Treatment of sexually transmitted infections (STIs) has been hypothesised to decrease HIV transmission. Although observational studies show an association between STIs and HIV, only one prospective randomised controlled trial (RCT) has confirmed this. Female genital schistosomiasis can cause genital lesions, accompanied by bloody discharge, ulcers or malodorous discharge. Genital schistosomiasis is common, starts before puberty and symptoms can be mistaken for STIs. Three observational studies have found an association between schistosomiasis and HIV. Genital lesions that develop in childhood are chronic. This paper sought to explore the possible effects of schistosomiasis on the RCTs of STI treatment for HIV prevention.
In the study sites, schistosomiasis was a likely cause of genital lesions. The studies recruited women that may have had genital schistosomal lesions established in childhood. Schistosomiasis endemic areas with different prevalence levels may have influenced HIV incidence in intervention and control sites differently, and some control group interventions may have influenced the impact of schistosomiasis on the study results. Schistosomiasis is a neglected cause of genital tract disease. It may have been an independent cause of HIV incidence in the RCTs of STI treatment for HIV prevention and may have obscured the findings of these trials.
GrosskurthHMoshaFToddJ. Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet1995; 346: 530–536.
2.
WawerMJSewankamboNKSerwaddaD. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group. Lancet1999; 353: 525–535.
3.
KamaliAQuigleyMNakiyingiJ. Syndromic management of sexually-transmitted infections and behaviour change interventions on transmission of HIV-1 in rural Uganda: a community randomised trial. Lancet2003; 361: 645–652.
4.
GregsonSAdamsonSPapayaS. Impact and process evaluation of integrated community and clinic-based HIV-1 control: a cluster-randomised trial in eastern Zimbabwe. PLoS Med2007; 4: e102–e102.
5.
Watson-JonesDWeissHARusizokaM. Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. N Engl J Med2008; 358: 1560–1571.
6.
CelumCWaldAHughesJ. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet2008; 371: 2109–2119.
7.
GhysPDDialloMOEttiegne-TraoreV. Effect of interventions to control sexually transmitted disease on the incidence of HIV infection in female sex workers. AIDS2001; 15: 1421–1431.
8.
KaulRKimaniJNagelkerkeNJ. Monthly antibiotic chemoprophylaxis and incidence of sexually transmitted infections and HIV-1 infection in Kenyan sex workers: a randomized controlled trial. JAMA2004; 291: 2555–2562.
9.
GrosskurthHGrayRHayesR. Control of sexually transmitted diseases for HIV-1 prevention: understanding the implications of the Mwanza and Rakai trials. Lancet2000; 355: 1981–1987.
10.
WhiteRGOrrothKKKorenrompEL. Can population differences explain the contrasting results of the Mwanza, Rakai, and Masaka HIV/sexually transmitted disease intervention trials?: A modeling study. J Acquir Immune Defic Syndr2004; 37: 1500–1513.
11.
KorenrompELWhiteRGOrrothKK. Determinants of the impact of sexually transmitted infection treatment on prevention of HIV infection: a synthesis of evidence from the Mwanza, Rakai, and Masaka intervention trials. J Infect Dis2005; 191: S168–S178.
12.
KjetlandEFLeutscherPDNdhlovuPD. A review of female genital schistosomiasis. Trends Parasitol2012; 28: 58–65.
13.
LeutscherPDRamarokotoCEHoffmannS. Coexistence of urogenital schistosomiasis and sexually transmitted infection in women and men living in an area where Schistosoma haematobium is endemic. Clin Infect Dis2008; 47: 775–782.
14.
SwaiBPoggenseeGMtweveS. Female genital schistosomiasis as an evidence of a neglected cause for reproductive ill-health: a retrospective histopathological study from Tanzania. BMC Infect Dis2006; 23: 134–134.
15.
Ndeffo MbahMLPoolmanEMDrainPK. HIV and Schistosoma haematobium prevalences correlate in sub-Saharan Africa. Tropical Med Int Health2013; 18: 1174–1179.
16.
Yirenya-TawiahDAmoahCApea-KubiKA. A survey of female genital schistosomiasis of the lower reproductive tract in the Volta Basin of Ghana. Ghana Med J2011; 45: 16–21.
LillerudLEStuestoelVMHoelRE. Exploring the feasibility and possible efficacy of mass treatment and education of young females as schistosomiasis influences the HIV epidemic. Arch Gynecol Obstet2010; 281: 455–460.
19.
KingCHDickmanKTischDJ. Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis. Lancet2005; 365: 1561–1569.
20.
MaddenF. A case of Bilharzia of the vagina. Lancet1899; 1: 1716–1710.
BerryA. A cytopathological and histopathological study of bilharziasis of the female genital tract. J Pathol Bacteriol1966; 91: 325–338.
23.
GelfandMRossCMBlairDM. Schistosomiasis of the male pelvic organs. Severity of infection as determined by digestion of tissue and histologic methods in 300 cadavers. Am J Trop Med Hyg1970; 19: 779–784.
24.
FriedbergDSchneiderJGynaecological Bilharziasis. In: CharlewoodGP (ed). Gynaecology in Southern Africa, Johannesburg: Witwaterstrand University Press, 1972, pp. 218–246.
25.
WHO. Statement – WHO working group on urogenital schistosomiasis and HIV transmission, Geneva: WHO, 2009.
26.
RenaudGDevidasADevelouxM. Prevalence of vaginal schistosomiasis caused by Schistosoma haematobium in an endemic village in Niger. Trans R Soc Trop Med Hyg1989; 83: 797–797.
27.
MbabaziPSAndanOFitzgeraldDW. Examining the relationship between urogenital schistosomiasis and HIV infection. PLoS Negl Trop Dis2011; 5: e1396–e1396.
28.
DownsJAMgutaCKaatanoGM. Urogenital schistosomiasis in women of reproductive age in Tanzania's Lake Victoria region. Am J Trop Med Hyg2011; 84: 364–369.
29.
KjetlandEFNdhlovuPDGomoE. Association between genital schistosomiasis and HIV in rural Zimbabwean women. AIDS2006; 20: 593–600.
30.
KjetlandEFKurewaENNdhlovuPD. Female genital schistosomiasis – a differential diagnosis to sexually transmitted disease: Genital itch and vaginal discharge as indicators of genital S. haematobium morbidity in a cross-sectional study in endemic rural Zimbabwe. Trop Med Int Health2008; 13: 1509–1517.
31.
HegertunIESulheim GundersenKMKleppaE. S. haematobium as a common cause of genital morbidity in girls: a cross-sectional study of children in South Africa. PLoS Negl Trop Dis2013; 7: e2104–e2104.
32.
MosunjacMBTadrosTBeachR. Cervical schistosomiasis, human papilloma virus (HPV), and human immunodeficiency virus (HIV): a dangerous coexistence or coincidence?Gynecol Oncol2003; 90: 211–214.
33.
DownsJAvan DamGJChangaluchaJM. Association of Schistosomiasis and HIV infection in Tanzania. Am J Trop Med Hyg2012; 87: 868–873.
34.
ChenineALShai-KobilerESteeleLN. Acute Schistosoma mansoni infection increases susceptibility to systemic SHIV clade C infection in rhesus macaques after mucosal virus exposure. PLoS Negl Trop Dis2008; 2: e265–e265.
35.
LeutscherPDPedersenMRaharisoloC. Increased prevalence of leukocytes and elevated cytokine levels in semen from Schistosoma haematobium-infected individuals. J Infect Dis2005; 191: 1639–1647.
36.
LeutscherPDRamarokotoCEReimertC. Community-based study of genital schistosomiasis in men from Madagascar [letter]. Lancet2000; 355: 117–118.
37.
Leutscher PD, Reimert CM, Christensen NO, et al. Male genital schistosomiasis (MGS) – A neglected risk factor for HIV transmission in Sub-Saharan Africa? In: 13th International AIDS conference, Durban, South Africa, 2000, p.53 (abstract no. LbPeC7079).
38.
KjetlandEFNdhlovuPDMduluzaT. Simple clinical manifestations of genital Schistosoma haematobium infection in rural Zimbabwean women. Am J Trop Med Hyg2005; 72: 311–319.
39.
PoggenseeGKiweluISariaM. Schistosomiasis of the lower reproductive tract without egg excretion in urine. Am J Trop Med Hyg1998; 59: 782–783.
40.
ClementsACBrookerSNyandindiU. Bayesian spatial analysis of a national urinary schistosomiasis questionnaire to assist geographic targeting of schistosomiasis control in Tanzania, East Africa. Int J Parasitol2008; 38: 401–415.
41.
KabatereineNBBrookerSTukahebwaEM. Epidemiology and geography of Schistosoma mansoni in Uganda: implications for planning control. Trop Med Int Health2004; 9: 372–380.
42.
NdhlovuPChandiwanaSKMakuraO. Progress in the control of schistosomiasis in Zimbabwe since 1984. Cent Afr J Med1992; 38: 316–321.
43.
NkyaWMShijaDGMayalaAP. Schistosoma haematobium: effect of non-schistosomicidal drugs (tetracycline and sulphadimidine) on schoolchildren. Trans R Soc Trop Med Hyg1986; 80: 25–28.
44.
BergeSTKabatereineNBGundersenSG. Generic praziquantel in South Africa: The necessity for policy change to avail cheap, safe and efficacious schistosomiasis drugs to the poor, rural population. Southern Afr J Epidemiol Infect2011; 26: 22–25.
45.
KjetlandEFPoggenseeGHelling-GieseG. Female genital schistosomiasis due to Schistosoma haematobium. Clinical and parasitological findings in women in rural Malawi. Acta Trop1996; 62: 239–255.
46.
JourdanPMRandrianasoloBSFeldmeierH. Pathologic mucosal blood vessels in active female genital schistosomiasis: new aspects of a neglected tropical disease. Int J Gynecol Pathol2013; 32: 137–140.
47.
JourdanPMRoaldBPoggenseeG. Increased vascularity in cervicovaginal mucosa with Schistosoma haematobium infection. PLoS Negl Trop Dis2011; 5: e1170–e1170.
48.
NmorsiOUkwanduNEgwungenyaO. Evaluation of CD4(+)/CD8(+) status and urinary tract infections associated with urinary schistosomiasis among some rural Nigerians. Afr Health Sci2005; 5: 126–130.
49.
SmithJChristieJ. The pathobiology of Schistosoma haematobium infection in humans. Hum Pathol1986; 17: 333–345.
50.
WrightEDChiphangwiJHuttMS. Schistosomiasis of the female genital tract. A histopathological study of 176 cases from Malawi. Trans R Soc Trop Med Hyg1982; 76: 822–829.
51.
El-ShouraSM. Human Bilharzial ureters III. Fine structure of egg granuloma. Appl Parasitol1993; 34: 265–273.
52.
El-ShouraSM. Human Bilharzial ureters II. Cellular dynamic against deposited eggs. Ann Parasitol Hum Comp1993; 68: 121–124.
53.
DeelderAMde JongeNFillieYE. Quantitative determination of circulating antigens in human schistosomiasis mansoni using an indirect hemagglutination assay. Am J Trop Med Hyg1989; 40: 50–54.
54.
Helling-GieseGSjaastadAPoggenseeG. Female genital schistosomiasis (FGS): relationship between gynecological and histopathological findings. Acta Trop1996; 62: 257–267.
55.
YeamanGRAsinSWeldonS. Chemokine receptor expression in the human ectocervix: implications for infection by the human immunodeficiency virus-type I. Immunology2004; 113: 524–533.
56.
HladikFSakchalathornPBallweberL. Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity2007; 26: 257–270.
57.
WuL. Biology of HIV mucosal transmission. Curr Opin HIV AIDS2008; 3: 534–540.
58.
MillerCJShattockRJ. Target cells in vaginal HIV transmission. Microbes Infect2003; 5: 59–67.
59.
MillerCJ. HIV transmission: migratory Langerhans cells are primary targets in vaginal HIV transmission. Immunol Cell Biol2007; 85: 269–270.
60.
FuCLOdegaardJIHerbertDR. A novel mouse model of Schistosoma haematobium egg-induced immunopathology. PLoS Pathog2012; 8: e1002605–e1002605.
61.
JourdanPMHolmenSDGundersenSG. HIV target cells in Schistosoma haematobium-infected female genital mucosa. Am J Trop Med Hyg2011; 85: 1060–1064.
62.
GreenheadPHayesPWattsPS. Parameters of human immunodeficiency virus infection of human cervical tissue and inhibition by vaginal virucides. J Virol2000; 74: 5577–5586.
63.
LevineWCPopeVBhoomkarA. Increase in endocervical CD4 lymphocytes among women with nonulcerative sexually transmitted diseases. J Infect Dis1998; 177: 167–174.
64.
SheffieldJSWendelGDJrMcIntireDD. Effect of Genital Ulcer Disease on HIV-1 Coreceptor Expression in the Female Genital Tract. J Infect Dis2007; 196: 1509–1516.
65.
SchustDJQuayleAJAmedeeAM. Mucosal co-infections and HIV-1 transmission and pathogenesis. Curr HIV Res2012; 10: 195–201.
66.
SecorWEShahAMwinziPM. Increased density of human immunodeficiency virus type 1 coreceptors CCR5 and CXCR4 on the surfaces of CD4(+) T cells and monocytes of patients with Schistosoma mansoni infection. Infect Immun2003; 71: 6668–6671.
67.
Shapira-NahorOKalinkovichAWeismanZ. Increased susceptibility to HIV-1 infection of peripheral blood mononuclear cells from chronically immune-activated individuals. AIDS1998; 12: 1731–1733.
68.
GopinathROstrowskiMJustementSJ. Filarial infections increase susceptibility to human immunodeficiency virus infection in peripheral blood mononuclear cells in vitro. J Infect Dis2000; 182: 1804–1808.
69.
SecorWEKaranjaDMColleyDG. Interactions between Schistosomiasis and human immunodeficiency virus in Western Kenya. Mem Inst Oswaldo Cruz2004; 99: 93–95.
70.
Shapira-NahorOMaayanSPedenKW. Replication of HIV-1 deleted Nef mutants in chronically immune activated human T cells. Virology2002; 303: 138–145.
71.
TaylorJJMohrsMPearceEJ. Regulatory T cell responses develop in parallel to Th responses and control the magnitude and phenotype of the Th effector population. J Immunol2006; 176: 5839–5847.
72.
BorkowGBentwichZ. HIV and helminth co-infection: is deworming necessary?Parasite Immunol2006; 28: 605–612.
73.
BrookerSHaySIIssaeW. Predicting the distribution of urinary schistosomiasis in Tanzania using satellite sensor data. Trop Med Int Health2001; 6: 998–1007.
74.
StothardJR. Improving control of African schistosomiasis: towards effective use of rapid diagnostic tests within an appropriate disease surveillance model. Trans R Soc Trop Med Hyg2009; 103: 325–332.
75.
WHO. Schistosomiasis progress report 2001–2011 and strategic plan 2012–2020. 2013.
76.
AppletonCCMaurihungirireMGouwsE. The distribution of helminth infections along the coastal plain of Kwazulu-Natal province, South Africa. Ann Trop Med Parasitol1999; 93: 859–868.
77.
KloosHDavidR. The paleoepidemiology of schistosomiasis in ancient Egypt. Res Human Ecol2002; 9: 14–25.
78.
ChandiwanaSKWoolhouseME. Heterogeneities in water contact patterns and the epidemiology of Schistosoma haematobium. Parasitology1991; 103: 363–370.
79.
AhmedESDaffallaAChristensenNO. Patterns of infection and transmission of human schistosomiasis mansoni and schistosomiasis haematobium in White Nile Province, Sudan. Ann Trop Med Parasitol1996; 90: 173–180.
80.
BrookerSAlexanderNGeigerS. Contrasting patterns in the small-scale heterogeneity of human helminth infections in urban and rural environments in Brazil. Int J Parasitol2006; 36: 1143–1151.
81.
ChandiwanaSKChristensenNOFrandsenF. Seasonal patterns in the transmission of Schistosoma haematobium, S. mattheei and S. mansoni in the highveld region of Zimbabwe. Acta Trop1987; 44: 433–444.
82.
KvalsvigJDSchutteCH. The role of human water contact patterns in the transmission of schistosomiasis in an informal settlement near a major industrial area. Ann Trop Med Parasitol1986; 80: 13–26.
83.
SharfiARHassanO. Evaluation of haematuria in Khartoum. East Afr Med J1994; 71: 29–31.
84.
FirmoJOLima CostaMFGuerraHL. Urban schistosomiasis: morbidity, sociodemographic characteristics and water contact patterns predictive of infection. Int J Epidemiol1996; 25: 1292–300.
85.
ErnouldJCKamanALabboR. Recent urban growth and urinary schistosomiasis in Niamey, Niger. Trop Med Int Health2000; 5: 431–437.
86.
JohnsonCLAppletonCC. Urban schistosomiasis transmission in Pietermaritzburg, South Africa. Southern Afr J Epidemiol Infect2005; 20: 103–107.
87.
AgboladeOMAguNCAdesanyaOO. Intestinal helminthiases and schistosomiasis among school children in an urban center and some rural communities in southwest Nigeria. Korean J Parasitol2007; 45: 233–238.
88.
KloosHCorrea-OliveiraRdos ReisDC. The role of population movement in the epidemiology and control of schistosomiasis in Brazil: a preliminary typology of population movement. Mem Inst Oswaldo Cruz2010; 105: 578–586.
89.
KriitmaaKTestaAOsmanM. HIV prevalence and characteristics of sex work among female sex workers in Hargeisa, Somaliland, Somalia. AIDS2010; 24: S61–S67.
90.
UNAIDS. Report on the global HIV/AIDS epidemic. Geneva: Joint United Nations Programme on HIV/AIDS (UNAIDS), 2002, pp.114–119.
91.
SerwaddaDWawerMJMusgraveSD. HIV risk factors in three geographic strata of rural Rakai District, Uganda. AIDS1992; 6: 983–989.
92.
BarongoLBorgdorffMWMoshaFF. The epidemiology of HIV -1 infection in urban areas roadside settlements and rural villages in Mwanza Region, Tanzania. AIDS1992; 6: 1521–1528.
93.
NdambaJChidimuMGZimbaM. An investigation of the schistosomiasis transmission status in Harare. Cent Afr J Med1994; 40: 337–342.
94.
UNFPA. State of world population. Unleashing the potential of urban growth, New York, United Nations Population Fund, 2007.
95.
HayesRWatson-JonesDCelumC. Treatment of sexually transmitted infections for HIV prevention: end of the road or new beginning?AIDS2010; 24: S15–S26.
96.
NazeraliHLevyL. Essential drugs list and standard treatment guidelines for Zimbabwe. EDLIZ, Harare, Zimbabwe, Ministry of Health and Child Welfare, 1994.
97.
EDLIZ. 4th essential drugs list and standard treatment guidelines for Zimbabwe. EDLIZ, Harare, Zimbabwe: Ministry of Health and Child Welfare, 2000.
98.
MoffattJ. Essential drugs list and standard treatment guidelines for Zimbabwe. EDLIZ, Harare, Zimbabwe: NDTPAC Publishing, 1985, pp. 50–51.
Al-WailiNS. Mebendazole in the treatment of Schistosoma haematobium. Trans R Soc Trop Med Hyg1987; 81: 781–781.
101.
NessimNGHassanSIWilliamS. Effect of the broad spectrum antihelmintic drug flubendazole upon Schistosoma mansoni experimentally infected mice. Arzneimittelforschung2000; 50: 1129–1133.
102.
Mkhize-KwitshanaZLTaylorMJoosteP. The influence of different helminth infection phenotypes on immune responses against HIV in co-infected adults in South Africa. BMC Infect Dis2011; 11: 273–273.
103.
KnoppSMohammedKAAliSM. Study and implementation of urogenital schistosomiasis elimination in Zanzibar (Unguja and Pemba islands) using an integrated multidisciplinary approach. BMC Public Health2012; 12: 930–930.
104.
GrayRHWawerMJ. Reassessing the hypothesis on STI control for HIV prevention. Lancet2008; 371: 2064–2065.
105.
KjetlandEFNdhlovuPDKurewaEN. Prevention of gynecologic contact bleeding and genital sandy patches by childhood anti-schistosomal treatment. Am J Tropic Med Hyg2008; 79: 79–83.
106.
FulfordAJButterworthAESturrockRF. On the use of age-intensity data to detect immunity to parasitic infections, with special reference to Schistosoma mansoni in Kenya. Parasitology1992; 105: 219–227.
107.
NdhlovuPCadmanHVennervaldBJ. Age-related antibody profiles in Schistosoma haematobium infections in a rural community in Zimbabwe. Parasite Immunol1996; 18: 181–191.
108.
NdhlovuPDMduluzaTKjetlandEF. Prevalence of urinary schistosomiasis and HIV in females living in a rural community of Zimbabwe: does age matter?Trans R Soc Trop Med Hyg2007; 101: 433–438.
109.
KoukounariAWebsterJPDonnellyCA. Sensitivities and specificities of diagnostic tests and infection prevalence of Schistosoma haematobium estimated from data on adults in villages northwest of Accra, Ghana. Am J Trop Med Hyg2009; 80: 435–441.
110.
ten HoveRVerweijJVereeckenK. 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 Hyg2008; 102: 179–185.
111.
KjetlandEFten HoveRJGomoE. Schistosomiasis PCR in vaginal lavage as an indicator of genital Schistosoma haematobium infection in rural Zimbabwean women. Am J Trop Med Hyg2009; 81: 1050–1055.
112.
PoggenseeGKiweluIWegerV. Female genital schistosomiasis of the lower genital tract: prevalence and disease-associated morbidity in Northern Tanzania. J Infect Dis2000; 181: 1210–1213.
113.
BasuniMMuhiJOthmanN. A pentaplex real-time polymerase chain reaction assay for detection of four species of soil-transmitted helminths. Am J Trop Med Hyg2011; 84: 338–343.
114.
LessingC. Essential drugs list and standard treatment guidelines for Zimbabwe. EDLIZ, Harare, Zimbabwe: NDTPAC Publishing, 1998.
115.
MatthysBTschannenABTian-BiNT. Risk factors for Schistosoma mansoni and hookworm in urban farming communities in western Cote d'Ivoire. Trop Med Int Health2007; 12: 709–723.
