Publications by authors named "Pratap Singhasivanon"

142 Publications

Dengue viremia kinetics in asymptomatic and symptomatic infection.

Int J Infect Dis 2020 Dec 28;101:90-97. Epub 2020 Sep 28.

Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Electronic address:

Background: Dengue infection is a global health threat. While symptomatic cases contribute to morbidity and mortality, the majority of infected people are asymptomatic but serve as an important reservoir. However, the kinetics of viremia in asymptomatic infections remains unknown.

Methods: We enrolled 279 hospital-based symptomatic index cases and quantified dengue virus (DENV) RNA at enrollment and at the day of defervescence. To identify asymptomatic cases, 175 household members of index cases were monitored for clinical symptoms during follow-up, and blood was taken twice weekly to test for and quantify DENV RNA until cleared.

Results: We detected DENV in thirteen asymptomatic household members (7.43%). Their DENV serotypes were primarily the same as those of their family index cases. The median peak DENV viremia in asymptomatic subjects was lower than that of symptomatic individuals during the febrile phase, and the viral decay rate was slower in asymptomatic infections.

Conclusions: DENV level and kinetics in asymptomatic individuals differed significantly from those of symptomatic cases. Despite the lower viremia, the slower decay rate in asymptomatic infections could lead to their prolonging the infectious reservoir. The improvement of transmission control to prevent such long-lived asymptomatic infections from transmitting the DENV is needed.
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http://dx.doi.org/10.1016/j.ijid.2020.09.1446DOI Listing
December 2020

Combining antimalarial drugs and vaccine for malaria elimination campaigns: a randomized safety and immunogenicity trial of RTS,S/AS01 administered with dihydroartemisinin, piperaquine, and primaquine in healthy Thai adult volunteers.

Hum Vaccin Immunother 2020 15;16(1):33-41. Epub 2019 Aug 15.

Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

: RTS,S/AS01 is currently the most advanced malaria vaccine but provides incomplete, short-term protection. It was developed for use within the expanded program on immunizations (EPI) for African children. Another use could be adding mass RTS,S/AS01 vaccination to the integrated malaria elimination strategy in the Greater Mekong Subregion (GMS), where multidrug-resistant strains have emerged and spread. Prior to evaluating RTS,S/AS01 in large-scale trials we assessed whether the vaccine, administered with and without antimalarial drugs, is safe and immunogenic in Asian populations.: An open-label, randomized, controlled phase 2 trial was conducted in healthy, adult Thai volunteers. Seven vaccine regimens with and without antimalarial drugs (dihydroartemisinin-piperaquine plus a single low dose primaquine) were assessed. Antibody titres against the CSP full-length (NANP) 6, CSP anti-C-term, CSP full-length (N + C-Terminal) were measured by standard enzyme-linked immunosorbent assays. Liquid chromatography was used to measure piperaquine, primaquine and carboxy-primaquine concentrations.: 193 volunteers were enrolled and 186 study participants completed the 6 months follow-up period. One month after the last vaccination all study participants had seroconverted to the CSP (NANP)6, and the CSP Full Length (N + C-Terminal). More than 90% had seroconverted to the anti-C-Term CSP. There was no indication that drug concentrations were influenced by vaccine regimens or the antibody levels by the drug regimens. Adverse events were similarly distributed between the seven treatment groups. No serious adverse events attributable to the study interventions were detected.: This study found that RTS,S/AS01 with and without dihydroartemisinin-piperaquine plus a single low dose primaquine was safe and immunogenic in a healthy, adult Asian population.
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http://dx.doi.org/10.1080/21645515.2019.1643675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012096PMC
August 2019

Sequential Open-Label Study of the Safety, Tolerability, and Pharmacokinetic Interactions between Dihydroartemisinin-Piperaquine and Mefloquine in Healthy Thai Adults.

Antimicrob Agents Chemother 2019 08 25;63(8). Epub 2019 Jul 25.

Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

Artemisinin-based combination therapies (ACTs) have contributed substantially to the global decline in morbidity and mortality, but resistance to artemisinins and their partner drugs is increasing in Southeast Asia, threatening malaria control. New antimalarial compounds will not be generally available soon. Combining three existing antimalarials in the form of triple ACTs, including dihydroartemisinin (DHA)-piperaquine + mefloquine, is a potential treatment option for multidrug-resistant malaria. In a sequential open-label study, healthy Thai volunteers were treated with DHA-piperaquine (120 to 960 mg), mefloquine (500 mg), and DHA-piperaquine + mefloquine (120 to 960 mg + 500 mg), and serial symptom questionnaires, biochemistry, full blood counts, pharmacokinetic profiles, and electrocardiographic measurements were performed. Fifteen healthy subjects were enrolled. There was no difference in the incidence or severity of adverse events between the three treatment arms. The slight prolongation in QTc (QT interval corrected for heart rate) associated with DHA-piperaquine administration did not increase after administration of DHA-piperaquine + mefloquine. The addition of mefloquine had no significant effect on the pharmacokinetic properties of piperaquine. However, coadministration of mefloquine significantly reduced the exposures to dihydroartemisinin for area under the concentration-time curve (-22.6%; 90% confidence interval [CI], -33.1, -10.4;  = 0.0039) and maximum concentration of drug in serum (-29.0%; 90% CI, -40.6, -15.1;  = 0.0079). Mefloquine can be added safely to dihydroartemisinin-piperaquine in malaria treatment. (This study has been registered at ClinicalTrials.gov under identifier NCT02324738.).
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http://dx.doi.org/10.1128/AAC.00060-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658739PMC
August 2019

Highly heterogeneous residual malaria risk in western Thailand.

Int J Parasitol 2019 05 4;49(6):455-462. Epub 2019 Apr 4.

Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Electronic address:

Over the past decades, the malaria burden in Thailand has substantially declined. Most infections now originate from the national border regions. In these areas, the prevalence of asymptomatic infections is still substantial and poses a challenge for the national malaria elimination program. To determine epidemiological parameters as well as risk factors for malaria infection in western Thailand, we carried out a cohort study in Kanchanaburi and Ratchaburi provinces on the Thailand-Myanmar border. Blood samples from 999 local participants were examined for malaria infection every 4 weeks between May 2013 and Jun 2014. Prevalence of Plasmodium falciparum and Plasmodium vivax was determined by quantitative PCR (qPCR) and showed a seasonal variation with values fluctuating from 1.7% to 4.2% for P. vivax and 0% to 1.3% for P. falciparum. Ninety percent of infections were asymptomatic. The annual molecular force of blood-stage infection (FOB) was estimated by microsatellite genotyping to be 0.24 new infections per person-year for P. vivax and 0.02 new infections per person-year for P. falciparum. The distribution of infections was heterogenous, that is, the vast majority of infections (>80%) were found in a small number of individuals (<8% of the study population) who tested positive at multiple timepoints. Significant risk factors were detected for P. vivax infections, including previous clinical malaria, occupation in agriculture and travel to Myanmar. In contrast, indoor residual spraying was associated with a protection from infection. These findings provide a recent landscape of malaria epidemiology and emphasize the importance of novel strategies to target asymptomatic and imported infections.
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http://dx.doi.org/10.1016/j.ijpara.2019.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996282PMC
May 2019

The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: A cluster randomised trial.

PLoS Med 2019 02 15;16(2):e1002745. Epub 2019 Feb 15.

Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Background: The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People's Democratic Republic, where artemisinin resistance is prevalent.

Methods And Findings: After establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention.

Conclusions: Added to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination.

Trial Registration: ClinicalTrials.gov NCT01872702.
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http://dx.doi.org/10.1371/journal.pmed.1002745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377128PMC
February 2019

Neutrophil Activation and Early Features of NET Formation Are Associated With Dengue Virus Infection in Human.

Front Immunol 2018 11;9:3007. Epub 2019 Jan 11.

Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.

The involvement of the immune system in the protection and pathology of natural dengue virus (DENV) has been extensively studied. However, despite studies that have referred to activation of neutrophils in DENV infections, the exact roles of neutrophils remain elusive. Here, we explored the phenotypic and functional responses of neutrophils in a cohort of adult dengue patients. Results indicated that during an acute DENV infection, neutrophils up-regulate CD66b expression, and produce a more robust respiratory response as compared with that in convalescent or healthy individuals; this confirmed neutrophil activation during DENV infection. Spontaneous decondensation of nuclei, an early event of neutrophil extracellular trap (NET) formation, was also markedly increased in cells isolated from DENV-infected patients during the acute phase of the infection. incubation of NETs with DENV-2 virus significantly decreased DENV infectivity. Interestingly, increased levels of NET components were found in the serum of patients with more severe disease form-dengue hemorrhagic fever (DHF), but not uncomplicated dengue fever, during the acute phase of the infection. Levels of pro-inflammatory cytokines IL-8 and TNFα were also increased in DHF patients as compared with those in healthy and DF subjects. This suggested that NETs may play dual roles during DENV infection. The increased ability for NET formation during acute DENV infection appeared to be independent of PAD4-mediated histone H3 hyper-citrullination. Our study suggests that neutrophils are involved in immunological responses to DENV infection.
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http://dx.doi.org/10.3389/fimmu.2018.03007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336714PMC
October 2019

The dynamic of asymptomatic Plasmodium falciparum infections following mass drug administrations with dihydroarteminisin-piperaquine plus a single low dose of primaquine in Savannakhet Province, Laos.

Malar J 2018 Nov 3;17(1):405. Epub 2018 Nov 3.

Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Background: The increase in multidrug resistant Plasmodium falciparum infections threatens the malaria elimination goals in countries within the Greater Mekong Sub-region. A multi-pronged approach assuring access to basic malaria control measures, including insecticide-treated bed nets and early diagnosis and treatment was followed by mass drug administrations (MDA) in southern Savannakhet Province, Laos. The main objective of this study was to evaluate the effectiveness and safety of mass drug administrations as well as their effects on the dynamic of asymptomatic P. falciparum infections in 4 malaria endemic villages.

Methods: Two villages were randomized to early MDA consisting of 3 rounds of a 3-day course of dihydroartemisinin-piperaquine with a single low dose of primaquine. In the other 2 villages MDA was deferred by 1 year. A total of 1036 residents were enrolled in early MDA villages and 883 in control villages (deferred-MDA). Tri-monthly parasitaemia surveys using uPCR were conducted for a year in the 4 villages.

Results: Eighty-four percent (872/1036) of the residents participated in the MDAs, of whom 90% (781/872) completed 3 rounds of MDA (9 doses). In intervention villages, the prevalence of asymptomatic P. falciparum infections decreased by 85% after MDA from 4.8% (95% CI 3.4-6.4) at baseline (month 0 or M0) to 0.7% (95% CI 0.3-1.6) at month 12. In control villages there was a decrease of 33% in P. falciparum prevalence between M0: 17.5% (95% CI 15.9-20.3) and M12: 11.6% (95% CI 9.3-14.2). In bivariate and multivariate analyses P. falciparum infections were significantly reduced with early MDA (adjusted incidence rate ratios (AIRR): 0.08, CI 0.01-0.091) and completion of 3 MDA rounds (AIRR: 0.06; CI 0.01-0.66). A quarter of participants (226/872) reported adverse events of which 99% were mild.

Conclusion: The study found a significant reduction in P. falciparum prevalence and incidence following MDA. MDA was safe, well tolerated, feasible, and achieved high population coverage and adherence. MDAs must be integrated in multi-pronged approaches such as vector control and preventive measures with a focus on specific risk groups such as mobile, migrant population and forest goers for a sustained period to eliminate the remaining parasite reservoirs. Trial registration ClinicalTrials.gov Identifier: NCT01872702.
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http://dx.doi.org/10.1186/s12936-018-2541-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215638PMC
November 2018

Evaluation of the GeneXpert MTB/RIF in patients with presumptive tuberculous meningitis.

PLoS One 2018 18;13(6):e0198695. Epub 2018 Jun 18.

Department of Neurology, University of Washington, Seattle, Washington, United States of America.

Background: Meningitis caused by Mycobacterium tuberculosis is a major cause of morbidity and mortality worldwide. We evaluated the performance of cerebrospinal fluid (CSF) testing with the GeneXpert MTB/RIF assay versus traditional approaches for diagnosing tuberculosis meningitis (TBM).

Methods: Patients were adults (n = 37) presenting with suspected TBM to the Hospital Nacional Dos de Mayo, Lima, Peru, during 12 months until 1st January 2015. Each participant had a single CSF specimen that was divided into aliquots that were concurrently tested for M. tuberculosis using GeneXpert, Ziehl-Neelsen smear and culture on solid and liquid media. Drug susceptibility testing used Mycobacteria Growth Indicator Tube (MGIT 960) and the proportions method.

Results: 81% (30/37) of patients received a final clinical diagnosis of TBM, of whom 63% (19/30, 95% confidence intervals, CI: 44-80%) were HIV-positive. 22% (8/37, 95%CI: 9.8-38%), of patients had definite TBM. Because definite TBM was defined by positivity in any laboratory test, all laboratory tests had 100% specificity. Considering the 30 patients who had a clinical diagnosis of TBM: diagnostic sensitivity was 23% (7/30, 95%CI: 9.9-42%) for GeneXpert and was the same for all culture results combined; considerably greater than 7% (2/30, 95%CI: 0.82-22%) for microscopy; whereas all laboratory tests had poor negative predictive values (20-23%). Considering only the 8 patients with definite TBM: diagnostic sensitivity was 88% (7/8, 95%CI: 47-100%) for GeneXpert; 75% (6/8, 95%CI: 35-97%) for MGIT culture or LJ culture; 50% (4/8, 95%CI 16-84) for Ogawa culture and 25% (2/8, 95%CI: 3.2-65%) for microscopy. GeneXpert and microscopy provided same-day results, whereas culture took 20-56 days. GeneXpert provided same-day rifampicin-susceptibility results, whereas culture-based testing took 32-71 days. 38% (3/8, 95%CI: 8.5-76%) of patients with definite TBM with data had evidence of drug-resistant TB, but 73% (22/30) of all clinically diagnosed TBM (definite, probable, and possible TBM) had no drug-susceptibility results available.

Conclusions: Compared with traditional culture-based methods of CSF testing, GeneXpert had similar yield and faster results for both the detection of M. tuberculosis and drug-susceptibility testing. Including use of the GeneXpert has the capacity to improve the diagnosis of TBM cases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198695PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005529PMC
January 2019

Women's Perceptions of Using Mobile Phones for Maternal and Child Health Support in Afghanistan: Cross-Sectional Survey.

JMIR Mhealth Uhealth 2018 Apr 10;6(4):e76. Epub 2018 Apr 10.

Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Background: Growing rates of global mobile subscriptions pave the way for implementation of mobile health (mHealth) initiatives, especially among hard-to-reach populations.

Objective: This study aimed to determine the perceptions of Afghan women regarding the use of mobile phones for maternal and child health services.

Methods: A cross-sectional survey was conducted in both rural and urban districts of Nangarhar Province, Afghanistan. The interviewer-administered questionnaire was used to assess participants' demographic profile, mobile phone usage, and perception of respondents toward different aspects of health care delivery via mobile phones.

Results: Of the 240 participants, 142 (59.2%) owned mobile phones and 220 (91.7%) routinely used mobile phones. Approximately 209 (87.1%) of participants were willing to receive health messages via a mobile phone. Automated voice call was the most preferred method for sending health messages. More than 90% of the women reported that they would like to receive reminders for their children's vaccinations and antenatal care visits.

Conclusions: Users' perception was associated with mobile phone ownership, literacy level, and experience using mobile phones. In the study area, where the literacy rate is low, mHealth was well perceived.
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http://dx.doi.org/10.2196/mhealth.9504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915672PMC
April 2018

Primaquine Pharmacokinetics in Lactating Women and Breastfed Infant Exposures.

Clin Infect Dis 2018 09;67(7):1000-1007

Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot.

Background: Primaquine is the only drug providing radical cure of Plasmodium vivax malaria. It is not recommended for breastfeeding women as it causes hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals, and breast milk excretion and thus infant exposure are not known.

Methods: Healthy G6PD-normal breastfeeding women with previous P. vivax infection and their healthy G6PD-normal infants between 28 days and 2 years old were enrolled. Mothers took primaquine 0.5 mg/kg/day for 14 days. Primaquine and carboxyprimaquine concentrations were measured in maternal venous plasma, capillary plasma, and breast milk samples and infant capillary plasma samples taken on days 0, 3, 7, and 13.

Results: In 20 mother-infant pairs, primaquine concentrations were below measurement thresholds in all but 1 infant capillary plasma sample (that contained primaquine 2.6 ng/mL), and carboxyprimaquine was likewise unmeasurable in the majority of infant samples (maximum value 25.8 ng/mL). The estimated primaquine dose received by infants, based on measured breast milk levels, was 2.98 µg/kg/day (ie, ~0.6% of a hypothetical infant daily dose of 0.5 mg/kg). There was no evidence of drug-related hemolysis in the infants. Maternal levels were comparable to levels in nonlactating patients, and adverse events in mothers were mild.

Conclusions: The concentrations of primaquine in breast milk are very low and therefore very unlikely to cause adverse effects in the breastfeeding infant. Primaquine should not be withheld from mothers breastfeeding infants or young children. More information is needed in neonates.

Clinical Trials Registration: NCT01780753.
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http://dx.doi.org/10.1093/cid/ciy235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137118PMC
September 2018

Spatiotemporal Bayesian networks for malaria prediction.

Artif Intell Med 2018 01 11;84:127-138. Epub 2017 Dec 11.

Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Rd, Bangkok 10400 Thailand.

Targeted intervention and resource allocation are essential for effective malaria control, particularly in remote areas, with predictive models providing important information for decision making. While a diversity of modeling technique have been used to create predictive models of malaria, no work has made use of Bayesian networks. Bayes nets are attractive due to their ability to represent uncertainty, model time lagged and nonlinear relations, and provide explanations. This paper explores the use of Bayesian networks to model malaria, demonstrating the approach by creating village level models with weekly temporal resolution for Tha Song Yang district in northern Thailand. The networks are learned using data on cases and environmental covariates. Three types of networks are explored: networks for numeric prediction, networks for outbreak prediction, and networks that incorporate spatial autocorrelation. Evaluation of the numeric prediction network shows that the Bayes net has prediction accuracy in terms of mean absolute error of about 1.4 cases for 1 week prediction and 1.7 cases for 6 week prediction. The network for outbreak prediction has an ROC AUC above 0.9 for all prediction horizons. Comparison of prediction accuracy of both Bayes nets against several traditional modeling approaches shows the Bayes nets to outperform the other models for longer time horizon prediction of high incidence transmission. To model spread of malaria over space, we elaborate the models with links between the village networks. This results in some very large models which would be far too laborious to build by hand. So we represent the models as collections of probability logic rules and automatically generate the networks. Evaluation of the models shows that the autocorrelation links significantly improve prediction accuracy for some villages in regions of high incidence. We conclude that spatiotemporal Bayesian networks are a highly promising modeling alternative for prediction of malaria and other vector-borne diseases.
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http://dx.doi.org/10.1016/j.artmed.2017.12.002DOI Listing
January 2018

Very high carriage of gametocytes in asymptomatic low-density Plasmodium falciparum and P. vivax infections in western Thailand.

Parasit Vectors 2017 Oct 24;10(1):512. Epub 2017 Oct 24.

Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Background: Low-density asymptomatic infections of Plasmodium spp. are common in low endemicity areas worldwide, but outside Africa, their contribution to malaria transmission is poorly understood. Community-based studies with highly sensitive molecular diagnostics are needed to quantify the asymptomatic reservoir of Plasmodium falciparum and P. vivax infections in Thai communities.

Methods: A cross-sectional survey of 4309 participants was conducted in three endemic areas in Kanchanaburi and Ratchaburi provinces of Thailand in 2012. The presence of P. falciparum and P. vivax parasites was determined using 18S rRNA qPCR. Gametocytes were also detected by pfs25 / pvs25 qRT-PCRs.

Results: A total of 133 individuals were found infected with P. vivax (3.09%), 37 with P. falciparum (0.86%), and 11 with mixed P. vivax/ P. falciparum (0.26%). The clear majority of both P. vivax (91.7%) and P. falciparum (89.8%) infections were not accompanied by any febrile symptoms. Infections with either species were most common in adolescent and adult males. Recent travel to Myanmar was highly associated with P. falciparum (OR = 9.0, P = 0.001) but not P. vivax infections (P = 0.13). A large number of P. vivax (71.5%) and P. falciparum (72.0%) infections were gametocyte positive by pvs25/pfs25 qRT-PCR. Detection of gametocyte-specific pvs25 and pfs25 transcripts was strongly dependent on parasite density. pvs25 transcript numbers, a measure of gametocyte density, were also highly correlated with parasite density (r  = 0.82, P < 0.001).

Conclusions: Asymptomatic infections with Plasmodium spp. were common in western Thai communities in 2012. The high prevalence of gametocytes indicates that these infections may contribute substantially to the maintenance of local malaria transmission.
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http://dx.doi.org/10.1186/s13071-017-2407-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655986PMC
October 2017

Village malaria worker performance key to the elimination of artemisinin-resistant malaria: a Western Cambodia health system assessment.

Malar J 2016 05 20;15(1):282. Epub 2016 May 20.

Division of Tropical Health and Medicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD, 4811, Australia.

Background: Village malaria workers (VMWs) and mobile malaria workers (MMWs) are a critical component of Cambodia's national strategy to eliminate Plasmodium falciparum malaria by 2025. Since 2004, VMWs have been providing malaria diagnosis through the use of rapid diagnostic tests and free-of-charge artemisinin-based combination therapy in villages more than 5 km away from the closest health facility. They have also played a key role in the delivery of behaviour change communication interventions to this target population. This study aimed to assess the job performance of VMWs/MMWs, and identify challenges they face, which may impede elimination efforts.

Methods: A mixed-methods assessment was conducted in five provinces of western Cambodia. One hundred and eighty five VMW/MMW participants were surveyed using a structured questionnaire. Qualitative data was gathered through a total of 60 focus group discussions and 65 in-depth interviews. Data triangulation of the qualitative and quantitative data was used during analysis.

Results: Overall, VMWs/MMWs met or exceeded the expected performance levels (80 %). Nevertheless, some performance gaps were identified. Misconceptions regarding malaria transmission and prevention were found among workers. The recommended approach for malaria treatment, directly-observed treatment (DOT), had low implementation rates. Stock-outs, difficulties in reaching out to migrant and mobile populations, insufficient means of transportation and dwindling worker satisfaction also affected job performance.

Discussion: VMW/MMW job performance must be increased from 80 to 100 % in order to achieve elimination. In order to do this, it is recommended for the national malaria programme to eliminate worker malaria knowledge gaps. Barriers to DOT implementation and health system failures also need to be addressed. The VMW programme should be expanded on several fronts in order to tackle remaining performance gaps. Findings from this evaluation are useful to inform the planning of future activities of the programme and to improve the effectiveness of interventions in a context where artemisinin drug resistance is a significant public health issue.
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http://dx.doi.org/10.1186/s12936-016-1322-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4875644PMC
May 2016

Genetic variations in regions of bovine and bovine-like enteroviral 5'UTR from cattle, Indian bison and goat feces.

Virol J 2016 Jan 25;13:13. Epub 2016 Jan 25.

Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Background: Bovine enteroviruses (BEV) are members of the genus Enterovirus in the family Picornaviridae. They are predominantly isolated from cattle feces, but also are detected in feces of other animals, including goats and deer. These viruses are found in apparently healthy animals, as well as in animals with clinical signs and several studies reported recently suggest a potential role of BEV in causing disease in animals. In this study, we surveyed the presence of BEV in domestic and wild animals in Thailand, and assessed their genetic variability.

Methods: Viral RNA was extracted from fecal samples of cattle, domestic goats, Indian bison (gaurs), and deer. The 5' untranslated region (5'UTR) was amplified by nested reverse transcription-polymerase chain reaction (RT-PCR) with primers specific to BEV 5'UTR. PCR products were sequenced and analyzed phylogenetically using the neighbor-joining algorithm to observe genetic variations in regions of the bovine and bovine-like enteroviral 5'UTR found in this study.

Results: BEV and BEV-like sequences were detected in the fecal samples of cattle (40/60, 67 %), gaurs (3/30, 10 %), and goats (11/46, 24 %). Phylogenetic analyses of the partial 5'UTR sequences indicated that different BEV variants (both EV-E and EV-F species) co-circulated in the domestic cattle, whereas the sequences from gaurs and goats clustered according to the animal species, suggesting that these viruses are host species-specific.

Conclusions: Varieties of BEV and BEV-like 5'UTR sequences were detected in fecal samples from both domestic and wild animals. To our knowledge, this is the first report of the genetic variability of BEV in Thailand.
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http://dx.doi.org/10.1186/s12985-016-0468-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727389PMC
January 2016

Numerical Distributions of Parasite Densities During Asymptomatic Malaria.

J Infect Dis 2016 Apr 17;213(8):1322-9. Epub 2015 Dec 17.

Mahidol Oxford Research Unit Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford.

Background: Asymptomatic parasitemia is common even in areas of low seasonal malaria transmission, but the true proportion of the population infected has not been estimated previously because of the limited sensitivity of available detection methods.

Methods: Cross-sectional malaria surveys were conducted in areas of low seasonal transmission along the border between eastern Myanmar and northwestern Thailand and in western Cambodia. DNA was quantitated by an ultrasensitive polymerase chain reaction (uPCR) assay (limit of accurate detection, 22 parasites/mL) to characterize parasite density distributions for Plasmodium falciparum and Plasmodium vivax, and the proportions of undetected infections were imputed.

Results: The prevalence of asymptomatic malaria as determined by uPCR was 27.5% (1303 of 4740 people tested). Both P. vivax and P. falciparum density distributions were unimodal and log normal, with modal values well within the quantifiable range. The estimated proportions of all parasitemic individuals identified by uPCR were >70% among individuals infected with P. falciparum and >85% among those infected with P. vivax. Overall, 83% of infections were predicted to be P. vivax infections, 13% were predicted to be P. falciparum infections, and 4% were predicted to be mixed infections. Geometric mean parasite densities were similar; 5601 P. vivax parasites/mL and 5158 P. falciparum parasites/mL.

Conclusions: This uPCR method identified most infected individuals in malaria-endemic areas. Malaria parasitemia persists in humans at levels that optimize the probability of generating transmissible gametocyte densities without causing illness.
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http://dx.doi.org/10.1093/infdis/jiv596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799672PMC
April 2016

Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR) Variants in a Thai Population.

PLoS One 2015 14;10(12):e0144555. Epub 2015 Dec 14.

Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.

Pyruvate kinase (PKLR) is a critical erythrocyte enzyme that is required for glycolysis and production of ATP. We have shown that Pklr deficiency in mice reduces the severity (reduced parasitemia, increased survival) of blood stage malaria induced by infection with Plasmodium chabaudi AS. Likewise, studies in human erythrocytes infected ex vivo with P. falciparum show that presence of host PK-deficiency alleles reduces infection phenotypes. We have characterized the genetic diversity of the PKLR gene, including haplotype structure and presence of rare coding variants in two populations from malaria endemic areas of Thailand and Senegal. We investigated the effect of PKLR genotypes on rich longitudinal datasets including haematological and malaria-associated phenotypes. A coding and possibly damaging variant (R41Q) was identified in the Thai population with a minor allele frequency of ~4.7%. Arginine 41 (R41) is highly conserved in the pyruvate kinase family and its substitution to Glutamine (R41Q) affects protein stability. Heterozygosity for R41Q is shown to be associated with a significant reduction in the number of attacks with Plasmodium falciparum, while correlating with an increased number of Plasmodium vivax infections. These results strongly suggest that PKLR protein variants may affect the frequency, and the intensity of malaria episodes induced by different Plasmodium parasites in humans living in areas of endemic malaria.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144555PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677815PMC
June 2016

The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand-Myanmar border areas, Cambodia, and Vietnam.

Malar J 2015 Sep 30;14:381. Epub 2015 Sep 30.

Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Background: The importance of the submicroscopic reservoir of Plasmodium infections for malaria elimination depends on its size, which is generally considered small in low transmission settings. The precise estimation of this reservoir requires more sensitive parasite detection methods. The prevalence of asymptomatic, sub-microscopic malaria was assessed by a sensitive, high blood volume quantitative real-time polymerase chain reaction method in three countries of the Greater Mekong Sub-region.

Methods: Cross-sectional surveys were conducted in three villages in western Cambodia, four villages along the Thailand-Myanmar border and four villages in southwest Vietnam. Malaria parasitaemia was assessed by Plasmodium falciparum/pan malaria rapid diagnostic tests (RDTs), microscopy and a high volume ultra-sensitive real-time polymerase chain reaction (HVUSqPCR: limit of detection 22 parasites/mL). All villagers older than 6 months were invited to participate.

Results: A census before the surveys identified 7355 residents in the study villages. Parasite prevalence was 224/5008 (4 %) by RDT, 229/5111 (5 %) by microscopy, and 988/4975 (20 %) when assessed by HVUSqPCR. Of these 164 (3 %) were infected with P. falciparum, 357 (7 %) with Plasmodium vivax, 56 (1 %) with a mixed infection, and 411 (8 %) had parasite densities that were too low for species identification. A history of fever, male sex, and age of 15 years or older were independently associated with parasitaemia in a multivariate regression model stratified by site.

Conclusion: Light microscopy and RDTs identified only a quarter of all parasitaemic participants. The asymptomatic Plasmodium reservoir is considerable, even in low transmission settings. Novel strategies are needed to eliminate this previously under recognized reservoir of malaria transmission.
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http://dx.doi.org/10.1186/s12936-015-0906-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590703PMC
September 2015

Advantages of using voiced questionnaire and image capture application for data collection from a minority group in rural areas along the Thailand-Myanmar border.

Inform Prim Care 2014 ;21(4):179-88

Department of Tropical Hygiene (Biomedical and Health Informatics), Faculty of Tropical Medicine, Mahidol University, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi Bangkok 10400, Thailand.

Aims: To compare the quality of data collection via electronic data capture (EDC) with voiced questionnaire (QNN) and data image capture features using a tablet versus standard paper-based QNN, to assess the user's perception of using the EDC tool, and to compare user satisfaction with the two methods.

Study Design: Randomised cross-over study. Study sites: This study was conducted in two villages along the Thailand-Myanmar border.

Methodology: This study included 30 community health volunteers (CHVs) and 120 Karen hill tribe villagers. Employing a cross-over study design, the CHVs were allocated randomly to two groups, in which they performed interviews in different sequences using EDC and QNN.

Results: Data discrepancies were found between the two data-collection methods, when data from the paper-based and image-capture methods were compared, and when conducting skip pattern questions. More than 90% of the CHVs perceived the EDC to be useful and easy to use. Both interviewers and interviewees were more satisfied with the EDC compared with QNN in terms of format, ease of use, and system speed.

Conclusion: The EDC can effectively be used as an alternative method to paper-based QNNs for data collection. It produces more accurate data that can be considered evidence-based.
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http://dx.doi.org/10.14236/jhi.v21i4.84DOI Listing
July 2015

Pregnancy outcome in relation to treatment of murine typhus and scrub typhus infection: a fever cohort and a case series analysis.

PLoS Negl Trop Dis 2014 Nov 20;8(11):e3327. Epub 2014 Nov 20.

Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Background: There is a paucity of published reports on pregnancy outcome following scrub and murine typhus despite these infections being leading causes of undifferentiated fever in Asia. This study aimed to relate pregnancy outcome with treatment of typhus.

Methodology/principal Findings: Data were analyzed from: i) pregnant women with a diagnosis of scrub and/or murine typhus from a fever cohort studies; ii) case series of published studies in PubMed using the search terms "scrub typhus" (ST), "murine typhus" (MT), "Orientia tsutsugamushi", "Rickettsia tsutsugamushi", "Rickettsia typhi", "rickettsiae", "typhus", or "rickettsiosis"; and "pregnancy", until February 2014 and iii) an unpublished case series. Fever clearance time (FCT) and pregnancy outcome (miscarriage and delivery) were compared to treatment. Poor neonatal outcome was a composite measure for pregnancies sustained to 28 weeks or more of gestation ending in stillbirth, preterm birth, or delivery of a growth restricted or low birth weight newborn.

Results: There were 26 women in the fever cohort. MT and ST were clinically indistinguishable apart from two ST patients with eschars. FCTs (median [range] hours) were 25 [16-42] for azithromycin (n=5), 34 [20-53] for antimalarials (n=5) and 92 [6-260] for other antibiotics/supportive therapy (n=16). There were 36.4% (8/22) with a poor neonatal outcome. In 18 years, 97 pregnancies were collated, 82 with known outcomes, including two maternal deaths. Proportions of miscarriage 17.3% (14/81) and poor neonatal outcomes 41.8% (28/67) were high, increasing with longer FCTs (p=0.050, linear trend). Use of azithromycin was not significantly associated with improved neonatal outcomes (p=0.610).

Conclusion: The published ST and MT world literature amounts to less than 100 pregnancies due to under recognition and under diagnosis. Evidence supporting the most commonly used treatment, azithromycin, is weak. Collaborative, prospective clinical trials in pregnant women are urgently required to reduce the burden of adverse maternal and newborn outcomes and to determine the safety and efficacy of antimicrobial treatment.
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http://dx.doi.org/10.1371/journal.pntd.0003327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238995PMC
November 2014

Chikungunya virus was isolated in Thailand, 2010.

Virus Genes 2014 Dec 12;49(3):485-9. Epub 2014 Aug 12.

Mahidol-Osaka Center for Infectious Diseases, Ratchathewi, Bangkok, 10400, Thailand.

Chikungunya fever (CHIKF) is an acute febrile illness caused by a mosquito-borne alphavirus, chikungunya virus (CHIKV). This disease re-emerged in Kenya in 2004, and spread to the countries in and around the Indian Ocean. The re-emerging epidemics rapidly spread to regions like India and Southeast Asia, and it was subsequently identified in Europe in 2007, probably as a result of importation of chikungunya cases. On the one hand, chikungunya is one of the neglected diseases and has only attracted strong attention during large outbreaks. In 2008-2009, there was a major outbreak of chikungunya fever in Thailand, resulting in the highest number of infections in any country in the region. However, no update of CHIKV circulating in Thailand has been published since 2009. In this study, we examined the viral growth kinetics and sequences of the structural genes derived from CHIKV clinical isolates obtained from the serum specimens of CHIKF-suspected patients in Central Thailand in 2010. We identified the CHIKV harboring two mutations E1-A226V and E2-I211T, indicating that the East, Central, and South African lineage of CHIKV was continuously circulating as an indigenous population in Thailand.
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http://dx.doi.org/10.1007/s11262-014-1105-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232745PMC
December 2014

Real-time monitoring of school absenteeism to enhance disease surveillance: a pilot study of a mobile electronic reporting system.

JMIR Mhealth Uhealth 2014 May 12;2(2):e22. Epub 2014 May 12.

Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Background: School absenteeism is a common source of data used in syndromic surveillance, which can eventually be used for early outbreak detection. However, the absenteeism reporting system in most schools, especially in developing countries, relies on a paper-based method that limits its use for disease surveillance or outbreak detection.

Objective: The objective of this study was to develop an electronic real-time reporting system on school absenteeism for syndromic surveillance.

Methods: An electronic (Web-based) school absenteeism reporting system was developed to embed it within the normal routine process of absenteeism reporting. This electronic system allowed teachers to update students' attendance status via mobile tablets. The data from all classes and schools were then automatically sent to a centralized database for further analysis and presentation, and for monitoring temporal and spatial patterns of absent students. In addition, the system also had a disease investigation module, which provided a link between absenteeism data from schools and local health centers, to investigate causes of fever among sick students.

Results: The electronic school absenteeism reporting system was implemented in 7 primary schools in Bangkok, Thailand, with total participation of approximately 5000 students. During May-October 2012 (first semester), the percentage of absentees varied between 1% and 10%. The peak of school absenteeism (sick leave) was observed between July and September 2012, which coincided with the peak of dengue cases in children aged 6-12 years being reported to the disease surveillance system.

Conclusions: The timeliness of a reporting system is a critical function in any surveillance system. Web-based application and mobile technology can potentially enhance the use of school absenteeism data for syndromic surveillance and outbreak detection. This study presents the factors that determine the implementation success of this reporting system.
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http://dx.doi.org/10.2196/mhealth.3114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114464PMC
May 2014

Major health problems of expressway workers in Thailand: an 8-year cohort study.

J Med Assoc Thai 2014 Feb;97(2):241-9

Background And Objective: Workers in the transportation sector may be expose to environmental hazards resulting in adverse health outcomes. The present study aimed to assess environmental-hazard-related morbidity among transportation workers over an eight-year period

Material And Method: Data were extracted from the registry database of a cohort of workers in the Expressway Authority of Thailand between 2004 and 2011. Annual trends and changes in health status were described. Factors associated with major health problems were also evaluated

Results: The cohort consisted of 2,000 to 2,700 workers. The trend of abnormal lung function, abnormal hearing, high blood pressure, high cholesterol, and asthma significantly increased over the period. Very few workers had high serum lead levels.

Conclusion: The present study revealed several major occupation-related health problems among transportation workers. In addition to an annual health assessment, other control measures should be instituted to protect workers from occupation-related exposures.
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February 2014

Towards malaria elimination in the Greater Mekong Subregion.

Southeast Asian J Trop Med Public Health 2013 ;44 Suppl 1:iii-iv

SEAMEO Regional Tropical Medicine and Public Health Network.

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January 2014

Detection and characterization of enteric viruses in flood water from the 2011 thai flood.

Jpn J Infect Dis 2013 ;66(5):398-403

Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University.

Severe flooding, which is associated with numerous outbreaks of a wide range of infectious diseases, particularly those caused by enteric viruses, occurred in all areas of Thailand in 2011. To determine the prevalence of five human enteric viruses, namely enterovirus, rotavirus (RV), norovirus (NV), hepatitis A virus (HAV), and hepatitis E virus, in the flood water, 100 water samples were collected from flood-damaged areas in central Thailand. Viral RNA was extracted from concentrated samples and analyzed by RT-PCR and sequencing. NV was the most commonly detected pathogen in the tested samples (14%). RV and HAV were detected in 9% and 7% of samples, respectively. This study is the first to detect enteric viral genes in flood water in Thailand. Furthermore, it is the first to detect an NV gene in any type of environmental water in Thailand. These results provide useful information for estimating the risk of flood waterborne viral infection.
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http://dx.doi.org/10.7883/yoken.66.398DOI Listing
March 2014

Leptospira species in floodwater during the 2011 floods in the Bangkok Metropolitan Region, Thailand.

Am J Trop Med Hyg 2013 Oct 3;89(4):794-796. Epub 2013 Sep 3.

Floodwater samples (N = 110) collected during the 2011 Bangkok floods were tested for Leptospira using culture and polymerase chain reaction (PCR); 65 samples were PCR-positive for putatively non-pathogenic Leptospira species, 1 sample contained a putatively pathogenic Leptospira, and 6 samples contained Leptospira clustering phylogenetically with the intermediate group. The low prevalence of pathogenic and intermediate Leptospira in floodwater was consistent with the low number of human leptospirosis cases reported to the Bureau of Epidemiology in Thailand. This study provides baseline information on environmental Leptospira in Bangkok together with a set of laboratory tests that could be readily deployed in the event of future flooding.
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http://dx.doi.org/10.4269/ajtmh.13-0124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795115PMC
October 2013

Gametocyte dynamics and the role of drugs in reducing the transmission potential of Plasmodium vivax.

J Infect Dis 2013 Sep 12;208(5):801-12. Epub 2013 Jun 12.

Global Health Division, Menzies School of Health Research, Charles Darwin University, Darwin 0811, Australia.

Background: Designing interventions that will reduce transmission of vivax malaria requires knowledge of Plasmodium vivax gametocyte dynamics.

Methods: We analyzed data from a randomized controlled trial in northwestern Thailand and 2 trials in Papua, Indonesia, to identify and compare risk factors for vivax gametocytemia at enrollment and following treatment.

Results: A total of 492 patients with P. vivax infections from Thailand and 476 patients (162 with concurrent falciparum parasitemia) from Indonesia were evaluable. Also, 84.3% (415/492) and 66.6% (209/314) of patients with monoinfection were gametocytemic at enrollment, respectively. The ratio of gametocytemia to asexual parasitemia did not differ between acute and recurrent infections (P = .48 in Thailand, P = .08 in Indonesia). High asexual parasitemia was associated with an increased risk of gametocytemia during follow-up in both locations. In Thailand, the cumulative incidence of gametocytemia between day 7 and day 42 following dihydroartemisinin + piperaquine (DHA + PIP) was 6.92% vs 29.1% following chloroquine (P < .001). In Indonesia, the incidence of gametocytemia was 33.6% following artesunate + amodiaquine (AS + AQ), 7.42% following artemether + lumefantrine, and 6.80% following DHA + PIP (P < .001 for DHA + PIP vs AS + AQ).

Conclusions: P. vivax gametocyte carriage mirrors asexual-stage infection. Prevention of relapses, particularly in those with high asexual parasitemia, is likely the most important strategy for interrupting P. vivax transmission.
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http://dx.doi.org/10.1093/infdis/jit261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733516PMC
September 2013

Malaria in the post-partum period; a prospective cohort study.

PLoS One 2013 13;8(3):e57890. Epub 2013 Mar 13.

Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand.

Background: Several studies have shown a prolonged or increased susceptibility to malaria in the post-partum period. A matched cohort study was conducted to evaluate prospectively the susceptibility to malaria of post-partum women in an area where P.falciparum and P.vivax are prevalent.

Methods: In an area of low seasonal malaria transmission on the Thai-Myanmar border pregnant women attending antenatal clinics were matched to a non-pregnant, non-post-partum control and followed up prospectively until 12 weeks after delivery.

Results: Post-partum women (n = 744) experienced significantly less P.falciparum episodes than controls (hazard ratio (HR) 0.39 (95%CI 0.21-0.72) p = 0.003) but significantly more P.vivax (HR 1.34 (1.05-1.72) p = 0.018). The reduced risk of falciparum malaria was accounted for by reduced exposure, whereas a history of P.vivax infection during pregnancy was a strong risk factor for P.vivax in post-partum women (HR 13.98 (9.13-21.41), p<0.001). After controlling for effect modification by history of P.vivax, post-partum women were not more susceptible to P.vivax than controls (HR: 0.33 (0.21-0.51), p<0.001). Genotyping of pre-and post-partum infections [Formula in text] showed that each post-partum P.falciparum was a newly acquired infection.

Conclusions: In this area of low seasonal malaria transmission post-partum women were less likely to develop falciparum malaria but more likely to develop vivax malaria than controls. This was explained by reduced risk of exposure and increased risk of relapse, respectively. There was no evidence for altered susceptibility to malaria in the post-partum period. The treatment of vivax malaria during and immediately after pregnancy needs to be improved.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057890PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596341PMC
September 2013

Malaria burden and artemisinin resistance in the mobile and migrant population on the Thai-Myanmar border, 1999-2011: an observational study.

PLoS Med 2013 5;10(3):e1001398. Epub 2013 Mar 5.

Shoklo Malaria Research Unit, Mae Sot, Thailand ; Mahidol Oxford University Research Unit, Bangkok, Thailand.

Background: The Shoklo Malaria Research Unit has been working on the Thai-Myanmar border for 25 y providing early diagnosis and treatment (EDT) of malaria. Transmission of Plasmodium falciparum has declined, but resistance to artesunate has emerged. We expanded malaria activities through EDT and evaluated the impact over a 12-y period.

Methods And Findings: Between 1 October 1999 and 30 September 2011, the Shoklo Malaria Research Unit increased the number of cross-border (Myanmar side) health facilities from two to 11 and recorded the number of malaria consultations. Changes in malaria incidence were estimated from a cohort of pregnant women, and prevalence from cross-sectional surveys. In vivo and in vitro antimalarial drug efficacy were monitored. Over this period, the number of malaria cases detected increased initially, but then declined rapidly. In children under 5 y, the percentage of consultations due to malaria declined from 78% (95% CI 76-80) (1,048/1,344 consultations) to 7% (95% CI 6.2-7.1) (767/11,542 consultations), p<0.001. The ratio of P. falciparum/P. vivax declined from 1.4 (95% CI 1.3-1.4) to 0.7 (95% CI 0.7-0.8). The case fatality rate was low (39/75,126; 0.05% [95% CI 0.04-0.07]). The incidence of malaria declined from 1.1 to 0.1 episodes per pregnant women-year. The cumulative proportion of P. falciparum decreased significantly from 24.3% (95% CI 21.0-28.0) (143/588 pregnant women) to 3.4% (95% CI 2.8-4.3) (76/2,207 pregnant women), p<0.001. The in vivo efficacy of mefloquine-artesunate declined steadily, with a sharp drop in 2011 (day-42 PCR-adjusted cure rate 42% [95% CI 20-62]). The proportion of patients still slide positive for malaria at day 3 rose from 0% in 2000 to reach 28% (95% CI 13-45) (8/29 patients) in 2011.

Conclusions: Despite the emergence of resistance to artesunate in P. falciparum, the strategy of EDT with artemisinin-based combination treatments has been associated with a reduction in malaria in the migrant population living on the Thai-Myanmar border. Although limited by its observational nature, this study provides useful data on malaria burden in a strategically crucial geographical area. Alternative fixed combination treatments are needed urgently to replace the failing first-line regimen of mefloquine and artesunate. Please see later in the article for the Editors' Summary.
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http://dx.doi.org/10.1371/journal.pmed.1001398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589269PMC
September 2013