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Publication Open Access Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker.(2015-04) Tun, Kyaw M; Mallika Imwong; มัลลิกา อิ่มวงศ์; Lwin, Khin M; Win, Aye A; Hlaing, Tin M; Hlaing, Thaung; Lin, Khin; Kyaw, Myat P; Plewes, Katherine; Faiz, M Abul; Dhorda, Mehul; Cheah, Phaik Yeong; Sasithon Pukrittayakamee; ศศิธร ผู้กฤตยาคามี; Ashley, Elizabeth A; Anderson, Tim J C; Nair, Shalini; McDew-White, Marina; Flegg, Jennifer A; Grist, Eric P M; Guerin, Philippe; Maude, Richard J; Smithuis, Frank; Dondorp, Arjen M; Day, Nicholas P J; Nosten, François; White, Nicholas J; Woodrow, Charles J; Mallika Imwong; Mahidol University. Faculty of Tropical Medicine. Department of Molecular Tropical Medicine and Genetics.; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Shoklo Malaria Research Unit.; Mahidol University. Faculty of Tropical Medicine.; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit.BACKGROUND: Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations. METHODS: We did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar. FINDINGS: Overall, 371 (39%) of 940 samples carried a K13-propeller mutation. We recorded 26 different mutations, including nine mutations not described previously in southeast Asia. In seven (70%) of the ten administrative regions of Myanmar, the combined K13-mutation prevalence was more than 20%. Geospatial mapping showed that the overall prevalence of K13 mutations exceeded 10% in much of the east and north of the country. In Homalin, Sagaing Region, 25 km from the Indian border, 21 (47%) of 45 parasite samples carried K13-propeller mutations. INTERPRETATION: Artemisinin resistance extends across much of Myanmar. We recorded P falciparum parasites carrying K13-propeller mutations at high prevalence next to the northwestern border with India. Appropriate therapeutic regimens should be tested urgently and implemented comprehensively if spread of artemisinin resistance to other regions is to be avoided. FUNDING: Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme and the Bill & Melinda Gates Foundation.Publication Open Access Prevalence of Vitamin D insufficiency and low bone mineral density in elderly Thai nursing home residents(2012) Anuk Kruavit; La-or Chailurkit; Ammarin Thakkinstian; Chutintorn Sriphrapradang; Rajata Rajatanavin; Mahidol University. Faculty of Medicine Ramathibodi Hospital. Department of MedicineBackground: Numerous emerging data from research on osteoporosis among Asians found differences from Caucasians. Therefore, the aim of this study was to determine the prevalence of vitamin D insufficiency and osteoporosis in elderly participants from two nursing homes in Thailand, a country located near the equator. Methods: The subjects of this cross-sectional study comprised 93 elderly Thai women who were living in institutional long-term nursing homes for the aged. Demographic data, daily food and calcium intake, physical activity, and sunlight exposure were measured. Lumbar spine and femoral neck bone mineral density (BMD) and biochemical levels including serum 25 hydroxyvitamin D [25(OH)D] and bone turnover markers were assessed. Vitamin D insufficiency was defined as 25(OH)D level < 70 nmol/l. Results: The mean age of subjects was 75.2 ± 6.0 (SD) years. Dietary calcium intake was low (322 ± 158 mg/day) The mean 25(OH)D level was 64.3 ± 14.9 nmol/L and the prevalence of vitamin D insufficiency was 38.7% (95% CI: 28.8%, 49.4%). There was no correlation between serum 25(OH)D concentrations and age (r = −.11, p = 0.3). The mean BMD of lumbar spine and femoral neck were 0.92 ± 0.19 and 0.65 ± 0.10 g/cm2, respectively. Nearly a half of the subjects had osteopenia (44.1%, 95% CI: 33.8%, 54.8%) and osteoporosis (47.3%, 95% CI: 36.9%, 57.9%). Circulating C-terminal telopeptide of type I collagen (CTx) level correlated significantly with both lumbar spine (r = −0.26, p = 0.01) and femoral neck BMD (r = −0.25, p = 0.02). Conclusions: More than one-third of Thai elderly women residing in nursing homes had vitamin D insufficiency. Almost all nursing home residents had osteoporosis and/or osteopenia.Publication Open Access การปนเปื้อนของโลหะหนัก โครเมียม แคดเมียม ตะกั่ว ปรอท และสารหนู ในโซ่อีลาสโตเมอร์จัดฟัน(2012-01) ฤดี สุราฤทธิ์; Rudee Surarit; วิทยา วสุเมธารัศมี; Witthaya Wasumaetharatsamee; สมพร เรืองผกา; Somporn Raungpaka; พาสน์ศิริ นิสาลักษณ์; Passiri Nisalak; ภูมิภดา จาวจักรศิริ; Poompada Jaochakarasiri; ฤดี สุราฤทธิ์; Rudee Surarit; มหาวิทยาลัยมหิดล. คณะทันตแพทยศาสตร์. ภาควิชาชีววิทยาช่องปาก; มหาวิทยาลัยมหิดล. คณะทันตแพทยศาสตร์. สาขาทันตกรรมจัดฟัน; มหาวิทยาลัยมหิดล. คณะทันตแพทยศาสตร์. ภาควิชาทันตกรรมจัดฟันวัตุประสงค์: เพื่อหาโลหะหนักได้แก่ แคดเมียม โครเมียม ตะกั่ว ปรอท และสารหนู ที่อาจปนเปื้อนหรือปลดปล่อยจากโซ่อีลาสโตเมอร์ ที่ใช้สำหรับการจัดฟัน วัสดุอุปกรณ์และวิธีการศึกษา: ตัวอย่างที่ใช้ในการศึกษานี้คือโซ่อีลาสโตเมอร์ โครงรูปเปิด 3 สี (สีใส สีเหลือง และสีชมพู) ยี่ห้อ Dynaflex (Dynaflex Company, St Louis, MO, USA) และ Chuang Xin Power chain (PR China) ในการศึกษานี้แบ่งออกเป็น 2 ส่วน คือ ส่วนแรก เป็นการหาปริมาณโลหะหนักที่ปล่อยออกมาจาก โซ่อีลาสโตเมอร์ นำโซ่อีลาสโตเมอร์จำนวน 40 วง มาตัดและแช่ในน้ำลายเทียมเป็นเวลา 28 วัน ทึกตัวอย่างจะผ่านกระบวนการวัฏจักรพีเอช และวัฏจักรความร้อน เพื่อจำลองสภาพให้เสมือนอยู่ในช่องปากเป็นเวลา 28 วัน หลังจากกระบวนการสิ้นสุด นำน้ำลายเทียมไปตรวจหาโลหะหนัก (แคดเมียม, โครเมียม, ตะกั่ว, ปรอท และสารหนู) ด้วยเครื่องอะตอมมิกแอบซอร์บชั่นสเปคโตรโฟโตมิเตอร์ ส่วนที่ 2 เป็นการวิเคราะห์หาปริฒาณโลหะหนักที่เป็นส่วนประกอบในโซ่อีลาสโตเมอร์ โดยวิธีการเผาโดยตรงในเครื่องเฟลมอะตอมมิกแอบซอร์บชั่น สเปคโตร โฟโตมิเตอร์เพื่อดูการปนเปื้อนของโลหะหนัก ตามวิธีมาตรฐานของสมาคมวิชาชีพสหรัฐอเมริกาเพื่อทดสอบและวัสดุ ASTMD4045-06 ผลการศึกษา: พบว่าไม่มีโลหะหนักปลดปล่อยออกมาจากโซ่อีลาสโตเมอร์ จักฟันทั้งสองยี่ห้อในช่วงเวลาทดสอบ 28 วัน โซ่อีลาสโตเมอร์สีใสของทั้ง 2 ยี่ห้อมีปริมาณ แคดเมียม และ ตะกั่ว มากที่สุดในจำนวน 3 สีที่ทำการทดลองปริมาณโลหะหนักที่พบอยู่ในระดับต่ำกว่าที่เสนอแนะไว้โดยองค์กรอนามัยโลกและองค์การอาหารและยา บทสรุป: โซ่อีลาสโตเมอร์จัดฟันของทั้งสองบริษัท คือ Dynaflex และ Chuang Xin Power chain ทั้ง 3 สี มีปริมาณโลหะหนักในระดับต่ำกว่าระดับความปลอดภัย ที่เสนอแนะไว้โดยองค์กรอนามัยโลกและองค์การอาหารและยาPublication Open Access Parasite clearance rates in Upper Myanmar indicate a distinctive artemisinin resistance phenotype: a therapeutic efficacy study(2016) Tun, Kyaw Myo; Atthanee Jeeyapant; Mallika Imwong; Min Thein; Sai Soe Moe Aung; Hlaing, Tin Maung; Prayoon Yuentrakul; Cholrawee Promnarate; Mehul Dhorda; Woodrow, Charles J.; Dondorp, Arjen M.; Ashley, Elizabeth A.; Smithuis, Frank M.; White, Nicholas J.; Day, Nicholas P. J.; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research UnitBackground: 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 halflife 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.Publication Open Access Effect of sex, age and strain on hematological and blood clinical chemistry in healthy canine(2012) Arunee Jangsangthong; Pongpun Suwanachat; Pariyakorn Jaykum; Supakit Buamas; Waraporn Kaewkongjan; Shutipen Buranasinsup; Mahidol University. Faculty of Veterinary Science. Department of Pre-clinic and Applied Animal Science; Mahidol University. Faculty of Veterinay Science. Laboratory of Prasuarthon hospitalThe hematological and blood clinical chemistry are essential for determine the physical health, diagnosis and prognosis of the disease. However, they may vary with race, nutrition, age, sex, stress and disease. The aim of the present study was to investigatethe effect of sex, age and strain on the hematology and blood clinical chemistry. Canines (n=134)were divided into 5 groups depend on age, 2 groups depend on sex and 4 groups depend on strain. The effect of age was found onmonocytes, neutrophils, hematocrit (Hct), plasma protein (PP) and alanine aminotransferase (ALT) values whilethe effect of sex was found onmean corpuscular hemoglobin concentration (MCHC) and ALT values. In addition, the effect of strain was found onmany parameters including neutrophils, lymphocytes, hemoglobin (Hb), Hct, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), MCHC, platelet (Plt), red cell distribution width (RDW), ALT and blood urea nitrogen (BUN). In conclusion, hematological and blood clinical chemistry in canine which are essential for determine the physical health and for further diagnosis as well as prognosis the disease are influenced by many parameters studied such as sex, age and strain.Publication Open Access Investigations on anopheline mosquitoes close to the nest sites of chimpanzees subject to malaria infection in Ugandan highlands(2012-04-17) Krief, Sabrina; Levrero, Florence; Krief, Jean-Michel; Supinya Thanapongpichat; สุภิญญา ธนาพงษ์ภิชาติ; Mallika Imwong; มัลลิกา อิ่มวงศ์; Snounou, Georges; Kasenene, John M.; Cibot, Marie; Gantier, Jean-Charles; Krief, Sabrina; Mahidol University. Faculty of Tropical MedicineBACKGROUND: Malaria parasites (Plasmodium sp.), including new species, have recently been discovered as low grade mixed infections in three wild chimpanzees (Pan troglodytes schweinfurthii) sampled randomly in Kibale National Park, Uganda. This suggested a high prevalence of malaria infection in this community. The clinical course of malaria in chimpanzees and the species of the vectors that transmit their parasites are not known. The fact that these apes display a specific behaviour in which they consume plant parts of low nutritional value but that contain compounds with anti-malarial properties suggests that the apes health might be affected by the parasite. The avoidance of the night-biting anopheline mosquitoes is another potential behavioural adaptation that would lead to a decrease in the number of infectious bites and consequently malaria. METHODS: Mosquitoes were collected over two years using suction-light traps and yeast-generated CO(2) traps at the nesting and the feeding sites of two chimpanzee communities in Kibale National Park. The species of the female Anopheles caught were then determined and the presence of Plasmodium was sought in these insects by PCR amplification. RESULTS: The mosquito catches yielded a total of 309 female Anopheles specimens, the only known vectors of malaria parasites of mammalians. These specimens belonged to 10 species, of which Anopheles implexus, Anopheles vinckei and Anopheles demeilloni dominated. Sensitive DNA amplification techniques failed to detect any Plasmodium-positive Anopheles specimens. Humidity and trap height influenced the Anopheles capture success, and there was a negative correlation between nest numbers and mosquito abundance. The anopheline mosquitoes were also less diverse and numerous in sites where chimpanzees were nesting as compared to those where they were feeding. CONCLUSIONS: These observations suggest that the sites where chimpanzees build their nests every night might be selected, at least in part, in order to minimize contact with anopheline mosquitoes, which might lead to a reduced risk in acquiring malaria infections.