Association of Group B Streptococcus (GBS) Serum Serotype-Specific Anticapsular Immunoglobulin G Concentration and Risk Reduction for Invasive GBS Disease in South African Infants: An Observational Birth-Cohort, Matched Case-Control Study.

BACKGROUND: Licensure of a group B Streptococcus (GBS) polysaccharide-protein conjugate vaccine for protecting infants against invasive GBS disease (IGbsD) will likely need to be based on demonstrating vaccine safety in pregnant women, and benchmarking immunogenicity against a serological threshold associated with risk reduction of IGbsD. We investigated the association between naturally derived GBS serotype Ia and III IgG and risk reduction of IGbsD in infants ≤90 days of age. METHODS: In a matched case-control study, IGbsD cases were identified from a cohort of 38 233 mother-newborn dyads. Mothers colonized vaginally with serotype Ia or III at birth and their healthy infants were eligible as matched controls. GBS serotype-specific anticapsular immunoglobulin G (IgG) was measured on maternal and cord blood/infant sera by multiplex Luminex assay, and the IgG threshold associated with 90% risk reduction of IGbsD was derived by estimating absolute disease risk. RESULTS: In infants born at ≥34 weeks' gestational age, cord-blood IgG geometric mean concentrations (GMCs) were lower in cases than controls for serotypes Ia (0.05 vs 0.50 µg/mL; P = .004) and III (0.20 vs 0.38 µg/mL; P = .078). Cord-blood IgG concentrations ≥1.04 and ≥1.53 µg/mL were associated with 90% risk reduction of serotype Ia and III IGbsD, respectively. The maternal sera IgG threshold associated with 90% risk reduction was ≥2.31 µg/mL and ≥3.41 µg/mL for serotypes Ia and III, respectively. CONCLUSIONS: The threshold associated with a reduced risk for serotype Ia and III IGbsD identified on infant sera supports the case for licensure of a GBS polysaccharide-protein conjugate vaccine based on an immunogenicity evaluation benchmarked against the defined thresholds. CLINICAL TRIALS REGISTRATION: NCT02215226.

An algorithmic approach to intracranial mass lesions in HIV/AIDS.

We developed a diagnostic and therapeutic algorithm for intracranial mass lesions in patients with HIV/AIDS that obviates the need for neurosurgical intervention. The approach is based upon CD4(+) lymphocyte count, serum toxoplasma immunoglobulin G (IgG) serology, chest X-ray, routine lumbar puncture studies, cerebrospinal fluid (CSF) cytology, CSF adenosine deaminase or Mycobacterium tuberculosis polymerase chain reaction testing, single positron emission-computed tomography (SPECT) scanning for intracranial enhancing lesions, and limited therapeutic trials. Over a 12-month period involving 26 patients, we found that the algorithm correctly identified the aetiology of focal intracranial lesions in all 23 evaluable patients. Costs for SPECT scanning for the entire study cohort were more than offset by the savings achieved by reduced hospital stays for the four patients with lymphoma alone. An algorithmic approach can accurately identify the cause(s) of central nervous system (CNS) mass lesions in HIV-infected patients, and SPECT scanning can replace stereotactic brain biopsy in most cases where opportunistic malignancy is suspected.

National sentinel site surveillance for antimicrobial resistance in Klebsiella pneumoniae isolates in South Africa, 2010 - 2012.

BACKGROUND: The increasing rates of antimicrobial resistance observed in the nosocomial pathogen Klebsiella pneumoniae are of major public health concern worldwide. OBJECTIVES: To describe the antibiotic susceptibility profiles of K. pneumoniae isolates from bacteraemic patients submitted by sentinel laboratories in five regions of South Africa from mid-2010 to mid-2012. Molecular methods were used to detect the most commonly found extended-spectrum beta-lactamase (ESBL) and carbapenemase resistance genes. METHODS: Thirteen academic centres serving the public healthcare sector in Gauteng, KwaZulu-Natal, Free State, Limpopo and Western Cape provinces submitted K. pneumoniae isolates from patients with bloodstream infections. Vitek 2 and MicroScan instruments were used for organism identification and susceptibility testing. Multiplex polymerase chain reactions (PCRs) were used to detect blaCTX-M, blaSHV and blaTEM genes in a proportion of the ESBL isolates. All isolates exhibiting reduced susceptibility to carbapenems were PCR tested for blaKPC and blaNDM-1 resistance genes. RESULTS: Overall, 68.3% of the 2,774 isolates were ESBL-positive, showing resistance to cefotaxime, ceftazidime and cefepime. Furthermore, 46.5% of all isolates were resistant to ciprofloxacin and 33.1% to piperacillin-tazobactam. The major ESBL genes were abundantly present in the sample analysed. Most isolates (95.5%) were susceptible to the carbapenems tested, and no isolates were positive for blaKPC or blaNDM-1. There was a trend towards a decrease in susceptibility to most antibiotics. CONCLUSION: The high proportion of ESBL-producing K. pneumoniae isolates observed, and the prevalence of ESBL genes, are of great concern. Our findings represent a baseline for further surveillance in SA, and can be used for policy and treatment decisions.

Genotypic and demographic characterization of invasive isolates of Salmonella Typhimurium in HIV co-infected patients in South Africa.

BACKGROUND: Non-typhoidal Salmonella are frequently food-borne zoonotic pathogens that may cause invasive disease in HIV-positive individuals. METHODOLOGY: Invasive isolates (n = 652) of Salmonella Typhimurium from human patients in Gauteng Province of South Africa were investigated for the years 2006 and 2007. Bacteria were identified using standard microbiological techniques and serotyping was performed using commercially available antisera. Susceptibility testing to antimicrobial agents was determined by the E-test. Genotypic relatedness of isolates was investigated by pulsed-field gel electrophoresis analysis of digested genomic DNA. RESULTS: Forty-five clusters of isolates were identified, of which four (clusters 3, 5, 6 and 11) were major clusters. Most isolates originated from hospital H2 and most were isolated from patients in the age range of 15 to 64 years. Ninety-three percent (213/230) of patients with a known HIV status were HIV-positive. Most isolates showed resistance to multiple antibiotics. The most commonly expressed antibiotic resistance profiles were ACSSuNa (14%; 75/555) and ACSSuTNa (13%; 72/555). Some evidence was found for nosocomial acquisition of isolates. Of the isolates from the major clusters 3, 5, 6, and 11, 33% (8/24), 6% (7/117), 4% (1/26) and 6% (3/52) were of nosocomial origin, respectively. CONCLUSIONS: In South Africa, Salmonella Typhimurium remains a major opportunistic infection of predominantly HIV-positive patients. Clonally diverse strains that are resistant to multiple antibiotics may circulate in patients aged between 15 and 64 years over prolonged periods within the hospital environment, adding to the health care burden.