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24 Pyit See Epub Download

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Throughout the GMS, Plasmodium falciparum parasites are increasingly resistant to artemisinin combination therapies. Given that there are no current alternative treatment therapies, one proposed solution to the threat of untreatable P. Several small-scale elimination projects have been piloted in the GMS, including along the Myanmar-Thailand border. Following the success of the pilot elimination project along the Myanmar-Thailand border, there was a scale up to a broad area of Eastern Kayin State, Myanmar. Here we describe the establishment of the scale up elimination project in Easter Kayin State. Methods: The scale up relied on geographic reconnaissance and a geographic information system, community engagement, generalized access to community-based early diagnosis and treatment, near real-time epidemiological surveillance, cross sectional malaria prevalence surveys and targeted mass drug administration in villages with high prevalence of P. Molecular markers of drug resistance were also monitored in individuals with symptomatic and asymptomatic infections. Discussion: This protocol illustrates the establishment of an elimination project and operational research in a remote, rural area encompassing several armed groups, multiple political organizations and a near-absent health care infrastructure. The establishment of the project relied on a strong rapport with the target community, on-the-ground knowledge through geographic surveys and community engagement , rapid decision making and an approach that was flexible enough to quickly adapt to a complex landscape. The elimination project is ongoing, now over three years in operation, and assessment of the impact of this operational research will follow. This project has relevance not only for other malaria elimination projects but also for operational research aimed at eliminating other diseases.

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Editorial Reviews. About the Author. Forman lives in the western Rockies. He tries to write.. Thousands of. Whalen Vankin is a great an honorable wizard, and he has only ever personally trained two other wizards. Large, village-scale meetings were combined with group discussions and activities specific for different population groups e.

During the MDA, the CE team members participated in the MDA process and participated in everyday village life, addressing individual and collective concerns in formal or informal discussions.

The MP system allowed for feedback to flow back to headquarters after this seven day period. In situations where villagers presented concerns or resistance to either surveys or MDA there were further discussions with important community, village and township leaders.

A few villagers voiced concerns with regard to loss of blood that were alleviated when medical experts explained that the amount of blood being taken was minimal and would not have an effect on villagers. There were also political concerns since the team signed a memorandum of understanding with the central government and since many of these communities have been involved in a longstanding civil conflict with the military. Through meetings between the CE team and villagers, the villagers came to understand that this program was not from a central government organization, but rather an outside organization that works under the auspices of all locally and nationally relevant organizations.

While participation varied in some communities, ultimately no communities completely refused to participate in MDA.

Some surveys 15 could not be conducted because of a lack of willing participants. In this case, clinical incidence and consultation rates were closely monitored to ensure that population continued to trust and consult the MP in case of fever. Malaria posts MPs MPs were established in all communities that accepted the responsibility. An original assumption of villages requiring a malaria post was revised to following reconnaissance efforts. Physical structures were not provided, but each MP had a trained, dedicated and salaried MPW, antimalarials, rapid diagnostic test RDT kits, and a few other basic supplies, such as paracetamol, pregnancy tests, scales, a banner to signal MP location, and stationery.

MPWs were selected by the village headman and the community, and attended a five-day training that covered malaria case management, referral and reporting systems and CE. Trainings were followed by a course completion test. A manual in Karen and Burmese was provided for reference, summarizing procedures, treatment algorithms Figure 3 and dosing tables Supplementary File 1. Figure 3.

Open in a separate window Fever case management algorithm at Malaria Posts. ACT, artemisinin combination therapy. Fever cases were systematically tested using a P. Uncomplicated P. A single low dose of primaquine 0. At the beginning of the project there was little-to-no cell phone coverage in the entire target area, but by most of the target area excluding parts of Hpapun and Hlaingbwe Townships was covered.

Data collection in areas with no cell phone coverage relied on runners who collected the forms and transported them using any convenient transportation means to the nearest place where they could be entered into an online data system Voozanoo. After aggregation, MP data completion and correctness was regularly assessed by searching for duplicate reports, missing weekly reports, through double entry of a subset of records and through integrated weekly GIS routines that link records to spatial references.

MP activities were continuously monitored via the weekly data reporting system and by a dedicated monitoring and evaluation team, which was recruited to make investigative visits, using standardized questionnaires Supplementary File 3 , to randomly selected MPs and MPs that ceased to transmit data, or reported no activity or stock outs.

A data evaluation algorithm was established in order to monitor data quality. Missing reports, abnormal data reporting, spikes in clinical malaria cases, or potential problems in stock inventories were checked weekly. After potential data entry errors were excluded, the malaria post supervisors in charge of any problematic MPs were contacted to assess the situation and the required response. Malaria prevalence surveys Procedures. Cross sectional surveys were conducted at the village level using an ultrasensitive high-volume qPCR assay in order to estimate the prevalence of P.

Surveys were originally planned in randomly selected villages. Following CE, survey teams approached village headmen to aid in selecting villagers for possible participation in a survey.

In most cases no village census was available. Survey teams took samples from adults who agreed to participate, attempting to balance samples across sex and broad age groups, until reaching the sample size needed based on the full village population Supplementary File 4 and Supplementary File 5.

This sample size represented a significant proportion of the village population. Participants were asked to provide 2mL blood by venous puncture after providing written informed consent.

Samples were collected in EDTA Ethylenediaminetetraacetic acid tubes, stored in an icebox and brought back to the field laboratory within 48h of collection. A RDT was performed in the field for all participants to the survey, and proposed to the rest of the village population.

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Malaria detection in the laboratory. The remaining blood was centrifuged and packed red blood cells were used for extraction and detection of malaria parasites by ultrasensitive qPCR 8. The detection by qPCR was conducted in two steps: 1 detection of Plasmodium infection using a highly sensitive genus-specific marker; 2 determination of P.

The species of some Plasmodium positive samples could therefore remain uncharacterized. In these instances microscopy and RDT results were used to attribute the species. If both RDT and microscopy were negative, malaria was attributed to either P. Sample and data management. Individual samples were identified using a barcode label that was used to trace field data and results obtained for the different malaria detection tests performed in the laboratory RDT, microscopy, qPCR.

All paper-recorded survey data participant demographic information, field RDT result, laboratory RDT and microscopy examination results were entered in a Microsoft Access Access version Result outputs from qPCR analysis were merged directly in the Access database.

Sample size.

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The within-village sample size was calculated, taking into account feasibility constraints small village sizes, sample conservation and cold chain and the expected precision of estimates. Hotspot definition. Such villages were targeted for mass drug administration. Targeted mass drug administration MDA Drug regimen and exclusion criteria. Women in their first trimester of pregnancy, children under one year of age, individuals with previous drug allergies and villagers who refused to participate were excluded from MDA.

Women within reproductive age roughly 14 — 44 years old and of unknown pregnancy status self-reported being unsure of pregnancy status were screened with a urinary human chorionic gonadotropin HCG test kit. Women in their second and third trimester of a pregnancy, as well as breastfeeding mothers, were eligible for DP treatment but were excluded from the single dose of primaquine.

Those who met the inclusion criteria were administered a three-day course of DP with a single low dose of primaquine on the first day and this was repeated over three consecutive months Supplementary File 3.

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All doses were directly observed. Participants who were unable to attend to the next take s were provided the remaining doses to complete unsupervised treatment. The MDA team stayed in each MDA village for seven days per visit to document side effects, to address concerns and to treat other minor illnesses. All adverse events AE that were reported by MDA participants within one week of taking an MDA course were carefully recorded and treated when necessary at a mobile clinic set up during the MDA period or referred to the nearest appropriate health care facility.

All drug administration data date, weight, dosage were recorded in a logbook as well as reasons for non-participation collected using a standardized questionnaire Supplementary File 6.

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All MDA data were checked onsite by the field teams and reviewed after the end of the 3 months. Logbooks and AE sheets were entered in an Access database Access version Antimalarial resistance monitoring Antimalarial resistance monitoring was conducted at two partner laboratories: one in the Faculty of Tropical Medicine at Mahidol University and the other at the Sanger Institute, both using dried blood spots from P.

Assessment of mutations in PfKelch13 associated with artemisinin resistance. Cross contamination was monitored by adding negative control samples in every run.

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Polymorphic patterns were assessed by two individuals blinded to the origin of the sample. Markers of ACT partner drug resistance. Every amplification run contained 9 replicates of calibrators and triplicates without template as negative controls. Tests for piperaquine resistance markers were also carried out on P.

DNA was extracted directly from blood samples taken from patients at admission time, after leukocyte depletion by CF11 filtration to minimize human DNA. Paired-end sequencing reads of length — bp were obtained, generating approximately 1 Gbp of read data per sample.

Polymorphism discovery, quality control and sample genotyping followed a process described in detail elsewhere The same sequencing data were used to estimate copy number for the pfmdr1 gene, using a method previously described in detail Briefly, the sequencing read coverage was normalized for each sample, and the pfmdr1 copy number was estimated by calculating the ratio between the coverage at a number of positions within that gene, and the median coverage of a set of 56 reference positions at various loci across the genome.

To improve estimates, the reference positions were chosen in genes with similar characteristics to pfmdr1: similar GC content, level of evolutionary conservation, exon length, median coverage, and low variation in relative coverage across the MalariaGEN dataset.

Statistical analyses Incidence rates of clinical P. Weekly incidence was calculated for each village and also aggregated over space and time e.

Total malaria, P. Statistical clustering of both incidence and prevalence was assessed using a range of geostatistical and cartographic approaches. It was necessary to carefully interpret results and to look for congruity between approaches because of the skewed nature of the data with many villages having low prevalence and few having high prevalence. Choropleth maps were created for incidence at the village tract level and point maps were created and used for operational needs e.

The evaluation of the impact of the program was conducted by monitoring the temporal trends in incidence at township, village tract and village level and by measuring the proportion of villages and village tracts achieving and sustaining low P.

The specific impact of MDA on malaria prevalence in hotspot villages was measured by comparing the baseline prevalences to follow-up survey prevalences 12 months after MDA.

Discussion This project illustrates the scale up of an elimination program in a region encompassing remote and rugged terrain, a complex political landscape, ongoing areas of active conflict, and a near-absent pre-existing health care infrastructure.

The key interventions of the project included the establishment of a dense network of community level early malaria diagnosis and treatment clinics MPs and targeted MDA.

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