Ascaris lumbricoides eggs or artefacts? A diagnostic conundrum.

Due to the presence of artefacts in stool samples, the copromicroscopic diagnosis of Ascaris lumbricoides is not always straightforward, particularly in the case of fertilized decorticated eggs. A total of 286 stool samples from 115 schoolchildren in India and 171 adult immigrants in Italy were screened for the presence of A. lumbricoides eggs by both Kato-Katz thick smear and Mini-FLOTAC. If the outer layer of A. lumbricoides eggs was absent, two aliquots of each stool sample were preserved: one for coproculture to identify larvae after development and one to compose a pool of stool for molecular analysis. A total of 64 stool samples (22.4%) were positive for A. lumbricoides using the Kato-Katz thick smear; 36 (56.3%) of these showed mammillated A. lumbricoides eggs, 25 (39.1%) showed elements resembling fertilized decorticated eggs, while three samples (4.7%) showed both mammillated and decorticated eggs. By Mini-FLOTAC, 39 stool samples (13.6%) were positive, while decorticated A. lumbricoides-like eggs were identified as artefacts. These results were confirmed by negative coprocultures and quantitative polymerase chain reaction. Mini-FLOTAC can be used for a reliable diagnosis of A. lumbricoides, thanks to the flotation and translation features which allow a clearer view, resulting in the correct identification of A. lumbricoides eggs.

Evaluation of the therapeutic efficacy of praziquantel against schistosomes in seven countries with ongoing large-scale deworming programs.

The World Health Organization (WHO) recommends periodic assessment of the therapeutic efficacy of praziquantel (PZQ) to detect reduced efficacy that may arise from drug resistance in schistosomes. In this multi-country study (2014), we assessed the therapeutic efficacy of a single oral dose of PZQ (40 mg/kg) against Schistosoma mansoni (Brazil, Cameroon, Ethiopia, Mali, Madagascar and Tanzania), S. haematobium (Cameroon, Ethiopia, Mali, Tanzania and Zanzibar) and S. japonicum (the Philippines) infections in school-aged children, across a total of 12 different trials. Each trial was performed according to the standardized methodology for evaluating PZQ efficacy as described by the WHO. Overall, therapeutic efficacy, measured as the reduction in arithmetic mean of schistosome egg counts following drug administration (egg reduction rate; ERR), was high for all three schistosome species (S. mansoni: 93.4% (95%CI: 88.8-96.8); S. haematobium: 97.7% (95%CI: 96.5-98.7) and S. japonicum: 90.0% (95%CI: 68.4-99.3). At the trial level, therapeutic efficacy was satisfactory (point estimate ERR ≥90%) for all three Schistosoma species with the exception of S. mansoni in Cameroon where the ERR was 88.5% (95%CI: 79.0-95.1). Furthermore, we observed that in some trials individual drug response could vary significantly (wide 95%CI) and that few non-responsive individuals could significantly impact ERR point estimates. In conclusion, these results do not suggest any established reduced efficacy of the standard PZQ treatment to any of the three schistosome species within these countries. Nevertheless, the substantial degree of variation in individual responses to treatment in some countries underpins the need for future monitoring. The reported ERR values serve as reference values to compare with outcomes of future PZQ efficacy studies to ensure early detection of reduced efficacies that could occur as drug pressure continues increase. Finally, this study highlights that 95%CI should be considered in WHO guidelines to classify the therapeutic efficacy of PZQ.

Preventive chemotherapy to control soil-transmitted helminthiasis averted more than 500 000 DALYs in 2015.

Background: Preventive chemotherapy (PC), the large-scale administration of anthelminthics, is recommended by the World Health Organization (WHO) for the control of soil-transmitted helminthiasis (STH). Since 2010, donated anthelminthics for STH have boosted the implementation of PC programmes in children, achieving global coverage of more than 60% in 2015. The WHO Global Health Estimates attribute an annual loss of over 3.3 million disability-adjusted life-years (DALYs) to STH. The aim of this study is to estimate the impact of PC programmes on child morbidity. Method: We used data from the WHO Global Health Estimates, national coverage data on PC and the results of an evaluation of the impact of PC in 17 countries on morbidity previously conducted by our group. Results: We estimated that the implementation of PC averted in 2015 over 44% of the DALYs that would have been caused in children by STH without the control intervention. A reduction in morbidity of over 75% is expected, if the global target is reached in 2020. If the programme is subsequently maintained, morbidity from STH will be almost totally removed by 2025. Conclusions: In endemic areas, preventive chemotherapy provides a significant health benefit. We consider this estimation potentially useful to evaluate the cost utility of the investment made by several endemic countries on PC to control STH.

Governance, organization, accountability and sustainability of a region-wide school-based deworming program in Loreto, Peru.

Chau Cuica was the name given by the regional government of Loreto in Peru for its school-based deworming program which was initiated in 2012 with a donation of mebendazole from an international non-governmental organization. Embedded in the program from the start was a sentinel surveillance component which consisted of 16 sentinel schools representing Loreto's seven provinces. Coverage rates varied between 35% and 61% over the first two years of the program (and seven deworming cycles). Initial prevalences of soil-transmitted helminth infections were high, with 82.4% of schoolchildren having at least one infection and prevalences of both Ascaris lumbricoides and Trichuris trichiura infections both exceeding 60%. After two years, these prevalences had dropped to 56% for any STH infection, 38% for A. lumbricoides and 34% for T. trichiura. Importantly, the proportions of children with moderate and heavy infections also dropped. Both the regional Ministry of Health and the Ministry of Education were jointly charged to implement this deworming program. The program's costs were estimated to be approximately 22 cents (USD) per child per deworming cycle. The responsibility for the surveillance component was initially undertaken by research partners from a local NGO and a Canadian university, which transferred gradually over the course of the deworming program to being entirely the responsibility of the Ministry of Health. This regional deworming program may serve as a model for other jurisdictions that are planning a school-based deworming program with an integrated surveillance component to monitor impact.

Monitoring the efficacy of drugs for neglected tropical diseases controlled by preventive chemotherapy.

In the last decade, pharmaceutical companies, governments and global health organisations under the leadership of the World Health Organization (WHO) have pledged large-scale donations of anthelmintic drugs, including ivermectin (IVM), praziquantel (PZQ), albendazole (ALB) and mebendazole (MEB). This worldwide scale-up in drug donations calls for strong monitoring systems to detect any changes in anthelmintic drug efficacy. This review reports on the outcome of the WHO Global Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy, which consists of three subgroups: (i) soil-transmitted helminthiases (ALB and MEB); (ii) onchocerciasis and lymphatic filariasis (IVM); and (iii) schistosomiasis (PZQ). Progress of ongoing work, challenges and research needs for each of the four main drugs used in helminthic preventive chemotherapy (PC) are reported, laying the ground for appropriate implementation of drug efficacy monitoring programmes under the co-ordination and guidelines of the WHO. Best practices for monitoring drug efficacy should be made available and capacity built as an integral part of neglected tropical disease (NTD) programme monitoring. Development of a disease-specific model to predict the impact of PC programmes, to detect outliers and to solicit responses is essential. Research studies on genetic polymorphisms in relation to low-efficacy phenotypes should be carried out to identify markers of putative resistance against all NTD drugs and ultimately to develop diagnostic assays. Development of combination and co-administration of NTD drugs as well as of new drug entities to boost the armamentarium of the few drugs available for NTD control and elimination should be pursued in parallel.

Preventive chemotherapy in human helminthiasis: theoretical and operational aspects.

Preventive chemotherapy (PC), the large-scale distribution of anthelminthic drugs to population groups at risk, is the core intervention recommended by the WHO for reducing morbidity and transmission of the four main helminth infections, namely lymphatic filariasis, onchocerciasis, schistosomiasis and soil-transmitted helminthiasis. The strategy is widely implemented worldwide but its general theoretical foundations have not been described so far in a comprehensive and cohesive manner. Starting from the information available on the biological and epidemiological characteristics of helminth infections, as well as from the experience generated by disease control and elimination interventions across the world, we extrapolate the fundamentals and synthesise the principles that regulate PC and justify its implementation as a sound and essential public health intervention. The outline of the theoretical aspects of PC contributes to a thorough understanding of the different facets of this strategy and helps comprehend opportunities and limits of control and elimination interventions directed against helminth infections.

Moderate and high endemicity of schistosomiasis is a predictor of the endemicity of soil-transmitted helminthiasis: a systematic review.

The authors conducted a systematic literature review with the following aims: to investigate how frequently soil-transmitted helminthiasis (STH) infections are endemic where schistosomiasis is present; and to assess the correlation between the risk level of schistosomiasis and that of STH. Among 155 sites on which data were collected and analyzed, schistosomiasis was present in 130, all of which were also co-endemic for STH, whereas 25 sites were endemic only for STH. Ninety percent (117 out of 130) of the areas eligible for preventive chemotherapy (PC) against schistosomiasis are also eligible for PC against STH. This fact provides managers of control programmes with the operationally important indication that use of available information on endemicity of schistosomiasis is a valid tool to predict the presence of STH in the same geographical area and to estimate the need of PC for STH. The implementation of this tool is expected to save financial and human resources and help accelerate the scale-up of PC throughout the world.

Estimation of the cost of large-scale school deworming programmes with benzimidazoles.

This study estimates the cost of distributing benzimidazole tablets in the context of school deworming programmes: we analysed studies reporting the cost of school deworming from seven countries in four WHO regions. The estimated cost for drug procurement to cover one million children (including customs clearance and international transport) is approximately US$20000. The estimated financial costs (including the cost of training of personnel, drug transport, social mobilization and monitoring) is, on average, equivalent to US$33000 per million school-age children with minimal variation in different countries and continents. The estimated economic costs of distribution (including the time spent by teachers, and health personnel at central, provincial and district level) to cover one million children approximately corresponds to US$19000. This study shows the minimal cost of school deworming activities, but also shows the significant contribution (corresponding to a quarter of the entire cost of the programme) provided by health and education systems in endemic countries even in the case of drug donations and donor support of distribution costs.

Field testing of the WHO dose pole for administration of praziquantel in the treatment of opisthorchiasis in Lao PDR.

In 2001, the WHO developed a dose pole that employs height measurements for estimation of the dose of praziquantel. In the present study, conducted in December 2005 during a mass treatment campaign for the control of opisthorchiasis in 232 individuals in Nala village, Keo Udom district, Lao PDR, performance of the dose pole in estimating dosages of praziquantel was compared with a bathroom scale; a digital scale was used as the gold standard. Results showed that the bathroom scale performed significantly better than the dose pole in delivering dosages of 40-50 mg/kg for opisthorchiasis treatment (70.7% vs. 44.8%). Furthermore, the dose pole performed significantly better for children than adults. The reason for the poor performance of the dose pole among adults is likely to be due to the high percentage (19.4%) of overweight individuals in the adult population of the village. It was concluded that the WHO dose pole is not recommended for distribution of praziquantel for the treatment of opisthorchiasis in populations where being overweight is common.

Arithmetic or geometric means of eggs per gram are not appropriate indicators to estimate the impact of control measures in helminth infections.

In helminthology, the mean number of eggs per gram of faeces (EPG) is a commonly used indicator for the severity of the infection in a population. The example presented here shows that, in my opinion, mean EPG (either calculated as arithmetic or geometric means) is not the best way to evaluate the impact of control measures, as helminth infections present an intensity/morbidity relationship, which should be considered when selecting indicators for the evaluation of control measures. In my opinion, an analysis by class of intensity is more informative.

Control of Schistosoma mekongi in Cambodia: results of eight years of control activities in the two endemic provinces.

In Cambodia, schistosomiasis is transmitted in the provinces of Kratie and Stung Treng where approximately 80000 individuals are estimated to be at risk of infection. The baseline prevalence of infection was estimated to be between 73% and 88%, and cases of severe morbidity (hepatosplenomegaly, puberty retardation) and mortality were very common. In 1994, the Ministry of Health of Cambodia started schistosomiasis control applying universal chemotherapy with praziquantel (40mg/kg). The coverage of the programme was between 62% and 86% for 8 years. This simple control measure resulted in the control of the disease: no cases were reported in 2004 and only three cases were reported in 2005. In addition, there are no longer reports of cases of severe morbidity due to schistosomiasis. Since the beginning of the control programme, a single dose of mebendazole (500mg) has been combined with praziquantel during the mass chemotherapy; as a result the prevalence of Ascaris lumbricoides and hookworms dropped from 74.5% to 10% and from 86% to 40% respectively. The experience in Cambodia demonstrates that, with political commitment, control of parasitic diseases is achievable even in a situation of minimal resources. The programme represents a successful model for other developing countries.

Substitution of Malachite Green with Nigrosin - Eosin Yellow Stain in the Kato-Katz Method: Microscopical Appearance of the Helminth Eggs

Background:The Kato-Katz thick smear technique is the standard technique recommended by the World Health Organisation for the quantitative diagnosis of Schistosoma mansoni and other intestinal helminth infections.The major problem of the technique is that a few hours after the preparation of slides hookworm eggs over clear and disappear due glycerin. Objective:To illustrate clear visibility of different helminth eggs microscopically in Odongo-Aginya method; substitution of malachite green with 7.5nigrosin in 10formalin and 5eosin in 10formalin. Method: Measured; strained stool specimen was stained with mixture of nigrosin/ eosin and covered with cellophane cover slips.The prepared slide was examined immediately microscopically. Result: Slides prepared with Odongo-Aginya method can be examined immediately or later without compromising the visibility of parasite eggs and larvae. Hookworm eggs remain visible for a long time. Conclusion:The present publication shows microscopic appearance of the helminth eggs using the Odongo-Aginya modification

Controlling lymphatic filariasis and soil-transmitted helminthiasis together in South Asia: opportunities and challenges.

Lymphatic filariasis (LF) and the major soil-transmitted helminth (STH) infections are co-endemic in many countries, particularly in Asia. Control strategies for both groups of infections have increasingly focused on the use of mass chemotherapy. With the use of albendazole, there is now a tool that is common to both. However, there are also important differences in their modes of transmission and epidemiology, and, as a result, in the overall control strategies. The Global Programme for the Elimination of Lymphatic Filariasis aims to eliminate LF through time-limited mass drug administration programmes. Control activities for STH are more diffuse, aiming to piggy-back de-worming onto existing services, such as school health activities; controlling morbidity, rather than eliminating infection, is the stated goal. In order to maximize health benefits to communities that are endemic for one or both of these infections, it is vitally important that policy makers and programme managers have a clear understanding of both commonalities and differences, and implement control strategies that allocate available resources in an optimal manner.

Evaluation of coverage of deworming interventions in Vietnam.

In 2004-2005, the school deworming program in Vietnam targeted 2,400,000 school-children in 25 provinces. A questionnaire survey of a random sample of schools throughout the country was organized to validate the teacher feedback, assess the real coverage of the program and estimate the occurrence of side-effects. A total of 91 schools in four different provinces were visited few days after drug distribution. A total of 2,323 children and 80 teachers were questioned. The total cost of the monitoring has been estimated at US dollar 7,000 (less than 10% of the deworming program). The survey demonstrated a coverage of 95% for school-children and of 86.3% for teachers (on average a coverage 2% lower than the one reported by the teachers through forms on the day of drug administration). Approximately 0.4% of those interviewed reported side-effects after deworming, while the occurrence of side effects through routine reports was 0.15%. In both cases, the side effects were described as mild forms of nausea, abdominal pain, or headaches that did no required pharmacological treatment. The survey confirmed the positive results of routine reporting; we consider the survey a cost-effective activity to maintain the control activities under monitoring.

Appreciation of school deworming program by parents in Ha Giang Province (Vietnam).

School-based deworming programs are one of the most cost-effective public health strategies to reach children with anthelminthics and health education. However, despite their low cost and high health impact, they are not implemented on a large scale. The present survey investigated a school-based deworming program in Ha Giang Province, Vietnam, to assess the community perception and support towards these programs. Information from 81 households, 88 primary school students, 25 teachers and 9 people in charge of commune health stations was collected by structured questionnaires. The survey displayed complete satisfaction and a high level of support within all 4 questioned groups. In addition 96.1% of all parents noticed an improvement in their children's health. The great appreciation of the deworming program by the community is an additional argument to convince decision makers to implement and scale up these programs. Even teachers that did not receive any specific training were able to distribute the drug successfully following the page of written instructions accompanying the drug.

Soil-transmitted helminths and haemoglobin status among Afghan children in World Food Programme assisted schools.

In recent years there have been major socio-economic changes within Afghanistan such that the present public health burden of soil-transmitted helminths (STH), especially that within school-aged children, remains to be determined. A baseline parasitological survey was therefore carried out in four defined areas of Afghanistan to better assess the distribution, prevalence and intensity of STH infections prior to a nationwide de-worming campaign beginning within World Food Programme assisted schools. A cross-sectional examination of 1001 children aged between 8 and 15 years old revealed that approximately half (47.2%) were infected with at least one STH. Infections with Ascaris lumbricoides were most widespread (40.9%) and elevated prevalences were detected in urban environments; for example, schoolchildren in Kabul were more likely to be infected (OR=2.2, 95% CI 1.6-3.0) than elsewhere and these infections were often of higher intensity (OR=7.6, 95% CI 4.9-11.8). Trichuris trichiura (9.9%) and hookworms (0.7%), previously unknown from Afghanistan, were encountered. The blood haemoglobin concentration of surveyed children was also assessed: 4% resulted to be anaemic (Hb<11 g dl(-1)), and 0.4% to be severely anaemic (Hb<7 g dl(-1)).

The WHO dose pole for the administration of praziquantel is also accurate in non-African populations.

In 2001, WHO developed a pole for the administration of praziquantel without the use of weighing scales, with encouraging results in African populations. In the present study, the pole was tested on height/weight data from 9354 individuals from 11 non-African countries. In more than 98% of the individuals (95% CI 97.8-98.4) the pole estimated an acceptable dosage (30-60 mg/kg), a performance statistically similar to that observed in African populations. Reproducing the present pole in the form of a strip of paper and including it in each container of praziquantel would greatly facilitate the administration of the drug in large-scale interventions.

Progress in the prevention and control of schistosomiasis and soil-transmitted helminthiasis.

In the last two decades important progress has been made in the understanding the epidemiology and the disease burden of schistosomiasis and soil-transmitted nematodes infection. In addition, practical tools for disease control have been developed and a strategy for the prevention and control of morbidy of schistosomaisis and soil-transmitted nematodes infection has been endorsed by the World Health Organization. This paper presents the recent progress in the prevention and control of these infections: the estimates of chronic and subtle morbidity in high risk groups and the evidence that these chronic and severe sequelae of infections can be reversed by appropriate treatment; the use of anthelminthic drugs during pregnancy and lactation; the relevance to control morbidity due to these infections also in pre-school children; the efficacy of anthelminthic drugs and the possible threat of drug resistance; price, quality and accessibility of treatment by delivering drugs through the school system and ways of reaching also non-enrolled school-age children. Finally, the strategy, targets and recommendations of the World Health Organization for the control of schistosomiasis and soil-transmitted nematodes infection are described.