Co-implementing vitamin A supplementation with seasonal malaria chemoprevention in Sokoto State, Nigeria: a feasibility and acceptability study.

BACKGROUND: Bi-annual high dose vitamin A supplements administered to children aged 6-59 months can significantly reduce child mortality, but vitamin A supplementation (VAS) coverage is low in Nigeria. The World Health Organization recommends that VAS be integrated into other public health programmes which are aimed at improving child survival. Seasonal malaria chemoprevention (SMC) provides a ready platform for VAS integration to improve health outcomes. This study explored the feasibility and acceptability of integrating VAS with SMC in one local government area in Sokoto State. METHODS: A concurrent QUAN-QUAL mixed methods study was used to assess the feasibility and acceptability of co-implementing VAS with SMC in one LGA of Sokoto state. Existing SMC implementation tools and job aids were revised and SMC and VAS were delivered using a door-to-door approach. VAS and SMC coverage were subsequently assessed using questionnaires administered to 188 and 197 households at baseline and endline respectively. The qualitative component involved key informant interviews and focus group discussions with policymakers, programme officials and technical partners to explore feasibility and acceptability. Thematic analysis was carried out on the qualitative data. RESULTS: At endline, the proportion of children who received at least one dose of VAS in the last six months increased significantly from 2 to 59% (p < 0.001). There were no adverse effects on the coverage of SMC delivery with 70% eligible children reached at baseline, increasing to 76% (p = 0.412) at endline. There was no significant change (p = 0.264) in the quality of SMC, measured by proportion of children receiving their first dose as directly observed treatment (DOT), at baseline (54%) compared to endline (68%). The qualitative findings are presented as two overarching themes relating to feasibility and acceptability of the integrated VAS-SMC strategy, and within each, a series of sub-themes describe study participants' views of important considerations in implementing the strategy. CONCLUSION: This study showed that it is feasible and acceptable to integrate VAS with SMC delivery in areas of high seasonal malaria transmission such as northern Nigeria, where SMC campaigns are implemented. SMC-VAS integrated campaigns can significantly increase vitamin A coverage but more research is required to demonstrate the feasibility of this integration in different settings and on a larger scale.

A practical approach for geographic prioritization and targeting of insecticide-treated net distribution campaigns during public health emergencies and in resource-limited settings.

BACKGROUND: The use of data in targeting malaria control efforts is essential for optimal use of resources. This work provides a practical mechanism for prioritizing geographic areas for insecticide-treated net (ITN) distribution campaigns in settings with limited resources. METHODS: A GIS-based weighted approach was adopted to categorize and rank administrative units based on data that can be applied in various country contexts where Plasmodium falciparum transmission is reported. Malaria intervention and risk factors were used to rank local government areas (LGAs) in Nigeria for prioritization during mass ITN distribution campaigns. Each factor was assigned a unique weight that was obtained through application of the analytic hierarchy process (AHP). The weight was then multiplied by a value based on natural groupings inherent in the data, or the presence or absence of a given intervention. Risk scores for each factor were then summated to generate a composite unique risk score for each LGA. This risk score was translated into a prioritization map which ranks each LGA from low to high priority in terms of timing of ITN distributions. RESULTS: A case study using data from Nigeria showed that a major component that influenced the prioritization scheme was ITN access. Sensitivity analysis results indicate that changes to the methodology used to quantify ITN access did not modify outputs substantially. Some 120 LGAs were categorized as 'extremely high' or 'high' priority when a spatially interpolated ITN access layer was used. When prioritization scores were calculated using DHS-reported state level ITN access, 108 (90.0%) of the 120 LGAs were also categorized as being extremely high or high priority. The geospatial heterogeneity found among input risk factors suggests that a range of variables and covariates should be considered when using data to inform ITN distributions. CONCLUSION: The authors provide a tool for prioritizing regions in terms of timing of ITN distributions. It serves as a base upon which a wider range of vector control interventions could be targeted. Its value added can be found in its potential for application in multiple country contexts, expediated timeframe for producing outputs, and its use of systematically collected malaria indicators in informing prioritization.

Current malaria infection, previous malaria exposure, and clinical profiles and outcomes of COVID-19 in a setting of high malaria transmission: an exploratory cohort study in Uganda.

BACKGROUND: The potential effects of SARS-CoV-2 and Plasmodium falciparum co-infection on host susceptibility and pathogenesis remain unknown. We aimed to establish the prevalence of malaria and describe the clinical characteristics of SARS-CoV-2 and P falciparum co-infection in a high-burden malaria setting. METHODS: This was an exploratory prospective, cohort study of patients with COVID-19 who were admitted to hospital in Uganda. Patients of all ages with a PCR-confirmed diagnosis of SARS-CoV-2 infection who had provided informed consent or assent were consecutively enrolled from treatment centres in eight hospitals across the country and followed up until discharge or death. Clinical assessments and blood sampling were done at admission for all patients. Malaria diagnosis in all patients was done by rapid diagnostic tests, microscopy, and molecular methods. Previous P falciparum exposure was determined with serological responses to a panel of P falciparum antigens assessed using a multiplex bead assay. Additional evaluations included complete blood count, markers of inflammation, and serum biochemistries. The main outcome was overall prevalence of malaria infection and malaria prevalence by age (including age categories of 0-20 years, 21-40 years, 41-60 years, and >60 years). The frequency of symptoms was compared between patients with COVID-19 with P falciparum infection versus those without P falciparum infection. The frequency of comorbidities and COVID-19 clinical severity and outcomes was compared between patients with low previous exposure to P falciparum versus those with high previous exposure to P falciparum. The effect of previous exposure to P falciparum on COVID-19 clinical severity and outcomes was also assessed among patients with and those without comorbidities. FINDINGS: Of 600 people with PCR-confirmed SARS-CoV-2 infection enrolled from April 15, to Oct 30, 2020, 597 (>99%) had complete information and were included in our analyses. The majority (502 [84%] of 597) were male individuals with a median age of 36 years (IQR 28-47). Overall prevalence of P falciparum infection was 12% (95% CI 9·4-14·6; 70 of 597 participants), with highest prevalence in the age groups of 0-20 years (22%, 8·7-44·8; five of 23 patients) and older than 60 years (20%, 10·2-34·1; nine of 46 patients). Confusion (four [6%] of 70 patients vs eight [2%] of 527 patients; p=0·040) and vomiting (four [6%] of 70 patients vs five [1%] of 527 patients; p=0·014] were more frequent among patients with P falciparum infection than those without. Patients with low versus those with high previous P falciparum exposure had a increased frequency of severe or critical COVID-19 clinical presentation (16 [30%] of 53 patients vs three [5%] of 56 patients; p=0·0010) and a higher burden of comorbidities, including diabetes (12 [23%] of 53 patients vs two [4%] of 56 patients; p=0·0010) and heart disease (seven [13%] of 53 patients vs zero [0%] of 56 patients; p=0·0030). Among patients with no comorbidities, those with low previous P falciparum exposure still had a higher proportion of cases of severe or critical COVID-19 than did those with high P falciparum exposure (six [18%] of 33 patients vs one [2%] of 49 patients; p=0·015). Multivariate analysis showed higher odds of unfavourable outcomes in patients who were older than 60 years (adjusted OR 8·7, 95% CI 1·0-75·5; p=0·049). INTERPRETATION: Although patients with COVID-19 with P falciparum co-infection had a higher frequency of confusion and vomiting, co-infection did not seem deleterious. The association between low previous malaria exposure and severe or critical COVID-19 and other adverse outcomes will require further study. These preliminary descriptive observations highlight the importance of understanding the potential clinical and therapeutic implications of overlapping co-infections. FUNDING: Malaria Consortium (USA).

Assessment of the Feasibility, Acceptability, and Impact of Implementing Seasonal Malaria Chemoprevention in Nampula Province, Mozambique: Protocol for a Hybrid Effectiveness-Implementation Study.

BACKGROUND: Malaria is a significant cause of morbidity and mortality in children aged under 5 years in Mozambique. The World Health Organization recommends seasonal malaria chemoprevention (SMC), the administration of four monthly courses of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ), to children aged 3-59 months during rainy season. However, as resistance to SP is widespread in East and Southern Africa, SMC has so far only been implemented across the Sahel in West Africa. OBJECTIVE: This protocol describes the first phase of a pilot project that aims to assess the protective effect of SP and AQ when used for SMC and investigate the levels of molecular markers of resistance of Plasmodium falciparum to antimalarial medicines in the study districts. In addition, it is important to understand whether SMC is a feasible and acceptable intervention in the context of Nampula Province, Mozambique. METHODS: This study will adopt a hybrid effectiveness-implementation design to conduct a mixed methods evaluation with six objectives: a molecular marker study, a nonrandomized controlled trial, an analysis of reported malaria morbidity indicators, a documentation exercise of the contextual SMC adaptation, an acceptability and feasibility assessment, and a coverage and quality assessment. RESULTS: Ethical approval for this study was granted by the Mozambican Ministry of Health National Bioethics Committee on September 15, 2020. Data collection began in October 2020, and data analysis is expected to be completed by August 2021. CONCLUSIONS: This research will make a unique contribution to our understanding of whether the combination of SP and AQ, when used for SMC, can confer a protective effect against malaria in children aged 3-59 months in a region where malaria transmission is seasonal and SP resistance is expected to be high. If the project is successful, subsequent phases are expected to provide a more comprehensive assessment of the effectiveness and sustainability of SMCs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/27855.

Assessment of the Feasibility, Acceptability, and Impact of Implementing Seasonal Malaria Chemoprevention in Nampula Province, Mozambique: Protocol for a Hybrid Effectiveness-Implementation Study

Background Malaria is a significant cause of morbidity and mortality in children aged under 5 years in Mozambique. The World Health Organization recommends seasonal malaria chemoprevention (SMC), the administration of four monthly courses of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ), to children aged 3-59 months during rainy season. However, as resistance to SP is widespread in East and Southern Africa, SMC has so far only been implemented across the Sahel in West Africa. Objective This protocol describes the first phase of a pilot project that aims to assess the protective effect of SP and AQ when used for SMC and investigate the levels of molecular markers of resistance of Plasmodium falciparum to antimalarial medicines in the study districts. In addition, it is important to understand whether SMC is a feasible and acceptable intervention in the context of Nampula Province, Mozambique. Methods This study will adopt a hybrid effectiveness-implementation design to conduct a mixed methods evaluation with six objectives: a molecular marker study, a nonrandomized controlled trial, an analysis of reported malaria morbidity indicators, a documentation exercise of the contextual SMC adaptation, an acceptability and feasibility assessment, and a coverage and quality assessment. Results Ethical approval for this study was granted by the Mozambican Ministry of Health National Bioethics Committee on September 15, 2020. Data collection began in October 2020, and data analysis is expected to be completed by August 2021. Conclusions This research will make a unique contribution to our understanding of whether the combination of SP and AQ, when used for SMC, can confer a protective effect against malaria in children aged 3-59 months in a region where malaria transmission is seasonal and SP resistance is expected to be high. If the project is successful, subsequent phases are expected to provide a more comprehensive assessment of the effectiveness and sustainability of SMCs.

Performance of five pulse oximeters to detect hypoxaemia as an indicator of severe illness in children under five by frontline health workers in low resource settings - A prospective, multicentre, single-blinded, trial in Cambodia, Ethiopia, South Sudan, and Uganda.

BACKGROUND: Low blood oxygen saturation (SpO2), or hypoxaemia, is an indicator of severe illness in children. Pulse oximetry is a globally accepted, non-invasive method to identify hypoxaemia, but rarely available outside higher-level facilities in resource-constrained countries. This study aims to evaluate the performance of different types of pulse oximeters amongst frontline health workers in Cambodia, Ethiopia, South Sudan, and Uganda. METHODS: Five pulse oximeters (POx) which passed laboratory testing, out of an initial 32 potential pulse oximeters, were evaluated by frontline health workers for performance, defined as agreement between the SpO2 measurements of the test device and the reference standard. The study protocol is registered with the Australia New Zealand Clinical Trials Registry (Ref: ACTRrn12615000348550). FINDINGS: Two finger-tip pulse oximeters (Contec and Devon), two handheld pulse oximeters (Lifebox and Utech), and one phone pulse oximeter (Masimo) passed the laboratory testing. They were evaluated for performance on 1,313 children under five years old by 207 frontline health workers between February and May 2015. Phone and handheld pulse oximeters had greater overall agreement with the reference standard (56%; 95% CI 0.52 - 0.60 to 68%; 95% CI 0.65 - 0.71) than the finger-tip POx (31%; 95% CI 0.26 to 0.36 and 47%; 95% CI 0.42 to 0.52). Fingertip POx performance was substantially lower in the 0-2 month olds; having just 17% and 25% agreement. The finger-tip devices more often underreported SpO2 readings (mean difference -7.9%; 95%CI -8.6,-7.2 and -3.9%; 95%CI -4.4,-3.4), and therefore over diagnosed hypoxaemia in the children assessed. INTERPRETATION: While the Masimo phone pulse oximeter performed best, all handheld POx with age-specific probes performed well in the hands of frontline health workers, further highlighting their suitability as a screening tool of severe illness. The poor performance of the fingertip POx suggests they should not be used in children under five by frontline health workers. It is essential that POx are performance tested on children in routine settings (in vivo), not only in laboratories or controlled settings (in vitro), before being introduced at scale. FUNDING: Bill & Melinda Gates Foundation [OPP1054367].

COVID-19 knowledge, beliefs, prevention behaviours and misinformation in the context of an adapted seasonal malaria chemoprevention campaign in six northern Nigerian States.

BACKGROUND: Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine and amodiaquine is an efficacious intervention for protection of children against Plasmodium falciparum malaria during the rainy season. In response to the global COVID-19 pandemic, Malaria Consortium adapted its SMC delivery model to ensure safety of distributors, data collectors and beneficiaries. We conducted a SMC monitoring survey in July 2020 in the states of Bauchi, Jigawa, Kano, Katsina, Sokoto and Yobe, with questions on COVID-19 prevention behaviours and symptoms, and belief in misinformation. We investigated the associations between receipt of information on COVID-19 by different sources, including from SMC distributors, and these three outcomes using logistic generalised estimating equations. We also considered moderation of effectiveness of message delivery by SMC distributors and adherence to use of face coverings. RESULTS: We obtained a representative sample of 40,157 caregivers of eligible children aged 3-59 months, of which 36,914 (91.92%) reported knowledge of COVID-19. The weighted proportions of respondents who correctly identified COVID-19 prevention behaviours and symptoms, and who reported belief in COVID-19 misinformation, were 80.52% (95% confidence interval [95% CI] 80.02-81.00), 81.72% (95% CI 81.23-82.20) and 22.90% (95% CI 22.24-23.57). Receipt of information on COVID-19 from SMC distributors during the campaign was significantly associated with higher odds of caregiver knowledge of COVID-19 prevention behaviours (odds ratio [OR] 1.78, 95% CI 1.64-1.94, p < 0.001) and symptoms (OR 1.74, 95% CI 1.59-1.90, p < 0.001) and lower odds of belief in COVID-19 misinformation (OR 0.92, 95% CI 0.85-1.00, p = 0.038). The associations between message delivery by SMC distributors and the three outcomes were moderated by their adherence to face covering use. Receipt of information by other sources used to deliver government public health messages, including radio and health facility workers, was also associated with knowledge of COVID-19. CONCLUSIONS: Malaria Consortium's SMC programme was successfully adapted in the context of COVID-19 and was a conduit for high-quality public health messages. Standard SMC monitoring and evaluation activities can be adapted to gather evidence on emerging public health issues such as the global COVID-19 pandemic.

Performance of Four Respiratory Rate Counters to Support Community Health Workers to Detect the Symptoms of Pneumonia in Children in Low Resource Settings: A Prospective, Multicentre, Hospital-Based, Single-Blinded, Comparative Trial.

BACKGROUND: Pneumonia is one of the leading causes of death in children under-five globally. The current diagnostic criteria for pneumonia are based on increased respiratory rate (RR) or chest in-drawing in children with cough and/or difficulty breathing. Accurately counting RR is difficult for community health workers (CHWs). Current RR counting devices are frequently inadequate or unavailable. This study analysed the performance of improved RR timers for detection of pneumonia symptoms in low-resource settings. METHODS: Four RR timers were evaluated on 454 children, aged from 0 to 59 months with cough and/or difficulty breathing, over three months, by CHWs in hospital settings in Cambodia, Ethiopia, South Sudan and Uganda. The devices were the Mark Two ARI timer (MK2 ARI), counting beads with ARI timer, Rrate Android phone and the Respirometer feature phone applications. Performance was evaluated for agreement with an automated RR reference standard (Masimo Root patient monitoring and connectivity platform with ISA CO2 capnography). This study is registered with ANZCTR [ACTRN12615000348550]. FINDINGS: While most CHWs managed to achieve a RR count with the four devices, the agreement was low for all; the mean difference of RR measurements from the reference standard for the four devices ranged from 0.5 (95% C.I. - 2.2 to 1.2) for the respirometer to 5.5 (95% C.I. 3.2 to 7.8) for Rrate. Performance was consistently lower for young infants (0 to < 2 months) than for older children (2 to ≤ 59 months). Agreement of RR classification into fast and normal breathing was moderate across all four devices, with Cohen's Kappa statistics ranging from 0.41 (SE 0.04) to 0.49 (SE 0.05). INTERPRETATION: None of the four devices evaluated performed well based on agreement with the reference standard. The ARI timer currently recommended for use by CHWs should only be replaced by more expensive, equally performing, automated RR devices when aspects such as usability and duration of the device significantly improve the patient-provider experience. FUNDING: Bill & Melinda Gates Foundation [OPP1054367].

Performance, Acceptability, and Usability of Respiratory Rate Timers and Pulse Oximeters When Used by Frontline Health Workers to Detect Symptoms of Pneumonia in Sub-Saharan Africa and Southeast Asia: Protocol for a Two-Phase, Multisite, Mixed-Methods Trial.

BACKGROUND: Pneumonia is one of the leading causes of death in children aged under 5 years in both sub-Saharan Africa and Southeast Asia. The current diagnostic criterion for pneumonia is based on the increased respiratory rate (RR) in children with cough or difficulty breathing. Low oxygen saturation, measured using pulse oximeters, is indicative of severe pneumonia. Health workers often find it difficult to accurately count the number of breaths, and the current RR counting devices are often difficult to use or unavailable. Nonetheless, improved counting devices and low-cost pulse oximeters are now available on the market. OBJECTIVE: The objective of our study was to identify the most accurate, usable, and acceptable devices for the diagnosis of pneumonia symptoms by community health workers and first-level health facility workers or frontline health workers in resource-poor settings. METHODS: This was a multicenter, prospective, two-stage, observational study to assess the performance and usability or acceptability of 9 potential diagnostic devices when used to detect symptoms of pneumonia in the hands of frontline health workers. Notably, 188 possible devices were ranked and scored, tested for suitability in a laboratory, and 5 pulse oximeters and 4 RR timers were evaluated for usability and performance by frontline health workers in hospital, health facility, and community settings. The performance was evaluated against 2 references over 3 months in Cambodia, Ethiopia, South Sudan, and Uganda. Furthermore, acceptability and usability was subsequently evaluated using both qualitative and quantitative methodologies in routine practice, over 3 months, in the 4 countries. RESULTS: This project was funded in 2014, and data collection has been completed. Data analysis is currently under way, and the first results are expected to be submitted for publication in 2018. CONCLUSIONS: This is the first large-scale evaluation of tools to detect symptoms of pneumonia at the community level. In addition, selecting an appropriate reference standard against which the devices were measured was challenging given the lack of existing standards and differences of opinions among experts. The findings from this study will help create a standardized and validated protocol for future studies and support further comparative testing of diagnostic devices in these settings. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000348550; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367306&isReview=true (Archived by Website at http://www.webcitation.org/72OcvgBcf). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/10191.

The use of formative research to inform the design of a seasonal malaria chemoprevention intervention in northern Nigeria.

BACKGROUND: Experience of seasonal malaria chemoprevention (SMC) is growing in the Sahel sub-region of Africa, though there remains insufficient evidence to recommend a standard deployment strategy. In 2012, a project was initiated in Katsina state, northern Nigeria, to design an appropriate and effective community-based delivery approach for SMC, in consultation with local stakeholders. Formative research (FR) was conducted locally to explore the potential feasibility and acceptability of SMC and to highlight information gaps and practical considerations to inform the intervention design. METHODS: The FR adopted qualitative methods; 36 in-depth interviews and 18 focus group discussions were conducted across 13 target groups active across the health system and within the community. Analysis followed the 'framework' approach. The process for incorporating the FR results into the project design was iterative which was initiated by a week-long 'intervention design' workshop with relevant stakeholders. RESULTS: The FR highlighted both supportive and hindering factors to be considered in the intervention design. Malaria control was identified as a community priority, the community health workers were a trusted resource and the local leadership exerted strong influence over household decisions. However, there were perceived challenges with quality of care at both community and health facility levels, referral linkage and supportive supervision were weak, literacy levels lower than anticipated and there was the potential for suspicion of 'outside' interventions. There was broad consensus across target groups that community-based SMC drug delivery would better enable a high coverage of beneficiaries and potentially garner wider community support. A mixed approach was recommended, including both community fixed-point and household-to-household SMC delivery. The FR findings were used to inform the overall distribution strategy, mechanisms for integration into the health system, capacity building and training approaches, supportive interventions to strengthen the health system, and the social mobilization strategy. CONCLUSIONS: Formative research played a valuable role in exploring local socio-cultural contexts and health system realities. Both opportunities and challenges for the introduction of SMC delivery were highlighted, which were appropriately considered in the design of the project.