The spread of chloroquine-resistant Plasmodium falciparum in Sub-Saharan Africa has led to significant health concerns for Peace Corps volunteers. Since 1986, more than 1,600 P. falciparum infections have been diagnosed among the approximately 2,000 volunteers in that region. Malaria prophylaxis is mandatory for all Peace Corps volunteers. Since chloroquine, either alone or in combination with proguanil, no longer provides adequate prophylaxis, the use of mefloquine is encouraged but not mandate.
When mefloquine was introduced in September 1989, the recommended regimen was 250 mg weekly for four weeks, followed by 250 mg every two weeks. Monitoring studies found that this regimen did not achieve blood concentrations of mefloquine capable of suppressing parasitemia, leading to the recommendation that 250 mg of mefloquine should be taken every week for effective prophylaxis. Lobel and colleagues compared the effectiveness of a weekly mefloquine regimen with that of other prophylactic regimens.
Peace Corps volunteers who were stationed in malaria-endemic regions of West Africa between October 1989 and May 1992 were studied. The study group included 1,322 volunteers who were at high risk of malarial infection. These volunteers were exposed to the possibility of infection for 13,487 person-months. A detailed history of the type and duration of malaria prophylaxis used was obtained from each volunteer, and blood samples were examined for evidence of malarial infection. In study subjects who used mefloguine, blood was also drawn for measurement of serum drug concentrations. The occurrence of side effects was measured by direct questionnaires completed every four months by the volunteers and by reports from the monitoring medical officers.
The original mefloquine regimen of 250 mg every two weeks was used for 3,328 person-months of prophylaxis. The incidence of malarial infections with this regimen was 1.4 per 100 volunteers per month, which is significantly lower than the rates of 3.1 and 2.1, respectively, achieved with chloroquine alone or chloroquine in combination with either proguanil or pyrimethamine-sulfadoxine. The change to a weekly regimen of mefloquine resulted in even lower rates of infection, at 0.2 cases per 100 volunteers per month.
The authors conclude that weekly mefloquine was 94 percent more effective than chloroquine, 86 percent more effective than chloroquine plus proguanil, and 82 percent more effective than mefloquine taken every other week. Analysis of blood concentrations of mefloquine during the study suggested that prophylactic efficacy of 99 percent can be achieved with blood mefloquine concentrations of 915 ng per mL. This rate falls to 90 percent at mefloquine concentrations of approximately 462 ng per mL.
Apart from serum drug concentrations, the only measure of compliance in this study was reports from the volunteers. Five percent of volunteers who used weekly mefloquine reported missing or delaying one or more doses. Comparable figures for the every-other-week mefloquine regimen and for chloroquine were 6 percent and 10 percent, respectively.
None of the regimens resulted in serious side effects. Mild effects were common and occurred in 40.6 percent of volunteers taking mefloquine and 45.8 percent of the volunteers taking chloroquine. The frequency and type of side effects of the two drugs were similar with the exception of nausea, which was significantly more common with chloroquine. The frequency of side effects decreased over time. Only 19 percent of those using mefloquine for more than one year reported side effects. Only seven of 802 volunteers discontinued this drug because of side effects.
In recent years, considerable confusion has existed over how travelers should be advised about malaria prophylaxis in Africa. By one report, 68 different drug regimens were used by European and North American travelers who visited Kenya for a short time. The authors conclude that mefloquine is safe and effective, and recommend it as the drug of choice for malaria prophylaxis in Africa. They believe that many of the questions raised about this drug are based on theoretical considerations that may not pertain to practice. However, they caution that continued monitoring is warranted to document any subgroups of patients for whom mefloquine is inappropriate and to detect the development of resistance.
COPYRIGHT 1993 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group
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