By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.

Better Medical Advice

Sources: Rack J, et al. Risk and Spectrum of Diseases in Travelers to Popular Tourist Destinations. J Travel Med. 2005;12:248-253; Hillel O, Potasman I. Correlation Between Adherence to Precautions Issued By the WHO and Diarrhea Among Long-Term Travelers to India. J Travel Med. 2005;12:243-247.

Following the tragedy on the Jamarat Bridge at Hajj in January 2006, many travel advisors felt the need to re-double their efforts in providing better travel advice. While it is widely acknowledged that this advice is inconsistently followed, this recent tragedy, and the rise of adventure travel, especially among younger travelers, raises an interesting opportunity for physicians practicing emporiatrics. Much the same as primary care physicians have been charged with providing routine safety advice (eg, wear your seatbelt), how can a travel medicine specialist provide more cogent advice to travelers, and will such advice result in meaningful changes in behavior during travel?

These 2 articles highlight the current trends and challenges faced by physicians practicing emporiatrics. Rack and colleagues tracked 794 Germans traveling to popular tourist destinations in tropical countries (Kenya, Tanzania, Senegal, the Gambia, Thailand, Nepal, India and Brazil), who consulted the Berlin Institute of Tropical Medicine for pre-travel medicine advice, 83% of whom responded to a follow-up questionnaire.

The average duration of travel was 24 days. Trauma occurred in 34 respondents (5.2% of all travelers), about one-fourth of which involved vehicular accidents and, by far, resulted in the most severe injuries. About one-fourth required medical care, hospitalization, or transport back to Germany. An additional 4 persons were assaulted or robbed. Overall, illness or injury affected nearly half of the group, including gastrointestinal complaints (35%), respiratory illness (14%), fever (6%), and dermatologic problems (4%). Ten percent reported more than one medical problem. However, medical illness was generally less severe, was self-treated in 60% of cases, and resulted in hospitalization or transport in only 2 of 282 cases of medical illness (< 1%).

On the other hand, Hillel and colleagues confirm the remarkably low rate of compliance rate with travel medicine advice. In this study, 20% of those traveling to malaria endemic areas did not bother to take their malaria prophylaxis. Only a fraction consistently adhered to precautions regarding food and water. Lack of compliance with pre-travel medicine advice is not just common, it appears to be the norm, especially for younger more adventuresome travelers. Lack of adherence to dietary restrictions is difficult, especially for long-term travelers, and lacks proven value (with the possible exception of eating in people’s homes, eating in restaurants and hotels vs street food seems to result in similar rate of gastrointestinal illness) (see Kemper March 2005).

Rather than emphasizing food and water precautions, clients may be better served by providing clearer statistics on the frequency of routine medical illness to certain areas, and arming them with symptomatic remedies for diarrheal and respiratory illness. Since injury more frequently results in a worse outcome, advice should be tailored to individual risk factors and personnel safety.

Khat Use in an HIV Methamphetamine User

An HIV-Infected patient recently presented for routine clinical evaluation. She had chronic HCV infection, a lengthy history of drug use, most recently methamphetamines. She was receiving Truvada and Fosamprenavir for about 9 months, to which she was poorly adherent but tolerated fairly well. Her CD4 counts ranged from 200-300s. On presentation, she complained of nausea, with a bilirubin of 9.4 and serum transaminases ~10 times the upper limit of normal. On further questioning, she was pleased to tell me that she had cut back on her methamphetamine use and, instead, was using something called khat. She relayed to me that khat was safe, and was used by all her Ethiopian friends in the local community.

After further investigation, it is believed that her khat use is the likely cause of her hepatic dysfunction. Khat is used throughout East Africa and Arabian countries as a mild central stimulant and euphoriant. Khat is derived from the Catha edulis plant (and is also referred to as Abyssinian Tea, Arabian Tea, Kat, Gat, Caat, Qut, Tobia or Tchaad). The leaf and stems contain cathine, which has about one-tenth the stimulant effect of d-amphetamine, and cathinone, which is a more powerful stimulant then cathine, and closely resembles ephedrine and amphetamine in chemical structure.

When taken orally, khat initially results in increased alertness, talkativeness, hyperactivity, and anxiety; higher doses result in aggressive behavior, mania, and paranoia. Cardiovascular side effects include tachycardia, palpitations, sweating, and hypertension. Chronic use can result in paranoia and psychosis, although psychotic breaks occur less commonly than with amphetamines. In men, Khat initially increases libido, but chronic use results in diminished sexual drive, spermatorrhea, and impotence. Other side effects include insomnia, malaise, pupillary dilation, stomatitis, esophagitis, periodontal disease, constipation, diminished appetite, and weight loss. It has also been linked to migraine, cerebral hemorrhage, pulmonary edema, myocardial infarction, hepatic dysfunction, and cirrhosis. Interestingly, cases of Fasciola hepatica have been reported in khat users, most likely from contamination of the freshly picked damp leaves.

Khat is considered to be a dependence-producing drug by the World Health Organization. It is not physically addicting, but it is associated with psychological dependence. Because of its stimulant properties, khat use has been, in part, blamed for the aggression and civil conflict in Somalia and in other Arab countries. It might be interesting to question patients of East African, Middle Eastern, or Arab decent regarding their use of khat, especially those with liver function test abnormalities. Whether the drug was grown locally or imported was not determined.

Rifaximin Prophylaxis for Travelers Diarrhea

DuPont HL. A Randomized, Double-Blind, Placebo-Controlled Trial of Rifaximin to Prevent Travelers’ Diarrhea. Ann Intern Med. 2005;142:805-812. Erratum in: Ann Intern Med. 2005;143:239

Rifaximin is a Rifamycin derivative that is poorly absorbed through the intestinal tract (< 0.4%), and has broad activity against many of the bacterial pathogens that commonly cause travelers diarrhea. DuPont and colleagues investigated the effectiveness of rifaximin in 210 young adults traveling from the United States to Mexico in the prevention of travelers’ diarrhea. Travelers were randomized to rifaximin 200 mg once, twice, or 3 times daily vs placebo for 14 days. The study was double-blinded. Stool samples were collected for culture at one and 2 weeks of study.

Rates of diarrhea (defined as ≥ 3 unformed stools per day plus at least one other gastrointestinal symptom or fever) were significantly lower in all rifaximin groups compared with placebo. At week 1, rates of diarrhea varied from 2% to 13.5% in the rifaximin group vs 31.5% in the placebo group (P < .001). At week 2, in those that had been diarrhea-free at week 1, rates of diarrhea varied from 6.7% to 10.2% in the rifaximin groups vs 32.4% in the placebo group (P < .01). In those who were diarrhea-free at the end of study, rates of diarrhea increased slightly in rifaximin users but not significantly more so than in placebo users.

Enterotoxigenic E. coli (ETEC) was the most important pathogen observed in this study. A statistical significant reduction was observed in the frequency of isolation of ETEC in those receiving rifaximin (7.1%) compared with the placebo group (40.7%). Median colony counts of coliforms and enterococcal species did not significantly differ between the treatment and placebo groups, and there was no apparent increase in resistance of gram positive and gram negative flora during rifaximin use. The protection rate of rifaximin against mild diarrhea and ETEC diarrhea was 83%. This is similar to the effectiveness of fluoroquinolones when used as prophylaxis, but better than that afforded by probiotics and bismuth-containing compounds. DuPont et al suggest that travelers take a single daily dose of rifaximin with their riskiest meal of the day.