Malaria prophylaxis policy for travellers from Europe to the Indian Sub Continent

Background

Thick blood films are routinely used to diagnose Plasmodium falciparum malaria. Here, they were used to diagnose volunteers exposed to experimental malaria challenge.

Methods

The frequency with which blood films were positive at given parasite densities measured by PCR were analysed. The poisson distribution was used to calculate the theoretical likelihood of diagnosis. Further in vitro studies used serial dilutions to prepare thick films from malaria cultures at known parasitaemia.

Results

Even in expert hands, thick blood films were considerably less sensitive than might have been expected from the parasite numbers measured by quantitative PCR. In vitro work showed that thick films prepared from malaria cultures at known parasitaemia consistently underestimated parasite densities.

Conclusion

It appears large numbers of parasites are lost during staining. This limits their sensitivity, and leads to erroneous estimates of parasite density.     

Malaria prophylaxis: postal questionnaire survey of general practitioners in south east Wales.

Postal questionnaires were sent to 494 general practitioners in south east Wales asking about their experience and understanding of antimalarial prophylaxis; 293 were returned, giving a response rate of 59%. Forty eight (16%) of the respondents reported being consulted by immigrants returning home for advice about malaria prophylaxis, of whom 13 (27%) overestimated the time for which their protective immunity might last after leaving the malarious area. Two hundred and eighty respondents (96%) considered that they were responsible for advising travellers and 195 (67%) would always consult a publication before giving chemoprophylactic advice (magazines were particularly popular), but only 18 (6%) would always consult a specialist centre--the Ross Institute in eight cases (3%), a local centre in 39 (13%). Only about half of the doctors were aware of chloroquine resistance in Kenya and Thailand. Over half would withhold chloroquine in pregnancy, and many chose pyrimethamine alone or sulfadoxine-pyrimethamine as suitable chemoprophylactic drugs, though neither is still recommended by the World Health Organisation. One hundred and ninety two respondents (66%) would give advice about protective measures other than chemoprophylaxis. More must be done to encourage general practitioners to contact specialist centres and to educate them in the use of antimalarial chemoprophylactic drugs.     

Malaria prophylaxis: taking aim at constantly moving targets.

The prevention of malaria infections is one of the most important functions that any clinician can perform for those traveling to tropical geographic regions where malaria risks are present. The prophylaxis question has become complicated by continued emergence of chloroquine-resistant strains of Plasmodium falciparum, the recent appearance of Plasmodium vivax resistance, and the availability of a wide choice of antimalarial pharmaceuticals. Chemoprophylaxis may produce different toxicities among various patient populations. With increasing numbers of women who travel during their professional lives, there are potential implications for using chemoprophylaxis during pregnancy. Children are unable to tolerate certain antimalarials because of toxicities unique for them. In some instances, the safest and most palatable formulations for children are not even available in the United States and must be purchased in Canada or elsewhere. Reliance upon chemoprophylaxis alone has proven to be increasingly futile. With the introduction of new repellent formulations and nontoxic insecticides for use on clothing or bed netting, there are non-pharmacologic adjunctive measures which can now be considered first-line for the prevention of malaria infections.     

Comparison of adverse events associated with use of mefloquine and combination of chloroquine and proguanil as antimalarial prophylaxis: postal and telephone survey of travellers.

OBJECTIVE: To compare the frequency of adverse events, particularly neuropsychiatric effects, from mefloquine and from chloroquine plus proguanil as used for malaria chemoprophylaxis. DESIGN: Retrospective questionnaire to travellers taking either regimen between November 1993 and February 1995; telephone interview with those reporting pronounced side effects. SETTING: Travellers from Britain who consulted an advisory helpline. SUBJECTS: 1214 adults taking mefloquine and 1181 taking chloroquine plus proguanil. MAIN OUTCOME MEASURES: Reported presence of and degree of disability from 12 neuropsychiatric and other symptoms, as assessed by the subjects and by referees and on the basis of behaviour change. RESULTS: There were equal rates of any side effects (40%) and of stopping or changing medication. Overall, neuropsychiatric adverse events were significantly more common in travellers taking mefloquine. In all, 333 neuropsychiatric adverse events were reported by 1214 travellers taking mefloquine, compared with 189 such events in 1181 travellers taking proguanil plus chloroquine (P < 0.001). In all, 0.7% of travellers taking mefloquine had disabling neuropsychiatric adverse effects, compared with 0.09% of those taking proguanil plus chloroquine (P = 0.021). Two travellers taking mefloquine (1 in 607) were admitted to hospital as a result of the adverse event, compared with 1 in 1181 travellers taking proguanil plus chloroquine. CONCLUSION: There is a significant excess of adverse neuropsychiatric events of intermediate degrees of severity associated with the use of mefloquine compared with proguanil plus chloroquine. This finding may also explain the discrepant findings between earlier studies and clinical experience.     

Comparison of three regimens for malaria prophylaxis in travellers to east,central, and southern Africa.

OBJECTIVES--Confirmation of breakthroughs in three different malaria chemoprophylactic regimens (chloroquine 300 mg weekly and proguanil 100 mg daily; chloroquine 300 mg weekly and proguanil 200 mg daily; proguanil 200 mg daily) and assessment of compliance. DESIGN--Prospective, randomised multicentre trial. SETTING--Five vaccination centres in the Netherlands. SUBJECTS--Dutch travellers to east, central, and southern Africa. MAIN OUTCOME MEASURES--Plasmodium falciparum seen on blood film; concentrations of drugs measured in blood spots. RESULTS--P falciparum infection was confirmed in 12 (21%) of 58 travellers with fever suspected to be due to malaria. No difference in prophylaxis failures between the regimens was found. Breakthroughs were difficult to confirm, as compliance could be determined in only 30% of the participants with fever and chloroquine in their regimen. One breakthrough was proved. The risk per 1000 people per month for travellers was 5.4 (95% confidence interval 2.4 to 12.6) for chloroquine 300 mg weekly and proguanil 100 mg daily, 2.8 (0.9 to 10.1) for chloroquine 300 mg weekly and proguanil 200 mg daily, and 6.0 (2.6 to 14.0) for proguanil 200 mg daily. CONCLUSION--Prophylaxis failures occurred in less than 1% of the participants, and only 21% of those with a fever were suffering from falciparum malaria. Compliance was moderate. The chloroquine-proguanil combination can still be recommended for visitors to east, central, and southern Africa.