Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women.

BACKGROUND: Malaria and HIV infection overlap geographically in sub-Saharan Africa and share risk factors. HIV infection increases malaria's severity, especially in pregnant women. The World Health Organization (WHO) recommends intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) for pregnant women living in areas of stable malaria transmission. However, HIV-positive women on daily cotrimoxazole prophylaxis (recommended for prevention of opportunistic infections in people with HIV) cannot receive SP due to adverse drug interactions, so malaria prevention in this vulnerable population currently relies on daily cotrimoxazole prophylaxis alone. This review is based on a new protocol and provides an update to the 2011 Cochrane Review that evaluated alternative drugs for IPTp to prevent malaria in HIV-positive women. OBJECTIVES: To compare the safety and efficacy of intermittent preventive treatment regimens for malaria prevention in HIV-positive pregnant women. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases, and two trial registries to 31 January 2024. To identify relevant additional studies or unpublished work, we checked references and contacted study authors and other researchers working on malaria and HIV. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing any intermittent preventive treatment regimen for preventing malaria in HIV-positive pregnant women against daily cotrimoxazole prophylaxis alone, placebo, current or previous standard of care, or combinations of these options. By 'standard of care' we refer to the country's recommended drug regimen to prevent malaria in pregnancy among HIV-positive women, or the treatment that a trial's research team considered to be the standard of care. DATA COLLECTION AND ANALYSIS: Review authors, in pairs, independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias in included trials, and extracted data. We contacted trial authors when additional information was required. We presented dichotomous outcomes using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes as mean differences (MDs). We presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach for what we considered to be the main comparisons and outcomes. MAIN RESULTS: We included 14 RCTs, with a total of 4976 HIV-positive pregnant women initially randomized. All trials assessed the efficacy and safety of one antimalarial used as IPTp (mefloquine, dihydroartemisinin/piperaquine, SP, or azithromycin) with or without daily cotrimoxazole, compared to daily cotrimoxazole alone, placebo, or a standard of care regimen. We grouped the trials into nine comparisons. Our main comparison evaluated the current standard of care (daily cotrimoxazole) with another drug regimen (mefloquine or dihydroartemisinin/piperaquine) versus daily cotrimoxazole with or without placebo. In this comparison, two trials evaluated mefloquine and three evaluated dihydroartemisinin/piperaquine. We conducted meta-analyses that included trials evaluating dihydroartemisinin/piperaquine plus cotrimoxazole, and trials that evaluated mefloquine plus cotrimoxazole, as we considered there to be no qualitative or quantitative heterogeneity among trials for most outcomes. We considered drug-related adverse events and HIV-related outcomes to be drug-specific. Daily cotrimoxazole prophylaxis plus another drug regimen (mefloquine or dihydroartemisinin/piperaquine) probably results in lower risk of maternal peripheral parasitaemia at delivery (RR 0.62, 95% CI 0.41 to 0.95; 2406 participants, 5 trials; moderate-certainty evidence). It results in little or no difference in maternal anaemia cases at delivery (RR 0.98, 95% CI 0.90 to 1.07; 2417 participants, 3 trials; high-certainty evidence). It probably results in a decrease in placental malaria measured by blood smear (RR 0.54, 95% CI 0.31 to 0.93; 1337 participants, 3 trials; moderate-certainty evidence), and probably results in little or no difference in low birth weight (RR 1.16, 95% CI 0.95 to 1.41; 2915 participants, 5 trials; moderate-certainty evidence). There is insufficient evidence to ascertain whether daily cotrimoxazole prophylaxis plus another drug regimen affects the risk of cord blood parasitaemia (RR 0.27, 95% CI 0.04 to 1.64; 2696 participants, 5 trials; very low-certainty evidence). Daily cotrimoxazole prophylaxis plus another drug regimen probably results in little or no difference in foetal loss (RR 1.03, 95% CI 0.73 to 1.46; 2957 participants, 5 trials; moderate-certainty evidence), and may result in little or no difference in neonatal mortality (RR 1.21, 95% CI 0.68 to 2.14; 2706 participants, 4 trials; low-certainty evidence). Due to the probability of an increased risk of mother-to-child HIV transmission and some adverse drug effects noted with mefloquine, we also looked at the results for dihydroartemisinin/piperaquine specifically. Dihydroartemisinin/piperaquine plus daily contrimoxazole probably results in little to no difference in maternal peripheral parasitaemia (RR 0.59, 95% CI 0.31 to 1.11; 1517 participants, 3 trials; moderate-certainty evidence) or anaemia at delivery (RR 0.95, 95% CI 0.82 to 1.10; 1454 participants, 2 trials; moderate-certainty evidence), but leads to fewer women having placental malaria when measured by histopathologic analysis (RR 0.67, 95% CI 0.50 to 0.90; 1570 participants, 3 trials; high-certainty evidence). The addition of dihydroartemisinin/piperaquine to daily cotrimoxazole probably made little to no difference to rates of low birth weight (RR 1.13, 95% CI 0.87 to 1.48; 1695 participants, 3 trials), foetal loss (RR 1.14, 95% CI 0.68 to 1.90; 1610 participants, 3 trials), or neonatal mortality (RR 1.03, 95% CI 0.39 to 2.72; 1467 participants, 2 trials) (all moderate-certainty evidence). We found low-certainty evidence of no increased risk of gastrointestinal drug-related adverse events (RR 1.42, 95% CI 0.51 to 3.98; 1447 participants, 2 trials) or mother-to-child HIV transmission (RR 1.54, 95% CI 0.26 to 9.19; 1063 participants, 2 trials). AUTHORS' CONCLUSIONS: Dihydroartemisinin/piperaquine and mefloquine added to daily cotrimoxazole seem to be efficacious in preventing malaria infection in HIV-positive pregnant women compared to daily cotrimoxazole alone. However, increased risk of HIV transmission to the foetus and poor drug tolerability may be barriers to implementation of mefloquine in practice. In contrast, the evidence suggests that dihydroartemisinin/piperaquine does not increase the risk of HIV mother-to-child transmission and is well tolerated.

[Qualitative analysis of health preparedness policies in ChileUma análise qualitativa das políticas de preparação na área de saúde no Chile]. / Un análisis cualitativo de las políticas de preparación en salud en Chile.

Objective: Analyze health preparedness policies in Chile and identify their strengths and weaknesses. No other studies to date provide an analysis of the country's preparedness policies. Methods: A desk review and semi-structured interviews with experts in emergency preparedness and response were conducted to identify the regulatory framework, key actors, and the strengths and weaknesses of health preparedness policies. Results: The researchers identified 103 standards and interviewed seven preparedness experts. The reviewed standards and interviews show that Chile is in a transitional phase between the old National Civil Protection System and the new National Disaster Prevention and Response System. Only three standards were directly related to health, but the preparedness regulations provide for a multidisciplinary set of actors to address any threat. The experts gave a positive assessment of the Chilean system, although they agreed that certain weaknesses must be corrected. The country's main strength is its disaster response experience, along with its coordination mechanisms. The main shortcomings include risk communication, mitigation, preparedness and assessment, and human resources. Conclusions: Chile has a solid regulatory framework with an all-hazards approach and a set of multisectoral institutions. The new National Disaster Prevention and Response System must build on its strengths to correct the weaknesses that limit its emergency preparedness and response capacity.

Objetivos: Analisar as políticas de preparação na área de saúde no Chile e identificar seus pontos fortes e fracos. Até o momento, não há outros estudos que analisem as políticas de preparação no país. Métodos: Foi realizada uma análise documental e entrevistas semiestruturadas com especialistas em preparação e resposta a emergências para identificar a estrutura regulatória, os principais atores e os pontos fortes e fracos das políticas de preparação na área de saúde. Resultados: Foram encontradas 103 normas, e 7 especialistas em preparação foram entrevistados. As normas analisadas e as entrevistas demostram que o Chile está em um momento de transição entre o antigo Sistema Nacional de Proteção Civil e o novo Sistema Nacional de Prevenção e Resposta a Desastres. Apenas três normas estavam diretamente relacionadas à saúde, mas a legislação de preparação prevê a abordagem de qualquer ameaça por um conjunto multidisciplinar de atores. Os especialistas fizeram uma avaliação positiva do sistema chileno, embora tenha havido consenso sobre alguns pontos fracos que precisam ser corrigidos. O principal ponto forte é a experiência na resposta a desastres, bem como seus mecanismos de coordenação. Os principais pontos fracos foram detectados na comunicação de riscos, na mitigação, na preparação e avaliação e nos recursos humanos. Conclusões: O Chile tem uma sólida estrutura regulatória, com uma perspectiva de múltiplas ameaças e um conjunto de instituições multissetoriais. O novo Sistema Nacional de Prevenção e Resposta a Desastres deve se basear em seus pontos fortes para corrigir as deficiências que limitam sua capacidade de preparação e resposta a emergências.

Un análisis cualitativo de las políticas de preparación en salud en Chile / Qualitative analysis of health preparedness policies in Chile / Uma análise qualitativa das políticas de preparação na área de saúde no Chile

RESUMEN Objetivo. Analizar las políticas de preparación en salud en Chile, e identificar sus fortalezas y debilidades. No hay hasta la fecha otros estudios que analicen las políticas de preparación en el país. Métodos. Se llevó a cabo una revisión documental y entrevistas semiestructuradas con expertos en preparación y respuesta a emergencias para identificar el marco normativo, los actores principales, y las fortalezas y debilidades de las políticas de preparación en salud. Resultados. Se encontraron 103 normas y se entrevistó a 7 personas expertas en preparación. Las normas revisadas y las entrevistas demuestran que Chile se encuentra en un momento de transición entre el antiguo Sistema Nacional de Protección Civil y el nuevo Sistema Nacional de Prevención y Respuesta ante Desastres. Solo tres normas tenían relación directa con salud, pero la normativa de preparación prevé el abordaje de cualquier amenaza desde un conjunto de actores multidisciplinario. Los expertos valoraron de manera positiva el sistema chileno, si bien hubo consenso en algunas debilidades que deben corregirse. La principal fortaleza es la experiencia en respuesta a desastres, así como sus mecanismos de coordinación. Las principales deficiencias se detectaron en la comunicación de riesgo, la mitigación, la preparación y evaluación, y los recursos humanos. Conclusiones. Chile cuenta con un marco normativo sólido con una perspectiva multiamenaza y un conjunto de instituciones multisectoral. El nuevo Sistema Nacional de Prevención y Respuesta ante Desastres debe apoyarse en sus fortalezas para corregir las debilidades que limitan su capacidad de preparación y respuesta ante emergencias.

ABSTRACT Objective. Analyze health preparedness policies in Chile and identify their strengths and weaknesses. No other studies to date provide an analysis of the country's preparedness policies. Methods. A desk review and semi-structured interviews with experts in emergency preparedness and response were conducted to identify the regulatory framework, key actors, and the strengths and weaknesses of health preparedness policies. Results. The researchers identified 103 standards and interviewed seven preparedness experts. The reviewed standards and interviews show that Chile is in a transitional phase between the old National Civil Protection System and the new National Disaster Prevention and Response System. Only three standards were directly related to health, but the preparedness regulations provide for a multidisciplinary set of actors to address any threat. The experts gave a positive assessment of the Chilean system, although they agreed that certain weaknesses must be corrected. The country's main strength is its disaster response experience, along with its coordination mechanisms. The main shortcomings include risk communication, mitigation, preparedness and assessment, and human resources. Conclusions. Chile has a solid regulatory framework with an all-hazards approach and a set of multisectoral institutions. The new National Disaster Prevention and Response System must build on its strengths to correct the weaknesses that limit its emergency preparedness and response capacity.

RESUMO Objetivos. Analisar as políticas de preparação na área de saúde no Chile e identificar seus pontos fortes e fracos. Até o momento, não há outros estudos que analisem as políticas de preparação no país. Métodos. Foi realizada uma análise documental e entrevistas semiestruturadas com especialistas em preparação e resposta a emergências para identificar a estrutura regulatória, os principais atores e os pontos fortes e fracos das políticas de preparação na área de saúde. Resultados. Foram encontradas 103 normas, e 7 especialistas em preparação foram entrevistados. As normas analisadas e as entrevistas demostram que o Chile está em um momento de transição entre o antigo Sistema Nacional de Proteção Civil e o novo Sistema Nacional de Prevenção e Resposta a Desastres. Apenas três normas estavam diretamente relacionadas à saúde, mas a legislação de preparação prevê a abordagem de qualquer ameaça por um conjunto multidisciplinar de atores. Os especialistas fizeram uma avaliação positiva do sistema chileno, embora tenha havido consenso sobre alguns pontos fracos que precisam ser corrigidos. O principal ponto forte é a experiência na resposta a desastres, bem como seus mecanismos de coordenação. Os principais pontos fracos foram detectados na comunicação de riscos, na mitigação, na preparação e avaliação e nos recursos humanos. Conclusões. O Chile tem uma sólida estrutura regulatória, com uma perspectiva de múltiplas ameaças e um conjunto de instituições multissetoriais. O novo Sistema Nacional de Prevenção e Resposta a Desastres deve se basear em seus pontos fortes para corrigir as deficiências que limitam sua capacidade de preparação e resposta a emergências.