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1.
Paediatr Drugs ; 26(2): 101-112, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38032456

RESUMO

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) in children, and is associated with long-term pulmonary sequelae for up to 30 years after infection. The mainstay of RSV management is supportive therapy such as supplemental oxygen. Palivizumab (Synagis™-AstraZeneca), a monoclonal antibody targeting the RSV F protein site II, has been licensed for the prevention of RSV in high-risk groups since 1998. There has been recent promising progress in preventative strategies that include vaccines and long-acting, high-potency monoclonal antibodies. Nirsevimab (Beyfortus™-AstraZeneca/Sanofi), a monoclonal antibody with an extended half-life, has recently been registered in the European Union and granted licensure by the US Food and Drug Administration. Furthermore, a pre-fusion sub-unit protein vaccine has been granted licensure for pregnant women, aimed at protecting their young infants, following established safety and efficacy in clinical trials (Abrysvo™-Pfizer). Also, multiple novel antiviral therapeutic options are in early phase clinical trials. The next few years have the potential to change the landscape of LRTI through improvements in the prevention and management of RSV LRTI. Here, we discuss these new approaches, current research, and clinical trials in novel therapeutics, monoclonal antibodies, and vaccines against RSV infection in infants and children.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas , Gravidez , Estados Unidos , Criança , Lactente , Feminino , Humanos , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Palivizumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , União Europeia
2.
Front Pediatr ; 11: 1247638, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37645034

RESUMO

Introduction: International guidelines recommend a multi-faceted approach for successful diagnoses of primary ciliary dyskinesia (PCD). In the absence of a gold standard test, a combination of genetic testing/microscopic analysis of structure and function/nasal nitric oxide measurement is used. In resource-limited settings, often none of the above tests are available, and in South Africa, only transmission electron microscopy (TEM) is available in central anatomical pathology departments. The aim of this study was to describe the clinical and ultrastructural findings of suspected PCD cases managed by pediatric pulmonologists at a tertiary-level state funded hospital in Johannesburg. Methods: Nasal brushings were taken from 14 children with chronic respiratory symptoms in keeping with a PCD phenotype. Ultrastructural analysis in accordance with the international consensus guidelines for TEM-PCD diagnostic reporting was undertaken. Results: TEM observations confirmed 43% (6) of the clinically-suspected cases (hallmark ultrastructural defects in the dynein arms of the outer doublets), whilst 57% (8) required another PCD testing modality to support ultrastructural observations. Of these, 25% (2) had neither ultrastructural defects nor did they present with bronchiectasis. Of the remaining cases, 83% (5) had very few ciliated cells (all of which were sparsely ciliated), together with goblet cell hyperplasia. There was the apparent absence of ciliary rootlets in 17% (1) case. Discussion: In resource-limited settings in which TEM is the only available testing modality, confirmatory and probable diagnoses of PCD can be made to facilitate early initiation of treatment of children with chronic respiratory symptoms.

3.
S Afr Med J ; 113(6): 20-23, 2023 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-37278266

RESUMO

Bronchiolitis, a common reason for infant hospitalisation in South Africa (SA), is caused by viral pathogens. Bronchiolitis is typically an illness of mild to moderate severity that occurs in well-nourished children. Hospitalised SA infants frequently have severe disease and/or coexisting medical conditions, and these cases of bronchiolitis may have bacterial co-infection that requires antibiotic therapy. However, the existence of widespread antimicrobial resistance in SA warrants the judicious use of antibiotics. This commentary describes: (i) common clinical pitfalls leading to an incorrect diagnosis of bronchopneumonia; and (ii) considerations for antibiotic therapy in hospitalised infants with bronchiolitis. If antibiotics are prescribed, the indication for their use should be clearly stated, and antibiotic therapy must be stopped promptly if investigations indicate that bacterial co-infection is unlikely. Until more robust data emerge, we recommend a pragmatic management strategy to inform antibiotic use in hospitalised SA infants with bronchiolitis in whom bacterial co-infection is suspected.


Assuntos
Infecções Bacterianas , Bronquiolite Viral , Bronquiolite , Broncopneumonia , Coinfecção , Lactente , Criança , Humanos , Antibacterianos/uso terapêutico , Broncopneumonia/tratamento farmacológico , Broncopneumonia/complicações , Coinfecção/tratamento farmacológico , África do Sul/epidemiologia , Bronquiolite/diagnóstico , Bronquiolite/tratamento farmacológico , Bronquiolite/complicações , Infecções Bacterianas/tratamento farmacológico , Bronquiolite Viral/complicações , Bronquiolite Viral/tratamento farmacológico
4.
Lancet Infect Dis ; 23(9): 1031-1041, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37141913

RESUMO

BACKGROUND: Non-pharmaceutical interventions affected the circulation of and illness due to endemic respiratory pathogens during the COVID-19 pandemic. We investigated the incidence of admissions to hospital for overall and specific pathogen-associated lower respiratory tract infection (LRTI) during the COVID-19 pandemic compared with incidence in the pre-pandemic period. METHODS: In this observational study, we analysed surveillance data for children younger than 5 years from two public hospitals in Soweto, South Africa, for all-cause LRTI, respiratory syncytial virus (RSV), influenza, human metapneumovirus, and Bordetella pertussis from Jan 1, 2015 to Dec 31, 2022. Data were obtained from an electronic database that includes information for all admissions to the general paediatric wards at the two hospitals, automatically identified by a computer program. We excluded children admitted to hospital with incidental SARS-CoV-2 infection or COVID-19 without LRTI diagnosis. Incidence during COVID-19 pandemic years (2020, 2021, and 2022) were compared with pre-pandemic rates (2015-19). FINDINGS: Overall, there were 42 068 all-cause hospital admissions, including 18 303 all-cause LRTI hospital admissions, from Jan 1, 2015, to Dec 31, 2022, 17 822 (42·4%) of whom were female, 23 893 (57·0%) were male, and 353 (0·8%) had missing data. All-cause LRTI incidence risk ratio (IRR) was 30% lower in 2020 (IRR 0·70, 95% CI 0·67-0·74) and 13% lower in 2021 (0·87, 0·83-0·91), but 16% higher in 2022 (1·16, 1·11-1·21) compared with the pre-pandemic period. Furthermore, compared with the pre-pandemic period, incidence of RSV-associated LRTI (0·52, 0·45-0·58), influenza-associated LRTI (0·05, 0·02-0·11), and pulmonary tuberculosis (0·52, 0·41-0·65) were lower in 2020, with similar trends observed for human-metapneumovirus-associated LRTI, pertussis, and invasive pneumococcal disease (IPD). Compared with the pre-pandemic period, by 2022, RSV-associated LRTI incidence was similar (1·04, 0·95-1·14) and influenza-associated LRTI showed a non-significant increase (1·14, 0·92-1·39), whereas incidence remained lower for tuberculosis (0·79, 0·65-0·94) and IPD (0·51, 0·24-0·99). In 2022, the incidence of COVID-19-associated LRTI hospital admission (65 per 100 000 children younger than 5 years) was lower than pre-pandemic RSV-associated LRTI (0·23, 0·19-0·27) but higher than pre-pandemic influenza-associated LRTI (1·19, 0·97-1·45), although the difference was not significant. All-cause LRTI death in 2022 (57 per 100 000 children younger than 5 years) was 28% higher than in the pre-pandemic period (1·28, 1·03-1·58). INTERPRETATION: The higher incidence of all-cause LRTI admissions to hospital in 2022 compared with the pre-pandemic period is partly due to ongoing COVID-19 admission to hospital, and could worsen if other endemic respiratory pathogens revert to pre-pandemic incidence. Interventions, including the introduction of vaccines for people who are pregnant that aim to prevent RSV and possibly COVID-19 in young children, are warranted. FUNDING: The Bill & Melinda Gates Foundation.


Assuntos
COVID-19 , Influenza Humana , Infecções Pneumocócicas , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Gravidez , Humanos , Masculino , Feminino , Criança , Lactente , Pré-Escolar , Pandemias , África do Sul/epidemiologia , Influenza Humana/epidemiologia , COVID-19/epidemiologia , COVID-19/complicações , SARS-CoV-2 , Infecções Respiratórias/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções Pneumocócicas/epidemiologia , Hospitais
5.
BMJ Open Respir Res ; 10(1)2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37169402

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of hospitalisation for lower respiratory tract infection (LRTI) in children. RSV LRTI during early childhood may increase susceptibility to recurrent wheezing and asthma. RESEARCH QUESTION: The aim of this study was to describe the pulmonary sequelae at 1 and 2 years of age following RSV LRTI hospitalisation during the first year of life in term infants. STUDY DESIGN AND METHODS: A longitudinal case-control study was undertaken from April 2016 to December 2019. Cases constituted children hospitalised with PCR-confirmed RSV LRTI during infancy and controls were children not previously hospitalised with LRTI. A questionnaire detailing environmental and medical history, as well as a modified International Study of Asthma and Allergies (ISAAC) questionnaire, was administered, and pulmonary function testing, including oscillometry, tidal breath flow-volume loops and multiple breath wash-out, was performed, at one and two years of age. RESULTS: One (n=308) and two-year-old (n=214) cases were more likely than one (n=292) and two-year-old (n=209) controls to have experienced clinical pulmonary symptoms, including wheezing ((55% vs 24%; p<0.001) and (61% vs 16%; p<0.001)), received treatment for wheezing ((17 vs 8%; p<0.001) and (51 vs 6%; p<0.001)) and had any admissions for wheezing ((31 vs 6%; p<0.001) and (46 vs 1.4%; p<0.001)) or any LRTI ((24 vs 2%; p<0.001) and (32 vs 1.4%; p<0.001)), after the initial RSV hospitalisation. RSV LRTI during infancy was associated with an increase in airway resistance by two years (22.46 vs 20.76 hPa.s.l-1 (p=0.022)), along with a decrease in compliance at both one (-4.61 vs -3.09 hPa.s/l (p<0.001)) and two years (-0.99 vs 0.33 hPa.s/l1 (p<0.001)). There was an increased work of breathing at one year, but this was no longer present at two years. INTERPRETATION: RSV LRTI during infancy in cases was associated with more clinical and pulmonary function sequelae through to two years of age.


Assuntos
Asma , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Humanos , Lactente , Pré-Escolar , Estudos de Casos e Controles , Sons Respiratórios/etiologia , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/terapia , Infecções Respiratórias/complicações , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/terapia , Asma/complicações , Progressão da Doença , Hospitalização
6.
BioDrugs ; 37(3): 295-309, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37097594

RESUMO

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) in children, causing approximately 3.6 million hospitalizations per year, and has been associated with long-term pulmonary sequelae for up to 30 years after infection, yet preventative strategies and active treatment options remain elusive. The associated morbidity and healthcare related costs could be decreased substantially with the development of these much-needed medications. After an initial false start in the development of an RSV vaccine, gradual progress is now being made with the development of multiple vaccine candidates using numerous different mechanisms of action. Furthermore, nirsevimab, a new monoclonal antibody for the prevention of RSV, has recently been registered in the European Union. New novel treatments for RSV infection are also in the pipeline, which would provide the clinician with much needed ammunition in the management of the acute disease. The next few years have the potential to change the landscape of LRTI forever through the prevention and management of RSV LRTI and thereby decrease the mortality and morbidity associated with it. In this review, we discuss these new approaches, current research, and clinical trials in monoclonal antibody and vaccine development against RSV.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Criança , Humanos , Lactente , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Imunização Passiva , Infecções Respiratórias/prevenção & controle , Anticorpos Monoclonais/uso terapêutico
7.
Lancet Infect Dis ; 23(7): 856-866, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36940703

RESUMO

BACKGROUND: Nirsevimab is an extended half-life monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that has been developed to protect infants for an entire RSV season. Previous studies have shown that the nirsevimab binding site is highly conserved. However, investigations of the geotemporal evolution of potential escape variants in recent (ie, 2015-2021) RSV seasons have been minimal. Here, we examine prospective RSV surveillance data to assess the geotemporal prevalence of RSV A and B, and functionally characterise the effect of the nirsevimab binding-site substitutions identified between 2015 and 2021. METHODS: We assessed the geotemporal prevalence of RSV A and B and nirsevimab binding-site conservation between 2015 and 2021 from three prospective RSV molecular surveillance studies (the US-based OUTSMART-RSV, the global INFORM-RSV, and a pilot study in South Africa). Nirsevimab binding-site substitutions were assessed in an RSV microneutralisation susceptibility assay. We contextualised our findings by assessing fusion-protein sequence diversity from 1956 to 2021 relative to other respiratory-virus envelope glycoproteins using RSV fusion protein sequences published in NCBI GenBank. FINDINGS: We identified 5675 RSV A and RSV B fusion protein sequences (2875 RSV A and 2800 RSV B) from the three surveillance studies (2015-2021). Nearly all (25 [100%] of 25 positions of RSV A fusion proteins and 22 [88%] of 25 positions of RSV B fusion proteins) amino acids within the nirsevimab binding site remained highly conserved between 2015 and 2021. A highly prevalent (ie, >40·0% of all sequences) nirsevimab binding-site Ile206Met:Gln209Arg RSV B polymorphism arose between 2016 and 2021. Nirsevimab neutralised a diverse set of recombinant RSV viruses, including new variants containing binding-site substitutions. RSV B variants with reduced susceptibility to nirsevimab neutralisation were detected at low frequencies (ie, prevalence <1·0%) between 2015 and 2021. We used 3626 RSV fusion-protein sequences published in NCBI GenBank between 1956 and 2021 (2024 RSV and 1602 RSV B) to show that the RSV fusion protein had lower genetic diversity than influenza haemagglutinin and SARS-CoV-2 spike proteins. INTERPRETATION: The nirsevimab binding site was highly conserved between 1956 and 2021. Nirsevimab escape variants were rare and have not increased over time. FUNDING: AstraZeneca and Sanofi.


Assuntos
COVID-19 , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Lactente , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estudos Prospectivos , Projetos Piloto , SARS-CoV-2 , Vírus Sincicial Respiratório Humano/genética , Glicoproteínas , Sítios de Ligação
8.
J Pediatric Infect Dis Soc ; 12(1): 53-55, 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36306473

RESUMO

Using hospital surveillance data, we estimated Human metapneumovirus (hMPV) hospitalization incidence by age and HIV-exposure status. hMPV-associated hospitalization incidence was highest in <1-year children. Incidence rate ratios of HIV-exposed over unexposed children were 1.5 (95%CI 0.9-2.4) for <6-month children, 1.4 (95%CI 0.7-2.4) for 6- to 11-month children and 0.9 (95%CI 0.4-1.9) for 12- to 59-month children.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Metapneumovirus , Infecções por Paramyxoviridae , Infecções Respiratórias , Criança , Humanos , Lactente , África do Sul/epidemiologia , Infecções por HIV/epidemiologia , Hospitalização , Infecções por Paramyxoviridae/epidemiologia
9.
Front Pediatr ; 10: 1033125, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440349

RESUMO

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed.

10.
Front Pediatr ; 10: 954608, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958169

RESUMO

Bronchiectasis (BE) is a chronic condition affecting the bronchial tree. It is characterized by the dilatation of large and medium-sized airways, secondary to damage of the underlying bronchial wall structural elements and accompanied by the clinical picture of recurrent or persistent cough. Despite an increased awareness of childhood BE, there is still a paucity of data on the epidemiology, pathophysiological phenotypes, diagnosis, management, and outcomes in Africa where the prevalence is mostly unmeasured, and likely to be higher than high-income countries. Diagnostic pathways and management principles have largely been extrapolated from approaches in adults and children in high-income countries or from data in children with cystic fibrosis. Here we provide an overview of pediatric BE in Africa, highlighting risk factors, diagnostic and management challenges, need for a global approach to addressing key research gaps, and recommendations for practitioners working in Africa.

11.
BMJ Open Respir Res ; 9(1)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35577452

RESUMO

BACKGROUND: Diagnosis of pneumonia remains challenging. Digitally recorded and remote human classified lung sounds may offer benefits beyond conventional auscultation, but it is unclear whether classifications differ between the two approaches. We evaluated concordance between digital and conventional auscultation. METHODS: We collected digitally recorded lung sounds, conventional auscultation classifications and clinical measures and samples from children with pneumonia (cases) in low-income and middle-income countries. Physicians remotely classified recordings as crackles, wheeze or uninterpretable. Conventional and digital auscultation concordance was evaluated among 383 pneumonia cases with concurrently (within 2 hours) collected conventional and digital auscultation classifications using prevalence-adjusted bias-adjusted kappa (PABAK). Using an expanded set of 737 cases that also incorporated the non-concurrently collected assessments, we evaluated whether associations between auscultation classifications and clinical or aetiological findings differed between conventional or digital auscultation using χ2 tests and logistic regression adjusted for age, sex and site. RESULTS: Conventional and digital auscultation concordance was moderate for classifying crackles and/or wheeze versus neither crackles nor wheeze (PABAK=0.50), and fair for crackles-only versus not crackles-only (PABAK=0.30) and any wheeze versus no wheeze (PABAK=0.27). Crackles were more common on conventional auscultation, whereas wheeze was more frequent on digital auscultation. Compared with neither crackles nor wheeze, crackles-only on both conventional and digital auscultation was associated with abnormal chest radiographs (adjusted OR (aOR)=1.53, 95% CI 0.99 to 2.36; aOR=2.09, 95% CI 1.19 to 3.68, respectively); any wheeze was inversely associated with C-reactive protein >40 mg/L using conventional auscultation (aOR=0.50, 95% CI 0.27 to 0.92) and with very severe pneumonia using digital auscultation (aOR=0.67, 95% CI 0.46 to 0.97). Crackles-only on digital auscultation was associated with mortality compared with any wheeze (aOR=2.70, 95% CI 1.12 to 6.25). CONCLUSIONS: Conventional auscultation and remotely-classified digital auscultation displayed moderate concordance for presence/absence of wheeze and crackles among cases. Conventional and digital auscultation may provide different classification patterns, but wheeze was associated with decreased clinical severity on both.


Assuntos
Percas , Pneumonia , Estetoscópios , Animais , Auscultação , Estudos de Casos e Controles , Criança , Saúde da Criança , Humanos , Pulmão , Pneumonia/diagnóstico , Sons Respiratórios/diagnóstico
12.
J Pediatric Infect Dis Soc ; 11(7): 341-344, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35390156

RESUMO

Transplacental hMPV-neutralizing antibody transfer was reduced from mothers living with HIV-1. However, a comparison of antibody titers at birth between hMPV hospitalization cases at <6 months and matched controls suggested that reduced maternal antibody might not be the primary cause of the previously reported elevated hMPV risk in HIV-1-exposed infants.


Assuntos
HIV-1 , Metapneumovirus , Infecções por Paramyxoviridae , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Recém-Nascido
13.
Influenza Other Respir Viruses ; 16(1): 34-47, 2022 01.
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.


Assuntos
COVID-19 , Adolescente , Criança , Pré-Escolar , Feminino , Hospitais , Humanos , Lactente , Masculino , Fatores de Risco , SARS-CoV-2 , África do Sul/epidemiologia
14.
Pediatr Infect Dis J ; 40(9S): S59-S68, 2021 09 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.


Assuntos
Pneumonia/etiologia , Teorema de Bayes , Estudos de Casos e Controles , Saúde da Criança , Pré-Escolar , Países em Desenvolvimento , Feminino , Infecções por HIV , Hospitalização , Humanos , Lactente , Modelos Logísticos , Masculino , Gravidade do Paciente , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Fatores de Risco , África do Sul/epidemiologia , Vacinação
15.
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.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/etiologia , Antirretrovirais/uso terapêutico , Coinfecção/etiologia , HIV-1 , Pneumonia/etiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Teorema de Bayes , Estudos de Casos e Controles , Saúde da Criança , Pré-Escolar , Coinfecção/diagnóstico , Coinfecção/epidemiologia , Coinfecção/prevenção & controle , Países em Desenvolvimento , Feminino , Hospitalização , Humanos , Lactente , Modelos Logísticos , Masculino , Gravidade do Paciente , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Fatores de Risco , África do Sul/epidemiologia
17.
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
18.
Clin Infect Dis ; 73(10): 1896-1900, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33949670

RESUMO

From April to September 2020, we investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in a cohort of 396 healthcare workers (HCWs) from 5 departments at Chris Hani Baragwanath Hospital, South Africa. Overall, 34.6% of HCWs had polymerase chain reaction-confirmed SARS-CoV-2 infection (132.1 [95% confidence interval, 111.8-156.2] infections per 1000 person-months); an additional 27 infections were identified by serology. HCWs in the internal medicine department had the highest rate of infection (61.7%). Among polymerase chain reaction-confirmed cases, 10.4% remained asymptomatic, 30.4% were presymptomatic, and 59.3% were symptomatic.


Assuntos
COVID-19 , SARS-CoV-2 , Estudos de Coortes , Pessoal de Saúde , Humanos , Estudos Longitudinais , África do Sul/epidemiologia
19.
Bone Rep ; 14: 100751, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33644265

RESUMO

INTRODUCTION: We hypothesized that the prevalence of vertebral fractures would be low and that bone mineral density (BMD) would be less severely affected in a black South African (SA) population treated with glucocorticoids (GCs) than that reported in mainly white populations. METHODS: All children aged 5-17.9 years with chronic non-malignant illnesses who were on GCs (intravenous or oral) for greater than 3 months duration were evaluated. DXA scans were performed using a Hologic Discovery machine (Software version Apex 4.0.2) and the Hologic paediatric reference database. Whole body less head (WBLH) and lumbar spine (LS) bone mineral content (BMC) and density (BMD) Z-scores unadjusted and adjusted for height were calculated using the Zemel equation calculator. RESULTS: Seventy-two patients (49% with renal, 24% with rheumatic, 14% with neurological, 11% with hepatic and 3% with respiratory conditions; mean age 11.6 ± 3.3 years, 57% boys, 92% SA black) were enrolled. The mean duration of GC treatment was 34.1 (±25.1) months. Mean WBLH and LS height adjusted BMD Z-scores were -1.2 ± 1.5 and -0.9 ± 1.0 respectively. Eleven percent of patients had a LS height adjusted BMD Z-score ≤ -2. The prevalence of vertebral fractures on lateral vertebral fracture assessment (VFA) was 15% (11 of 72 patients). CONCLUSION: The prevalence of vertebral fractures (15%) in predominantly black children on GCs with chronic non-malignant illnesses is similar to that reported from North America suggesting that routine yearly DXA scans including VFA are warranted in this highly at-risk population.

20.
Pediatr Infect Dis J ; 40(5): 479-485, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33480663

RESUMO

BACKGROUND: Human metapneumovirus (hMPV) has been associated with upper and lower respiratory tract infections (LRTI) in children and adults. This systematic review evaluated the epidemiology of hMPV-associated LRTI, including severe acute respiratory infection (SARI) hospitalization or clinically diagnosed severe pneumonia, in African children under 5 years of age. METHODS: We searched Science Direct, PubMed, Cochrane Central, Scopus, and WHO regional databases using the terms "("Human metapneumovirus" AND "Africa") OR ("hMPV" AND "Africa")" up to September 17, 2020. Other sources included ClinicalTrials.gov to obtain unpublished data. Studies were included if children were less than 5 years of age and hospitalized with hMPV-associated LRTI, SARI or if clinically diagnosed with severe pneumonia in the community. The main outcomes were prevalence of hMPV identified among children with hospitalized LRTI or SARI. We further calculated odds ratios for hMPV in cases with LRTI compared with non-LRTI controls. Pooled results were calculated using a random-effects model. RESULTS: Thirty studies were eligible for inclusion in the review. The prevalence of hMPV-LRTI/SARI among hospitalized and severe pneumonia cases was 4.7% [95% confidence interval (CI): 3.9-5.6, I2 = 95.0]. The case-control studies indicated that hMPV was 2.0-fold (95% CI: 0.9-4.4) more likely to be identified in LRTI cases (10.3%) than controls (6.0%). Three of 5 studies reported hMPV-associated LRTI case fatality risk, with a pooled estimate of 1.3% (95% CI: 0.3-2.9; I2 = 49). CONCLUSIONS: hMPV was associated with approximately 5% of LRTI/SARI hospitalizations or severe pneumonia cases in Africa.


Assuntos
Metapneumovirus , Infecções por Paramyxoviridae/epidemiologia , Infecções Respiratórias/epidemiologia , África/epidemiologia , Pré-Escolar , Hospitalização , Humanos , Lactente , Infecções por Paramyxoviridae/virologia , Pneumonia/epidemiologia , Pneumonia/virologia , Prevalência , Infecções Respiratórias/virologia
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