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BACKGROUND: Despite the reduction in global under-5 mortality over the last decade, childhood deaths remain high. To combat this, there has been a shift in focus from disease-specific interventions to use of healthcare data for resource allocation, evaluation of performance and impact, and accountability. This is a descriptive analysis of data derived from a prospective cohort study describing paediatric admissions to a tertiary referral hospital in Malawi for the purpose of process evaluation and quality improvement. METHODS: Using a REDCap database, we collected data for patients admitted acutely to Kamuzu Central Hospital, a tertiary referral centre in the central region. Data were collected from 17 123 paediatric inpatients from 2017 to 2020. RESULTS: Approximately 6% of patients presented with either two or more danger signs or severely abnormal vital signs. Infants less than 6 months, who had the highest mortality rate, were also the most critically ill on arrival to the hospital. Sepsis was diagnosed in about 20% of children across all age groups. Protocols for the management of high-volume, lower-acuity conditions such as uncomplicated malaria and pneumonia were generally well adhered to, but there was a low rate of completion for labs, radiology studies and subspecialty consultations required to provide care for high acuity or complex conditions. The overall mortality rate was 4%, and 60% of deaths occurred within the first 48 hours of admission. CONCLUSION: Our data highlight the need to improve the quality of care provided at this tertiary-level centre by focusing on the initial stabilisation of high-acuity patients and augmenting resources to provide comprehensive care. This may include capacity building through the training of specialists, implementation of clinical processes, provision of specialised equipment and increasing access to and reliability of ancillary services. Data collection, analysis and routine use in policy and decision-making must be a pillar on which improvement is built.
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Melhoria de Qualidade , Centros de Atenção Terciária , Humanos , Malaui/epidemiologia , Lactente , Pré-Escolar , Feminino , Masculino , Criança , Estudos Prospectivos , Recém-Nascido , Adolescente , Hospitalização/estatística & dados numéricosRESUMO
BACKGROUND: RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the control group. METHODS: To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria (to exclude the effect of naturally acquired immunity) using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009-2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and background malaria incidence. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01. RESULTS: We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by background incidence or parasitemia during the primary vaccination series. CONCLUSIONS: We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that control-group immunity is likely a major reason for lower efficacy in high transmission settings, not reduced immune responses to RTS,S/AS01. This may be reassuring for implementation in high transmission settings, though further studies are needed.
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Vacinas Antimaláricas , Malária Falciparum , Malária , Humanos , Formação de Anticorpos , Incidência , Malária/epidemiologia , Malária/prevenção & controle , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Parasitemia/epidemiologia , Plasmodium falciparum , Vacinação , Ensaios Clínicos Fase III como AssuntoRESUMO
Background: RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the control group. Methods: To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria to exclude the delayed malaria effect using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009-2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and malaria transmission intensity. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01. Results: We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by transmission intensity or parasitemia during the primary vaccination series. Conclusions: We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that delayed malaria is likely the main reason for lower efficacy in high transmission settings, not reduced immune responses. This may be reassuring for implementation in high transmission settings, though further studies are needed.
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Diagnosis-specific mortality is a measure of pediatric healthcare quality that has been incompletely studied in sub-Saharan African hospitals. Identifying the mortality rates of multiple conditions at the same hospital may allow leaders to better target areas for intervention. In this secondary analysis of routinely collected data, we investigated hospital mortality by admission diagnosis in children aged 1-60 months admitted to a tertiary care government referral hospital in Malawi between October 2017 and June 2020. The mortality rate by diagnosis was calculated as the number of deaths among children admitted with a diagnosis divided by the number of children admitted with the same diagnosis. There were 24,452 admitted children eligible for analysis. Discharge disposition was recorded in 94.2% of patients, and 4.0% (N = 977) died in the hospital. The most frequent diagnoses among admissions and deaths were pneumonia/bronchiolitis, malaria, and sepsis. The highest mortality rates by diagnosis were found in surgical conditions (16.1%; 95% CI: 12.0-20.3), malnutrition (15.8%; 95% CI: 13.6-18.0), and congenital heart disease (14.5%; 95% CI: 9.9-19.2). Diagnoses with the highest mortality rates were alike in their need for significant human and material resources for medical care. Improving mortality in this population will require sustained capacity building in conjunction with targeted quality improvement initiatives against both common and deadly diseases.
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Governo , Hospitalização , Criança , Humanos , Lactente , Malaui/epidemiologia , Atenção Terciária à Saúde , Centros de Atenção TerciáriaRESUMO
BACKGROUND: RTS,S/AS01 is the first malaria vaccine to be approved and recommended for widespread implementation by the World Health Organization (WHO). Trials reported lower vaccine efficacies in higher-incidence sites, potentially due to a "rebound" in malaria cases in vaccinated children. When naturally acquired protection in the control group rises and vaccine protection in the vaccinated wanes concurrently, malaria incidence can become greater in the vaccinated than in the control group, resulting in negative vaccine efficacies. METHODS: Using data from the 2009-2014 phase III trial (NCT00866619) in Lilongwe, Malawi; Kintampo, Ghana; and Lambaréné, Gabon, we evaluate this hypothesis by estimating malaria incidence in each vaccine group over time and in varying transmission settings. After estimating transmission intensities using ecological variables, we fit models with 3-way interactions between vaccination, time, and transmission intensity. RESULTS: Over time, incidence decreased in the control group and increased in the vaccine group. Three-dose efficacy in the lowest-transmission-intensity group (0.25 cases per person-year [CPPY]) decreased from 88.2% to 15.0% over 4.5 years, compared with 81.6% to -27.7% in the highest-transmission-intensity group (3 CPPY). CONCLUSIONS: These findings suggest that interventions, including the fourth RTS,S dose, that protect vaccinated individuals during the potential rebound period should be implemented for high-transmission settings.
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Vacinas Antimaláricas , Malária Falciparum , Malária , Criança , Humanos , Lactente , Malária Falciparum/epidemiologia , Gana , Malaui , Gabão , Plasmodium falciparumRESUMO
Black South Africans accounted for 6.2 out of 6.4 million people living with HIV in South Africa in 2012, highlighting extreme racial disparities in HIV infection. These racial disparities are the result of structural and historical factors, specifically, the racist policies which were facilitated by segregation before, during, and after Apartheid. First, we describe the theoretical context of how racist policies and segregation are linked to HIV prevalence. Next, using data from a 2012 national survey of South Africans (SABSSM IV) and Statistics South Africa (StatsSA), we describe the race-specific geospatial distribution of HIV in South Africa, provide empirical evidence for the impact of Apartheid on important risk factors for HIV infection, and describe the relationship between these risk factors and HIV within racial groups. Using multilevel logistic regression, we find that segregation increases the odds of HIV infection among Black South Africans, even after adjusting for many covariates which are sometimes blamed, in place of structural factors, for a higher HIV prevalence in Black South Africans. We found that the estimated odds of infection in the most segregated municipality was 1.95 (95% CI: 1.15, 3.32) times the odds of infection in the least segregated municipality for Black South Africans. In addition to segregation, we also find other covariates to be differentially associated with HIV infection depending on race, such as gender, age, and sexual behavior. We also find that the HIV infection odds ratio comparing Black and Coloured (i.e., multiple ethnic groups with mixed ancestries from Africa, Asia, and Europe) South Africans varies over space. These results continue to build evidence for the influence of structural and historical factors on the modern geospatial and demographic distribution of HIV.
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Apartheid , Infecções por HIV , Etnicidade , Infecções por HIV/epidemiologia , Humanos , Políticas , África do Sul/epidemiologiaRESUMO
The interleukin-6 receptor antagonist tocilizumab became widely used early in the coronavirus disease 2019 (COVID-19) pandemic based on small observational studies that suggested clinical benefit in COVID-19 patients with a hyperinflammatory state. To inform our local treatment algorithms in the absence of randomized clinical trial results, we performed a rapid analysis of the first 11 hospitalized COVID-19 patients treated with tocilizumab at our academic medical center. We report their early clinical outcomes and describe the process by which we assembled a team of diverse trainees and stakeholders to extract, analyze, and disseminate data during a time of clinical uncertainty.
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Tratamento Farmacológico da COVID-19 , Anticorpos Monoclonais Humanizados , Tomada de Decisão Clínica , Síndrome da Liberação de Citocina , Humanos , Uso Off-Label , Pandemias , SARS-CoV-2 , Resultado do Tratamento , IncertezaRESUMO
PURPOSE OF REVIEW: Global malaria elimination has little chance of success without an effective vaccine. The first malaria vaccine, RTS,S/AS01e, demonstrated moderate efficacy against clinical malaria in phase III trials and is undergoing large-scale effectiveness trials in Africa. Importantly, the vaccine did not perform equally well between phase III study sites. Though reasons for the moderate efficacy and this variation are unclear, various mechanisms have been suggested. This review summarizes the recent literature on such mechanisms, with a focus on those involving landscape ecology, parasite antigenic variation, and human host genetic differences. RECENT FINDINGS: Transmission intensity may have a role pre- and post-vaccination in modulating immune responses to the vaccine. Furthermore, malaria incidence may "rebound" in vaccinated populations living in high transmission intensity settings. There is growing evidence that both genetic variation in the parasite circumsporozoite protein and variation of human host genetic factors affect RTS,S vaccine efficacy. These genetic factors may be interacting in complex ways to produce variation in the natural and vaccine-induced immune responses that protect against malaria. SUMMARY: Due to the modest efficacy of RTS,S/AS01e, the combinations of factors (ecological, parasite, human host) impacting its effectiveness must be clearly understood, as this information will be critical for implementation policy and future vaccine designs.
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SARS-CoV-2 testing data in North Carolina during the first three months of the state's COVID-19 pandemic were analyzed to determine if there were disparities among intersecting axes of identity including race, Latinx ethnicity, age, urban-rural residence, and residence in a medically underserved area. Demographic and residential data were used to reconstruct patterns of testing metrics (including tests per capita, positive tests per capita, and test positivity rate which is an indicator of sufficient testing) across race-ethnicity groups and urban-rural populations separately. Across the entire sample, 13.1% (38,750 of 295,642) of tests were positive. Within racial-ethnic groups, 11.5% of all tests were positive among non-Latinx (NL) Whites, 22.0% for NL Blacks, and 66.5% for people of Latinx ethnicity. The test positivity rate was higher among people living in rural areas across all racial-ethnic groups. These results suggest that in the first three months of the COVID-19 pandemic, access to COVID-19 testing in North Carolina was not evenly distributed across racial-ethnic groups, especially in Latinx, NL Black and other historically marginalized populations, and further disparities existed within these groups by gender, age, urban-rural status, and residence in a medically underserved area.
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Negro ou Afro-Americano/estatística & dados numéricos , Teste para COVID-19/estatística & dados numéricos , COVID-19/diagnóstico , Disparidades em Assistência à Saúde/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , População Branca/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Criança , Pré-Escolar , Feminino , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , North Carolina , População Rural , SARS-CoV-2/isolamento & purificação , População Urbana , Adulto JovemRESUMO
Deep tubewells are a key component of arsenic mitigation programs in rural Bangladesh. Compared to widely prevalent shallow tubewells, deep tubewells reduce ground-water arsenic exposure and provide better microbial water quality at source. However, the benefits of clean drinking-water at these more distant sources may be abated by higher levels of microbial contamination at point-of-use. One such potential pathway is the use of contaminated surface water for washing drinking-water storage containers. The aim of this study is to compare the prevalence of surface water use for washing drinking-water storage containers among deep and shallow tubewell users in a cohort of 499 rural residents in Matlab, Bangladesh. We employ a multi-level logistic regression model to measure the effect of tubewell type and ownership status on the odds of washing storage containers with surface water. Results show that deep tubewell users who do not own their drinking-water tubewell, have 6.53 times the odds [95% CI: 3.56, 12.00] of using surface water for cleaning storage containers compared to shallow tubewell users, who own their drinking-water source. Even deep tubewell users who own a private well within walking distance have 2.53 [95% CI: 1.36, 4.71] times the odds of using surface water compared to their shallow tubewell counterparts. These results highlight the need for interventions to limit risk substitution, particularly the increased use of contaminated surface water when access to drinking water is reduced. Increasing ownership of and proximity to deep tubewells, although crucial, is insufficient to achieve equity in safe drinking-water access across rural Bangladesh.
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Arsênio , Monitoramento Ambiental/métodos , Água Subterrânea , Poluentes Químicos da Água/análise , Abastecimento de Água , Arsênio/análise , Arsênio/toxicidade , Bangladesh , HumanosRESUMO
BACKGROUND: RTS,S/AS01 is the first vaccine against malaria to undergo pilot implementation, beginning in 2019 and vaccinating 360,000 children per year in Malawi, Ghana, and Kenya. The four-dose vaccine is given as a primary three-dose series with a fourth dose given approximately 18 months later. The efficacy of RTS,S/AS01 was variable among the 11 sites participating in the 2009-2014 phase III trial (MALARIA-055, NCT00866619), possibly due to differences in transmission intensity. However, a within-site examination of environmental factors related to transmission intensity and their impact on vaccine efficacy has yet to be conducted. METHODS: We implemented the phase III RTS,S/AS01 trial at the Malawi site, which enrolled 1578 infants (6-12 weeks) and children (5-17 months) living in the Lilongwe District in Central Malawi and followed them for 3 years between 2009 and 2014. A global positioning system survey and an ecological questionnaire were conducted to collect participant household locations and characteristics, while additional data on background malaria prevalence were obtained from a concurrent Malaria Transmission Intensity (MTI) survey. Negative binomial regression models were used to assess whether the efficacy of the vaccine varied by estimated background malaria prevalence, household roof type, or amount of nearby vegetation. RESULTS: Vaccine efficacy did not significantly vary by estimated malaria prevalence or by roof type. However, increased vegetation cover was associated with an increase in the efficacy of the three-dose primary RTS,S/AS01 series in the 18 months before the fourth dose and a decrease in the efficacy of the primary vaccine series in the second 18 months following, if the fourth dose was not given. Vegetation cover did not alter the efficacy of the fourth dose in a statistically or practically significant manner. CONCLUSIONS: Vegetation coverage in this study site might be a proxy for nearness to rivers or branching, shallow wetlands called "dambos" which could serve as breeding sites for mosquitoes. We observed statistically significant modification of the efficacy of RTS,S/AS01 by forest cover, suggesting that initial vaccine efficacy and the importance of the fourth dose varies based on ecological context. TRIAL REGISTRATION: Efficacy of GSK Biologicals' Candidate Malaria Vaccine (257049) Against Malaria Disease Caused by P. falciparum Infection in Infants and Children in Africa. NCT00866619 prospectively registered 20 March 2009.
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Vacinas Antimaláricas/imunologia , Malária Falciparum/epidemiologia , Plasmodium falciparum/imunologia , Criança , Meio Ambiente , Feminino , Sistemas de Informação Geográfica , Humanos , Lactente , Malária Falciparum/prevenção & controle , Malaui/epidemiologia , Masculino , Análise Espacial , Inquéritos e Questionários , VacinaçãoRESUMO
BACKGROUND: RTS,S/AS01, the most advanced vaccine against malaria, is now undergoing pilot implementation in Malawi, Ghana, and Kenya where an estimated 360,000 children will be vaccinated each year. In this study we evaluate RTS,S/AS01 alongside bed net use and estimate cost-effectiveness. METHODS: RTS,S/AS01 phase III trial and bed net prevalence data were used to determine the effect of vaccination in the urban/periurban and rural areas of Lilongwe, Malawi. Cost data were used to calculate the cost-effectiveness of various interventions over three years. FINDINGS: Since bed nets reduce malaria incidence and homogeneous vaccine efficacy was assumed, participants without bed nets received greater relative benefit from vaccination with RTS,S/AS01 than participants with bed nets. Similarly, since malaria incidence in rural Lilongwe is higher than in urban Lilongwe, the impact and cost-effectiveness of vaccine interventions is increased in rural areas. In rural Lilongwe, we estimated that vaccinating one child without a bed net would prevent 2·59 (1·62 to 3·38) cases of malaria over three years, corresponding to a cost of $10·08 (7·71 to 16·13) per case averted. Alternatively, vaccinating one child with a bed net would prevent 1·59 (0·87 to 2·57) cases, corresponding to $16·43 (10·16 to 30·06) per case averted. Providing RTS,S/AS01 to 30,000 children in rural Lilongwe was estimated to cost $782,400 and to prevent 58,611 (35,778 to 82,932) cases of malaria over a three-year period. Joint interventions providing both vaccination and bed nets (to those without them) were estimated to prevent additional cases of malaria and to be similarly cost-effective, compared to vaccine-only interventions. INTERPRETATION: To maximize malaria prevention, vaccination and bed net distribution programs could be integrated. FUNDING: Impacts of Environment, Host Genetics and Antigen Diversity on Malaria Vaccine Efficacy (1R01AI137410-01).