Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries

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

Vaccine response in hematopoietic stem cell transplantation at the Clinical Hospital of the Faculty of Medicine of Ribeirão Preto

Introdução: Nos pacientes que realizam transplante de células-tronco hematopoiéticas (TCTH), a morbilidade e a mortalidade estão frequentemente relacionadas com doenças infecciosas, muitas delas passíveis de prevenção imunológica. Rotineiramente, esquemas de revacinação são aplicados após o transplante, porém seu potencial imunogênico nesses pacientes é pouco conhecido. O presente estudo visa avaliar a resposta imunológica de pacientes submetidos a TCTH a vacinas inativadas e vivas atenuadas. Metodologia: Trata-se de um estudo longitudinal, prospectivo, com coleta de dados clínicos e amostras de sangue de pacientes em seguimento pós-transplante autólogo ou alogênico, para tratamento de leucemias, falências medulares, doenças autoimunes e hemoglobinopatias. Dois grupos de pacientes foram avaliados de janeiro de 2018 até dezembro de 2020. No grupo A avaliou-se a resposta vacinal para difteria, tétano e pertussis aos 6 meses pós-transplante (prévacinação), e aos 12 meses pós-transplante (pós-vacinação); e no grupo B avaliou-se a resposta vacinal ao sarampo aos 24 meses pós-transplante (pré-vacinação) e aos 30 meses póstransplante (pós-vacinação). Os grupos foram analisados quanto à resposta vacinal, definida através de títulos de anticorpos específicos contra as vacinas, antes e após a imunização. Os resultados foram correlacionados com características clínicas dos pacientes e dos transplantes. Resultados: Em nosso estudo, identificamos que a vacina dTpa provoca uma adequada resposta vacinal contra difteria e tétano em pacientes pós-transplante de células-tronco hematopoiéticas. Porém, uma proporção importante de pacientes não atingiu níveis adequados para garantir proteção de longo prazo. Além disso, a resposta vacinal contra a pertussis mostrou-se deficiente. Também identificamos uma melhor resposta vacinal contra difteria nas crianças do que nos adultos, resultado que precisa ser comprovado por estudos com maior número de pacientes, mas que demonstra especificidades do sistema imunológico infantil. Com relação à imunização contra o sarampo, metade do grupo respondeu, porém com um número muito pequeno de pacientes para definir se houve resposta adequada à vacinação. Fatores como o tipo de transplante, regime de condicionamento, e uso de globulina anti-timocítica não influenciaram a resposta vacinal em nenhum dos grupos. Conclusões: Consideramos importantes os achados do nosso estudo com relação à resposta vacinal no pós-transplante de células-tronco hematopoiéticas no Brasil. Acreditamos que novos estudos poderão dar continuidade a esses achados iniciais, contribuindo para melhorar e padronizar a assistência vacinal aos pacientes transplantados. Os transplantes são uma área da saúde em franco progresso, com cada vez maior sobrevida do paciente transplantado, portanto torna-se importante garantir a adequada proteção contra infecções.Background: in hematopoietic stem cell transplantation, morbidity and mortality are largely related to infectious diseases, many of them subject to immunological prevention. Routinely, revaccination regimens are applied after transplantation, although their immunogenic potential in patients is poorly evaluated. The present study aims to evaluate the immune response to inactivated and live vaccines in patients treated with hematopoietic stem cell transplantation (HSCT). Methodology: This is a prospective, longitudinal study, including patients that underwent autologous or allogeneic post-transplantation for the treatment of leukemias, bone marrow failure, autoimmune diseases, and hemoglobinopathies. Patients were recruited from January 2018 to December 2020 and were divided into two groups. Group A was evaluated for vaccine responses to diphtheria, tetanus and pertussis at 6 months after transplant (pre-vaccination), and at 12 months after transplant (post-vaccination). Group B was evaluated for vaccine responses to measles at 24 months post-transplant (pre-vaccination), and 30 months after transplant (postvaccination). Vaccine response was determined according to specific anti-vaccine antibody titers, before and after immunizations. The results were correlated with patients and transplant characteristics. Results: In our study we identified that the dTpa vaccine induced an adequate vaccine response for diphtheria and tetanus in patients after HSCT. However, an important proportion of patients did not meet long-term protection antibody levels. In addition, the vaccine response to pertussis immunization was insufficient to warrant protection. We also identified better vaccine responses against diphtheria in children than in adults. While these results should be confirmed by studies with a larger number of patients, they show how the child\'s immune system has specificities. Regarding the measles response, half of the group responded, but with few patients to define an adequate response to vaccination. Type of transplant, conditioning regimen, and use of anti-thymocyte globulin did not affect responses to vaccination. Conclusions: This is an important study that evaluated vaccine responses after HSCT in Brazil. Further studies can help to improve and standardize the vaccination in the post-transplantation setting. Transplants are an area of health in full progress and increasing importance. As survival of the transplanted patient increases, it becomes essential to ensure adequate protection against infections

Is community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) an emerging pathogen among children in Brazil?

ABSTRACT Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is spreading worldwide, but little is known about the epidemiology of this pathogen in Brazil. Objective: To evaluate clinical and microbiological features of children with S. aureus infections admitted to a university hospital. Methods: This was a cross-sectional study evaluating the potential risk factors for CA-MRSA, and a retrospective cohort evaluating in-hospital clinical outcomes. To include patients with both community and hospital-associated infections, we screened the results of the microbiological laboratory tests from January 1, 2012, to December 31, 2016. According to the phenotype, we classified the isolates in Methicillin-Susceptible S. aureus (MSSA), Hospital-Associated Methicillin-Resistant S. aureus (HA-MRSA), and CA-MRSA. Clinical data were collected from the patients’ medical records. Results: We identified 279 cases of S. aureus infections (MSSA = 163, CA-MRSA = 69, HA-MRSA = 41). Overall, the incidence density of CA-MRSA and MSSA infections increased while the HA-MRSA incidence density decreased over the study period. CA-MRSA infected patients were more likely to present with skin and soft tissue infections (OR: 2.83, 95%CI: 1.54–5.33, p < 0.001) and osteomyelitis (OR: 4.76; 95%CI: 1.16–22.71, p = 0.014) when compared to MSSA and HA-MRSA infections. Unadjusted case fatality rates were similar between MSSA-infected patients (3.14%, 5/159) and CA-MRSA infected patients (3.80%, 3/79, p = 0.792), while HA-MRSA infected patients were more likely to die in the hospital (12.20%, 5/41, p = 0.013). Conclusions: CA-MRSA is an emergent pediatric pathogen in Brazil. Our results highlight the relevance of choosing an appropriate initial antimicrobial drug for treating children with severe S. aureus infections

Treatment of multisystem inflammatory syndrome in children

BACKGROUND: Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.METHODS: We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.RESULTS: Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.CONCLUSIONS: We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).</p

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

BackgroundMultisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments.MethodsThe Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370.FindingsWe enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p&lt;0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p&lt;0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups.InterpretationRecovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries.FundingImperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health