Improving the Cost-efficiency of Preventive Chemotherapy: Impact of New Diagnostics on Stopping Decisions for Control of Schistosomiasis.

BACKGROUND: Control of schistosomiasis (SCH) relies on the regular distribution of preventive chemotherapy (PC) over many years. For the sake of sustainable SCH control, a decision must be made at some stage to scale down or stop PC. These "stopping decisions" are based on population surveys that assess whether infection levels are sufficiently low. However, the limited sensitivity of the currently used diagnostic (Kato-Katz [KK]) to detect low-intensity infections is a concern. Therefore, the use of new, more sensitive, molecular diagnostics has been proposed. METHODS: Through statistical analysis of Schistosoma mansoni egg counts collected from Burundi and a simulation study using an established transmission model for schistosomiasis, we investigated the extent to which more sensitive diagnostics can improve decision making regarding stopping or continuing PC for the control of S. mansoni. RESULTS: We found that KK-based strategies perform reasonably well for determining when to stop PC at a local scale. Use of more sensitive diagnostics leads to a marginally improved health impact (person-years lived with heavy infection) and comes at a cost of continuing PC for longer (up to around 3 years), unless the decision threshold for stopping PC is adapted upward. However, if this threshold is set too high, PC may be stopped prematurely, resulting in a rebound of infection levels and disease burden (+45% person-years of heavy infection). CONCLUSIONS: We conclude that the potential value of more sensitive diagnostics lies more in the reduction of survey-related costs than in the direct health impact of improved parasite control.

Understanding and maximising the community impact of seasonal malaria chemoprevention in Burkina Faso (INDIE-SMC): study protocol for a cluster randomised evaluation trial.

INTRODUCTION: Seasonal malaria chemoprevention (SMC) involves repeated administrations of sulfadoxine-pyrimethamine plus amodiaquine to children below the age of 5 years during the peak transmission season in areas of seasonal malaria transmission. While highly impactful in reducing Plasmodium falciparum malaria burden in controlled research settings, the impact of SMC on infection prevalence is moderate in real-life settings. It remains unclear what drives this efficacy decay. Recently, the WHO widened the scope for SMC to target all vulnerable populations. The Ministry of Health (MoH) in Burkina Faso is considering extending SMC to children below 10 years old. We aim to assess the impact of SMC on clinical incidence and parasite prevalence and quantify the human infectious reservoir for malaria in this population. METHODS AND ANALYSIS: We will perform a cluster randomised trial in Saponé Health District, Burkina Faso, with three study arms comprising 62 clusters of three compounds: arm 1 (control): SMC in under 5-year-old children, implemented by the MoH without directly observed treatment (DOT) for the full course of SMC; arm 2 (intervention): SMC in under 5-year-old children, with DOT for the full course of SMC; arm 3 (intervention): SMC in under 10-year-old children, with DOT for the full course of SMC. The primary endpoint is parasite prevalence at the end of the malaria transmission season. Secondary endpoints include the impact of SMC on clinical incidence. Factors affecting SMC uptake, treatment adherence, drug concentrations, parasite resistance markers and transmission of parasites will be determined. ETHICS AND DISSEMINATION: The London School of Hygiene & Tropical Medicine's Ethics Committee (29193) and the Burkina Faso National Medical Ethics Committee (Deliberation No 2023-05-104) approved this study. The findings will be presented to the community; disease occurrence data and study outcomes will also be shared with the Burkina Faso MoH. Findings will be published irrespective of their results. TRIAL REGISTRATION NUMBER: NCT05878366.

Compliance With Guidelines on Seasonal Malaria Chemoprevention in Kwara State, Northcentral Nigeria.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is an effective strategy for reducing malaria morbidity and mortality in children aged 3-59 months in areas with seasonal malaria transmission. Sulphadoxine-pyrimethamine plus amodiaquine is given to an eligible child at monthly intervals during the peak malaria transmission season. The aim of this study was to determine the level of compliance with SMC guidelines by community drug distributors during SMC implementation in Kwara State. METHOD: Caregivers of eligible children from six Local Government Areas were interviewed using a structured questionnaire on the KoboCollect app downloaded on hand-held android devices. The questionnaire was composed of questions on caregiver's demographics, SMC drug administration, and adherence to SMC protocol. RESULTS: A total of 1,314 caregivers were interviewed, most of them were female 1076 (81.9%), married 1200 (91.3%) and literate 795 (60.5%). The mean SMC coverage for the 4 cycles was 1183(88.5%). SMC information was received by 1166 (88.7%) of caregivers. Most of the caregivers 1166 (88.7%) heard about SMC. Overall, SPAQ administration was directly observed in most cases 1169 (91.5%), second dose was given 1226 (96.0%) and drugs were fully ingested 1140(89.3%). Poor compliance was observed in home visits by lead mothers 988 (77.4%). The report of adverse drug reactions was low 132 (10.3% [95% CI: 8.8-12.3%]), the commonest being severe vomiting 50 (37.9%). There were significant (P<0.05) variations in SMC implementation across the 6 LGAs in virtually all the performance indicators. SPAQ administration to over-age children was low 128 (10.0%). CONCLUSION: Overall, the compliance with SMC implementation guidelines in Kwara state was good though significant differences in performance were observed across the six LGAs. Home visits by lead mothers were generally poor. The self-reported coverage of SMC by caregivers was commendable.

CONTEXTE: La chimioprévention saisonnière du paludisme (CSP) est une stratégie efficace pour réduire la morbidité et la mortalité liées au paludisme chez les enfants âgés de 3 à 59 mois dans les zones à transmission saisonnière du paludisme. La sulfadoxine-pyriméthamine associée à l'amodiaquine est administrée à un enfant éligible à intervalles mensuels pendant la saison de transmission maximale du paludisme. L'objectif de cette étude était de déterminer le niveau de conformité aux directives de la CSP par les distributeurs de médicaments communautaires lors de la mise en œuvre de la CSP dans l'État de Kwara. MÉTHODE: Les aidants des enfants éligibles de six zones de gouvernement local ont été interrogés à l'aide d'un questionnaire structuré sur l'application KoboCollect sur des appareils android portables. Le questionnaire comprenait des questions sur les caractéristiques démographiques des aidants, l'administration des médicaments de la CSP et l'adhésion au protocole de la CSP. RÉSULTATS: Au total, 1 314 aidants ont été interrogés, la plupart étaient des femmes 1 076 (81,9 %), mariées 1 200 (91,3 %) et alphabétisées 795 (60,5 %). La couverture moyenne de la CSP pour les 4 cycles était de 1 183 (88,5 %). La plupart des aidants 1 166 (88,7 %) avaient entendu parler de la CSP. Dans l'ensemble, la première administration de SPAQ a été observée directement dans la plupart des cas 1 169 (91,5 %), la deuxième dose a été administrée par 1 226 (96,0 %) aidants et les médicaments ont été entièrement ingérés sans cracher partiellement ou totalement par 1 140 (89,3 %) enfants. Une mauvaise conformité a été observée lors des visites à domicile par les mères responsables 988 (77,4 %). Le signalement des réactions indésirables aux médicaments était faible 132 (10,3 % [IC à 95 % : 8,8-12,3 %]), la plus courante étant les vomissements sévères 50 (37,9 %). Des variations significatives (P<0,05) dans la mise en œuvre de la CSP ont été observées dans les 6 LGAs pour pratiquement tous les indicateurs de performance. L'administration de SPAQ aux enfants plus âgés était faible 128 (10,0 %). CONCLUSION: Dans l'ensemble, la conformité aux directives de mise en œuvre de la CSP dans l'État de Kwara était bonne bien que des différences significatives dans les performances aient été observées dans les six LGAs. Les visites à domicile par les mères responsables étaient généralement mauvaises. La couverture autodéclarée de la CSP par les aidants était louable. MOTS-CLÉS: Chimioprévention saisonnière du paludisme, SPAQ, Conformité, Enfants, Centre-nord du Nigeria, Saison des pluies.

Malaria trends in districts that were targeted and not-targeted for seasonal malaria chemoprevention in children under 5 years of age in Guinea, 2014-2021.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is a main intervention to prevent and reduce childhood malaria. Since 2015, Guinea has implemented SMC targeting children aged 3-59 months (CU5) in districts with high and seasonal malaria transmission. OBJECTIVE: We assessed the programmatic impact of SMC in Guinea's context of scaled up malaria intervention programming by comparing malaria-related outcomes in 14 districts that had or had not been targeted for SMC. METHODS: Using routine health management information system data, we compared the district-level monthly test positivity rate (TPR) and monthly uncomplicated and severe malaria incidence for the whole population and disaggregated age groups (<5 years and ≥5 years of age). Changes in malaria indicators through time were analysed by calculating the district-level compound annual growth rate (CAGR) from 2014 to 2021; we used statistical analyses to describe trends in tested clinical cases, TPR, uncomplicated malaria incidence and severe malaria incidence. RESULTS: The CAGR of TPR of all age groups was statistically lower in SMC (median=-7.8%) compared with non-SMC (median=-3.0%) districts. Similarly, the CAGR in uncomplicated malaria incidence was significantly lower in SMC (median=1.8%) compared with non-SMC (median=11.5%) districts. For both TPR and uncomplicated malaria incidence, the observed difference was also significant when age disaggregated. The CAGR of severe malaria incidence showed that all age groups experienced a decline in severe malaria in both SMC and non-SMC districts. However, this decline was significantly higher in SMC (median=-22.3%) than in non-SMC (median=-5.1%) districts for the entire population, as well as both CU5 and people over 5 years of age. CONCLUSION: Even in an operational programming context, adding SMC to the malaria intervention package yields a positive epidemiological impact and results in a greater reduction in TPR, as well as the incidence of uncomplicated and severe malaria in CU5.

Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial.

Importance: Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions. Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention. Design, Setting, and Participants: This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities. Interventions: Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023. Main Outcomes and Measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census. Results: A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months. Conclusions and Relevance: Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03676764.

Monitoring of adverse drug reactions during seasonal malaria chemoprevention campaigns in children aged 3­59 months in Burkina Faso / Surveillance des effets indésirables lors des campagnes de la chimioprévention du paludisme saisonnier chez les enfants de 3-59 mois au Burkina Faso

Introduction: Seasonal malaria chemoprevention (SMC) by mass administration of sulfadoxine pyrimethamine + amodiaquine (SPAQ) reduces the burden of malaria in children aged 3­59 months. The occurrence of adverse drug reaction (ADR) may affect the success of this intervention. There are few studies of SMC adverse event surveillance in sub-Saharan Africa, particularly in Burkina Faso, a highly endemic country. Our main objective was to characterize the ADRs reported during SMC campaigns in Burkina Faso. Secondly, we evaluated the performance of the pharmacovigilance integrated into the SMC program in order to support safe administration of SMC. Method: This was a retrospective descriptive study of SMC individual case safety reports recorded in VigiBase® in Burkina Faso from 2014 to 2021. We used the P-method for the analysis of preventable serious adverse drug reactions and WHO criteria for assessing the performance of pharmacovigilance integrated into the SMC program. Results: A total of 1,105 SMC individual case safety reports were registered in VigiBase® for 23,311,453 doses of SPAQ given between 2014 and 2021. No pharmacovigilance signal was detected. The number of serious cases was 101, of which 23 (22.8%) were preventable. In 38.1% of children, the occurrence of ADRs led to discontinuation of SMC treatment. Vomiting was the most frequently reported adverse drug reaction (48.0%). The proportion of children whose treatment was discontinued due to vomiting was 42.7%, while the proportion of treatment discontinuation for other ADRs was 32.8% (p = 0.01). The SMC program contributed at 46.2% to the national pharmacovigilance database. The reporting rate was 0.03 per 1,000 exposed children in 2021. The median completeness score of the ICSRs was 0.7 (IQR: 0.5­0.7), and the median time to register the ICSRs in VigiBase® was 204 (IQR: 143­333) days. Conclusions: Post-drug administration vomiting may interfere with the purpose of SMC. Measures to manage this adverse drug reaction should be taken to improve the success of the SMC program. Based on the information on reporting time and reporting rate, spontaneous reporting should be supported by active surveillance, including cohort event monitoring, in Burkina Faso.

Introduction: La chimioprévention du paludisme saisonnier (CPS) par l'administration en masse de la sulfadoxine-pyriméthamine + amodiaquine (SPAQ) permet de réduire le fardeau du paludisme chez les enfants de 3-59 mois. La survenue d'effets indésirables (EI) pourrait nuire au succès de cette intervention. Il existe peu d'études sur la surveillance des EI de la CPS en Afrique subsaharienne et plus particulièrement au Burkina Faso, pays de forte endémicité palustre. Notre objectif principal était de caractériser les effets indésirables notifiés au cours des campagnes CPS au Burkina Faso. Secondairement, nous avons évalué la performance de la pharmacovigilance intégrée au programme de CPS dans le but de soutenir la sécurité d'administration de la CPS. Méthodes: Nous avons réalisé une analyse rétrospective à visée descriptive des rapports d'effets indésirables de la CPS enregistrés dans VigiBase® entre le 1er janvier 2014 et le 31 décembre 2021. Nous avons utilisé la P-method pour l'analyse de l'évitabilité des effets indésirables graves et les critères de l'OMS pour évaluer la performance de la pharmacovigilance intégrée au programme de CPS. Résultats: Au total, 1 105 cas individuels de rapports de sécurité de la CPS ont été analysés dans VigiBase® pour 23 311 453 doses administrées. Aucun signal de pharmacovigilance n'a été détecté. Le nombre des cas graves était de 101, dont 23 (22,8 %) évitables. Chez 38,1 % des enfants, la survenue des EI a occasionné l'arrêt de l'administration du traitement de la CPS. Le vomissement était l'effet indésirable le plus fréquemment rapporté (48,0 %). La proportion d'enfants dont le traitement a été arrêté pour motif de vomissement était de 42,7 %, tandis que la proportion d'arrêts de traitement pour les autres EI était de 32,8 % (p=0,01). La pharmacovigilance de la CPS a contribué à 46,2 % à l'alimentation de la base de données nationale de pharmacovigilance. Le taux de notification était de 0,03 pour 1 000 enfants exposés en 2021. Le score d'exhaustivité médian des rapports était de 0,7 (P25-P75 : 0,5-0,7) et le délai médian d'enregistrement des rapports dans VigiBase® était de 204 (P25-P75 : 143-333) jours. Conclusions: Les vomissements peuvent nuire à l'objectif de la CPS. Des mesures de gestion de cet effet indésirable doivent être prises pour améliorer le succès de la CPS. Au regard des informations sur le délai de notification et le taux de notification, la notification spontanée devrait être soutenue par une surveillance active, notamment une « cohort event monitoring ¼ au Burkina Faso.

Systematic Review and Meta-Analysis of Seasonal Malaria Chemoprevention.

Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in 2012 and has been implemented in 13 countries in the Sahel, reaching more than 30 million children annually. Malaria control programs implementing SMC have asked the WHO to consider expanding the age range or number of monthly cycles. We conducted a systematic review and meta-analysis of SMC among children up to 15 years of age and up to six monthly cycles. Twelve randomized studies were included, with outcomes stratified by age (< 5/≥ 5 years), by three or four versus five or six cycles, and by drug where possible. Drug regimens included sulfadoxine-pyrimethamine + amodiaquine, amodiaquine-artesunate, and sulfadoxine-pyrimethamine + artesunate. Included studies were all conducted in Sahelian countries in which high-grade resistance to sulfadoxine-pyrimethamine was rare and in zones with parasite prevalence ranging from 1% to 79%. Seasonal malaria chemoprevention resulted in substantial reductions in uncomplicated malaria incidence measured during that transmission season (rate ratio: 0.27, 95% CI: 0.25-0.29 among children < 5 years; rate ratio: 0.27, 95% CI: 0.25-0.30 among children ≥ 5 years) and in the prevalence of malaria parasitemia measured within 4-6 weeks from the final SMC cycle (risk ratio: 0.38, 95% CI: 0.34-0.43 among children < 5 years; risk ratio: 0.23, 95% CI: 0.11-0.48 among children ≥ 5 years). In high-transmission zones, SMC resulted in a moderately reduced risk of any anemia (risk ratio: 0.77, 95% CI: 0.72-0.83 among children < 5 years; risk ratio: 0.70, 95% CI: 0.52-0.95 among children ≥ 5 years [one study]). Children < 10 years of age had a moderate reduction in severe malaria (risk ratio: 0.53, 95% CI: 0.37-0.76) but no evidence of a mortality reduction. The evidence suggests that in areas in which sulfadoxine-pyrimethamine and amodiaquine remained efficacious, SMC effectively reduced malaria disease burden among children both < 5 and ≥ 5 years old and that the number of cycles should be commensurate with the length of the transmission season, up to six cycles.

Contextual Factors to Improve Implementation of Malaria Chemoprevention in Children: A Systematic Review.

Malaria remains a leading cause of childhood morbidity and mortality in sub-Saharan Africa, particularly among children under 5 years of age. To help address this challenge, the WHO recommends chemoprevention for certain populations. For children and infants, the WHO recommends seasonal malaria chemoprevention (SMC), perennial malaria chemoprevention (PMC; formerly intermittent preventive treatment in infants [IPTi]), and, more recently, intermittent preventive treatment in school children (IPTsc). This review describes the contextual factors, including feasibility, acceptability, health equity, financial considerations, and values and preferences, that impact implementation of these strategies. A systematic search was conducted on July 5, 2022, and repeated April 13, 2023, to identify relevant literature. Two reviewers independently screened titles for eligibility, extracted data from eligible articles, and identified and summarized themes. Of 6,295 unique titles identified, 65 were included. The most frequently evaluated strategy was SMC (n = 40), followed by IPTi (n = 18) and then IPTsc (n = 6). Overall, these strategies were highly acceptable, although with IPTsc, there were community concerns with providing drugs to girls of reproductive age and the use of nonmedical staff for drug distribution. For SMC, door-to-door delivery resulted in higher coverage, improved caregiver acceptance, and reduced cost. Lower adherence was noted when caregivers were charged with giving doses 2 and 3 unsupervised. For SMC and IPTi, travel distances and inclement weather limited accessibility. Sensitization and caregiver education efforts, retention of high-quality drug distributors, and improved transportation were key to improving coverage. Additional research is needed to understand the role of community values and preferences in chemoprevention implementation.

Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial.

BACKGROUND: The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. METHODS: Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. RESULTS: From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63). CONCLUSIONS: Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. TRIAL REGISTRATION: The study is registered at Clinical Trial.gov NCT05354258.

Revisiting Proton Pump Inhibitors as Chemoprophylaxis Against the Progression of Barrett's Esophagus.

PURPOSE OF REVIEW: Barrett's esophagus (BE) is associated with chronic gastroesophageal reflux disease and is a known precursor to esophageal adenocarcinoma. While endoscopic surveillance strategies and the role for endoscopic eradication therapy have been well established, there has been much interest in identifying chemopreventive agents to disrupt or halt the metaplasia-dysplasia-carcinoma sequence in patients with BE. RECENT FINDINGS: No pharmacological agent has held more hope in reducing the risk of neoplastic progression in BE than proton pump inhibitors (PPIs). However, data supporting PPIs for chemoprevention have largely been from observational cohort and case-control studies with mixed results. In this review, we revisit the literature and highlight the role of PPIs in patients with BE as it pertains to chemoprophylaxis against the progression of BE to dysplasia and esophageal adenocarcinoma.

Evidence of malarial chemoprophylaxis among travellers who died from malaria: a systematic review and meta-analysis.

BACKGROUND: Chemoprophylaxis is a prevention method for malaria during travel in malaria-endemic countries. This study aimed to collate and synthesize the evidence of malarial chemoprophylaxis among malaria death cases. METHODS: Studies documenting malarial chemoprophylaxis related to malaria deaths were searched in PubMed, Scopus, MEDLINE, Embase, and CENTRAL until 3 July 2022. The pooled proportion of malarial chemoprophylaxis among death cases was synthesized using logit transformation and back transformation to a proportion performed using generalized linear mixed models. The pooled log odds ratio (log-OR) with a 95% confidence interval (CI) of malarial chemoprophylaxis in death cases compared to survivors were synthesized. RESULTS: Fifty-eight studies were included in the systematic review and the meta-analysis. Of 602 pooled malaria death cases, the number of patients who took chemoprophylaxis was 187 (30%) (95% CI 22-40, P < 0.01, 58 studies), and those who took adequate chemoprophylaxis were 24 (5%) (95% CI 2-13, P < 0.01, 42 studies). A comparable log-OR of underwent chemoprophylaxis was observed between malaria death cases and survivors (P = 0.94, pooled log-OR: - 0.02, 95% CI - 0.46-0.42, I2: 0%, 17 studies). Similarly, a comparable log-OR of adequate chemoprophylaxis was identified between malaria death cases and survivors (P = 0.15, pooled log-OR: 0.83, 95% CI - 0.30-1.97, I2: 47.08%, 11 studies). CONCLUSIONS: Among the studies where malarial chemoprophylaxis was reported, approximately 30% of malaria death cases had taken such prophylaxis. Notably, only 5% of these cases adhered fully or adequately to the recommended chemoprophylactic regimen. However, the analysis did not reveal a significant difference in the odds of malarial chemoprophylaxis between malaria death cases and survivors.

An exploratory study of seasonal malaria chemoprevention and pharmacovigilance for under-five children in Kebbi State, Nigeria.

Background: Seasonal malaria chemoprevention (SMC) is an important public health intervention that is being used to reduce the burden of malaria in sub-Saharan Africa. Objectives: This study aimed to evaluate the implementation of SMC and pharmacovigilance practices in under-five children in Kebbi State, Nigeria. Materials and Methods: The methodology involved a comprehensive review of tools for managing SMC commodities, training data collectors, and fieldwork to evaluate all local government area (LGA) stores, the central medical store (CMS), and selected health facilities based on the sample size determined. Data were collected using SurveyCTO software and analyzed using MS Excel. Twenty-one data reviewers visited the CMS, 21 LGA stores, and 315 health facilities. Results: Our study uncovered significant inaccuracies in documentation, which led to many commodities needing to be more effectively accounted for regarding sources. Data triangulation showed inconsistencies between tools and physical counts that do not match the quantities on inventory control cards. Most primary health-care (PHC) staff in charge of SMC have been formally trained in pharmacovigilance. About 75% (237) of PHCs referred cases of adverse drug reactions (ADRs) to a secondary health-care facility, while 14% (45) treated the symptoms of the ADR with another drug, and 7% (21) took no action, and the reaction resolved on its own. Conclusions: This study provides insight into the challenges and opportunities for improving the implementation of SMC and pharmacovigilance practices in Kebbi State, Nigeria, and has important implications for other settings with similar challenges.

Using systems thinking to understand the scale-up and sustainability of health innovation: a case study of seasonal malaria chemoprevention processes in Burkina Faso.

BACKGROUND: Scale-up and sustainability are often studied separately, with few studies examining the interdependencies between these two processes and the implementation contexts of innovations towards malaria prevention and control. Researchers and implementers offer much more attention to the content of innovations, as they focus on the technological dimensions and the conditions for expansion. Researchers have often considered innovation a linear sequence in which scaling up and sustainability represented the last stages. Using systems thinking in this manuscript, we analyze complex scaling and sustainability processes through adopting and implementing seasonal malaria chemoprevention (SMC) in Burkina Faso from 2014 to 2018. METHODS: We conducted a qualitative case study involving 141 retrospective secondary data (administrative, press, scientific, tools and registries, and verbatim) spanning from 2012 to 2018. We complemented these data with primary data collected between February and March 2018 in the form of 15 personal semi-structured interviews with SMC stakeholders and non-participant observations. Processual analysis permitted us to conceptualize scale-up and sustainability processes over time according to different vertical and horizontal levels of analysis and their interconnections. RESULTS: Our results indicated six internal and external determinants of SMC that may negatively or positively influence its scale-up and sustainability. These determinants are effectiveness, monitoring and evaluation systems, resources (financial, material, and human), leadership and governance, adaptation to the local context, and other external elements. Our results revealed that donors and implementing actors prioritized financial resources over other determinants. In contrast, our study clearly showed that the sustainability of the innovation, as well as its scaling up, depends significantly on the consideration of the interconnectedness of the determinants. Each determinant can concurrently constitute an opportunity and a challenge for the success of the innovation. CONCLUSION: Our findings highlight the usefulness of the systemic perspective to consider all contexts (international, national, subnational, and local) to achieve large-scale improvements in the quality, equity, and effectiveness of global health interventions. Thus, complex and systems thinking have made it possible to observe emergent and dynamic innovation behaviors and the dynamics particular to sustainability and scaling up processes.

Prophylactic anticoagulation after minimally invasive hysterectomy for endometrial cancer: a cost-effectiveness analysis.

OBJECTIVE: To determine our institutional rate of venous thromboembolism (VTE) following minimally invasive surgery for endometrial cancer and to perform a cost-effectiveness analysis of extended prophylactic anticoagulation after minimally invasive staging surgery for endometrial cancer. METHODS: All patients with newly diagnosed endometrial cancer who underwent minimally invasive staging surgery from January 1, 2017 to December 31, 2020 were identified retrospectively, and clinicopathologic and outcome data were obtained through chart review. Event probabilities and utility decrements were obtained through published clinical data and literature review. A decision model was created to compare 28 days of no post-operative pharmacologic prophylaxis, prophylactic enoxaparin, and prophylactic apixaban. Outcomes included no complications, deep vein thrombosis (DVT), pulmonary embolism, clinically relevant non-major bleeding, and major bleeding. We assumed a willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained. RESULTS: Three of 844 patients (0.36%) had a VTE following minimally invasive staging surgery for endometrial cancer. In this model, no pharmacologic prophylaxis was less costly and more effective than prophylactic apixaban and prophylactic enoxaparin over all parameters examined. When all patients were assigned prophylaxis, prophylactic apixaban was both less costly and more effective than prophylactic enoxaparin. If the risk of DVT was ≥4.8%, prophylactic apixaban was favored over no pharmacologic prophylaxis. On Monte Carlo probabilistic sensitivity analysis for the base case scenario, no pharmacologic prophylaxis was favored in 41.1% of iterations at a willingness-to-pay threshold of $100 000 per QALY. CONCLUSIONS: In this cost-effectiveness model, no extended pharmacologic anticoagulation was superior to extended prophylactic enoxaparin and apixaban in clinically early-stage endometrial cancer patients undergoing minimally invasive surgery. This model supports use of prophylactic apixaban for 7 days post-operatively in select patients when the risk of DVT is 4.8% or higher.

Preferences of Patients and Providers in High-Burden Malaria Settings for Long-Acting Malaria Chemoprevention.

Antimalarial medications are recommended for chemoprevention as part of malaria control programs to decrease the morbidity and mortality related to more than 200 million infections each year. We sought to evaluate patient and provider acceptability of malaria chemoprevention in a long-acting formulation. We administered questionnaires to patients and providers in malaria endemic districts in Kenya and Zambia. Questions explored preferences and concerns around long-acting antimalarial formulations compared with oral formulations. We recruited 202 patient respondents (Kenya, n = 102; Zambia, n = 100) and 215 provider respondents (Kenya, n = 105; Zambia, n = 110). Long-acting injection was preferred to oral pills, whereas oral pills were preferred to implant or transdermal administration by patient respondents. Of 202 patient respondents, 80% indicated that they 'definitely would try' malaria chemoprevention offered by injection instead of oral pills. Of parents or guardians, 84% of 113 responded that they 'definitely would' have their child age < 12 years and 90% of 88 'definitely would' have their child ≥12 years receive an injection for malaria prevention. Provider respondents indicated that they would be more likely to prescribe a long-acting injectable product compared with an oral product for malaria chemoprevention in adults (70%), adolescents ages 12 years and older (67%), and children <12 years (81%). Potential for prolonged adverse effects with long-acting products was the highest concern for patient respondents, while higher medication-related cost was cited as the most concerning barrier to implementation by providers. Overall, these findings indicate enthusiasm for the development of long-acting injectable antimalarials to provide individual delivery method options across age groups.

A proposed method of grading malaria chemoprevention efficacy.

The efficacy and effectiveness of antimalarial drugs are threatened by increasing levels of resistance and therefore require continuous monitoring. Chemoprevention is increasingly deployed as a malaria control measure, but there are no generally accepted methods of assessment. We propose a simple method of grading the parasitological response to chemoprevention (focusing on seasonal malaria chemoprevention) that is based on pharmacometric assessment.