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1.
Sci Rep ; 11(1): 19920, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620928

RESUMO

Streptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determines the serotype and influences disease severity but the mechanism is largely unknown. Due to evidence of elevated cytokines levels in the meningeal inflammatory response, we measured 41 cytokines/chemokines and growth factors in cerebrospinal fluid (CSF) samples from 57 South African meningitis patients (collected in the period 2018-2019), with confirmed S. pneumoniae serotypes, using a multiplexed bead-based immunoassay. Based on multivariable Bayesian regression, using serotype 10A as a reference and after adjusting for HIV and age, we found IL-6 concentrations significantly lower in patients infected with serotypes 6D (undetectable) and 23A (1601 pg/ml), IL-8 concentrations significantly higher in those infected with 22A (40,459 pg/ml), 7F (32,400 pg/ml) and 15B/C (6845 pg/ml), and TNFα concentration significantly higher in those infected with serotype 18A (33,097 pg/ml). Although a relatively small number of clinical samples were available for this study and 28% of samples could not be assigned to a definitive serotype, our data suggests 15B/C worthy of monitoring during surveillance as it is associated with in-hospital case fatality and not included in the 13-valent polysaccharide conjugate vaccine, PCV13. Our data provides average CSF concentrations of a range of cytokines and growth factors for 18 different serotypes (14, 19F, 3, 6A, 7F, 19A, 8, 9N, 10A, 12F, 15B/C, 22F, 16F, 23A, 31, 18A, 6D, 22A) to serve as a basis for future studies investigating host-pathogen interaction during pneumococcal meningitis. We note that differences in induction of IL-8 between serotypes may be particularly worthy of future study.

2.
BMC Health Serv Res ; 21(1): 941, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503508

RESUMO

INTRODUCTION: Despite prioritization, routine antenatal influenza vaccine coverage is < 16% in South Africa. We aimed to describe maternal influenza vaccine coverage in 27 antenatal clinics (ANCs) in Gauteng and Western Cape (WC) Provinces, where in collaboration with the Department of Health (DoH), we augmented the annual influenza vaccination programme among pregnant women. METHODS: From 2015 through 2018, 40,230 additional doses of influenza vaccine were added to the available stock and administered as part of routine antenatal care. Educational talks were given daily and data were collected on women attending ANCs. We compared characteristics of vaccinated and unvaccinated women using multivariable logistic regression. RESULTS: We screened 62,979 pregnant women during the period when Southern Hemisphere influenza vaccines were available (27,068 in Gauteng and 35,911 in WC). Vaccine coverage at the targeted clinics was 78.7% (49,355/62682), although pregnant women in WC were more likely to be vaccinated compared to those in the Gauteng (Odds ratio (OR) =3.7 p < 0.001). Women aged 25-29 and > 35 years were less likely to be vaccinated than women aged 18-24 years (OR = 0.9 p = 0.053; OR = 0.9 p < 0.001). HIV positive status was not associated with vaccination (OR = 1.0 p = 0.266). Reasons for not vaccinating included: vaccine stock-outs where ANCs depleted available stock of vaccines and/or were awaiting delivery of vaccines (54.6%, 6949/12723), refusal/indecision (25.8%, 3285), and current illness that contraindicated vaccination (19.6%, 2489). CONCLUSION: Antenatal vaccination uptake was likely improved by the increased vaccine supply and vaccine education offered during our campaign.


Assuntos
Vacinas contra Influenza , Influenza Humana , Complicações Infecciosas na Gravidez , Feminino , Humanos , Programas de Imunização , Influenza Humana/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Gestantes , África do Sul , Vacinação
3.
Clin Infect Dis ; 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34389845

RESUMO

BACKGROUND: Invasive meningococcal disease (IMD) is a devastating illness with high mortality. Like influenza, endemic IMD is seasonal peaking in winter. Studies suggest that circulation of influenza virus may influence timing and magnitude of IMD winter peaks. METHODS: This ecological study used weekly data from two nationwide surveillance programmes: Viral Watch (proportion of out-patient influenza-positive cases from throat/nasal swabs) and GERMS-SA (laboratory-confirmed cases of IMD) occurring across South Africa from 2003 through 2018 in all age-bands. A bivariate time-series analysis using wavelet transform was conducted to determine co-circulation of the diseases and the time lag between the peak seasons. We modelled excess meningococcal disease cases attributable to influenza co-circulation using univariate regression spline models. Stata and R statistical packages were used for the analysis. RESULTS: 5256 laboratory-confirmed IMD cases were reported, with an average annual incidence of 0.23 episodes per 100 000 population and a mean seasonal peak during week 32 (+3 weeks). Forty-two percent (10 421/24 741) of swabs were positive for influenza during the study period. The mean peak for all influenza occurred at week 26 (+4 weeks). There was an average lag-time of 5 weeks between annual influenza and IMD seasons. Overall, 5% (1-9%) of meningococcal disease can be attributable to influenza co-circulation with, on average, 17 excess IMD cases per year attributable to influenza. CONCLUSION: A quantifiable proportion of meningococcal disease in South Africa is associated with influenza co-circulation, therefore seasonal influenza vaccination may have an effect on preventing a small portion of meningococcal disease in addition to preventing influenza.

4.
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
5.
Nat Med ; 27(4): 622-625, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33654292

RESUMO

SARS-CoV-2 501Y.V2 (B.1.351), a novel lineage of coronavirus causing COVID-19, contains substitutions in two immunodominant domains of the spike protein. Here, we show that pseudovirus expressing 501Y.V2 spike protein completely escapes three classes of therapeutically relevant antibodies. This pseudovirus also exhibits substantial to complete escape from neutralization, but not binding, by convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and foreshadows reduced efficacy of spike-based vaccines.


Assuntos
COVID-19/imunologia , Evasão da Resposta Imune , Testes de Neutralização , SARS-CoV-2/imunologia , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologia , Doadores de Sangue , Vacinas contra COVID-19/imunologia , Humanos , Glicoproteína da Espícula de Coronavírus/imunologia
6.
bioRxiv ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33501446

RESUMO

SARS-CoV-2 501Y.V2 (B.1.351), a novel lineage of coronavirus causing COVID-19, contains substitutions in two immunodominant domains of the spike protein. Here, we show that pseudovirus expressing 501Y.V2 spike protein completely escapes three classes of therapeutically relevant antibodies. This pseudovirus also exhibits substantial to complete escape from neutralization, but not binding, by convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and foreshadows reduced efficacy of spike-based vaccines.

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.

8.
Clin Infect Dis ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32369560

RESUMO

BACKGROUND: Invasive meningococcal disease clusters occur amongst university students and may reflect higher carriage prevalence amongst this population. We aimed to measure meningococcal carriage prevalence, acquisition and risk factors amongst first-year university students in South Africa, a middle-income country. METHODS: In summer to autumn 2017, after consenting to participate, we collected oropharyngeal swabs and questionnaires on carriage risk factors and tested students for HIV infection at two universities, during registration week (survey one) and 6-8 weeks later (survey two). Meningococci were detected by culture and polymerase chain reaction. RESULTS: We enrolled 2120 students at registration. Mean age was 18.5 years, 59% (1252/2120) were female and 0.8% (16/1984) were HIV-infected. Seventy-eight percent of students returned for survey two (1655/2120).Amongst the cohort, carriage prevalence was 4.7% (77/1655) at registration; increasing to 7.9% (130/1655) at survey two: 5.0% (83) acquired new carriage, 2.8% (47) had persistent carriage, 1.8% (30) cleared the initial carriage and 90.3% (1495) remained carriage-free. At both surveys, non-genogroupable meningococci predominated, followed by genogroups Y, B, W and C. On multinomial analysis risk factors for carriage acquisition included attending nightclubs (adjusted relative risk ratio (aRRR) 2.1 (95%CI=1.1-4.0)), having intimate kissing partners (aRRR 1.8 (95%CI=1.1-2.9)) and being HIV-infected (aRRR 5.0 (95%CI=1.1-24.4)). CONCLUSION: Meningococcal carriage amongst first-year university students increased after two months. Social-behavioural risk factors were associated with increased carriage for all analyses. HIV-infection was associated with carriage acquisition. Until vaccination programmes become mandatory in South African universities, data suggest that HIV-infected students could benefit most from meningococcal vaccination.

9.
PLoS One ; 15(1): e0227945, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995597

RESUMO

Streptococcus pneumoniae (pneumococcus) remains an important cause of morbidity and mortality. Pneumococcal vaccination is part of the South African pediatric public immunization program but the potential cost-effectiveness of such an intervention for adults is unknown. This study aimed to compare the cost-effectiveness of two widely used pneumococcal vaccines: pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23) in South African adults, 18 years and older. Four analyses were carried out in a) both the private and public health care sectors; and b) for the HIV-infected population alone and for the total mixed population (all HIV-infected and -uninfected people). A previously published global pharmacoeconomic model was adapted and populated to represent the South African adult population. The model utilized a Markov-type process to depict the lifetime clinical and economic outcomes of patients who acquire pneumococcal disease in 2015, from a societal perspective. Costs were sourced in South African rand and converted to US dollar (USD). The incremental cost divided by the incremental effectiveness (expressed as quality-adjusted life years gained) represented the incremental cost-effectiveness ratio for PCV13 compared to PPSV23. Results indicated that the use of PCV13 compared to PPSV23 is highly cost-effective in the public sector cohorts with incremental cost-effectiveness ratios of $771 (R11,106)/quality-adjusted life year and $956 (R13,773)/quality-adjusted life year for the HIV-infected and mixed populations, respectively. The private sector cohort showed similar highly cost-effective results for the mixed population (incremental cost-effectiveness ratio $626 (R9,013)/quality-adjusted life year) and the HIV-infected cohort (dominant). In sensitivity analysis, the model was sensitive to vaccine price and effectiveness. Probabilistic sensitivity analyses found predominantly cost-effective ICERs. From a societal perspective, these findings provide some guidance to policy makers for consideration and implementation of an immunization strategy for both the public and private sector and amongst different adult patient pools in South Africa.


Assuntos
Análise Custo-Benefício , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunização , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/economia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , África do Sul/epidemiologia , Vacinas Conjugadas/economia , Vacinas Conjugadas/uso terapêutico , Adulto Jovem
10.
Pediatr Infect Dis J ; 38(4): 424-430, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30882740

RESUMO

BACKGROUND: Neonatal invasive pneumococcal disease (IPD) in developing countries is poorly described. We provide a baseline description of neonatal IPD in South Africa, before implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2009. METHODS: Data from children (age ≤ 2 years) with IPD (pneumococcus identified from a normally sterile specimen) from January 2003 to December 2008 were extracted from a national laboratory-based surveillance database. Clinical and laboratory characteristics of IPD among neonates (0-27 days old) was compared with IPD among young children (≥ 28 days ≤ 2 years). Early-onset IPD (0-6 days old) was compared with late-onset IPD (≥ 7-27 days old). Isolates were serotyped using the Quellung reaction. RESULTS: Overall 27,630 IPD cases were reported. Of the 26,277 (95%) with known ages, 6583 (25%) were ≤ 2 years of age, of which 4.5% (294/6583) were neonates. The estimated annual incidence of neonatal IPD in 2008 was 5 per 100,000 live births. Fifty-one percent of neonates with IPD presented with early-onset IPD. Case fatality ratios (CFRs) were high in both groups, 31% (28/89) in neonatal IPD versus 26% (614/2383) in non-neonatal IPD (P = 0.18). Among neonates, the meningitis cases (15/37, 41%) were associated with the highest CFR. The 13-valent pneumococcal conjugate vaccine (PCV13) serotypes accounted for 69% (134/194) of neonatal IPD isolates. CONCLUSIONS: Pneumococcal neonatal disease in South Africa was not uncommon before PCV introduction and is associated with a high CFR. The indirect effect on neonatal IPD of PCV rollout requires further evaluation.


Assuntos
Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Mortalidade , Infecções Pneumocócicas/mortalidade , África do Sul/epidemiologia
11.
Clin Infect Dis ; 69(3): 495-504, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-30351372

RESUMO

BACKGROUND: Invasive meningococcal disease (IMD) is endemic to South Africa, where vaccine use is negligible. We describe the epidemiology of IMD in South Africa. METHODS: IMD cases were identified through a national, laboratory-based surveillance program, GERMS-SA, from 2003-2016. Clinical data on outcomes and human immunodeficiency virus (HIV) statuses were available from 26 sentinel hospital sites. We conducted space-time analyses to detect clusters of serogroup-specific IMD cases. RESULTS: Over 14 years, 5249 IMD cases were identified. The incidence was 0.97 cases per 100 000 persons in 2003, peaked at 1.4 cases per 100 000 persons in 2006, and declined to 0.23 cases per 100 000 persons in 2016. Serogroups were confirmed in 3917 (75%) cases: serogroup A was present in 4.7% of cases, B in 23.3%, C in 9.4%; W in 49.5%; Y in 12.3%, X in 0.3%; Z in 0.1% and 0.4% of cases were non-groupable. We identified 8 serogroup-specific, geo-temporal clusters of disease. Isolate susceptibility was 100% to ceftriaxone, 95% to penicillin, and 99.9% to ciprofloxacin. The in-hospital case-fatality rate was 17% (247/1479). Of those tested, 36% (337/947) of IMD cases were HIV-coinfected. The IMD incidence in HIV-infected persons was higher for all age categories, with an age-adjusted relative risk ratio (aRRR) of 2.5 (95% confidence interval [CI] 2.2-2.8; P < .001) from 2012-2016. No patients reported previous meningococcal vaccine exposure. Patients with serogroup W were 3 times more likely to present with severe disease than those with serogroup B (aRRR 2.7, 95% CI 1.1-6.3); HIV coinfection was twice as common with W and Y diseases (aRRR W = 1.8, 95% CI 1.1-2.9; aRRR Y = 1.9, 95% CI 1.0-3.4). CONCLUSIONS: In the absence of significant vaccine use, IMD in South Africa decreased by 76% from 2003-2016. HIV was associated with an increased risk of IMD, especially for serogroup W and Y diseases.


Assuntos
Coinfecção/epidemiologia , Infecções Meningocócicas/epidemiologia , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Mortalidade Hospitalar , Humanos , Incidência , Masculino , Infecções Meningocócicas/tratamento farmacológico , Infecções Meningocócicas/mortalidade , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neisseria meningitidis/imunologia , Fatores de Risco , Sorogrupo , África do Sul/epidemiologia , Adulto Jovem
12.
Expert Rev Vaccines ; 18(1): 15-30, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30526162

RESUMO

INTRODUCTION: The 2018 Global Meningococcal Initiative (GMI) meeting focused on evolving invasive meningococcal disease (IMD) epidemiology, surveillance, and protection strategies worldwide, with emphasis on emerging antibiotic resistance and protection of high-risk populations. The GMI is comprised of a multidisciplinary group of scientists and clinicians representing institutions from several continents. AREAS COVERED: Given that the incidence and prevalence of IMD continually varies both geographically and temporally, and surveillance systems differ worldwide, the true burden of IMD remains unknown. Genomic alterations may increase the epidemic potential of meningococcal strains. Vaccination and (to a lesser extent) antimicrobial prophylaxis are the mainstays of IMD prevention. Experiences from across the globe advocate the use of conjugate vaccines, with promising evidence growing for protein vaccines. Multivalent vaccines can broaden protection against IMD. Application of protection strategies to high-risk groups, including individuals with asplenia, complement deficiencies and human immunodeficiency virus, laboratory workers, persons receiving eculizumab, and men who have sex with men, as well as attendees at mass gatherings, may prevent outbreaks. There was, however, evidence that reduced susceptibility to antibiotics was increasing worldwide. EXPERT COMMENTARY: The current GMI global recommendations were reinforced, with several other global initiatives underway to support IMD protection and prevention.


Assuntos
Antibacterianos/administração & dosagem , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Antibacterianos/farmacologia , Surtos de Doenças , Farmacorresistência Bacteriana , Saúde Global , Humanos , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/microbiologia , Fatores de Risco , Vacinação
13.
J Infect ; 77(5): 368-378, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29964140

RESUMO

OBJECTIVES: Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV). METHODS: We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0-23, 24-29, and 0-59 months and by invasive clinical syndromes. RESULTS: In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0-23 and 0-59 months for all IPD and clinical syndromes (OR > 5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0.1-0.3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum. CONCLUSIONS: There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines.


Assuntos
Portador Sadio/microbiologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/classificação , Fatores Etários , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Estudos Observacionais como Assunto , Prevalência , Sorogrupo , Streptococcus pneumoniae/patogenicidade , Vacinação/estatística & dados numéricos
14.
PLoS One ; 12(7): e0179905, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28671978

RESUMO

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


Assuntos
Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/administração & dosagem , Pré-Escolar , Humanos , Infecções Pneumocócicas/patologia , Infecções Pneumocócicas/prevenção & controle , Índice de Gravidade de Doença , África do Sul/epidemiologia
15.
Lancet Glob Health ; 5(3): e359-e369, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28139443

RESUMO

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was designed to include disease-causing serotypes that are important in low-income and middle-income countries. Vaccine effectiveness estimates are scarce in these settings. South Africa replaced PCV7 with PCV13 in 2011 using a 2 + 1 schedule. We aimed to assess the effectiveness of two or more doses of PCV13 against invasive pneumococcal disease in children with HIV infection and in those not infected with HIV. METHODS: Cases of invasive pneumococcal disease in children aged 5 years or younger were identified through national laboratory-based surveillance. Isolates were serotyped with the Quellung reaction or PCR. We sought in-hospital controls for every case, matched for age, HIV status, and study site. We aimed to enrol four controls for every case not infected with HIV and six controls for every case with HIV infection (case-control sets). With conditional logistic regression, we calculated vaccine effectiveness as a percentage, with the equation 1 - [adjusted odds ratio for vaccination] × 100. We included data from an earlier investigation of PCV7 to assess vaccine effectiveness in children exposed to but not infected with HIV and in malnourished children not infected with HIV. FINDINGS: Between January, 2012, and December, 2014, we enrolled children aged 16 weeks or older to our study: 240 were cases not infected with HIV, 75 were cases with HIV infection, 1118 were controls not infected with HIV, and 283 were controls with HIV infection. The effectiveness of two or more doses of PCV13 against PCV13-serotype invasive pneumococcal disease was 85% (95% CI 37 to 96) among 11 case-control sets of children not infected with HIV and 91% (-35 to 100) among three case-control sets of children with HIV infection. PCV13 effectiveness among 26 case-control sets of children not infected with HIV was 52% (95% CI -12 to 79) against all-serotype invasive pneumococcal disease and 94% (44 to 100) for serotype 19A. Vaccine effectiveness against PCV7-serotype invasive pneumococcal disease was 87% (95% CI 38 to 97) in children exposed to HIV but uninfected and 90% (53 to 98) in malnourished children not infected with HIV. INTERPRETATION: Our results indicate that PCV13 in a 2 + 1 schedule is effective for preventing vaccine-type pneumococcal infections in young children not infected with HIV, including those who are malnourished or who have been exposed to HIV. Although the point estimate for PCV13 vaccine effectiveness in children infected with HIV was high, it did not reach significance, possibly because of the small sample size. These findings support recommendations for widespread use of pneumococcal conjugate vaccine in low-income and middle-income countries. FUNDING: Gavi, The Vaccine Alliance.


Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Sorogrupo , Streptococcus pneumoniae/imunologia , Vacinação , Vacinas Conjugadas/imunologia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Infecções por HIV/complicações , Humanos , Lactente , Modelos Logísticos , Masculino , Razão de Chances , Infecções Pneumocócicas/microbiologia , África do Sul , Streptococcus pneumoniae/classificação , Resultado do Tratamento
16.
BMC Microbiol ; 17(1): 40, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-28222677

RESUMO

BACKGROUND: The meningococcal capsule is an important virulence determinant. Unencapsulated meningococci lacking capsule biosynthesis genes and containing the capsule null locus (cnl) are predominantly non-pathogenic. Rare cases of invasive meningococcal disease caused by cnl isolates belonging to sequence types (ST) and clonal complexes (cc) ST-845 (cc845), ST-198 (cc198), ST-192 (cc192) and ST-53 (cc53) have been documented. The clinical significance of these isolates however remains unclear. We identified four invasive cnl meningococci through laboratory-based surveillance in South Africa from 2003 through 2013, which we aimed to characterize using whole genome data. RESULTS: One isolate [NG: P1.7-2,30: F1-2: ST-53 (cc53)] contained cnl allele 12, and caused empyema in an adult male with bronchiectasis from tuberculosis, diabetes mellitus and a smoking history. Three isolates were NG: P1.18-11,42-2: FΔ: ST-192 (cc192) and contained cnl allele 2. One patient was an adolescent male with meningitis. The remaining two isolates were from recurrent disease episodes (8 months apart) in a male child with deficiency of the sixth complement component, and with the exception of two single nucleotide polymorphisms, contained identical core genomes. The ST-53 (cc53) isolate possessed alleles for NHBA peptide 191 and fHbp variant 2; whilst the ST-192 (cc192) isolates contained NHBA peptide 704 and fHbp variant 3. All four isolates lacked nadA. Comparison of the South African genomes to 61 additional cnl genomes on the PubMLST Neisseria database ( http://pubmlst.org/neisseria/ ), determined that most putative virulence genes could be found in both invasive and carriage phenotypes. CONCLUSIONS: Although rare, invasive disease by cnl meningococci may be associated with host immunodeficiency and such patients may benefit from protein-based meningococcal vaccines.


Assuntos
Cápsulas Bacterianas/genética , Genes Bacterianos/genética , Infecções Meningocócicas/microbiologia , Neisseria meningitidis/genética , Adesinas Bacterianas/genética , Adolescente , Alelos , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Sequência de Bases , Bronquiectasia/complicações , Proteínas de Transporte/genética , Criança , Pré-Escolar , Complicações do Diabetes , Diabetes Mellitus , Empiema/microbiologia , Loci Gênicos , Marcadores Genéticos/genética , Humanos , Masculino , Meningite Meningocócica/epidemiologia , Infecções Meningocócicas/epidemiologia , Vacinas Meningocócicas/imunologia , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Neisseria meningitidis/citologia , Neisseria meningitidis/isolamento & purificação , Neisseria meningitidis/patogenicidade , Fenótipo , Filogenia , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Fumar , África do Sul/epidemiologia , Tuberculose/complicações , Virulência/genética , Adulto Jovem
17.
PLoS Negl Trop Dis ; 10(7): e0004865, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27467556

RESUMO

BACKGROUND: We aimed to establish the prevalence of amphotericin B deoxycholate (AmBd)-related toxicities among South African patients with cryptococcosis and determine adherence to international recommendations to prevent, monitor and manage AmBd-related toxicities. METHODS: Clinical data were collected from cases of laboratory-confirmed cryptococcosis at 25 hospitals, October 2012 -February 2013. Anemia was defined as hemoglobin (Hb) concentration <10 g/dl, hypokalemia as serum potassium (K) <3.4 mEq/L and nephrotoxicity as an increase in serum creatinine (Cr) to >1.1 times the upper limit of normal. To determine adherence to toxicity prevention recommendations, we documented whether baseline Hb, K and Cr tests were performed, whether pre-emptive hydration and IV potassium chloride (KCl) was administered prior to 80% and 60% of AmBd doses and whether daily oral KCl supplementation was given ≥60% of the time. To determine adherence to monitoring recommendations, we ascertained whether a daily fluid chart was completed, Hb was monitored weekly and K or Cr were monitored bi-weekly. RESULTS: Of 846 patients, clinical data were available for 76% (642/846), 82% (524/642) of whom received AmBd. Sixty-four per cent (n = 333) had documented baseline laboratory tests, 40% (n = 211) were given pre-emptive hydration and 14% (n = 72) and 19% (n = 101) received intravenous and oral KCl. While on AmBd, 88% (n = 452) had fluid monitoring; 27% (n = 142), 45% (n = 235) and 44% (n = 232) had Hb, K and Cr levels monitored. Toxicities developed frequently during treatment: anemia, 16% (86/524); hypokalemia, 43% (226/524) and nephrotoxicity, 32% (169/524). CONCLUSION: AmBd-related toxicities occurred frequently but were potentially preventable with adequate monitoring, supplemental fluid and electrolyte therapies.


Assuntos
Anfotericina B/efeitos adversos , Ácido Desoxicólico/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/etiologia , Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Ácido Desoxicólico/administração & dosagem , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Feminino , Hospitalização , Humanos , Masculino , Prevalência , Estudos Retrospectivos , África do Sul/epidemiologia
18.
PLoS One ; 11(4): e0152524, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27055184

RESUMO

Data on neonatal group B streptococcal (GBS) invasive disease burden are needed to refine prevention policies. Differences in surveillance methods and investigating for cases can lead to varying disease burden estimates. We compared the findings of laboratory-based passive surveillance for GBS disease across South Africa, and for one of the provinces compared this to a real-time, systematic, clinical surveillance in a population-defined region in Johannesburg, Soweto. Passive surveillance identified a total of 799 early-onset disease (EOD, <7 days age) and 818 LOD (late onset disease, 7-89 days age) cases nationwide. The passive surveillance provincial incidence varied for EOD (range 0.00 to 1.23/1000 live births), and was 0.03 to 1.04/1000 live births for LOD. The passive surveillance rates for Soweto, were not significantly different compared to those from the systematic surveillance (EOD 1.23 [95%CI 1.06-1.43] vs. 1.50 [95%CI 1.30-1.71], respectively, rate ratio 0.82 [95%CI 0.67-1.01]; LOD 1.04 [95% CI 0.90-1.23] vs. 1.22 [95%CI 1.05-1.42], rate ratio 0.85 [95% CI 0.68-1.07]). A review of the few cases missed in the passive system in Soweto, suggested that missing key identifiers, such as date of birth, resulted in their omission during the electronic data extraction process. Our analysis suggests that passive surveillance provides a modestly lower estimate of invasive GBS rates compared to real time sentinel-site systematic surveillance, however, this is unlikely to be the reason for the provincial variability in incidence of invasive GBS disease in South Africa. This, possibly reflects that invasive GBS disease goes undiagnosed due to issues related to access to healthcare, poor laboratory capacity and varying diagnostic procedures or empiric antibiotic treatment of neonates with suspected sepsis in the absence of attempting to making a microbiological diagnosis. An efficacious GBS vaccine for pregnant women, when available, could be used as a probe to better quantify the burden of invasive GBS disease in low-middle resourced settings such as ours. From our study passive systems are important to monitor trends over time as long as they are interpreted with caution; active systems give better detailed information and will have greater representivity when expanded to other surveillance sites.


Assuntos
Monitoramento Epidemiológico , Complicações Infecciosas na Gravidez/epidemiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae , Adulto , Feminino , Humanos , Incidência , Nascido Vivo , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , África do Sul/epidemiologia , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/administração & dosagem
19.
PLoS One ; 11(2): e0149104, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26863135

RESUMO

INTRODUCTION: Streptococcus pneumoniae is the commonest cause of bacteremic pneumonia among HIV-infected persons. As more countries with high HIV prevalence are implementing infant pneumococcal conjugate vaccine (PCV) programs, we aimed to describe the baseline clinical characteristics of adult invasive pneumococcal disease (IPD) in the pre-PCV era in South Africa in order to interpret potential indirect effects following vaccine use. METHODS: National, active, laboratory-based surveillance for IPD was conducted in South Africa from 1 January 2003 through 31 December 2008. At 25 enhanced surveillance (ES) hospital sites, clinical data, including HIV serostatus, were collected from IPD patients ≥ 5 years of age. We compared the clinical characteristics of individuals with IPD in those HIV-infected and -uninfected using multivariable analysis. PCV was introduced into the routine South African Expanded Program on Immunization (EPI) in 2009. RESULTS: In South Africa, from 2003-2008, 17 604 cases of IPD occurred amongst persons ≥ 5 years of age, with an average incidence of 7 cases per 100 000 person-years. Against a national HIV-prevalence of 18%, 89% (4190/4734) of IPD patients from ES sites were HIV-infected. IPD incidence in HIV-infected individuals is 43 times higher than in HIV-uninfected persons (52 per 100 000 vs. 1.2 per 100 000), with a peak in the HIV-infected elderly population of 237 per 100 000 persons. Most HIV-infected individuals presented with bacteremia (74%, 3 091/4 190). HIV-uninfected individuals were older; and had more chronic conditions (excluding HIV) than HIV-infected persons (39% (210/544) vs. 19% (790/4190), p<0.001). During the pre-PCV immunization era in South Africa, 71% of serotypes amongst HIV-infected persons were covered by PCV13 vs. 73% amongst HIV-uninfected persons, p = 0.4, OR 0.9 (CI 0.7-1.1). CONCLUSION: Seventy to eighty-five percent of adult IPD in the pre-PCV era were vaccine serotypes and 93% of cases had recognized risk factors (including HIV-infection) for pneumococcal vaccination. These data describe the epidemiology of IPD amongst HIV-infected and -uninfected adults during the pre-PCV era and provide a robust baseline to calculate the indirect effect of PCV in future studies.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções Pneumocócicas/complicações , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/uso terapêutico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Vacinas Pneumocócicas/imunologia , Prevalência , Fatores de Risco , Sorogrupo , África do Sul/epidemiologia , Streptococcus pneumoniae , Vacinação , Vacinas Conjugadas/imunologia , Vacinas Conjugadas/uso terapêutico , Adulto Jovem
20.
Emerg Infect Dis ; 22(2): 261-70, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26812214

RESUMO

In South Africa, 7-valent pneumococcal conjugate vaccine (PCV) was introduced in April 2009 and replaced with 13-valent PCV in April 2011. We describe the epidemiology of serotype 1 Streptococcus pneumoniae disease during the pre- and post-PCV eras (2003-2013). Using laboratory-based invasive pneumococcal disease (IPD) surveillance, we calculated annual incidences, identified IPD clusters, and determined serotype 1-associated factors. Of 46,483 IPD cases, 4,544 (10%) were caused by serotype 1. Two clusters of serotype 1 infection were detected during 2003-2004 and 2008-2012, but incidence decreased after 2011. Among children <5 years of age, those who had non-serotype 1 IPD had shorter hospital stays, fewer cases of penicillin-nonsusceptible disease, and lower HIV prevalence and in-hospital death rates than did those with serotype 1 IPD; similar factors were noted for older patients. Serotype 1 IPD had distinctive clinical features in South Africa, and annual incidences fluctuated, with decreases noted after the introduction of PCV13.


Assuntos
Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/classificação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , História do Século XXI , Hospitalização , Humanos , Incidência , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Mortalidade , Razão de Chances , Infecções Pneumocócicas/história , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Fatores de Risco , Sorogrupo , África do Sul/epidemiologia , Análise Espaço-Temporal , Adulto Jovem
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