Efficacy and safety of single-dose artesunate plus sulfalene/pyrimethamine combined with praziquantel for the treatment of children with Schistosoma mansoni or Schistosoma haematobium in western Kenya: a randomised, open-label controlled trial.

BACKGROUND: Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis. METHODS: This was an open-label, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment. RESULTS: Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported. CONCLUSIONS: A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.

Re-assessment of schistosomiasis in nine endemic districts with cluster sampling in Sierra Leone.

Background: Baseline mapping showed that schistosomiasis was highly/moderately endemic in nine districts in Sierra Leone. Mass drug administration (MDA) with praziquantel started in 2009, and after multiple rounds of treatment, an impact assessment was conducted in 2016 followed by a second re-assessment in 2022 using cluster sampling to provide more granular data for refining chiefdom (sub-district) treatment strategies. Methods: On average, 20 rural villages were systematically selected per district by probability proportional to population size across the nine districts. Surveys were conducted in schools, and 24 school children aged between 5 and 14 years were randomly selected, with an equal number of boys and girls. One stool sample and one urine sample were collected per child. Two Kato-Katz slides were examined per stool for Schistosoma mansoni infection. Hemastix strips were used as a proxy for S. haematobium infection with urine filtration used for egg counts on hematuria-positive samples. Results: In total, 4,736 stool samples and 4,618 urine samples were examined across 200 schools in 125 chiefdoms. Overall, the prevalence of S. mansoni was 16.3% (95% CI: 15.3-17.4%), while the overall prevalence of S. haematobium was 2.0% (95% CI: 1.6-2.4%) by hematuria. The prevalence of heavy infections for S. mansoni and S. haematobium was 1.5% (95% CI: 1.1-1.9%) and 0.02% (95% CI: 0.0-0.14%), respectively. Among 125 chiefdoms surveyed, the overall schistosomiasis prevalence was <10% in 65 chiefdoms, 10-49.9% in 47 chiefdoms, and ≥ 50% in 13 chiefdoms. There was a mixed relationship between schistosomiasis in school children and WASH access in schools. Conclusion: Sierra Leone has made significant progress in reducing schistosomiasis prevalence across the country after a decade of MDA intervention. However, high prevalence remains in some hotspot chiefdoms. The next steps are for the national program to investigate and address any potential issues such as low coverage or poor knowledge of schistosomiasis risk behaviors and, where appropriate, consider broadening to community-wide treatment in hotspot chiefdoms or communities.

Meta-analysis and public policy: Reconciling the evidence on deworming.

The WHO recommends mass drug administration (MDA) for intestinal worm infections in areas with over 20% infection prevalence. Recent Cochrane meta-analyses endorse treatment of infected individuals but recommend against MDA. We conducted a theory-agnostic random-effects meta-analysis of the effect of multiple-dose MDA and a cost-effectiveness analysis. We estimate significant effects of MDA on child weight (0.15 kg, 95% CI: 0.07, 0.24; P < 0.001), mid-upper arm circumference (0.20 cm, 95% CI: 0.03, 0.37; P = 0.02), and height (0.09 cm, 95% CI: 0.01, 0.16; P = 0.02) when prevalence is over 20% but not on Hb (0.06 g/dL, 95% CI: -0.01, 0.14; P = 0.1). These results suggest that MDA is a cost-effective intervention, particularly in the settings where it is recommended by the WHO.

An in vivo appraisal of Punica granatum peel extract's ultrastructural effect on cystic echinococcosis in mice.

In the past decade, interest has significantly increased regarding the medicinal and nutritional benefits of pomegranate (Punica granatum) peel. This study examined the effects of using pomegranate peel extract (PGE) alone and in combination with albendazole (ABZ) on ultrastructural and immunological changes in cystic echinococcosis in laboratory-infected mice. Results revealed that the smallest hydatid cyst size and weight (0.48 ± 0.47mm, 0.17 ± 0.18 gm) with the highest drug efficacy (56.2%) was detected in the PGE + ABZ group, which also exhibited marked histopathological improvement. Ultrastructural changes recorded by transmission electron microscopy including fragmentation of the nucleus, glycogen depletion, and multiple lysosomes in vacuolated cytoplasm were more often observed in PGE + ABZ group. IFN-γ levels were significantly increased in the group treated with ABZ, with a notable reduction following PGE treatment, whether administered alone or in combination with ABZ. Thus, PGE enhanced the therapeutic efficiency of ABZ, with improvement in histopathological and ultrastructural changes.

A single subcutaneous dose of eprinomectin (Eprecis®) is effective against common gastrointestinal nematodes and lungworms in experimentally infected lactating goats.

BACKGROUND: The health and productivity of dairy goats continue to be impacted by gastrointestinal nematodes (GIN) and lungworms (LW). Eprinomectin (EPN) is frequently selected for treatment because it is generally effective and does not require a milk withdrawal period. However, some factors, such as lactation, can have an impact on EPN pharmacokinetics and potentially its efficacy. To evaluate whether this can alter the efficacy of Eprecis® 2%, an eprinomectin injectable solution, a study was performed in lactating goats using the dose currently registered in cattle, sheep and goats (0.2 mg/kg). METHODS: This study was a blinded, randomized, controlled trial performed according to the VICH guidelines. Eighteen (18) worm-free lactating goats were included and experimentally challenged on day 28 with a mixed culture of infective gastrointestinal and lung nematode larvae (Haemonchus contortus, Trichostrongylus colubriformis, Teladorsagia circumcincta, Dictyocaulus filaria). At D-1, fecal samples were collected to confirm patent infection in all animals. On D0, the goats were randomly allocated into two groups of nine goats; group 1 was treated with Eprecis® 2% at 0.2 mg/kg BW by subcutaneous injection, while group 2 remained untreated. Fecal samples for egg counts were collected from all animals on days 3, 5, 7, 9, 11 and 14. On D14, all goats were killed, and the abomasum, small intestine and lungs were removed, processed and subsampled to record the number and species of worms. RESULTS: The treatment was well tolerated. After treatment, the arithmetic mean FEC decreased in the treated group and remained < 5 EPG until the end of the study, while the arithmetic mean FEC in the control group remained > 849.0 EPG. At D14, goats in the treated group had very limited or zero total worm counts, whereas all animals from the control group had a high worm burden. The measured efficacy was 100.0% against H. contortus and T. colubriformis, 99.9% against T. circumcincta and 98.0% against D. filaria. CONCLUSIONS: Eprinomectin (Eprecis®, 20 mg/ml), administered at the label dose (0.2 mg/kg), is highly effective against gastrointestinal nematodes and lungworms in lactating goats.

Praziquantel-related visual disorders among recipients in mass drug administration campaigns in schistosomiasis endemic settings: Systematic review and meta-analysis protocol.

BACKGROUND: Hundreds of millions of doses of Praziquantel (PZQ) have been administered to persons with and without schistosomiasis living in schistosomiasis endemic settings, through the mass drug administration (MDA) strategy which started in the early 2000s. A recent publication suggested high risk of PZQ-related visual disorders, raising public health concerns. We aim to systematically synthesize evidence on the magnitude of PZQ-related visual disorders. METHODS: We will search PubMed, Google Scholar, CINAHL, SCOPUS, CENTRAL and LILACS from 1977 (when the first human clinical trials on PZQ started) to 31st May 2024, with no language restrictions. The key search terms will include "Praziquantel", "PZQ", "visual disorder", "adverse events", "side effects", "blurry vision" and "visual impairment" together with alternative terms and synonyms. All the countries endemic for schistosomiasis will be included as search terms. We will also search HINARI, Africa Journals Online, Thesis Databases and Preprint Repositories. Where necessary, we will contact expert researchers working in the field of schistosomiasis, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), pharmaceutical industries, country-specific Food and Drug Authorities (FDAs) and the European Medicines Agency databases. We will search Conference Proceedings and reference lists of relevant studies for additional studies. At least two authors will independently select studies, extract data and assess risk of bias in the included studies. Any disagreements or discrepancies will be resolved through discussion between the reviewers. Heterogeneity will be explored graphically, and statistically using the I2-statistic. We will conduct random-effects meta-analysis when heterogeneity is appreciable, and express dichotomous outcomes (visual adverse events including excessive lacrimation, blurry vision and visual impairments) as risk ratio (RR) or Odds Ratio (OR) with their 95% confidence interval (CI). We will perform subgroup analysis to assess the impact of heterogeneity, and sensitivity analyses to test the robustness of the effect estimates. The overall level of evidence will be assessed using GRADE. EXPECTED OUTCOMES: The present review expects to identify and categorize visual disorders occurring after administration of PZQ, alone or in combination with other drugs. By synthesizing the data from multiple studies, the review aims to present a quantitative assessment of the risk or odds of experiencing a visual disorder in different populations after ingesting PZQ. The review will also generate insights into whether PZQ in combination with other drugs are associated with increased odds of visual disorders and whether the occurrence of visual disorders correlates with dosage or treatment duration. Policymakers, public health experts and stakeholders could rely on the review findings to deliver context-sensitive preventive chemotherapy programs by adjusting drug combinations or dosing schedules to reduce risk of visual adverse effects in populations treated with PZQ. The review aims to identify gaps in the current evidence regarding visual disorders following PZQ administration in schistosomiasis endemic settings which can serve as the basis for future research on important but unanswered questions. DISSEMINATION AND PROTOCOL REGISTRATION: The findings of this study will be disseminated through stakeholder forums, conferences, and peer-review publications. The review protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO)- CRD42023417963.

Preparation and evaluation of fenbendazole methyl-ß-cyclodextrin inclusion complexes.

As an orally effective benzimidazole anthelmintic agent, fenbendazole was not only widely used in agriculture and animal husbandry to prevent and treat parasites, but also shows anti-cancer effects against several types of cancer, exhibits anti-cancer effects in paclitaxel and doxorubicin-resistant cancer cells. However, fenbendazole's poor in water solubility (0.3 µg/mL), limits its clinical applications. Even great efforts were made toward increasing its water solubility, the results were not significant to reach anti-cancer drug delivery requirement (5-10 mg/mL). Through single factor and orthogonal strategy, many complex conditions were designed and used to prepare the complexes, the inclusion complex with methyl-ß-cyclodextrin with 29.2 % of inclusion rate and 89.5% of inclusion yield can increase drug's water solubility to 20.21 mg/mL, which is the best result so far. Its structure was confirmed by differential scanning calorimetry, scanning electron microscopic image, 1D and 2D NMR spectra in D2O. In its in vitro pharmacokinetic study, fenbendazole was 75% released in 15 min., in its in vivo pharmacokinetic study, the bio-availabilities of fenbendazole, its major metabolic anthelmintic agent oxfendazole and its minor metabolic anthelmintic agent oxfendazole were increased to 138%, 149% and 169% respectively, which would allow for fewer drug doses to achieve the same therapeutic effect and suggest that the complex can be used as a potential anticancer agent.

Health workers' perspectives on school-based mass drug administration control programs for soil-transmitted helminthiasis and schistosomiasis in Ogun State, Nigeria.

BACKGROUND: Soil-transmitted helminthiasis (STH) and schistosomiasis (SCH) are among the most prevalent neglected tropical diseases (NTDs), affecting 1.5 billion globally, with a significant burden in sub-Saharan Africa, particularly Nigeria. These diseases impair health and contribute to socio-economic challenges, especially in children, undermining educational and future economic prospects. The 2030 NTD Roadmap highlights Mass Drug Administration (MDA) as a critical strategy for controlling these NTDs, targeting vulnerable populations like school-age children. Despite some successes, challenges persist, indicating the need for deeper insights into program implementation. This study focuses on the perspectives of health workers implementing MDA in selected local government areas (LGAs) of Ogun State, Nigeria, aiming to identify challenges and enablers that align with the broader NTD 2030 goals. METHODOLOGY/PRINCIPAL FINDINGS: The study used a qualitative research approach involving focus group discussions and in-depth interviews with health workers engaged in neglected tropical disease control programs in Ogun State, Nigeria, between July and September 2022. A semi-structured questionnaire guided the exploration of ideas, and the data were analyzed using the QRS Nvivo 12 software package. The study found that the school-based MDA control program's efficacy largely relies on strong collaborations and partnerships, particularly with educators, community heads, and other stakeholders. These alliances and strategic communication methods, like town announcements and media campaigns, have been pivotal in reaching communities. However, the program does grapple with hurdles such as parental misconceptions, limited funds, insufficient staffing, and misalignment with the Ministry of Education. It is recommended to boost funding, foster early stakeholder involvement, enhance mobilization techniques, and consider introducing a monitoring card system similar to immunization. CONCLUSIONS/SIGNIFICANCE: The MDA Integrated Control Programs for STH and SCH in Ogun State schools demonstrate a holistic approach, integrating knowledge, collaboration, communication, and feedback. Health workers have shown commitment and adeptness in their roles. However, achieving maximum efficacy requires addressing critical barriers, such as parental misconceptions and funding challenges. Adopting the recommended strategies, including proactive communication, increased remuneration, and introducing a tracking system, can significantly enhance the program's reach and impact. The involvement of all stakeholders, from health workers to community leaders and parents, is essential for the program's sustainability and success.

Efficacy of praziquantel drug against Schistosoma haematobium and performance of urine reagent strips among pre-and-school aged children during the high transmission season in North-Western Tanzania.

The World Health Organization calls for schistosomiasis endemic countries to regularly monitor the efficacy of Praziquantel (PZQ) drug, the only antischistosomal drug used for four decades in Tanzania. In response to that call, the current study investigated the efficacy of single dose of PZQ against Schistosoma haematobium during the high transmission season and further assessed, the sensitivity and specificity of urine reagent strips before and after treatment. The study recruited a total of 2,498 -children aged (4 -17 years old) who provided a single urine sample that was visually examined for macro-haematuria, then using urine dipstick and urine filtration technique for microhaematuria and the presence of S. haematobium eggs. The baseline prevalence of S. haematobium eggs positive based on urine filtration test was 29.2 % (95 %CI:27.5-31.0) and that of microhaematuria was 43.1 % (95 %CI:41.1-45.0). Of the infected participants, 40.9 % (95 %CI:37.4-44.6) had a heavy intensity of infection and the geometrical mean intensity (GMI) of infection was 33.7 eggs/10mls of urine. A single dose of PZQ reduced the prevalence of infection to 16.2 %, the GMI of infection to 18.8eggs/10mls of urine and that of microhaematuria to 27.9 %. Cure rate and egg reduction rates (ERR) were 83.8 % and 44.3 % respectively. At baseline, the sensitivity and specificity of the urine reagent strips were 59.7 % and 93.8 %, whereas at post-treatment they were 16.7 % and 93.6 %. When PZQ drug is administered during the high transmission season, its efficacy in term of ERR is poor. The urine reagent strips had low sensitivity but high specificity at pre-and-post PZQ treatment.

Comparison between a complete preconditioning programme and conventional conduct on behaviour, health and performance of young bulls from small cow-calf herds.

Bovine respiratory diseases (BRDs) have major socioeconomic impacts in the beef sector. Antimicrobials have been traditionally used to prevent the development of BRDs upon arrival in fattening units. Currently, from a "One Health and One Welfare" perspective, alternative solutions are being investigated. Preconditioning programmes that aim at reducing stress and reinforcing immune functions have been proposed to decrease BRDs incidence. In this study, we assessed the effect of a preconditioning protocol set up in nine commercial beef herds on young bulls' behaviour, health, and performance. Preconditioned bulls (PREC) were weaned indoors 50 days before departure, and progressively fed a concentrate diet supplemented with vitamins and trace elements. They also received an anthelmintic treatment, and two doses of a trivalent vaccine against respiratory pathogens at 4-week intervals. In contrast, controls (CTRL) were kept on pasture with their dams with no vaccination or particular diets. All calves were transported together to a single sorting facility to be sorted by experimental groups, origins, and BW, forming new groups before dispatch to four fattening units. At arrival, CTRL were treated with anthelmintic drugs and received one injection of the same BRDs vaccine. No intervention was performed on PREC bulls. BRD-scores were 0.73 in PREC versus 0.07 in CTRL (P = 0.01) during the preconditioning period and 0.96 in PREC versus 0.54 in CTRL (P = 0.41) after 15 days in the fattening units. Morbidity estimates were 18% in PREC versus 1% in CTRL (P < 0.001) during the preconditioning period and 32% in PREC versus 19% (P = 0.07) in CTRL after 15 days in the fattening units. Poor housing conditions during preconditioning and a different aetiology could partly explain these results. At arrival to fattening, the average daily gain (ADG) was 1 605 g for PREC versus 1 140 g (P = 0.012) for CTRL. After fattening for 180 days, differences in BW, ADG, carcass weight and conformation were inconclusive. In Europe, preconditioning programmes including vaccination must be set up coherently with good husbandry practices and with a global adaptation of batch management of the beef sector otherwise, they may be less effective than expected.

Pattern and predictor of hookworm re-infection among schoolchildren in three districts of Amhara Region, northwest Ethiopia.

BACKGROUND: Despite integrated prevention and control measures, the prevalence of hookworm is still high in Ethiopia. The re-infection rates and predictors are poorly addressed. Therefore, this study aimed to determine the patterns of hookworm re-infection rates and predictors among schoolchildren in northwest Ethiopia. METHODS: A prospective follow-up study was conducted among 86 schoolchildren from May to December 2022. Data on predictors was collected using a questionnaire. Stool samples were collected and processed via Kato-Katz, McMaster, and spontaneous tube sedimentation techniques. All hookworm-infected children were treated with albendazole and followed for six months. The re-infection rates of hookworm were checked in the 4th and 6th months. Data was entered into Epi-data version 3.1 and analysed using SPSS version 25. Descriptive statistics were used to compute the re-infection rate. The associations of predictors with hookworm re-infection rates were calculated by logistic regression. Variables with a p-value < 0.05 were considered statistically significant. RESULTS: Of the 86, 81 schoolchildren completed the study. The prevalence of hookworm re-infection in the 4th and 6th months was 23.5% and 33.3%, respectively. Living with family members greater than five (p = .017), poor utilization of latrine (p = .008), infrequent shoe wear (p = .039), and participating in irrigation (p = .020) were the predictors significantly associated with hookworm re-infections. CONCLUSIONS: The re-infection rate was high during the fourth and sixth months. Participating in irrigation, infrequent shoe wear, and poor latrine utilization were predictors of hookworm re-infection. Therefore, mass drug administration, regular shoe wearing, and health education should be advocated.

How Does Treatment Coverage and Proportion Never Treated Influence the Success of Schistosoma mansoni Elimination as a Public Health Problem by 2030?

BACKGROUND: The 2030 target for schistosomiasis is elimination as a public health problem (EPHP), achieved when the prevalence of heavy-intensity infection among school-aged children (SAC) reduces to <1%. To achieve this, the new World Health Organization guidelines recommend a broader target of population to include pre-SAC and adults. However, the probability of achieving EPHP should be expected to depend on patterns in repeated uptake of mass drug administration by individuals. METHODS: We employed 2 individual-based stochastic models to evaluate the impact of school-based and community-wide treatment and calculated the number of rounds required to achieve EPHP for Schistosoma mansoni by considering various levels of the population never treated (NT). We also considered 2 age-intensity profiles, corresponding to a low and high burden of infection in adults. RESULTS: The number of rounds needed to achieve this target depends on the baseline prevalence and the coverage used. For low- and moderate-transmission areas, EPHP can be achieved within 7 years if NT ≤10% and NT <5%, respectively. In high-transmission areas, community-wide treatment with NT <1% is required to achieve EPHP. CONCLUSIONS: The higher the intensity of transmission, and the lower the treatment coverage, the lower the acceptable value of NT becomes. Using more efficacious treatment regimens would permit NT values to be marginally higher. A balance between target treatment coverage and NT values may be an adequate treatment strategy depending on the epidemiological setting, but striving to increase coverage and/or minimize NT can shorten program duration.

Endemic status of urogenital schistosomiasis and the efficacy of a single-dose praziquantel treatment in unmapped rural farming communities in Oyo East Local Government Area, Oyo State, Nigeria.

BACKGROUND: Schistosomiasis is endemic in Nigeria, and the treatment is largely concentrated on children enrolled in schools. Consequently, the coverage of non-enrolled school-aged children is often neglected. Ajagba and Awosan are two communities in Nigeria that have never had any control intervention. Hence, this survey was designed to determine the endemicity of urogenital schistosomiasis and to evaluate the efficacy of a single-dose praziquantel in the communities. METHODS: Urine sample (10 mL) of each participant from Ajagba and Awosan communities was filtered through 12µm polycarbonate filter. The filter was placed on a microscope slide, and stained with a drop of 1% Lugol iodine solution. The stained slides were examined under the microscope and the numbers of S. haematobium eggs were counted. Water contact sites were searched for snail hosts and the snails collected were shed for Schistosoma cercariae. Data were analyzed using SPSS version 24.0 and the significance level was set at 95%. RESULTS: The overall prevalence of infection in the Ajagba community was 45.6% with a mean intensity of 61.1 ± 144.5 eggs/10 mL of urine, while the prevalence of infection in the Awosan community was 5.7% with a mean intensity of 1.4 ± 6.8 eggs/10 mL of urine. The school-aged children had a prevalence and mean intensity of infection of 73.1% and 111.6 ± 177.9 eggs/10 mL of urine, respectively. Following treatment, women had a higher egg reduction rate than men (p = 0.0283). Bulinus globosus were found in Ajagba but not in Awosan, with 5.7% shedding Schistosoma spp, cercariae. CONCLUSION: Urogenital schistosomiasis was hyperendemic in the Ajagba community, and hypoendemic in the Awosan community. The presence of Bulinus globosus supported the transmission of the schistosomiasis in the Ajagba community. Communities where schistosomiasis is still actively transmitted in Nigeria should be identified for effective intervention through the MDA programs.

Efficacy of Bravecto® Plus spot-on solution for cats (280 mg/ml fluralaner and 14 mg/ml moxidectin) in the prevention of feline Aelurostrongylus abstrusus infection evaluated in a multi-diagnostic approach.

BACKGROUND: Aelurostrongylus abstrusus is one of the most important respiratory nematodes of felines. Infections may lead to respiratory clinical signs with varying severity or even death, emphasizing the need for preventive treatment of cats with outdoor access to circumvent patent infections. METHODS: Therefore, the preventive efficacy of a spot-on formulation of 280 mg/ml fluralaner and 14 mg/ml moxidectin (Bravecto® Plus spot-on solution for cats, MSD) against A. abstrusus was evaluated in a negative controlled, randomized and partially blinded efficacy study with 28 purpose-bred cats in a non-terminal design. In three different treatment regimes, the minimum recommended dose of 40 mg fluralaner and 2.0 mg moxidectin/kg bodyweight (BW) was administered once at 12, 8 or 4 weeks (study group G1, G2 and G3, respectively) prior to experimental infection with 300 third-stage A. abstrusus larvae, while G4 served as placebo-treated control. RESULTS: From 30 to 46 days post infection (dpi; SD 114 to 130), faeces were sampled to monitor first-stage larvae (L1) excretion for efficacy determination. Secondary efficacy criteria, including respiratory parameters, serological antibody levels and computed tomography (CT) findings, were assessed once before enrolment (SD -7 to -1) and before infection (SD 75 to 83). After infection, CT evaluation was performed once at 47-50 dpi (SD 131 to 134), and respiratory parameters and antibody levels were regularly assessed twice or once a week, respectively (1 up to 78 dpi, SD 85 up to 162). All animals in the control group excreted L1 by 33-37 dpi and remained positive throughout the study period from 41 to 46 dpi (SD 125 to 130). In the treatment groups, only one animal each of G1 and G2 excreted L1 at two consecutive days, and four cats of G1, two of G2 and three of G3 were positive on single occasions. While the geometric mean (GM) of the maximum number of excreted L1 per 5 g of faeces was 7380.89 in the control group (G4), GMs were significantly lower in the treatment groups with 1.63 in G1, 1.37 in G2 and 0.79 in G3. Thus, based on GMs, the reduction in excreted L1 exceeded 99.9% in all three treatment groups. Based on CT severity scores, all lungs of the animals of the control group showed severe pulmonary changes post infection, whereas lungs of the cats of the treatment groups were either unaltered (4 animals), mildly (11 animals), or moderately altered (5 animals). Moreover, seroconversion was observed in all cats of the control group, but not in those of the treatment groups. CONCLUSIONS: The combination of diagnostic methods used in this non-terminal study yielded coherent and reliable results. A single administration of Bravecto® Plus spot-on solution for cats was well tolerated and effective in the prevention of aelurostrongylosis for at least 12 weeks.

Oxfendazole Nitazoxanide combination in experimental neurocysticercosis - Anti-inflammatory and cysticidal effects.

Neurocysticercosis (NCC) is a parasitic infection caused by the larval stage of the pork tapeworm, Taenia solium. The complications of NCC include seizures, headaches, cognitive impairment, and focal neurological deficits. In addition to antiparasitic drugs and surgery, the management of NCC includes the use of corticosteroids to reduce inflammation and control symptoms. The traditional treatment with albendazole and praziquantel has not been altered over 30 years and present several side effects. There are other anti-helminthic drugs such as oxfendazole and nitazoxanide that may show efficacy in NCC treatment. The aim of this study was to determine the histopathologic aspects of experimental NCC after in vivo treatment with the combination of oxfendazole and nitazoxanide. Balb/c mice were infected with T. crassiceps cysticerci and divided into groups of 10 animals each that received a single dose through gavage as follows: group treated with NaCl 0.9% (control group); group treated by monotherapy of the anti-helminthic drugs, 30 mg/kg in single dose of oxfendazole (OXF) or nitazoxanide (NTZ); and groups treated with the combination of the drugs (OXF/NTZ group). Macroscopic and microscopic analysis were performed. There was greater presence of final stage cysticerci after treatment. The microscopic analysis of the general pathological processes showed that the monotherapy with all treatment groups induced higher perivasculitis than what was observed in the control group. In contrast, the combination treatment showed a lower observation of PMN and MN inflammatory infiltration in comparison to the other treatments and to the control one. These results show that indeed the association of benzimidazole derivatives which present both anti-helminthic and anti-inflammatory properties with other cysticidal drugs are beneficial for the NCC treatment in which the aim is to destroy parasite without inducing inflammatory damage in the brain tissue.

A randomized assessors-blind clinical trial to evaluate the safety and the efficacy of albendazole alone and in combination with mebendazole or pyrantel for the treatment of Trichuris trichiura infection in school-aged children in Lambaréné and surroundings.

Helminthiasis remains a public health issue in endemic areas. Various drugs have been proposed to improve efficacy against helminths. The study aimed to assess the safety and efficacy of three different anthelmintic combinations to treat Trichuris trichiura infections. We conducted a randomized assessors-blind clinical trial involving children aged 2-17 years with T. trichiura. Participants were randomly assigned to one of three treatment arms. On the first and third days, all participants got albendazole 400 mg, and on the second day, albendazole (arm A), mebendazole 500 mg (arm B), or pyrantel 125 mg/kg (arm C). We assessed treatment efficacy using the cure rate (CR) and egg reduction rate (ERR) at 3 and 6 weeks post-treatment. At 3 weeks post-treatment, ERR and CR were highest in study arm A [ERR = 94%, 95% confidence interval (CI): 92-95; CR = 71%; 95% CI: 58-81] compared to the B and C arms. Decrease in ERR was significant only for arm B versus arm A (P-value <0.001); decrease in ERR was significant for arms B and C (P-value <0.001). No statistical difference was observed in CR when comparing arms A and B (P-value =1.00) and C (P-value =0.27). At 6 weeks, a decrease in ERR was observed in three arms, significant only for arm C, 81% (95% CI: 78-83). A significant increase in egg counts was observed between 3 and 6 weeks post-treatment. All treatments were safe with mild adverse events. Albendazole 400 mg/day (arm A) showed the highest efficacy against trichuriasis. Nonetheless, this treatment regimen was able to cure half of the treated individuals highlighting concerns about controlling the transmission of T. trichiura.CLINICAL TRIALRegistered at ClinicalTrials.gov (NCT04326868).

Appraisal of Chitosan-Coated Lipid Nano-Combination with Miltefosine and Albendazole in the Treatment of Murine Trichinellosis: Experimental Study with Evaluation of Immunological and Immunohistochemical Parameters.

PURPOSE: Resistance and adverse consequences of albendazole (ABZ) in treating trichinellosis urged demand for secure and effective new drugs. The current study aimed to assess the effect of chitosan-coated lipid nano-combination with albendazole and miltefosine (MFS) in treating experimental murine trichinellosis and evaluating pathological and immunological changes of trichinellosis. MATERIALS AND METHODS: One hundred twenty Swiss albino mice were divided into six groups. Each group was subdivided into a and b subgroups based on the scarification time, which was 7- and 40-days post-infection (PI), respectively. The treatment efficacy was evaluated using parasitological, histopathological, serological (interleukin (IL)-12 and IL-4 serum levels), immunohistochemical (GATA3, glutathione peroxidase1 (GPX1) and caspase-3), and scanning electron microscopy (SEM) methods. RESULTS: The most effective drug was nanostructured lipid carriers (NLCs) loaded with ABZ (G5), which showed the most significant reduction in adults and larval count (100% and 92.39%, respectively). The greatest amelioration in histopathological changes was reported in G4 treated with MFS. GATA3 and caspase-3 were significantly reduced in all treated groups. GPX1 was significantly increased in G6 treated with MFS + NLCs. The highest degenerative effects on adults and larvae by SEM were documented in G6. CONCLUSION: Loading ABZ or MFS on chitosan-coated NLCs enhanced their efficacy against trichinellosis. Although ABZ was better than MFS, their combination should be considered as MFS caused a significant reduction in the intensity of infection. Furthermore, MFS showed anti-inflammatory (↓GATA3) and antiapoptotic effects (↓caspase-3), especially in the muscular phase. Also, when loaded with NLCS, it showed an antioxidant effect (↑GPX1).

Relapse of toxocariasis after completion of four-week treatment with albendazole.

Food-borne toxocariasis caused by the consumption of raw meat or liver has occasionally been reported from East Asia. We treated a 38-year-old Japanese man who was infected with Toxocara in China and underwent a four-week treatment with albendazole. The liver and lung lesions disappeared after the treatment, suggesting that the treatment was successful. One month after the end of the treatment, the patient relapsed, and albendazole was administered again for eight weeks. The patient has remained relapse-free for one year. Although toxocariasis can heal spontaneously, in some cases, such as the present case, the disease relapses even after long-term treatment. In conclusion, different durations of treatment are recommended by various guidelines, and the duration of treatment needs to be modified with each case, considering the response to the treatment.

Efficacy of afoxolaner or the combination of afoxolaner with milbemycin oxime against Otodectes cynotis in naturally infested dogs.

Otodectes cynotis, commonly known as "the ear mite," is a highly contagious ectoparasite and a significant cause of otitis externa in canines. The objective of the current study was to determine the efficacy of the isoxazoline afoxolaner (Nexgard®), and the combination of afoxolaner with milbemycin oxime (Nexgard Spectra®), in dogs naturally infested with O. cynotis. In total, 32 infested client-owned dogs from two different sites in Greece were included. The animals were randomly divided into four equal groups based on their infestation score. Group 1 served as the negative control, group 2 received one oral administration of Nexgard (Day 0), group 3 received two monthly oral administrations of Nexgard (Days 0, 30), and group 4 received two monthly oral administrations of Nexgard Spectra (Days 0, 30), according to label instructions. Otoscopic examinations for mites and observations on debris/cerumen in the ears were carried out on Days 0, 15, 30, and 45. A quantitative assessment of ear mites by ear duct flushing and live mite counts was performed on Day 45. The results demonstrated that a single oral dose of afoxolaner and two monthly doses of afoxolaner or afoxolaner with milbemycin oxime resulted in a 99.9% reduction in live mite counts compared to the untreated control group by Day 45. Additionally, treated dogs showed improved clinical symptoms, such as ear cerumen/debris decrease, while untreated dogs experienced worsening symptoms over the study duration. No adverse events were reported. Overall, these results support the use of afoxolaner-based products to treat O. cynotis infestation in dogs.

Comparative growth performance of backgrounded beef heifers treated with an injectable fixed-dose combination (0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride) or single-active (0.2 mg/kg ivermectin) endectocide.

Gastrointestinal nematodes (GINs) can negatively impact all production classes of cattle, particularly growing cattle. A global decline in efficacy of broad-spectrum single-active anthelmintics requires alternative GIN control methods without the aid of novel drug classes. Here, we present a new fixed-dose combination injectable (FDCI) endectocide for cattle that combines doramectin (5 mg/ml) and levamisole hydrochloride (150 mg/ml). A 56-day comparative performance confinement backgrounding trial was conducted in stocker beef heifers (n = 1548) with confirmed GIN infections to (1) compare the Day 14 post-treatment effectiveness of the new FDCI endectocide to pen mates treated with the injectable single-active endectocide ivermectin, as evidenced by fecal egg counts (FECs) conducted for a randomly selected subset (10%) of both treatment groups, and (2) determine if the greater GIN control by the FDCI evidenced in the subsample improved growth performance in all FDCI-treated heifers. Heifers were procured in four cohorts, with a 10-week timeframe between enrollment of the first and last cohort. Treatment groups were comingled within dirt-floor pens (n = 31; 7-8 per cohort) and offered a standard backgrounding diet ad libitum for the study duration. Heifers with enrollment FEC ≥ 30 eggs per gram (EPG) were randomly allocated to receive the FDCI (n = 773) or ivermectin (n = 775) on Day 0. Day 0 FECs conducted on 10% of enrolled heifers (FDCI, n = 78; ivermectin, n = 79) were not different between treatment groups (p = 0.491). Day 14 FECs for the same heifers were reduced compared to Day 0 within each treatment group. Heifers given the FDCI had lower Day 14 AM FECs and higher FEC reduction test (FECRT) result (0.07 EPG; 0.999) than ivermectin-treated heifers (21.58 EPG; FECRT = 0.850). Mean body weight (BW) was not different between treatment groups on Day 0 (p = 0.2762) and Day 14 (p = 0.2010) but was significantly greater (p = 0.0007) for FDCI-treated heifers compared to ivermectin-treated heifers on Day 56. Compared to ivermectin-treated heifers, overall average daily gain from all evaluation periods (Day 0-14, Day 14-56, and Day 0-56) was greater (p ≤ 0.0052) in FDCI-treated heifers, and FDCI-treated heifers had 4.223 kg greater total weight gain over the 56-day study. The FDCI (0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride) was highly effective in reducing GIN infections and thus promoted improved growth performance in beef heifers over a 56-day backgrounding period.