The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting ... more The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme. This case-control study was done at seven hospitals in South Africa between April 19, 2010, and Oct 31, 2012. The hospitals were located in a range of urban, peri-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14, 2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 - adjusted odds ratio × 100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247. Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40-68) for two doses and 40% (16-57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks-11 months (54%, 95% CI 32-68) and 12-23 months (61%, 35-77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34-80) and HIV-unexposed-uninfected children (54%, 31-69). Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries. GAVI Alliance (with support from PATH).
Pneumococcal nasopharyngeal colonization is a prerequisite to developing pneumococcal disease. We... more Pneumococcal nasopharyngeal colonization is a prerequisite to developing pneumococcal disease. We investigated the dynamics of pneumococcal colonization in perinatal HIV-unexposed and HIV-exposed children and their mothers and risk factors associated with new serotypes acquisition. Two hundred forty-three 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. The rate of new serotype acquisition during the 16 months did not differ between HIV-exposed (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 HIV-uninfected 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 breast-feeding had a protective effect on PCV7-serotype acquisition in HIV-uninfected children. New acquisition of PCV7 and PCV13 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). There is an association of acquisition of PCV7 and PCV13 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.
These studies assessed the immunogenicity and reactogenicity of booster vaccination with diphther... more These studies assessed the immunogenicity and reactogenicity of booster vaccination with diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-adsorbed conjugated Haemophilus influenzae type b (DTaP-HBV-IPV/Hib) at 18-20 months, and with DTaP during the fifth year of life in children who had been born prematurely (<37 weeks gestation). Open-label, parallel group studies in which preterm and full-term subjects primed with DTaP-HBV-IPV/Hib received booster vaccination with DTaP-HBV-IPV/Hib (Infanrix hexa) at 18-20 months and DTaP (Infanrix) at 4 years of age. Immunogenicity was assessed before and 1 month after DTaP-HBV-IPV/Hib dose and 1 month after DTaP administration. Local and general symptoms were recorded for 4 days, unsolicited symptoms for 31 days after each dose. Before the second year booster, Hib, hepatitis-B, and polio type 3 seroprotection rates were higher in the full-term group (antipolyribosyl ribitol phosphate > or =0.15 microg/mL observed in 76.2%/83.6% preterm/full term respectively, anti-HBs > or =10 mIU/mL in 75.0%/80.6% respectively). One month after the DTaP-HBV-IPV/Hib booster, > or =98% in both groups were seroprotected/seropositive for all vaccine antigens, except hepatitis-B in preterms (seroprotection rate 91.6%). By the fifth year hepatitis-B seroprotection rates were 85.3%/70.5% (preterm/full term) in subjects who had previously responded to hepatitis-B vaccination, and seroprotection rates for polio and polyribosyl ribitol phosphate were >95%. No differences between groups were observed after the DTaP booster. Both booster doses were generally well tolerated with minimal differences observed between groups. Local symptoms occurred more frequently after the fifth vaccination at 4 years of age. Despite trends for lower immune responses to some vaccine antigens in preterm subjects, these findings support undelayed primary and booster vaccination in infants and children born before term. Booster vaccinations with DTaP-HBV-IPV/Hib and DTaP were well tolerated in this susceptible group.
Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in human immunod... more Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected children. A systematic review of studies that were published between January 1990 and February 2009 on the etiology and antimicrobial or adjunctive systemic management of CAP in HIV-infected children. Pneumocystis jirovecii had the strongest association with HIV infection, with a summary odds ratio of 10.1 (95% confidence interval [CI], 17.7-62.1) and 9.1 (95% CI, 2.5-33.1) in antemortem and postmortem studies, respectively. Cytomegalovirus was strongly associated with HIV positivity among fatal cases of pneumonia (summary odds ratio = 14.4 [95% CI, 6.7-30.8]). There was a trend toward a greater prevalence of Staphylococcus aureus (odds ratio, 2.5; 95% CI, 0.95-6.4) in HIV-infected children. Major limitations identified included substantial methodological heterogeneity across studies, limited sensitivity of assays for diagnosing bacterial pneumonia, and studies primarily being undertaken in the absence of antiretroviral treatment or cotrimoxazole prophylaxis. No a priori-planned randomized controlled trials on antimicrobial management of CAP in HIV-infected children were identified. A World Health Organization panel used this review as well as analysis of risks and benefits to revise recommendations for antimicrobial treatment of CAP. Ampicillin plus gentamicin or ceftriaxone is now recommended as first-line empiric regimens for treating severe and very severe CAP in HIV-infected children. In addition, treatment with cloxacillin or vancomycin is recommended in settings with a high incidence of methicillin-resistant S. aureus, and particularly if clinical or microbiological evidence of S. aureus pneumonia exist. Further studies in HIV-infected children on CAP etiology and antibiotic treatment are required in the era of antiretroviral treatment.
Data on human metapneumovirus (HMPV)-associated severe acute respiratory illness (SARI) are limit... more Data on human metapneumovirus (HMPV)-associated severe acute respiratory illness (SARI) are limited in settings with high human immunodeficiency virus (HIV) infection prevalence. To describe clinical characteristics and seasonality (all sites), and incidence (Soweto only) of HMPV-associated SARI among children and adults. Active, prospective, hospital-based, sentinel surveillance for patients hospitalised with SARI was conducted at four sites in South Africa from February 2009-December 2013. Upper respiratory tract samples were tested by multiplex real-time polymerase chain reaction assays for HMPV and other respiratory viruses. Incidence of hospitalisation, stratified by age and HIV-infection status, was calculated for one hospital with population denominators. HMPV was identified in 4.1% of patients enrolled, including 5.6% (593/10503) in children and 1.7% in adults (≥18 years; 119/6934). The majority of adults (84.0%) had an underlying medical condition, including HIV infection in 87/110 (79.1%). HMPV detection occurred perennially with periods of increased detection, which varied from year to year. The incidence of HMPV-associated hospitalisation in Soweto was highest in infants (653.3 per 100,000 person years; 95% confidence interval (CI) 602.2-707.6). The incidence was higher in HIV-infected persons compared to HIV-uninfected persons in age-groups 5-17 years (RR 6.0; 1.1-20.4), 18-44 years (RR 67.6; 38.0-132.6) and 45-64 years (RR 5.3; 3.4-8.3), while not differing in other age-groups. The burden of HMPV-associated SARI hospitalisation among adults occurred predominantly in HIV-infected persons. Among children, infants were at highest risk, with similar burden of hospitalisation in HIV-infected and HIV-uninfected children.
Local disease burden data are necessary to set national influenza vaccination policy. In 2010 the... more Local disease burden data are necessary to set national influenza vaccination policy. In 2010 the population of South Africa was 50 million and the HIV prevalence was 11%. We used a previously developed methodology to determine severe influenza burden in South Africa. Hospitalized severe acute respiratory illness (SARI) incidence was calculated, stratified by HIV status, for four age groups using data from population-based surveillance in one site situated in Gauteng Province for 2009-2011. These rates were adjusted for each of the remaining 8 provinces based on their prevalence of risk factors for pneumonia and healthcare-seeking behavior. We estimated non-hospitalized influenza-associated SARI from healthcare utilization surveys at two sites and used the percent of SARI cases positive for influenza from sentinel surveillance to derive the influenza-associated SARI rate. We applied rates of hospitalized and non-hospitalized influenza-associated SARI to census data to calculate the ...
About 500,000 sepsis-related deaths per year arise in the first 3 days of life. On the basis of r... more About 500,000 sepsis-related deaths per year arise in the first 3 days of life. On the basis of results from non-randomised studies, use of vaginal chlorhexidine wipes during labour has been proposed as an intervention for the prevention of early-onset neonatal sepsis in developing countries. We therefore assessed the efficacy of chlorhexidine in early-onset neonatal sepsis and vertical transmission of group B streptococcus. In a trial in Soweto, South Africa, 8011 women (aged 12-51 years) were randomly assigned in a 1:1 ratio to chlorhexidine vaginal wipes or external genitalia water wipes during active labour, and their 8129 newborn babies were assigned to full-body (intervention group) or foot (control group) washes with chlorhexidine at birth, respectively. In a subset of mothers (n=5144), we gathered maternal lower vaginal swabs and neonatal skin swabs after delivery to assess colonisation with potentially pathogenic bacteria. Primary outcomes were neonatal sepsis in the first 3 days of life and vertical transmission of group B streptococcus. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00136370. Rates of neonatal sepsis did not differ between the groups (chlorhexidine 141 [3%] of 4072 vs control 148 [4%] of 4057; p=0.6518). Rates of colonisation with group B streptococcus in newborn babies born to mothers in the chlorhexidine (217 [54%] of 401) and control groups (234 [55%] of 429] did not differ (efficacy -0.05%, 95% CI -9.5 to 7.9). Because chlorhexidine intravaginal and neonatal wipes did not prevent neonatal sepsis or the vertical acquisition of potentially pathogenic bacteria among neonates, we need other interventions to reduce childhood mortality. US Agency for International Development, National Vaccine Program Office and Centers for Disease Control's Antimicrobial Resistance Working Group, and Bill & Melinda Gates Foundation.
We identified factors associated with pneumococcal colonization, high colonization density, and i... more We identified factors associated with pneumococcal colonization, high colonization density, and invasive pneumococcal pneumonia among patients hospitalized with acute lower respiratory tract infections (ALRTIs). In 2010, 4025 cases were enrolled in surveillance in South Africa. A total of 969 of 4025 systematically selected nasopharyngeal-oropharyngeal specimens (24%) were tested for respiratory viruses and Streptococcus pneumoniae by real-time polymerase chain reaction. Of these, 749 (77%) had blood tested for S. pneumoniae. Pneumococcal colonization was detected in 55% of cases (534 of 969). On multivariable analysis that controlled for age and tuberculosis treatment, infection with influenza virus (adjusted odds ratio [OR], 2.2; 95% confidence interval [CI], 1.1-4.5), adenovirus (adjusted OR, 1.7; 95% CI, 1.1-2.7), rhinovirus (adjusted OR, 1.6; 95% CI, 1.1-2.3), and human immunodeficiency virus (HIV; adjusted OR, 1.6; 95% CI, 1.1-2.4) were associated with pneumococcal colonization. High colonization density was associated with respiratory virus coinfection (adjusted OR, 1.7; 95% CI, 1.1-2.6) and invasive pneumococcal pneumonia (adjusted OR, 2.3; 95% CI, 1.3-4.0), after adjustment for age and sex. Seven percent (52 of 749) had pneumococci detected in blood. On multivariable analysis among colonized cases, invasive pneumococcal pneumonia was associated with HIV (adjusted OR, 3.2; 95% CI, 1.4-7.5), influenza virus (adjusted OR, 8.2; 95% CI, 2.7-25.0), high colonization density (adjusted OR, 18.7; 95% CI, 2.3-155.1), and ≥5 days of hospitalization (adjusted OR, 3.7; 95% CI, 1.7-8.2). Respiratory virus infection was associated with elevated colonization density and, in turn, invasive pneumococcal pneumonia.
The Journal of Infection in Developing Countries, 2012
Pneumonia is the leading cause of mortality in both human immunodeficiency virus (HIV)-infected a... more Pneumonia is the leading cause of mortality in both human immunodeficiency virus (HIV)-infected and HIV-exposed children. Administration of appropriate empirical antimicrobial and/or adjunctive systemic therapies may improve clinical outcomes. To identify effective antimicrobial and/or adjunctive systemic therapy for pneumonia in HIV-infected and HIV-exposed, uninfected children, we searched for published and unpublished studies from 11 databases including MedLine, Global Health Database, Biological Abstracts (BIOSIS), the Cochrane Central Register of Controlled Trials, the World Health Organization Library Information System, AIDSLine, and the System for Information on Grey Literature in Europe, along with additional four regional databases including African Index Medicus, Latin America and Caribbean, Eastern Mediterranean, and South-East Asian databases. Data from full articles of selected studies were independently extracted by two reviewers. No a priori planned randomized controlled trials (RCT) were identified, only subgroup analyses of an RCT comparing oral amoxicillin versus parenteral penicillin for severe pneumonia in children. HIV-infected children had significantly higher treatment failure rates compared to their uninfected counterparts. An RCT study investigating adjunctive corticosteroid therapy for Pneumocystis jiroveci pneumonia (PCP) failed to identify a statistically significant reduction in mortality in the treatment group with a relative risk of 0.57 (95% CI 0.30-1.07). A before-after observational study showed substantial beneficial effect of corticosteroid treatment in reducing mortality among HIV-infected children with PCP. Insufficient evidence exists to identify effective antimicrobial treatment regimens for HIV-associated pneumonia in paediatric populations or confirm the beneficial effect of corticosteroid treatment for HIV-infected children with PCP.
Immunisation has contributed greatly to the control of vaccine-preventable diseases and therefore... more Immunisation has contributed greatly to the control of vaccine-preventable diseases and therefore to improvements in health and survival, especially among young children, and remains one of the most successful and cost-effective public health interventions. This remains true for many of the newer, more expensive vaccines. Vaccines against invasive pneumococcal disease and rotavirus infection were introduced into the South African Expanded Programme on Immunization in April 2009. This article describes the rationale for and process of the introduction of these two vaccines, pneumococcal conjugate vaccine and rotavirus vaccine. It also aims to evaluate the success of and challenges related to their introduction, in terms of both achieving universal coverage and improving survival and health in South African children.
The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting ... more The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme. This case-control study was done at seven hospitals in South Africa between April 19, 2010, and Oct 31, 2012. The hospitals were located in a range of urban, peri-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14, 2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 - adjusted odds ratio × 100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247. Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40-68) for two doses and 40% (16-57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks-11 months (54%, 95% CI 32-68) and 12-23 months (61%, 35-77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34-80) and HIV-unexposed-uninfected children (54%, 31-69). Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries. GAVI Alliance (with support from PATH).
Pneumococcal nasopharyngeal colonization is a prerequisite to developing pneumococcal disease. We... more Pneumococcal nasopharyngeal colonization is a prerequisite to developing pneumococcal disease. We investigated the dynamics of pneumococcal colonization in perinatal HIV-unexposed and HIV-exposed children and their mothers and risk factors associated with new serotypes acquisition. Two hundred forty-three 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. The rate of new serotype acquisition during the 16 months did not differ between HIV-exposed (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 HIV-uninfected 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 breast-feeding had a protective effect on PCV7-serotype acquisition in HIV-uninfected children. New acquisition of PCV7 and PCV13 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). There is an association of acquisition of PCV7 and PCV13 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.
These studies assessed the immunogenicity and reactogenicity of booster vaccination with diphther... more These studies assessed the immunogenicity and reactogenicity of booster vaccination with diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-adsorbed conjugated Haemophilus influenzae type b (DTaP-HBV-IPV/Hib) at 18-20 months, and with DTaP during the fifth year of life in children who had been born prematurely (<37 weeks gestation). Open-label, parallel group studies in which preterm and full-term subjects primed with DTaP-HBV-IPV/Hib received booster vaccination with DTaP-HBV-IPV/Hib (Infanrix hexa) at 18-20 months and DTaP (Infanrix) at 4 years of age. Immunogenicity was assessed before and 1 month after DTaP-HBV-IPV/Hib dose and 1 month after DTaP administration. Local and general symptoms were recorded for 4 days, unsolicited symptoms for 31 days after each dose. Before the second year booster, Hib, hepatitis-B, and polio type 3 seroprotection rates were higher in the full-term group (antipolyribosyl ribitol phosphate > or =0.15 microg/mL observed in 76.2%/83.6% preterm/full term respectively, anti-HBs > or =10 mIU/mL in 75.0%/80.6% respectively). One month after the DTaP-HBV-IPV/Hib booster, > or =98% in both groups were seroprotected/seropositive for all vaccine antigens, except hepatitis-B in preterms (seroprotection rate 91.6%). By the fifth year hepatitis-B seroprotection rates were 85.3%/70.5% (preterm/full term) in subjects who had previously responded to hepatitis-B vaccination, and seroprotection rates for polio and polyribosyl ribitol phosphate were >95%. No differences between groups were observed after the DTaP booster. Both booster doses were generally well tolerated with minimal differences observed between groups. Local symptoms occurred more frequently after the fifth vaccination at 4 years of age. Despite trends for lower immune responses to some vaccine antigens in preterm subjects, these findings support undelayed primary and booster vaccination in infants and children born before term. Booster vaccinations with DTaP-HBV-IPV/Hib and DTaP were well tolerated in this susceptible group.
Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in human immunod... more Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected children. A systematic review of studies that were published between January 1990 and February 2009 on the etiology and antimicrobial or adjunctive systemic management of CAP in HIV-infected children. Pneumocystis jirovecii had the strongest association with HIV infection, with a summary odds ratio of 10.1 (95% confidence interval [CI], 17.7-62.1) and 9.1 (95% CI, 2.5-33.1) in antemortem and postmortem studies, respectively. Cytomegalovirus was strongly associated with HIV positivity among fatal cases of pneumonia (summary odds ratio = 14.4 [95% CI, 6.7-30.8]). There was a trend toward a greater prevalence of Staphylococcus aureus (odds ratio, 2.5; 95% CI, 0.95-6.4) in HIV-infected children. Major limitations identified included substantial methodological heterogeneity across studies, limited sensitivity of assays for diagnosing bacterial pneumonia, and studies primarily being undertaken in the absence of antiretroviral treatment or cotrimoxazole prophylaxis. No a priori-planned randomized controlled trials on antimicrobial management of CAP in HIV-infected children were identified. A World Health Organization panel used this review as well as analysis of risks and benefits to revise recommendations for antimicrobial treatment of CAP. Ampicillin plus gentamicin or ceftriaxone is now recommended as first-line empiric regimens for treating severe and very severe CAP in HIV-infected children. In addition, treatment with cloxacillin or vancomycin is recommended in settings with a high incidence of methicillin-resistant S. aureus, and particularly if clinical or microbiological evidence of S. aureus pneumonia exist. Further studies in HIV-infected children on CAP etiology and antibiotic treatment are required in the era of antiretroviral treatment.
Data on human metapneumovirus (HMPV)-associated severe acute respiratory illness (SARI) are limit... more Data on human metapneumovirus (HMPV)-associated severe acute respiratory illness (SARI) are limited in settings with high human immunodeficiency virus (HIV) infection prevalence. To describe clinical characteristics and seasonality (all sites), and incidence (Soweto only) of HMPV-associated SARI among children and adults. Active, prospective, hospital-based, sentinel surveillance for patients hospitalised with SARI was conducted at four sites in South Africa from February 2009-December 2013. Upper respiratory tract samples were tested by multiplex real-time polymerase chain reaction assays for HMPV and other respiratory viruses. Incidence of hospitalisation, stratified by age and HIV-infection status, was calculated for one hospital with population denominators. HMPV was identified in 4.1% of patients enrolled, including 5.6% (593/10503) in children and 1.7% in adults (≥18 years; 119/6934). The majority of adults (84.0%) had an underlying medical condition, including HIV infection in 87/110 (79.1%). HMPV detection occurred perennially with periods of increased detection, which varied from year to year. The incidence of HMPV-associated hospitalisation in Soweto was highest in infants (653.3 per 100,000 person years; 95% confidence interval (CI) 602.2-707.6). The incidence was higher in HIV-infected persons compared to HIV-uninfected persons in age-groups 5-17 years (RR 6.0; 1.1-20.4), 18-44 years (RR 67.6; 38.0-132.6) and 45-64 years (RR 5.3; 3.4-8.3), while not differing in other age-groups. The burden of HMPV-associated SARI hospitalisation among adults occurred predominantly in HIV-infected persons. Among children, infants were at highest risk, with similar burden of hospitalisation in HIV-infected and HIV-uninfected children.
Local disease burden data are necessary to set national influenza vaccination policy. In 2010 the... more Local disease burden data are necessary to set national influenza vaccination policy. In 2010 the population of South Africa was 50 million and the HIV prevalence was 11%. We used a previously developed methodology to determine severe influenza burden in South Africa. Hospitalized severe acute respiratory illness (SARI) incidence was calculated, stratified by HIV status, for four age groups using data from population-based surveillance in one site situated in Gauteng Province for 2009-2011. These rates were adjusted for each of the remaining 8 provinces based on their prevalence of risk factors for pneumonia and healthcare-seeking behavior. We estimated non-hospitalized influenza-associated SARI from healthcare utilization surveys at two sites and used the percent of SARI cases positive for influenza from sentinel surveillance to derive the influenza-associated SARI rate. We applied rates of hospitalized and non-hospitalized influenza-associated SARI to census data to calculate the ...
About 500,000 sepsis-related deaths per year arise in the first 3 days of life. On the basis of r... more About 500,000 sepsis-related deaths per year arise in the first 3 days of life. On the basis of results from non-randomised studies, use of vaginal chlorhexidine wipes during labour has been proposed as an intervention for the prevention of early-onset neonatal sepsis in developing countries. We therefore assessed the efficacy of chlorhexidine in early-onset neonatal sepsis and vertical transmission of group B streptococcus. In a trial in Soweto, South Africa, 8011 women (aged 12-51 years) were randomly assigned in a 1:1 ratio to chlorhexidine vaginal wipes or external genitalia water wipes during active labour, and their 8129 newborn babies were assigned to full-body (intervention group) or foot (control group) washes with chlorhexidine at birth, respectively. In a subset of mothers (n=5144), we gathered maternal lower vaginal swabs and neonatal skin swabs after delivery to assess colonisation with potentially pathogenic bacteria. Primary outcomes were neonatal sepsis in the first 3 days of life and vertical transmission of group B streptococcus. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00136370. Rates of neonatal sepsis did not differ between the groups (chlorhexidine 141 [3%] of 4072 vs control 148 [4%] of 4057; p=0.6518). Rates of colonisation with group B streptococcus in newborn babies born to mothers in the chlorhexidine (217 [54%] of 401) and control groups (234 [55%] of 429] did not differ (efficacy -0.05%, 95% CI -9.5 to 7.9). Because chlorhexidine intravaginal and neonatal wipes did not prevent neonatal sepsis or the vertical acquisition of potentially pathogenic bacteria among neonates, we need other interventions to reduce childhood mortality. US Agency for International Development, National Vaccine Program Office and Centers for Disease Control's Antimicrobial Resistance Working Group, and Bill & Melinda Gates Foundation.
We identified factors associated with pneumococcal colonization, high colonization density, and i... more We identified factors associated with pneumococcal colonization, high colonization density, and invasive pneumococcal pneumonia among patients hospitalized with acute lower respiratory tract infections (ALRTIs). In 2010, 4025 cases were enrolled in surveillance in South Africa. A total of 969 of 4025 systematically selected nasopharyngeal-oropharyngeal specimens (24%) were tested for respiratory viruses and Streptococcus pneumoniae by real-time polymerase chain reaction. Of these, 749 (77%) had blood tested for S. pneumoniae. Pneumococcal colonization was detected in 55% of cases (534 of 969). On multivariable analysis that controlled for age and tuberculosis treatment, infection with influenza virus (adjusted odds ratio [OR], 2.2; 95% confidence interval [CI], 1.1-4.5), adenovirus (adjusted OR, 1.7; 95% CI, 1.1-2.7), rhinovirus (adjusted OR, 1.6; 95% CI, 1.1-2.3), and human immunodeficiency virus (HIV; adjusted OR, 1.6; 95% CI, 1.1-2.4) were associated with pneumococcal colonization. High colonization density was associated with respiratory virus coinfection (adjusted OR, 1.7; 95% CI, 1.1-2.6) and invasive pneumococcal pneumonia (adjusted OR, 2.3; 95% CI, 1.3-4.0), after adjustment for age and sex. Seven percent (52 of 749) had pneumococci detected in blood. On multivariable analysis among colonized cases, invasive pneumococcal pneumonia was associated with HIV (adjusted OR, 3.2; 95% CI, 1.4-7.5), influenza virus (adjusted OR, 8.2; 95% CI, 2.7-25.0), high colonization density (adjusted OR, 18.7; 95% CI, 2.3-155.1), and ≥5 days of hospitalization (adjusted OR, 3.7; 95% CI, 1.7-8.2). Respiratory virus infection was associated with elevated colonization density and, in turn, invasive pneumococcal pneumonia.
The Journal of Infection in Developing Countries, 2012
Pneumonia is the leading cause of mortality in both human immunodeficiency virus (HIV)-infected a... more Pneumonia is the leading cause of mortality in both human immunodeficiency virus (HIV)-infected and HIV-exposed children. Administration of appropriate empirical antimicrobial and/or adjunctive systemic therapies may improve clinical outcomes. To identify effective antimicrobial and/or adjunctive systemic therapy for pneumonia in HIV-infected and HIV-exposed, uninfected children, we searched for published and unpublished studies from 11 databases including MedLine, Global Health Database, Biological Abstracts (BIOSIS), the Cochrane Central Register of Controlled Trials, the World Health Organization Library Information System, AIDSLine, and the System for Information on Grey Literature in Europe, along with additional four regional databases including African Index Medicus, Latin America and Caribbean, Eastern Mediterranean, and South-East Asian databases. Data from full articles of selected studies were independently extracted by two reviewers. No a priori planned randomized controlled trials (RCT) were identified, only subgroup analyses of an RCT comparing oral amoxicillin versus parenteral penicillin for severe pneumonia in children. HIV-infected children had significantly higher treatment failure rates compared to their uninfected counterparts. An RCT study investigating adjunctive corticosteroid therapy for Pneumocystis jiroveci pneumonia (PCP) failed to identify a statistically significant reduction in mortality in the treatment group with a relative risk of 0.57 (95% CI 0.30-1.07). A before-after observational study showed substantial beneficial effect of corticosteroid treatment in reducing mortality among HIV-infected children with PCP. Insufficient evidence exists to identify effective antimicrobial treatment regimens for HIV-associated pneumonia in paediatric populations or confirm the beneficial effect of corticosteroid treatment for HIV-infected children with PCP.
Immunisation has contributed greatly to the control of vaccine-preventable diseases and therefore... more Immunisation has contributed greatly to the control of vaccine-preventable diseases and therefore to improvements in health and survival, especially among young children, and remains one of the most successful and cost-effective public health interventions. This remains true for many of the newer, more expensive vaccines. Vaccines against invasive pneumococcal disease and rotavirus infection were introduced into the South African Expanded Programme on Immunization in April 2009. This article describes the rationale for and process of the introduction of these two vaccines, pneumococcal conjugate vaccine and rotavirus vaccine. It also aims to evaluate the success of and challenges related to their introduction, in terms of both achieving universal coverage and improving survival and health in South African children.
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