Human and Simian Malaria in the Greater Mekong Subregion and Challenges for Elimination

In recent years malaria initiatives have increasingly shifted from malaria control to a focus on achieving malaria elimination in the Southeast Asia region. However, this region experiences unique challenges in this transition due to its distinctive malaria ecosystem (mainly related to forests) and high volume of population movement (both within and between countries). These bioenvironmental factors increase the exposure of populations at higher risk due to their close association with forest, and contributes to outdoor and residual transmission. Given that this region has also historically been the source of resistance to anti-malarial drugs, the potential spread of artemisinin resistance via global transportation routes would pose a major threat to malaria control and elimination efforts worldwide. In addition, other factors also hinder the malaria elimination goal such as importation of parasite infection, uncontrolled monkey malaria (Plasmodium knowlesi), or the fact that many countries in this region experience mixed infections where P. vivax becomes a more predominant species as overall malaria transmission decreases. This chapter addresses these challenges in detail and provide recommendations and key priorities to overcome these obstacles to accelerate efforts for achieving malaria elimination

The Role of Adaptive Surveillance as a Core Intervention to Achieve Malaria Elimination

Adaptive surveillance systems are essential for national programmes to achieve their malaria elimination goals. Core principles of surveillance systems including accurate diagnosis and reporting of malaria cases, integration of health data across administrative levels and the need to link data to a response are well defined by international guidelines. Nevertheless, while the requirements of surveillance systems along the transmission continuum are clearly documented, the operationalization remains challenging for national programmes. Firstly, because the multi-level increase of surveillance efforts demanding real-time and case-based data as well as the capacity of the health force to trigger locally customized responses, is resource intensive and requires substantial investment. Secondly, because there is a gap in international alignment on best tools and practices on how to operationally implement these requirements. Recently, several initiatives have started to address this gap in international coordination, aiming to establish the operational guidance for elimination programmes to successfully implement adaptive surveillance systems

Age-Patterns of Malaria Vary with Severity, Transmission Intensity and Seasonality in Sub-Saharan Africa: A Systematic Review and Pooled Analysis

BACKGROUND: There is evidence that the age-pattern of Plasmodium falciparum malaria varies with transmission intensity. A better understanding of how this varies with the severity of outcome and across a range of transmission settings could enable locally appropriate targeting of interventions to those most at risk. We have, therefore, undertaken a pooled analysis of existing data from multiple sites to enable a comprehensive overview of the age-patterns of malaria outcomes under different epidemiological conditions in sub-Saharan Africa. METHODOLOGY/PRINCIPAL FINDINGS: A systematic review using PubMed and CAB Abstracts (1980-2005), contacts with experts and searching bibliographies identified epidemiological studies with data on the age distribution of children with P. falciparum clinical malaria, hospital admissions with malaria and malaria-diagnosed mortality. Studies were allocated to a 3x2 matrix of intensity and seasonality of malaria transmission. Maximum likelihood methods were used to fit five continuous probability distributions to the percentage of each outcome by age for each of the six transmission scenarios. The best-fitting distributions are presented graphically, together with the estimated median age for each outcome. Clinical malaria incidence was relatively evenly distributed across the first 10 years of life for all transmission scenarios. Hospital admissions with malaria were more concentrated in younger children, with this effect being even more pronounced for malaria-diagnosed deaths. For all outcomes, the burden of malaria shifted towards younger ages with increasing transmission intensity, although marked seasonality moderated this effect. CONCLUSIONS: The most severe consequences of P. falciparum malaria were concentrated in the youngest age groups across all settings. Despite recently observed declines in malaria transmission in several countries, which will shift the burden of malaria cases towards older children, it is still appropriate to target strategies for preventing malaria mortality and severe morbidity at very young children who will continue to bear the brunt of malaria deaths in sub-Saharan Africa

Malaria and the mobile and migrant population in Cambodia: a population movement framework to inform strategies for malaria control and elimination.

BACKGROUND: The relationships between human population movement (HPM) and health are a concern at global level. In the case of malaria, those links are crucial in relation to the spread of drug resistant parasites and to the elimination of malaria in the Greater Mekong sub-Region (GMS) and beyond. The mobile and migrant populations (MMP) who are involved in forest related activities are both at high risk of being infected with malaria and at risk of receiving late and sub-standard treatment due to poor access to health services. In Cambodia, in 2012, the National Malaria Control Programme (NMCP) identified, as a key objective, the development of a specific strategy for MMPs in order to address these challenges. A population movement framework (PMF) for malaria was developed and operationalized in order to contribute to this strategy. METHODS: A review of the published and unpublished literature was conducted. Based on a synthesis of the results, information was presented and discussed with experienced researchers and programme managers in the Cambodian NMCP and led to the development and refinement of a PMF for malaria. The framework was "tested" for face and content validity with national experts through a workshop approach. RESULTS: In the literature, HPM has been described using various spatial and temporal dimensions both in the context of the spread of anti-malarial drug resistance, and in the context of malaria elimination and previous classifications have categorized MMPs in Cambodia and the GMS through using a number of different criteria. Building on these previous models, the PMF was developed and then refined and populated with in-depth information relevant to Cambodia collected from social science research and field experiences in Cambodia. The framework comprises of the PMF itself, MMP activity profiles and a Malaria Risk Index which is a summation of three related indices: a vulnerability index, an exposure index and an access index which allow a qualitative ranking of malaria risk in the MMP population. Application of currently available data to the framework illustrates that the highest risk population are those highly mobile populations engaged in forest work. CONCLUSION: This paper describes the process of defining MMPs in Cambodia, identifying the different activities and related risks to appropriately target and tailor interventions to the highest risk groups. The framework has been used to develop more targeted behaviour change and outreach interventions for MMPs in Cambodia and its utility and effectiveness will be evaluated as part of those interventions

Evaluation of intensified behaviour change communication strategies in an artemisinin resistance setting

Background: In Cambodia, behaviour change communication (BCC) represents an integral component of malaria efforts aimed at fighting artemisinin resistant parasites and achieving elimination. The multi-pronged BCC interventions include interpersonal communication through village health volunteers (VHVs) and village malaria workers (VMWs), broadcasting malaria prevention, diagnosis and treatment messages via TV, radio and mobile broadcasting units (MBUs), distributing information education and communication (IEC) materials and introducing mobile malaria workers (MMWs) in endemic villages. Methods: This was a cross sectional household survey using a stratified multi-stage cluster sampling approach, conducted in December 2012. A stratified multi-stage cluster sampling approach was used; 30 villages were selected (15 in each stratum) and a total of 774 households were interviewed. This survey aimed to assess the potential added effect of 'intense' BCC interventions in three Western provinces. Conducted 2 years after start of these efforts, 'non-intense' BCC (niBBC) interventions (e.g., radio or TV) were compared to "intense" BCC (iBBC) implemented through a set of interpersonal communication strategies such as VMWs, VHVs, mobile broadcasting units and listener viewer clubs. Results: In both groups, the knowledge of the mode of malaria transmission was high (96.9 vs 97.2 %; p = 0.83), as well as of fever as a symptom (91.5 vs 93.5 %; p = 0.38). Knowledge of local risk factors, such as staying in the forest (39.7 vs 30.7 %; p = 0.17) or the farm (7.1 vs 5.1 %; p = 0.40) was low in both groups. Few respondents in either group knew that they must get tested if they suspected malaria (0.3 vs 0.1; p = 0.69). However, iBBC increased the discussions about malaria in the family (51.7 vs 35.8 %; p = 0.002) and reported prompt access to treatment in case of fever (77.1 vs 59.4 %; p < 0.01). Conclusion: The use of iBCC supported positive improvements in both attitudes and behaviours among the population with regard to malaria compared to mass media (niBCC) only. The significantly increase in people seeking treatment for fever in iBCC villages supports Objective Five of the Strategic Plan in the Cambodia Malaria Elimination Action Framework (2016-2020). Therefore, this study provides evidence for the planning and implementation of future BCC interventions to achieve the elimination of artemisinin resistant Plasmodium falciparum malaria

COVID-19 knowledge, beliefs, prevention behaviours and misinformation in the context of an adapted seasonal malaria chemoprevention campaign in six northern Nigerian States.

BACKGROUND: Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine and amodiaquine is an efficacious intervention for protection of children against Plasmodium falciparum malaria during the rainy season. In response to the global COVID-19 pandemic, Malaria Consortium adapted its SMC delivery model to ensure safety of distributors, data collectors and beneficiaries. We conducted a SMC monitoring survey in July 2020 in the states of Bauchi, Jigawa, Kano, Katsina, Sokoto and Yobe, with questions on COVID-19 prevention behaviours and symptoms, and belief in misinformation. We investigated the associations between receipt of information on COVID-19 by different sources, including from SMC distributors, and these three outcomes using logistic generalised estimating equations. We also considered moderation of effectiveness of message delivery by SMC distributors and adherence to use of face coverings. RESULTS: We obtained a representative sample of 40,157 caregivers of eligible children aged 3-59 months, of which 36,914 (91.92%) reported knowledge of COVID-19. The weighted proportions of respondents who correctly identified COVID-19 prevention behaviours and symptoms, and who reported belief in COVID-19 misinformation, were 80.52% (95% confidence interval [95% CI] 80.02-81.00), 81.72% (95% CI 81.23-82.20) and 22.90% (95% CI 22.24-23.57). Receipt of information on COVID-19 from SMC distributors during the campaign was significantly associated with higher odds of caregiver knowledge of COVID-19 prevention behaviours (odds ratio [OR] 1.78, 95% CI 1.64-1.94, p < 0.001) and symptoms (OR 1.74, 95% CI 1.59-1.90, p < 0.001) and lower odds of belief in COVID-19 misinformation (OR 0.92, 95% CI 0.85-1.00, p = 0.038). The associations between message delivery by SMC distributors and the three outcomes were moderated by their adherence to face covering use. Receipt of information by other sources used to deliver government public health messages, including radio and health facility workers, was also associated with knowledge of COVID-19. CONCLUSIONS: Malaria Consortium's SMC programme was successfully adapted in the context of COVID-19 and was a conduit for high-quality public health messages. Standard SMC monitoring and evaluation activities can be adapted to gather evidence on emerging public health issues such as the global COVID-19 pandemic

The age patterns of severe malaria syndromes in sub-Saharan Africa across a range of transmission intensities and seasonality settings

BACKGROUND: A greater understanding of the relationship between transmission intensity, seasonality and the age-pattern of malaria is needed to guide appropriate targeting of malaria interventions in different epidemiological settings. METHODS: A systematic literature review identified studies which reported the age of paediatric hospital admissions with cerebral malaria (CM), severe malarial anaemia (SMA), or respiratory distress (RD). Study sites were categorized into a 3 × 2 matrix of Plasmodium falciparum transmission intensity and seasonality. Probability distributions were fitted by maximum likelihood methods, and best fitting models were used to estimate median ages and to represent graphically the age-pattern of each outcome for each transmission category in the matrix. RESULTS: A shift in the burden of CM towards younger age groups was seen with increasing intensity of transmission, but this was not the case for SMA or RD. Sites with 'no marked seasonality' showed more evidence of skewed age-patterns compared to areas of 'marked seasonality' for all three severe malaria syndromes. CONCLUSIONS: Although the peak age of CM will increase as transmission intensity decreases in Africa, more than 75% of all paediatric hospital admissions of severe malaria are likely to remain in under five year olds in most epidemiological settings

Reactive case-detection of malaria in Pailin Province, Western Cambodia: lessons from a year-long evaluation in a pre-elimination setting.

BACKGROUND: As momentum towards malaria elimination grows, strategies are being developed for scale-up in elimination settings. One prominent strategy, reactive case detection (RACD), involves screening and treating individuals living in close proximity to passively detected, or "index" cases. This study aims to use RACD to quantify Plasmodium parasitaemia in households of index cases, and identify risk factors for infection; these data could inform reactive screening approaches and identify target risk groups. METHODS: This study was conducted in the Western Cambodian province of Pailin between May 2013 and March 2014 among 440 households. Index participants/index cases (n = 270) and surrounding households (n = 110) were screened for Plasmodium infection with rapid diagnostic tests (RDT), microscopy and real-time polymerase chain reaction (PCR). Participants were interviewed to identify risk factors. A comparison group of 60 randomly-selected households was also screened, to compare infection levels of RACD and non-RACD households. In order to identify potential risk factors that would inform screening approaches and identify risk groups, multivariate logistic regression models were applied. RESULTS: Nine infections were identified in households of index cases (RACD approach) through RDT screening of 1898 individuals (seven Plasmodium vivax, two Plasmodium falciparum); seven were afebrile. Seventeen infections were identified through PCR screening of 1596 individuals (15 P. vivax, and 22 % P. falciparum/P. vivax mixed infections). In the control group, 25 P. falciparum infections were identified through PCR screening of 237 individuals, and no P. vivax was found. Plasmodium falciparum infection was associated with fever (p = 0.013), being a member of a control household (p ≤ 0.001), having a history of malaria infection (p = 0.041), and sleeping without a mosquito net (p = 0.011). Significant predictors of P. vivax infection, as diagnosed by PCR, were fever (p = 0.058, borderline significant) and history of malaria infection (p ≤ 0.001). CONCLUSION: This study found that RACD identified very few secondary infections when targeting index and neighbouring households for screening. The results suggest RACD is not appropriate, where exposure to malaria occurs away from the community, and there is a high level of treatment-seeking from the private sector. Piloting RACD in a range of transmission settings would help to identify the ideal environment for feasible and effective reactive screening methods

Modelling the Contributions of Malaria, HIV, Malnutrition and Rainfall to the Decline in Paediatric Invasive Non-typhoidal Salmonella Disease in Malawi.

INTRODUCTION: Nontyphoidal Salmonellae (NTS) are responsible for a huge burden of bloodstream infection in Sub-Saharan African children. Recent reports of a decline in invasive NTS (iNTS) disease from Kenya and The Gambia have emphasised an association with malaria control. Following a similar decline in iNTS disease in Malawi, we have used 9 years of continuous longitudinal data to model the interrelationships between iNTS disease, malaria, HIV and malnutrition. METHODS: Trends in monthly numbers of childhood iNTS disease presenting at Queen's Hospital, Blantyre, Malawi from 2002 to 2010 were reviewed in the context of longitudinal monthly data describing malaria slide-positivity among paediatric febrile admissions, paediatric HIV prevalence, nutritional rehabilitation unit admissions and monthly rainfall over the same 9 years, using structural equation models (SEM). RESULTS: Analysis of 3,105 iNTS episodes identified from 49,093 blood cultures, showed an 11.8% annual decline in iNTS (p < 0.001). SEM analysis produced a stable model with good fit, revealing direct and statistically significant seasonal effects of malaria and malnutrition on the prevalence of iNTS disease. When these data were smoothed to eliminate seasonal cyclic changes, these associations remained strong and there were additional significant effects of HIV prevalence. CONCLUSIONS: These data suggest that the overall decline in iNTS disease observed in Malawi is attributable to multiple public health interventions leading to reductions in malaria, HIV and acute malnutrition. Understanding the impacts of public health programmes on iNTS disease is essential to plan and evaluate interventions