells in vitro and in ex vivo adult T-cell leukemia/lymphoma (ATLL) samples, but not asymptomatic carriers. Although Tax impaired induction of human telomerase reverse transcriptase (hTERT) mRNA in response to mitogenic stimulation, transduction of Tax into primary lymphocytes was sufficient to activate and maintain telomerase expression and telomere length when cultured in the absence of any exogenous stimulation. Transient transfection assays revealed that Tax stimulates the hTERT promoter through the nuclear factor kappaB (NF-kappaB) pathway. Consistently, Tax mutants inactive for NF-kappaB activation could not activate the hTERT or sustain telomere length in transduced primary lymphocytes. Analysis of the hTERT promoter occupancy in vivo using chromatin immunoprecipitation assays suggested that an increased binding of c-Myc and Sp1 is involved in the NF-kappaB-mediated activation of the hTERT promoter. This study establishes the role of Tax in regulation of telomerase expression, which may cooperate with other functions of Tax to promote HTLV-I-associated adult T-cell leukemia.

Adult T-cell leukaemia/lymphoma (ATLL) is a malignant T-cell proliferation that occurs in 3-5% of individuals infected with human T-cell leukaemia virus-1 (HTLV-1). HTLV-1 infection is also linked to the development of infective dermatitis (ID), an exudative dermatitis of children that has been proposed as a cofactor of ATLL. Here, HTLV-1 replication was investigated over time in a girl with ID and multiparasitic infestation including strongyloidiasis, a disease also known to predispose HTLV-1 carriers to ATLL. Quantitative polymerase chain reaction (PCR) revealed extremely high proviral loads. During the 2-year period of the present study, the proportion of circulating infected cells ranged between 12% and 36%. Quadruplicate linker-mediated PCR amplification of HTLV-1 flanking sequences identified a pattern of extensive and persistent oligoclonal expansion of infected lymphocytes. As viral loads, both the number and the degree of infected T-cell expansion were independent of treatment or clinical signs. However, the temporal fluctuation of proviral loads correlated significantly with the degree of infected T-cell expansion, but not with the overall number of detected clones. This pattern of HTLV-1 replication over time is very different from that observed in asymptomatic carriers and reminiscent of that observed in ATLL, a result consistent with the proposal of ID as an ATLL cofactor.

We review here the epidemiological studies performed by our group on human retrovirus HTLV-I and HTLV-II infections and the associated diseases in French Guiana since 1984. French Guiana is an overseas French administrative district located between Brazil and Surinam. Its population is characterized by a large variety of ethnic groups, including several populations of African origin and various populations of Amerindian origin. Several epidemiological studies of large samples of pregnant women and in remote villages showed that HTLV-I is highly endemic in this area but is restricted to groups of African origin, especially the Noir-Marrons. In this endemic population, the results of segregation analysis in a genetic epidemiological study were consistent with the presence of a dominant major gene predisposing to HTLV-I infection, especially in children. In contrast, HTLV-II infection appears to be rare in French Guiana, having been found in only a few individuals of Brazilian origin. From a molecular point of view, the HTLV-I strains present in the Noir-Marrons, Creoles and Amerindians appear to originate from Africa, as they belong to the large cosmopolitan molecular subtype A.

Primates have long been used as models to study the basic mechanisms of human disease. The squirrel monkey, Saimiri sciureus,is a New World monkey that can be satisfactorily bred in captivity and infected with various human pathogens. The basic immunological parameters of squirrel monkeys, including immunoglobulin subclasses and markers for lymphocyte subsets, have already been characterized. However, immunological reagents and assays specific for the detection and quantification of squirrel monkey cytokines are required to elucidate the immunological and physiopathological changes that occur during experimental infection of these animals with pathogens. We therefore cloned, sequenced, and characterized the cDNAs encoding various squirrel monkey Th1 and Th2 cytokines, including interleukin (IL)-1 beta, IL-2, IL-5, IL-6, IL-10, tumor necrosis factor alpha, and gamma interferon. We found 91.4%-98.1% homology between the nucleotide sequence of the squirrel monkey cytokine genes and published sequences of equivalent human and non-human primate genes. The aligned sequences of cytokines for Saimiriand several New and Old World primates and human are shown, and a phylogenetic analysis of published sequences of selected cytokines in other species and those of non-human primates is given. In addition, we adapted a previously described quantitative, reverse transcriptase, competitive polymerase chain reaction technique to measure the mRNA expression of those cytokines in squirrel monkeys. The primer and competitor plasmids that allowed quantification are described. We showed that the assay is sensitive and reproducible.