Background.In the African meningitis belt, Neisseria meningitidis serogroup W135 has emerged as a cause of epidemic disease. The establishment of W13

All fully sequenced strains of Streptococcus pneumoniae possess a version of the blp locus, which is responsible for bacteriocin production and immunity. Activation of the blp locus is stimulated by accumulation of the peptide pheromone, BlpC, following its secretion by the ABC transporter, BlpA. The blp locus is characterized by significant diversity in blpC type and in the region of the locus containing putative bacteriocin and immunity genes. In addition, the blpA gene can represent a single large open reading frame or be divided into several smaller fragments due to the presence of frameshift mutations. In this study, we use a collection of strains with blp -dependent inhibition and immunity to define the genetic changes that bring about phenotypic differences in bacteriocin production or immunity. We demonstrate that alterations in blpA , blpC , and bacteriocin/immunity content likely play an important role in competitive interactions between pneumococcal strains. Importantly, strains with a highly conserved frameshift mutation in blpA are unable to secrete bacteriocins or BlpC, but retain the ability to respond to exogenous peptide pheromone produced by cocolonizing strains, stimulating blp -mediated immunity. These “cheater” strains can only coexist with bacteriocin-producing strains that secrete their cognate BlpC and share the same immunity proteins. The variable outcome of these interactions helps to explain the heterogeneity of the blp pheromone, bacteriocin, and immunity protein content. IMPORTANCE Streptococcus pneumoniae resides in a polymicrobial environment and competes for limited resources by the elaboration of small antimicrobial peptides called bacteriocins. A conserved cluster of genes in the S. pneumoniae genome is involved in the production of bacteriocins and their associated protective immunity proteins through secretion of a signaling pheromone. In this study, we show that a significant number of strains have lost the ability to secrete bacteriocins and signaling pheromones due to a specific mutation in a dedicated transporter protein. Because the regulatory and immunity portion of the locus is retained, these “cheater” strains can survive in the face of invasion from a bacteriocin-producing strain without the cost of bacteriocin secretion. The outcome of such interactions depends on each strain’s repertoire of pheromone, immunity protein, and bacteriocin genes, such that intrastrain competition drives the diversity in bacteriocin, immunity protein, and pheromone content.

Highly active antiretroviral treatment (HAART) programs have been associated with declines in the burden of invasive pneumococcal disease (IPD) in industrialized countries. The aim of this study was to evaluate trends in IPD hospitalizations in HIV-infected adults in Soweto, South Africa, associated with up-scaling of the HAART program from 2003 to 2008. Laboratory-confirmed IPD cases were identified from 2003 through 2008 through an existing surveillance program. The period 2003-04 was designated as the early-HAART era, 2005–06 as the intermediate-HAART era and 2007–08 as the established-HAART era. The incidence of IPD was compared between the early-HAART and established-HAART eras in HIV-infected and–uninfected individuals. A total of 2,567 IPD cases among individuals older than 18 years were reported from 2003 through 2008. Overall incidence of IPD (per 100,000) did not change during the study period in HIV-infected adults (207.4 cases in the early-HAART and 214.0 cases in the established-HAART era; p = 0.55). IPD incidence, actually increased 1.16-fold (95% CI: 1.01; 1.62) in HIV-infected females between the early-and established-HAART eras (212.1 cases and 246.2 cases, respectively; p = 0.03). The incidence of IPD remained unchanged in HIV-uninfected adults across the three time periods. Despite a stable prevalence of HIV and the increased roll-out of HAART for treatment of AIDS patients in our setting, the burden of IPD has not decreased among HIV-infected adults. The study indicates a need for ongoing monitoring of disease and HAART program effectiveness to reduce opportunistic infections in African adults with HIV/AIDS, as well as the need to consider alternate strategies including pneumococcal conjugate vaccine immunization for the prevention of IPD in HIV-infected adults.

Objective: HIV infection is a major risk factor for invasive pneumococcal disease (IPD). A national antiretroviral program was initiated in South Africa in 2004. This study evaluates the impact of the highly active antiretroviral therapy (HAART) treatment program on the burden of IPD among African children. Design: Retrospective analysis of laboratory-confirmed IPD among children under 18 years of age, from 2003 to 2008. Methods: The periods 2003–2004, 2005–2006 and 2007–2008 were defined as the early, intermediate and established HAART eras, respectively. Pneumococcal conjugate vaccine was not introduced into public immunization during this period. Results: One thousand, one hundred and seventy-one episodes of IPD were identified over the study period. Among HIV-infected children under 18 years, the burden of IPD decreased by 50.8% [95% confidence interval (CI) 41.5–58.7] and the incidence of IPD-related mortality declined by 65.2% (95% CI 47.2–77.0) from the early compared to the established HAART era. This decline in HIV-infected children was evident for pneumococcal bacteremia and pneumococcal meningitis. In addition, similar reductions were observed for serotypes included in a 7-valent pneumococcal conjugate vaccine and nonvaccine serotypes. The burden of IPD remained unchanged in HIV-uninfected children under 18 years of age over these periods. The risk of IPD, however, remained 42-fold greater in HIV-infected compared to HIV-uninfected children in the established HAART era. Conclusions: Although the HAART program has been associated with significant declines in IPD morbidity and mortality, HIV-infected African children with access to HAART remain a high-risk group for IPD. These children should therefore be prioritized in the prevention of IPD.

Objectives: We aimed to compare the incidence of meningococcal disease amongst HIV-infected and uninfected individuals and to evaluate whether HIV is a risk factor for mortality and bacteremia amongst patients with meningococcal disease. Design: Cohort surveillance study. Methods: We conducted laboratory-based surveillance for meningococcal disease in Gauteng Province, South Africa. HIV status and outcome data were obtained at sentinel sites. Incidence in HIV-infected and uninfected persons was calculated assuming a similar age-specific HIV prevalence in tested and untested individuals. Risk factors for death and bacteremia (as compared with meningitis) were evaluated using multivariable logistic regression. Results: From 2003 to 2007, 1336 meningococcal cases were reported. Of 504 patients at sentinel sites with known outcome, 308 (61%) had HIV serostatus data. HIV prevalence amongst cases of meningococcal disease was higher than the population HIV prevalence in all age groups. The incidence of meningococcal disease in HIV-infected individuals was elevated in all age groups with an age-adjusted relative risk of 11.3 [95% confidence interval (CI) 8.9–14.3, P < 0.001]. The case-fatality ratio (CFR) was 20% (27/138) amongst HIV-infected and 11% (18/170) amongst HIV-uninfected individuals [odds ratio (OR) 2.1, 95% CI 1.1–3.9]. On multivariable analysis, CFR was greater amongst patients with bacteremia (35%, 29/82) compared with meningitis (7%, 16/226) (OR 7.8, 95% CI 3.4–17.7). HIV infection was associated with increased odds of bacteremia (OR 2.7, 95% CI 1.5–5.0). Conclusion: HIV-infected individuals may be at increased risk of meningococcal disease. The increased CFR in HIV-infected patients may be explained by their increased odds of bacteremia compared to meningitis.

To describe findings from an external quality assessment programme involving laboratories in Africa that routinely investigate epidemic-prone diseases. Beginning in 2002, the Regional Office for Africa of the World Health Organization (WHO) invited national public health laboratories and related facilities in Africa to participate in the programme. Three surveys comprising specimens and questionnaires associated with bacterial enteric diseases, bacterial meningitis, plague, tuberculosis and malaria were sent annually to test participants' diagnostic proficiency. Identical surveys were sent to referee laboratories for quality control. Materials were prepared, packaged and shipped in accordance with standard protocols. Findings and reports were due within 30 days. Key methodological decisions and test results were categorized as acceptable or unacceptable on the basis of consensus feedback from referees, using established grading schemes. Between 2002 and 2009, participation increased from 30 to 48 Member States of the WHO and from 39 to 78 laboratories. Each survey was returned by 64-93% of participants. Mean turnaround time was 25.9 days. For bacterial enteric diseases and meningitis components, bacterial identification was acceptable in 65% and 69% of challenges, respectively, but serotyping and antibiotic susceptibility testing and reporting were frequently unacceptable. Microscopy was acceptable for 73% of plague challenges. Tuberculosis microscopy was satisfactorily performed, with 87% of responses receiving acceptable scores. In the malaria component, 82% of responses received acceptable scores for species identification but only 51% of parasite quantitation scores were acceptable. The external quality assessment programme consistently identified certain functional deficiencies requiring strengthening that were present in African public health microbiology laboratories.