BackgroundThe potential of genetic testing to rapidly diagnose drug resistance has lead to the development of new diagnostic assays. However, prior to implementation in a given setting, the association of specific mutations with specific drug resistance phenotypes should be evaluated. The purpose of this study was to evaluate molecular markers in predicting drug resistance in the Central Region of Cameroon.ResultsFrom April 2010 and March 2011, 725 smear positive pulmonary tuberculosis patients were enrolled and all positive cultures were tested for drug susceptibility. A total of 63 drug resistant and 100 drug sensitive Mycobacterium tuberculosis complex clinical isolates were screened for genetic mutations in katG, inhA, ahpC, rpoB, rpsL, rrs, gidB and embCAB loci using DNA sequencing. Of the 44 isoniazid resistant (INHR) isolates (24 high level, 1 μg/ml and 20 low level, 0.2 μg/ml), 73% (32/44) carried the katG315 and/or the -15 inhA promoter mutations. Of the 24 high level INHR, 17 (70.8%) harbored katG315 mutation, 1 a point mutation (-15C → T) in the inhA promoter and 6 were (25.0%) wild types. Thus, for INHR high level detection, katG315 mutation had a specificity and a sensitivity of 100% and 70.8% respectively. Of the 20 low level INHR, 10 (50.0%) had a -15C → T mutation in the inhA promoter region, and 1 (2.2%) a -32G → A mutation in the ahpC promoter region. All of the 7 rifampicin resistant (RIFR) isolates carried mutations in the rpoB gene (at codons Ser531Leu (71.4%), His526Asp (14.3%), and Asp516Val (14.3%)). Of the 27 streptomycin resistant (SMR) isolates, 7 carried mutations at the rpsL and the gidB genes. 1 of the 2 ethambutol resistant (EMBR) isolates displayed a mutation in embB gene.ConclusionThis study provided the first molecular investigation assessing the correlation of phenotypic to genotypic characteristics on MTB isolates from the Central Region of Cameroon using DNA sequencing. Mutations on rpoB, katG315 and -15 point mutations in inhA promoter loci could be used as markers for RIF and INH -resistance detection respectively.
BackgroundLoss to follow-up (LTFU) is a cause of potential bias in clinical studies. Differing LTFU between study groups may affect internal validity and generalizability of the results. Understanding reasons for LTFU could help improve follow-up in clinical studies and thereby contribute to goals for prevention, treatment, or research being achieved. We explored factors associated with LTFU of mother-child pairs after inclusion in the ANRS 12140-Pediacam study.MethodsFrom November 2007 to October 2010, 4104 infants including 2053 born to HIV-infected mothers and 2051 born to HIV-uninfected mothers matched individually on gender and study site were enrolled during the first week of life in three referral hospitals in Cameroon and scheduled for visits at 6, 10 and 14 weeks of age. Visits were designated 1, 2 and 3, in chronological order, irrespective of the child’s age at the time of the visit. Mother-child pairs were considered lost to follow-up if they never returned for a clinical visit within the first six months after inclusion. Uni- and multivariable logistic regression were adjusted on matching variables to identify factors associated with LTFU according to maternal HIV status.ResultsLTFU among HIV-unexposed infants was four times higher than among HIV-exposed infants (36.7% vs 9.8%, p < 0.001). Emergency caesarean section (adjusted Odds Ratio (aOR) = 2.46 95% Confidence Interval (CI) [1.47-4.13]), young maternal age (aOR = 2.29, 95% CI [1.18-4.46]), and absence of antiretroviral treatment for prophylaxis (aOR = 3.45, 95% CI [2.30-5.19]) were independently associated with LTFU among HIV-exposed infants. Factors associated with LTFU among HIV-unexposed infants included young maternal age (aOR = 1.96, 95% CI [1.36-2.81]), low maternal education level (aOR = 2.77, 95% CI [1.95-3.95]) and housewife/unemployed mothers (aOR = 1.56, 95% CI [1.16-2.11]).ConclusionFailure to return for at least one scheduled clinical visit is a problem especially among HIV-unexposed infants included in studies involving HIV-exposed infants. Factors associated with this type of LTFU included maternal characteristics, socio-economic status, quality of antenatal care and obstetrical context of delivery. Enhanced counselling in antenatal and intrapartum services is required for mothers at high risk of failure to return for follow-up visits.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-015-1555-2) contains supplementary material, which is available to authorized users.
Mycobacterium tuberculosis complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over 5 continents, by employing 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping (MIRU-VNTR) and drug susceptibility testing. We further combined whole-genome sequencing (WGS) and phylogeographic analysis for 373 strains representing the global L3 genetic diversity. Ancestral state reconstruction confirmed that the origin of L3 strains is located in Southern Asia and further revealed multiple independent introduction events into North-East and East Africa. This study provides a systematic understanding of the global diversity of L3 strains and reports phylogenetic variations that could inform clinical trials which evaluate the effectivity of new drugs/regimens or vaccine candidates.
The present study investigates the genetic diversity among Mycobacterium tuberculosis complex circulating in the Centre region of Cameroon and analyzes the relationship between genotypes and drug resistance patterns. Spoligotyping was performed by PCR-amplification followed by the reverse hybridization of 298 cultured specimens. Spoligotypes patterns were identified by comparison to reference strains in SPolDB4 database via the MIRU VNTR plus web application. About 97.65% of all tuberculosis (TB) cases were attributed to M. tuberculosis. A total of 65 different profiles were identified. Of these, 40 were represented as Shared Types (ST) while the others were orphans. LAM10_CAM and Haarlem families were the most prevalent genetic families with 51.01% and 14.09% respectively. ST 61, a member of the LAM10_ CAM family formed the largest cluster with 128 (42.95%) isolates. No association was found between genotypes with regard to drug resistance and HIV sero-status. However, there was a significant association between genotypes and age groups. Patients belonging to 15 -24 and 35 -44 age groups were more likely infected by LAM10_CAM strains compared to others. The population structure of Mycobacterium tuberculosis complex strains from the Centre region was found to be diverse and the spoligotype 61 of the LAM10_CAM family was highly predominant. Isolates of the LAM10_CAM seem to be not associated with drug resistance.
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