BACKGROUND: Soil-transmitted helminth (STH) infections are responsible for a huge public health burden, however treatment options are limited. The discovery and development of novel efficacious drugs or drug combinations for the treatment of STH infections therefore has a high research priority. METHODS: We studied drug combination effects using the main standard anthelmintics, albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin in the Trichuris muris model. Drug combinations were first tested in vitro and additive and synergistic combinations investigated further in vivo in female mice using ratios based on the ED50 of the respective drugs. RESULTS: In vitro all 10 combinations of the standard anthelmintics tested against T. muris revealed synergistic behaviour. We identified three drug combinations in vivo as strongly synergistic, namely mebendazole-ivermectin (Combination index (CI)=0.16), mebendazole-levamisole (CI=0.17) and albendazole-mebendazole (CI=0.23). For albendazole-ivermectin, moderate synergism was observed (CI=0.81) and for albendazole-levamisole a nearly additive effect was documented (CI=0.93) in vivo. Five combinations (albendazole-pyrantel pamoate, mebendazole-pyrantel pamoate, levamisole-pyrantel pamoate, levamisole-ivermectin and pyrantel pamoate-ivermectin) were antagonistic in vivo. CONCLUSION: Our results strengthen the evidence that combination chemotherapy might play a role in the treatment of Trichuris infections. Albendazole-mebendazole should be studied in greater detail in preclinical studies.
Infection with intestinal helminths results in immunological changes that influence co-infections, and might influence fecundity by inducing immunological states affecting conception and pregnancy. We investigated associations between intestinal helminths and fertility in women, using 9 years of longitudinal data from 986 Bolivian forager-horticulturalists, experiencing natural fertility and 70% helminth prevalence. We found that different species of helminth are associated with contrasting effects on fecundity. Infection with roundworm (Ascaris lumbricoides) is associated with earlier first births and shortened interbirth intervals, whereas infection with hookworm is associated with delayed first pregnancy and extended interbirth intervals. Thus, helminths may have important effects on human fertility that reflect physiological and immunological consequences of infection.
The anthelminthic drug tribendimidine has been approved by Chinese authorities for human use in 2004, and a first comprehensive review was published in Acta Tropica in 2005. Here, we summarise further advances made through additional clinical trials and laboratory investigations. Two phase IV trials have been conducted in the People’s Republic of China, the first one enrolling 1,292 adolescents and adults aged 15-70 years and the second one conducted with 899 children aged 4-14 years who were infected with one or multiple species of soil-transmitted helminths. Oral tribendimidine (single 400mg enteric-coated tablet given to adolescents/adults and 200mg to children) showed high cure rates against Ascaris lumbricoides (90.1-95.0%) and moderate-to-high cure rates against hookworm (82.0-88.4%). Another trial done in school-aged children using a rigorous diagnostic approach found a cure rate against hookworm of 76.5%. A single oral dose of tribendimidine showed only low cure rates against Trichuris trichiura (23.9-36.8%) confirming previous results. Tribendimidine administered to children infected with Enterobius vermicularis (two doses of 200mg each on consecutive days) resulted in a high cure rate (97.1%). Importantly, a series of randomised, exploratory trials revealed that tribendimidine shows interesting activity against the liver flukes Opisthorchis viverrini and Clonorchis sinensis, the tapeworm Taenia spp. and the threadworm Strongyloides stercoralis with respective cure rates of 70.0%, 40.0%, 53.3% and 36.4%. Pharmacokinetic studies in healthy Chinese volunteers indicated that after oral administration of tribendimidine, no parent drug was detected in plasma, but its primary metabolite, p-(1-dimethylamino ethylimino) aniline (aminoamidine, deacylated amidantel) (dADT), was found in plasma. dADT is then further metabolized to acetylated dADT (AdADT). dADT exhibits activity against several species of hookworm and C. sinensis in experimental studies, similar to that of tribendimidine. First studies elucidating the mechanism of action suggested that tribendimidine is an L-type nicotinic acetylcholine receptor agonist. Additional experimental studies revealed that the anti-parasite spectrum of tribendimidine is very broad. Indeed, to date, activity has been documented against 20 different nematode, trematode and cestode species. Taken together, tribendimidine warrants further scientific inquiry, including more comprehensive toxicity appraisals mechanism of action studies and clinical investigation as it holds promise as a broad spectrum anthelminthics.
Pinworms (Nematoda: Oxyurida) are common contaminants in most laboratory rodent colonies. The aim of the study was to monitor the transmission of Syphacia muris eggs in laboratory rat breeding facilities. Dust in a breeding room was investigated using special grids (free fallout, or through the help suction chamber). Furthermore, the ventilation system, breeding cages and the hands of the laboratory technical staff were examined. In the case of free fallout, the percentage of positive grids increased slightly over time: from 5.5% (after 24 h) to 8.2% (72 h). Similar values were also found when using the suction chamber (7.6%). Many more pinworm eggs were found in samples collected every second month from suction holes of the ventilation system (28.7%). One-half of the samples taken from the breeding cages (before washing) exhibited pinworm eggs (50.8%). Examination of the hands of technical staff showed positive detection in 37.9% of cases. In this study, certain transmission factors (dust, unclean cages and technicians) were proved to be significant in the distribution of pinworm infection in laboratory rodent facilities.
Syphacia muris (Nematoda: Oxyuridae) is a ubiquitous nematode that commonly infects rats in the laboratory which can interfere in the development of biological assays. The somatic extract of S. muris adults collected from infected rats was investigated using a proteomic approach. A shot-gun liquid chromatography/tandem mass spectrometry procedure was used. We used the MASCOT search engine (Matrix-Science) and ProteinPilot software v2.0 (Applied Biosystems) for the database search. A total of 359 proteins were accurately identified from the worms. The largest protein families consisted of metabolic enzymes and those involved in the nucleic metabolism and cell cycle. Proteins of transmembrane receptors and those involved in protein metabolism, chaperones, structural and motor, signalling and calcium-binding proteins also were identified in the proteome of S. muris. Proteome array of S. muris may contribute to further elucidation of biological system of S. muris as well as host-parasite relationships.
Enterobius vermicularis infection remains one of the most common parasitic infections, particularly prevalent in children. Enterobiasis, although not usually dangerous, may cause significant morbidity. Elimination of the parasite from a family or an institution often poses problems, either because of an incomplete cure or re-infection. While there have been limited reports of ectopic enterobiasis throughout the world, ours is probably one of the rarest reports of recurrent vaginal E. vermicularis infection in the absence of any gastrointestinal symptoms despite complete treatment. A 4-year-old girl presented with recurrent episodes of vulval itching on 3-4 occasions over 2 years. There was no pruritis ani nor urinary/gastrointestinal complaints. The vulva was inflamed with 4-5 living worms, 6-7 mm in length, emerging from the anterior vaginal fornix, but with no vaginal discharge. Direct microscopic examination of vaginal swabs revealed adult worms of Enterobius but no eggs. Repeated stool samples from the patient, parents and a sibling were negative. The patient was treated orally with 100 mg of mebendazole for 3 days followed by two more courses at 3-week intervals over a period of 3 months. Recurrent vaginal enterobiasis despite complete treatment and in the absence of any gastrointestinal involvement suggests that the vagina is a potential reservoir for E. vermicularis, which supports the theory of rare ectopic enterobiasis through the ascending pathway of the female genital tract.
Solid evidence regarding the epidemiology of intestinal helminth infections in Tajikistan is currently lacking. As such information is essential for the evidence-based design, implementation and evaluation of control interventions, a national intestinal helminth survey was conducted with the following objectives: i) to assess the prevalence of intestinal helminth infections among school-aged children nationally and stratified by region; ii) to identify locally relevant risk factors for infection; and iii) to better understand the children’s knowledge and perception of intestinal helminth infections, and asses their haemoglobin status. Standard field and laboratory procedures including the Kato-Katz thick smear and tape test were employed. Complete data was obtained for 1642 children from 33 randomly selected primary schools from different parts of the country. Across the country, prevalences of E. vermicularis, A. lumbricoides, H. nana and T. trichiura were 26.5%, 16.9%, 15.5% and 2.7% respectively. The prevalence of common soil-transmitted helminth (A. lumbricoides and T. trichiura) infections was 19.4%. No hookworm infections were detected, and prevalences of various infections differed significantly between administrative districts (all P<0.05). Hand washing after toilet usage (OR=0.78; P=0.047) and handling animals (OR=0.66; P=0.009) were identified as significant protective factors against E. vermicularis infections. H. nana infection was associated with a 2.85g/L decrease in haemoglobin levels (P<0.001) despite already low average haemoglobin levels. The proportions of children with knowledge about intestinal helminths and protective hygiene practices varied significantly between regions (both P<0.001). Mass albendazole administration to school-aged children and women of child-bearing age against intestinal helminths has now been initiated in Tajikistan, to be followed by mass albendazole and praziquantel distribution to school-aged children. In the longer term, an integrated approach including chemotherapy, provision of safe water and proper sanitation as well as targeted health education will be necessary to achieve sustainable control.
AIM: To propose an aetiology and treatment for distressing perineal and vaginal pain in a paediatric female population. METHODS: Between 1997 and 2011, we saw 24 prepubertal girls (mean age of seven years, 11 months) with distressing vaginal pain, both before and after we suspected that pinworms (Enterobius vermicularis) were the cause. RESULTS: Prior to 2005, two of six girls had resolution of their symptoms, one of whom had repeated courses of mebendazole. After 2005, when pinworms were discovered in one patient, treatment with mebendazole 100 mg weekly for three weeks resolved symptoms in 18 girls. Three girls had a recurrence of symptoms within 2-4 months, and repeat treatment with mebendazole was successful. CONCLUSIONS: Pinworms should be considered when prepubertal girls present with distressing perineal or vaginal pain, and treatment with weekly mebendazole should be offered.
Quantifying the burden of parasitic diseases in relation to other diseases and injuries requires reliable estimates of prevalence for each disease and an analytic framework within which to estimate attributable morbidity and mortality. Here we use data included in the Global Atlas of Helminth Infection to derive new global estimates of numbers infected with intestinal nematodes (soil-transmitted helminths, STH: Ascaris lumbricoides, Trichuris trichiura and the hookworms) and use disability-adjusted life years (DALYs) to estimate disease burden.
Soil-transmitted helminths (STHs) are the most prevalent intestinal helminths of humans, and a major cause of morbidity in tropical and subtropical countries. The benzimidazole (BZ) drugs albendazole (ABZ) and mebendazole (MBZ) are used for treatment of human STH infections and this use is increasing dramatically with massive drug donations. Frequent and prolonged use of these drugs could lead to the emergence of anthelmintic resistance as has occurred in nematodes of livestock. Previous molecular assays for putative resistance mutations have been based mainly on PCR amplification and sequencing. However, these techniques are complicated and time consuming and not suitable for resource-constrained situations. A simple, rapid and sensitive genotyping method is required to monitor for possible developing resistance to BZ drugs.