Stefanie Knopp

Time to set the agenda for schistosomiasis elimination

It is time to raise global awareness to the possibility of schistosomiasis elimination and to support endemic countries in their quest to determine the most appropriate approaches to eliminate this persistent and debilitating disease. The main interventions for schistosomiasis control are reviewed, including preventive chemotherapy using praziquantel, snail control, sanitation, safe water supplies, and behaviour change strategies supported by information, education and communication (IEC) materials. Differences in the biology and transmission of the three main Schistosoma species (i.e. Schistosoma haematobium, S. mansoni and S. japonicum), which impact on control interventions, are considered. Sensitive diagnostic procedures to ensure adequate surveillance in areas attaining low endemicity are required. The importance of capacity building is highlighted. To achieve elimination, an intersectoral approach is necessary, with advocacy and action from local communities and the health community to foster cooperative ventures with engineers, the private sector, governments and non-governmental organizations specialized in water supply and sanitation. Examples of successful schistosomiasis control programmes are reviewed to highlight what has been learnt in terms of strategy for control and elimination. These include St. Lucia and other Caribbean islands, Brazil and Venezuela for S. mansoni; Saudi Arabia and Egypt for both S. mansoni and S. haematobium; Morocco, Tunisia, Algeria, Mauritius and the Islamic Republic of Iran for S. haematobium; Japan and the Peoples Republic of China for S. japonicum. Additional targets for elimination or even eradication could be the two minor human schistosome species S. guineenisis and S. intercalatum, which have a restricted distribution in West and Central Africa. The examples show that elimination of schistosomiasis is an achievable and desirable goal requiring full integration of preventive chemotherapy with the tools of transmission control. An agenda for the elimination of schistosomiasis would aim to identify the gaps in knowledge, and define the tools, strategies and guidelines that will help national control programmes move towards elimination, including an internationally accepted mechanism that allows verification/confirmation of elimination.

Diagnosis of Soil-Transmitted Helminths in the Era of Preventive Chemotherapy: Effect of Multiple Stool Sampling and Use of Different Diagnostic Techniques

Background Soil-transmitted helminth infections are common throughout the tropics and subtropics and they disproportionately affect the poorest of the poor. In view of a growing global commitment to control soil-transmitted helminthiasis, there is a need to elucidate the effect of repeated stool sampling and the use of different diagnostic methods in areas targeted for preventive chemotherapy that are characterized by low-infection intensities. In this study, we focused on schoolchildren on Unguja Island, Zanzibar, an area where anthelminthic drugs have been repeatedly administered over the past decade. Methodology/Principal Findings Three serial stool samples from each of 342 schoolchildren were examined using the Kato-Katz (K-K), Koga agar plate (KAP), and Baermann (BM) techniques. These methods were used individually or in combination for the diagnosis of Ascaris lumbricoides (K-K), Trichuris trichiura (K-K), hookworm (K-K and KAP), and Strongyloides stercoralis (KAP and BM). The examination of multiple stool samples instead of a single one resulted in an increase of the observed prevalence; e.g., an increase of 161% for hookworm using the K-K method. The diagnostic sensitivity of single stool sampling ranged between 20.7% for BM to detect S. stercoralis and 84.2% for K-K to diagnose A. lumbricoides. Highest sensitivities were observed when different diagnostic approaches were combined. The observed prevalences for T. trichiura, hookworm, A. lumbricoides, and S. stercoralis were 47.9%, 22.5%, 16.5%, and 10.8% after examining 3 stool samples. These values are close to the ‘true’ prevalences predicted by a mathematical model. Conclusion/Significance Rigorous epidemiologic surveillance of soil-transmitted helminthiasis in the era of preventive chemotherapy is facilitated by multiple stool sampling bolstered by different diagnostic techniques.

Comparative cost assessment of the Kato-Katz and FLOTAC techniques for soil-transmitted helminth diagnosis in epidemiological surveys.

BackgroundThe Kato-Katz technique is widely used for the diagnosis of soil-transmitted helminthiasis in epidemiological surveys and is believed to be an inexpensive method. The FLOTAC technique shows a higher sensitivity for the diagnosis of light-intensity soil-transmitted helminth infections but is reported to be more complex and expensive. We assessed the costs related to the collection, processing and microscopic examination of stool samples using the Kato-Katz and FLOTAC techniques in an epidemiological survey carried out in Zanzibar, Tanzania.MethodsWe measured the time for the collection of a single stool specimen in the field, transfer to a laboratory, preparation and microscopic examination using standard protocols for the Kato-Katz and FLOTAC techniques. Salaries of health workers, life expectancy and asset costs of materials, and infrastructure costs were determined. The average cost for a single or duplicate Kato-Katz thick smears and the FLOTAC dual or double technique were calculated.ResultsThe average time needed to collect a stool specimen and perform a single or duplicate Kato-Katz thick smears or the FLOTAC dual or double technique was 20 min and 34 sec (20:34 min), 27:21 min, 28:14 min and 36:44 min, respectively. The total costs for a single and duplicate Kato-Katz thick smears were US

Albendazole and Mebendazole Administered Alone or in Combination with Ivermectin against Trichuris trichiura: A Randomized Controlled Trial

1.73 and US

An evaluation of urine-CCA strip test and fingerprick blood SEA-ELISA for detection of urinary schistosomiasis in schoolchildren in Zanzibar

2.06, respectively, and for the FLOTAC double and dual technique US

Diagnostic accuracy of Kato-Katz and FLOTAC for assessing anthelmintic drug efficacy

2.35 and US

Nematode Infections: Soil-Transmitted Helminths and Trichinella

2.83, respectively. Salaries impacted most on the total costs of either method.ConclusionsThe time and cost for soil-transmitted helminth diagnosis using either the Kato-Katz or FLOTAC method in epidemiological surveys are considerable. Our results can help to guide healthcare decision makers and scientists in budget planning and funding for epidemiological surveys, anthelminthic drug efficacy trials and monitoring of control interventions.

New diagnostic tools in schistosomiasis

BACKGROUND Single-dose albendazole and mebendazole show limited efficacy in the treatment of trichuriasis. The combination of albendazole with ivermectin improves efficacy, but a mebendazole-ivermectin combination has not been previously investigated. METHODS We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of albendazole (400 mg) plus placebo, albendazole plus ivermectin (200 μg/kg), mebendazole (500 mg) plus placebo, and mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. RESULTS Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a mebendazole-ivermectin combination (55%). Low CRs were observed with albendazole-ivermectin (38%), mebendazole (19%), and albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the mebendazole-ivermectin combination, followed by albendazole-ivermectin (91%; 95% CI, 87%-94%), mebendazole (67%; 95% CI, 52%-77%), and albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. CONCLUSIONS Addition of ivermectin improves the therapeutic outcomes of both albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN08336605.

Patterns and risk factors of helminthiasis and anemia in a rural and a peri-urban community in Zanzibar, in the context of helminth control programs.

To develop better monitoring protocols for detection of urinary schistosomiasis during ongoing control interventions, two commercially available diagnostic tests - the urine-circulating cathodic antigen (CCA) strip and the soluble egg antigen enzyme-linked immunosorbent assay (SEA-ELISA) - were evaluated for detection of Schistosoma haematobium infections in 150 schoolchildren from Zanzibar. The children originated from five primary schools representative of different levels of disease endemicity across the island; using standard urine filtration assessment with microscopy, mean prevalence of S. haematobium was 30.7% (95% confidence interval (CI)=23.4-38.7%) and a total of 35.3% (95% CI=27.7-43.5%) and 8.0% (95% CI=4.2-13.6%) children presented with micro- and macro-haematuria, respectively. Diagnostic scores of the urine-CCA strip were not satisfactory, a very poor sensitivity of 9% (95% CI=2-21%) was observed, precluding any further consideration. By contrast, the performance of the SEA-ELISA using sera from fingerprick blood was good; a sensitivity of 89% (95% CI=76-96%), a specificity of 70% (95% CI=60-79%), a positive predictive value of 57% (95% CI=45-69%) and a negative predictive value of 90% (95% CI=86-98%) were found. At the unit of the school, a positive linear association between prevalence inferred from parasitological examination and SEA-ELISA methods was found. The SEA-ELISA holds promise as a complementary field-based method for monitoring infection dynamics in schoolchildren over and above standard parasitological methods.

Persistent digestive disorders in the tropics: causative infectious pathogens and reference diagnostic tests

Background Sensitive diagnostic tools are required for an accurate assessment of prevalence and intensity of helminth infections in areas undergoing regular deworming, and for monitoring anthelmintic drug efficacy. We compared the diagnostic accuracy of the Kato-Katz and FLOTAC techniques in the frame of a drug efficacy trial. Methodology/Principal Findings Stool samples from 343 Zanzibari children were subjected to duplicate Kato-Katz thick smears and the FLOTAC basic technique in a baseline screening in early 2009. The FLOTAC showed a higher sensitivity than the Kato-Katz method for the diagnosis of Trichuris trichiura (95% vs. 88%, p = 0.012) and Ascaris lumbricoides (88% vs. 68%, p = 0.098), but a lower sensitivity for hookworm diagnosis (54% vs. 81%, p = 0.006). Considering the combined results from both methods as ‘gold’ standard, the prevalences of T. trichiura, hookworm and A. lumbricoides were 71% (95% confidence interval (CI): 66–75%), 22% (95% CI: 17–26%) and 12% (95% CI: 8–15%), respectively. At follow-up, 3–5 weeks after 174 among the 269 re-examined children were administered anthelmintic drugs, we observed cure rates (CRs) against A. lumbricoides, hookworm and T. trichiura of 91% (95% CI: 80–100%), 61% (95% CI: 48–75%) and 41% (95% CI: 34–49%), respectively, when using the Kato-Katz method. FLOTAC revealed lower CRs against A. lumbricoides (83%, 95% CI: 67–98%) and T. trichiura (36%, 95% CI: 29–43%), but a higher CR against hookworm (69%, 95% CI: 57–82%). These differences, however, lacked statistical significance. Considerable differences were observed in the geometric mean fecal egg counts between the two methods with lower egg reduction rates (ERRs) determined by FLOTAC. Conclusion/Significance Our results suggest that the FLOTAC technique, following further optimization, might become a viable alternative to the Kato-Katz method for anthelmintic drug efficacy studies and for monitoring and evaluation of deworming programs. The lower CRs and ERRs determined by FLOTAC warrant consideration and could strategically impact future helminth control programs.