Search

BACKGROUND: Primaquine (PQ) is the prototype 8-aminoquinoline drug, a class which targets gametocytes and hypnozoites. The World Health Organization (WHO) recommends adding a single low dose of primaquine to the standard artemisinin-based combination therapy (ACT) in order to block malaria transmission in regions with low malaria transmission. However, the haemolytic toxicity is a major adverse outcome of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects. This study aimed to characterize the pharmacokinetic properties of primaquine and its major metabolites in G6PD-deficient subjects. METHODS: A single low-dose of primaquine (0.4-0.5 mg/kg) was administered in twenty-eight African males. Venous and capillary plasma were sampled up to 24 h after the drug administration. Haemoglobin levels were observed up to 28 days after drug administration. Only PQ, carboxy-primaquine (CPQ), and primaquine carbamoyl-glucuronide (PQCG) were present in plasma samples and measured using liquid chromatography mass spectrometry. Drug and metabolites pharmacokinetic properties were investigated using nonlinear mixed-effects modelling. RESULTS: Population pharmacokinetic properties of PQ, CPQ, and PQCG can be described by one-compartment disposition kinetics with a transit-absorption model. Body weight was implemented as an allometric function on the clearance and volume parameters for all compounds. None of the covariates significantly affected the pharmacokinetic parameters. No significant correlations were detected between the exposures of the measured compounds and the change in haemoglobin or methaemoglobin levels. There was no significant haemoglobin drop in the G6PD-deficient patients after administration of a single low dose of PQ. CONCLUSIONS: A single low-dose of PQ was haematologically safe in this population of G6PD-normal and G6PD-deficient African males without malaria. Trial registration NCT02535767.

BACKGROUND: Global interest in malaria elimination has prompted research on active test and treat (TaT) strategies. METHODS: A systematic review and meta-analysis were conducted to assess the effectiveness of TaT strategies to reduce malaria transmission. RESULTS: A total of 72 empirical research and 24 modelling studies were identified, mainly focused on proactive mass TaT (MTaT) and reactive case detection (RACD) in higher and lower transmission settings, respectively. Ten intervention studies compared MTaT to no MTaT and the evidence for impact on malaria incidence was weak. No intervention studies compared RACD to no RACD. Compared to passive case detection (PCD) alone, PCD + RACD using standard diagnostics increased infection detection 52.7% and 11.3% in low and very low transmission settings, respectively. Using molecular methods increased this detection of infections by 1.4- and 1.1-fold, respectively. CONCLUSION: Results suggest MTaT is not effective for reducing transmission. By increasing case detection, surveillance data provided by RACD may indirectly reduce transmission by informing coordinated responses of intervention targeting.

BackgroundLong-lasting insecticidal nets (LLINs) are the main vector control tool for pregnant women, but their efficacy may be compromised, in part, due to pyrethroid resistance. In 2017, the Ugandan Ministry of Health embedded a cluster randomized controlled trial into the national LLIN campaign, where a random subset of health subdistricts (HSDs) received LLINs treated with piperonyl butoxide (PBO), a chemical synergist known to partially restore pyrethroid sensitivity. Using data from a small, non-randomly selected subset of HSDs, this secondary analysis used quasi-experimental methods to quantify the overall impact of the LLIN campaign on pregnancy outcomes. In an exploratory analysis, differences between PBO and conventional (non-PBO) LLINs on pregnancy outcomes were assessed.MethodsBirth registry data (n = 39,085) were retrospectively collected from 21 health facilities across 12 HSDs, 29 months before and 9 months after the LLIN campaign (from 2015 to 2018). Of the 12 HSDs, six received conventional LLINs, five received PBO LLINs, and one received a mix of conventional and PBO LLINs. Interrupted time-series analyses (ITSAs) were used to estimate changes in monthly incidence of stillbirth and low birthweight (LBW;

BackgroundIn Namibia, as in many malaria elimination settings, reactive case detection (RACD), or malaria testing and treatment around index cases, is a standard intervention. Reactive focal mass drug administration (rfMDA), or treatment without testing, and reactive focal vector control (RAVC) in the form of indoor residual spraying, are alternative or adjunctive interventions, but there are limited data regarding their community acceptability.MethodsA parent trial aimed to compare the effectiveness of rfMDA versus RACD, RAVC versus no RAVC, and rfMDA + RAVC versus RACD only. To assess acceptability of these interventions, a mixed-methods study was conducted using key informant interviews (KIIs) and focus group discussions (FGDs) in three rounds (pre-trial and in years 1 and 2 of the trial), and an endline survey.ResultsIn total, 17 KIIs, 49 FGDs were conducted with 449 people over three annual rounds of qualitative data collection. Pre-trial, community members more accurately predicted the level of community acceptability than key stakeholders. Throughout the trial, key participant motivators included: malaria risk perception, access to free community-based healthcare and IRS, and community education by respectful study teams. RACD or rfMDA were offered to 1372 and 8948 individuals in years 1 and 2, respectively, and refusal rates were low (

BackgroundIn April 2017, the Thai Ministry of Public Health (MoPH) was alerted to a potential malaria outbreak among civilians and military personnel in Sisaket Province, a highly forested area bordering Cambodia. The objective of this study was to present findings from the joint civilian-military outbreak response.MethodsA mixed-methods approach was used to assess risk factors among cases reported during the 2017 Sisaket malaria outbreak. Routine malaria surveillance data from January 2013 to March 2018 obtained from public and military medical reporting systems and key informant interviews (KIIs) (n = 72) were used to develop hypotheses about potential factors contributing to the outbreak. Joint civilian-military response activities included entomological surveys, mass screen and treat (MSAT) and vector control campaigns, and scale-up of the "1-3-7" reactive case detection approach among civilians alongside a pilot "1-3-7" study conducted by the Royal Thai Army (RTA).ResultsBetween May-July 2017, the monthly number of MoPH-reported cases surpassed the epidemic threshold. Outbreak cases detected through the MoPH mainly consisted of Thai males (87%), working as rubber tappers (62%) or military/border police (15%), and Plasmodium vivax infections (73%). Compared to cases from the previous year (May-July 2016), outbreak cases were more likely to be rubber tappers (OR = 14.89 [95% CI: 5.79-38.29]; p

Abstract Background The importation of parasites across borders remains a threat to malaria elimination. The Southern African Development Community Malaria Elimination Eight (E8) established 39 border health facilities on 5 key international borders between high and low-burden countries. These clinics aimed to improve access to prevention, diagnosis, and treatment of malaria for residents in border areas and for mobile and migrant populations who frequently cross borders. Studies were conducted in each of the four high-burden E8 countries (Angola, Mozambique, Zambia, and Zimbabwe) to evaluate malaria services in border areas. Methods Cross-sectional surveys were conducted within 30 km of recently established E8 Border Health Posts. Structured questionnaires were administered to randomly selected respondents to assess malaria-related knowledge and behavior, access to malaria prevention, diagnosis and treatment of malaria, and risk factors for malaria associated with local and cross-border travel. Results Results showed that most providers followed appropriate guidelines performing blood tests when individuals presented with fever, and that nearly all those who reported a positive blood test received medication. Lack of access to health care due to distance, cost or mistrust of the provider was rare. A minority of respondents reported not receiving timely diagnosis either because they did not seek help, or because they were not offered a blood test when presenting with fever. There was a high level of correct knowledge of causes, symptoms, and prevention of malaria. A majority, of border residents had access to primary prevention against malaria through either long-lasting insecticidal nets (LLINs) or indoor residual spraying (IRS). Cross border travel was common with travellers reporting sleeping outside without protection against malaria. Conclusions The study demonstrated the importance of border health facilities in providing access to malaria services. Prevention needs to be improved for people who travel and sleep outdoors. Community health workers can play a key role in providing access to information, testing and treating malaria.

Abstract Background Global interest in malaria elimination has prompted research on active test and treat (TaT) strategies. Methods A systematic review and meta-analysis were conducted to assess the effectiveness of TaT strategies to reduce malaria transmission. Results A total of 72 empirical research and 24 modelling studies were identified, mainly focused on proactive mass TaT (MTaT) and reactive case detection (RACD) in higher and lower transmission settings, respectively. Ten intervention studies compared MTaT to no MTaT and the evidence for impact on malaria incidence was weak. No intervention studies compared RACD to no RACD. Compared to passive case detection (PCD) alone, PCD + RACD using standard diagnostics increased infection detection 52.7% and 11.3% in low and very low transmission settings, respectively. Using molecular methods increased this detection of infections by 1.4- and 1.1-fold, respectively. Conclusion Results suggest MTaT is not effective for reducing transmission. By increasing case detection, surveillance data provided by RACD may indirectly reduce transmission by informing coordinated responses of intervention targeting.

BackgroundFocus for improved malaria programme performance is often placed on the technical challenges, while operational issues are neglected. Many of the operational challenges that inhibit malaria programme effectiveness can be addressed by improving communication and coordination, increasing accountability, maintaining motivation, providing adequate training and supervision, and removing bureaucratic silos.MethodsA programme of work was piloted in Zimbabwe with one malaria eliminating province, Matabeleland South in 2016-2017, and scaled up to include two other provinces, Matabeleland North and Midlands, in 2017-2018. The intervention included participatory, organization development and quality improvement methods.ResultsWorkshop participants in Matabeleland South reported an improvement in data management. In Matabeleland North, motivation among nurses improved as they gained confidence in case management from training, and overall staff morale improved. There was also an improvement in data quality and data sharing. In Midlands, the poorly performing district was motivated to improve, and both participating districts became more goal-oriented. They also became more focused on monitoring their data regularly. Participants from all provinces reported having gained skills in listening, communicating, facilitating discussions, and making presentations. Participation in the intervention changed the mindset of malaria programme staff, increasing ownership and accountability, and empowering them to identify and solve problems, make decisions, and act within their sphere of influence, elevating challenges when appropriate.ConclusionsThis pilot demonstrates that a participatory, organization development and quality improvement approach has broad ranging effects, including improving local delivery of interventions, tailoring strategies to target specific populations, finding efficiencies in the system that could not be found using the traditional top-down approach, and improving motivation and communication between different cadres of health workers. Scale-up of this simple model can be achieved and benefits sustained over time if the process is imbedded into the programme with the training of health staff who can serve as management improvement coaches. Methods to improve operational performance that are scalable at the district level are urgently needed: this approach is a possible tactic that can significantly contribute to the achievement of global malaria eradication goals.

BackgroundIn light of increasing complexity of identifying and treating malaria cases in low transmission settings, operational solutions are needed to increase effective delivery of interventions. Community engagement (CE) is at the forefront of this conversation given the shift toward creating local and site-specific solutions. Malaria programmes often confuse CE with providing information to the community or implementing community-based interventions. This study seeks to expand on CE approaches for malaria by looking to a variety of health and development programmes for lessons that can be applied to malaria elimination.MethodsQualitative data was collected from key informant interviews and community-based focus group discussions. Manual analysis was conducted with a focus on key principles, programme successes and challenges, the operational framework, and any applicable results.ResultsTen programmes were included in the analysis: Ebola, HIV/Hepatitis C, Guinea worm, malaria, nutrition, and water, sanitation and hygiene. Seven focus group discussions (FGDs) with 69 participants, 49 key informant (KI) interviews with programme staff, and 7 KI interviews with thought leaders were conducted between October-April 2018. Participants discussed the critical role that village leaders and community health workers play in CE. Many programmes stated understanding community priorities is key for CE and that CE should be proactive and iterative. A major theme was prioritizing bi-directional interpersonal communication led by local community health workers. Programmes reported that measuring CE is difficult, particularly since CE is ongoing and fluid.ConclusionsResults overwhelmingly suggest that CE must be an iterative process that relies on early involvement, frequent feedback and active community participation to be successful. Empowering districts and communities in planning and executing community-based interventions is necessary. Communities affected by the disease will ultimately achieve malaria elimination. For this to happen, the community itself must define, believe in, and commit to strategies to interrupt transmission.

BackgroundSubpatent malaria infections, or low-density infections below the detection threshold of microscopy or standard rapid diagnostic testing (RDT), can perpetuate persistent transmission and, therefore, may be a barrier for countries like Namibia that are pursuing malaria elimination. This potential burden in Namibia has not been well characterized.MethodsUsing a two-stage cluster sampling, cross-sectional design, subjects of all age were enrolled during the end of the 2015 malaria transmission season in Zambezi region, located in northeast Namibia. Malaria RDTs were performed with subsequent gold standard testing by loop-mediated isothermal amplification (LAMP) using dried blood spots. Infection prevalence was measured and the diagnostic accuracy of RDT calculated. Relationships between recent fever, demographics, epidemiological factors, and infection were assessed.ResultsPrevalence of Plasmodium falciparum malaria infection was low: 0.8% (16/1919) by RDT and 2.2% (43/1919) by LAMP. All but one LAMP-positive infection was RDT-negative. Using LAMP as gold standard, the sensitivity and specificity of RDT were 2.3% and 99.2%, respectively. Compared to LAMP-negative infections, a higher portion LAMP-positive infections were associated with fever (45.2% vs. 30.4%, p = 0.04), though 55% of infections were not associated with fever. Agricultural occupations and cattle herding were significantly associated with LAMP-detectable infection (Adjusted ORs 5.02, 95% CI 1.77-14.23, and 11.82, 95% CI 1.06-131.81, respectively), while gender, travel, bed net use, and indoor residual spray coverage were not.ConclusionsThis study presents results from the first large-scale malaria cross-sectional survey from Namibia using molecular testing to characterize subpatent infections. Findings suggest that fever history and standard RDTs are not useful to address this burden. Achievement of malaria elimination may require active case detection using more sensitive point-of-care diagnostics or presumptive treatment and targeted to high-risk groups.

Abstract Background Focus for improved malaria programme performance is often placed on the technical challenges, while operational issues are neglected. Many of the operational challenges that inhibit malaria programme effectiveness can be addressed by improving communication and coordination, increasing accountability, maintaining motivation, providing adequate training and supervision, and removing bureaucratic silos. Methods A programme of work was piloted in Zimbabwe with one malaria eliminating province, Matabeleland South in 2016–2017, and scaled up to include two other provinces, Matabeleland North and Midlands, in 2017–2018. The intervention included participatory, organization development and quality improvement methods. Results Workshop participants in Matabeleland South reported an improvement in data management. In Matabeleland North, motivation among nurses improved as they gained confidence in case management from training, and overall staff morale improved. There was also an improvement in data quality and data sharing. In Midlands, the poorly performing district was motivated to improve, and both participating districts became more goal-oriented. They also became more focused on monitoring their data regularly. Participants from all provinces reported having gained skills in listening, communicating, facilitating discussions, and making presentations. Participation in the intervention changed the mindset of malaria programme staff, increasing ownership and accountability, and empowering them to identify and solve problems, make decisions, and act within their sphere of influence, elevating challenges when appropriate. Conclusions This pilot demonstrates that a participatory, organization development and quality improvement approach has broad ranging effects, including improving local delivery of interventions, tailoring strategies to target specific populations, finding efficiencies in the system that could not be found using the traditional top-down approach, and improving motivation and communication between different cadres of health workers. Scale-up of this simple model can be achieved and benefits sustained over time if the process is imbedded into the programme with the training of health staff who can serve as management improvement coaches. Methods to improve operational performance that are scalable at the district level are urgently needed: this approach is a possible tactic that can significantly contribute to the achievement of global malaria eradication goals.

Abstract Background Primaquine is a gametocytocidal drug recommended by the World Health Organization (WHO) in a single-low dose combined with artemisinin-based combination therapy (ACT) for the treatment and prevention of Plasmodium falciparum malaria transmission. Safety monitoring concerns and the lack of a universal validated and approved primaquine pharmacovigilance tool is a challenge for a national rollout in many countries. This study aimed to explore the acceptance, reliability and perceived effectiveness of the primaquine roll out monitoring pharmacovigilance tool (PROMPT). Methods This study was conducted in three dispensaries in the Coastal region of Eastern Tanzania. The study held six in-depth interviews with healthcare providers and six participatory focus group discussions with malaria patients (3) and parents/guardians of sick children (3). Participants were purposively sampled. Thematic analysis was conducted with the aid of NVivo qualitative analysis software. Results The respondents’ general acceptance and perceived effectiveness of the single-low dose primaquine and PROMPT was good. Screening procedure for treatment eligibility and explaining to patients about the possible adverse events was considered very useful for safety reasons. Crushing and dissolving of primaquine tablet to get the appropriate dose, particularly in children, was reported by all providers to be challenging. Transport costs and poor access to the health facility were the main reasons for a patient failing to return to the clinic for a scheduled follow-up visit. Treatment was perceived to be safe by both providers and patients and reported no case of a severe adverse event. Some providers were concerned with the haemoglobin drop observed on day 7. Conclusion Single-low dose primaquine was perceived to be safe and acceptable among providers and patients. PROMPT demonstrated to be a reliable and user-friendly tool among providers. Further validation of the tool by involving the National Malaria Control Programme is pivotal to addressing key challenges and facilitating primaquine adoption in the national policy.

BackgroundCountries remain reluctant to adopt the 2012 World Health Organization recommendation for single low-dose (0.25 mg/kg) primaquine (SLD PQ) for Plasmodium falciparum transmission-blocking due to concerns over drug-related haemolysis risk, especially among glucose-6-phosphate dehydrogenase-deficient (G6PDd) people, without evidence demonstrating that it can be safely deployed in their settings. Pharmacovigilance methods provide a systematic way of collecting safety data and supporting the rollout of SLD PQ.MethodsThe Primaquine Roll Out Monitoring Pharmacovigilance Tool (PROMPT), comprising: (1) a standardized form to support the surveillance of possible adverse events following SLD PQ treatment; (2) a patient information card to enhance awareness of known adverse drug reactions of SLD PQ use; and (3) a database compiling recorded information, was developed and piloted. Data on patient characteristics, malaria diagnosis and treatment are collected. Blood samples are taken to measure haemoglobin (Hb) and test for G6PD deficiency. Active follow-up includes a repeat Hb measurement and adverse event monitoring on or near day 7. A 13-month prospective pilot study in two hospital facilities in Swaziland alongside the introduction of SLD PQ generated preliminary evidence on the feasibility and acceptability of PROMPT.ResultsPROMPT was well received by nurses as a simple, pragmatic approach to active surveillance of SLD PQ safety data. Of the 102 patients enrolled and administered SLD PQ, none were G6PDd. 93 (91.2 %) returned on or near day 7 for follow-up. Four (4.6 %) patients had falls in Hb ≥25 % from baseline, none of whom presented with signs or symptoms of anaemia. No patient's Hb fell below 7 g/dL and none required a blood transfusion. Of the 11 (11 %) patients who reported an adverse event over the study period, three were considered serious and included two deaths and one hospitalization; none were causally related to SLD PQ. Four non-serious adverse events were considered definitely, probably, or possibly related to SLD PQ.ConclusionImproved pharmacovigilance to monitor and promote the safety of the WHO recommendation is needed. The successful application of PROMPT demonstrates its potential as an important tool to rapidly generate locally acquired safety data and support pharmacovigilance in resource-limited settings.

BackgroundA malaria eradication goal has been proposed, at the same time as a new global strategy and implementation framework. Countries are considering the strategies and tools that will enable progress towards malaria goals. The eliminating malaria case-study series reports were reviewed to identify successful programme management components using a cross-case study analytic approach.MethodsNine out of ten case-study reports were included in the analysis (Bhutan, Cape Verde, Malaysia, Mauritius, Namibia, Philippines, Sri Lanka, Turkey, Turkmenistan). A conceptual framework for malaria elimination programme management was developed and data were extracted and synthesized. Findings were reviewed at a consultative workshop, which led to a revision of the framework and further data extraction and synthesis. Success factors of implementation, programme choices and changes, and enabling factors were distilled.ResultsDecentralized programmes enhanced engagement in malaria elimination by sub-national units and communities. Integration of the malaria programme into other health services was also common. Decentralization and integration were often challenging due to the skill and experience levels of newly tasked staff. Accountability for programme impact was not clarified for most programmes. Motivation of work force was a key factor in maintaining programme quality but there were few clear, detailed strategies provided. Different incentive schemes targeted various stakeholders. Training and supervision, although not well described, were prioritized by most programmes. Multi-sectoral collaboration helped some programmes share information, build strategies and interventions and achieve a higher quality of implementation. In most cases programme action was spurred by malaria outbreaks or a new elimination goal with strong leadership. Some programmes showed high capacity for flexibility through introduction of new strategies and tools. Several case-studies described methods for monitoring implementation quality and coverage; however analysis and feedback to those implementing malaria elimination in the periphery was not well described. Political commitment and sustained financing contributed to malaria programme success. Consistency of malaria programmes depends on political commitment, human and financial resources, and leadership. Operational capacity of the programme and the overall health system structure and strength are also important aspects.ConclusionsMalaria eradication will require adaptive, well-managed malaria programmes that are able to tailor implementation of evidence-based strategies, founded upon strong sub-national surveillance and response, with adequate funding and human resources.

Abstract Background Malaria was first reported in Rwanda in the early 1900s with significant heterogeneity and volatility in transmission over subsequent decades. Here, a comprehensive literature review of malaria transmission patterns and control strategies in Rwanda between 1900 and 2018 is presented to provide insight into successes and challenges in the country and to inform the future of malaria control in Rwanda. Methods A systematic literature search of peer-reviewed publications (Web of Knowledge, PubMed, Google Scholar, and the World Health Organization Library (WHOLIS) and grey literature on malaria control in Rwanda between 1900 and 2019 was conducted with the following search terms: “malaria”“, “Rwanda”, “epidemiology”, “control”, “treatment”, and/or “prevention.” Reports and other relevant documents were also obtained from the Rwanda National Malaria Control Programme (NMCP). To inform this literature review and evidence synthesis, epidemiologic and intervention data were collated from NMCP and partner reports, the national routine surveillance system, and population surveys. Results Two hundred sixty-eight peer-reviewed publications and 56 grey literature items were reviewed, and information was extracted. The history of malaria control in Rwanda is thematically described here according to five phases: 1900 to 1954 before the launch of the Global Malaria Eradication Programme (GMEP); (2) Implementation of the GMEP from 1955 to 1969; (3) Post- GMEP to 1994 Genocide; (4) the re-establishment of malaria control from 1995 to 2005, and (5) current malaria control efforts from 2006 to 2018. The review shows that Rwanda was an early adopter of tools and approaches in the early 2000s, putting the country ahead of the curve and health systems reforms created an enabling environment for an effective malaria control programme. The last two decades have seen unprecedented investments in malaria in Rwanda, resulting in significant declines in disease burden from 2000 to 2011. However, in recent years, these gains appear to have reversed with increasing cases since 2012 although the country is starting to make progress again. Conclusion The review shows the impact and fragility of gains against malaria, even in the context of sustained health system development. Also, as shown in Rwanda, country malaria control programmes should be dynamic and adaptive to respond and address changing settings.

Abstract Despite huge investments and implementation of effective interventions for malaria, progress has stalled, with transmission being increasingly localized among difficult-to-reach populations and outdoor-biting vectors. Targeting difficult pockets of transmission will require the development of tailored and targeted approaches suited to local context, drawing from insights close to the frontlines. Districts are best placed to develop tailored, locally appropriate approaches. We propose a reorganization of how malaria services are delivered. Firstly, enabling district health officers to serve as conduits between technical experts in national malaria control programmes and local community leaders with knowledge specific to local, at-risk populations; secondly, empowering district health teams to make malaria control decisions. This is a radical shift that requires the national programme to cede some control. Shifting towards a district or provincial level approach will necessitate deliberate planning, and repeated, careful assessment, starting with piloting and learning through experience. Donors will need to alter current practice, allowing for flexible funding to be controlled at sub-national levels, and to mix finances between case management, vector control and surveillance, monitoring and evaluation. System-wide changes proposed are challenging but may be necessary to overcome stalled progress in malaria control and elimination and introduce targeted interventions tailored to the needs of diverse malaria affected populations.

BackgroundThere has been progress towards malaria elimination in the last decade. In response, WHO launched the Global Technical Strategy (GTS), in which vector surveillance and control play important roles. Country experiences in the Eliminating Malaria Case Study Series were reviewed to identify success factors on the road to elimination using a cross-case study analytic approach.MethodsReports were included in the analysis if final English language draft reports or publications were available at the time of analysis (Bhutan, Cape Verde, Malaysia, Mauritius, Namibia, Philippines, Sri Lanka, Turkey, Turkmenistan). A conceptual framework for vector control in malaria elimination was developed, reviewed, formatted as a matrix, and case study data was extracted and entered into the matrix. A workshop was convened during which participants conducted reviews of the case studies and matrices and arrived at a consensus on the evidence and lessons. The framework was revised and a second round of data extraction, synthesis and summary of the case study reports was conducted.ResultsCountries implemented a range of vector control interventions. Most countries aligned with integrated vector management, however its impact was not well articulated. All programmes conducted entomological surveillance, but the response (i.e., stratification and targeting of interventions, outbreak forecasting and strategy) was limited or not described. Indoor residual spraying (IRS) was commonly used by countries. There were several examples of severe reductions or halting of IRS coverage and subsequent resurgence of malaria. Funding and operational constraints and poor implementation had roles. Bed nets were commonly used by most programmes; coverage and effectiveness were either not measured or not articulated. Larval control was an important intervention for several countries, preventing re-introduction, however coverage and impact on incidence were not described. Across all interventions, coverage indicators were incomparable, and the rationale for which tools were used and which were not used appeared to be a function of the availability of funding, operational issues and cost instead of evidence of effectiveness to reduce incidence.ConclusionsMore work is required to fill gaps in programme guidance, clarify the best methods for choosing and targeting vector control interventions, and support to measure cost, cost-effectiveness and cost-benefit of vector surveillance and control interventions.

Abstract Background Recent progress in malaria control has caused renewed interest in mass drug administration (MDA) as a potential elimination strategy but the evidence base is limited. China has extensive experience with MDA, but it is not well documented. Methods An ecological study was conducted to describe the use of MDA for the control and elimination of Plasmodium vivax in Jiangsu Province and explore the association between MDA and malaria incidence. Two periods were focused on: 1973 to 1983 when malaria burden was high and MDA administered to highly endemic counties province-wide, and 2000 to 2009, when malaria burden was low and a focal approach was used in two counties. All available data about the strategies implemented, MDA coverage, co-interventions, incidence, and adverse events were collected and described. Joinpoint analysis was used to describe trends in incidence and the relationship between MDA coverage and incidence was explored in negative binomial regression models. Results From 1973 to 1983, MDA with pyrimethamine and primaquine was used on a large scale, with up to 30 million people in target counties covered in a peak year (50% of the total population). Joinpoint analyses identified declines in annual incidence, -56.7% (95% CI -75.5 to -23.7%) from 1973–1976 and -12.4% (95% CI -24.7 to 2.0%) from 1976–1983. Population average negative binomial models identified a relationship between higher total population MDA coverage and lower monthly incidence from 1973–1976, IRR 0.98 (95% CI 0.97 to 1.00), while co-interventions, rainfall and GDP were not associated. From 2000–2009, incidence in two counties declined (annual change -43.7 to -14.0%) during a time when focal MDA using chloroquine and primaquine was targeted to villages and/or individuals residing near passively detected index cases (median 0.04% of total population). Although safety data were not collected systematically, there were rare reports of serious but non-fatal events. Conclusions In Jiangsu Province, China, large-scale MDA was implemented and associated with declines in high P. vivax malaria transmission; a more recent focal approach may have contributed to interruption of transmission. MDA should be considered a potential key strategy for malaria control and elimination.

Abstract Background Moving from malaria control to elimination requires national malaria control programmes to implement strategies to detect both symptomatic and asymptomatic cases in the community. In order to do this, malaria elimination programmes follow up malaria cases reported by health facilities to carry out case investigations that will determine the origin of the infection, whether it has been imported or is due to local malaria transmission. If necessary, the malaria programme will also carry out active surveillance to find additional malaria cases in the locality to prevent further transmission. To understand current practices and share information on malaria elimination strategies, a survey specifically addressing country policies on case investigation and reactive case detection was carried out among fourteen countries of the Asia Pacific Malaria Elimination Network (APMEN). Methods A questionnaire was distributed to the malaria control programme managers amongst 14 countries in the Asia Pacific who have national or sub-national malaria elimination goals. Results Results indicate that there are a wide variety of case investigation and active case detection activities employed by the 13 countries that responded to the survey. All respondents report conducting case investigation as part of surveillance activities. More than half of these countries conduct investigations for each case. Over half aim to accomplish the investigation within one to two days of a case report. Programmes collect a broad array of demographic data during investigation procedures and definitions for imported cases are varied across respondents. Some countries report intra-national (from a different province or district) importation while others report only international importation (from a different country). Reactive case detection in respondent countries is defined as screening households within a pre-determined radius in order to identify other locally acquired infections, whether symptomatic or asymptomatic. Respondents report that reactive case detection can be triggered in different ways, in some cases with only a single case report and in others if a defined threshold of multiple cases occurs. The spatial range of screening conducted varies from a certain number of households to an entire administrative unit (e g, village). Some countries target symptomatic people whereas others target all people in order to detect asymptomatic infections. The majority of respondent programmes collect a range of information from those screened for malaria, similar to the range of information collected during case investigation. Conclusion Case investigation and reactive case detection are implemented in the malaria elimination programmes in the Asia Pacific, however practices vary widely from country to country. There is little evidence available to support countries in deciding which methods to maintain, change or adopt for improved effectiveness and efficiency. The development and use of common evaluation metrics for these activities will allow malaria programmes to assess performance and results of resource-intensive surveillance measures and may benefit other countries that are considering implementing these activities.

Abstract Background At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Methods Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Results Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. Conclusion The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings.

Abstract Background Swaziland has made great progress towards its goal of malaria elimination by 2015. However, malaria importation from neighbouring high-endemic Mozambique through Swaziland’s eastern border remains a major factor that could prevent elimination from being achieved. In order to reach elimination, Swaziland must rapidly identify and treat imported malaria cases before onward transmission occurs. Methods A nationwide formative assessment was conducted over eight weeks to determine if the imported cases of malaria identified by the Swaziland National Malaria Control Programme could be linked to broader social networks and to explore methods to access these networks. Results Using a structured format, interviews were carried out with malaria surveillance agents (6), health providers (10), previously identified imported malaria cases (19) and people belonging to the networks identified through these interviews (25). Most imported malaria cases were Mozambicans (63%, 12/19) making a living in Swaziland and sustaining their families in Mozambique. The majority of imported cases (73%, 14/19) were labourers and self-employed contractors who travelled frequently to Mozambique to visit their families and conduct business. Social networks of imported cases with similar travel patterns were identified through these interviews. Nearly all imported cases (89%, 17/19) were willing to share contact information to enable network members to be interviewed. Interviews of network members and key informants revealed common congregation points, such as the urban market places in Manzini and Malkerns, as well as certain bus stations, where people with similar travel patterns and malaria risk behaviours could be located and tested for malaria. Conclusion This study demonstrated that imported cases of malaria belonged to networks of people with similar travel patterns. This study may provide novel methods for screening high-risk groups of travellers using both snowball sampling and time-location sampling of networks to identify and treat additional malaria cases. Implementation of a proactive screening programme of importation networks may help Swaziland halt transmission and achieve malaria elimination by 2015.

Abstract Background Malaria transmission has declined dramatically in Zanzibar in recent years. Continuing use of preventive measures such as long-lasting insecticidal-treated nets (LLINs), and use of malaria rapid diagnostic tests (RDTs) are essential to prevent malaria resurgence. This study employed qualitative methods to explore community perceptions of malaria risk and adherence to prevention measures in two districts in Zanzibar. Methods Key informant interviews with 24 primary health care providers and 24 focus group discussions with local residents in Zanzibar districts Wete and Central were conducted during April and May 2012 focusing on perception of malaria risk, current preventive practices used, reasons for using preventive practices and effective strategies for malaria control. Results Health care providers and residents appear to be aware of the decreasing incidence of malaria. Both groups continue the use of malaria preventive practices in this low and seasonal transmission setting. The most important preventive measures identified were LLINs, indoor residual spraying (IRS), and education. Barriers to malaria prevention include: lack of staff at clinics, insufficient number of LLINs distributed, and inadequate malaria education. Reasons for continued use of preventive practices include: fear of malaria returning to high levels, presence of mosquitoes during rainy seasons, and concern about local cases from other villages or imported cases from mainland Tanzania. Mosques, clinics, schools and community meetings were listed as most important sources of education. However, residents express the desire for more education. Conclusion Health care providers and residents generally reported consistent use of malaria preventive measures. However, maintaining and continuing to reduce malaria transmission will require ongoing education for both health care providers and residents to reinforce the importance of using preventive measures. Successful efforts to reduce malaria in Zanzibar will be jeopardized if residents believe that they are no longer at risk for malaria. In future studies, a year-round evaluation of the perception of malaria risk and use of preventive measures will inform the timing of education and prevention strategies for sustained malaria control.

Abstract Following the recent successes of malaria control in sub-Saharan Africa, the gametocytocidal drug primaquine needs evaluation as a tool to further reduce the transmission of Plasmodium falciparum malaria. The drug has scarcely been used in Africa because of concerns about its safety in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The evidence base for the use of primaquine as a transmission blocker is limited by a lack of comparable clinical and parasitological endpoints between trials. In March 2012, a group of experts met in London to discuss the existing evidence on the ability of primaquine to block malaria transmission, to define the roadblocks to the use of primaquine in Africa and to develop a roadmap to enable its rapid, safe and effective deployment. The output of this meeting is a strategic plan to optimize trial design to reach desired goals efficiently. The roadmap includes suggestions for a series of phase 1, 2, 3 and 4 studies to address specific hurdles to primaquine’s deployment. These include ex-vivo studies on efficacy, primaquine pharmacokinetics and pharmacodynamics and dose escalation studies for safety in high-risk groups. Phase 3 community trials are proposed, along with Phase 4 studies to evaluate safety, particularly in pregnancy, through pharmacovigilance in areas where primaquine is already deployed. In parallel, efforts need to be made to address issues in drug supply and regulation, to map G6PD deficiency and to support the evaluation of alternative gametocytocidal compounds.

Abstract 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.

Abstract 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.

Abstract Background Policy makers have speculated that one of the economic benefits of malaria elimination includes increases in foreign direct investment, particularly tourism. Methods This study examines the empirical relationship between the demand for travel and malaria cases in two countries with large tourism industries around the time in which they carried out malaria-elimination campaigns. In Mauritius, this analysis examines historical, yearly tourist arrivals and malaria cases from 1978–1999, accounting for the background secular trend of increasing international travel. In Dominican Republic, a country embarking upon malaria elimination, it employs a time-series analysis of the monthly, international tourist arrivals from 1998–2010 to determine whether the timing of significant deviations in tourist arrivals coincides with malaria outbreaks. Results While naïve relationships exist in both cases, the results show that the relationships between tourist arrivals and malaria cases are relatively weak and statistically insignificant once secular confounders are accounted for. Conclusions This suggests that any economic benefits from tourism that may be derived from actively pursuing elimination in countries that have high tourism potential are likely to be small when measured at a national level. Rather, tourism benefits are likely to be experienced with greater impact in more concentrated tourist areas within countries, and future studies should seek to assess these relationships at a regional or local level.

Abstract 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.

Abstract Swaziland is working to be the first country in mainland sub-Saharan Africa to eliminate malaria. The highest level of Swaziland's government recently approved a national elimination policy, which endorses Swaziland's robust national elimination strategic plan. This commentary outlines Swaziland's progress towards elimination as well as the challenges that remain, primarily around securing long-term financial resources and managing imported cases from neighbouring countries.

Abstract Swaziland is working to be the first country in mainland sub-Saharan Africa to eliminate malaria. The highest level of Swaziland's government recently approved a national elimination policy, which endorses Swaziland's robust national elimination strategic plan. This commentary outlines Swaziland's progress towards elimination as well as the challenges that remain, primarily around securing long-term financial resources and managing imported cases from neighbouring countries.

Abstract Background IPTi delivered through EPI has been shown to reduce the incidence of clinical malaria by 20–59%. However, new health interventions can only be effective if they are also socially and culturally acceptable. It is also crucial to ensure that attitudes to IPTi do not negatively influence attitudes to and uptake of immunization, or that people do not misunderstand IPTi as immunization against malaria and neglect other preventive measures or delay treatment seeking. Methods These issues were studied in five African countries in the context of clinical trials and implementation studies of IPTi. Mixed methods were used, including structured questionnaires (1,296), semi-structured interviews (168), in-depth interviews (748) and focus group discussions (95) with mothers, fathers, health workers, community members, opinion leaders, and traditional healers. Participant observation was also carried out in the clinics. Results IPTi was widely acceptable because it resonated with existing traditional preventive practices and a general concern about infant health and good motherhood. It also fit neatly within already widely accepted routine vaccination. Acceptance and adherence were further facilitated by the hierarchical relationship between health staff and mothers and by the fact that clinic attendance had a social function for women beyond acquiring health care. Type of drug and regimen were important, with newer drugs being seen as more effective, but potentially also more dangerous. Single dose infant formulations delivered in the clinic seem to be the most likely to be both acceptable and adhered to. There was little evidence that IPTi per se had a negative impact on attitudes to EPI or that it had any affect on EPI adherence. There was also little evidence of IPTi having a negative impact on health seeking for infants with febrile illness or existing preventive practices. Conclusion IPTi is generally acceptable across a wide range of settings in Africa and involving different drugs and regimens, though there is a strong preference for a single dose infant formulation. IPTi does not appear to have any negative effect on attitudes to EPI, and it is not interpreted as immunization against malaria.

Abstract Background Intermittent preventive (or presumptive) treatment of infants (IPTi), the administration of a curative anti-malarial dose to infants whether or not they are known to be infected, is being considered as a new strategy for malaria control. Five of the six trials using sulphadoxine-pyrimethamine (SP) for IPTi showed protective efficacies (PEs) against clinical malaria ranging from 20.1 – 33.3% whilst one, the Ifakara study, showed a protective efficacy of 58.6%. Materials and methods The possible mechanisms that could explain the differences in the reported PE of IPTi were examined by comparing output from a mathematical model to data from the six published IPTi trials. Results Under stable transmission, the PE of IPTi predicted by the model was comparable with the observed PEs in all but the Ifakara study (ratio of the mean predicted PE to that observed was 1.02, range 0.39 – 1.59). When a reduction in the incidence of infection during the study was included in the model, the predicted PE of IPTi increased and extended into the second year of life, as observed in the Ifakara study. Conclusion A decrease in malaria transmission during the study period may explain part of the difference in observed PEs of IPTi between sites and the extended period of protection into the second year of life observed in the Ifakara study. This finding of continued benefit of interventions in settings of decreasing transmission may explain why rebound of clinical malaria was absent in the large scale trials of insecticide-treated bed nets.