Bladder Cancer and Urinary Schistosomiasis in Angola
Monica
C. Botelho, Jacinta Figueiredo, Helena Alves
Monica C. Botelho, Helena Alves, INSA, National Institute of Health Dr. Ricardo Jorge, Rua
Alexandre Herculano, 321, 4000-055 Porto, Portugal
Monica C. Botelho, IPATIMUP, Institute of Pathology and
Molecular Immunology of the University of Porto, Portugal
Jacinta Figueiredo,
Department of Urology, Hospital Americo
Boavida, Luanda, Angola
Correspondence to: Monica C. Botelho, INSA, National Institute of Health Dr.
Ricardo Jorge, Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal
Email:
monicabotelho@hotmail.com
Telephone: +351-223401114
Received: March 30,
2015
Revised: May 22, 2015
Accepted: May 26, 2015
Published online: June 26, 2015
ABSTRACT
Schistosomiasis
haematobia is among the most prevalent parasitosis in Angola. The pathology is
characterized by serious and irreversible lesions in the urogenital tract
induced by chronic infection with the parasite that can eventually lead to
squamous cell carcinoma of the bladder. Considering the frequency and severe
morbidity observed, even in younger ages, the purpose of this study was to
assess the prevalence and morbidity of S. haematobium infection in
Angola. A baseline survey was conducted between November 2007 and February
2008. A randomly sample of 300 inhabitants aged 15 to 75 years old participated
in this study. Prevalence of S. haematobium infection was 71.7 %
(215/300). Infection was higher in females (56.3 %) but no significant
difference was found in prevalence and intensity between gender and age groups.
The predominant self-reported symptoms were dysuria (91.2 %), hypogastralgia
(88.7 %) and haematuria (87.1%) and these symptoms were strongly associated
with S. haematobium infection (p<0.05). Ultrasound and cystoscopy
examinations performed in a sub-sample of 29 individuals revealed pathological
conditions at the urinary tract in all examined. Considering the high
prevalence of S. haematobium infections in Angola and
schistosomiasis-associated bladder cancer, our results indicate that this
population should be targeted for follow-up and implementation of measures for
treatment and control of schistosomiasis.
© 2015 ACT. All
rights reserved.
Key words: Schistosomiasis haematobia; Urogenital schistosomiasis;
Squamous cell carcinoma of the bladder; Angola
Botelho MC,
Figueiredo J, Alves H. Bladder Cancer and Urinary Schistosomiasis in Angola. Journal of Nephrology Research 2015; 1(1): 22-24 Available from: URL:
http://www.ghrnet.org/index.php/jnr/article/view/1138
EDITORIal
Schistosomiasis is an endemic disease in 76 countries of America,
Africa and Asia. According to World Health Organization (WHO)[1],
this disease affects 200 to 300 million people and 650 millions are estimated
to be at risk of infection. In some countries transmission of this disease was
interrupted namely Portugal, Cyprus, Tunisia, Israel and Japan[2],
but the risk of re-introduction persists as recently observed in Corsica,
France[3].
In the case of
S. haematobium 120 millions show urinary symptoms, of which 70 millions
have haematuria, 18 millions morphological alterations of the vesical wall[4]
and 10-40 millions have obstructive uropathy[5]. Lesions in urinary
tract caused by S. haematobium in sub-Saharan Africa are characterized
by signs and symptoms like haematuria, dysuria and hipogastralgy, and in
advanced stages can evolve to cancer[6,7]. Ultrasound analysis
permits the detection of alterations of urinary tract, kidneys
(hydronephrosis), as well as lesions and presence of “sandy patches” in the
vesical wall[1,8,9].
Angola is
situated in the western part of Western Africa. It occupies a territory of
1,246,700 Km2. Its political frontiers are north Republic of Congo,
south Namibia, east Republic of Zambia and Democratic Republic of Congo
(ex-Zaire) and west the Atlantic Ocean. The territory is divided in 18
provinces: Bengo, Benguela, Bié, Cabinda, Kunene, Huambo, Huíla, Kwanza Norte,
Kwanza South, Kwando Kubango, Luanda, Lunda North, Lunda South, Malange,
Moxico, Namibe, Uíge and Zaire. In 2007 the population was estimated in
12,263,600 inhabitants. Angola has 5 major rivers: Kwanza, Kunene, Kubango,
Cuvo and Bengo. Like other water born diseases, deficient sewerage and water
treatment, as well as population education, are the main causes of
schistosomiasis which is characterized as a neglected disease.
Given the
increase in the migratory flux of the rural population to urban areas, and the
degradation of socio-economic conditions in the last years, the consequences of
this infection are underestimated.
Our study
addressed S. haematobium infection in a population of 300 individuals
aged 15-75 years in Angola. This is the first report involving such a wide
region in this country where we have obtained an appalling prevalence of 71.7%
(215/300). This region should be considered hiperendemic in as much as its
prevalence of schistosomiasis is above the 50 % threshold determined by WHO[9].
The infection
pattern in the study population is normal in males showing a decrease in
prevalence and intensity of infection with age. This is explained by the
reduction of exposure to contaminated water[10]. On the contrary
females, besides being more infected, presented a pattern of infection highest
in the intermediate age group (25-34). This reflects an association between
reproductive age and higher exposure to contaminated water due to domestic
activities.
This study
proved that in the rural environment, agriculture is the main source of
subsistence and also the main activity responsible for exposure to S.
haematobium infection in both gender, followed by domestic activity
affecting only females.
Haematuria,
dysuria and hypogastralgia are signs and symptoms of the acute phase of
schistosomiasis and easily percepted by infected individuals. Therefore they
are of great value to alert health authorities in endemic areas of S.
haematobium[11]. In our report dysuria (91.2%), hypogastralgia (88.7%)
and haematuria (74%) were the most frequent complaints by the participants and
they were significantly associated with infection.
Twenty nine
(9.7%) individuals with ages ranging between 25 and 34 years were selected for
ultrasonographic analysis because of the severity of their complaints. All of
them exhibited thickening of the vesical wall. This is due to the
aggressiveness of eggs deposited in the venules of the bladder, leading to
decreased volume of the bladder and later to vesico-ureteral reflux and
hydronephrosis[11,12]. Here hydronephrosis was identified in 7
(24.1%) cases.
Cystoscopy
confirmed the lesions from ultrasonography as well as allowed to evaluate the
extension of lesions. This exam indentified granulomas in 13 cases (44.8%),
calcifications of the bladder wall in 3 cases (10.3%) and 1 vesical tumor
(3.4%). This tumor was classified as squamous cell carcinoma (SCC). The low
frequency of tumors found in our series is in agreement with other authors who
reported that the incidence of SCC is 3-4/100 000 cases[7].
Histopathological exam of biopsies confirmed the lesions in which were
predominantly granulomas with calcified eggs (72.4%). Presence of these lesions
in younger ages (15-24 years) were 17.2%. This is in agreement with other
reports[12].
The
alterations detected by ultrasonography and cystoscopy allowed the detection
and grading of the lesions in the urogenital tract of 29 patients. Given the
significantly elevated prevalence of vesical schistosomiasis in Angola, these
exams should be mandatory in all cases with severe symptoms.
Future studies
should be developed for non-invasive, indirect tests to detect precursor
lesions of bladder cancer. Our group has been developing such methodology with
the use of biomarkers specific of S. haematobium[13,14]. We
have previously described estrogen metabolites to be associated with
schistosomiasis infected persons[15-18]. These metabolites can be
expected to provide deeper insights into the carcinogenesis of urinary schistosomiasis-induced
bladder cancer, and as biomarkers for diagnosis and/or prognosis of this
neglected tropical disease-associated cancer.
CONFLICT OF INTERESTS
The authors declare no conflict of interest.
REFERENCES
1.
WHO. Division of control of tropical
diseases schistosomiasis, Bull World Health Organ Geneva, 2006.
2. Botelho MC, Machado JC, Brindley
PJ, Correia da Costa JM. Targeting molecular signaling pathways of Schistosoma
haemotobium infection in bladder cancer. Virulence. 2011; 2: 267-79.
3. Holtfreter MC, Moné H, Müller-Stöver i,
Mouahid G, Richter J. Schistosoma haematobium infections acquired in Corsica,
France, August 2013. Eurosurveillance, 2014; 19.
4. Van der Werf MJ, de Vlas SJ,
Brooker S, Looman CW, Nagelkerke NJ, Habbema JD, Engels D. Quantification of
clinical morbidity associated with schistosome infection in sub-Saharan Africa.
Acta Trop. 2003; 86: 125-39.
5. WHO. Guidelines for the evaluation
of soil-transmitted helminthiasis and schistosomiasis at community level. Bull
World Health Organization. Geneva. 1998; 53.
6. Van Le TS, Myers J, Konety BR,
Barder T, Getzenberg RH. Functional characterization of the bladder cancer
marker, BLCA-4. Clin Cancer Res. 2004; 10: 1384-91.
7. Shiff C, Veltri R, Naples J,
Quartey J, Otchere J, Anyan W, Marlow C, Wiredu E, Adjei A, Brakohiapa E,
Bosompem K. Ultrasound verification of bladder damage is associated with known
biomarkers of bladder cancer in adults chronically infected with Schistosoma
haematobium in Ghana. Trans R Soc Trop Med Hyg. 2006; 100: 847-54.
8. WHO. Expert Committee on the
Control of Schistosomiasis. Public health impact of schistosomiasis disease and
mortality. Bull World Health Organization. Geneva, 2003; 71: 657-662.
9. WHO. Prevention and control of
schistosomiasis and soil-transmitted helminthiasis: report of a WHO expert
committee. Bull World Health Organization, Geneva, 2002.
10. Okoli CG, Iwuala MO. The prevalence,
intensity and clinical signs of urinary schistosomiasis in Imo state, Nigeria.
J Helminthol. 2004, 78: 337-42.
11. King CH, Keating CE, Muruka JF, Ouma JH,
Houser H, Siongok TK, Mahmoud AA. Urinary tract morbidity in schistosomiasis
haematobia: associations with age and intensity of infection in an endemic area
of Coast Province, Kenya. Am J Trop Med Hyg, 1988; 39: 361-8.
12. Abdel-Wahab MF, Ramzy I, Esmat G, el
Kafass H, Strickland GT. Ultrasound for detecting Schistosoma haematobium
urinary tract complications: comparison with radiographic procedures. J Urol,
1992; 148: 346-50.
13. Botelho
MC, Soares R, Vale N, Ribeiro R, Camilo V, Almeida R, Medeiros R, Gomes P,
Machado JC, Correia da Costa JM. Schistosoma haematobium: identification of new
estrogenic molecules with estradiol antagonistic activity and ability to
inactivate estrogen receptor in mammalian cells. Exp Parasitol. 2010; 126:
526-35.
14. Botelho MC, Ribeiro R, Vale N, Oliveira
P, Medeiros R, Lopes C, Machado JC, Correia da Costa JM. Inactivation of
estrogen receptor by Schistosoma haematobium total antigen in bladder
urothelial cells. Oncol Rep. 2012; 27: 356-62.
15. Botelho MC, Vale N, Gouveia MJ, Rinaldi
G, Santos J, Santos LL, Gomes P, Brindley PJ, Correia da Costa JM. Tumour-like
phenotypes in urothelial cells after exposure to antigens from eggs of
Schistosoma haematobium: an oestrogen-DNA adducts mediated pathway? Int J
Parasitol. 2013; 43: 17-26.
16. Santos J, Gouveia MJ, Vale N, Delgado Mde
L, Gonçalves A, da Silva JM, Oliveira C, Xavier P, Gomes P, Santos LL, Lopes C,
Barros A, Rinaldi G, Brindley PJ, da Costa JM, Sousa M, Botelho MC. Urinary
estrogen metabolites and self-reported infertility in women infected with
Schistosoma haematobium. PLoS One. 2014; 9: e96774. doi:
10.1371/journal.pone.0096774.
17. Botelho MC, Sousa M. New biomarkers to
fight urogenital schistosomiasis: a major neglected tropical disease. Biomark
Med. 2014; 8: 1061-3. doi: 10.2217/bmm.14.68.
18. Botelho MC, Alves H, Barros A, Rinaldi G,
Brindley PJ, Sousa M. The role of estrogens and estrogen receptor signaling
pathways in cancer and infertility: the case of schistosomes. Trends Parasitol.
2015; doi: 10.1016/j.pt.2015.03.005.
Peer
reviewers:
Sakip Erturhan, Professor, MD, Gaziantep University, Faculty of Medicine,
Department of Urology, 27310, Şahinbey / Gaziantep , Turkey, Draga Ivanova
Toncheva, Professor, Department of Medical Genetics, Medical University-Sofia,
“Zdrave” 2 str., 1431 Sofia, Bulgaria.
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