Epidemiology and diagnosis of "Schistosoma japonicum", other helminth infections and multiparasitism in Yunnan province, People's Republic of China

Background: Schistosomiasis is a water-based disease, endemic in over 70 countries in the
tropics and subtropics. At present, the bulk of the global burden is concentrated in sub-
Saharan Africa. Some important foci exist in South America, the Middle East, Southeast Asia
and in China. We reviewed the literature, used the latest population statistics and estimate that
globally, 207 million people are infected and 779 millions are at risk of infection. Soiltransmitted
helminthiasis caused by Ascaris lumbricoides, hookworms and Trichuris trichiura,
is highly endemic throughout the tropics and elsewhere, particularly in resource-constraint
settings. At least 1 billion people worldwide are infected, many of whom harbour multiple
species concurrently. Strongyloides stercoralis is a far less recognized and researched soiltransmitted
helminth. Taenia spp. is transmitted via raw and undercooked meat dishes and is
endemic globally but, similar to S. stercoralis, accurate statistics and distribution maps are
lacking. All these parasites belong to the group of the so-called neglected tropical diseases. In
recent years, different programmes have been launched with an aim to providing regular
anthelminthic treatment to millions of people worldwide. However, only a handful of safe and
efficacious drugs are available, but none of them covers the entire parasite spectrum. While
chemotherapy is a key strategy to reduce morbidity, other measures are necessary to achieve
sustainable control.
Schistosoma japonicum, soil-transmitted helminths, Taenia spp. and other helminths are
common throughout China. In view of the profound demographic, ecological and socioeconomic
transformations China has gone through over the past 30 years, the distribution and
frequency of many parasites has changed. Shifts have been attributed to regional variations in
control efforts, socio-economic development and changing customs.
Objectives: This Ph.D. thesis pursued five specific objectives. First, to systematically review
the literature with regard to the effects of water resources development on the local
epidemiology of schistosomiasis. Second, to study the epidemiology of S. japonicum and
other helminth infections across Eryuan county, Yunnan province, China. Third, to identify
risk factors for S. japonicum seropositivity in Eryuan county, and to put forward predictive
risk maps. Fourth, to study intestinal multiparasitism, the local endemicity of S. stercoralis
and the performance of diagnostic tools in Menghai county, Yunnan province. Fifth, to assess
the safety and efficacy of tribendimidine against S. stercoralis and Taenia spp.
Methods: The available data regarding the number and spatial extent of large dam reservoirs
and surface-irrigation in schistosome-endemic areas were compiled and multiplied with
country-specific rural population density estimates. We systematically reviewed the literature
to identify studies pertaining to the effect of water resources development projects on
schistosomiasis, and carried out a meta-analysis and calculated risk ratios.
The cross-sectional survey in Eryuan county involved 3220 individuals from 35 villages.
They were screened by parasitological (S. japonicum, intestinal helminths) and serological
methods (schistosomiasis, cysticercosis, trichinellosis). Questionnaires were administered to
obtain demographic, behavioural, and socio-economic data. Geographical, remotely-sensed
environmental, demographic, and epidemiological data were used in a spatially-explicit
Bayesian model to predict the risk of schistosomiasis japonica seroprevalence across the
county. The endemic spectrum of intestinal parasites was assessed in Nongyang village in
southern Yunnan province where 2-3 stool samples were collected from 215 individuals, and
analysed by four different diagnostic approaches, i.e. Kato-Katz, Baermann, Koga agar plate
and ether-concentration after conservation of the stool sample in sodium acetate-acetic acidformaline
solution. The effect of the sampling effort on the measured prevalence, and the
diagnostic performance of the different techniques were assessed. The safety and efficacy of
tribendimidine for treating S. stercoralis and Taenia spp. infections was investigated in
Nanweng village. A single oral dose of tribendimidine was administered to 57 individuals,
and results were compared to the effect of a single oral dose of albendazole given to 66
individuals. The efficacy was assessed 2-3 weeks post-treatment based on 2-3 stool samples
screened before and after treatment using different methods.
Results: A predicted 106 million people at risk of schistosomiasis live adjacent (≤5 km) to
large dam reservoirs or in irrigated areas. We identified 58 studies, mainly from African
settings, and included a subset of 24 studies containing 35 datasets to calculate pooled random
risk ratios. People living in close proximity to large dam reservoirs were at a 2.4-fold (95%
confidence interval [CI]: 1.4-3.9) higher risk of S. haematobium and at a 2.6-fold (95% CI:
1.4-5.0) risk of S. mansoni. In irrigated areas, the pooled random risk ratios were 1.1 (95% CI:
0.02-7.3) for S. haematobium and 4.7 (95% CI: 0.49-23.0) for S. mansoni.
The most common helminth in Eryuan county was A. lumbricoides (15.4%), followed by
Taenia spp. (3.5%) and S. japonicum (2.7%) in known schistosome-endemic villages.
Seroprevalences were high; 58.8% for trichinellosis, 49.5% for schistosomiasis japonica in
known S. japonicum-endemic villages, and 18.5% for cysticercosis. Prevalences as well as the
socio-economic status of the families showed strong spatial heterogeneity; most helminths
were more prevalent among the poor in mountainous areas but S. japonicum and trichinellosis
were mainly found among the better-off inhabitants of plain areas. Being Han and growing
tobacco were additional risk factors for S. japonicum. Sero- and egg-positive individuals were
also found outside the recognized S. japonicum-endemic villages. The spatially-explicit
Bayesian model identified demographic (age and sex) and geographical (slope and elevation)
risk factors, and predicted higher S. japonicum seroprevalences for the plain areas when
compared to mountainous regions.
Fifteen parasite species were identified in Nongyang village, eight helminths and seven
protozoa. The prevalence of the three common soil-transmitted helminth exceeded 85% each.
We found a S. stercoralis prevalence of 11.7% with a predominance among adult males. The
prevalence of intestinal protozoa was lower; the most common was Blastocystis hominis
(20.0%). Most study participants harboured three intestinal parasites concurrently (range 1-6).
Infection intensities were mainly light for T. trichiura and hookworm, but moderate for
A. lumbricoides. The collection of multiple stool samples resulted in higher prevalences, most
notably for S. stercoralis and hookworms. Pooling results from multiple methods consistently
increased the overall sensitivity.
A single oral dose of tribendimidine (200 mg for those 5-14 years old; 400 mg for those
≥15 years old) reduced the S. stercoralis prevalence from 19.3% to 8.8% (cure rate: 54.5%,
P = 0.107) and the Taenia spp. prevalence from 26.3% to 8.8% (cure rate: 66.7%, P = 0.014).
Albendazole treatment resulted in comparable prevalence reductions. At treatment evaluation,
additional infections were discovered among those previously declared uninfected. These
infections were most likely missed before due to lack of diagnostic sensitivity. Considering
these “new” infections reduced the net cure rate, most notably for Taenia spp. among the
albendazole group. For Taenia spp., the difference between the tribendimidine and
albendazole-specific cure rates became significant (P = 0.001).
Conclusions/significance: The distribution map of human helminth infections in Yunnan
province, China still has many white spots and important shifts in the spectrum and
prevalence of endemic parasites are expected in the face of the ongoing socio-economic
development. New survey approaches, diagnostic tools and risk profiling techniques have
been introduced, and the local epidemiology of S. japonicum and further parasites including
helminths and intestinal protozoa has been elucidated. S. stercoralis is endemic in Yunnan
province. The safety and efficacy of a potentially additional tool in future control efforts for
treating S. stercoralis and Taenia spp. – i.e. tribendimidine – was studied. The studies
conducted in the frame of this Ph.D. thesis document the current situation pertaining to
various currently neglected parasites and in hitherto unexplored settings, thus providing a
base for the articulation of much needed control programmes which respond to local needs.