par Nguyen, Thi Bich Thao
Président du jury Donnen, Philippe
Promoteur Vandenberg, Olivier
Co-Promoteur Do, Dung Trung
Publication Non publié, 2025-09-11
Thèse de doctorat
Résumé : Background: Foodborne zoonotic trematodes (FZT) are a group of parasitic flukes that inhabit various organs within the host's body, including the liver (Clonorchis sinensis, Opisthorchis spp., and Fasciola spp.), lungs (Paragonimus spp.), and intestines (Echinostoma spp., Fasciolopsis buski, Metagonimus spp., heterophyids). Human infection with FZT commonly occurs through the consumption of inadequately cooked or raw freshwater fish (C. sinensis, Opisthorchis spp., Echinostoma spp., Metagonimus spp., heterophyids), freshwater crab or crayfish (Paragonimus spp.), aquatic plants (Fasciola spp., F. buski), or by ingesting water (Fasciola spp.) contaminated with the metacercaria of these parasites. Infection with FZT is associated with diverse and severe morbidity; for example, a chronic infection with C. sinensis or O. viverrini can cause fibrosis, biliary obstruction, cholecystitis, cholangitis, and may lead to cholangiocarcinoma (CCA), a potentially fatal bile duct cancer.In northern Vietnam, notably in several rural regions, the consumption of raw fish, uncooked vegetables, or undercooked meals is not only prevalent but also deeply rooted in the local culture. Additionally, agricultural practices such as utilizing human or animal feces as fertilizer, allowing animals to roam freely, and applying a VAC system (combining gardens, fishponds, and pigsties or poultry sheds) are commonplace in certain rural areas. However, these conditions foster a conducive environment for the transmission of FZT. The prevalence of FZT, particularly C. sinensis, has been documented across nearly all northern provinces. Some intervention programs of FZT have been conducted in North Vietnam, mainly focusing on mass drug administration (MDA). However, these programs are often not sustainable as re-infection occurs. Besides, the limitation of diagnostic capacity at the local level may lead to an underestimation of the current situation of FZT infections (FZTi).Objectives: This PhD thesis pursued five specific objectives:1. To investigate the FZTi in humans in north and central Vietnam.2. To assess the incidence and risk factors of fish-borne trematode infections.3. To improve awareness on FZTi, with a focus on clonorchiasis in high-risk communities.4. To assess the laboratory capacities for diagnosis of FZTi.5. To improve laboratory capacities for diagnosing FZTi at the local level.Methods: The research was divided into two parts: a community-based study and a health center-based study. For the community-based part, in 2018, a cross-sectional study was conducted in 4 communes in Yen Bai and Thanh Hoa provinces, including 841 participants. Stool samples were collected and examined using Kato-Katz (KK) and Formalin-ether concentration techniques (FECT) to diagnose C. sinensis, minute intestinal flukes (MIF), and other helminths. Blood samples were collected, and the sera analysed by using a commercial Enzyme-linked immunosorbent assay (ELISA) kit to detect Fasciola antibodies. Additionally, a knowledge, attitude and practices (KAP) questionnaire related to clonorchiasis and some practice questions related to fascioliasis were used for interviewing participants of 15 years old and above. Between 2018 – 2019, a cohort study was carried out in 2 communes in Yen Bai province with 111 individuals being followed up. Besides collecting stool samples to determine the fish-borne trematode (FiBT) eggs, some questions on food consumption history were also recorded. From 2020 – 2021, an intervention-control trial study was conducted with the participation of 344 local people and 297 schoolchildren. The intervention approach included health education activities implemented in the intervention group (Yen Bai province), while no activities were conducted in the control group (Thanh Hoa province) during the intervention period.In the health center-based study, a cross-sectional survey was conducted in 2022 at 14 health centers in Yen Bai and Thanh Hoa provinces. Data collection included information on the laboratory's quality management system and diagnostic activities related to FZT, and data was collected from 28 technicians and 14 laboratory managers. After the survey, a training course on diagnosis of FZT was organized for 30 technicians and managers.Results: Our first cross-sectional study of FZTi conducted in Yen Bai and Thanh Hoa provinces showed a high C. sinensis prevalence rate of 40.4% among 841 participants, with commune prevalence ranging between 26.5% and 53.3%. Risk of infection increased for males (OR=2.00; 95%CI: 1.31 – 3.05), in individuals between 19 to 39 years old (OR=6.46; 95%CI: 1.25 – 33.37), with low education level (OR=5.57; 95%CI: 2.37 – 13.07), lack of treatment (OR=1.82; 95%CI: 1.15 – 2.89), and using an unhygienic toilet (OR=2.74; 95% CI:1.53 – 4.92). The most important risk factor was raw fish consumption during the last year. People who consumed raw fish in the last year had a significantly higher risk for a C. sinensis infection than those who did not (OR=8.00, 95%CI: 4.78 – 13.36). Baseline surveys indicated a low seroprevalence of fascioliasis (2.6%) among communities in Yen Bai and Thanh Hoa, which classified these provinces as mesoendemic areas of the disease. Higher seroprevalence was associated with non-Kinh minority ethnic groups (OR=14.03, 95%CI: 2.39 – 82.17), being farmer (OR=3.42, 95%CI: 1.04 – 11.25), and never heard about fascioliasis (OR=0.3, 95%CI:0.11-0.87).The 13-month follow-up cohort study showed that 20/111 people became infected with FiBT (C. sinensis and MIF), calculated as an incidence rate of 21.4/100 person-years. The incidence risk at months 4, 9, and 13 was 9.0%, 6.4% and 5.1%, respectively. The univariate analysis indicated that consumption of raw fish, being male, and drinking alcohol were the associated risk factors. In the multivariable analysis, only consumption of raw fish dishes was significantly associated with FiBT infection (RR=3.44, 95%CI: 1.11 – 10.70).The intervention study showed that the knowledge of FZTi, mainly focused on clonorchiasis, was poor at the baseline survey in local people and schoolchildren. The health education programs improved clonorchiasis knowledge, attitude and practices for local people and schoolchildren. The people in the intervention group had higher odds for correct knowledge response (OR=2.80, 95%CI=1.84 – 4.27), increased average mean attitude score (Mean=0.363, 95%CI = 0.182 – 0.544), and reduced odds of consuming raw fish (OR=0.15, 95% CI=0.06 – 0.40) compared to those in the control group. Furthermore, people in the intervention group exhibited improved basic knowledge of fascioliasis and MIF infection at post-intervention. For schoolchildren, health education programs showed a significantly increased clonorchiasis knowledge score (Score=6.54, 95%CI = 6.07 – 7.01), an increased average mean attitude score (Mean=0.25, 95%CI = 0.18 – 0.33), and reduced odds of consuming raw fish (OR=0.25, 95%CI: 0.13 – 0.45) in the intervention school compared to the control school at post-intervention versus baseline. The last study of this thesis, the health center–based study, indicated the quality system's limitations in the laboratories of the district health centers and Centers for disease control (CDC) in Thanh Hoa and Yen Bai provinces. The diagnostic capacity of FZTi in those centers was weak. A training course on diagnosis of FZT improved the knowledge and skills of technicians on diagnosis of FZT.Conclusions: FZTi is a public health problem, particularly C. sinensis which has a high prevalence and incidence in Yen Bai and Thanh Hoa provinces. Intervention programs through health education activities effectively improved disease knowledge and changed the risky habit of food consumption. Furthermore, the pilot training course on diagnosis of FZT showed the benefits for technicians on improving their knowledge and skills in performing diagnostic techniques for FZT. For sustained control of FZT, especially clonorchiasis, comprehensive intervention using a One Health/Eco Health approach is a potential strategy. The control program should integrate MDA, health education activities, management of human/animal feces, control of animal-free roaming, and animal deworming.

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