Abstract
Background
Praziquantel is the only drug recommended against Clonorchis sinensis, while adverse events are usually high. Albendazole is documented in treatment of clonorchiasis, but the evidence is low due to lack of high-quality randomized controlled trials.
Methods
We did an exploratory randomized controlled trial in Binyang county, Guangxi, China. Eligible participants were adults aged 18–70 years with C. sinensis infection. Patients with light intensity (eggs per gram of feces (EPG): 1-999) and moderate plus heavy intensity (EPG: ≥ 1000) were randomly assigned to treatment groups respectively, with block sizes of two, four, and six, to receive praziquantel (25 mg/kg three times a day for 1 day) or albendazole (400 mg twice a day for 4 days) in a 1:1 ratio. Laboratory diagnosis technicians were blinded to group assignment. We assessed efficacy as cure rate and egg reduction rate in available-case analysis, while adverse events were also analyzed.
Results
Fifty-two patients with light intensity and 50 with moderate plus heavy intensity were assigned, when three were lost to follow-up. The cure rate was 84.0% (21/25, 95% confidential intervals: 63.9%-95.5%) using praziquantel and 30.8% (8/26, 14.3%-51.8%) using albendazole in light intensity stratum (χ²=14.7, p < 0.001). It was 60.9% (14/23, 38.5%-80.3%) using praziquantel and 8.0% (2/25, 1.0%-26.0%) using albendazole in moderate plus heavy intensity stratum (χ²=15.1, p < 0.001). The corresponding egg reduction rate using geometric mean of EPG was 99.9% (99.7%-100.0%), 97.1% (94.1%-98.8%), 100.0% (99.9%-100.0%), and 98.9% (97.8%-99.5%), respectively. The overall cure rate was 72.9% (35/48, 58.2%-84.7%) in praziquantel groups and 19.6% (10/51, 9.8%-33.1%) in albendazole groups (χ²=28.3, p < 0.001), while the corresponding egg reduction rate was 99.9% (99.8%-100.0%) and 98.3% (97.1%-99.1%). The proportion of adverse events was higher in praziquantel than albendazole in light intensity stratum (46.2% vs. 15.4%), while there was no difference in moderate plus heavy intensity stratum (20% vs. 20%). The overall proportion was 33.3% in praziquantel groups and 17.6% in albendazole groups.
Conclusions
Albendazole (400 mg twice a day for 4 days) demonstrates high egg reduction rate and low adverse events, but low cure rate in C. sinensis infection. Its application in preventive chemotherapy for morbidity control deserves further exploration.
Trial registration
Controlled-Trials.com, ISRCTN46268871.
Supplementary Information
The online version contains supplementary material available at https://doi.org/10.1186/s12916-026-05071-9.
Keywords: Albendazole, Adverse events, Clonorchis sinensis, Cure rate, Egg reduction rate, Praziquantel
Background
Clonorchiasis is caused by the ingestion of raw freshwater fish containing infective metacercariae of Clonorchis sinensis, which belongs to food-borne trematodes [1, 2]. C. sinensis infection results in diverse symptoms and morbidities, e.g., cholelithiasis, cholangitis, cholecystitis, and especially fatal cholangiocarcinoma [3–5]. Globally, a conservative estimation of 13.24 million people is infected with C. sinensis, distributing in China, South Korea, northern Vietnam, and far east part of Russia [6–8]. Due to the high prevalence and morbidity, chemotherapy is currently the mainstay in tackling clonorchiasis. The World Health Organization (WHO) aims to intensify the control of clonorchiasis and other food-borne trematodiases in endemic countries, in which preventive chemotherapy is the core [9]. Only praziquantel is now recommended for clonorchiasis treatment by WHO and the US Food and Drug Administration [10]. The regimens of 25 mg/kg 3 times daily for 2–3 consecutive days and single dose of 40 mg/kg are recommended [10]. However, a regimen of 25 mg/kg 3 times daily for 1 day is usually employed in endemic areas owing to the simplicity and high efficacy [11, 12]. On one hand, there is some concern that this strategy might result in the development and spread of drug-resistant parasites [13]. On the other hand, praziquantel could cause high adverse events, which weakens the adherence especially in preventive chemotherapy [14]. There reported that high dose of albendazole is efficacious against C. sinensis, while adverse events are low [15]. Indeed, albendazole is recommended as an alternative drug for clonorchiasis by the US Centers for Disease Control and Prevention [16]. Especially, albendazole (usually 400 mg twice a day for 4 days) is employed in some clonorchiasis-endemic areas in China [17, 18]. This regimen showed a cure rate of 90.1% in a clinical trial [19], but in a network meta-analysis the cure rate was estimated at only 64.2% while other potential covariates were considered [20]. Overall, the evidence of albendazole against C. sinensis is inadequate, due to the unavailability of randomized controlled trials using head-to-head comparator of praziquantel [20].
This study aimed to evaluate the performance of albendazole against C. sinensis through an exploratory open-label phase 2 randomized controlled trial, in which strict diagnostic methods would be employed and the infection intensity difference also considered. For albendazole, we adopted a dose of 400 mg twice a day for 4 days, because its application in field [17, 18], differential results from literatures [19, 20], and advantage in high compliance and low cost compared to the long-term regimens (e.g. 400 mg twice a day for 7 days) [21]. Praziquantel with a regimen of 25 mg/kg 3 times daily for 1 day was used as a comparator.
Methods
Participants
This study was conducted between 2 April and 17 May, 2025, in Shangshi village, Zhonghua township, Binyang county, Guangxi Zhuang Autonomous Region, China. Eligible individuals were adults of both sexes, aged between 18 and 70 years old, while the following C. sinensis diagnostic criteria were met: they provided two stool samples and had one C. sinensis egg in at least two of three Kato–Katz thick smears from each sample.
During the clinical examination by physicians, villagers who had no major systemic, acute, or chronic illnesses, no known or reported psychiatric or neurological disorders, or hypersensitivity to praziquantel or albendazole, were invited to participate in the study. Individuals were excluded if they had used any anthelmintic within the past month, were attending other clinical trials during the same period, or were pregnant female.
The study was approved by the Ethical Review Committee of National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research) (ref: 2024-009). Written informed consents were obtained from all participants. This trial was registered with isrctn.com on 27 February 2025, number ISRCTN46268871 (https://www.isrctn.com/ISRCTN46268871).
Randomization and masking
According to the baseline eggs per gram of feces (EPG), individuals were classified into two strata, namely light intensity stratum (EPG: 1–999) and moderate plus heavy intensity stratum (EPG: ≥1000; 1000–9999 for moderate, and ≥ 10 000 for heavy) [22]. Using a computer-generated randomization, participants were assigned 1:1 to receive either praziquantel (25 mg/kg 3 times daily for 1 day) or albendazole (400 mg twice a day for 4 days) in each intensity stratum. The allocation sequences were separately generated using random blocks with block sizes of two, four or six for the two intensity strata. Treatment assignment envelopes were numbered and stacked chronologically, separated by two intensity strata. According to the participant’s infection intensity, the envelope on top was chosen after the participant’s eligibility was confirmed.
The randomization sequences were prepared by an independent statistician. Participants, study pharmacologist and clinicians were not masked to treatment allocation, but the laboratory technicians were blinded throughout the study.
Procedures
Villagers with a history of ingesting raw freshwater fish were invited and provided container labelled with their participant identification number and name. Two stool samples were collected from each participant within one week and examined for the presence of C. sinensis eggs using the Kato–Katz method with 41.7 mg templates [23]. Three smears were examined for each sample and independently read quantitatively by three different technicians. The individuals with C. sinensis egg in at least two of three smears in both samples were eligible, and underwent full clinical examination by experienced physicians for the presence of any acute and chronic disease. Measurements of height (measured to the nearest 0.5 cm), weight (measured to the nearest 0.1 kg), blood pressure (measured with a sphygmomanometer to the nearest 1 mm Hg) were done. Additionally, forehead temperature (measured with battery-powered thermometers to the nearest 0·1 °C) was measured, and axillary temperature was measured again by mercury thermometer if forehead temperature was abnormal. Urine samples were collected from female participants for pregnancy test using a colloidal gold immunochromatography.
Praziquantel was purchased from Nanjing Pharmaceutical Factory Co, Ltd (China, 200 mg tablet), while albendazole from Sino-American Tianjin SmithKline and French Lab., Ltd (China, 200 mg tablet). Praziquantel was given as 25 mg/kg 3 times a day for 1 day, and albendazole as 400 mg twice a day for 4 days. All tablets were administered in the presence of the investigator and ingestion confirmed, of which the time and date were recorded. Vomiting within 1-hour post-dosing required re-dosing. The subjects would not be allowed more than one repeated dose. No re-administration would be needed for subjects vomiting after 1 h. The subjects came back to the treatment site and received the assessment on adverse events by the clinicians 3 h and 24 h after dosing (Additional file 1: Fig. S1). Some completed the assessment through telephone. The individuals reporting adverse events were examined carefully by the clinicians and, when necessary, medical action taken on the spot or patients referred to a nearby hospital. Adverse events were graded (i.e., mild, moderate, and severe), and recorded in the case report forms. At the endpoint (three–four weeks after treatment), another two stool samples were collected and examined as the baseline.
Outcomes
The primary outcomes of this study were the cure status and egg reduction of C. sinensis. The secondary outcome was the occurrence of adverse events.
Statistical analysis
All data were double entered with EpiData software (version 3.1). Statistical analyses were done with R (version 4.1.2). We aimed to recruit 25 individuals in each treatment group, a commonly used sample size for exploratory phase 2 trials [22, 24, 25]. Thus, the overall sample size was 100 participants, with 50 ones in per intensity stratum. We did available-case analysis of all participants with primary endpoint data. The two treatment groups in same infection intensity stratum (namely light, and moderate plus heavy) were first compared respectively, and then data from the same treatment regimen in different strata were combined and compared. EPG was calculated by multiplying the mean of the egg counts from the six Kato-Katz thick smears by a factor of 24. Cure rate is defined as the proportion of participants who turned from egg-positive to egg-negative, while egg reduction rate as the percentage reduction of geometric mean (GM) or arithmetic mean of EPG. Geometric mean egg reduction rate was calculated as follows: [26]
 |
Where ERRGM represents the geometric mean egg reduction rate. Pearson’s χ² test was employed to compare the cure rate in different groups, while 95% confidential intervals (95% CI) were calculated. To estimate the 95% CI for egg reduction rate, bootstrap resampling was adopted with 5000 replicates. For two-sided tests, significance was defined as p less than 0.05.
Results
Basic profiles of participants
Totally, 189 participants were first assessed for the enrolment. Among them, 145 met the infection criteria, of which 71 belonged to light intensity stratum and 74 moderate plus heavy intensity stratum (Fig. 1). Finally, 52 were included in light intensity stratum (26 in praziquantel group and 26 in albendazole group), and 50 in moderate plus heavy intensity stratum (25 in praziquantel group and 25 in albendazole group). Three individuals had heavy intensity, of which two were assigned to albendazole and one to praziquantel.
Fig. 1.
Consolidated Standards of Reporting Trials (CONSORT) flow diagram
Three persons from praziquantel group in light intensity stratum demonstrated moderate adverse events after taking the second dose of praziquantel, and thus the third dose was adjusted to the second day morning when the symptoms were alleviated. One person from albendazole group in moderate plus heavy intensity stratum presented with periodontitis. Although it was judged not related to the medicine, albendazole treatment was discontinued after four doses. Stool samples of these four individuals were collected at the follow-up, and hence they were included in the available-case analysis. During follow-up, three individuals from praziquantel groups (one in light intensity and two in moderate plus heavy intensity) were lost to follow up due to working outside.
Overall, the baseline characteristics of treatment groups were comparable (Table 1). However, in light intensity stratum, the mean of EPG of albendazole group was higher than that of praziquantel group (Table 2).
Table 1.
Baseline demographic and clinical characteristics
| Parameter | Light intensity | Moderate plus heavy intensity | Total | |||
|---|---|---|---|---|---|---|
| Praziquantel | Albendazole | Praziquantel | Albendazole | Praziquantel | Albendazole | |
| Males/females (N) | 21/5 | 20/6 | 23/2 | 24/1 | 44/7 | 44/7 |
| Mean (SD) age, years | 55.7 (7.0) | 51.9 (10.5) | 55.3 (6.5) | 51.2 (8.0) | 55.5 (6.7) | 51.6 (9.3) |
| Mean (SD) weight, kg | 62.9 (9.2) | 64.0 (10.6) | 65.4 (8.7) | 68.2 (8.7) | 64.1 (9.0) | 66.1 (9.9) |
| Mean (SD) height, cm | 163.7 (7.5) | 164.2 (8.5) | 166.0 (5.8) | 167.9 (6.9) | 164.8 (6.8) | 166.0 (7.9) |
| Median (Q1, Q3) of eggs per gram of feces | 204 (168, 366) | 382 (213, 633) | 3888 (1656, 5480) | 3240 (1604, 5756) | 884 (204, 3822) | 984 (382, 3148) |
| Range of eggs per gram of feces | 40–884 | 24–984 | 1208–18,456 | 1128–13,748 | 40–18,456 | 24–13,748 |
Table 2.
Cure rates and egg reduction rates of praziquantel and albendazole
| Light intensity | Moderate plus heavy intensity | Total | ||||
|---|---|---|---|---|---|---|
| Praziquantel (n = 25) | Albendazole (n = 26) | Praziquantel (n = 23) | Albendazole (n = 25) | Praziquantel (n = 48) | Albendazole (n = 51) | |
| Participants cured after treatment | 21 | 8 | 14 | 2 | 35 | 10 |
| Cure rate (95% confidential intervals, %) | 84.0 (63.9–95.5) | 30.8 (14.3–51.8) | 60.9 (38.5–80.3) | 8.0 (1.0–26.0) | 72.9 (58.2–84.7) | 19.6 (9.8–33.1) |
| Geometric mean of EPG | ||||||
| Before treatment | 226.0 | 350.4 | 3318.3 | 3198.9 | 819.9 | 1036.6 |
| After treatment | 0.3 | 9.7 | 1.4 | 31.2 | 0.7 | 17.3 |
| Egg reduction rate (%) | 99.9 (99.7–100.0) | 97.1 (94.1–98.8) | 100.0 (99.9–100.0) | 98.9 (97.8–99.5) | 99.9 (99.8–100.0) | 98.3 (97.1–99.1) |
| Arithmetic mean of EPG | ||||||
| Before treatment | 290.7 | 461.1 | 4332.7 | 4216.6 | 2227.5 | 2302.0 |
| After treatment | 0.8 | 66.5 | 4.0 | 175.5 | 2.3 | 119.9 |
| Egg reduction rate (%) | 99.7 (99.4–100.0) | 85.7 (76.4–93.6) | 99.9 (99.8–100.0) | 95.7 (90.7–98.8) | 99.9 (99.8–100.0) | 94.6 (90.0-97.6) |
One person from praziquantel group in light intensity and two from praziquantel group in moderate plus heavy intensity were lost to follow up due to working outside
Efficacy
In the available-case analysis, the cure rate of praziquantel group in light intensity stratum was 84.0% (21/25, 95% CI: 63.9%-95.5%), higher than that of albendazole group (30.8%, 8/26, 95% CI: 14.3%-51.8%) (χ²=14.7, p < 0.001) (Table 2). The cure rate of praziquantel group in moderate plus heavy intensity stratum was 60.9% (14/23, 95% CI: 38.5%-80.3%), also higher than that of albendazole group (8.0%, 2/25, 95% CI: 1.0%-26.0%) (χ²=15.1, p < 0.001). In total, the cure rate was 72.9% (35/48, 95% CI: 58.2%-84.7%) in praziquantel groups, and 19.6% (10/51, 95% CI: 9.8%-33.1%) in albendazole groups (χ²=28.3, p < 0.001). The three individuals with heavy intensity were all uncured.
The egg reduction rate using geometric mean of EPG was 99.9% (95% CI: 99.7%-100.0%) in praziquantel group of light intensity, 97.1% (95% CI: 94.1%-98.8%) in albendazole group of light intensity, 100.0% (95% CI: 99.9%-100.0%) in praziquantel group of moderate plus heavy intensity, and 98.9% (95% CI: 97.8%-99.5%) in albendazole group of moderate plus heavy intensity. Totally, the egg reduction rate was 99.9% (95% CI: 99.8%-100.0%) in praziquantel groups and 98.3% (95% CI: 97.1%-99.1%) in albendazole groups.
Safety
In light intensity stratum, the proportion of individuals with adverse events was 46.2% (12/26) in praziquantel group and 15.4% (4/26) in albendazole group. In moderate plus heavy intensity stratum, the proportion was 20% (5/25) in praziquantel group and 20% (5/25) in albendazole group (Table 3). Totally, the proportion was 33.3% (17/51) in praziquantel groups and 17.6% (9/51) in albendazole groups.
Table 3.
Adverse events of praziquantel and albendazole
| Light infection | Moderate and heavy infection | Total | ||||
|---|---|---|---|---|---|---|
| Praziquantel (n = 26) | Albendazole (n = 26) | Praziquantel (n = 25) | Albendazole (n = 25) | Praziquantel (n = 51) | Albendazole (n = 51) | |
| Headache | ||||||
| None | 26 (100.0%) | 24 (92.3%) | 25 (100.0%) | 25 (100.0%) | 51 (100.0%) | 49 (96.1%) |
| Mild | 0 (0.0%) | 2 (7.7%) | 0 (0.0%) | 2 (3.9%) | ||
| Vertigo | ||||||
| None | 20 (76.9%) | 26 (100.0%) | 22 (88.0%) | 25 (100.0%) | 42 (82.4%) | 51 (100.0%) |
| Mild | 5 (19.2%) | 0 (0.0%) | 3 (12.0%) | 0 (0.0%) | 8 (15.7%) | 0 (0.0%) |
| Moderate | 1 (3.8%) | 0 (0.0%) | 1 (2.0%) | 0 (0.0%) | ||
| Abdominal pain | ||||||
| None | 26 (100.0%) | 25 (96.2%) | 25 (100.0%) | 24 (96.0%) | 51 (100.0%) | 49 (96.1%) |
| Mild | 0 (0.0%) | 1 (3.8%) | 0 (0.0%) | 1 (4.0%) | 0 (0.0%) | 2 (3.9%) |
| Fatigue | ||||||
| None | 20 (76.9%) | 26 (100.0%) | 21 (84.0%) | 23 (92.0%) | 41 (80.4%) | 49 (96.1%) |
| Mild | 6 (23.1%) | 0 (0.0%) | 4 (16.0%) | 2 (8.0%) | 10 (19.6%) | 2 (3.9%) |
| Allergic reactions | ||||||
| None | 25 (96.2%) | 26 (100.0%) | 25 (100.0%) | 25 (100.0%) | 50 (98.0%) | 51 (100.0%) |
| Moderate | 1 (3.8%) | 0 (0.0%) | 1 (2.0%) | 0 (0.0%) | ||
| Nausea | ||||||
| None | 22 (84.6%) | 26 (100.0%) | 25 (100.0%) | 25 (100.0%) | 47 (92.2%) | 51 (100.0%) |
| Mild | 3 (11.5%) | 0 (0.0%) | 3 (5.9%) | 0 (0.0%) | ||
| Moderate | 1 (3.8%) | 0 (0.0%) | 1 (2.0%) | 0 (0.0%) | ||
| Vomitting | ||||||
| None | 26 (100.0%) | 26 (100.0%) | 25 (100.0%) | 25 (100.0%) | 51 (100.0%) | 51 (100.0%) |
| Diarrhoea | ||||||
| None | 26 (100.0%) | 25 (96.2%) | 25 (100.0%) | 25 (100.0%) | 51 (100.0%) | 50 (98.0%) |
| Mild | 0 (0.0%) | 1 (3.8%) | 0 (0.0%) | 1 (2.0%) | ||
| Fever | ||||||
| None | 26 (100.0%) | 26 (100.0%) | 25 (100.0%) | 25 (100.0%) | 51 (100.0%) | 51 (100.0%) |
| Palpitation | ||||||
| None | 26 (100.0%) | 26 (100.0%) | 24 (96.0%) | 25 (100.0%) | 50 (98.0%) | 51 (100.0%) |
| Mild | 1 (4.0%) | 0 (0.0%) | 1 (2.0%) | 0 (0.0%) | ||
| Abdominal distension | ||||||
| None | 26 (100.0%) | 24 (92.3%) | 25 (100.0%) | 23 (92.0%) | 51 (100.0%) | 47 (92.2%) |
| Mild | 0 (0.0%) | 2 (7.7%) | 0 (0.0%) | 2 (8.0%) | 0 (0.0%) | 4 (7.8%) |
| Total | ||||||
| None | 14 (53.8%) | 22 (84.6%) | 20 (80.0%) | 20 (80.0%) | 34 (66.7%) | 42 (82.4%) |
| Mild | 9 (34.6%) | 4 (15.4%) | 5 (20.0%) | 5 (20.0%) | 14 (27.5%) | 9 (17.6%) |
| Moderate | 3 (11.5%) | 0 (0.0%) | 3 (5.9%) | 0 (0.0%) | ||
For the single event, the higher intensity was calculated when an individual presented with same symptom with different intensities in different observation times; for the total event, the higher intensity was calculated when an individual presented with same symptom with different intensities in different observation times and/or different symptoms with different intensities. One participant from albendazole group in moderate plus heavy intensity presented with periodontitis which was judged not related to the medicine discontinued taking albendazole after four doses
Most adverse events were mild. However, three individuals from praziquantel group in light intensity stratum (11.5%, 3/26) demonstrated moderate adverse events. Major adverse events in praziquantel groups included fatigue (19.6%, 10/51), vertigo (17.6%, 9/51), and nausea (7.8%, 4/51), while that in albendazole groups were abdominal distension (7.8%, 4/51).
Discussion
This study demonstrates moderate cure rate and high egg reduction rate of praziquantel (25 mg/kg 3 times a day for 1 day), and high egg reduction rate but low cure rate of albendazole (400 mg twice a day for 4 days), as well as the relatively lower adverse events of albendazole compared to praziquantel. Furthermore, it is also revealed that cure rate is influenced by the infection intensity in both drugs.
Praziquantel administrated 25 mg/kg three times a day for 1 day is usually adopted owing to the relative simplicity and lower adverse events compared to the higher doses [11, 12]. This is important in preventive chemotherapy, in which coverage and compliance of drug administration determine the effectiveness of control [27, 28]. The moderate cure rate and high egg reduction rate of praziquantel (25 mg/kg three times a day) demonstrated in this study is consistent to the reports in other studies. The overall cure rate of 72.9% (58.2%-84.7%) is consistent to the combined cure rate of 79.8% (53.6%–93.1%) revealed in a systematic review which included six trials using praziquantel (25 mg/kg three times a day) [20]. Higher cure rate was also demonstrated in light intensity as in other studies [14, 22]. A low cure rate was demonstrated in albendazole (400 mg twice a day for 4 days) in this study, which is not consistent to the findings (> 90% cure rate) showed in other studies [17, 19]. However, it is not quite astonishing, because those studies usually didn’t use strict diagnosis techniques and praziquantel as head-to-head comparator. Strict diagnosis methods impact the detection sensitivity, especially in low intensity as post-treatment [29, 30]. Furthermore, the examination of a single stool doesn’t take in to account day to day variability in egg output. In our study, two stool samples were collected, and three Kato-Katz smears were prepared for each sample, which were read respectively and blindly by three technicians. The egg reduction rate is high in both praziquantel and albendazole. The number of EPG indicates the burden of worms, which is directly related to the morbidities [4, 31]. Thus, a high egg reduction rate but low cure rate could also be valuable in control of the morbidities. Additionally, the individuals with C. sinensis infection are transmission source in completing the life cycle, and thus a significant decrease in egg output will contribute to the decrease of environmental contamination and subsequent re-infection.
Adverse events impact the compliance in taking drugs in control of helminthiases including clonorchiasis [32, 33]. Thus, the occurrence of adverse events is also an important indicator in assessing drugs. The proportion of adverse events in praziquantel was relatively higher, and nervous system was involved in with fatigue and vertigo as the two most important types, which is consistent to other studies [14, 19]. A relatively lower proportion of adverse events was demonstrated in albendazole, which shows the good tolerability of albendazole [17]. Unlike praziquantel, digestion system is usually affected in albendazole, which is also demonstrated in this study [34, 35]. The proportion of adverse events using albendazole was similar in the two strata, namely light vs. moderate plus heavy intensity, but it is a little confused that the proportion was higher in praziquantel group from light intensity stratum than from moderate plus heavy intensity stratum. We argued that high intensity means a long accumulation of infection and thus patients probably develop an adaptation to the worms as well as subsequent deworming. Moderate adverse events were only presented in three individuals taking praziquantel. Especially, one case experienced hypersensitive reaction. Hypersensitive reaction to praziquantel has been documented in the literatures, although the probability is low [36, 37]. This highlights the importance to monitor potential adverse events when praziquantel is used especially in preventive chemotherapy. Additionally, which also needs to be concerned is the organization of four days’ treatment in albendazole. The comprehensive effect from high compliance in treatment owing to low adverse events and high complexity in organization of four days’ treatment needs to be explored in future researches.
This study has several limitations. First, the sample size is small. Although there reported the performance of albendazole against C. sinensis infection, the evidence is inadequate and thus this study is an exploratory phase 2 trial. Studies are expected to further verify the high egg reduction rate and low adverse events of albendazole. Second, participants, study pharmacologist and clinicians were not masked to treatment allocation, because masking them would require the design of drugs with same characteristics (e.g. color and taste) and introduction of placebo. However, the laboratory technicians were blinded throughout the study. Third, although randomization was strictly employed, arithmetic mean of EPG in light intensity stratum was higher in albendazole group than in praziquantel group. However, geometric mean of EPG was comparable between the two groups. Fourth, only three individuals with heavy intensity were enrolled, because light and moderate intensity dominate the infection spectrum in the study area. It could be expected a low cure rate will be shown in heavy intensity, but trials are needed to verify.
Conclusions
This study demonstrates the high efficacy in both cure rate and egg reduction rate of praziquantel against clonorchiasis, and refutes the high cure rate of albendazole (400 mg twice a day for 4 days) in previous studies but also shows its high egg reduction rate and low adverse events. Thus, this study has several implications. First, praziquantel is first choice in preventive chemotherapy against clonorchiasis, when albendazole (400 mg twice a day for 4 days) shows potential value owing to the high egg reduction rate and low adverse events, which deserves to be further verified in trials with large participants. Second, praziquantel other than albendazole (400 mg twice a day for 4 days) is recommended in treatment for the individual with definite C. sinensis infection. Reexamination after treatment is suggested for the individual with high intensity of infection. Third, adverse events need to be monitored especially when praziquantel is used. Fourth, high-quality randomized controlled trials are also needed to verify the long-term regimens of albendazole, e.g., 7 days.
Supplementary Information
Below is the link to the electronic supplementary material.
Supplementary Material 1: Additional file 1: Fig. S1. Observation time for adverse events.
Acknowledgements
We thank the technicians from Guangxi Center for Disease Control and Prevention, Binyang Center for Disease Control and Prevention, Zhonghua Township Hospital, and Clinic of Shangshi Village for helping organize the work, and collect and examine stool samples.
Abbreviations
- WHO
World Health Organization
- EPG
eggs per gram of feces
- GM
geometric mean
Author contributions
MBQ, JGZ, XQG, JM, and SZL conceived and designed this study. MBQ, JGZ, XPH, LL, CHZ, JLH, and YYZ implemented the study. MBQ, JGZ, and XPH collected the data. MBQ and XPH analysed the data. MBQ and SZL interpreted the data. MBQ created the data visualisations. MBQ wrote the first draft and manuscript revisions. MBQ and SZL reviewed and edited the manuscript. All authors read and approved the final manuscript.
Funding
This study was supported by the National Disease Control and Prevention Administration, National Natural Science Foundation of China (Grant No. 82373645), Shanghai Talent Program.
Data availability
De-identified individual participant data and the data dictionary, or supporting clinical trial documents, will be made available upon request following publication for at least 2 years. Access will be granted to researchers who provide a methodologically sound proposal. The sponsor, investigators, and collaborators will approve the proposals on the basis of scientific merit. Requests should be directed to the corresponding author. Researchers requesting data will need to sign a data access agreement before they are granted access.
Declarations
Ethics approval and consent to participate
The study was approved by the Ethical Review Committee of National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research) (ref: 2024-009). This trial was registered with isrctn.com on 27 February 2025, number ISRCTN46268871 (https://www.isrctn.com/ISRCTN46268871). The study was conducted in accordance with the Declaration of Helsinki. Written informed consents were obtained from all participants. After the study, the participants who remained positive after treatment, or who were positive but excluded due to exclusionary criteria (except for pregnant women or the individuals with other contraindications) were provided with praziquantel (25 mg/kg 3 times daily for 1 day) free.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Men-Bao Qian, Email: qianmb@nipd.chinacdc.cn.
Shi-Zhu Li, Email: lisz@chinacdc.cn.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary Material 1: Additional file 1: Fig. S1. Observation time for adverse events.
Data Availability Statement
De-identified individual participant data and the data dictionary, or supporting clinical trial documents, will be made available upon request following publication for at least 2 years. Access will be granted to researchers who provide a methodologically sound proposal. The sponsor, investigators, and collaborators will approve the proposals on the basis of scientific merit. Requests should be directed to the corresponding author. Researchers requesting data will need to sign a data access agreement before they are granted access.