Decreased Sensitivity of Schistosoma sp. Egg Microscopy in Women and HIV-Infected Individuals

Soledad Colombe Weill Cornell Medicine, New York, New York;

Search for other papers by Soledad Colombe in
Current site
Google Scholar
PubMed
Close
,
Myung Hee Lee Weill Cornell Medicine, New York, New York;

Search for other papers by Myung Hee Lee in
Current site
Google Scholar
PubMed
Close
,
Peter J. Masikini Catholic University of Health and Allied Sciences, Mwanza, Tanzania;

Search for other papers by Peter J. Masikini in
Current site
Google Scholar
PubMed
Close
,
Lisette van Lieshout Leiden University Medical Center, Leiden, The Netherlands;

Search for other papers by Lisette van Lieshout in
Current site
Google Scholar
PubMed
Close
,
Claudia J. de Dood Leiden University Medical Center, Leiden, The Netherlands;

Search for other papers by Claudia J. de Dood in
Current site
Google Scholar
PubMed
Close
,
Pytsje T. Hoekstra Leiden University Medical Center, Leiden, The Netherlands;

Search for other papers by Pytsje T. Hoekstra in
Current site
Google Scholar
PubMed
Close
,
Paul L. A. M. Corstjens Leiden University Medical Center, Leiden, The Netherlands;

Search for other papers by Paul L. A. M. Corstjens in
Current site
Google Scholar
PubMed
Close
,
Julius Mngara National Institute of Medical Research, Mwanza, Tanzania;

Search for other papers by Julius Mngara in
Current site
Google Scholar
PubMed
Close
,
Govert J. van Dam Leiden University Medical Center, Leiden, The Netherlands;

Search for other papers by Govert J. van Dam in
Current site
Google Scholar
PubMed
Close
, and
Jennifer A. Downs Weill Cornell Medicine, New York, New York;
Bugando Medical Centre, Mwanza, Tanzania

Search for other papers by Jennifer A. Downs in
Current site
Google Scholar
PubMed
Close
Restricted access

It has been postulated that impaired host immunity due to HIV infection reduces parasite egg excretion. Schistosoma/HIV interactions have also been shown to differ by sex. We hypothesized that egg excretion would vary based on both HIV status and sex. We examined data from more than 1,700 participants in eight studies conducted in northwest Tanzania between 2010 and 2016. Schistosoma infection was defined by circulating anodic antigen (CAA) serum levels ≥ 30 pg/mL and/or egg positivity in either stool by Kato Katz method or urine by filtration. We used multivariable analyses to determine the impact of confounding factors such as sex, age, previous praziquantel treatment, and worm burden as measured by serum CAA level, on the relationship between egg excretion and HIV status. HIV-infected individuals were significantly less likely to excrete schistosome eggs than HIV-uninfected individuals, even after controlling for worm burden and sex (OR = 0.6 [0.4, 0.9], P = 0.005). Furthermore, after controlling for worm burden and HIV status, women had lower odds of egg excretion than men (OR = 0.4 [0.3, 0.5], P < 0.001). Sensitivity of egg microscopy was lower in HIV-infected women than HIV-uninfected men (41% versus 61%, P < 0.001), whereas sensitivity in women remained low in both groups (33% versus 37%, P = 0.664). Our study is the first to report that women with Schistosoma infection excrete fewer eggs than men for a given worm burden, regardless of HIV the status. These findings suggest that guidelines for use of microscopy to diagnose Schistosoma infections in HIV-infected individuals and in women merit reconsideration.

Author Notes

Address correspondence to Soledad Colombe, Center for Global Health, Weill Cornell Medicine, 402 East 67th Street, 2nd Floor, New York, NY 10065. E-mail: soledad.colombe@gmail.com

Financial support: This study was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases (K23 AI 110238 to J. A. D.).

Authors’ addresses: Soledad Colombe, Myung Hee Lee, and Jennifer A. Downs, Weill Cornell Medicine, New York, NY, E-mails: soledad.colombe@gmail.com, myl2003@med.cornell.edu, and jna2002@med.cornell.edu. Peter J. Masikini, Catholic University of Health and Allied Sciences, Mwanza, Tanzania, E-mail: mpeterissara@yahoo.com. Lisette van Lieshout, Claudia J. de Dood, Pytsje T. Hoekstra, Paul L. A. M. Corstjens, and Govert J. van Dam, Leiden University Medical Center, Leiden, The Netherlands, E-mails: e.a.van_lieshout@lumc.nl, c.j.de_dood@lumc.nl, p.t.hoekstra-mevius@lumc.nl, p.l.a.m.corstjens@lumc.nl, and g.j.van_dam@lumc.nl. Julius Mngara, National Institute of Medical Research, Mwanza, Tanzania, E-mail: juliusmngara@yahoo.com.

  • 1.

    WHO, 2017. Schistosomiasis Factsheet. Available at: http://www.who.int/mediacentre/factsheets/fs115/en/. Accessed April 15, 2017.

    • PubMed
    • Export Citation
  • 2.

    Doehring E, Feldmeier H, Daffalla AA, 1983. Day-to-day variation and circadian rhythm of egg excretion in urinary schistosomiasis in the Sudan. Ann Trop Med Parasitol 77: 587594.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Birrie H, Medhin G, Erko B, 1994. Variability of egg excretion in Schistosoma mansoni infection in Ethiopia: a case report. East Afr Med J 71: 545547.

  • 4.

    Agnew A et al. 1996. Age-dependent reduction of schistosome fecundity in Schistosoma haematobium but not Schistosoma mansoni infections in humans. Am J Trop Med Hyg 55: 338343.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Bethony J et al. 2002. Additive host genetic factors influence fecal egg excretion rates during Schistosoma mansoni infection in a rural area in Brazil. Am J Trop Med Hyg 67: 336343.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    De Vlas SJ, Gryseels B, Van Oortmarssen GJ, Polderman AM, Habbema JDF, 1993. A pocket chart to estimate true Schistosoma mansoni prevalences. Parasitol Today 9: 306307.

  • 7.

    Van Lieshout L, Polderman AM, Deelder AM, 2000. Immunodiagnosis of schistosomiasis by determination of the circulating antigens CAA and CCA, in particular in individuals with recent or light infections. Acta Trop 77: 6980.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Doenhoff MJ, Chiodini PL, Hamilton JV, 2004. Specific and sensitive diagnosis of schistosome infection: can it be done with antibodies? Trends Parasitol 20: 3539.

  • 9.

    Corstjens PL, van Lieshout L, Zuiderwijk M, Kornelis D, Tanke HJ, Deelder AM, van Dam GJ, 2008. Up-converting phosphor technology-based lateral flow assay for detection of Schistosoma circulating anodic antigen in serum. J Clin Microbiol 46: 171176.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Corstjens PL et al. 2014. Tools for diagnosis, monitoring and screening of Schistosoma infections utilizing lateral-flow based assays and upconverting phosphor labels. Parasitol 141: 18411855.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Corstjens PL, Nyakundi RK, de Dood CJ, Kariuki TM, Ochola EA, Karanja DM, Mwinzi PNM, van Dam GJ, 2015. Improved sensitivity of the urine CAA lateral-flow assay for diagnosing active Schistosoma infections by using larger sample volumes. Parasit Vectors 8: 241.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Wilson AR, van Dam GJ, Kariuki TM, Farah IO, Deelder AM, Coulson PS, 2006. The detection limits for estimates of infection intensity in schistosomiasis mansoni established by a study in non-human primates. Int J Parasitol 36: 12411244.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Utzinger J, Becker SL, van Lieshout L, van Dam GJ, Knopp S, 2015. New diagnostic tools in schistosomiasis. Clin Microbiol Infect 21: 529542.

  • 14.

    De Clercq D, Sacko M, Vercruysse J, Diarra A, Landoure A, vanden Bussche V, Gryseels B, Deelder A, 1995. Comparison of the circulating anodic antigen detection assay and urine filtration to diagnose Schistosoma haematobium infections in Mali. Trans R Soc Trop Med Hyg 89: 395397.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Van Lieshout L, Polman K, Gryseels B, Deelder AM, 1998. Circulating anodic antigen levels in two areas endemic for schistosomiasis mansoni indicate differences in worm fecundity. Trans R Soc Trop Med Hyg 92: 115119.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Cai YC et al. 2014. Field comparison of circulating antibody assays versus circulating antigen assays for the detection of schistosomiasis japonica in endemic areas of China. Parasit Vectors 7: 138.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Knopp S et al. 2015. Sensitivity and specificity of a urine circulating anodic antigen test for the diagnosis of Schistosoma haematobium in low endemic settings. PLoS Negl Trop Dis 9: e0003752.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    van Dam GJ et al. 2015. An ultra-sensitive assay targeting the circulating anodic antigen for the diagnosis of Schistosoma japonicum in a low-endemic area, People’s Republic of China. Acta Trop 141: 190197.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Balahbib A et al. 2017. Selecting accurate post-elimination monitoring tools to prevent reemergence of urogenital schistosomiasis in Morocco: a pilot study. Infect Dis Poverty 6: 75.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Vonghachack Y et al. 2017. Comparison of novel and standarddiagnostic tools for the detection of Schistosoma mekongi infection in Lao People’s Democratic Republic and Cambodia. Infect Dis Poverty 6: 127.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Doenhoff MJ, Hassounah OA, Lucas SB, 1985. Does the immunopathology induced by schistosome eggs potentiate parasite survival? Immunol Today 6: 203206.

  • 22.

    Karanja DM, Colley DG, Nahlen BL, Ouma JH, Secor WE, 1997. Studies on schistosomiasis in western Kenya: I. Evidence for immune-facilitated excretion of schistosome eggs from patients with Schistosoma mansoni and human immunodeficiency virus coinfections. Am J Trop Med Hyg 56: 515521.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Muok EM, Simiyu EW, Ochola EA, Ng’ang’a ZW, Secor WE, Karanja DM, Mwinzi PM, 2013. Association between CD4+ T-lymphocyte counts and fecal excretion of Schistosoma mansoni eggs in patients coinfected with S. mansoni and human immunodeficiency virus before and after initiation of antiretroviral therapy. Am J Trop Med Hyg 89: 4245.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Mwanakasale V, Vounatsou P, Sukwa TY, Ziba M, Ernest A, Tanner M, 2003. Interactions between Schistosoma haematobium and human immunodeficiency virus type 1: the effects of coinfection on treatment outcomes in rural Zambia. Am J Trop Med Hyg 69: 420428.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Sanya RE, Muhangi L, Nampijja M, Nannozi V, Nakawungu PK, Abayo E, Webb EL, Elliott AM, 2015. Schistosoma mansoni and HIV infection in a Ugandan population with high HIV and helminth prevalence. Trop Med Int Health 20: 12011208.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Fontanet AL, Woldemichael T, Sahlu T, van Dam GJ, Messele T, Rinke de Wit T, Masho W, Yeneneh H, Coutinho RA, van Lieshout L, 2000. Epidemiology of HIV and Schistosoma mansoni infections among sugar-estate residents in Ethiopia. Ann Trop Med Parasitol 94: 145155.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Kleppa E, Klinge KF, Galaphaththi-Arachchige HN, Holmen SD, Lillebo K, Onsrud M, Gundersen SG, Taylor M, Ndhlovu P, Kjetland EF, 2015. Schistosoma haematobium infection and CD4+ T-cell levels: a cross-sectional study of young South African women. PLoS One 10: e0119326.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Kallestrup P, Zinyama R, Gomo E, Butterworth AE, van Dam GJ, Erikstrup C, Ullum H, 2005. Schistosomiasis and HIV-1 infection in rural Zimbabwe: implications of coinfection for excretion of eggs. J Infect Dis 191: 13111320.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Mazigo HD, Dunne DW, Wilson S, Kinung’hi SM, Pinot de Moira A, Jones FM, Morona D, Nuwaha F, 2014. Co-infection with Schistosoma mansoni and human immunodeficiency virus-1 (HIV-1) among residents of fishing villages of north-western Tanzania. Parasit Vectors 7: 587.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Ssetaala A et al. 2015. Schistosoma mansoni and HIV acquisition in fishing communities of Lake Victoria, Uganda: a nested case–control study. Trop Med Int Health 20: 11901195.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Downs JA et al. 2012. Association of schistosomiasis and HIV infection in Tanzania. Am J Trop Med Hyg 87: 868873.

  • 32.

    Downs JA et al. 2017. Schistosomiasis and human immunodeficiency virus in men in Tanzania. Am J Trop Med Hyg 96: 856862.

  • 33.

    van Dam GJ, Claudia J, Lewis M, Deelder AM, van Lieshout L, Tanke HJ, van Rooyen LH, Corstjens PL, 2013. A robust dry reagent lateral flow assay for diagnosis of active schistosomiasis by detection of Schistosoma circulating anodic antigen. Exp Parasitol 135: 274282.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Ndyomugyenyi R, Minjas JN, 2001. Urinary schistosomiasis in schoolchildren in Dar-es-Salaam, Tanzania, and the factors influencing its transmission. Ann Trop Med Parasitol 95: 697706.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Delmas M-C, Jadand C, De Vincenzi I, Deveau C, Persoz A, Sobel A, Kazatchkine M, Brunet JB, Meyer L, 1997. Gender differences in CD4+ cell counts persist after HIV-1 infection. AIDS 11: 10711073.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Loupa CV, Rodriguez B, McComsey G, Gripshover B, Salata RA, Valdez H, Lisgaris MV, Fulton SA, Lederman MM, 2006. Gender differences in human immunodeficiency virus (HIV) RNA and CD4 cell counts among new entrants to HIV care. Clin Microbiol Infect 12: 389391.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Cheever AW, Kamel IA, Elwi AM, Mosimann JE, Danner R, 1977. Schistosoma mansoni and S. haematobium infections in Egypt. Am J Trop Med Hyg 26: 702716.

  • 38.

    Wilson S, Jones FM, van Dam GJ, Corstjens PL, Riveau G, Fitzsimmons CM, Sacko MBJ, Vennervald BJ, Dunne DW, 2014. Human Schistosoma haematobium antifecundity immunity is dependent on transmission intensity and associated with immunoglobulin G1 to worm-derived antigens. J Infect Dis 210: 20092016.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Stete K, Krauth SJ, Coulibaly JT, Knopp S, Hattendorf J, Müller I, Lohourignon LK, Kern WV, N’Goran EK, Utzinger J, 2012. Dynamics of Schistosoma haematobium egg output and associated infection parameters following treatment with praziquantel in school-aged children. Parasit Vectors 5: 298.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Kallestrup P, Zinyama R, Gomo E, Butterworth AE, van Dam GJ, Gerstoft J, Erikstrup C, Ullum H, 2006. Schistosomiasis and HIV in rural Zimbabwe: efficacy of treatment of schistosomiasis in individuals with HIV coinfection. Clin Infect Dis 42: 17811789.

    • PubMed
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 111 111 16
Full Text Views 529 13 1
PDF Downloads 143 6 0
 
Membership Banner
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save