Progress towards malaria elimination in the Greater Mekong Subregion: perspectives from the World Health Organization.

Malaria remains a global health challenge, disproportionately affecting vulnerable communities. Despite substantial progress, the emergence of anti-malarial drug resistance poses a constant threat. The Greater Mekong Subregion (GMS), which includes Cambodia, China's Yunnan province, Lao People's Democratic Republic, Myanmar, Thailand, and Viet Nam has been the epicentre for the emergence of resistance to successive generations of anti-malarial therapies. From the perspective of the World Health Organization (WHO), this article considers the collaborative efforts in the GMS, to contain Plasmodium falciparum artemisinin partial resistance and multi-drug resistance and to advance malaria elimination. The emergence of artemisinin partial resistance in the GMS necessitated urgent action and regional collaboration resulting in the Strategy for Malaria Elimination in the Greater Mekong Subregion (2015-2030), advocating for accelerated malaria elimination interventions tailored to country needs, co-ordinated and supported by the WHO Mekong malaria elimination programme. The strategy has delivered substantial reductions in malaria across all GMS countries, with a 77% reduction in malaria cases and a 97% reduction in malaria deaths across the GMS between 2012 and 2022. Notably, China was certified malaria-free by WHO in 2021. Countries' ownership and accountability have been pivotal, with each GMS country outlining its priorities in strategic and annual work plans. The development of strong networks for anti-malarial drug resistance surveillance and epidemiological surveillance was essential. Harmonization of policies and guidelines enhanced collaboration, ensuring that activities were driven by evidence. Challenges persist, particularly in Myanmar, where security concerns have limited recent progress, though an intensification and acceleration plan aims to regain momentum. Barriers to implementation can slow progress and continuing innovation is needed. Accessing mobile and migrant populations is key to addressing remaining transmission foci, requiring effective cross-border collaboration. In conclusion, the GMS has made significant progress towards malaria elimination, particularly in the east where several countries are close to P. falciparum elimination. New and persisting challenges require sustained efforts and continued close collaboration. The GMS countries have repeatedly risen to every obstacle presented, and now is the time to re-double efforts and achieve the 2030 goal of malaria elimination for the region.

Epidemiology of dengue reported in the World Health Organization's Western Pacific Region, 2013-2019.

The global burden of dengue, an emerging and re-emerging mosquito-borne disease, increased during the 20-year period ending in 2019, with approximately 70% of cases estimated to have been in Asia. This report describes the epidemiology of dengue in the World Health Organization's Western Pacific Region during 2013-2019 using regional surveillance data reported from indicator-based surveillance systems from countries and areas in the Region, supplemented by publicly available dengue outbreak situation reports. The total reported annual number of dengue cases in the Region increased from 430 023 in 2013 to 1 050 285 in 2019, surpassing 1 million cases for the first time in 2019. The reported case-fatality ratio ranged from 0.19% (724/376 972 in 2014 and 2030/1 050 285 in 2019) to 0.30% (1380/458 843 in 2016). The introduction or reintroduction of serotypes to specific areas caused several outbreaks and rare occurrences of local transmission in places where dengue was not previously reported. This report reinforces the increased importance of dengue surveillance systems in monitoring dengue across the Region.

Accelerating malaria elimination in Cambodia: an intensified approach for targeting at-risk populations.

BACKGROUND: Malaria in Cambodia has decreased by 90.8% between 2010 and 2020, driven by the commitment of the National Center for Parasitology, Entomology and Malaria (CNM) and the achievements of the roll-out of a village malaria worker programme. However, in the first seven months of 2018, CNM identified a 207% increase (11,969 to 36,778) in confirmed malaria cases compared to the same months in the previous year. To address this increase, CNM developed the "Intensification Plan" (IP), implemented between October 2018 and December 2020. METHODS: The structure of the IP was summarized, including the selection of sites, the interventions implemented in the selected health facility catchment areas (HFCAs) and the monitoring and evaluation process. Data on IP interventions were collected by CNM and civil society organisations. Data on malaria cases and tests from all HFCAs in Cambodia from January 2018 to December 2020 were sourced from the Cambodia Malaria Information System (MIS) and WHO Malaria Elimination Database. Malaria data from IP HFCAs and non-IP HFCAs was analysed and compared to present the changes in malaria testing and confirmed cases before and during implementation of the IP. RESULTS: Between October 2018 and December 2020, through the IP 16,902 forest packs and 293,090 long-lasting insecticide treated nets were distributed. In the 45 HFCAs included in the IP, 431,143 malaria tests were performed and 29,819 malaria cases were diagnosed, 5364 (18%) of which were Plasmodium falciparum/mixed cases. During the intervention period, over all HFCAs included in IP, P. falciparum/mixed cases declined from 1029 to 39, a 96.2% decrease, and from 25.4 P. falciparum/mixed cases per HFCA to 0.9. HFCAs not included in IP declined from 468 to 43 cases, a 90.8% decrease, showing that routine malaria activities in Cambodia were also playing an important contribution to malaria control. CONCLUSIONS: Over the course of IP implementation there was a substantial increase in malaria testing and both overall malaria cases and P. falciparum/mixed cases decreased month on month. The initiative yields lessons learned for Cambodia to reach the final stage of elimination as well as for other countries aiming to accelerate their malaria control programmes.

Tools to accelerate falciparum malaria elimination in Cambodia: a meeting report.

Cambodia targets malaria elimination by 2025. Rapid elimination will depend on successfully identifying and clearing malaria foci linked to forests. Expanding and maintaining universal access to early diagnosis and effective treatment remains the key to malaria control and ultimately malaria elimination in the Greater Mekong Subregion (GMS) in the foreseeable future. Mass Drug Administration (MDA) holds some promise in the rapid reduction of Plasmodium falciparum infections, but requires considerable investment of resources and time to mobilize the target communities. Furthermore, the most practical drug regimen for MDA in the GMS-three rounds of DHA/piperaquine-has lost some of its efficacy. Mass screening and treatment benefits asymptomatic P. falciparum carriers by clearing chronic infections, but in its current form holds little promise for malaria elimination. Hopes that "highly sensitive" diagnostic tests would provide substantial advances in screen and treat programmes have been shown to be misplaced. To reduce the burden on P. falciparum and Plasmodium vivax infections in people working in forested areas novel approaches to the use of malaria prophylaxis in forest workers should be explored. During an October 2019 workshop in Phnom Penh researchers and policymakers reviewed evidence of acceptability, feasibility and effectiveness of interventions to target malaria foci and interrupt P. falciparum transmission and discussed operational requirements and conditions for programmatic implementation.

A Report from the Cambodia Training Event for Awareness of Melioidosis (C-TEAM), October 2017.

Melioidosis is an endemic infection in Cambodia, a lower middle income SE Asian country. Despite more laboratories isolating and identifying Burkholderia pseudomallei in recent years, the infection remains under-recognised and under-diagnosed, particularly in the adult population. Lack of knowledge about the disease and lack of utilization of microbiology laboratories contributes to this, along with laboratory capacity issues. Treatment costs often hamper optimal management. In response to these issues, a national one-health training event was held in October 2017 to raise awareness of the disease amongst clinical, laboratory, and public health professionals. The meeting format, findings, and outcomes are described here.

Free mass distribution of long lasting insecticidal nets lead to high levels of LLIN access and use in Madagascar, 2010: A cross-sectional observational study.

BACKGROUND: Madagascar conducted the first two phases of a national free mass distribution campaign of long-lasting insecticidal nets (LLINs) during a political crisis in 2009 aiming to achieve coverage of two LLINs per household as part of the National Malaria Control Strategy. The campaign targeted households in 19 out of 91 total health districts. METHODS: A community-based cross-sectional household survey using a three-stage cluster sample design was conducted four months post campaign to assess LLIN ownership, access and use. Multivariable logistic regression analysis was used to identify factors associated with household LLIN access and individual LLIN use. RESULTS: A total of 2211 households were surveyed representing 8867 people. At least one LLIN was present in 93.5% (95% confidence interval [CI], 91.6-95.5%) of households and 74.8% (95% CI, 71.0-78.6%) owned at least two LLINs. Access measured as the proportion of the population that could potentially be covered by household-owned LLINs was 77.2% (77.2% (95% CI, 72.9-81.3%) and LLIN use by all individuals was 84.2% (95% CI, 81.2-87.2%). LLIN use was associated with knowledge of insecticide treated net use to prevent malaria (OR = 3.58, 95% CI, 1.85-6.94), household ownership of more LLINs (OR 2.82, 95% CI 1.85-4.3), presence of children under five (OR = 2.05, 95% CI, 1.67-2.51), having traveled to the distribution point and receiving information about hanging a bednet (OR = 1.56, 95% CI, 1.41-1.74), and having received a post-campaign visit by a community mobilizer (OR = 1.75, 95% CI, 1.26-2.43). Lower LLIN use was associated with increasing household size (OR = 0.81 95% CI 0.77-0.85) and number of sleeping spaces (OR = 0.55, 95% CI, 0.44-0.68). CONCLUSIONS: A large scale free mass LLIN distribution campaign was feasible and effective at achieving high LLIN access and use in Madagascar. Campaign process indicators highlighted potential areas for strengthening implementation to optimize access and equity.

World Malaria Day 2016 in the Kingdom of Cambodia: high-level governmental support embodies the WHO call for "political will to end malaria".

On World Malaria Day 2016, The Kingdom of Cambodia's National celebrations served as a prime of example of how political will is currently being exercised in Cambodia through high-level governmental support for malaria elimination. The main country event was well-planned and coordinated by the National Programme for Parasitology, Entomology and Malaria Control (CNM), and included key contributions from high-ranking political figures, such as His Excellency (H.E) Mam Bun Heng (Minister of Health), and H.E. Keut Sothea (Governor of Pailin Province). There were more than 1000 attendees, ranging from Village Malaria Workers and high school students to CNM's director and other officials in Pailin Province, Western Cambodia. A strong inter-sectoral participation included attendances from the Ministry of Education and high-level representatives of the Cambodian Armed Forces, as well as Malaria Partners like the World Health Organization.

History and current status of Plasmodium falciparum antimalarial drug resistance in Madagascar.

Malaria remains a major health problem in Madagascar. Over past decades, the burden of malarial disease has fluctuated over time, partly in line with the successes and failures of antimalarial policy. In the 1950s and 1960s, a sharp decline in malaria transmission was observed in the central highlands due to indoor spraying with DDT and to the massive use of chloroquine by the population. Following this, the discontinuation of the 'nivaquinization' policy was followed by devastating outbreaks in the central highlands in the 1980s. Currently, the rate of in vitro chloroquine-resistant Plasmodium falciparum isolates does not exceed 5%. This figure appears disconnected from the high level of clinical treatment failure (near 40%). pfcrt mutant isolates are found in less than 1% of isolates on the Island. Conversely, pfmdr1 mutant isolates are found in more than 60% of isolates and may be responsible for the bulk of resistance to chloroquine in Madagascar. Other antimalarials remain generally effective in Madagascar. Recent clinical and in vitro data support the complete efficacy of the combination artesunate-amodiaquine in Madagascar. As such, this artemisinin combination therapy should play a central role in the control and possible elimination of P. falciparum malaria in Madagascar

Assessment of the efficacy of antimalarial drugs recommended by the National Malaria Control Programme in Madagascar: up-dated baseline data from randomized and multi-site clinical trials.

BACKGROUND: In order to improve the monitoring of the antimalarial drug resistance in Madagascar, a new national network based on eight sentinel sites was set up. In 2006/2007, a multi-site randomized clinical trial was designed to assess the therapeutic efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP), amodiaquine (AQ) and artesunate plus amodiaquine combination (ASAQ), the antimalarial therapies recommended by the National Malaria Control Programme (NMCP). METHODS: Children between six months and 15 years of age, with uncomplicated falciparum malaria, were enrolled. Primary endpoints were the day-14 and day-28 risks of parasitological failure, either unadjusted or adjusted by genotyping. Risks of clinical and parasitological treatment failure after adjustment by genotyping were estimated using Kaplan-Meier survival analysis. Secondary outcomes included fever clearance, parasite clearance, change in haemoglobin levels between Day 0 and the last day of follow-up, and the incidence of adverse events. RESULTS: A total of 1,347 of 1,434 patients (93.9%) completed treatment and follow-up to day 28. All treatment regimens, except for the chloroquine (CQ) treatment group, resulted in clinical cure rates above 97.6% by day-14 and 96.7% by day-28 (adjusted by genotyping). Parasite and fever clearance was more rapid with artesunate plus amodiaquine, but the extent of haematological recovery on day-28 did not differ significantly between the four groups. No severe side-effects were observed during the follow-up period. CONCLUSION: These findings (i) constitute an up-dated baseline data on the efficacy of antimalarial drugs recommended by the NMCP, (ii) show that antimalarial drug resistance remains low in Madagascar, except for CQ, compared to the bordering countries in the Indian Ocean region such as the Comoros Archipelago and (iii) support the current policy of ASAQ as the first-line treatment in uncomplicated falciparum malaria.

Randomized clinical trial of artemisinin versus non-artemisinin combination therapy for uncomplicated falciparum malaria in Madagascar.

BACKGROUND: Data concerning antimalarial combination treatment for uncomplicated malaria in Madagascar are largely lacking. Randomized clinical trial was designed to assess therapeutic efficacies of chloroquine (CQ), amodiaquine (AQ), sulphadoxine-pyrimethamine (SP), amodiaquine plus sulphadoxine-pyrimethamine combination (AQ+SP) and artesunate plus amodiaquine combination (AQ+AS). METHODS: 287 children between 6 months and 15 years of age, with uncomplicated falciparum malaria, were enrolled in the study. Primary endpoints were the day-14 and day-28 risks of parasitological failure, either unadjusted or adjusted by genotyping. RESULTS: All treatment regimens, except for CQ treatment, gave clinical cure rates above 97% by day-14 and 92% by day-28 (PCR-corrected). AQ+SP was as effective as AQ+AS. The risk of new infection within the month after therapy was generally higher for AQ+AS than AQ+SP. CONCLUSION: These findings show that the inexpensive and widely available combination AQ+SP may be valuable in for the treatment of uncomplicated malaria in Madagascar and could have an important role in this country, where much of the drugs administered go to patients who do not have malaria.