Molecular characterisation of group A streptococcus isolates recovered from the north-west of Pretoria, South Africa.

BACKGROUND: Group A streptococcus (GAS) is a human pathogen responsible for a wide range of invasive and non-invasive infections. Pharyngitis caused by GAS may have complications such as acute rheumatic fever subsequently leading to rheumatic heart disease (RHD). RHD continues to have high morbidity and mortality and affects millions of children and young adults, mostly in developing countries. An effective preventive vaccine against GAS may reduce the morbidity and mortality. A 30-valent M-protein-based vaccine is currently at the clinical trials stage of development. Potential vaccine coverage will depend on the geographical distribution of GAS emm (M protein) types. OBJECTIVES: To determine the emm types of GAS isolates circulating in the north-west of Pretoria, South Africa. METHODS: Throat swabs were collected from patients aged 3 - 20 years presenting with pharyngitis at one local clinic. In addition, GAS clinical isolates were collected from the National Health Laboratory Service diagnostic laboratory. Emm genotyping was done on the GAS isolates by amplification of the emm gene followed by sequencing of the 5' portion of the gene. The emm types were correlated with the types in the vaccine. RESULTS: A total of 54 GAS isolates were collected, comprising 19 pharyngitis and 35 clinical isolates. We found 15 different emm types among the 43 GAS isolates that were successfully sequenced. Eleven isolates (20%) could not be typed. The most prevalent emm type was 92 (26%), which is part of the 30-valent vaccine. This was followed by emm 25 and 75, each accounting for 12% of the isolates. Up to 67% of the emm types are not covered in the 30-valent vaccine. CONCLUSIONS: Fifteen emm types were identified, of which 92 was the most prevalent. It is concerning that 67% of the emm types are not covered in the vaccine currently under development. It is recommended that surveillance studies be extended to include other parts of the country in order to expand knowledge of the circulating emm types.

What do South African adolescents want in a sexual health service? Evidence from the South African Studies on HIV in Adolescents (SASHA) project.

BACKGROUND: Young people in sub-Saharan Africa (SSA) are disproportionately affected by HIV, sexually transmitted infections and unplanned pregnancies. The provision of accessible sexual and reproductive health services (SRHS) for young people in SSA is vital to reduce this burden. OBJECTIVES: To examine the needs of South African (SA) adolescents with regard to differentiated, accessible and adolescent-responsive SRHS. METHODS: Data were drawn from a larger project examining the feasibility of conducting HIV vaccine trials in adolescents. Fifteen focus group discussions were conducted across five research sites in four SA provinces with 120 male and female adolescent human papillomavirus vaccine trial participants aged 12 - 19 years from low-income areas with a high incidence of HIV. Transcribed data were double-coded using framework analysis. RESULTS: Three main themes emerged on how best to improve SRHS for adolescents in resource-limited settings: adolescent-friendly services, availability of developmentally appropriate and tailored information, and improved relationships between healthcare workers and clinic attendees. Participants wanted more flexible opening hours at SRHS to account for travel time to clinics from school and home. They suggested that services include contraception, counselling, educational materials, links to adoption services, emergency vehicles, pre- and postnatal care, and improved service quality from clinic staff. CONCLUSIONS: While dedicated adolescent SRHS might best meet the needs of young people in SA, the study suggests that failing this, existing SRHS should be more responsive to adolescent use. Innovations such as mobile outreach services, self-testing and flexible hours will help SRHS respond to adolescents' needs.

Feasibility and acceptability of conducting HIV vaccine trials in adolescents in South Africa: Going beyond willingness to participate towards implementation.

BACKGROUND: HIV/AIDS remains a leading cause of death in adolescents (aged 15 - 25 years), and in sub-Saharan Africa HIV-related deaths continue to rise in this age group despite a decline in both adult and paediatric populations. This is attributable in part to high adolescent infection rates and supports the urgent need for more efficacious prevention strategies. In particular, an even partially effective HIV vaccine, given prior to sexual debut, is predicted to significantly curb adolescent infection rates. While adolescents have indicated willingness to participate in HIV vaccine trials, there are concerns around safety, uptake, adherence, and ethical and logistic issues. OBJECTIVES: To initiate a national, multisite project with the aim of identifying obstacles to conducting adolescent HIV vaccine trials in South Africa (SA). METHOD: A simulated HIV vaccine trial was conducted in adolescents aged 12 - 17 years across five SA research sites, using the already licensed Merck human papillomavirus vaccine Gardasil as a proxy for an HIV vaccine. Adolescents were recruited at community venues and, following a vaccine discussion group, invited to participate in the trial. Consent for trial enrolment was obtained from a parent or legal guardian, and participants aged 16 - 17 years were eligible only if sexually active. Typical vaccine trial procedures were applied during the five study visits, including the administration of vaccination injections at study visits 2, 3 and 4. RESULTS: The median age of participants was 14 years (interquartile range 13 - 15), with 81% between the ages of 12 and 15 years at enrolment. Overall, 98% of screened participants opted to receive the vaccine, 588 participants enrolled, and 524 (89%) attended the final visit. CONCLUSIONS: This trial showed that adolescents can be recruited, enrolled and retained in clinical prevention trials with parental support. While promising, these results were tempered by the coupling of sexual-risk eligibility criteria and the requirement for parental/guardian consent, which was probably a barrier to the enrolment of high-risk older adolescents. Further debate around appropriate consent approaches for such adolescents in HIV prevention studies is required.

Feasibility and acceptability of conducting HIV vaccine trials in adolescents in South Africa: Going beyond willingness to participate towards implementation

Background. HIV/AIDS remains a leading cause of death in adolescents (aged 15 - 25 years), and in sub-Saharan Africa HIV-related deaths continue to rise in this age group despite a decline in both adult and paediatric populations. This is attributable in part to high adolescent infection rates and supports the urgent need for more efficacious prevention strategies. In particular, an even partially effective HIV vaccine, given prior to sexual debut, is predicted to significantly curb adolescent infection rates. While adolescents have indicated willingness to participate in HIV vaccine trials, there are concerns around safety, uptake, adherence, and ethical and logistic issues.Objectives. To initiate a national, multisite project with the aim of identifying obstacles to conducting adolescent HIV vaccine trials in South Africa (SA).Method. A simulated HIV vaccine trial was conducted in adolescents aged 12 - 17 years across five SA research sites, using the already licensed Merck human papillomavirus vaccine Gardasil as a proxy for an HIV vaccine. Adolescents were recruited at community venues and, following a vaccine discussion group, invited to participate in the trial. Consent for trial enrolment was obtained from a parent or legal guardian, and participants aged 16 - 17 years were eligible only if sexually active. Typical vaccine trial procedures were applied during the five study visits, including the administration of vaccination injections at study visits 2, 3 and 4.Results. The median age of participants was 14 years (interquartile range 13 - 15), with 81% between the ages of 12 and 15 years at enrolment. Overall, 98% of screened participants opted to receive the vaccine, 588 participants enrolled, and 524 (89%) attended the final visit.Conclusions. This trial showed that adolescents can be recruited, enrolled and retained in clinical prevention trials with parental support. While promising, these results were tempered by the coupling of sexual-risk eligibility criteria and the requirement for parental/guardian consent, which was probably a barrier to the enrolment of high-risk older adolescents. Further debate around appropriate consent approaches for such adolescents in HIV prevention studies is required

Does participation in an HIV vaccine efficacy trial affect risk behaviour in South Africa?

BACKGROUND: Increased sexual risk behaviour in participants enrolled in HIV prevention trials has been a concern. The HVTN 503/Phambili study, a phase 2B study of the Merck Ad-5 multiclade HIV vaccine in South Africa, suspended enrollment and vaccinations following the results of the Step study. Participants were notified of their treatment allocation and continue to be followed. We investigated changes in risk behaviour over time and assessed the impact of study unblinding. METHODS: 801 participants were enrolled. Risk behaviours were assessed with an interviewer-administered questionnaire at 6-month intervals. We assessed change from enrolment to the first 6-month assessment pre-unblinding and between enrolment and at least 6 months post-unblinding on all participants with comparable data. A one-time unblinding risk perception questionnaire was administered post-unblinding. RESULTS: A decrease in participants reporting unprotected sex was observed in both measured time periods for men and women, with no differences by treatment arm. At 6 months (pre-unblinding), 29.6% of men and 35.8% of women reported changing from unprotected to protected sex (p<0.0001 for each). Men (22%) were more likely than women (14%) to report behaviour change after unblinding (p=0.009). Post-enrolment, 142 (45%) of 313 previously uncircumcised men underwent medical circumcision. 663 participants completed the unblinding questionnaire. More vaccine (24.6%) as compared to placebo recipients (12.0%) agreed that they were more likely to get HIV than most people (p<0.0001), and attributed this to receiving the vaccine. CONCLUSION: We did not find evidence of risk compensation during this clinical trial. Some risk behaviour reductions including male circumcision were noted irrespective of treatment allocation.

Drug-susceptibility patterns of Mycobacterium tuberculosis in Mpumalanga province, South Africa: possible guiding design of retreatment regimen.

Multidrug-resistant tuberculosis (MDR-TB) has been a cause of concern in both developed and developing countries. The prevalence of drug resistance in Mycobacterium tuberculosis (MTB) isolates (n=692) from Mpumalanga province was assessed. In total, 692 (64%) MTB strains from cases with pulmonary TB were tested for susceptibility against rifampicin, isoniazid, ethambutol, and streptomycin using the MGIT 960 instrument. Two hundred and nine (30.2%) strains were resistant to one or more drugs. Resistance to one drug ranged from 1.4% for ethambutol to 17.7% for rifampicin. The prevalence of MDR-TB ranged from 6.7% for three drugs to 34% for four drugs, with significant predictors being patients' age-groups of 25-54 years (p=0.0012) and >55 years (p=0.007). The result showed a high level (58.4%) of MDR-TB from cases in Mpumalanga province. To achieve a higher cure rate in this province, drug-susceptibility tests must be done for every case.

Antimicrobial Susceptibility Patterns of Selected Invasive Pathogens from Public Sector Hospitals in South Africa; 2007

Retrospective antibiotic surveillance data of selected invasive pathogens isolated from blood and cerebrospinal fluid at public sector hospitals in South Africa in 2007 are presented. Antimicrobial susceptibilities were determined according to the 2007 Clinical and Laboratory Standards Institute criteria. Klebsiella pneumoniae remains a highly resistant pathogen; with approximately half of all strains producing extended-spectrum beta-lactamases. All laboratories reported considerable resistance among Acinetobacter spp. Approximately 50-60of Staphylococcus aureus isolates from blood were resistant to cloxacillin. Among Streptococcus pneumoniae isolates from blood and cerebrospinal intermediate resistance to penicillin. Resistance to ceftriaxone in S. pneumoniae was rare

Emergence of multi-drug-resistant Acinetobacter anitratus species in neonatal and paediatric intensive care units in a developing country: concern about antimicrobial policies.

Antimicrobial abuse is a serious risk factor for the emergence of multi-drug-resistant (MDR) pathogens. We report on the emergence of multi-drug-resistant Acinetobacter anitratus species over two 8-week periods in 1999 in the neonatal and paediatric intensive care units (NICU and PICU) of King Edward VII Hospital, Durban, South Africa. The source, transmission dynamics, microbiological evaluations, antibiotic utilization patterns and outcome were evaluated. MDR Acinetobacter anitratus was isolated from different body sites in 23 infants less than 2 months of age, 18 in the PICU and five in the NICU. The mortality was 56.5% and two survivors required re-admission. Ten of the 23 cases had entered the ICU with MDR Acinetobacter anitratus. Eleven of the study infants had received broad-spectrum antimicrobial agents before entering the ICU, while all infants with nosocomially acquired MDR Acinetobacter anitratus had received broad-spectrum antimicrobial agents. All the surgical cases with MDR Acinetobacter anitratus died. Microbiological data from both ICUs for 1999 indicated that gram-negative bacteria accounted for two-thirds of isolates, Acinetobacter anitratus and Klebsiella pneumoniae accounting for 33% and 27% of the isolates, respectively. Only 53% and 57% of all Acinetobacter spp isolates were susceptible to piperacillin/tazobactam and carbepenems, respectively. MDR Acinetobacter anitratus is an emerging problem to which antimicrobial abuse contributes.