Artemisinin Resistance Containment Research Articles

Multisectoral Approach to Support Use of Insecticide-Treated Net for Malaria Prevention Among Mobile and Migrant Populations in Myanmar: A Systematic Review.

BackgroundMyanmar is a premalaria elimination country with artemisinin-resistant malaria. A strategy for transmission control is focused on vulnerable groups such as mobile and migrant populations (MMPs), and includes improving access to insecticide-treated bed nets in the Myanmar artemisinin resistance containment (MARC) zones using multisectoral approaches (MSA).MethodsThis narrative systematic review addressed MSAs targeted to MMPs in Myanmar for malaria prevention. We searched relevant studies in electronic databases and present the narrative findings in 4 domains: stakeholder groups, net coverage and utilization, social determinates, and facilitators/barriers.ResultsNine studies were included. The review identified stakeholders involved in intersectoral collaboration. Net ownership was higher than utilization rates in the MARC zones and rates remained below the WHO recommended target of 100%. There was inadequate description of roles and responsibilities for implementation and on channels of communication within the partnerships and with the Government.ConclusionsFindings show that interventions to distribute treated bed nets were supported by the multiple stakeholders. Due to the design of the primary studies, analysis of the added value of intersectoral collaboration was limited. More attention must be paid to designing studies to document and evaluate the contributions and outcomes of intersectoral collaboration.

Phenotypic and genotypic characterization of Thai isolates of Plasmodium falciparum after an artemisinin resistance containment project

BackgroundIn Thailand, artemisinin-based combination therapy (ACT) has been used to treat uncomplicated falciparum malaria since 1995. Unfortunately, artemisinin resistance has been reported from Thailand and other Southeast Asian countries since 2003. Malarone®, a combination of atovaquone–proguanil (ATQ–PG), has been used to cease artemisinin pressure in some areas along Thai–Cambodia border, as part of an artemisinin resistance containment project since 2009. This study aimed to determine genotypes and phenotypes of Plasmodium falciparum isolates collected from the Thai–Cambodia border after the artemisinin resistance containment project compared with those collected before.ResultsOne hundred and nine of P. falciparum isolates collected from Thai–Cambodia border from Chanthaburi and Trat provinces during 1988–2016 were used in this study. Of these, 58 isolates were collected after the containment. These parasite isolates were characterized for in vitro antimalarial sensitivities including chloroquine (CQ), quinine (QN), mefloquine (MQ), piperaquine (PPQ), artesunate (AS), dihydroartemisinin (DHA), ATQ and PG and genetic markers for drug resistance including the Kelch13 (k13), Plasmodium falciparum chloroquine resistance transporter (pfcrt), P. falciparum multidrug resistance 1 (pfmdr1) and cytochrome b (cytb) genes. Mean CQ, QN, MQ, PPQ and AS IC50s of the parasite isolates collected from 2009 to 2016 exhibited significantly higher than those of parasites collected before 2009. Approximately 57% exhibited in vitro MQ resistance. Approximately 94% of the isolates collected from 2009 to 2016 contained the pfmdr1 184F allele. Mutations of the k13 gene were detected in approximately 90% of the parasites collected from 2009 to 2016 which were significantly higher than the parasite isolates collected before. No ATQ-resistant genotype and phenotype of P. falciparum were found among the isolates collected after the containment project.ConclusionsAlthough the containment project had been implemented in this area, the expansion of artemisinin-resistant parasites did not decline. In addition, reduced sensitivity of the partner drugs of ACT including MQ and PPQ were identified.

Assessment of household ownership of bed nets in areas with and without artemisinin resistance containment measures in Myanmar

BackgroundMyanmar lies in the Greater Mekong Subregion where there is artemisinin-resistant Plasmodium falciparum malaria. As the artemisinin compound is the pillar of effective antimalarial therapies, containing the spread of artemisinin resistance is a national and global priority. The use of insecticide-treated bed nets/long-lasting insecticidal nets (ITNs/LLINs) is the key intervention for ensuring the reduction of malaria transmission and the spread of resistant strains, and for eventually eliminating malaria. This study aimed at assessing household ownership of, access to, and utilization of bed nets in areas of Myanmar with and without artemisinin resistance containment measures.MethodsSecondary data from a nationwide community-based malaria survey conducted by the National Malaria Control Program in 2014 were analyzed. Based on evidence of artemisinin resistance, Myanmar was divided into tiers 1, 2, and 3: townships in tiers 1 and 2 were aggregated as the Myanmar Artemisinin Resistance Containment (MARC) areas and were compared with tier 3 townships, which were defined as non-MARC areas. The chi-square test was used to compare groups, and the level of significance was set at P ≤ 0.05.ResultsOf the 6328 households assessed, 97.2% in both MARC and non-MARC areas had at least one bed net (any type), but only 63% of households had ITNs/LLINs. Only 44% of households in MARC areas and 24% in non-MARC areas had adequate numbers of ITNs/LLINs (one ITN/LLIN per two persons, P < 0.001). Nearly 44% of household members had access to ITNs/LLINs. Regarding the utilization of ITNs/LLINs, 45% of household members used them in MARC areas and 36% used them in non-MARC areas (P < 0.001, desired target = 100%). Utilization of ITNs/LLINs among children aged below five years and pregnant women (high malaria risk groups) was low, at 44% and 42%, respectively.ConclusionsThis study highlights the nationwide shortfalls in the ownership of, access to, and utilization of ITNs/LLINs in Myanmar, which is of particular concern in terms of containing the spread of artemisinin resistance. It highlights the need for priority attention to be paid and mobilization of resources in order to improve bed net coverage and utilization through bed net distribution and/or social marketing, information dissemination, and awareness-raising.

Knowledge, access and utilization of bed-nets among stable and seasonal migrants in an artemisinin resistance containment area of Myanmar

BackgroundMyanmar lies in the Greater Mekong sub-region of South-East Asia faced with the challenge of emerging resistance to artemisinin combination therapies (ACT). Migrant populations are more likely than others to spread ACT resistance. A vital intervention to reduce malaria transmission, resistance spread and eliminate malaria is the use of bed nets. Among seasonal and stable migrants in an artemisinin resistance containment region of Myanmar, we compared a) their household characteristics, b) contact with health workers and information material, and c) household knowledge, access and utilization of bed nets.MethodsSecondary data from community-based surveys on 2484 migrant workers (2013 and 2014, Bago Region) were analyzed of which 37% were seasonal migrants. Bed net access and utilization were assessed using a) availability of at least one bed net per household, and b) one bed net per two persons, and c) proportion of household members who slept under abed net during the previous night (Indicator targets = 100%).ResultsOver 70% of all migrants were from unstable work settings with short transitory stays. Average household size was five (range 1–25) and almost half of all households had children under-five years. Roughly 10 % of migrants were night-time workers.Less than 40% of households had contact with health workers and less than 30% had exposure to information education and communication (IEC) materials, the latter being significantly lower among seasonal migrants. About 70% of households were aware of the importance of insecticide-treated bed-nets/long-lasting insecticidal nets (ITNs/LLINs), but knowledge on insecticide impregnation and retreatment of ITNs was poor (< 10%).Although over 95% of households had access to at least one bed net, the number with one bed net per two persons was grossly inadequate (13% for stable migrants and 9% for seasonal migrants, P = 0.001). About half of all household members slept under a bed net during the previous night.ConclusionsThis study reveals important short-falls in knowledge, access and utilization of bed nets among migrants in Myanmar. Possible ways forward include frequent distribution campaigns to compensate for short transitory stays, matching household distributions to household size, enhanced information campaigns and introducing legislation to make mosquito repellents available for night-time workers at plantations and farms. Better understanding through qualitative research is also merited.

Ivermectin susceptibility and sporontocidal effect in Greater Mekong Subregion Anopheles

BackgroundNovel vector control methods that can directly target outdoor malaria transmission are urgently needed in the Greater Mekong Subregion (GMS) to accelerate malaria elimination and artemisinin resistance containment efforts. Ivermectin mass drug administration (MDA) to humans has been shown to effectively kill wild Anopheles and suppress malaria transmission in West Africa. Preliminary laboratory investigations were performed to determine ivermectin susceptibility and sporontocidal effect in GMS Anopheles malaria vectors coupled with pharmacokinetic models of ivermectin at escalating doses.MethodsA population-based pharmacokinetic model of ivermectin was developed using pre-existing data from a clinical trial conducted in Thai volunteers at the 200 µg/kg dose. To assess ivermectin susceptibility, various concentrations of ivermectin compound were mixed in human blood meals and blood-fed to Anopheles dirus, Anopheles minimus, Anopheles sawadwongporni, and Anopheles campestris. Mosquito survival was monitored daily for 7 days and a non-linear mixed effects model with probit analyses was used to calculate concentrations of ivermectin that killed 50% (LC50) of mosquitoes for each species. Blood samples were collected from Plasmodium vivax positive patients and offered to mosquitoes with or without ivermectin at the ivermectin LC25 or LC5 for An. dirus and An. minimus.ResultsThe GMS Anopheles displayed a range of susceptibility to ivermectin with species listed from most to least susceptible being An. minimus (LC50 = 16.3 ng/ml) > An. campestris (LC50 = 26.4 ng/ml) = An. sawadwongporni (LC50 = 26.9 ng/ml) > An. dirus (LC50 = 55.6 ng/ml). Mosquito survivorship results, the pharmacokinetic model, and extensive safety data indicated that ivermectin 400 µg/kg is the ideal minimal dose for MDA in the GMS for malaria parasite transmission control. Ivermectin compound was sporontocidal to P. vivax in both An. dirus and An. minimus at the LC25 and LC5 concentrations.ConclusionsIvermectin is lethal to dominant GMS Anopheles malaria vectors and inhibits sporogony of P. vivax at safe human relevant concentrations. The data suggest that ivermectin MDA has potential in the GMS as a vector and transmission blocking control tool to aid malaria elimination efforts.

Malaria profiles and challenges in artemisinin resistance containment in Myanmar

BackgroundThis study examined evolving malaria profiles from January, 2010 to December, 2014 to evaluate achievements and challenges of implementing measures to prevent and control spread of artemisinin resistance in Myanmar.MethodsUsing National Malaria Control Programme (NMCP) data, a cross-sectional descriptive study of 52 townships in artemisinin-resistant containment areas in Myanmar was conducted. Annual program data were analysed, and trends over time are graphically presented.ResultsIn the 52 study townships populated by 8.7 million inhabitants, malaria incidence showed a decreasing trend from 10.54 per 1 000 population in 2010 to 2.53 in 2014, and malaria mortalities also decreased from 1.83 per 100 000 population in 2010 to 0.17 in 2014. The proportion of confirmed to total tested malaria cases also decreased from 6 to 1%, while identification of cases improved. All cases from all parasites species, including Plasmodium falciparum, decreased. Coverage of LLIN (long-lasting insecticidal net)/ITN (insecticide-treated mosquito nets) and indoor residual spraying (IRS) was high in targeted areas with at-risk persons, even though the total population was not covered. In addition to passive case detection (PCD), active case detection (ACD) was conducted in hard-to-reach areas and worksites where mobile migrant populations were present. ACD improved in most areas from 2012 to 2014, but continues to need to be strengthened.ConclusionsThe findings provide useful data on the malaria situation in artemisinin-resistant initiative areas, which may be useful for the NMCP to meet its elimination goal. These profiles could contribute to better planning, implementation, and evaluation of intervention activities.

Molecular Evidence of Drug Resistance in Asymptomatic Malaria Infections, Myanmar, 2015.

Artemisinin resistance containment in Myanmar was initiated in 2011 after artemisinin-resistant Plasmodium falciparum malaria was reported. Molecular evidence suggests that asymptomatic malaria infections harboring drug resistance genes are present among residents of the Myanmar artemisinin resistance containment zone. This evidence supports efforts to eliminate these hidden infections.

FOSMIDOMYCIN-PIPERAQUINE AS NON-ARTEMISININ-BASED COMBINATION FOR ACUTE UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA

BackgroundAs investment in research related to artemisinin resistance is a key objective of the Global Plan for Artemisinin Resistance Containment (GPARC), fosmidomycin and piperaquine are being developed to address the...

Using supply side evidence to inform oral artemisinin monotherapy replacement in Myanmar: a case study.

BackgroundIn 2012, alarmingly high rates of oral artemisinin monotherapy availability and use were detected along Eastern Myanmar, threatening efforts to halt the spread of artemisinin resistance in the Greater Mekong Subregion (GMS), and globally. The aim of this paper is to exemplify how the use of supply side evidence generated through the ACTwatch project shaped the artemisinin monotherapy replacement malaria (AMTR) project’s design and interventions to rapidly displace oral artemisinin monotherapy with subsidized, quality-assured ACT in the private sector.MethodsThe AMTR project was implemented as part of the Myanmar artemisinin resistance containment (MARC) framework along Eastern Myanmar. Guided by outlet survey and supply chain evidence, the project implemented a high-level subsidy, including negotiations with a main anti-malarial distributor, with the aim of squeezing oral artemisinin monotherapy out of the market through price competition and increased availability of quality-assured artemisinin-based combinations. This was complemented with a plethora of demand-creation activities targeting anti-malarial providers and consumers. Priority outlet types responsible for the distribution of oral artemisinin monotherapy were identified by the outlet survey, and this evidence was used to target the AMTR project’s supporting interventions.ConclusionsThe widespread availability and use of oral artemisinin monotherapy in Myanmar has been a serious threat to malaria control and elimination in the country and across the region. Practical anti-malarial market evidence was rapidly generated and used to inform private sector approaches to address these threats. The program design approach outlined in this paper is illustrative of the type of evidence generation and use that will be required to ensure effective containment of artemisinin drug resistance and progress toward regional and global malaria elimination goals.

Challenges encountered by local health volunteers in early diagnosis and prompt treatment of malaria in Myanmar artemisinin resistance containment zones.

Background After artemisinin resistance was reported, the Myanmar artemisinin resistance containment (MARC) project was initiated in 2011. One of the activities of MARC is to train volunteers for early diagnosis and prompt treatment by providing rapid diagnostic tests (RDT) and artemisinin combination therapy. This study aimed to fulfil the gap of information on the challenges faced by malaria volunteers in artemisinin-containment areas.MethodsA cross-sectional, descriptive study was conducted in 11 townships in MARC areas to assess the challenges in early diagnosis of malaria and treatment by malaria volunteers using qualitative and quantitative approaches.ResultsAltogether 405 volunteers participated in the study. Although 97.5 % of volunteers can interpret a positive result for malaria, only 41.2 % correctly stated the persistence of a positive result in recently infected cases. Over 80 % knew the effects of temperature and humidity on performance of the malaria RDT. Unexpectedly, 15.1 % perceived that expired RDTs can still be useful for diagnosis although 98.3 % of respondents cited that the overall results of RDTs were reliable. Although most of them knew the treatment for malaria based on RDT results, some could not give the correct answer, while a few (2 %) mentioned artesunate monotherapy for RDT-negative cases. Training received by volunteers was also varied in study sites and 92.1 % believed that it was not sufficient. A certain portion of them faced the problem of regular supply of RDTs (9.9 %) and drugs (47.5 %), interpretation of result of RDTs (30 %), and performing blood test (20 %). The median RDT tested per month (25th, 75th percentile) was 6.0 (2.0, 15.0) indicating the need for prioritization based on endemicity. Regular reporting, supervision, monitoring system, and proper refresher training using uniform content of guideline to correct misconception of the volunteers, were needed to be strengthened. Moreover, the reliable and regular supply of materials and exchange system for expired RDTs and anti-malarials was important in the effectiveness of volunteers in MARC zones.ConclusionsAdequate refresher training, monitoring, supervision, and regular reliable supply of RDTs and anti-malarials were needed for capacity strengthening of volunteers in MARC zones.

Oral artemisinin monotherapy removal from the private sector in Eastern Myanmar between 2012 and 2014.

BackgroundIn 2012 the Artemisinin Monotherapy Therapy Replacement (AMTR) project was implemented in Eastern Myanmar to increase access to subsidized, quality-assured artemisinin combination therapy (ACT) and to remove oral artemisinin monotherapy (AMT) from the private sector. The aim of this paper is to examine changes over time in the private sector anti-malarial landscape and to illustrate the value of complementary interventions in the context of a national ACT subsidy.MethodsThree rounds of cross-sectional malaria medicine outlet surveys were conducted, in 2012, 2013 and 2014. Project intervention areas were selected from the Myanmar Artemisinin Resistance Containment (MARC) area. Provider detailing was implemented in these selected areas. Comparison areas were selected outside of this catchment area, from townships in close proximity to the MARC framework. Within each domain, multi-staged sampling was used to select areas for the survey. Outlets with the potential to sell or distribute anti-malarials in the private sector were screened for eligibility.ResultsThe total number of outlets approached for an interview was as follows in the intervention and comparison areas, respectively: 2012, N = 2046 and 1612; 2013, N = 1636 and 1884; 2014, N = 2939 and 2941. The percentage of pharmacies, general retailers and mobile providers (classed as ‘priority outlets’) with oral AMT in stock on the day of the survey decreased over time in the intervention areas (2012 = 68 %; 2013 = 48 %; 2014 = 10 %). Conversely, quality-assured ACT availability increased among these outlets (2012 = 4 %; 2013 = 62 %; 2014 = 79 %). Relative oral AMT market share among priority outlets also decreased over time (2012 = 44 %; 2013 = 18 %; 2014 = 14 %), while market share of quality-assured ACT increased (2012 = 3 %; 2013 = 59 %; 2014 = 51 %). Among priority outlets in the comparison area, similar trends were observed, though changes over time were less substantial compared to the intervention area. Other outlet types (community health workers and health facilities) performed relatively well over time though modest improvements were also observed.ConclusionThe findings point to the successful design and implementation of a strategy to rapidly remove oral AMT from pharmacies, general retailers and mobile providers and to replace its use with quality-assured ACT. The evidence also highlights the importance of supporting interventions in the context of a high-level subsidy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1292-8) contains supplementary material, which is available to authorized users.

Evaluation of the behaviour change communication and community mobilization activities in Myanmar artemisinin resistance containment zones.

BackgroundBehaviour change communication (BCC) can improve malaria prevention and treatment behaviour. As a one of the activities under Myanmar Artemisinin Resistance Containment (MARC) programme, BCC have been conducting. This study aimed to evaluate the effectiveness of the behaviour change communication and community mobilization activities in MARC zones in Myanmar.MethodsA cross sectional descriptive survey was conducted in randomly selected 16 townships in Tier I and II areas of MARC zones by quantitative and qualitative approaches.ResultsIn 832 households resided by 4664 people, there were 3797 bed nets. Around 54 % were untreated while 45.6 % were insecticide-treated nets (ITN) and 36.2 % were long-lasting insecticide-treated nets (LLINs). Proportion of households with at least one ITN was 625 (75.12 %), proportion of households with at least one ITN for every two peoples was 487 (58.53 %), and proportion of existing ITNs used in previous night was 1225 (70.65 %) respectively. Nearly 23 % of households had old nets while 52 % had new and unused extra bed nets reflecting the adequacy. Interestingly, 38 % could not mention the benefit of the use of ITN/LLINs. Although 88.2 % knew the disease “malaria”, 11.9 % could not be able to mention the symptoms. More than 80 % provided correct responses that mosquito bite can cause malaria while only 36.9 % could mention the blood test for malaria diagnosis. Only 36.6 % received malaria information within previous year but nearly 15 % could not recognize it. Mostly, 80 % of fever episodes were treated at rural health centers (38.24 %) followed by drug shops (17.65 %) and private clinics (16.18 %) respectively.ConclusionsEfforts should focus on correcting misconceptions about malaria transmission, prevention and universal use of ITN/LLINs. Although BCC activities have been documented, it is still necessary to intensify community mobilization through all accessible multiple channels in MARC areas.

Mobility dynamics of migrant workers and their socio-behavioral parameters related to malaria in Tier II, Artemisinin Resistance Containment Zone, Myanmar.

BackgroundAreas with dynamic population movements are likely to be associated with higher levels of drug-resistant malaria. Myanmar Artemisinin Resistance Containment (MARC) Project has been launching since 2012. One of its components includes enhancing strategic approaches for mobile/migrant populations. We aimed to ascertain the estimated population of mobile migrant workers and their families in terms of stability in work setting in townships classified as tier II (areas with significant inflows of people from areas with credible evidence of artemisinin resistance) for Artemisinin resistance; to identify knowledge, attitudes and practices related to prevention and control of malaria and to recommend cost-effective strategies in planning for prevention and control of malaria.MethodsA prospective cross-sectional study conducted between June to December 2013 that covered 1,899 migrant groups from 16 tier II townships of Bago Region, and Kayin and Kayah States. Trained data collectors used a pre-tested and subsequently modified questionnaire and interviewed 2,381 respondents. Data of migrant groups were analyzed and compared by category depending upon the stability of their work setting.ResultsThe estimated population of the 1,899 migrant groups categorized into three on the nature of their work setting was 56,030. Bago region was the commonest reported source of origin of migrant groups as well as their transit. Malaria volunteers were mostly within the reach of category 1 migrant groups (43/66, 65.2 %). Less stable migrant groups in category 3 had limited access to malaria information (14.7 %) and malaria care providers (22.1 %), low level of awareness and use of long-lasting insecticide-treated nets (46.6 and 38.8 %). Also, they had poor knowledge on malaria prevention on confirming suspected malaria and on using artemisinin combined therapy (ACT). Within two weeks prior to the survey, only 16.5 % of respondents in all categories combined reported acute undifferentiated fever.Discussion and ConclusionsMobility dynamics of migrant groups was complex and increased their vulnerability to malaria. This phenomenon was accentuated in less stable areas. Even though migrant workers were familiar with rapid diagnostic tests for malaria, ACT still needed wide recognition to improve practices supportive of MARC including the use of appropriate personal protection. High mobility calls for re-designation of tier II townships to optimize ACT resistance containment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-015-2241-0) contains supplementary material, which is available to authorized users.

Selection and spread of artemisinin-resistant alleles in Thailand prior to the global artemisinin resistance containment campaign.

The recent emergence of artemisinin resistance in the Greater Mekong Subregion poses a major threat to the global effort to control malaria. Tracking the spread and evolution of artemisinin-resistant parasites is critical in aiding efforts to contain the spread of resistance. A total of 417 patient samples from the year 2007, collected during malaria surveillance studies across ten provinces in Thailand, were genotyped for the candidate Plasmodium falciparum molecular marker of artemisinin resistance K13. Parasite genotypes were examined for K13 propeller mutations associated with artemisinin resistance, signatures of positive selection, and for evidence of whether artemisinin-resistant alleles arose independently across Thailand. A total of seven K13 mutant alleles were found (N458Y, R539T, E556D, P574L, R575K, C580Y, S621F). Notably, the R575K and S621F mutations have previously not been reported in Thailand. The most prevalent artemisinin resistance-associated K13 mutation, C580Y, carried two distinct haplotype profiles that were separated based on geography, along the Thai-Cambodia and Thai-Myanmar borders. It appears these two haplotypes may have independent evolutionary origins. In summary, parasites with K13 propeller mutations associated with artemisinin resistance were widely present along the Thai-Cambodia and Thai-Myanmar borders prior to the implementation of the artemisinin resistance containment project in the region.

Molecular Determinants of Artemisinin Resistance in k13 Gene of Plasmodium falciparum

Artemisinin-based combination therapy (ACT) is the first-line therapy in most malaria endemic countries. An impressive 47% reduction in the global mortality rate between 2000 and 2013 has been achieved by ACT and artemisinin (ART) monotherapy. However, artemisinin resistance (AR) by Plasmodium falciparum (P. falciparum) is now prevalent across south-east Asia (SEA). AR is indicated by delayed parasite clearance of more than 3 days after standard ART treatment and reduced in vitrosusceptibility. Recent work has shown association of AR with mutations in the propeller domain of the kelch gene on chromosome 13 (PF3D7_1343700, k13gene) of P. falciparum. The C580Y mutation of thek13gene is highly prevalent in Cambodia, Myanmar and eastern and western Thailand, while the F446I mutation is predominant in the China-Myanmar border regions as well as in Myanmar. AR has not reached India and Africa, where non-synonymous mutations not associated with delayed parasite clearance are present. Because the location of Myanmar is central between SEA and Africa, a country-specific strategy for Myanmar Artemisinin Resistance Containment (MARC) is necessary. Moreover, regular periodic tracking of prevalent molecular determinants such as C580Y and F446I mutations will be beneficial.

Spatial distribution, work patterns, and perception towards malaria interventions among temporary mobile/migrant workers in artemisinin resistance containment zone.

BackgroundMobile populations are at a high risk of malaria infection and suspected to carry and spread resistant parasites. The Myanmar National Malaria Control Programme focuses on preventive interventions and vector control measures for the temporary mobile/migrant workers in Myanmar Artemisinin Resistance Containment Zones.MethodsA prospective cross-sectional study was conducted in 2012 in Kawthaung and Bokepyin townships of Tanintharyi Region, Myanmar, covering 192 mobile/migrant aggregates. The objectives were to identify the spatial distribution of the mobile/migrant populations, and to assess knowledge, attitudes, perceptions, and practices concerning malaria prevention and control, and their preferred methods of interventions. The structure of the192 migrant aggregates was investigated using a migrant mapping tool. Individual and household information was collected by structured interviews of 408 respondents from 39 aggregates, supplemented by 12 in-depth interviews of health care providers, authorities, volunteers, and employers. Data were analyzed by triangulating quantitative and qualitative data.ResultsThe primary reasons for the limitation in access to formal health services for suspected malaria within 24 hours were identified to be scattered distribution of migrant aggregates, variable working hours and the lack of transportation. Only 19.6% of respondents reported working at night from dusk to dawn. Among study populations, 73% reported a perceived risk of contracting malaria and 60% reported to know how to confirm a suspected case of malaria. Moreover, only 15% was able to cite correct antimalarial drugs, and less than 10% believed that non-compliance with antimalarial treatment may be related to the risk of drug resistance. About 50% of study population reported to seeking health care from the public sector, and to sleep under ITNs/LLINs the night before the survey. There was a gap in willingness to buy ITNs/LLINs and affordability (88.5% vs. 60.2%) which may affect their sustained and consistent use. Only 32.4% across all aggregates realized the importance of community participation in effective malaria prevention and control.ConclusionsCommunity-based innovative approaches through strong collaboration and coordination of multi-stakeholders are desirable for relaying information on ITNs/LLINs, rapid diagnostic test, and artemisinin combination therapy and drug resistance successfully across the social and economic diversity of mobile/migrant aggregates in Myanmar.

Use of Artemisinin and Its Derivatives for the Treatment of Malaria in Children

Use of Artemisinin and Its Derivatives for the Treatment of Malaria in Children

Severe malaria in Battambang Referral Hospital, an area of multidrug resistance in Western-Cambodia: a retrospective analysis of cases from 2006-2009.

BackgroundDespite recent malaria containment and control efforts leading to reduced incidence, Cambodia remains endemic for both Plasmodium vivax and multidrug-resistant Plasmodium falciparum malaria. Little has been reported in the peer-reviewed literature regarding the burden of severe malaria (SM) in Cambodia.MethodsMedical records for all patients admitted to the Battambang Referral Hospital (BRH) with an admitting or discharge diagnosis of SM from 2006 to 2009 (suspected SM cases) were reviewed. Those meeting the case definition of SM according to retrospective chart review and investigator assessment of probable cases, based on published national guidelines available at the time, were analysed for trends in demographics, mortality and referral patterns.ResultsOf the 537 suspected SM cases at BRH during the study period, 393 (73%) met published WHO criteria for SM infection. Despite limited diagnostic and treatment facilities, overall mortality was 14%, with 7% mortality in children 14 and under, but 19% in adults (60% of cases). Cerebral malaria with coma was relatively rare (17%), but mortality was disproportionately high at 35%. Mean time to hospital presentation was five days (range one to 30 days) after onset of symptoms. While patients with delays in presentation had worse outcomes, there was no excess mortality based on treatment referral times, distance travelled or residence in artemisinin-resistance containment (ARC) Zone 1 compared to Zone 2.ConclusionsDespite limitations in diagnosis and treatment, and multiple confounding co-morbidities, mortality rates at BRH were similar to reports from other countries in the region. Interventions to improve access to early diagnosis and effective treatment, combined with modest improvements in intensive care, are likely to reduce mortality further. Patients referred from Zone 1 did not have excess mortality compared to Zone 2 ARC areas. A steep decrease in SM cases and deaths observed in the first half of 2009 has since continued, indicating some success from containment efforts despite the emergence of artemisinin resistance in this area.

Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems

Artemisinin-resistant Plasmodium falciparum malaria has emerged in western Cambodia and has been detected in western Thailand. The situation is ominously reminiscent of the emergence of resistance to chloroquine and to sulfadoxine-pyrimethamine several decades ago. Artemisinin resistance is a major threat to global public health, with the most severe potential effects in sub-Saharan Africa, where the disease burden is highest and systems for monitoring and containment of resistance are inadequate. The mechanisms that underlie artemisinin resistance are not fully understood. The main phenotypic trait associated with resistance is a substantial delay in parasite clearance, so far reported in southeast Asia but not in Africa. One of the pillars of the WHO global plan for artemisinin resistance containment is to increase monitoring and surveillance. In this Personal View, we propose strategies that should be adopted by malaria-endemic countries in Africa: resource mobilisation to reactivate regional surveillance networks, establishment of baseline parasite clearance profiles to serve as benchmarks to track emerging artemisinin resistance, improved data sharing to allow pooled analyses to identify rare events, modelling of risk factors for drug resistance, and development and validation of new approaches to monitor resistance.

The global challenge of antimalarial drug resistance

The continued geographic expansion of Plasmodium falciparum resistance to artemisinin derivatives is an urgent public health concern. The last decade has witnessed dramatic progress in global malaria control and elimination efforts, in large part because of the scale-up of vector control interventions and improved access to effective antimalarials, especially artemisinin-based combination therapies (ACTs). Malaria cases have fallen by >50% in 43 countries since 2001. Since 2000, malaria mortality rates have declined by >25% globally, and by >33% in the WHO African Region. Malaria patients worldwide are dependent on the efficacy of ACTs. In 2010, more than 180 million ACT treatment courses were procured for the public sector alone. Resistance to artemisinins was first confirmed on the Cambodia-Thailand border in late 2006, and reported in 2008. The first containment project - the Artemisinin Resistance Containment and Elimination (ARCE) project -was funded by BMGF and coordinated by WHO-GMP; it ran from late2008-2011. The project did not eliminate malaria from the affected area; however, active case detection, strengthened community case management and better vector control did result in a sustained and dramatic reduction in Plasmodium falciparum burden. To mobilize global and local stakeholders for containment and ultimately elimination of artemisinin resistance, WHO, together with RBM, launched the Global Plan for Artemisinin Resistance Containment (GPARC) in January 2011. The GPARC defines priorities to contain or eliminate artemisinin resistance where it already exists, or to prevent it where it has not yet appeared. While strong country-level activities are the central building blocks in the response, artemisinin resistance does not respect national boundaries. Resistance has generally been identified in areas with high numbers of migrants and close to national borders. Consequently, national responses to the threat of resistance are not sufficient; strong regional coordination is crucial. Despite the emergence of artemisinin resistance in the Greater Mekong subregion, ACTs remain the most effective treatment for uncomplicated falciparum malaria; most patients with delayed response are cured if the partner drug remains effective. However, mefloquine resistance is widespread in Thailand and Cambodia, and piperaquine resistance may have emerged in Western Cambodia, limiting the number of treatment options for uncomplicated malaria. In addition to the existing foci, there is growing evidence of resistance to artemisinin, as defined by delayed parasite clearance times in south-eastern Myanmar and southern and central Vietnam. It is not known if these new foci represent spread or de novo emergence of artemisinin resistance. In response to new data, containment efforts have been started in western Thailand, south-eastern Myanmar and Vietnam. These new programmes will draw on the lessons learned during the containment project in Cambodia and Thailand. In addition, routine monitoring must be strengthened for the early detection of artemisinin resistance, ensure that recommended first-line ACTs are effective, and that timely changes in treatment policies can be made. Many aspects of artemisinin resistance are still not well understood. Consequently, there is an urgent need for further research to refine our knowledge of artemisinin resistance, including the identification of molecular markers and better in vitro sensitivity tests. These efforts require full funding to ensure that artemisinin resistance does not spread and compromise global success in malaria control and elimination.