The Pan African Vivax and Ovale Network (PAVON): Refocusing on Plasmodium vivax,ovale and asymptomatic malaria in sub-Saharan Africa

The recent World Malaria report shows that progress in malaria elimination has stalled. Current data acquisition by NMCPs depend on passive case detection and clinical reports focused mainly on Plasmodium falciparum (Pf). In recent times, several countries in sub-Saharan Africa have reported cases of Plasmodium vivax (Pv) with a considerable number being Duffy negative. The burden of Pv and Plasmodium ovale (Po) appear to be more than acknowledged. Similarly, the contribution of asymptomatic malaria in transmission is hardly considered by NMCPs in Africa. Inclusion of these as targets in malaria elimination agenda is necessary to achieve elimination goal, as these harbor hypnozoites.The Pan African Vivax and Ovale Network (PAVON) is a new consortium of African Scientists working in Africa on the transmission profile of Pv and Po. The group collaborates with African NMCPs to train in Plasmodium molecular diagnostics, microscopy, and interpretation of molecular data from active surveys to translate into policy. Details of the mission, rational and modus operandi of the group are outlined.     

A sticky situation: the unexpected stability of malaria elimination

Malaria eradication involves eliminating malaria from every country where transmission occurs. Current theory suggests that the post-elimination challenges of remaining malaria-free by stopping transmission from imported malaria will have onerous operational and financial requirements. Although resurgent malaria has occurred in a majority of countries that tried but failed to eliminate malaria, a review of resurgence in countries that successfully eliminated finds only four such failures out of 50 successful programmes. Data documenting malaria importation and onwards transmission in these countries suggests malaria transmission potential has declined by more than 50-fold (i.e. more than 98%) since before elimination. These outcomes suggest that elimination is a surprisingly stable state. Elimination''s ‘stickiness’ must be explained either by eliminating countries starting off qualitatively different from non-eliminating countries or becoming different once elimination was achieved. Countries that successfully eliminated were wealthier and had lower baseline endemicity than those that were unsuccessful, but our analysis shows that those same variables were at best incomplete predictors of the patterns of resurgence. Stability is reinforced by the loss of immunity to disease and by the health system''s increasing capacity to control malaria transmission after elimination through routine treatment of cases with antimalarial drugs supplemented by malaria outbreak control. Human travel patterns reinforce these patterns; as malaria recedes, fewer people carry malaria from remote endemic areas to remote areas where transmission potential remains high. Establishment of an international resource with backup capacity to control large outbreaks can make elimination stickier, increase the incentives for countries to eliminate, and ensure steady progress towards global eradication. Although available evidence supports malaria elimination''s stickiness at moderate-to-low transmission in areas with well-developed health systems, it is not yet clear if such patterns will hold in all areas. The sticky endpoint changes the projected costs of maintaining elimination and makes it substantially more attractive for countries acting alone, and it makes spatially progressive elimination a sensible strategy for a malaria eradication endgame.     

Human movement data for malaria control and elimination strategic planning

ABSTRACT: Recent increases in funding for malaria control have led to the reduction in transmission in many malaria endemic countries, prompting the national control programmes of 36 malaria endemic countries to set elimination targets. Accounting for human population movement (HPM) in planning for control, elimination and post-elimination surveillance is important, as evidenced by previous elimination attempts that were undermined by the reintroduction of malaria through HPM. Strategic control and elimination planning, therefore, requires quantitative information on HPM patterns and the translation of these into parasite dispersion. HPM patterns and the risk of malaria vary substantially across spatial and temporal scales, demographic and socioeconomic sub-groups, and motivation for travel, so multiple data sets are likely required for quantification of movement. While existing studies based on mobile phone call record data combined with malaria transmission maps have begun to address within-country HPM patterns, other aspects remain poorly quantified despite their importance in accurately gauging malaria movement patterns and building control and detection strategies, such as cross-border HPM, demographic and socioeconomic stratification of HPM patterns, forms of transport, personal malaria protection and other factors that modify malaria risk. A wealth of data exist to aid filling these gaps, which, when combined with spatial data on transport infrastructure, traffic and malaria transmission, can answer relevant questions to guide strategic planning. This review aims to (i) discuss relevant types of HPM across spatial and temporal scales, (ii) document where datasets exist to quantify HPM, (iii) highlight where data gaps remain and (iv) briefly put forward methods for integrating these datasets in a Geographic Information System (GIS) framework for analysing and modelling human population and Plasmodium falciparum malaria infection movements.     

The United States Army and malaria control in World War II

The United States Army faced difficult malaria control problems both at home and abroad during World War II. This challenge forced the Army to develop new tools and strategies for use in malarious areas where fighting was occurring. Due to the severe malaria problems being faced in some combat areas and the need to solve these problems quickly, intensive malaria research and operational programs were developed and implemented. With these concerted efforts and the simultaneous development of new control technologies, malaria was successfully controlled in most locations. In order to accomplish this high level of control both in the US and overseas, the Army developed a very organized approach to the malaria problem and implemented it in an effective manner. The creation of new technical solutions was also strongly emphasized and out of this effort came the development of effective antimalaria drugs to replace quinine, of new insecticides and of more effective systems for delivering these insecticides. Some of the major new tools which came out of this research were DDT and drugs such as Atabrine and chloroquine. The availability of Atabrine and DDT revolutionized malaria control throughout the world. The knowledge and experience gained through the use of these new tools by the US Army and other agencies in World War II provided the basis for a new optimism regarding malaria control which then led to the development of the global malaria eradication strategy in the post-war years.     

Molecular surveillance and temporal monitoring of malaria parasites in focal Vietnamese provinces

In the past decade substantial reduction in malaria morbidity and mortality has been observed through well-implemented case management and vector control strategies. India has also achieved a significant reduction in malaria burden in 2018 and has committed to eliminate malaria by 2030. The Mandla Malaria Elimination Demonstration Project (MEDP) was started in 2017 in 1233 villages of District Mandla to demonstrate malaria elimination in a tribal district with hard-to-reach areas was possible using active and passive surveillance, case management, vector control, and targeted information, education and communication campaigns. An operational plan was developed to strengthen the existing surveillance and malaria elimination systems, through fortnightly active case detection to ensure that all cases including those that are introduced into the communities are rapidly identified and treated promptly. The plan also focused on the reduction of human-mosquito contact through the use of Long-Lasting Insecticial Nets (LLINs) and Indoor Residual Spray (IRS). The operational plan was modified in view of the present COVID-19 pandemic by creating systems of assistance for the local administration for COVID-related work while ensuring the operational integrity of malaria elimination efforts. The use of MEDP study design and operational plan, with its built-in management control systems, has yielded significant (91%) reduction of indigenous cases of malaria during the period from June 2017 to May 2020. The malaria positivity rate was 0.33% in 2017–18, 0.13% in 2018–19, and 0.06% in 2019–20. Mass screening revealed 0.18% malaria positivity in September–October 2018, followed by 0.06% in June 2019, and 0.03% in December 2019, and these were mostly asymptomatic cases in the community. The project has been able to sustain the gains of the past three years during the ongoing COVID-19 pandemic. This paper provides the study design and the operational plan for malaria elimination in a high-burden district of Central India, which presented difficulties of hard to reach areas, forest malaria, and complex epidemiology of urban and rural malaria. The lessons learned could be used for malaria elimination efforts in rest of the country and other parts of South Asia with comparable demography and epidemiology.     

Prospects for Malaria Elimination in Mesoamerica and Hispaniola

Malaria remains endemic in 21 countries of the American continent with an estimated 427,000 cases per year. Approximately 10% of these occur in the Mesoamerican and Caribbean regions. During the last decade, malaria transmission in Mesoamerica showed a decrease of ~85%; whereas, in the Caribbean region, Hispaniola (comprising the Dominican Republic [DR] and Haiti) presented an overall rise in malaria transmission, primarily due to a steady increase in Haiti, while DR experienced a significant transmission decrease in this period.The significant malaria reduction observed recently in the region prompted the launch of an initiative for Malaria Elimination in Mesoamerica and Hispaniola (EMMIE) with the active involvement of the National Malaria Control Programs (NMCPs) of nine countries, the Regional Coordination Mechanism (RCM) for Mesoamerica, and the Council of Health Ministries of Central America and Dominican Republic (COMISCA). The EMMIE initiative is supported by the Global Fund for Aids, Tuberculosis and Malaria (GFATM) with active participation of multiple partners including Ministries of Health, bilateral and multilateral agencies, as well as research centers. EMMIE’s main goal is to achieve elimination of malaria transmission in the region by 2020. Here we discuss the prospects, challenges, and research needs associated with this initiative that, if successful, could represent a paradigm for other malaria-affected regions.     

A research agenda for malaria eradication: health systems and operational research

Health systems research and development is needed to support the global malaria eradication agenda. In this paper, we (the malERA Consultative Group on Health Systems and Operational Research) focus on the health systems needs of the elimination phase of malaria eradication and consider groupings of countries at different stages along the pathway to elimination. We examine the difference between the last attempt at eradication of malaria and more recent initiatives, and consider the changing health system challenges as countries make progress towards elimination. We review recent technological and theoretical developments related to health systems and the renewed commitment to strengthening health systems for universal access and greater equity. Finally, we identify a number of needs for research and development, including tools for analyzing and improving effective coverage and strengthening decision making and discuss the relevance of these needs at all levels of the health system from the community to the international level.     

A research agenda for malaria eradication: cross-cutting issues for eradication

Discipline-specific Malaria Eradication Research Agenda (malERA) Consultative Groups have recognized several cross-cutting issues that must be addressed to prevent repetition of some of the mistakes of past malaria elimination campaigns in future programs. Integrated research is required to develop a decision-making framework for the switch from malaria control to elimination. Similarly, a strong economic case is needed for the very long-term financial support that is essential for elimination. Another cross-cutting priority is the development of improved measures of intensity of transmission, especially at low and nonrandom levels. Because sustained malaria elimination is dependent on a functioning health system, a further key cross-cutting research question is to determine how inputs for malaria can strengthen health systems, information systems, and overall health outcomes. Implementation of elimination programs must also be accompanied by capacity building and training to allow the assessment of the impact of new combinations of interventions, new roles for different individuals, and the operational research that is needed to facilitate program expansion. Finally, because community engagement, knowledge management, communication, political, and multisectoral support are critical but poorly understood success factors for malaria elimination, integrated research into these issues is vital.     

A nowcasting framework for correcting for reporting delays in malaria surveillance

Time lags in reporting to national surveillance systems represent a major barrier for the control of infectious diseases, preventing timely decision making and resource allocation. This issue is particularly acute for infectious diseases like malaria, which often impact rural and remote communities the hardest. In Guyana, a country located in South America, poor connectivity among remote malaria-endemic regions hampers surveillance efforts, making reporting delays a key challenge for elimination. Here, we analyze 13 years of malaria surveillance data, identifying key correlates of time lags between clinical cases occurring and being added to the central data system. We develop nowcasting methods that use historical patterns of reporting delays to estimate occurred-but-not-reported monthly malaria cases. To assess their performance, we implemented them retrospectively, using only information that would have been available at the time of estimation, and found that they substantially enhanced the estimates of malaria cases. Specifically, we found that the best performing models achieved up to two-fold improvements in accuracy (or error reduction) over known cases in selected regions. Our approach provides a simple, generalizable tool to improve malaria surveillance in endemic countries and is currently being implemented to help guide existing resource allocation and elimination efforts.     

The impact of a malaria elimination initiative on school outcomes: Evidence from Southern Mozambique

Despite the significant improvements achieved over the last ten years, primary education attainment in Mozambique is still low. Potential reasons acting from the demand perspective include ill health, among other factors. In Mozambique, ill health is still largely linked to malaria, which is a leading cause of outpatient contacts, hospital admissions and death, particularly among under-five and school-aged children. Despite this, in Mozambique and more generally, in malaria endemic countries, the identification and measurement of how improved malaria indicators may contribute to better school outcomes remains largely unknown. In particular, there is a low understanding of the extent to which better health translates immediately into school indicators, such as absenteeism and grades. In this study, we exploit the first year of a malaria elimination initiative implemented in Magude district (Southern Mozambique) that started in 2015, as a quasi-experiment to estimate the impact of malaria on selected primary school outcomes. While malaria was not eliminated, its incidence drastically dropped. We use as control a neighbouring district (Manhiça) with similar socio-economic and epidemiological characteristics. By employing a difference-in-differences (DiD) approach, we examine whether the positive health shock translated into improved school outcomes. Using information from school registers, we generated a dataset on school attendance and grades for 9,848 primary-school students from 9 schools (4 in the treated district and 5 in the control district). In our main specification, a repeated cross-section analysis, we find that the elimination initiative led to a 28% decrease in school absenteeism and a 2% increase in students’ grades. Our results are robust across different specifications, including a panel DiD individual fixed effects estimate on a sub-sample of students. These findings provide evidence on the negative impact of malaria on primary education attainment and suggest remarkable economic benefits consequent to its elimination.     

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.     

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.     

Overview of malaria control in the Americas

The malaria endemic countries of the Americas have adopted in 1992 the WHO Global Malaria Control Strategy whose difficulties of implementation have been compounded to a major reform in the health sector, as the countries adjust to conform to financial scarcity and new economic policies. Most countries of the Region have reoriented its control program from eradication of malaria to the elimination of malaria mortality and morbidity. The Region has advanced towards these objectives having already reduced its mortality by 60% and is now in the final stages of applying new tools to control transmission and rapidly advance to reduce the incidence of malaria in the Americas.     

Risk factors for severe malaria in Bamako, Mali: a matched case-control study

The aim of this case-control study was to identify epidemiological risk factors for severe malaria among children living in Bamako, a malaria-endemic area. For this, 260 healthy community controls were matched to 130 patients with severe malaria. Conditional multiple logistic regression analysis indicated that all examined independent factors associated with severe malaria are directly related to characteristics of the child's mother, with the exception of the child's own yellow fever vaccination history (odds ratio (OR): 1.93, 95% confidence intervals (CI(95%)) [1.10-3.37]). The following characteristics were all associated with a decreased risk of severe malaria in the child: maternal education (OR: 0.52, CI(95%) [0.31-0.86]), the mother's adequate knowledge about malaria (OR: 0.46, 95% CI(95%) [0.25-0.86]), her use of mosquito bed nets (OR: 0.53, CI(95%) [0.30-0.92]) and breast-feeding for at least 2 years (OR: 0.57, CI(95%) [0.33-0.94]). Conversely, chronic maternal disease (OR: ?3.16, CI(95%) [1.31-7.61]) was associated with an increased risk of severe malaria. These findings strongly support the hypothesis that maternal factors are central to the development of severe malaria in children. Programmes aiming to improve both maternal health and maternal education may reduce the incidence of severe malaria in children and should therefore be advocated in Bamako and in areas with similar epidemiological patterns for malaria.     

Implementation of malaria control

Global trends of infant and child mortality have decreased over the last 30 years, while the proportion of malaria deaths has progressively increased due to the deteriorating situation in sub-Saharan Africa. The Global Malaria Control Strategy promoted by WHO has encountered several obstacles to its implementation. Early diagnosis and prompt treatment can reduce malaria mortality, but there is still low investment on safe and effective modalities of care delivery at the periphery, where most of the malaria burden exists. Selective vector control (indoor residual spraying and insecticide-treated nets) plays a significant role outside Africa, but its wider use is limited by cost/affordability problems and operational issues (supply, delivery and logistics). Alternative methods such as environmental management and biological control are cost-effective only under very specific epidemiological situations. In most countries forecasting, early detection and containment of malaria epidemics is deficient, and there is separation between the research and control communities, particularly in Africa. Involvement of the internal agencies, strategic investments in capacity building and institutional networking are needed to strengthen capacity for malaria and research in the countries. The major responsibility is to guide the expenditure made by the communities (which far out-weigh the limited share of national health budgets) towards the most cost-effective approaches to reduce malaria mortality and morbidity.     

The architecture and effect of participation: a systematic review of community participation for communicable disease control and elimination. Implications for malaria elimination

Background

Community engagement and participation has played a critical role in successful disease control and elimination campaigns in many countries. Despite this, its benefits for malaria control and elimination are yet to be fully realized. This may be due to a limited understanding of the influences on participation in developing countries as well as inadequate investment in infrastructure and resources to support sustainable community participation. This paper reports the findings of an atypical systematic review of 60 years of literature in order to arrive at a more comprehensive awareness of the constructs of participation for communicable disease control and elimination and provide guidance for the current malaria elimination campaign.

Methods

Evidence derived from quantitative research was considered both independently and collectively with qualitative research papers and case reports. All papers included in the review were systematically coded using a pre-determined qualitative coding matrix that identified influences on community participation at the individual, household, community and government/civil society levels. Colour coding was also carried out to reflect the key primary health care period in which community participation programmes originated. These processes allowed exhaustive content analysis and synthesis of data in an attempt to realize conceptual development beyond that able to be achieved by individual empirical studies or case reports.

Results

Of the 60 papers meeting the selection criteria, only four studies attempted to determine the effect of community participation on disease transmission. Due to inherent differences in their design, interventions and outcome measures, results could not be compared. However, these studies showed statistically significant reductions in disease incidence or prevalence using various forms of community participation. The use of locally selected volunteers provided with adequate training, supervision and resources are common and important elements of the success of the interventions in these studies. In addition, qualitative synthesis of all 60 papers elucidates the complex architecture of community participation for communicable disease control and elimination which is presented herein.

Conclusions

The current global malaria elimination campaign calls for a health systems strengthening approach to provide an enabling environment for programmes in developing countries. In order to realize the benefits of this approach it is vital to provide adequate investment in the 'people' component of health systems and understand the multi-level factors that influence their participation. The challenges of strengthening this component of health systems are discussed, as is the importance of ensuring that current global malaria elimination efforts do not derail renewed momentum towards the comprehensive primary health care approach. It is recommended that the application of the results of this systematic review be considered for other diseases of poverty in order to harmonize efforts at building 'competent communities' for communicable disease control and optimising health system effectiveness.

     

Self-reported malaria and mosquito avoidance in relation to household risk factors in a Kenyan coastal city

A geographically stratified cross-sectional survey was conducted in 2002 to investigate household-level factors associated with use of mosquito control measures and self-reported malaria in Malindi, Kenya. A total of 629 households were surveyed. Logistic regressions were used to analyse the data. Half of all households (51%) reported all occupants using an insecticide-treated bed net and at least one additional mosquito control measure such as insecticides or removal of standing water. Forty-nine per cent reported a history of malaria in the household. Of the thirteen household factors analysed, low (OR=0.23, CI 0.11, 0.48) and medium (OR=0.50, CI 0.29, 0.86) education, mud--wood--coral (OR=0.0.39, CI 0.24, 0.66) and mud block--plaster (OR=0.47, CI 0.25, 0.87) wall types, farming (OR=1.38, CI 1.01, 1.90) and travel to rural areas (OR=0.48, CI 0.26, 0.91) were significantly associated with the use of mosquito control, while controlling for other covariates in the model. History of reported malaria was not associated with the use of mosquito control (OR=1.22, CI 0.79, 1.88). Of the thirteen covariates analysed in the second model, only two household factors were associated with history of malaria: being located in the well-drained stratum (OR=0.49, CI 0.26, 0.96) and being bitten while in the house (OR=1.22, CI 0.19, 0.49). These results suggest that high socioeconomic status is associated with increased household-level mosquito control use, although household-level control may not be enough, as many people are exposed to biting mosquitoes while away from the house and in areas that are more likely to harbour mosquitoes.     

Determining the impact of community awareness-raising activities on the prevention of malaria transmission in Palawan,the Philippines

Palawan has the highest malaria endemicity in the Philippines, and malaria remains a major health burden in the region. In 1999, 344 microscopists were trained in Palawan. This allowed for early diagnosis and prompt treatment throughout the island. To take a significant step toward the elimination of malaria on the island, microscopists implemented community awareness-raising activities aimed at preventing transmission of malaria. The objective of the present study was to determine the impact of these activities on the self-implemented preventive measures against malaria by the ex-patients of the microscopists. Structured interviews were carried out from January to February in 2012, in 20 remote malaria-endemic villages throughout Palawan. In total, 141 ex-patients who had previously been diagnosed malaria-positive by the microscopists, volunteered to participate in the present study. Structural equation modeling was conducted to determine factors associated with self-implemented preventive measures against malaria, which included: (1) place of residence; (2) socio-demographic characteristics; (3) knowledge on malaria; (4) participation in community awareness-raising activities for malaria prevention; and (5) satisfaction with microscopists. Structural equation modeling identified six significant factors independently associated with self-implemented preventive measures against malaria; ethnicity, knowledge on malaria transmission, knowledge on vector species, knowledge on vector's most active time, participation in awareness-raising activities for malaria prevention by microscopists, and satisfaction with microscopists. Tagalog ethnicity (the predominant ethnic group) was positively related to better self-implemented preventive measures. In conclusion, aside from providing early diagnosis and treatment, microscopists played a significant role in self-implemented preventive measures against malaria. The strengthening of awareness-raising activities by microscopists was suggested to be an effective strategy for reducing malaria re-infection in Palawan. These activities should be strengthened to improve preventive measures implemented by ex-patients traveling to mountain areas and to enhance the knowledge on malaria transmission particularly among indigenous residents.     

Surveillance for malaria elimination in Swaziland: a national cross-sectional study using pooled PCR and serology

Background

To guide malaria elimination efforts in Swaziland and other countries, accurate assessments of transmission are critical. Pooled-PCR has potential to efficiently improve sensitivity to detect infections; serology may clarify temporal and spatial trends in exposure.

Methodology/Principal Findings

Using a stratified two-stage cluster, cross-sectional design, subjects were recruited from the malaria endemic region of Swaziland. Blood was collected for rapid diagnostic testing (RDT), pooled PCR, and ELISA detecting antibodies to Plasmodium falciparum surface antigens. Of 4330 participants tested, three were RDT-positive yet false positives by PCR. Pooled PCR led to the identification of one P. falciparum and one P. malariae infection among RDT-negative participants. The P. falciparum-infected participant reported recent travel to Mozambique. Compared to performing individual testing on thousands of samples, PCR pooling reduced labor and consumable costs by 95.5%. Seropositivity was associated with age ≥20 years (11·7% vs 1·9%, P<0.001), recent travel to Mozambique (OR 4.4 [95% CI 1.0–19.0]) and residence in southeast Swaziland (RR 3.78, P<0.001).

Conclusions

The prevalence of malaria infection and recent exposure in Swaziland are extremely low, suggesting elimination is feasible. Future efforts should address imported malaria and target remaining foci of transmission. Pooled PCR and ELISA are valuable surveillance tools for guiding elimination efforts.