Epidemiology of Acute Lower Respiratory Tract Infection in HIV-Exposed Uninfected Infants

Cohen, Cheryl; Moyes, Jocelyn; Tempia, Stefano; Groome, Michelle; Walaza, Sibongile; Pretorius, Marthi; Naby, Fathima; Mekgoe, Omphile; Kahn, Kathleen; Gottberg, Anne von; Wolter, Nicole; Cohen, Adam L.; Mollendorf, Claire von; Venter, Marietjie; Madhi, Shabir А.

doi:10.1542/peds.2015-3272

Cited by 102 publications

(106 citation statements)

References 39 publications

(23 reference statements)

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“…The inter‐rater agreement for study selection was high ( κ = 0.81). Finally, 66 full texts including 67 studies were included (one paper included two studies) …”

Section: Resultsmentioning

confidence: 99%

Prevalence of human respiratory syncytial virus infection in people with acute respiratory tract infections in Africa: A systematic review and meta‐analysis

Kenmoe

Bigna

Well

et al. 2018

Influenza Resp Viruses

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AimThe epidemiology of human respiratory syncytial virus (HRSV) infection has not yet been systematically investigated in Africa. This systematic review and meta‐analysis are to estimate the prevalence of HRSV infections in people with acute respiratory tract infections (ARTI) in Africa.MethodWe searched PubMed, EMBASE, Africa Journal Online, and Global Index Medicus to identify observational studies published from January 1, 2000, to August 1, 2017. We used a random‐effects model to estimate the prevalence across studies. Heterogeneity (I 2) was assessed via the chi‐square test on Cochran's Q statistic. Review registration: PROSPERO CRD42017076352.ResultsA total of 67 studies (154 000 participants) were included. Sixty (90%), seven (10%), and no studies had low, moderate, and high risk of bias, respectively. The prevalence of HRSV infection varied widely (range 0.4%‐60.4%). The pooled prevalence was 14.6% (95% CI 13.0‐16.4, I 2 = 98.8%). The prevalence was higher in children (18.5%; 95% CI 15.8‐21.5) compared to adults (4.0%; 95% CI 2.2‐6.1) and in people with severe respiratory tract infections (17.9%; 95% CI 15.8‐20.1) compared to those with benign forms (9.4%; 95% CI 7.4‐11.5); P‐values <0.0001. The HRSV prevalence was not associated with sex, subregion in Africa, setting, altitude, latitude, longitude, and seasonality.ConclusionThis study suggests a high prevalence of HRSV in people with ARTI in Africa, particularly among children and people with severe clinical form. All innovative strategies to curb the burden should first focus on children which present the highest HRSV‐related burden.

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“…The inter‐rater agreement for study selection was high ( κ = 0.81). Finally, 66 full texts including 67 studies were included (one paper included two studies) …”

Section: Resultsmentioning

confidence: 99%

Prevalence of human respiratory syncytial virus infection in people with acute respiratory tract infections in Africa: A systematic review and meta‐analysis

Kenmoe

Bigna

Well

et al. 2018

Influenza Resp Viruses

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“…With regards to risk groups in South Africa HIV-infected and HIV-exposed-uninfected children were shown to have a higher incidence of invasive pneumococcal disease (IPD) [3] and acute lower respiratory tract infections (LRTIs) compared to HIV-unexposed-uninfected children. [4]. …”

Section: Introductionmentioning

confidence: 99%

Estimated severe pneumococcal disease cases and deaths before and after pneumococcal conjugate vaccine introduction in children younger than 5 years of age in South Africa

et al. 2017

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IntroductionStreptococcus pneumoniae is a leading cause of severe bacterial infections globally. A full understanding of the impact of pneumococcal conjugate vaccine (PCV) on pneumococcal disease burden, following its introduction in 2009 in South Africa, can support national policy on PCV use and assist with policy decisions elsewhere.MethodsWe developed a model to estimate the national burden of severe pneumococcal disease, i.e. disease requiring hospitalisation, pre- (2005–2008) and post-PCV introduction (2012–2013) in children aged 0–59 months in South Africa. We estimated case numbers for invasive pneumococcal disease using data from the national laboratory-based surveillance, adjusted for specimen-taking practices. We estimated non-bacteraemic pneumococcal pneumonia case numbers using vaccine probe study data. To estimate pneumococcal deaths, we applied observed case fatality ratios to estimated case numbers. Estimates were stratified by HIV status to account for the impact of PCV and HIV-related interventions. We assessed how different assumptions affected estimates using a sensitivity analysis. Bootstrapping created confidence intervals.ResultsIn the pre-vaccine era, a total of approximately 107,600 (95% confidence interval [CI] 83,000–140,000) cases of severe hospitalised pneumococcal disease were estimated to have occurred annually. Following PCV introduction and the improvement in HIV interventions, 41,800 (95% CI 28,000–50,000) severe pneumococcal disease cases were estimated in 2012–2013, a rate reduction of 1,277 cases per 100,000 child-years. Approximately 5000 (95% CI 3000–6000) pneumococcal-related annual deaths were estimated in the pre-vaccine period and 1,900 (95% CI 1000–2500) in 2012–2013, a mortality rate difference of 61 per 100,000 child-years.ConclusionsWhile a large number of hospitalisations and deaths due to pneumococcal disease still occur among children 0–59 months in South Africa, we found a large reduction in this estimate that is temporally associated with PCV introduction. In HIV-infected individuals the scale-up of other interventions, such as improvements in HIV care, may have also contributed to the declines in pneumococcal burden.

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“…Compared with HIV-unexposed uninfected (HUU) infants, HEU infants are at increased risk of morbidity and mortality from lower respiratory tract infections (LRTI), sepsis, and gastrointestinal infections (1–5). The pathogens responsible for infections in HEU infants include respiratory syncytial virus (RSV) and parainfluenza viruses (6, 7), as well as encapsulated bacteria such as Pneumococcus and group B Streptococcus (8–10). HEU infants also have impaired vaccine responses, including decreased T-cell responses to the BCG vaccine (11–14), decreased cellular and humoral immune responses to the tetanus vaccine (14, 15), and low antibody titers and avidity in response to the measles and Haemophilus influenzae type b vaccines (16, 17).…”

Section: Introductionmentioning

confidence: 99%

Altered Natural Killer Cell Function in HIV-Exposed Uninfected Infants

et al. 2017

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ObjectivesHIV-exposed uninfected (HEU) infants have higher rates of severe and fatal infections compared with HIV-unexposed (HUU) infants, likely due to immune perturbations. We hypothesized that alterations in natural killer (NK) cell activity might occur in HEU infants and predispose them to severe infections.DesignCase–control study using cryopreserved peripheral blood mononuclear cells (PBMCs) at birth and 6 months from HEU infants enrolled from 2002 to 2009 and HUU infants enrolled from 2011 to 2013.MethodsNK cell phenotype and function were assessed by flow cytometry after 20-h incubation with and without K562 cells.ResultsThe proportion of NK cells among PBMCs was lower at birth in 12 HEU vs. 22 HUU (1.68 vs. 10.30%, p < 0.0001) and at 6 months in 52 HEU vs. 72 HUU (3.09 vs. 4.65%, p = 0.0005). At birth, HEU NK cells demonstrated increased killing of K562 target cells (p < 0.0001) and increased expression of CD107a (21.65 vs. 12.70%, p = 0.047), but these differences resolved by 6 months. Stimulated HEU NK cells produced less interferon (IFN)γ at birth (0.77 vs. 2.64%, p = 0.008) and at 6 months (4.12 vs. 8.39%, p = 0.001), and showed reduced perforin staining at 6 months (66.95 vs. 77.30%, p = 0.0008). Analysis of cell culture supernatants indicated that lower NK cell activity in HEU was associated with reduced interleukin (IL)-12, IL-15, and IL-18. Addition of recombinant human IL-12 to stimulated HEU PBMCs restored IFNγ production to that seen in stimulated HUU cultures.ConclusionNK cell proportion, phenotype, and function are altered in HEU infants. NK cell cytotoxicity and degranulation are increased in HEU at birth, but HEU NK cells have reduced IFNγ and perforin production, suggesting an adequate initial response, but decreased functional reserve. NK cell function improved with addition of exogenous IL-12, implicating impaired production of IL-12 by accessory cells. Alterations in NK cell and accessory cell function may contribute to the increased susceptibility to infection in HEU infants.

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Epidemiology of Acute Lower Respiratory Tract Infection in HIV-Exposed Uninfected Infants

Cited by 102 publications

References 39 publications

Prevalence of human respiratory syncytial virus infection in people with acute respiratory tract infections in Africa: A systematic review and meta‐analysis

Prevalence of human respiratory syncytial virus infection in people with acute respiratory tract infections in Africa: A systematic review and meta‐analysis

Estimated severe pneumococcal disease cases and deaths before and after pneumococcal conjugate vaccine introduction in children younger than 5 years of age in South Africa

Altered Natural Killer Cell Function in HIV-Exposed Uninfected Infants

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