Research that influences policy and practice – characteristics of operational research to improve malaria control in Mpumalanga Province, South Africa

Background  

Much communicable disease control research has had little impact on local control programme policy and practice for want of an operational component. The operational research model – the systematic search for knowledge on interventions, tools or strategies that enhance programme effectiveness – is gaining recognition as an appropriate method for addressing perplexing questions within public health programmes.     

Safety of insecticide-treated mosquito nets for infants and their mothers: randomized controlled community trial in Burkina Faso

The Asia Pacific Malaria Elimination Network (APMEN) is a collaboration of 18 country partners committed to eliminating malaria from within their borders. Over the past 5 years, APMEN has helped to build the knowledge, tools and in-country technical expertise required to attain this goal. At its inaugural meeting in Brisbane in 2009, Plasmodium vivax infections were identified across the region as a common threat to this ambitious programme; the APMEN Vivax Working Group was established to tackle specifically this issue. The Working Group developed a four-stage strategy to identify knowledge gaps, build regional consensus on shared priorities, generate evidence and change practice to optimize malaria elimination activities. This case study describes the issues faced and the solutions found in developing this robust strategic partnership between national programmes and research partners within the Working Group. The success of the approach adopted by the group may facilitate similar applications in other regions seeking to deploy evidence-based policy and practice.     

Italian Development Cooperation: the commitment for the struggle against malaria in Africa

The Italian Development Cooperation (DGCS) support the health reform process in Developing Countries, with the aim to provide populations in greatest need with access to decentralized health services. DGCS acts in close coordination with the donor community, United Nations' system and the World Bank, in agreement with sector-wide approach (SWAP) for health sector development. Since malaria control in endemic countries is a relevant component of the health system, DGCS is actively involved in the struggle against malaria in sub-Saharan Africa, supporting control activities and research capability strengthening. The following African countries are presently receiving bilateral support for antimalaria activities: Burkina Faso, Centre de Lutte contre le Paludisme in Ouagadougou; Ethiopia, community-based malaria control in Tigray; Eritrea, malaria control at national level in the framework of the Public Health and Rehabilitation Programme for Eritrea (PHARPE) initiative; Madagascar, malaria surveillance at national level; Tanzania, feasibility study for the support to the national malaria control programme. Support is provided by technical/financial assistance involving Italian academic and research institutions. On the multilateral channel, DGCS has provided regular contribution for WHO's work in malaria control and participates to the WHO Roll Back Malaria initiative. A new commitment to malaria is the trilateral joint scientific endeavour USA-Italy-Burkina Faso for the development and field testing of a candidate vaccine suitable for African populations.     

Helminth-infected patients with malaria: a low profile transmission hub?

The scale-up of malaria control efforts in recent years, coupled with major investments in malaria research, has produced impressive public health impact in a number of countries and has led to the development of new tools and strategies aimed at further consolidating malaria control goals. As a result, there is a growing need for the malaria policy setting process to rapidly review increasing amounts of evidence. The World Health Organization Global Malaria Programme, in keeping with its mandate to set evidence-informed policies for malaria control, has convened the Malaria Policy Advisory Committee as a mechanism to increase the timeliness, transparency, independence and relevance of its recommendations to World Health Organization member states in relation to malaria control and elimination. The Malaria Policy Advisory Committee, composed of 15 world-renowned malaria experts, will meet in full twice a year, with the inaugural meeting scheduled for 31 January to 2 February 2012 in Geneva. Policy recommendations, and the evidence to support them, will be published within two months of every meeting as part of an open access Malaria Journal thematic series. This article is a prelude to that series and provides the global malaria community with the background and overview of the Committee and its terms of reference.     

Strategies for malaria control in Colombia

Attempts at malaria eradication this century have been highly effective but early successes have not been sustained. This has been ascribed to the lack of community involvement in these campaigns. Colombia has put huge effort into malaria control on a number of fronts, from vaccine development to the evaluation of the integrated use of more traditional methods. William Rojas, Fernando Pe?aranda and Mouricio Echavarria describe a pilot programme for integrated malaria control in Colombia whose success they attribute to committed community participation.     

Community-based malaria control in Tigray, northern Ethiopia

Community-based control activities have been a major component of the Tigray regional malaria control programme since 1992. A team of 735 volunteer community health workers treat on average 60,000 clinical malaria cases monthly during the high malaria transmission season. Ensuring access for the rural population to early diagnosis and treatment has contributed to a significant decrease in death rate in under-five children at the village level from 1994 to 1996. Mapping and geographic information system (GIS) technologies have been introduced to support planning for control by assessment of community-based coverage. With further development, GIS will be used in stratification, and to assess the impact of water resources development on malaria transmission and intensity.     

Malaria control and elimination in sri lanka: documenting progress and success factors in a conflict setting

Background

Sri Lanka has a long history of malaria control, and over the past decade has had dramatic declines in cases amid a national conflict. A case study of Sri Lanka''s malaria programme was conducted to characterize the programme and explain recent progress.

Methods

The case study employed qualitative and quantitative methods. Data were collected from published and grey literature, district-level and national records, and thirty-three key informant interviews. Expenditures in two districts for two years – 2004 and 2009 – were compiled.

Findings

Malaria incidence in Sri Lanka has declined by 99.9% since 1999. During this time, there were increases in the proportion of malaria infections due to Plasmodium vivax, and the proportion of infections occurring in adult males. Indoor residual spraying and distribution of long-lasting insecticide-treated nets have likely contributed to the low transmission. Entomological surveillance was maintained. A strong passive case detection system captures infections and active case detection was introduced. When comparing conflict and non-conflict districts, vector control and surveillance measures were maintained in conflict areas, often with higher coverage reported in conflict districts. One of two districts in the study reported a 48% decline in malaria programme expenditure per person at risk from 2004 to 2009. The other district had stable malaria spending.

Conclusions/Significance

Malaria is now at low levels in Sri Lanka – 124 indigenous cases were found in 2011. The majority of infections occur in adult males and are due to P. vivax. Evidence-driven policy and an ability to adapt to new circumstances contributed to this decline. Malaria interventions were maintained in the conflict districts despite an ongoing war. Sri Lanka has set a goal of eliminating malaria by the end of 2014. Early identification and treatment of infections, especially imported ones, together with effective surveillance and response, will be critical to achieving this goal.     

Best practices for an insecticide-treated bed net distribution programme in sub-Saharan eastern Africa

Insecticide-treated bed nets are the preeminent malaria control means; though there is no consensus as to a best practice for large-scale insecticide-treated bed net distribution. In order to determine the paramount distribution method, this review assessed literature on recent insecticide treated bed net distribution programmes throughout sub-Saharan Eastern Africa. Inclusion criteria were that the study had taken place in sub-Saharan Eastern Africa, targeted malaria prevention and control, and occurred between 1996 and 2007. Forty-two studies were identified and reviewed. The results indicate that distribution frameworks varied greatly; and consequently so did outcomes of insecticide-treated bed net use. Studies revealed consistent inequities between urban and rural populations; which were most effectively alleviated through a free insecticide-treated bed net delivery and distribution framework. However, cost sharing through subsidies was shown to increase programme sustainability, which may lead to more long-term coverage. Thus, distribution should employ a catch up/keep up programme strategy. The catch-up programme rapidly scales up coverage, while the keep-up programme maintains coverage levels. Future directions for malaria should include progress toward distribution of long-lasting insecticide-treated nets.     

A research agenda for malaria eradication: modeling

Malaria modeling can inform policy and guide research for malaria elimination and eradication from local implementation to global policy. A research and development agenda for malaria modeling is proposed, to support operations and to enhance the broader eradication research agenda. Models are envisioned as an integral part of research, planning, and evaluation, and modelers should ideally be integrated into multidisciplinary teams to update the models iteratively, communicate their appropriate use, and serve the needs of other research scientists, public health specialists, and government officials. A competitive and collaborative framework will result in policy recommendations from multiple, independently derived models and model systems that share harmonized databases. As planned, modeling results will be produced in five priority areas: (1) strategic planning to determine where and when resources should be optimally allocated to achieve eradication; (2) management plans to minimize the evolution of drug and pesticide resistance; (3) impact assessments of new and needed tools to interrupt transmission; (4) technical feasibility assessments to determine appropriate combinations of tools, an associated set of target intervention coverage levels, and the expected timelines for achieving a set of goals in different socio-ecological settings and different health systems; and (5) operational feasibility assessments to weigh the economic costs, capital investments, and human resource capacities required.     

New World monkey efficacy trials for malaria vaccine development: critical path or detour?

Neither GMP malaria antigens nor GMP vaccines have been compared for efficacy in monkeys and humans. It is too risky to base categorical (go/no go) development decisions on results obtained using partially characterized (non-GMP) antigens, adjuvants that are too toxic for human use or unvalidated primate models. Such practices will lead to serious errors (e.g. failure to identify and stop flawed efforts, rejection of effective vaccine strategies) and unjustifiable delays. Successful malaria vaccine development will emphasize definitive field trials in populations at risk of malaria to define and improve vaccine efficacy.     

How Well Are Malaria Maps Used to Design and Finance Malaria Control in Africa?

Introduction

Rational decision making on malaria control depends on an understanding of the epidemiological risks and control measures. National Malaria Control Programmes across Africa have access to a range of state-of-the-art malaria risk mapping products that might serve their decision-making needs. The use of cartography in planning malaria control has never been methodically reviewed.

Materials and Methods

An audit of the risk maps used by NMCPs in 47 malaria endemic countries in Africa was undertaken by examining the most recent national malaria strategies, monitoring and evaluation plans, malaria programme reviews and applications submitted to the Global Fund. The types of maps presented and how they have been used to define priorities for investment and control was investigated.

Results

91% of endemic countries in Africa have defined malaria risk at sub-national levels using at least one risk map. The range of risk maps varies from maps based on suitability of climate for transmission; predicted malaria seasons and temperature/altitude limitations, to representations of clinical data and modelled parasite prevalence. The choice of maps is influenced by the source of the information. Maps developed using national data through in-country research partnerships have greater utility than more readily accessible web-based options developed without inputs from national control programmes. Although almost all countries have stratification maps, only a few use them to guide decisions on the selection of interventions allocation of resources for malaria control.

Conclusion

The way information on the epidemiology of malaria is presented and used needs to be addressed to ensure evidence-based added value in planning control. The science on modelled impact of interventions must be integrated into new mapping products to allow a translation of risk into rational decision making for malaria control. As overseas and domestic funding diminishes, strategic planning will be necessary to guide appropriate financing for malaria control.     

Pharmacokinetic profiles of artesunate following multiple intravenous doses of 2, 4, and 8 mg/kg in healthy volunteers: Phase 1b study

ABSTRACT: BACKGROUND: Severe malaria results in over a million deaths every year, most of them in children aged less than five years and living in sub-Saharan Africa. Injectable artesunate (AS) was recommended as initial treatment for severe malaria by WHO in 2006. The Walter Reed Army Institute of Research (WRAIR) has been developing a novel good manufacturing practice (GMP) injection of AS, which was approved by the US FDA for investigational drug use and distribution by the CDC. METHODS: Tolerability and pharmacokinetics of current GMP intravenous AS, as an anti-malarial agent, were evaluated after ascending multiple doses of 2, 4, and 8 mg/kg daily for three days with 2-minute infusion in 24 healthy subjects (divided into three groups) in the Phase 1 clinical trial study. RESULTS: Results showed that there were no dose-dependent increases in any adverse events. Drug concentrations showed no accumulation and no decline of the drug during the three days of treatment. After intravenous injection, parent drug rapidly declined and was converted to dihydroartemisinin (DHA) with overall mean elimination half-lives ranging 0.15-0.23 hr for AS and 1.23-1.63 hr for DHA, but the peak concentration (Cmax) of AS was much higher than that of DHA with a range of 3.08-3.78-folds. In addition, the AUC and Cmax values of AS and DHA were increased proportionally to the AS climbing multiple doses. DISCUSSION: The safety of injectable AS, even at the highest dose of 8 mg/kg increases the probability of therapeutic success of the drug even in patients with large variability of parasitaemia.     

Getting ready for malaria elimination: a check list of critical issues to consider

In recent years, a renewed interest in malaria elimination and eradication has emerged and seems to be rooting in the minds of the scientific community, public health specialists, funding bodies, policy makers and politicians. Malaria eradication will certainly benefit from improved and innovative tools; notwithstanding novel knowledge in fields ranging from basic science to mathematical modelling and health systems research. However, the elimination of malaria also encompasses a broad range of essential aspects that countries and other actors need to consider when thinking of embarking on such an adventure, including the implementation of innovative strategies, the ability to incorporate the most up-to-date evidence into policy, the integration of malaria into the broader health agenda, the strengthening of surveillance and health systems, capacity building, funding, advocacy and, very importantly, research. While in some cases this enthusiasm is clearly justified, some countries are still a long way from realistically advancing towards elimination. This paper attempts to provide guidance on all the necessary issues that should be considered when initiating a malaria elimination program.     

Plasmodium falciparum: isolation and characterisation of a gene encoding protozoan GMP synthase

The final step in guanylate nucleotide biosynthesis is catalysed by GMP synthase. This paper presents the first isolation of a gene encoding a protozoan GMP synthase. The deduced amino acid sequence from Plasmodium falciparum shares 40% identity with yeast GMP synthase and contains motifs conserved in catalysis. Expression of the gene is regulated through the parasite's development in human red blood cells with maximal expression during the point of DNA replication. Psicofuranine, which inhibits GMP synthase, interrupts parasite growth, supporting the role of this enzyme. These findings will aid development of inhibitors of purine salvage in malaria parasites.     

Control to elimination: implications for malaria research

Recent reports indicate that a high level of malaria control can be achieved with existing control tools once their use has been scaled up. This has led to renewed interest in the possibility of malaria elimination, an approach that is now supported by several influential organisations. An increasing focus on elimination requires a review of priorities within the malaria research agenda. The development of drugs and vaccines with a strong transmission-blocking potential becomes increasingly important. Novel approaches to surveillance will be necessary to ensure that once elimination has been achieved, it is not threatened by a rapid reintroduction of malaria from neighbouring areas.     

The current status of drug resistance in malaria

Drug resistant malaria is a major health problem; it poses a threat to the lives of millions of people and renders it less possible for the worldwide eradication programme to attain its goal in the foreseeable future. At present Plasmodium falciparum is resistant to varying degrees to all antimalarial drugs available e.g. chloroquine, sulfadoxine and pyrimethamine, quinine and even to the new compound, mefloquine.Chloroquine-resistant P. falciparum originated in Thailand some 25 years ago has spread in all directions to Southeast Asia, Western Pacific, to central and southeast India, East Africa and West Africa. In South America, it started in Colombia and now affects the whole of Central and South America with the exception of Argentina, Paraguay and Peru which practically have no falciparum malaria.The mechanism of drug resistance in malaria parasites is believed to be due to gene mutation selected under drug pressure. It may be one-step as in pyrimethamine or multi-step as in chloroquine. Resistant mutation occurs both in schizogony and sporogony. The parasites lose their S strains through hybridization or overgrowth, shifting in character progressively towards high grade resistance.Policies that may help to minimise further development of resistance to existing compounds and to safeguard any new drugs that may be developed in the future include (1) limit the distribution of antimalarials; (2) select priority groups for prophylaxis; (3) use the gametocidal drug primaquine to restrict transmission of resistant strains; (4) establish an effective drug monitoring system; (5) only deploy drugs for control as part of an integrated campaign; (6) control use of new antimalarial; (7) encourage the use of tested effective drug regimens for treatment and (8) encourage research on antimalarials.     

A research agenda for malaria eradication: drugs

Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or "attack" phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission.     

Malaria in India: Challenges and opportunities

India contributes about 70% of malaria in the South East Asian Region of WHO. Although annually India reports about two million cases and 1000 deaths attributable to malaria, there is an increasing trend in the proportion of Plasmodium falciparum as the agent. There exists heterogeneity and variability in the risk of malaria transmission between and within the states of the country as many ecotypes/paradigms of malaria have been recognized. The pattern of clinical presentation of severe malaria has also changed and while multi-organ failure is more frequently observed in falciparum malaria, there are reports of vivax malaria presenting with severe manifestations. The high burden populations are ethnic tribes living in the forested pockets of the states like Orissa, Jharkhand, Madhya Pradesh, Chhattisgarh and the North Eastern states which contribute bulk of morbidity and mortality due to malaria in the country. Drug resistance, insecticide resistance, lack of knowledge of actual disease burden along with new paradigms of malaria pose a challenge for malaria control in the country. Considering the existing gaps in reported and estimated morbidity and mortality, need for estimation of true burden of malaria has been stressed. Administrative, financial, technical and operational challenges faced by the national programme have been elucidated. Approaches and priorities that may be helpful in tackling serious issues confronting malaria programme have been outlined.