Different factors associated with loss to follow-up of infants born to HIV-infected or uninfected mothers: observations from the ANRS 12140-PEDIACAM study in Cameroon.

BACKGROUND: Loss 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. METHODS: From 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. RESULTS: LTFU 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]). CONCLUSION: Failure 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.

Sequence analysis for detection of drug resistance in Mycobacterium tuberculosis complex isolates from the Central Region of Cameroon.

BACKGROUND: The 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. RESULTS: From 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. CONCLUSION: This 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.

Strong decrease in streptomycin-resistance and absence of XDR 12 years after the Reorganization of the National Tuberculosis Control Program in the Central Region of Cameroon.

BACKGROUND: In the 1990s, resistance rates of 15% for streptomycin-resistance and 0.6% for multidrug-resistance (MDR) were reported from the Central Region of Cameroon. This work assesses drug resistant tuberculosis in this region 12 years after reorganization of the National Tuberculosis Control Program (NTCP). METHODS: This cross-sectional study was conducted from April 2010 to March 2011 in Jamot Hospital in Yaoundé, Cameroon. Only patients with smear positive pulmonary tuberculosis were included. Sputa were cultured and subsequently underwent drug susceptibility testing (DST). All consenting individuals were tested for their HIV status. RESULTS: A total of 665 smear positive pulmonary tuberculosis patients were enrolled. The HIV prevalence was 28.5% (95%CI [25.2-32.1]). Of the 582 sputa that grew Mycobacterium tuberculosis complex species, DST results were obtained for 576. The overall resistance rate was 10.9% (63/576). The overall resistance rates for single drug resistance were: isoniazid-resistance 4.7% (27/576), streptomycin-resistance 3.3% (19/576), rifampicin-resistance 0.2% (1/576), kanamycin-resistance 0.2% (1/576) and ofloxacin-resistance 0.2% (1/576). The MDR rate was 1.1% (6/576) and no extensively drug resistant tuberculosis (XDR) was detected. CONCLUSIONS: The data show that reorganization of the NTCP resulted in a strong decrease in streptomycin-resistance and suggest that it prevented the emergence of XDR in the Central Region of Cameroon.