Maternal postpartum deworming and infant milk intake: Secondary outcomes from a trial.

The World Health Organization recommends deworming to reduce soil-transmitted helminth (STH)-attributable morbidity in women of reproductive age, including pregnant and lactating women, to reduce blood loss, iron deficiency anaemia and nutrient malabsorption. This study assessed the impact of maternal postpartum deworming with albendazole approximately 1 day after delivery on infant milk intake among a subset of 216 randomly selected mother-infant pairs recruited into a large trial in Peru. Infant milk intake was measured using the deuterium-oxide method at 1- and 6-month postpartum. Maternal STH infection was measured at 6-month postpartum. At 1-month postpartum, mean intake was 756 ± 16 and 774 ± 18 mL day-1 in the albendazole and placebo groups, respectively (mean difference: -18 mL day-1 ; 95% CI: -65, 30). At 6-month postpartum, mean intake was 903 ± 16 and 908 ± 18 mL day-1 in the albendazole and placebo groups, respectively (mean difference: -5 mL day-1 ; 95% CI: -52, 43). There was no statistically significant difference in milk intake between groups at either time point. At 6-month postpartum, mothers infected with Trichuris trichiura had infants with higher milk intakes (adjusted mean difference: 70 mL day-1 ; 95% CI: 20, 120) compared with uninfected mothers. However, there was no statistically significant difference in infant milk intake between mothers who had moderate-and-heavy intensity infection compared with the comparison group (mothers with no and light intensity infection). A lower prevalence and intensity of infection, and inclusion of uninfected mothers in both arms of the trial, resulting in effect dilution, may explain the null findings.

Paragonimus and paragonimiasis in West and Central Africa: unresolved questions.

Paragonimiasis, human lung fluke disease, is a foodborne anthropozoonosis caused by the trematodes assigned to Paragonimus and is regarded by the World Health Organization as a Neglected Tropical Disease (NTD). The life cycle of this medically important parasite centres on a complex freshwater biological community that includes two intermediate hosts: a mollusc and a decapod, usually a brachyuran. Although there is a perception that the biology, symptoms, diagnosis and treatment of Paragonimus is well understood, in reality, this is not the case, especially in Africa. Much remains unknown concerning the life-cycle of the parasite, its transmission, the current epidemiology of the disease, diagnosis and the effectiveness of treatment. Furthermore, cases of paragonimiasis may be misdiagnosed as resistant tuberculosis (TB) because of the similar pulmonary symptoms and no remission after anti TB therapy. The endemic foci of human paragonimiasis in Africa have been reported mainly in the forest zones of Upper Guinea (Liberia, Guinea and Ivory Coast) and Lower Guinea (Nigeria, Cameroon, Equatorial Guinea and Gabon). Despite the perceived medical importance of paragonimiasis, relatively little attention has been paid to this NTD since its discovery in Africa in the 1960s. This review focuses on the current understanding of the life cycle and transmission of Paragonimus in Africa, discusses its diagnosis and public health importance and highlights many outstanding gaps in the knowledge that still exist for this NTD.

Control of helminth ruminant infections by 2030.

Helminth infections have large negative impacts on production efficiency in ruminant farming systems worldwide, and their effective management is essential if livestock production is to increase to meet future human needs for dietary protein. The control of helminths relies heavily on routine use of chemotherapeutics, but this approach is unsustainable as resistance to anthelmintic drugs is widespread and increasing. At the same time, infection patterns are being altered by changes in climate, land-use and farming practices. Future farms will need to adopt more efficient, robust and sustainable control methods, integrating ongoing scientific advances. Here, we present a vision of helminth control in farmed ruminants by 2030, bringing to bear progress in: (1) diagnostic tools, (2) innovative control approaches based on vaccines and selective breeding, (3) anthelmintics, by sustainable use of existing products and potentially new compounds, and (4) rational integration of future control practices. In this review, we identify the technical advances that we believe will place new tools in the hands of animal health decision makers in 2030, to enhance their options for control and allow them to achieve a more integrated and sustainable approach to helminth control in support of animal welfare and production.

Risk factors for the presence of Fasciola hepatica antibodies in bulk-milk samples and their association with milk production decreases, in Cuban dairy cattle.

BACKGROUND: Worldwide, Fasciola hepatica infection causes high production losses in the livestock industry. Recently, studies have analyzed the association between measurements of F. hepatica infection intensity and herd management practices. The aim of the present study, the first of its kind in a subtropical region, was to evaluate associations between F. hepatica bulk-tank milk ELISA results with herd management factors and milk yield in dairy herds, in Camagüey, Cuba. The SVANOVIR® F. hepatica-AB ELISA was used to measure F. hepatica antibody levels in a random sample of 516 dairy herds during the period of May-July of 2014. Farm management practice data were collected using a questionnaire. RESULTS: With 82% of the herds testing positive, the results indicate that F. hepatica is very widespread in this area. Reductions in milk production of 18 and 32% were observed in herds with Optical Density Ratios (ODR) of 0.3-0.6 and > 0.6, respectively, when compared to herds with ODR <  0.3. Overall, the longer the milking cows were put out to pasture, the higher the levels of anti-parasite antibodies. Co-grazing with sheep and goats also significantly increased the risk of high ODR. CONCLUSIONS: Our data show a widespread occurrence of the parasite as well as a major potential impact of the infection on the Cuban development goal of becoming self-sufficient in milk production. Our risk factor analysis suggests that the prevention of infection around water sources, and the separation of cattle from small ruminants could be useful control measures. This is the first epidemiological survey of F. hepatica abundance, and associated reductions in milk yield, in dairy herds in Cuba.

Prevalence and Associated Risk Factors of Toxocara vitulorum Infections in Buffalo and Cattle Calves in Three Provinces of Central Cambodia.

The prevalence and associated risk factors of Toxocara vitulorum infection in buffalo and cattle calves was studied in 3 provinces in central Cambodia. Fecal samples were collected from 517 calves between the age of 1-15 weeks and processed for nematode egg counts by a modified McMaster method. A total of 64 calves were found to excrete T. vitulorum eggs in their feces (12.4%; 95% exact CI: 9.7-15.5). The mean fecal egg count was 2,798 EPG (SD=16,351; range=0-224,400). A multivariable generalized linear mixed model showed higher odds of T. vitulorum infection for buffalo versus cattle, for animals aged 4-8 weeks versus younger and older ones, and for animals with strongyle infection. There was no association with fecal consistency. Farmers should be aware of the potential impact of T. vitulorum , and treat their calves at the age of 2-3 weeks with anthelmintics such as benzimidazoles or pyrantel.

Occurrence and potential health risk of Cryptosporidium and Giardia in different water catchments in Belgium.

Human wastewater and livestock can contribute to contamination of surface water with Cryptosporidium and Giardia. In countries where a substantial proportion of drinking water is produced from surface water, e.g., Belgium, this poses a constant threat on drinking water safety. Our objective was to monitor the presence of Cryptosporidium and Giardia in different water catchment sites in Belgium and to discriminate between (oo)cysts from human or animal origin using genotyping. Monthly samples were collected from raw water and purified drinking water at four catchment sites. Cryptosporidium and Giardia were detected using USEPA method 1623 and positive samples were genotyped. No contamination was found in purified water at any site. In three catchments, only low numbers of (oo)cysts were recovered from raw water samples (<1/liter), but raw water samples from one catchment site were frequently contaminated with Giardia (92 %) and Cryptosporidium (96 %), especially in winter and spring. Genotyping of Giardia in 38 water samples identified the presence of Giardia duodenalis assemblage AI, AII, BIV, BIV-like, and E. Cryptosporidium andersoni, Cryptosporidium suis, Cryptosporidium horse genotype, Cryptosporidium parvum, and Cryptosporidium hominis were detected. The genotyping results suggest that agriculture may be a more important source of surface water contamination than human waste in this catchment. In catchment sites with contaminated surface water, such as the Blankaart, continuous monitoring of treated water for the presence of Cryptosporidium and Giardia would be justified and (point) sources of surface water contamination should be identified.

Advances in the diagnosis of Ascaris suum infections in pigs and their possible applications in humans.

Ascariasis is one of the most common parasitic diseases in both humans and pigs. It has been shown to cause growth deficits in both species and to impair cognitive development in children. Notwithstanding its substantial impact on pig economy and public health, diagnosis of ascariasis has mostly relied on the detection of eggs in stool and further development of novel, more sensitive methods has been limited or non-existent. Here, we discuss the currently available techniques for the diagnosis of ascariasis in pigs, their caveats, and the implications of a new serological detection technique for the evaluation of both pig and human ascariasis.

Effect of sampling and diagnostic effort on the assessment of schistosomiasis and soil-transmitted helminthiasis and drug efficacy: a meta-analysis of six drug efficacy trials and one epidemiological survey.

It is generally recommended to perform multiple stool examinations in order to improve the diagnostic accuracy when assessing the impact of mass drug administration programmes to control human intestinal worm infections and determining efficacy of the drugs administered. However, the collection and diagnostic work-up of multiple stool samples increases costs and workload. It has been hypothesized that these increased efforts provide more accurate results when infection and drug efficacy are summarized by prevalence (proportion of subjects infected) and cure rate (CR, proportion of infected subjects that become egg-negative after drug administration), respectively, but not when these indicators are expressed in terms of infection intensity and egg reduction rate (ERR). We performed a meta-analysis of six drug efficacy trials and one epidemiological survey. We compared prevalence and intensity of infection, CR and ERR based on collection of one or two stool samples that were processed with single or duplicate Kato-Katz thick smears. We found that the accuracy of prevalence estimates and CR was lowest with the minimal sampling effort, but that this was not the case for estimating infection intensity and ERR. Hence, a single Kato-Katz thick smear is sufficient for reporting infection intensity and ERR following drug treatment.

Non-invasive indicators associated with the milk yield response after anthelmintic treatment at calving in dairy cows.

BACKGROUND: Gastrointestinal nematodes are an important cause of reduced performance in cattle. Previous studies in Europe showed that after anthelmintic treatment an average gain in milk production of around 1 kg per day/cow can be expected. However, (1) these studies have mainly evaluated group-based anthelmintic treatments during the grazing season or at housing and (2) little is known about parameters affecting variations in the treatment response amongst cows. A better knowledge of such parameters could help to select animals that benefit most from treatment and thus lead to a more rational use of anthelmintics. Therefore, a randomized, non-blinded, controlled clinical trial was performed on 11 commercial dairy farms (477 animals) in Belgium, aiming (1) to study the effect of eprinomectin treatment at calving on milk production and (2) to investigate whether the milk yield response was related to non-invasive animal parameters such that these could be used to inform targeted selective treatment decisions. RESULTS: Analyses show that eprinomectin treatment around calving resulted in an average (± standard error) increase of 0.97 (±0.41) kg in daily milk yield that was followed up over 274 days on average. Milk yield responses were higher in multiparous compared to primiparous cows and in cows with a high (4(th) quartile) anti-O. ostertagi antibody level in a milk sample from the previous lactation. Nonetheless, high responses were also seen in animals with a low (1(st) quartile) anti-O. ostertagi antibody level. In addition, positive treatment responses were associated with higher faecal egg counts and a moderate body condition score at calving (2(nd) quartile). CONCLUSIONS: In conclusion, this study provides novel insights into the production response after anthelmintic treatment at calving and factors which influence this. The data could be used to support the development of evidence-based targeted selective anthelmintic treatment strategies in dairy cattle.

A stochastic frontier approach to study the relationship between gastrointestinal nematode infections and technical efficiency of dairy farms.

The impact of gastrointestinal (GI) nematode infections in dairy farming has traditionally been assessed using partial productivity indicators. But such approaches ignore the impact of infection on the performance of the whole farm. In this study, efficiency analysis was used to study the association of the GI nematode Ostertagia ostertagi on the technical efficiency of dairy farms. Five years of accountancy data were linked to GI nematode infection data gained from a longitudinal parasitic monitoring campaign. The level of exposure to GI nematodes was based on bulk-tank milk ELISA tests, which measure the antibodies to O. ostertagi and was expressed as an optical density ratio (ODR). Two unbalanced data panels were created for the period 2006 to 2010. The first data panel contained 198 observations from the Belgian Farm Accountancy Data Network (Brussels, Belgium) and the second contained 622 observations from the Boerenbond Flemish farmers' union (Leuven, Belgium) accountancy system (Tiber Farm Accounting System). We used the stochastic frontier analysis approach and defined inefficiency effect models specified with the Cobb-Douglas and transcendental logarithmic (Translog) functional form. To assess the efficiency scores, milk production was considered as the main output variable. Six input variables were used: concentrates, roughage, pasture, number of dairy cows, animal health costs, and labor. The ODR of each individual farm served as an explanatory variable of inefficiency. An increase in the level of exposure to GI nematodes was associated with a decrease in technical efficiency. Exposure to GI nematodes constrains the productivity of pasture, health, and labor but does not cause inefficiency in the use of concentrates, roughage, and dairy cows. Lowering the level of infection in the interquartile range (0.271 ODR) was associated with an average milk production increase of 27, 19, and 9L/cow per year for Farm Accountancy Data Network farms and 63, 49, and 23L/cow per year for Tiber Farm Accounting System farms in the low- (0-90), medium- (90-95), and high- (95-99) efficiency score groups, respectively. The potential milk increase associated with reducing the level of infection was higher for highly efficient farms (6.7% of the total possible milk increase when becoming fully technically efficient) than for less efficient farms (3.8% of the total possible milk increase when becoming fully technically efficient).

In-depth proteomic and glycomic analysis of the adult-stage Cooperia oncophora excretome/secretome.

Cooperia oncophora is one of the most common intestinal parasitic nematodes in cattle worldwide. To date, C. oncophora infections are treated using broad-spectrum anthelmintics. However, during the past decade, reports of anthelmintic resistance in this parasite species have emerged worldwide, necessitating new avenues for its control, possibly through vaccination. In this frame, we analyzed the adult-stage C. oncophora excretome/secretome (ES), covering both the protein and glycan components, since this fraction constitutes the primary interface between parasite and host and may hold potential vaccine candidates. Two-dimensional gel electrophoretic separation of the ES material enabled the MALDI-TOF mass spectrometry (MS)-directed identification of 12 distinct proteins, grouped in three separate molecular weight fractions: (i) a high molecular weight fraction consisting of a double-domain activation-associated secreted protein (ASP), (ii) a midmolecular weight fraction predominantly containing a single-domain ASP, a thioredoxin peroxidase and innexin, and (iii) a low molecular weight protein pool essentially holding two distinct low molecular weight antigens. Further MS-driven glycan analysis mapped a variety of N-glycans to the midmolecular weight single-domain ASP, with Man6GlcNAc2 oligomannosyl glycans as the major species. The predominance of the nonglycosylated double-domain ASP in the high-molecular weight fraction renders it ideal for advancement toward vaccine trials and development.

Granule exocytosis of granulysin and granzyme B as a potential key mechanism in vaccine-induced immunity in cattle against the nematode Ostertagia ostertagi.

Ostertagia ostertagi is considered one of the most economically important bovine parasites. As an alternative to anthelmintic treatment, an experimental host-protective vaccine was previously developed on the basis of ASP proteins derived from adult worms. Intramuscular injection of this vaccine, combined with QuilA as an adjuvant, significantly reduced fecal egg counts by 59%. However, the immunological mechanisms triggered by the vaccine are still unclear. Therefore, in this study, the differences in immune responses at the site of infection, i.e., the abomasal mucosa, between ASP-QuilA-vaccinated animals and QuilA-vaccinated control animals were investigated on a transcriptomic level by using a whole-genome bovine microarray combined with histological analysis. Sixty-nine genes were significantly impacted in animals protected by the vaccine, 48 of which were upregulated. A correlation study between the parasitological parameters and gene transcription levels showed that the transcription levels of two of the upregulated genes, those for granulysin (GNLY) and granzyme B (GZMB), were negatively correlated with cumulative fecal egg counts and total worm counts, respectively. Both genes were also positively correlated with each other and with another upregulated gene, that for the IgE receptor subunit (FCER1A). Surprisingly, these three genes were also correlated significantly with CMA1, which encodes a mast cell marker, and with counts of mast cells and cells previously described as globule leukocytes. Furthermore, immunohistochemical data showed that GNLY was present in the granules of globule leukocytes and that it was secreted in mucus. Overall, the results suggest a potential role for granule exocytosis by globule leukocytes, potentially IgE mediated, in vaccine-induced protection against O. ostertagi.

Structure of Ostertagia ostertagi ASP-1: insights into disulfide-mediated cyclization and dimerization.

The cysteine-rich secretory/antigen 5/pathogenesis-related 1 (CAP) protein superfamily is composed of a functionally diverse group of members that are found in both eukaryotes and prokaryotes. The excretome/secretome of numerous helminths (parasitic nematodes) contains abundant amounts of CAP members termed activation-associated secreted proteins (ASPs). Although ASPs are necessary for the parasitic life cycle in the host, the current lack of structural and functional information limits both understanding of their actual role in host-parasite interactions and the development of new routes in controlling parasitic infections and diseases. Alleviating this knowledge gap, a 1.85 Å resolution structure of recombinantly produced Oo-ASP-1 from Ostertagia ostertagi, which is one of the most prevalent gastrointestinal parasites in cattle worldwide, was solved. Overall, Oo-ASP-1 displays the common hallmark architecture shared by all CAP-superfamily members, including the N-terminal CAP and C-terminal cysteine-rich domains, but it also reveals a number of highly peculiar features. In agreement with studies of the natively produced protein, the crystal structure shows that Oo-ASP-1 forms a stable dimer that has been found to be primarily maintained via an intermolecular disulfide bridge, hence the small interaction surface of only 306.8 Å(2). Moreover, unlike any other ASP described to date, an additional intramolecular disulfide bridge links the N- and C-termini of each monomer, thereby yielding a quasi-cyclic molecule. Taken together, the insights presented here form an initial step towards a better understanding of the actual biological role(s) that this ASP plays in host-parasite interactions. The structure is also essential to help to define the key regions of the protein suitable for development of ASP-based vaccines, which would enable the current issues surrounding anthelmintic resistance in the treatment of parasitic infections and diseases to be circumvented.

Analysis of cell hyperplasia and parietal cell dysfunction induced by Ostertagia ostertagi infection.

Infections in cattle with the gastric nematode Ostertagia ostertagi are associated with decreased acid secretion and profound physio-morphological changes of the gastric mucosa. The purpose of the current study was to investigate the mechanisms triggering these pathophysiological changes. O. ostertagi infection resulted in a marked cellular hyperplasia, which can be explained by increased transcriptional levels of signaling molecules related to the homeostasis of gastric epithelial cells such as HES1, WNT5A, FGF10, HB-EGF, AREG, ADAM10 and ADAM17. Intriguingly, histological analysis indicated that the rapid rise in the gastric pH, observed following the emergence of adult worms, cannot be explained by a loss of parietal cells, as a decrease in the number of parietal cells was only observed following a long term infection of several weeks, but is likely to be caused by an inhibition of parietal cell activity. To investigate whether this inhibition is caused by a direct effect of the parasites, parietal cells were co-cultured with parasite Excretory/Secretory products (ESP) and subsequently analyzed for acid production. The results indicate that adult ESP inhibited acid secretion, whereas ESP from the L4 larval stages did not alter parietal cell function. In addition, our data show that the inhibition of parietal cell activity could be mediated by a marked upregulation of inflammatory factors, which are partly induced by adult ESP in abomasal epithelial cells. In conclusion, this study shows that the emergence of adult O. ostertagi worms is associated with marked cellular changes that can be partly triggered by the worm's Excretory/secretory antigens.

Seroepidemiological study of ovine toxoplasmosis in East and West Shewa Zones of Oromia Regional State, Central Ethiopia.

BACKGROUND: Toxoplasmosis is a globally distributed zoonosis. Consumption of raw or undercooked meat, which is among the main risk factors for acquiring human infection, is a popular tradition in Ethiopia. However, studies on toxoplasmosis in food animals used for human consumption in Ethiopia are very scarce. Thus, the objectives of the present study were to estimate the seroprevalence and the risk factors of T. gondii infection in sheep in Ambo, Ada'a-Liben and Fentale districts of Central Ethiopia. Sera from 1130 sheep were analyzed for Toxoplasma gondii specific IgG antibodies using an indirect enzyme linked immunosorbent assay (ELISA) with the P30 antigen. A questionnaire was administered to assess potential risk factors for T. gondii seropositivity. Association of seroprevalence with potential risk factors related to altitude, host and farm characteristics were analyzed by univariable and multivariable logistic regression. RESULTS: Overall flock and animal level seroprevalences were 70.48% (160/227; 95% CI: 64.51, 76.46) and 31.59% (357/1130; 95% CI: 28.88, 34.31), respectively. The multivariable logistic regression model indicated that the probability of acquiring T. gondii was higher in sheep from highland (2300 - 3200 meters above sea level) [Odds ratio (OR) = 4.11, 95% confidence interval (CI): 2.65, 6.36; P < 0.001] and midland (OR = 4.54, 95% CI: 2.76, 7.49; P < 0.001) than from lowland (<1500 meters above sea level), in females than in males (OR = 1.60, 95% CI: 1.04, 2.43, P = 0.033), in adult than in young animals (OR = 2.93, 95% CI: 1.97, 4.35, P < 0.001), in small than in large flocks (OR = 3.34, 95% CI: 1.26, 8.86, P = 0.016), and in sheep that were given tap water (OR = 4.07, 95% CI: 1.07, 15.42, P = 0.039) and river water (OR = 4.18, 95% CI: 1.54, 11.35, P = 0.005) than in those that drunk water from mixed sources (i.e., river, well, lake and pond). CONCLUSIONS: The high flock and animal level seroprevalence of toxoplasmosis in sheep is a good marker of the potential risk for human infections. Altitude, sex, age, flock size and source of water were identified as important risk factors to acquire the infection. Public education and awareness training are imperative in order to alleviate the danger posed to consumers. Further detailed studies to assess the impact of infections are warranted.

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guideline for diagnosing anthelmintic resistance using the faecal egg count reduction test in ruminants, horses and swine.

The faecal egg count reduction test (FECRT) remains the method of choice for establishing the efficacy of anthelmintic compounds in the field, including the diagnosis of anthelmintic resistance. We present a guideline for improving the standardization and performance of the FECRT that has four sections. In the first section, we address the major issues relevant to experimental design, choice of faecal egg count (FEC) method, statistical analysis, and interpretation of the FECRT results. In the second section, we make a series of general recommendations that are applicable across all animals addressed in this guideline. In the third section, we provide separate guidance details for cattle, small ruminants (sheep and goats), horses and pigs to address the issues that are specific to the different animal types. Finally, we provide overviews of the specific details required to conduct an FECRT for each of the different host species. To address the issues of statistical power vs. practicality, we also provide two separate options for each animal species; (i) a version designed to detect small changes in efficacy that is intended for use in scientific studies, and (ii) a less resource-intensive version intended for routine use by veterinarians and livestock owners to detect larger changes in efficacy. Compared to the previous FECRT recommendations, four important differences are noted. First, it is now generally recommended to perform the FECRT based on pre- and post-treatment FEC of the same animals (paired study design), rather than on post-treatment FEC of both treated and untreated (control) animals (unpaired study design). Second, instead of requiring a minimum mean FEC (expressed in eggs per gram (EPG)) of the group to be tested, the new requirement is for a minimum total number of eggs to be counted under the microscope (cumulative number of eggs counted before the application of a conversion factor). Third, we provide flexibility in the required size of the treatment group by presenting three separate options that depend on the (expected) number of eggs counted. Finally, these guidelines address all major livestock species, and the thresholds for defining reduced efficacy are adapted and aligned to host species, anthelmintic drug and parasite species. In conclusion, these new guidelines provide improved methodology and standardization of the FECRT for all major livestock species.

A general framework to support cost-efficient fecal egg count methods and study design choices for large-scale STH deworming programs-monitoring of therapeutic drug efficacy as a case study.

BACKGROUND: Soil-transmitted helminth (STH) control programs currently lack evidence-based recommendations for cost-efficient survey designs for monitoring and evaluation. Here, we present a framework to provide evidence-based recommendations, using a case study of therapeutic drug efficacy monitoring based on the examination of helminth eggs in stool. METHODS: We performed an in-depth analysis of the operational costs to process one stool sample for three diagnostic methods (Kato-Katz, Mini-FLOTAC and FECPAKG2). Next, we performed simulations to determine the probability of detecting a truly reduced therapeutic efficacy for different scenarios of STH species (Ascaris lumbricoides, Trichuris trichiura and hookworms), pre-treatment infection levels, survey design (screen and select (SS); screen, select and retest (SSR) and no selection (NS)) and number of subjects enrolled (100-5,000). Finally, we integrated the outcome of the cost assessment into the simulation study to estimate the total survey costs and determined the most cost-efficient survey design. PRINCIPAL FINDINGS: Kato-Katz allowed for both the highest sample throughput and the lowest cost per test, while FECPAKG2 required both the most laboratory time and was the most expensive. Counting of eggs accounted for 23% (FECPAKG2) or ≥80% (Kato-Katz and Mini-FLOTAC) of the total time-to-result. NS survey designs in combination with Kato-Katz were the most cost-efficient to assess therapeutic drug efficacy in all scenarios of STH species and endemicity. CONCLUSIONS/SIGNIFICANCE: We confirm that Kato-Katz is the fecal egg counting method of choice for monitoring therapeutic drug efficacy, but that the survey design currently recommended by WHO (SS) should be updated. Our generic framework, which captures laboratory time and material costs, can be used to further support cost-efficient choices for other important surveys informing STH control programs. In addition, it can be used to explore the value of alternative diagnostic techniques, like automated egg counting, which may further reduce operational costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03465488.

Human soil-transmitted helminths: implications of mass drug administration.

PURPOSE OF REVIEW: With the London Declaration on neglected tropical disease (NTD), we are entering a new era of combating NTDs. However, the worldwide prospects of increased mass drug administration (MDA) treatments warrant caution on the development of anthelmintic resistance. In this review, we discuss the practical implications of MDA programs on the development of anthelmintic resistance in human soil-transmitted helminths (STH). RECENT FINDINGS: There is poor evidence of anthelmintic resistance in human STH. Moreover, there is presumptive evidence that the refugia in MDA programs to control human STH is currently large, suggesting that the development of anthelmintic resistance in STH will be slow or may not occur. It remains unclear whether the current MDA strategy to control STH will sufficiently delay or prevent the development of anthelmintic resistance. First, differences in efficacy across and within STH species, and seasonal transmission of STH have not yet been considered. Second, any surveillance system to monitor drug efficacy is lacking. Finally, there is still no agreed strategy on how to deal with anthelmintic resistance once it emerges. SUMMARY: Although anthelmintic resistance in human STH is currently of limited concern, various actions should be put in place for its delay and monitoring, and strategies should be developed in case anthelmintic resistance occurs.

Epidemiology of Taenia solium in Nepal: is it influenced by the social characteristics of the population and the presence of Taenia asiatica?

The transmission of the zoonotic pork tapeworms Taenia solium and T. asiatica depends on a combination of specific risk factors, such as open defecation, backyard pig raising and the consumption of raw or undercooked pork and viscera. A community-based survey was conducted among 289 households in south-eastern Nepal to study the heterogeneity of these risk factor frequencies as a function of the social composition of the population. The frequency of open defecation, backyard pig raising and pork consumption differed significantly (P < 0.005) among the different coexisting caste and ethnic groups. In the same survey, the taeniosis prevalence was examined among the different groups. Tapeworm carriers were identified at a high prevalence among the Dum, one of the most disadvantaged communities of Nepal. A PCR-RFLP assay revealed that all collected tapeworm specimens were T. asiatica, a species thus far not known to occur in South Asia. These results can help to understand the epidemiology of T. solium in Nepal, which appears to be more complex than thought so far.

Confounding factors affecting faecal egg count reduction as a measure of anthelmintic efficacy.

Increasing anthelmintic resistance (AR) in livestock has stimulated growing efforts to monitor anthelmintic effectiveness (AE) on livestock farms. On-farm assessment of AE relies on measuring the reduction in faecal egg count (FEC) following treatment; and if conducted rigorously, qualifies as a formal FEC reduction test (FECRT) for AR. Substantial research effort has been devoted to designing robust protocols for the FECRT and its statistical interpretation; however, a wide range of factors other than AR can affect FEC reduction on farms. These are not always possible to control, and can affect the outcome and repeatability of AE measurements and confound the on-farm classification of AR using FECRT. This review considers confounders of FEC reduction, focusing on gastrointestinal nematodes of ruminants, including host and parasite physiology and demography; pharmacokinetic variation between drugs, parasites and hosts; and technical performance. Drug formulation and delivery, host condition and diet, and seasonal variation in parasite species composition, can all affect AE and hence observed FEC reduction. Causes of variation in FEC reduction should be attenuated, but this is not always possible. Regular monitoring of AE can indicate a need to improve anthelmintic administration practices, and detect AR early in its progression. Careful interpretation of FEC reduction, however, taking into account possible confounders, is essential before attributing reduced FEC reduction to AR. Understanding of confounders of FEC reduction will complement advances in FECRT design and interpretation to provide measures of anthelmintic efficacy that are both rigorous and accessible.

Title: Facteurs de confusion affectant la réduction du nombre d'œufs fécaux comme mesure de l'efficacité anthelminthique. Abstract: L'augmentation de la résistance aux anthelminthiques (RA) chez le bétail a stimulé des efforts croissants pour mesurer l'efficacité des anthelminthiques (EA) dans les élevages. L'évaluation à la ferme de l'EA repose sur la mesure de la réduction du nombre d'œufs dans les selles (NOS) après le traitement ; si effectué rigoureusement, celui-ci est qualifié de test formel de réduction du NOS (TFRNOS) pour la RA. Des efforts de recherche substantiels ont été consacrés à la conception de protocoles robustes pour le TFRNOS et son interprétation statistique, mais un large éventail de facteurs autres que la RA peuvent affecter la réduction du NOS dans les exploitations. Ces facteurs ne sont pas toujours contrôlables et peuvent affecter le résultat et la répétabilité des mesures de l'EA et introduire de la confusion dans la classification à la ferme de la RA à l'aide de la TFRNOS. Cette revue examine les facteurs de confusion de la réduction du NOS, en se concentrant sur les nématodes gastro-intestinaux des ruminants, et considère la physiologie et la démographie de l'hôte et du parasite, la variation pharmacocinétique entre les médicaments, les parasites et les hôtes, et les performances techniques. La formulation et l'administration de médicaments, la condition et le régime alimentaire de l'hôte, ainsi que les variations saisonnières de la composition des espèces de parasites, peuvent tous affecter l'EA et donc la réduction du NOS observé. Les causes de variation de la réduction du NOS doivent être atténuées, mais cela n'est pas toujours possible. Une surveillance régulière de l'EA peut indiquer la nécessité d'améliorer les pratiques d'administration des anthelminthiques et de détecter la RA au début de sa progression. Une interprétation prudente de la réduction du NOS, cependant, en tenant compte des facteurs de confusion possibles, est essentielle avant d'attribuer la réduction du NOS à la RA. La compréhension des facteurs de confusion d'une moindre réduction du NOS complétera les progrès sur la conception et l'interprétation du TFRNOS, pour fournir des mesures de l'efficacité des anthelminthiques à la fois rigoureuses et accessibles.