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    Dreyer G, Coutinho A, Miranda D, Noroes J, Rizzo JA, Galdino E, Rocha A, Medeiros Z, Andrade LD, Santos A, Figueredo-Silva J, Ottesen EA, 1995. Treatment of bancroftian filariasis in Recife, Brazil: a two-year comparative study of the efficacy of single treatments with ivermectin or diethylcarbamazine. Trans R Soc Trop Med Hyg 89 :98–102.

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TOLERANCE AND EFFICACY OF COMBINED DIETHYLCARBAMAZINE AND ALBENDAZOLE FOR TREATMENT OF WUCHERERIA BANCROFTI AND INTESTINAL HELMINTH INFECTIONS IN HAITIAN CHILDREN

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  • 1 Epidemic Intelligence Service, Epidemiology Program Office, and Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Hôpital Sainte Croix, Leogane, Haiti

This randomized, placebo-controlled trial investigated the tolerance, efficacy, and nutritional benefit of combining chemotherapeutic treatment of intestinal helminths and lymphatic filariasis. Children were infected with Ascaris (30.7%), Trichuris (53.4%), and hookworm (9.7%) with 69.9% having more than one of these parasites. A total of 15.8% of the children had Wuchereria bancrofti microfilariae. Children were randomly assigned treatment with placebo, albendazole (ALB), diethylcarbamazine (DEC), or combined therapy. The combination of DEC/ALB reduced microfilarial density compared with placebo, ALB, or DEC (P ≤ 0.03). Albendazole and DEC/ALB reduced the prevalence of Ascaris, Trichuris, and hookworm more than placebo or DEC (P ≤ 0.03). Among Trichuris-infected children, those receiving ALB and DEC/ALB demonstrated greater gains in weight compared with placebo (P ≤ 0.05). Albendazole and DEC/ALB were equally efficacious in treating intestinal helminths and for children with W. bancrofti microfilaremia, DEC/ALB was more effective than DEC, with no increase in severity of adverse reactions.

INTRODUCTION

Both lymphatic filariasis and intestinal helminth infections are important public health problems throughout tropical areas of the world. Wuchereria bancrofti, the parasite that is the major cause of lymphatic filariasis, infects 120 million persons worldwide, more than 40 million of whom have lymphedema, elephantiasis, or scrotal hydrocele.1,2 The World Health Assembly has called for the global elimination of lymphatic filariasis as a public health problem.1 Additionally, more than a billion persons are infected with Ascaris lumbricoides, Trichuris trichiura, or hookworm, and child growth, nutrition and cognitive development have been shown to be adversely affected by infections with intestinal helminths.38

The major strategy for the lymphatic filariasis elimination effort consists of mass distribution of combined albendazole (ALB) and either diethylcarbamazine (DEC) or ivermectin.9 Previously published clinical trials have demonstrated the effectiveness of the two-drug regimen of ALB and ivermectin for the treatment of lymphatic filariasis.1013 Additionally, previous evaluations of combined ALB and ivermectin have demonstrated significant nutritional benefits and improved efficacy against intestinal worms and filariasis compared with treatment with either drug alone.11,14,15 Mass treatment programs in filariasis-endemic communities have also demonstrated substantial reductions in intestinal helminth infections.16 In much of the world, DEC and ALB are being used for the lymphatic filariasis elimination program; however, there are fewer data that document the parasitologic or nutritional benefit of such a combination.

We report here the results of a clinical trial to study the efficacy of single-dose (combined DEC/ALB) therapy in reducing microfilaremia and intestinal helminth infections in Haitian school children, assess adverse reactions associated with therapy, and document the nutritional benefits, if any, of such treatment.

METHODS

Study design.

The protocol for this double blind, placebo-controlled study was reviewed and approved by the Centers for Disease Control and Prevention (CDC) Institutional Review Board and the Ethics Committee of Hôpital Sainte Croix. The study began in October 1998 in Leogane, Haiti, a coastal town with a population of 10,000–15,000. After obtaining verbal informed consent from schoolmasters and parents, all children 5–11 years of age attending any of 12 selected primary schools (grades 1–4) in the Leogane commune were invited to participate in the study. Headmasters verified the absence of any deworming programs in their schools during the previous year and the fact that no other treatment would take place in the schools during the study period. Initial assessment included height (in triplicate to nearest 0.1 cm using a height measuring board) and weight measurements (in triplicate to nearest 0.1 pound wearing a school uniform without shoes and socks, Seca 770 scale; Seca Corporation, Hanover, MD); a stool examination for intestinal helminths; and a finger prick blood specimen collected between 7:30 PM and 9:30 PM for evaluating W. bancrofti microfilarial (MF) density in a 20 μL–thick smear and circulating filarial anti-genemia (CFA).17,18 The Og4C3 assay (James Cook University Tropical Biotechnology Pty. Ltd., Townsville, Queensland, Australia) for circulating filarial antigen was used.18 Quantitative antigen assay results ≥ 250 units were considered positive and specimens with a response ≥ 32,000 antigen units were assigned a fixed value of 32,000. Blood was collected by finger stick because venipuncture was not acceptable to the children or their parents. Criteria for inclusion in the final analysis group included: 1) an age of 5–11 years, 2) anthropometric measurements collected before and six months after treatment, 3) stool specimens collected before and five weeks after treatment, 4) MF smears prepared before and six months after treatment, and 4) random assignment to a treatment group. Placebo treatment consisted of two tablets of vitamin C and those children who received ALB alone or DEC alone also received one tablet of vitamin C. At the end of the study in May 1999, those children who had received placebo or ALB alone were treated with DEC and ALB, while those children who received the DEC/ALB combination or DEC alone received ALB. All laboratory specimens were collected and coded before treatment group assignment and the code, kept by CDC researchers, was only broken after completion of sample testing.

For each school, all eligible students were assigned using a random number table to one of four treatment groups and within seven days were given by CDC staff either a placebo (250 mg of vitamin C), 400 mg of ALB (Zentel®; SmithKline Beecham, Philadelphia, PA or generic drug; BeltaPharm Srl., Milan, Italy), a single 6 mg/kg dose of DEC (Hetrazan®; Lederle, Grosport, Hampshire, United Kingdom), or a combination of DEC and ALB. Children took the medication orally between 8:00 am and noon under direct investigator observation. Five weeks post-treatment (December 1998) another stool specimen was collected, three months post-treatment (February 1999) a 20 μL–thick smear for microfilaria was prepared, and six months after treatment (May 1999) all measurements made and tests conducted before treatments were repeated. Laboratory personnel, measurement teams, and personnel evaluating students for adverse reactions were blinded to the treatment status of the children.

Assessment of adverse effects.

Every day for seven days after treatment, a clinician who was blinded as to treatment group questioned and examined the children at school for adverse reactions. If the child was not at school for two consecutive days, visits were made to the home. Information was collected on adverse reactions that included headache, fever, myalgias, abdominal pain, passage of worms in the stool, vomiting, diarrhea, cough, and dyspnea. Children with fever or myalgias were treated with acetaminophen. A treatment impact score, as shown in Table 1, was determined for each child.

Because earlier studies had demonstrated an association between MF density and severity of systemic adverse reactions, all children with MF densities ≥ 50 per 20 μL of blood were hospitalized on the day of treatment to allow closer monitoring for adverse reactions.1924 In the hospital, their temperature was measured every 4–6 hours, symptoms and severity of adverse reactions were assessed, and acetaminophen was given for fever.

Semi-quantitative stool examination.

Limited personnel and the need to collect and preserve hundreds of stool samples per day made the Kato-Katz protocol for helminth egg quantitation unsuitable. Therefore, a modification to the method of Stoll was used as previously reported by Beach and others.11,25 The intensity of geohelminth infections was defined by egg count (eggs/gram [epg] of stool as follows: Ascaris: light < 7,000 epg; moderate = 7,000 to ≤ 35,000 epg; heavy > 35,000 epg; Trichuris: light < 1,000 epg; moderate = 1,000 to ≤ 10,000 epg; heavy > 10,000 epg; hookworm: light < 2,000 epg; moderate = 2,000 to ≤ 7,000 epg; heavy > 7,000 epg.26,27 Reductions after treatment (in epg) are reported as geometric means, using the (n + 1) transformation.28 Negative changes in egg count were set to 0 before the (n + 1) transformation.

Statistical analysis.

Assuming 50% prevalence, a sample of 1,000 children was selected to ensure an 80% probability (power) of detecting an actual 25% minimum change in any of three anthropometric measurements while maintaining a 5% probability (α) of falsely concluding there was a change. Data were analyzed using Epi-Info version 6.04 (CDC, Stone Mountain, GA) and SAS version 8 (SAS Institute, Cary, NC) and paired analyses were performed for all continuous variables. Anthropometric indices are reported as Z-scores and were calculated using the Epi-Nut segment of Epi-Info. Treatment efficacy for W. bancrofti microfilaremia was assessed as 1) the percentage of children in each treatment group who had no microfilaria detected in their blood three and six months after treatment; 2) mean percentage reduction in MF density three and six months after treatment; and 3) geometric mean percentage reduction in MF density three and six months after treatment. Treatment efficacy for CFA was assessed as 1) the percentage of children in each treatment group who had negative CFA levels in their blood six months after treatment; 2) mean percentage reduction in CFA density six months after treatment; and 3) geometric mean percentage reduction in CFA density six months after treatment. Geometric mean MF density reduction and CFA density reduction were calculated as described by Addiss and others using the (n + 1) transformation.10,28 Negative changes in microfilaremia and antigenemia were set to 0 before the (n + 1) transformation. Differences between the four treatment groups were evaluated with the chi-square test and two-sided Fisher’s exact test for dichotomous variables and the Wilcoxon rank sum test for continuous variables. The Kruskal-Wallis test for statistical significance was used on the log-transformed values of geometric mean MF density, geometric mean CFA density, geometric mean percent reduction in MF density, and geometric mean percent reduction in CFA density.

RESULTS

Descriptive epidemiology.

Children (n = 1,325) were enrolled in October 1998 (Figure 1). The treatment study group was composed of 1,292 children. Thirty-three children were excluded because they were either < 5 years of age or > 11 years of age or because they did not receive treatment in one of the four treatment arms. The filarial study group was composed of 990 children; 302 lacked either pretreatment or post-treatment night MF smears required for analysis. The intestinal helminth study group was composed of 1,249 children; 43 did not have either pretreatment or post-treatment stool examinations required for analysis. Children in the treatment study group (n = 1,292) had a mean age of 7.7 years and 656 (50.8%) were female. The prevalence of intestinal helminths at enrollment in the intestinal helminth study group was 30.7% (383 of 1,249) for Ascaris, 9.7% (121 of 1,249) for hookworm, and 53.4% (667 of 1,249) for Trichuris; 69.9% (873 of 1,249) of the children had one or more intestinal helminth infections. Most infections were categorized as light for Ascaris (90.3%), hookworm (100%), and Trichuris (94.2%). There were three heavy infections observed for Ascaris, none for hookworm, and one for Trichuris. The four treatment groups did not differ significantly with regard to pretreatment prevalence of intestinal helminths after randomization. Although the diagnostic method used was suboptimal for the diagnosis of Strongyloides stercoralis, 1.5% (19 of 1,279) of the children were found to have S. stercoralis larvae in their stools.29 Prior to treatment, W. bancrofti microfilaremia as detected by 20 μL–thick smears was present in 15.8% (156 of 990) of the children in the filarial study group, and 33.0% (327 of 990) of the children had a positive circulating filarial antigen test result. In the total study group (n = 1,292), the prevalence of microfilaremia was 16.2% (145 of 897) in children with intestinal helminth infection and 9.6% (38 of 394) in children without intestinal helminth infection (P = 0.003).The four treatment groups did not differ significantly by age, sex, pretreatment MF density or circulating filarial antigen density.

Assessment of adverse affects.

Adverse reactions were assessed at the initial time of treatment of 180 microfilaria-positive children. The adverse reactions were generally mild and well tolerated, but fever was reported more frequently among children who received the combination of DEC/ALB than those who received ALB alone (P = 0.007) (Table 1). Myalgias were also reported more frequently among the children who received DEC alone compared with ALB alone (P = 0.03). Mean treatment impact scores were highest on days 1 and 2 of treatment. Treatment impact scores on day 1 were significantly greater among children who received DEC and the DEC/ALB combination than among those who received placebo (placebo versus DEC alone; P = 0.009 and placebo versus DEC/ALB; P = 0.0005) or ALB alone (ALB versus DEC alone; P = 0.008 and ALB versus DEC/ALB; P = 0.0002). Among the 34 children who were hospitalized, indicating a MF density ≥ 50, a higher mean treatment impact score was seen for the DEC and combination groups on day 1 (2.14 and 2.33) and on day 2 (1.43 and 0.89). No significant differences were observed in the frequency or severity of symptoms between children who were treated with DEC alone and those who received the DEC/ALB combination, even among the children who were hospitalized. No severe reactions, either life-threatening or requiring hospitalization, or local adverse reactions, including scrotal nodules in boys, were noted. Symptom severity was associated with pretreatment MF density, with increasing mean treatment impact scores associated with higher peripheral MF counts.

Prevalence and intensity of filarial infections three and six months after treatment.

A total of 990 children had pretreatment and post-treatment filarial testing performed (mean age = 7.6 years). Table 2 details the effect of treatment on the subgroup of microfilaria-positive and filarial antigen–positive children. Of note, 16 (1.9%) of 834 microfilaria-negative children became microfilaria positive at the six-month follow-up. Three months after treatment, only children who had received either DEC or combination therapy had a significantly lower geometric mean MF density when compared with placebo. The combination group demonstrated a geometric mean percent reduction of 37.3%, which was lower than the placebo group. Six months after treatment, there was a significant reduction in the prevalence of W. bancrofti microfilaremia in children who had received both DEC and the combination treatment compared with those who had received placebo or ALB alone. There was no difference in microfilaria prevalence between the DEC group and the combination group. Geometric mean MF density six months after treatment was 89.7% of pretreatment levels among children who received placebo, compared with 49.6% for children who were treated with DEC alone (P = 0.0005) and 19.6% for children who received both DEC and ALB (P = 0.0001). Combination therapy reduced the geometric mean MF density by 80.4% and was significantly more effective than placebo (P = 0.0001), ALB (P = 0.0001), and DEC (P = 0.02). Similarly, six months post-treatment, both DEC alone and the DEC/ALB combination reduced the geometric mean CFA density when compared with placebo (P = 0.0001) and ALB (P = 0.0001). There was no statistically significant difference in the prevalence of filarial antigenemia six months after treatment between DEC and combination treatment.

Prevalence and intensity of intestinal helminth infections five weeks after treatment.

Albendazole and the DEC/ALB combination both significantly decreased the prevalence by 96.8% and 93.3% and the intensity by 99.8% and 93.0% of Ascaris infection compared with placebo or DEC alone (P = 0.0001 and 0.0001, respectively) (Table 3).

Albendazole and combined therapy reduced the prevalence by 84.0% and 81.6% of hookworm infection compared with placebo (28.7%) or DEC alone (21.6%). ALB also reduced the intensity (82.7%) of hookworm infection compared with DEC alone (19.1%), and combination treatment also significantly reduced the intensity (99.2%) of hookworm infection compared with placebo (48.8%) or DEC alone (19.1%), but not ALB alone.

In Trichuris infection, ALB alone or in combination with DEC was significantly, but only moderately, more effective than placebo or DEC alone. Both ALB and the DEC/ALB combination reduced the prevalence by 38.5% and 27.4% and intensity by 29.2% and 26.8% of infection compared with placebo or DEC alone.

Nutritional and anthropometric analysis of children after treatment.

For children infected only with Ascaris or hookworm, anthropometric changes did not differ significantly between treatment and placebo groups. However, among the 400 children who were infected with Trichuris before treatment (Table 4), weight gain was greater six months after treatment in children who received ALB (0.28 kg) or the combination therapy (0.31 kg) than in those who received placebo. In addition, there was an increase in weight-for-age Z-scores in the ALB group compared with placebo at six month assessment (WAZ score 0.160 versus 0.094, P = 0.03). Height-for-age Z-scores and weight-for-height Z-scores did not show significantly greater improvement with ALB than with placebo at the six-month assessment.

DISCUSSION

This study demonstrates the public health benefit of adding ALB to a mass treatment program for lymphatic filariasis. Specifically, the combination of DEC and ALB was well tolerated, efficacious at reducing W. bancrofti microfilaremia, antigenemia, and intestinal helminth infection and resulted in improved weight gain in Trichuris-infected children.

Similar to previous trials, no severe adverse events were reported in any group in this trial.30,31 Mean treatment impact scores, indicative of systemic adverse reactions, were higher in the children treated with DEC or the combination compared with those treated with placebo or ALB. The frequency and severity of these symptoms was associated with MF density, but did not differ between children who received the combination and those who received DEC alone, as seen in other studies.11 These adverse events were transient (lasting two days) and mild. They included fever, headache, and myalgia. We detected no local adverse reactions indicative of drug efficacy against the adult worm in this pediatric study, as has been seen in other studies in adults, perhaps due to the different anatomic distributions of adult worms in children and adults.32,33

Data from this study indicate that combination therapy was significantly more effective at suppressing microfilaremia when compared with placebo, ALB, or DEC alone at the six-month assessment. Although both combination therapy and DEC alone demonstrated a decrease in the prevalence of microfilaremia, combination therapy decreased the geometric mean MF density to a greater extent than did DEC alone, resulting in a geometric mean reduction of 80.4% in MF density six-months post-treatment. Although this study was not designed to detect the macrofilaricidal effects of DEC or ALB, particularly since there was no ultrasonographic assessment of adult worms, DEC and combination therapy both demonstrated modest, but significant reductions in filarial antigen densities six-months post-treatment when compared with placebo or ALB alone, which is suggestive of a macrofilaricidal effect of DEC.

Additionally, this study suggests a microfilaricidal role for ALB.34 Although there was no difference in prevalence of microfilaremia, at the six-month follow-up, a significant geometric mean percent reduction in MF density was seen between ALB and placebo (34.7% versus 10.3%, respectively). However, this microfilaricidal effect is less than has been seen in studies of ivermectin.30,35 Moreover, this data differs from previous trials where no statistically significant differences have been seen in either MF prevalence or density between ALB and placebo.12,30

Compared with the ivermectin/ALB combination, for which reductions in geometric mean MF density of between 98.9% at four months and 88.6% at 12 months, respectively, have been shown, the DEC/ALB combination exhibited a slightly lower MF density reduction of 80.4% at six months, suggesting the enhanced microfilaricidal properties of the ivermectin/ALB combination.10,30 Since we re-treated the children in this study at six months, we were unable to determine if MF prevalence and density would continue to decrease after six months, as suggested by others.36,37

In this study, ALB and combination therapy successfully reduced both the prevalence and intensity of intestinal helminths, although less of a decrease was seen with Trichuris than with Ascaris or hookworm (Table 3). Similar to previous studies with children in Haiti, our study population was parasitized to a lesser degree (the prevalence of each helminth infection was less than 55%) and the intensity of helminth infection in this population was comparatively low (> 90% were light infections).11

Although other studies have shown a nutritional benefit after deworming of Ascaris- and hookworm-infected children, we were unable to demonstrate such a benefit, perhaps as a result of the low initial infection intensities.4,5,11 In contrast, children in the ALB and combination therapy group who were infected with Trichuris had significant increases in weight (0.28 kg and 0.31 kg, respectively). This significant weight gain is notable given the short six-month follow-up period, and the low intensity of helminth infections. These improvements are similar to those seen in previous studies and highlight the subtle effects of even light intensity infections on the growth and development of children.11 Nevertheless, it is possible that both the low initial infection intensities and limitations in sample size prevented us from detecting improvements in Z-scores (particularly height-for-age and weight-for-age) in this population.

Assessing the effectiveness of combinations of different antifilarial drugs, specifically adding ALB to single-dose regimens of ivermectin or DEC is important for mass drug administration programs whose goal is the elimination of lymphatic filariasis. Here, we provide data that support the filaricidal effects of ALB in combination with DEC, demonstrate the safety of co-administration of ALB with DEC, and reveal the benefits of ALB as an anti-helminthic to increase the public health benefit of mass drug administration. In this study, ALB either alone or in combination with DEC reduced the prevalence of Ascaris, Trichuris, and hookworm, and both ALB and combination therapy resulted in improved weight gain in Trichuris-infected children not seen with DEC alone. Additionally, combination therapy significantly reduced the prevalence and intensity of W. bancrofti microfilaremia with no measurable increase in severity of adverse reactions. These data suggest a role for combined DEC/ALB treatment in lymphatic filariasis elimination programs.

Table 1

Symptoms and treatment impact scores associated with single-dose treatment in Leogane, Haiti*

Treatment group
CharacteristicPlacebo (n = 43)ALB (n = 46)DEC (n = 44)DEC and ALB (n = 47)
* ALB = albendazole; DEC = diethylcarbamazine; mf = microfilaria.
† Significantly different from albendazole (P < 0.05).
‡ Treatment impact score grading: 1 = symptoms were noticed but did not interfere with daily activities: 2 = symptoms caused some interference with daily activities; 3 = symptoms prevented usual daily activities.
§ Significantly different from placebo (P < 0.05).
Geometric mean pretreatment microfilarial density (mf/20 μL) (range)13.3 (1–190)12.1 (1–163)12.5 (1–162)11.6 (1–158)
Self-reported or documented fever10 (23%)9 (20%)16 (36%)25 (53%)†
Headache12 (28%)11 (24%)19 (43%)23 (49%)
Myalgias7 (16%)†1 (2%)8 (18%)†5 (11%)
Cough7 (16%)†1 (2%)6 (14%)7 (15%)
Mean treatment impact score (range)‡
    Day 10.79 (0–3)0.76 (0–3)1.46†§ (0–3)1.66†§ (0–3)
    Day 20.49 (0–2)0.26 (0–1)0.84† (0–3)0.66† (0–3)
    Day 30.16 (0–1)0.20 (0–2)0.36 (0–3)0.32 (0–3)
    Day 40.16 (0–3)0.07 (0–1)0.20 (0–3)0.13 (0–1)
    Day 50.05 (0–1)0.02 (0–1)0.11 (0–2)0.06 (0–2)
    Day 60 (0)0.02 (0–1)0.07 (0–2)0.02 (0–1)
    Day 70 (0)0 (0)0 (0)0 (0)
Table 2

Characteristics of treatment groups and responses of Wuchereria bancrofti microfilaremia to single-dose treatment in Leogane, Haiti*

Treatment group
CharacteristicPlacebo (n = 243)ALB (n = 256)DEC (n = 246)DEC and ALB (n = 245)
* ALB = albendazole; DEC = diethylcarbamazine; mf = microfilaria; Ag = antigen.
† Three-month analysis based on a subset of the cohort with both pre-treatment and three-month post-treatment values: (n = 822), placebo (n = 204), ALB (n = 204), DEC (n = 213), and DEC and ALB (n = 201).
‡ Significantly different from placebo (P < 0.05).
§ Significantly different from albendazole (P < 0.05).
¶ Significantly different from DEC (P < 0.05).
Mean age (years)7.77.67.67.7
Male sex111 (45.7%)112 (43.8%)115 (46.8%)119 (48.6%)
Pretreatment
    Number of microfilaria positive (prevalence)34 (14.0%)42 (16.4%)39 (15.9%)41 (16.7%)
    Geometric mean microfilarial density (mf/20 μL) (range)17.3 (1–190)12.1 (1–163)12.9 (1–162)13.4 (1–158)
    Number of antigen positive (prevalence)74 (30.5%)89 (34.8%)79 (32.1%)85 (34.7%)
    Geometric mean antigen density (Ag units/mL) (range)2,298 (266–32,000)2,640 (283–32,000)2,194 (260–32,000)2,116 (281–32,000)
Three-months post-treatment†
    Number of microfilaria positive (prevalence)30 (12.4%)28 (10.9%)24 (9.8%)23 (9.4%)
    Geometric mean microfilarial density (mf/20 μL) (range)8.7 (0–171)4.7 (0–248)2.9 (0–72)‡2.3 (0–76)‡
    Geometric mean percent reduction in mf density8.222.031.337.3
Six-months post-treatment
    Number of microfilaria positive (prevalence)36 (14.8%)38 (14.8%)21 (8.5%)‡§13 (5.3%)‡§
    Geometric mean microfilarial density (mf/20 μL) (range)11.2 (0–200)4.4 (0–204)‡2.8 (0–136)‡0.76 (0–36)‡§¶
    Geometric mean percent reduction in mf density10.334.7‡50.4‡80.4‡§¶
    Number of antigen positive (prevalence)81 (33.3%)94 (36.7%)73 (29.7%)75 (30.6%)
    Geometric mean antigen density (Ag units/mL) (range)2,479 (250–32,000)2,428 (264–32,000)1,597 (251–32,000)‡§1,350 (275–32,000)‡§
    Geometric mean percent reduction in antigen density1.73.217.0‡§26.7‡§
Table 3

Helminth prevalence and intensity in Leogane, Haiti*

Treatment groupPretreatment % prevalence†Post-treatment % prevalence 5 weeksPost-treatment % prevalence reduction 5 weeksPretreatment intensity, geometric mean, eggs/gram (arithmetic range)Geometric mean % intensity reduction (paired) 5 weeks
* DEC = diethylcarbamazine.
† No significant differences between treatment groups.
‡ Non-exclusive infection; could have other intestinal helminth or filarial coinfections.
§ Significantly different from placebo and DEC (P < 0.05).
¶ Significantly different from DEC (P < 0.05).
# Significantly different from placebo (P < 0.05).
** Significantly different from placebo, albendazole, and combination.
AscarisPlacebo31.7 (97/306)30.1 (92/306)5.0393 (40–24,0000)11.7
Albendazole28.4 (91/320)0.9 (3/320)96.8§535 (40–34,800)99.8§
DEC28.1 (88/313)23.3 (73/313)17.1617 (40–40,760)18.0
Combination34.5 (107/310)2.3 (7/310)93.3§564 (40–36,000)93.0§
Hookworm‡Placebo10.1 (31/306)7.2 (22/306)28.784 (40–440)48.8
Albendazole8.1 (26/320)1.3 (4/320)84.0§66 (40–320)82.7¶
DEC10.2 (32/313)8.0 (25/313)21.659 (40–400)#19.1
Combination10.3 (32/310)1.9 (6/310)81.6§83 (40–1,840)99.2§
TrichurisPlacebo51.0 (156/306)55.9 (171/306)−9.6153 (40–7,520)9.6
Albendazole51.9 (166/320)31.9 (102/320)38.5§134 (40–6,600)29.2§
DEC55.3 (173/313)58.1 (182/313)−5.1105 (40–6,480)**9.8
Combination55.5 (172/310)40.3 (125/310)27.4§160 (40–30,840)26.8§
Table 4

Height and weight measurements for Trichuris*-infected children†

Treatment group‡Mean pretreatment valuesMean post-treatment valuesMean differences (paired)P (2-tailed)Differences compared to placebo
* Trichuris only; did not have other intestinal helminth infections, but could have filarial infection.
† DEC = diethylcarbamazine.
‡ Placebo (n = 93); albendazole (n = 98); DEC (n = 111); albendazole and DEC (n = 98).
§ Significantly different from placebo.
Height (cm)Placebo122.1125.63.50
Albendazole121.6125.53.48
DEC122.6125.93.38
Combination124.8127.73.26
Weight (kg)Placebo22.924.21.16
Albendazole22.824.41.440.038§0.28 kg
DEC22.924.21.39
Combination24.025.21.470.046§0.31 kg
Figure 1.
Figure 1.

Trial profile.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 73, 1; 10.4269/ajtmh.2005.73.115

*

Address correspondence to Dr. Michael J. Beach, Division of Parasitic Diseases, Centers for Disease Control and Prevention, 4770 Bu-ford Highway, Mailstop F-22, Atlanta, GA 30341-3724, E-mail: mbeach@cdc.gov

Authors’ addresses: LeAnne M. Fox, Center for International Health and Development, Boston University School of Public Health, 85 East Concord Street, Boston, MA 02118, Telephone: 617-414-1209, Fax: 617-414-1261, E-mail: lfox@bu.edu. Bruce W. Furness, STD Control Program, Washington, DC, 20005, Telephone: 202-727-9066, Fax: 202-727-3345, E-mail: bff0@cdc.gov. Jennifer K. Haser, Oregon Health and Science University, Portland, OR 97239, Telephone: 503-494-8428, Fax: 503-494-8120, E-mail: haserj@ohsu.edu. Dardith Desire, Jean-Marc Brissau, Marie-Denise Milord, and Jack Lafontant, Filariasis Program, Hôpital Sainte Croix, Leogane, Haiti, Telephone: 509-557-6424, Fax: 509-235-1845, E-mails: jbrissau@nd.edu, mmilord@nd.edu, and gastro@hopital-stecroix.org. Patrick J. Lammie and Michael J. Beach, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 4770 Buford Highway, Mailstop F-22, Atlanta, GA 30341-3724, Telephone: 770-488-4054 and 770-488-7760, Fax: 770-488-4108 and 770-488-7761, E-mails: pjl1@cdc.gov and mbeach@cdc.gov.

Acknowledgments: We thank Amanda Freeman and Thomas Streit for their contributions to the study, as well as the children of Leogane who participated in this study, their parents, and the headmasters and staff of the participating schools.

Financial support: This study was supported by the Emerging Infections Program of the Centers for Disease Control and Prevention and by an Institutional Strengthening Grant from the World Health Organization to the Hôpital Sainte Croix.

Disclaimer: Use of trade names is for identification only and does not imply endorsement by the Public Health Service or by the U.S. Department of Health and Human Services.

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Author Notes

Reprint requests: Michael J. Beach, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 4770 Buford Highway, Mailstop F-22, Atlanta, GA 30341-3724.
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