Albendazole Treatment Research Articles

Management of a ruptured hydatid cyst involving the ribs: Dealing with a challenging case and review of the literature

IntroductionHydatid liver cysts can rupture into neighboring structures in 15–60% of patients, and most often involves the bile duct, the bronchi, and the peritoneal/pleural cavities. Rarely, chest or abdominal wall involvement occurs that are challenging to manage. This case report and literature review describes the management of patients with chest wall and rib invasion. Presentation of caseA 74-year-old woman, of Spanish origin, presented with right upper quadrant abdominal pain and tender localized swelling. On computer tomography (CT) assessment, the rupture of a hydatid cyst into the right anterior chest wall was identified. Partial involvement of the 10th and 11th rib were noted. The diagnosis was confirmed by a serological test. Surgical treatment involved a radical en bloc right hepatic resection together with resection of the involved ribs, diaphragm and subcutaneous tissue. Primary diaphragm and wall closures were performed. The postoperative course was uneventful with three weeks of albendazole treatment. CT follow-up at six months demonstrated the absence of recurrence. DiscussionComplete resection is the gold standard treatment of patients with hydatid cysts with the aim to remove all parasitic and pericystic tissues. ConclusionThe present report illustrates that an aggressive surgical en bloc resection is feasible and should be preferred for the treatment of hydatid cysts with rupture into the chest wall, even when the ribs are involved.

Lessons from a study in a rural community from southern Mexico: risk factors associated to transmission and reinfection of gastrointestinal parasites after albendazole treatment.

To determine the prevalence of gastrointestinal parasites and evaluate the effect of a single dose of treatment with albendazole in a sentinel group from a rural community in southern Mexico. Stool samples were collected from 1456 individuals aged ≥1 year during consecutive days, and examined for helminth infection using the modified Stoll dilution method. Additionally, 104 individuals were treated with a single dose of albendazole and evaluated over 21 weeks to assess reinfection. Questionnaires were administered to obtain individual and household-level data pertaining to behavior, demography, and socioeconomic status. Risk factors for reinfection after albendazole administration were determined using multiple logistic regression analyses. The prevalence of Ascaris lumbricoides was 73.9% (95% confidence interval [CI] = 71.56%-76.14%). Albendazole was 100% effective, but eggs began to be detected by 9-12 weeks posttreatment, increasing to 100% after 21 weeks. Logistic regression analysis revealed that all individuals from this study had a probability of reinfection of 1.65× each week after treatment. The prevalence of Trichuris trichiura was 57.2% (95% CI = 54.62%-59.77%) and chemotherapy was 34.7% effective. The prevalence for other minor gastrointestinal parasites ranged from 0.2% to 29.7%. This was a comprehensive study on gastrointestinal parasites in a rural community from southern Mexico and, to the best of the authors' knowledge, is the first time that the effect of albendazole has been evaluated for a period of over 21 weeks following its administration. Risk factors associated with parasite transmission were linked to poverty and lack of hygiene, such as, defecating in open places, living customs (drinking piped water and/or from a well), and absence of knowledge about transmission life cycle of the parasites. Studies of this kind should be linked to health education and improvement of access to clean water and adequate sanitation to consolidate morbidity control and enhance sustainability.

Primary Pancreatic Hydatid Cyst Resembling a Pseudocyst

Hydatid cyst is a parasitic disease that is commonly seen in certain areas. It may localize in many organs in the body. Pancreas is a rarely involved organ. A 48 years old patient who could not be diagnosed before surgery was then diagnosed with hydatid cyst localized in the uncinate process of the pancreas post-operatively. Albendazole treatment was begun after the operation. No problem was observed in the follow-up ultrasonography. This rare case may be mistaken for cystic malignancies and pseudocysts of pancreas.

Effects of infection intensity with Strongyloides papillosus and albendazole treatment on development of oxidative/nitrosative stress in sheep

The objective of this study was to estimate and evaluate oxidative/nitrosative stress parameters in sheep infected with Strongyloides papillosus and after antihelminthic treatment with albendazole (ABZ). This parasite, especially during development stages can seriously damage parenchaematous organs during migration within the host. The presence of parasites leads to increased productions of reactive oxygen species (ROS) and reactive nitrogen species (RNS). It is also well known that certain drugs can be very harmful for the delicate oxidant–antioxidant equilibrium, provoking oxidative stress during their biotransformation. ABZ is a broad spectrum antihelminthic drug, frequently used in veterinary medicine for therapy of parasitic infections. The current research was performed on female Württemberg sheep (n=48). The distribution of parasites in sheep was evaluated using the native smear coprological technique, by sedimentation and flotation methods, revealing the presence of S. papillosus. The degree of infection intensity per sheep was quantitatively established by the method of McMaster, the animals having been divided into three groups according to the intensity of infection; mild, moderate and high. The control group consisted of sheep negative to the parasites. After determining the type of parasite infection, the sheep were treated with ABZ, per orally, in single doses of 5mg/kg per body weight. Sampling of feces for parasitological and blood for biochemical assaying was performed on the 0 and 21st day after treatment with ABZ. The oxidative stress parameters were measured for catalase activity (CAT), the red cell membrane damage by level of malondialdehyde (MDA), while carbonyl and thiol plasma protein group concentrations were used as indicators of the degree of protein oxidative modification. The activity of Cu,Zn-superoxide dismutase (SOD) and relative distribution of lactate dehydrogenase (LDH1–LDH5) activity were determined electrophoretically. The distribution of LDH isoenzymes in sheep moderately and highly infected with S. papillosus revealed that the parasite induced damage to the myocardial (LDH2), lung (LDH3) and liver cells (LDH5) in infected animals, while ABZ treatment only damaged liver cells (LDH5). The MDA concentration revealed that lipid peroxidation increased both in the presence of parasites and the antihelminthic formulation tested (p<0.001) when compared to the control sheep, while the increase of carbonyl concentration (p<0.001), as well as the observed decrease of thiol concentration (p<0.001) indicated significant oxidative damage of plasma proteins in experimental sheep, when compared to the control animals. Our results indicate that S. papillosus induces oxidative/nitrosative stress in sheep. The antihelminthic treatment with ABZ further promotes the disbalance of oxidative–antioxidative equilibrium in all tested sheep.

Curcumin alleviates eosinophilic meningitis through reduction of eosinophil count following albendazole treatment againstAngiostrongylus cantonensisin mice

Angiostrongylus cantonensis (A. cantonensis) is the most common cause of parasitic eosinophilic meningitis worldwide. By using an animal model of BALB/c mice infected with A. cantonensis, previous studies indicated that the anthelmintic drug, albendazole, could kill A. cantonensis larvae and prevent further infection. However, the dead larvae will induce severe immune responses targeting at brain tissues. To alleviate the detrimental effects caused by the dead larvae, we administered curcumin, a traditional anti-inflammatory agent, as a complementary treatment in addition to albendazole therapy, to determine whether curcumin could be beneficial for treatment. The results showed that although curcumin treatment alone did not reduce worm number, combined treatment by albendazole and curcumin helped to reduce eosinophil count in the cerebrospinal fluid, better than using albendazole alone. This alleviating effect did not affect albendazole treatment alone, since histological analysis showed similar worm eradication with or without addition of curcumin. Nevertheless, curcumin treatment alone and combined albendazole-curcumin treatment did not inhibit MMP-9 expression in the brain tissue. In conclusion, curcumin, when used as a complementary treatment to albendazole, could help to alleviate eosinophilic meningitis through suppression of eosinophil count in the cerebrospinal fluid.

Efficacy of albendazole combined with a marine fungal extract (m2-9) against Angiostrongylus cantonensis-induced meningitis in mice

The pathogenesis of angiostrongyliasis, resulting from Angiostrongylus cantonensis invasion of the human central nervous system, remains elusive. Anthelmintics are usually used to kill worms, although dead worms in the brain may cause severe inflammation which will lead to central nervous system damage. Therefore, combination therapy with anthelmintics and anti-inflammatory drugs in the treatment of human angiostrongyliasis needs further study. To evaluate the efficacy of albendazole combined with a marine fungal extract (m2-9) in A. cantonensis infection, BALB/c mice infected by the third-stage larvae of A. cantonensis were divided into three groups: mice treated with albendazole or m2-9 alone or in combination from day 5 post-inoculation (PI). Several efficacy parameters were recorded, including weight change, worm recovery, neurological function, behavioural analysis, eosinophil and leucocyte counts. The results showed that combination therapy increased body weight, reduced worm burden, improved learning ability, memory and action, decreased neurological dysfunction and leucocyte response in these mice. The combination of albendazole and m2-9 treatment significantly decreased leucocyte response and increased the frequency of rearing, compared to infected mice treated with either drug alone. Therefore, m2-9 is a natural product with potentially significant therapeutic value for angiostrongyliasis and is worthy of further study.

Post-Treatment Follow-Up Study of Abdominal Cystic Echinococcosis in Tibetan Communities of Northwest Sichuan Province, China

BackgroundHuman cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus, with the liver as the most frequently affected organ, is known to be highly endemic in Tibetan communities of northwest Sichuan Province. Antiparasitic treatment with albendazole remains the primary choice for the great majority of patients in this resource-poor remote area, though surgery is the most common approach for CE therapy that has the potential to remove cysts and lead to complete cure. The current prospective study aimed to assess the effectiveness of community based use of cyclic albendazole treatment in Tibetan CE cases, and concurrently monitor the changes of serum specific antibody levels during treatment.Methodology/Principal FindingsUltrasonography was applied for diagnosis and follow-up of CE cases after cyclic albendazole treatment in Tibetan communities of Sichuan Province during 2006 to 2008, and serum specific IgG antibody levels against Echinococcus granulosus recombinant antigen B in ELISA was concurrently monitored in these cases. A total of 196 CE cases were identified by ultrasound, of which 37 (18.9%) showed evidence of spontaneous healing/involution of hepatic cyst(s) with CE4 or CE5 presentations. Of 49 enrolled CE cases for treatment follow-up, 32.7% (16) were considered to be cured based on B-ultrasound after 6 months to 30 months regular albendazole treatment, 49.0% (24) were improved, 14.3% (7) remained unchanged, and 4.1% (2) became aggravated. In general, patients with CE2 type cysts (daughter cysts present) needed a longer treatment course for cure (26.4 months), compared to cases with CE1 (univesicular cysts) (20.4 months) or CE3 type (detached cyst membrane or partial degeneration of daughter cysts) (9 months). In addition, the curative duration was longer in patients with large (>10 cm) cysts (22.3 months), compared to cases with medium (5–10 cm) cysts (17.3 months) or patients with small (<5 cm) cysts (6 months). At diagnosis, seven (53.8%) of 13 cases with CE1 type cysts without any previous intervention showed negative specific IgG antibody response to E. granulosus recombinant antigen B (rAgB). However, following 3 months to 18 months albendazole therapy, six of these 7 initially seronegative CE1 cases sero-converted to be specific IgG antibody positive, and concurrently ultrasound scan showed that cysts changed to CE3a from CE1 type in all the six CE cases. Two major profiles of serum specific IgG antibody dynamics during albendazole treatment were apparent in CE cases: (i) presenting as initial elevation followed by subsequent decline, or (ii) a persistent decline. Despite a decline, however, specific antibody levels remained positive in most improved or cured CE cases.ConclusionsThis was the first attempt to follow up community-screened cystic echinococcosis patients after albendazole therapy using ultrasonography and serology in an endemic Tibetan region. Cyclic albendazole treatment proved to be effective in the great majority of CE cases in this resource-poor area, but periodic abdominal ultrasound examination was necessary to guide appropriate treatment. Oral albendazole for over 18 months was more likely to result in CE cure. Poor drug compliance resulted in less good outcomes. Serology with recombinant antigen B could provide additional limited information about the effectiveness of albendazole in CE cases. Post-treatment positive specific IgG antibody seroconversion, in initially seronegative, CE1 patients was considered a good indication for positive therapeutic efficacy of albendazole.

Comparative Performances of Flubendazole and Albendazole in Cystic Echinococcosis: Ex Vivo Activity, Plasma/Cyst Disposition, and Efficacy in Infected Mice

The need to identify improved therapy against cystic echinococcosis (CE) has motivated pharmacology-based research. The comparative pharmacological performances of the benzimidazole compounds flubendazole (FLBZ) and albendazole (ABZ) were addressed here. The goals of the work were as follows: (i) to evaluate the ex vivo activities of FLBZ, ABZ, and their respective metabolites against Echinococcus granulosus protoscoleces, (ii) to compare the plasma and cyst disposition kinetics for the two drugs in infected mice, and (iii) to compare the clinical efficacies of FLBZ and ABZ against CE in mice. For the ex vivo study, E. granulosus protoscoleces were incubated with FLBZ, reduced FLBZ (R-FLBZ), ABZ, and ABZ-sulfoxide (ABZSO) (10 nmol/ml). Protoscolex viability was monitored by the methylene blue exclusion test and scanning electron microscopy (SEM). For the pharmacokinetic study, BALB/c mice with CE were allocated to two different groups and orally treated with either FLBZ or ABZ (5 mg/kg of body weight), both formulated as a cyclodextrin-based solution. Blood and cyst samples were taken up to 12 h posttreatment and analyzed by high-performance liquid chromatography (HPLC). For the efficacy study, CE-infected BALB/c mice were divided into three groups: the unmedicated control group and the FLBZ- and ABZ-treated groups. Oral treatments were performed twice a day during 25 days. After treatment, all animals were killed and the weight of the cysts was recorded. Loss of protoscolex viability was observed after drug incubation. FLBZ was detected in plasma (area under the concentration-versus-time curve [AUC] = 1.8 μg · h/ml) and cysts (AUC = 0.3 μg · h/g) collected from treated infected animals. Conversely, ABZSO was the only active molecule measured in plasma (AUC = 4.4 μg·h/ml) and cysts (AUC = 1.5 μg·h/g) after ABZ treatment. FLBZ induced a 90% reduction in cyst weight in comparison to those collected from untreated control mice (P < 0.05). However, no differences in cyst weight were observed between the ABZ-treated (8.2 g) and unmedicated control (10.5 g) groups. Due to these results, we consider flubendazole to have great potential to become a drug of choice in the treatment of cystic echinococcosis.

The Appropriate Indicator Should be Used to Assess Treatment Failure in STH Infections

Dear Sir: We write to comment on the article by Humphries and others1 recently published in the American Journal of Tropical Medicine and Hygiene: in our opinion, the study is well conducted, however, we respectfully disagree with the conclusions and in particular with the claim made by the authors about the failure of albendazole treatment of hookworms. We summarize here the reasons of our disagreement: Humphries and others base the claim for albendazole failure in treating hookworm infection on the analysis of cure rate (CR) results that they measured at 61%; however, in the case of infections caused by hookworm and other soil-transmitted helminths (STHs), the CR is not a good indicator of drug efficacy because it is influenced by the intensity of infection at baseline and by the sensitivity of the parasitological method used to recover eggs from stool.2 As a result, it is very difficult to compare CRs obtained in different settings and reach meaningful conclusions about differences in drug efficacy. Our opinion is that drug efficacy in STH infections should be assessed with a more apt indicator, namely the egg reduction rate (ERR). The data presented by Humphries and others show an ERR of over 80% and this corresponds to the normal range of efficacy of albendazole against this parasite,3 as correctly reported by the authors. We would also like to stress the fact that the main objective of preventive chemotherapy against hookworm and other STH infections (those by Ascaris lumbricoides and Trichuris trichiura) is not to achieve cure of infected individuals, but rather to significantly reduce the number of worms harbored by such individuals4; this is because the average observed reduction (that can be measured by counting the number of eggs passed out in feces) is sufficient to cause the parallel decrease: • of transmission (because of the reduced number of eggs contaminating the environment)5; and • of morbidity (because the few surviving worms—that cannot replicate in the human host—cause less harm to the human host).6 As an additional comment, we would also like to express our concern about the method used by the authors to assess drug quality (i.e., in vitro anthelminthic activity), because this method has never been validated for albendazole that is insoluble in water; in addition, in our experience, the key factors in determining the quality of drugs used against STH are the tablet dissolution and disintegration times, and none of them was tested by the authors. Finally, we strongly disagree with the authors' statement that “mebendazole and pyrantel are not any longer recommended for the treatment of hookworm infection”; again, the studies on which the authors formulate their conclusion are based on the evaluation of the cure rate,7,8 and therefore, for the reasons mentioned previously, not conclusive. As a matter of fact, the World Health Organization (WHO) continues to include mebendazole and pyrantel in the list of recommended drugs for the treatment of STH infections. The WHO is seriously concerned about unjustified claims of drug resistance made on the basis of incorrect interpretations of parasitological results and on the poor understanding of the STH biology and control strategies. These claims create uncertainty among the managers of control programs about the efficacy of the control measures to be implemented and undermine the scaling up of STH control activities. As a consequence, a working group reporting to the WHO Strategic and Technical Advisory Group on Neglected Tropical Diseases (NTD) was established with the aim of developing a Standard Operating Procedure to be implemented whenever a control manager suspects a reduction of the drug activity (report available at http://www.who.int/neglected_diseases/NTD_STAG_Report_2011.pdf). Although we hope that this much needed tool will be available before the end of the year, we take this opportunity to invite AJTMH and other scientific journals to carefully assess the grounds on which claims of drug failure are based should similar papers be submitted for publication.

Perilesional gliosis around solitary cerebral parenchymal cysticerci and long-term seizure outcome: A prospective study using serial magnetization transfer imaging

Epilepsy following solitary cerebral cysticercosis (SCC) is possibly caused by perilesional gliosis, best visualized on magnetization transfer imaging (MTI).This study aims to describe development of gliosis around SCC by prospective serial MTI and to correlate this gliosis with long-term seizure outcome. We randomized 123 patients with SCC and new-onset seizures to treatment with albendazole plus antiepileptics (treatment), or antiepileptics only (control), and performed magnetic resonance imaging (MRI) scans at 0, 3, 6, 12, and 24 months. Prospective follow-up data regarding seizure outcome up to 5 years later were collected. MRI studies were analyzed for lesion characteristics and perilesional magnetization transfer (MT) hyperintensity. Clinical and radiologic data of 77 patients were analyzed. Demographic and seizure characteristics were similar in treatment and control groups. Clinical data were available up to 64 months after enrollment. At 12 months, 89.5% patients were seizure-free. MTI is more sensitive than routine imaging for detection of perilesional gliosis. Albendazole treatment did not affect imaging or clinical outcome, including development of gliosis. Independent of duration of follow-up, gliosis was associated with more seizures, and with seizure recurrence at 12 months; duration of seizures and antiepileptic therapy was longer. Gliosis was not dependent on seizure type or stage of degeneration at enrollment or persistence/calcification of the lesion. Perilesional gliosis around SCC helps prognosticate seizure outcome. Poorer outcome in patients with persistent lesions is likely to be related to mechanisms other than gliosis. The lack of effect of albendazole on seizure outcome may be due to its inability to decrease formation of gliosis.

Efficacy of integrated school based de-worming and prompt malaria treatment on helminths -Plasmodium falciparum co-infections: A 33 months follow up study

BackgroundThe geographical congruency in distribution of helminths and Plasmodium falciparum makes polyparasitism a common phenomenon in Sub Saharan Africa. The devastating effects of helminths-Plasmodium co-infections on primary school health have raised global interest for integrated control. However little is known on the feasibility, timing and efficacy of integrated helminths-Plasmodium control strategies. A study was conducted in Zimbabwe to evaluate the efficacy of repeated combined school based antihelminthic and prompt malaria treatment.MethodsA cohort of primary schoolchildren (5-17 years) received combined Praziquantel, albendazole treatment at baseline, and again during 6, 12 and 33 months follow up surveys and sustained prompt malaria treatment. Sustained prompt malaria treatment was carried out throughout the study period. Children's infection status with helminths, Plasmodium and helminths-Plasmodium co-infections was determined by parasitological examinations at baseline and at each treatment point. The prevalence of S. haematobium, S. mansoni, STH, malaria, helminths-Plasmodium co-infections and helminths infection intensities before and after treatment were analysed.ResultsLongitudinal data showed that two rounds of combined Praziquantel and albendazole treatment for schistosomiasis and STHs at 6 monthly intervals and sustained prompt malaria treatment significantly reduced the overall prevalence of S. haematobium, S. mansoni, hookworms and P. falciparum infection in primary schoolchildren by 73.5%, 70.8%, 67.3% and 58.8% respectively (p < 0.001, p < 0.001, p < 0.001, p < 0.001 respectively). More importantly, the prevalence of STH + schistosomes, P. f + schistosomes, and P. f + STHs + schistosomes co-infections were reduced by 68.0%, 84.2%, and 90.7%, respectively. The absence of anti-helminthic treatment between the 12 mth and 33 mth follow-up surveys resulted in the sharp increase in STHs + schistosomes co-infection from 3.3% at 12 months follow up survey to 10.7%, slightly more than the baseline level (10.3%) while other co-infection combinations remained significantly low. The overall prevalence of heavy S. haematobium, S. mansoni and hookworms infection intensities were significantly reduced from: 17.9-22.4% to 2.6-5.1%, 1.6-3.3% to 0.0% and 0.0-0.7% to 0.0% respectively.ConclusionBiannual Integrated school based antihelminthic and sustained prompt malaria treatment has a potential to reduce the burden of helminths-plasmodium co-infections in primary school children. In areas of stable malaria transmission, active case finding is recommended to track and treat asymptomatic malaria cases as these may sustain transmission in the community.

Hydatid Cyst Disease Mimicking Metastatic Lung Disease: A Case Report

Pulmonary hydatid cysts usually present as a single lesion, whereas multiple cases are rare. It is not easy to distinguish hydatid cyst and nodular lesions radiologically. Chest radiograph of a 22 years-old male patient who was admitted due to right sided chest pain, revealed bilateral pulmonary nodules. His computerized tomography (CT) showed 34 nodular densities in the right lung and 21 nodular densities in the left lung. At that time, metastatic lung disease was suggested . Tru-cut lung biopsy was non-diagnostic. Anti-E. granulosus IgG (ELISA) was positive and hydatid cyst disease (HCD) was set as a prediagnosis. A right thoracotomy was performed and more cysts in number than those in tomography were observed intraoperatively. Postoperatively, 800 mg per day albendazole treatment was started. CT at the second month of medical therapy revealed that the lesions were stable in number but their sizes were smaller. CT of the fourth month showed that some of the lesions became cavitary. HCD should be kept in to mind in case of doubtful radiological findings. Although main treatment modality is surgery for HCD, when all cysts can not remove with the surgical treatment in patient with multiple cysts, medical treatment can be administered.

Epidemiology of Hookworm Infection in Kintampo North Municipality, Ghana: Patterns of Malaria Coinfection, Anemia, and Albendazole Treatment Failure

A cross-sectional pilot study of hookworm infection was carried out among 292 subjects from 62 households in Kintampo North, Ghana. The overall prevalence of hookworm infection was 45%, peaking in those 11-20 years old (58.5%). In children, risk factors for hookworm infection included coinfection with malaria and increased serum immunoglobulin G reactivity to hookworm secretory antigens. Risk factors for infection in adults included poor nutritional status, not using a latrine, not wearing shoes, and occupation (farming). Although albendazole therapy was associated with an overall egg reduction rate of 82%, 37 subjects (39%) remained infected. Among those who failed therapy, treatment was not associated with a significant reduction in egg excretion, and nearly one-third had higher counts on repeat examination. These data confirm a high prevalence of low-intensity hookworm infection in central Ghana and its association with poor nutritional status. The high rate of albendazole failure raises concern about emerging resistance.

Anthelminthic treatment during pregnancy is associated with increased risk of infantile eczema: randomised‐controlled trial results

BackgroundAllergy is commoner in developed than in developing countries. Chronic worm infections show inverse associations with allergy, and prenatal exposures may be critical to allergy risk.ObjectiveTo determine whether anthelminthic treatment during pregnancy increases the risk of allergy in infancy.MethodsA randomised, double-blind, placebo-controlled trial on treatment in pregnancy with albendazole versus placebo and praziquantel versus placebo was conducted in Uganda, with a 2 × 2 factorial design; 2507 women were enrolled; infants’ allergy events were recorded prospectively. The main outcome was doctor-diagnosed infantile eczema.ResultsWorms were detected in 68% of women before treatment. Doctor-diagnosed infantile eczema incidence was 10.4/100 infant years. Maternal albendazole treatment was associated with a significantly increased risk of eczema [Cox HR (95% CI), p: 1.82 (1.26–2.64), 0.002]; this effect was slightly stronger among infants whose mothers had no albendazole-susceptible worms than among infants whose mothers had such worms, although this difference was not statistically significant. Praziquantel showed no effect overall but was associated with increased risk among infants of mothers with Schistosoma mansoni [2.65 (1.16–6.08), interaction p = 0.02]. In a sample of infants, skin prick test reactivity and allergen-specific IgE were both associated with doctor-diagnosed eczema, indicating atopic aetiology. Albendazole was also strongly associated with reported recurrent wheeze [1.58 (1.13–2.22), 0.008]; praziquantel showed no effect.ConclusionsThe detrimental effects of treatment suggest that exposure to maternal worm infections in utero may protect against eczema and wheeze in infancy. The results for albendazole are also consistent with a direct drug effect. Further studies are required to investigate mechanisms of these effects, possible benefits of worms or worm products in primary prevention of allergy, and the possibility that routine deworming during pregnancy may promote allergic disease in the offspring.

Epidemiology of Hookworm Infection in Kintampo North Municipality, Ghana: Patterns of Malaria Coinfection, Anemia, and Albendazole Treatment Failure

Epidemiology of Hookworm Infection in Kintampo North Municipality, Ghana: Patterns of Malaria Coinfection, Anemia, and Albendazole Treatment Failure

Effect of single-dose anthelmintic treatment during pregnancy on an infant's response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial

SummaryBackgroundHelminth infections affect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections affects development of an infant's immune response to immunisations and unrelated infections.MethodsIn this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computer-generated random number sequence in blocks of 100, we assigned patients to 440 mg albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole-matching placebo (n=626), or an albendazole-matching placebo and praziquantel-matching placebo (n=628). All participants and hospital staff were masked to allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus, and measles immunisation; incidence of infectious diseases during infancy; and vertical HIV transmission. Analysis was by intention-to-treat. This trial is registered, number ISRCTN32849447.FindingsData were available at delivery for 2356 women, with 2345 livebirths; 2115 (90%) of liveborn infants remained in follow-up at 1 year of age. Neither albendazole nor praziquantel treatments affected infant response to BCG, tetanus, or measles immunisation. However, in infants of mothers with hookworm infection, albendazole treatment reduced interleukin-5 (geometric mean ratio 0·50, 95% CI 0·30–0·81, interaction p=0·02) and interleukin-13 (0·52, 0·34–0·82, 0·0005) response to tetanus toxoid. The rate per 100 person-years of malaria was 40·9 (95% CI 38·3–43·7), of diarrhoea was 134·1 (129·2–139·2), and of pneumonia was 22·3 (20·4–24·4). We noted no effect on infectious disease incidence for albendazole treatment (malaria [hazard ratio 0·95, 95% CI 0·79–1.14], diarrhoea [1·06, 0·96–1·16], pneumonia [1·11, 0·90–1·38]) or praziquantel treatment (malaria [1·00, 0·84–1·20], diarrhoea [1·07, 0·98–1·18], pneumonia [1·00, 0·80–1·24]). In HIV-exposed infants, 39 (18%) were infected at 6 weeks; vertical transmission was not associated with albendazole (odds ratio 0·70, 95% CI 0·35–1·42) or praziquantel (0·60, 0·29–1·23) treatment.InterpretationThese results do not accord with the recently advocated policy of routine antenatal anthelmintic treatment, and the value of such a policy may need to be reviewed.FundingWellcome Trust.

In Vitro and In Vivo Efficacies of Mefloquine-Based Treatment against Alveolar Echinococcosis

Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis and causes severe disease in the human liver, and occasionally in other organs, that is fatal when treatment is unsuccessful. The present chemotherapy against AE is based on mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some instances, is parasitostatic rather than parasiticidal, and usually involves the lifelong uptake of large doses of drugs. Thus, new treatment options are urgently needed. In this study we investigated the in vitro and in vivo efficacy of mefloquine against E. multilocularis metacestodes. Treatment using mefloquine (20 μM) against in vitro cultures of metacestodes resulted in rapid and complete detachment of large parts of the germinal layer from the inner surface of the laminated layer within a few hours. The in vitro activity of mefloquine was dependent on the dosage. In vitro culture of metacestodes in the presence of 24 μM mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 μM was not. Oral application of mefloquine (25 mg/kg of body weight administered twice a week for a period of 8 weeks) in E. multilocularis-infected mice was ineffective in achieving any reduction of parasite weight, whereas treatment with albendazole (200 mg/kg/day) was highly effective. However, when the same mefloquine dosage was applied intraperitoneally, the reduction in parasite weight was similar to the reduction seen with oral albendazole application. Combined application of both drugs did not increase the treatment efficacy. In conclusion, mefloquine represents an interesting drug candidate for the treatment of AE, and these results should be followed up in appropriate in vivo studies.

Chronic Trichuris trichiura Infection Presenting as Ileocecal Valve Swelling Mimicking Malignancy

A 46-year-old man presented with a history of passing bright red blood per rectum over the last one month. He also had on and off diarrhea with visible mucus in the stool for two months' duration. Further history was unremarkable, and physical examination revealed hemorrhoids which were subsequently banded. A colonoscopy was arranged in view of the prolonged diarrhea whereby an edematous and swollen ileocecal valve was seen. This was shown to be due to Trichuris trichiura infection, confirmed on histopathological examination of biopsies taken from the site. The patient was started on oral albendazole treatment and has been asymptomatic on latest followup. This case illustrates an accidental finding of T. trichuria infection on colonoscopic examination, which was done to investigate the patient's prolonged diarrhea.

Stimulation of pro-inflammatory responses by mebendazole in human monocytic THP-1 cells through an ERK signaling pathway

Oral helminthic mebendazole (MBZ) has been reported to cause liver injury with inflammatory responses. However, the underlying mechanism remains unknown. To examine the inflammatory reactions, we investigated whether MBZ and other helminthic drugs increase the release of pro-inflammatory cytokines and chemokines using human monocytic cells. The release of interleukin (IL)-8 and tumor necrosis factor (TNF) α from human monocytic THP-1 cells was significantly increased by treatment with MBZ, albendazole (ABZ), fenbendazole (FBZ), or oxibendazole (OBZ), but not by albendazole sulfoxide or praziquantel, suggesting that MBZ and structurally similar drugs can stimulate monocytes and increase the release of pro-inflammatory cytokines. MBZ also significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2 in THP-1 cells. Pretreatment with the MAP kinase/ERK kinase 1/2 inhibitor U0126 significantly suppressed the increase of IL-8 and TNFα levels by MBZ, ABZ, FBZ, or OBZ treatment in THP-1 cells, but the p38 mitogen-activated protein kinase inhibitor SB203580 or JNK1/2 inhibitor SP600125 did not. These results suggested that an ERK1/2 pathway plays an important role in the release of IL-8 and TNFα in THP-1 cells treated with MBZ and structurally similar drugs. In conclusion, the release of inflammatory mediators by MBZ might be one of the mechanisms underlying immune-mediated liver injury. This in vitro method may be useful to predict adverse inflammatory reactions that lead to hepatotoxicity.

Programme for ultrasound diagnoses and treatment with albendazole of cystic echinococcosis in asymptomatic carriers: 10 years of follow-up of cases

Cystic echinococcosis is an endemic disease in the Province of Rio Negro, Argentina. Ultrasound surveys carried out in 1984 found prevalence rates of 5.6% in children between 6 and 14 years of age. Objective To describe and to evaluate the results of the strategy applied in school children by hospital services of the Province of Rio Negro with regard to diagnosis, treatment and monitoring of cystic echinococcosis and to evaluate simultaneously the results of the control program against cystic echinococcosis. Materials and methods In 1997 ultrasound was chosen to carry out population surveys and the medical treatment criteria for the detected cases were standardized. The population under study involved 5745 students in the first survey and 22,793 in subsequent studies. The detected cases were classified according to Gharbi's scheme. A treatment algorithm was defined based only on monitoring (“watch and wait”), albendazole, surgery (open or laparoscopic) or mini-invasive procedures, according to type, location and size of the cyst. Information was also obtained on cases notified to the Health System between 1980 and 2008. Results In the first survey, 70 carriers (1.2%) were detected; of these, 25 started albendazole treatment (35.7%) and only 3 (4.3%) underwent surgery. Ten years after treatment, 60.1% of 42 cases, presented Types IV and V cysts and 14.5% presented total involution of their cysts. In subsequent studies, 87 (0.4%) cases were detected, 49 of which started albendazole treatment (56.3%) and 9 underwent surgery (10.3%). The incidence rate of cystic echinococcosis cases decreased from 38 × 100,000 in 1980 to 3.7 × 100,000 in 2008. Discussion A strong decrease in cystic echinococcosis was obtained although persistent levels of transmission were maintained. The cases produced under these conditions are diagnosed by means of ultrasound surveys and are treated using a plan based on albendazole and monitoring by the Health System during a period of 10 years.