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1.
Clin Infect Dis ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34725702

RESUMO

BACKGROUND: Sepsis and meningitis are amongst the leading causes of neonatal deaths in Sub-Saharan Africa (SSA). Neonatal sepsis caused around 400000 deaths globally in 2015, half occurring in Africa. Despite this, there are few published data on the acute costs of neonatal sepsis or meningitis, particularly in low- and middle-income countries, and none in SSA. METHODS: We collected data on neonates admitted to two hospitals between April 16, 2020 and April 1, 2021. In South Africa cases were microbiologically confirmed either by culture or PCR. In Mozambique clinically suspected and microbiologically confirmed cases were included. Data were collected on healthcare resource use and length-of-stay. A caregivers questionnaire gathered data on expenditure and caregiving. We used unit costs of healthcare resources in local currencies to estimate average healthcare provider cost per patient and average costs per household. Results were converted to 2019 international dollars (I$). RESULTS: We enrolled 11 neonates in Mozambique, 18 neonates in South Africa. Mean length-of-stay was 10 days (median=9; IQR=4-14)) and 16 days (median=15; IQR=13-18). In Mozambique we estimated mean household costs of I$49.62 (median=10.19, IQR=5.10-95.12) and hospitalisation costs of I$307.58 (median=275.12; IQR=149.43-386.12). In South Africa these costs were I$52.31 (median=30.82; IQR=19.25-73.08) and I$684.06 (median=653.62; IQR=543.33-827.53), respectively. On average, parents in Mozambique spent an extra 52 hours (median=38.5; IQR=19-86) on caregiving, and in South Africa an extra 76 (median=3.5; IQR=0-120). CONCLUSION: We found substantial costs associated with acute neonatal bacterial (all-cause) sepsis and meningitis in SSA. Our estimates will inform cost-effectiveness analyses of interventions to prevent invasive bacterial infections in neonates.

2.
Clin Infect Dis ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34725706

RESUMO

BACKGROUND: Invasive Group B Streptococcus (iGBS) sepsis and meningitis are important causes of child mortality, but studies on neurodevelopmental impairment (NDI) after iGBS are limited. Using Griffiths Mental Development Scales-Extended Revised (GMDS-ER), we described NDI in iGBS survivors and non-iGBS children from South Africa, as part of a five-country study. METHODS: We identified children aged 5 -8 years with a history of iGBS and children with no history of iGBS between October 2019 - January 2021. Children were matched on sex, and birth data (month, year) (matched cohort study). Moderate-severe NDI was the primary outcome as a composite of GMDS-ER motor, GMDS-ER cognition, hearing and vision. Secondary outcomes included mild NDI, any emotional-behavioural problems, and GMDS-ER developmental quotients (DQ) calculated by dividing the age equivalent GMDS-ER score by the chronological age. RESULTS: 160 children (iGBS survivors, 43; non-iGBS, 117) were assessed. Amongst iGBS survivors 13 (30.2%) had meningitis and 30 (69.8%) had sepsis. Six (13.9%) iGBS survivors, and five (4.3%) non-iGBS children had moderate-severe NDI. iGBS exposure was associated with a 5.56 (95%CI: 1.07-28.93; p=0.041) adjusted odds of moderate-severe NDI at 5-8 years. Compared to the non-iGBS children, iGBS meningitis survivors had a significantly lower global median DQ (p < 0.05), as well as a lower median DQ for the language and performance GMDS-ER subscale (p<0.05). CONCLUSIONS: Children surviving iGBS, particularly meningitis, are more likely to have NDI at 5 - 8 years compared to non-iGBS children. Further research is required to improve detection and care for at-risk newborns.

3.
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.

4.
Int J Epidemiol ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34718591

RESUMO

BACKGROUND: Limitations in laboratory testing capacity undermine the ability to quantify the overall burden of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. METHODS: We undertook a population-based serosurvey for SARS-CoV-2 infection in 26 subdistricts, Gauteng Province (population 15.9 million), South Africa, to estimate SARS-CoV-2 infection, infection fatality rate (IFR) triangulating seroprevalence, recorded COVID-19 deaths and excess-mortality data. We employed three-stage random household sampling with a selection probability proportional to the subdistrict size, stratifying the subdistrict census-sampling frame by housing type and then selecting households from selected clusters. The survey started on 4 November 2020, 8 weeks after the end of the first wave (SARS-CoV-2 nucleic acid amplification test positivity had declined to <10% for the first wave) and coincided with the peak of the second wave. The last sampling was performed on 22 January 2021, which was 9 weeks after the SARS-CoV-2 resurgence. Serum SARS-CoV-2 receptor-binding domain (RBD) immunoglobulin-G (IgG) was measured using a quantitative assay on the Luminex platform. RESULTS: From 6332 individuals in 3453 households, the overall RBD IgG seroprevalence was 19.1% [95% confidence interval (CI): 18.1-20.1%] and similar in children and adults. The seroprevalence varied from 5.5% to 43.2% across subdistricts. Conservatively, there were 2 897 120 (95% CI: 2 743 907-3 056 866) SARS-CoV-2 infections, yielding an infection rate of 19 090 per 100 000 until 9 January 2021, when 330 336 COVID-19 cases were recorded. The estimated IFR using recorded COVID-19 deaths (n = 8198) was 0.28% (95% CI: 0.27-0.30) and 0.67% (95% CI: 0.64-0.71) assuming 90% of modelled natural excess deaths were due to COVID-19 (n = 21 582). Notably, 53.8% (65/122) of individuals with previous self-reported confirmed SARS-CoV-2 infection were RBD IgG seronegative. CONCLUSIONS: The calculated number of SARS-CoV-2 infections was 7.8-fold greater than the recorded COVID-19 cases. The calculated SARS-CoV-2 IFR varied 2.39-fold when calculated using reported COVID-19 deaths (0.28%) compared with excess-mortality-derived COVID-19-attributable deaths (0.67%). Waning RBD IgG may have inadvertently underestimated the number of SARS-CoV-2 infections and conversely overestimated the mortality risk. Epidemic preparedness and response planning for future COVID-19 waves will need to consider the true magnitude of infections, paying close attention to excess-mortality trends rather than absolute reported COVID-19 deaths.

6.
Surv Ophthalmol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34626620

RESUMO

Tubercular uveitis (TBU) is an inflammation/infection of the eye secondary to Mycobacterium tuberculosis infection. The difficulty in making the diagnosis has resulted in variable prevalence and clinical response rates. We aimed to determine the global prevalence of TBU in uveitis patients stratified by TB high-burden countries (HBCs) and non-HBCs and by geographic regions and the clinical response of TBU to antitubercular treatment We performed a systematic review and meta-analysis of TBU studies published in PubMed, Scopus and EMBASE, up to June 30, 2020. A random effects model was used for all meta-analyses. Of 5,018 articles identified, 70 prevalence studies (65,607 uveitis and 3,166 TBU cases) and 18 clinical outcome studies (1,570 TBU cases; 1,304 responded to anti-tubercular therapy [ATT]) were analyzed. The overall weighted prevalence of TBU was 4.0% (95% CI, 3-5); in TB HBCs it was 7.0% (95% CI, 5-11), non-HBCs 3.0% (95% CI, 2-4), and sub-Saharan Africa 11.0% (95% CI, 8-15). The overall weighted clinical response was 82.0% (95% CI, 75-89). Despite the difficulty in diagnosing TBU, the prevalence is expectantly higher in HBCs, and sub-Saharan Africa and the clinical outcome is poor. Standardization of diagnostic criteria and ATT is warranted in future cohort studies.

7.
Vaccine ; 39(47): 6813-6816, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34688499

RESUMO

Past studies have mainly investigated the association of serotype-specific capsular IgG in the mother and risk reduction of invasive Group B Streptococcus (GBS) in their young infants. The efficiency of transplacental transfer of IgG could be affected by multiple maternal factors. Hence, investigation of infant serum GBS anti-capsular IgG and risk reduction for invasive GBS disease may be more robust and generalizable. In a matched case-control study, infant serum serotype-specific capsular polysaccharide Ia and III IgG concentrations were analyzed in infants with invasive GBS cases and healthy controls born to women with recto-vaginal colonization by the homotypic serotype. Using Bayesian modeling, an antibody concentration of 2.5 µg/mL and 1 µg/mL predicted a 90% reduced risk of invasive disease for serotype Ia and III, respectively. These data contribute to the possible licensure of a GBS polysaccharide-protein conjugate vaccine, targeted at pregnant women, based on serological correlates of protection against invasive GBS disease.

8.
Clin Infect Dis ; 73(Suppl_3): S229-S237, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472576

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. METHODS: The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. RESULTS: We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8-3.3) was lower than in-hospital (2.4 months; IQR: 1.5-4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). CONCLUSIONS: We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Distribuição por Idade , Criança , Hospitalização , Humanos , Lactente , Morte do Lactente , Recém-Nascido , Infecções por Vírus Respiratório Sincicial/epidemiologia
9.
Clin Infect Dis ; 73(Suppl_3): S218-S228, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472577

RESUMO

BACKGROUND: Lower respiratory tract infections are a leading cause of death in young children, but few studies have collected the specimens needed to define the role of specific causes. The Child Health and Mortality Prevention Surveillance (CHAMPS) platform aims to investigate causes of death in children aged <5 years in high-mortality rate settings, using postmortem minimally invasive tissue sampling and other advanced diagnostic techniques. We examined findings for deaths identified in CHAMPS sites in 7 countries in sub-Saharan Africa and south Asia to evaluate the role of respiratory syncytial virus (RSV). METHODS: We included deaths that occurred between December 2016 and December 2019. Panels determined causes of deaths by reviewing all available data including pathological results from minimally invasive tissue sampling, polymerase chain reaction screening for multiple infectious pathogens in lung tissue, nasopharyngeal swab, blood, and cerebrospinal fluid samples, clinical information from medical records, and verbal autopsies. RESULTS: We evaluated 1213 deaths, including 695 in neonates (aged <28 days), 283 in infants (28 days to <12 months), and 235 in children (12-59 months). RSV was detected in postmortem specimens in 67 of 1213 deaths (5.5%); in 24 deaths (2.0% of total), RSV was determined to be a cause of death, and it contributed to 5 other deaths. Younger infants (28 days to <6 months of age) accounted for half of all deaths attributed to RSV; 6.5% of all deaths in younger infants were attributed to RSV. RSV was the underlying and only cause in 4 deaths; the remainder (n = 20) had a median of 2 (range, 1-5) other conditions in the causal chain. Birth defects (n = 8) and infections with other pathogens (n = 17) were common comorbid conditions. CONCLUSIONS: RSV is an important cause of child deaths, particularly in young infants. These findings add to the substantial body of literature calling for better treatment and prevention options for RSV in high-mortality rate settings.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Criança , Saúde da Criança , Mortalidade da Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções Respiratórias/epidemiologia
10.
PLoS Med ; 18(9): e1003814, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34591862

RESUMO

BACKGROUND: The current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death. METHODS AND FINDINGS: We examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child <5 years deaths for which results from Determination of Cause of Death (DeCoDe) panels were complete. DeCoDe panelists included all conditions in the causal chain according to the ICD-10 guidelines and assessed if prevention or effective management of the condition would have prevented the death. We analyzed the distribution of all conditions listed as causal, including underlying, antecedent, and immediate causes of death. Among 1,232 deaths with an underlying condition determined, we found a range of 0 to 6 (mean 1.5, IQR 0 to 2) additional conditions in the causal chain leading to death. While pathology provides very helpful clues, we cannot always be certain that conditions identified led to death or occurred in an agonal stage of death. For neonates, preterm birth complications (most commonly respiratory distress syndrome) were the most common underlying condition (n = 282, 38%); among those with preterm birth complications, 256 (91%) had additional conditions in causal chains, including 184 (65%) with a different preterm birth complication, 128 (45%) with neonatal sepsis, 69 (24%) with lower respiratory infection (LRI), 60 (21%) with meningitis, and 25 (9%) with perinatal asphyxia/hypoxia. Of the 278 infant deaths, 212 (79%) had ≥1 additional cause of death (CoD) beyond the underlying cause. The 2 most common underlying conditions in infants were malnutrition and congenital birth defects; LRI and sepsis were the most common additional conditions in causal chains, each accounting for approximately half of deaths with either underlying condition. Of the 241 child deaths, 178 (75%) had ≥1 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had ≥1 other condition in the causal chain, most commonly sepsis, followed by LRI, malaria, and diarrheal disease. Including all positions in the causal chain for neonatal deaths resulted in 19-fold and 11-fold increases in attributable roles for meningitis and LRI, respectively. For infant deaths, the proportion caused by meningitis and sepsis increased by 16-fold and 11-fold, respectively; for child deaths, sepsis and LRI are increased 12-fold and 10-fold, respectively. While comprehensive CoD determinations were done for a substantial number of deaths, there is potential for bias regarding which deaths in surveillance areas underwent minimally invasive tissue sampling (MITS), potentially reducing representativeness of findings. CONCLUSIONS: Including conditions that appear anywhere in the causal chain, rather than considering underlying condition alone, markedly changed the proportion of deaths attributed to various diagnoses, especially LRI, sepsis, and meningitis. While CHAMPS methods cannot determine when 2 conditions cause death independently or may be synergistic, our findings suggest that considering the chain of events leading to death can better guide research and prevention priorities aimed at reducing child deaths.

12.
Pediatr Infect Dis J ; 40(9S): S1-S6, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34448739

RESUMO

The Pneumonia Etiology Research for Child Health (PERCH) study evaluated the etiology of severe and very severe pneumonia in children hospitalized in 7 African and Asian countries. Here, we summarize the highlights of in-depth site-specific etiology analyses published separately in this issue, including how etiology varies by age, mortality status, malnutrition, severity, HIV status, and more. These site-specific results impart important lessons that can inform disease control policy implications.

13.
Pediatr Infect Dis J ; 40(9S): S59-S68, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34448745

RESUMO

BACKGROUND: Pneumonia is the major contributor to under 5 childhood mortality globally. We evaluated the etiology of pneumonia amongst HIV-uninfected South African children enrolled into the Pneumonia Etiology Research for Child Health case-control study. METHODS: Cases, 1-59 months of age hospitalized with World Health Organization clinically defined severe/very severe pneumonia, were frequency-matched by age and season to community controls. Nasopharyngeal-oropharyngeal swabs were analyzed using polymerase chain reaction for 33 respiratory pathogens, and whole blood was tested for pneumococcal autolysin. Cases were also tested for Mycobacterium tuberculosis. Population etiologic fractions (EF) of pneumonia with radiologic evidence of consolidation/infiltrate were derived for each pathogen through Bayesian analysis. RESULTS: Of the 805 HIV-uninfected cases enrolled based on clinical criteria, radiologically confirmed pneumonia was evident in 165 HIV-exposed, -uninfected, and 246 HIV-unexposed children. In HIV-exposed and HIV-unexposed children, respiratory syncytial virus was the most important pathogen with EFs of 31.6% [95% credible interval (CrI), 24.8%-38.8%] and 36.4% (95% CrI, 30.5%-43.1%), respectively. M. tuberculosis contributed EFs of 11.6% (95% CrI, 6.1%-18.8%) in HIV-exposed and 8.3% (95% CrI, 4.5%-13.8%) in HIV-unexposed children, including an EF of 16.3% (95% CrI, 6.1%-33.3%) in HIV-exposed children ≥12 months of age. Bacteremia (3.0% vs. 1.6%) and case fatality risk (3.6% vs. 3.7%) were similar in HIV-exposed and HIV-unexposed children. CONCLUSIONS: Vaccination strategies targeting respiratory syncytial virus should be prioritized for prevention of pneumonia in children. Furthermore, interventions are required to address the high burden of tuberculosis in the pathogenesis of acute community-acquired pneumonia in settings such as ours.

14.
Pediatr Infect Dis J ; 40(9S): S69-S78, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34448746

RESUMO

BACKGROUND: HIV-1 infection predisposes to an increased burden of pneumonia caused by community-acquired and opportunistic pathogens. METHODS: Within the context of the Pneumonia Etiology Research for Child Health case-control study of under 5 pneumonia, we investigated the etiology of World Health Organization-defined severe/very severe pneumonia requiring hospitalization in South African HIV-infected children. Nasopharyngeal-oropharyngeal swabs and blood, collected from cases and age- and season-matched HIV-infected controls attending outpatient antiretroviral therapy (ART) clinics, were analyzed using molecular diagnostic methods. Cases were also investigated for tuberculosis. Etiologic fractions among cases with radiologically confirmed pneumonia were derived using Bayesian analytic techniques. RESULTS: Of 115 HIV-infected cases, 89 (77.4%) had radiologically confirmed pneumonia. Severe immunosuppression (adjusted odds ratio, 32.60; 95% confidence interval, 7.25-146.64) was significantly associated with radiologically confirmed pneumonia. Cotrimoxazole prophylaxis (46.4% vs. 77.4%) and ART (28.2% vs. 83.1%) coverage were significantly lower in cases compared with ART-clinic controls. An etiologic agent was identified in 99.0% of the radiologically confirmed cases. The 'top 4' pathogens associated with radiologically confirmed pneumonia were Pneumocystis jirovecii [23.0%; 95% credible interval (CrI), 12.4%-31.5%], Staphylococcus aureus (10.6%; 95% CrI, 2.2%-20.2%), pneumococcus (9.5%; 95% CrI, 2.2%-18.0%) and respiratory syncytial virus (9.3%; 95% CrI, 2.2%-14.6%). Bacteremia (6.7%) and in-hospital death (10.1%) were frequent among those with radiologically confirmed disease. CONCLUSIONS: Pneumocystis jirovecii, S. aureus, pneumococcus and respiratory syncytial virus contribute a considerable burden of radiologically confirmed pneumonia in South African HIV-infected children under 5 years. Expediting access to ART and cotrimoxazole prophylaxis would decrease the burden of pneumonia in these children.

15.
Pediatr Infect Dis J ; 40(9): e323-e332, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397776

RESUMO

BACKGROUND: Globally, very few childhood deaths have been attributed to coronavirus disease 2019 (COVID-19). We evaluated clinical, microbiologic and postmortem histopathologic findings in childhood deaths in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified antemortem or postmortem. METHODS: Surveillance of childhood deaths was ongoing during the initial COVID-19 outbreak in South Africa from April 14, 2020, to August 31, 2020. All children hospitalized during this time had a SARS-CoV-2 test done as part of standard of care. Postmortem sampling included minimally invasive tissue sampling (MITS) of lung, liver and heart tissue; blood and lung samples for bacterial culture and molecular detection of viruses (including SARS-CoV-2) and bacteria. The cause of death attribution was undertaken by a multidisciplinary team and reported using World Health Organization framework for cause of death attribution. RESULTS: SARS-CoV-2 was identified on antemortem and/or postmortem sampling in 11.7% (20/171) of deceased children, including 13.2% (12/91) in whom MITS was done. Eighteen (90%) of 20 deaths with SARS-CoV-2 infection were <12 months age. COVID-19 was attributed in the causal pathway to death in 91.7% (11/12) and 87.5% (7/8) cases with and without MITS, respectively. Lung histopathologic features in COVID-19-related deaths included diffuse alveolar damage (n = 6, 54.5%), type 2 pneumocyte proliferation (n = 6, 54.5%) and hyaline membrane formation (n = 5, 36.4%). Culture-confirmed invasive bacterial disease was evident in 54.5% (6/11) of COVID-19 attributed deaths investigated with MITS. CONCLUSIONS: COVID-19 was in the causal pathway of 10.5% (18/171) of all childhood deaths under surveillance. The postmortem histopathologic features in fatal COVID-19 cases in children were consistent with reports on COVID-19 deaths in adults; although there was a high prevalence of invasive bacterial disease in the children.


Assuntos
COVID-19/mortalidade , SARS-CoV-2/isolamento & purificação , Adolescente , COVID-19/complicações , COVID-19/patologia , COVID-19/terapia , Criança , Pré-Escolar , Feminino , Gastroenterite/complicações , Humanos , Lactente , Recém-Nascido , Masculino , Respiração Artificial , Doenças Respiratórias/complicações , Convulsões/complicações , África do Sul/epidemiologia
16.
Viruses ; 13(8)2021 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-34452378

RESUMO

Endemic human coronaviruses (HCoV) are capable of causing a range of diseases from the common cold to pneumonia. We evaluated the epidemiology and seasonality of endemic HCoVs in children hospitalized with clinical pneumonia and among community controls living in countries with a high HIV burden, namely South Africa and Zambia, between August 2011 to October 2013. Nasopharyngeal/oropharyngeal swabs were collected from all cases and controls and tested for endemic HCoV species and 12 other respiratory viruses using a multiplex real-time PCR assay. We found that the likelihood of detecting endemic HCoV species was higher among asymptomatic controls than cases (11% vs. 7.2%; 95% CI: 1.2-2.0). This was however only observed among children > 6 months and was mainly driven by the Betacoronavirus endemic species (HCoV-OC43 and -HKU1). Endemic HCoV species were detected through the year; however, in Zambia, the endemic Betacoronavirus species tended to peak during the winter months (May-August). There was no association between HIV status and endemic HCoV detection.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Coronavirus/fisiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Coronavirus/classificação , Coronavirus/genética , Coronavirus/isolamento & purificação , Infecções por Coronavirus/terapia , Hospitalização , Humanos , Lactente , Masculino , Nasofaringe/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Estações do Ano , África do Sul/epidemiologia , Zâmbia/epidemiologia
17.
Lancet HIV ; 8(9): e568-e580, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34416193

RESUMO

BACKGROUND: People living with HIV are at an increased risk of fatal outcome when admitted to hospital for severe COVID-19 compared with HIV-negative individuals. We aimed to assess safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV and HIV-negative individuals in South Africa. METHODS: In this ongoing, double-blind, placebo-controlled, phase 1B/2A trial (COV005), people with HIV and HIV-negative participants aged 18-65 years were enrolled at seven South African locations and were randomly allocated (1:1) with full allocation concealment to receive a prime-boost regimen of ChAdOx1 nCoV-19, with two doses given 28 days apart. Eligibility criteria for people with HIV included being on antiretroviral therapy for at least 3 months, with a plasma HIV viral load of less than 1000 copies per mL. In this interim analysis, safety and reactogenicity was assessed in all individuals who received at least one dose of ChAdOx1 nCov 19 between enrolment and Jan 15, 2021. Primary immunogenicity analyses included participants who received two doses of trial intervention and were SARS-CoV-2 seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinicals Trials Registry, PACTR202006922165132. FINDINGS: Between June 24 and Nov 12, 2020, 104 people with HIV and 70 HIV-negative individuals were enrolled. 102 people with HIV (52 vaccine; 50 placebo) and 56 HIV-negative participants (28 vaccine; 28 placebo) received the priming dose, 100 people with HIV (51 vaccine; 49 placebo) and 46 HIV-negative participants (24 vaccine; 22 placebo) received two doses (priming and booster). In participants seronegative for SARS-CoV-2 at baseline, there were 164 adverse events in those with HIV (86 vaccine; 78 placebo) and 237 in HIV-negative participants (95 vaccine; 142 placebo). Of seven serious adverse events, one severe fever in a HIV-negative participant was definitely related to trial intervention and one severely elevated alanine aminotranferase in a participant with HIV was unlikely related; five others were deemed unrelated. One person with HIV died (unlikely related). People with HIV and HIV-negative participants showed vaccine-induced serum IgG responses against wild-type Wuhan-1 Asp614Gly (also known as D614G). For participants seronegative for SARS-CoV-2 antigens at baseline, full-length spike geometric mean concentration (GMC) at day 28 was 163·7 binding antibody units (BAU)/mL (95% CI 89·9-298·1) for people with HIV (n=36) and 112·3 BAU/mL (61·7-204·4) for HIV-negative participants (n=23), with a rising day 42 GMC booster response in both groups. Baseline SARS-CoV-2 seropositive people with HIV demonstrated higher antibody responses after each vaccine dose than did people with HIV who were seronegative at baseline. High-level binding antibody cross-reactivity for the full-length spike and receptor-binding domain of the beta variant (B.1.351) was seen regardless of HIV status. In people with HIV who developed high titre responses, predominantly those who were receptor-binding domain seropositive at enrolment, neutralising activity against beta was retained. INTERPRETATION: ChAdOx1 nCoV-19 was well tolerated, showing favourable safety and immunogenicity in people with HIV, including heightened immunogenicity in SARS-CoV-2 baseline-seropositive participants. People with HIV showed cross-reactive binding antibodies to the beta variant and Asp614Gly wild-type, and high responders retained neutralisation against beta. FUNDING: The Bill & Melinda Gates Foundation, South African Medical Research Council, UK Research and Innovation, UK National Institute for Health Research, and the South African Medical Research Council.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Infecções por HIV/epidemiologia , SARS-CoV-2/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/epidemiologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Reações Cruzadas , Método Duplo-Cego , Feminino , Humanos , Imunogenicidade da Vacina , Masculino , Mutação , SARS-CoV-2/genética , Segurança , Vacinação
18.
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.

19.
Pediatr Surg Int ; 37(10): 1361-1370, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34213589

RESUMO

PURPOSE: We assessed management and outcomes for intussusception at nine academic hospitals in South Africa. METHODS: Patients ≤ 3 years presenting with intussusception between September 2013 and December 2017 were prospectively enrolled at all sites. Additionally, patients presenting between July 2012 and August 2013 were retrospectively enrolled at one site. Demographics, clinical information, diagnostic modality, reduction methods, surgical intervention and outcomes were reviewed. RESULTS: Four hundred seventy-six patients were enrolled, [54% males, median age 6.5 months (IQR 2.6-32.6)]. Vomiting (92%), bloody stool (91%), abdominal mass (57%), fever (32%) and a rectal mass (29%) represented advanced disease: median symptom duration was 3 days (IQR 1-4). Initial reduction attempts included pneumatic reduction (66%) and upfront surgery (32%). The overall non-surgical reduction rate was 28% and enema perforation rate was 4%. Surgery occurred in 334 (70%), 68 (20%) patients had perforated bowel, bowel resection was required in 61%. Complications included recurrence (2%) and nosocomial sepsis (4%). Length of stay (LOS) was significantly longer in patients who developed complications. Six patients died-a mortality rate of 1%. There was a significant difference in reduction rates, upfront surgery, bowel resection, LOS and mortality between centres with shorter symptom duration compared longer symptom duration. CONCLUSION: Delayed presentation was common and associated with low success for enema reduction, higher operative rates, higher rates of bowel resection and increased LOS. Improved primary health-care worker education and streamlining referral pathways might facilitate timely management.


Assuntos
Perfuração Intestinal , Intussuscepção , Criança , Enema , Feminino , Humanos , Lactente , Intussuscepção/diagnóstico , Intussuscepção/epidemiologia , Intussuscepção/cirurgia , Masculino , Estudos Retrospectivos , África do Sul/epidemiologia
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