DEET mosquito repellent provides personal protection against malaria: a household randomized trial in an Afghan refugee camp in Pakistan

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1 Tropical Medicine and International Health volume 9 no 3 pp march 2004 DEET mosquito repellent provides personal protection against malaria: a household randomized trial in an Afghan refugee camp in Pakistan Mark Rowland 1,2, Gerald Downey 2, Abdur Rab 1, Tim Freeman 1, Nasir Mohammad 1, Hamid Rehman 1, Naeem Durrani 1, Hugh Reyburn 1,2, Chris Curtis 2, Jo Lines 2 and Mohammad Fayaz 1 1 HealthNet International, Peshawar, Pakistan 2 London School of Hygiene and Tropical Medicine, London, UK Summary Synthetic repellents based on di-ethyl 3-methyl benzamide (DEET) are a popular method of obtaining protection from mosquitoes and yet clear evidence for a protective effect against malaria has hitherto never been convincingly demonstrated. A household randomized trial was undertaken among a study population of 127 families (25%) in an Afghan refugee village in Pakistan to compare the efficacy of repellent soap (Mosbar TM containing 20% DEET and 0.5% permethrin) vs. a placebo lotion. Cases of falciparum and vivax malaria were detected by passive case detection at the camp s clinic. At the end of the 6 month trial 3.7% (23 of 618) of individuals in the Mosbar group had presented with one or more episodes of falciparum malaria compared with 8.9% (47 of 530) of the placebo group (odds ratio 0.44, 95% CI ). 16.7% of the Mosbar group (103 of 618) presented with vivax malaria compared with 11.7% (62 of 530) of the placebo group, and thus no effect was shown against vivax malaria (odds ratio 1.29, 95% CI ). A considerable proportion of individuals (22%) had presented with vivax malaria during the 7 months leading up to the trial and thus any intervention effect would be partially masked by relapsed infections. The distribution of mosquitoes among households was broadly similar between Mosbar and placebo groups. The repellent was popularly received and very few side-effects were reported. There is a case for giving repellents more prominence in public health as a preventive measure in regions where vectors bite in the early evening or in emergency situations such as epidemics or newly established refugee camps. keywords mosquito, malaria, repellent, di-ethyl 3-methyl benzamide, refugee, emergency, epidemic, cluster randomized trial Introduction DEET (di-ethyl 3-methyl benzamide) is an effective and well-known mosquito repellent, as testified by several decades of entomological research (McCabe et al. 1954; Schreck 1977; Curtis et al. 1990; Gupta & Rutledge 1994; Barnard 2000). Despite the intuitive appeal of synthetic repellents there have been surprisingly few attempts at demonstrating protection against malaria and no trial has been fully successful. An early study in which DEET was distributed to one member of a pair of Indian villages produced no evidence for a reduction in transmission (Vittal & Limaye 1984). A study on schoolchildren in Tanzania did not show a significant effect (Curtis et al. 1994). A third study on Karen pregnant women in Thailand was thwarted by an unexpected decline in transmission caused by other factors (McGready et al. 2001). A community randomized trial in South America showed no effect on malaria incidence rates (Kroeger et al. 1997). A recent outbreak of malaria in a village in South Africa did subside after distribution of DEET repellent among the affected population (Durrheim & Govere 2002) but it is not clear whether this was due to other undetermined factors as there was no control group. Whereas an unequivocal epidemiological demonstration in favour of repellents is still lacking, there can be no doubt that insecticide-treated nets (ITN) are in many regions of the tropics a highly effective method of malaria prevention (Lengeler & Snow 1996; Lengeler 1998). We share the conviction that ITN constitute the most feasible method of obtaining protection against malaria and one that needs to be made much more widely available. By comparison, skin repellents may appear a false economy or a distraction from the main public health challenges of improving ITN ª 2004 Blackwell Publishing Ltd 335

2 usage and establishing early diagnosis and treatment. But in certain situations repellents may have a significant role as a supplement to ITN: for example, in regions where the vectors bite in the early evening (Lindsay et al. 1998; Pates et al. 2002) or as a response to temporary upsurges of malaria because of local outbreaks, political emergencies, or refugee displacements (McGready et al. 2001; Rowland & Nosten 2001). In Afghanistan and Pakistan there is a potential market for a good mosquito repellent. Malaria vectors such as Anopheles stephensi, A. culicifacies, A. nigerrimus and A. pulcherrimus bite in the evening as well as at night (Reisen & Aslamkhan 1978; Rowland et al. 2002a). Repellents are not commonly used in Afghanistan at present, but neither were ITN before the social marketing drives of the last decade (Rowland et al. 2002b) and repellents may give added protection (Pates et al. 2002). It is not clear whether, through appropriate health education and product promotion, the practice of using repellents might be successfully instilled. The aim of the study was to investigate the efficacy and acceptability of a commercially available mosquito repellent, Mosbar TM repellent soap (Yap 1986; Frances 1987) as a technique for malaria prevention in refugee settings. This paper describes a cluster randomized trial in an Afghan refugee camp in Pakistan in which households were randomly assigned to receive the repellent or a placebo, and the impact of the intervention measured through monitoring of clinical episodes of Plasmodium falciparum and P. vivax malaria over a period of 6 months. to June, reaches a peak in July August, and then declines. Significant numbers of falciparum malaria cases are first observed in August and reach a peak in October November. Transmission is unstable, particularly that of falciparum malaria. According to passive case detection records, the ratio of vivax to falciparum infections in 1999 was 5:1 and incidence was 0.80 malaria episodes per person year. Repellent Mosbar is a commercially available repellent formulation (Yap 1986; Frances 1987). The active ingredients are DEET (20%) and permethrin (0.5%), a pyrethroid insecticide with some repellent action. Unlike other repellents Mosbar is a portable solid formulation considered to be more appropriate for use in developing countries (Rozendaal 1997). The bar is used by making a lather in water which is applied to wetted skin. The foam dries to an invisible film, much like standard liquid formulations of DEET, and should not be rinsed off after drying. Thus, the term repellent soap is somewhat misleading. The repellent was obtained from a Zimbabwean manufacturer at a cost of US $0.40 per bar. Preliminary tests showed that a single application to face and exposed skin would give several hours protection confirming the findings of earlier studies (Frances 1987; Kroeger et al. 1997) and that one bar would last an individual several weeks of nightly use. Study design and procedure Materials and methods Study area and malaria transmission The trial was carried out in Adizai refugee settlement (population 3945) near Peshawar, in North-West Frontier Province, Pakistan. The settlement was established in the early 1980s on waterlogged land on the banks of the Kabul river and is endemic for malaria. The houses are made from mud and each building is surrounded by a courtyard and perimeter wall in a style typical of rural Pakistan and Afghanistan. A health centre run by the non-governmental organization HealthNet International provides free microscopical diagnosis and treatment of malaria to the 510 refugee families living in the camp. Transmission of malaria occurs from late June to November. The vectors include A. culicifacies, A. stephensi, A. nigerrimus, and A. pulcherrimus, among others. Mosquito biting starts after dusk, peaks around 9 11 p.m. then declines gradually through the night (Rowland et al. 2004). According to health centre records, vivax malaria increases from March The study took place over 7 months between August 1999 and February Each house compound in the camp had been assigned a unique number for census purposes. Sample size calculations were based on P. falciparum incidence of 12% in the control group as indicated by the previous year s incidence rate, the assumption of an intracluster correlation of 0.04, and a treatment effect of 50% as a result of the intervention. To receive 80% power to detect a difference in P. falciparum rates of 6%, assuming a drop out rate of 10%, we would require 1100 subjects to be enrolled into this study. By applying simple randomization 13% (67 of 510) of households were allocated to the repellent soap group and a similar proportion (12%, 60 of 510) to the placebo control. It was assumed that an intervention group of this magnitude would not unduly affect transmission rates in the remainder of the population and hence the study would give an accurate measure of personal protection. The rationale behind using households rather than individuals was twofold: it was logistically easier and more 336 ª 2004 Blackwell Publishing Ltd

3 acceptable to administer the intervention at the household level, and the risk of different treatments being shared within households, which would have seriously interfered with a trial based on individual randomization, was averted. The placebo formulation was a moisturizing lotion imported from UK, unknown to Afghan refugees and shown in pre-tests to have no repellent effect on mosquitoes. Both the lotion and the repellent bars were issued without packaging or identifying labels. Heads of families were invited to group meetings and informed about the aims of the study, namely to determine whether repellents protected against malaria and which of two products was better than the other. Informed consent was obtained from each head of family on behalf of other family members. Names and details of each family were reconciled with the clinic s family records. Women and family members received health education in the home and were shown how to apply the repellent or placebo lotion according to which group they had been allocated. We advised parents not to use Mosbar or the lotion on children <5 years of age to avoid the risk of discomfort caused by involuntary rubbing into eyes. This accords with the advice of the US Environmental Projection Agency which concluded after reviewing 20 studies on the toxicology of DEET (USEPA 1998) that the repellent does not cause unreasonable risks but might be restricted to protect young children with skin sensitivity (Barnard 2000). Families of the placebo group were given the same health information as families of the Mosbar group. Each family was given a month s supply of product, and was visited fortnightly for topping up and monitoring of usage and side-effects. The village health workers implementing the trial were blinded as to which product was the true repellent as both products were described as such. No other malaria preventive intervention (e.g. nets, chemoprophylaxis) was being implemented in this camp at this time. For baseline comparisons, clinic records of malaria infections were compiled for the period January July 1999 leading up to the start of the trial. This provided a suitable database for showing the history of previous infections. Cases of vivax and falciparum malaria were diagnosed by microscopy using a process of passive case detection at the clinic. At the start of the trial study families were encouraged to use the clinic in the event of febrile illness but did not receive any preferential treatment over other inhabitants. Clinic workers responsible for treatment (medical officers) and diagnosis (microscopists) were blind to the allocation of families to the two study groups (they too assumed both products were effective) and were not informed about which families were in the trial. Confirmed cases of falciparum and vivax malaria were treated with 25 mg chloroquine per kg body weight and falciparum treatment failures were treated with sulphadoxinepyrimethamine. Primaquine was not used in treatment. Recording of malaria in trial families started on 9 August and ended on 31 January. A non-registered private microscopist was present in the camp, but the clinic s family registration system indicated that over 90% of families attended the HealthNet clinic. Afghans sometimes self-treat with chloroquine, but this was not monitored during the present study. Entomological surveillance was conducted in 30 sentinel households randomly selected from each group, once in July before the repellent/placebo products were issued and again in October. A mosquito catch was made by space spraying a living room and animal shelter of each house with a commercial aerosol pyrethroid after closing all exits and covering the floor with sheets. The night before the space spraying was done a CDC light trap collection was made outdoors close to where people were sleeping (the majority of people sleep outdoors from May to October). Collections were identified to species and scored. Towards the end of the study, 20 heads of family from each group and their wives were interviewed about their own and their family s experiences. The structured questionnaire included questions about usage, perceived effectiveness, acceptability, convenience and side-effects. Ethical clearance was obtained from Pakistan Medical Research Council and the LSHTM Ethics Committee. Analysis The trial was primarily designed to determine whether the repellent could be considered an effective intervention against falciparum and vivax infections, with efficacy measured in terms of whether or not an individual became infected. All malaria episodes used in the analysis occurred 3 weeks after the start of the trial (the assumed incubation period). It was not possible to distinguish new infections of vivax malaria from relapsed infections. All members of every household that entered the trial were included in the analysis. This intention-to-treat approach was an attempt to negate the opportunity for bias to enter the trial. For the analysis, we used the method of Generalized Estimating Equations (GEEs), using the robust variance estimator and an exchangeable working correlation matrix (Liang & Zeger 1986). This approach, an extension of standard multiple logistic regression, adjusted for the effect of clustering at the household level. Bias due to relapse was minimized by including a binary covariate in the model that indicated whether an individual had contracted malaria during the period leading up to the trial. Subgroup analyses have been presented, with inferences based on statistical tests of interaction. All ª 2004 Blackwell Publishing Ltd 337

4 efficacy analyses used an intent-to-treat approach. No losses to follow-up were reported throughout the duration of the trial, with the reason for this being that Adizai is a relatively stable refugee camp. Entomological outcomes were analysed using Poisson regression analysis. Results A total of 127 households and 1148 individuals were enrolled into the study. This represented 29% of the camp population. A summary of study characteristics upon admission is presented in Table 1. The age distribution and the number of individuals with previous malaria infections during the 7 months leading up to the trial were comparable across the treatment groups. The same conclusion is reached when data is presented at the household level. The intra-cluster correlation coefficient for P. falciparum is As expected, only a small number of P. falciparum infections occurred during the pre-intervention period of January July because this was the low season for malaria transmission. Table 2 presents a simple summary at the individual level, unadjusted for household clustering, by species of malaria. Irrespective of treatment or malaria species, the Table 1 Study characteristics at baseline Mosbar Placebo lotion Number of households Number of individuals Median household size (IQR) 9 (5) 9 (3) Median age in years (IQR) 12 (21) 13 (23) Gender (female %) Previously infected with malaria* Individual level For Plasmodium falciparum Yes (%) 11 (1.8) 7 (1.3) No (%) 607 (98.2) 523 (98.7) For Plasmodium vivax Yes (%) 137 (22.2) 122 (23.0) No (%) 481 (77.8) 408 (77.0) Household level For Plasmodium falciparum Yes (%) 9 (13.4) 7 (11.7) No (%) 58 (86.6) 53 (88.3) For Plasmodium vivax Yes (%) 54 (80.6) 45 (75.0) No (%) 13 (19.4) 15 (25.0) IQR, inter-quartile range. * This includes any infections up to 7 months prior to the trial starting in August One or more individual pre-intervention infections within a household are classified as yes. Table 2 Summaries of malaria infection, including count of infections, categorized by age and species of malaria, using the individual as the unit of analysis Individual level Mosbar (%) Placebo lotion (%) For Plasmodium falciparum Total number infected (%) 23 (3.7) 47 (8.9) Age category (year) <5 6 (5.5) 5 (5.3) (6.2) 19 (17.3) (1.3) 11 (9.7) >20 7 (3.1) 12 (5.7) Number of individuals with No infections 595 (96.3) 483 (91.1) 1 infection 15 (2.4) 29 (5.5) 2 infections 7 (1.1) 12 (2.3) 3+ infections 1 (0.2) 6 (1.1) For Plasmodium vivax Total number infected (%) 103 (16.7) 62 (11.7) Age category (year)* <5 25 (22.9) 15 (16.0) (28.5) 25 (22.7) (13.0) 11 (9.7) >20 20 (9.0) 11 (5.2) Number of individuals with No infections 515 (83.3) 468 (88.3) 1 infection 85 (13.8) 48 (9.0) 2 infections 13 (2.1) 11 (2.1) 3+ infections 5 (0.8) 3 (0.6) * There was one more case of malaria (Plasmodium vivax on Mosbar) but the age of the infected individual was missing, and so does not appear here in this cross-classification. percentage infected initially increased with age, reaching a peak in children aged between 5 and 10 years, and then decreased with age. For P. falciparum, the percentage of infections was lower in the Mosbar group than in placebo group. A clear difference was shown between the two interventions for P. falciparum malaria across individuals with 1, 2 or 3+ infections, with the percentage of infections in these categories more than double for individuals on placebo than for those on Mosbar. For P. vivax the percentage of infections were slightly higher in the Mosbar group. The percentage of P. falciparum infections peaked in October for the placebo group (19 of 511, 3.7%) and in November for the Mosbar group (12 of 611, 2.0%). The later peak in the Mosbar group may have been due to some individuals ceasing to use repellent in late-october, despite continuing vulnerability to infection, when mosquito numbers began to decline and people started sleeping indoors. The pattern of P. vivax infections was similar for both interventions, with a gradual reduction in the number of infections from September 1999 to January 2000, 338 ª 2004 Blackwell Publishing Ltd

5 Table 3 Logistic regression analysis showing associations between treatment effect and malaria infection, adjusted by baseline covariates (previous infection, gender and age) Variables included in model Plasmodium falciparum Plasmodium vivax Odds ratio (95% CI) P-value Odds ratio (95% CI) P-value Treatment Placebo lotion 1 1 Mosbar soap 0.44 (0.25, 0.76) (0.86, 1.94) Previous infection No 1 1 Yes 9.86 (3.74, 26.02) < (3.82, 8.34) <0.001 Gender Female 1 1 Male 0.80 (0.52, 1.23) (0.83, 1.59) Age (years) < (0.93, 4.76) 1.26 (0.82, 1.92) (0.36, 2.18) 0.62 (0.40, 0.94) > (0.37, 1.83) (0.27, 0.67) <0.001 The method of Generalized Estimaing Equations (GEEs) used in this logistic regression analysis, adjusts for the effect of clustering at the household level. followed by an increase in February as a result of relapsed infections. Findings with the household as the unit of analysis were consistent with that shown at the individual level. There were more households with at least one episode of P. falciparum malaria in the placebo group (27 of 60, 45%) than in the Mosbar group (18 of 67, 27%). For P. vivax, 66% of households in the Mosbar group (44 of 67) had at least one infection compared with 52% in the placebo group (31 of 60). Baseline covariates that may predict subsequent malarial infection were included in the model to increase the validity of estimates of treatment effects. Results are presented in Table 3. When expressed in terms of protective efficacy [100(1 ) odds ratio)%], the odds of being infected with P. falciparum malaria were reduced by 56% (95% CI 24 75%, P ¼ 0.004) in the Mosbar group. Similar conclusions are reached when the effect of Mosbar was modelled unadjusted for the baseline covariates (protective efficacy ¼ 53%, 95% CI 20 73%). As expected, previous P. falciparum infections were a strong indicator for later P. falciparum infections. There was evidence of a treatment age interaction with the effect of Mosbar use being significant only among individuals aged between 5 and 20 years (test of interaction P ¼ 0.04). There was no evidence that the effect of Mosbar use varied by previous P. falciparum infection or gender (tests of interaction P ¼ 0.63 and P ¼ 0.26 respectively). There was no evidence of an effect of Mosbar use on P. vivax infections (P ¼ 0.226), although the estimated odds of being infected appeared to be higher in individuals on Mosbar than placebo. Similar conclusions are reached when the effect of Mosbar soap was modelled unadjusted for the baseline covariates (P ¼ 0.193). In depth interviews with 20 Mosbar group families confirmed that 19 families used the repellent regularly and considered it effective. Sixteen families considered Mosbar easy to apply, but 10 considered oil-based formulations easier to use. Nineteen considered the smell to be acceptable. One person complained of skin irritation and stopped using the repellent. Interviews with 20 placebo group families confirmed that 12 families considered the lotion ineffective as a repellent, citing mosquito biting and disrupted sleep as the two main problems. But all continued to use it and all considered it easy to apply and the aroma pleasant. A total of 2225 mosquitoes were captured in space spray collections. Anopheles culicifacies comprised 47%, A. stephensi 25%, Culex spp. 24%, and A. fluviatilus, A. annularis, A. maculatus and A. subpictus made up the remaining 4%. Culicines were more abundant in the July pre-intervention survey (average 13.4 per house) than in October survey (average 7.7 per house), whereas Anophelines were much more abundant in October (52.4 per house) than pre-intervention (6.8 per house). Culicines were equally abundant in living quarters and animal shelters, whereas anophelines were seven times more abundant in animal shelters than living quarters. During the intervention significantly fewer mosquitoes were caught in the light traps close to where people of the Mosbar group were sleeping outdoors, although curiously the number of culicines were significantly higher in this group (Table 4). There were significantly more culicine mosquitoes in the living quarters of ª 2004 Blackwell Publishing Ltd 339

6 Table 4 Mosquito density per room as determined by space spray and light trap catches in houses before (July) and during (October) the intervention Anopheles stephensi Anopheles culicifacies Culex Placebo Mosbar Placebo Mosbar Placebo Mosbar Survey AM GM AM GM Density ratio AM GM AM GM Density ratio AM GM AM GM Density ratio Living room Before (0.11, 3.99) * (0.01, 0.71) (0.72, 1.52) During * (1.19, 4.05) (0.98, 2.77) * (3.07, 9.60) Animal shelter Before (0.35, 1.47) (0.83, 1.67) (0.67, 1.12) During (0.93, 1.33) (0.85, 1.11) (0.44, 1.01) Light trap Before (0.18, 22.0) (0.45, 35.8) (0.92, 1.99) During * (0.17, 0.99) (0.26, 2.16) * (1.01, 4.88) AM, arithmetic mean density per room; GM, geometric mean density per room. Fifteen sentinel houses were monitored in each intervention group. Density ratios were calculated using Poisson regression analysis. * P < Mosbar households than in placebo group households during October survey. However, this may have been a chance effect because people were mainly sleeping outdoors during this time. There was no difference between Mosbar and placebo group households in the density of mosquitoes in animal shelters either before or during the intervention. Discussion This placebo controlled trial appears to be the first clear demonstration of a skin repellent providing protection against falciparum malaria, the potentially fatal species of malaria. The protective effect was greatest among those at greatest risk of malaria: individuals between 5 and 20 years of age. The absence of effect in children under five was most likely due to parents responding to our expressed concern about the possibility of skin sensitivity in young children. This inference may be drawn from the results of an earlier intervention trial involving a different method of protection (permethrin treated top-sheets and blankets) in the same camp in which we placed no restriction on age but did observe a protective effect in children aged 0 5 years (Rowland et al. 1999). In the present study no effect of Mosbar was observed in adults over 20 years old. Again this result is consistent with the earlier treated blanket study and may reflect reluctance or conservatism among adults to adopt new preventive measures for personal use, compounded by a greater immunity to new infections. But older children clearly benefited from use of repellents and are an appropriate group to target, perhaps via concerned parents. Our purpose was to measure absolute efficacy, as protection against malaria had been never before demonstrated using a skin repellent, and to extend user choice in personal protection. This necessitated comparison with a placebo. The trial was designed to be double-blind initially, but we realized that blinding would gradually be lost as users of placebo lotion discovered the formulation was ineffective. Compliance to the allocated treatment might at that point become lower in the placebo lotion group and lead to a dilution of the placebo effect which could, in turn, inflate the true Mosbar effect. This was a limitation of the study. In reality, compliance and demand for the lotion was unexpectedly high throughout the study, due partly to the pleasing effect of the lotion on the skin and partly to some continuing faith in its effectiveness. The question remains whether any dilution of the placebo effect could have impacted upon the trial. Because the parasitological outcome was assessed although passive case detection and study participants had to take the initiative to go to the health centre, members of the lotion group might have felt more inclined to go with minor febrile ailments if they believed these to be malaria whereas members of the repellent group might not have felt so inclined if they thought they were protected. If malaria attacks were self-limiting this might indeed lead to a proportion of malaria cases in the repellent group going undetected. However, for this line of argument to hold we would expect to see a more notable treatment effect in the more-immune older groups as only among these would malaria be self-limiting (in this region, where malaria is hypoendemic or mesoendemic, development of immunity is only partial and is more observed in adults see Table 2 for evidence of this). Furthermore, if this line of argument held up we would expect to see a greater treatment effect against the more benign and self-limiting vivax malaria than was observed. The more serious falciparum malaria is rarely 340 ª 2004 Blackwell Publishing Ltd

7 self-limiting in this region and usually grows worse unless treated, particularly in children. Children with this disease would be motivated to attend the clinic regardless of which group they were allocated, and it was among children (over 5 years) of course that the greatest treatment effect was observed. Another possible source of bias might result from microscopists being less rigorous in slide reading if they knew the blood film came from a Mosbar user. However, because microscopists were blind to the allocation, this source of bias is considered unlikely. The trial showed that Mosbar use was effective in reducing P. falciparum infections in an Afghan refugee population in which there was no use of ITNs. The intervention and placebo groups appeared to be comparable at baseline, as indicated by similar mosquito densities in living rooms or animal shelters, and the similar rates of malaria infection in the lead up to the trial. The absence of effect against P. vivax is unexplained, and was surprising considering the two groups showed similar rates of infection in the 7 month lead up. The number of vivax cases in Adizai in 1999 reached a peak 2 months before the start of the trial, which was timed primarily to coincide with the season of falciparum transmission from September to December. A recent case control study in nearby Afghanistan was deliberately started 2 months earlier on 1 July at the beginning of the vivax transmission season and this study did demonstrate a negative association between Mosbar use and vivax infections after adjusting for ITN use and other covariates (Rowland et al. 2004). Had the cluster randomized trial started earlier an effect against vivax might have been observed. A high proportion of observed cases in the two groups were probably relapses of infections contracted before the trial, as indicated by the odds ratio of 5.6 for previous infections, and these would have masked any treatment effect. A significant reduction in anopheline density was observed in the vicinity of individuals in the Mosbar group sleeping outdoors. An effect on indoor resting anopheline density (in living rooms and animal shelters) was not observed nor was one expected because of the outdoor sleeping habit. The significantly higher density of culicines in living rooms and light traps of the Mosbar group during the trial remains a puzzle. The sample size would need to be increased and the entomological surveys would need to be repeated at regular intervals during the trial before drawing any firm conclusion. The overall benefit to be gained from using Mosbar should be weighed against the potential risks. Safety concerns exist as to the long-term use of DEET particularly on young children (USEPA 1998). DEET repellent is cost-effective over the short-term, but ITN are more practical and cost-effective when the need for protection extends over more than one season. Mosbar remained popular over a single season but some users said they preferred oil-based formulations and adherence long-term is unknown. For reasons of safety and cost we advocate that DEET-based repellents be restricted as a short-term intervention in situations such as epidemics or temporary crises such as newly established refugee camps, where ITN may be too costly, inappropriate for existing living conditions or unobtainable in sufficient numbers fast enough. The suitability of repellents in emergencies or epidemics should be weighed against other potential short-term interventions such as insecticide-treated blankets or tarpaulins (Rowland et al. 1999; Graham et al. 2002). Repellents would be more useful where vectors bite in early evening (i.e. Asia more than Africa) or where it is too hot to use insecticide-treated blankets. Repellents are less bulky than any of these alternatives and stockpiles could be air-freighted and distributed quickly. Potential drawbacks with repellents are the need for self-discipline and some health education initially, unlike the other interventions which are needed anyway for purposes of warmth or shelter and whose use is guaranteed. An argument sometimes raised against the use of repellents is the possibility that infective mosquitoes might simply be diverted to feed on unprotected individuals, particularly if the vector species are strongly anthropophilic. This possibility still needs to be tested. But in regions where vector species are seasonal, bite all night, and are partially zoophilic, such as South Asia, we would expect combined use of ITN and repellents (in adults and children over 3 years) to provide all-night protection with little risk of diversion to unprotected neighbours. Repellents need to be taken more seriously as a public heath measure. Acknowledgements Authors wish to thank the staff of Adizai clinic, microscopist Naeem Sherpao, community health workers Zahoor and Isra, and entomologists Mushtaq Ahmad and Mohammed Kamal for their support. HealthNet International s malaria control and research programme is supported by the European Commission (DG1), the United Nations High Commissioner for Refugees, and WHO/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases. MR and JL are supported by the UK Department for International Development and the Gates Malaria Partnership, and CC by the Medical Research Council. However, none of these donors can accept responsibility for any information provided or views expressed. ª 2004 Blackwell Publishing Ltd 341

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Journal of the American Mosquito Control Association 2, Authors Mark Rowland (corresponding author), Abdur Rab, Tim Freeman, Nasir Mohammad, Hamid Rehman, Naeem Durrani, Hugh Reyburn and Mohammad Fayaz, HealthNet International, 11A Circular Lane, Peshawar, Pakistan. Fax: ; mark.rowland@lshtm.ac.uk Gerald Downey, Chris Curtis and Jo Lines, Department of Parasitology, London School of Hygiene and Tropical Medicine, Keppel Street, Lomdon WC1E 7HT, UK. gdowney@hsph.harvard.edu, chris.curtis@lshtm.ac.uk, jo.lines@lshtm.ac.uk 342 ª 2004 Blackwell Publishing Ltd