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Published in: BMC Infectious Diseases 1/2005

Open Access 01-12-2005 | Research article

A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to bacille Calmette-Guérin (BCG) immunisation [ISRCTN32849447]

Authors: Alison M Elliott, Proscovia B Namujju, Patrice A Mawa, Maria A Quigley, Margaret Nampijja, Peter M Nkurunziza, John T Belisle, Moses Muwanga, James AG Whitworth, the "Mother and Baby" study team

Published in: BMC Infectious Diseases | Issue 1/2005

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Abstract

Background

Maternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG) immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown.

Methods

In Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG. Interferon-gamma (IFN-γ) and interleukin (IL)-5 responses to a mycobacterial antigen (crude culture filtrate proteins (CFP) of Mycobacterium tuberculosis) were measured in a whole blood assay. We analysed results for binary variables using χ2 tests and logistic regression. We analysed continuous variables using Wilcoxon's tests.

Results

Maternal hookworm was associated with reduced maternal IFN-γ responses to CFP (adjusted odds ratio for IFN-γ > median response: 0.14 (95% confidence interval 0.02–0.83, p = 0.021). Conversely, maternal hookworm was associated with subsequent increased IFN-γ responses in their one-year-old infants (adjusted OR 17.65 (1.20–258.66; p = 0.013)). Maternal albendazole tended to reduce these effects.

Conclusion

Untreated hookworm infection in pregnancy was associated with reduced maternal IFN-γ responses to mycobacterial antigens, but increased responses in their infants one year after BCG immunisation. The mechanisms of these effects, and their implications for protective immunity remain, to be determined.
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Literature
1.
go back to reference Colditz GA, Brewer TF, Berkley CS, Wilson ME, Burdick E, Fineberg HV, Mosteller F: Efficacy of BCG vaccine in the prevention of tuberculosis. JAMA. 1994, 271: 698-702. 10.1001/jama.271.9.698.CrossRefPubMed Colditz GA, Brewer TF, Berkley CS, Wilson ME, Burdick E, Fineberg HV, Mosteller F: Efficacy of BCG vaccine in the prevention of tuberculosis. JAMA. 1994, 271: 698-702. 10.1001/jama.271.9.698.CrossRefPubMed
2.
go back to reference Maizels RM, Yazdanbakhsh M: Immune regulation by helminth parasites: cellular and molecular mechanisms. Nature Reviews in Immunology. 2003, 3: 733-744. 10.1038/nri1183.CrossRefPubMed Maizels RM, Yazdanbakhsh M: Immune regulation by helminth parasites: cellular and molecular mechanisms. Nature Reviews in Immunology. 2003, 3: 733-744. 10.1038/nri1183.CrossRefPubMed
3.
go back to reference Bundy D, Sher A, Michael E: Good worms or bad worms: do worm infections affect the epidemiological patterns of other diseases?. Parasitology Today. 2000, 16: 273-312. 10.1016/S0169-4758(00)01689-6.CrossRefPubMed Bundy D, Sher A, Michael E: Good worms or bad worms: do worm infections affect the epidemiological patterns of other diseases?. Parasitology Today. 2000, 16: 273-312. 10.1016/S0169-4758(00)01689-6.CrossRefPubMed
4.
go back to reference Malhotra I, Mungai P, Wamachi A, Kioko J, Ouma JH, Kazura JW, King CL: Helminth- and Bacillus-Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. Journal of Immunology. 1999, 162: 6843-6848. Malhotra I, Mungai P, Wamachi A, Kioko J, Ouma JH, Kazura JW, King CL: Helminth- and Bacillus-Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. Journal of Immunology. 1999, 162: 6843-6848.
5.
go back to reference Hotez PJ, Brooker S, Bethony JM, Bottazzi ME, Loukas A, Xiao S: Hookworm infection. New England Journal of Medicine. 2004, 49-56. Hotez PJ, Brooker S, Bethony JM, Bottazzi ME, Loukas A, Xiao S: Hookworm infection. New England Journal of Medicine. 2004, 49-56.
6.
go back to reference Quinnell RJ, Pritchard DI, Raiko A, Brown AP, Shaw M-A: Immune responses in human necatoriasis: Interleukin-5 responses are associated with resistance to reinfection. Journal of Infectious Diseases. 2004, 190: 430-438. 10.1086/422256.CrossRefPubMed Quinnell RJ, Pritchard DI, Raiko A, Brown AP, Shaw M-A: Immune responses in human necatoriasis: Interleukin-5 responses are associated with resistance to reinfection. Journal of Infectious Diseases. 2004, 190: 430-438. 10.1086/422256.CrossRefPubMed
7.
go back to reference Bradley M, Horton J: Assessing the risk of benzimidazole therapy during pregnancy. Transactions of the Royal Society of Tropical Medicine & Hygiene. 2001, 95: 72-73. 10.1016/S0035-9203(01)90338-4.CrossRef Bradley M, Horton J: Assessing the risk of benzimidazole therapy during pregnancy. Transactions of the Royal Society of Tropical Medicine & Hygiene. 2001, 95: 72-73. 10.1016/S0035-9203(01)90338-4.CrossRef
8.
go back to reference News & Analysis: Soil-transmitted helminthiasis. Nature Reviews in Microbiology. 2004, 2: 618-619. 10.1038/nrmicro962.CrossRef News & Analysis: Soil-transmitted helminthiasis. Nature Reviews in Microbiology. 2004, 2: 618-619. 10.1038/nrmicro962.CrossRef
9.
go back to reference Allen HE, Crompton DWT, de Silva N, LoVerde PT, Olds GR: New policies for using anthelminthics in high risk groups. Trends in Parasitology. 2002, 18: 381-382. 10.1016/S1471-4922(02)02386-3.CrossRefPubMed Allen HE, Crompton DWT, de Silva N, LoVerde PT, Olds GR: New policies for using anthelminthics in high risk groups. Trends in Parasitology. 2002, 18: 381-382. 10.1016/S1471-4922(02)02386-3.CrossRefPubMed
10.
go back to reference Bukusuba JW, Hughes P, Kizza M, Muhangi L, Muwanga M, Whitworth JAG, Elliott AM: Screening for intestinal helminth infection in a semi-urban cohort of pregnant women in Uganda. Tropical Doctor. 2004, 34: 27-28.PubMed Bukusuba JW, Hughes P, Kizza M, Muhangi L, Muwanga M, Whitworth JAG, Elliott AM: Screening for intestinal helminth infection in a semi-urban cohort of pregnant women in Uganda. Tropical Doctor. 2004, 34: 27-28.PubMed
11.
go back to reference Melrose WD, Turner PF, Pisters P, Turner B: An improved Knott's concentration test for the detection of microfilariae. Transactions of the Royal Society for Tropical Medicine & Hygiene. 2000, 94: 176-10.1016/S0035-9203(00)90266-9.CrossRef Melrose WD, Turner PF, Pisters P, Turner B: An improved Knott's concentration test for the detection of microfilariae. Transactions of the Royal Society for Tropical Medicine & Hygiene. 2000, 94: 176-10.1016/S0035-9203(00)90266-9.CrossRef
12.
go back to reference Elliott AM, Hurst TJ, Baleyku M, Quigley M, Kaleebu P, French N, Biryawaho B, Whitworth JAG, Dockrell HM, Hayes RJ: The immune response to Mycobacterium tuberculosis in HIV infected and uninfected adults: Application of the whole blood cytokine assay in an epidemiological study in Uganda. International Journal of Tuberculosis and Lung Disease. 1999, 3: 239-247.PubMed Elliott AM, Hurst TJ, Baleyku M, Quigley M, Kaleebu P, French N, Biryawaho B, Whitworth JAG, Dockrell HM, Hayes RJ: The immune response to Mycobacterium tuberculosis in HIV infected and uninfected adults: Application of the whole blood cytokine assay in an epidemiological study in Uganda. International Journal of Tuberculosis and Lung Disease. 1999, 3: 239-247.PubMed
13.
go back to reference Moir M, Holbrook RH: Application of the hemoglobin alkaline denaturation test to determine the fetal origin of blood: applicability to funipuncture. Obstetrics & Gynecology. 1993, 81: 793-796. Moir M, Holbrook RH: Application of the hemoglobin alkaline denaturation test to determine the fetal origin of blood: applicability to funipuncture. Obstetrics & Gynecology. 1993, 81: 793-796.
14.
go back to reference Hall A: Quantitative variability of nematode egg counts in faeces: a study among rural Kenyans. Transaction of the Royal Society of Tropical Medicine and Hygiene. 1981, 75: 682-687. 10.1016/0035-9203(81)90148-6.CrossRef Hall A: Quantitative variability of nematode egg counts in faeces: a study among rural Kenyans. Transaction of the Royal Society of Tropical Medicine and Hygiene. 1981, 75: 682-687. 10.1016/0035-9203(81)90148-6.CrossRef
15.
go back to reference Pearlman E, Kazura JW, Hazlett FE, Boom WH: Modulation of murine cytokine responses to mycobacterial antigens by helminth-induced T helper 2 cell responses. Journal of Immunology. 1993, 151: 4857-4864. Pearlman E, Kazura JW, Hazlett FE, Boom WH: Modulation of murine cytokine responses to mycobacterial antigens by helminth-induced T helper 2 cell responses. Journal of Immunology. 1993, 151: 4857-4864.
16.
go back to reference Erb KJ, Trujillo C, Fugate M, Moll H: Infection with the helminth Nippostrongylus brasiliensis does not interfere with efficient elimination of Mycobacterium bovis BCG from the lungs of mice. Clinical and Diagnostic Laboratory Immunology. 2002, 9: 727-730. 10.1128/CDLI.9.3.727-730.2002.PubMedPubMedCentral Erb KJ, Trujillo C, Fugate M, Moll H: Infection with the helminth Nippostrongylus brasiliensis does not interfere with efficient elimination of Mycobacterium bovis BCG from the lungs of mice. Clinical and Diagnostic Laboratory Immunology. 2002, 9: 727-730. 10.1128/CDLI.9.3.727-730.2002.PubMedPubMedCentral
17.
go back to reference Elias D, Akuffo H, Thors C, Pawlowski A, Britton S: Low dose chronic Schistosoma mansoni infection increases susceptibility to Mycobacterium bovis BCG infection in mice. Clinical and Experimental Immunology. 2005, 139: 398-404. 10.1111/j.1365-2249.2004.02719.x.CrossRefPubMedPubMedCentral Elias D, Akuffo H, Thors C, Pawlowski A, Britton S: Low dose chronic Schistosoma mansoni infection increases susceptibility to Mycobacterium bovis BCG infection in mice. Clinical and Experimental Immunology. 2005, 139: 398-404. 10.1111/j.1365-2249.2004.02719.x.CrossRefPubMedPubMedCentral
18.
go back to reference Elias D, Akuffo H, Pawlowski A, Haile M, Schon T, Britton S: infection reduces the protective efficacy of BCG vaccination against virulent Mycobacterium tuberculosis. Schistosoma mansoni. Vaccine. 2005, 23: 1326-1334. 10.1016/j.vaccine.2004.09.038.CrossRefPubMed Elias D, Akuffo H, Pawlowski A, Haile M, Schon T, Britton S: infection reduces the protective efficacy of BCG vaccination against virulent Mycobacterium tuberculosis. Schistosoma mansoni. Vaccine. 2005, 23: 1326-1334. 10.1016/j.vaccine.2004.09.038.CrossRefPubMed
19.
go back to reference El-Kalouby AH, Amer R, Abdel-Wahab MF, El-Raziky EH: Delayed hypersensitivity to specific antigen and heterologous PPD antigen in patients infected with Schistosoma mansoni and/or Schistosoma haematobium. Egyptian Journal of Bilharzia. 1979, 6: 43-49. El-Kalouby AH, Amer R, Abdel-Wahab MF, El-Raziky EH: Delayed hypersensitivity to specific antigen and heterologous PPD antigen in patients infected with Schistosoma mansoni and/or Schistosoma haematobium. Egyptian Journal of Bilharzia. 1979, 6: 43-49.
20.
go back to reference Kilian HD, Nielsen G: Cell mediated and humoral immune responses to BCG and rubella vaccinations and to recall antigens in onchocerciasis patients. Tropical Medicine and Parasitology. 1989, 40: 445-453.PubMed Kilian HD, Nielsen G: Cell mediated and humoral immune responses to BCG and rubella vaccinations and to recall antigens in onchocerciasis patients. Tropical Medicine and Parasitology. 1989, 40: 445-453.PubMed
21.
go back to reference Elkhalifa MY, Ghalib HW, Dafa'alla T, Williams JF: Suppression of human lymphocyte responses to specific and non-specific stimuli in human onchocerciasis. Clinical Experimental Immunology. 1991, 86: 433-439.CrossRefPubMedPubMedCentral Elkhalifa MY, Ghalib HW, Dafa'alla T, Williams JF: Suppression of human lymphocyte responses to specific and non-specific stimuli in human onchocerciasis. Clinical Experimental Immunology. 1991, 86: 433-439.CrossRefPubMedPubMedCentral
22.
go back to reference Pelly TF, Santillan CF, Gilman RH, Cabrera LZ, Garcia E, Vidal C, Zimic MJ, Moore DAJ, Evans CA: Tuberculosis skin testing, anergy and protein malnutrition in Peru. International Journal of Tuberculosis and Lung Disease. 2005, 9: 977-984.PubMedPubMedCentral Pelly TF, Santillan CF, Gilman RH, Cabrera LZ, Garcia E, Vidal C, Zimic MJ, Moore DAJ, Evans CA: Tuberculosis skin testing, anergy and protein malnutrition in Peru. International Journal of Tuberculosis and Lung Disease. 2005, 9: 977-984.PubMedPubMedCentral
23.
go back to reference Rougemont A, Boisson-Pontal ME, Pontal PG, Gridel F: Tuberculin skin tests and BCG vaccination in hyperendemic area of onchocerciasis. 1977, i: 309- Rougemont A, Boisson-Pontal ME, Pontal PG, Gridel F: Tuberculin skin tests and BCG vaccination in hyperendemic area of onchocerciasis. 1977, i: 309-
24.
go back to reference Elias D, Wolday D, Akuffo H, Petros B, Bronner U, Britton S: Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guerin (BCG) vaccination. Clinical Experimental Immunology. 2001, 123: 219-225. 10.1046/j.1365-2249.2001.01446.x.CrossRefPubMedPubMedCentral Elias D, Wolday D, Akuffo H, Petros B, Bronner U, Britton S: Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guerin (BCG) vaccination. Clinical Experimental Immunology. 2001, 123: 219-225. 10.1046/j.1365-2249.2001.01446.x.CrossRefPubMedPubMedCentral
25.
go back to reference Power CA, Wei G, Bretscher PA: Mycobacterial dose defines the Th1/Th2 nature of the immune response independently of whether immunization is administered by intravenous, subcutaneous or intradermal route. Infection and Immunity. 1998, 66: 5743-5750.PubMedPubMedCentral Power CA, Wei G, Bretscher PA: Mycobacterial dose defines the Th1/Th2 nature of the immune response independently of whether immunization is administered by intravenous, subcutaneous or intradermal route. Infection and Immunity. 1998, 66: 5743-5750.PubMedPubMedCentral
26.
go back to reference Gruppo V, Orme IM: Dose of BCG does not influence the efficient generation of protective immunity in mice challenged with Mycobacterium tuberculosis. Tuberculosis. 2002, 82: 267-273. 10.1054/tube.2002.0340.CrossRefPubMed Gruppo V, Orme IM: Dose of BCG does not influence the efficient generation of protective immunity in mice challenged with Mycobacterium tuberculosis. Tuberculosis. 2002, 82: 267-273. 10.1054/tube.2002.0340.CrossRefPubMed
27.
go back to reference Elliott AM, Hodsdon WS, Kyosiimire J, Quigley MA, Nakiyingi JS, Namujju PB, Watera C, French N, Gilks CF, Dockrell HM, Whitworth JAG: Cytokine responses and progression to active tuberculosis in HIV-1 infected Ugandans: a prospective study. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2004, 98: 660-670.CrossRefPubMed Elliott AM, Hodsdon WS, Kyosiimire J, Quigley MA, Nakiyingi JS, Namujju PB, Watera C, French N, Gilks CF, Dockrell HM, Whitworth JAG: Cytokine responses and progression to active tuberculosis in HIV-1 infected Ugandans: a prospective study. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2004, 98: 660-670.CrossRefPubMed
Metadata
Title
A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to bacille Calmette-Guérin (BCG) immunisation [ISRCTN32849447]
Authors
Alison M Elliott
Proscovia B Namujju
Patrice A Mawa
Maria A Quigley
Margaret Nampijja
Peter M Nkurunziza
John T Belisle
Moses Muwanga
James AG Whitworth
the "Mother and Baby" study team
Publication date
01-12-2005
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2005
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-5-115

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