• 1

    Asiedu K, Raviglione M, Scherpbier R, 1998. International Conference on Buruli Ulcer Control and Research. Yamoussoukro, Côte d’Ivoire. July 6–8, 1998. Geneva: World Health Organization.

  • 2

    Amofah G, Bonsu F, Tetteh C, Okrah J, Asamoa K, Asiedu K, Addy J, 2002. Buruli ulcer in Ghana: results of a national case search. Emerg Infect Dis 8 :167–170.

    • Search Google Scholar
    • Export Citation
  • 3

    Marston BJ, Diallo MO, Horsburgh CR Jr, Diomande I, Saki MZ, Kanga JM, Patrice G, Lipman HB, Ostroff SM, Good RC, 1995. Emergence of Buruli ulcer disease in the Daloa region of Côte d’Ivoire. Am J Trop Med Hyg 52 :219–224.

    • Search Google Scholar
    • Export Citation
  • 4

    Asiedu K, Scherpbier RW, Raviglione M, 2000. Buruli Ulcer-Mycobacterium ulcerans Infection. Geneva: World Health Organization.

  • 5

    Stienstra Y, van der Graaf WT, te Meerman GJ, The TH, de Leij LF, van der Werf TS, 2001. Susceptibility to development of Mycobacterium ulcerans disease: review of possible risk factors. Trop Med Int Health 6 :554–562.

    • Search Google Scholar
    • Export Citation
  • 6

    Bellamy R, Hill AV, 1998. Genetic susceptibility to mycobacteria and other infectious pathogens in humans. Curr Opin Immunol 10 :483–487.

    • Search Google Scholar
    • Export Citation
  • 7

    Ross AG, Bartley PB, Sleigh AC, Olds GR, Li Y, Williams GM, McManus DP, 2002. Schistosomiasis. N Engl J Med 346 :1212–1220.

  • 8

    Wagatsuma Y, Aryeetey ME, Sack DA, Morrow RH, Hatz C, Kojima S, 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.

    • Search Google Scholar
    • Export Citation
  • 9

    Aryeetey ME, Wagatsuma Y, Yeboah G, Asante M, Mensah G, Nkrumah FK, Kojima S, 2000. Urinary schistosomiasis in southern Ghana: 1. Prevalence and morbidity assessment in three (defined) rural areas drained by the Densu River. Parasitol Int 49 :155–163.

    • Search Google Scholar
    • Export Citation
  • 10

    Yamamura M, Uyemura K, Deans RJ, Weinberg K, Rea TH, Bloom BR, Modlin RL, 1991. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science 254 :277–279.

    • Search Google Scholar
    • Export Citation
  • 11

    Yamamura M, 1992. Defining protective responses to pathogens: cytokine profiles in leprosy lesions (erratum). Science 255 :12.

  • 12

    Chensue SW, Warmington K, Ruth JH, Lukacs N, Kunkel SL, 1997. Mycobacterial and schistosomal antigen-elicited granuloma formation in IFN-gamma and IL-4 knockout mice: analysis of local and regional cytokine and chemokine networks. J Immunol 159 :3565–3573.

    • Search Google Scholar
    • Export Citation
  • 13

    Pearce EJ, Caspar P, Grzych JM, Lewis FA, Sher A, 1991. Down-regulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni.J Exp Med 173 :159–166.

    • Search Google Scholar
    • Export Citation
  • 14

    Borkow G, Leng Q, Weisman Z, Stein M, Galai N, Kalinkovich A, Bentwich Z, 2000. Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy. J Clin Invest 106 :1053–1060.

    • Search Google Scholar
    • Export Citation
  • 15

    Deelder AM, De Jonge N, Boerman OC, Fillie YE, Hilberath GW, Rotmans JP, Gerritse MJ, Schut DW, 1989. Sensitive determination of circulating anodic antigen in Schistosoma mansoni infected individuals by an enzyme-linked immunosorbent assay using monoclonal antibodies. Am J Trop Med Hyg 40 :268–272.

    • Search Google Scholar
    • Export Citation
  • 16

    Agnew A, Fulford AJ, De Jonge N, Krijger FW, Rodriguez-Chacon M, Gutsmann V, Deelder AM, 1995. The relationship between worm burden and levels of a circulating antigen (CAA) of five species of Schistosoma in mice. Parasitology 111 :67–76.

    • Search Google Scholar
    • Export Citation
  • 17

    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 :69–80.

    • Search Google Scholar
    • Export Citation
  • 18

    Diniz LM, Zandonade E, Dietze R, Pereira FE, Ribeiro-Rodrigues R, 2001. Short report: do intestinal nematodes increase the risk for multibacillary leprosy? Am J Trop Med Hyg 65 :852–854.

    • Search Google Scholar
    • Export Citation
  • 19

    Mwinzi PN, Karanja DM, Colley DG, Orago AS, Secor WE, 2001. Cellular immune responses of schistosomiasis patients are altered by human immunodeficiency virus type 1 coinfection. J Infect Dis 184 :488–496.

    • Search Google Scholar
    • Export Citation
  • 20

    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 :515–521.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

BURULI ULCER AND SCHISTOSOMIASIS: NO ASSOCIATION FOUND

View More View Less
  • 1 Department of Internal Medicine, Groningen University Hospital, Groningen, The Netherlands; National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia; Ministry of Health, Accra Ghana; Agogo Presbyterian Hospital, Agogo, Ghana; St. Martin’s Catholic Hospital, Agroyesum, Ghana; Dunkwa Governmental Hospital, Dunkwa, Ghana

Helminth infections elicit an immune response potentially enhancing susceptibility to mycobacterial diseases. Schistosomiasis and infection with Mycobacterium ulcerans show a remarkable similarity in epidemiologic characteristics in Ghana. In 2000, a case-control study was conducted in three districts in Ghana endemic for M. ulcerans. One hundred six patients with confirmed M. ulcerans disease and 106 matched community controls were included. Schistosome infection of these patients and controls was measured by an enzyme-linked immunosorbent assay that detected circulating anodic antigen in serum. Fifty percent of the participants tested positive for schistosomiasis. There was no difference in detection rates among patients and matched controls. Similarly, there were no differences in worm burden between patients and controls. These results do not support the hypothesis that susceptibility to M. ulcerans disease is driven by a co-infection with schistosomes.

INTRODUCTION

Buruli ulcer disease (BUD) is a devastating infectious disease caused by Mycobacterium ulcerans. Since the 1980s, the disease has emerged in several west African countries, including Ghana, Côte d’Ivoire, Benin, and Togo.1 In some districts in Ghana, prevalence of BUD is approximately 150 per 100,000 persons.2–4 According to the World Health Organization (WHO) clinical case definition, the first stage of BUD typically starts as a firm, non-tender nodule; other possible pre-ulcerative lesions include plaques or edema. From these pre-ulcerative lesions, ulceration of the skin with an undermined edge may develop. Later, a granulomatous healing response occurs, and fibrosis, scarring, calcification, and contractures with permanent disabilities may result.5 Surgery is currently the standard treatment. The mode of transmission of BUD is unclear, but it is probably acquired from the natural environment.

As with M. tuberculosis, where only 10% of infected persons ever develop clinical disease,6 it is likely that a significant proportion of the population living in an endemic area are infected with M. ulcerans, but never develop BUD. We explored whether co-infection with schistosome parasites predisposes individuals with M. ulcerans infections to express the pathologic consequences of this infection.5 Schistosomiasis is one of the most widespread parasitic diseases.7 In some rural communities northwest of Accra, up to 60% of the urine samples are positive for S. haematobium by a urine filtration technique.8,9 Schistosoma mansoni is far less common in Ghana than S. haematobium.8 Based on our own clinical experience and that of others working in hospitals in Ghana, S. haematobium is one of the most common parasitic condition encountered in addition to malaria and other intestinal helminths. Schistosome eggs are a common finding during routine urine laboratory examination in outpatient departments of hospitals in Ghana. Schistosome infections are more prevalent in Ghana since the building of the Akosombo Dam.9 In the same areas, Buruli ulcer became more prevalent in the same age groups.

The pivotal indigenous host defense against mycobacterial infections is a protective Th1 cellular response while Th2 cells dominate the immune response to helminthic infections, e.g., S. mansoni.10–12 Th2 dominant responses inhibit differentiation of Th0 cells to Th1 cells and macrophage activation, thus compromising the capacity of the host to destroy pathogens susceptible to the Th1 response.13 Thus, as schistosomiasis drives the immune system towards a predominant Th2 pattern, schistosome-infected individuals may become more susceptible to infections with M. ulcerans and/or development of BUD.5 Apart from the Th1/Th2 paradigm, helminth infection may impair several important post-receptor transduction pathways such as tyrosine kinases and mitogen-activated protease kinases, which are important defense mechanisms against mycobacteria.14

The Human Development Report states a human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) prevalence in Ghana of 3.6% (www.undp.org/hdr2001). Infection with HIV was considered a potential confounder in this study. Therefore, the HIV status of the participants was determined.

METHODS

A case-control study was performed from September to November 2000 in three districts endemic for BUD (Amansi West, Upper Denkyira, and Ashanti Akim North) in Ghana. Suspect BUD patients were identified though active surveillance efforts by village health care volunteers. Using the WHO clinical case definition,4,5 159 patients were identified as BUD patients by attending physicians at health clinics.

One hundred fifty community- and age-matched controls were identified in the house nearest to the house of the BUD patient by village health care workers. Standardized questionnaires were completed, blood specimens were collected, and skin biopsies were obtained from BUD patients. For the present study, only patients with confirmed BUD and with blood available for both the patient and the community control were included. Confirmation of BUD was based on clinical case definition combined with one of the confirmation tests: culture, histopathology, acid-fast bacilli, or polymerase chain reaction. One hundred six patients and their 106 age-and community-matched controls were included. The study was reviewed and approved by the medical ethical committees of participating institutions, and informed consent was given by the individuals and/or their guardians.

Detection of circulating anodic antigen.

Levels of circulating anodic antigen (CAA) in serum were determined by an enzyme-linked immunosorbent assay as described by Deelder and others.15 Briefly, plates were coated with 2 μg/mL of monoclonal antibody to CAA in phosphate-buffered saline (PBS). Additional protein binding sites were blocked with 0.33 mg/mL of bovine serum albumin in PBS. Sera were pre-treated with 4% trichloroacetic acid (TCA) for five minutes and centrifuged at 14,000 rpm for four minutes. The supernatants were removed and an equal volume of neutralization buffer was added to achieve a pH of 6.8–7.6. A standard dilution curve of the TCA-soluble fraction of schistosome adult worm antigen (AWA-TCA), reference samples, and the pretreated sera were added to the plate in duplicate. After incubation, a biotin conjugate of the monoclonal antibody to CAA was added, followed by an alkaline phosphatase conjugate of streptavidin. Plates were developed with p-nitrophenyl phosphate substrate in 0.1 M diethanolamine containing 0.5 mM MgCl2, and color development was measured at 405 nm after overnight incubation at 4°C. All steps (except developing) were performed in a heated shaking incubator system for 30 minutes. Washings were done between steps with Tris-buffered saline (TBS) containing 0.05% Tween 20 and with TBS before developing with substrate. A standard dilution curve of AWA-TCA was calculated, and antigen concentrations were calculated with a four parametric curve fitting method, using this dilution curve.

The lower detection limit of the assay was 1 ng/mL of AWA-TCA (0.03 ng of CAA/mL). Antibodies, AWA-TCA, reference samples, and the alkaline phosphate conjugated streptavidin were obtained from the Department of Parasitology, Leiden University Medical Center (Leiden, The Netherlands).

Seroprevalence of HIV-1 and HIV-2.

Antibodies to HIV-1 and HIV-2 were detected using HIV-1 and HIV-2 antibody enzyme immunoassay kits (Abbott Laboratories, Abbott Park, IL). A reactive sample was retested in duplicate. If either or both duplicate retests were reactive, the specimen was considered repeatably reactive. These samples were confirmed by a Western blot for HIV-1 and HIV-2 and a recombinant immunoblot assay.

Statistical analysis.

For statistical analysis, the chi-square test, Fisher’s exact test, the McNemar test, the Mann-Whitney U test, and the Wilcoxon matched pairs signed ranks test were used, as appropriate.

RESULTS

Study subjects characteristics.

The median age of patients and controls in the study population was 12.0 (range = 2–53) years. Forty-nine percent of the participants were male. There was no significant difference in the male:female ratio between BUD patients and controls (P = 0.583, by chi-square test). Sex distribution was the same in this subset included in this study and in the overall group of participants (P = 0.131, by chi-square test).

Intensity of infection.

The level of serum CAA reflects the worm burden16 for both S. haematobium and S. mansoni.17 Detection of serum CAA has a specificity of virtually 100% and a sensitivity of 65–100%.17 Forty-nine percent of the BUD patients had detectable serum CAA compared with 51% of the community controls (96% confidence interval for differences between population proportions = −11.8% to −15.8%). We found no association between a detectable serum CAA and presence of BUD (P = 0.860, by McNemar test) (Table 1). When BUD patients were stratified by disease stage (pre-ulcerative versus ulcerative), there was no difference in detection rate of CAA (P = 0.395, by chi-square test). A subset of 74 of the 106 sets of BUD patients and controls for whom both patient and controls had a test result above the lower detection limit was selected for quantitative comparison in level of serum CAA. Within this group of study subjects, no difference was found in the level of CAA between BUD patients and controls (P = 0.24, by Wilcoxon signed rank test).

Twenty-seven percent of the children between two and four years of age, 43% of the participants between 5 and 14 years of age, and 65% of the participants more than 15 years of age tested positive for serum CAA. The association between older age group and detectable worm loads was significant (P = 0.011, by Mann-Whitney U test). Males were more often found to be positive than females (59% versus 42%; P = 0.013, by chi-square test).

Five of the BUD patients tested positive for HIV-1 and only one of the controls tested positive for HIV-2. This difference did not reach statistical significance (P = 0.212, by Fisher’s exact test). Within this small group of HIV-positive participants, no difference was detected in serum CAA compared with the HIV-negative participants (P = 0.359, by Mann-Whitney U test).

DISCUSSION

In the years following the construction of the Akosombo Dam in 1964, the prevalence of schistosomiasis has increased in areas around Lake Volta. Currently, schistosomiasis is widely distributed in Ghana.9

Serum CAA reflects the current schistosomal worm burden. In this study, 50% of the 212 participants had detectable CAA, a percentage similar to levels described earlier.9 With the high sensitivity of the CAA assay even mild infections can be detected.

Contrary to other reports with those 5–14 years old most affected,9 we found that participants more than 15 years old had the highest rates of infection. This difference may be explained by differences in daily activities that lead to differences in exposure to schistosomes between participants in this and earlier studies.

There were no differences in detection rates of serum CAA or a difference in CAA levels between BUD patients and controls. Contrary to a study in leprosy that showed that the presence of intestinal helminths may facilitate the progression to more severe, multibacillary forms of leprosy,18 detection rates for CAA nor CAA levels differed along the spectrum of diseases stages of BUD in our study.

Infection with HIV-1 affects immune response patterns of patients with schistosomiasis.19 Karanja and others showed that HIV seropositivity affected fecal egg excretion, but did not influence CCA.20 In this study with a small group of HIV-1-positive participants, we could not detect a difference in CAA levels compared with the HIV-1 negative participants. Our finding that schistosome burden was similar among BUD patients and control subjects was not affected by differences in HIV-1 seroprevalence between groups in this study. No difference in HIV-1 seroprevalence could be found between BUD patients and their controls. However, in other populations with a higher HIV-1 seroprevalence, HIV/AIDS might be an important confounding factor.

We hypothesized that schistosomiasis may increase susceptibility to BUD,5 but our results in this case-control design does not support this hypothesis. Perhaps a more robust design to detect a correlation would be a longitudinal cohort study to evaluate the possible influence of ongoing schistosoma infection and development of BUD.

From our data, we conclude that the difference in prevalence of schistosomiasis between BUD patients and matched controls is less than 15.8%. Smaller differences in prevalence would not yield new treatment options or prevention strategies for BUD.

Other chronic infections, such as intestinal helminths may also predispose individuals with M. ulcerans infections to express the pathologic consequences. In addition to schistosomiasis, other host susceptibility and environmental factors should be studied to understand and influence the emergence of BUD in west Africa.

Table 1

Schistosomiasis assessed by circulating anodic antigen (CAA) in serum in patients with Buruli ulcer disease (BUD) and matched controls*

Detection of serum CAABUD patientsControlsTotal
* No significant difference was observed between a detectable serum CAA and the presence of BUD (P = 0.860, by McNemar test).
Negative5452106
Positive5254106
Total106106212

Authors’ addresses: Ymkje Stienstra, Tjip S. van der Werf, and Winette T. A. van der Graaf, Department of Internal Medicine, Groningen University Hospital, PO Box 30.001, 9700 RB Groningen, The Netherlands, Telephone: 31-50-361-1501, Fax: 31-50-361-3216, E-mails: y.stienstra@int.azg.nl and t.s.van.der.werf@int.azg.nl. W. Evan Secor, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341. Stacey L Kihlstrom, Karen M. Dobos, and C. Harold King, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30303. Kwame Asamoa, Ministry of Health, National Buruli Ulcer Control Programme, Korle Bu Accra, Ghana. Eric Quarshi, Agogo Presbyterian Hospital, Agogo, Ghana. Samual N. Etuaful, St. Martin’s Catholic Hospital, Agroyesum, Ghana. Erasmus Y. Klutse, Dunkwa Governmental Hospital, Dunkwa, Ghana.

Acknowledgments: We thank Ellen Spotts Whitney, Pratima Raghunathan, Jeanette Guarner, Jordan Tappero, and David Ashford (Centers for Disease Control and Prevention, Atlanta, GA) for their assistance. We also thank Ablordey and D. Ofori-Adjei (Noguchi Memorial Institute, Accra, Ghana) for their assistance with data and specimen collection.

Financial support: This research was supported in part by a grant from the Centers for Disease Control and Prevention (HHS U50/CCU416560), a grant from the NWO (Dutch Organization for Scientific Research), from the Dr. L. A. Buma foundation, and from the Nicolaas Mulerius foundation in the Netherlands.

REFERENCES

  • 1

    Asiedu K, Raviglione M, Scherpbier R, 1998. International Conference on Buruli Ulcer Control and Research. Yamoussoukro, Côte d’Ivoire. July 6–8, 1998. Geneva: World Health Organization.

  • 2

    Amofah G, Bonsu F, Tetteh C, Okrah J, Asamoa K, Asiedu K, Addy J, 2002. Buruli ulcer in Ghana: results of a national case search. Emerg Infect Dis 8 :167–170.

    • Search Google Scholar
    • Export Citation
  • 3

    Marston BJ, Diallo MO, Horsburgh CR Jr, Diomande I, Saki MZ, Kanga JM, Patrice G, Lipman HB, Ostroff SM, Good RC, 1995. Emergence of Buruli ulcer disease in the Daloa region of Côte d’Ivoire. Am J Trop Med Hyg 52 :219–224.

    • Search Google Scholar
    • Export Citation
  • 4

    Asiedu K, Scherpbier RW, Raviglione M, 2000. Buruli Ulcer-Mycobacterium ulcerans Infection. Geneva: World Health Organization.

  • 5

    Stienstra Y, van der Graaf WT, te Meerman GJ, The TH, de Leij LF, van der Werf TS, 2001. Susceptibility to development of Mycobacterium ulcerans disease: review of possible risk factors. Trop Med Int Health 6 :554–562.

    • Search Google Scholar
    • Export Citation
  • 6

    Bellamy R, Hill AV, 1998. Genetic susceptibility to mycobacteria and other infectious pathogens in humans. Curr Opin Immunol 10 :483–487.

    • Search Google Scholar
    • Export Citation
  • 7

    Ross AG, Bartley PB, Sleigh AC, Olds GR, Li Y, Williams GM, McManus DP, 2002. Schistosomiasis. N Engl J Med 346 :1212–1220.

  • 8

    Wagatsuma Y, Aryeetey ME, Sack DA, Morrow RH, Hatz C, Kojima S, 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.

    • Search Google Scholar
    • Export Citation
  • 9

    Aryeetey ME, Wagatsuma Y, Yeboah G, Asante M, Mensah G, Nkrumah FK, Kojima S, 2000. Urinary schistosomiasis in southern Ghana: 1. Prevalence and morbidity assessment in three (defined) rural areas drained by the Densu River. Parasitol Int 49 :155–163.

    • Search Google Scholar
    • Export Citation
  • 10

    Yamamura M, Uyemura K, Deans RJ, Weinberg K, Rea TH, Bloom BR, Modlin RL, 1991. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science 254 :277–279.

    • Search Google Scholar
    • Export Citation
  • 11

    Yamamura M, 1992. Defining protective responses to pathogens: cytokine profiles in leprosy lesions (erratum). Science 255 :12.

  • 12

    Chensue SW, Warmington K, Ruth JH, Lukacs N, Kunkel SL, 1997. Mycobacterial and schistosomal antigen-elicited granuloma formation in IFN-gamma and IL-4 knockout mice: analysis of local and regional cytokine and chemokine networks. J Immunol 159 :3565–3573.

    • Search Google Scholar
    • Export Citation
  • 13

    Pearce EJ, Caspar P, Grzych JM, Lewis FA, Sher A, 1991. Down-regulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni.J Exp Med 173 :159–166.

    • Search Google Scholar
    • Export Citation
  • 14

    Borkow G, Leng Q, Weisman Z, Stein M, Galai N, Kalinkovich A, Bentwich Z, 2000. Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy. J Clin Invest 106 :1053–1060.

    • Search Google Scholar
    • Export Citation
  • 15

    Deelder AM, De Jonge N, Boerman OC, Fillie YE, Hilberath GW, Rotmans JP, Gerritse MJ, Schut DW, 1989. Sensitive determination of circulating anodic antigen in Schistosoma mansoni infected individuals by an enzyme-linked immunosorbent assay using monoclonal antibodies. Am J Trop Med Hyg 40 :268–272.

    • Search Google Scholar
    • Export Citation
  • 16

    Agnew A, Fulford AJ, De Jonge N, Krijger FW, Rodriguez-Chacon M, Gutsmann V, Deelder AM, 1995. The relationship between worm burden and levels of a circulating antigen (CAA) of five species of Schistosoma in mice. Parasitology 111 :67–76.

    • Search Google Scholar
    • Export Citation
  • 17

    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 :69–80.

    • Search Google Scholar
    • Export Citation
  • 18

    Diniz LM, Zandonade E, Dietze R, Pereira FE, Ribeiro-Rodrigues R, 2001. Short report: do intestinal nematodes increase the risk for multibacillary leprosy? Am J Trop Med Hyg 65 :852–854.

    • Search Google Scholar
    • Export Citation
  • 19

    Mwinzi PN, Karanja DM, Colley DG, Orago AS, Secor WE, 2001. Cellular immune responses of schistosomiasis patients are altered by human immunodeficiency virus type 1 coinfection. J Infect Dis 184 :488–496.

    • Search Google Scholar
    • Export Citation
  • 20

    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 :515–521.

    • Search Google Scholar
    • Export Citation
Save