Letters

Prophylaxis against malaria

Preventing mosquito bites is also effective

Preferred prophylaxis varies by region

More studies of mefloquine prophylaxis must be done in tourists

Preventing mosquito bites is also effective

EDITORBerger's list of measures for protecting travellers against malaria is extremely useful.¹ The particular emphasis on compliance with drug regimens should not, however, detract from the importance of strict adherence to effective measures for preventing contact with mosquitoes and bites. No drug is totally effective, and in areas of low transmission the risk of adverse events attributed to chemoprophylaxis may well exceed the benefit of avoided infections.²

Although the World Health Organisation advocates protection against mosquito bites as the first line of defence against malaria, the basis for this recommendation has until recently been questionable.³ Evidence for a protective effect of insect repellants applied to the skin, air conditioners, fans, coils, vaporising mats, and long sleeved clothing has been largely speculative; use of these measures has been shown to result in decreased feeding by mosquito vectors, but direct evidence of a protective effect against malaria infection has not been gathered. Use of personal protection measures may have been compromised by widely publicised reports of encephalopathic reactions in children associated with the most widely used insect repellant, diethyltoluamide (DEET), and the nonchalance of many travellers.

This is exemplified by the results of a postal survey of visitors to the Kruger National Park, South Africa, during the seasonal high risk period. Over 95% (7034/7387) of tourists provided responses to the section investigating use of personal protection measures. Altogether 912 (13%) of these travellers used no personal protection measures and only 1209 (17.1%) used four or more. Neglect of these measures was positively associated with non-use of chemoprophylaxis, with 17.3% of tourists who were not taking chemoprophylaxis neglecting to use personal protection measures compared with 11.9% of those who were (²=28.24, df=1; or Fisher's exact P<0.001).

The most commonly used personal protection measures were insect repellants applied to the skin (by 5525 people), long sleeved clothing (by 2815), socks and shoes (by 2374), coils (by 1651), and vaporising mats (by 1076). Specific effective protection measures were little used, particularly aerosolised insecticides, usually synthetic pyrethroids, administered by spraying under pressure by a handled canister, much like a large deodorant can (by 548), bed nets (by 49) and impregnation of clothing with insecticide (by 12). Some travellers relied on ineffective measures, including ultrasonic buzzers (12 people), alcohol consumption (9), and ingestion of garlic (4).

Two recent papers are enlightening. A review of the toxicity of diethyltoluamide showed only two case reports of systemic toxicity after topical application in adults and 13 of encephalopathic toxicity in children despite 40 years of extensive use.⁴ A questionnaire survey of over 100 000 European tourists to east Africa found that air conditioned rooms (²=4.01, P=0.05) and clothing that covered arms and legs (²=5.25, P=0.02) effectively reduced the risk of malaria.⁵ Regular use of all or some of the four most important personal protection measures (air conditioned room and/or bed net, adequate clothing, insecticides and/or coils, repellants) reduced the risk of malaria to about half compared with that of other travellers using no such precautions (²=8.47, P=0.04).

Geographic knowledge of the distribution, drug resistance, and prevalence of malaria should be used to determine the type and necessity of chemoprophylaxis. Travellers should also be aware of the best personal protection measures against mosquito bites.

David N Durrheim, Consultant in communicable disease control. 
Mpumalanga Department of Health, Private Bag X11285, Nelspruit 1200, South Africa daved{at}social.mpu.gov.za

Peter A Leggat, Associate professor. 
School of Public Health and Tropical Medicine, James Cook University, Townsville, Queensland 4811, Australia

^a Competing interests: None declared.

1. Reid AJC, Whitty CJM, Ayles HM, Jennings RM, Bovill BA, Felton JM, et al. Malaria at Christmas: risks of prophylaxis versus risks of malaria. [With science commentary by A Berger.] BMJ 1998; 317: 1506-1508[Free Full Text]. (28 November.)
2. Durrheim DN, Braack LEO, Waner S, Gammon S. Risk of malaria in visitors to the Kruger National Park, South Africa. J Travel Med 1998; 5: 173-177.[Medline]
3. World Health Organisation. International travel and health: vaccination requirements and health advice. Geneva: WHO , 1998.
4. Fradin MS. Mosquitoes and mosquito repellents: a clinician's guide. Ann Intern Med 1998; 128: 931-940[Abstract/Free Full Text].
5. Schoepke A, Steffen R, Gratz N. Effectiveness of personal protection measures against mosquito bites for malaria prophylaxis in travelers. J Travel Med 1998; 5: 188-192.

Preferred prophylaxis varies by region

EDITORReid et al's lesson of the week on prophylaxis against malaria, and Berger's science commentary on it, made me think yet again how regional preferences affect the choice of prophylaxis against malaria.¹

British travellers are currently in the invidious position of choosing between mefloquine, which in most people's minds has a terrifying reputation, and the relatively ineffective combination of chloroquine and proguanil. Passing reference is made to pyrimethamine with dapsone (Maloprim), which is indicated for few destinations. Why is doxycyclinea drug that is deemed important for malaria prophylaxis by the rest of the worldnot even mentioned? There is good clinical evidence that it is effective,²⁴ and it has the advantage of not being tainted by media reports. Interestingly, North America steadfastly continues to ignore the existence of proguanilfurther perpetuating another anachronistic regional idiosyncrasy.

Andrew Jamieson, Medical director, British Airways travel clinics (South Africa). 
PO Box 2631, Knysna 6570, South Africa aj.plett{at}pixie.co.za

[Medline]
1. Reid AJC, Whitty CJM, Ayles HM, Jennings RM, Bovill BA, Felton JM, et al. Malaria at Christmas: risks of prophylaxis versus risks of malaria. [With science commentary by A Berger.] BMJ 1998; 317: 1506-1508. (28 November.)
2. Lobel HO, Kozarsky PE. Update on prevention of malaria for travelers. JAMA 1997; 278: 1767-1771[Abstract].
3. Ohrt C, Richie TL, Widjaja H, Shanks GD, Fitriadi J, Fryauff DJ, et al. Mefloquine compared with doxycycline for the prophylaxis of malaria in Indonesian soldiers. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1997; 126: 963-972[Abstract/Free Full Text].
4. Shanks GD, Roessler P, Edstein MD, Rieckmann KH. Doxycycline for malaria prophylaxis in Australian soldiers deployed to United Nations missions in Somalia and Cambodia. Mil Med 1995; 160: 443-445[Medline].

More studies of mefloquine prophylaxis must be done in tourists

EDITORIn their paper on the risks of malaria to travellers Reid et al state categorically that mefloquine is the most effective antimalarial agent.¹ Unfortunately, they adduce only one study in general travellers in support of this view.²

The much cited study by Steffen et al was an uncontrolled, questionnaire based survey of non-immune tourists visiting east Africa.² The tourists were taking either mefloquine (once a week) or one of the other antimalarial drug regimens commonly prescribed at that time. Because of the limitations of its design this survey does not show conclusively that mefloquine is any more or less effective than the other compounds assessed.

Steffen et al's survey was funded wholly by the manufacturers of mefloquine (Roche), but Reid et al do not mention this potential for bias; one of Reid's coauthors recently declared elsewhere in the BMJ that he has received research funds from Roche.³ Reid et al cite no evidence that mefloquine is more effective than other more recent antimalarials that are available for travellers, such as doxycycline and atovaquone-proguanil (now licensed for prophylaxis in Denmark).

It was pointed out a decade ago that the effectiveness of prophylactic mefloquine needs to be evaluated rigorously by means of a randomised controlled trial in appropriately characterised travellers.⁴ Such a trial has still not taken place.⁵ Reid et al castigate the media for spreading confusion about mefloquine's adverse effects, but we believe that the media have performed a valuable service to travellers by highlighting an area of clinical practice that is governed by opinion rather than sound scientific evidence.

Members of the public who seek medical advice before travelling expect a clear and unambiguous exposition of the benefits and harms of any prophylactic drugs that they may be advised to take. Such advice needs to be informed by evidence from randomised controlled field trials carried out recently in tourists and business travellers. Studies carried out on soldiers undergoing training, prisoners, and non-travelling occupational groups (such as Peace Corps volunteers) are not an adequate substitute for well designed field trials in an appropriate travelling population.⁵ Instead of criticising the media we should devote our energies to ensuring that this research now takes place.

Ashley M Croft, Consultant in public health medicine. 
Headquarters Defence Secondary Care Agency, Ministry of Defence, London WC2H 8LD

Dominic P Whitehouse, Physician. 
Institute of Occupational Health, University of Birmingham, Birmingham B15 2TT

1. Reid AJC, Whitty CJM, Ayles HM, Jennings RM, Bovill BA, Felton JM, et al. Malaria at Christmas: risks of prophylaxis versus risks of malaria. [With science commentary by A Berger.] BMJ 1998; 317: 1506-1508. (28 November.)
2. Steffen R, Fuchs E, Schildknecht J, Naef U, Funk M, Schlagenhauf P, et al. Mefloquine compared with other malaria chemoprophylactic regimens in tourists visiting east Africa. Lancet 1993; 341: 1299-1303[Medline].
3. Behrens RH. Mefloquine to prevent malaria. BMJ 1998; 316: 1980[Free Full Text].
4. Petersen E, Høgh B, Bygbjerg IC, Black FT. Malaria chemoprophylaxis: why mefloquine? Lancet 1990; 336(8718): 811[Medline].
5. Croft AM, Garner P, Squire SB. Malaria prevention for travelers. JAMA 1998; 279: 990[Free Full Text].