RESUMEN
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.
Asunto(s)
Helmintiasis , Helmintos , Animales , Humanos , Ascaris lumbricoides , Heces , Helmintiasis/tratamiento farmacológico , Helmintiasis/diagnóstico , Sensibilidad y Especificidad , Suelo , TrichurisRESUMEN
BACKGROUND: Efforts to control soil-transmitted helminth (STH) infections have intensified over the past decade. Field-survey data on STH prevalence, infection intensity and drug efficacy is necessary to guide the implementation of control programs and should be of the best possible quality. METHODOLOGY: During four clinical trials designed to evaluate the efficacy of albendazole against STHs in Brazil, Ethiopia, Lao PDR and Tanzania, quality control (QC) was performed on the duplicate Kato-Katz thick smears and the data entry. We analyzed datasets following QC on both fecal egg counts (FECs) and data entry, and compared the prevalence of any STH infection and moderate-to-heavy intensity (MHI) infections and the drug efficacy against STH infections. RESULTS: Across the four study sites, a total of 450 out of 4,830 (9.3%) Kato-Katz thick smears were re-examined. Discrepancies in FECs varied from ~3% (hookworms) to ~6.5% (Ascaris lumbricoides and Trichuris trichiura). The difference in STH prevalence and prevalence of MHI infections using the datasets with and without QC of the FECs did not exceed 0.3%, except for hookworm infections in Tanzania, where we noted a 2.2 percentage point increase in MHI infections (pre-QC: 1.6% vs. post-QC: 3.8%). There was a 100% agreement in the classification of drug efficacy of albendazole against STH between the two datasets. In total, 201 of the 28,980 (0.65%) data entries that were made to digitize the FECs were different between both data-entry clerks. Nevertheless, the overall prevalence of STH, the prevalence of MHI infections and the classification of drug efficacy remained largely unaffected. CONCLUSION/SIGNIFICANCE: In these trials, where staff was informed that QC would take place, minimal changes in study outcomes were reported following QC on FECs or data entry. Nevertheless, imposing QC did reduce the number of errors. Therefore, application of QC together with proper training of the personnel and the availability of clear standard operating procedures is expected to support higher data quality.
Asunto(s)
Albendazol/uso terapéutico , Helmintiasis/tratamiento farmacológico , Control de Calidad , Ancylostomatoidea , Animales , Ascaris , Brasil/epidemiología , Ensayos Clínicos como Asunto , Etiopía/epidemiología , Heces/parasitología , Guías como Asunto , Helmintiasis/epidemiología , Helmintiasis/transmisión , Infecciones por Uncinaria/tratamiento farmacológico , Infecciones por Uncinaria/epidemiología , Humanos , Laos/epidemiología , Recuento de Huevos de Parásitos , Prevalencia , Suelo/parasitología , Tanzanía/epidemiología , TrichurisRESUMEN
Soil-transmitted helminth (STH) infections are the most widespread of the neglected tropical diseases, primarily affecting marginalized populations in low- and middle-income countries. More than one billion people are currently infected with STHs. For the control of these infections, the World Health Organization (WHO) recommends an integrated approach, which includes access to appropriate sanitation, hygiene education, and preventive chemotherapy (i.e., large-scale, periodic distribution of anthelmintic drugs). Since 2010, WHO has coordinated two large donations of benzimidazoles to endemic countries. Thus far, more than 3.3 billion benzimidazole tablets have been distributed in schools for the control of STH infections, resulting in an important reduction in STH-attributable morbidity in children, while additional tablets have been distributed for the control of lymphatic filariasis. This paper (i) summarizes the progress of global STH control between 2008 to 2018 (based on over 690 reports submitted by endemic countries to WHO); (ii) provides regional and country details on preventive chemotherapy coverage; and (iii) indicates the targets identified by WHO for the next decade and the tools that should be developed to attain these targets. The main message is that STH-attributable morbidity can be averted with evidence-informed program planning, implementation, and monitoring. Caution will still need to be exercised in stopping control programs to avoid any rebound of prevalence and loss of accrued morbidity gains. Over the next decade, with increased country leadership and multi-sector engagement, the goal of eliminating STH infections as a public health problem can be achieved.
Asunto(s)
Antihelmínticos/uso terapéutico , Salud Global/tendencias , Helmintiasis/prevención & control , Suelo/parasitología , Organización Mundial de la Salud , Antihelmínticos/administración & dosificación , Humanos , Factores SocioeconómicosRESUMEN
BACKGROUND: Preventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz. METHODS: An ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy. PRINCIPAL FINDINGS AND CONCLUSIONS: The results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the ß-tubulin gene that have previously been linked to anthelmintic resistance. TRIAL REGISTRATION: ClinicalTrials.gov NCT03465488.
Asunto(s)
Albendazol/uso terapéutico , Antihelmínticos/uso terapéutico , Helmintiasis/diagnóstico , Helmintiasis/tratamiento farmacológico , Suelo/parasitología , Administración Oral , Albendazol/administración & dosificación , Animales , Brasil , Niño , Pruebas Diagnósticas de Rutina/métodos , Etiopía , Heces/parasitología , Femenino , Helmintos/genética , Humanos , Laos , Masculino , Recuento de Huevos de Parásitos/métodos , Sensibilidad y Especificidad , Tanzanía , Tubulina (Proteína)/genética , Organización Mundial de la SaludRESUMEN
Helminth infections are the cause of morbidity in Cambodian cattle but other factors such as nutritional deficiencies and concurrent diseases may enhance the effects of parasites. The present study aimed to investigate the impact of anthelmintic treatment, feed supplementation, or both on gastrointestinal strongyle (GIS) and trematode infections as well as on morbidity parameters in Cambodian village cattle. At the beginning of the dry season, cattle populations in six villages were randomly assigned to a group: (A) receiving anthelmintic treatment (ivermectin+clorsulon) at week 0; (P) feed pellet supplementation during week 0-13 or both (AP). On five visits (week 0-29), faecal and blood samples were obtained for parasitological examination and haematocrit determination, respectively. Body condition (BCS), hind quarter fouling (HQFS), diarrhoea (DS), and conjunctiva colour (FAMACHA©) were scored and heart girth circumference was determined. To investigate the impact of treatment over time (week 0-29), a mixed model was used with treatment, time, and their interaction as fixed effects, and animal and village as random factors. At baseline, the proportion of GIS positive animals was high (67.9%), whereas trematode infections were low (Paramphistomum: 8.8%; Fasciola: 2.6%). Very thin to emaciated cattle (BCS 1-2) were more prevalent (11.4%) and FAMACHA© scores of ≤3 or below (65.8%) less prevalent than in an earlier study in the region. A Time ⨯ Treatment interaction was present for faecal egg counts (FEC) of GIS, GIS prevalence (both p<0.0001), PCV (p=0.0034), DS (p=0.0086) and HQFS (p=0.0241). For GIS FEC, treatment groups differed at a specific time point, with levels of treatment group P being higher than in A at week 6 (p=0.0054). For Paramphistomum prevalence as well as FAMACHA© scoring, heart girth and BCS, the interaction between treatment and time was not significant, yet, time in itself had a significant impact on all (p<0.0001). The beneficial effects of protein supplementation were unclear from the current study.
Asunto(s)
Antihelmínticos/uso terapéutico , Enfermedades de los Bovinos/tratamiento farmacológico , Proteínas en la Dieta/administración & dosificación , Parasitosis Intestinales/veterinaria , Infecciones por Nematodos/veterinaria , Infecciones por Trematodos/veterinaria , Animales , Cambodia/epidemiología , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/parasitología , Suplementos Dietéticos , Fasciola/efectos de los fármacos , Fascioliasis/tratamiento farmacológico , Fascioliasis/veterinaria , Femenino , Hematócrito/veterinaria , Parasitosis Intestinales/tratamiento farmacológico , Parasitosis Intestinales/epidemiología , Masculino , Morbilidad , Nematodos/efectos de los fármacos , Infecciones por Nematodos/tratamiento farmacológico , Infecciones por Nematodos/epidemiología , Paramphistomatidae/efectos de los fármacos , Infecciones por Trematodos/tratamiento farmacológico , Infecciones por Trematodos/epidemiologíaRESUMEN
BACKGROUND: There is a paucity of studies that compare efficacy of drugs obtained by different diagnostic methods. METHODS: We compared the efficacy of a single oral dose albendazole (400 mg), measured as egg reduction rate, against soil-transmitted helminth infections in 210 school children (Jimma Town, Ethiopia) using both Kato-Katz thick smear and McMaster egg counting method. RESULTS: Our results indicate that differences in sensitivity and faecal egg counts did not imply a significant difference in egg reduction rate estimates. CONCLUSION: The choice of a diagnostic method to assess drug efficacy should not be based on sensitivity and faecal egg counts only.
Asunto(s)
Albendazol/uso terapéutico , Antihelmínticos/uso terapéutico , Helmintiasis/tratamiento farmacológico , Helmintiasis/transmisión , Recuento de Huevos de Parásitos/métodos , Suelo/parasitología , Animales , Niño , Etiopía/epidemiología , Heces/parasitología , Femenino , Helmintiasis/diagnóstico , Helmintiasis/epidemiología , Humanos , Masculino , Sensibilidad y EspecificidadRESUMEN
In the present study, we present a hierarchical model based on faecal egg counts (FECs; expressed in eggs per 1g of stool) in which we first describe the variation in FECs between individuals in a particular population, followed by describing the variance due to counting eggs under a microscope separately for each stool sample. From this general framework, we discuss how to calculate a sample size for assessing a population mean FEC and the impact of an intervention, measured as reduction in FECs, for any scenario of soil-transmitted helminth (STH) epidemiology (the intensity and aggregation of FECs within a population) and diagnostic strategy (amount of stool examined (â¼sensitivity of the diagnostic technique) and examination of individual/pooled stool samples) and on how to estimate prevalence of STH in the absence of a gold standard. To give these applications the most wide relevance as possible, we illustrate each of them with hypothetical examples.
Asunto(s)
Antihelmínticos/uso terapéutico , Heces/parasitología , Helmintiasis/tratamiento farmacológico , Helmintiasis/prevención & control , Modelos Teóricos , Suelo/parasitología , Animales , Helmintiasis/epidemiología , Helmintiasis/parasitología , Helmintos/fisiología , Humanos , Recuento de Huevos de ParásitosRESUMEN
BACKGROUND: Recently, WHO has developed a predictive model to evaluate the impact of preventive chemotherapy programs to control the morbidity of soil-transmitted helminths (STHs). To make predictions, this model needs baseline information about the proportion of infections classified as low, moderate and high intensity, for each of the three STH species. However, epidemiological data available are often limited to prevalence estimates. METHODS: We reanalyzed available data from 19 surveys in 10 countries and parameterized the relationship between prevalence of STH infections and the proportion of moderate and heavy intensity infections. RESULTS: The equations derived allow feeding the WHO model with estimates of the proportion of the different classes of infection intensity when only prevalence data is available. CONCLUSIONS: The prediction capacities of the STH model using the equations developed in the present study, should be tested by comparing it with the changes on STH epidemiological data observed in control programs operating for several years.
Asunto(s)
Antihelmínticos/uso terapéutico , Heces/parasitología , Helmintiasis/epidemiología , Helmintiasis/transmisión , Microbiología del Suelo/normas , Suelo/parasitología , Animales , Humanos , Cadenas de Markov , Pobreza , Prevalencia , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The presence of poor quality medicines in the market is a global threat on public health, especially in developing countries. Therefore, we assessed the quality of two commonly used anthelminthic drugs [mebendazole (MEB) and albendazole (ALB)] and one antiprotozoal drug [tinidazole (TNZ)] in Ethiopia. METHODS/PRINCIPAL FINDINGS: A multilevel stratified random sampling, with as strata the different levels of supply chain system in Ethiopia, geographic areas and government/privately owned medicines outlets, was used to collect the drug samples using mystery shoppers. The three drugs (106 samples) were collected from 38 drug outlets (government/privately owned) in 7 major cities in Ethiopia between January and March 2012. All samples underwent visual and physical inspection for labeling and packaging before physico-chemical quality testing and evaluated based on individual monographs in Pharmacopoeias for identification, assay/content, dosage uniformity, dissolution, disintegration and friability. In addition, quality risk was analyzed using failure mode effect analysis (FMEA) and a risk priority number (RPN) was assigned to each quality attribute. A clinically rationalized desirability function was applied in quantification of the overall quality of each medicine. Overall, 45.3% (48/106) of the tested samples were substandard, i.e. not meeting the pharmacopoeial quality specifications claimed by their manufacturers. Assay was the quality attribute most often out-of-specification, with 29.2% (31/106) failure of the total samples. The highest failure was observed for MEB (19/42, 45.2%), followed by TNZ (10/39, 25.6%) and ALB (2/25, 8.0%). The risk analysis showed that assay (RPNâ=â512) is the most critical quality attribute, followed by dissolution (RPNâ=â336). Based on Derringer's desirability function, samples were classified into excellent (14/106,13%), good (24/106, 23%), acceptable (38/106, 36%%), low (29/106, 27%) and bad (1/106,1%) quality. CONCLUSIONS/SIGNIFICANCE: This study evidenced that there is a relatively high prevalence of poor quality MEB, ALB and TNZ in Ethiopia: up to 45% if pharmacopoeial acceptance criteria are used in the traditional, dichotomous approach, and 28% if the new risk-based desirability approach was applied. The study identified assay as the most critical quality attributes. The country of origin was the most significant factor determining poor quality status of the investigated medicines in Ethiopia.
Asunto(s)
Antihelmínticos/normas , Giardiasis/tratamiento farmacológico , Helmintiasis/tratamiento farmacológico , Suelo/parasitología , Albendazol/normas , Animales , Antihelmínticos/farmacología , Etiopía/epidemiología , Humanos , Mebendazol/normas , Prevalencia , Encuestas y Cuestionarios , Tinidazol/normasRESUMEN
The visualization of vector occurrence in space and time is an important aspect of studying vector-borne diseases. Detailed maps of possible vector habitats provide valuable information for the prediction of infection risk zones but are currently lacking for most parts of the world. Nonetheless, monitoring vector habitats from the finest scales up to farm level is of key importance to refine currently existing broad-scale infection risk models. Using Fasciola hepatica, a parasite liver fluke, as a case in point, this study illustrates the potential of very high resolution (VHR) optical satellite imagery to efficiently and semi-automatically detect detailed vector habitats. A WorldView2 satellite image capable of <5m resolution was acquired in the spring of 2013 for the area around Bruges, Belgium, a region where dairy farms suffer from liver fluke infections transmitted by freshwater snails. The vector thrives in small water bodies (SWBs), such as ponds, ditches and other humid areas consisting of open water, aquatic vegetation and/or inundated grass. These water bodies can be as small as a few m2 and are most often not present on existing land cover maps because of their small size. We present a classification procedure based on object-based image analysis (OBIA) that proved valuable to detect SWBs at a fine scale in an operational and semi-automated way. The classification results were compared to field and other reference data such as existing broad-scale maps and expert knowledge. Overall, the SWB detection accuracy reached up to 87%. The resulting fine-scale SWB map can be used as input for spatial distribution modelling of the liver fluke snail vector to enable development of improved infection risk mapping and management advice adapted to specific, local farm situations.
Asunto(s)
Vectores de Enfermedades , Ecosistema , Fasciola hepatica , Imágenes Satelitales , Animales , Bélgica/epidemiología , Procesamiento de Imagen Asistido por Computador , Imágenes Satelitales/métodos , HumedalesRESUMEN
BACKGROUND: The fecal egg count reduction test (FECRT) is recommended to monitor drug efficacy against soil-transmitted helminths (STHs) in public health. However, the impact of factors inherent to study design (sample size and detection limit of the fecal egg count (FEC) method) and host-parasite interactions (mean baseline FEC and aggregation of FEC across host population) on the reliability of FECRT is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: A simulation study was performed in which FECRT was assessed under varying conditions of the aforementioned factors. Classification trees were built to explore critical values for these factors required to obtain conclusive FECRT results. The outcome of this analysis was subsequently validated on five efficacy trials across Africa, Asia, and Latin America. Unsatisfactory (<85.0%) sensitivity and specificity results to detect reduced efficacy were found if sample sizes were small (<10) or if sample sizes were moderate (10-49) combined with highly aggregated FEC (k<0.25). FECRT remained inconclusive under any evaluated condition for drug efficacies ranging from 87.5% to 92.5% for a reduced-efficacy-threshold of 90% and from 92.5% to 97.5% for a threshold of 95%. The most discriminatory study design required 200 subjects independent of STH status (including subjects who are not excreting eggs). For this sample size, the detection limit of the FEC method and the level of aggregation of the FEC did not affect the interpretation of the FECRT. Only for a threshold of 90%, mean baseline FEC <150 eggs per gram of stool led to a reduced discriminatory power. CONCLUSIONS/SIGNIFICANCE: This study confirms that the interpretation of FECRT is affected by a complex interplay of factors inherent to both study design and host-parasite interactions. The results also highlight that revision of the current World Health Organization guidelines to monitor drug efficacy is indicated. We, therefore, propose novel guidelines to support future monitoring programs.