Watcharapong Piyaphanee

Pharmacokinetics of High-Dose Oseltamivir in Healthy Volunteers

ABSTRACT 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.

Rabies Exposure Risk among Foreign Backpackers in Southeast Asia

Rabies remains a problem in Southeast Asia where large numbers of backpackers visit each year. During May-June 2008, a survey study was conducted of foreign backpackers in Bangkok, Thailand to assess their risk of rabies exposure. Eight hundred seventy (870) questionnaires were collected and analyzed. The median age of the backpackers was 25.5 years. Most of them were European (68.4%), followed by North American (13.2%). Although 80.7% had sought health information before traveling, only 55.6% had received information about rabies. Only 18.1% had completed pre-exposure rabies vaccination (3 shots) before travel, whereas 70.9% had not been vaccinated for rabies at all. In this study, the incidence of being licked was 3.56%, and of being bitten 0.69%, on average stays of 30.06 days in Southeast Asia. More than a half (54%) of exposures occurred in the first 10 days after arrival in Southeast Asia.

Regional Variation in Travel-related Illness acquired in Africa, March 1997-May 2011

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.

Risk of potentially rabid animal exposure among foreign travelers in Southeast Asia.

Background Each year millions of travelers visit Southeast Asia where rabies is still prevalent. This study aimed to assess the risk of rabies exposure, i.e., by being bitten or licked by an animal, among travelers in Southeast Asia. The secondary objective was to assess their attitudes and practices related to rabies. Methodology/Principal Findings Foreign travelers departing to the destination outside Southeast Asia were invited to fill out the study questionnaire in the departure hall of Bangkok International Airport. They were asked about their demographic profile, travel characteristics, pre-travel health preparations, their possible exposure and their practices related to rabies during this trip. From June 2010 to February 2011, 7,681 completed questionnaires were collected. Sixty-two percent of the travelers were male, and the median age was 32 years. 34.0% of the participants were from Western/Central Europe, while 32.1% were from East Asia. Up to 59.3% had sought health information before this trip. Travel clinics were the source of information for 23.6% of travelers. Overall, only 11.6% of the participants had completed their rabies pre-exposure prophylaxis, and 15.3% had received only 1–2 shots, while 73.1% had not been vaccinated at all. In this study, the risk of being bitten was 1.11 per 100 travelers per month and the risk of being licked was 3.12 per 100 travelers per month. Among those who were bitten, only 37.1% went to the hospital to get post exposure treatment. Travelers with East Asian nationalities and longer duration of stay were significantly related to higher risk of animal exposure. Reason for travel was not related to the risk of animal exposure. Conclusions Travelers were at risk of being exposed to potentially rabid animals while traveling in Southeast Asia. Many were inadequately informed and unprepared for this life-threatening risk. Rabies prevention advice should be included in every pre-travel visit.

Travel Medicine for Asian Travelers—Do We Need New Approaches?

Travel medicine evolved as an interdisciplinary field in the late 1980s with an initial focus on travelers from Europe, North America, Australia, and New Zealand (referred to as “Western” countries) visiting developing countries. The basis of travel medicine was to try to decrease the risks of disease and injury for individual travelers when visiting environments perceived as having excess health risks compared to the home country. Owing to economic growth in large parts of Asia, the number of outbound travelers from this region is dramatically increasing. In 1990, only 50 million Asians traveled abroad, while this number reached 100 million in the year 2000 and 190 million in 2010. 1 The outbound tourism growth rate among Asian travelers is the highest in the world. Thus, travelers from Asia are becoming a major proportion of world tourism. In 1980 less than 10% of international travelers were from Asia. This proportion doubled in 2010 and it is expected to reach 30% in 2030, equal to 500 million. 1 So far, the concept of travel medicine is not well known in Asia among both travelers and health care professionals. Only 21% to 40% of Asian travelers sought pre‐travel health information before their trip; 2,3,4 this proportion being far lower as compared to 60% to 80% in “Western” travelers. 5,6 Recent evidence is even more concerning; only 4% of Chinese travelers who traveled to high malaria risk areas visited a travel clinic before their trip, 7and only 5% of Japanese travelers who traveled to developing countries … Corresponding Author: Watcharapong Piyaphanee, MD, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, Ratchathewi, Bangkok 10400, Thailand. E‐mail: watcharapongpiy{at}mahidol.ac.th

Animal-associated exposure to rabies virus among travelers, 1997-2012.

No demographic characteristics identified who might benefit most from pretravel counseling.

Determinants of pre-exposure rabies vaccination among foreign backpackers in Bangkok, Thailand.

Important variations were observed regarding the proportion of backpackers seeking information about travel-associated diseases before departing for Thailand. The main determinants were nationality, reason for travel and age. Sources of information used by travelers varied substantially according to nationality. Moreover, significant differences were recorded regarding pre-exposure vaccination rates against rabies. Having British or Irish citizenship and seeking advice from travel clinic specialists or friends were the strongest and most significant determinants of rabies vaccination history. A significant relationship between vaccine cost and vaccination coverage was also evidenced.

Incidence and Spectrum of Health Problems Among Travelers to Laos

BACKGROUND The number of travelers visiting Laos has more than doubled in the last 5 years. Little is known about their pre-travel preparations and the incidence of health problems during their trips. METHODS At three border posts between Laos and Thailand, travelers were invited to complete a study questionnaire. They were asked about their demographic profile, travel characteristics, pre-travel health preparations, and health problems during their stay in Laos. RESULTS From September 2011 to April 2012, 1,205 questionnaires from Thais and 1,191 from foreigners were collected. Approximately 60% of the travelers were male; the overall median age among the Thais was 43 years, and among the foreigners was 32 years. Most foreign visitors were from Europe (66.8%), followed by other Asian countries (19.0%) and North America (7.1%). Almost half of the foreigners (47.8%) traveled as individual backpackers, whereas the majority of Thais traveled as package tourists. Foreigners were more likely to trek, cycle, and swim during their trips. There were also significant differences in the average length of stay between foreigners (16.1 days) and Thais (3.8 days, p < 0.001). Health problems were reported in 24.9% of foreigners, the most common being diarrhea, cough, animal exposure, and fever. Only 6.1% of Thais reported health problems, the most common being cough and diarrhea. The relative risk adjusted for duration of stay was 1.63 (95% confidence interval: 1.01-2.64). Occurrence of health problems was associated with younger age group, non-Asian nationality, length of stay, and participation in adventurous activities. CONCLUSIONS Health problems are rather frequent among non-Thai travelers in contrast to Thais during their trips to Lao Peoples Democratic Republic. There were significant differences in terms of risk profile and prevalence of health problems between these two groups.

Residency training in travel medicine—a 3-year journey to become a specialist

Originally, travel medicine providers were practitioners from several disciplines such as infectious diseases, tropical medicine, internists, General practitioners (GPs), public health, also nurses and pharmacists. All providers have the same objective i.e. keep travellers safe and healthy. Unfortunately, good intention is not enough. In the past few decades Travel Medicine has become increasingly complex with a dramatically expanded body of knowledge (BOK). Practitioners who take care for travellers are expected to have a unique interdisciplinary knowledge as formulated in the International Society of Travel Medicine’s (ISTM) BOK.1–3 Special training in travel medicine is essential for practicing in a travel clinic. Previous research demonstrated that the knowledge and experience acquired in medical school or even postgraduate study in related fields are usually insufficient.4–7 For example, up to 61% of infectious diseases physicians were aware that they are not well-prepared to take care of travellers.8 Currently, various training courses in Travel Medicine are offered around the world.5 Their duration varies from a few days to few years and resulting in a diploma or Master degree. The best known example is the Certificate of Travel Health issued by the ISTM for which short preparation courses are offered and additionally the study of textbooks and other publications are expected. Although all courses aim to provide necessary …

A Bubble Turtle: Bullous Contact Dermatitis after a Black Henna Tattoo in a Backpacker in Thailand

An 18-year-old British male backpacker attended the Travel Clinic at the Bangkok Hospital for Tropical Diseases with large, itchy, and painful blisters arranged in a turtle-shaped pattern on the right forearm for 9 days. Thirteen days prior to attending the Travel Clinic, he had had a temporary black henna tattoo applied to that area by a street vendor. Two days after that, he developed itching and irritation in that area, and then 2 days later, turtle-shaped vesicles developed. His skin lesion is shown in Figure 1a and the diagnosis was contact dermatitis caused by black henna tattoo. Figure 1 (a) Severe reaction of contact dermatitis: …