'Forest malaria' in Myanmar? Tracking transmission landscapes in a diversity of environments.

BACKGROUND: In the Greater Mekong Subregion, case-control studies and national-level analyses have shown an association between malaria transmission and forest activities. The term 'forest malaria' hides the diversity of ecosystems in the GMS, which likely do not share a uniform malaria risk. To reach malaria elimination goals, it is crucial to document accurately (both spatially and temporally) the influence of environmental factors on malaria to improve resource allocation and policy planning within given areas. The aim of this ecological study is to characterize the association between malaria dynamics and detailed ecological environments determined at village level over a period of several years in Kayin State, Myanmar. METHODS: We characterized malaria incidence profiles at village scale based on intra- and inter-annual variations in amplitude, seasonality, and trend over 4 years (2016-2020). Environment was described independently of village localization by overlaying a 2-km hexagonal grid over the region. Specifically, hierarchical classification on principal components, using remote sensing data of high spatial resolution, was used to assign a landscape and a climate type to each grid cell. We used conditional inference trees and random forests to study the association between the malaria incidence profile of each village, climate and landscape. Finally, we constructed eco-epidemiological zones to stratify and map malaria risk in the region by summarizing incidence and environment association information. RESULTS: We identified a high diversity of landscapes (n = 19) corresponding to a gradient from pristine to highly anthropogenically modified landscapes. Within this diversity of landscapes, only three were associated with malaria-affected profiles. These landscapes were composed of a mosaic of dense and sparse forest fragmented by small agricultural patches. A single climate with moderate rainfall and a temperature range suitable for mosquito presence was also associated with malaria-affected profiles. Based on these environmental associations, we identified three eco-epidemiological zones marked by later persistence of Plasmodium falciparum, high Plasmodium vivax incidence after 2018, or a seasonality pattern in the rainy season. CONCLUSIONS: The term forest malaria covers a multitude of contexts of malaria persistence, dynamics and populations at risk. Intervention planning and surveillance could benefit from consideration of the diversity of landscapes to focus on those specifically associated with malaria transmission.

Malaria temporal dynamic clustering for surveillance and intervention planning.

BACKGROUND: Targeting interventions where most needed and effective is crucial for public health. Malaria control and elimination strategies increasingly rely on stratification to guide surveillance, to allocate vector control campaigns, and to prioritize access to community-based early diagnosis and treatment (EDT). We developed an original approach of dynamic clustering to improve local discrimination between heterogeneous malaria transmission settings. METHODS: We analysed weekly malaria incidence records obtained from community-based EDT (malaria posts) in Karen/Kayin state, Myanmar. We smoothed longitudinal incidence series over multiple seasons using functional transformation. We regrouped village incidence series into clusters using a dynamic time warping clustering and compared them to the standard, 5-category annual incidence standard stratification. RESULTS: We included 1115 villages from 2016 to 2020. We identified eleven P. falciparum and P. vivax incidence clusters which differed by amplitude, trends and seasonality. Specifically the 124 villages classified as "high transmission area" in the standard P. falciparum stratification belonged to the 11 distinct groups when accounting to inter-annual trends and intra-annual variations. Likewise for P. vivax, 399 "high transmission" villages actually corresponded to the 11 distinct dynamics. CONCLUSION: Our temporal dynamic clustering methodology is easy to implement and extracts more information than standard malaria stratification. Our method exploits longitudinal surveillance data to distinguish local dynamics, such as increasing inter-annual trends or seasonal differences, providing key information for decision-making. It is relevant to malaria strategies in other settings and to other diseases, especially when many countries deploy health information systems and collect increasing amounts of health outcome data. FUNDING: The Bill & Melinda Gates Foundation, The Global Fund against AIDS, Tuberculosis and Malaria (the Regional Artemisinin Initiative) and the Wellcome Trust funded the METF program.

Outdoor residual spraying for malaria vector-control in Kayin (Karen) state, Myanmar: A cluster randomized controlled trial.

Outdoor and early biting by mosquitoes challenge the efficacy of bed nets and indoor residual spraying against malaria in the Greater Mekong Subregion. The objective of this study was to assess the efficacy of outdoor residual spraying (ORS) for malaria vector-control in this region. A cluster randomized controlled trial was conducted between July 2018 and April 2019 in twelve villages in Karen (Kayin) state, Myanmar. Villages were randomly assigned to receive either a single round of ORS with a capsule suspension of lambda-cyhalothrin for two days in October or no intervention (six villages per group). The primary endpoint was the biting rate of malaria mosquitoes assessed with human-landing catch and cow-baited trap collection methods, and was analyzed with a Bayesian multi-level model. In the intervention villages, the proportion of households located within the sprayed area ranged between 42 and 100% and the application rate ranged between 63 and 559 g of active ingredient per hectare. At baseline, the median of Anopheles biting rate estimates in the twelve villages was 2 bites per person per night (inter-quartile range [IQR] 0-5, range 0-48) indoors, 6 bites per person per night (IQR 2-16, range 0-342) outdoors and 206 bites per cow per night (IQR 83-380, range 19-1149) in the cow-baited trap. In intention-to-treat analysis, it was estimated that ORS reduced biting rate by 72% (95% confidence interval [CI] 63-79) from Month 0 to Month 3 and by 79% (95% CI 62-88) from Month 4 to Month 6, considering control villages as the reference. In conclusion, ORS rapidly reduces the biting rates of malaria mosquitoes in a Southeast Asian setting where the vectors bite mostly outdoors and at a time when people are not protected by mosquito bed nets.

Evaluating Effectiveness of Mass and Continuous Long-lasting Insecticidal Net Distributions Over Time in Madagascar: A Sentinel Surveillance Based Epidemiological Study.

BACKGROUND: The reduction of global malaria burden over the past 15 years is much attributed to the expansion of mass distribution campaigns (MDCs) of long-lasting insecticidal nets (LLIN). In Madagascar, two LUN MDCs were implemented and one district also benefited from a community-based continuous distribution (CB-CD). Malaria incidence dropped but eventually rebounded after a decade. METHODS: Data from a sentinel surveillance network over the 2009-2015 period was analyzed. Alerts were defined as w eekly number o f malaria cases exceeding the 90th percentile value for three consecutive weeks. Statistical analyses assessed the temporal relationship between LLIN MDCs and (i) number of malaria cases and (ii) malaria alerts detected, and (iii) the effect of a combination of MDCs and a CB-CD in Toamasina District. FINDINGS: Analyses showed an increase of 13.6 points and 21.4 points in the percentile value of weekly malaria cases during the second and the third year following the MDC of LLINs respectively. The percentage of alert-free sentinel sites was 98.2% during the first year after LLIN MDC, 56.7% during the second year and 31.5% during the third year. The number of weekly malaria cases decreased by 14% during the CB-CD in Toamasina District. In contrast, sites without continuous distribution had a 12% increase of malaria cases. INTERPRETATION: These findings support the malaria-preventive effectiveness of MDCs in Madagascar but highlight their limited duration when not followed by continuous distribution. The resulting policy implications are crucial to sustain reductions in malaria burden in high transmission settings.

Analysing trends and forecasting malaria epidemics in Madagascar using a sentinel surveillance network: a web-based application.

BACKGROUND: The use of a malaria early warning system (MEWS) to trigger prompt public health interventions is a key step in adding value to the epidemiological data routinely collected by sentinel surveillance systems. METHODS: This study describes a system using various epidemic thresholds and a forecasting component with the support of new technologies to improve the performance of a sentinel MEWS. Malaria-related data from 21 sentinel sites collected by Short Message Service are automatically analysed to detect malaria trends and malaria outbreak alerts with automated feedback reports. RESULTS: Roll Back Malaria partners can, through a user-friendly web-based tool, visualize potential outbreaks and generate a forecasting model. The system already demonstrated its ability to detect malaria outbreaks in Madagascar in 2014. CONCLUSION: This approach aims to maximize the usefulness of a sentinel surveillance system to predict and detect epidemics in limited-resource environments.

Nationwide evaluation of malaria infections, morbidity, mortality, and coverage of malaria control interventions in Madagascar.

BACKGROUND: In the last decade, an important scale-up was observed in malaria control interventions. Madagascar entered the process for pre-elimination in 2007. Policy making needs operational indicators, but also indicators about effectiveness and impact of malaria control interventions (MCI). This study is aimed at providing data about malaria infection, morbidity, and mortality, and MCI in Madagascar. METHODS: Two nationwide surveys were simultaneously conducted in 2012-2013 in Madagascar: a study about non-complicated clinical malaria cases in 31 sentinel health facilities, and a cross-sectional survey (CSS) in 62 sites. The CSS encompassed interviews, collection of biological samples and verbal autopsies (VA). Data from CSS were weighted for age, sex, malaria transmission pattern, and population density. VA data were processed with InterVA-4 software. RESULTS: CSS included 15,746 individuals of all ages. Parasite rate (PR) as measured by rapid diagnostic tests was 3.1%, and was significantly higher in five to 19 year olds, in males, poorer socio-economic status (SES) quintiles and rural areas. Long-lasting insecticidal nets (LLIN) use was 41.7% and was significantly lower in five to 19 year olds, males and wealthier SES quintiles. Proportion of persons covered by indoor residual spraying (IRS) was 66.8% in targeted zones. Proportion of persons using other insecticides than IRS was 22.8%. Coverage of intermittent preventive treatment during pregnancy was 21.5%. Exposure to information, education and communication messages about malaria was significantly higher in wealthier SES for all media but information meetings. The proportion of fever case managements considered as appropriate with regard to malaria was 15.8%. Malaria was attributed as the cause of death in 14.0% of 86 VA, and 50% of these deaths involved persons above the age of five years. The clinical case study included 818 cases of which people above the age of five accounted for 79.7%. In targeted zones, coverage of LLIN and IRS were lower in clinical cases than in general population. CONCLUSIONS: This study provides valuable data for the evaluation of effectiveness and factors affecting MCI. MCI and evaluation surveys should consider the whole population and not only focus on under-fives and pregnant women in pre-elimination or elimination strategies.

Analysing spatio-temporal clustering of meningococcal meningitis outbreaks in Niger reveals opportunities for improved disease control.

BACKGROUND: Meningococcal meningitis is a major health problem in the "African Meningitis Belt" where recurrent epidemics occur during the hot, dry season. In Niger, a central country belonging to the Meningitis Belt, reported meningitis cases varied between 1,000 and 13,000 from 2003 to 2009, with a case-fatality rate of 5-15%. METHODOLOGY/PRINCIPAL FINDINGS: In order to gain insight in the epidemiology of meningococcal meningitis in Niger and to improve control strategies, the emergence of the epidemics and their diffusion patterns at a fine spatial scale have been investigated. A statistical analysis of the spatio-temporal distribution of confirmed meningococcal meningitis cases was performed between 2002 and 2009, based on health centre catchment areas (HCCAs) as spatial units. Anselin's local Moran's I test for spatial autocorrelation and Kulldorff's spatial scan statistic were used to identify spatial and spatio-temporal clusters of cases. Spatial clusters were detected every year and most frequently occurred within nine southern districts. Clusters most often encompassed few HCCAs within a district, without expanding to the entire district. Besides, strong intra-district heterogeneity and inter-annual variability in the spatio-temporal epidemic patterns were observed. To further investigate the benefit of using a finer spatial scale for surveillance and disease control, we compared timeliness of epidemic detection at the HCCA level versus district level and showed that a decision based on threshold estimated at the HCCA level may lead to earlier detection of outbreaks. CONCLUSIONS/SIGNIFICANCE: Our findings provide an evidence-based approach to improve control of meningitis in sub-Saharan Africa. First, they can assist public health authorities in Niger to better adjust allocation of resources (antibiotics, rapid diagnostic tests and medical staff). Then, this spatio-temporal analysis showed that surveillance at a finer spatial scale (HCCA) would be more efficient for public health response: outbreaks would be detected earlier and reactive vaccination would be better targeted.

A refined estimate of the malaria burden in Niger.

BACKGROUND: The health authorities of Niger have implemented several malaria prevention and control programmes in recent years. These interventions broadly follow WHO guidelines and international recommendations and are based on interventions that have proved successful in other parts of Africa. Most performance indicators are satisfactory but, paradoxically, despite the mobilization of considerable human and financial resources, the malaria-fighting programme in Niger seems to have stalled, as it has not yet yielded the expected significant decrease in malaria burden. Indeed, the number of malaria cases reported by the National Health Information System has actually increased by a factor of five over the last decade, from about 600,000 in 2000 to about 3,000,000 in 2010. One of the weaknesses of the national reporting system is that the recording of malaria cases is still based on a presumptive diagnosis approach, which overestimates malaria incidence. METHODS: An extensive nationwide survey was carried out to determine by microscopy and RDT testing, the proportion of febrile patients consulting at health facilities for suspected malaria actually suffering from the disease, as a means of assessing the magnitude of this problem and obtaining a better estimate of malaria morbidity in Niger. RESULTS: In total, 12,576 febrile patients were included in this study; 57% of the slides analysed were positive for the malaria parasite during the rainy season, when transmission rates are high, and 9% of the slides analysed were positive during the dry season, when transmission rates are lower. The replacement of microscopy methods by rapid diagnostic tests resulted in an even lower rate of confirmation, with only 42% of cases testing positive during the rainy season, and 4% during the dry season. Fever alone has a low predictive value, with a low specificity and sensitivity. These data highlight the absolute necessity of confirming all reported malaria cases by biological diagnosis methods, to increase the accuracy of the malaria indicators used in monitoring and evaluation processes and to improve patient care in the more remote areas of Niger. This country extends over a large range of latitudes, resulting in the existence of three major bioclimatic zones determining vector distribution and endemicity. CONCLUSION: This survey showed that the number of cases of presumed malaria reported in health centres in Niger is largely overestimated. The results highlight inadequacies in the description of the malaria situation and disease risk in Niger, due to the over-diagnosis of malaria in patients with simple febrile illness. They point out the necessity of confirming all cases of suspected malaria by biological diagnosis methods and the need to take geographic constraints into account more effectively, to improve malaria control and to adapt the choice of diagnostic method to the epidemiological situation in the area concerned. Case confirmation will thus also require a change in behaviour, through the training of healthcare staff, the introduction of quality control, greater supervision of the integrated health centres, the implementation of good clinical practice and a general optimization of the use of available diagnostic methods.