Onchocerciasis and lymphatic filariasis (LF) are human filarial diseases belonging to the group of neglected tropical diseases, leading to permanent and long-term disability in infected individuals in the endemic countries such as Africa and India. Microfilaricidal drugs such as ivermectin and albendazole have been used as the standard therapy in filariasis, although their efficacy in eliminating the diseases is not fully established. Anti-Wolbachia therapy employs antibiotics and is a promising approach showing potent macrofilaricidal activity and also prevents embryogenesis. This has translated to clinical benefits resulting in successful eradication of microfilarial burden, thus averting the risk of adverse events from target species as well as those due to co-infection with loiasis. Doxycycline shows potential as an anti-Wolbachia treatment, leading to the death of adult parasitic worms. It is readily available, cheap and safe to use in adult non-pregnant patients. Besides doxycycline, several other potential antibiotics are also being investigated for the treatment of LF and onchocerciasis. This review aims to discuss and summarise recent developments in the use of anti-Wolbachia drugs to treat onchocerciasis and LF.
Hookworm-related cutaneous larva migrans (CLM) is characterized clinically by erythematous and slightly raised tracks, located especially on the feet. These tracks may be single or multiple, linear or serpiginous, more or less ramified and intertwined. The length is variable (up to many cm); the width ranges from 1 mm to 4 mm. Tracks are often accompanied by severe pruritus.
We studied asymptomatic primary schoolchildren in northeastern Malaysia with light to moderate trichuriasis to determine the effect of albendazole treatment on growth rates and TNF-alpha levels. Thirty-seven schoolchildren aged 6-7 years with stool samples positive for Trichuris trichiura and negative for other geohelminths and protozoa were randomized to receive albendazole 400 mg or a placebo daily for 2 days. Anthropometric parameters at baseline, 3, 6 and 12 months were compared between the 2 groups. The placebo group had a significantly greater increase in height (p = 0.04) than the albendazole treatment group. There were no significant differences in urinary TNF-alpha levels (p = 0.8) between the 2 groups and no significant changes between baseline and 1 month post-treatment levels. Further studies are needed to determine the etiology of this apparent association between the albendazole treatment group and the delay in growth rate at 6 months post-treatment.
Five local Malaysian patients with clinical manifestations consistent with lymphatic filariasis were referred to our medical centre between 2003 and 2006. Although no microfilariae (mf) were detected in their nocturnal blood samples, all were diagnosed to have lymphatic filariasis on the basis of clinical findings and positive serology results. PCR on their blood samples revealed that two of the patients were infected with Brugia pahangi, an animal filarial worm hitherto not known to cause human disease in the natural environment. All the patients were successfully treated with anti-filarial drugs: four patients were treated with a combination of diethylcarbamazine (DEC) and albendazole, and one with doxycycline. Four of them were residents of Petaling Jaya, a residential suburbia located 10 km southwest of Kuala Lumpur city, Malaysia. The fifth patient was a frequent visitor of the suburbia. This suburbia has no history or record of B. malayi infection. The most likely vector of the worm was Armigeres subalbatus as extensive entomological surveys within the suburbia revealed only adult females of this mosquito species were infected with B. pahangi larvae. Wild monkeys caught in the suburbia were free from B. pahangi mf, but domestic cats were mf positive. This suggests that infected cats might be the source of the zoonotic infection in the suburbia.
DEC or ivermectin (IVM) in combination with albendazole (ALB) has been the recommended strategy of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) since 2000. Despite effective population coverage (> 65%) with several rounds of MDA with DEC or combination of DEC plus ALB, microfilariae persist in few individuals and they continue to be the source of infection for transmitting LF. We report an individual's variability in response to DEC by defining the response as complete absence of microfilaria (mf) (post-treatment mf count = 0) and non-response as presence of mf (post-treatment mf count ≥ 1). We analyzed follow-up data on individual's response to treatment from two randomized clinical trials in which 46 microfilaremic individuals were treated with single-dose DEC (6 mg/kg body weight). They were classified into low, medium, and high mf density categories based on their pre-treatment mf counts. Of the 46 individuals, 65.2% have not responded throughout the 12-month post-treatment period. Application of a logistic regression model with fixed (age, gender, mf density, post-treatment time, and their interactions) and random (individual's response over time) effects indicated that treatment response is independent of age, gender, and time. The overall treatment response increases in low and decreases in high mf density categories. Furthermore, the estimates for the random coefficients model showed that there is a greater variability in response between individuals over post-treatment time. The results substantiate that individual variation in response to DEC exists which indicate the importance of studying the parasite as well as host genetic factors associated with DEC action.
Fecal specimens collected from 456 school children in Gombak, Malaysia, revealed an overall prevalence rate of 62.9%. The most common parasite found was Trichuris trichiura (47.1%) followed by Giardia intestinalis (14.7%), Entamoeba coli (11.4%), Entamoeba histolytica (9.9%) and Ascaris lumbricoides (7.9%). Infection rates were high among the Indonesian immigrant workers' children (90%) followed by the Orang Asli (79.5%), Malay (59.4%) and Indians (36.4%). Females (66.3%) had a higher prevalence rate than the males (58.5%). The prevalence of infection was found to be associated with the socio-economic status, water supply, sanitary disposal of feces and family size. Albendazole administered as a single dose (400 mg) was found to be effective against Ascaris (100%) and hookworm (92.3%) but was not effective against Trichuris (39.2%).
A study to determine the effect of antihelminthic treatment on growth and nutritional status was undertaken on 103 children in the second grade of primary school, 71 of whom were found to be infected with Ascaris lumbricoides or Trichuris trichiura. The median Ascaris and Trichuris intensities in the infected group were 19,600 (range; 0-488,000) and 2,800 (range; 0-84,600) eggs per gram of feces respectively. Forty-three children harbored both types of worm. Fourteen weeks after two 400 mg doses of albendazole were administered to infected children, the increases in weight, height, weight for age, height for age and weight for height were significantly higher among infected children than controls who were uninfected at baseline. The observed gains were independent of sex and socioeconomic status. Decrease in log transformed Trichuris intensity correlated with increases in weight (r=0.24; p=0.02) and weight for age (r=0.20; p=0.06) but decrease in Ascaris intensity did not correlate with increases in any of the anthropometric parameters. The results suggest that antihelminthic treatment has beneficial short-term effects on growth and nutritional status of a modest magnitude among early primary schoolchildren in the area.
Intestinal permeability of 246 early primary schoolchildren at 2 schools (106 of whom were infected with intestinal helminths) was assessed by using the lactulose/mannitol differential absorption test. The ratio of the urinary recoveries of lactulose and mannitol was determined after oral administration of a standard solution of the 2 sugars. Assessment of intestinal permeability was repeated on 100 infected children after treatment and on a cohort of 68 uninfected children. Infected and uninfected groups were compared with respect to baseline lactulose/mannitol ratio (L/M1) and change in lactulose/mannitol ratio between assessments (delta L/M). The correlations between baseline intensity of infection and L/M1, and between fall in intensity and delta L/M, were evaluated. Based on a crude index of socioeconomic status, each child was assigned to one of 3 socioeconomic groups; all but 3 children belonged to either groups 2 or 3. Trichuris trichiura and Ascaris lumbricoides were the 2 predominant infections; the hookworm infection rate was relatively low. The results suggested that helminthiasis exerted only a marginal effect on intestinal permeability, the impact of which in children from lower socioeconomic backgrounds was negligible in comparison with the cumulative effects of other factors.
Stool examination of 249 early primary schoolchildren at 2 schools in north-eastern peninsular Malaysia revealed that 73 were infected with Ascaris lumbricoides, 103 with Trichuris trichiura, and 18 with hookworms. Infected children were treated with a single dose of 400 mg of albendazole. The school attendance records during a 60 d period before treatment and 2 consecutive 60 d periods after treatment were examined. The absenteeism rate did not improve more among infected children after treatment than it did among the uninfected control children. The correlation between worm intensity and the number of lost school-days was poor. There was no evidence that intestinal helminthiasis caused school absenteeism among this group of children.
Trials using albendazole and mebendazole, as single 400 mg dose treatments, against soil-transmitted helminths, were carried out in 7-9 and 10-12 years-old schoolchildren living in urban and rural environments in Penang, Malaysia. Both drugs were equally effective in treating trichuriasis and ascariasis in both age groups and environments. However, mebendazole is not so effective in the treatment for hookworms when compared to albendazole. It is suggested that albendazole should be considered the drug of choice for mass chemotherapy for Penang.
A previous study had suggested that local strains of goat trichostrongyles, comprising largely Haemonchus contortus, might have developed resistance to benzimidazole anthelmintics. A trial involving 18 goats was conducted to confirm this. There was a significant (P < 0.01) reduction in worm burdens in goats given levamisole, but this was not so for those animals given albendazole, fenbendazole, oxfendazole and mebendazole (P > 0.05).
A community study was carried out to evaluate the efficacy of a 3-day course of 400 mg albendazole daily in the treatment of Trichuris trichiura and Giardia intestinalis infection. This treatment regimen was effective in the treatment of Trichuris trichiura and Giardia intestinalis infection with cure rates of 91.5% and 96.6% respectively. Uses of a 3-day course of 400 mg albendazole daily should be considered in mass or targeted soil-transmitted helminths chemotherapy particularly in areas where the prevalence of Trichuris trichiura is high and polyparasitism is common.
Strongyloidiasis is an infection caused by the intestinal nematode Strongyloides stercoralis. Infected healthy individuals are usually asymptomatic, however it is potentially fatal in immunocompromised hosts due to its capacity to cause an overwhelming hyperinfection. Strongyloidiasis could be missed during routine screening because of low and intermittent larval output in stool and variable manifestations of the symptoms. We present two cases of strongyloidiasis occurring in children with solid organ malignancies suspected to have the infection based on their clinical conditions and treatment history for cancer. Both patients were diagnosed by molecular and serological tests and were successfully treated. Thus, strongyloidiasis in patients undergoing intensive treatment for malignancies should be suspected, properly investigated and treated accordingly.
The efficacy of a single-dose 400 mg albendazole to treat Ascaris, Trichuris and hookworm infection was studied in Orang Asli community. Kato-Katz examination was performed on fecal samples which were collected before treatment, 1 and 4 months after treatment. A total of 123 children were involved in all three surveys. The cure rate of Ascaris infection was 97.4% and the egg reduction after treatment was 99.9%. The cure rate for hookworm infection was 93.1% with 96.6% egg reduction. Although the cure rate was low in Trichuris infection (5.5%), egg reduction was more evident (49.1%). The reinfection rate at 4 months after treatment was 54.5%, 3.6% and 10.3% for Ascaris, Trichuris and hookworm infection, respectively. Within 4 months after treatment almost one-fifth children with Ascaris and hookworm infection reached pre-treatment intensity infection. In Trichuris infection, however more than half of the children reached their pre-treatment intensity infection at 4 months after treatment. Findings suggest that 4-monthly targeted periodic treatment with 400 mg single-dose albendazole in highly endemic areas can have a significant impact on intensity infection of Ascaris and hookworm, but not on Trichuris infection.
A previously healthy 20-year-old man presented with prolonged intermittent low grade fever and cough for 6months. He had bilateral calf pain and lower limb weakness 2days prior to admission. Physical examination revealed multiple enlarged lymph nodes with hepatomegaly. There was bilateral calf tenderness with evidence of proximal myopathy. Full blood picture showed lymphocytosis with reactive lymphocytes and eosinophilia. Creatine kinase and lactate dehydrogenase were markedly elevated. Over 2 weeks of admission, patient was treated symptomatically until the muscle biopsy of right calf revealed eosinophilic myositis with muscular sarcocystosis. He was treated with albendazole and high-dose corticosteroids. Symptoms subsided on reviewed at 2weeks and the dose of corticosteroid was tapered down slowly over a month. Due to poor compliance, he was readmitted 1month later because of relapsed. High-dose corticosteroid was restarted and duration for albendazole was prolonged for 1month. His symptom finally resolved over 2weeks.