Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
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Query Trace: Venter M[original query] |
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ICTV Virus Taxonomy Profile: Peribunyaviridae 2024
de Souza WM , Calisher CH , Carrera JP , Hughes HR , Nunes MRT , Russell B , Tilson-Lunel NL , Venter M , Xia H . J Gen Virol 2024 105 (11) Peribunyavirids produce enveloped virions with three negative-sense RNA segments comprising 10.7-12.5 kb in total. The family includes globally distributed viruses in multiple genera. While most peribunyavirids are maintained in geographically restricted vertebrate-arthropod transmission cycles, others are arthropod-specific or do not have a known vector. Arthropods can be persistently infected. Human and other vertebrate animal infections occur through blood feeding by an infected vector arthropod, resulting in diverse human and veterinary clinical outcomes in a strain-specific manner. Reassortment can occur between members of the same genus. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Peribunyaviridae, which is available at ictv.global/report/peribunyaviridae. |
Prenatal exposure to poly- and perfluoroalkyl substances and the incidence of asthma in early childhood
Zell-Baran LM , Venter C , Dabelea D , Norris JM , Glueck DH , Adgate JL , Brown JM , Calafat AM , Pickett-Nairne K , Starling AP . Environ Res 2023 239 117311 EXPOSURE TO POLY: and perfluoroalkyl substances (PFAS) in early life may increase the risk of childhood asthma, but evidence has been inconsistent. We estimated associations between maternal serum concentrations of PFAS during pregnancy and clinician-diagnosed asthma incidence in offspring through age eight. We included 597 mother-child pairs with PFAS quantified in mid-pregnancy serum and childhood medical records reviewed for asthma diagnoses. We used separate Cox proportional hazards models to assess the relationship between log-transformed concentrations of five PFAS and the incidence of asthma. We estimated associations between the PFAS mixture and clinician-diagnosed asthma incidence using quantile-based g-computation. PFAS concentrations were similar to those among females in the US general population. Seventeen percent of children (N = 104) were diagnosed with asthma during follow-up. Median (interquartile range) duration of follow-up was 4.7 (4.0, 6.2) years, and median age at asthma diagnosis was 1.7 (0.9, 2.8) years. All adjusted hazard ratios (HRs) were elevated, but all 95% confidence intervals (CI) included the null. The HR (95% CI) of asthma for a one-quartile increase in the PFAS mixture was 1.17 (0.86, 1.61). In this cohort of children followed to eight years of age, prenatal PFAS concentrations were not significantly associated with incidence of clinician-diagnosed asthma. |
Results from the second WHO external quality assessment for the molecular detection of respiratory syncytial virus, 2019-2020.
Williams T , Jackson S , Barr I , Bi S , Bhiman J , Ellis J , von Gottberg A , Lindstrom S , Peret T , Rughooputh S , Viegas M , Hirve S , Zambon M , Zhang W , Dia N , Razanazatovo N , Al-Nabet Admh , Abubakar A , Tivane A , Barakat A , Naguib A , Aziz A , Vicari A , Moen A , Govindakarnavar A , Hall A , Darmaa B , Nathalie B , Herring B , Caetano BC , Whittaker B , Baumeister E , Nakouné E , Guthrie E , Inbanathan F , Nair H , Campbell H , Kadjo HA , Oumzil H , Heraud JM , Mott JA , Namulondo J , Leite J , Nahapetyan K , Al Ariqi L , Gazo MHI , Chadha M , Pisareva M , Venter M , Siqueira MM , Lumandas M , Niang M , Albuaini M , Salman M , Oberste S , Srikantiah P , Tang P , Couto P , Smith P , Coyle PV , Dussart P , Nguyen PN , Okada PA , Wijesinghe PR , Samuel R , Brown R , Pebody R , Fasce R , Jha R , Lindstrom S , Gerber S , Potdar V , Dong X , Deng YM . Influenza Other Respir Viruses 2023 17 (1) e13073 ![]() ![]() Background: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019–2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019–2020 WHO RSV EQA. Methods: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories. Results: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping. Conclusions: The WHO RSV EQA 2019–2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets. © 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. |
Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study
Smith J , Bansi-Matharu L , Cambiano V , Dimitrov D , Bershteyn A , van de Vijver D , Kripke K , Revill P , Boily MC , Meyer-Rath G , Taramusi I , Lundgren JD , van Oosterhout JJ , Kuritzkes D , Schaefer R , Siedner MJ , Schapiro J , Delany-Moretlwe S , Landovitz RJ , Flexner C , Jordan M , Venter F , Radebe M , Ripin D , Jenkins S , Resar D , Amole C , Shahmanesh M , Gupta RK , Raizes E , Johnson C , Inzaule S , Shafer R , Warren M , Stansfield S , Paredes R , Phillips AN . Lancet HIV 2023 10 (4) e254-e265 BACKGROUND: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa. METHODS: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of $500 per disability-adjusted life years averted, and a discount rate of 3% per year. FINDINGS: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2·6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1·5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1·7% (0-6·4%) without cabotegravir-PrEP introduction but 13·1% (4·1-30·9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0·9% (-2·5% to 0·3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13 000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151·3 million vs $150·7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82% of setting-scenarios at the cost of $144 per year, in 52% at $264, and in 87% at $114. INTERPRETATION: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing. FUNDING: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health. |
Drug resistance and use of long-acting ART.
daSilva J , Siedner M , McCluskey S , Chandiwana N , Venter F , Raizes E . Lancet HIV 2022 9 (6) e374-e375 ![]() ![]() The approval, in 2021, of long-acting cabotegravir plus rilpivirine as the first long-term antiretroviral therapy (ART) has engendered enthusiasm for its use among patients with adherence challenges, given its potential to address stigma and other challenges associated with daily pill intake. Several factors could prevent the implementation of long-acting cabotegravir plus rilpivirine in resource-poor settings, such as cold chain requirement; inactivity of long-acting cabotegravir plus rilpivirine against hepatitis B; and the requirement for dosing once a month or every 2 months, which conflicts with differentiated service delivery models that allow patients to attend clinics every 6 months. However, the greatest challenge to implementation of long-acting cabotegravir plus rilpivirine in sub-Saharan Africa involves its efficacy in the face of widespread non-nucleoside reverse-transcriptase inhibitor resistance (NNRTI). |
Human respiratory syncytial virus diversity and epidemiology among patients hospitalized with severe respiratory illness in South Africa, 2012-2015.
Valley-Omar Z , Tempia S , Hellferscee O , Walaza S , Variava E , Dawood H , Kahn K , McMorrow M , Pretorius M , Mtshali S , Mamorobela E , Wolter N , Venter M , von Gottberg A , Cohen C , Treurnicht FK . Influenza Other Respir Viruses 2021 16 (2) 222-235 ![]() BACKGROUND: We aimed to describe the prevalence of human respiratory syncytial virus (HRSV) and evaluate associations between HRSV subgroups and/or genotypes and epidemiologic characteristics and clinical outcomes in patients hospitalized with severe respiratory illness (SRI). METHODS: Between January 2012 and December 2015, we enrolled patients of all ages admitted to two South African hospitals with SRI in prospective hospital-based syndromic surveillance. We collected respiratory specimens and clinical and epidemiological data. Unconditional random effect multivariable logistic regression was used to assess factors associated with HRSV infection. RESULTS: HRSV was detected in 11.2% (772/6908) of enrolled patients of which 47.0% (363/772) were under the age of 6 months. There were no differences in clinical outcomes of HRSV subgroup A-infected patients compared with HRSV subgroup B-infected patients but among patients aged <5 years, children with HRSV subgroup A were more likely be coinfected with Streptococcus pneumoniae (23/208, 11.0% vs. 2/90, 2.0%; adjusted odds ratio 5.7). No significant associations of HRSV A genotypes NA1 and ON1 with specific clinical outcomes were observed. CONCLUSIONS: While HRSV subgroup and genotype dominance shifted between seasons, we showed similar genotype diversity as noted worldwide. We found no association between clinical outcomes and HRSV subgroups or genotypes. |
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
Ayeni OA , Walaza S , Tempia S , Groome M , Kahn K , Madhi SA , Cohen AL , Moyes J , Venter M , Pretorius M , Treurnicht F , Hellferscee O , von Gottberg A , Wolter N , Cohen C . PLoS One 2021 16 (8) e0255941 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. |
The HIV drug optimization agenda: promoting standards for earlier investigation and approvals of antiretroviral drugs for use in adolescents living with HIV
Rojo P , Carpenter D , Venter F , Turkova A , Penazzato M . J Int AIDS Soc 2020 23 Suppl 5 e25576 INTRODUCTION: Most clinical trials for new antiretroviral (ARV) agents are conducted among narrowly defined adult populations. Only after safety and efficacy have been clearly demonstrated among adults living with HIV are trials including adolescents, children and infants conducted. This approach contributes to significant delays in the availability of optimal new ARV regimens for infants, children and adolescents. This commentary discusses issues related to the inclusion of adolescents aged 12 to 18 years in initial HIV clinical phase 3 trials of novel antiretrovirals (ARVs) or conducting parallel phase 3 clinical trials among adolescents. DISCUSSION: The absorption, metabolic and excretion or elimination pathways for drugs do not significantly differ between adolescents and adults. In fact, dosing recommendations for ARVs are the same for adults and adolescents who meet the age and weight criteria. Although conducting clinical trials among adolescents present special challenges (e.g. consenting minors and concerns about trial completion and contraception), these challenges can be addressed to obtain high-quality trial results. Importantly, new agents and optimized combinations have more favourable dosing schedules and side-effect profiles and are more effective ARV agents with higher HIV drug resistance thresholds, which would be extremely beneficial to improve outcomes among HIV-positive adolescents. CONCLUSIONS: Adolescents may not present with significantly different pharmacokinetic characteristics from those in adults. Including HIV-positive adolescents in phase 3 ARV clinical trials, either with adults or in specific adolescent studies conducted in parallel, would allow adolescents to access promising, more effective treatment for HIV years earlier than with the current stepwise approach. |
Results from the WHO external quality assessment for the respiratory syncytial virus pilot, 2016-17
Jackson S , Peret TCT , Ziegler TT , Thornburg NJ , Besselaar T , Broor S , Barr I , Baumeister E , Chadha M , Chittaganpitch M , Darmaa B , Ellis J , Fasce R , Herring B , Herve K , Hirve S , Li Y , Pisareva M , Moen A , Naguib A , Palekar R , Potdar V , Siqueira M , Treurnicht F , Tivane A , Venter M , Wairagkar N , Zambon M , Zhang W . Influenza Other Respir Viruses 2020 14 (6) 671-677 BACKGROUND: External quality assessments (EQAs) for the molecular detection of respiratory syncytial virus (RSV) are necessary to ensure the provision of reliable and accurate results. One of the objectives of the pilot of the World Health Organization (WHO) Global RSV Surveillance, 2016-2017, was to evaluate and standardize RSV molecular tests used by participating countries. This paper describes the first WHO RSV EQA for the molecular detection of RSV. METHODS: The WHO implemented the pilot of Global RSV Surveillance based on the WHO Global Influenza Surveillance and Response System (GISRS) from 2016 to 2018 in 14 countries. To ensure standardization of tests, 13 participating laboratories were required to complete a 12 panel RSV EQA prepared and distributed by the Centers for Disease Control and Prevention (CDC), USA. The 14th laboratory joined the pilot late and participated in a separate EQA. Laboratories evaluated a RSV rRT-PCR assay developed by CDC and compared where applicable, other Laboratory Developed Tests (LDTs) or commercial assays already in use at their laboratories. RESULTS: Laboratories performed well using the CDC RSV rRT-PCR in comparison with LDTs and commercial assays. Using the CDC assay, 11 of 13 laboratories reported correct results. Two laboratories each reported one false-positive finding. Of the laboratories using LDTs or commercial assays, results as assessed by Ct values were 100% correct for 1/5 (20%). With corrective actions, all laboratories achieved satisfactory outputs. CONCLUSIONS: These findings indicate that reliable results can be expected from this pilot. Continued participation in EQAs for the molecular detection of RSV is recommended. |
Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines
Phillips AN , Bansi-Matharu L , Venter F , Havlir D , Pozniak A , Kuritzkes DR , Wensing A , Lundgren JD , Pillay D , Mellors J , Cambiano V , Jahn A , Apollo T , Mugurungi O , Ripin D , Da Silva J , Raizes E , Ford N , Siberry GK , Gupta RK , Barnabas R , Revill P , Cohn J , Calmy A , Bertagnolio S . Lancet HIV 2020 7 (3) e193-e200 BACKGROUND: The integrase inhibitor dolutegravir is being considered in several countries in sub-Saharan Africa instead of efavirenz for people initiating antiretroviral therapy (ART) because of superior tolerability and a lower risk of resistance emergence. WHO requested updated modelling results for its 2019 Antiretroviral Guidelines update, which was restricted to the choice of dolutegravir or efavirenz in new ART initiators. In response to this request, we modelled the risks and benefits of alternative policies for initial first-line ART regimens. METHODS: We updated an existing individual-based model of HIV transmission and progression in adults to consider information on the risk of neural tube defects in women taking dolutegravir at time of conception, as well as the effects of dolutegravir on weight gain. The model accounted for drug resistance in determining viral suppression, with consequences for clinical outcomes and mother-to-child transmission. We sampled distributions of parameters to create various epidemic setting scenarios, which reflected the diversity of epidemic and programmatic situations in sub-Saharan Africa. For each setting scenario, we considered the situation in 2018 and compared ART initiation policies of an efavirenz-based regimen in women intending pregnancy, and a dolutegravir-based regimen in others, and a dolutegravir-based regimen, including in women intending pregnancy. We considered predicted outcomes over a 20-year period from 2019 to 2039, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted. FINDINGS: Considering updated information on risks and benefits, a policy of ART initiation with a dolutegravir-based regimen rather than an efavirenz-based regimen, including in women intending pregnancy, is predicted to bring population health benefits (10 990 DALYs averted per year) and to be cost-saving (by $2.9 million per year), leading to a reduction in the overall population burden of disease of 16 735 net DALYs per year for a country with an adult population size of 10 million. The policy involving ART initiation with a dolutegravir-based regimen in women intending pregnancy was cost-effective in 87% of our setting scenarios and this finding was robust in various sensitivity analyses, including around the potential negative effects of weight gain. INTERPRETATION: In the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators. FUNDING: Bill & Melinda Gates Foundation. |
Replacement of neuraminidase inhibitor susceptible influenza A(H1N1) with resistant phenotype in 2008 and circulation of susceptible influenza A and B viruses during 2009-2013, South Africa.
Treurnicht FK , Buys A , Tempia S , Seleka M , Cohen AL , Walaza S , Glass AJ , Rossouw I , McAnerney J , Blumberg L , Cohen C , Venter M . Influenza Other Respir Viruses 2019 13 (1) 54-63 ![]() ![]() BACKGROUND: Data on the susceptibility of influenza viruses from South Africa to neuraminidase inhibitors (NAIs) are scarce, and no extensive analysis was done. OBJECTIVES: We aimed to determine oseltamivir and zanamivir susceptibility of influenza A and B virus neuraminidases (NAs), 2007-2013, South Africa. PATIENTS/METHODS: We enrolled participants through national influenza-like illness surveillance, 2007-2013. Influenza diagnosis was by virus isolation and quantitative polymerase chain reaction (qPCR). Drug susceptibility was determined by chemiluminescence-based NA-STAR/NA-XTD assay. Sanger sequencing was used to determine molecular markers of NAI resistance. RESULTS: Forty percent (6341/15 985) of participants were positive for influenza viruses using virus isolation (2007-2009) and qPCR (2009-2013) methods. A total of 1236/6341 (19.5%) virus isolates were generated of which 307/1236 (25%) were tested for drug susceptibility. During 2007-2008, the median 50% inhibitory concentration (IC50 ) of oseltamivir for seasonal influenza A(H1N1) increased from of 0.08 nmol/L (range 0.01-3.60) in 2007 to 73 nmol/L (range 1.56-305 nmol/L) in 2008. Influenza A isolates from 2009 to 2013 were susceptible to oseltamivir [A(H3N2) median IC50 = 0.05 nmol/L (range 0.01-0.08); A(H1N1)pdm09 = 0.11 nmol/L (range 0.01-0.78)] and zanamivir [A(H3N2) median IC50 = 0.56 nmol/L (range 0.47-0.66); A(H1N1)pdm09 = 0.35 nmol/L (range 0.27-0.533)]. Influenza B viruses were susceptible to both NAIs. NAI resistance-associated substitutions H275Y, E119V, and R150K (N1 numbering) were not detected in influenza A viruses that circulated in 2009-2013. CONCLUSIONS: We confirm replacement of NAI susceptible by resistant phenotype influenza A(H1N1) in 2008. Influenza A and B viruses (2009-2013) remained susceptible to NAIs; therefore, these drugs are useful for treating influenza-infected patients. |
The impact of HIV exposure on respiratory syncytial virus-associated severe respiratory illness in South African infants, 2011-2016
McMorrow ML , Tempia S , Walaza S , Treurnicht FK , Moyes J , Cohen AL , Pretorius M , Hellferscee O , Wolter N , von Gottberg A , Nguweneza A , McAnerney JM , Naby F , Mekgoe O , Venter M , Madhi SA , Cohen C . Clin Infect Dis 2019 69 (12) 2208-2211 During 2011-2016, we conducted surveillance for severe respiratory illness in infants. HIV exposure statistically significantly increased the risk of RSV-associated hospitalization in infants aged <5 months. Over 60% of RSV-associated hospitalizations occurred in the first 4 months of life and may be preventable through maternal vaccination or birth-dose monoclonal antibody. |
The impact of influenza and tuberculosis interaction on mortality among individuals aged 15 years hospitalized with severe respiratory illness in South Africa, 2010-2016
Walaza S , Tempia S , Dawood H , Variava E , Wolter N , Dreyer A , Moyes J , Von Mollendorf C , McMorrow M , Von Gottberg A , Haffejee S , Venter M , Treurnicht FK , Hellferscee O , Martinson NA , Ismail N , Cohen C . Open Forum Infect Dis 2019 6 (3) ofz020 Background: Data on the prevalence and impact of influenza-tuberculosis coinfection on clinical outcomes from high-HIV and -tuberculosis burden settings are limited. We explored the impact of influenza and tuberculosis coinfection on mortality among hospitalized adults with lower respiratory tract infection (LRTI). Methods: We enrolled patients aged >/=15 years admitted with physician-diagnosed LRTI or suspected tuberculosis at 2 hospitals in South Africa from 2010 to 2016. Combined nasopharyngeal and oropharyngeal swabs were tested for influenza and 8 other respiratory viruses. Tuberculosis testing of sputum included smear microscopy, culture, and/or Xpert MTB/Rif. Results: Among 6228 enrolled individuals, 4253 (68%) were tested for both influenza and tuberculosis. Of these, the detection rate was 6% (239/4253) for influenza, 26% (1092/4253) for tuberculosis, and 77% (3113/4053) for HIV. One percent (42/4253) tested positive for both influenza and tuberculosis. On multivariable analysis, among tuberculosis-positive patients, factors independently associated with death were age group >/=65 years compared with 15-24 years (adjusted odds ratio [aOR], 3.6; 95% confidence interval [CI], 1.2-11.0) and influenza coinfection (aOR, 2.3; 95% CI, 1.02-5.2). Among influenza-positive patients, laboratory-confirmed tuberculosis was associated with an increased risk of death (aOR, 4.5; 95% CI, 1.5-13.3). Coinfection with other respiratory viruses was not associated with increased mortality in patients positive for tuberculosis (OR, 0.7; 95% CI, 0.4-1.1) or influenza (OR, 1.6; 95% CI, 0.4-5.6). Conclusions: Tuberculosis coinfection is associated with increased mortality in individuals with influenza, and influenza coinfection is associated with increased mortality in individuals with tuberculosis. These data may inform prioritization of influenza vaccines or antivirals for tuberculosis patients and inform tuberculosis testing guidelines for patients with influenza. |
Human bocavirus, coronavirus, and polyomavirus detected among patients hospitalised with severe acute respiratory illness in South Africa, 2012 to 2013
Subramoney K , Hellferscee O , Pretorius M , Tempia S , McMorrow M , von Gottberg A , Wolter N , Variava E , Dawood H , Kahn K , Walaza S , Madhi SA , Cohen C , Venter M , Treurnicht FK . Health Sci Rep 2018 1 (8) e59 Aim: To investigate the prevalence of human bocavirus (hBoV), human coronaviruses (hCoV), and human polyomaviruses (hPyV) among patients with severe acute respiratory illness (SARI), in South Africa. Methods: The study included 680 South African patients randomly selected in age-defined categories from hospitalised patients enrolled through SARI surveillance during 2012 to 2013. A multiplex reverse transcription real-time polymerase chain reaction assay was used to detect hBoV; hCoV-OC43, hCoV-229E, hCoV-NL63, and hCoV-HKU1; and Washington University hPyV (hPyV-WU) and Karolinska Insitute hPyV (hPyV-KI), in respiratory tract specimens collected from patients with SARI. All respiratory specimens from patients enrolled through SARI surveillance were also routinely tested by multiplex reverse transcription real-time polymerase chain reaction for adenovirus; enterovirus; human metapneumovirus; parainfluenza virus types 1, 2, and 3; respiratory syncytial virus; rhinovirus; influenza A, and influenza B. Results: Human bocavirus, hCoV-229E, and hPyV-WU were detected in 3.7% (25/680), 4.1% (28/680), and 4.1% (28/680) of respiratory specimens, respectively. All other viruses were detected in <2% of specimens. Rhinovirus was the most common coinfecting virus (21.4%-60.7%), followed by adenovirus (21.4%-39.3%), and respiratory syncytial virus (10.7%-24.0%). Testing for the additional viruses (hBoV, hCoV, and hPyV) decreased the number of specimens that initially tested negative by 2.9% (20/680). Conclusion: Inclusion of laboratory tests for hBoV, hCoV-229E, and hPyV-WU in differential testing algorithms for surveillance and diagnostics for suspected cases of respiratory illness of unknown cause may improve our understanding of the etiology of SARI, especially in a country like South Africa with a high number of immune compromised persons. |
The fraction of rhinovirus detections attributable to mild and severe respiratory illness in a high HIV-prevalence setting, South Africa, 2013-2015
Hellferscee O , Treurnicht FK , Walaza S , du Plessis M , von Gottberg A , Wolter N , Moyes J , Dawood H , Variava E , Pretorius M , Venter M , Cohen C , Tempia S . J Infect Dis 2018 219 (11) 1697-1704 Background: The association of rhinoviruses (RV) detection to illness is poorly understood. Methods: We enrolled case-patients hospitalized with severe respiratory illness (SRI) at two hospitals and outpatients with influenza-like-illness (ILI) and asymptomatic individuals (controls) from two affiliated clinics during 2013-2015. We compared the RV prevalence among ILI and SRI cases to those of controls stratified by HIV-serostatus using penalized logistic regression. All analyses were adjusted for underlying medical conditions and viral coinfections. The attributable fraction (AF) was calculated from the adjusted odds ratio (aOR) using the following formula: (aOR-1)/aOR*100. Results: During 2013-2015 RV was detected in 17.4% (368/2120), 26.8% (979/3654) and 23.0% (1003/4360) of controls, ILI and SRI cases, respectively. The RV attributable fraction (AF) was statistically significant among children aged <5 years (ILI:44.6%; 95% CI: 30.7%-55.7% and SRI:50.3%; 95% CI: 38.6%-59.9%; p<0.001) and individuals aged >/=5 years (ILI:62.9%; 95% CI: 54.4%-69.8% and SRI:51.3%; 95% CI: 38.7%-61.3%; p<0.001) as well as among HIV-infected (ILI:59.9%; 95% CI: 45.8%-70.3% and SRI 39.8%; 95% CI: 22.3%-53.3%; p<0.001) and HIV-uninfected (ILI:53.6%; 95% CI: 44.7%-61.1% and SRI:55.3%; 95% CI: 45.6%-63.2%; p<0.001) individuals. Conclusions: Although rhinoviruses detection was common among controls, it was also associated with a substantial proportion of clinical illness across age groups, irrespective of HIV status. |
Household transmission of seasonal influenza from HIV-infected and -uninfected individuals in South Africa, 2013-2014
Cohen C , Tshangela A , Valley-Omar Z , Iyengar P , von Mollendorf C , Walaza S , Hellferscee O , Venter M , Martinson N , Mahlase G , McMorrow M , Cowling BJ , Treurnicht FK , Cohen AL , Tempia S . J Infect Dis 2018 219 (10) 1605-1615 Background: Differential transmission from HIV-infected compared to HIV-uninfected individuals may impact influenza burden. We estimated the household secondary infection risk (SIR) and serial interval (SI) for influenza transmission from HIV-infected and HIV-uninfected index cases and identified associated factors. Methods: Index cases were the first symptomatic person in a household with influenza-like illness, testing influenza positive on real-time reverse transcription polymerase chain reaction (rRT-PCR). Nasopharyngeal swabs collected from household contacts every four days were tested by rRT-PCR. Factors associated with SIR were evaluated using logistic regression. Results: We enrolled 28 HIV-infected and 57 HIV-uninfected index cases. On multivariable analysis, HIV-infected index cases were less likely to transmit influenza to household contacts (odds ratio (OR) 0.2 95% CI 0.1-0.6)(SIR 16%, 18/113 vs 27%, 59/220). Factors associated with increased SIR included index age group 1-4 years (OR 3.6, 95% CI 1.2-11.3) and 25-44 years (OR 8.0, 95% CI 1.8-36.7) and contact age group 1-4 years (OR 3.5, 95%CI 1.2-10.3) compared to 5-14 years and sleeping with index case (OR 2.7, 95%CI 1.3-5.5). HIV-infection of index case was not associated with SI. Conclusions: HIV-infection was not associated with SI. Increased infectiousness of HIV-infected individuals is likely not an important driver of community influenza transmission. |
The role of HIV in influenza- and respiratory syncytial virus-associated hospitalizations in South African children, 2011-2016
McMorrow ML , Tempia S , Walaza S , Treurnicht FK , Moyes J , Cohen AL , Pretorius M , Hellferscee O , Wolter N , von Gottberg A , Nguweneza A , McAnerney JM , Naby F , Mekgoe O , Venter M , Madhi SA , Cohen C . Clin Infect Dis 2018 68 (5) 773-780 Background: Few data describe influenza- or respiratory syncytial virus (RSV)-associated hospitalized illness in children aged <5 years in sub-Saharan Africa. Methods: During 2011-2016, we conducted prospective surveillance for severe respiratory illness (SRI) in children aged <5 years in three South African hospitals. Nasopharyngeal aspirates were tested for influenza and RSV by real-time reverse transcription polymerase chain reaction. We estimated rates of influenza- and RSV-associated hospitalized SRI by HIV status and compared children who tested positive for influenza versus 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 versus 4.4 months for RSV (p<0.01). Annual influenza-associated hospitalization rates per 100,000 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, 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. The case-fatality rate was 0.8% among children hospitalized with influenza or RSV. Conclusions: Influenza- and RSV-associated hospitalization are common among South African infants. HIV infection, and HIV exposure in infants, increase risk of influenza- and RSV-associated hospitalization. |
Distribution of influenza virus types by age using case-based global surveillance data from twenty-nine countries, 1999-2014
Caini S , Spreeuwenberg P , Kusznierz GF , Rudi JM , Owen R , Pennington K , Wangchuk S , Gyeltshen S , Ferreira de Almeida WA , Pessanha Henriques CM , Njouom R , Vernet MA , Fasce RA , Andrade W , Yu H , Feng L , Yang J , Peng Z , Lara J , Bruno A , de Mora D , de Lozano C , Zambon M , Pebody R , Castillo L , Clara AW , Matute ML , Kosasih H , Nurhayati , Puzelli S , Rizzo C , Kadjo HA , Daouda C , Kiyanbekova L , Ospanova A , Mott JA , Emukule GO , Heraud JM , Razanajatovo NH , Barakat A , El Falaki F , Huang SQ , Lopez L , Balmaseda A , Moreno B , Rodrigues AP , Guiomar R , Ang LW , Lee VJM , Venter M , Cohen C , Badur S , Ciblak MA , Mironenko A , Holubka O , Bresee J , Brammer L , Hoang PVM , Le MTQ , Fleming D , Seblain CE , Schellevis F , Paget J . BMC Infect Dis 2018 18 (1) 269 BACKGROUND: Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data from twenty-nine countries during 1999-2014 (N=358,796 influenza cases). METHODS: For each virus, we calculated a Relative Illness Ratio (defined as the ratio of the percentage of cases in an age group to the percentage of the country population in the same age group) for young children (0-4 years), older children (5-17 years), young adults (18-39 years), older adults (40-64 years), and the elderly (65+ years). We used random-effects meta-analysis models to obtain summary relative illness ratios (sRIRs), and conducted meta-regression and sub-group analyses to explore causes of between-estimates heterogeneity. RESULTS: The influenza virus with highest sRIR was A(H1N1) for young children, B for older children, A(H1N1)pdm2009 for adults, and (A(H3N2) for the elderly. As expected, considering the diverse nature of the national surveillance datasets included in our analysis, between-estimates heterogeneity was high (I(2)>90%) for most sRIRs. The variations of countries' geographic, demographic and economic characteristics and the proportion of outpatients among reported influenza cases explained only part of the heterogeneity, suggesting that multiple factors were at play. CONCLUSIONS: These results highlight the importance of presenting burden of disease estimates by age group and virus (sub)type. |
Influenza viral shedding in a prospective cohort of HIV-infected and -uninfected children and adults in 2 provinces of South Africa, 2012-2014
von Mollendorf C , Hellferscee O , Valley-Omar Z , Treurnicht FK , Walaza S , Martinson NA , Lebina L , Mothlaoleng K , Mahlase G , Variava E , Cohen AL , Venter M , Cohen C , Tempia S . J Infect Dis 2018 218 (8) 1228-1237 Background: Prolonged shedding of influenza viruses may be associated with increased transmissibility and resistance mutation acquisition due to therapy. We compared duration and magnitude of influenza shedding between HIV-infected and -uninfected individuals. Methods: A prospective cohort study during three influenza seasons enrolled patients with influenza-like illness and a positive influenza rapid test. Influenza viruses were detected by real-time reverse transcription polymerase chain reaction. Weibull accelerated failure time regression models were used to describe influenza virus shedding. Mann-Whitney U tests explored initial influenza viral loads (VL). Results: Influenza virus shedding duration was similar in 65 HIV-infected (6 [interquartile range (IQR) 3-10] days) and 176 HIV-uninfected individuals (7 [IQR 4-11] days, p=0.97), as was initial influenza VL (HIV-uninfected 5.28 +/- 1.33 log10 copies/mL, HIV-infected 4.73 +/- 1.68 log10 copies/mL, p=0.08). Adjusted for age, HIV-infected individuals with low CD4 counts shed influenza virus for longer than those with higher counts (adjusted hazard ratio [aHR] 3.55, 95% confidence interval [CI] 1.05-12.08). Discussion: A longer duration of influenza virus shedding in HIV-infected individuals with low CD4 counts may suggest a possible increased risk for transmission or viral evolution in severely immunocompromised individuals. HIV-infected individuals should be prioritized for annual influenza immunization. |
The effects of the attributable fraction and the duration of symptoms on burden estimates of influenza-associated respiratory illnesses in a high HIV prevalence setting, South Africa, 2013-2015
Tempia S , Walaza S , Moyes J , Cohen AL , von Mollendorf C , McMorrow ML , Mhlanga S , Treurnicht FK , Venter M , Pretorius M , Hellferscee O , Wolter N , von Gottberg A , Nguweneza A , McAnerney JM , Dawood H , Variava E , Madhi SA , Cohen C . Influenza Other Respir Viruses 2017 12 (3) 360-373 BACKGROUND: The attributable fraction of influenza virus detection to illness (INF-AF) and the duration of symptoms as a surveillance inclusion criterion could potentially have substantial effects on influenza disease burden estimates. METHODS: We estimated rates of influenza-associated influenza-like illness (ILI) and severe acute (SARI-10) or chronic (SCRI-10) respiratory illness (using a symptom duration cut-off of ≤10 days) among HIV-infected and HIV-uninfected patients attending 3 hospitals and 2 affiliated clinics in South Africa during 2013-2015. We calculated the unadjusted and INF-AF adjusted rates and relative risk (RR) due to HIV infection. Rates were expressed per 100 000 population. RESULTS: The estimated mean annual unadjusted rates of influenza-associated illness were 1467.7, 50.3 and 27.4 among patients with ILI, SARI-10 and SCRI-10, respectively. After adjusting for the INF-AF the percent reduction of the estimated rates was 8.9% (rate: 1336.9), 11.0% (rate: 44.8) and 16.3% (rate: 22.9) among patients with ILI, SARI-10 and SCRI-10, respectively. HIV-infected compared to HIV-uninfected individuals experienced a 2.3 (95% CI: 2.2-2.4), 9.7 (95% CI: 8.0-11.8) and 10.0 (95% CI: 7.9-12.7) fold increased risk of influenza-associated illness among patients with ILI, SARI-10 and SCRI-10, respectively. Overall 34% of the estimated influenza-associated hospitalizations had symptom duration of >10 days; 8% and 44% among individuals aged <5 and ≥5 years, respectively. CONCLUSION: The marginal differences between unadjusted and INF-AF adjusted rates are unlikely to affect policies on prioritization of interventions. HIV-infected individuals experienced an increased risk of influenza-associated illness and may benefit more from annual influenza immunization. The use of a symptom duration cut-off of ≤10 days may underestimate influenza-associated disease burden, especially in older individuals. This article is protected by copyright. All rights reserved. |
Enterovirus D68 and other enterovirus serotypes identified in South African patients with severe acute respiratory illness, 2009-2011
Hellferscee O , Treurnicht FK , Tempia S , Variava E , Dawood H , Kahn K , Cohen AL , Pretorius M , Cohen C , Madhi SA , Venter M . Influenza Other Respir Viruses 2017 11 (3) 211-219 BACKGROUND: Human enteroviruses (EV) have been associated with severe acute respiratory illness (SARI) in South Africa. OBJECTIVES: We aimed to describe the molecular epidemiology of EV serotypes among patients hospitalized with SARI during 2009-2011. PATIENTS/METHODS: Study samples from patients were tested for the presence of enterovirus using a polymerase chain reaction assay. RESULTS: 8.2% (842/10 260) of SARI cases tested positive for enterovirus; 16% (7/45) were species EV-A, 44% (20/45) EV-B, 18% (8/45) EV-C and 22% (10/45) EV-D. Seventeen different EV serotypes were identified within EV-A to EV-D, of which EV-D68 (22%; 10/45) and Echovirus 3 (11%; 5/45) were the most prevalent. CONCLUSIONS: EV-D68 should be monitored in South Africa to assess the emergence of highly pathogenic strains. |
West Nile virus lineage 2 in horses and other animals with neurologic disease, South Africa, 2008-2015
Venter M , Pretorius M , Fuller JA , Botha E , Rakgotho M , Stivaktas V , Weyer C , Romito M , Williams J . Emerg Infect Dis 2017 23 (12) 2060-2064 During 2008-2015 in South Africa, we conducted West Nile virus surveillance in 1,407 animals with neurologic disease and identified mostly lineage 2 cases in horses (7.4%, 79/1,069), livestock (1.5%, 2/132), and wildlife (0.5%, 1/206); 35% were fatal. Geographic correlation of horse cases with seropositive veterinarians suggests disease in horses can predict risk in humans. |
Risk of human infections with highly pathogenic H5N2 and low pathogenic H7N1 avian influenza strains during outbreaks in ostriches in South Africa
Venter M , Treurnicht FK , Buys A , Tempia S , Samudzi R , McAnerney J , Jacobs CA , Thomas J , Blumberg L . J Infect Dis 2017 216 S512-s519 Background: Risk factors for human infection with highly pathogenic (HP) and low-pathogenic (LP) avian influenza (AI) H5N2 and H7N1 were investigated during outbreaks in ostriches in the Western Cape province, South Africa. Methods: Serum surveys were conducted for veterinarians, farmworkers, and laboratory and abattoir workers involved in 2 AI outbreaks in the Western Cape province: (1) controlling and culling of 42000 ostriches during (HPAI)H5N2 outbreaks in ostriches (2011) (n = 207); (2) movement control during (LPAI)H7N1 outbreaks in 2012 (n = 66). A third serosurvey was conducted on state veterinarians from across the country in 2012 tasked with disease control in general (n = 37). Antibodies to H5 and H7 were measured by means of hemagglutination inhibition and microneutralization assays, with microneutralization assay titers >40 considered positive. Results: Two of 207 (1%) participants were seropositive for H5 and 4 of 207 (2%) for H7 in 2011, compared with 1 of 66 (1.5%) and 8 of 66 (13%) in 2012. Although individuals in all professions tested seropositive, abattoir workers (10 of 97; 10.3%) were significantly more at risk of influenza A(H7N1) infection (P = .001) than those in other professions (2 of 171;1.2%). Among state veterinarians, 4 of 37(11%) were seropositive for H7 and 1 of 37 (2.7%) for H5. Investigations of (LP)H7N1-associated fatalities in wild birds and quarantined exotic birds in Gauteng, AI outbreaks in poultry in KwaZulu-Natal, and ostriches in Western Cape province provide possible exposure events. Conclusion: (LPAI)H7N1 strains pose a greater infection-risk than (HPAI)H5N2 strains to persons involved in control of outbreaks in infected birds, with ostrich abattoir workers at highest risk. |
Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study
Shi T , McAllister DA , O'Brien KL , Simoes EAF , Madhi SA , Gessner BD , Polack FP , Balsells E , Acacio S , Aguayo C , Alassani I , Ali A , Antonio M , Awasthi S , Awori JO , Azziz-Baumgartner E , Baggett HC , Baillie VL , Balmaseda A , Barahona A , Basnet S , Bassat Q , Basualdo W , Bigogo G , Bont L , Breiman RF , Brooks WA , Broor S , Bruce N , Bruden D , Buchy P , Campbell S , Carosone-Link P , Chadha M , Chipeta J , Chou M , Clara W , Cohen C , de Cuellar E , Dang DA , Dash-Yandag B , Deloria-Knoll M , Dherani M , Eap T , Ebruke BE , Echavarria M , de Freitas Lazaro Emediato CC , Fasce RA , Feikin DR , Feng L , Gentile A , Gordon A , Goswami D , Goyet S , Groome M , Halasa N , Hirve S , Homaira N , Howie SRC , Jara J , Jroundi I , Kartasasmita CB , Khuri-Bulos N , Kotloff KL , Krishnan A , Libster R , Lopez O , Lucero MG , Lucion F , Lupisan SP , Marcone DN , McCracken JP , Mejia M , Moisi JC , Montgomery JM , Moore DP , Moraleda C , Moyes J , Munywoki P , Mutyara K , Nicol MP , Nokes DJ , Nymadawa P , da Costa Oliveira MT , Oshitani H , Pandey N , Paranhos-Baccala G , Phillips LN , Picot VS , Rahman M , Rakoto-Andrianarivelo M , Rasmussen ZA , Rath BA , Robinson A , Romero C , Russomando G , Salimi V , Sawatwong P , Scheltema N , Schweiger B , Scott JAG , Seidenberg P , Shen K , Singleton R , Sotomayor V , Strand TA , Sutanto A , Sylla M , Tapia MD , Thamthitiwat S , Thomas ED , Tokarz R , Turner C , Venter M , Waicharoen S , Wang J , Watthanaworawit W , Yoshida LM , Yu H , Zar HJ , Campbell H , Nair H . Lancet 2017 390 (10098) 946-958 BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. METHODS: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. FINDINGS: We estimated that globally in 2015, 33.1 million (uncertainty range [UR] 21.6-50.3) episodes of RSV-ALRI, resulted in about 3.2 million (2.7-3.8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1.4 million (UR 1.2-1.7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. FUNDING: The Bill & Melinda Gates Foundation. |
Attributable fraction of influenza virus detection to mild and severe respiratory illnesses in HIV-infected and HIV-uninfected patients, South Africa, 2012-2016
Tempia S , Walaza S , Moyes J , Cohen AL , von Mollendorf C , McMorrow ML , Treurnicht FK , Venter M , Pretorius M , Hellferscee O , Wolter N , von Gottberg A , Nguweneza A , McAnerney JM , Dawood H , Variava E , Madhi SA , Cohen C . Emerg Infect Dis 2017 23 (7) 1124-1132 The attributable fraction (AF) of influenza virus detection to illness has not been described for patients in different age groups or with different HIV infection statuses. We compared the age group-specific prevalence of influenza virus infection among patients with influenza-like illness (ILI) or severe acute or chronic respiratory illness (SARI and SCRI, respectively) with that among controls, stratified by HIV serostatus. The overall AF for influenza virus detection to illness was 92.6% for ILI, 87.4% for SARI, and 86.2% for SCRI. Among HIV-uninfected patients, the AF for all syndromes was highest among persons <1 and >65 years of age and lowest among persons 25-44 years of age; this trend was not observed among HIV-infected patients. Overall, influenza viruses when detected in patients with ILI, SARI, or SCRI are likely attributable to illness. This finding is particularly likely among children and the elderly irrespective of HIV serostatus and among HIV-infected persons irrespective of age. |
Respiratory syncytial virus in adults with severe acute respiratory illness in a high HIV prevalence setting
Moyes J , Walaza S , Pretorius M , Groome M , von Gottberg A , Wolter N , Haffejee S , Variava E , Cohen AL , Tempia S , Kahn K , Dawood H , Venter M , Cohen C , Madhi SA . J Infect 2017 75 (4) 346-355 BACKGROUND: There are limited data on the epidemiology of respiratory syncytial virus (RSV) illness in HIV-infected adults or the elderly in Africa. We studied the epidemiology of RSV-associated severe acute respiratory illness (SARI) hospitalizations in adults in South Africa from 2009 through 2013. METHODS: Individuals admitted to sentinel surveillance hospitals were investigated by respiratory tract swabs for RSV, using a multiplex real-time polymerase chain reaction assay. The incidence of RSV-associated SARI was calculated for the one site with population denominators. RESULTS: Of 7796 participants investigated, 329 (4%) tested positive for RSV. On multivariable analysis, HIV-infected individuals with RSV-associated SARI had greater odds of being in the age groups 18-44 and 45-64 years (odd ratios (OR) 26.3; 95% confidence interval (CI) 6.2-112.1 and OR 11.4; 95% CI 2.6-50.0) compared with those ≥65 years and being female (OR 2.7; 95% CI 1.4-5.4). The relative risk of hospitalization with RSV-associated SARI was 12 to 18 times higher in HIV infected individual compared to that of HIV-uninfected. CONCLUSION: The incidence of RSV-associated SARI was higher in HIV-infected individuals and those aged 65 years and older. Further studies are warranted to describe the disease association of RSV detected in adults with SARI. |
Epidemiology of influenza B/Yamagata and B/Victoria lineages in South Africa, 2005-2014
Seleka M , Treurnicht FK , Tempia S , Hellferscee O , Mtshali S , Cohen AL , Buys A , McAnerney JM , Besselaar TG , Pretorius M , von Gottberg A , Walaza S , Cohen C , Madhi SA , Venter M . PLoS One 2017 12 (5) e0177655 BACKGROUND: Studies describing the epidemiology of influenza B lineages in South Africa are lacking. METHODS: We conducted a prospective study to describe the circulation of influenza B/Victoria and B/Yamagata lineages among patients of all ages enrolled in South Africa through three respiratory illness surveillance systems between 2005 and 2014: (i) the Viral Watch (VW) program enrolled outpatients with influenza-like illness (ILI) from private healthcare facilities during 2005-2014; (ii) the influenza-like illnesses program enrolled outpatients in public healthcare clinics (ILI/PHC) during 2012-2014; and (iii) the severe acute respiratory illnesses (SARI) program enrolled inpatients from public hospitals during 2009-2014. Influenza B viruses were detected by virus isolation during 2005 to 2009 and by real-time reverse transcription polymerase chain reaction from 2009-2014. Clinical and epidemiological characteristics of patients hospitalized with SARI and infected with different influenza B lineages were also compared using unconditional logistic regression. RESULTS: Influenza viruses were detected in 22% (8,706/39,804) of specimens from patients with ILI or SARI during 2005-2014, of which 24% (2,087) were positive for influenza B. Influenza B viruses predominated in all three surveillance systems in 2010. B/Victoria predominated prior to 2011 (except 2008) whereas B/Yamagata predominated thereafter (except 2012). B lineages co-circulated in all seasons, except in 2013 and 2014 for SARI and ILI/PHC surveillance. Among influenza B-positive SARI cases, the detection of influenza B/Yamagata compared to influenza B/Victoria was significantly higher in individuals aged 45-64 years (adjusted odds ratio [aOR]: 4.2; 95% confidence interval [CI]: 1.1-16.5) and ≥65 years (aOR: 12.2; 95% CI: 2.3-64.4) compared to children aged 0-4 years, but was significantly lower in HIV-infected patients (aOR: 0.4; 95% CI: 0.2-0.9). CONCLUSION: B lineages co-circulated in most seasons except in 2013 and 2014. Hospitalized SARI cases display differential susceptibility for the two influenza B lineages, with B/Victoria being more prevalent among children and HIV-infected persons. |
Risk factors for influenza-associated severe acute respiratory illness hospitalization in South Africa, 2012-2015
Tempia S , Walaza S , Moyes J , Cohen AL , von Mollendorf C , Treurnicht FK , Venter M , Pretorius M , Hellferscee O , Mtshali S , Seleka M , Tshangela A , Nguweneza A , McAnerney JM , Wolter N , von Gottberg A , Dawood H , Variava E , Madhi SA , Cohen C . Open Forum Infect Dis 2017 4 (1) ofw262 Background. Data on risk factors for influenza-associated hospitalizations in low- and middle-income countries are limited. Methods. We conducted active syndromic surveillance for hospitalized severe acute respiratory illness (SARI) and outpatient influenza-like illness (ILI) in 2 provinces of South Africa during 2012-2015. We compared the characteristics of influenza-positive patients with SARI to those with ILI to identify factors associated with severe disease requiring hospitalization, using unconditional logistic regression. Results. During the study period, influenza virus was detected in 5.9% (110 of 1861) and 15.8% (577 of 3652) of SARI and ILI cases, respectively. On multivariable analysis factors significantly associated with increased risk of influenza-associated SARI hospitalization were as follows: younger and older age ( < 6 months [adjusted odds ratio (aOR), 37.6], 6-11 months [aOR, 31.9], 12-23 months [aOR, 22.1], 24-59 months [aOR, 7.1], and ≥65 years [aOR, 40.7] compared with 5-24 years of age), underlying medical conditions (aOR, 4.5), human immunodeficiency virus infection (aOR, 4.3), and Streptococcus pneumoniae colonization density ≥1000 deoxyribonucleic acid copies/mL (aOR, 4.8). Underlying medical conditions in children aged < 5 years included asthma (aOR, 22.7), malnutrition (aOR, 2.4), and prematurity (aOR, 4.8); in persons aged ≥5 years, conditions included asthma (aOR, 3.6), diabetes (aOR, 7.1), chronic lung diseases (aOR, 10.7), chronic heart diseases (aOR, 9.6), and obesity (aOR, 21.3). Mine workers (aOR, 13.8) and pregnant women (aOR, 12.5) were also at increased risk for influenza-associated hospitalization. Conclusions. The risk groups identified in this study may benefit most from annual influenza immunization, and children < 6 months of age may be protected through vaccination of their mothers during pregnancy. |
Development of a respiratory severity score for hospitalized adults in a high HIV-prevalence setting-South Africa, 2010-2011
Millman AJ , Greenbaum A , Walaza S , Cohen AL , Groome MJ , Reed C , McMorrow M , Tempia S , Venter M , Treurnicht FK , Madhi SA , Cohen C , Variava E . BMC Pulm Med 2017 17 (1) 28 BACKGROUND: Acute lower respiratory tract infections (LRTI) are a frequent cause of hospitalization and mortality in South Africa; however, existing respiratory severity scores may underestimate mortality risk in HIV-infected adults in resource limited settings. A simple predictive clinical score for low-resource settings could aid healthcare providers in the management of patients hospitalized with LRTI. METHODS: We analyzed 1,356 LRTI hospitalizations in adults aged ≥18 years enrolled in Severe Acute Respiratory Illness (SARI) surveillance in three South African hospitals from January 2010 to December 2011. Using demographic and clinical data at admission, we evaluated potential risk factors for in-hospital mortality. We evaluated three existing respiratory severity scores, CURB-65, CRB-65, and Classification Tree Analysis (CTA) Score assessing for discrimination and calibration. We then developed a new respiratory severity score using a multivariable logistic regression model for in-hospital mortality and assigned points to risk factors based on the coefficients in the multivariable model. Finally we evaluated the model statistically using bootstrap resampling techniques. RESULTS: Of the 1,356 patients hospitalized with LRTI, 101 (7.4%) died while hospitalized. The CURB-65, CRB-65, and CTA scores had poor calibration and demonstrated low discrimination with c-statistics of 0.594, 0.548, and 0.569 respectively. Significant risk factors for in-hospital mortality included age ≥ 45 years (A), confusion on admission (C), HIV-infection (H), and serum blood urea nitrogen >7 mmol/L (U), which were used to create the seven-point ACHU clinical predictor score. In-hospital mortality, stratified by ACHU score was: score ≤1, 2.4%, score 2, 6.4%, score 3, 11.9%, and score ≥ 4, 29.3%. Final models showed good discrimination (c-statistic 0.789) and calibration (chi-square 1.6, Hosmer-Lemeshow goodness-of-fit p-value = 0.904) and discriminated well in the bootstrap sample (average optimism of 0.003). CONCLUSIONS: Existing clinical predictive scores underestimated mortality in a low resource setting with a high HIV burden. The ACHU score incorporates a simple set a risk factors that can accurately stratify patients ≥18 years of age with LRTI by in-hospital mortality risk. This score can quantify in-hospital mortality risk in an HIV-endemic, resource-limited setting with limited clinical information and if used to facilitate timely treatment may improve clinical outcomes. |
Severity of respiratory syncytial virus lower respiratory tract infection with viral coinfection in HIV-uninfected children
Mazur NI , Bont L , Cohen AL , Cohen C , von Gottberg A , Groome MJ , Hellferscee O , Klipstein-Grobusch K , Mekgoe OT , Naby F , Moyes J , Tempia S , Treurnicht FK , Venter M , Walaza S , Wolter N , Madhi SA . Clin Infect Dis 2016 64 (4) 443-450 BACKGROUND: Molecular diagnostics enable sensitive detection of respiratory viruses but their clinical significance remains unclear in pediatric lower respiratory tract infections (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) hospitalisation 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 2,322 HIV-uninfected children with respiratory syncytial virus (RSV)-associated lower respiratory tract infection (LRTI), 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus (RV), 347 (14.9%) had adenovirus (ADV) and 30 (1.3%) had influenza virus (Infl). RSV and any other viral coinfection was not associated with severe disease (OR: 1.4; 95% 0.7-2.6), ADV coinfection had increased odds of life-threatening disease (aOR: 3.4, 95%CI: 1.6 - 7.2, p=0.001), and Infl coinfection had increased odds of life-threatening disease and prolonged length of stay (aOR: 2.1,95%CI: 1.0-4.5, p=0.05) compared to RSV monoinfection. CONCLUSION: 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-Infl coinfection warrants further study. |
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