สมัครสมาชิก เข้าสู่การทำงาน รายงาน รายงาน CCANET
ผู้แต่ง : Panuwat Prathumkam (panuwat@thaimedresnet.org)
ผู้แต่งร่วม : Bandit Thinkamrop (karawa@gmail.com)
ภายใต้โครงการ :
ติดต่อ Panuwat Prathumkam
Data Management and Statistical Analysis Center Faculty of Public Health Khon Kaen University
Tel: 0801841938   Fax:
panuwat@thaimedresnet.org

Abstract

Background: Praziquantel (PZQ) has been the mainstay of liver-fluke control. Favorite raw fermented or uncooked fish in northeast of Thailand caused re-infections and repeated treatments. Since PZQ and its metabolites are excreted in the kidney. However, Nephrotoxic effects of PZQ are unknown.

Objective: To investigate a relationship between repeated treatments with PZQ and kidney parenchymal change.

Methods: A cross-sectional study was carried out on participants from the Cholangiocarcinoma Screening and Care Program (CASCAP). Subjects were 40 years or older, had been infected with liver- fluke or had been treated with PZQ. Kidney parenchymal change was diagnosed by ultrasonography. Number of treatments with PZQ and other potentially confounding factors that associated with kidney abnormality were determined by odds ratio (ORs) and 95% confidence interval (95%CI) using multiple logistic regression.

Results: Among 56,555 subjects with a mean age of 53.8 (±9.45) years, 57.9% were female. The overall prevalence of treatment with PZQ was 43.6% (95%CI: 43.2 to 44.0). Compared with non-treatment, one treatment (OR 1.13; 95%CI: 1.04 to 1.23), two treatments (OR 1.33; 95%CI: 1.16 to 1.52), three treatments (OR 1.56; 95%CI: 1.21 to 2.00) and more than three treatments (OR 1.70; 95%CI: 1.40 to 2.07) with adjusted for all other factors including age, gender, diabetes mellitus and alcohol consumption.

Conclusions: Repeated treatment with PZQ may cause kidney parenchymal change. The necessity for policy change to provide health education about realization and prevention on repeated treatment with PZQ.

Keywords: praziquantel, repeated treatment, kidney parenchymal change, renal parenchymal change. 

 


INTRODUCTION

Opisthorchis viverrini (OV), common name Southeast Asian liver-fluke, is a parasite from Opisthorchiidae family. OV infection was acquired when people eat raw or undercooked fish[1] and endemic throughout Thailand, Lao People's Democratic Republic, Vietnam and Cambodia[2]. In Northeast Thailand - a highest incidence of liver-fluke infection and Cholangiocarcinoma (CCA) in the world, Praziquantel (PZQ) has been the mainstay of anthelmintic for liver-fluke control and widely distributed.

Raw fish and fermented fish in several favorite dishes across this region caused high re-infections and repeated treatments with PZQ [3]. In pharmacokinetic, PZQ was found to concentrate especially in the liver and kidneys[4]. Since 80% of PZQ and its metabolites are excreted in the kidneys[5]. However, little is known about effects of repeated treatment with PZQ on kidney parenchymal change (KPC).

This study aimed to investigate a relationship between repeated treatments with PZQ and KPC.

 

MATERIALS AND METHODS

Study design

This study was conducted at primary and secondary hospitals around 21 provinces in Northeast Thailand as part of the Cholangiocarcinoma Screening and Care Program (CASCAP, www.cascap.in.th). All people in risk group who have age more than 40 years and have been infected or treated with liver-fluke were carried out in 2013-2015 as a cross-sectional data. Subjects with incomplete information were excluded. A total 57,687 subjects were included in the analysis.

Study outcome

Ultrasound examinations were performed in secondary hospital by doctor or radiologist. The type and classification of kidney abnormality were defined as renal cyst, parenchyma change, post nephrectomy and renal stone.

Statistical analysis

Demographic characteristics of subjects were described using frequency and percentage for categorical data such as gender, age, education level, occupation, smoking, alcohol consumption and diabetes mellitus. For continuous data such as age of subjects was described by mean, standard deviation, median, minimum and maximum.

Prevalence of KPC was calculated in percentage based on a normal approximation to the binomial distribution. Number of treatments with PZQ and other potentially confounding factors that associated with KPC were determined by odds ratio (ORs) and 95% confidence intervals (95%CIs) using multiple logistic regression.

All analysises were performed using R version 3.2.2 (The R foundation for statistical computing). All statistics test were two-sided and a p-value of less than 0.05 was considered statistical significant. This project was approved by …….

RESULTS

A total 105,919 subjects were registered in CASCAP database. From the 60,281 subjects who had Ultrasound examination results, there were 3,726 subjects excluded from the study due to incomplete information of data, hence 56,555 subjects were included in the analysis (Fig.1)

Figure 1. Classification diagram

 

 

Demographic Characteristics

Among 56,555 subjects with a mean age 53.8 (±9.4) years ranging from 25.2 to 99.8 years. More than half of them were female (57.9%), and most of them graduated from primary school (74.7%) and work as farmer (79.9%) (Table 1.)

 

Table 1. Demographic and characteristic

 

Characteristics

Number

Percent

Gender

 

 

Male

23,739

42.1

Female

32,685

57.9

Age in years

 

 

Less than 40

1,083

2.1

40 to 44

9,069

17.3

45 to 49

10,417

19.9

50 to 54

10,093

19.3

55 to 59

8,524

16.3

60+

13,235

25.3

Mean (±SD)

53.8

±9.4

Median (Min : Max)

52.8

(25.2 : 99.8)

Education level

 

 

None

500

0.9

Primary

41,902

74.7

Secondary (M1)

4,275

7.6

Secondary (M2)

5,051

9.0

Certificate

882

1.6

Bachelor

2,625

4.7

Higher than bachelor

846

1.5

Occupation

 

 

Unemployed

1,373

2.5

Farmer

44,803

79.9

Labor

3,164

5.6

Own business

1,686

3.0

Government official/State enterprises

3,386

6.0

Others

1,678

3.0

Smoking

 

 

No

42,623

76.5

Yes

13,078

23.5

Alcohol consumption

 

 

No

31,029

54.9

Yes, current or previous

25,526

45.1

Diabetes Mellitus

 

 

No

53,694

94.9

Yes

2,861

5.1

 

 

 

 

Prevalence of Kidney Parechymal Change (KPC)

From 56,555 subjects, the overall prevalence of KPC was 5.9%. KPC was found in 8.4% in male, but only 4.1% in female. Prevalence of KPC was linearity increased  from 5.2%, 6.2%, 7.5%, 7.8% and 9.7% for none, one, two, three and more than three treatments with PZQ. The association between Number of treatments with PZQ and KPC from crude analysis were highly significant compared with none treatments: one treatment (OR 1.20; 95%CI: 1.11 to 1.30), two treatments (OR 1.52; 95%CI: 1.34 to 1.74), three treatments (OR 1.82; 95%CI: 1.43 to 2.30) and more than three treatments (OR 1.95; 95%CI: 1.61 to 2.35). Other factors were significant associated such as gender, age, education level, occupation, smoking, alcohol consumption and diabetes mellitus. (Table 2)

 

Table 2. Prevalence of kidney parenchymal change and odds ratio of the factors.

 

Factors

Number

% KPC

Crude
OR

95% CI

p-value

Overall

56,555

5.9

 

 

 

Number of treatment with PZQ

 

 

 

 

<0.001

None

29,850

5.2

1

 

 

One

18,634

6.2

1.20

1.11 – 1.30

 

Two

3,625

7.5

1.52

1.34 – 1.74

 

Three

857

7.8

1.82

1.43 – 2.30

 

More than three

1,320

9.7

1.95

1.61 – 2.35

 

Gender

 

 

 

 

<0.001

Male

23,739

8.4

1

 

 

Female

32,685

4.1

0.47

0.44 – 0.51

 

Age

 

 

 

 

<0.001

Less than 40

1,083

1.8

1

 

 

40 to 44

9,069

3.3

1.93

1.21 – 3.08

 

45 to 49

10,417

4.0

2.30

1.45 -3.66

 

50 to 54

10,093

4.9

2.91

1.83 – 4.63

 

55 to 59

8,524

6.4

3.86

2.43 – 6.12

 

60+

13,235

10.3

6.44

4.08 – 10.17

 

Age in years

 

 

1.051

1.05 – 1.06

<0.001

Education level

 

 

 

 

<0.001

None

500

6.2

1

 

 

Primary

41,902

6.3

1.01

0.70 – 1.46

 

Secondary (M1)

4,275

5.1

0.81

0.55 – 1.19

 

Secondary (M2)

5,051

5.0

0.79

0.54 – 1.16

 

Certificate

882

5.4

0.87

0.54 – 1.39

 

Bachelor

2,625

3.9

0.61

0.40 – 0.92

 

Higher than bachelor

846

3.1

0.48

0.28 – 0.82

 

Occupation

 

 

 

 

<0.001

Unemployed

1,373

8.7

1

 

 

Farmer

44,803

6.0

0.67

0.55 – 0.81

 

Labor

3,164

6.0

0.66

0.52 – 0.84

 

Own business

1,686

4.3

0.47

0.35 – 0.64

 

Government

3,386

3.8

0.41

0.32 – 0.53

 

Others

1,678

6.2

0.69

0.53 – 0.91

 

Smoking

 

 

 

 

<0.001

No

42,623

5.0

1

 

 

Yes

13,078

8.7

1.80

1.67 – 1.94

 

 

 

 

 

 

 

Alcohol consumption

 

 

 

 

<0.001

No

31,029

5,0

1

 

 

Yes, current or previous

25,526

7.0

1.43

1.33 – 1.53

 

Diabetes Mellitus

 

 

 

 

<0.001

No

53,694

5.7

1

 

 

Yes

2,861

9.6

1.75

1.53 – 1.99

 

Factors associated with kidney parenchymal change.

Using multiple logistic regressions, the association between number of treatments with PZQ and KPC was adjusted for all other factors including gender, age, alcohol consumption, and diabetes mellitus. The risk of number of treatments with PZQ still remained significant compared with none treatments: one treatment (OR 1.13; 95%CI: 1.04 to 1.23), two treatments (OR 1.33; 95%CI: 1.16 to 1.52), three treatments (OR 1.54; 95%CI: 1.21 to 2.00) and more than three treatments (OR 1.70; 95%CI: 1.40 to 2.07). (Table 3.)

 

Table 3. Adjusted odds ratio of factors associated with kidney parenchymal change.

 

Factors

Number

% KPC

Crude OR

Adj. OR

95% CI

p-value

Overall

56,555

5.9

 

 

 

 

Number of treatment with PZQ

 

 

 

 

 

<0.001

None

29,850

5.2

1

1

 

 

One

18,634

6,2

1.20

1.13

1.04 – 1.23

 

Two

3,625

7.5

1.52

1.33

1.16 – 1.52

 

Three

857

7.8

1.82

1.54

1.21 – 2.00

 

More than three

1,320

9.7

1.95

1.70

1.40 – 2.07

 

Gender

 

 

 

 

 

<0.001

Male

23,739

8.4

1

1

 

 

Female

32,685

4.1

0.47

0.54

0.50 – 0.59

 

Age in years

 

 

1.05

1.05

1.04 – 1.05

<0.001

Alcohol consumption

 

 

 

 

 

<0.001

No

31,029

5,0

1

1

 

 

Yes, current or previous

25,526

7.0

1.43

1.16

1.06 – 1.26

 

Diabetes Mellitus

 

 

 

 

 

<0.001

No

53,694

5.7

1

1

 

 

Yes

2,861

9.6

1.75

1.58

1.38 – 1.80

 

Education level

 

 

 

 

 

0.007

None

500

6.2

1

1

 

 

Primary

41,902

6.3

1.01

1.30

0.88 – 1.92

 

Secondary (M1)

4,275

5.1

0.81

1.30

0.86 – 1.97

 

Secondary (M2)

5,051

5.0

0.79

1.23

0.81 – 1.86

 

Certificate

882

5.4

0.87

1.19

0.72 – 1.97

 

Bachelor

2,625

3.9

0.61

0.93

0.60 – 1.45

 

Higher than bachelor

846

3.1

0.48

0.82

0.47 – 1.42

 

 

 

 

 

 

 

 

 

 

DISCUSSIONS

 

Explaining the findings

<copy narrative parts of the Results followed by explaining each important findings in turn , 5-10 references needed here in this section where about half of them are the same as the one cited in the Introduction section of the manuscript>

 

Strength of the study

<to be written>

 

Limitation of the study

 

Conclusions

There was association between number of treatment with PZQ and kidney parechymal change. Repeated treatment with PZQ may cause kidney parechymal change. The necessity for policy change to provide health education about realization and prevention on repeated treatment with PZQ.

 

 

 

Recommendations

<to be written>

 

Acknowledgements:

Funds:

[5-7]

REFERENCES

 

 

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2. Young ND, Campbell BE, Hall RS, Jex AR, Cantacessi C, Laha T, Sohn WM, Sripa B, Loukas A, Brindley PJ et al: Unlocking the transcriptomes of two carcinogenic parasites, Clonorchis sinensis and Opisthorchis viverrini. PLoS neglected tropical diseases 2010, 4(6):e719.

3. Hinz E, Saowakontha S, Pipitgool V: Opisthorchiasis control in northeast Thailand: proposal for a new approach. Applied parasitology 1994, 35(2):118-124.

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7. Chen MG, Fu S, Hua XJ, Wu HM: A retrospective survey on side effects of praziquantel among 25,693 cases of schistosomiasis japonica. The Southeast Asian journal of tropical medicine and public health 1983, 14(4):495-500.