1. |
- Ayeni, Oluwatosin A., et al.
(author)
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Mortality in children aged <5 years with severe acute respiratory illness in a high HIV-prevalence urban and rural areas of South Africa, 2009–2013
- 2021
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:8
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Journal article (peer-reviewed)abstract
- Background: Severe acute respiratory illness (SARI) is an important cause of mortality in young children, especially in children living with HIV infection. Disparities in SARI death in children aged <5 years exist in urban and rural areas.Objective: To compare the factors associated with in-hospital death among children aged <5 years hospitalized with SARI in an urban vs. a rural setting in South Africa from 2009–2013.Methods: Data were collected from hospitalized children with SARI in one urban and two rural sentinel surveillance hospitals. Nasopharyngeal aspirates were tested for ten respiratory viruses and blood for pneumococcal DNA using polymerase chain reaction. We used multivariable logistic regression to identify patient and clinical characteristics associated with in-hospital death.Results: From 2009 through 2013, 5,297 children aged <5 years with SARI-associated hospital admission were enrolled; 3,811 (72%) in the urban and 1,486 (28%) in the rural hospitals. In-hospital case-fatality proportion (CFP) was higher in the rural hospitals (6.9%) than the urban hospital (1.3%, p<0.001), and among HIV-infected than the HIV-uninfected children (9.6% vs. 1.6%, p<0.001). In the urban hospital, HIV infection (odds ratio (OR):11.4, 95% confidence interval (CI):5.4–24.1) and presence of any other underlying illness (OR: 3.0, 95% CI: 1.0–9.2) were the only factors independently associated with death. In the rural hospitals, HIV infection (OR: 4.1, 95% CI: 2.3–7.1) and age <1 year (OR: 3.7, 95% CI: 1.9–7.2) were independently associated with death, whereas duration of hospitalization ≥5 days (OR: 0.5, 95% CI: 0.3–0.8) and any respiratory virus detection (OR: 0.4, 95% CI: 0.3–0.8) were negatively associated with death.Conclusion: We found that the case-fatality proportion was substantially higher among children admitted to rural hospitals and HIV infected children with SARI in South Africa. While efforts to prevent and treat HIV infections in children may reduce SARI deaths, further efforts to address health care inequality in rural populations are needed.
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2. |
- Cohen, Adam L., et al.
(author)
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Epidemiology of Influenza Virus Types and Subtypes in South Africa, 2009-2012
- 2014
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In: Emerging Infectious Diseases. - Atlanta, USA : Centers Disease Control. - 1080-6040 .- 1080-6059. ; 20:7, s. 1162-1169
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Journal article (peer-reviewed)abstract
- To determine clinical and epidemiologic differences between influenza caused by different virus types and subtypes, we identified patients and tested specimens. Patients were children and adults hospitalized with confirmed influenza and severe acute respiratory illness (SARI) identified through active, prospective, hospital-based surveillance from 2009-2012 in South Africa. Respiratory specimens were tested, typed, and subtyped for influenza virus by PCR. Of 16,005 SARI patients tested, 1,239 (8%) were positive for influenza virus. Patient age and co-infections varied according to virus type and subtype, but disease severity did not. Case-patients with influenza B were more likely than patients with influenza A to be HIV infected. A higher proportion of case-patients infected during the first wave of the 2009 influenza pandemic were 5-24 years of age (19%) than were patients infected during the second wave (9%). Although clinical differences exist, treatment recommendations do not differ according to subtype; prevention through vaccination is recommended.
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3. |
- Cohen, Adam L, et al.
(author)
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Parainfluenza Virus Infection Among Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Children and Adults Hospitalized for Severe Acute Respiratory Illness in South Africa, 2009-2014
- 2015
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In: Open forum infectious diseases. - : Oxford University Press. - 2328-8957. ; 2:4
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Journal article (peer-reviewed)abstract
- Background. Parainfluenza virus (PIV) is a common cause of acute respiratory tract infections, but little is known about PIV infection in children and adults in Africa, especially in settings where human immunodeficiency virus (HIV) prevalence is high. Methods. We conducted active, prospective sentinel surveillance for children and adults hospitalized with severe acute respiratory illness (SARI) from 2009 to 2014 in South Africa. We enrolled controls (outpatients without febrile or respiratory illness) to calculate the attributable fraction for PIV infection. Respiratory specimens were tested by multiplex real-time reverse-transcription polymerase chain reaction assay for parainfluenza types 1, 2, and 3. Results. Of 18 282 SARI cases enrolled, 1188 (6.5%) tested positive for any PIV type: 230 (19.4%) were type 1; 168 (14.1%) were type 2; 762 (64.1%) were type 3; and 28 (2.4%) had coinfection with 2 PIV types. After adjusting for age, HIV serostatus, and respiratory viral coinfection, the attributable fraction for PIV was 65.6% (95% CI [ confidence interval], 47.1-77.7); PIV contributed to SARI among HIV-infected and -uninfected children < 5 years of age and among individuals infected with PIV types 1 and 3. The observed overall incidence of PIV-associated SARI was 38 (95% CI, 36-39) cases per 100 000 population and was highest in children < 1 year of age (925 [ 95% CI, 864-989] cases per 100 000 population). Compared with persons without HIV, persons with HIV had an increased relative risk of PIV hospitalization (9.4; 95% CI, 8.5-10.3). Conclusions. Parainfluenza virus causes substantial severe respiratory disease in South Africa among children < 5 years of age, especially those that are infected with HIV.
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4. |
- Cohen, Cheryl, et al.
(author)
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Epidemiology of Acute Lower Respiratory Tract Infection in HIV-Exposed Uninfected Infants
- 2016
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In: Pediatrics. - : American Academy of Pediatrics. - 0031-4005 .- 1098-4275. ; 137:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Increased morbidity and mortality from lower respiratory tract infection (LRTI) has been suggested in HIV-exposed uninfected (HEU) children; however, the contribution of respiratory viruses is unclear. We studied the epidemiology of LRTI hospitalization in HIV-unexposed uninfected (HUU) and HEU infants aged <6 months in South Africa. METHODS: We prospectively enrolled hospitalized infants with LRTI from 4 provinces from 2010 to 2013. Using polymerase chain reaction, nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence for 2010-2011 was estimated at 1 site with population denominators. RESULTS: We enrolled 3537 children aged <6 months. HIV infection and exposure status were determined for 2507 (71%), of whom 211 (8%) were HIV infected, 850 (34%) were HEU, and 1446 (58%) were HUU. The annual incidence of LRTI was elevated in HEU (incidence rate ratio [IRR] 1.4; 95% confidence interval [CI] 1.3-1.5) and HIV infected (IRR 3.8; 95% CI 3.3-4.5), compared with HUU infants. Relative incidence estimates were greater in HEU than HUU, for respiratory syncytial virus (RSV; IRR 1.4; 95% CI 1.3-1.6) and human metapneumovirus-associated (IRR 1.4; 95% CI 1.1-2.0) LRTI, with a similar trend observed for influenza (IRR 1.2; 95% CI 0.8-1.8). HEU infants overall, and those with RSV-associated LRTI had greater odds (odds ratio 2.1, 95% CI 1.1-3.8, and 12.2, 95% CI 1.7-infinity, respectively) of death than HUU. CONCLUSIONS: HEU infants were more likely to be hospitalized and to die in-hospital than HUU, including specifically due to RSV. This group should be considered a high-risk group for LRTI.
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5. |
- Cohen, Cheryl, et al.
(author)
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Epidemiology of Severe Acute Respiratory Illness (SARI) among Adults and Children Aged >= 5 Years in a High HIV-Prevalence Setting, 2009-2012
- 2015
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:2
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Journal article (peer-reviewed)abstract
- Objective There are few published studies describing severe acute respiratory illness ( SARI) epidemiology amongst older children and adults from high HIV-prevalence settings. We aimed to describe SARI epidemiology amongst individuals aged >= 5 years in South Africa. Methods We conducted prospective surveillance for individuals with SARI from 2009-2012. Using polymerase chain reaction, respiratory samples were tested for ten viruses, and blood for pneumococcal DNA. Cumulative annual SARI incidence was estimated at one site with population denominators. Findings We enrolled 7193 individuals, 9% (621/7067) tested positive for influenza and 9%(600/6519) for pneumococcus. HIV-prevalence was 74% (4663/6334). Among HIV-infected individuals with available data, 41% of 2629 were receiving antiretroviral therapy (ART). The annual SARI hospitalisation incidence ranged from 325-617/100,000 population. HIV-infected individuals experienced a 13-19 times greater SARI incidence than HIV-uninfected individuals (p<0.001). On multivariable analysis, compared to HIV-uninfected individuals, HIV-infected individuals were more likely to be receiving tuberculosis treatment (odds ratio (OR): 1.7; 95% CI:1.1-2.7), have pneumococcal infection (OR 2.4; 95% CI: 1.7-3.3) be hospitalised for >7 days rather than <2 days (OR1.7; 95% CI: 1.2-2.2) and had a higher case-fatality ratio (8% vs 5%; OR1.7; 95% CI: 1.2-2.3), but were less likely to be infected with influenza (OR 0.6; 95% CI: 0.5-0.8). On multivariable analysis, independent risk indicators associated with death included HIV infection (OR 1.8; 95% CI: 1.3-2.4), increasing age-group, receiving mechanical ventilation (OR 6.5; 95% CI: 1.3-32.0) and supplemental-oxygen therapy (OR 2.6; 95% CI: 2.1-3.2). Conclusion The burden of hospitalized SARI amongst individuals aged >= 5 years is high in South Africa. HIV-infected individuals are the most important risk group for SARI hospitalization and mortality in this setting.
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6. |
- Cohen, Cheryl, et al.
(author)
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Epidemiology of Viral-associated Acute Lower Respiratory Tract Infection Among Children < 5 Years of Age in a High HIV Prevalence Setting, South Africa, 2009-2012
- 2015
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In: The Pediatric Infectious Disease Journal. - 0891-3668 .- 1532-0987. ; 34:1, s. 66-72
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Journal article (peer-reviewed)abstract
- Background: Data on the epidemiology of viral-associated acute lower respiratory tract infection (LRTI) from high HIV prevalence settings are limited. We aimed to describe LRTI hospitalizations among South African children aged < 5 years. Methods: We prospectively enrolled hospitalized children with physician-diagnosed LRTI from 5 sites in 4 provinces from 2009 to 2012. Using polymerase chain reaction (PCR), nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence was estimated at 1 site with available population denominators. Results: We enrolled 8723 children aged < 5 years with LRTI, including 64% < 12 months. The case-fatality ratio was 2% (150/8512). HIV prevalence among tested children was 12% (705/5964). The overall prevalence of respiratory viruses identified was 78% (6517/8393), including 37% rhinovirus, 26% respiratory syncytial virus (RSV), 7% influenza and 5% human metapneumovirus. Four percent (253/6612) tested positive for pneumococcus. The annual incidence of LRTI hospitalization ranged from 2530 to 3173/100,000 population and was highest in infants (8446-10532/100,000). LRTI incidence was 1.1 to 3.0-fold greater in HIV-infected than HIV-uninfected children. In multivariable analysis, compared to HIV-uninfected children, HIV-infected children were more likely to require supplemental-oxygen [odds ratio (OR): 1.3, 95% confidence interval (CI): 1.1-1.7)], be hospitalized > 7 days (OR: 3.8, 95% CI: 2.8-5.0) and had a higher case-fatality ratio (OR: 4.2, 95% CI: 2.6-6.8). In multivariable analysis, HIV-infection (OR: 3.7, 95% CI: 2.2-6.1), pneumococcal coinfection (OR: 2.4, 95% CI: 1.1-5.6), mechanical ventilation (OR: 6.9, 95% CI: 2.7-17.6) and receipt of supplemental-oxygen (OR: 27.3, 95% CI: 13.2-55.9) were associated with death. Conclusions: HIV-infection was associated with an increased risk of LRTI hospitalization and death. A viral pathogen, commonly RSV, was identified in a high proportion of LRTI cases.
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7. |
- Cohen, Cheryl, et al.
(author)
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Mortality amongst Patients with Influenza-Associated Severe Acute Respiratory Illness, South Africa, 2009-2013
- 2015
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Journal article (peer-reviewed)abstract
- Introduction Data on the burden and risk groups for influenza-associated mortality from Africa are limited. We aimed to estimate the incidence and risk-factors for in-hospital influenza-associated severe acute respiratory illness (SARI) deaths.Methods Hospitalised patients with SARI were enrolled prospectively in four provinces of South Africa from 2009-2013. Using polymerase chain reaction, respiratory samples were tested for ten respiratory viruses and blood for pneumococcal DNA. The incidence of influenza-associated SARI deaths was estimated at one urban hospital with a defined catchment population.Results We enrolled 1376 patients with influenza-associated SARI and 3% (41 of 1358 with available outcome data) died. In patients with available HIV-status, the case-fatality proportion (CFP) was higher in HIV-infected (5%, 22/419) than HIV-uninfected individuals (2%, 13/620; p = 0.006). CFPs varied by age group, and generally increased with increasing age amongst individuals >5 years (p<0.001). On multivariable analysis, factors associated with death were age-group 45-64 years (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.01-16.3) and >= 65 years (OR 6.5, 95% CI 1.2-34.3) compared to 1-4 year age-group who had the lowest CFP, HIV-infection (OR 2.9, 95% CI 1.1-7.8), underlying medical conditions other than HIV (OR 2.9, 95% CI 1.2-7.3) and pneumococcal co-infection (OR 4.1, 95% CI 1.5-11.2). The estimated incidence of influenza-associated SARI deaths per 100,000 population was highest in children <1 year (20.1, 95% CI 12.1-31.3) and adults aged 45-64 years (10.4, 95% CI 8.4-12.9). Adjusting for age, the rate of death was 20-fold (95% CI 15.0-27.8) higher in HIV-infected individuals than HIV-uninfected individuals.Conclusion Influenza causes substantial mortality in urban South Africa, particularly in infants aged <1 year and HIV-infected individuals. More widespread access to antiretroviral treatment and influenza vaccination may reduce this burden.
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8. |
- Cohen, Cheryl, et al.
(author)
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Severe Influenza-associated Respiratory Infection in High HIV Prevalence Setting, South Africa, 2009-2011
- 2013
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In: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 19:11, s. 1766-1774
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Journal article (peer-reviewed)abstract
- Data on influenza epidemiology in HIV-infected persons are limited, particularly for sub-Saharan Africa, where HIV infection is widespread. We tested respiratory and blood samples from patients with acute lower respiratory tract infections hospitalized in South Africa during 2009-2011 for viral and pneumococcal infections. Influenza was identified in 9% (1,056/11,925) of patients enrolled; among influenza case-patients, 358 (44%) of the 819 who were tested were infected with HIV. Influenza-associated acute lower respiratory tract infection incidence was 4-8 times greater for HIV-infected (186-228/100,000) than for HIV-uninfected persons (26-54/100,000). Furthermore, multivariable analysis showed HIV-infected patients were more likely to have pneumococcal co-infection; to be infected with influenza type B compared with type A; to be hospitalized for 2-7 days or >7 days; and to die from their illness. These findings indicate that HIV-infected persons are at greater risk for severe illnesses related to influenza and thus should be prioritized for influenza vaccination.
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9. |
- Dangor, Ziyaad, et al.
(author)
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Association of infant Rib and Alp1 surface protein N-terminal domain immunoglobulin G and invasive Group B Streptococcal disease in young infants
- 2023
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In: Vaccine. - : Elsevier BV. - 0264-410X. ; 41:10, s. 1679-1683
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Journal article (peer-reviewed)abstract
- Background: Vaccine development for Group B Streptococcus (GBS), a common cause of invasive disease in early-infancy and adverse pregnancy outcomes, include exploring widely-expressed GBS surface proteins as vaccine epitopes. We investigated the association between natural infant serum IgG against the RibN and Alp1N domains and risk of invasive GBS disease caused by isolates expressing these proteins. Methods: We analyzed maternal and infant serum samples from GBS disease cases and infants born to GBS-colonized women controls. Bayesian modelling was used to calculate the GBS homotypic IgG concentration associated with risk reduction of invasive disease in the infant. Results: PCR-based typing of 85 GBS invasive isolates showed 46 and 24 possessing the gene for Rib and Alp1, respectively. These were matched to 46 and 36 infant controls whose mothers were colonized with GBS expressing Rib and Alp1, respectively. RibN IgG geometric mean concentrations (GMC) were lower in cases than controls among infants (0.01; 95 %CI: 0.01–0.02 vs 0.04; 95 %CI: 0.03–0.06; p < 0.001), no significant difference was found between maternal RibN IgG GMC in cases compared to controls. Alp1N IgG GMC was also lower in infant cases (0.02; 95 %CI: 0.01–0.03) than controls (0.05; 95 %CI: 0.04–0.07; p < 0.001); albeit not so in mothers. An infant IgG threshold ≥ 0.428 and ≥ 0.112 µg/mL was associated with 90 % risk reduction of invasive GBS disease due to Rib and Alp1 expressing strains, respectively. Discussion: Lower serum RibN and Alp1N IgG GMC were evident in infants with invasive GBS disease compared with controls born to women colonized with GBS expressing the homotypic protein. These data support the evaluation of Alp family proteins as potential vaccine candidates against invasive GBS disease.
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10. |
- Groome, Michelle J., et al.
(author)
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Effectiveness of monovalent human rotavirus vaccine against admission to hospital for acute rotavirus diarrhoea in South African children : a case-control study
- 2014
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In: The Lancet - Infectious diseases. - : Elsevier. - 1473-3099 .- 1474-4457. ; 14:11, s. 1096-1104
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Journal article (peer-reviewed)abstract
- Background 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. Methods 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, pen-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 x100%) 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. Findings 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). Interpretation 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.
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