The use of illustrated medication diaries to improve outcomes for children initiated on highly active antiretroviral therapy

Background: Human immunodeficiency virus (HIV) represents a huge burden of disease in South Africa. Highly active antiretroviral therapy (HAART) is effective in reducing HIVrelated morbidity and mortality. Simple, inexpensive methods like adherence diaries to optimise effects of HAART would be useful.Methods: This quasi-experimental study was performed at a paediatric antiretroviral clinic in KwaZulu-Natal, South Africa. Children, from birth to 15 years, initiated on HAART from 01 August 2015 to 31 July 2016 were given illustrated medication diaries to be completed by caregivers. Viral load suppression and improvement in growth parameters and CD4+ percentage were determined at six months and one year. These outcomes were compared to those of a group of children who had been initiated on HAART from 01 August 2014 to 31 July 2015 and who had not received diaries.Results: Ninety-nine children were included in the historical control group and 35 children in the intervention group. Viral load suppression (HIV-1 RNA of < 400 copies/mL) was 72% in the control group and 71% in the diary group at 6 months (p = 0.6). At 12 months, 73% of children in the control group and 57% of the diary group had suppressed viral loads (p = 0.18). At 6 months, 63% of children in the control group and 57% of the diary group had improved weight for height z-scores (p = 0.09). At 12 months, when compared with baseline weight for height z-scores, there was improvement in 34% and 41% of the control and diary groups, respectively (p = 0.6). CD4+ percentages improved in 51% of the control group and 50% of the diary group at 6 months (p = 0.70); improvement was noted in 44% and 49%, respectively, at 12 months (p = 0.33).Conclusion: The addition of an illustrated medication diary to routine adherence counselling did not improve outcomes for children initiated on HAART

The performance of different case definitions for severe influenza surveillance among HIV-infected and HIV-uninfected children aged <5 years in South Africa, 2011–2015

In 2014, the World Health Organization (WHO) proposed a new severe influenza surveillance case definition, which has not been evaluated in a high human immunodeficiency virus (HIV) prevalence setting. Our study aimed to assess the performance of this proposed case definition in identifying influenza among HIV-uninfected and HIV-infected children aged <5 years in South Africa. We prospectively enrolled children aged <5 years hospitalised with physician-diagnosed lower respiratory tract infection (LRTI) at two surveillance sites from January 2011 to December 2015. Epidemiologic and clinical data were collected. We tested nasopharyngeal aspirates for influenza using reverse transcription polymerase chain reaction. We used logistic regression to assess factors associated with influenza positivity among HIV-infected and HIV-uninfected children. We calculated sensitivity and specificity for different signs and symptoms and combinations of these for laboratory-confirmed influenza. We enrolled 2,582 children <5 years of age with LRTI of whom 87% (2,257) had influenza and HIV results, of these 14% (318) were HIV-infected. The influenza detection rate was 5% (104/1,939) in HIV-uninfected and 5% (16/318) in HIV-infected children. Children with measured fever (≥38°C) were two times more likely to test positive for influenza than those without measured fever among the HIV-uninfected (OR 2.2, 95% Confidence Interval (CI) 1.5–3.4; p<0.001). No significant association was observed between fever and influenza infection among HIV-infected children. Cough alone had sensitivity of 95% (95% CI 89–98%) in HIV-uninfected and of 100% (95% CI 79–100%) in HIV-infected children but low specificity: 7% (95% CI 6–8%) and 6% (95% CI 3–9%) in HIV-uninfected and HIV-infected children, respectively. The WHO post-2014 case definition for severe acute respiratory illness (SARI—an acute respiratory infection with history of fever or measured fever of ≥ 38°C and cough; with onset within the last ten days and requires hospitalization), had a sensitivity of 66% (95% CI 56–76%) and specificity of 46% (95% CI 44–48%) among HIV-uninfected and a sensitivity of 63% (95% CI 35–84%) and a specificity of 42% (95% CI 36–48%) among HIV-infected children. The sensitivity and specificity of the WHO post-2014 case definition for SARI were similar among HIV-uninfected and HIV-infected children. Our findings support the adoption of the 2014 WHO case definition for children aged <5 years irrespective of HIV infection status.MassGenicshttps://journals.plos.org/plosonehj2020School of Health Systems and Public Health (SHSPH

Epidemiology of acute lower respiratory tract infection in HIV exposed uninfected infants

BACKGROUND : Increased morbidity and mortality from lower respiratory tract infection (LRTI) abstract 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 HIVunexposed 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.http://pediatrics.aappublications.orgam2017Medical Virolog

The role of human immunodeficiency virus in influenza- and respiratory syncytial virus-associated hospitalizations in South African children, 2011-2016

BACKGROUND : Data describing influenza– or respiratory syncytial virus (RSV)–associated hospitalized illness in children aged <5 years in Africa are limited. METHODS : During 2011–2016, we conducted surveillance for severe respiratory illness (SRI) in children aged <5 years in 3 South African hospitals. Nasopharyngeal aspirates were tested for influenza and RSV using real-time reverse transcription polymerase chain reaction. We estimated rates of influenza- and RSV-associated hospitalized SRI by human immunodeficiency virus (HIV) status and compared children who tested positive for influenza vs RSV using multivariable penalized logistic regression. RESULTS : Among 3650 hospitalized children, 203 (5.6%) tested positive for influenza viruses, 874 (23.9%) for RSV, and 19 (0.5%) for both. The median age of children hospitalized with influenza was 13.9 months vs 4.4 months for RSV (P < .01). Annual influenza-associated hospitalization rates per 100000 were highest among infants aged 6–11 months (545; 95% confidence interval [CI], 409–703), while RSV-associated hospitalization rates were highest in infants aged 0–2 months (6593; 95% CI, 5947–7217). HIV exposure was associated with increased incidence of influenza- and RSV-associated hospitalization in infants aged 0–5 months, with relative risk (RR) 2.2 (95% CI, 1.4–3.4) and 1.4 (95% CI, 1.3–1.6), respectively. HIV infection was associated with increased incidence of influenza- and RSV-associated hospitalization in all age groups; RR 2.7 (95% CI, 2.0–3.5) and 3.8 (95% CI, 3.1–4.8), respectively. CONCLUSIONS : Influenza- and RSV-associated hospitalizations are common among South African infants. HIV infection and HIV exposure in infants increase risk of influenza- and RSV-associated hospitalization.The CDC through a cooperative agreement with the National Institute for Communicable Diseases, South Africa (5U01IP001048).http://cid.oxfordjournals.orghj2019Medical Virolog

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

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 physiciandiagnosed 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, HIVinfected 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.http://journals.lww.com/pidjhb201

Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis

Background: Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (≥65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control. Methods: In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5° by 5° grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628. Findings: We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0·3 months [95% CI −0·3 to 0·9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3·8 months [3·6 to 4·0]) in temperate sites and longer duration (5·2 months [4·9 to 5·5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4·6 months [4·3 to 4·8]), as it was for metapneumovirus (4·8 months [4·4 to 5·1]). By comparison, parainfluenza virus had longer duration of epidemics (6·3 months [6·0 to 6·7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus −0·2 months [−0·6 to 0·1]; respiratory syncytial virus 0·1 months [−0·2 to 0·4]). Interpretation: This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination. Funding: European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU)

The performance of different case definitions for severe influenza surveillance among HIV-infected and HIV-uninfected children aged <5 years in South Africa, 2011-2015.

In 2014, the World Health Organization (WHO) proposed a new severe influenza surveillance case definition, which has not been evaluated in a high human immunodeficiency virus (HIV) prevalence setting. Our study aimed to assess the performance of this proposed case definition in identifying influenza among HIV-uninfected and HIV-infected children aged <5 years in South Africa. We prospectively enrolled children aged <5 years hospitalised with physician-diagnosed lower respiratory tract infection (LRTI) at two surveillance sites from January 2011 to December 2015. Epidemiologic and clinical data were collected. We tested nasopharyngeal aspirates for influenza using reverse transcription polymerase chain reaction. We used logistic regression to assess factors associated with influenza positivity among HIV-infected and HIV-uninfected children. We calculated sensitivity and specificity for different signs and symptoms and combinations of these for laboratory-confirmed influenza. We enrolled 2,582 children <5 years of age with LRTI of whom 87% (2,257) had influenza and HIV results, of these 14% (318) were HIV-infected. The influenza detection rate was 5% (104/1,939) in HIV-uninfected and 5% (16/318) in HIV-infected children. Children with measured fever (≥38°C) were two times more likely to test positive for influenza than those without measured fever among the HIV-uninfected (OR 2.2, 95% Confidence Interval (CI) 1.5-3.4; p<0.001). No significant association was observed between fever and influenza infection among HIV-infected children. Cough alone had sensitivity of 95% (95% CI 89-98%) in HIV-uninfected and of 100% (95% CI 79-100%) in HIV-infected children but low specificity: 7% (95% CI 6-8%) and 6% (95% CI 3-9%) in HIV-uninfected and HIV-infected children, respectively. The WHO post-2014 case definition for severe acute respiratory illness (SARI-an acute respiratory infection with history of fever or measured fever of ≥ 38°C and cough; with onset within the last ten days and requires hospitalization), had a sensitivity of 66% (95% CI 56-76%) and specificity of 46% (95% CI 44-48%) among HIV-uninfected and a sensitivity of 63% (95% CI 35-84%) and a specificity of 42% (95% CI 36-48%) among HIV-infected children. The sensitivity and specificity of the WHO post-2014 case definition for SARI were similar among HIV-uninfected and HIV-infected children. Our findings support the adoption of the 2014 WHO case definition for children aged <5 years irrespective of HIV infection status

Severity of Respiratory Syncytial Virus Lower Respiratory Tract Infection With Viral Coinfection in HIV-Uninfected Children

Background.: Molecular diagnostics enable sensitive detection of respiratory viruses, but their clinical significance remains unclear in pediatric lower respiratory tract infection (LRTI). We aimed to determine whether viral coinfections increased life-threatening disease in a large cohort. Methods.: Molecular testing was performed for respiratory viruses in nasopharyngeal aspirates collected from children aged <5 years within 24 hours of hospital admission during sentinel surveillance for severe acute respiratory illness (SARI) hospitalization conducted in South Africa during February 2009-December 2013. The primary outcome was life-threatening disease, defined as mechanical ventilation, intensive care unit admission, or death. Results.: Of 2322 HIV-uninfected children with respiratory syncytial virus (RSV)-associated LRTI, 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus, 347 (14.9%) had adenovirus (ADV), and 30 (1.3%) had influenza virus. RSV and any other viral coinfection was not associated with severe disease (odds ratio [OR], 1.4; 95% confidence interval [CI], OR, 0.74; 95% CI, .39-1.4), ADV coinfection had increased odds of life-threatening disease (adjusted OR, 3.4; 95% CI, 1.6-7.2; P = .001), and influenza coinfection had increased odds of life-threatening disease and prolonged length of stay (adjusted OR, 2.1; 95% CI, 1.0-4.5; P = .05) compared with RSV monoinfection. Conclusions.: RSV coinfection with any respiratory virus is not associated with more severe disease when compared to RSV alone in this study. However, increased life-threatening disease in RSV-ADV and RSV-influenza coinfection warrants further study