Studies on Measures to Prevent and Control Small Liver Flukes

Humans or livestock used for fish farming can be infected with small liver flukes [55]. Therefore, it is necessary to train, educate and propagate so that managers and people have more knowledge about preventing and controlling SLGN infection. Using fresh manure in aquaculture is one of the important causes of parasitic infections in aquaculture in general and SLGN transmission in particular. Research in Nam Dinh province shows that 26.7% of aquaculture facilities still use fresh manure and 10.0% of farming facilities use fresh unfermented manure to irrigate and fertilize green vegetables, this is a risk factor for spreading parasitic pathogens in the environment [1].

In My Quang commune, Phu My district, Binh Dinh province, the study showed that, in terms of knowledge, 47.7% had general knowledge about SLGN; 62.7% of subjects knew the transmission route, 49.2% knew that the food that causes SLGN infection is crucian carp salad; 61.2% had knowledge about the dangers of SLGN and only 33.5% had knowledge about SLGN prevention. In terms of attitude, the general attitude about SLGN of the subjects was 41.7%. Regarding the dangers of SLGN, 46.3% of subjects had satisfactory attitudes, regarding the ability to prevent and control SLGN, 54.7% of subjects had satisfactory attitudes. In terms of practice, 34.7% had general practice [68].

The two studies mentioned above show that, although different in location and time of study, people's knowledge, attitude and practice on prevention and control of SLGN infection are still low and there is a relationship between gender, knowledge, attitude, eating raw fish, hygienic toilet use and general practice of the subjects with SLGN infection status. The group with satisfactory knowledge, attitude and practice has a lower rate of SLGN infection than the group that does not meet the requirements [39, 68]. Therefore, it is necessary to promote information, education and communication on SLGN prevention and control to improve knowledge, attitude and practice on SLGN prevention for the community.

- Eating raw or undercooked fish

In Vietnam, the Northern Delta region has the custom of eating raw fish salad such as carp, silver carp, and grass carp in thin slices. Some central provinces have the custom of eating raw crucian carp in the form of eating the whole fish swimming in a bowl, also known as

Fish salad [9, 12]. Eating habits are formed under specific economic and social conditions [101]. A survey of 1,612 people in 7 communes of 3 districts of Hai Hau, Nghia Hung and Giao Thuy, Nam Dinh province showed that 54.8% had eaten fish salad. The rate of eating fish salad in men (80.7%) was higher than that of women (29.8%). Fish salad is a favorite dish of people in this area, up to 41% of people think it is delicious; 26.7% is due to habit and 32.6% is because it is cool and nutritious. The favorite fish to make fish salad to eat at the survey points is silver carp (51.0%). Regarding the source of fish used to make salad, the research results showed that 71.2% of respondents answered that they took fish from their pond to make salad to eat, fish bought at the market to make salad to eat accounted for only 12.8%. 4.9% of people make fish salad from seawater fish or brackish water fish, 35.1% of respondents said they have ever eaten undercooked fish (fish hotpot, grilled fish, dipped fish, steamed fish, fried fish) [46]. In Hoa Nghia ward, Duong Kinh district, Hai Phong city, the percentage of respondents who have the habit of eating undercooked shrimp, crab, and fish is 62.16% [17]. The percentage of people eating fish salad in Yen Loc and Tan Thanh communes, Kim Son district, Ninh Binh province is 75% [62]; The percentage of managers and people in 4 coastal communes of Tien Hai district, Thai Binh province who have ever eaten fish salad is 90.2% and 11.4%, respectively [58]. In Nga An commune, Nga Son district, Thanh Hoa province in 2004, the rate of eating raw fish was 68.8% [39], in 2014 the rate of eating raw fish was 45.5% [66]. In My Quang commune, Phu My district, Binh Dinh province, the rate of eating raw fish was 37.7%, 62.1% of people ate raw fish 5 times or more per year [68]. The habit of eating raw fish increased the risk of C. sinensis infection by 53 times; 3% of people interviewed did not eat raw fish but were still infected with SLGN, this may be due to sharing utensils for preparing raw food and food used for immediate consumption. The study's recommendation is that a simple dietary questionnaire could be used to screen people living in areas where SLGN is endemic, allowing for large-scale treatment with praziquantel to avoid the time-consuming and costly process of stool testing for SLGN eggs. The study also showed that hygienic food preparation and eating practices are important in the prevention and control of SLGN [64].

- Use the same utensils to prepare raw and cooked food

In 2010, a survey by the United Nations Children's Fund showed that in 64 provinces and cities in Vietnam, 46% of people used the same utensils to prepare raw food, cooked food, and food for immediate consumption [132]. Another survey in Dak Lak found that 73 people who did not eat raw fish salad were also infected with SLGN. Thus, even though they did not eat raw fish salad, if they ate undercooked fish or used the same utensils to prepare raw fish such as knives, cutting boards, etc. with food for immediate consumption, they could also be infected with SLGN [19].

- Using fresh human and animal manure to fertilize fields and raise fish

Many communities in Vietnam still have the custom of using human and livestock feces to raise fish and fertilize crops. This practice is even more dangerous in communities with many people suffering from SLGN and eating raw fish. Because this practice has actively spread SLGN. In Nga An commune, Nga Son district, Thanh Hoa province, out of a total of 241 households using feces, only 14.5% treat feces hygienically. Of which, the number of households with hygienic latrines accounts for only 29.6% [39]. A study in 3 coastal districts of Nam Dinh province showed that the percentage of households with hygienic flushing latrines is 39.3%, while 1.7% of households still use human feces and 9.9% of households use poorly composted manure to raise fish [46].

1.7. Studies on measures to prevent and control small liver flukes

Prevention and control of Fascioliasis often involves a combination of two or more measures including health promotion, treatment, and environmental improvement [138]. The strategies for prevention and control of Fascioliasis proposed by the US Centers for Disease Control and Prevention (CDC), WHO, and the National Health and Family Planning Commission of China (NHFPC) are as follows:.

Table 1.1. Strategies for prevention and control of fascioliasis

Organization

propose

Content

References

survey

CDC

Do not eat raw, undercooked freshwater fish. Cook fish thoroughly (Temperature about > 63 o C), refrigerate.

(≤ -20 o C for 7 days; ≤ -35 o C for 15 hours)

http://www.cdc.gov

/parasites/clonorchi s/faqs.html [80]

Maybe you are interested!

Organization

propose

Content

References

survey

WHO

Recommend public health measures, veterinary hygiene and food safety practices to reduce the risk of SLGN infection, and enhance the safety and efficacy of anthelmintics to control the infestation.

disease

http://www.who.int

/mediacentre/factsh eets/fs368/en/[137]

NHFPC

Increase coverage of standard anthelmintic drugs and hygienic latrines; increase knowledge about parasite prevention and control and health-protective behaviors; and improve the qualifications of primary health care workers.

http://www.nhfpc.g ov.cn/zhuzhan/zcjd

/201304/cba68ffe5 44c4902bd48b1cd7 d41e733.shtml

[114]

- Treatment for people infected with small liver flukes

SLGN can be effectively treated with praziquantel if diagnosed early and the SLGN species is correctly identified [84].

According to WHO recommendations, treatment with a dose of 25 mg/kg three times daily for two consecutive days can achieve a cure rate of 93.9–100% [100, 139].

In China, a project to control SLGN in an endemic area in China during 2001-2004, selected treatment groups were residents who tested positive for eggs in their stools and those who tested positive were treated with 25 mg/kg x 3 times/day x 1 day of praziquantel approximately 5 hours apart each dose for 1 day for all residents treated in the mass treatment groups. In high-endemic areas, mass treatment twice for all residents in 2001 and 2003 reduced prevalence from 69.5% to 18.8%, while mass treatment four times annually reduced prevalence from 48.0% in 2001 to 8.4% in 2004. Selective annual treatment of egg-positive subjects reduced egg-positive prevalence from 54.9% in 2001 to 15.0% in 2004 and from 73.2% in 2001 to 12.3% in 2004. Selective treatment every 6 months reduced prevalence from 54.9% in 2001 to 15.0% in 2004 and from 73.2% in 2001 to 12.3% in 2004.

Notably, prevalence decreased from 59.5% in 2001 to 7.5% in 2004. All subjects who received repeat treatment had a significant reduction in egg/gram stool. Annual mass treatment and 6-monthly selective treatment reduced prevalence, reinfection rates, and egg reduction rates more than annual selective treatment. In moderately endemic areas, egg positivity rates were 24.8% and 29.7% in 2001 but were 1.9% and 1.3% after 2 or 3 selective treatments. Prevalence, incidence, and reinfection rates in a moderately endemic area were significantly lower than those in highly endemic areas. Studies have shown that repeated mass treatment or selective treatment with praziquantel followed by 6- to 12-month repeat treatment is highly effective for SLGN prevention in areas with severe epidemics. In contrast, selective treatment once or twice with health education is effective in areas with moderate epidemics [87].

In North Korea, a program involving repeated praziquantel treatments at 6-month intervals was implemented in a village, and the prevalence of SLGN decreased from 22.7% (in 1994) to 6.3% (in 1998), but treatment alone was not sufficient to achieve complete control of SLGN [84]. Praziquantel has sometimes failed to reduce SLGN prevalence in the poor, despite long-term repeated treatment [131]. In North Korea, the prevalence of C. sinensis remains high because case detection in the community is difficult and detected cases are often not completely cured due to treatment failure. Research on SLGN prevention and control by praziquantel treatment with repeat treatment after 6 months, through stool testing, the positive rate for tapeworm eggs was 22.7%, but decreased to 19.6% after 6 months, 15.1% after 12 months, 12.2% after 18 months.

months, 6.3% at 24 months, 11.4% at 30 months, and 6.3% at 42 months from the start of repeat praziquantel treatment [93].

In Laos, a study was conducted in 2006-2010 on 217 patients who visited the Department of Infectious Diseases, Hospital 103, Vientiane, Laos. Group 1 followed regimen A (praziquantel 75mg/kg for 1 day divided into 3 doses, taken 6-8 hours apart), group 2 followed regimen B (praziquantel 25mg/kg/day for 3 consecutive days, taken at a certain time of day). The rate of egg clearance in regimen A at the following times:

after 7 days, after 1 month, after 3 months, after 6 months are: 90.74%; 95.37%; 96.30% and

97.22%, while regimen B was: 72.48%; 71.56%; 88.99% and 87.16%. Patients treated with the 2 regimens experienced undesirable effects such as: hot flashes, fatigue, nausea, abdominal cramps, dizziness, abdominal pain and headache. Regimen A with the corresponding rates: 54.63%; 30.56%; 28.70%; 27.78%; 21.30%; 12.04% and 8.33%. Regimen

Figure B: 55.95%; 44.95%; 24.77%; 26.61%; 25.69%; 9.17% and 5.50%. Treatment efficiency

Treatment regimen A at 3 schools in Champhon district, Savanakhett, Laos: egg-free rate after 7 days, after 1 month, after 3 months, after 6 months was: 74.46%; 94.81%; 82.25% and 48.48%. Undesirable effects were mild and transient; decreased gradually with subsequent doses and disappeared within 60 minutes after taking the drug [50].

In Vietnam, in 1997, a study conducted in Northern Vietnam achieved only a 29% cure rate after treating SLGN patients with praziquantel 25 mg/kg x 1 time/day x 3 days; this dose of praziquantel may be inappropriate [131]. In addition, transient side effects including dizziness, headache, vomiting, drowsiness, diarrhea, headache, and allergies can occur after taking praziquantel [80,106,120]. Studies using a dose of praziquantel 25 mg/kg divided 3 times/day x 3 days resulted in 80-100% egg clearance [10]. Treatment with praziquantel 25 mg/kg x 3 times/day x 1 day is highly effective in treating C. sinensis in the field with an egg clearance rate of over 96% and egg reduction of over 99% after 6 months of intervention. The above regimen applied to the community is safe and stable over many years, easy to apply and accepted by the community [62]. Research on the treatment effectiveness of specific drugs shows that the treatment of liver flukes with delagyl 0.5g/day x 10 days x

2 courses, 45% clean eggs; cloxyl 3g/day x 5 days, 70% clean eggs; azinox 25mg/kg/day x 3 days, 51% clean eggs; medamin 10mg/kg/day x 5 days, 19% clean eggs; mebendazole 10mg/kg/day x 5 days, 11.6% clean eggs; artemisinin 500mg/day x 5 days, 28.6% clean eggs; Praziquantel 25mg/kg/day x 3 days, 65-91% cured. Partial intervention with specific treatment significantly reduced liver fluke infection. Treatment once a year reduced the rate of liver fluke infection from 27.4% to 23.9% after one year and to 11.8% after two years. The infection intensity decreased from 1167 eggs/g feces to 671 eggs/g feces after one year and to 431 eggs/g feces after one year.

eggs/g of feces after 2 years. Treatment once every two years reduced the liver fluke infection rate from 29.6% to 19.1% after two years and to 10.3% after four years, the infection intensity did not change significantly (448 eggs/g of feces compared to 437 eggs/g of feces). Treatment once every three years reduced the liver fluke infection rate from 36.9% to 29.2%, the infection intensity changed significantly (303 eggs/g of feces compared to 321 eggs/g of feces) [20]. According to research by the Central Institute of Malaria - Parasitology - Entomology, drugs in the Benzimidazole group were used in the treatment of SLGN with low results, specifically: medamin 10mg/kg/day x 5 days, the result of egg clearance was 19%; mebendazole 10mg/kg/day x 5 days, the result of egg clearance was 11.6%; albendazole 400mg/kg/day x 3 days after 6 months, the result was 37.5% egg clearance, 45.6% egg reduction rate [22]. Praziquantel dose 25 mg/kg x 3 times/day x 1 day was highly effective in treating C. sinensis SLGN in the field with an egg clearance rate of over 96% and egg reduction of over 99% after 6 months of intervention [62].

Table 1.2. Studies on treatment regimens and drugs for small liver flukes

Medication

Dosage	Information about disease	Effective treatment	Reference survey
Praziquantel	For oral use, 18.8 mg/kg x 2 times/day x 2 days	Co-infection with other worms	Cure Rate (TLKB): 56.8% (times) 1) and 75% (2nd time).	[141]
	For oral use, 25mg/kg x 3 times/day x 1 day	No other worms	TLKB: 56%	[119]
	For oral use, 25mg/kg x 3 times	Not infected other worms	TLKB: 62.9%	[86]

Medication

Dosage	Information about disease	Effective treatment	Reference survey
Tribendimidine	For oral use, 400 mg single dose	Co-infection with other worms	TLKB: 50% (first time); 78.1% (times) 2).	[141]
	For oral use, 200 mg x 2 times x 1 day	Copper other worm infections	TLKB: 33%	[141]
	For oral use, 400 mg single dose	Not infected other worms	TLKB: 44%	[119]
Mebendazole	For oral use, 400 mg single dose	Co-infection with other worms	TLKB: 0% (first time); 78.1% (times) 2).	[141]

- Food hygiene measures

SLGN is mainly related to eating habits that are rooted in cultural and social traditions. Therefore, to prevent the disease, new methods are needed to communicate to the community about food selection, food preparation and food processing. Diagnosis and treatment are only part of SLGN control because diagnosis and treatment themselves will only have a short-term impact without a good prevention program[82].

In Thailand, a 10-year SLGN control program, in addition to other efforts to eliminate the habit of eating raw fish in northeastern Thailand, was implemented to reduce the regular consumption of raw fish by half, but the occasional consumption of raw fish remained unchanged [100]. This is the reason for the persistence of SLGN infection in the community and the high rate of reinfection with SLGN after treatment without communication and education measures.

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