Randomized, controlled, double-blind trial of daily oral azithromycin in adults for the prophylaxis of Plasmodium vivax malaria in Western Thailand

We assessed the prophylactic efficacy of azithromycin (250 mg/day) against malaria in 276 adults in western Thailand in a randomized, double-blind, placebo-controlled trial. After antimalarial suppressive treatment, volunteers were randomized in a 2:1 ratio to either the azithromycin or placebo, respectively. Study medication was given for an average of 74 days. The azithromycin group (n = 179) had five endpoint parasitemias (1 Plasmodium vivax and 4 P. falciparum), and the placebo group (n = 97) had 28 endpoint parasitemias (21 P. vivax, 5 P. falciparum, and 2 mixed infections). Adverse events and compliance and withdrawal rates were similar in both groups. The protective efficacy (PE) of azithromycin was 98% for P. vivax (95% confidence interval [CI] = 88-100%). There were too few cases to reliably estimate the efficacy of azithromycin for P. falciparum (PE =71%, 95% C =-14-94%). We conclude that daily azithromycin was safe, well-tolerated, and had a high efficacy for the prevention of P. vivax malaria.     

Double-blind, randomized, placebo-controlled assessment of chloroquine/primaquine prophylaxis for malaria in nonimmune Colombian soldiers.

To improve upon the efficacy of primaquine prophylaxis for malaria (94%, Plasmodium falciparum malaria; 85%, Plasmodium vivax malaria), we administered chloroquine (300 mg weekly) in combination with primaquine (30 mg daily) to nonimmune Colombian soldiers during 16 weeks of patrol in a region of endemicity and for a further 1 week in base camp. The occurrence of symptomatic parasitemia was determined during those 17 weeks and during a further 3 weeks in base camp. The protective efficacy for the chloroquine/primaquine treatment group of 100 subjects, compared with that for the placebo treatment group of 51 subjects, was 88% (95% confidence interval [CI], 76-94) against all types of malaria, 89% (95% CI, 61-97) against P. falciparum malaria, and 88% (95% CI, 58-93) against P. vivax malaria. Two chloroquine/primaquine recipients had severe gastrointestinal distress. Comparison of these data with data from a previous study indicates that the addition of chloroquine did not increase the prophylactic efficacy of primaquine.     

Chloroquine/doxycycline combination versus chloroquine alone, and doxycycline alone for the treatment of Plasmodium falciparum and Plasmodium vivax malaria in northeastern Irian Jaya, Indonesia.

Combination therapy is one method of overcoming the global challenge of drug-resistant Plasmodium falciparum malaria. We conducted a hospital-based 28-day in vivo test comparing chloroquine/doxycycline to chloroquine or doxycycline alone for treating P. falciparum and Plasmodium vivax malaria in Irian Jaya, Indonesia. Eighty-nine patients with uncomplicated falciparum malaria were randomized to standard dose chloroquine (n = 30), doxycycline (100 mg every 12 hours [7 days], n = 20), or chloroquine with doxycycline (n = 39); corresponding numbers for vivax malaria (n = 63) were 23, 16, 24. Endpoints were parasite sensitivity (S) or resistance (RI/RII/RIII). Of the 105 evaluable patients, chloroquine/doxycycline cured (S) 20/22 (90.9% [95% CI 78.9-100%]) patients with P. falciparum malaria; 2/22 (9.1% [0-21%]) were RIII resistant. Doxycycline cured 11/17 (64.7% [42.0-87.4%]) patients, and chloroquine 4/20 (20% [2.5-37.5%]). Against P. vivax, chloroquine/doxycycline cured (S) 12/17 (70.6% [48.9-92.2%]) patients, doxycycline 4/12 (33.3% [6.6-59.9%]), and chloroquine 5/17 (29.4% [7.7-51.1%]). Chloroquine/doxycycline was effective against P. falciparum but only modestly effective against P. vivax. These findings support the use of chloroquine/doxycycline as an inexpensive alternative to mefloquine for treating chloroquine-resistant P. falciparum but not chloroquine-resistant P. vivax in this setting.     

Randomized, double-blind, placebo-controlled study of Malarone for malaria prophylaxis in non-immune Colombian soldiers

Malarone was compared with placebo in a double-blind, randomized, placebo-controlled trial of prophylaxis of malaria in predominately Plasmodium vivax areas of Colombia. The study population consisted of 180 completely non-immune Colombian soldiers, male, average age 19 years, and average weight 63 kg. Twenty-four subjects were considered unevaluable because of compliance issues, including one Malarone subject (with no detectable drug levels) who became infected with P. vivax. Of the 97 evaluable subjects who received Malarone (250 mg atovaquone plus 100 mg proguanil hydrochloride) daily from 1 day before entering the endemic area to 7 days after leaving the endemic area, none became parasitemic. Of the 46 evaluable placebo subjects, 11 became infected with P. vivax and 2 became infected with Plasmodium falciparum. The protective efficacy of Malarone for all malaria and for P. vivax malaria was 100% (LL 95% CI = 63%) and 100% (LL 95% CI = 58%), respectively, and was 96% if the one case with undetectable blood levels was included. Malarone has high protective efficacy for P. vivax in Colombia.     

Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multidrug-resistant P. falciparum malaria

We assessed monthly doses of tafenoquine for preventing Plasmodium vivax and multidrug-resistant P. falciparum malaria. In a randomized, double-blind, placebo-controlled study, 205 Thai soldiers received either a loading dose of tafenoquine 400 mg (base) daily for 3 days, followed by single monthly 400-mg doses (n = 104), or placebo (n = 101), for up to 5 consecutive months. In volunteers completing follow-up (96 tafenoquine and 91 placebo recipients), there were 22 P. vivax, 8 P. falciparum, and 1 mixed infection. All infections except 1 P. vivax occurred in placebo recipients, giving tafenoquine a protective efficacy of 97% for all malaria (95% confidence interval [CI], 82%-99%), 96% for P. vivax malaria (95% CI, 76%-99%), and 100% for P. falciparum malaria (95% CI, 60%-100%). Monthly tafenoquine was safe, well tolerated, and highly effective in preventing P. vivax and multidrug-resistant P. falciparum malaria in Thai soldiers during 6 months of prophylaxis.     

Primaquine as prophylaxis for malaria for nonimmune travelers: A comparison with mefloquine and doxycycline.

Malaria prophylaxis for travelers is a controversial issue. The commonly used regimens are associated with side effects, low compliance, or low efficacy, which have raised concern regarding their use. In addition, they are inefficient against the tissue stage of the parasite and thus do not prevent relapses of Plasmodium vivax infection. Primaquine is aimed at the pre-erythrocytic stage and thus may be a potential causal-prophylactic treatment that can abolish the need for long postexposure therapy. During 1995-1998, we followed retrospectively travelers who joined rafting trips to an area in Ethiopia where both P. vivax and Plasmodium falciparum are hyperendemic. Of the 106 travelers who received primaquine, 5.7% developed malaria; of the 19 doxycycline recipients, 53% developed malaria; and of the 25 mefloquine recipients, 52% developed P. vivax malaria (>/=3 months after return from the area of endemicity). Primaquine was well tolerated, and only 1 withdrawal from therapy (due to gastrointestinal symptoms) was reported. Primaquine was shown to be a safe and effective prophylactic drug against both P. falciparum malaria and P. vivax malaria in travelers.     

A double-blind, randomized study of azithromycin compared to chloroquine for the treatment of Plasmodium vivax malaria in India

Azithromycin has demonstrated activity in a prevention of Plasmodium vivax infection, but no controlled treatment studies have been performed. We conducted a double-blinded trial in P. vivax malaria in which patients were randomized to either azithromycin 1,000 mg q.d. x 3 or chloroquine 600 mg q.d. x 2 then 300 mg on Day 3 followed by primaquine on Days 7 through 20. Eighty-five of 97 (88%) of those on azithromycin and 101 of 102 (99%) of those on chloroquine [difference 11%; 95% CI: -18, -4] were clinically cured at Day 7. The Day 28 results were similar [89% versus 99%, azithromycin versus chloroquine, respectively]. Parasitologic success was seen in 81 of 97 (84%) on azithromycin and 100 of 102 (98%) on chloroquine [difference 14%; 95% CI: -22, -6]. The median parasite clearance time was 55 hours on azithromycin and 20 hours on chloroquine (P < 0.001). Drug-related adverse events were seen in 13 of 98 (13%) on azithromycin and 24 of 102 (24%) on chloroquine (P = 0.062). Resolution of parasitemia was significantly faster with chloroquine compared with azithromycin, but azithromycin was better tolerated. These data provide support for further study of azithromycin to better define its role in the treatment of P. vivax malaria, either alone as second-line treatment or in combination with other active therapies.     

Clinical features of children hospitalized with malaria--a study from Bikaner, northwest India

Severe Plasmodium vivax malaria in adults has been reported from Bikaner (northwestern India) but the reports on children are scanty. This prospective study was done on 303 admitted children of malaria. The diagnosis was done by peripheral blood smear and rapid diagnostic test. Further confirmation of severe P. vivax monoinfection was done by polymerase chain reaction (PCR). The proportion of P. falciparum, P. vivax, and mixed (P. falciparum and P. vivax) infection was 61.01%, 33.99%, and 4.95%, respectively. Severe disease was present in 49.5% (150/303) children with malaria, with the risk greatest among P. vivax monoinfection (63.1% [65/103]) compared with P. falciparum, either alone (42.7% [79/185]; odds ratio [OR] = 2.3 [95% confidence interval (CI) = 1.40-3.76], P = 0.001) or mixed infections (40% [6/15]; OR = 2.57 [95% CI = 0.88-7.48]). In children < 5 years of age, the proportion of severe malaria attributable to P. vivax rose to 67.4% (31/46) compared with 30.4% (14/46) of P. falciparum (OR = 4.7 [95% CI = 2.6-8.6], P < 0.0001) and 2.2% (1/46) of mixed infection (OR = 92 [95% CI = 24.6-339.9], P < 0.0001). The proportion of patients having severe manifestations, which included severe anemia, thrombocytopenia, cerebral malaria, acute respiratory distress syndrome, hepatic dysfunction, renal dysfunction, abnormal bleeding was significantly high in association with P. vivax monoinfection in 0-5 year age group, while the same was significantly high in association with P. falciparum monoinfection in 5-10 year age group. Similarly P. vivax monoinfection had greatest propensity to cause multiorgan dysfunction in 0-5 year age group (34.1% [17/41], P < 0.0001) in comparison to P. falciparum monoinfection, which had similar propensity in 5-10 year age group (36.8% [35/95], P = 0.039). Plasmodium vivax monoinfection was almost equally serious to cause significant mortality in comparison to P. falciparum (case fatality rate of severe P. vivax was 3.9% versus 3.2% of severe P. falciparum malaria; P = 1.0). This study reaffirms the evidence of severe P. vivax malaria in children in Bikaner.     

Very high risk of therapeutic failure with chloroquine for uncomplicated Plasmodium falciparum and P. vivax malaria in Indonesian Papua

Chloroquine remains the first-line therapy for uncomplicated malaria in Indonesia. Among a series of trials of chloroquine for malaria on this archipelago conducted since 1990, we now report the highest risk of therapeutic failure yet observed. A clinical trial of standard chloroquine therapy for uncomplicated malaria at Arso PIR V in northeastern Indonesian Papua was conducted during 1995. We enrolled 104 non-immune subjects infected with Plasmodium falciparum (n = 55), P. vivax (n = 29), or P. falciparum plus P. vivax (n = 20) and administered supervised standard chloroquine therapy (10 + 10 + 5 mg/kg at 24-hour intervals). The 28-day cumulative incidence of therapeutic failure was 95% for P. falciparum, 84% for P. vivax, and 100% for mixed infections. Only one subject each for P. falciparum and P. vivax remained free of parasites at day 28. All recurrent parasitemias occurred with whole blood levels of chloroquine plus desethylchloroquine exceeding 100 ng/ml. These findings document almost complete failure of chloroquine against P. falciparum or P. vivax near the northeastern coast of Indonesian Papua.     

Assessing the Parasight-F test in northeastern Papua,Indonesia, an area of mixed Plasmodium falciparum and Plasmodium vivax transmission

User-friendly, reliable, and inexpensive methods for diagnosing malaria are needed at the primary health care level. During a randomized treatment trial, the Parasight-F test was assessed on days 0, 3, 7, and 28 against standard light microscopy of Giemsa-stained thick blood smears for diagnosing Plasmodium falciparum parasitemia in patients with P. falciparum (n = 84) or P. vivax (n = 59) malaria. The median P. falciparum parasite count on day 0 was 2,373/microL (range = 20-74,432/microL). At the start of treatment, the Parasight-F test had a sensitivity of 95.2% (80 of 84; 95% confidence interval [CI] = 88.2-98.7), and a specificity of 94.9% (56 of 59; 95% CI = 85.8-98.9). On day 7, this test showed false-positive results in 17 (16.3%) of 104 patients (95% CI = 9.8-24.9). The Parasight-F test performed well when compared with light microscopy in detecting P. falciparum parasitemia in patients presenting with clinical malaria. However, the high false-positive rate on day 7 limits its use for patient follow-up.     

Prospective risk of morbidity in relation to malaria infection in an area of high endemicity of multiple species of Plasmodium.

In an area of Papua New Guinea with high prevalence of Plasmodium falciparum (39.6%), Plasmodium vivax (18.3%), and Plasmodium malariae (13.8%), cross-sectional analysis found P. falciparum infection to be independent of the other species despite heterogeneities in transmission. Plasmodium vivax and P. malariae infections were negatively correlated. Plasmodium malariae infection was positively associated with homologous infection four months previously and with prior P. falciparum, but not P. vivax infection. There were no other indications that any Plasmodium species protected against heterologous infection. Prospective analysis of health-center morbidity supported the idea that P. malariae infection protects against disease, but indicated greater protection against non-malaria than P. falciparum-associated fevers. Plasmodium vivax appeared to protect against P. falciparum disease but not against other forms of morbidity. Covariate adjustment had considerable effects on estimated relationships between species, and confounding variables may account for many differences among reports of inter-species interactions in human malaria.     

Travel histories as risk factors in the analysis of urban malaria in Colombia

Self-reported travel histories were used in a case-control study to determine whether movement of local residents to neighboring endemic areas was a risk factor for malaria in the town of Quibdo, Colombia. Multivariate analyses showed that among residents of Quibdo, traveling to an endemic area 8-14 days before disease onset was the strongest risk factor for both Plasmodium falciparum (adjusted odds ratio [OR] = 28.96, 95% confidence interval [CI] = 13.9-60.32) and P. vivax (adjusted OR = 14.24, 95% CI = 5.27-38.46) malaria. For P. falciparum, individuals who did not travel outside Quibdo during the 8-14 days before disease onset, but who reported traveling 1-7, 15-21, or 22-30 days before disease onset also had an increased risk of malaria. Conversely, use of protection against mosquitoes was negatively associated with P. falciparum. These results highlight the need for malaria control measures that target mobile populations. A definition of imported malaria that allows distinction of imported from autochthonous cases in Quibdo town is proposed.     

Comparison of mefloquine, chloroquine plus pyrimethamine-sulfadoxine (Fansidar), and chloroquine as malarial prophylaxis in eastern Thailand

From July 1983 to March 1984 a randomized double blind prophylactic trial in Thai gem miners working across the border in Cambodia was conducted to determine the prophylactic efficacy of 3 drug regimens against P. falciparum and P. vivax malaria along the Thai-Cambodian border. Gem miners have a high incidence of malaria. Maximum duration of individual participation was 14 weeks. Of 334 participants in this study who were seen every 2 weeks, 145 received mefloquine 500 mg fortnightly, 112 received chloroquine 300 mg base weekly plus Fansidar (1000 mg sulfadoxine and 50 mg pyrimethamine) fortnightly and 77 received chloroquine as 300 mg base weekly. The significant reduction of vivax malaria in study subjects (compared to background incidence) implied good compliance with self administration of chloroquine in the intervening weeks between scheduled appointments. The attack rate in each prophylactic regimen was 2188 cases/1000/year with mefloquine, 8338 cases/1000/year with chloroquine-Fansidar and 10,207 cases/1000/year receiving chloroquine alone. There was a 79% prophylactic efficacy for mefloquine and 18% efficacy for the chloroquine plus Fansidar regimen compared to chloroquine. Using life table analysis, 56% of the mefloquine group, 6% of the chloroquine-Fansidar group and 4% of the chloroquine group were malaria free at the end of the 14 weeks study. The chloroquine plus sulfadoxine-pyrimethamine regimen prescribed for prophylaxis is no longer effective for multidrug resistant strains of P. falciparum in the study area. This study also seriously questions the efficacy of mefloquine prophylaxis.     

The influence of zinc supplementation on morbidity due to Plasmodium falciparum: a randomized trial in preschool children in Papua New Guinea

Zinc is crucial for normal immune function and can reduce morbidity from multiple infectious diseases. To determine the influence of zinc on malaria morbidity we conducted a randomized placebo-controlled trial of daily zinc supplementation in children residing in a malaria endemic region of Papua New Guinea. A total of 274 preschool children aged 6 to 60 months were given 10 mg elemental zinc (n = 136) or placebo (n = 138) for 6 days a week for 46 weeks. Slide-confirmed malaria episodes were detected by surveillance of cases self-reporting to a local health center. Cross-sectional surveys were conducted at the beginning, middle, and end of the study to assess infection rates, parasite density, spleen enlargement, and hemoglobin levels. Zinc supplementation resulted in a 38% (95% CI 3-60, P = 0.037) reduction in Plasmodium falciparum health center-based episodes, defined as parasitemia > or = 9200 parasites/microl with axial temperature > or = 37.5 degreesC or reported fever. Episodes accompanied by any parasitemia were also reduced by 38% (95% CI 5-60, P = 0.028), and episodes with parasitemia > or = 100,000/microl were reduced by 69% (95% CI 25-87, P = 0.009). There was no evidence of the effects of zinc on Plasmodium vivax morbidity or on health center attendance for causes other than P. falciparum. Zinc had no consistent effect on cross-sectional malariometric indices. Although P. falciparum prevalence tended to be lower at the end of the study in children given the placebo, such changes were absent at the mid-study survey. These results suggest that improved dietary zinc intake may reduce morbidity due to P. falciparum.     

Rapid diagnostic devices for malaria: field evaluation of a new prototype immunochromatographic assay for the detection of Plasmodium falciparum and non-falciparum Plasmodium

The NOW ICT Malaria P.f./P.v. for Whole Blood (Binax, Inc., Portland, ME) is a new malaria rapid diagnostic device that represents a technical advance over previous assays, such as ICT Malaria P.f./P.v. and ICT Malaria P.f.. We evaluated this device in March 2001 in symptomatic patients at malaria clinics in Maesod, Thailand. Microscopic examination of Giemsa-stained blood smears was the reference standard. In 246 patients, microscopy showed 32 (13.0%) infected with Plasmodium falciparum, 63 (25.6%) with P. vivax, 6 (2.4%) with mixed infections of P. falciparum and P. vivax, 5 (2.0%) with P. malariae, and 140 (56.9%) negative. Sensitivity for P. falciparum was 100% and specificity was 96.2% (200 of 208; 95% confidence interval [CI] = 92-98). For P. vivax, sensitivity was 87.3% (55 of 63; 95% CI = 77-93) and specificity was 97.7% (173 of 177; 95% CI = 95-99), but all the four false-positive results were microscopically positive for P. malariae; thus, specificity for non-falciparum Plasmodium was 100%. These results suggest improved performance over NOW ICT predecessors.     

Epidemiology of malaria in an area of low transmission in central India

A longitudinal study on malaria was carried out from 2003 to 2005 in an area of unstable malaria in the Panna district in central India. Both Plasmodium vivax and P. falciparum were prevalent; however, the risk of P. falciparum malaria was 31.6% (95% confidence interval [CI] = 29.6-33.6%), which is four times higher compared with that of P. vivax malaria (7.8%, 95% CI = 6.7-9%). An increasing trend was recorded in malaria prevalence from 30.2% in 2003 to 46.6% in 2004 (odds ratio [OR] = 2.0, 95% CI = 1.6-2.5) that increased to 58.6% in 2005 (OR = 1.6, 95% CI = 1.2-2.1). This increase was statistically significant (chi(2) = 120.5, degrees of freedom = 2, P < 0.0001). Anopheles culicifacies was the dominant vector of malaria and showed partial (< 50%) resistance to DDT, which indicated that DDT can still be used. Improved access to treatment facilities, combination therapy, and vector control appears to be the most promising method for controlling malaria in this region.     

Chloroquine prophylaxis against vivax malaria in pregnancy: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To assess the safety of chloroquine (CQ) as prophylaxis against Plasmodium vivax infection during pregnancy. METHOD: One thousand pregnant Karen women were enrolled in a randomized, double-blind, placebo-controlled trial of chemoprophylaxis with chloroquine (500 mg phosphate (or 300 mg base) weekly). Women received a median (range) chloroquine phosphate total dose of 9500 (1500-17 500) mg. The mothers were actively followed from inclusion to delivery and their infants until 12 months of age. RESULTS: Chloroquine prophylaxis completely prevented P. vivax episodes; 10.1% (95%CI: 7.3-14.5) of women in the placebo group experienced at least one episode of vivax malaria but no episode occurred in women in the CQ group. By contrast, the numbers of P. falciparum episodes were similar in each group: 7.4% (95%CI: 3.7-11.1) and 5.6% (95%CI: 3.3-7.9) in the placebo and CQ groups respectively (P = 0.56). Chloroquine prophylaxis was well tolerated and there was no difference in the proportions of reported side effects between CQ treated and placebo groups except for the duration of palpitations and sleeping disorders which were more frequent in those who had received CQ. Chloroquine prophylaxis had no impact on maternal anaemia, birth weight, gestational age, development of newborns or on growth, neurological development or visual acuity in infants at 1 year of age. CONCLUSION: Chloroquine is safe and effective as prophylaxis against P. vivax during pregnancy in this population.     

Assessing drug sensitivity of Plasmodium vivax to halofantrine or choroquine in southern, central Vietnam using an extended 28-day in vivo test and polymerase chain reaction genotyping

Chloroquine-resistant Plasmodium vivax malaria is emerging in Oceania, Asia, and Latin America. We assessed the drug sensitivity of P. vivax to chloroquine or halofantrine in two villages in southern, central Vietnam. This area has chloroquine-resistant Plasmodium falciparum but no documented chloroquine-resistant P. vivax. Standard dose chloroquine (25 mg/kg, over 48 hours) or halofantrine (8 mg/kg, 3 doses) was administered to 29 and 25 patients, respectively. End points were parasite sensitivity or resistance determined at 28 days. Of the evaluable patients, 23/23 100% (95% confidence interval [CI] 85.1-100) chloroquine and 21/24 (87.5%) (95% CI 67.6-97.3) halofantrine-treated patients were sensitive. Three halofantrine recipients had initial clearance but subsequent recurrence of their parasitemias. Genotyping of the recurrent and Day 0 parasitemias differed, suggesting either new infections or relapses of liver hypnozoites from antecedent infections. Among these Vietnamese patients, P. vivax was sensitive to chloroquine and halofantrine. Genotyping was useful for differentiating the recurrent vivax parasitemias.     

Therapeutic responses of Plasmodium vivax and P. falciparum to chloroquine, in an area of western India where P. vivax predominates

In 2003-2005, following an increase in the local incidence of human malaria, the therapeutic efficacy of chloroquine (CQ) in the treatment of Plasmodium vivax and P. falciparum malaria was evaluated in the Anand district of Gujarat state, in western India. After oral administration of CQ, clinical and parasitological responses were measured over a follow-up period of 28 days, following the standard protocol of the World Health Organization. Most of the recurrent infections were checked, by genotyping, to see whether they were the result of treatment failure or re-infection during the follow-up. At the primary health centre (PHC) in Deva, all 57 P. vivax cases included in the study responded to CQ within 3 days. At the Pansora PHC, however, only 59 [90.8%, with a 95% confidence interval (CI) of 83.7%-97.8%] of the 65 P. vivax cases appeared to respond completely, recurrent infections being observed in the other six cases (9.2%; CI=2.2%-16.3%). Of the four recurrent infections checked by genotyping, however, only two appeared to be the result of true treatment failure. Twenty-seven (81.8%; CI=67.2%-94.4%) of the 33 P. falciparum cases who were enrolled in the study, all from Pansora PHC also showed apparent treatment failure, with one early failure, 17 late clinical failures and nine late parasitological failures. All 23 P. falciparum cases that showed apparent treatment failure and were investigated by genotyping appeared to be true cases of failure, none showing any evidence of re-infection during follow-up. The mean parasite-clearance times for those infected with P. falciparum, both those considered CQ-sensitive and the treatment failures, exceeded 2 days. These results indicate the presence of CQ-resistant P. vivax and P. falciparum in Anand district. The high frequency of CQ failure against P. falciparum observed in this study led to a change in the drug policy at the Pansora PHC, with artemisinin-based combination therapy now being used for the first-line treatment of P. falciparum malaria. Chloroquine remains the recommended first-line treatment for P. vivax infections in the area but the treatment failure seen in at least two P. vivax cases indicates a need for further monitoring of the therapeutic efficacy of CQ against such infections, in central Gujarat and elsewhere.     

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

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 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.