Epidemiology, burden and diagnosis of intestinal parasites with particular consideration to strongyloidiasis in Yunnan province, China
 
Parasitic infections are common among poor communities in the developing world. Soil-transmitted and food-borne helminths (e.g. Ascaris lumbricoides, Trichuris trichiura, hookworms, Taenia spp.) cause widespread, yet often neglected morbidity in infected people, particularly in children and pregnant women. Intestinal protozoa (e.g. Entamoeba histolytica, Giardia intestinalis) and the helminth Strongyloides stercoralis are also endemic in many regions. Yet, these parasites remain undetected by the widely employed Kato-Katz thick smear technique. As a consequence, we lack detailed understanding of the epidemiology of intestinal protozoa and some helminth infections. Multiple species parasite infections are common in poor communities, and might aggravate negative health effects. The combination of different diagnostic techniques and repeated sample collection from the same individual are necessary to detect the full range of intestinal parasites with a high sensitivity. A small number of safe and efficacious drugs are available to treat human intestinal parasite infections, but no single drug covers the whole range of parasites. There are also fears that resistance might develop against the most common drugs as it has already happened in veterinary medicine. Tribendimidine is a new anthelminthic drug that has been registered in China in 2004. Research carried out at the Swiss Tropical Institute has indicated activity of tribendimidine also against Strongyloides ratti and different cestodes in animal models.
Yunnan is the south-western border province of China which extends into the tropical climate zone. The social and economic development lags behind that of eastern China, especially in rural settings, and the knowledge about the local epidemiology of most human intestinal parasites is partial at the best.
The objectives of this project were:

1. to further our understanding of the epidemiology and burden of intestinal parasitic infections in Xishuangbanna prefecture, Yunnan province, by means of parasitological and questionnaire surveys,
2. to comparatively assess the performance of different diagnostic tools, and
3. to investigate the safety and efficacy of tribendimidine compared to albendazole in a setting with high multiparasitism rates and with a focus on the effects against S. stercoralis and Taenia spp.

The project was carried out in close collaboration with two Chinese institutions, namely the National Institute for Parasitic Diseases, Chinese Center for Disease Control and Prevention in Shanghai and the Yunnan Institute for Parasitic Diseases Control and Prevention, Simao Branch.
The study focused on Nanweng village in Menghai county, a community entirely inhabited by members of the Bulang ethnic group. All 294 inhabitants aged ≥2 years present at the time of our epidemiological survey were invited to submit up to 3 stool samples and to answer a questionnaire. Stool samples were analyzed for the presence of parasite infections by a range of diagnostic techniques, including Kato-Katz, Koga agar plate and Baermann techniques. Additionally, samples were conserved in sodium acetate-acetic acid-formalin (SAF) for later analysis by the formalin-ether concentration technique and the FLOTAC method. Study participants aged ≥5 years who had submitted ≥1 stool sample were randomly assigned to either albendazole or tribendimidine administered at a single oral dose (5-14 years: 200 mg, ≥15 years: 400 mg). Actual treatment was decided on the spot (inclusion criteria: good general health status, no alcohol consumed on day of treatment and non-pregnant). The treatment evaluation was performed 2-3 weeks post-treatment and included collection of up to 3 stool samples that were examined with the same diagnostic approaches as at baseline. The final study cohort comprised those 123 individuals from whom 2-3 stool samples were available at baseline and again for treatment evaluation. Among them, 66 were treated with albendazole and 57 with tribendimidine.
The results available so far confirm the high prevalence of intestinal multiparasitism in the area: The baseline prevalences of T. trichiura, hookworm and A. lumbricoides were 87.8%, 74.8% and 72.4% among the final study cohort. In the same group, the prevalence of Taenia spp. and S. stercoralis was 26.0% and 17.9%, respectively. The latter two parasites were more frequently found among adult men than among women or younger age groups. Albendazole and tribendimidine treatment reduced the prevalence of S. stercoralis from 16.7% to 10.6% (p=0.307) and from 19.3% to 8.8% (p=0.107), respectively. The drug-specific difference between the S. stercoralis cure rates was 18.1% (p=0.394). The prevalence of Taenia spp. was reduced from 25.8% to 10.6% (p=0.024) after a single oral dose of albendazole and from 26.3% to 8.8% (p=0.014) after tribendimidine treatment (difference between cure rates: 7.9%, p=0.645). At treatment evaluation, a considerable number of ‘new’ infections were recorded among those considered negative at baseline, resulting in reduced net cure rates. Most newly detected infections were Taenia spp. in the albendazole-group and the difference between the drug-specific net cure rates became highly significant for this parasite and in favour of tribendimidine (p=0.001). The detection of additional infections can most likely be attributed to the lack of sensitivity of the techniques used, which could not be compensated despite the analysis of multiple stool samples. No treatment-related adverse events were recorded in the final study cohort.
We conclude that multiparasitism is pervasive in the study area and that various human intestinal helminths occur at prevalences which justify regular mass treatment using standard drugs without previous diagnosis. Such campaigns are strongly recommended and should be accompanied by health education and the provision of safe water supply and sanitation infrastructure to achieve sustainable reductions of the prevalence, burden and infection pressure. Tribendimidine was shown to be safe if used in a setting of high multiparasitism rates, and to exhibit some activity against S. stercoralis and Taenia spp. The measured efficacy, however, is unsatisfactory and the evaluation of alternative dosage options, e.g. 3 daily doses over consecutive days, should be investigated.

Contacts:
Peter Steinmann
Department of Public Health and Epidemiology
Swiss Tropical Institute
Socinstrasse 57
P.O. Box
CH-4002 Basel, Switzerland
Telephone: +41 61 284-8226
E-mail: peter.steinmann@unibas.ch

Prof. Xiao-Nong Zhou
National Institute of Parasitic Diseases
Chinese Center for Disease Control and Prevention
207 Rui Jin Er Road
Shanghai 200025
People’s Republic of China
Telephone: +86 21 6473-8058
E-mail: ipdzhouxn@sh163.net