Exposure to deltamethrin affects development of Plasmodium falciparum inside wild pyrethroid resistant Anopheles gambiae s.s. mosquitoes in Uganda.

BACKGROUND: Pyrethroid resistance in African vector mosquitoes is a threat to malaria control. Resistant mosquitoes can survive insecticide doses that would normally be lethal. We studied effects of such doses on Plasmodium falciparum development inside kdr-resistant Anopheles gambiae s.s. in Uganda. METHODS: We collected An. gambiae s.s. homozygous for kdr-L1014S mutation, fed them on blood samples from 42 P. falciparum-infected local patients, then exposed them either to nets treated with sub-lethal doses of deltamethrin or to untreated nets. After seven days, we dissected 692 mosquitoes and examined their midguts for oocysts. Prevalence (proportion infected) and intensity of infection (number of oocysts per infected mosquito) were recorded for each group. RESULTS: Both prevalence and intensity of infection were significantly reduced in deltamethrin-exposed mosquitoes, compared to those exposed to untreated nets. With low doses (2.5-5.0 mg/m(2)), prevalence was reduced by 59% (95% CI = 22%-78%) and intensity by 41% (95% CI = 25%-54%). With high doses (10-16.7 mg/m(2)), prevalence was reduced by 80% (95% CI = 67%-88 %) and intensity by 34 % (95 % CI = 20%-46%). CONCLUSIONS: We showed that, with locally-sampled parasites and mosquitoes, doses of pyrethroids that are sub-lethal for resistant mosquitoes can interfere with parasite development inside mosquitoes. This mechanism could enable pyrethroid-treated nets to prevent malaria transmission despite increasing vector resistance

Supervising community health workers in low-income countries--a review of impact and implementation issues.

BACKGROUND: Community health workers (CHWs) are an increasingly important component of health systems and programs. Despite the recognized role of supervision in ensuring CHWs are effective, supervision is often weak and under-supported. Little is known about what constitutes adequate supervision and how different supervision strategies influence performance, motivation, and retention. OBJECTIVE: To determine the impact of supervision strategies used in low- and middle-income countries and discuss implementation and feasibility issues with a focus on CHWs. DESIGN: A search of peer-reviewed, English language articles evaluating health provider supervision strategies was conducted through November 2013. Included articles evaluated the impact of supervision in low- or middle-income countries using a controlled, pre-/post- or observational design. Implementation and feasibility literature included both peer-reviewed and gray literature. RESULTS: A total of 22 impact papers were identified. Papers were from a range of low- and middle-income countries addressing the supervision of a variety of health care providers. We classified interventions as testing supervision frequency, the supportive/facilitative supervision package, supervision mode (peer, group, and community), tools (self-assessment and checklists), focus (quality assurance/problem solving), and training. Outcomes included coverage, performance, and perception of quality but were not uniform across studies. Evidence suggests that improving supervision quality has a greater impact than increasing frequency of supervision alone. Supportive supervision packages, community monitoring, and quality improvement/problem-solving approaches show the most promise; however, evaluation of all strategies was weak. CONCLUSION: Few supervision strategies have been rigorously tested and data on CHW supervision is particularly sparse. This review highlights the diversity of supervision approaches that policy makers have to choose from and, while choices should be context specific, our findings suggest that high-quality supervision that focuses on supportive approaches, community monitoring, and/or quality assurance/problem solving may be most effective

Artemisinin resistance--modelling the potential human and economic costs.

BACKGROUND: Artemisinin combination therapy is recommended as first-line treatment for falciparum malaria across the endemic world and is increasingly relied upon for treating vivax malaria where chloroquine is failing. Artemisinin resistance was first detected in western Cambodia in 2007, and is now confirmed in the Greater Mekong region, raising the spectre of a malaria resurgence that could undo a decade of progress in control, and threaten the feasibility of elimination. The magnitude of this threat has not been quantified. METHODS: This analysis compares the health and economic consequences of two future scenarios occurring once artemisinin-based treatments are available with high coverage. In the first scenario, artemisinin combination therapy (ACT) is largely effective in the management of uncomplicated malaria and severe malaria is treated with artesunate, while in the second scenario ACT are failing at a rate of 30%, and treatment of severe malaria reverts to quinine. The model is applied to all malaria-endemic countries using their specific estimates for malaria incidence, transmission intensity and GDP. The model describes the direct medical costs for repeated diagnosis and retreatment of clinical failures as well as admission costs for severe malaria. For productivity losses, the conservative friction costing method is used, which assumes a limited economic impact for individuals that are no longer economically active until they are replaced from the unemployment pool. RESULTS: Using conservative assumptions and parameter estimates, the model projects an excess of 116,000 deaths annually in the scenario of widespread artemisinin resistance. The predicted medical costs for retreatment of clinical failures and for management of severe malaria exceed US$32 million per year. Productivity losses resulting from excess morbidity and mortality were estimated at US$385 million for each year during which failing ACT remained in use as first-line treatment. CONCLUSIONS: These 'ballpark' figures for the magnitude of the health and economic threat posed by artemisinin resistance add weight to the call for urgent action to detect the emergence of resistance as early as possible and contain its spread from known locations in the Mekong region to elsewhere in the endemic world

Evaluation of community-based systems for the surveillance of day three-positive Plasmodium falciparum cases in Western Cambodia.

BACKGROUND: Delayed clearance of Plasmodium falciparum parasites is used as an operational indicator of potential artemisinin resistance. Effective community-based systems to detect P. falciparum cases remaining positive 72 hours after initiating treatment would be valuable for guiding case follow-up in areas of known resistance risk and for detecting areas of emerging resistance. METHODS: Systems incorporating existing networks of village malaria workers (VMWs) to monitor day three-positive P. falciparum cases were piloted in three provinces in western Cambodia. Quantitative and qualitative data were used to evaluate the wider feasibility and sustainability of community-based surveillance of day three-positive P. falciparum cases. RESULTS: Of 294 day-3 blood slides obtained across all sites (from 297 day-0 positives), 63 were positive for P. falciparum, an overall day-3 positivity rate of 21%. There were significant variations in the systems implemented by different partners. Full engagement of VMWs and health centre staff is critical. VMWs are responsible for a range of individual tasks including preparing blood slides on day-0, completing forms, administering directly observed therapy (DOT) on days 0-2, obtaining follow-up slides on day-3 and transporting slides and paperwork to their supervising health centre. When suitably motivated, unsalaried VMWs are willing and able to produce good quality blood smears and achieve very high rates of DOT and day-3 follow-up. CONCLUSIONS: Community-based surveillance of day-3 P. falciparum cases is feasible, but highly intensive, and as such needs strong and continuous support, particularly supervision and training. The purpose and role of community-based day-3 surveillance should be assessed in the light of resource requirements; scaling-up would need to be systematic and targeted, based on clearly defined epidemiological criteria. To be truly comprehensive, the system would need to be extended beyond VMWs to other public and private health providers

Mobile health (mHealth) approaches and lessons for increased performance and retention of community health workers in low- and middle-income countries: a review.

BACKGROUND: Mobile health (mHealth) describes the use of portable electronic devices with software applications to provide health services and manage patient information. With approximately 5 billion mobile phone users globally, opportunities for mobile technologies to play a formal role in health services, particularly in low- and middle-income countries, are increasingly being recognized. mHealth can also support the performance of health care workers by the dissemination of clinical updates, learning materials, and reminders, particularly in underserved rural locations in low- and middle-income countries where community health workers deliver integrated community case management to children sick with diarrhea, pneumonia, and malaria. OBJECTIVE: Our aim was to conduct a thematic review of how mHealth projects have approached the intersection of cellular technology and public health in low- and middle-income countries and identify the promising practices and experiences learned, as well as novel and innovative approaches of how mHealth can support community health workers. METHODS: In this review, 6 themes of mHealth initiatives were examined using information from peer-reviewed journals, websites, and key reports. Primary mHealth technologies reviewed included mobile phones, personal digital assistants (PDAs) and smartphones, patient monitoring devices, and mobile telemedicine devices. We examined how these tools could be used for education and awareness, data access, and for strengthening health information systems. We also considered how mHealth may support patient monitoring, clinical decision making, and tracking of drugs and supplies. Lessons from mHealth trials and studies were summarized, focusing on low- and middle-income countries and community health workers. RESULTS: The review revealed that there are very few formal outcome evaluations of mHealth in low-income countries. Although there is vast documentation of project process evaluations, there are few studies demonstrating an impact on clinical outcomes. There is also a lack of mHealth applications and services operating at scale in low- and middle-income countries. The most commonly documented use of mHealth was 1-way text-message and phone reminders to encourage follow-up appointments, healthy behaviors, and data gathering. Innovative mHealth applications for community health workers include the use of mobile phones as job aides, clinical decision support tools, and for data submission and instant feedback on performance. CONCLUSIONS: With partnerships forming between governments, technologists, non-governmental organizations, academia, and industry, there is great potential to improve health services delivery by using mHealth in low- and middle-income countries. As with many other health improvement projects, a key challenge is moving mHealth approaches from pilot projects to national scalable programs while properly engaging health workers and communities in the process. By harnessing the increasing presence of mobile phones among diverse populations, there is promising evidence to suggest that mHealth can be used to deliver increased and enhanced health care services to individuals and communities, while helping to strengthen health systems

Reactive case-detection of malaria in Pailin Province, Western Cambodia: lessons from a year-long evaluation in a pre-elimination setting.

BACKGROUND: As momentum towards malaria elimination grows, strategies are being developed for scale-up in elimination settings. One prominent strategy, reactive case detection (RACD), involves screening and treating individuals living in close proximity to passively detected, or "index" cases. This study aims to use RACD to quantify Plasmodium parasitaemia in households of index cases, and identify risk factors for infection; these data could inform reactive screening approaches and identify target risk groups. METHODS: This study was conducted in the Western Cambodian province of Pailin between May 2013 and March 2014 among 440 households. Index participants/index cases (n = 270) and surrounding households (n = 110) were screened for Plasmodium infection with rapid diagnostic tests (RDT), microscopy and real-time polymerase chain reaction (PCR). Participants were interviewed to identify risk factors. A comparison group of 60 randomly-selected households was also screened, to compare infection levels of RACD and non-RACD households. In order to identify potential risk factors that would inform screening approaches and identify risk groups, multivariate logistic regression models were applied. RESULTS: Nine infections were identified in households of index cases (RACD approach) through RDT screening of 1898 individuals (seven Plasmodium vivax, two Plasmodium falciparum); seven were afebrile. Seventeen infections were identified through PCR screening of 1596 individuals (15 P. vivax, and 22 % P. falciparum/P. vivax mixed infections). In the control group, 25 P. falciparum infections were identified through PCR screening of 237 individuals, and no P. vivax was found. Plasmodium falciparum infection was associated with fever (p = 0.013), being a member of a control household (p ≤ 0.001), having a history of malaria infection (p = 0.041), and sleeping without a mosquito net (p = 0.011). Significant predictors of P. vivax infection, as diagnosed by PCR, were fever (p = 0.058, borderline significant) and history of malaria infection (p ≤ 0.001). CONCLUSION: This study found that RACD identified very few secondary infections when targeting index and neighbouring households for screening. The results suggest RACD is not appropriate, where exposure to malaria occurs away from the community, and there is a high level of treatment-seeking from the private sector. Piloting RACD in a range of transmission settings would help to identify the ideal environment for feasible and effective reactive screening methods

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