Maria Makuwa - Academia.edu (original) (raw)

Papers by Maria Makuwa

Immunology letters, Jan 21, 2002

Several mechanisms have been proposed for explaining the protection of young children with hemogl... more Several mechanisms have been proposed for explaining the protection of young children with hemoglobin AS from severe Plasmodium falciparum malaria. In a previous study carried out in Gabon, we have shown an association between hemoglobin AS carriage and a greater P. falciparum infection complexity. In the present study, we have investigated the presence and fine specificity of merozoite surface protein 2 (MSP2) reactive antibodies using different peptides covering conserved and polymorphic regions (Blocks 1-3) of P. falciparum MSP2 molecules. A cross-sectional study was conducted in the city of Bakoumba (Gabon), where malaria is hyperendemic with perennial P. falciparum transmission. Among the 641 children included, 135 were heterozygous for the sickle cell trait (HbAS). There was no significant difference in age distribution (mean age: 5 years, 0.5-11 years) and sex ratio in both hemoglobin groups (HbAA vs. HbAS). Blood group O was, however, associated with the sickle cell trait (P=0.02). P. falciparum isolates obtained from children with HbAS had a trend to higher infection complexity before the age of 5 years. Plasma samples were tested for the presence of antibodies to the different MSP2 peptides. Total IgG antibodies with a predominant reactivity against the FC27 type (the predominant P. falciparum MSP2 genotype) were found in serum samples from both groups. The profile of the IgG subclasses varied according to the hemoglobin phenotype. IgG3 and IgG2 were predominantly detected in plasma samples from HbAS children, whereas mainly IgG3 was found in children with HbAA. The role of the high multiclonal carriage associated with high family-specific antibodies reactive to MSP2 in HbAS children with asymptomatic P. falciparum parasitism is discussed.

The Journal of general virology, 2007

In order to determine whether geographical or species clustering accounts for the distribution of... more In order to determine whether geographical or species clustering accounts for the distribution of hepatitis B virus (HBV) in subspecies of chimpanzees in Africa, four complete chimpanzee HBV (ChHBV) genome sequences were obtained from eight hepatitis B surface antigen-positive wild-born chimpanzees from Cameroon, Republic of Congo and Gabon. The serological profiles of these chimpanzees corresponded to the acute or chronic highly replicative phase of HBV infection, as confirmed by high plasma HBV loads. Analysis of the sequence alignment of 256 aa (S region) from the eight HBV-infected chimpanzees allowed us to determine the HBV amino acid patterns specific to each chimpanzee subspecies and to their geographical origin. Phylogenetic analysis of both the S region and the complete genome confirmed this distinctive clustering of eight novel ChHBV strains within Pan troglodytes. The strong phylogenetic associations of ChHBV sequences with both chimpanzee subspecies and their geographical origin were therefore confirmed.

Intervirology, 2015

Given the magnitude of the HIV epidemic infection, many viral and human factors were analyzed, an... more Given the magnitude of the HIV epidemic infection, many viral and human factors were analyzed, and the most decisive was the variant CCR5-Δ32. The presence of a low HIV prevalence (1.8%) in Gabon in the 1990s, compared to neighboring countries, represents a paradox that led us to search for viral and human genetic variants in this country. In this study, only variants of coreceptors and chemokines were investigated. Variants of the coding region of the CCR5 gene were analyzed by denaturing gradient gel electrophoresis, and then variants of SDF1 and CCR2b were determined by polymerase chain reaction-restriction fragment length polymorphism. Four rare variants of the CCR5 coreceptor were found, while CCR5-Δ32 and CCR5m303 variants were not found. No association with CCR2b-V64I (17%) and SDF1-3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;A (2%) variants was determined in relation to HIV-1 infection in Gabonese patients. The paradox of HIV seroprevalence in Gabon, which ended in the 2000s, was not caused by human genetic variants but rather by environmental factors. © 2015 S. Karger AG, Basel.

BMC Infectious Diseases, 2008

Background Hepatitis C virus (HCV) infection is a major global public health problem in both deve... more Background Hepatitis C virus (HCV) infection is a major global public health problem in both developed and developing countries. The prevalence and genetic diversity of HCV in pregnant women in Gabon, central Africa, is not known. We therefore evaluated the prevalence and the circulating genotypes of HCV in a large population cohort of pregnant women. Methods Blood samples (947) were collected from pregnant women in the five main cities of the country. The prevalence was evaluated by two ELISA tests, and the circulating genotypes were characterized by sequencing and phylogenetic analysis. Results Twenty pregnant women (2.1%) were infected with HCV. The seroprevalence differed significantly by region (p = 0.004) and increased significantly with age (p = 0.05), being 1.3% at 14–20 years, 1.1% at 21–25 years, 1.9% at 26–30 years, 4.1% at 31–35 years and 6.0% at > 35 years. Sequencing in the 5'-UTR and NS5B regions showed that the circulating strains belonged to genotypes 4 (4e and 4c). Conclusion We found that the HCV seroprevalence in pregnant women in Gabon is almost as high as that in other African countries and increases with age. Furthermore, only genotype 4 (4e and 4c) was found. More extensive studies aiming to evaluate the prevalence and heterogeneity of HCV genotypes circulating in the general population of the country are needed.

Science, 2010

Simian immunodeficiency virus (SIV) lineages have been identified that are endemic to Bioko Islan... more Simian immunodeficiency virus (SIV) lineages have been identified that are endemic to Bioko Island. The time the island formed offers a geological time scale calibration point for dating the most recent common ancestor of SIV. The Bioko viruses cover the whole range of SIV genetic diversity, and each Bioko SIV clade is most closely related to viruses circulating in hosts of the same genus on the African mainland rather than to SIVs of other Bioko species. Our phylogeographic approach establishes that SIV is ancient and at least 32,000 years old. Our conservative calibration point and analyses of gene sequence saturation and dating bias suggest it may be much older.

Human T-cell leukemia virus type 1 (HTLV-1) is highly endemic in areas of central Africa; mother-... more Human T-cell leukemia virus type 1 (HTLV-1) is highly endemic in areas of central Africa; mother-to-child transmission and sexual transmission are considered to be the predominant routes. To determine the prevalence and subtypes of HTLV-1/2 in pregnant women in Gabon, we conducted an epidemiological survey in the five main cities of the country. In 907 samples, the HTLV-1 seroprevalence was 2.1%, which is lower than that previously reported. Only one case of HTLV-2 infection was found. The HTLV-1 seroprevalence increased with age and differed between regions (P < 0.05), with the highest prevalence (5%) in the southeastern region. A wide range of HTLV-1 proviral loads was observed among the infected women. The level of the proviral load was correlated with a high HTLV-1 antibody titer (P < 0.02). Sequencing of HTLV-1 env and long terminal repeat fragments showed that all but one strain belonged to the central African subtype B; the outlier was of cosmopolitan subtype A. The new strains of subtype B exhibited wide genetic diversity, but there was no evidence of clustering of specific genomes within geographical regions of the country. Some strains were closely related to simian T-cell leukemia virus type 1 strains of great apes, suggesting that in these areas some HTLV-1 strains could arise from relatively recent interspecies transmission. The sole HTLV-2 strain belonged to subtype B. In this study we showed that the prevalence of HTLV-1 in the southeast is one of the highest in the world for pregnant women.

Journal of Clinical Virology - J CLIN VIROL, 2009

Background: Intrafamilial and sexual transmission of hepatitis C virus (HCV) are still being deba... more Background: Intrafamilial and sexual transmission of hepatitis C virus (HCV) are still being debated, and little is known about such transmission in central Africa.

BMC Infectious Diseases, 2012

Background: In Africa, the wide genetic diversity of HIV has resulted in emergence of new strains... more 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.

AIDS Research and Human Retroviruses, 2001

SIVcpz/HIV-1 (groups M, O, N, and SIVcpz-gab), SIVmnd, SIVagm, and SIVsm/SIVmac/HIV-2. This strat... more SIVcpz/HIV-1 (groups M, O, N, and SIVcpz-gab), SIVmnd, SIVagm, and SIVsm/SIVmac/HIV-2. This strategy was evaluated with panels of sera originating from both humans and nonhuman primates. The human reference panel consisted of 144 HIV Western blot (WB)-positive sera in which the corresponding virus had been genotyped (HIV-1: 72 group M, 28 group O, and 6 group N; HIV-2: 21 subtype A and 10 subtype B; and 7 HIV-11 2) and 105 HIV WB-negative samples. The nonhuman primate reference panel consisted of 24 sera from monkeys infected by viruses belonging to the four lineages included in the PIV-ELISA strategy (5 chimpanzees, 5 macaques, 8 mandrills, and 6 vervets) and 42 samples from seronegative animals. Additional field evaluation panels consisted of 815 human sera from Gabon, Cameroon, and France and 537 samples from 25 nonhuman primate species. All the samples from the two reference panels were correctly detected and discriminated by PIV-ELISA. In the human field evaluation panel, the gp41/36 component correctly identified all the test samples, with 98% specificity. The V3 component discriminated 206 HIV-1 group M, 98 group O, 12 group M1 O, and 128 HIV-2 sera.

AIDS, 2009

To evaluate the efficacy of postexposure prophylaxis with a combination of zidovudine (ZDV), lami... more To evaluate the efficacy of postexposure prophylaxis with a combination of zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV), after vaginal exposure to HIV. : Experimental intravaginal exposure of female cynomolgus macaques to SIVmac251. 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. 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. 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.

PLoS Pathogens, 2012

Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated wi... more Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of 3 human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo (DRC), Africa. The cases, presenting over a 3-week period, were characterized by abrupt disease onset, high fever, mucosal hemorrhage, and, in two patients, death within 3 days. BASV was detected in an acute serum sample from the lone survivor at a concentration of 1.09 × 10(6) RNA copies/mL, and 98.2% of the genome was subsequently de novo assembled from ≈ 140 million sequence reads. Phylogenetic analysis revealed that BASV is highly divergent and shares less than 34% amino acid identity with any other rhabdovirus. High convalescent neutralizing antibody titers of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1:1000 were detected in the survivor and an asymptomatic nurse directly caring for him, both of whom were health care workers, suggesting the potential for human-to-human transmission of BASV. The natural animal reservoir host or arthropod vector and precise mode of transmission for the virus remain unclear. BASV is an emerging human pathogen associated with acute hemorrhagic fever in Africa.