Comparison of whole blood and serum levels of mefloquine and its carboxylic acid metabolite.

Because of the widespread presence of chloroquine-resistant Plasmodium falciparum malaria, mefloquine is now the recommended drug of choice for long-term malaria prophylaxis in these areas. Although several studies have compared plasma and whole blood concentrations of either mefloquine or its carboxylic acid metabolite, we report the first comparison of serum and whole blood levels in 86 Dutch marines taking 250 mg of mefloquine weekly for 18 weeks while deployed in western Cambodia. All samples were taken during steady-state and at 42-48 hr after the most recent dose. The concentration of mefloquine in serum (mean = 979 ng/ml) was significantly greater than in whole blood (mean = 788 ng/ml) (P < 0.00001, by paired t-test) with an overall mean ratio of 1.28. The concentration of the metabolite in serum (mean = 3,039 ng/ml) was also significantly greater than in whole blood (mean = 1,390 ng/ml) (P < 0.00001, by paired t-test) with an overall mean ratio of 2.25. These findings are similar to previous reports of plasma-to-whole blood levels. Furthermore, we report that the within-individual ratios of the metabolite concentration to the mefloquine concentration were also found to be significantly different in serum (3.79; P < 0.00001, by paired t-test) and in whole blood (2.02; P < 0.00001, by paired t-test). Appropriate attention must be given to these differences when comparing serum and whole blood concentrations of either mefloquine or its metabolite to avoid misinterpretation of their respective levels. Also, the determination of the relative mefloquine ratios in various blood fluids, as well as the documentation of the metabolite levels and their ratios, is critical to the appropriate interpretation of both chemoprophylaxis and chemotherapy, especially in the presence of resistant strains.

Immunogenicity of an inactivated hepatitis A vaccine in Dutch United Nations troops.

Limited information existed on the immunogenicity of an inactivated hepatitis A vaccine as part of an extensive vaccination schedule. Dutch marines bound for duty in Cambodia received inactivated hepatitis A vaccine (720 ELISA units of antigen, two intra-gluteal doses at a 2-week interval before departure and an intra-deltoid booster vaccination after 8 months) simultaneously with several other vaccines. Hepatitis A antibodies were determined in blood-samples drawn before and after the booster vaccination, using two laboratory tests (modified HAVAB and SBB-ELISA). At 8 months, before the booster vaccination, 52% (modified HAVAB) and 81% (SBB-ELISA) had seroconverted. Risk factors for non-seroconversion were increasing age and a typhoid vaccination. At 11 months 97.6% (modified HAVAB) and 100% (SBB-ELISA) had seroconverted. Non-seroconversion at 8 months was remarkably high. SBB-ELISA was more sensitive in lower titre ranges.

Tolerance of mefloquine chemoprophylaxis in Dutch military personnel.

From June until October 1993, a battalion of Dutch marines was stationed in Cambodia for a United Nations deployment. In 73 volunteers who used mefloquine as malaria chemoprophylaxis, possible mefloquine-related adverse events were monitored with special emphasis on QT prolongation. All participants started mefloquine chemoprophylaxis with a loading dose (250 mg a day for three days) one week before departure, followed by a weekly dose (250 mg) for approximately 25 weeks. One month before (t - 1) and one (t + 1) and three (t + 3) months after mefloquine prophylaxis was started, an at rest electrocardiogram was made. Frequency, PR-, and QT-intervals were measured; blood samples for liver transaminases, total white blood cell count, and mefloquine concentration were obtained after one and three months. Adverse events such as dizziness, headache, coordination problems, and nausea were spontaneously reported in one (1.4%) and three (4.1%) persons at t + 1 and t + 3, respectively, while specific questioning revealed adverse events in nine (12.3%) and five (6.9%) persons, respectively, at the same time point. Three months after starting chemoprophylaxis, the heart rate at rest and total white blood cell count were lower (P < 0.05), while the QTc-interval was longer and levels of liver transaminases increased (P < 0.05), although both were still within the normal range. There was no extreme prolongation of the QTc-interval or increased levels of liver transaminases that resulted in a need to stop the chemoprophylaxis. No accumulation of mefloquine in the serum occurred, and no relationship was observed between the incidence of adverse events and serum mefloquine concentrations. The incidence of self reported mefloquine-related adverse events was low. In conclusion, mefloquine chemoprophylaxis was safe and well-tolerated in this group.

Long-term malaria chemoprophylaxis with mefloquine in Dutch marines in Cambodia.

Three Dutch marine battalions (n=2289) serving in Western Cambodia during 1992-1993 used mefloquine as weekly malaria chemoprophylaxis. One battalion started with a loading dose. Full compliance with prophylaxis was reported by 86.3%, and possible mefloquine-related adverse events were reported by 30.2%. Sixty-four periods of malaria were diagnosed in 59 marines. During deployment, 31 Plasmodium falciparum and no Plasmodium vivax infections occurred. After return, there were 11 cases of falciparum malaria and 22 of vivax malaria, 16-72 days and 30-540 days, respectively, after stopping prophylaxis. Mefloquine-resistant parasites were isolated from 4 Dutch and 4 Khmer patients. Long-term mefloquine prophylaxis was well tolerated but not totally effective.

Sexual behaviour and sexually transmitted diseases in Dutch marines and naval personnel on a United Nations mission in Cambodia.

OBJECTIVES: To determine the sexual risk behaviour and the incidence of sexually transmitted diseases (STD) among Dutch marines and naval personnel during a United Nations (UN) deployment. METHODS: Surveillance by post deployment questionnaire, administered to 2289 persons in three successive battalions who served for 6 months on a UN deployment in Cambodia during June 1992-November 1993. On site the medical history of all individuals was kept up to date in a database. All personnel received extra education on STD prevention prior to deployment. Condoms were freely obtainable during deployment. RESULTS: 1885 persons (82%) handed in the questionnaire of whom 842 (45%) reported to have had sexual contacts with prostitutes or local population. Being younger and single were independent risk factors for having contact. Out of these 842 persons, 750 (89.1%) reported condom use at all times, while 82 (9.7%) reported inconsistent use and 10 persons (1.2%) reported not to have used condoms. Risk factors for inconsistent and non use were being 40 years or older and a higher number of contacts. From the 832 (750 + 82) condom users, 248 (30%) reported condom failure. Risk factors for failure were: inconsistent condom use, having had more than six contacts and being in the second battalion. The patient recording database showed 43 STD cases registered in the total population of 2289 persons (1.9%). CONCLUSIONS: A low STD incidence was found despite a considerable number of reported sexual contacts. The reported condom use was high but the failure rate was considerable and needs further attention.