Improving community health worker treatment for malaria, diarrhoea, and pneumonia in Uganda through inSCALE community and mHealth innovations: A cluster randomised controlled trial.

The inSCALE cluster randomised controlled trial in Uganda evaluated two interventions, mHealth and Village Health Clubs (VHCs) which aimed to improve Community Health Worker (CHW) treatment for malaria, diarrhoea, and pneumonia within the national Integrated Community Case Management (iCCM) programme. The interventions were compared with standard care in a control arm. In a cluster randomised trial, 39 sub-counties in Midwest Uganda, covering 3167 CHWs, were randomly allocated to mHealth; VHC or usual care (control) arms. Household surveys captured parent-reported child illness, care seeking and treatment practices. Intention-to-treat analysis estimated the proportion of appropriately treated children with malaria, diarrhoea, and pneumonia according to WHO informed national guidelines. The trial was registered at ClinicalTrials.gov (NCT01972321). Between April-June 2014, 7679 households were surveyed; 2806 children were found with malaria, diarrhoea, or pneumonia symptoms in the last one month. Appropriate treatment was 11% higher in the mHealth compared to the control arm (risk ratio [RR] 1.11, 95% CI 1.02, 1.21; p = 0.018). The largest effect was on appropriate treatment for diarrhoea (RR 1.39; 95% CI 0.90, 2.15; p = 0.134). The VHC intervention increased appropriate treatment by 9% (RR 1.09; 95% CI 1.01, 1.18; p = 0.059), again with largest effect on treatment of diarrhoea (RR 1.56, 95% CI 1.04, 2.34, p = 0.030). CHWs provided the highest levels of appropriate treatment compared to other providers. However, improvements in appropriate treatment were observed at health facilities and pharmacies, with CHW appropriate treatment the same across the arms. The rate of CHW attrition in both intervention arms was less than half that of the control arm; adjusted risk difference mHealth arm -4.42% (95% CI -8.54, -0.29, p = 0.037) and VHC arm -4.75% (95% CI -8.74, -0.76, p = 0.021). Appropriate treatment by CHWs was encouragingly high across arms. The inSCALE mHealth and VHC interventions have the potential to reduce CHW attrition and improve the care quality for sick children, but not through improved CHW management as we had hypothesised. Trial Registration:ClinicalTrials.gov (NCT01972321).

Improving outcomes for children with malaria, diarrhoea and pneumonia in Mozambique: A cluster randomised controlled trial of the inSCALE technology innovation.

BACKGROUND: The majority of post-neonatal deaths in children under 5 are due to malaria, diarrhoea and pneumonia (MDP). The WHO recommends integrated community case management (iCCM) of these conditions using community-based health workers (CHW). However iCCM programmes have suffered from poor implementation and mixed outcomes. We designed and evaluated a technology-based (mHealth) intervention package 'inSCALE' (Innovations At Scale For Community Access and Lasting Effects) to support iCCM programmes and increase appropriate treatment coverage for children with MDP. METHODS: This superiority cluster randomised controlled trial allocated all 12 districts in Inhambane Province in Mozambique to receive iCCM only (control) or iCCM plus the inSCALE technology intervention. Population cross-sectional surveys were conducted at baseline and after 18 months of intervention implementation in approximately 500 eligible households in randomly selected communities in all districts including at least one child less than 60 months of age where the main caregiver was available to assess the impact of the intervention on the primary outcome, the coverage of appropriate treatment for malaria, diarrhoea and pneumonia in children 2-59months of age. Secondary outcomes included the proportion of sick children who were taken to the CHW for treatment, validated tool-based CHW motivation and performance scores, prevalence of cases of illness, and a range of secondary household and health worker level outcomes. All statistical models accounted for the clustered study design and variables used to constrain the randomisation. A meta-analysis of the estimated pooled impact of the technology intervention was conducted including results from a sister trial (inSCALE-Uganda). FINDINGS: The study included 2740 eligible children in control arm districts and 2863 children in intervention districts. After 18 months of intervention implementation 68% (69/101) CHWs still had a working inSCALE smartphone and app and 45% (44/101) had uploaded at least one report to their supervising health facility in the last 4 weeks. Coverage of the appropriate treatment of cases of MDP increased by 26% in the intervention arm (adjusted RR 1.26 95% CI 1.12-1.42, p<0.001). The rate of care seeking to the iCCM-trained community health worker increased in the intervention arm (14.4% vs 15.9% in control and intervention arms respectively) but fell short of the significance threshold (adjusted RR 1.63, 95% CI 0.93-2.85, p = 0.085). The prevalence of cases of MDP was 53.5% (1467) and 43.7% (1251) in the control and intervention arms respectively (risk ratio 0.82, 95% CI 0.78-0.87, p<0.001). CHW motivation and knowledge scores did not differ between intervention arms. Across two country trials, the estimated pooled effect of the inSCALE intervention on coverage of appropriate treatment for MDP was RR 1.15 (95% CI 1.08-1.24, p <0.001). INTERPRETATION: The inSCALE intervention led to an improvement in appropriate treatment of common childhood illnesses when delivered at scale in Mozambique. The programme will be rolled out by the ministry of health to the entire national CHW and primary care network in 2022-2023. This study highlights the potential value of a technology intervention aimed at strengthening iCCM systems to address the largest causes of childhood morbidity and mortality in sub-Saharan Africa.

Perennial malaria chemoprevention with and without malaria vaccination to reduce malaria burden in young children: a modelling analysis.

BACKGROUND: A recent WHO recommendation for perennial malaria chemoprevention (PMC) encourages countries to adapt dose timing and number to local conditions. However, knowledge gaps on the epidemiological impact of PMC and possible combination with the malaria vaccine RTS,S hinder informed policy decisions in countries where malaria burden in young children remains high. METHODS: The EMOD malaria model was used to predict the impact of PMC with and without RTS,S on clinical and severe malaria cases in children under the age of two years (U2). PMC and RTS,S effect sizes were fit to trial data. PMC was simulated with three to seven doses (PMC-3-7) before the age of eighteen months and RTS,S with three doses, shown to be effective at nine months. Simulations were run for transmission intensities of one to 128 infectious bites per person per year, corresponding to incidences of < 1 to 5500 cases per 1000 population U2. Intervention coverage was either set to 80% or based on 2018 household survey data for Southern Nigeria as a sample use case. The protective efficacy (PE) for clinical and severe cases in children U2 was calculated in comparison to no PMC and no RTS,S. RESULTS: The projected impact of PMC or RTS,S was greater at moderate to high transmission than at low or very high transmission. Across the simulated transmission levels, PE estimates of PMC-3 at 80% coverage ranged from 5.7 to 8.8% for clinical, and from 6.1 to 13.6% for severe malaria (PE of RTS,S 10-32% and 24.6-27.5% for clinical and severe malaria, respectively. In children U2, PMC with seven doses nearly averted as many cases as RTS,S, while the combination of both was more impactful than either intervention alone. When operational coverage, as seen in Southern Nigeria, increased to a hypothetical target of 80%, cases were reduced beyond the relative increase in coverage. CONCLUSIONS: PMC can substantially reduce clinical and severe cases in the first two years of life in areas with high malaria burden and perennial transmission. A better understanding of the malaria risk profile by age in early childhood and on feasible coverage by age, is needed for selecting an appropriate PMC schedule in a given setting.

Developing African arbovirus networks and capacity strengthening in arbovirus surveillance and response: findings from a virtual workshop.

This meeting report presents the key findings and discussion points of a 3-h virtual workshop, held on 21 September 2022, and organized by the "Resilience Against Future Threats through Vector Control (RAFT)" research consortium. The workshop aimed to identify priorities for advancing arbovirus research, network and capacity strengthening in Africa. Due to increasing human population growth, urbanization and global movement (trade, tourism, travel), mosquito-borne arboviral diseases, such as dengue, Chikungunya and Zika, are increasing globally in their distribution and prevalence. This report summarizes the presentations that reviewed the current status of arboviruses in Africa, including: (i) key findings from the recent WHO/Special Programme for Research & Training in Tropical Diseases (WHO/TDR) survey in 47 African countries that revealed deep and widespread shortfalls in the capacity to cope with arbovirus outbreak preparedness, surveillance and control; (ii) the value of networking in this context, with examples of African countries regarding arbovirus surveillance; and (iii) the main priorities identified by the breakout groups on "research gaps", "networks" and "capacity strengthening".

A non-randomized controlled trial to assess the protective effect of SMC in the context of high parasite resistance in Uganda.

BACKGROUND: Until recently, due to widespread prevalence of molecular markers associated with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) resistance in east and southern Africa, seasonal malaria chemoprevention (SMC) has not been used at scale in this region. This study assessed the protective effectiveness of monthly administration of SP + AQ (SPAQ) to children aged 3-59 months in Karamoja sub-region, Uganda, where parasite resistance is assumed to be high and malaria transmission is seasonal. METHODS: A two-arm quasi-experimental, open-label prospective non-randomized control trial (nRCT) was conducted in three districts. In two intervention districts, 85,000 children aged 3-59 months were targeted to receive monthly courses of SMC using SPAQ during the peak transmission season (May to September) 2021. A third district served as a control, where SMC was not implemented. Communities with comparable malaria attack rates were selected from the three districts, and households with at least one SMC-eligible child were purposively selected. A total cohort of 600 children (200 children per district) were selected and followed using passive surveillance for breakthrough confirmed malaria episodes during the five-month peak transmission season. Malaria incidence rate per person-months and number of malaria episodes among children in the two arms were compared. Kaplan-Meier failure estimates were used to compare the probability of a positive malaria test. Other factors that may influence malaria transmission and infection among children in the two arms were also assessed using multivariable cox proportional hazards regression model. RESULTS: The malaria incidence rate was 3.0 and 38.8 per 100 person-months in the intervention and control groups, respectively. In the intervention areas 90.0% (361/400) of children did not experience any malaria episodes during the study period, compared to 15% (29/200) in the control area. The incidence rate ratio was 0.078 (95% CI 0.063-0.096), which corresponds to a protective effectiveness of 92% (95% CI 90.0-94.0) among children in the intervention area. CONCLUSION: SMC using SPAQ provided high protective effect against malaria during the peak transmission season in children aged 3-59 months in the Karamoja sub-region of Uganda.

Baseline prevalence of molecular marker of sulfadoxine/pyrimethamine resistance in Ebonyi and Osun states, Nigeria: amplicon deep sequencing of dhps-540.

BACKGROUND: Chemoprevention plays an important role in malaria control strategy. Perennial malaria chemoprevention (PMC) using sulfadoxine/pyrimethamine (SP) is a WHO-approved strategy to combat malaria in young children and may lead to drug pressure. Introducing SP-PMC may therefore be compromised due to the emergence of Plasmodium falciparum resistant to SP, particularly mutation at K540E of the dihydropteroate synthase (dhps) gene. Molecular surveillance of resistance markers can support assessment of antimalarial efficacy and effectiveness. High prevalence of 540E is associated with reduced effectiveness of SP, and areas with more than 50% prevalence are considered unsuitable for intermittent preventative treatment in pregnancy (IPTp) implementation. Assessing 540E prevalence is an important undertaking before implementation of SP-PMC. METHODS: We conducted a rapid surveillance of dhps-540E to assess the suitability of SP as PMC in field studies from Ebonyi and Osun states in Nigeria. We used an in-house developed amplicon deep-sequencing method targeting part of the dhps gene. RESULTS: Our data reveal that 18.56% of individuals evaluated carried the 540E mutation mixed with the WT K540. Mutant variant 540E alone was not found, and 80% of isolates harboured only WT (K540). Clonal analysis of the sequencing data shows a very low proportion of 540E circulating in both states. CONCLUSIONS: Our data show that both states are suitable for SP-PMC implementation and, based on this finding, SP-PMC was implemented in Osun in 2022. Continuous monitoring of 540E will be required to ensure the chemoprevention effectiveness of SP in Nigeria.

A hybrid effectiveness-implementation study protocol to assess the effectiveness and chemoprevention efficacy of implementing seasonal malaria chemoprevention in five districts in Karamoja region, Uganda.

Background: The World Health Organization (WHO) recommends seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SPAQ) for children aged 3 to 59 months, living in areas where malaria transmission is highly seasonal. However, due to widespread prevalence of resistance markers, SMC has not been implemented at scale in East and Southern Africa. An initial study in Uganda showed that SMC with SPAQ was feasible, acceptable, and protective against malaria in eligible children in Karamoja region. Nonetheless, exploration of alternative regimens is warranted since parasite resistance threats persist. Objective: The study aims to test the effectiveness of SMC with Dihydroartemisinin-piperaquine (DP) or SPAQ (DP-SMC & SPAQ-SMC), chemoprevention efficacy as well as the safety and tolerability of DP compared to that of SPAQ among 3-59 months old children in Karamoja region, an area of Uganda where malaria transmission is highly seasonal. Methods: A Type II hybrid effectiveness-implementation study design consisting of four components: 1) a cluster randomized controlled trial (cRCT) using passive surveillance to establish confirmed malaria cases in children using both SPAQ and DP; 2a) a prospective cohort study to determine the chemoprevention efficacy of SPAQ and DP (if SPAQ or DP clears sub-patent infection and provides 28 days of protection from new infection) and whether drug concentrations and/or resistance influence the ability to clear and prevent infection; 2b) a sub study examining pharmacokinetics of DP in children between 3 to <6 months; 3) a resistance markers study in children 3-59 months in the research districts plus the standard intervention districts to measure changes in resistance marker prevalence over time and finally; 4) a process evaluation. Discussion: This study evaluates the effects of SPAQ-SMC versus DP-SMC on clinical malaria in vulnerable children in the context of high parasite SP resistance, whilst informing on the best implementation strategies. Conclusion: This study will inform malaria policy in high-burden countries, specifically on utility of SMC outside the sahel, and contribute to progress in malaria control.

The private sector market for malaria rapid diagnostic tests in Nigeria: results of the 2018 market survey.

BACKGROUND: To avoid misuse of anti-malarials, correct diagnosis of fever prior to drug prescription is essential. Presumptive treatment in the private healthcare sector is a concern in Nigeria, where availability of affordable artemisinin-based combination therapy (ACT) is high following the implementation of subsidy schemes from 2010 to 2017. Similar subsidies have not, however, been implemented for malaria rapid diagnostic tests (RDTs). A market survey in 2018 predominantly designed to assess the ACT market in the private sector also collected data related to RDTs, results of which are presented herein. METHODS: A 2018 market survey consisted of (i) an outlet survey targeting private pharmacies and Proprietary and Patent Medicine Vendors (PPMVs) across different regions of Nigeria to assess supply-side market factors related to availability of RDTs (defined as having stock available for purchase at the time of the survey) and (ii) a household survey to determine demand-side factors related to knowledge of RDTs, healthcare-seeking practices and affordability. RESULTS: Availability of RDTs at the time of the survey was low in both outlet types and significantly lower in PPMVs (22.1%, 95% CI) among pharmacies versus (13.6%, 95% CI) among PPMVs (p < 0.01). Reasons for not restocking RDTs included low demand and no supply. The majority of households diagnose malaria based on experience, while one-third would visit a PPMV or pharmacy. Half of households had heard of RDTs (48.4%) and 38.6% thought they were affordable. CONCLUSIONS: Low availability of RDTs among PPMVs and pharmacies may be attributed to lack of demand, supply-side issues and cost. Increasing household knowledge of RDTs may aid increasing demand, while subsidized RDTs may address supply and price issues. Addressing the deficit in RDT provision is important for targeting of ACT medicines.

The impact of the private sector co-payment mechanism (PSCM) on the private market for ACT in Nigeria: results of the 2018 cross-sectional outlet and household market surveys.

BACKGROUND: The private sector plays a large role in malaria treatment provision in Nigeria. To improve access to, and affordability of, quality-assured artemisinin-based combination therapy (QA-ACT) within this sector, the Affordable Medicines Facility-Malaria began operations in 2010 and transitioned to a private sector co-payment mechanism (PSCM) until 2017. To assess the impact of the scheme on the ACT market, cross-sectional household and outlet surveys were conducted in 2018 to coincide with the final stockages of ACT medicines procured under the PSCM. METHODS: An outlet survey was conducted targeting private pharmacies and Proprietary and Patent Medicine Vendors (PPMVs) across different regions of Nigeria to assess supply-side market factors related to availability and cost of anti-malarials, including artemisinin-based combinations subsidised under the PSCM (called green leaf ACT on account of their green leaf logo) and those not subsidised (non-green leaf ACT). A concurrent household survey was conducted to determine demand-side factors related to treatment-seeking practices, ACT brand preference and purchase decision. Data were compared with previous ACTWatch surveys to consider change over time. RESULTS: Availability of artemisinin-based combinations increased significantly over the PSCM period and was almost universal by the time of the 2018 market survey. This increase was seen particularly among PPMVs. While the cost of green leaf ACT remained relatively stable over time, the cost of non-green leaf ACT reduced significantly so that by 2018 they had equivalent affordability. Unsubsidised brands were also available in different formulations and dosages, with double-strength artemisinin-based combination reported as the most frequently purchased dosage type, and child artemisinin-based combinations popular in suspension and dispersible forms (forms not subsidised by the PSCM). CONCLUSIONS: The PSCM had a clear impact on increasing not only the reach of subsidized QA brands, but also of non-subsidised brands. Increased market competition led to innovation from unsubsidised brands and large reductions in costs to make them competitive with subsidised brands. Concerns are drawn from the large market share that non-QA brands have managed to gain as well as the continued market share of oral artemisinin monotherapies. Continued monitoring of the market is recommended, along with improved local capacity for QA-certification and monitoring.

District-led malaria surveillance and response as an effective way to manage malaria upsurges following the withdrawal of indoor residual spraying: a case study from Nwoya District, northern Uganda.

BACKGROUND: Malaria remains the number one cause of morbidity and mortality in Uganda. In 2009, the United States President's Malaria Initiative (PMI) funded an indoor residual spraying (IRS) project in 10 mid-northern districts, resulting in marked reductions in malaria prevalence over 5 years, from 62.5 percent to 7.2 percent. When the project ended and IRS withdrawn, malaria prevalence increased exponentially to pre-IRS level of 63 percent in 2016 and was characterized by frequent life-threatening upsurges that were exacerbated by a weak national led malaria surveillance system with delayed and piece meal responses. Malaria Consortium, in collaboration with Nwoya district local government implemented a district led malaria surveillance and response system. This study was conducted to compare the impact of District led and national led surveillance and response systems on overall malaria burden in two sub-counties in Nwoya district, Northern Uganda. METHODS: The assessment was conducted between week 41 of 2018 and week 10 of 2019 in Anaka and Alero sub counties following the shift from the national to district led malaria surveillance and response system. A district multi-sectoral malaria response taskforce team, known as the District Malaria Surveillance and Response Team (DMSRT), was formed by the Nwoya District Health Team (DHT). The DMSRT was trained and equipped with new surveillance tools for early detection of and response to malaria upsurges within the district, and were mandated to develop a costed district specific malaria response plan. RESULTS: All (18) targeted health facilities provided weekly malaria reports and continuously updated the malaria normal channel graphs. There was an overall reduction in weekly new malaria cases from 12.9 in week 41 of 2018 to 6.2 cases in week 10 of 2019. Malaria positivity rates (TPR) for Alero and Anaka sub-counties reduced from 76.0 percent and 69.3 percent at week 42 of 2018 to 28 percent and 30.3 percent, respectively at week 10 of 2019. CONCLUSIONS: Malaria surveillance and response, with precisely targeted multipronged activities, when led and implemented by local district health authorities is an effective, efficient, and sustainable approach to prevent malaria upsurges and associated morbidity and mortality.

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).

Determinants of malaria testing at health facilities: the case of Uganda.

BACKGROUND: The World Health Organization (WHO) recommends prompt malaria diagnosis with either microscopy or malaria rapid diagnostic tests (RDTs) and treatment with an effective anti-malarial, as key interventions to control malaria. However, in sub-Saharan Africa, malaria diagnosis is still often influenced by clinical symptoms, with patients and care providers often interpreting all fevers as malaria. The Ministry of Health in Uganda defines suspected malaria cases as those with a fever. A target of conducting testing for at least 75% of those suspected to have malaria was established by the National Malaria Reduction Strategic Plan 2014-2020. METHODS: This study investigated factors that affect malaria testing at health facilities in Uganda using data collected in March/April 2017 in a cross-sectional survey of health facilities from the 52 districts that are supported by the US President's Malaria Initiative (PMI). The study assessed health facility capacity to provide quality malaria care and treatment. Data were collected from all 1085 public and private health facilities in the 52 districts. Factors assessed included supportive supervision, availability of malaria management guidelines, laboratory infrastructure, and training health workers in the use of malaria rapid diagnostic test (RDT). Survey data were matched with routinely collected health facility malaria data obtained from the district health information system Version-2 (DHIS2). Associations between testing at least 75% of suspect malaria cases with several factors were examined using multivariate logistic regression. RESULTS: Key malaria commodities were widely available; 92% and 85% of the health facilities reported availability of RDTs and artemether-lumefantrine, respectively. Overall, 933 (86%) of the facilities tested over 75% of patients suspected to have malaria. Predictors of meeting the testing target were: supervision in the last 6 months (OR: 1.72, 95% CI 1.04-2.85) and a health facility having at least one health worker trained in the use of RDTs (OR: 1.62, 95% CI 1.04-2.55). CONCLUSION: The study findings underscore the need for malaria control programmes to provide regular supportive supervision to health facilities and train health workers in the use of RDTs.

Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria and prevalence of molecular markers associated with artemisinin and partner drug resistance in Uganda.

BACKGROUND: In Uganda, artemether-lumefantrine (AL) is first-line therapy and dihydroartemisinin-piperaquine (DP) second-line therapy for the treatment of uncomplicated malaria. This study evaluated the efficacy and safety of AL and DP in the management of uncomplicated falciparum malaria and measured the prevalence of molecular markers of resistance in three sentinel sites in Uganda from 2018 to 2019. METHODS: This was a randomized, open-label, phase IV clinical trial. Children aged 6 months to 10 years with uncomplicated falciparum malaria were randomly assigned to treatment with AL or DP and followed for 28 and 42 days, respectively. Genotyping was used to distinguish recrudescence from new infection, and a Bayesian algorithm was used to assign each treatment failure a posterior probability of recrudescence. For monitoring resistance, Pfk13 and Pfmdr1 genes were Sanger sequenced and plasmepsin-2 copy number was assessed by qPCR. RESULTS: There were no early treatment failures. The uncorrected 28-day cumulative efficacy of AL ranged from 41.2 to 71.2% and the PCR-corrected cumulative 28-day efficacy of AL ranged from 87.2 to 94.4%. The uncorrected 28-day cumulative efficacy of DP ranged from 95.8 to 97.9% and the PCR-corrected cumulative 28-day efficacy of DP ranged from 98.9 to 100%. The uncorrected 42-day efficacy of DP ranged from 73.5 to 87.4% and the PCR-corrected 42-day efficacy of DP ranged from 92.1 to 97.5%. There were no reported serious adverse events associated with any of the regimens. No resistance-associated mutations in the Pfk13 gene were found in the successfully sequenced samples. In the AL arm, the NFD haplotype (N86Y, Y184F, D1246Y) was the predominant Pfmdr1 haplotype, present in 78 of 127 (61%) and 76 of 110 (69%) of the day 0 and day of failure samples, respectively. All the day 0 samples in the DP arm had one copy of the plasmepsin-2 gene. CONCLUSIONS: DP remains highly effective and safe for the treatment of uncomplicated malaria in Uganda. Recurrent infections with AL were common. In Busia and Arua, the 95% confidence interval for PCR-corrected AL efficacy fell below 90%. Further efficacy monitoring for AL, including pharmacokinetic studies, is recommended. Trial registration The trail was also registered with the ISRCTN registry with study Trial No. PACTR201811640750761.

A feasibility study to assess non-clinical community health workers' capacity to use simplified protocols and tools to treat severe acute malnutrition in Niger state Nigeria.

BACKGROUND: Severe acute malnutrition (SAM) is a major determinant of childhood mortality and morbidity. Although integrated community case management (iCCM) of childhood illnesses is a strategy for increasing access to life-saving treatment, malnutrition is not properly addressed in the guidelines. This study aimed to determine whether non-clinical Community Health Workers (called Community-Oriented Resource Persons, CORPs) implementing iCCM could use simplified tools to treat uncomplicated SAM. METHODS: The study used a sequential multi-method design and was conducted between July 2017 and May 2018. Sixty CORPs already providing iCCM services were trained and deployed in their communities with the target of enrolling 290 SAM cases. Competency of CORPs to treat and the treatment outcomes of enrolled children were documented. SAM cases with MUAC of 9 cm to < 11.5 cm without medical complications were treated for up to 12 weeks. Full recovery was at MUAC≥12.5 cm for two consecutive weeks. Supervision and quantitative data capturing were done weekly while qualitative data were collected after the intervention. RESULTS: CORPs scored 93.1% on first assessment and increment of 0.11 (95% CI, 0.05-0.18) points per additional supervision conducted. The cure rate from SAM to full recovery, excluding referrals from the denominator in line with the standard for reporting SAM recovery rates, was 73.5% and the median length of treatment was 7 weeks. SAM cases enrolled at 9 cm to < 10.25 cm MUAC had 31% less likelihood of recovery compared to those enrolled at 10.25 cm to < 11.5 cm. CORPs were not burdened by the integration of SAM into iCCM and felt motivated by children's recovery. Operational challenges like bad terrains for supervision, supply chain management and referrals were reported by supervisors, while Government funding was identified as key for sustainability. CONCLUSION: The study demonstrated that with training and supportive supervision, CORPs in Nigeria can treat SAM among under-fives, and refer complicated cases using simplified protocols as part of an iCCM programme. This approach seemed acceptable to all stakeholders, however, the effect of the extra workload of integrating SAM into iCCM on the quality of care provided by the CORPs should be assessed further.

An assessment of the knowledge, practices and resources during the delivery of malaria health care services among private health care practitioners: a cross section study in the Mid-Western Region of Uganda.

BACKGROUND: Approximately 50 % of the population in Uganda seeks health care from private facilities but there is limited data on the quality of care for malaria in these facilities. This study aimed to document the knowledge, practices and resources during the delivery of malaria care services, among private health practitioners in the Mid-Western region of Uganda, an area of moderate malaria transmission. METHODS: This was a cross sectional study in which purposive sampling was used to select fifteen private-for-profit facilities from each district. An interviewer-administered questionnaire that contained both quantitative and open-ended questions was used. Information was collected on availability of treatment aides, knowledge on malaria, malaria case management, laboratory practices, malaria drugs stock and data management. We determined the proportion of health workers that adequately provided malaria case management according to national standards. RESULTS: Of the 135 health facilities staff interviewed, 61.48 % (52.91-69.40) had access to malaria treatment protocols while 48.89 % (40.19-57.63) received malaria training. The majority of facilities, 98.52 % (94.75-99.82) had malaria diagnostic services and the most commonly available anti-malarial drug was artemether-lumefantrine, 85.19 % (78-91), followed by Quinine, 74.81 % (67-82) and intravenous artesunate, 72.59 % (64-80). Only 14.07 % (8.69-21.10) responded adequately to the acceptable cascade of malaria case management practice. Specifically, 33.33 % (25.46-41.96) responded correctly to management of a patient with a fever, 40.00 % (31.67-48.79) responded correctly to the first line treatment for uncomplicated malaria, whereas 85.19 % (78.05-90.71) responded correctly to severe malaria treatment. Only 28.83 % submitted monthly reports, where malaria data was recorded, to the national database. CONCLUSIONS: This study revealed sub-optimal malaria case management knowledge and practices at private health facilities with approximately 14 % of health care workers demonstrating correct malaria case management cascade practices. To strengthen the quality of malaria case management, it is recommended that the NMCD distributes current guidelines and tools, coupled with training; continuous mentorship and supportive supervision; provision of adequate stock of essential anti-malarials and RDTs; reinforcing communication and behavior change; and increasing support for data management at private health facilities.

The impact of malaria coinfection on Ebola virus disease outcomes: A systematic review and meta-analysis.

INTRODUCTION: Viral outbreaks present a particular challenge in countries in Africa where there is already a high incidence of other infectious diseases, including malaria which can alter immune responses to secondary infection. Ebola virus disease (EVD) is one such problem; understanding how Plasmodium spp. and Ebolavirus (EBOV) interact is important for future outbreaks. METHODS: We conducted a systematic review in PubMed and Web of Science to find peer-reviewed papers with primary data literature to determine 1) prevalence of EBOV/Plasmodium spp. coinfection, 2) effect of EBOV/Plasmodium spp. coinfection on EVD pathology and the immune response, 3) impact of EBOV/Plasmodium spp. coinfection on the outcome of EVD-related mortality. Random effects meta-analyses were conducted with the R package meta to produce overall proportion and effect estimates as well as measure between-study heterogeneity. RESULTS: From 322 peer-reviewed papers, 17 were included in the qualitative review and nine were included in a meta-analysis. Prevalence of coinfection was between 19% and 72%. One study reported significantly lower coagulatory response biomarkers in coinfected cases but no difference in inflammatory markers. Case fatality rates were similar between EBOV(+)/Pl(+) and EBOV(+)/Pl(-) cases (62.8%, 95% CI 49.3-74.6 and 56.7%, 95% CI 53.2-60.1, respectively), and there was no significant difference in risk of mortality (RR 1.09, 95% CI 0.90-1.31) although heterogeneity between studies was high. One in vivo mouse model laboratory study found no difference in mortality by infection status, but another found prior acute Plasmodium yoeli infection was protective against morbidity and mortality via the IFN-γ signalling pathway. CONCLUSION: The literature was inconclusive; studies varied widely and there was little attempt to adjust for confounding variables. Laboratory studies may present the best option to answer how pathogens interact within the body but improvement in data collection and analysis and in diagnostic methods would aid patient studies in the future.