Ivermectin and albendazole alone and in combination for the treatment of lymphatic filariasis in Ghana: follow-up after re-treatment with the combination

The efficacy of re-treatment with the combination of ivermectin (150-200 micrograms/kg bodyweight) and albendazole (400 mg) on Wuchereria bancrofti microfilaraemia was assessed in 1997-99 in 4 groups of individuals from coastal Ghana, which 1 year previously had received a primary treatment with placebo (n = 38), albendazole (n = 39), ivermectin (n = 34) or combination of albendazole and ivermectin (n = 42), respectively. One year after the re-treatment, an overall mean reduction in microfilarial intensity of 76.2% in relation to the intensity before re-treatment was observed, with no statistical significant difference between the 4 groups. The groups given primary treatment with placebo or the drug combination showed re-treatment reductions which were lower (72.5% and 69.8%, respectively) but not statistically significantly different from the reduction observed 1 year after the primary treatment with the combination (86.7%). The efficacy of the combination treatment thus appeared to be largely independent of the type of primary treatment given and multiplicative when used repeatedly.     

A placebo-controlled double-blind trial for the treatment of bancroftian filariasis with ivermectin or diethylcarbamazine.

Therapeutic efficacy and clinical side-effects of ivermectin (single dose of 100 micrograms/kg) and diethylcarbamazine (DEC) (3 mg/kg for one day, then 6 mg/kg daily for 12 d) were evaluated for microfilaricidal effect in Bancroftian filariasis. Seventy-one microfilaraemic consenting adult male patients (greater than or equal to 100 microfilariae (mf)/ml) were randomly assigned to receive ivermectin, DEC or placebo and kept in hospital for 15 d. Those receiving placebo were treated with ivermectin on day 9. Ivermectin (19 'double-blinded' and 22 'unblinded' patients) caused an abrupt reduction in mf count to 1.5% of the pre-treatment level 12 h after drug administration and to 0.06% on day 14, with recrudescence to 1.8% after one month and to 9.2% after 3 months. DEC (30 patients) caused a gradual drop in mf count to 1.1% of the pre-treatment level on day 14, which increased to 2.4% after one and 3 months. The total scores of side-effects were 77 (1%), 305 (2.1%) and 311.5 (3.0%) for placebo, ivermectin and DEC respectively; the differences between DEC or ivermectin and placebo were statistically significant. Ivermectin produced lower side-reaction scores than DEC and the differences were highly significant at the 95% confidence level. Side-effects were mainly headache and body aches in the ivermectin patients, which appeared as early as 4 h after drug administration, resolved within 36 to 48 hours, and were significantly related to mf densities. Side-effects in DEC patients were mainly testicular and epididymal pain and swelling, unrelated to mf densities, which began at day 2 and continued to day 7.(ABSTRACT TRUNCATED AT 250 WORDS)     

A randomized, double-blind, placebo-controlled study with diethylcarbamazine for the treatment of hydrocoele in an area of Tanzania endemic for lymphatic filariasis.

Hydrocoele is common in men in Wuchereria bancrofti-endemic areas, the treatment for which is currently surgical intervention. Two community studies have recently suggested that the antifilarial drug diethylcarbamazine (DEC) may have a beneficial effect of reducing the size of hydrocoeles of filarial origin. To test this hypothesis, a double-blind, placebo-controlled study was carried out in 1998 and 1999 in an area of north-eastern Tanzania where microfilaria (mf) carrier rates and hydrocoele prevalence rates were known to be high. Ninety-eight adult male volunteers (aged > or = 15 years) with chronic hydrocoele received DEC 300 mg per day for 12 days (49 patients), or placebo (49 patients). Circumferential and ultrasonographic measurements of the scrotum, and a serum sample for measuring W. bancrofti antigen, were obtained at the onset and after 3, 6 and 12 months. Scrotal size and hydrocoele fluid volume indices were calculated. No statistically significant differences in volumetric measurements between the DEC and placebo groups were found at any of the follow-ups. Separate analyses dividing patients by antigen status, hydrocoele size or presence of thickening of the scrotal skins gave similar results. Geometric mean intensity of W. bancrofti antigen was significantly lower in the DEC group than in the placebo group (P = 0.008), indicating that lack of compliance was not a significant factor. Two months into the treatment trial, mass treatment with monthly low-dose DEC was given to the rest of the community. We conclude that DEC is not effective in reducing the size of hydrocoele of filarial origin. Interventions to replace or supplement hydrocoelectomy should be investigated.     

Long-term efficacy of single-dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis

In a 'blinded' trial (in Sri Lanka, 1996-98) of 47 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of 3 single-dose combination regimens were compared: albendazole 400 mg with ivermectin 200 micrograms/kg, albendazole 400 mg with diethylcarbamazine citrate (DEC) 6 mg/kg or albendazole 600 mg with ivermectin 400 micrograms/kg. Treated subjects were followed-up for 24 months. This represents the first long-term study using combinations of albendazole with DEC or ivermectin in the above doses against bancroftian filariasis. All subjects had pre-treatment microfilaria (mf) counts over 100/mL. All 3 treatments significantly reduced mf counts, with the albendazole-DEC-treated group showing the lowest mf levels at 18 and 24 months post-treatment. Filarial antigen tests suggested that all 3 treatments had significant activity against adult W. bancrofti; albendazole-DEC combination had the greatest activity according to this test, with antigen levels decreasing to 30.5% of pre-treatment antigen levels, 24 months after therapy. All 3 treatments were clinically safe and well tolerated. These results suggest that a single dose of albendazole 400 mg together with DEC 6 mg/kg is a safe and effective combination for suppression of microfilaraemia of bancroftian filariasis that could be considered for use in filariasis control programmes based on mass treatment of endemic populations.     

Single-dose treatment of Wuchereria bancrofti infections with ivermectin and albendazole alone or in combination: evaluation of the potential for control at 12 months after treatment

The effect of single-dose ivermectin (150-200 micrograms/kg) and albendazole (400 mg) treatment alone and in combination on Wuchereria bancrofti microfilaraemia, antigenaemia and clinical manifestations was compared 12 months after treatment in a double-blind placebo-controlled field trial carried out in Ghana in 1996-98, to evaluate the potential of these treatments for control. Both ivermectin and combination treatments resulted in pronounced reductions in microfilaraemia among individuals who were microfilaria positive before treatment. Among individuals who were positive for circulating filarial antigen before treatment, antigen levels increased considerably over the 1-year period after treatment in the placebo group, whereas they decreased in the ivermectin and combination groups. However, the post-treatment difference reached statistical significance in neither microfilaraemia nor antigenaemia between the ivermectin and the combination groups. Albendazole treatment alone showed only a minor effect on microfilaraemia and antigenaemia. No effect of the treatments on the incidence of new cases of microfilaraemia or antigenaemia, or on clinical manifestations, was observed. Both ivermectin and combination treatment thus appeared effective for control of W. bancrofti infections, but the difference in efficacy between the 2 treatments after 12 months appeared to be minimal.     

Topiramate treatment in bulimia nervosa patients: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: The aim of the current study was to test the influence of topiramate on behavior, body weight, and health-related quality of life (HRQOL) in bulimic patients. METHOD: Thirty patients with bulimia nervosa were treated with topiramate in a 10-week randomized, double-blind, placebo-controlled study. The subjects were randomly assigned to receive topiramate (topiramate group [TG]; n = 30) or a placebo (control group [CG]; n = 30). Primary outcome measures were changes in the frequency of binging/purging, in body weight, and on the SF-36 Health Survey (SF-36) scales. RESULTS: In comparison to the CG group (according to the intent-to-treat principle), significant changes in the frequency of binging/purging (a > 50% reduction: TG, n = 11 [36.7%]; CG, n = 1 [3.3%]; p < .001), body weight (difference in weight loss between the two groups: 3.8 kg, 95% confidence interval [CI] = -5.4 to -2.1; p < .001), and SF-36 (all ps < .001) could be seen. All patients tolerated topiramate well. CONCLUSION: Topiramate appears to safe and effective in influencing the frequency of binging/purging, body weight, and HRQOL in bulimic patients.     

A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse

The opioid antagonist, naltrexone, is reported, in single centre studies, to improve the clinical outcome of individuals with alcohol dependence participating in outpatient psychosocial programmes. This is the first multicentre controlled study to evaluate the efficacy and safety of naltrexone as adjunctive treatment for alcohol dependence or abuse. Patients who met criteria for alcohol dependence (n = 169) or alcohol abuse (n = 6) were randomly assigned to receive double-blind oral naltrexone 50 mg daily (n = 90) or placebo (n = 85) for 12 weeks as an adjunct to psychosocial treatment. The primary efficacy variable was time to first episode of heavy drinking; secondary efficacy assessments included time to first drink, alcohol consumption, craving, and changes in the serum biological markers gamma-glutamyl transferase (GGT), and aspartate and alanine aminotransferases. Compliance was assessed by tablet counts and, in the naltrexone-treated group, by measurement of urinary concentrations of 6-ss-naltrexol. Forty-nine (58%) patients randomized to placebo and 53 (59%) randomized to naltrexone did not complete the study. In intention-to-treat analyses, there was no difference between groups on measures of drinking. The median reduction from baseline of serum GGT (P: < 0.05) and the reductions in alcohol craving (Obsessive and Compulsive Drinking Scale: OCDS) were greater in the naltrexone group (P: < 0.05), from approximately half-way through the study. Of 70 patients (35 placebo; 35 naltrexone) who met an a priori definition of compliance (80% tablet consumption, attendance at all follow-up appointments), those allocated to naltrexone reported consuming half the amount of alcohol (P: < 0.05), had greater median reduction in serum GGT activity (P: < 0.05), and greater reduction in alcohol craving (OCDS total score: P: < 0.05; Obsessive subscale score: P: < 0.05), compared to patients in the placebo group. Use of naltrexone raised no safety concerns. Naltrexone is effective in treating alcohol dependence/abuse in conjunction with psychosocial therapy, in patients who comply with treatment.     

Neurocysticercosis in children: clinical findings and response to albendazole therapy in a randomized, double-blind, placebo-controlled trial in newly diagnosed cases

The clinical findings of neurocysticercosis, diagnosed primarily on the basis of computed tomography (CT), and response to albendazole therapy in a randomized, double-blind, placebo-controlled trial were studied in 72 newly diagnosed children aged 1.5-12 years admitted to hospital in New Delhi, India, during March to July 2000. The lesions by initial CT were mostly single with perilesional oedema, and were located in the parietal lobes. The most common clinical finding was partial seizure (79.2%). The outcome of the albendazole trial was assessed through changes in CT lesions and status of seizure after 6 months of follow-up; about 55% of the lesions had disappeared and about 80% of the children were seizure-free. The frequency of healing of CT lesions in the albendazole-treated group and placebo group was 54.2% and 55.2%, respectively, and the frequency of a seizure-free state in the albendazole-treated group and placebo group was 87.5% and 77.5%, respectively; the differences were not statistically significant. Changes in lesions by CT and the recurrence of seizures after 6 months of follow-up were not related to the number of lesions by initial CT and albendazole was not beneficial in neurocysticercosis in children with ring-enhancing lesions in CT.     

Oral magnesium supplementation in asthmatic children: a double-blind randomized placebo-controlled trial

OBJECTIVE: To investigate the long-term effect of oral magnesium supplementation on clinical symptoms, bronchial reactivity, lung function and allergen-induced skin responses in children and adolescents with moderate persistent asthma. DESIGN: A double-blind randomized parallel placebo-controlled study. SETTING AND SUBJECTS: The patients were recruited from the Pediatric Outpatient Clinic, Division of Pulmonology, Allergy and Immunology, and followed at the Center for Investigation in Pediatrics at State University of Campinas Hospital, Brazil. Thirty-seven out of 72 patients met the study criteria. There were no dropouts. INTERVENTION: The 37 patients (aged 7-19 years, 19 males) were randomized in two groups: magnesium (n=18, 300 mg/day) and placebo (n=19), during 2 months. Both patient groups received inhaled fluticasone (250 microg twice a day) and salbutamol as needed. The primary outcome was bronchial reactivity evaluated with methacholine challenge test (PC20). RESULTS: After a follow-up of 2 months, the methacholine PC20 for testing bronchial reactivity has augmented significantly in the magnesium group only. The skin responses to recognized antigens have also decreased in patients treated with magnesium. The forced vital capacity (FVC), the forced expiratory volume at first second (FEV1), the forced expiratory flow at 25-75 and the FEV1/FVC ratio were similar in both groups. The magnesium group presented fewer asthma exacerbations and used less salbutamol compared to the placebo group. CONCLUSIONS: Oral magnesium supplementation helped to reduce bronchial reactivity to methacholine, to diminish their allergen-induced skin responses and to provide better symptom control in pediatric patients with moderate persistent asthma treated with inhaled fluticasone.     

A randomized, double-blind, placebo-controlled trial of antivenom for local effects of green pit viper bites

Although systemic administration of antivenom can promptly reverse coagulopathy, efficacy on local effects of viper venom remains to be determined. Currently, there has been no proven specific treatment for snakebite patients with severe local effects. This study is a randomized, double-blind, placebo-controlled trial. Patients bitten by green pit vipers (Trimeresurus albolabris or T. macrops) with marked limb swelling, but no severe coagulopathy requiring antivenom, were randomized to receive either equine F(ab')2 antivenom, or placebo. Twenty-eight cases were included, 14 in each group, and they had their limb circumferences measured on days 1, 2, 4 and 6 after interventions. The percentage reduction in limb circumference was significantly better in the antivenom group compared with the placebo group (ANOVA, P = 0.03), especially in the first 24 h (1.14 vs. 3.62%, in placebo and antivenom group, respectively, P = 0.014). The reduction in pain score was similar. The plasma venom levels were not different at presentation but lower in the antivenom group 24h after intervention (P = 0.033). These data suggest that intravenous antivenom could accelerate local oedema resolution in humans. However, the degree is not clinically significant, and, therefore, general use is not recommended.     

Health-related stigma among women with lymphatic filariasis from the Dominican Republic and Ghana

People fearful of being stigmatized by a health-related condition often do not embrace prevention behaviors or seek medical help. They may adhere poorly to treatment regimes for disease and abruptly terminate much needed treatment. Globally, 120 million--many poor women--suffer consequences of lymphatic filariasis that include stigmatizing lymphedema or elephantiasis of the leg. We investigated how women with lymphedema from two different cultures experience stigma and its consequences. Our qualitative data were collected from 56 Dominican women and 48 Ghanaian women with lymphedema. A lymphedema-related stigma framework was developed from constructs derived from the literature and emergent themes from the data. Women described a spectrum of enacted, perceived, and internalized stigma experiences, such as being criticized and isolated by the community, health providers, and even by friends and relatives; they were often denied access to education and meaningful work roles. Some antecedents, consequences, coping strategies, and outcomes of these experiences varied across cultures, with Dominican women faring somewhat better than Ghanaians. Poverty, poor access to health care resources, limited education, and diminished social support challenged the coping strategies of many women and exacerbated negative consequences of lymphedema-related stigma.     

Artesunate and sulfadoxine-pyrimethamine combinations for the treatment of uncomplicated Plasmodium falciparum malaria in Uganda: a randomized, double-blind, placebo-controlled trial

Drug-resistant malaria is spreading in Africa. The few available drugs might be safeguarded if combined with an artemisinin derivative. We investigated the efficacy, safety, and tolerability of 2 combinations of artesunate with sulfadoxine-pyrimethamine (SP) in a mesoendemic region in Uganda with SP resistance, from September 1999 to June 2000. In a randomized, double-blind, placebo-controlled trial, 420 children aged 6-59 months with uncomplicated Plasmodium falciparum malaria were assigned SP alone (25 mg/kg sulfadoxine, 1.25 mg/kg pyrimethamine) or combined with artesunate (AS; 4 mg/kg/d) for either 1 d (SPAS1) or 3 d (SPAS3). Children were followed-up for 28 d. Day 14 cure rates were 84.6% (99/117) with SPAS3 and 61.9% (73/118) with SPAS1 compared with 55.8% (86/154) with SP. Corresponding day 28 results were 74.4% (87/117) and 45.2% (52/115) compared with 40.5% (62/153). A significant improvement was obtained with the addition of 3 d, but not 1 d, of artesunate (risk ratio [RR] = 1.5, 95% CI 1.3-1.8 at 14 d and RR = 1.8, 95% CI 1.5-2.3 at 28 d). Both AS regimens achieved significantly faster parasite clearance and lower gametocyte carriage. All drug regimens were well tolerated, but SP alone was ineffective. Treatment efficacy improved with SPAS3 but the cure rate at day 28 was modest. The combinations were well tolerated and safe. In areas where SP resistance is prevalent other combinations should be considered.     

Comparative efficacy of annual and semi-annual doses of ivermectin or diethylcarbamazine for the prevention of lymphatic filariasis]

A double blind randomized trial was performed on 58 healthy Polynesian Wuchereria bancrofti carriers, they were randomly allocated to treatments with repeated annual or semi-annual doses of ivermectin 100 mcg/kg or diethylcarbamazine (DEC) 3 mg/kg, or with repeated annual doses of DEC 6 mg/kg. After the 12-month treatment, the clearance of microfilaremia was complete in 7 of the 23 carriers treated with ivermectin and in 3 of the 35 treated with DEC. Nine months after that treatment, the lowest mean microfilaremia was observed in the carriers treated with 3 successive semi-annual doses of DEC 3 mg/kg. Adverse reactions were comparable in carriers treated with ivermectin and in those treated with DEC, and did not interfere with daily activities of treated subjects.