No abstract

SummarySynthetic 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 0.25-0.76). 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 0.86-1.94). 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.

Insecticide-treated mosquito nets (ITN) provide excellent protection against malaria; however, they have a number of shortcomings that are particularly evident in politically unstable countries or countries at war: not everyone at risk can necessarily afford a net, nets may be difficult to obtain or import, nets may not be suitable for migrants or refugees sleeping under tents or plastic shelter. There is a need to develop cheaper, locally appropriate alternatives for the most impoverished and for victims of complex emergencies. Afghan women, in common with many Muslim peoples of Asia, wear a veil or wrap known as a chaddar to cover the head and upper body. This cloth doubles as a sheet at night, when they are used by both sexes. A randomized controlled trial was undertaken in which 10% of the families of an Afghan refugee camp (population 3950) in north-western Pakistan had their chaddars and top-sheets treated with permethrin insecticide at a dosage of 1 g/m2 while a further 10% had their chaddars treated with placebo formulation. Malaria episodes were recorded by passive case detection at the camp's health centre. From August to November the odds of having a falciparum or vivax malaria episode were reduced by 64% in children aged 0-10 years and by 38% in refugees aged < 20 years in the group using permethrin-treated chaddars and top-sheets. Incidence in refugees over 20 years of age was not significantly reduced. The cost of the permethrin treatment per person protected (US$0.17) was similar to that for treating bednets (and cost only 10-20% of the price of a new bednet). An entomological study simulating real-life conditions indicated that host-seeking mosquitoes were up to 70% less successful at feeding on men sleeping under treated chaddars and some were killed by the insecticide. Permethrin-treated top-sheets and blankets should provide appropriate and effective protection from malaria in complex emergencies. In Islamic and non-Islamic countries in Asia, treated chaddars and top-sheets should offer a satisfactory solution for the most vulnerable who cannot afford treated nets.

Mutations in the Plasmodium falciparum genes pfcrt and pfmdr1 are selected by amodiaquine treatment in Africa. To examine the importance of these mutations in amodiaquine-treated Asian parasites, we determined pre-and posttreatment genotypes for amodiaquine treatment failures from a clinical trial in Afghanistan. The pfcrt codon 72 to 76 haplotype SVMNT was present in all samples tested, both before and after treatment. Amodiaquine did not clearly select for any pfmdr1 genotype, but a novel mutation, pfmdr1 N86F, was detected in four samples. We provide in vivo data to support the in vitro correlation between pfcrt SVMNT and increased resistance to the metabolite of amodiaquine.Amodiaquine (AQ), a 4-aminoquinoline related to chloroquine (CQ), has been used commonly as a monotherapy and now as a partner drug in artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated Plasmodium falciparum malaria. In many countries, predominantly in Africa, the in vivo efficacy of AQ was found to be good even in the face of increasing CQ resistance (12). However, reports of AQ resistance have come from South America, Asia, and East Africa (7,8,10).Mutations in the P. falciparum chloroquine resistance transporter gene (pfcrt) and multidrug resistance gene 1 (pfmdr1) have been associated with clinical resistance to both CQ and AQ (13). The presence of the pfcrt codon 72 to 76 haplotype SVMNT (Ser-Val-Met-Asn-Thr) correlates with high-level resistance to the AQ metabolite desethylamodiaquine (DEAQ) in in vitro tests (14) and has been detected with a high prevalence in parasite populations from Brazil, Papua New Guinea, Laos, Iran, and India (9,18). Clinical trials in East Africa have also demonstrated high levels of in vivo resistance to AQ; in those studies, the parasites carried pfcrt codon 72 to 76 haplotype CVIET, and pfmdr1 polymorphisms 86Y, 184Y, and 1246Y were found to be selected after AQ treatment failure (5, 6, 11).A clinical trial performed in Nangahar Province, East Afghanistan, in 2002 and 2003 to explore possible replacement treatments for CQ showed very poor efficacies of both CQ and AQ monotherapy (adequate clinical and parasitological responses were seen in 11% and 9% of cases, respectively, by day 42) (4). Our aim in this study was to evaluate pre-and posttreatment samples from patients treated with AQ for pfcrt and pfmdr1 mutations and to determine which, if any, polymorphisms are associated with AQ treatment failure in Afghanistan. MATERIALS AND METHODSWe analyzed samples collected from AQ-treated participants during a clinical trial of AQ versus CQ versus sulfadoxine-pyrimethamine versus AQ plus artesunate in East Afghanistan between October 2002 and January 2003. The clinical and parasitological results of drug efficacy testing have been reported elsewhere (4). Amodiaquine (Basoquin) was supplied by Parke-Davis. Ethical approval for the in vivo study and collection of samples for genotyping was given by the LSHTM Ethics Committee and also locally, by the Ministry of Public Health, Afgh...

The only available treatment that can eliminate the latent hypnozoite reservoir of vivax malaria is a 14 d course of primaquine (PQ). A potential problem with long-course chemotherapy is the issue of compliance after clinical symptoms have subsided. The present study, carried out at an Afghan refugee camp in Pakistan, between June 2000 and August 2001, compared 14 d treatment in supervised and unsupervised groups in which compliance was monitored by comparison of relapse rates. Clinical cases recruited by passive case detection were randomised by family to placebo, supervised, or unsupervised groups, and treated with chloroquine (25 mg/kg) over 3 days to eliminate erythrocytic stages. Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency were excluded from the trial. Cases allocated to supervision were given directly observed treatment (0.25 mg PQ/kg body weight) once per day for 14 days. Cases allocated to the unsupervised group were provided with 14 PQ doses upon enrollment and strongly advised to complete the course. A total of 595 cases were enrolled. After 9 months of follow up PQ proved equally protective against further episodes of P. vivax in supervised (odds ratio 0.35, 95% CI 0.21-0.57) and unsupervised (odds ratio 0.37, 95% CI 0.23-0.59) groups as compared to placebo. All age groups on supervised or unsupervised treatment showed a similar degree of protection even though the risk of relapse decreased with age. The study showed that a presumed problem of poor compliance may be overcome with simple health messages even when the majority of individuals are illiterate and without formal education. Unsupervised treatment with 14-day PQ when combined with simple instruction can avert a significant amount of the morbidity associated with relapse in populations where G6PD deficiency is either absent or readily diagnosable.

SummaryMalaria is often a major health problem in countries undergoing war or conflict owing to breakdown of health systems, displacement of vulnerable populations, and the increased risk of epidemics. After 23 years of conflict, malaria has become prevalent in many rural areas of Afghanistan. From 1993 to the present, a network of non-governmental organizations, co-ordinated by HealthNet International, has operated a programme of bednet sales and re-treatment in lowland areas. To examine whether a strategy based on insecticide-treated nets (ITN) is a viable public health solution to malaria, communities were given the opportunity to buy nets and then monitored to determine population coverage and disease control impact. This was carried out using two contrasting methods: cross-sectional surveys and passive surveillance from clinics using a case-control design. Nets were purchased by 59% of families. Crosssectional surveys demonstrated a 59% reduction in the risk of Plasmodium falciparum infection among ITN users compared with non-users (OR 0.41; 95% CI 0.25-0.66). The passive surveillance method showed a comparable reduction in the risk of symptomatic P. falciparum malaria among ITN users (OR 0.31; 95% CI 0.21-0.47). The cross-sectional method showed a 50% reduction in risk of P. vivax infection in ITN users compared with non-users (OR 0.50; 95% CI 0.17-1.49) but this effect was not statistically significant. The passive surveillance method showed a 25% reduction in the risk of symptomatic P. vivax malaria (OR 0.75; 95% CI 0.66-0.85). ITN appeared to be less effective against P. vivax because of relapsing infections; hence an effect took more than one season to become apparent. Passive surveillance was cheaper to perform and gave results consistent with cross-sectional surveys. Untreated nets provided some protection. Data on socioeconomic status, a potential confounding factor, was not collected. However, at the time of net sales, there was no difference in malaria prevalence between buyers and non-buyers. The abundance of Anopheles stephensi, the main vector, did not appear to be affected by ITN. ITN constitute one of the few feasible options for protection against malaria in chronic emergencies.keywords insecticide-treated bednets, malaria, Plasmodium falciparum, Plasmodium vivax, Pakistan correspondence Mark Rowland,

Cutaneous leishmaniasis (CL) due to Leishmania tropica appears to be an emerging disease in parts of north-east Afghanistan and north-west Pakistan. Timargara, an Afghan refugee camp of 17 years' standing, in the district of Dir, North West Frontier Province of Pakistan, experienced a major outbreak of CL in 1997 for the first time. As part of the investigation, each section of the camp was surveyed for CL. Around 38% of the 9200 inhabitants bore active lesions and a further 13% had scars from earlier attacks. According to interview statements, 99% of earlier infections had healed within the previous 2 years. To confirm the diagnosis, a sample of current CL lesions was examined parasitologically. Amastigotes were detectable by microscopy in only 36% of lesions. However, 48% of slide-negative cases produced positive cultures and some cases negative to both microscopy and culture were positive by PCR. Overall detection rate was about 80%. The sandfly Phlebotomus sergenti, a known vector of L. tropica, was captured within the camp, indicating local transmission. CL has not been reported from this area of Pakistan before. Although the majority of refugees left Afghanistan 2 decades ago, cross-border movement of men is common. The Afghanistan capital, Kabul, is currently experiencing a major epidemic of CL; infected migrant carriers from Kabul are probably the source of the outbreak in Timargara.

A field trial of permethrin-impregnated bed nets (PIBs) was conducted in 2 Afghan refugee villages in Pakistan. Nets were issued to only 10% of families (= 1398 people); this simulated a situation in which bed nets are gradually adopted by villagers in Afghanistan. A further 10% lacking bed nets were selected as controls from the same villages. An initial survey showed that 86% of household heads were aware that malaria was transmitted by mosquito bites, but only 2% had used bed nets before. Trial families were encouraged to attend the village health centres if they fell ill. Microscopy records showed that, between July and December 1991, 22.4% of the control group became infected with Plasmodium vivax and 13.0% contracted P. falciparum while in the intervention group only 9.9% contracted P. vivax (relative risk 0.58, confidence interval [CI] 95% 0.49-0.68) and only 3.8% contracted P. falciparum (relative risk 0.39, 95% CI 0.29-0.53). A single treatment of the nets with permethrin at 0.5g/m2 remained protective throughout the 6 months' transmission season. 73% of families claimed to use their nets every night; members of families who claimed to use nets less regularly showed an incidence similar to that of the control group. There was no sex or age difference in net use or protective efficacy. Headlouse infestation rates were reduced in PIB users. Few nets were washed, given away or sold. The prospect for PIBs as personal protection appears good, despite people's lack of previous experience.