Primary and acquired drug resistance in adult black patients with tuberculosis in South Africa: results of a continuous national drug resistance surveillance programme involvement.

Drug resistance is a major problem in the treatment of tuberculosis, and monitoring programmes are essential in control of this disease. The extent of primary resistance in a community is an important indication of the effectiveness of treatment schedules. Since 1965 the Tuberculosis Research Institute (TBRI) of the South African Medical Research Council has performed 25 annual surveys of drug resistance in adult black tuberculosis patients where the disease is most prevalent. Methodology for patient selection, specimen collection, laboratory procedures and criteria for drug resistance were strictly adhered to. All specimens were processed in a central laboratory supervised by the same two technologists. Between 1965 and 1988 a total of 33,111 strains of Mycobacterium tuberculosis were isolated from new cases and 19,134 from old cases. Both primary and acquired resistance to the 5 major antituberculosis drugs has decreased dramatically. Sex and age do not influence resistance rates, while patients' ethnic origin and geographical location do. The results indicate that current tuberculosis treatment practices are satisfactory. The prevalence of primary drug resistance in black South Africans is now intermediate between those countries where eradication of tuberculosis is well advanced and those where the disease remains a public health problem. Also, it can be shown that comparable and clinically significant data can be obtained from a central laboratory employing unsophisticated and inexpensive drug susceptibility testing procedures.     

Evidence for insulin resistance in black women from South Africa

OBJECTIVE: The rate of glucose disposal was determined in 10 black and 10 white obese nondiabetic urban women from South Africa to assess insulin resistance. DESIGN AND METHODS: Euglycemic hyperinsulinemic clamp and body composition analysis. RESULTS: Age, body mass index (BMI), anthropometric measurements and body composition were similar in both groups of women. A five-level computed tomography (CT) scan showed a similar mean subcutaneous fat mass in both groups of women (black obese women 555 +/- 9.0 vs white obese women 532 +/- 6.0 cm2), but less visceral fat in black obese women (90 +/- 3.0 vs 121 +/- 3.1 cm2; P< 0.05). Black obese women had higher fasting free fatty acid (997 +/- 69 vs 678 +/- 93 micromol/l; P < 0.05) and lactate concentrations (1,462 +/- 94 vs 1,038 +/- 39 micromol/l; P < 0.05), but lower fasting insulin levels (87 +/- 12 vs 155 +/- 9 pmol/l; P < 0.001). Black obese women also had a more favorable HDL: total cholesterol ratio (30.5% vs 23.0%; P< 0.04). The mean glucose disposal rate (M) and disposal expressed as glucose sensitivity index (M/I) were reduced in the black obese women vs white obese women (M: 7.1 +/- 0.8 vs 13.7 +/- 1.0 mmol/kg min(-1) x 100; P< 0.01, and M/I: 0.12 +/- 0.01 vs 0.24 +/- 0.02 mmol/kg x min(-1)/pmol/1 x 1,000; P < 0.01). Only black obese women showed a significant decrease in C-peptide levels during the clamp (2.9 +/- 0.22 vs 1.2 +/- 0.12 nmol/l; P<0.001). During the euglycemic period, the black obese women had higher lactate levels at all time points, but only the white obese women had increased lactate levels (918 +/- 66 to 1,300 +/- 53 micromol/l; P< 0.05). CONCLUSION: Black obese women demonstrate a higher degree of insulin resistance, despite less visceral fat and a higher HDL: total-cholesterol ratio. In addition, endogenous beta-cell secretory function in black obese women appears to be more sensitive to the suppressive effect of exogenous insulin administration. The significant increase in lactate levels in white obese women confirms that they are more insulin sensitive.     

Rapid development of antiretroviral drug resistance mutations in HIV-infected children less than two years of age initiating protease inhibitor-based therapy in South Africa

Data on the development of antiretroviral drug resistance in HIV-1-infected children receiving protease inhibitor (PI)-based antiretroviral therapy (ART) are limited. We examined antiretroviral resistance among a cohort of 323 South African HIV-infected children <2 years old exposed to nevirapine for prevention of mother-to-child transmission. Ritonavir (RTV) was used initially for 138 children who were <6 months old or receiving antimycobacterial therapy; otherwise children received lopinavir/ritonavir (LPV/r)-based ART. HIV-1 population sequencing of the pol gene was conducted on all pretreatment samples and on posttreatment samples for children who did not achieve HIV-1 plasma RNA <400 copies/ml by 52 weeks. Among children in the cohort, 38 died, 22 had <24 weeks follow-up, 209 achieved virologic suppression, and 54 did not. Of 41 children without virologic suppression with posttreatment HIV genotype data available, major resistance mutations were found in 32 (78%): 14 (36%) had PI mutations including V82A, M46I, and L90M; 29 (71%) had M184V/I; and three had NNRTI mutations (K103N, Y181C, and G190A). Among the children who did not achieve virologic suppression, none of the seven children treated exclusively with LPV/r developed PI-related mutations, compared with 14 of 32 (44%) who received RTV-based regimens (p=0.036); PI genotypes were unavailable for two children. Seventy-eight percent of children without virologic suppression developed resistance mutations that impact second-line ART options. Only children who received RTV-based ART developed major PI-related resistance mutations, and use of this regimen should be avoided.     

Accumulation of HIV drug resistance mutations in patients failing first-line antiretroviral treatment in South Africa

Patients failing antiretroviral treatment for extended periods of time are at risk of accumulating HIV drug resistance mutations (DRMs), which negatively influences second-line treatment. This retrospective study assessed the rate of DRM accumulation among South African patients with continued virological failure. Serial genotypic resistance testing was performed and DRMs were scored according to the 2009 IAS-USA list. Among 43 patients, 38 (88.4%) harbored ≥1 DRM. The median time between two sequential resistance tests was 5 months (IQR: 3-10). Thymidine analogue mutations accumulated at a rate of 0.07 mutation per month of drug exposure, which is faster than previously reported. Routine virological monitoring should be implemented in resource-limited settings to preserve susceptibility to second-line regimens.     

Drug coverage surveys for neglected tropical diseases: 10 years of field experience

Abstract. Mass drug administration is one of the public health strategies recommended by the World Health Organization for the control and elimination of seven neglected tropical diseases (NTDs). Because adequate coverage is vital to achieve program goals, periodically conducting surveys to validate reported coverage to guide NTD programs is recommended. Over the past decade, the Centers for Disease Control and Prevention (CDC) and collaborators conducted more than 30 two-stage cluster household surveys across three continents. The questionnaires gathered coverage data and information relevant to improving NTD programs including NTD-related attitudes and practices. From the 37 coverage survey estimates obtained in those surveys, 73.3% indicated an over reporting of coverage, including all three that assessed school-based distributions. It took an average of 1 week to conduct a survey. Our experiences led us to conclude that coverage surveys are useful and feasible tools to ensure NTD elimination and control goals are reached.