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Hennig B.J.,London School of Hygiene and Tropical Medicine | Hennig B.J.,University of Oxford | Velez-Edwards D.R.,Unita di Genetica Medica | Velez-Edwards D.R.,Vanderbilt University | And 13 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2011

Objectives: The human genetics of HIV-2 infection and disease progression is understudied. Therefore, we studied the effect of variation in 2 genes that encode products critical to HIV pathogenesis and disease progression: CD4 and CD209. Design: This cross-sectional study consisted of 143 HIV-2, 30 HIV-1 + HIV-2 and 29 HIV-1-infected subjects and 194 uninfected controls recruited from rural Guinea-Bissau. Methods: We genotyped 14 CD4 and 4 CD209 single nucleotide polymorphisms (SNPs) that were tested for association with HIV infection, HIV-2 plasma viral load (high vs. low), and CD4 T-cell count (high vs. low). Results: The most significant association was between a CD4 haplotype rs11575097-rs10849523 and high viral load [odds ratio (OR): = 2.37, 95% confidence interval (CI): 1.35 to 4.19, P = 0.001, corrected for multiple testing], suggesting increased genetic susceptibility to HIV-2 disease progression for individuals carrying the high-risk haplotype. Significant associations were also observed at a CD4 SNP (rs2255301) with HIV-2 infection (OR: = 2.36, 95% CI: 1.19 to 4.65, P = 0.01) and any HIV infection (OR: = 2.50, 95% CI: 1.34 to 4.69, P = 0.004). Conclusions: Our results support a role of CD4 polymorphisms in HIV-2 infection, in agreement with recent data showing that CD4 gene variants increase risk to HIV-1 in Kenyan female sex workers. These findings indicate at least some commonality in HIV-1 and HIV-2 susceptibility. © 2010 by Lippincott Williams & Wilkins.

Kwambana B.A.,Medical Research Council Laboratories UK | Kwambana B.A.,University of Leicester | Barer M.R.,University of Leicester | Bottomley C.,London School of Hygiene and Tropical Medicine | And 3 more authors.
BMC Infectious Diseases | Year: 2011

Background: Although Haemophilus influenzae type b (Hib), Staphylococcus aureus and Moraxella catarrhalis are important causes of invasive and mucosal bacterial disease among children, co-carriage with Streptococcus pneumoniae during infancy has not been determined in West Africa.Methods: Species specific PCR was applied to detect each microbe using purified genomic DNA from 498 nasopharyngeal (NP) swabs collected from 30 Gambian neonates every two weeks from 0 to 6 months and bi-monthly up to 12 months.Results: All infants carried S. pneumoniae, H. influenzae and M. catarrhalis at several time points during infancy. S.pneumoniae co-colonized the infant nasopharynx with at least one other pathogen nine out of ten times. There was early colonization of the newborns and neonates, the average times to first detection were 5, 7, 3 and 14 weeks for S. pneumoniae, H. influenzae, M. catarrhalis and S. aureus respectively. The prevalence of S. pneumoniae, H. influenzae and M. catarrhalis increased among the neonates and exceeded 80% by 13, 15 and 23 weeks respectively. In contrast, the prevalence of S. aureus decreased from 50% among the newborns to 20% amongst nine-week old neonates. S. pneumoniae appeared to have a strong positive association with H. influenzae (OR 5.03; 95% CI 3.02, 8.39; p < 0.01) and M. catarrhalis (OR 2.20; 95% CI 1.29; p < 0.01) but it was negatively associated with S. aureus (OR 0.53; 95% CI 0.30, 0.94; p = 0.03).Conclusion: This study shows early acquisition and high co-carriage of three important respiratory pathogens with S. pneumoniae in the nasopharyngeal mucosa among Gambian neonates and infants. This has important potential implications for the aetiology of respiratory polymicrobial infections, biofilm formation and vaccine strategies. © 2011 Kwambana et al; licensee BioMed Central Ltd.

Fryer H.R.,University of Oxford | Van Tienen C.,Medical Research Council Laboratories UK | Van Tienen C.,Erasmus Medical Center | Van Der Loeff M.S.,Center for Infection and Immunity Amsterdam | And 7 more authors.
AIDS | Year: 2015

Objective: This article predicts the future epidemiology of HIV-2 in Caió, a rural region of Guinea Bissau; and investigates whether HIV-2, which has halved in prevalence between 1990 and 2007 and is now almost absent in young adults in Caió, can persist as an infection of the elderly. Design: A mathematical model of the spread of HIV-2 was tailored to the epidemic in Caió, a village in Guinea-Bissau. Methods: An age-stratified difference equation model of HIV-2 transmission was fitted to age-stratified HIV-2 incidence and prevalence data from surveys conducted in Caió in 1990, 1997 and 2007. A stochastic version of the same model was used to make projections. Results: HIV-2 infection is predicted to continue to rapidly decline in Caió such that new infections will cease and prevalence will reach low levels (e.g. below 0.1%) within a few decades. HIV-2 is not predicted to persist in the elderly. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Kwambana B.A.,Medical Research Council Laboratories UK | Kwambana B.A.,University of Leicester | Mohammed N.I.,Medical Research Council Laboratories UK | Jeffries D.,Medical Research Council Laboratories UK | And 4 more authors.
BMC Clinical Pathology | Year: 2011

Background: Frozen storage often precedes metagenomic analysis of biological samples; however, the freezing process can have adverse effects on microbial composition. The effect of freezing on the detection of bacteria inhabiting the infant nasopharynx, a major reservoir of bacterial pathogens, was investigated. Methods. 16S ribosomal RNA (rRNA) gene-based terminal restriction fragment length polymorphism (T-RFLP) analysis of nasopharyngeal (NP) swabs from twelve Gambian infants was employed. NP swabs were analysed within hours of collection and then after 30 days of storage at -70°C. Results: There was substantial heterogeneity among subjects with respect to the effect of freezing on the number of operational taxonomic units (OTUs) detected. Nevertheless, the mean number of OTUs decreased after frozen storage and the relative abundance for 72% of the OTUs changed by less than 0.5% after deep frozen storage. There were differences in the odds of detection and relative abundance of OTUs matched with Moraxella sp., Haemophilus sp./Burkholderia sp., and Pseudomonas sp. A strong interaction between sex and the effect of freezing was found, whereby there was no significant change observed for males while the mean number of OTUs significantly declined among female infants following frozen storage. Conclusions: Although frozen storage of biological samples is often necessary for archiving and logistic purposes, the potential effects on the number of taxa (composition) detected in microbial community studies are significant and should not be overlooked. Moreover, genetic factors such as sex may influence the integrity of nucleic acids during the freezing process. © 2011 Kwambana et al; licensee BioMed Central Ltd.

Estevez P.T.,London School of Hygiene and Tropical Medicine | Satoguina J.,Medical Research Council Laboratories UK | Satoguina J.,University Abomey Calavi | Nwakanma D.C.,Medical Research Council Laboratories UK | And 4 more authors.
Malaria Journal | Year: 2011

Background: Antibody responses to malaria antigens reflect exposure to parasites, and seroprevalence correlates with malaria transmission intensity. Antibodies are routinely measured in sera or on dried blood spots but a non-invasive method would provide extra utility in sampling general populations. Saliva is already in use in the detection of plasma-derived IgM and IgG to viral infections. In this study, antibodies to Plasmodium falciparum merozoite antigens were compared between blood and saliva samples from the same individuals in unlinked surveys conducted in Tanzania and The Gambia. Methods. In Tanzania, 53 individuals provided paired fingerprick blood and saliva sample using two commercially available sampling devices. In the Gambia, archived plasma and saliva samples collected from 200 children in the Farafenni area in a cross-sectional survey were analyzed. IgG antibodies against P. falciparum antigens, Merozoite Surface Protein-1 (MSP-119) and Apical membrane Antigen (AMA-1) were measured by ELISA in paired saliva and blood samples from both sites. Antibody levels were compared as continuous optical density (OD) values and by sero-positivity. Results: Significant correlations between saliva and plasma antibody levels were seen in Tanzania for both antigens, AMA-1(r 2 range 0.93 to 0.89, p < 0.001) and MSP-119(r 2 range 0.93 to 0.75, p < 0.001), with a weaker correlation for results from The Gambia (r2range 0.64 to 0.63, p < 0.01). When assessed as seropositivity and compared with plasma, sensitivity and specificity were good with saliva antibody levels to both AMA-1 and MSP-1 19(sensitivity range 64-77% and specificity range 91-100% & 47-67% and 90-97% respectively) over the different sample sets. Conclusions: These data demonstrate anti-malarial antibodies can be detected in saliva and correlate strongly with levels in plasma. This non-invasive relatively simple collection method will be potentially useful for general population surveys, and particularly in migratory populations or those with infrequent contact with health services or opposed to blood withdrawal. Further studies will be needed to optimize collection methods, standardize volumes and content and develop controls. © 2011 Estévez et al; licensee BioMed Central Ltd.

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