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Pneumonia is a leading cause of hospitalization and death among elderly adults. We performed a retrospective and prospective observational study to describe the etiology, clinical course, and outcomes of pneumonia for patients 60 years and older in Thailand. We enrolled 490 patients; 440 patients were included in the retrospective study and 50 patients were included in the prospective study. The CURB-65 score and a modified SMART-COP score (SMART-CO score) were used to assess disease severity. The median patient age was 80 years (interquartile range, 70–87 years); 51.2% were men. Klebsiella pneumoniae (20.4%) and Pseudomonas aeruginosa (15.5%) were the most common causative agents of pneumonia. A significant minority (23%) of patients were admitted to the intensive care unit (ICU), and mortality among this subset of patients was 45%. Most patients (80.8%) survived and were discharged from the hospital. The median duration of hospitalization was 8 days (interquartile range, 4–16 days). In contrast, 17.6% of patients died while undergoing care and 30-day mortality was 14%. Factors significantly associated with mortality were advanced age (P = 0.004), male sex (P = 0.005), multiple bacterial infections (P = 0.007; relative risk [RR], 1.88; 95% confidence interval [CI], 1.19–2.79), infection with multi-drug-resistant/extended-spectrum B-lactamase-producing organisms (P < 0.001; RR, 2.82; 95% CI, 1.83–4.85), ICU admission (P < 0.001; RR, 1.8; 95% CI, 1.4–2.3), and complications of pneumonia (P < 0.001; RR, 2.5; 95% CI, 1.8–3.4). Patients with higher SMART-CO and CURB-65 scores had higher rates of ICU admission and higher 30-day mortality rates (P < 0.001). These results emphasize the importance of Gram-negative bacteria, particularly K. pneumoniae and P. aeruginosa, as major causes of pneumonia among the elderly in contrast to other reports, Streptococcus pneumoniae is a common cause of pneumonia among elderly individuals worldwide. The SMART-COP and CURB-65 scores were developed to assess pneumonia severity and predict mortality of young adults with pneumonia. Few studies have examined the appropriateness of these scores for elderly patients with multiple comorbidities. A limited number of studies have used modified versions of these scores among elderly individuals. We found that Gram-negative bacteria has a major role in the etiology of pneumonia among elderly individuals in Southeast Asia. A significant proportion of elderly individuals with low CURB-65 scores were admitted to the hospital, indicating that hospital admission may reflect fragility among elderly individuals with low CURB-65 scores. The modified SMART-COP score (SMART-CO score) sufficiently predicted intensive care unit admission and the need for intensive vasopressor or respiratory support. A SMART-CO score ≥ 7 accurately predicted 30-day mortality.

During the mobile clinic activities in Tak Province, Thailand, Paragonimus sp. eggs were found in a fecal sample of a 72-year-old Karen resident. Paragonimus DNA was amplified from the stool sample and identified to P. heterotremus. The patient did not have any symptoms. Apparent pulmonary lesion was not found on the chest X-ray. The patient admitted habitual consumption of semi-cooked or roasted waterfall crabs for several years. The waterfall crabs collected from stream near the village were found negative for Paragonimus metacercariae. In northern Thailand, paragonimiasis remains as one of the public health concerns and should be ruled out for asymptomatic pulmonary patients.

Lung ultrasound (LUS) is a more sensitive method of detecting pathological pulmonary changes than chest X-ray. Therefore, LUS for patients with dengue could be an important tool for the early detection of pleural effusions and pulmonary edema signifying capillary plasma leakage, which is the hallmark of severe dengue pathophysiology. We conducted a prospective observational study of pulmonary changes identifiable with LUS in dengue patients admitted to the Hospital for Tropical Diseases in Mahidol University, Bangkok, and the Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand. The LUS findings were described according to standard criteria, including the presence of A, B1, B2, and C patterns in eight chest regions and the presence of pleural effusions. From November 2017 to April 2018, 50 patients with dengue were included in the study. LUS was performed during the febrile phase for nine patients (18%) and during the critical-convalescence phase for 41 patients (82%). A total of 33 patients (66%) had at least one abnormality discovered using LUS. Abnormal LUS findings were observed more frequently during the critical-convalescence phase (N = 30/41; 73%) than during the febrile phase (N = 3/9; 33%) (P = 0.047). Abnormal aeration patterns were observed in 31 patients (62%). Only B patterns with only multiple B lines were observed in 21 patients (42%); of these patients, three had already exhibited B patterns during the febrile phase (N = 3). C patterns (N = 10; 24%), pleural effusion (N = 10; 24%), and subpleural abnormalities (N = 11; 27%) were observed only during the critical-convalescence phase. LUS can detect signs of capillary leakage, including interstitial edema and pleural effusions, early during the course of dengue.

Background Effective pre-travel consultations cannot be achieved only through individual risk assessment and advice on vaccinations and chemoprophylaxis. Travelers’ perceptions of the risk of health problems represent another key factor in successful risk communication and co-operation with pre-travel advice. The objective of this study was to determine perception of travel-related health risks among Thais and westerners visiting the Thai Travel Clinic for consultation before visiting developing countries. Methods A novel pictorial scale questionnaire-based study was conducted with both Thai and western travelers who visited the Thai Travel Clinic for pre-travel consultation. All participants were approached before and after completing the consultation, and were asked about their demographic data and perceptions of travel-related health risk. The perceptions of risk before and after consultation were compared using the McNemar test, and were also compared with the actual estimated risk. Results During May to November 2019, 594 travelers (330 Thais and 264 Westerners) were enrolled and completed the pictorial scale questionnaires. Most Thai travelers visited Africa/South America (63%), and 20% had previously received counseling. Westerners were mostly backpackers (37.5%), traveling for > 30 days (71.6%), while 43.6% had previously received counseling. Overall, the westerners (n = 264) changed their risk perceptions slightly after counseling in contrast with the Thais. The change in perception of most health problems was observed statistically significant (p-value Conclusions Risk perception of health problems plays an important role in successful risk communication and their response to pre-travel advices. Differences in risk perceptions were evident between the two groups. Therefore, this highlight the importance of obtaining pre-travel advice in one’s home country before travelling. Raised awareness of the risks should be emphasized during consultations for underestimated health risks, especially for rabid animal exposure and sexually transmitted diseases.

Additional file 2. Subgroup analysis of risk perception pre- and post-travel counseling differentiated by nationality of western travelers toward 14 health problems.

Additional file 1. The funnel plots illustrated the distribution of answer in 14 health problems on pre- and post-travel counseling among both groups of the participants.

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.

Acute undifferentiated febrile illness (AUFI) has been a diagnostic dilemma in the tropics. Without accurate point-of-care tests, information on local pathogens and clinical parameters is essential for presumptive diagnosis. A prospective hospital-based study was conducted at the Bangkok Hospital for Tropical Diseases from 2013 to 2015 to determine common etiologies of AUFI. A total of 397 adult AUFI cases, excluding malaria by blood smear, were enrolled. Rapid diagnostic tests for tropical infections were performed on admission, and acute and convalescent samples were tested to confirm the diagnosis. Etiologies could be identified in 271 (68.3%) cases. Dengue was the most common cause, with 157 cases (39.6%), followed by murine typhus (20 cases; 5.0%), leptospirosis (16 cases; 4.0%), influenza (14 cases; 3.5%), and bacteremia (six cases; 1.5%). Concurrent infection by at least two pathogens was reported in 37 cases (9.3%). Furthermore, characteristics of dengue and bacterial infections (including leptospirosis and rickettsioses) were compared to facilitate dengue triage, initiate early antibiotic treatment, and minimize unnecessary use of antibiotics. In conclusion, dengue was the most common pathogen for AUFI in urban Thailand. However, murine typhus and leptospirosis were not uncommon. Empirical antibiotic treatment using doxycycline or azithromycin might be more appropriate, but cost-benefit studies are required. Physicians should recognize common causes of AUFI in their localities and use clinical and laboratory clues for provisional diagnosis to provide appropriate treatment while awaiting laboratory confirmation.

BackgroundMyanmar faces a health security threat, with an increasing number of multidrug-resistant tuberculosis (MDR-TB) cases. Long delays in the initiation of treatment are a barrier to MDR-TB control.ObjectivesThe main objectives of this study were (1) to identify the determinants of delay in treatment initiation after MDR-TB diagnosis, and (2) to explore the effects of treatment delay on disease infectivity, severity, treatment adherence, and treatment outcomes.MethodsThis retrospective study reviewed 330 MDR-TB treatment cards for patients enrolled for treatment at Yangon Regional Tuberculosis Centre, in 2014.ResultsMedian treatment delay was 105 days, interquartile range (IQR) 106 (61-167) days; (51.5%) of patients experienced a long treatment delay (≥ 105 days). Regarding the determinants of treatment delay, this study identified important patient-healthcare system interaction factors. Significant risk factors of long treatment delay included female sex, age > 30 years, and prior contact with patients with MDR-TB. Patients with long treatment delays were significantly different from those with short delays, in terms of having high sputum smear grade, resistance to more than two main drugs (isoniazid and rifampicin), and long culture conversion time. In this study, delay in the initiation of treatment was associated with poor treatment outcome, but this was not statistically significant after adjusting for other risk factors. Median treatment-delay times were longer among patients with poor outcomes (144 days) than those with successful outcomes (102 days).ConclusionsPost-diagnosis delays in the initiation of treatment among MDR-TB patients were significantly long. The study results showed that inadequate MDR-TB treatment initiation center, centralization of treatment initiation, limitation of human resources, were health-system factors delaying timely treatment initiation and implementation of an effective TB-control program. Our findings highlight the need for immediate interventions to reduce treatment delay and improve treatment outcomes, including scaling up diagnostic capacity with Xpert MTB/RIF at township level, expansion of decentralized MDR-TB treatment initiation centers, ensuring a productive health workforce comprising trained health personnel, and providing health education and treatment-adherence counseling to patients and family members.

Tuberculosis (TB) is common in Thailand and the prevalence of diabetes mellitus (DM) is increasing. We conducted this study to determine the impact of DM on the outcome of pulmonary TB treatment in northern Thailand by retrospectively reviewing TB registry data. Data for all pulmonary TB patients being treated at 95 TB clinics in eight provinces from northern Thailand during January 2010-December 2012 were retrospectively analyzed. TB treatment outcomes were assessed by sputum tests at 2 months and 6 months after starting treatment, and the overall success rate at the end of the treatment course was determined. Factors associated with treatment outcome were evaluated. A total of 7,807 new pulmonary TB patients were included in the analysis. Among those, 555 (7%) had history of diabetes. At 2-month after the intensive phase treatment, a negative sputum result was found in 85% of all tested patients. The proportion of negative sputum at 2-month was similar in both TB with and without DM (85%). The overall treatment success rate was 77%. TB treatment outcomes were not significantly different between TB patients with DM (84%) and without DM (77%). In conclusion, having DM did not affect the TB treatment outcome in the studied population. More detailed studies of TB treatment outcome and level of DM control are underway.

Background Rabies has become a forgotten and neglected disease in Japan. In 2006, there was a slight increase in social awareness of rabies when Japan had two reported cases of human rabies, originating in the Philippines. Although the number of Japanese either traveling or living in other Asian countries has been increasing, the exact risk of this population contracting rabies is unknown. Thus, this study utilized a questionnaire to investigate the incidence of rabies exposure, as well as the knowledge, attitude, and practice toward rabies prevention among Japanese expatriates and travelers in Thailand. Methods Japanese travelers and expatriates were asked questions related to knowledge, attitude, practice toward rabies risk, and experiences of potential rabies exposure such as animal bites, licks, and scratches. Questionnaires were either completed at the Bangkok Suvarnabhumi International Airport and other tourist areas or distributed within Japanese associations in Thailand. Results A total of 1,208 questionnaires from Japanese expatriates and 590 from Japanese travelers were collected and analyzed. We found high incidence rates of potential exposure events among these populations. In particular, Japanese travelers had the highest incidence rate compared to previous studies of international travelers in Thailand. While expatriates' incidence rates of animal bites, licks, and scratches were 1.7, 6.9, and 1.8/1,000 person-months, travelers have much higher incidence rates of 43.1, 136.1, and 33.0/1,000 person-months. Generally, travelers, compared to expatriates, tended to have less accurate knowledge and less often had the pre-exposure prophylaxis vaccination. Moreover, survey answers indicated that 55.0% of expatriates and 88.9% of travelers who were bitten would not seek proper treatment. Conclusions Since rabies is a preventable disease as long as one has the appropriate knowledge, attitude, and practice, it is essential to promote prevention activities for the Japanese population in Thailand to avert serious consequences of this disease.

To understand geographic variation in travel-related illness acquired in distinct African regions, we used the GeoSentinel Surveillance Network database to analyze records for 16,893 ill travelers returning from Africa over a 14-year period. Travelers to northern Africa most commonly reported gastrointestinal illnesses and dog bites. Febrile illnesses were more common in travelers returning from sub-Saharan countries. Eleven travelers died, 9 of malaria; these deaths occurred mainly among male business travelers to sub-Saharan Africa. The profile of illness varied substantially by region: malaria predominated in travelers returning from Central and Western Africa; schistosomiasis, strongyloidiasis, and dengue from Eastern and Western Africa; and loaisis from Central Africa. There were few reports of vaccine-preventable infections, HIV infection, and tuberculosis. Geographic profiling of illness acquired during travel to Africa guides targeted pretravel advice, expedites diagnosis in ill returning travelers, and may influence destination choices in tourism.

Summary Background The emergence of highly pathogenic avian influenza H5N1 viruses has raised concerns about their pandemic potential. Vaccination is the most effective way of preventing influenza. In this study, we investigated the safety and immunogenicity of an avian H5N2 live attenuated influenza vaccine (LAIV H5N2) in healthy Thai adults and its priming immune responses with an H5N1 inactivated vaccine boost. Methods This study was done at the Vaccine Trial Centre at Mahidol University, Bangkok, Thailand and was divided into two parts. Part 1 consisted of a randomised, double-blind, placebo-controlled trial done over 18 months. We randomly assigned (2:1) healthy Thai adults aged 18–49 years with a computer generated randomisation sequence (blocks of six) to receive either two intranasal doses (0·25 mL per nostril) of LAIV H5N2 (101 participants) or placebo (51 participants) 21 days apart. For part 2, an open-label trial was done in which previously vaccinated participants (40 from LAIV H5N2 group and 20 placebo) were given one intramuscular dose (0·5 mL) of H5N1 booster vaccine. Participants, investigators, and site-study workers were blinded from randomisation. Immune responses after subsequent immunisation were evaluated using haemagglutination-inhibition and microneutralisation assays and circulating follicular T-helper cells and plasmablast cells were measured in serum and whole blood. The trials are registered with ClinicalTrials.gov, numbers NCT01841918 and NCT02229357. Findings Between Feb 4, 2013, and Feb 28, 2013, 256 individuals were screened, of whom 152 participants were enrolled in part 1 of this study. LAIV H5N2 vaccine was well tolerated. Viral shedding was detected in only six (6%) of 101 participants in the vaccine group 1 day after the first vaccination and in and two (2%) of 98 participants in the group after the second vaccination. There was no serious adverse event in both groups. 51 (50%) of 101 participants in the vaccine group and 28 (55%) of 51 in the placebo group reported at least one adverse event. 80 (84%) of 95 events in the vaccine group and 32 (78%) of 43 events in the placebo groups were reportedly suspected adverse events, probably related to the vaccine; however, most were mild in nature. After two doses of vaccine, 13 (13%) of 100 participants in the vaccine group had an increase in haemagglutination-inhibition titre of more than four-fold and four (4%) of 100 vaccinees developed a rise in neutralisng antibody titre of more than four-fold. 1 year later, after a booster with an inactivated H5N1 vaccine (part 2), 39 (98%) of 40 participants who had previously been vaccinated with LAIV H5N2 had an increase in haemagglutination-inhibition titre of greater than four-fold as early as day 7 compared with three (15%) of 20 participants in the placebo group. Peak geometric mean titre (GMT) for haemagglutination-inhibition antibodies in the previously LAIV H5N2 vaccinated group (566·89 [95% CI 436·97–735·44]) were significantly higher than among those who previously received placebo (25·49 [11·82–54·96]; p

The clinical manifestations of dengue infection in the adult are different from those in children, i.e. having less prevalence to bleeding, and more commonly, abnormal liver function tests.The primary objective is to describe the clinical manifestations of dengue infection in adult patients. The secondary objective is to compare the clinical manifestations of dengue infection between the groups of normal and abnormal liver function tests in adult patients.Retrospective study was done in adults (age 15 years) dengue patients admitted at the Hospital for Tropical Diseases from 2000-2002. Dengue infection diagnosed by WHO clinical criteria 1997 with serological tests confirmed by ELISA test or Rapid Immunochromatographic test. Liver function test was recorded by day of fever.There were 127 adult dengue patients with mean age 26.4 ± 11.5 years. Classifications of dengue infection by WHO criteria were DF 4.7%, DHF grade 126.0%, DHF grade 2 63.0% and DHF grade 3 6.3%. Mean duration of fever clearance time was 6.0 ± 1.9 days but the fever lasted longer in cases of high-level transaminases (10 folds). The common presenting symptoms and signs were myalgia (95.9%), nausea/vomiting (87.7%), positive tourniquet test (77.2%), abdominal pain (42.7%), hepatomegaly (34.6%), and bleeding (20.5%). The ratio of AST and ALTwas 1.8:1. Abnormal AST and ALT were found in 88.2% and 69.3% of the patients, respectively. Patients with nausea/vomiting, petechiae or duration of fever7 days more frequently had abnormal transaminases. Abnormal AST during the febrile stage was associated with bleeding. High-level AST and ALT occurred in 11.0% and 7.0%, respectively. Shock was associated with high-level ALT during the febrile stage.Adult dengue patients commonly showed abnormal liver function tests and accounted for at least two-thirds of them. High-level ALT during the febrile stage showed association with shock.

Background. DB289 is the orally active prodrug of the diamidine DB75, which was developed for the treatment of human African trypanosomiasis. Methods. We tested the safety and efficacy of DB289 for the treatment of Plasmodium vivax and acute, uncomplicated P. falciparum infections in an open-label pilot study at the Hospital for Tropical Diseases in Bangkok. Nine patients with P. vivax infections and 23 patients with P. falciparum infections were admitted and treated with 100 mg of DB289 given orally twice a day for 5 days and were followed for 28 days. Patients with P. vivax infections were also treated with primaquine on days 10-23. Results. All patients cleared parasites by day 7, with a mean ± SD clearance time of 43 ± 41 h. One patient with a P. vivax infection had a recurrence of parasitemia on day 9. Of the 23 patients with P. falciparum infections, 3 had recurrences of parasitemia caused by P. vivax and 2 had recurrences of parasitemia caused by P. falciparum. In only 1 of 2 recurrences of parasitemia caused by P. falciparum were the parasites genotypically distinct from the infecting parasites the patient had at enrollment, which means there was a 96% cure rate. Conclusions. DB289 is a promising new antimalarial compound that could become an important component of new antimalarial combinations.

Background. Tafenoquine is an 8-aminoquinoline developed as a more effective replacement for primaquine. In a previous dose-ranging study in Thailand, 3 tafenoquine regimens with total doses ranging from 500 mg to 3000 mg prevented relapse of Plasmodium vivax malaria in most patients when administered 2 days after receipt of a blood schizonticidal dose of chloroquine. Methods. To improve convenience and to begin comparison of tafenoquine with primaquine, 80 patients with P vivax infection were randomized to receive 1 of the following 5 treatments 1 day after receiving a blood schizonticidal dose of chloroquine: (A) tafenoquine, 300 mg per day for 7 days (n = 18); (B) tafenoquine, 600 mg per day for 3 days (n = 19); (C) tafenoquine, 600 mg as a single dose (n = 18); (D) no further treatment (n = 13); or (E) primaquine base, 15 mg per day for 14 days (n = 12). The minimum duration of protocol follow-up was 8 weeks, with additional follow-up to 24 weeks. Results. Forty-six of 55 tafenoquine recipients, 10 of 13 recipients of chloroquine only, and 12 of 12 recipients of chloroquine plus primaquine completed at least 8 weeks of follow-up (or had relapse). There was 1 relapse among recipients of chloroquine plus tafenoquine, 8 among recipients of chloroquine only, and 3 among recipients of chloroquine plus primaquine. The rate of protective efficacy (determined on the basis of reduction in incidence density) for all recipients of chloroquine plus tafenoquine, compared with recipients of chloroquine plus primaquine, was 92.6% (95% confidence interval, 7.3%-99.9%; P = .042, by Fisher's exact test). Conclusions. Tafenoquine doses as low as a single 600-mg dose may be useful for prevention of relapse of P. vivax malaria in Thailand.

The combination of artesunate and mefloquine is currently one of the most effective treatments against multidrug-resistant Plasmodium falciparum malaria. To improve patient compliance to such a combination, the two agents have been combined in a prepacked single blister. Patients were instructed to simultaneously co-administer the drugs once a day for three days. In the present randomized, double-blind, parallel group, comparative, single center study in Thailand, this concept was investigated in 204 adults and children with acute, uncomplicated P. falciparum malaria. Patients were randomized into two treatment groups and received once a day over a three-day period the following: Group A received artesunate, 4-5 mg/kg/day, and mefloquine, total dose = 25 mg/kg, approximately 8.5 mg/kg/day, simultaneously. Group B received artesunate, 4-5 mg/kg/day, and mefloquine, total dose = 25 mg/kg, sequentially (i.e., no mefloquine dose on the first day, 15 mg/kg on the second day, and 10 mg/kg on the third day). Both treatment groups showed no relevant differences in baseline demographic and clinical characteristics. Intent-to-treat analysis revealed a cure rate at day 28 (primary endpoint) of 100% in group A and 99% in group B (difference not significant). The secondary endpoints of mean time to fever clearance (group A = 34 hours, group B = 31 hours) and mean time to parasite clearance (group A = 44 hours group B = 48 hours) were similar between groups (both differences not significant). Tolerability was good in both treatment groups, with no difference in the overall incidence of adverse events. There was a low incidence of nausea/vomiting (4.9% in both groups) and central nervous system side effects (4.9% in group A versus 8.8% in group B). These were comparable between groups and generally of a mild nature. The three-day combination of artesunate and mefloquine (Artequin, Mepha, Ltd., Aesch, Switzerland) with the introduction of mefloquine on day 1 offers a practical dosing regimen that is highly effective and well tolerated in patients of different ages with uncomplicated P. falciparum malaria. It is likely that the prepacked blister approach translates clinically into a better patient compliance, thereby contributing to limit the development of drug resistance.

One hundred and fifty patients with severe falciparum malaria were administered sequential combination of dihydroartemisinin suppository followed by an oral mefloquine tablet. Dihydroartemisinin suppositories (80 mg/capsule) were given rectally once daily for 3 days with a total dose of 8-10 mg/kg. Two doses of mefloquine, 15 mg/kg/dose and 10 mg/kg/dose, were given at 72 hr and 84 hr, respectively. The mean [SD] parasite clearance time and fever clearance time were 46.1 [15.7] hr and 82.5 [59.6] hr, respectively. No death or major adverse drug effects occurred. The cure rate at 28 days of inpatient follow-up was 95% (113 of 119 patients). In severe malaria, dihydroartemisinin suppository followed by oral mefloquine is a suitable alternative treatment to parenteral drugs.

Chloroquine-induced itch in black-skinned African malaria patients is common and frequently leads to poor compliance or treatment defaulting. To assess the frequency and severity of chloroquine-induced pruritus in an Asian population, we reviewed case records of 1189 Plasmodium vivax malaria patients treated with chloroquine (25 mg/kg over 3days) at the Bangkok Hospital for Tropical Diseases from 1992 through 1997. The majority of patients were Thais or ethnic Burmese (light brown skin), referred from the western border of Thailand. Overall, there were 23 patients (1.9%) with complaints of pruritus during chloroquine therapy. Of these, 12 (52%) had palm and sole involvement, eight (35%) had generalized pruritus including the palms and soles, and three (13%) had palm itching only. One patient developed pruritus on the palms and soles on two consecutive admissions. The pruritus did not interfere with daily activity, was reduced in intensity by anti-histamine therapy, and did not affect the patient's willingness to complete the chloroquine regimen. Therapeutic responses in the 23 patients with chloroquine itch was similar to those without itch. Among the itch patients, there was no association with gender or level of parasitaemias. Our findings indicate that the frequency of chloroquine-induced pruritus in Asian patients treated with chloroquine for P. vivax malaria is low in comparison with black-skinned Africans. This may be related to pharmacogenetic factors, the infective Plasmodium species, drug metabolism or drug-parasite interactions, or a lower affinity of chloroquine for less pigmented skin.

To define the current efficacy of Fansidar (F. Hoffmann-La Roche Ltd., Basel Switzerland) (pyrimethamine and sulfadoxine), primaquine in a high dose, and artesunate for treating acute Plasmodium vivax malaria, we conducted a comparative clinical trial of these 3 drugs in an open-label study. Patients (15-65 years old) were assigned to 1 of 4 treatments regimens in a serial order. Ninety percent of the patients were infected at Thailand-Myanmar border. Patients in group I (n = 23) received Fansidar (3 tablets, 75 mg of pyrimethamine and 1,500 mg of sulfadoxine, a single dose on the first day), group II (n = 23) received Fansidar (3 tablets, 75 mg of pyrimethamine and 1,500 mg of sulfadoxine, a single dose on the first day) and then received primaquine (30 mg a day for 14 days), group III (n = 23) received primaquine (30 mg a day for 14 days), and group IV (n = 23) received artesunate (200 mg once a day for 3 days) and then primaquine (30 mg a day for 14 days). Cure rates on day 28 of follow-up were 40%, 100%, 100%, and 100% in groups I, II, II, and IV, respectively. There were 4 and 5 patients in group I showing post-treatment reappearance of parasitemia at < or = 16 days and between 17 and 28 days, respectively. Patients in the other 3 groups showed negative parasitemias within 7 days after treatment. Artesunate plus primaquine (group IV) cleared parasitemia faster than the other 3 regimens. There is a high proportion of ineffectiveness of Fansidar for treatment of P. vivax malaria and it should be no longer used for treatment of P. vivax malaria acquired at the Thailand-Myanmar border. A high dose of primaquine is safe and effective in the treatment of P. vivax malaria during the 28-day follow-up period.

BACKGROUND—A study was undertaken to evaluate the diagnostic value of pleural fluid concentrations of interferon gamma (IFN-γ) as a marker of tuberculosis. METHODS—Patients admitted to King Chulalongkorn Memorial Hospital between April 1997 and January 1998 with a lymphocytic exudative pleural effusion were enrolled into the study. The pleural fluids were examined for cytology, staining for acid fast bacilli, and mycobacterial culture. Pathological examination and mycobacterial culture were performed on each pleural biopsy specimen. The diagnosis of tuberculosis was made when one of the following criteria was met: (1) Mycobacterium tuberculosis was isolated from either the pleural fluid or pleural tissue; (2) granulomas were demonstrated in the pleural tissue which stained positive for acid fast bacilli (AFB); or (3) in the presence of granulomas negative on staining for AFB in pleural tissue there was a response to antituberculous treatment on follow up. All pleural fluid samples were stored at -70°C and the IFN-γ level was measured by immunoassay. Analysis was made using sensitivity, specificity, and likelihood ratio for a positive test result. The best cut off point was determined by the highest likelihood ratio and receiver operating characteristic curve. RESULTS—A total of 66 patients were enrolled and tuberculosis was confirmed in 39 of them. The diagnoses in the non-tuberculous group included malignancy (15), paramalignancy (11), and chronic pleuritis secondary to infective endocarditis (1). The mean (SE) IFN-γ level in the pleural fluid was significantly higher in the tuberculous group than in the non-tuberculous group (1493.3 (131.3) pg/ml versus 80.1 (50.4) pg/ml, p

Clinical manifestations of malaria are nonspecific and range from asymptomatic to severe. The clinical presentations reflect complex interactions between the host, the environment, and the parasites. Signs and symptoms include fever, headache, muscle pain, abdominal pain, anorexia, nausea, vomiting, hepatosplenomegaly, jaundice and dark urine. In mild malaria, these signs and symptoms cannot differentiate malaria from common cold, influenza or other systemic diseases. Fever and malaise in malaria are believed to result from the release of endogenous cytokines [e. g. interleukin 1, 6 and 8 (IL-1, IL-6, IL-8) and tumor necrotic factor-α (TNF-α)] in response to parasite antigens. Other signs and symptoms of malaria are also associated with the rupture of parasitized red cells. In severe malaria, the clinical manifestations included cerebral malaria, pulmonary edema, renal failure, anaemia, and jaundice. Signs and symptoms of cerebral malaria are as follow alteration of consciousness, coma, dysconjugated eyeballs and convulsions. Among fatal cases, 80% died within the first 48 hrs of admission while the rest, death resulted from complications such as acute renal failure, pulmonary edema, bacterial infection, and lactic acidosis. 92% of the survivors had completed recovery. Treatment of multidrug resistant falciparum malaria in Thailand is complicated. New antimalarial drugs have been investigated at the Hospital for Tropical Diseases in the recent years. Artemisinine derivatives such as artesunate, artemether, arteether, dihydroartemisinin are also tested at the Bangkok Hospital for Tropical Diseases. Artesunate and artemether alone with a total dose of 600 to 750 mg produced cure rates of 80 to 95%. Artesunate suppositories have been proved successfully for the treatment of severe malaria. The artemisinin derivatives when used in combination with mefloquine cure rates improved to 95-100%. Dihydroartemisinin alone with a total dose of 480 mg given over 5 days gave a cure rate of 90%. At present, studies with the combination of artemisinin derivatives plus mefloquine in various doses and duration of treatment are being investigated. Until proven otherwise, the drug combinations are still recommended for all adult patients suffering from acute uncomplicated falciparum malaria contracted in multidrug resistant areas.In severe malaria, the choice of antimalarial chemotherapy depends on the clinical severity, the drug sensitivity of the parasites, and the availability and preparation of the drug. Quinine is widely available drug. Qinghaosu and its derivatives have been used successfully in treating both uncomplicated and severe falciparum malaria. Their effectiveness in eliminating the parasites have been extensively documented, however, the recrudescent rate is rather high (10-30%). In treating severe malaria, early diagnosis and early treatment are vital and the aim is to save patient's life. Prompt administration of an adequate and effective antimalarial drug is needed once the diagnosis is made. Other symptomatic and supportive treatment includes careful monitoring of fluid intake and urine output, frequent observations for complications with appropriate treatment and good nursing care.

Travelers play a role in the spread of sexually transmitted diseases, including HIV because of having unprotected sex. We studied the incidence of casual sex among foreign backpack tourists in the Khao San Road area of Bangkok, Thailand. We also evaluated their attitudes about sexual health and their actual practices. A cross sectional study was conducted using a self-administered, anonymous questionnaire. The target population was backpackers agedor =18 years, from Europe, North America and Australia. In total, 415 questionnaires were filled out and analyzed. Sixty-four percent of participants were male, the overall median age was 27 years and the mean duration of stay was 14.6 days. One hundred seven respondents (25%) had casual sex while staying in Thailand; of these, 55% always used condoms. The selection of sex partner influenced the use of condoms. The highest rate of condom use was among backpackers who had sex with sex workers (63%), while those who had sex with their travel partners had the lowest rate of condom use (35.6%). One-fourth of backpackers in our study had casual sex during their trip. Their attitudes towards safe sex practices were not ideal. Methods to change attitudes and behavior about unprotected sex need to be explored in this population.

Background: Drug resistance substantially increases tuberculosis (TB) mortality. This study aimed to describe the prevalence of mycobacterial drug resistance pattern and association of common resistance patterns with TB mortality in Thailand. Method: A retrospective cohort study was conducted using TB surveillance data. A total of 9,518 culture-confirmed, pulmonary TB patients registered from 1 October 2004 to 31 December 2008 from the Thailand TB Active Surveillance Network were included in this study. Patients were followed up until TB treatment completion or death. Mycobacterial drug resistance patterns were categorized as pan-susceptible, rifampicin resistance, isoniazid monoresistance, and ethambutol/streptomycin resistance. Drug susceptibility testing (DST) was determined by Mycobacterial Growth Indicator Tube (MGIT) liquid culture systems. Survival analysis was applied. Result: Isoniazid monoresistance was the most common pattern, while rifampicin resistance had the largest impact on mortality. Cox regression analysis showed a significantly higher risk of death among patients with rifampicin resistance (adjusted hazard ratio (aHR) 1.9, 95% confident interval (CI), 1.5-2.5) and isoniazid monoresistance (aHR 1.4, 95% CI 1.1-1.7) than those with pan-susceptible group after adjustment for age, nationality, human immunodeficiency virus (HIV) and antiretroviral therapy (ART) status, diabetes mellitus, cavitary disease on chest x-ray, treatment observation, and province. HIV co-infection was associated with higher mortality in patients both on ART (aHR 1.9, 95% CI 1.5-2.5) and not on ART (aHR 8.1, 95% CI 6.8-9.8). Conclusion: Rifampicin resistance and isoniazid monoresistance were associated with increased TB mortality. HIV-coinfection was associated with a higher risk of death including among those taking antiretroviral therapy.

During late 2011, Thailand experienced its worst flooding in 50 years with over 4.6 million people directly affected. During the flooding we conducted a cross sectional survey of backpackers in the Khao San Road area of Bangkok to determine awareness, practices, and their incidence of health problems during the flooding. A total of 422 subjects completed questionnaires which were analyzed. Seventy percent were European and 12.3% were North American. The overall median age was 27 years and the median stay in Thailand was 22 days. Most of the backpackers were aware of the flooding in Thailand; some had sought travel health information prior to their trip from various sources including the internet, their family physician or a travel clinic. However, even in travel clinics specific health advice related to flooding, such as leptospirosis risk/prevention, was rarely given to travelers. Fifteen point four percent of subjects (65/422) had come into contact with floodwater; 30.8% of those (20/65) washed their feet/legs afterward. Our findings indicate most backpackers were inadequately aware of potential health hazards, such as leptospirosis, during the floods.

Immune reconstitution inflammatory syndrome (IRIS) is an important adverse event among human immunodeficiency virus (HIV)-infected patients taking highly active antiretroviral therapy (HAART). The epidemiology of IRIS in Thailand has not been well examined, especially among adult HIV-infected patients. In the present study, we reviewed the medical records of 174 HIV-infected, antiretroviral therapy-naive patients older than 15 years (the median CD4 count at commencement of HAART was 37 cells/mm3) and compared characteristics of patients with and without IRIS. During a 12-month follow-up period after commencement of HAART, 11 cases (6.3%) of IRIS were identified (4.2/100 patient-years HAART). The cases included nine cases with mycobacterial infection, one with cytomegalovirus retinitis and one with cryptococcal meningitis. The patients with IRIS were significantly younger than those without IRIS (29 vs 36 on medians, p = 0.022). The median interval between commencement of HAART and the onset of IRIS was 22 days. Although all patients with IRIS improved with or without corticosteroids, they were more frequently hospitalized during a 12-month follow-up period while taking HAART (1 vs 0 on medians, p0.001). The incidence of IRIS in advanced adult HIV-infected patients in Thailand was lower than that reported from Europe and the United States, which may be attributable to deferment of HAART after diagnosing opportunistic infections.

Paragonimiasis is an infection by flukes of the genus Paragonimus, with foci of disease in Asia, Africa, and Central and South America. Humans acquire infection by eating metacercariae in improperly cooked freshwater crabs or crayfish. Acute inflammatory and allergic symptoms are rarely serious and usually resolve spontaneously. Chronic manifestations may be (1) pulmonary—most remarkably with a chronic, productive cough with jam-like, brownish-red sputum; and (2) extrapulmonary—most importantly in the central nervous system, often presenting with seizures. Diagnosis is by demonstrating ova in sputum, stool, or pleural fluid. Serology can be used to support the diagnosis, especially in extrapulmonary paragonimiasis. Treatment with praziquantel is almost always effective. Prevention is by health education and the mass treatment of infected people in an endemic area.

Background and Aims: Plasmodium falciparum (PF) infection can lead to severe complications. Ursodeoxycholic acid (UDCA) is increasingly used for the treatment of cholestatic liver diseases. The present study aims to determine the effects of combined UDCA and artesunate compared to placebo and artesunate on the improvement of liver tests in severe PF jaundiced patients. Methods: All severe PF jaundiced patients, aged ≥ 15 years and diagnosed as having severe malaria according to WHO 2000 criteria, were enrolled. Patients with evidence of biliary obstruction, other cholestatic liver diseases and those who were pregnant were excluded. Patients were randomized to receive either oral UDCA or placebo for 2 weeks in additional to artesunate. All patients were admitted for at least 14 days to monitor the result of the treatment. Results: Seventy-four severe PF malaria patients with jaundice were enrolled. Both groups had similar demographic and laboratory tests, with the exception being more males in the UDCA group than in the placebo group (P = 0.04). The median of percentage change of total bilirubin and aminotransferase levels at the end of weeks 1, 2, 3 and 4 showed no difference between the two groups. Only the median of percentage change of alkaline phosphatase at the end of week one compared with the baseline values showed less increment in the UDCA group than in the placebo group (P = 0.04). No serious adverse events were seen during the 4 weeks of follow up. Conclusions: In severe PF malaria patients with jaundice, combined therapy with UDCA and artesunate is safe, but does not significantly improve liver tests compared to placebo and artesunate.

Background Malaria is still prevalent in Southeast Asia where large numbers of backpackers visit each year. This study aimed to assess the knowledge, attitude, and practices among foreign backpackers toward malaria risk in Southeast Asia. Methods Questionnaires were administered to foreign backpackers in Bangkok, Thailand. They were asked about their general background, their attitude to malaria risk, and their preventive measures against malaria. Their knowledge about malaria was assessed by 10 true–false questions in the questionnaires. Results In total, 434 questionnaires were evaluated. Fifty‐five percent of travelers were male and the median age was 28 years. The main reason for travel was tourism (91%). Almost all travelers (94%) were aware of the risk of malaria. Twenty‐two percent of them would take antimalarial prophylaxis and 33% would use measures against mosquito bite, but nearly 40% had “no prevention” at all. Mean knowledge score was only 5.52 of 10. Most backpackers (92%) knew that malaria is a serious disease and sometime fatal and 74% knew that some travelers could develop malaria after they return. However, up to 35% believed that eating contaminated food could lead to malaria infection. And 49% believed that malaria could be 100% prevented by chemoprophylaxis. In backpackers, who had traveled in the forest ( n = 65), only 54% used insect repellent regularly. Among those who had taken antimalarial prophylaxis, nearly 30% had stopped the medication prematurely. Conclusions Although most backpackers perceive the risk of malaria in Southeast Asia, they have some misunderstandings about malaria and tend to comply poorly with mosquito bite prevention and chemoprophylactic strategies.

The effects of loading doses and probenecid coadministration on oseltamivir pharmacokinetics at four increasing dose levels in groups of eight healthy adult Thai volunteers (125 individual series) were evaluated. Doses of up to 675 mg were well-tolerated. The pharmacokinetics were dose linear. Oseltamivir phosphate (OS) was rapidly and completely absorbed and converted (median conversion level, 93%) to the active carboxylate metabolite. Median elimination half-lives (and 95% confidence intervals [CI]) were 1.0 h (0.9 to 1.1 h) for OS and 5.1 h (4.7 to 5.7 h) for oseltamivir carboxylate (OC). One subject repeatedly showed markedly reduced OS-to-OC conversion, indicating constitutionally impaired carboxylesterase activity. The coadministration of probenecid resulted in a mean contraction in the apparent volume of distribution of OC of 40% (95% CI, 37 to 44%) and a reduction in the renal elimination of OC of 61% (95% CI, 58 to 62%), thereby increasing the median area under the concentration-time curve (AUC) for OC by 154% (range, 71 to 278%). The AUC increase for OC in saliva was approximately three times less than the AUC increase for OC in plasma. A loading dose 1.25 times the maintenance dose should be given for severe influenza pneumonia. Probenecid coadministration may allow considerable dose saving for oseltamivir, but more information on OC penetration into respiratory secretions is needed to devise appropriate dose regimens.

In a retrospective study of 1415 patients aged 15 and over, we determined the incidence of clinically important hyponatraemia and hypokalaemia in adults with uncomplicated malaria. On admission, serum concentrations of sodium (135–145 mmol/L) and potassium (3.5–5.0 mmol/L) were found outside these reference ranges in 81% of patients. Severe hypokalaemia (K+ 100 mg/dL) were all independent factors ( P < 0.001). Other independent predictors for hypokalaemia were Plasmodium vivax infection, female gender; and for hyponatraemia, P. falciparum infection, male gender, concentrations of G-6-PD and serum bicarbonate.

The aims of this study were to determine tuberculosis patients' treatment-seeking behaviors, to describe knowledge of TB among TB patients, how that knowledge affected their treatment-seeking behaviors, and to develop an appropriate model to strengthen the existing DOTS program. A cross-sectional study was conducted in all government TB clinics in Samut Prakan Province, Thailand during November 2005-May 2006. The triad model, which emphasizes the role of a triad of persons (the healthcare provider, the TB patient, and his/her treatment supporter), can improve patient adherence to TB treatment regimen. The results showed that only about a quarter (27.7%) of TB patients chose the hospitals with TB clinic for first treatment, while others chose alternative healthcare modes, including self-care and purchasing drugs from drugstores. The rate of successful treatment was higher for the experimental group (96.0%) than the control group (84.9%) (p = 0.057). The confirmed cure rate was also significantly higher in the experimental group (95.3% vs 78.9%, p = 0.02). The program could be utilized to strengthen the existing DOTS program.

Malaria and concurrent bacteremia has been described in many reports, most of them with P. falciparum. Concurrent bacteremia with P. vivax infected patients is very rare. We reported 2 cases of salmonella bacteremia with P. vivax infection. Both patients presented with fever and the diagnosis of P. vivax was confirmed microscopically. The first patient presented with fever, jaundice, shock and renal failure which rarely occurs with P. vivax infection. The second patient had no clinical response after receiving standard antimalarial drugs. Hemoculture was positive for Salmonella spp in both cases. They recovered completely after appropriate antibiotics and antimalarial treatment.

Previous studies have revealed that ivermectin treatment for gnathostomiasis can reduce parasitic loads in animals and make recurrent subcutaneous swelling subside in 76% of patients. Our study aimed to evaluate the efficacy of ivermectin for cutaneous gnathostomiasis treatment in a placebo-controlled trial. This study was a prospective randomized placebo-controlled study performed at The Bangkok Hospital for Tropical Diseases, Mahidol University, Thailand. Thirty patients with a serologically confirmed diagnosis of cutaneous gnathostomiasis were enrolled. Seventeen patients in the ivermectin treated group received a single dose of 12 mg ivermectin (200 microg/kg bodyweight), while 13 patients in the control group received a single dose of 40 mg of vitamin B1. The follow-up period was 1 year. Of the 17 patients, 7 (41.2%) responded to ivermectin, while no patient responded to placebo. The mean (95% Cl) time to the first recurrence of subcutaneous swelling with ivermectin and in the placebo groups were 257 (184-331) and 146 (42-250) days, respectively, (p=0.102). Although this study revealed no significant difference in the mean time to first recurrence of swelling between the ivermectin and placebo groups, there was a trend towards ivermectin efficacy against gnathostomiasis in previous animal and human studies. Further studies with different doses of ivermectin and larger sample sizes, and close monitoring for ivermectin tolerability and treatment response are necessary to confirm an efficacy of ivermectin.

We retrospectively examined the charts of travelers admitted to the Hospital for Tropical Diseases, Bangkok, Thailand, with malaria during the years 2000-2005. Twenty-one cases of malaria were identified, of which 12 (57%) were Plasmodium vivax infections and 9 (43%) were P. falciparum infections. There was one mixed case with vivax and falciparum infection. Only 1 P. falciparum case had complications. All cases were successfully treated with standard antimalarial drugs. Only 3 of the 21 cases were thought to be acquired in Thailand, the rest were regarded to be imported.

Background. Because antimalarial drug resistance is spreading, there is an urgent need for new combination treatments for malaria, which kills >1 million people every year. Azithromycin is a macrolide antibiotic that is particularly attractive as an antimalarial because of its safety in children and the extensive experience with its use during pregnancy.Methods. We undertook a randomized, controlled, 28-day inpatient trial involving patients with acute, uncomplicated Plasmodium falciparum malaria. We compared the safety and efficacy of 2 azithromycin-artesunate combinations and 2 azithromycin-quinine regimens in adults with malaria. Treatments were as follows: cohort 1 received 3 days of azithromycin (750 mg twice daily) plus artesunate (100 mg twice daily), cohort 2 received 3 days of azithromycin (1000 mg once daily) plus artesunate (200 mg once daily), cohort 3 received 3 days of azithromycin (750 mg twice daily) plus quinine (10 mg/kg twice daily), and cohort 4 received 3 days of azithromycin (500 mg 3 times daily) plus quinine (10 mg/kg 3 times daily). The enrollment target was 25 evaluable subjects per group.Results. The 28-day cure rates were similarly high in the artesunate and the standard-dose quinine cohorts: 92.0% (95% confidence interval [CI], 74.0%–99.0%), 88.9% (95% CI, 70.8%–97.6%), and 92.0% (95% CI, 74.0%–99.0%), for cohorts 1, 2, and 4, respectively. Late R1 treatment failures were seen in each of the artesunate and the standard-dose quinine cohorts. The cure rate for cohort 3 was 73.3% (95% CI, 44.9%–92.2%). In this cohort, 3 early treatment failures led to the termination of enrollment after 16 subjects had been enrolled. With mean parasite and fever clearance times (±SD) of 34 ± 13 h and 20 ± 20 h, the artesunate combinations were found to have led to a significantly (P < .001) faster clinical and parasitological improvement than occurred in the quinine cohorts (74 ± 32 h and 43 ± 37 h, respectively). Treatment-related adverse events were significantly more common in the quinine cohorts (P < .001). No deaths or drug-related serious adverse events were observed. In vitro results suggest that the treatment failures—particularly in the low-dose quinine cohort—were associated with decreased susceptibility to quinine, as well as with mefloquine cross-resistance.Conclusions. These data suggest that azithromycin-artesunate, even when given only once daily for 3 days, and azithromycin-quinine, given 3 times daily, are safe and efficacious combination treatments for uncomplicated falciparum malaria, and they deserve additional study in special patient populations.

We reviewed the records of 1,175 patients with uncomplicated Plasmodium falciparum malaria to determine the prevalence of gametocytemia. All patients were admitted and received artemisinin combination therapy. Blood films were checked daily until discharge. Circulating gametocytes were observed in 240 (20.2%) of patients and in most cases (222 of 240, 92.5%) gametocytemia was detected during the first 24 hours after admission. Gametocytes were first seen in 174 cases on admission, in 24 cases at 12 hours, and in 24 cases at 24 hours. The longest interval between admission and first appearance of gametocytes was 192 hours. The median gametocyte clearance time was 163 hours (range = 12-806) in the 219 patients in whom gametocytemia resolved. However, 21 patients (9.8%) still had gametocytemia on discharge. Gametocytemia generally is present within the first 24 hours after admission, and emerges in only 1.9% of patients later on during treatment with artemisinin.