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1.
Hum Genome Var ; 8(1): 7, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542200

RESUMO

Pharmacogenomics can enhance the outcome of treatment by adopting pharmacogenomic testing to maximize drug efficacy and lower the risk of serious adverse events. Next-generation sequencing (NGS) is a cost-effective technology for genotyping several pharmacogenomic loci at once, thereby increasing publicly available data. A panel of 100 pharmacogenes among Southeast Asian (SEA) populations was resequenced using the NGS platform under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm). Here, we present the frequencies of pharmacogenomic variants and the comparison of these pharmacogenomic variants among different SEA populations and other populations used as controls. We investigated the different types of pharmacogenomic variants, especially those that may have a functional impact. Our results provide substantial genetic variations at 100 pharmacogenomic loci among SEA populations that may contribute to interpopulation variability in drug response phenotypes. Correspondingly, this study provides basic information for further pharmacogenomic investigations in SEA populations.

2.
Public Health Genomics ; 22(3-4): 132-139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587001

RESUMO

Pharmacogenomics (PGx) is increasingly being recognized as a potential tool for improving the efficacy and safety of drug therapy. Therefore, several efforts have been undertaken globally to facilitate the implementation process of PGx into routine clinical practice. Part of these efforts include the formation of PGx working groups working on PGx research, synthesis, and dissemination of PGx data and creation of PGx implementation strategies. In Asia, the Southeast Asian Pharmacogenomics Research Network (SEAPharm) is established to enable and strengthen PGx research among the various PGx communities within but not limited to countries in SEA; with the ultimate goal to support PGx implementation in the region. From the perspective of SEAPharm member countries, there are several key elements essential for PGx implementation at the national level. They include pharmacovigilance database, PGx research, health economics research, dedicated laboratory to support PGx testing for both research and clinical use, structured PGx education, and supportive national health policy. The status of these essential elements is presented here to provide a broad picture of the readiness for PGx implementation among the SEAPharm member countries, and to strengthen the PGx research network and practice in this region.


Assuntos
Relações Interprofissionais , Farmacogenética/estatística & dados numéricos , Ásia , Ásia Sudeste , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Difusão de Inovações , Erupção por Droga/prevenção & controle , Humanos , Farmacogenética/economia
3.
Nat Commun ; 10(1): 2665, 2019 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-31209259

RESUMO

Estimates of Plasmodium falciparum migration may inform strategies for malaria elimination. Here we elucidate fine-scale parasite population structure and infer recent migration across Southeast Asia using identity-by-descent (IBD) approaches based on genome-wide single nucleotide polymorphisms called in 1722 samples from 54 districts. IBD estimates are consistent with isolation-by-distance. We observe greater sharing of larger IBD segments between artemisinin-resistant parasites versus sensitive parasites, which is consistent with the recent spread of drug resistance. Our IBD analyses reveal actionable patterns, including isolated parasite populations, which may be prioritized for malaria elimination, as well as asymmetrical migration identifying potential sources and sinks of migrating parasites.


Assuntos
Resistência a Medicamentos/genética , Monitoramento Epidemiológico , Genoma de Protozoário/genética , Malária Falciparum/microbiologia , Plasmodium falciparum/genética , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Ásia Sudeste , Biodiversidade , Genótipo , Geografia Médica , Malária Falciparum/tratamento farmacológico , Malária Falciparum/prevenção & controle , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/isolamento & purificação , Polimorfismo de Nucleotídeo Único
4.
Malar J ; 17(1): 428, 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30445962

RESUMO

BACKGROUND: One challenge in moving towards malaria elimination is cross-border malaria infection. The implemented measures to prevent and control malaria re-introduction across the demarcation line between two countries require intensive analyses and interpretation of data from both sides, particularly in border areas, to make correct and timely decisions. Reliable maps of projected malaria distribution can help to direct intervention strategies. In this study, a Bayesian spatiotemporal analytic model was proposed for analysing and generating aggregated malaria risk maps based on the exceedance probability of malaria infection in the township-district adjacent to the border between Myanmar and Thailand. Data of individual malaria cases in Hlaingbwe Township and Tha-Song-Yang District during 2016 were extracted from routine malaria surveillance databases. Bayesian zero-inflated Poisson model was developed to identify spatial and temporal distributions and associations between malaria infections and risk factors. Maps of the descriptive statistics and posterior distribution of predicted malaria infections were also developed. RESULTS: A similar seasonal pattern of malaria was observed in both Hlaingbwe Township and Tha-Song-Yang District during the rainy season. The analytic model indicated more cases of malaria among males and individuals aged ≥ 15 years. Mapping of aggregated risk revealed consistently high or low probabilities of malaria infection in certain village tracts or villages in interior parts of each country, with higher probability in village tracts/villages adjacent to the border in places where it could easily be crossed; some border locations with high mountains or dense forests appeared to have fewer malaria cases. The probability of becoming a hotspot cluster varied among village tracts/villages over the year, and some had close to no cases all year. CONCLUSIONS: The analytic model developed in this study could be used for assessing the probability of hotspot cluster, which would be beneficial for setting priorities and timely preventive actions in such hotspot cluster areas. This approach might help to accelerate reaching the common goal of malaria elimination in the two countries.


Assuntos
Malária/epidemiologia , Topografia Médica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mianmar/epidemiologia , Medição de Risco , Fatores de Risco , Análise Espaço-Temporal , Tailândia/epidemiologia , Adulto Jovem
5.
BMC Health Serv Res ; 18(1): 878, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30458776

RESUMO

BACKGROUND: Delays in diagnosis and treatment initiation may allow the emergence of new cases by transmission to the community, and is one of the challenges facing programme management of drug resistance in Myanmar. This study aimed to explore delays in diagnosis and treatment initiation, and associated factors among patients with multidrug-resistant tuberculosis. METHODS: A cross-sectional study was conducted at Yangon Regional Tuberculosis Centre, Myanmar. Data were collected by face-to-face interviews and treatment-card reviews of all adult patients who had registered and started treatment with the standard regimen from May to November, 2017. Delay time was categorized by using median cut-off and analyzed using SPSS version 23.0. Logistic regression analysis was performed to assess the relative impact of predictor variables on diagnosis and treatment delays. RESULTS: A total of 210 patients participated in this study. The median diagnosis delay was 9 days, IQR 3 (8-11) and 58.6% of the patients experienced a long diagnosis delay. Below middle school education (adjusted odds ratio [AOR] = 2.75, 95% CI = 1.22-6.21), non-permanent salaried employment (AOR = 3.03, 95% CI = 1.32-6.95), co-existing diabetes mellitus (AOR = 5.06, 95% CI = 1.97-13.01) and poor awareness (AOR = 2.99, 95% CI = 1.29-6.92) were independent predictors of long diagnosis delay. The median treatment delay was 13 days, IQR 9 (8-17) and 51% of the patients experienced long treatment delay. Age 31-50 years (AOR = 4.50, 95% CI = 1.47-13.97) and age > 50 years (AOR = 9.40, 95% CI = 2.55-34.83), history with MDR-TB patient (AOR = 3.16, 95% CI = 1.29-7.69), > 20 km away from a Regional TB Centre (AOR = 14.33, 95% CI = 1.91-107.64) and poor awareness (AOR = 4.62, 95% CI = 1.56-13.67) were independent predictors of long treatment delay. CONCLUSIONS: Strengthening comprehensive health education, enhancing treatment adherence counseling, providing more Xpert MTB/RIF machines, expanding decentralized MDR-TB treatment centers, ensuring timely sputum transportation, provision of a patient support package immediately after confirmation, and strengthening contact-tracing for all household contacts with MDR-TB patients and active tuberculosis screening were the most effective ways to shorten delays in MDR-TB diagnosis and treatment initiation.


Assuntos
Diagnóstico Tardio , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Estudos Transversais , Atenção à Saúde/normas , Complicações do Diabetes/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mianmar , Razão de Chances , Tempo para o Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/complicações , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/tratamento farmacológico
6.
Data Brief ; 21: 354-357, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30364728

RESUMO

This article contains microbiome data from the upper respiratory tract of patients living with HIV/TB, HIV and TB from Meiktila, a town in Myanmar where there is a high incidence of HIV and TB. Microbiomes were compared for HIV/TB infected and healthy adults from the same population. We collected nasopharyngeal and oropharyngeal swabs from a total of 33 participants (Healthy {5}, HIV/TB {8}, HIV {14}, and TB {6}). DNA was extracted from the swabs and subjected to custom single step 16s rRNA sequencing on an Illumina MiSeq platform. The sequencing data is available via http://www.ncbi.nlm.nih.gov/bioproject/ PRJNA432583.

7.
Am J Trop Med Hyg ; 98(5): 1300-1302, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29557332

RESUMO

Burkholderia pseudomallei, the etiologic agent of melioidosis, is an important but under-recognized cause of disease in the tropics. Although first described over a century ago as a septicemic illness associated with morphine addicts in Rangoon, Burma, there is little information regarding the incidence of melioidosis in present-day Myanmar. To address this issue, we used two recently developed and validated serological assays to detect B. pseudomallei-specific antibodies in 124 serum samples obtained from febrile patients in the delta region of Myanmar. Using cutoff values derived from culture-confirmed melioidosis cases in neighboring Thailand, 3.2% of the samples exhibited reactivity profiles consistent with active B. pseudomallei infections. Collectively, these findings indicate that melioidosis likely represents a significant cause of morbidity and mortality in Myanmar and support the need for further studies to assess the true burden of disease in this country.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Melioidose/diagnóstico , Melioidose/epidemiologia , Anticorpos Antibacterianos/sangue , Burkholderia pseudomallei/imunologia , Humanos , Melioidose/microbiologia , Mianmar/epidemiologia , Sensibilidade e Especificidade
8.
Malar J ; 16(1): 138, 2017 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-28376883

RESUMO

BACKGROUND: Myanmar has the heaviest burden of malaria in the Greater Mekong Sub-region. Asymptomatic Plasmodium spp. infections are common in this region and may represent an important reservoir of transmission that must be targeted for malaria elimination. METHODS: A mass blood survey was conducted among 485 individuals from six villages in Kayah State, an area of endemic but low transmission malaria in eastern Myanmar. Malaria infection was screened by rapid diagnostic test (RDT), light microscopy and real-time polymerase chain reaction (PCR), and its association with demographic factors was explored. RESULTS: The prevalence of asymptomatic Plasmodium spp. infection was 2.3% (11/485) by real-time PCR. Plasmodium vivax accounted for 72.7% (8/11) and Plasmodium falciparum for 27.3% (3/11) of infections. Men were at greater risk of infection by Plasmodium spp. than women. Individuals who worked as farmers or wood and bamboo cutters had an increased risk of infection. CONCLUSION: A combination of RDT, light microscopy and PCR diagnostics were used to identify asymptomatic malaria infection, providing additional information on asymptomatic cases in addition to the routine statistics on symptomatic cases, so as to determine the true burden of disease in the area. Such information and risk factors can improve malaria risk stratification and guide decision-makers towards better design and delivery of targeted interventions in small villages, representative of Kayah State.


Assuntos
Doenças Assintomáticas , Malária/epidemiologia , Parasitemia/epidemiologia , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Demografia , Testes Diagnósticos de Rotina , Feminino , Humanos , Lactente , Malária/diagnóstico , Malária/parasitologia , Masculino , Programas de Rastreamento , Microscopia , Pessoa de Meia-Idade , Mianmar/epidemiologia , Exposição Ocupacional , Parasitemia/diagnóstico , Parasitemia/parasitologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Fatores Sexuais , Adulto Jovem
9.
Lancet Infect Dis ; 17(5): 491-497, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28161569

RESUMO

BACKGROUND: Evidence suggests that the PfKelch13 mutations that confer artemisinin resistance in falciparum malaria have multiple independent origins across the Greater Mekong subregion, which has motivated a regional malaria elimination agenda. We aimed to use molecular genotyping to assess antimalarial drug resistance selection and spread in the Greater Mekong subregion. METHODS: In this observational study, we tested Plasmodium falciparum isolates from Myanmar, northeastern Thailand, southern Laos, and western Cambodia for PfKelch13 mutations and for Pfplasmepsin2 gene amplification (indicating piperaquine resistance). We collected blood spots from patients with microscopy or rapid test confirmed uncomplicated falciparum malaria. We used microsatellite genotyping to assess genetic relatedness. FINDINGS: As part of studies on the epidemiology of artemisinin-resistant malaria between Jan 1, 2008, and Dec 31, 2015, we collected 434 isolates. In 2014-15, a single long PfKelch13 C580Y haplotype (-50 to +31·5 kb) lineage, which emerged in western Cambodia in 2008, was detected in 65 of 88 isolates from northeastern Thailand, 86 of 111 isolates from southern Laos, and 14 of 14 isolates from western Cambodia, signifying a hard transnational selective sweep. Pfplasmepsin2 amplification occurred only within this lineage, and by 2015 these closely related parasites were found in ten of the 14 isolates from Cambodia and 15 of 15 isolates from northeastern Thailand. C580Y mutated parasites from Myanmar had a different genetic origin. INTERPRETATION: Our results suggest that the dominant artemisinin-resistant P falciparum C580Y lineage probably arose in western Cambodia and then spread to Thailand and Laos, outcompeting other parasites and acquiring piperaquine resistance. The emergence and spread of fit artemisinin-resistant P falciparum parasite lineages, which then acquire partner drug resistance across the Greater Mekong subregion, threatens regional malaria control and elimination goals. Elimination of falciparum malaria from this region should be accelerated while available antimalarial drugs still remain effective. FUNDING: The Wellcome Trust and the Bill and Melinda Gates Foundation.


Assuntos
Artemisininas/uso terapêutico , Resistência a Medicamentos/genética , Malária Falciparum/epidemiologia , Epidemiologia Molecular/métodos , Plasmodium falciparum/genética , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Camboja/epidemiologia , Genótipo , Humanos , Laos/epidemiologia , Malária Falciparum/tratamento farmacológico , Repetições de Microssatélites , Mutação , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/isolamento & purificação , Quinolinas/uso terapêutico , Tailândia/epidemiologia
10.
Malar J ; 15: 185, 2016 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-27036739

RESUMO

BACKGROUND: Artemisinin resistance in Plasmodium falciparum extends across Southeast Asia where it is associated with worsening partner drug resistance and a decline in the efficacy of frontline artemisinin-based combination therapy. Dihydroartemisinin-piperaquine (DP) is an essential component of preventive and curative treatment in the region, but its therapeutic efficacy has fallen in Cambodia. METHODS: A prospective clinical and parasitological evaluation of DP was conducted at two sites in Upper Myanmar between August 2013 and December 2014, enrolling 116 patients with acute uncomplicated falciparum malaria. Patients received DP orally for 3 days together with primaquine 0.25 mg/kg on admission. Parasite clearance half-lives based on 6 hourly blood smears, and day 42 therapeutic responses were assessed as well as parasite K13 genotypes. RESULTS: Median parasite clearance half-life was prolonged, and clearance half-life was greater than 5 h in 21% of patients. Delayed parasite clearance was significantly associated with mutations in the propeller region of the parasite k13 gene. The k13 F446I mutation was found in 25.4% of infections and was associated with a median clearance half-life of 4.7 h compared with 2.7 h for infections without k13 mutations (p < 0.001). There were no failures after 42 days of follow-up, although 18% of patients had persistent parasitaemia on day 3. CONCLUSION: The dominant k13 mutation observed in Upper Myanmar, F446I, appears to be associated with an intermediate rate of parasite clearance compared to other common mutations described elsewhere in the Greater Mekong Subregion. Discerning this phenotype requires relatively detailed clearance measurements, highlighting the importance of methodology in assessing artemisinin resistance.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Resistência a Medicamentos , Malária Falciparum/tratamento farmacológico , Parasitemia/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Mianmar , Parasitemia/parasitologia , Estudos Prospectivos , Proteínas de Protozoários/genética , Quinolinas/uso terapêutico , Adulto Jovem
11.
Malar J ; 14: 520, 2015 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-26701778

RESUMO

BACKGROUND: Highly sensitive, scalable diagnostic methods are needed to guide malaria elimination interventions. While traditional microscopy and rapid diagnostic tests (RDTs) are suitable for the diagnosis of symptomatic malaria infection, more sensitive tests are needed to screen for low-density, asymptomatic infections that are targeted by interventions aiming to eliminate the entire reservoir of malaria infection in humans. METHODS: A reverse transcription polymerase chain reaction (RT- PCR) was developed for multiplexed detection of the 18S ribosomal RNA gene and ribosomal RNA of Plasmodium falciparum and Plasmodium vivax. Simulated field samples stored for 14 days with sample preservation buffer were used to assess the analytical sensitivity and specificity. Additionally, 1750 field samples from Southeastern Myanmar were tested both by RDT and ultrasensitive RT-PCR. RESULTS: Limits of detection (LoD) were determined under simulated field conditions. When 0.3 mL blood samples were stored for 14 days at 28 °C and 80% humidity, the LoD was less than 16 parasites/mL for P. falciparum and 19.7 copies/µL for P. vivax (using a plasmid surrogate), about 10,000-fold lower than RDTs. Of the 1739 samples successfully evaluated by both ultrasensitive RT-PCR and RDT, only two were RDT positive while 24 were positive for P. falciparum, 108 were positive for P. vivax, and 127 were positive for either P. vivax and/or P. falciparum using ultrasensitive RT-PCR. CONCLUSIONS: This ultrasensitive RT-PCR method is a robust, field-tested screening method that is vastly more sensitive than RDTs. Further optimization may result in a truly scalable tool suitable for widespread surveillance of low-level asymptomatic P. falciparum and P. vivax parasitaemia.


Assuntos
Infecções Assintomáticas , Sangue/parasitologia , Malária Falciparum/diagnóstico , Malária Vivax/diagnóstico , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , DNA de Protozoário/genética , DNA Ribossômico/genética , Humanos , Mianmar , Plasmodium falciparum/genética , Plasmodium vivax/genética , RNA de Protozoário/genética , RNA Ribossômico 18S/genética , Sensibilidade e Especificidade
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