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Publication Open Access Artemisinin resistance containment project in Thailand. (I): Implementation of electronic-based malaria information system for early case detection and individual case management in provinces along the Thai-Cambodian border(2012-07-29) Amnat Khamsiriwatchara; Prayuth Sudathip; Surasak Sawang; Saowanit Vijakadge; Thanapon Potithavoranan; Aumnuyphan Sangvichean; Wichai Satimai; Delacollette, Charles; Pratap Singhasivanon; ประตาป สิงหศิวานนท์; Saranath Lawpoolsri; สารนาถ ล้อพูลศรี; Jaranit Kaewkungwal; จรณิต แก้วกังวาล; Jaranit Kaewkungwal; Mahidol University. Faculty of Tropical Medicine. Department of Tropical Hygiene; Mahidol University. Faculty of Tropical Medicine. Center of Excellence for Biomedical and Public Health Informatics.infections. The eMIS was designed as an evidence-based and near real-time system to capture data for early case detection, intensive case investigation, monitoring drug compliance and on/off-site tracking of malarial patients, as well as collecting dataPublication Open Access Application of smart phone in "Better Border Healthcare Program": a module for mother and child care(2010-11) Jaranit Kaewkungwal; จรณิต แก้วกังวาล; Pratap Singhasivanon; ประตาป สิงหศิวานนท์; Amnat Khamsiriwatchara; อำนาจ คำศิริวัชรา; Surasak Sawang; Pongthep Meankaew; พงษ์เทพ เมียนแก้ว; Apisit Wechsart; Jaranit Kaewkungwal; Mahidol University. Faculty of Tropical Mediicine. Department of Tropical HygieneBACKGROUND: To assess the application of cell phone integrating into the healthcare system to improve antenatal care (ANC) and expanded programme on immunization (EPI) services for the under-served population in border area. METHODS: A module combining web-based and mobile technology was developed to generate ANC/EPI visit schedule dates in which the healthcare personnel can cross-check, identify and update the mother's ANC and child's EPI status at the healthcare facility or at the household location when performing home visit; with additional feature of sending appointment reminder directly to the scheduled mother in the community. RESULTS: The module improved ANC/EPI coverage in the study area along the country border including for both Thai and non-Thai mothers and children who were either permanent resident or migrants; numbers of ANC and EPI visit on-time as per schedule significantly increased; there was less delay of antenatal visits and immunizations. CONCLUSIONS: The module integrated and functioned successfully as part of the healthcare system; it is proved for its feasibility and the extent to which community healthcare personnel in the low resource setting could efficiently utilize it to perform their duties.Publication Open Access Application of mobile-technology for disease and treatment monitoring of malaria in the "Better Border Healthcare Programme"(2010-08) Pongthep Meankaew; พงษ์เทพ เมียนแก้ว; Jaranit Kaewkungwal; จรณิต แก้วกังวาล; Amnat Khamsiriwatchara; อำนาจ คำศิริวัชรา; Podjadeach Khunthong; พจเดช ขุนทอง; Pratap Singhasivanon; ประตาป สิงหศิวานนท์; Wichai Satimai; Jaranit Kaewkungwal; Mahidol University. Faculty of Tropical Medicine. Department of Tropical HygieneBACKGROUND: The main objective of this study was to assess the effectiveness of integrating the use of cell-phones into a routine malaria prevention and control programme, to improve the management of malaria cases among an under-served population in a border area. The module for disease and treatment monitoring of malaria (DTMM) consisted of case investigation and case follow-up for treatment compliance and patients' symptoms. METHODS: The module combining web-based and mobile technologies was developed as a proof of concept, in an attempt to replace the existing manual, paper-based activities that malaria staff used in treating and caring for malaria patients in the villages for which they were responsible. After a patient was detected and registered onto the system, case-investigation and treatment details were recorded into the malaria database. A follow-up schedule was generated, and the patient's status was updated when the malaria staff conducted their routine home visits, using mobile phones loaded with the follow-up application module. The module also generated text and graph messages for a summary of malaria cases and basic statistics, and automatically fed to predetermined malaria personnel for situation analysis. Following standard public-health practices, access to the patient database was strictly limited to authorized personnel in charge of patient case management. RESULTS: The DTMM module was developed and implemented at the trial site in late November 2008, and was fully functioning in 2009. The system captured 534 malaria patients in 2009. Compared to paper-based data in 2004-2008, the mobile-phone-based case follow-up rates by malaria staff improved significantly. The follow-up rates for both Thai and migrant patients were about 94-99% on Day 7 (Plasmodium falciparum) and Day 14 (Plasmodium vivax) and maintained at 84-93% on Day 90. Adherence to anti-malarial drug therapy, based on self-reporting, showed high completion rate for P. falciparum-infected cases, but lower rate for P. vivax cases. Patients' symptoms were captured onto the mobile phone during each follow-up visit, either during the home visit or at Malaria Clinic; most patients had headache, muscle pain, and fatigue, and some had fever within the first follow-up day (day 7/14) after the first anti-malarial drug dose. CONCLUSIONS: The module was successfully integrated and functioned as part of the malaria prevention and control programme. Despite the bias inherent in sensitizing malaria workers to perform active case follow-up using the mobile device, the study proved for its feasibility and the extent to which community healthcare personnel in the low resource settings could potentially utilize it efficiently to perform routine duties, even in remote areas. The DTMM has been modified and is currently functioning in seven provinces in a project supported by the WHO and the Bill & Melinda Gates Foundation, to contain multi-drug resistant malaria on the Thai-Cambodian border.Publication Open Access The impact of human reservoir of malaria at a community-level on individual malaria occurrence in a low malaria transmission setting along the Thai-Myanmar border(2010-05) Saranath Lawpoolsri; สารนาถ ล้อพูลศรี; Chavez, Irwin F.; Surapon Yimsamran; สุรพล ยิ้มสำราญ; Supalap Puangsa-art; สุภลาภ พวงสอาด; Nipon Thanyavanich; นิพนธ์ ธัญญวานิช; Wanchai Maneeboonyang; Wuthichai Chaimungkun; Pratap Singhasivanon; ประตาป สิงหศิวานนท์; Maguire, James H.; Hungerford, Laura L.; Saranath Lawpoolsri; Mahidol University. Faculty of Tropical Medicine. Department of Tropical HygieneBACKGROUND: The probability of contracting malaria in a given individual is determined not only by the individual's characteristics, but also the ecological factors that characterize the level of human-vector contact in the population. Examination of the relationship between "individual" and "supra-individual" variables over time is important for understanding the local malaria epidemiology. This is essential for planning effective intervention strategies specifically for each location. METHODS: A retrospective cohort study was conducted, which followed a community-cohort of about 3,500 residents in seven hamlets along the Thai-Myanmar border between 1999 and 2006. Potential malaria determinants measured at different levels (temporal variables, individual variables, and hamlet variables) were incorporated into multilevel models to estimate their effects on an individual's risk of malaria attack. RESULTS: The monthly minimum temperature was significantly associated with the seasonal variation of malaria risk. An individual risk of malaria attack decreased by about 50% during the period that active surveillance was conducted; an additional 15% and 25% reduction of Plasmodium falciparum and Plasmodium vivax incidence, respectively, was observed after the use of artesunate-mefloquine combination therapy (ACT) for treatment of P. falciparum. Male children (age < 16 years old) were at highest risk of both P. falciparum and P. vivax attack. An increase in the hamlet's incidence of P. falciparum and P. vivax by 1 per 100 persons in a previous month resulted in 1.14 and 1.34 times increase in the risk of P. falciparum and P. vivax, respectively, among individuals in a particular hamlet. CONCLUSION: In a small area with low malaria transmission intensity, the variation in mosquito abundance is relatively similar across the residential areas; incidence of malaria between hamlets, which reflects the community level of human infectious reservoirs, is an important predictor for the malaria risk among individuals within these hamlets. Therefore, local malaria control strategies should focus on interventions that aim to reduce the gametocyte carriage in the population, such as early detection and treatment programmes and the use of ACT for P. falciparum.Publication Open Access The effects of serum lipids on the in vitro activity of lumefantrine and atovaquone against Plasmodium falciparum(2012-05-28) Kesinee Chotivanich; เกศินี โชติวานิช; Mathirut Mungthin; มฑิรุทธ มุ่งถิ่น; Ronnatrai Ruengweerayuth; Rachanee Udomsangpetc; รัชนีย์ อุดมแสงเพ็ชร; Dondorp, Arjen M.; Pratap Singhasivanon; ประตาป สิงหศิวานนท์; Sasithon Pukrittayakamee; ศศิธร ผู้กฤตยาคามี; White, Nicholas J.; White, Nicholas J.; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit; Mahidol University. Faculty of Science. Department of PathobiologyBACKGROUND: Lumefantrine and atovaquone are highly lipophilic anti-malarial drugs. As a consequence absorption is increased when the drugs are taken together with a fatty meal, but the free fraction of active drug decreases in the presence of triglyceride-rich plasma lipoproteins. In this study, the consequences of lipidaemia on anti-malarial drug efficacy were assessed in vitro. METHODS: Serum was obtained from non-immune volunteers under fasting conditions and after ingestion of a high fat meal and used in standard Plasmodium falciparum in-vitro susceptibility assays. Anti-malarial drugs, including lumefantrine, atovaquone and chloroquine in five-fold dilutions (range 0.05 ng/ml-1 ug/mL) were diluted in culture medium supplemented with fasting or post-prandial 10% donor serum. The in-vitro drug susceptibility of parasite isolates was determined using the ³H-hypoxanthine uptake inhibition method and expressed as the concentration which gave 50% inhibition of hypoxanthine uptake (IC₅₀). RESULTS: Doubling plasma triglyceride concentrations (from 160 mg/dL to 320 mg/dL), resulted in an approximate doubling of the IC₅₀ for lumefantrine (191 ng/mL to 465 ng/mL, P < 0.01) and a 20-fold increase in the IC₅₀ for atovaquone (0.5 ng/mL to 12 ng/ml; P < 0.01). In contrast, susceptibility to the hydrophilic anti-malarial chloroquine did not change in relation to triglyceride content of the medium. CONCLUSIONS: Lipidaemia reduces the anti-malarial activity of lipophilic anti-malarial drugs. This is an important confounder in laboratory in vitro testing and it could have therapeutic relevance.Publication Open Access Are there any changes in burden and management of communicable diseases in areas affected by Cyclone Nargis?(2011-06-28) Myint, Nyan Win; Jaranit Kaewkungwal; จรณิต แก้วกังวาล; Pratap Singhasivanon; ประตาป สิงหศิวานนท์; Kamron Chaisiri; Pornpet Panjapiyakul; Pichit Siriwan; Mallik, Arun K.; Nyein, Soe Lwin; Mu, Thet Thet; Jaranit Kaewkungwal; Mahidol University. Faculty of Tropical MedicineBACKGROUND: This study aims to assess the situation of communicable diseases under national surveillance in the Cyclone Nargis-affected areas in Myanmar (Burma) before and after the incident. METHODS: Monthly data during 2007, 2008 and 2009 from the routine reporting system for disease surveillance of the Myanmar Ministry of Health (MMOH) were reviewed and compared with weekly reporting from the Early Warning and Rapid Response (EWAR) system. Data from some UN agencies, NGOs and Tri-Partite Core Group (TCG) periodic reviews were also extracted for comparisons with indicators from Sphere and the Inter-Agency Standing Committee. RESULTS: Compared to 2007 and 2009, large and atypical increases in diarrheal disease and especially dysentery cases occurred in 2008 following Cyclone Nargis. A seasonal increase in ARI reached levels higher than usual in the months of 2008 post-Nargis. The number of malaria cases post-Nargis also increased, but it was less clear if this reflected normal seasonal patterns or was specifically associated with the disaster event. There was no significant change in the occurrence of other communicable diseases in Nargis-affected areas. Except for a small decrease in mortality for diarrheal diseases and ARI in 2008 in Nargis-affected areas, population-based mortality rates for all other communicable diseases showed no significant change in 2008 in these areas, compared to 2007 and 2009. Tuberculosis control programs reached their targets of 70% case detection and 85% treatment success rates in 2007 and 2008. Vaccination coverage rates for DPT 3rd dose and measles remained at high though measles coverage still did not reach the Sphere target of 95% even by 2009. Sanitary latrine coverage in the Nargis-affected area dropped sharply to 50% in the months of 2008 following the incident but then rose to 72% in 2009. CONCLUSION: While the incidence of diarrhea, dysentery and ARI increased post-Nargis in areas affected by the incident, the incidence rate for other diseases and mortality rates did not increase, and normal disease patterns resumed by 2009. This suggests that health services as well as prevention and control measures provided to the Nargis-affected population mitigated what could have been a far more severe health impact.Publication Open Access Auditory assessment of patients with acute uncomplicated Plasmodium falciparum malaria treated with three-day mefloquine-artesunate on the north-western border of Thailand.(2008-11-06) Carrara, Verena I; Phyo, Aung P; Nwee, Paw; Soe, Ma; Htoo, Hsar; Jaruwan Arunkamomkiri; Pratap Singhasivanon; ประตาป สิงหศิวานนท์; Nosten, François; Nosten, François; Mahidol University. Faculty of Tropical Medicine.; Mahidol University. Faculty of Tropical Medicine. Shoklo Malaria Research Unit.BACKGROUND: The use of artemisinin derivatives has increased exponentially with the deployment of artemisinin combination therapy (ACT) in all malarious areas. They are highly effective and are considered safe, but in animal studies artemisinin derivatives produce neurotoxicity targeting mainly the auditory and vestibular pathways. The debate remains as to whether artemisinin derivatives induce similar toxicity in humans. METHODS: This prospective study assessed the effects on auditory function of a standard 3-day oral dose of artesunate (4 mg/kg/day) combined with mefloquine (25 mg/kg) in patients with acute uncomplicated falciparum malaria treated at the Shoklo Malaria Research Unit, on the Thai-Burmese border. A complete auditory evaluation with tympanometry, audiometry and auditory brainstem responses (ABR) was performed before the first dose and seven days after initiation of the antimalarial treatment. RESULTS: Complete auditory tests at day 0 (D0) and day 7 (D7) were obtained for 93 patients. Hearing loss (threshold > 25 dB) on admission was common (57%) and associated with age only. No patient had a threshold change exceeding 10 dB between D0 and D7 at any tested frequency. No patient showed a shift in Wave III peak latency of more than 0.30 msec between baseline and D7. CONCLUSION: Neither audiometric or the ABR tests showed clinical evidence of auditory toxicity seven days after receiving oral artesunate and mefloquine.Publication Open Access A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand(2005-09) Hutagalung, Robert; Paiphun, Lucy; Ashley, Elizabeth A.; McGready, Rose; Brockman, Alan; Thwai, Kaw L.; Pratap Singhasivanon; ประตาป สิงหศิวานนท์; Jelinek, Thomas; White, Nicholas J.; Nosten, François H.; Nosten, François H.; Mahidol University. Faculty of Tropical Medicine.BACKGROUND: The use of antimalarial drug combinations with artemisinin derivatives is recommended to overcome drug resistance in Plasmodium falciparum. The fixed combination of oral artemether-lumefantrine, an artemisinin combination therapy (ACT) is highly effective and well tolerated. It is the only registered fixed combination containing an artemisinin. The trial presented here was conducted to monitor the efficacy of the six-dose regimen of artemether-lumefantrine (ALN) in an area of multi-drug resistance, along the Thai-Myanmar border. METHODS: The trial was an open-label, two-arm, randomized study comparing artemether-lumefantrine and mefloquine-artesunate for the treatment of uncomplicated falciparum malaria with 42 days of follow up. Parasite genotyping by polymerase chain reaction (PCR) was used to distinguish recrudescent from newly acquired P. falciparum infections. The PCR adjusted cure rates were evaluated by survival analysis. RESULTS: In 2001-2002 a total of 490 patients with slide confirmed uncomplicated P. falciparum malaria were randomly assigned to receive artemether-lumefantrine (n = 245) or artesunate and mefloquine (n = 245) and were followed for 42 days. All patients had rapid initial clinical and parasitological responses. In both groups, the PCR adjusted cure rates by day 42 were high: 98.8% (95% CI 96.4, 99.6%) for artemether-lumefantrine and 96.3% (95% CI 93.1, 98.0%) for artesunate-mefloquine. Both regimens were very well tolerated with no serious adverse events observed attributable to either combination. CONCLUSION: Overall, this study confirms that these two artemisinin-based combinations remain highly effective and result in equivalent therapeutic responses in the treatment of highly drug-resistant falciparum malaria.