Short Report
Sonographic response in the liver and urinary bladder of children 14 months after treatment for schistosomiasis
Tropical Doctor 43(2) 71–74 ! The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0049475513490422 tdo.sagepub.com
Rodney Strahan1, David McAdam2 and Michal E Schneider3
Abstract After praziquantel treatment for schistosomiasis, parasitological cure rates of 60%–90% are usual. Does this response to treatment correlate with the improvement in liver and bladder changes seen on ultrasound in children? This study shows that ultrasound is an effective way to evaluate liver and bladder changes caused by schistosomiasis infection in children and to assess treatment effects after mass treatment programmes.
Keywords Schistosomiasis, Africa, treatment, digestive, urologic
Introduction
Patients/method
The eggs of Schistosoma mansoni and S. haematobium, when trapped in hepatic sinusoids or bladder mucosa, induce granulomatous lesions and deposition of extra cellular matrix along the portal vein branches in the liver or the bladder mucosa. The latter may lead to the development of periportal fibrosis or bladder wall masses, which are associated with a higher incidence of portal hypertension, variceal haemorrhage and bladder tumours. Following a praziquantel dose of 40 mg/kg, parasitological cure rates of 60%–90% and egg count reduction rates of more than 90% are usual.1,2 Reduction in the prevalence of periportal fibrosis and bladder wall lesions is central to the control of morbidity and mortality from schistosomiasis but there are only a few published reports on follow-up after treatment using ultrasound and none dealing only with children. Ultrasonographic findings of schistosomal liver changes and bladder lesions are well-correlated with histology.3,4 Is the reduction in egg counts based on stool and urine samples also accompanied by a resolution or improvement of liver and bladder lesions? This study assesses the efficacy of praziquantel to treat S. mansoni and S. haematobium changes in the liver and bladder of school children, as demonstrated by ultrasound.
The study was carried out at Chitokoloki Day School, located on the Zambezi River, North Western Province, Zambia. The students in the study cohort came from grades 1 to 12 and were aged between 5 and 22 years. Informed consent was obtained from the students as well as the village headmen and the school principals. At the initial study in 2010, 763 students were examined by ultrasound and treated with a 40 mg/kg dose of praziquantel. At follow-up, in 2011, 704 were examined by ultrasound and again treated. There were 397 students who were examined and treated in both years.
Hepatic ultrasound The portable ultrasound machine used in the study was a Sonosite M-Turbo. A single radiologist performed the 1
Consultant Radiologist, Chitokoloki Mission Hospital, Zambia Medical Director, Chitokoloki Mission Hospital, Zambia 3 Deputy Head, Department of Medical Imaging and Radiation Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Australia 2
Corresponding author: Dr R Strahan, Department of Diagnostic Imaging, Monash Health, Monash Medical Centre, Locked Bag 29, Clayton, Victoria 3169, Australia. Email:
[email protected]
72
Tropical Doctor 43(2)
Table 1. Follow up liver ultrasound (US) findings of schoolchildren in Zambia according to age group at presentation (n/N, %). Ultrasound Exam
P-value*
2010
2011
231/397 (58.2) 94/231(42.4) 98/231 (40.7) 39/231 (16.9)
250/397 106/250 104/250 40/250
(62.8) (42.4) (41.6) (16.0)
0.47 0.88 0.9 0.84
120/397 35/120 59/120 26/120
(30.2) (29.2) (49.2) (21.7)
0.26 0.13 0.39 0.36
27/397 (6.8) 11/27 (40.7) 13/27 (48.1) 3/27 (11.1)
0.01 0.10 0.67 0.11
US negative
Total (n) 5–10 years 11–15 years 16–20 years
US positive (2–4SD)
Total (n) 5–10 years 11–15 years 16–20 years
94/397 37/94 41/94 16/94
(23.7) (39.4) (43.6) (17.0)
US positive (>4SD)
Total (n) 5–10 years 11–15 years 16–20 years
72/397 22/72 36/72 14/72
(18.1) (30.6) (50.0) (19.4)
*Chi Square test (not computed when N < 5/group). SD: standard deviation.
examinations using the protocol developed by the Niamey documents for the World Health Organization5 and was blinded to the 2010 ultrasound results. The liver pattern was determined, based on an image pattern based assessment according to the WHO protocol and data by King et al.6 For image pattern A or B no further measurements were performed. Periportal wall thickness was recorded for liver patterns C, D, E and F which were increasing degrees of periportal thickening/fibrosis.7 For periportal thickness, 2 or 3 second-order portal vein branches from the left and/or right portal veins were measured. The normal range was taken as two standard deviations above the mean height adjusted values for the periportal branch wall thickness (PBWT). Abnormalities of PBWT were graded between two and four standard deviations above the mean, or greater than four standard deviations.
students with normal or abnormal periportal thickening, as well as with positive or negative ultrasound findings, in each age group were compared using chi square analysis. All analyses were carried out using SPSS V 18.0 and a P-value of 20 years (n ¼ 22). The fourth group was excluded from statistical analysis because of the small sample size and because these participants were part of the adult population.
Liver ultrasound findings Renal tract ultrasound Both the kidneys and the bladder were examined. Bladder wall changes were recorded as irregular, thickened, masses or pseudopolyps.
Statistical analysis The students were subdivided into three fairly even age groups for analysis of the data and in keeping with previous published work.2,4,6 The proportion of
The 397 students examined in 2010 and again in 2011 were divided into age groups (Table 1). The only statistically significant result was a decrease in the most severe findings, that is, the group with >4 standard deviation (SD) changes in PBWT, which decreased from 18.1% to 6.8% (P ¼ 0.01). However, when the overall positive findings were combined in 2010 (n ¼ 166), 94/166 (56.6%) had resolution of PBWT (changes of 2SD to 4SD and >4SD) and a further 27/166 (16.3%) improved (i.e. >4SD to 2SD-4SD; Table 2). Hence, a total of 121 (72.9%) demonstrated resolution/improvement after only one treatment.
Strahan et al.
73
Table 2. Follow-up of abnormal liver ultrasounds 14 months after treatment (Rx) with praziquantel (n (%)). Pre Rx
Post Rx
No change
Resolved
Improved
Normal 2-4 SD >4SD
2010 – 94 72
2011 94 59 13
32 (34.0) 13 (18.1)
– 63 (67.0) 31 (43.1)
– 27 (37.0)
Total (n)
166
166
45 (27.1)
94 (56.6)
27 (16.3)
Follow-up of bladder lesions 14 months after treatment with praziquantel (n (%)). Pre Rx Post Rx No change 2010 2011 Normal – 15 – Bladder lesion 15 – –
15 (100)
Total (n)
15 (100)
15
15
–
Resolved
SD: standard deviation.
This outcome is within the 60%–90% cure rate that would be expected.1,2
Bladder ultrasound findings Fifteen of the 22 (68%) students with bladder lesions in 2010 were followed-up in 2011 and all were normal, 100% resolution (Table 2).
possible in children after treatment. In our cohort of students, a possible explanation for this is that periportal inflammatory changes may not have progressed to periportal fibrosis. Improvement rates in adults are thought to be lower because, with the progression of the disease to fibrosis, reversibility is not possible.10 The outcomes demonstrated here highlight that treatment changes are easily demonstrated on ultrasound and can provide useful information on the morbidity and mortality of those who have been treated.
Discussion Our study shows that the improvement in liver and bladder changes observed on ultrasound correlates with the parasitological cure rates after praziquantel, quoted in the literature. The children with liver changes demonstrated a resolution and/or improvement rate of 72.9% for PBWT. The 72.9% improvement rate may be due to the relatively young age of our participants (5–20 years; mean age 12.9 years). A study by Berhe et al. investigated participants aged 7–68 years and the resolution/ improvement rate was only 52.3%.8 Cota et al. (2006) studied 84 children and adults, four years after treatment with oxamniquine and confirmed regression of fibrosis in 32%.3 In a further study of patients aged 8–54 years, Ruiz-Guevara et al. demonstrated complete reversal of periportal lesions in 28.2% following treatment with praziquantel.9 In our study, 56.6% of those treated had a complete resolution.
Conclusion This study shows that a reversibility of schistosomal based periportal thickening and bladder wall lesions is
Declaration of conflicting interests None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Greyseels B, Mbaye A, De Vlas SJ, et al. Are poor responses to praziquantel for the treatment of Schistosoma mansoni infections in Senegal due to resistance? An overview of the evidence. Trop Med Int Health 2001; 6: 864–873. 2. Utzinger J, N’Goran EK, N’Dri A, et al. Efficacy of praziquantel against Schistosoma mansoni with particular consideration for intensity of infection. Trop Med Int Health 2000; 5: 771–778. 3. Cota GF, Pinto-Silva RA, Antunes CMF, et al. Ultrasound and clinical investigation of hepatosplenic schistosomiasis: evaluation of splenomegaly and liver fibrosis four years after mass chemotherapy with Oxamniquine. Am J Trop Med Hyg 2006; 74: 103–107.
74 4. Burchard GD, Guisse-Sow F, Diop M, et al. Schistosoma mansoni infection in a recently exposed community in Senegal: lack of correlation between liver morphology in ultrasound and connective tissue metabolites in serum. Trop Med Int Health 1998; 3: 234–241. 5. Richter J, Hatz C, Campagne G, et al., eds. Ultrasound in Schistosomiasis: a Practical Guide to the Standardized Use of Ultrasonography for the Assessment of Schistosomiasisrelated Morbidity. Geneva: World Health Organization. http://whqlibdoc.who.int/hq/2000/TDR_STR_SCH_00.1. pdf (accessed 20 August 2012). 6. King CH, Magak P, Salam EA, et al. Measuring morbidity in Schistosoma mansoni: relationship between image pattern, portal vein diameter and portal branch thickness in large-scale surveys using new WHO coding guidelines for ultrasound in schistosomiasis. Trop Med Int Health 2003; 8: 109–117.
Tropical Doctor 43(2) 7. Berhe N, Geitung JT, Medhin G, et al. Large scale evaluation of WHO’s ultrasonographic staging system of schistosomal periportal fibrosis in Ethiopia. Trop Med Int Health 2006; 11: 1286–1294. 8. Berhe N, Myrvang B and Gundersen SG. Reversibility of schistosomal periportal thickening/fibrosis after praziquantel therapy: a twenty-six month follow-up study in Ethiopia. Am J Trop Med Hyg 2008; 78: 228–234. 9. Ruiz-Guevara R, de Noya BA, Valero SK, et al. Clinical and ultrasound findings before and after praziquantel treatment among Venezuelan schistosomiasis patients. Rev Soc Brasileira Med Trop 2007; 40: 505–511. 10. Black CL, Steinauer ML, Mwinzi PNM, et al. Impact of intense, longitudinal retreatment with praziquantel on cure rates of Schistosomiasis mansoni in a cohort of occupationally exposed adults in western Kenya. Trop Med Int Health 2009; 14: 450–457.
