Effectiveness and cost-effectiveness of reactive, targeted indoor residual spraying for malaria control in low-transmission settings: a cluster-randomised, non-inferiority trial in South Africa.

BACKGROUND: Increasing insecticide costs and constrained malaria budgets could make universal vector control strategies, such as indoor residual spraying (IRS), unsustainable in low-transmission settings. We investigated the effectiveness and cost-effectiveness of a reactive, targeted IRS strategy. METHODS: This cluster-randomised, open-label, non-inferiority trial compared reactive, targeted IRS with standard IRS practice in northeastern South Africa over two malaria seasons (2015-17). In standard IRS clusters, programme managers conducted annual mass spray campaigns prioritising areas using historical data, expert opinion, and other factors. In targeted IRS clusters, only houses of index cases (identified through passive surveillance) and their immediate neighbours were sprayed. The non-inferiority margin was 1 case per 1000 person-years. Health service costs of real-world implementation were modelled from primary and secondary data. Incremental costs per disability-adjusted life-year (DALY) were estimated and deterministic and probabilistic sensitivity analyses conducted. This study is registered with ClinicalTrials.gov, NCT02556242. FINDINGS: Malaria incidence was 0·95 per 1000 person-years (95% CI 0·58 to 1·32) in the standard IRS group and 1·05 per 1000 person-years (0·72 to 1·38) in the targeted IRS group, corresponding to a rate difference of 0·10 per 1000 person-years (-0·38 to 0·59), demonstrating non-inferiority for targeted IRS (p<0·0001). Per additional DALY incurred, targeted IRS saved US$7845 (2902 to 64 907), giving a 94-98% probability that switching to targeted IRS would be cost-effective relative to plausible cost-effectiveness thresholds for South Africa ($2637 to $3557 per DALY averted). Depending on the threshold used, targeted IRS would remain cost-effective at incidences of less than 2·0-2·7 per 1000 person-years. Findings were robust to plausible variation in other parameters. INTERPRETATION: Targeted IRS was non-inferior, safe, less costly, and cost-effective compared with standard IRS in this very-low-transmission setting. Saved resources could be reallocated to other malaria control and elimination activities. FUNDING: Joint Global Health Trials.

Insecticide resistance status of the malaria mosquitoes: Anopheles gambiae and Anopheles funestus in eastern and northern Uganda.

BACKGROUND: Uganda's malaria burden includes the sixth highest number of annual deaths in Africa (10,500) with approximately 16 million cases (2013) and the entire population at risk. The President's Malaria Initiative has been supporting the malaria control interventions of indoor residual spraying (IRS) and distribution of long-lasting insecticidal nets (LLIN) in Uganda since 2007. These interventions are threatened by emerging and spreading insecticide resistance, known to exist in Ugandan malaria vectors. Pyrethroid insecticides have been used in agriculture since the early 1990s and in IRS programmes from the mid-2000s until 2010. A universal LLIN coverage campaign was executed in 2013-2014, distributing pyrethroid-treated LLINs throughout the country. This study investigated insecticide susceptibility, intensity, and oxidase detoxification in Anopheles gambiae sensu lato and Anopheles funestus to permethrin and deltamethrin in four eastern Ugandan sites. METHODS: The susceptibility status of An. gambiae and An. funestus to bendiocarb, permethrin and deltamethrin was determined using the CDC (Centers for Disease Control and Prevention) bottle bioassay. Presence of oxidative enzyme detoxification mechanisms were determined by pre-exposing mosquitoes to piperonyl butoxide followed with exposure to discriminating doses of deltamethrin- and permethrin-coated CDC bottles. Resistance intensity was investigated using serial dosages of 1×, 2×, 5× and 10× the diagnostic dose and scored at 30 min to determine the magnitude of resistance to both of these LLIN pyrethroids. Testing occurred in the Northern and Eastern Regions of Uganda. RESULTS: Anopheles gambiae and An. funestus were fully susceptible to bendiocarb where tested. Anopheles gambiae resistance to deltamethrin and permethrin was observed in all four study sites. Anopheles funestus was resistant to deltamethrin and permethrin in Soroti. Oxidative resistance mechanisms were found in An. gambiae conferring pyrethroid resistance in Lira and Apac. 14.3% of An. gambiae from Tororo survived exposure of 10× concentrations of permethrin. CONCLUSIONS: Both An. gambiae and An. funestus are resistant to pyrethroids but fully susceptible to bendiocarb at all sites. Susceptibility monitoring guided the Ministry of Health's decision to rotate between IRS insecticide classes. Intensity bioassay results may indicate encroaching control failure of pyrethroid-treated LLINs and should inform decision-makers when choosing LLINs for the country.

Harnessing Integrated Vector Management for Enhanced Disease Prevention.

The increasing global threat of emerging and re-emerging vector-borne diseases (VBDs) poses a serious health problem. The World Health Organization (WHO) recommends integrated vector management (IVM) strategy for combating VBD transmission. An IVM approach requires entomological knowledge, technical and infrastructure capacity, and systems facilitating stakeholder collaboration. In sub-Saharan Africa, successful operational IVM experience comes from relatively few countries. This article provides an update on the extent to which IVM is official national policy, the degree of IVM implementation, the level of compliance with WHO guidelines, and concordance in the understanding of IVM, and it assesses the operational impact of IVM. The future outlook encompasses rational and sustainable use of effective vector control tools and inherent improved return for investment for disease vector control.

Consolidating tactical planning and implementation frameworks for integrated vector management in Uganda.

BACKGROUND: Integrated vector management (IVM) is the recommended approach for controlling some vector-borne diseases (VBD). In the face of current challenges to disease vector control, IVM is vital to achieve national targets set for VBD control. Though global efforts, especially for combating malaria, now focus on elimination and eradication, IVM remains useful for Uganda which is principally still in the control phase of the malaria continuum. This paper outlines the processes undertaken to consolidate tactical planning and implementation frameworks for IVM in Uganda. CASE DESCRIPTION: The Uganda National Malaria Control Programme with its efforts to implement an IVM approach to vector control was the 'case' for this study. Integrated management of malaria vectors in Uganda remained an underdeveloped component of malaria control policy. In 2012, knowledge and perceptions of malaria vector control policy and IVM were assessed, and recommendations for a specific IVM policy were made. In 2014, a thorough vector control needs assessment (VCNA) was conducted according to WHO recommendations. The findings of the VCNA informed the development of the national IVM strategic guidelines. Information sources for this study included all available data and accessible archived documentary records on VBD control in Uganda. The literature was reviewed and adapted to the local context and translated into the consolidated tactical framework. DISCUSSION: WHO recommends implementation of IVM as the main strategy to vector control and has encouraged member states to adopt the approach. However, many VBD-endemic countries lack IVM policy frameworks to guide implementation of the approach. In Uganda most VBD coexists and could be managed more effectively if done in tandem. In order to successfully control malaria and other VBD and move towards their elimination, the country needs to scale up proven and effective vector control interventions and also learn from the experience of other countries. The IVM strategy is important in consolidating inter-sectoral collaboration and coordination and providing the tactical direction for effective deployment of vector control interventions along the five key elements of the approach and to align them with contemporary epidemiology of VBD in the country. CONCLUSIONS: Uganda has successfully established an evidence-based IVM approach and consolidated strategic planning and operational frameworks for VBD control. However, operating implementation arrangements as outlined in the national strategic guidelines for IVM and managing insecticide resistance, as well as improving vector surveillance, are imperative. In addition, strengthened information, education and communication/behaviour change and communication, collaboration and coordination will be crucial in scaling up and using vector control interventions.

An Operational Framework for Insecticide Resistance Management Planning.

Arthropod vectors transmit organisms that cause many emerging and reemerging diseases, and their control is reliant mainly on the use of chemical insecticides. Only a few classes of insecticides are available for public health use, and the increased spread of insecticide resistance is a major threat to sustainable disease control. The primary strategy for mitigating the detrimental effects of insecticide resistance is the development of an insecticide resistance management plan. However, few examples exist to show how to implement such plans programmatically. We describe the formulation and implementation of a resistance management plan for mosquito vectors of human disease in Zambia. We also discuss challenges, steps taken to address the challenges, and directions for the future.

Strengthening tactical planning and operational frameworks for vector control: the roadmap for malaria elimination in Namibia.

BACKGROUND: Namibia has made tremendous gains in malaria control and the epidemiological trend of the disease has changed significantly over the past years. In 2010, the country reoriented from the objective of reducing disease morbidity and mortality to the goal of achieving malaria elimination by 2020. This manuscript outlines the processes undertaken in strengthening tactical planning and operational frameworks for vector control to facilitate expeditious malaria elimination in Namibia. CASE DESCRIPTION: The information sources for this study included all available data and accessible archived documentary records on malaria vector control in Namibia. A methodical assessment of published and unpublished documents was conducted via a literature search of online electronic databases, Google Scholar, PubMed and WHO, using a combination of search terms. DISCUSSION AND EVALUATION: To attain the goal of elimination in Namibia, systems are being strengthened to identify and clear all infections, and significantly reduce human-mosquito contact. Particularly, consolidating vector control for reducing transmission at the identified malaria foci will be critical for accelerated malaria elimination. Thus, guarding against potential challenges and the need for evidence-based and sustainable vector control instigated the strengthening of strategic frameworks by: adopting the integrated vector management (IVM) strategy; initiating implementation of the global plan for insecticide resistance management (GPIRM); intensifying malaria vector surveillance; improving data collection and reporting systems on DDT; updating the indoor residual spraying (IRS) data collection and reporting tool; and, improving geographical reconnaissance using geographical information system-based satellite imagery. CONCLUSIONS: Universal coverage with IRS and long-lasting insecticidal nets, supplemented by larval source management in the context of IVM and guided by vector surveillance coupled with rational operationalization of the GPIRM, will enable expeditious attainment of elimination in Namibia. However, national capacity to plan, implement, monitor and evaluate interventions will require adequate and sustained support for technical, physical infrastructure, and human and financial resources for entomology and vector control operations.

Preventing malaria transmission by indoor residual spraying in Malawi: grappling with the challenge of uncertain sustainability.

BACKGROUND: In the past decade, there has been rapid scale-up of insecticide-based malaria vector control in the context of integrated vector management (IVM) according to World Health Organization recommendations. Endemic countries have deployed indoor residual spraying (IRS) and long-lasting insecticidal nets as hallmark vector control interventions. This paper discusses the successes and continued challenges and the way forward for the IRS programme in Malawi. CASE DESCRIPTION: The National Malaria Control Programme in Malawi, with its efforts to implement an integrated approach to malaria vector control, was the 'case' for this study. Information sources included all available data and accessible archived documentary records on IRS in Malawi. A methodical assessment of published and unpublished documents was conducted via a literature search of online electronic databases. DISCUSSION: Malawi has implemented IRS as the main malaria transmission-reducing intervention. However, pyrethroid and carbamate resistance in malaria vectors has been detected extensively across the country and has adversely affected the IRS programme. Additionally, IRS activities have been characterized by substantial inherent logistical and technical challenges culminating into missed targets. As a consequence, programmatic IRS operations have been scaled down from seven districts in 2010 to only one district in 2014. The future of the IRS programme in Malawi is uncertain due to limited funding, high cost of alternative insecticides and technical resource challenges being experienced in the country. CONCLUSIONS: The availability of a long-lasting formulation of the organophosphate pirimiphos-methyl makes the re-introduction of IRS a possibility and may be a useful approach for the management of pyrethroid resistance. Implementing the IVM strategy, advocating for sustainable domestic funding, including developing an insecticide resistance monitoring and management plan and vector surveillance guidelines will be pivotal in steering entomologic monitoring and future vector control activities in Malawi.

Response to: Bouwman, H. et al. Hallogenated pollutants in terrestrial and aquatic bird eggs: converging patterns of pollutant profiles, and impacts and risks from higher levels Environ. Res. (2013) http://dx.doi.org/10.1016/j.envres.2013.06.003.

Bouwman and coauthors present data and analyses of DDT and other halogenated pollutants in environmental samples and based on their data and analyses thereof, argue against the use of DDT for malaria control. Regrettably, the analyses, presentations, and interpretations of data presented by Bouwman and coauthors are biased and erroneous.

Integrated vector management: a critical strategy for combating vector-borne diseases in South Sudan.

BACKGROUND: Integrated vector management (IVM) based vector control is encouraged by the World Health Organization (WHO). However, operational experience with the IVM strategy has mostly come from countries with relatively well-established health systems and with malaria control focused programmes. Little is known about deployment of IVM for combating multiple vector-borne diseases in post-emergency settings, where delivery structures are less developed or absent. This manuscript reports on the feasibility of operational IVM for combating vector-borne diseases in South Sudan. CASE DESCRIPTION: A methodical review of published and unpublished documents on vector-borne diseases for South Sudan was conducted via systematic literature search of online electronic databases, Google Scholar, PubMed and WHO, using a combination of search terms. Additional, non-peer reviewed literature was examined for information related to the subject. DISCUSSION: South Sudan is among the heartlands of vector-borne diseases in the world, characterized by enormous infrastructure, human and financial resource constraints and a weak health system against an increasing number of refugees, returnees and internally displaced people. The presence of a multiplicity of vector-borne diseases in this post-conflict situation presents a unique opportunity to explore the potential of a rational IVM strategy for multiple disease control and optimize limited resource utilization, while maximizing the benefits and providing a model for countries in a similar situation. CONCLUSION: The potential of integrating vector-borne disease control is enormous in South Sudan. However, strengthened coordination, intersectoral collaboration and institutional and technical capacity for entomological monitoring and evaluation, including enforcement of appropriate legislation are crucial.

Review of the malaria epidemiology and trends in Zambia.

A comprehensive desk review of malaria trends was conducted between 2000-2010 in Zambia to study malaria epidemiology and trends to guide strategies and approaches for effective malaria control. This review considered data from the National Health Information Management System, Malaria Surveys and Programme Review reports and analyzed malaria in-patient cases and deaths in relation to intervention coverage for all ages. Data showed three distinct epidemiological strata after a notable malaria reduction (66%) in in-patient cases and deaths, particularly between 2000-2008. These changes occurred following the (re-)introduction and expansion of indoor residual spraying up to 90% coverage, scale-up of coverage of long-lasting insecticide-treated nets in household from 50% to 70%, and artemisin-based combination therapy nationwide. However, malaria cases and deaths re-surged, increasing in 2009-2010 in the northern-eastern parts of Zambia. Delays in the disbursement of funds affected the implementation of interventions, which resulted in resurgence of cases and deaths. In spite of a decline in malaria disease burden over the past decade in Zambia, a reversal in impact is notable in the year 2009-2010, signifying that control gains are fragile and must be sustained to eliminate malaria.

Integrated vector management: the Zambian experience.

BACKGROUND: The Zambian Malaria Control Programme with the Roll Back Malaria (RBM) partners have developed the current National Malaria Strategic Plan (NMSP 2006-2011) which focuses on prevention based on the Integrated Vector Management (IVM) strategy. The introduction and implementation of an IVM strategy was planned in accordance with the World Health Organization (WHO) steps towards IVM implementation namely Introduction Phase, Consolidation Phase and Expansion Phase. ACHIEVEMENTS: IVM has created commitment for Legal and Regulatory policy review, monitoring, Research and a strong stewardship by the chemical suppliers. It has also leveraged additional resources, improved inter-sectoral collaboration, capacity building and enhanced community participation which facilitated a steady scaling up in coverage and utilisation of key preventive interventions. Thus, markedly reducing malaria incidence and case fatalities in the country. CONCLUSION: Zambia has successfully introduced, consolidated and expanded IVM activities. Resulting in increased coverage and utilization of interventions and markedly reducing malaria-related morbidity and mortality while ensuring a better protection of the environment.

Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria.

BACKGROUND: Although malaria treatment aims primarily to eliminate the asexual blood stages that cause illness, reducing the carriage of gametocytes is critical for limiting malaria transmission and the spread of resistance. METHODS: Clinical and parasitological responses to the fixed-dose combination of sulfadoxine and pyrimethamine in patients with uncomplicated falciparum malaria were assessed biannually since implementation of this treatment policy in 1998 in Mpumalanga Province, South Africa. RESULTS: Despite sustained cure rates of > 90% (P = .14), the duration of gametocyte carriage increased from 3 to 22 weeks (per 1000 person-weeks) between 1998 and 2002 (P < .001). The dhfr and dhps mutations associated with sulfadoxine-pyrimethamine resistance were the most important drivers of the increased gametocytemia, although these mutations were not associated with increased pretreatment asexual parasite density or slower asexual parasite clearance times. The geometric mean gametocyte duration and area under the gametocyte density time curve (per 1000 person-weeks) were 7.0 weeks and 60.8 gametocytes/microL per week, respectively, among patients with wild-type parasites, compared with 45.4 weeks (P = .016) and 1212 gametocytes/microL per week (P = .014), respectively, among those with parasites containing 1-5 dhfr/dhps mutations. CONCLUSIONS: An increased duration and density of gametocyte carriage after sulfadoxine-pyrimethamine treatment was an early indicator of drug resistance. This increased gametocytemia among patients who have primary infections with drug-resistant Plasmodium falciparum fuels the spread of resistance even before treatment failure rates increase significantly.

The sympatric occurrence of two molecular forms of the malaria vector Anopheles gambiae Giles sensu stricto in Kanyemba, in the Zambezi Valley, Zimbabwe.

The complexity of Anopheles gambiae Giles sensu stricto, a sibling species of the A. gambiae complex, has been shown by the extent of chromosomal inversion polymorphisms and more recently, by divergence at the molecular level. Analysis by PCR of a field population of A. gambiae complex from the Zambezi Valley area of Kanyemba, northern Zimbabwe, showed the co-existence of three sibling species: A. arabiensis (90%), A. gambiae (4%), and A. quadriannulatus (6%). Molecular characterization of the A. gambiae s.s. material revealed the sympatric presence of the two molecular forms S and M within a sample of eight. This is the first record of the co-existence of these two molecular forms in southern Africa.