Effective management of district-level malaria control and elimination: implementing quality and participative process improvements.

Although it is widely recognized that strong program management is essential to achieving better health outcomes, this priority is not recognized in malaria programmatic practices. Increased management precision offers the opportunity to improve the effectiveness of malaria interventions, overcoming operational barriers to intervention coverage and accelerating the path to elimination. Here we propose a combined approach involving quality improvement, quality management, and participative process improvement, which we refer to as Combined Quality and Process Improvement (CQPI), to improve upon malaria program management. We draw on evidence from other areas of public health, as well as pilot implementation studies in Eswatini, Namibia and Zimbabwe to support the proposal. Summaries of the methodological approaches employed in the pilot studies, overview of activities and an outline of lessons learned from the implementation of CQPI are provided. Our findings suggest that a malaria management strategy that prioritizes quality and participative process improvements at the district-level can strengthen teamwork and communication while enabling the empowerment of subnational staff to solve service delivery challenges. Despite the promise of CQPI, however, policy makers and donors are not aware of its potential. Investments are therefore needed to allow CQPI to come to fruition.

Effectiveness of reactive focal mass drug administration and reactive focal vector control to reduce malaria transmission in the low malaria-endemic setting of Namibia: a cluster-randomised controlled, open-label, two-by-two factorial design trial.

BACKGROUND: In low malaria-endemic settings, screening and treatment of individuals in close proximity to index cases, also known as reactive case detection (RACD), is practised for surveillance and response. However, other approaches could be more effective for reducing transmission. We aimed to evaluate the effectiveness of reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in the low malaria-endemic setting of Zambezi (Namibia). METHODS: We did a cluster-randomised controlled, open-label trial using a two-by-two factorial design of 56 enumeration area clusters in the low malaria-endemic setting of Zambezi (Namibia). We randomly assigned these clusters using restricted randomisation to four groups: RACD only, rfMDA only, RAVC plus RACD, or rfMDA plus RAVC. RACD involved rapid diagnostic testing and treatment with artemether-lumefantrine and single-dose primaquine, rfMDA involved presumptive treatment with artemether-lumefantrine, and RAVC involved indoor residual spraying with pirimiphos-methyl. Interventions were administered within 500 m of index cases. To evaluate the effectiveness of interventions targeting the parasite reservoir in humans (rfMDA vs RACD), in mosquitoes (RAVC vs no RAVC), and in both humans and mosquitoes (rfMDA plus RAVC vs RACD only), an intention-to-treat analysis was done. For each of the three comparisons, the primary outcome was the cumulative incidence of locally acquired malaria cases. This trial is registered with ClinicalTrials.gov, number NCT02610400. FINDINGS: Between Jan 1, 2017, and Dec 31, 2017, 55 enumeration area clusters had 1118 eligible index cases that led to 342 interventions covering 8948 individuals. The cumulative incidence of locally acquired malaria was 30·8 per 1000 person-years (95% CI 12·8-48·7) in the clusters that received rfMDA versus 38·3 per 1000 person-years (23·0-53·6) in the clusters that received RACD; 30·2 per 1000 person-years (15·0-45·5) in the clusters that received RAVC versus 38·9 per 1000 person-years (20·7-57·1) in the clusters that did not receive RAVC; and 25·0 per 1000 person-years (5·2-44·7) in the clusters that received rfMDA plus RAVC versus 41·4 per 1000 person-years (21·5-61·2) in the clusters that received RACD only. After adjusting for imbalances in baseline and implementation factors, the incidence of malaria was lower in clusters receiving rfMDA than in those receiving RACD (adjusted incidence rate ratio 0·52 [95% CI 0·16-0·88], p=0·009), lower in clusters receiving RAVC than in those that did not (0·48 [0·16-0·80], p=0·002), and lower in clusters that received rfMDA plus RAVC than in those receiving RACD only (0·26 [0·10-0·68], p=0·006). No serious adverse events were reported. INTERPRETATION: In a low malaria-endemic setting, rfMDA and RAVC, implemented alone and in combination, reduced malaria transmission and should be considered as alternatives to RACD for elimination of malaria. FUNDING: Novartis Foundation, Bill & Melinda Gates Foundation, and Horchow Family Fund.

Targeting populations at higher risk for malaria: a survey of national malaria elimination programmes in the Asia Pacific.

BACKGROUND: Significant progress has been made in reducing the malaria burden in the Asia Pacific region, which is aggressively pursuing a 2030 regional elimination goal. Moving from malaria control to elimination requires National Malaria Control Programmes (NMCPs) to target interventions at populations at higher risk, who are often not reached by health services, highly mobile and difficult to test, treat, and track with routine measures, and if undiagnosed, can maintain parasite reservoirs and contribute to ongoing transmission. METHODS: A qualitative, free-text questionnaire was developed and disseminated among 17 of the 18 partner countries of the Asia Pacific Malaria Elimination Network (APMEN). RESULTS: All 14 countries that responded to the survey identified key populations at higher risk of malaria in their respective countries. Thirteen countries engage in the dissemination of malaria-related Information, Education, and Communication (IEC) materials. Eight countries engage in diagnostic screening, including of mobile and migrant workers, military staff, and/or overseas workers. Ten countries reported distributing or recommending the use of long-lasting insecticide-treated nets (LLINs) among populations at higher risk with fewer countries engaging in other prevention measures such as indoor residual spraying (IRS) (two countries), spatial repellents (four countries), chemoprophylaxis (five countries), and mass drug administration (MDA) (three countries). Though not specifically tailored to populations at higher risk, 11 countries reported using mass blood surveys as a surveillance tool and ten countries map case data. Most NMCPs lack a monitoring and evaluation structure. CONCLUSION: Countries in the Asia Pacific have identified populations at higher risk and targeted interventions to these groups but there is limited information on the effectiveness of these interventions. Platforms like APMEN offer the opportunity for the sharing of protocols and lessons learned related to finding, targeting and successfully clearing malaria from populations at higher risk. The sharing of programme data across borders may further strengthen national and regional efforts to eliminate malaria. This exchange of real-life experience is invaluable to NMCPs when scarce scientific evidence on the topic exists to aid decision-making and can further support NMCPs to develop strategies that will deliver a malaria-free Asia Pacific by 2030.

The changing epidemiology of malaria elimination: new strategies for new challenges.

Malaria-eliminating countries achieved remarkable success in reducing their malaria burdens between 2000 and 2010. As a result, the epidemiology of malaria in these settings has become more complex. Malaria is increasingly imported, caused by Plasmodium vivax in settings outside sub-Saharan Africa, and clustered in small geographical areas or clustered demographically into subpopulations, which are often predominantly adult men, with shared social, behavioural, and geographical risk characteristics. The shift in the populations most at risk of malaria raises important questions for malaria-eliminating countries, since traditional control interventions are likely to be less effective. Approaches to elimination need to be aligned with these changes through the development and adoption of novel strategies and methods. Knowledge of the changing epidemiological trends of malaria in the eliminating countries will ensure improved targeting of interventions to continue to shrink the malaria map.

Baseline characterization of entomological drivers of malaria transmission in Namibia: a targeted operational entomological surveillance strategy.

BACKGROUND: Namibia's focus on the elimination of malaria requires an evidence-based strategy directed at understanding and targeting the entomological drivers of malaria transmission. In 2018 and 2019, the Namibia National Vector-borne Diseases Control Program (NVDCP) implemented baseline entomological surveillance based on a question-based approach outlined in the Entomological Surveillance Planning Tool (ESPT). In the present study, we report on the findings of the ESPT-based NVDCP on baseline vector species composition and bionomic traits in malaria endemic regions in northern Namibia, which has the aim of generating an evidence base for programmatic decision-making. METHODS: Nine representative sentinel sites were included in the 2018 entomological surveillance program (Kunene, Omusati, Oshana, Ohangwena, Oshikoto, Otjozondjupa, Kavango West, Kavango East and Zambezi); the number was reduced to four sites in 2019 due to limited funding (Ohangwena, Kavango West, Kavango East, and Zambezi). In the 2018 baseline collections, multiple sampling methods (human landing catches, pyrethroid spray catches, U.S. Centers for Disease Control and Prevention light traps [CDC-LTs], resting boxes [RBs] and larval sampling) were utilized to evaluate indoor/outdoor human biting rates, resting behaviors and insecticide resistance (IR). CDC-LTs and RBs were not used in 2019 due to low and non-representative sampling efficacies. RESULTS: Overall, molecular evidence demonstrated the presence of three primary mosquito vectors, namely Anopheles arabiensis, rediscovered Anopheles gambiae sensu stricto and Anopheles funestus sensu stricto, alongside Anopheles squamosus and members of the Anopheles coustani complex. Vectors were found to bite throughout the night (1800 hours 0600 hours) both indoors and outdoors, with An. arabiensis having the highest biting rates outdoors. Low numbers of indoor resting Anopheles point to possible low indoor residual spraying (IRS) efficacy-with An. arabiensis found to be the major vector species resting indoors. The IR tests demonstrated varying country-wide resistance levels to the insecticide deltamethrin, with the resistance levels confirmed to have increased in 2019, evidence that impacts national programmatic decision-making. Vectors demonstrated susceptibility to the insecticides dichlorodiphenyltrichloroethane, bendiocarb and Actellic 300CS in 2018, with mosquitoes from only one site (Kavango West) demonstrating possible resistance to DDT. Targeted and question-based entomological surveillance enabled a rapid and focused evidence base to be built, showing where and when humans were being bitten and providing entomological data on long-lasting insecticidal nets, IRS efficacy and insecticide resistance, which the Ministry of Health and Social Services-Namibia can use to further build a monitoring and evaluation framework for understanding the drivers of transmission. CONCLUSION: Identification and characterization of species-specific bionomic traits allows for an understanding of where and when vector human contact may occur as well as the potential impact of interventions. Low indoor resting rates as well as the presence of insecticide resistance (and the increase in its frequency) point to the need for mosquito-behavior-directed and appropriate interventions as well as the requirement for a resistance mitigation strategy. The ESPT-based question- and minimal essential indicator-based operational research strategy provides programs with directed and focused data for facilitating decision-making while requiring limited funding and capacity.

Parasites and vectors carry no passport: how to fund cross-border and regional efforts to achieve malaria elimination.

BACKGROUND: Tremendous progress has been made in the last ten years in reducing morbidity and mortality caused by malaria, in part because of increases in global funding for malaria control and elimination. Today, many countries are striving for malaria elimination. However, a major challenge is the neglect of cross-border and regional initiatives in malaria control and elimination. This paper seeks to better understand Global Fund support for multi-country initiatives. METHODS: Documents and proposals were extracted and reviewed from two main sources, the Global Fund website and Aidspan.org. Documents and reports from the Global Fund Technical Review Panel, Board, and Secretariat documents such as guidelines and proposal templates were reviewed to establish the type of policies enacted and guidance provided from the Global Fund on multi-country initiatives and applications. From reviewing this information, the researchers created 29 variables according to eight dimensions to use in a review of Round 10 applications. All Round 10 multi-country applications (for HIV, malaria and tuberculosis) and all malaria multi-country applications (6) from Rounds 1 - 10 were extracted from the Global Fund website. A blind review was conducted of Round 10 applications using the 29 variables as a framework, followed by a review of four of the six successful malaria multi-country grant applications from Rounds 1 - 10. FINDINGS: During Rounds 3 - 10 of the Global Fund, only 5.8% of grants submitted were for multi-country initiatives. Out of 83 multi-country proposals submitted, 25.3% were approved by the Technical Review Panel (TRP) for funding, compared to 44.9% of single-country applications. The majority of approved multi-country applications were for HIV (76.2%), followed by malaria (19.0%), then tuberculosis (4.8%). TRP recommendations resulted in improvements to application forms, although guidance was generally vague. The in-depth review of Round 10 multi-country proposals showed that applicants described their projects in one of two ways: a regional 'network approach' by which benefits are derived from economies of scale or from enhanced opportunities for mutual support and learning or the development of common policies and approaches; or a 'cross-border' approach for enabling activities to be more effectively delivered towards border-crossing populations or vectors. In Round 10, only those with a 'network approach' were recommended for funding. The Global Fund has only ever approved six malaria multi-country applications. Four approved applications stated strong arguments for a multi-country initiative, combining both 'cross-border' and 'network' approaches. CONCLUSION: With the cancellation of Round 11 and the proposal that the Global Fund adopt a more targeted and strategic approach to funding, the time is opportune for the Global Fund to develop a clear consensus about the key factors and criteria for funding malaria specific multi-country initiatives. This study found that currently there was a lack of guidance on the key features that a successful multi-country proposal needs to be approved and that applications directed towards the 'network' approach were most successful in Round 10. This type of multi-country proposal may favour other diseases such as HIV, whereas the need for malaria control and elimination is different, focusing on cross-border coordination and delivery of interventions to specific groups. The Global Fund should seek to address these issues and give better guidance to countries and regions and investigate disease-specific calls for multi-country and regional applications.

Malaria control in Bhutan: case study of a country embarking on elimination.

BACKGROUND: Bhutan has achieved a major reduction in malaria incidence amid multiple challenges. This case study seeks to characterize the Bhutan malaria control programme over the last 10 years. METHODS: A review of the malaria epidemiology, control strategies, and elimination strategies employed in Bhutan was carried out through a literature review of peer-reviewed and grey national and international literature with the addition of reviewing the surveillance and vector control records of the Bhutan Vector-Borne Disease Control Programme (VDCP). Data triangulation was used to identify trends in epidemiology and key strategies and interventions through analysis of the VDCP surveillance and programme records and the literature review. Enabling and challenging factors were identified through analysis of socio-economic and health indicators, corroborated through a review of national and international reports and peer-review articles. FINDINGS: Confirmed malaria cases in Bhutan declined by 98.7% from 1994 to 2010. The majority of indigenous cases were due to Plasmodium vivax (59.9%) and adult males are most at-risk of malaria. Imported cases, or those in foreign nationals, varied over the years, reaching 21.8% of all confirmed cases in 2006. Strategies implemented by the VDCP are likely to be related to the decline in cases over the last 10 years. Access to malaria diagnosis in treatment was expanded throughout the country and evidence-based case management, including the introduction of artemisinin-based combination therapy (ACT) for P. falciparum, increasing coverage of high risk areas with Indoor Residual Spraying, insecticide-treated bed nets, and long-lasting insecticidal nets are likely to have contributed to the decline alongside enabling factors such as economic development and increasing access to health services. CONCLUSION: Bhutan has made significant strides towards elimination and has adopted a goal of national elimination. A major challenge in the future will be prevention and management of imported malaria infections from neighbouring Indian states. Bhutan plans to implement screening at border points to prevent importation of malaria and to targeted prevention and surveillance efforts towards at-risk Bhutanese and migrant workers in construction sites.

Malaria elimination gaining ground in the Asia Pacific.

Countries in the Asia Pacific region are making substantial progress toward eliminating malaria, but their success stories are rarely heard by a global audience. "Malaria 2012: Saving Lives in the Asia-Pacific," a conference hosted by the Australian Government in Sydney, Australia from October 31 to November 2, 2012, will provide a unique opportunity to showcase the region's work in driving down malaria transmission. One of the features of Malaria 2012 will be the Asia Pacific Malaria Elimination Network (APMEN), which has focused on harnessing the collective experiences of 13 countries through regional political and technical collaboration since its inception in 2009. Run by country partners, APMEN unites a range of partners - from national malaria programmes and academic institutions to global and regional policymaking bodies - to support each country's malaria elimination goals through knowledge sharing, capacity building, operational research and advocacy.

Human and vector behaviors determine exposure to Anopheles in Namibia.

BACKGROUND: Although the Republic of Namibia has significantly reduced malaria transmission, regular outbreaks and persistent transmission impede progress towards elimination. Towards an understanding of the protective efficacy, as well as gaps in protection, associated with long-lasting insecticidal nets (LLINs), human and Anopheles behaviors were evaluated in parallel in three malaria endemic regions, Kavango East, Ohangwena and Zambezi, using the Entomological Surveillance Planning Tool to answer the question: where and when are humans being exposed to bites of Anopheles mosquitoes? METHODS: Surveillance activities were conducted during the malaria transmission season in March 2018 for eight consecutive nights. Four sentinel structures per site were selected, and human landing catches and human behavior observations were consented to for a total of 32 collection nights per site. The selected structures were representative of local constructions (with respect to building materials and size) and were at least 100 m from each other. For each house where human landing catches were undertaken, a two-person team collected mosquitoes from 1800 to 0600 hours. RESULTS: Surveillance revealed the presence of the primary vectors Anopheles arabiensis, Anopheles gambiae sensu stricto (s.s.) and Anopheles funestus s.s., along with secondary vectors (Anopheles coustani sensu lato and Anopheles squamosus), with both indoor and outdoor biting behaviors based on the site. Site-specific human behaviors considerably increased human exposure to vector biting. The interaction between local human behaviors (spatial and temporal presence alongside LLIN use) and vector behaviors (spatial and temporal host seeking), and also species composition, dictated where and when exposure to infectious bites occurred, and showed that exposure was primarily indoors in Kavango East (78.6%) and outdoors in Ohangwena (66.7%) and Zambezi (81.4%). Human behavior-adjusted exposure was significantly different from raw vector biting rate. CONCLUSIONS: Increased LLIN use may significantly increase protection and reduce exposure to malaria, but may not be enough to eliminate the disease, as gaps in protection will remain both indoors (when people are awake and not using LLINs) and outdoors. Alternative interventions are required to address these exposure gaps. Focused and question-based operational entomological surveillance together with human behavioral observations may considerably improve our understanding of transmission dynamics as well as intervention efficacy and gaps in protection.

Serological evaluation of the effectiveness of reactive focal mass drug administration and reactive vector control to reduce malaria transmission in Zambezi Region, Namibia: Results from a secondary analysis of a cluster randomised trial.

BACKGROUND: Due to challenges in measuring changes in malaria at low transmission, serology is increasingly being used to complement clinical and parasitological surveillance. Longitudinal studies have shown that serological markers, such as Etramp5.Ag1, can reflect spatio-temporal differences in malaria transmission. However, these markers have yet to be used as endpoints in intervention trials. METHODS: Based on data from a 2017 cluster randomised trial conducted in Zambezi Region, Namibia, evaluating the effectiveness of reactive focal mass drug administration (rfMDA) and reactive vector control (RAVC), this study conducted a secondary analysis comparing antibody responses between intervention arms as trial endpoints. Antibody responses were measured on a multiplex immunoassay, using a panel of eight serological markers of Plasmodium falciparum infection - Etramp5.Ag1, GEXP18, HSP40.Ag1, Rh2.2030, EBA175, PfMSP119, PfAMA1, and PfGLURP.R2. FINDINGS: Reductions in sero-prevalence to antigens Etramp.Ag1, PfMSP119, Rh2.2030, and PfAMA1 were observed in study arms combining rfMDA and RAVC, but only effects for Etramp5.Ag1 were statistically significant. Etramp5.Ag1 sero-prevalence was significantly lower in all intervention arms. Compared to the reference arms, adjusted prevalence ratio (aPR) for Etramp5.Ag1 was 0.78 (95%CI 0.65 - 0.91, p = 0.0007) in the rfMDA arms and 0.79 (95%CI 0.67 - 0.92, p = 0.001) in the RAVC arms. For the combined rfMDA plus RAVC intervention, aPR was 0.59 (95%CI 0.46 - 0.76, p < 0.0001). Significant reductions were also observed based on continuous antibody responses. Sero-prevalence as an endpoint was found to achieve higher study power (99.9% power to detect a 50% reduction in prevalence) compared to quantitative polymerase chain reaction (qPCR) prevalence (72.9% power to detect a 50% reduction in prevalence). INTERPRETATION: While the observed relative reduction in qPCR prevalence in the study was greater than serology, the use of serological endpoints to evaluate trial outcomes measured effect size with improved precision and study power. Serology has clear application in cluster randomised trials, particularly in settings where measuring clinical incidence or infection is less reliable due to seasonal fluctuations, limitations in health care seeking, or incomplete testing and reporting. FUNDING: This study was supported by Novartis Foundation (A122666), the Bill & Melinda Gates Foundation (OPP1160129), and the Horchow Family Fund (5,300,375,400).

Effective program management: a cornerstone of malaria elimination.

Effective program management is essential for successful elimination of malaria. In this perspective article, evidence surrounding malaria program management is reviewed by management science and malaria experts through a literature search of published and unpublished gray documents and key informant interviews. Program management in a malaria elimination setting differs from that in a malaria control setting in a number of ways, although knowledge and understanding of these distinctions are lacking. Several core features of successful health program management are critical to achieve elimination, including effective leadership and supervision at all levels, sustained political and financial commitment, reliable supply and control of physical resources, effective management of data and information, appropriate incentives, and consistent accountability. Adding to the complexity, the requirements of an elimination program may conflict with those of a control regimen. Thus, an additional challenge is successfully managing program transitions along the continuum from control to elimination to prevention of reintroduction. This article identifies potential solutions to these challenges by exploring managerial approaches that are flexible, relevant, and sustainable in various cultural and health system contexts.