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1.
Artigo em Inglês | MEDLINE | ID: mdl-34528769

RESUMO

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.

2.
Euro Surveill ; 26(29)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34296675

RESUMO

BackgroundIn South Africa, COVID-19 control measures to prevent SARS-CoV-2 spread were initiated on 16 March 2020. Such measures may also impact the spread of other pathogens, including influenza virus and respiratory syncytial virus (RSV) with implications for future annual epidemics and expectations for the subsequent northern hemisphere winter.MethodsWe assessed the detection of influenza and RSV through facility-based syndromic surveillance of adults and children with mild or severe respiratory illness in South Africa from January to October 2020, and compared this with surveillance data from 2013 to 2019.ResultsFacility-based surveillance revealed a decline in influenza virus detection during the regular season compared with previous years. This was observed throughout the implementation of COVID-19 control measures. RSV detection decreased soon after the most stringent COVID-19 control measures commenced; however, an increase in RSV detection was observed after the typical season, following the re-opening of schools and the easing of measures.ConclusionCOVID-19 non-pharmaceutical interventions led to reduced circulation of influenza and RSV in South Africa. This has limited the country's ability to provide influenza virus strains for the selection of the annual influenza vaccine. Delayed increases in RSV case numbers may reflect the easing of COVID-19 control measures. An increase in influenza virus detection was not observed, suggesting that the measures may have impacted the two pathogens differently. The impact that lowered and/or delayed influenza and RSV circulation in 2020 will have on the intensity and severity of subsequent annual epidemics is unknown and warrants close monitoring.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Adulto , Criança , Humanos , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , SARS-CoV-2 , África do Sul/epidemiologia
3.
Influenza Other Respir Viruses ; 15(6): 789-803, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34296810

RESUMO

PURPOSE: The PHIRST study (Prospective Household cohort study of Influenza, Respiratory Syncytial virus, and other respiratory pathogens community burden and Transmission dynamics in South Africa) aimed to estimate the community burden of influenza and respiratory syncytial virus (RSV) including the incidence of infection, symptomatic fraction, and to assess household transmission. PARTICIPANTS: We enrolled 1684 individuals in 327 randomly selected households in a rural and an urban site over three consecutive influenza and two RSV seasons. A new cohort of households was enrolled each year. Participants were sampled with nasopharyngeal swabs twice-weekly during the RSV and influenza seasons of the year of enrolment. Serology samples were collected at enrolment and before and after the influenza season annually. FINDINGS TO DATE: There were 122 113 potential individual follow-up visits over the 3 years, and participants were interviewed for 105 783 (87%) of these. Out of 105 683 nasopharyngeal swabs, 1258 (1%) and 1026 (1%) tested positive on polymerase chain reaction (PCR) for influenza viruses and RSV, respectively. Over one third of individuals had PCR-confirmed influenza each year. Overall, there was influenza transmission to 10% of household contacts of an index case. FUTURE PLANS: Future planned analyses include analysis of influenza serology results and RSV burden and transmission. Households enrolled in the PHIRST study during 2016-2018 were eligible for inclusion in a study of SARS-CoV-2 transmission initiated in July 2020. This study uses similar testing frequency to assess the community burden of SARS-CoV-2 infection and the role of asymptomatic infection in virus transmission.


Assuntos
COVID-19 , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Estudos de Coortes , Humanos , Influenza Humana/epidemiologia , Estudos Prospectivos , Infecções por Vírus Respiratório Sincicial/epidemiologia , SARS-CoV-2 , África do Sul/epidemiologia
4.
Lancet Glob Health ; 9(8): e1077-e1087, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34166626

RESUMO

BACKGROUND: Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0-5 months, 6-11 months, and 12-59 months of age. METHODS: We did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case-fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570). FINDINGS: 203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8-28·9) ALRI cases, 725 000 (433 000-1 260 000) ALRI hospital admissions, and 34 400 (16 400-73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0-5 months and 26% for 6-11 months) of the hospital admissions and 66% (42% for infants aged 0-5 months and 24% for 6-11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46-65% for the adjustment for health-care use, 59-77% for patient groups excluded, 54-93% for case definition, 42-93% for sampling strategy, and 67-77% for test methods. Heterogeneity in estimates was found between studies for each outcome. INTERPRETATION: We report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4-14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions. FUNDING: Bill & Melinda Gates Foundation.


Assuntos
Saúde Global/estatística & dados numéricos , Infecções por Paramyxoviridae/complicações , Paramyxovirinae/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Pré-Escolar , Humanos , Lactente , Recém-Nascido
5.
Lancet Glob Health ; 9(6): e863-e874, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34019838

RESUMO

BACKGROUND: Data on influenza community burden and transmission are important to plan interventions especially in resource-limited settings. However, data are limited, particularly from low-income and middle-income countries. We aimed to evaluate the community burden and transmission of influenza in a rural and an urban setting in South Africa. METHODS: In this prospective cohort study approximately 50 households were selected sequentially from both a rural setting (Agincourt, Mpumalanga Province, South Africa; with a health and sociodemographic surveillance system) and an urban setting (Klerksdorp, Northwest Province, South Africa; using global positioning system data), enrolled, and followed up for 10 months in 2017 and 2018. Different households were enrolled in each year. Households of more than two individuals in which 80% or more of the occupants agreed to participate were included in the study. Nasopharyngeal swabs were collected twice per week from participating household members irrespective of symptoms and tested for influenza using real-time RT-PCR. The primary outcome was the incidence of influenza infection, defined as the number of real-time RT-PCR-positive episodes divided by the person-time under observation. Household cumulative infection risk (HCIR) was defined as the number of subsequent infections within a household following influenza introduction. FINDINGS: 81 430 nasopharyngeal samples were collected from 1116 participants in 225 households (follow-up rate 88%). 917 (1%) tested positive for influenza; 178 (79%) of 225 households had one or more influenza-positive individual. The incidence of influenza infection was 43·6 (95% CI 39·8-47·7) per 100 person-seasons. 69 (17%) of 408 individuals who had one influenza infection had a repeat influenza infection during the same season. The incidence (67·4 per 100 person-seasons) and proportion with repeat infections (22 [23%] of 97 children) were highest in children younger than 5 years and decreased with increasing age (p<0·0001). Overall, 268 (56%) of 478 infections were symptomatic and 66 (14%) of 478 infections were medically attended. The overall HCIR was 10% (109 of 1088 exposed household members infected [95% CI 9-13%). Transmission (HCIR) from index cases was highest in participants aged 1-4 years (16%; 40 of 252 exposed household members) and individuals with two or more symptoms (17%; 68 of 396 exposed household members). Individuals with asymptomatic influenza transmitted infection to 29 (6%) of 509 household contacts. HIV infection, affecting 167 (16%) of 1075 individuals, was not associated with increased incidence or HCIR. INTERPRETATION: Approximately half of influenza infections were symptomatic, with asymptomatic individuals transmitting influenza to 6% of household contacts. This suggests that strategies, such as quarantine and isolation, might be ineffective to control influenza. Vaccination of children, with the aim of reducing influenza transmission might be effective in African settings given the young population and high influenza burden. FUNDING: US Centers for Disease Control and Prevention.


Assuntos
Infecções Assintomáticas/epidemiologia , Influenza Humana/epidemiologia , Influenza Humana/transmissão , Saúde da População Rural/estatística & dados numéricos , Saúde da População Urbana/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estações do Ano , África do Sul/epidemiologia , Adulto Jovem
6.
Clin Infect Dis ; 73(3): e745-e753, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-33530100

RESUMO

BACKGROUND: Policy recommendations on pertussis vaccination need to be guided by data, which are limited from low- and middle-income countries. We aimed to describe the epidemiology of pertussis in South Africa, a country with high human immunodeficiency virus (HIV) prevalence and routine pertussis vaccination for 6 decades including the acellular vaccine since 2009. METHODS: Hospitalized patients of all ages were enrolled at 5 sentinel sites as part of a pneumonia surveillance program from January 2013 through December 2018. Nasopharyngeal specimens and induced sputum were tested by polymerase chain reaction (PCR) for Bordetella pertussis. In addition, demographic and clinical information were collected. Incidence rates were calculated for 2013-2016, and multivariable logistic regression performed to identify factors associated with pertussis. RESULTS: Over the 6-year period 19 429 individuals were enrolled, of which 239 (1.2%) tested positive for B. pertussis. Detection rate was highest in infants aged <6 months (2.8%, 155/5524). Mean annual incidence was 17 cases per 100 000 population, with the highest incidence in children <1 year of age (228 per 100 000). Age-adjusted incidence was 65.9 per 100 000 in HIV-infected individuals compared to 8.5 per 100 000 in HIV-uninfected individuals (risk ratio 30.4, 95% confidence interval: 23.0-40.2). Ten individuals (4.2%) with pertussis died; of which 7 were infants aged <6 months and 3 were immunocompromised adults. CONCLUSIONS: Pertussis continues to be a significant cause of illness and hospitalization in South Africa, despite routine vaccination. The highest burden of disease and death occurred in infants; however, HIV-infected adults were also identified as an important group at risk of B. pertussis infection.


Assuntos
Coqueluche , Adulto , Bordetella pertussis , Criança , Humanos , Incidência , Lactente , Vacina contra Coqueluche , África do Sul/epidemiologia , Coqueluche/epidemiologia
7.
Influenza Other Respir Viruses ; 15(4): 446-456, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33452708

RESUMO

BACKGROUND: There are conflicting data concerning the impact of antenatal influenza vaccination on birth outcomes including low birthweight (LBW), preterm birth, small for gestational age (SGA), and stillbirth. METHODS: We conducted a retrospective observational cohort study of infants born to women residing in Mitchells Plain, Cape Town. Infants were born at 4 health facilities during May 28 - December 31, 2015 and April 15 - December 31, 2016. We performed crude and multivariable logistic regression, propensity score (PS) matching logistic regression, and inverse probability of treatment weighted (IPTW) regression to assess vaccine effectiveness (VE) against LBW, preterm birth, SGA, and stillbirth adjusting for measured confounders. RESULTS: Maternal vaccination status, antenatal history, and ≥1 birth outcome(s) were available for 4084/5333 (76.6%) pregnancies, 2109 (51.6%) vaccinated, and 1975 (48.4%) unvaccinated. The proportion LBW was lower in vaccinated (6.9%) vs. unvaccinated (12.5%) in multivariable [VE 0.27 (95% CI 0.07-0.42)], PS [VE 0.30 (95% CI 0.09-0.51)], and IPTW [VE 0.24 (95% CI 0.04-0.45)]. Preterm birth was less frequent in vaccinated (8.6%) than unvaccinated (16.4%) in multivariable [VE 0.26 (0.09-0.40)], PS [VE 0.25 (95% CI 0.09-0.41)], and IPTW [VE 0.34 (95% CI 0.18-0.51)]. The proportion SGA was lower in vaccinated (6.0%) than unvaccinated (8.8%) but not in adjusted models. There were few stillbirths in our study population, 30/4084 (0.7%). CONCLUSIONS: Using multiple analytic approaches, we found that influenza vaccination was associated with lower prevalence of LBW (24-30%) and preterm birth (25-34%) in Cape Town during 2015-2016.


Assuntos
Vacinas contra Influenza , Influenza Humana , Nascimento Prematuro , Feminino , Humanos , Lactente , Recém-Nascido , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controle , Estudos Retrospectivos , África do Sul/epidemiologia , Vacinação
8.
Lancet Glob Health ; 9(1): e33-e43, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33248481

RESUMO

BACKGROUND: Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years. METHODS: We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus-associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths. FINDINGS: In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries. INTERPRETATION: Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries. FUNDING: Bill & Melinda Gates Foundation.


Assuntos
Efeitos Psicossociais da Doença , Saúde Global/estatística & dados numéricos , Infecções por Paramyxoviridae/epidemiologia , Infecções Respiratórias/epidemiologia , Doença Aguda , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Metapneumovirus
9.
Vaccine ; 38(45): 7007-7014, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-32980198

RESUMO

BACKGROUND: Data on influenza economic burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource-limited settings. However, this information is limited in low- and middle-income countries. METHODS: We estimated the cost (from a health system and societal perspective) and years of life lost (YLL) for influenza-associated illness in South Africa during 2013-2015 among (i) children aged 6-59 months, (ii) individuals aged 5-64 years with HIV, pulmonary tuberculosis (PTB) and selected underlying medical conditions (UMC), separately, (iii) pregnant women and (iv) individuals aged ≥65 years, using publicly available data and data collected through laboratory-confirmed influenza surveillance and costing studies. All costs were expressed in 2015 prices using the South Africa all-items Consumer Price Index. RESULTS: During 2013-2015, the mean annual cost of influenza-associated illness among the selected risk groups accounted for 52.1% ($140.9/$270.5 million) of the total influenza-associated illness cost (for the entire population of South Africa), 45.2% ($52.2/$115.5 million) of non-medically attended illness costs, 43.3% ($46.7/$107.9 million) of medically-attended mild illness costs and 89.3% ($42.0/$47.1 million) of medically-attended severe illness costs. The YLL among the selected risk groups accounted for 86.0% (262,069 /304,867 years) of the total YLL due to influenza-associated death. CONCLUSION: In South Africa, individuals in risk groups for severe influenza accounted for approximately half of the total influenza-associated illness cost but most of the cost of influenza-associated medically attended severe illness and YLL. This study provides the foundation for future studies on the cost-effectiveness of influenza immunization among risk groups.


Assuntos
Efeitos Psicossociais da Doença , Influenza Humana , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise Custo-Benefício , Feminino , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pessoa de Meia-Idade , Gravidez , África do Sul/epidemiologia , Vacinação , Adulto Jovem
10.
Vaccine ; 38(27): 4288-4297, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32389494

RESUMO

BACKGROUND: Data on influenza burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource limited settings. However, this information is limited overall and in particular in low- and middle-income countries. We sought to assess the mean annual national burden of medically and non-medically attended influenza-associated mild, severe-non-fatal and fatal illness among potential target groups for influenza immunization in South Africa during 2013-2015. METHODS: We used published mean national annual estimates of mild, severe-non-fatal, and fatal influenza-associated illness in South Africa during 2013-2015 and estimated the number of such illnesses occurring among the following risk groups: (i) children aged 6-59 months; (ii) individuals aged 5-64 years with HIV, and/or pulmonary tuberculosis (PTB), and/or selected underlying medical conditions (UMC); (iii) pregnant women; and (iv) individuals aged ≥65 years. We also estimated the number of individuals among the same risk groups in the population. RESULTS: During 2013-2015, individuals in the selected risk groups accounted for 45.3% (24,569,328/54,086,144) of the population and 43.5% (4,614,763/10,598,138), 86.8% (111,245/128,173) and 94.5% (10,903/11,536) of the mean annual estimated number of influenza-associated mild, severe-non-fatal and fatal illness episodes, respectively. The rates of influenza-associated illness were highest in children aged 6-59 months (23,983 per 100,000 population) for mild illness, in pregnant women (930 per 100,000 population) for severe-non-fatal illness and in individuals aged ≥65 years (138 per 100,000 population) for fatal illness. CONCLUSION: Influenza immunization of the selected risk groups has the potential to prevent a substantial number of influenza-associated severe illness. Nonetheless, because of the high number of individuals at risk, South Africa, due to financial resources constrains, may need to further prioritize interventions among risk populations. Cost-burden and cost-effectiveness estimates may assist with further prioritization.


Assuntos
Influenza Humana , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Feminino , Humanos , Lactente , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pessoa de Meia-Idade , Gravidez , África do Sul/epidemiologia , Vacinação , Adulto Jovem
11.
Lancet Glob Health ; 8(4): e497-e510, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32087815

RESUMO

BACKGROUND: Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018. METHODS: We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and population-based childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries. FINDINGS: In 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1-190·6), 10·1 million influenza-virus-associated ALRI cases (6·8-15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 in-hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries. INTERPRETATION: A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries. FUNDING: WHO; Bill & Melinda Gates Foundation.


Assuntos
Saúde Global/estatística & dados numéricos , Influenza Humana/complicações , Infecções Respiratórias/epidemiologia , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Estações do Ano
12.
Vaccine ; 37(46): 6874-6884, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31575494

RESUMO

BACKGROUND: Pregnant women and infants are at increased risk of severe disease from influenza. Antenatal influenza vaccination is safe and can reduce the risk of illness for women and their infants. We evaluated for South Africa the health effects of antenatal influenza vaccination among pregnant women and their infants aged <6 months old and assessed its cost-effectiveness. METHODS: We constructed a decision tree model to simulate the population of pregnant women and infants aged <6 months in South Africa using TreeAge Pro Suite 2015. The model evaluated the change in societal costs and outcomes associated with a vaccination campaign that prioritized HIV-infected over HIV-uninfected pregnant women compared with no vaccination. We also examined the impacts of a campaign without prioritization. Upper and lower 90% uncertainty intervals (90% UI) were generated using probabilistic sensitivity analysis on 10000 Monte Carlo simulations. The cost-effectiveness threshold was set to the 2015 per capita gross domestic product of South Africa, US$5724. RESULTS: Antenatal vaccination with prioritization averted 9070 (90% UI: 7407-11217) total cases of influenza among pregnant women and infants, including 411 (90% UI: 305-546) hospitalizations and 30 (90% UI: 22-40) deaths. This corresponds to an averted fraction of 13.5% (90% UI: 9.0-20.5%). Vaccinating without prioritization averted 7801 (90% UI: 6465-9527) cases of influenza, including 335 (90% UI: 254-440) hospitalizations and 24 (90% UI: 18-31) deaths. This corresponds to an averted fraction of 11.6% (90% UI: 7.8-17.4%). Vaccinating the cohort of pregnant women with prioritization had societal cost of $4689 (90% UI: $3128-$7294) per Quality Adjusted Life Year (QALY) gained while vaccinating without prioritization had a cost of $5924 (90% UI: $3992-$9056) per QALY. CONCLUSIONS: Antenatal influenza vaccination campaigns in South Africa would reduce the impact of influenza and could be cost-effective.


Assuntos
Influenza Humana/prevenção & controle , Análise Custo-Benefício , Feminino , Infecções por HIV/imunologia , Humanos , Recém-Nascido , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Masculino , Método de Monte Carlo , Gravidez , África do Sul/epidemiologia , Vacinação/estatística & dados numéricos
13.
PLoS One ; 14(9): e0222294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31536552

RESUMO

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.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/complicações , Influenza Humana/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Coinfecção/diagnóstico , Coinfecção/virologia , Tosse/etiologia , Feminino , Febre/etiologia , Infecções por HIV/epidemiologia , Humanos , Lactente , Influenza Humana/diagnóstico , Influenza Humana/etiologia , Masculino , Vigilância da População/métodos , Estudos Prospectivos , África do Sul/epidemiologia
14.
Influenza Other Respir Viruses ; 13(5): 484-495, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31187609

RESUMO

BACKGROUND: Economic burden estimates are essential to guide policy-making for influenza vaccination, especially in resource-limited settings. METHODS: We estimated the cost, absenteeism, and years of life lost (YLL) of medically and non-medically attended influenza-associated mild and severe respiratory, circulatory and non-respiratory/non-circulatory illness in South Africa during 2013-2015 using a modified version of the World Health Organization (WHO) worksheet based tool for estimating the economic burden of seasonal influenza. Additionally, we restricted the analysis to influenza-associated severe acute respiratory illness (SARI) and influenza-like illness (ILI; subsets of all-respiratory illnesses) as suggested in the WHO manual. RESULTS: The estimated mean annual cost of influenza-associated illness was $270.5 million, of which $111.3 million (41%) were government-incurred costs, 40.7 million (15%) were out-of-pocket expenses, and $118.4 million (44%) were indirect costs. The cost of influenza-associated medically attended mild illness ($107.9 million) was 2.3 times higher than that of severe illness ($47.1 million). Influenza-associated respiratory illness costs ($251.4 million) accounted for 93% of the total cost. Estimated absenteeism and YLL were 13.2 million days and 304 867 years, respectively. Among patients with influenza-associated WHO-defined ILI or SARI, the costs ($95.3 million), absenteeism (4.5 million days), and YLL (65 697) were 35%, 34%, and 21% of the total economic and health burden of influenza. CONCLUSION: The economic burden of influenza-associated illness was substantial from both a government and a societal perspective. Models that limit estimates to those obtained from patients with WHO-defined ILI or SARI substantially underestimated the total economic and health burden of influenza-associated illness.


Assuntos
Absenteísmo , Efeitos Psicossociais da Doença , Hospitalização/economia , Influenza Humana/economia , Expectativa de Vida , Hospitalização/estatística & dados numéricos , Humanos , Vacinas contra Influenza/administração & dosagem , Influenza Humana/complicações , Influenza Humana/epidemiologia , Estações do Ano , Vigilância de Evento Sentinela , África do Sul/epidemiologia , Vacinação/legislação & jurisprudência
15.
Clin Infect Dis ; 69(12): 2208-2211, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30963178

RESUMO

From 2011 through 2016, we conducted surveillance for severe respiratory illness in infants. Human immunodeficiency virus exposure significantly increased the risk of respiratory syncytial virus (RSV)-associated hospitalization in infants aged <5 months. More than 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.


Assuntos
Coinfecção , Infecções por HIV/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano , Feminino , Infecções por HIV/virologia , História do Século XXI , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/história , Índice de Gravidade de Doença , África do Sul/epidemiologia
16.
Open Forum Infect Dis ; 6(3): ofz020, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30906797

RESUMO

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.

17.
Influenza Other Respir Viruses ; 13(1): 54-63, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30218485

RESUMO

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.


Assuntos
Farmacorresistência Viral/genética , Inibidores Enzimáticos/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza B/efeitos dos fármacos , Substituição de Aminoácidos , Humanos , Vírus da Influenza A Subtipo H1N1/enzimologia , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/virologia , Concentração Inibidora 50 , Neuraminidase/antagonistas & inibidores , Oseltamivir/uso terapêutico , Fenótipo , Estações do Ano , Vigilância de Evento Sentinela , África do Sul , Proteínas Virais/antagonistas & inibidores , Zanamivir/uso terapêutico
18.
Clin Infect Dis ; 68(5): 773-780, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29961814

RESUMO

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.


Assuntos
Infecções por HIV/complicações , Influenza Humana/complicações , Infecções por Vírus Respiratório Sincicial/complicações , Pré-Escolar , Coinfecção , Infecções por HIV/epidemiologia , Hospitalização , Humanos , Lactente , Influenza Humana/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Fatores de Risco , Estações do Ano , África do Sul/epidemiologia , Fatores de Tempo
19.
Vaccine ; 37(1): 25-33, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30471956

RESUMO

BACKGROUND: Due to competing health priorities, low- and middle-income countries (LMIC) may need to prioritize between different influenza vaccine risk groups. Risk group prioritization may differ in LMIC based upon programmatic feasibility, country-specific prevalence of risk conditions and influenza-associated morbidity and mortality. METHODS: In South Africa, we collected local disease burden data (both published and unpublished) and published vaccine efficacy data in risk groups and healthy adults. We used these data to aid policy makers with risk group prioritization for influenza vaccination. We used the following formula to assess potential vaccine averted disease in each risk group: rate of influenza-associated hospitalization (or death) per 100,000 population * influenza vaccine efficacy (VE). We further estimated the cost per hospital day averted and the cost per year of life saved by influenza vaccination. RESULTS: Pregnant women, HIV-infected adults, and adults and children with tuberculosis disease had among the highest estimates of hospitalizations averted per 100,000 vaccinated and adults aged 65 years and older had the highest estimated deaths averted per 100,000 vaccinated. However, when assessing both the cost per hospital day averted (range: USD148-1,344) and the cost per year of life saved (range: USD112-1,230); adults and children with TB disease, HIV-infected adults and pregnant women had the lowest cost per outcome averted. DISCUSSION: An assessment of the potential disease outcomes averted and associated costs may aid policymakers in risk group prioritization for influenza vaccination.


Assuntos
Prioridades em Saúde , Recursos em Saúde , Vacinas contra Influenza/economia , Influenza Humana/prevenção & controle , Vacinação/economia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Feminino , Infecções por HIV/epidemiologia , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Vacinas contra Influenza/uso terapêutico , Influenza Humana/mortalidade , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , África do Sul , Tuberculose/epidemiologia , Adulto Jovem
20.
J Infect Dis ; 219(10): 1605-1615, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30541140

RESUMO

BACKGROUND: We estimated the household secondary infection risk (SIR) and serial interval (SI) for influenza transmission from HIV-infected and HIV-uninfected index cases. 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 4 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% confidence interval [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.


Assuntos
Infecções por HIV/complicações , Influenza Humana/epidemiologia , Influenza Humana/transmissão , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Características da Família , Feminino , Infecções por HIV/epidemiologia , Humanos , Lactente , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Fatores de Risco , África do Sul/epidemiologia , Adulto Jovem
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