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1.
Artigo em Inglês | MEDLINE | ID: mdl-34796674

RESUMO

INTRODUCTION: We describe epidemiology and outcomes of confirmed SARS-CoV-2 infection and positive admissions among children <18 years in South Africa, an upper-middle income setting with high inequality. METHODS: Laboratory and hospital COVID-19 surveillance data, 28 January - 19 September 2020 was used. Testing rates were calculated as number of tested for SARS-CoV-2 divided by population at risk; test positivity rates were calculated as positive tests divided by total number of tests. In-hospital case fatality ratio (CFR) was calculated based on hospitalized positive admissions with outcome data who died in-hospital and whose death was judged SARS-CoV-2 related by attending physician. FINDINGS: 315 570 children aged <18 years were tested for SARS-CoV-2; representing 8.9% of all 3 548 738 tests and 1.6% of all children in the country. Of children tested, 46 137 (14.6%) were positive. Children made up 2.9% (n = 2007) of all SARS-CoV-2 positive admissions to sentinel hospitals. Among children, 47 died (2.6% case-fatality). In-hospital deaths were associated with male sex [adjusted odds ratio (aOR) 2.18 (95% confidence intervals [CI] 1.08-4.40)] vs female; age <1 year [aOR 4.11 (95% CI 1.08-15.54)], age 10-14 years [aOR 4.20 (95% CI1.07-16.44)], age 15-17 years [aOR 4.86 (95% 1.28-18.51)] vs age 1-4 years; admission to a public hospital [aOR 5.07(95% 2.01-12.76)] vs private hospital and ≥1 underlying conditions [aOR 12.09 (95% CI 4.19-34.89)] vs none. CONCLUSIONS: Children with underlying conditions were at greater risk of severe SARS-CoV-2 outcomes. Children > 10 years, those in certain provinces and those with underlying conditions should be considered for increased testing and vaccination.

2.
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.

3.
Health Sci Rep ; 4(3): e367, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34557595

RESUMO

Background: A group of Victoria lineage influenza B viruses with a two amino acid deletion in the hemagglutinin (HA) at residues K162 and N163, was detected during the 2016 to 2017 Northern Hemisphere influenza season and continues to spread geographically. We describe the first identification of viruses with these deletions from South Africa in 2018. Methods: Nasopharyngeal samples were obtained from the syndromic surveillance programs. Real-time reverse transcription-polymerase chain reaction was used for virus detection and lineage determination. Influenza genetic characterization was done using next-generation sequencing on the MiSeq platform. The duration of virus circulation was determined using thresholds calculated using the Moving Epidemic Method; duration was used as an indicator of disease transmissibility and impact. Results: In 2018, 42% (426/1015) of influenza-positive specimens were influenza B viruses. Of 426 influenza B-positive samples, 376 (88%) had the lineage determined of which 75% (283/376) were Victoria lineage. The transmissibility of the 2018 South African influenza season was high for a few weeks, although the severity remained moderate through most of the season. The sequenced 2018 South African Victoria lineage influenza B viruses clustered in sub-clade V1A.1 with the 162-163 deletions. Conclusions: We report the first detection of the 162-163 deletion variant of influenza B/Victoria viruses from South Africa in 2018, and suggest that this deletion variant replaced the previous circulating influenza B/Victoria viruses. These deletions putatively affect the antigenic properties of the viruses because they border an immune-dominant region at the tip of the HA. Therefore, close monitoring of these newly emerging viruses is essential.

4.
Emerg Infect Dis ; 27(12): 3020-3029, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34477548

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections may be underestimated because of limited access to testing. We measured SARS-CoV-2 seroprevalence in South Africa every 2 months during July 2020-March 2021 in randomly selected household cohorts in 2 communities. We compared seroprevalence to reported laboratory-confirmed infections, hospitalizations, and deaths to calculate infection-case, infection-hospitalization, and infection-fatality ratios in 2 waves of infection. Post-second wave seroprevalence ranged from 18% in the rural community children <5 years of age, to 59% in urban community adults 35-59 years of age. The second wave saw a shift in age distribution of case-patients in the urban community (from persons 35-59 years of age to persons at the extremes of age), higher attack rates in the rural community, and a higher infection-fatality ratio in the urban community. Approximately 95% of SARS-CoV-2 infections were not reported to national surveillance.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Criança , Humanos , Pessoa de Meia-Idade , População Rural , Estudos Soroepidemiológicos , África do Sul/epidemiologia
5.
EClinicalMedicine ; 39: 101072, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34405139

RESUMO

Background: We describe the epidemiology of COVID-19 in South Africa following importation and during implementation of stringent lockdown measures. Methods: Using national surveillance data including demographics, laboratory test data, clinical presentation, risk exposures (travel history, contacts and occupation) and outcomes of persons undergoing COVID-19 testing or hospitalised with COVID-19 at sentinel surveillance sites, we generated and interpreted descriptive statistics, epidemic curves, and initial reproductive numbers (Rt). Findings: From 4 March to 30 April 2020, 271,670 SARS-CoV-2 PCR tests were performed (462 tests/100,000 persons). Of these, 7,892 (2.9%) persons tested positive (median age 37 years (interquartile range 28-49 years), 4,568 (58%) male, cumulative incidence of 13.4 cases/100,000 persons). Hospitalization records were found for 1,271 patients (692 females (54%)) of whom 186 (14.6%) died. Amongst 2,819 cases with data, 489/2819 (17.3%) travelled internationally within 14 days prior to diagnosis, mostly during March 2020 (466 (95%)). Cases diagnosed in April compared with March were younger (median age, 37 vs. 40 years), less likely female (38% vs. 53%) and resident in a more populous province (98% vs. 91%). The national initial Rt was 2.08 (95% confidence interval (CI): 1.71-2.51). Interpretation: The first eight weeks following COVID-19 importation were characterised by early predominance of imported cases and relatively low mortality and transmission rates. Despite stringent lockdown measures, the second month following importation was characterised by community transmission and increasing disease burden in more populous provinces.

6.
PLoS One ; 16(8): e0255941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34383824

RESUMO

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.

7.
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
8.
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
9.
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
10.
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
11.
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
12.
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
13.
Microb Genom ; 5(10)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31617841

RESUMO

Most pneumococci express a polysaccharide capsule, a key virulence factor and target for pneumococcal vaccines. However, pneumococci showing no serological evidence of capsule expression [nontypeable pneumococci (NTPn)] are more frequently isolated from carriage studies than in invasive disease. Limited data exist about the population structure of carriage NTPn from the African continent. We aimed to characterize carriage NTPn and compare them to previously described invasive NTPn. Carriage and invasive NTPn isolates were obtained from South African cross-sectional studies (2009 and 2012) and laboratory-based surveillance for invasive pneumococcal disease (2003-2013), respectively. Isolates were characterized by capsular locus sequence analysis, multilocus sequence typing, antimicrobial non-susceptibility patterns and phylogenetic analysis. NTPn represented 3.7 % (137/3721) of carriage isolates compared to 0.1 % (39/32 824) of invasive isolates (P<0.001), and 24 % (33/137) of individuals were co-colonized with encapsulated pneumococci. Non-susceptibility to cotrimoxazole [84 % (112/133) vs 44 % (17/39)], penicillin [77 % (102/133) vs 36 % (14/39)], erythromycin [53 % (70/133) vs 31 % (12/39)] and clindamycin [36 % (48/133) vs 18 % (7/39)] was higher (P=0.03) among carriage than invasive NTPn. Ninety-one per cent (124/137) of carriage NTPn had complete deletion of the capsular locus and 9 % (13/137) had capsule genes, compared to 44 % (17/39) and 56 % (22/39) of invasive NTPn, respectively. Carriage NTPn were slightly less diverse [Simpson's diversity index (D)=0.92] compared to invasive NTPn [D=0.97]. Sixty-seven per cent (92/137) of carriage NTPn belonged to a lineage exclusive to NTPn strains compared to 23 % (9/39) of invasive NTPn. We identified 293 and 275 genes that were significantly associated with carriage and invasive NTPn, respectively. NTPn isolates detected in carriage differed from those causing invasive disease, which may explain their success in colonisation or in causing invasive disease.


Assuntos
Portador Sadio/microbiologia , Farmacorresistência Bacteriana/genética , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae , Fatores de Virulência/genética , Proteínas de Bactérias/genética , Portador Sadio/epidemiologia , Estudos Transversais , Genômica , Humanos , Filogenia , Infecções Pneumocócicas/epidemiologia , Sorotipagem , África do Sul/epidemiologia , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação
14.
Methods Enzymol ; 626: 375-406, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31606083

RESUMO

Tyrosine kinases are important for many cellular processes and disruption of their regulation is a factor in diseases like cancer, therefore they are a major target of anticancer drugs. There are many ways to measure tyrosine kinase activity in cells by monitoring endogenous substrate phosphorylation, or by using peptide substrates and incubating them with cell lysates containing active kinases. However, most of these strategies rely on antibodies and/or are limited in how accurately they model the intracellular environment. In cases in which activity needs to be measured in cells, but endogenous substrates are not known and/or suitable phosphospecific antibodies are not available, cell-deliverable peptide substrates can be an alternative and can provide information on activation and inhibition of kinases in intact, live cells. In this chapter, we review this methodology and provide a protocol for measuring Abl kinase activity in human cells using enzyme-linked immunosorbent assay (ELISA) with a generic antiphosphotyrosine antibody for detection.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Tirosina/metabolismo , Humanos , Células K562 , Fosforilação , Proteínas Proto-Oncogênicas c-abl/metabolismo , Especificidade por Substrato
15.
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
16.
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
17.
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
18.
PLoS One ; 14(4): e0214077, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30970036

RESUMO

BACKGROUND: Globally, over 400,000 neonatal deaths in 2015 were attributed to sepsis, however, the incidence and etiologies of these infections are largely unknown in low-middle income countries. We aimed to determine incidence and etiology of community-acquired early-onset (<72 hours age) sepsis (EOS) using culture and molecular diagnostics. METHODS: This was a prospective observational study, in which we conducted a surveillance for pathogens using a combination of blood culture and a polymerase chain reaction (PCR)-based test. Blood culture was performed on all neonates with suspected EOS. Among the subset fulfilling criteria for protocol-defined EOS, blood and nasopharyngeal (NP) respiratory swabs were tested by quantitative real-time reverse-transcriptase PCR using a Taqman Array Card (TAC) with 15 bacterial and 12 viral targets. Blood and NP samples from 312 healthy newborns were also tested by TAC to estimate background positivity rates. We used variant latent-class methods to attribute etiologies and calculate pathogen-specific proportions and incidence rates. RESULTS: We enrolled 2,624 neonates with suspected EOS and from these 1,231 newborns met criteria for protocol-defined EOS (incidence- 39.3/1,000 live-births). Using the partially latent-class modelling, only 26.7% cases with protocol-defined EOS had attributable etiology, and the largest pathogen proportion were Ureaplasma spp. (5.4%; 95%CI: 3.6-8.0) and group B Streptococcus (GBS) (4.8%; 95%CI: 4.1-5.8), and no etiology was attributable for 73.3% of cases. Blood cultures were positive in 99/1,231 (8.0%) with protocol-defined EOS (incidence- 3.2/1,000 live-births). Leading pathogens on blood culture included GBS (35%) and viridans streptococci (24%). Ureaplasma spp. was the most common organism identified on TAC among cases with protocol-defined EOS. CONCLUSION: Using a combination of blood culture and a PCR-based test the common pathogens isolated in neonates with sepsis were Ureaplasma spp. and GBS. Despite documenting higher rates of protocol-defined EOS and using a combination of tests, the etiology for EOS remains elusive.


Assuntos
Sepse Neonatal/sangue , Complicações Infecciosas na Gravidez/sangue , Infecções Estreptocócicas/sangue , Streptococcus agalactiae/isolamento & purificação , Idade de Início , Hemocultura , Feminino , Humanos , Recém-Nascido , Sepse Neonatal/epidemiologia , Sepse Neonatal/microbiologia , Sepse Neonatal/patologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/patologia , África do Sul , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/patologia , Streptococcus agalactiae/genética , Streptococcus agalactiae/patogenicidade , Ureaplasma/isolamento & purificação , Ureaplasma/patogenicidade
19.
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.

20.
BMC Infect Dis ; 19(1): 276, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30898099

RESUMO

BACKGROUND: We assessed the utility of a multi-target, real-time PCR assay for Bordetella pertussis detection and diagnosis in patients with severe respiratory illness (SRI), influenza-like illness (ILI), and asymptomatic controls. METHODS: Real-time PCR detection of IS481, pIS1001, hIS1001 and ptxS1 was performed on nasopharyngeal specimens (SRI, ILI and controls) and induced sputum (SRI) collected from June 2012 to May 2016 through respiratory illness surveillance. Using PCR cycle threshold (Ct) value cut-offs, IS481 positive cases were classified as confirmed (Ct < 35) or possible (Ct 35-39) pertussis disease. RESULTS: Among 12,922 samples, 146 (1.1%) were IS481 positive of which 62% (90/146) were classified as confirmed. The attributable fraction (AF) was 92.2% (95% CI, 65.6 to 98.2%) and 90.5% (95% CI, 57.5 to 97.9%) amongst SRI and ILI PCR-confirmed pertussis cases, respectively. Amongst possible pertussis cases, AF was 36.9% (95% CI, - 142.3 to 83.6%) and 67.5% (95% CI, - 30.6 to 91.9%) in the SRI and ILI groups, respectively. CONCLUSION: All IS481 positive specimens could be considered as B. pertussis infection, and potentially pertussis disease with supportive clinical information.


Assuntos
Bordetella pertussis/genética , Tipagem Molecular , Coqueluche/diagnóstico , Diagnóstico Diferencial , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , África do Sul , Coqueluche/epidemiologia , Coqueluche/microbiologia
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