Background The global distribution map of schistosomiasis shows a large overlap of Schistosoma haematobium- and S. mansoni-endemic areas in Africa. Yet, little is known about the consequences of mixed Schistosoma infections for the human host. A recent study in two neighboring co-endemic communities in Senegal indicated that infection intensities of both species were higher in mixed than in single infections. Here, we investigated the relationship between mixed Schistosoma infections and morbidity in the same population. So far, this has only been studied in children. Methods Schistosoma infection was assessed by microscopy. Schistosoma-specific morbidity was assessed by ultrasound according to WHO guidelines. Multivariable logistic regression models were used to identify independent risk factors for morbidity. Principal Findings Complete parasitological and morbidity data were obtained from 403 individuals. Schistosoma haematobium-specific bladder morbidity was observed in 83% and S. mansoni-specific hepatic fibrosis in 27% of the participants. Bladder morbidity was positively associated with S. haematobium infection intensity (OR = 1.9 (95% CI 1.3–2.9) for a 10-fold increase in intensity). Moreover, people with mixed infections tended to have less bladder morbidity than those with single S. haematobium infections (OR = 0.3 (95% CI 0.1–1.1)). This effect appeared to be related to ectopic S. mansoni egg elimination in urine. Hepatic fibrosis on the other hand was not related to S. mansoni infection intensity (OR = 0.9 (95% CI 0.6–1.3)), nor to mixed infections (OR = 1.0 (95% CI 0.7–1.7)). Conclusions/Significance This is the first population-wide study on the relationship between mixed Schistosoma infections and morbidity. Mixed infections did not increase the risk of S. mansoni-associated morbidity. They even tended to reduce the risk of S. haematobium-associated morbidity, suggesting a protective effect of S. mansoni infection on bladder morbidity. These unexpected results may have important consequences for schistosomiasis control in co-endemic areas and warrant further investigation.
References
[1]
WHO (2010 February) Schistosomiasis fact sheet. Available: http://www.who.int/mediacentre/factsheet？s/fs115/en/index.html. Accessed 2012 Aug 30.
[2]
Gryseels B, Polman K, Clerinx J, Kestens L (2006) Human schistosomiasis. Lancet 368: 1106–1118. doi: 10.1016/S0140-6736(06)69440-3
[3]
Montgomery S (2011) Infectious Diseases Related To Travel - Schistosomiasis. In: Brunette GW, editors. Yellow Book. New York: Oxford University Press.
[4]
Doumenge JP, Mott KE, Cheung C, Villenave D, Chapuis O, et al.. (1987) Atlas of the global distribution of schistosomiasis. Bordeaux: Presses Universitaires de Bordeaux.
[5]
King CH (2002) Ultrasound monitoring of structural urinary tract disease in Schistosoma haematobium infection. Mem Inst Oswaldo Cruz 97 Suppl 1: 149–152. doi: 10.1590/S0074-02762002000900028
[6]
Smith JH, Christie JD (1986) The pathobiology of Schistosoma haematobium infection in humans. Hum Pathol 17: 333–345. doi: 10.1016/S0046-8177(86)80456-7
[7]
Wilson S, Vennervald BJ, Dunne DW (2011) Chronic hepatosplenomegaly in african school children: a common but neglected morbidity associated with schistosomiasis and malaria. PLoS Negl Trop Dis 5: e1149. doi: 10.1371/journal.pntd.0001149
[8]
Friis H, Ndhlovu P, Kaondera K, Franke D, Vennervald BJ, et al. (1996) Ultrasonographic assessment of Schistosoma mansoni and S. haematobium morbidity in Zimbabwean schoolchildren. Am J Trop Med Hyg 55: 290–294.
[9]
Koukounari A, Donnelly CA, Sacko M, Keita AD, Landoure A, et al. (2010) The impact of single versus mixed schistosome species infections on liver, spleen and bladder morbidity within Malian children pre- and post-praziquantel treatment. BMC Infect Dis 10: 227. doi: 10.1186/1471-2334-10-227
[10]
Richter J, Hatz C, Campagne N, Bergquist R, Jenkins JM (1996) Ultrasound in schistosomiasis: A practical guide to the standardized use of ultrasonography for the assessment of schistosomiasis-related morbidity. TDR/STR/SCH/00.1.
[11]
De Clercq D, Vercruysse J, Picquet M, Shaw DJ, Diop M, et al. (1999) The epidemiology of a recent focus of mixed Schistosoma haematobium and Schistosoma mansoni infections around the ‘Lac de Guiers’ in the Senegal River Basin, Senegal. Trop Med Int Health 4: 544–550. doi: 10.1046/j.1365-3156.1999.00444.x
[12]
Ernould JC, Ba K, Sellin B (1999) Increase of intestinal schistosomiasis after praziquantel treatment in a Schistosoma haematobium and Schistosoma mansoni mixed focus. Acta Trop 73: 143–152. doi: 10.1016/S0001-706X(99)00013-3
[13]
Huyse T, Webster BL, Geldof S, Stothard JR, Diaw OT, et al. (2009) Bidirectional introgressive hybridization between a cattle and human schistosome species. PLoS Pathog 5: e1000571. doi: 10.1371/journal.ppat.1000571
[14]
Southgate V, Tchuem Tchuente LA, Sene M, De Clercq D, Theron A, et al. (2001) Studies on the biology of schistosomiasis with emphasis on the Senegal river basin. Mem Inst Oswaldo Cruz 96 Suppl: 75–78. doi: 10.1590/S0074-02762001000900010
[15]
Ten Hove RJ, Verweij JJ, Vereecken K, Polman K, Dieye L, et al. (2008) Multiplex real-time PCR for the detection and quantification of Schistosoma mansoni and S. haematobium infection in stool samples collected in northern Senegal. Trans R Soc Trop Med Hyg 102: 179–185. doi: 10.1016/j.trstmh.2007.10.011
[16]
Van der Werf MJ, Mbaye A, Sow S, Gryseels B, de Vlas SJ (2002) Evaluation of staff performance and material resources for integrated schistosomiasis control in northern Senegal. Trop Med Int Health 7: 70–79. doi: 10.1046/j.1365-3156.2002.00823.x
[17]
Talla I, Kongs A, Verle P (1992) Preliminary study of the prevalence of human schistosomiasis in Richard-Toll (the Senegal river basin). Trans R Soc Trop Med Hyg 86: 182. doi: 10.1016/0035-9203(92)90562-Q
[18]
Talla I, Kongs A, Verle P, Belot J, Sarr S, et al. (1990) Outbreak of intestinal schistosomiasis in the Senegal River Basin. Ann Soc Belg Med Trop 70: 173–180.
[19]
Picquet M, Ernould JC, Vercruysse J, Southgate VR, Mbaye A, et al. (1996) Royal Society of Tropical Medicine and Hygiene meeting at Manson House, London, 18 May 1995. The epidemiology of human schistosomiasis in the Senegal river basin. Trans R Soc Trop Med Hyg 90: 340–346. doi: 10.1016/S0035-9203(96)90501-5
[20]
Meurs L, Mbow M, Vereecken K, Menten J, Mboup S, et al. (2012) Epidemiology of mixed Schistosoma mansoni and Schistosoma haematobium infections in northern Senegal. Int J Parasitol 42: 305–311. doi: 10.1016/j.ijpara.2012.02.002
[21]
WHO (1991) Basic laboratory methods in medical parasitology. Geneva: World Health Organization.
[22]
Katz N, Chaves A, Pellegrino J (1972) A simple device for quantitative stool thick-smear technique in schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo 14: 397–400.
[23]
WHO (2006) Preventive chemotherapy in human helminthiasis - Coordinated use of anthelminthic drugs in control interventions: a manual for health professionals and programme managers.
[24]
Koukounari A, Sacko M, Keita AD, Gabrielli AF, Landoure A, et al. (2006) Assessment of ultrasound morbidity indicators of schistosomiasis in the context of large-scale programs illustrated with experiences from Malian children. Am J Trop Med Hyg 75: 1042–1052.
[25]
Hatz C, Savioli L, Mayombana C, Dhunputh J, Kisumku UM, et al. (1990) Measurement of schistosomiasis-related morbidity at community level in areas of different endemicity. Bull World Health Organ 68: 777–787.
[26]
King CL, Malhotra I, Mungai P, Wamachi A, Kioko J, et al. (2001) Schistosoma haematobium-induced urinary tract morbidity correlates with increased tumor necrosis factor-alpha and diminished interleukin-10 production. J Infect Dis 184: 1176–1182. doi: 10.1086/323802
[27]
Shiff C, Veltri R, Naples J, Quartey J, Otchere J, et al. (2006) 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 100: 847–854. doi: 10.1016/j.trstmh.2005.10.010
[28]
Kouriba B, Traore HA, Dabo A, Sangare L, Guindo H, et al. (2005) Urinary disease in 2 Dogon populations with different exposure to Schistosoma haematobium infection: progression of bladder and kidney diseases in children and adults. J Infect Dis 192: 2152–2159. doi: 10.1086/498214
[29]
Leutscher PD, Reimert CM, Vennervald BJ, Ravaoalimalala VE, Ramarokoto CE, et al. (2000) Morbidity assessment in urinary schistosomiasis infection through ultrasonography and measurement of eosinophil cationic protein (ECP) in urine. Trop Med Int Health 5: 88–93. doi: 10.1046/j.1365-3156.2000.00522.x
[30]
Medhat A, Zarzour A, Nafeh M, Shata T, Sweifie Y, et al. (1997) Evaluation of an ultrasonographic score for urinary bladder morbidity in Schistosoma haematobium infection. Am J Trop Med Hyg 57: 16–19.
[31]
King CH, Magak P, Salam EA, Ouma JH, Kariuki HC, et al. (2003) Measuring morbidity in schistosomiasis 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 8: 109–117. doi: 10.1046/j.1365-3156.2003.00994.x
[32]
Malenganisho WL, Magnussen P, Friis H, Siza J, Kaatano G, et al. (2008) Schistosoma mansoni morbidity among adults in two villages along Lake Victoria shores in Mwanza District, Tanzania. Trans R Soc Trop Med Hyg 102: 532–541. doi: 10.1016/j.trstmh.2008.03.006
[33]
Boisier P, Ramarokoto CE, Ravoniarimbinina P, Rabarijaona L, Ravaoalimalala VE (2001) Geographic differences in hepatosplenic complications of schistosomiasis mansoni and explanatory factors of morbidity. Trop Med Int Health 6: 699–706. doi: 10.1046/j.1365-3156.2001.00781.x
[34]
Booth M, Vennervald BJ, Kabatereine NB, Kazibwe F, Ouma JH, et al. (2004) Hepatosplenic morbidity in two neighbouring communities in Uganda with high levels of Schistosoma mansoni infection but very different durations of residence. Trans R Soc Trop Med Hyg 98: 125–136. doi: 10.1016/S0035-9203(03)00018-X
[35]
Booth M, Mwatha JK, Joseph S, Jones FM, Kadzo H, et al. (2004) Periportal fibrosis in human Schistosoma mansoni infection is associated with low IL-10, low IFN-gamma, high TNF-alpha, or low RANTES, depending on age and gender. J Immunol 172: 1295–1303.
[36]
Garba A, Pion S, Cournil A, Milet J, Schneider D, et al. (2010) Risk factors for Schistosoma haematobium infection and morbidity in two villages with different transmission patterns in Niger. Acta Trop 115: 84–89. doi: 10.1016/j.actatropica.2010.02.007
[37]
King CH, Blanton RE, Muchiri EM, Ouma JH, Kariuki HC, et al. (2004) Low heritable component of risk for infection intensity and infection-associated disease in urinary schistosomiasis among Wadigo village populations in Coast Province, Kenya. Am J Trop Med Hyg 70: 57–62.
[38]
Berhe N, Myrvang B, Gundersen SG (2007) Intensity of Schistosoma mansoni, hepatitis B, age, and sex predict levels of hepatic periportal thickening/fibrosis (PPT/F): a large-scale community-based study in Ethiopia. Am J Trop Med Hyg 77: 1079–1086.
[39]
Butterworth AE, Curry AJ, Dunne DW, Fulford AJ, Kimani G, et al. (1994) Immunity and morbidity in human schistosomiasis mansoni. Trop Geogr Med 46: 197–208.
[40]
Pinot de Moira A, Fulford AJ, Kabatereine NB, Kazibwe F, Ouma JH, et al. (2007) Microgeographical and tribal variations in water contact and Schistosoma mansoni exposure within a Ugandan fishing community. Trop Med Int Health 12: 724–735. doi: 10.1111/j.1365-3156.2007.01842.x
[41]
Robert CF, Bouvier S, Rougemont A (1989) Epidemiology of schistosomiasis in the riverine population of Lagdo Lake, northern Cameroon: mixed infections and ethnic factors. Trop Med Parasitol 40: 153–158.
[42]
Anderson RM, May RM (1985) Helminth infections of humans: mathematical models, population dynamics, and control. Adv Parasitol 24: 1–101.
[43]
Mohamed-Ali Q, Elwali NE, Abdelhameed AA, Mergani A, Rahoud S, et al. (1999) Susceptibility to periportal (Symmers) fibrosis in human Schistosoma mansoni infections: evidence that intensity and duration of infection, gender, and inherited factors are critical in disease progression. J Infect Dis 180: 1298–1306. doi: 10.1086/314999
[44]
Brouwer KC, Ndhlovu PD, Wagatsuma Y, Munatsi A, Shiff CJ (2003) Epidemiological assessment of Schistosoma haematobium-induced kidney and bladder pathology in rural Zimbabwe. Acta Trop 85: 339–347. doi: 10.1016/S0001-706X(02)00262-0
[45]
El Khoby T, Galal N, Fenwick A, Barakat R, El Hawey A, et al. (2000) The epidemiology of schistosomiasis in Egypt: summary findings in nine governorates. Am J Trop Med Hyg 62: 88–99.
[46]
Traore M, Traore HA, Kardorff R, Diarra A, Landoure A, et al. (1998) The public health significance of urinary schistosomiasis as a cause of morbidity in two districts in Mali. Am J Trop Med Hyg 59: 407–413.
[47]
Serieye J, Boisier P, Ravaoalimalala VE, Ramarokoto CE, Leutscher P, et al. (1996) Schistosoma haematobium infection in western Madagascar: morbidity determined by ultrasonography. Trans R Soc Trop Med Hyg 90: 398–401. doi: 10.1016/S0035-9203(96)90521-0
[48]
Heurtier Y, Lamothe F, Develoux M, Docquier J, Mouchet F, et al. (1986) Urinary tract lesions due to Schistosoma haematobium infection assessed by ultrasonography in a community based study in Niger. Am J Trop Med Hyg 35: 1163–1172.
[49]
Wagatsuma Y, Aryeetey ME, Sack DA, Morrow RH, Hatz C, et al. (1999) Resolution and resurgence of Schistosoma haematobium-induced pathology after community-based chemotherapy in ghana, as detected by ultrasound. J Infect Dis 179: 1515–1522. doi: 10.1086/314786
[50]
Brouwer KC, Munatsi A, Ndhlovu PD, Wagatsuma Y, Shiff CJ (2004) Urinary schistosomiasis in Zimbabwean school children: predictors of morbidity. Afr Health Sci 4: 115–118.
[51]
Webster BL, Southgate VR, Tchuem Tchuente LA (1999) Mating interactions between Schistosoma haematobium and S. mansoni. J Helminthol 73: 351–356.
[52]
Cunin P, Tchuem Tchuente LA, Poste B, Djibrilla K, Martin PM (2003) Interactions between Schistosoma haematobium and Schistosoma mansoni in humans in north Cameroon. Trop Med Int Health 8: 1110–1117. doi: 10.1046/j.1360-2276.2003.01139.x
[53]
Ratard RC, Ndamkou CN, Kouemeni LE, Ekani Bessala MM (1991) Schistosoma mansoni eggs in urine. J Trop Med Hyg 94: 348–351.
[54]
Khalil SB, Mansour NS (1995) Worm development in hamsters infected with unisex and cross-mated Schistosoma mansoni and Schistosoma haematobium. J Parasitol 81: 8–11. doi: 10.2307/3283998
[55]
Southgate VR, Jourdane J, Tchuente LA (1998) Recent studies on the reproductive biology of the schistosomes and their relevance to speciation in the Digenea. Int J Parasitol 28: 1159–1172. doi: 10.1016/S0020-7519(98)00021-6
[56]
Jourdane J, Imbert-Establet D, Tchuente LA (1995) Parthenogenesis in schistosomatidae. Parasitol Today 11: 427–430. doi: 10.1016/0169-4758(95)80029-8
[57]
Mansour NS, Soliman GN, El-Assal FM (1984) Studies on experimental mixed infections of Schistosoma mansoni and S. haematobium in hamsters. Z Parasitenkd 70: 345–357. doi: 10.1007/BF00927821
[58]
Soliman GN, el Assal FM, Mansour NS, Garo K (1986) Comparison of two Egyptian strains of Schistosoma mansoni in hamsters. Z Parasitenkd 72: 353–363. doi: 10.1007/BF00928746
[59]
Webbe G, James C, Nelson GS, Ismail MM, Shaw JR (1979) Cross resistance between Schistosoma haematobium and S. mansoni in the baboon. Trans R Soc Trop Med Hyg 73: 42–54. doi: 10.1016/0035-9203(79)90128-7
[60]
Guyatt H, Gryseels B, Smith T, Tanner M (1995) Assessing the public health importance of Schistosoma mansoni in different endemic areas: attributable fraction estimates as an approach. Am J Trop Med Hyg 53: 660–667.
[61]
Kardorff R, Stelma FF, Vocke AK, Yazdanpanah Y, Thomas AK, et al. (1996) Ultrasonography in a Senegalese community recently exposed to Schistosoma mansoni infection. Am J Trop Med Hyg 54: 586–590.
[62]
Mahmoud, A A. (2001) Schistosomiasis. London: Imperial College Press.
[63]
Chan MS, Guyatt HL, Bundy DA, Medley GF (1996) Dynamic models of schistosomiasis morbidity. Am J Trop Med Hyg 55: 52–62.
