Shabir A Madhi

Publications (139) View all

• Article: Community-onset Staphylococcus aureus bacteraemia in hospitalised African children: high incidence in HIV-infected children and high prevalence of multidrug resistance.

  M J Groome, W C Albrich, J Wadula, M Khoosal, S A Madhi
  [show abstract] [hide abstract]
  ABSTRACT: Invasive bacterial disease causes significant morbidity and mortality in children in developing countries. The burden of invasive disease caused by Staphylococcus aureus and S. aureus antimicrobial resistance patterns in African children in settings with a high prevalence of HIV infection remain ill-defined. To describe the burden of community-onset bacteraemic S. aureus infections in children in an area with a high prevalence of paediatric HIV infection, and to describe the antimicrobial resistance patterns. A retrospective record review of children hospitalised at Chris Hani Baragwanath Hospital, Soweto, with S. aureus bacteraemia between January 2005 and December 2006 was conducted. Community-onset S. aureus bloodstream infections were defined as S. aureus cultured from blood obtained within 48 hours of admission. Community-onset S. aureus bacteraemia was identified in 161 children, representing an incidence of 26/100,000, with 63 (39%) isolates identified as methicillin-resistant (10/100,000). The incidence of community-onset S. aureus bacteraemia, both methicillin-susceptible and methicillin-resistant, was inversely related to age and greater in HIV-infected than uninfected children. High rates of antibiotic resistance were observed in MRSA isolates and only resistance to amikacin, fusidic acid and ciprofloxacin was <40%. MRSA isolates were frequently multidrug-resistant. Among HIV-infected children, resistance to trimethoprim-sulfamethoxazole was 100% and to rifampicin was 78%. This study highlights the burden of S. aureus bacteraemia in a setting with a high prevalence of paediatric HIV infection. The high incidence of S. aureus bacteraemia coupled with a high prevalence of methicillin resistance, particularly in HIV-infected children, needs to be considered in the empirical management of paediatric sepsis in settings such as ours.
  Paediatrics and international child health. 01/2012; 32(3):140-6.
• Article: Antibody Persistence and Booster Vaccination of a Fully Liquid Hexavalent Vaccine Co-Administered with Measles/Mumps/Rubella and Varicella Vaccines at 15-18 Months of Age in Healthy South African Infants.

  Shabir A Madhi, Anthonet Koen, Clare Cutland, Michelle Groome, Eduardo Santos-Lima
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVE:: To assess antibody persistence and booster immunogenicity and safety of a new, fully liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine. METHODS:: Phase III, open-label, two-center trial. Infants previously primed at 6, 10 14 weeks of age with DTaP-IPV-Hep B-PRP-T either without (Group 1:N=218) or with hepatitis B at birth (Group 3:N=130) or control DTwP-Hib, hepatitis B, and OPV vaccines (Group 2:N=219) received the same vaccine(s) as booster (except hepatitis B for Group 2) at 15-18 months of age, co-administered with measles/mumps/rubella and varicella vaccines (MMR+V). All participants had received measles vaccine at 9 months of age. Antibodies were measured pre- and 1 month post-booster vaccination. Safety was evaluated from parental reports. Analyses were descriptive. RESULTS:: Antibody persistence (seroprotection [SP] and concentration) at 15-18 months of age was high for each valence and similar in each group, except for Hep B (highest in Group 3 [extra dose of hepatitis B]), and PRP (highest in Group 2). Post-booster seroprotection (D, T, IPV, Hep B, PRP) and seroconversion (PT, FHA) rates were high and similar in each group (excluding Hep B in Group 2 [no booster]); geometric mean antibody levels increased markedly in all groups. The response to MMR+V was similar in each group. All vaccines were well tolerated. CONCLUSIONS:: A booster dose of the new DTaP-IPV-Hep B-PRP-T vaccine at 15-18 months of age is highly immunogenic and safe compared to licensed comparators, following primary series administration in the EPI schedule, with or without a hepatitis B vaccine at birth and co-administered with MMR+V.
  The Pediatric Infectious Disease Journal 03/2013; · 3.58 Impact Factor
• Article: Impact of the Antiretroviral Treatment Program on the Burden of Hospitalization for Culture-Confirmed Tuberculosis in South African Children: A Time-Series Analysis.

  Ziyaad Dangor, Alane Izu, Kelty Hillier, Fatima Solomon, Natalie Beylis, David P Moore, Marta C Nunes, Shabir A Madhi
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND:: The HIV-epidemic increased the burden of tuberculosis (TB) in Sub-Saharan Africa. We evaluated the impact that scaling-up of the public-funded anti-retroviral treatment (ART) program had on incidence of hospitalization for culture-confirmed and overall-TB in HIV-infected and HIV-uninfected children from 2005 to 2009. METHODS:: The study was undertaken in Soweto, South Africa, where ART coverage of HIV-infected children increased from 43% in 2005 to 84% by 2009. Trends in incidence of hospitalization for clinically-diagnosed and culture-confirmed TB in children 3 months to <15 years of age, identified through laboratory and electronic databases, were analyzed by comparing crude incidence and regression analysis. RESULTS:: The incidence (per 100 000) of culture-confirmed TB declined by 63.1% from 2005 (69.8) compared to 2009 (25.8; p<0.0001). This included a 70.6% reduction between 2005 and 2009 among HIV-infected children (incidence: 1 566.3 vs. 460.7, respectively; p<0.0001) and 41.3% decrease in HIV-uninfected children (18.7 vs. 11.0, respectively; p=0.0003). The month-by-month rate of decline of culture-confirmed TB was 2.3% in HIV-infected and 1.1% in HIV-uninfected children over the study-period. The residual burden of TB remained 42-fold greater in HIV-infected children, 78% of whom were severely immune-compromised, compared to HIV-uninfected children by 2009. CONCLUSION:: Increase in ART coverage was associated with significant decline in TB hospitalizations in HIV-infected children. This reduction may also in-part have been due to reduced Mycobacterium tuberculosis transmission resulting from increased ART-access among HIV-infected adults, which may have contributed to the reduction of culture-confirmed TB in HIV-uninfected children.
  The Pediatric Infectious Disease Journal 03/2013; · 3.58 Impact Factor
• Article: Review of a new fully liquid, hexavalent vaccine: Hexaxim.

  Marta C Nunes, Shabir A Madhi
  [show abstract] [hide abstract]
  ABSTRACT: Introduction: The introduction of injectable vaccines targeting new diseases into childhood immunization programs has resulted in the need for combination vaccines to reduce the number of injections given during early childhood and maintain acceptability of targeting multiple pathogens by vaccination. Currently, there is only one licensed hexavalent combination vaccine which targets diphtheria, polio, tetanus, Haemophilus influenzae type b, hepatitis B and pertussis. A new, fully liquid formulation hexavalent vaccine ( Hexaxim ) has been developed and is currently undergoing licensure for use in childhood immunization programs. Areas covered: Safety and immunogenicity studies of Hexaxim have been undertaken in a diversity of settings, been evaluated with different dosing schedules and in comparison to the other licensed hexavalent vaccine (Infanrix hexa). This review of published journal articles and conference proceeding is focused on the studies in which Hexaxim has been evaluated and which are contributing to its pending licensure. Non-inferiority was demonstrated at the level of proportion of children developing seroprotective titers or showing seroconversion following the primary series of vaccine compared to the same target-antigens included in licensed combination vaccines. Also, Hexaxim was associated with a favorable safety and tolerability profile when administered during the first 6 months of life. Adequate and robust memory responses were elicited following a booster dose in the second year of life. Expert opinion: The development of new hexavalent combination vaccines targeting established pathogens is likely to assist in improving compliance and timeliness of vaccination in infants. These formulations will, however, need to be monitored for medium- and long-term effectiveness amidst growing concern of waning immunity against diseases such as pertussis when using acellular-pertussis vaccine and possibly hepatitis B when using combination vaccines. Nevertheless, the development of such combination vaccines remains necessary to help with the introduction of other new vaccines into an already crowded childhood immunization schedules.
  Expert opinion on biological therapy 02/2013; · 3.22 Impact Factor
• Article: Acquisition of Streptococcus pneumoniae in Pneumococcal Conjugate Vaccine-Naïve South African Children and Their Mothers.

  Marta C Nunes, Tinevimbo Shiri, Nadia van Niekerk, Clare L Cutland, Michelle J Groome, Anthonet Koen, Anne von Gottberg, Linda de Gouveia, Keith P Klugman, Peter V Adrian, Shabir A Madhi
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND:: Pneumococcal nasopharyngeal colonization is a pre-requisite to developing pneumococcal-disease. We investigated the dynamics of pneumococcal colonization in peri-natal HIV-unexposed and HIV-exposed children and their mothers, and risk-factors associated with new serotypes acquisition. METHODS:: 243 mother/child pairs (120 HIV-infected, 123 HIV-uninfected mothers) were studied at 4.4, 7.2, 9.4, 12.3 and 16.0 months of the child's age. Demographic data, nasopharyngeal swabs, as well as oropharyngeal swabs from mothers were collected for pneumococcal conventional culture and serotyping by the Quellung method. RESULTS:: The rate of new serotype acquisition during the 16 months did not differ between HIVexposed (49.1%) and HIV-unexposed (52.0%) children, or between HIV-infected (18.9%) and HIV-uninfected (19.5%) mothers. Serotypes included in the 7-valent pneumococcal conjugate vaccine (PCV7) were acquired more often by HIV-infected (10.0%) compared with HIVuninfected mothers (6.4%; p=0.03). On multivariate analysis, day-care attendance (adjusted odds ratio (AOR) 1.80, p=0.02) and maternal pneumococcal colonization (AOR 1.54, p=0.01) were positively associated with pneumococcal acquisition in the child, whereas breastfeeding had a protective effect on PCV7-serotype acquisition in HIV-uninfected children. New acquisition of 7- and 13-valent PCV serotypes in the mother was positively associated with colonization in the child (AOR 2.01, p=0.006 and AOR 2.04, p=0.002; respectively). CONCLUSIONS:: There is an association of acquisition of 7- and 13-valent PCV serotypes between young children and their mothers. The higher prevalence of PCV7 serotype in HIV-infected mothers suggests that they may be a reservoir for transmission of these serotypes, which could delay indirect effects of PCV in settings with a high HIV burden.
  The Pediatric Infectious Disease Journal 01/2013; · 3.58 Impact Factor