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Soil-transmitted helminths (Ascaris lumbricoides, hookworm and Trichuris trichiura) infect about one-fifth of the world’s population. The currently available drugs are all highly efficacious against A. lumbricoides. However, they are only moderately efficacious against hookworm and poorly efficacious against T. trichiura. Oxantel, a tetrahydropyrimidine derivative discovered in the 1970s, has recently been brought back to our attention given its high efficacy against T. trichiura infections (estimated 76% cure rate and 85% egg reduction rate at a 20 mg/kg dose). This review summarizes the current knowledge on oxantel pamoate and its use against T. trichiura infections in humans. Oxantel pamoate acts locally in the human gastrointestinal tract and binds to the parasite’s nicotinic acetylcholine receptor (nAChR), leading to a spastic paralysis of the worm and subsequent expulsion. The drug is metabolically stable, shows low permeability and low systemic bioavailability after oral use. Oxantel pamoate was found to be safe in humans, with only a few mild adverse events reported. Several clinical trials have investigated the efficacy of this drug against T. trichiura and suggest that oxantel pamoate is more efficacious against T. trichiura than the currently recommended drugs, which makes it a strong asset to the depleted drug armamentarium and could help delay or even prevent the development of resistance to existing drugs. We highlight existing data to support the use of oxantel pamoate against T. trichiura infections. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01505-1.

Drug repurposing from veterinary to human medicine has been the main strategy to develop the four recommended human anthelminthics, albendazole, mebendazole, levamisole, and pyrantel pamoate, for the treatment of soil-transmitted helminthiasis. A systematic, head-to-head comparison of the anthelminthic activity profile of derivatives of these drugs and other anthelminthics developed in succession has not been conducted to date. We studied eight benzimidazoles, five macrocyclic lactones, tribendimidine, levamisole, and pyrantel pamoate in laboratory models of human intestinal nematode infections. In vitro studies were performed on Trichuris muris L1 larval stage and adults, as well as Ancylostoma ceylanicum, Necator americanus, Heligmosomoides polygyrus, and Strongyloides ratti L3 larvae and adults. The benzimidazoles showed pronounced differences against larval and adult stages, with low activity against larvae and the highest activity observed against adult N. americanus (IC50 of flubendazole 1.1 μM). The macrocyclic lactones, on the other hand, revealed a higher activity on the larval stages, with the lowest IC50 values observed against N. americanus L3 (IC50 values of 0.03-3 μM). In vivo studies were performed in the T. muris and H. polygyrus mice models, with moxidectin and milbemycin oxime showing the highest activity against H. polygyrus (ED50 values of 0.009 and 0.006 mg/kg, respectively) and moxidectin and abamectin being the most effective drugs against T. muris (ED50 values of 0.2 and 0.5 mg/kg, respectively). Laboratory models for soil-transmitted helminthiasis can assist characterizing potential drug candidates. Drugs should be evaluated against different species, and both the adult and larval stages as activities could differ considerably.

The efficacy of pyrantel pamoate, pyrvinium pamoate, ivermectin, and piperazine citrate against pinworm in cockroach was evaluated. Laboratory-reared German cockroaches naturally infected with Blatticola blattae were treated with the anthelmintics and necropsied at 3 to 35 days after treatment. Ivermectin at over 5 ppm and piperazine citrate at over 2000 ppm killed all the treated cockroaches. Pinworms were still detected in cockroaches given lower concentration of the aforementioned drugs. Administration of pyrantel pamoate (100-1000 ppm) and pyrvinium pamoate (2000 ppm) did not kill the cockroaches, and no pinworms were detected at 3 and 17 days after treatment. Thus, pyrantel pamoate and pyrvinium pamoate were found to be effective for deworming B. blattae in the German cockroaches, without causing mortality for the host. Our results showed that anthelmintics selection is essential for eradication of pinworms in cockroaches because of the toxicity for the host such as ivermectin or piperazine citrate. This is the first report of piperazine citrate toxicity in cockroaches.

We describe the case of a 7-year-old girl with repeated vaginal Enterobius vermicularis infection, never detected as a digestive tract infection. Two-dose pyrantel pamoate or 2-dose albendazole could not suppress recurrence. Finally, 3-dose albendazole after 2-week intervals was successful in preventing relapse.

Albendazole and mebendazole are commonly used to control hookworm, but have shortcomings in their efficacy profiles. We assessed whether triple drug therapy (TDT) with albendazole, pyrantel pamoate, and oxantel pamoate was more effective than the co-administration of two drugs for the treatment of hookworm infections.A randomised, single-blind trial was done from Sept 27 until Nov 17, 2017, in Laos. Children (6-15 years) from six schools were invited to participate. Hookworm-positive children were randomly assigned (2:2:1:1) by a computer stratified list (block sizes of six and 12) to TDT with albendazole (400 mg), pyrantel pamoate (20 mg/kg), and oxantel pamoate (20 mg/kg); albendazole plus oxantel pamoate; pyrantel pamoate plus oxantel pamoate; or mebendazole (500 mg) combined with both pyrantel pamoate and oxantel pamoate (used as proof of concept to compare the two TDTs). Two stool samples were collected at baseline and follow-up (17-30 days after treatment) and analysed with the Kato-Katz method. The primary outcome was the proportion of hookworm egg-negative children at follow-up in all Kato-Katz slides (cure rate [CR]) in the TDT with albendazole, pyrantel pamoate, and oxantel pamoate group compared with the albendazole plus oxantel pamoate and pyrantel pamoate plus oxantel pamoate groups. Secondary outcomes were tolerability 3 h and 24 h after treatment, egg reduction rates (ERRs) against hookworm, and efficacy against concomitant soil-transmitted helminth infections. Participating children and field and laboratory technicians were masked to treatment allocation. All children with follow-up data were included in the primary analysis. This trial is registered with ClinicalTrials.gov, number NCT03278431.1529 children were assessed for eligibility, of whom 533 provided complete baseline data and 414 provided complete outcome data. The CR was higher for the TDT albendazole, pyrantel pamoate, and oxantel pamoate (116 [84%] of 138) than with albendazole plus oxantel pamoate (73 [53%] of 138; odds ratio 4·7, 95% CI 2·7-8·3; p0·0001) and pyrantel pamoate plus oxantel pamoate (36 [52%] of 69; 4·8, 2·5-9·3; p0·0001). The geometric ERR of the TDT albendazole, pyrantel pamoate, and oxantel pamoate (99·9%) was higher than that for albendazole plus oxantel pamoate (99·0%; difference in ERR 0·9 percentage points, 95% CI 0·5-1·4), and pyrantel pamoate plus oxantel pamoate (99·2%; 0·7 percentage points, 0·3-1·3). Adverse events were reported by six (1%) children 3 h and none 24 h after treatment, without any difference across treatment groups.TDT with albendazole, pyrantel pamoate, and oxantel pamoate could make a difference, in particular in the context of soil-transmitted helminth elimination. Pyrantel pamoate might be a useful alternative to prevent benzimidazole resistance; however, larger trials are needed to confirm this finding.Swiss National Science Foundation.

Background Diagnosis of soil-transmitted helminths (STHs) in developing countries is commonly based on microscopic detection of eggs in stool samples, using the Kato-Katz (KK) method, which has a poor sensitivity for detecting light intensity infections. We compared the performance of the KK method and real-time PCR in the framework of a randomized trial, which evaluated four novel treatments against Trichuris trichiura and concomitant STH infections. Results Two stool samples obtained from 320 participants were examined at baseline and follow-up with quadruplicate KK and PCR analyses of one of the two samples using “bead-beating” for DNA extraction. At follow-up, 80 samples were negative according to both PCR and KK and 173 were positive with both methods for any of the STHs. Relative to PCR, the calculated sensitivity of KK at follow-up was 83.6%, 43.0% and 53.8% for T. trichiura, for hookworm and for Ascaris lumbricoides, respectively. The sensitivity of PCR compared with KK at this time point was 89.1% for T. trichiura, 72.7% for hookworm and 87.5% for A. lumbricoides. Cure rates (CRs) for T. trichiura and A. lumbricoides were slightly lower with the PCR method. For hookworm CRs with KK were mostly significantly lower, namely 36.7%, 91.1%, 72.2% and 77.8% for moxidectin, moxidectin in combination with tribendimidine, moxidectin in combination with albendazole and albendazole in combination with oxantel pamoate, respectively, whereas with PCR the CRs were 8.3%, 82.6%, 37.1% and 57.1%, respectively. Conclusions In conclusion, a single real-time PCR is as sensitive as quadruplicate KK for T. trichiura and A. lumbricoides detection but more sensitive for hookworm, which has an influence on the estimated treatment efficacy. PCR method with DNA extraction using the “bead-beating protocol” should be further promoted in endemic areas and laboratories that can afford the needed equipment. The study is registered at ISRCTN (no. 20398469).

Albendazole is an effective anthelmintic intensively used for decades. However, profound pharmacokinetic (PK) characterization is missing in children, the population mostly affected by helminth infections. Blood microsampling would facilitate PK studies in pediatric populations but has not been applied to quantify albendazole's disposition. Quantification methods were developed and validated using liquid chromatography-tandem mass spectrometry to analyze albendazole and its metabolites albendazole sulfoxide and albendazole sulfone in wet samples (plasma and blood) and blood microsamples (dried-blood spots [DBS]; Mitra). The use of DBS was limited by a matrix effect and poor recovery, but the extraction efficiency was constant throughout the concentration range. Hookworm-infected adolescents were venous and capillary blood sampled posttreatment with 400 mg albendazole and 25 mg/kg oxantel pamoate. Similar half-life (; t; 1/2; = ∼1.5 h), time to reach the maximum concentration (; t; max; = ∼2 h), and maximum concentration (; C; max; = 12.5 to 26.5 ng/ml) of albendazole were observed in the four matrices. The metabolites reached; C; max; after ∼4 h with a; t; 1/2; of ca. 7 to 8 h. A statistically significant difference in albendazole sulfone's; t; 1/2; as determined by using DBS and wet samples was detected.; C; max; of albendazole sulfoxide (288 to 380 ng/ml) did not differ among the matrices, but higher; C; max; of albendazole sulfone were obtained in the two microsampling devices (22 ng/ml) versus the wet matrices (14 ng/ml). In conclusion, time-concentration profiles and PK results of the four matrices were similar, and the direct comparison of the two microsampling devices indicates that Mitra extraction was more robust during validation and can be recommended for future albendazole PK studies.

Ancylostoma (A.) ceylanicum, one of the most common species of hookworms infecting dogs and cats, also causes patent infections in humans and is now considered to be the second most common hookworm species infecting populations in southeast Asia. A Japanese patient who returned from a visit to Thailand and Lao People's Democratic Republic (PDR) was presented with intermittent watery diarrhea with eosinophilia. Hookworm eggs were found in feces samples, and adult worms were confirmed to be present in the jejunum with capsule endoscopy and double balloon enteroscopy. A diagnosis of A. ceylanicum infection was made based on the morphology of the adult worms along with findings of a PCR-based molecular study using larvae obtained from a fecal sample culture. The infection was considered likely to have been obtained during a 1-month stay in a Laotian village, where the patient had eaten local food, worn sandals on bare feet, and lived as a local native villager, though he had stayed in modern hotels during the visit to Thailand.

Soil-transmitted helminths infect 1.5 billion people worldwide. Treatment with anthelminthics is the key intervention but interactions between anthelminthic agents and the gut microbiota have not yet been studied. In this study, the effects of four anthelminthic drugs and combinations (tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel-pamoate, and albendazole plus oxantel-pamoate) on the gut microbiota were assessed. From each hookworm infected adolescent, one stool sample was collected prior to treatment, 24 h post-treatment and 3 weeks post-treatment, and a total of 144 stool samples were analyzed. The gut bacterial composition was analyzed using 16S rRNA gene sequencing. Tribendimidine given alone or together with oxantel-pamoate, and the combination of albendazole and oxantel pamoate were not associated with any major changes in the taxonomic composition of the gut microbiota in this population, at both the short-term post-treatment (24 h) and long-term post-treatment (3 weeks) periods. A high abundance of the bacterial phylum Bacteroidetes was observed following administration of tribendimidine plus ivermectin 24 h after treatment, due predominantly to difference in abundance of the families Prevotellaceae and Candidatus homeothermaceae. This effect is transient and disappears three weeks after treatment. Higher abundance of Bacteroidetes predicts an increase in metabolic pathways involved in the synthesis of B vitamins. This study highlights a strong relationship between tribendimidine and ivermectin administration and the gut microbiota and additional studies assessing the functional aspects as well as potential health-associated outcomes of these interactions are required., Graphical abstract Image 1, Highlights • Tribendimidine in combination with ivermectin modulate the gut microbiota. • Bacteroidetes phylum is more abundant 24 h after treatment. • B vitamins biosynthesis pathways are over-represented 24 h post-treatment. • Tribendimidine/ivermectin effect is transient and disappears within 3 weeks.

Summary Background The recommended anthelmintics show low efficacy in a single-dose regimen against Trichuris trichiura . Moxidectin, a new treatment for river blindness, might complement the drug armamentarium for the treatment and control of soil-transmitted helminthiasis. However, its efficacy against T trichiura has not yet been studied. The aim of the study was to assess the efficacy of moxidectin alone and in co-administrations against T trichiura infection. Methods A randomised, single-blind, non-inferiority trial was done in two primary schools and one secondary school in Pemba, Tanzania. Adolescents aged 12–18 years who tested positive for T trichiura were randomly assigned (5:5:3:3) with a computer-generated sequence to receive moxidectin (8 mg) plus albendazole (400 mg), albendazole (400 mg) plus oxantel pamoate (25 mg/kg; reference treatment), moxidectin (8 mg) plus tribendimidine (200 mg or 400 mg), or moxidectin (8 mg) alone. Study group assignments were masked from participants and laboratory technicians. The primary outcome was non-inferiority with a 2 percentage point margin for egg reduction rate (ERR) against T trichiura assessed as the relative change in the geometric mean egg counts from baseline to 14–21 days after treatment with the Kato-Katz method, based on the available case population. Cure rates (CR) and tolerability (assessed 3, 24, and 48 h post treatment) were secondary outcomes. The study is registered at ISRCTN (number 20398469) and is closed to accrual. Findings 701 students were enrolled between April 1, and Aug 7, 2017. Primary outcome data were available for 634 students. We observed ERRs of 98·5% for moxidectin plus albendazole and 99·8% for albendazole plus oxantel pamoate, resulting in an absolute difference of −1·2 percentage points (95% CI −1·8 to −0·8), meeting the non-inferiority margin. 100 (51%) of 197 students receiving moxidectin plus albendazole and 166 (83%) of 200 receiving albendazole plus oxantel pamoate were cured, indicating a difference of 32 percentage points (odds ratio 5·3, 95% CI 3·3 to 8·7). ERRs were 91·6% for moxidectin–tribendimidine and 83·2% for moxidectin. Only mild adverse events (mainly headache and stomach pain) were reported. The largest number of adverse events (126 [20%] of 632 students) was observed 24 h post treatment, with no difference among the individual treatment arms (ranging from 23 [19%] of 118 students treated with moxidectin to 38 [19%] of 199 with moxidectin plus albendazole). Interpretation Moxidectin plus albendazole showed non-inferiority to albendazole plus oxantel pamoate in terms of ERR; however, albendazole plus oxantel pamoate showed a considerably higher cure rate. Dose-optimisation studies with moxidectin and moxidectin plus albendazole should be considered since the efficacy of the dose used for the treatment of onchocerciasis (8 mg) in this study might not be optimal for the treatment of T trichiura infections. Funding Thrasher Foundation.

Rationale: Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction that can be triggered by anticholinergic agents. Patient concerns: We present a 4-year-old female patient who was admitted to the outpatient clinic. She complained of drooped eyelids, which first appeared 2 days after taking a 200 mg dose of pyrantel pamoate. Past medical history is negative. Diagnoses and treatment: She was hospitalized with a diagnosis of ocular type MG, and pyridostigmine (40 mg/day) treatment was started. Outcomes: The patient recovered, and subsequently, the treatment dose was tapered. Conclusion: Pyrantel is an antihelminthic that acts as an agonist of nicotinic acetylcholine receptors (AChRs) of nematodes and exerts its therapeutic effects by depolarizing their muscle membranes. Consequently, there may be an association between pyrantel pamoate and MG.

Background Giardia parasites cause gastrointestinal disease in humans, dogs, and many other animals worldwide. The treatment of dogs for giardiasis requires further investigation to ascertain levels of drug efficacy and the possibility of adverse side effects. Nitazoxanide (NTZ) has shown good clinical anti-Giardia activity in humans, yet it has not been evaluated for the treatment of giardiasis in dogs. Methods Thirty-five dogs, naturally infected with Giardia were divided into five groups (n = 7): dogs in group NTZ1, NTZ2, and NTZ3 were treated with a single oral dose of 37.5 mg/kg, 75 mg/kg, and 150 mg/kg, respectively, of NTZ on days 0 and 14. The fourth group was treated with a commercially available regimen that includes a combination of pyrantel, praziquantel, and febantel (FEB) administered orally for three consecutive days. Additionally, an untreated control group was established. Giardia cysts from the stool of each dog were quantified on days -3, 0, 5, 7, 9, 11, 14, 18, 25, and 28. Biochemical parameters were evaluated in all dogs, before the first treatment and after concluding the experiment. Results Shedding of Giardia cysts was reduced in all treated groups when compared to untreated controls (P

A case of acanthocephaliasis in an 18-month-old child caused by Macracanthorhynchus ingens is reported from Florida. This represents only the third documented case of this species in a human host. An overview of human cases of acanthocephaliasis in the literature is presented, along with a review of the biology, clinical manifestations and pathology in the human host, morphology, and diagnosis.

A case of enterobiasis in pregnancy that presented as copious nocturnal vaginal discharge is reported. Enterobius vermicularis is the most common parasite infecting humans. Transmission can be fecal-oral or via fomites, and recently arrived immigrants from developing countries and individuals who live in households with young children are particularly at risk. Pinworms are most frequently found in the gastrointestinal tract but can also enter the vagina and bladder. Patients typically present with nocturnal anal itching, and diagnosis can be made by clinical history. Treatment includes an antihelminthic agent for the patient and members of the household as well as home hygiene measures to prevent transmission.

Background The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define the characteristics of these combinations in vivo. Methodology/Principal findings Working with the hookworm Ancylostoma ceylanicum-hamster infection system, we establish a laboratory paradigm for studying anti-nematode combinations in vivo using Cry5B and the nicotinic acetylcholine receptor (nAChR) agonists tribendimidine and pyrantel pamoate. We demonstrate that Cry5B strongly synergizes in vivo with both tribendimidine and pyrantel at specific dose ratios against hookworm infections. For example, whereas 1 mg/kg Cry5B and 1 mg/kg tribendimidine individually resulted in only a 0%-6% reduction in hookworm burdens, the combination of the two resulted in a 41% reduction (P = 0.020). Furthermore, when mixed at synergistic ratios, these combinations eradicate hookworm infections at doses where the individual doses do not. Using cyathostomin nematode parasites of horses, we find based on inhibitory concentration 50% values that a strongylid parasite population doubly resistant to nAChR agonists and benzimidazoles is more susceptible or “hypersusceptible” to Cry5B than a cyathostomin population not resistant to nAChR agonists, consistent with previous Caenhorhabditis elegans results. Conclusions/Significance Our study provides a powerful means by which anthelmintic combination therapies can be examined in vivo in the laboratory. In addition, we demonstrate that Cry5B and nAChR agonists have excellent combinatorial properties—Cry5B combined with nAChR agonists gives rise to potent cures that are predicted to be recalcitrant to the development of parasite resistance. These drug combinations highlight bright spots in new anthelmintic development for human and veterinary animal intestinal nematode infections., Author summary Intestinal nematodes are roundworm parasites of humans and animals, causing significant morbidity in both. In humans, these parasites are leading causes of morbidity in children, e.g., causing growth stunting, cognitive impairment, and malnutrition. Few drugs are used to treat these parasites in humans and animals and there is increasing evidence that the drugs are losing efficacy and/or have low efficacy. Infectious diseases are best treated with drug combinations and not single drugs. However, there has been little work to characterize in detail how various anti-nematode drugs combine. Here we establish a new laboratory model to study anti-nematode drug combinations using the human hookworm Ancylostoma ceylanicum infection in hamsters. We show that two classes of anti-nematode drugs, Cry5B and the nicotinic acetylcholine receptor agonists tribendimidine and pyrantel, combine (synergize) in a way that is more powerful at specific drug ratios than predicted from their individual impacts. Furthermore, when combined at these ratios, these combinations completely eliminated parasites at doses where normally neither drug has that effect. Horse parasites resistant to pyrantel also appear to be hypersensitive (more sensitive than wild-type parasites) to Cry5B. These characteristics predict that combinations of Cry5B with tribendimidine or pyrantel will be extremely effective therapeutically and relatively recalcitrant to the development of parasite resistance.

Context More than a quarter of the human population is likely infected with soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) in highly endemic areas. Preventive chemotherapy is the mainstay of control, but only 4 drugs are available: albendazole, mebendazole, levamisole, and pyrantel pamoate. Objective To assess the efficacy of single-dose oral albendazole, mebendazole, levamisole, and pyrantel pamoate against A lumbricoides, hookworm, and T trichiura infections. Data Sources A systematic search of PubMed, ISI Web of Science, ScienceDirect, the World Health Organization library database, and the Cochrane Central Register of Controlled Trials (1960 to August 2007). Study Selection From 168 studies, 20 randomized controlled trials were included. Data Extraction and Data Synthesis Information on study year and country, sample size, age of study population, mean infection intensity before treatment, diagnostic method used, time between evaluations before and after treatment, cure rate (the percentage of individuals who became helminth egg negative following treatment with an anthelminthic drug), egg reduction rate, adverse events, and trial quality was extracted. Relative risk, including a 95% confidence interval (CI), was used to measure the effect of the drugs on the risk of infection prevalence with a random-effects model. Results Single-dose oral albendazole, mebendazole, and pyrantel pamoate for infection with A lumbricoides resulted in cure rates of 88% (95% CI, 79%-93%; 557 patients), 95% (95% CI, 91%-97%; 309 patients), and 88% (95% CI, 79%-93%; 131 patients), respectively. Cure rates for infection with T trichiura following treatment with single-dose oral albendazole and mebendazole were 28% (95% CI, 13%-39%; 735 patients) and 36% (95% CI, 16%-51%; 685 patients), respectively. The efficacy of single-dose oral albendazole, mebendazole, and pyrantel pamoate against hookworm infections was 72% (95% CI, 59%-81%; 742 patients), 15% (95% CI, 1%-27%; 853 patients), and 31% (95% CI, 19%-42%; 152 patients), respectively. No pooled relative risks could be calculated for pyrantel pamoate against T trichiura and levamisole for any of the parasites investigated. Conclusions Single-dose oral albendazole, mebendazole, and pyrantel pamoate show high cure rates against A lumbricoides. For hookworm infection, albendazole was more efficacious than mebendazole and pyrantel pamoate. Treatment of T trichiura with single oral doses of current anthelminthics is unsatisfactory. New anthelminthics are urgently needed.

Nasal myiasis is a rare condition, with only a few reported cases and no treatment consensus. We propose a conservative treatment approach with saline irrigation and debridement. Two patients in the ICU of Norfolk General Hospital, a tertiary academic referral center, presented simultaneously with nasal myiasis. Both patients were negative for necrotic masses or tumors, and neither patient had any contributory medical comorbidities. Both patients were treated conservatively with a single dose of pyrantel pamoate, daily sinus irrigation with saline, and daily bedside endoscopic debridement. After 2 days, the nasal myiasis resolved, and both patients recovered without sequelae. We conclude that this conservative, nonsurgical approach to management is both safe and effective.

Summary Background Commonly used drugs for preventive chemotherapy against soil-transmitted helminths (ie, albendazole and mebendazole) show low efficacy against Trichuris trichiura . Recent studies with oxantel pamoate revealed good cure rates and high egg-reduction rates against T trichiura . We aimed to assess the nature of the dose–response relation to determine the optimum dose. Methods We did a parallel, randomised, placebo-controlled, single-blind trial with oxantel pamoate in school-aged children (aged 6–14 years) infected with T trichiura on Pemba Island, Tanzania. Children were asked to provide two stool samples and children positive for T trichiura were eligible to participate in the trial. Children were excluded if they suffered from any systematic illness. Children were randomly assigned to six different oxantel pamoate doses (5–30 mg/kg) or a placebo. Randomisation was stratified by baseline infection intensity using random block sizes of seven and 14. The primary endpoints were cure rates and egg-reduction rates against T trichiura , both analysed by available case. Drug safety was assessed 2 h and 24 h after treatment. The trial is registered at www.isrctn.com, number ISRCTN86603231. Findings Between Oct 14, and Nov 28, 2014, we enrolled 480 participants and randomly assigned 350 children to the different oxantel pamoate doses or the placebo. 5 mg/kg oxantel pamoate was the minimum effective dose (10 of 46 children cured [cure rate 22%, 95% CI 11–36]; egg-reduction rate 85·0%, 64·5–92·9). An increased probability of being cured and reduced egg counts with escalating doses was recorded. At 25 mg/kg oxantel pamoate 27 of 45 children were cured (cure rate 60%, 95% CI 44–65) with an egg-reduction rate of 97·5% (94·4–98·9), and at 30 mg/kg 27 of 46 children were cured (59%, 43–73) with an egg-reduction rate of 98·8% (96·8–99·6). Oxantel pamoate was well tolerated across all treatment groups; only mild adverse events were reported by the participants 2 h (27 [10%]) and 24 h (12 [4%]) after treatment. Interpretation Our dose-finding study revealed an excellent tolerability profile of oxantel pamoate in children infected with T trichiura . An optimum therapeutic dose range of 15–30 mg/kg oxantel pamoate was defined. With a weight independent dose of 500 mg oxantel pamoate 95% of children aged 7–14 years in sub-Saharan Africa would receive doses of 11·7–32·0 mg/kg. Future research should include studies with oxantel pamoate in younger children and on different continents with the ultimate goal to be able to add oxantel pamoate to soil-transmitted helminth control programmes. Funding Swiss National Science Foundation.

BACKGROUND Anthelmintics are commonly used in tropical areas, but are also prescribed in Western countries with other climates. However, pharmacoepidemiologic studies of these drugs are rare. OBJECTIVE To investigate adverse drug reactions (ADRs) due to anthelmintics. METHODS All spontaneous reports of ADRs associated with albendazole, diethylcarbamazine, flubendazole, ivermectin, mebendazole, niclosamide, praziquantel, pyrantel pamoate, and thiabendazole were identified in the French Pharmacovigilance Database from January 1, 1985, to August 31, 1999. For each case, the following data were recorded: age, gender, weight, ADRs, drug, dosage, and indication. RESULTS A total of 243 cases were found corresponding to 291 ADRs. Serious ADRs (hematologic or hepatic injury) to albendazole most often occurred when the drug was used for the treatment of echinococcosis or cysticercosis, thus requiring both high dosage and long duration of therapy. Our data show that the profile and seriousness of anthelmintic-induced ADRs vary according to their use. Furthermore, the low number of spontaneous reporting of ADRs suggests a high rate of underreporting for these drugs, which are often considered in France as orphan drugs CONCLUSION The improvement of reporting of serious or unrecognized (unlabeled) anthelmintic-induced ADRs will increase our knowledge of the benefit/risk ratio associated with these agents and optimize their use.

Human lagochilascariasis (HL) is a parasite produced by Lagochilascaris minor Leiper 1909 that also can be found in cats and dogs. HL is considered an emerging zoonosis in the Americas, spreading from Mexico to Argentina, and the Caribbean Islands. The present paper describes three HL cases from the Peninsula of Yucatan, Mexico, recorded in the last decade. It describes the characteristics of the lesions and discusses the route of transmission in humans and particularly in the observed patients.

Summary Background Existing anthelmintic drugs (eg, albendazole and mebendazole) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted. We aimed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened. Methods In this randomised controlled trial, we compared three drug combinations and one standard drug alone in children aged 6–14 years in two schools on Pemba Island, Tanzania infected with T trichiura and concomitant intestinal nematodes. We assigned children, via a randomisation list with block sizes of either four or eight, to orally receive albendazole (400 mg) plus ivermectin (200 μg/kg); albendazole (400 mg) plus mebendazole (500 mg); albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or mebendazole (500 mg) alone. The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means, both analysed by available case. This study is registered with ISRCTN, number ISRCTN80245406. Findings We randomly assigned 440 eligible children infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four treatment groups (110 children per group). Data for 431 children were included in the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of 108 children cured [68·5%, 95% CI 59·6–77·4]; egg reduction 99·2%, 98·7–99·6) and albendazole plus ivermectin (30 of 109 cured [27·5%, 19·0–36·0]; egg reduction 94·5%, 91·7–96·3) were significantly more effective against T trichiura than mebendazole alone (nine of 107 cured [8·4%, 3·1–13·8]; egg reduction 58·5%, 45·2–70·9). Albendazole plus mebendazole had similar low efficacy (nine of 107 cured [8·4%, 3·1–13·8; egg reduction 51·6%, 35·0–65·3) to mebendazole alone. About a fifth of the children reported adverse events, which were mainly mild. Abdominal cramps and headache were the most common adverse events after treatment; abdominal cramps were reported by 13 (12·0%) children for albendazole plus ivermectin, 10 (9·3%) for albendazole plus mebendazole, 20 (18·2%) for albendazole plus oxantel pamoate, and 16 (14·5%) for mebendazole; headaches were reported by 5 (4·6%) children for albendazole plus ivermectin, 6 (5·6%) for albendazole plus mebendazole, 12 (10·9%) for albendazole plus oxantel pamoate, and 7 (6·4%) for mebendazole. Interpretation Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes. Funding Medicor Foundation and Swiss National Science Foundation.

Drug-induced renal injury represents a frequent clinical entity. The most common drugs associated with acute tubular necrosis are aminoglycosides, amphotericin B, radiocontrast agents, and cyclosporine, but no data exist about the potential renal toxicity due to anthelmintics administration. Anthelmintics are commonly considered quite safe agents, and side effects such as gastrointestinal, neurologic, hematologic, or hepatic injury have been only rarely described. We report a 4-year-old boy with persistent massive proteinuria without any other symptoms/signs suggesting nephrotic syndrome (NS). The only relevant anamnestic data was the administration of pyrantel pamoate due to oxyuriasis 7 days before the proteinuria development. The patient was affected by NS diagnosed 6 months before and treated with a 12-week course of corticosteroids. During follow-up, carried out at 3 and 6 months after discharge, he did not show further episodes of proteinuria, and no clinical symptoms/signs suggesting a relapse of NS were ever detected. Considering that the proteinuria observed in our patient spontaneously disappeared after 10 days without any treatment, apart from the interruption of the anthelmintic therapy, we would like to alert pediatricians about the possible occurrence of anthelmintics-related renal complications especially among predisposed patients and to perform a watchful waiting not considering the presence of even massive proteinuria as a certain sign of NS relapse.

A 18-year-old Japanese woman seen as an outpatient for refractory enterobiasis had been treated with pyrantel pamoate over 40 times since the age of 11. She washed her hands and cleaned house frequently, and all family members took pyrantel pamoate, but Enterobius vermicularis eggs remained. She was orally administered 400 mg of albendazole 3 times in clinic visits, after which eggs have not been seen for 1 year. Pyrantel pamoate is used widely against enterobiasis in Japan. Our case shows albendazole to also be effective against enterobiasis. Albendazole thus appears to be a useful anti-helminthic in enterobiasis patients in whom pyrantel pamoate is not effective. This is, to our knowledge, the first case of enterobiasis treated with albendazole in Japan.

Ascaris lumbricoides infection is rare among children in developed countries. Although large numbers of adult Ascaris in the small intestine can cause various abdominal symptoms, this infection remains asymptomatic until the number of worms in the intestine considerably increases in most cases. Ascaris causing bilious vomiting suggesting ileus is rare, especially in developed countries. A 6-year-old boy who lived in Japan, presented with abdominal colic, bilious vomiting at the pediatric emergency room. He appeared pale, and had no abdominal distention, tenderness, palpable abdominal mass, or findings of dehydration. He experienced bilious vomiting again during a physical examination. Laboratory tests showed mild elevation of white blood cells and C-reactive protein levels. Antigens of adenovirus, rotavirus, and norovirus were not detected from his stool, and stool culture showed normal flora. Ultrasonography showed multiple, round-shaped structures within the small intestine, and a tubular structure in a longitudinal scan of the small intestine. Capsule endoscopy showed a moving worm of Ascaris in the jejunum. Intestinal ascariasis should be considered as a cause of bilious vomiting in children, even at the emergency room in industrial countries. Ultrasound examination and capsule endoscopy are useful for diagnosis of pediatric intestinal ascariasis.

In 2012, more than 260 million tablets of albendazole (at a dose of 400 mg) and mebendazole (at a dose of 500 mg) were distributed to school-age children as preventive chemotherapy against soil-transmitted helminthiases; altogether, more than 700 million people received such treatment.1,2 Preventive chemotherapy means large-scale preventive treatment against human helminthiasis and trachoma with the use of safe, single-dose, quality-assured medicines.1 Regular treatment of at-risk populations is used as a public health tool to prevent illness and, for certain infections, to reduce transmission.1,3 The strategy relies on large-scale donations of medicines every year by the pharmaceutical industry, . . .

The Ascaris lumbricoides expelled by 1765 people in a poor urban community in Bangladesh were recovered and counted after the subjects had been treated with pyrantel pamoate. The subjects were divided into 22 classes by age and sex (mean n = 80) to examine how prevalence, mean worm burdens and measures of aggregation of worms varied with age and between the sexes, and to see how a measure of aggregation, k, calculated in 3 ways (by maximum likelihood, from moments, or from the percentage uninfected) compared with an empirical aggregation index (the percentage of subjects who expelled an arbitrary 80% of all worms) and with the proportion who were moderately to heavily infected (defined as > or = 15 worms). The prevalence of infection ranged from 64% to 95%, mean worm burdens ranged from 7 to 23 worms, and k ranged from 0.3 to 1.2. There were significant differences between adult males and females in the prevalence of infection, mean worm burdens and measures of aggregation, differences which are probably driven more by behaviour than immunity. The parameter k was better described in terms of the proportion who were moderately to heavily infected (linear; range 0.15-0.58) than by the empirical aggregation index (non-linear; range 0.30-0.49).

Dipylidium caninum, the dog tapeworm, is a common intestinal cestode of domestic dogs and cats, but few cases have been reported of human infection by this parasite in Japan. We repot a case of D. caninum infection in a 17 month-old girl, who sometimes had symptoms of abdominal pain, diarrhea, and dysphoria at night. Her mother noted the appearance of small white worms in her stool, and she was seen by a local pediatrician. Despite antiparasitic therapy wiht pyrantel pamoate, the problem persisted and was eventually referred for further workup to Kurume University Hospital. The diagnosis was made by microscopic examination of the excreted proglottids, which contained characteristic egg capsules. She was successfully treated with a singledose of praziquantel and four adult parasites were recovered. The longest intact worm was 32cm. Her family had household pets (a dog and a cat). The pets were seen by the local veterinary and both were evidenced D. caninum. Humans, primarily children, become infected when they accidentally ingest fleas. Parents usually find proglottids as multiple white objects, often described as cucumber, melon, or pumpkin seeds, in stool, diapers, or on the perineum. Most general practitioners and pediatricians may treat children with enterobiasis (pinworm) infection, and in case the treatment fails, other parasite infection should be considered such as this worm. A history of dog or cat pets, fleas, and flea bites may be important clues to diagnosis. Pets found to be infected should also be treated.

It has recently been shown using genetic markers that Ascaris in humans and pigs in Central America comprise reproductively isolated populations. We present a similar analysis for a region of China in which close association between pigs and humans has been the norm for thousands of years, and agricultural practices will result in frequent exposure to eggs from both sources. DNA fragments from selected regions of mitochondrial and ribosomal DNA were amplified by PCR and allelic forms identified following digestion with a panel of restriction enzymes, using DNA from a total of 115 individual worms from both people and pigs from 2 neighbouring villages. Significant frequency differences in both mtDNA haplotypes and the rDNA spacer were found between the 2 host-associated populations, indicating that they represented reproductively isolated populations. Mitochondrial haplotype frequencies were different from those observed in Guatemala and also from other Asian Ascaris populations, suggesting low levels of gene flow between populations. However, we found no evidence for significant heterogeneity in the genetic composition of Ascaris infrapopulations in either humans or pigs, possibly indicative of agricultural practices in China which have resulted in a random distribution of alleles within the parasite populations.

SUMMARYAppetite and growth were studied in primary schoolboys (6–10 years) infected with Ascaris lumbricoides (86%) and Trichuris trichiura (100%) who received a single dose of pyrantel pamoate (which has little or no effect on Trichuris trichiura ) or a placebo. Boys were examined, allocated at random by descending Ascaris egg count to pyrantel (PR, n = 36) or placebo (PL, n = 36) groups, treated, and re-examined 3 and 7 weeks later. The 2 groups did not differ significantly before treatment in helminth infections, appetite, or growth. Three and 7 weeks after treatment, the PR group exhibited significantly greater increases than did the PL group in weight (0·2 kg and 0·4 kg more, respectively) and percentage weight-for-age (0·6% and 1·7% points more, respectively). Appetite increased significantly in the PR group at 3 and 7 weeks (P < 0·0005 and P < 0·01, respectively) but not in the PL group. The prevalence and intensity of A. lumbricoides infection were greatly reduced in the PR group at 3 and 7 weeks (both P < 0·0001) but not in the PL group. We conclude that treatment with pyrantel pamoate may improve appetite and growth in schoolchildren in areas where A. lumbricoides infections and poor growth are highly prevalent.

Drugs that are largely restricted to the gastro-intestinal tract (GIT) for their therapeutic efficacy and that are not substantially absorbed into the body are usually inadequately studied in terms of systemic bioavailability. The possibility of systemic effects requires that bioavailabilities be studied to ensure against enhanced toxicity resulting from formulation differences. Pyrantel pamoate falls into this category. High-performance liquid chromatography was employed in this study to determine plasma levels of pyrantel in nine healthy human subjects after administration of tablet and suspension dosage forms. Mean peak plasma concentrations of 37.56 +/- 9.37, 35.89 +/- 8.94, and 36.22 +/- 10.10 ng mL-1 were obtained following administration of 750 mg pyrantel pamoate in three different formulations. The mean tmax values were 2.02 +/- 0.12, 2.05 +/- 0.356, and 2.05 +/- 0.339 h respectively for the above dosage forms; the respective AUC0-9 values were 81.01 +/- 12.97, 94.59 +/- 17.18, and 101.47 +/- 19.59 h ng mL-1. There was no statistically significant difference between the bioavailabilities of the dosage forms tested. Large inter-subject variations were observed. One subject experienced abdominal discomfort and one experienced dizziness. It was not possible to clearly correlate individual variations in absorption with the observed adverse effect because the number of incidents was low (two out of 27 treatments).

Ascaris lumbricoides is the most common parasite affecting humans, especially in countries and regions with lower socio-economic conditions. A 2-year-old female child underwent right pulmonary angioplasty using cardiopulmonary bypass. Serious hyperthermia continued after surgery, and, therefore, a re-exploration of the mediastinum was performed because mediastinitis was suspected. No evidence of wound infection was revealed. Ascaris lumbricoides was subsequently isolated from her stool. The patient had no further hyperthermia throughout her hospitalization and was discharged uneventfully on post-operative day 12. The probable origin of the fever was an A. lumbricoides infection and ascariasis may cause the occurrence of serious hyperthermia during the perioperative period. Ascaris lumbricoides infection may, therefore, cause high-grade fever after cardiac surgery.

Known agonists of the orphan receptor GPR35 are kynurenic acid, zaprinast, 5-nitro-2-(3-phenylproplyamino) benzoic acid, and lysophosphatidic acids. Their relatively low affinities for GPR35 and prominent off-target effects at other pathways, however, diminish their utility for understanding GPR35 signaling and for identifying potential therapeutic uses of GPR35. In a screen of the Prestwick Library of drugs and drug-like compounds, we have found that pamoic acid is a potent GPR35 agonist. Pamoic acid is considered by the Food and Drug Administration as an inactive compound that enables long-acting formulations of numerous drugs, such as the antihelminthics oxantel pamoate and pyrantel pamoate; the psychoactive compounds hydroxyzine pamoate (Vistaril) and imipramine pamoate (Tofranil-PM); and the peptide hormones triptorelin pamoate (Trelstar) and octreotide pamoate (OncoLar). We have found that pamoic acid induces a Gi/o-linked, GPR35-mediated increase in the phosphorylation of extracellular signal-regulated kinase 1/2, recruitment of β-arrestin2 to GPR35, and internalization of GPR35. In mice, it attenuates visceral pain perception, indicating an antinociceptive effect, possibly through GPR35 receptors. We have also identified in collaboration with the Sanford-Burnham Institute Molecular Libraries Probe Production Center new classes of GPR35 antagonist compounds, including the nanomolar potency antagonist methyl-5-[(tert-butylcarbamothioylhydrazinylidene)methyl]-1-(2,4-difluorophenyl)pyrazole-4-carboxylate (CID2745687). Pamoic acid and potent antagonists such as CID2745687 present novel opportunities for expanding the chemical space of GPR35, elucidating GPR35 pharmacology, and stimulating GPR35-associated drug development. Our results indicate that the unexpected biological functions of pamoic acid may yield potential new uses for a common drug constituent.

Phongsaly Province, located in the northernmost area of Lao PDR, was previously suggested to be endemic for the liver fluke Opisthorchis viverrini infection. To confirm, or rule out, this suggestion, the Phonxay village in the Khoua District, Phongsaly Province, was selected for a survey. Ten volunteers (8 men and 2 women aged 31-57 years) who consumed raw freshwater fish and had gastrointestinal troubles were treated with a single dose of praziquantel (40 mg/kg) and pyrantel pamoate (10 mg/kg) and purged with magnesium sulfate to recover any worm parasites. Eight of the 10 volunteers expelled 1 or more species of trematodes, nematodes, or cestodes (worm positive rate; 80%). The worms were morphologically identified as H. taichui (861 worms from 8 people), H. yokogawai (59 from 6 people), Phaneropsolus bonnei (1 from 1 person), Trichostrongylus sp. (2 from 2 people), Ascaris lumbricoides (2 from 1 person), Enterobius vermicularis (11 from 3 people), and Taenia saginata (1 strobila with scolex from 1 person). The results indicate that the mountainous area of Phongsaly Province, Lao PDR, is not endemic for the liver fluke but endemic for intestinal flukes, in particular, Haplorchis taichui and H. yokogawai.

A man in his 40s who had made frequent visits abroad was admitted to our hospital complaining of epigastric pain. Ultrasonography (US) revealed an "inner tube sign" in the gallbladder, which suggested a diagnosis of ascariasis in the gallbladder. Pyrantel pamoate was directly injected into the gallbladder via a percutaneous transhepatic catheter. The worm was dead 10 minutes after the injection. US revealed reduction of the worm's length and then the disappearance of the worm from the gallbladder at both 13 days and 2 months after the injection. This method is less invasive than operation and therefore is possibly more safe. It is known that the number of cases of ascariasis may increase in Japan due to increased organic vegetable consumption and foreign travel. We need to consider this disease in the differential diagnosis of epigastric pain.

A. lumbricoides is the largest of the common nematode parasites of man and has been associated with intestinal pathology, respiratory symptoms and malnutrition in children from endemic areas. Current anthelmintic treatments have proven to be safe. However, a reduced efficacy of single dose drugs has been reported. In veterinary practice, anthelmintic drug resistance is an irreversible problem. Thus, research and development of sensitive tools for early detection of drug resistance as well as new anthelmintic approaches are urgently needed. In this review, we summarized data providing information about current drug therapy against A. lumbricoides and other intestinal helminths, new drugs in experimental trials, future drugs perspectives and the identification of immunogenic parasite molecules that may be suitable vaccine targets. In addition to the WHO recommended drugs (albendazole, mebendazole, levamisole, and pyrantel pamoate), new anthelmintic alternatives such as tribendimidine and Nitazoxanide have proved to be safe and effective against A. lumbricoides and other soil-transmitted helminthiases in human trials. Also, some new drugs for veterinary use, monepantel and cyclooctadepsipeptides (e.g., PF1022A), will probably expand future drug spectrum for human treatments. The development of genomic technology has provided a great amount of available nematode DNA sequences, coupled with new gene function data that may lead to the identification of new drug targets through efficient mining of nematode genomic databases. On the other hand, the identification of nematode antigens involved in different parasite vital functions as well as immunomodulatory molecules in animals and humans may contribute to future studies of new therapeutic approaches.

Infestation with Ascaris lumbricoides in children has a varied manifestation, but encephalopathy is a very rare presentation. This report describes a case of ascariasis-associated encephalopathy in a child. An 18-month-old boy was admitted with altered sensorium. He had a history of vomiting and was passing Ascaris worms in the vomitus. The cerebrospinal fluid analysis did not reveal any abnormality. The patient was treated with an antihelminthic drug and he recovered completely. Worm encephalopathy should be considered as a differential diagnosis for unexplained encephalopathy in tropical areas.

An 87-year-old man with heart failure caused by severe anemia was referred to our hospital. Gastroenteroscopy revealed the existence of several parasites in the duodenum. Examination of the stool by a formalin-ethyl acetate concentration technique detected hookworm eggs. After a single dose of pyrantel pamoate, his symptoms including dyspnea on exertion and edema diminished. And also hemoglobin and B-type natriuretic peptide (BNP) had improved dramatically. Hookworm infection is an extremely rare cause of heart failure, and furthermore this parasitic infection is not common in advanced countries. We suggest the possible relationship between parasite infection and organic foods.

A retrospective clinical study to evaluate the effects of paralyzing vermifuges on the course of intestinal obstructions complicating ascariasis was performed. Forty-two patients, 26 patients with partial and 16 patients with complete intestinal obstructions, were treated over 7 years. Although 24 patients have not received any medications two patients with partial obstructions received flaccid paralyzing agent before referral. However, 12 of 16 patients with complete obstruction received spastic paralyzing agent, and the remaining patients received flaccid paralyzing agent before referral. Paralyzing agents, especially those causing spastic paralysis, should be avoided in patients with abdominal symptoms presumed to be related to ascariasis because of the risk of causing complete obstruction and making surgery more complex.

Background Pinworms are the most common helminth infection in the USA and Western Europe, with prevalence rates in some communities of as high as 30–50%. Pinworms generally live in the gastrointestinal tract, and helminth infestations have been noted in over one-quarter of acute appendectomies on histologic examination. Results & Conclusions Although transmission is often attributed to the ingestion of infective eggs by nail biting and inadequate hand washing, inhalation and ingestion of airborne eggs also occur. The female Enterobius vermicularis migrates nightly to the perianal area to deposit her eggs, but some worms find their way into adjacent orifices, most commonly the female genitourinary tract, producing an array of symptoms. More consideration of this entity is justified in patients presenting with genitourinary complaints not responding to normal therapies. In the treatment of pinworms affecting genitourinary organs, treatment with possibly two oral agents, namely mebendazole and ivermectin, and a topical therapy for the eggs may be warranted.

Ascariasis is a helminthic infection of humans caused by the nematode Ascaris lumbricoides. Biliary ascariasis is one of the most common and well described entities caused by ascaris. In endemic areas pregnant women are prone to develop biliary ascariasis. Its management poses a great challenge to both the attending surgeon and the endoscopist. Between January 1993 and March 2003, 15 cases of biliary ascariasis were seen in pregnant patients in our institution. Ultrasonography was used as the main investigative tool. Treatment involved management by conservative, endoscopic, and surgical methods, taking due care of both the mother and the fetus. Ten patients (66.6%) were in the third trimester of pregnancy, and 10 (66.6%) patients were in their third pregnancy. Ultrasonography proved to be the best tool for diagnosing and monitoring worms inside the biliary ductal system. Nine (60%) patients responded to the conservative treatment; endoscopic extraction was successful in 4 (66.6%) patients. Surgical treatment was required in 2 (13.3%) patients. One (6.6%) patient had had spontaneous abortion at 12 weeks gestation, and one (6.6%) patient had a premature labor. The remaining patients had normal pregnancies. Management of biliary ascariasis in pregnancy is a challenge for both the attending surgeon and the endoscopist. Safe and effective management requires special attention to the gestational age and accurate recognition of the specific pathology in the patient. The majority of patients respond to conservative treatment, but endoscopic extraction may be needed in nonresponsive cases. Lead shielding of the fetus and limitation of the total fluoroscopic exposure during therapeutic endoscopy can minimize the teratogenic risk of ionizing radiation. Failures of endoscopic extraction may lead to surgical intervention, which carries risks of fetal wastage and premature labor. Routine worming of women in the child-bearing years is recommended in endemic areas of ascariasis. Though ascariasis is a problem in developing countries, because of increased travel and population migration, clinicians elsewhere should be aware of the problems associated with ascariasis.

Parasitic infections are highly prevalent in the general population. A relation between a parasitic infection and absorption of minerals is not an easy task. Serum levels of copper, zinc and magnesium were prospectively measured in 64 children with intestinal parasitic infection. Thirty-nine children with Enterobius vermicularis were treated with pyrantel pamoate and 25 children with Giardia lamblia with tinidazole and metronidazole. Three months after treatment, significant differences in serum copper, zinc and magnesium were seen in patients with E. vermicularis infection, and in serum magnesium levels in patients with G. lamblia. Although the pathogenic mechanism is not clear, these findings could reflect a deficiency related to malabsorption due to mucous affection. Early detection and treatment of intestinal parasitosis could avoid these serum mineral deficiencies.

To compare the structures of natural and re-established populations of Ascaris in humans, universal (mass) chemotherapy was carried out at the beginning and the end of the study year using pyrantel pamoate. Worms expelled within 48 h of treatment were collected, their sex determined, and measurements made of length, width and weight. Length was used as the criterion for estimating the developmental stage of the worms. In comparison with the natural population, the re-established population displayed similar sex ratio as well as distribution patterns among individuals and age groups of the host. However, the mean worm burden of the re-established population was significantly decreased, with a reduction of burdens in children aged 5–9 years. Also, the re-established population showed significant changes in population structure and worm measurements in that it comprised more immature and less fertile males, less fertile and more senile females, smaller and lighter males, larger (but not heavier) females than the natural population. The results suggested that the re-established Ascaris population did not restore to its original status in relation to mean density, composition and fecundity. Therefore, universal treatment once a year should decrease the transmission of Ascaris in humans. Combined with previous results for the same study sites, the present findings also indicated that caution is warranted to avoid misleading conclusions when using prevalence and faecal egg counts as parameters for evaluating the success of control programmes.