Skip to main content
×
Home

Treatment with anthelminthics during pregnancy: what gains and what risks for the mother and child?

  • ALISON M. ELLIOTT (a1) (a2), JULIET NDIBAZZA (a1), HARRIET MPAIRWE (a1), LAWRENCE MUHANGI (a1), EMILY L. WEBB (a2), DENNISON KIZITO (a1), PATRICE MAWA (a1), ROBERT TWEYONGYERE (a3) and MOSES MUWANGA (a4)...
Summary
SUMMARY

In 1994 and 2002, respectively, the World Health Organisation proposed that treatment for hookworm and schistosomiasis could be provided during pregnancy. It was hoped that this might have benefits for maternal anaemia, fetal growth and perinatal mortality; a beneficial effect on the infant response to immunisation was also hypothesised. Three trials have now been conducted. Two have examined the effects of benzimidazoles; one (the Entebbe Mother and Baby Study) the effects of albendazole and praziquantel. All three were conducted in settings of high prevalence but low intensity helminth infection. Results suggest that, in such settings and given adequate provision of haematinics, the benefit of routine anthelminthics during pregnancy for maternal anaemia may be small; none of the other expected benefits has yet been demonstrated. The Entebbe Mother and Baby Study found a significant adverse effect of albendazole on the incidence of infantile eczema in the whole study population, and of praziquantel on the incidence of eczema among infants of mothers with Schistosoma mansoni. Further studies are required in settings that differ in helminth species and infection intensities. Further research is required to determine whether increased rates of infantile eczema translate to long-term susceptibility to allergy, and to explore the underlying mechanisms of these effects. The risks and benefits of routine anthelminthic treatment in antenatal clinics may need to be reconsidered.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Treatment with anthelminthics during pregnancy: what gains and what risks for the mother and child?
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Treatment with anthelminthics during pregnancy: what gains and what risks for the mother and child?
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Treatment with anthelminthics during pregnancy: what gains and what risks for the mother and child?
      Available formats
      ×
Copyright
The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence . The written permission of Cambridge University Press must be obtained for commercial re-use.
Corresponding author
Corresponding author: Alison M. Elliott, MRC/UVRI Uganda Research Unit on AIDS, P.O. Box 49, Entebbe, Uganda. Tel: +256 752 720609; Fax: +256 414 321137; E-mail: alison.tom@infocom.co.ug
References
Hide All
Adam I., Elwasila E. and Homeida M. (2005). Praziquantel for the treatment of schistosomiasis mansoni during pregnancy. Annals of Tropical Medicine and Parasitology 99, 3740.
Ajanga A., Lwambo N. J., Blair L., Nyandindi U., Fenwick A. and Brooker S. (2006). Schistosoma mansoni in pregnancy and associations with anaemia in northwest Tanzania. Transactions of the Royal Society of Tropical Medicine and Hygiene 100, 5963.
Albonico M., Stoltzfus R. J., Savioli L., Tielsch J. M., Chwaya H. M., Ercole E. and Cancrini G. (1998). Epidemiological evidence for a differential effect of hookworm species, Ancylostoma duodenale or Necator americanus, on iron status of children. International Journal of Epidemiology 27, 530537.
Allen H. E., Crompton D. W., de Silva N., LoVerde P. T. and Olds G. R. (2002). New policies for using anthelmintics in high risk groups. Trends in Parasitology 18, 381382.
Allen L. H. (2000). Anemia and iron deficiency: effects on pregnancy outcome. American Journal of Clinicial Nutrition 71 (Suppl 5), 1280S1284S.
Atukorala T. M., de Silva L. D., Dechering W. H., Dassenaeike T. S. and Perera R. S. (1994). Evaluation of effectiveness of iron-folate supplementation and anthelminthic therapy against anemia in pregnancy – a study in the plantation sector of Sri Lanka. American Journal of Clinicial Nutrition 60, 286292.
Bach J. F. (2002). The effect of infections on susceptibility to autoimmune and allergic diseases. New England Journal of Medicine 347, 911920.
Brown M., Mawa P. A., Joseph S., Bukusuba J., Watera C., Whitworth J. A., Dunne D. W. and Elliott A. M. (2005). Treatment of Schistosoma mansoni infection increases helminth-specific type 2 cytokine responses and HIV-1 loads in coinfected Ugandan adults. Journal of Infectious Diseases 191, 16481657.
Burke M. L., Jones M. K., Gobert G. N., Li Y. S., Ellis M. K. and McManus D. P. (2009). Immunopathogenesis of human schistosomiasis. Parasite Immunology 31, 163176.
Christian P., Khatry S. K. and West K. P. Jr. (2004). Antenatal anthelmintic treatment, birthweight, and infant survival in rural Nepal. Lancet 364, 981983.
Cooper P. J., Chico M. E., Vaca M. G., Moncayo A. L., Bland J. M., Mafla E., Sanchez F., Rodrigues L. C., Strachan D. P. and Griffin G. E. (2006). Effect of albendazole treatments on the prevalence of atopy in children living in communities endemic for geohelminth parasites: a cluster-randomised trial. Lancet 367, 15981603.
Cruz M. C. and Edlind T. (1997). beta-Tubulin genes and the basis for benzimidazole sensitivity of the opportunistic fungus Cryptococcus neoformans. Microbiology 143, 20032008.
Dayan A. D. (2003). Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics. Acta Tropica 86, 141159.
de Silva N. R., Sirisena J. L., Gunasekera D. P., Ismail M. M. and de Silva H. J. (1999). Effect of mebendazole therapy during pregnancy on birth outcome. Lancet 353, 11451149.
Diav-Citrin O., Shechtman S., Arnon J., Lubart I. and Ornoy A. (2003). Pregnancy outcome after gestational exposure to mebendazole: a prospective controlled cohort study. American Journal of Obstetrics and Gynecology 188, 282285.
Doenhoff M. J., Cioli D. and Utzinger J. (2008). Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Current Opinion in Infectious Diseases 21, 659667.
Elliott A. M., Kizza M., Quigley M. A., Ndibazza J., Nampijja M., Muhangi L., Morison L., Namujju P. B., Muwanga M., Kabatereine N. and Whitworth J. A. (2007). The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447]. Clinical Trials 4, 4257.
Elliott A. M., Mawa P. A., Joseph S., Namujju P. B., Kizza M., Nakiyingi J. S., Watera C., Dunne D. W. and Whitworth J. A. (2003). Associations between helminth infection and CD4+ T cell count, viral load and cytokine responses in HIV-1-infected Ugandan adults. Transactions of the Royal Society of Tropical Medicine and Hygiene 97, 103108.
Elliott A. M., Mawa P. A., Webb E. L., Nampijja M., Lyadda N., Bukusuba J., Kizza M., Namujju P. B., Nabulime J., Ndibazza J., Muwanga M. and Whitworth J. A. (2010). Effects of maternal and infant co-infections, and of maternal immunisation, on the infant response to BCG and tetanus immunisation. Vaccine 29, 247255.
Elliott A. M., Mpairwe H., Quigley M. A., Nampijja M., Muhangi L., Oweka-Onyee J., Muwanga M., Ndibazza J. and Whitworth J. A. (2005). Helminth infection during pregnancy and development of infantile eczema. Journal of the American Medical Association 294, 20322034.
Endara P., Vaca M., Chico M. E., Erazo S., Oviedo G., Quinzo I., Rodriguez A., Lovato R., Moncayo A. L., Barreto M. L., Rodrigues L. C. and Cooper P. J. (2010). Long-term periodic anthelmintic treatments are associated with increased allergen skin reactivity. Clinical Experimental Allergy 40, 16691677.
Flohr C., Quinnell R. J. and Britton J. (2009). Do helminth parasites protect against atopy and allergic disease? Clinical Experimental Allergy 39, 2032.
Flohr C., Tuyen L. N., Quinnell R. J., Lewis S., Minh T. T., Campbell J., Simmons C., Telford G., Brown A., Hien T. T., Farrar J., Williams H., Pritchard D. I. and Britton J. (2010). Reduced helminth burden increases allergen skin sensitization but not clinical allergy: a randomized, double-blind, placebo-controlled trial in Vietnam. Clinical Experimental Allergy 40, 131142.
Friedman J. F., Mital P., Kanzaria H. K., Olds G. R. and Kurtis J. D. (2007). Schistosomiasis and pregnancy. Trends in Parasitology 23, 159164.
Haider B. A., Humayun Q. and Bhutta Z. A. (2009). Effect of administration of antihelminthics for soil transmitted helminths during pregnancy. Cochrane Database of Systematic Reviews (2), CD005547.
Hall A. (1981). Quantitative variability of nematode egg counts in faeces: a study among rural Kenyans. Transactions of the Royal Society of Tropical Medicine and Hygiene 75, 682687.
Illi S., von Mutius E., Lau S., Nickel R., Gruber C., Niggemann B. and Wahn U. (2004). The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. Journal of Allergy and Clinical Immunology 113, 925931.
Illi S., von Mutius E., Lau S., Niggemann B., Gruber C. and Wahn U. (2006). Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study. Lancet 368, 763770.
Keiser J. and Utzinger J. (2008). Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis. Journal of the American Medical Association 299, 19371948.
Labeaud A. D., Malhotra I., King M. J., King C. L. and King C. H. (2009). Do antenatal parasite infections devalue childhood vaccination? PLoS Neglected Tropical Diseases 3, e442.
Lacey E. (1990). Mode of action of benzimidazoles. Parasitology Today 6, 112115.
Lammie P. J., Hitch W. L., Walker Allen E. M., Hightower W. and Eberhard M. L. (1991). Maternal filarial infection as risk factor for infection in children. Lancet 337, 10051006.
Larocque R., Casapia M., Gotuzzo E. and Gyorkos T. W. (2005). Relationship between intensity of soil-transmitted helminth infections and anemia during pregnancy. American Journal of Tropical Medicine and Hygiene 73, 783789.
Larocque R., Casapia M., Gotuzzo E., MacLean J. D., Soto J. C., Rahme E. and Gyorkos T. W. (2006). A double-blind randomized controlled trial of antenatal mebendazole to reduce low birthweight in a hookworm-endemic area of Peru. Tropical Medicine and International Health 11, 14851495.
Leonardi-Bee J., Pritchard D. and Britton J. (2006). Asthma and current intestinal parasite infection: systematic review and meta-analysis. American Journal of Tropical Medicine and Hygiene 174, 514523.
Lynch N. R., Hagel I., Perez M., Di Prisco M. C., Lopez R. and Alvarez N. (1993). Effect of anthelmintic treatment on the allergic reactivity of children in a tropical slum. Journal of Allergy and Clinical Immunology 92, 404411.
MacDonald L. M., Armson A., Thompson A. R. and Reynoldson J. A. (2004). Characterisation of benzimidazole binding with recombinant tubulin from Giardia duodenalis, Encephalitozoon intestinalis, and Cryptosporidium parvum. Molecular and Biochemical Parasitology 138, 8996.
Malhotra I., Mungai P., Wamachi A., Kioko J., Ouma J. H., Kazura J. W. and King C. L. (1999). Helminth- and Bacillus Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. Journal of Immunology 162, 68436848.
Malhotra I., Mungai P. L., Wamachi A. N., Tisch D., Kioko J. M., Ouma J. H., Muchiri E., Kazura J. W. and King C. L. (2006). Prenatal T cell immunity to Wuchereria bancrofti and its effect on filarial immunity and infection susceptibility during childhood. Journal of Infectious Diseases 193, 10051013.
Malhotra I., Ouma J., Wamachi A., Kioko J., Mungai P., Omollo A., Elson L., Koech D., Kazura J. W. and King C. L. (1997). In utero exposure to helminth and mycobacterial antigens generates cytokine responses similar to that observed in adults. Journal of Clinical Investigation 99, 17591766.
Mpairwe H., Webb E. L., Muhangi L., Ndibazza J., Akishule D., Nampijja M., Ngom-Wegi S., Tumusiime J., Muwanga M., Rodrigues L. C. and Elliott A. M. (2011). De-worming during pregnancy is associated with an increased risk of allergic conditions in infancy: results from a randomised controlled trial. Pediatric Allergy and Immunology 22, 305–12.
Muhangi L., Woodburn P., Omara M., Omoding N., Kizito D., Mpairwe H., Nabulime J., Ameke C., Morison L. A. and Elliott A. M. (2007). Associations between mild-to-moderate anaemia in pregnancy and helminth, malaria and HIV infection in Entebbe, Uganda. Transactions of the Royal Society of Tropical Medicine and Hygiene 101, 899907.
Ndibazza J., Muhangi L., Akishule D., Kiggundu M., Ameke C., Oweka J., Kizindo R., Duong T., Kleinschmidt I., Muwanga M. and Elliott A. M. (2010). Effects of deworming during pregnancy on maternal and perinatal outcomes in Entebbe, Uganda: a randomized controlled trial. Clinical Infectious Diseases 50, 531540.
Novato-Silva E., Gazzinelli G. and Colley D. G. (1992). Immune responses during human schistosomiasis mansoni. XVIII. Immunologic status of pregnant women and their neonates. Scandanavian Journal of Immunology 35, 429437.
Pena-Rosas J. P. and Viteri F. E. (2006). Effects of routine oral iron supplementation with or without folic acid for women during pregnancy. Cochrane Database of Systematic Reviews 3, CD004736.
Plotkin S. A. (2010). Correlates of protection induced by vaccination. Clinical and Vaccine Immunology 17, 10551065.
Roche M. and Layrisse M. (1966). The nature and causes of “hookworm anemia”. American Journal of Tropical Medicine and Hygiene 15, 10291102.
Skinner-Adams T. S., Davis T. M., Manning L. S. and Johnston W. A. (1997). The efficacy of benzimidazole drugs against Plasmodium falciparum in vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene 91, 580584.
Smits H. H., Everts B., Hartgers F. C. and Yazdanbakhsh M. (2010). Chronic helminth infections protect against allergic diseases by active regulatory processes. Current Allergy and Asthma Reports 10, 312.
Solaymani-Mohammadi S., Genkinger J. M., Loffredo C. A. and Singer S. M. (2010). A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infections with Giardia duodenalis. PLoS Neglected Tropical Diseases 4(5), e682.
Steel C., Guinea A., McCarthy J. S. and Ottesen E. A. (1994). Long-term effect of prenatal exposure to maternal microfilaraemia on immune responsiveness to filarial parasite antigens. Lancet 343, 890893.
Torlesse H. and Hodges M. (2001). Albendazole therapy and reduced decline in haemoglobin concentration during pregnancy (Sierra Leone). Transactions of the Royal Society of Tropical Medicine and Hygiene 95, 195201.
Tweyongyere R., Mawa P. A., Emojong N. O., Mpairwe H., Jones F. M., Duong T., Dunne D. W., Vennervald B. J., Katunguka-Rwakishaya E. and Elliott A. M. (2009). Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens: results of a randomised, placebo-controlled trial. BMC Infectious Diseases 9, 32.
Tweyongyere R., Mawa P. A., Ngom-Wegi S., Ndibazza J., Duong T., Vennervald B. J., Dunne D. W., Katunguka-Rwakishaya E. and Elliott A. M. (2008). Effect of praziquantel treatment during pregnancy on cytokine responses to schistosome antigens: results of a randomized, placebo-controlled trial. Journal of Infectious Diseases 198, 18701879.
Utzinger J., Booth M., N'Goran E. K., Muller I., Tanner M. and Lengeler C. (2001). Relative contribution of day-to-day and intra-specimen variation in faecal egg counts of Schistosoma mansoni before and after treatment with praziquantel. Parasitology, 122, 537544.
van den Biggelaar A. H., Rodrigues L. C., van Ree R., van der Zee J. S., Hoeksma-Kruize Y. C., Souverijn J. H., Missinou M. A., Borrmann S., Kremsner P. G. and Yazdanbakhsh M. (2004). Long-term treatment of intestinal helminths increases mite skin-test reactivity in Gabonese schoolchildren. Journal of Infectious Diseases 189, 892900.
van Riet E., Hartgers F. C. and Yazdanbakhsh M. (2007). Chronic helminth infections induce immunomodulation: consequences and mechanisms. Immunobiology, 212, 475490.
Venn A., Yemaneberhan H., Lewis S., Parry E. and Britton J. (2005). Proximity of the home to roads and the risk of wheeze in an Ethiopian population. Occupational and Environmental Medicine 62, 376380.
Venn A. J., Yemaneberhan H., Bekele Z., Lewis S. A., Parry E. and Britton J. (2001). Increased risk of allergy associated with the use of kerosene fuel in the home. American Journal of Tropical Medicine and Hygiene 164, 16601664.
von Mutius E. and Le Souef P. N. (2007). Early gene-environment interactions: can they inform primary preventive strategies for asthma? Seminars in Respiratory Critical Care Medicine 28, 255263.
Webb E. L., Mawa P. A., Ndibazza J., Kizito D., Namatovu A., Kyosiimire-Lugemwa J., Nanteza B., Nampijja M., Muhangi L., Woodburn P. W., Akurut H., Mpairwe H., Akello M., Lyadda N., Bukusuba J., Kihembo M., Kizza M., Kizindo R., Nabulime J., Ameke C., Namujju P. B., Tweyongyere R., Muwanga M., Whitworth J. A. and Elliott A. M. (2011). Effect of single-dose anthelmintic treatment during pregnancy on an infant's response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial. Lancet 377, 5262.
WHO (1995). Report of the WHO informal consultation on hookworm infection and anaemia in girls and women. Geneva, 5–7 December 1994. WHO/CTD/SIP/96.1.
WHO (1999). Monitoring Helminth Control Programmes. Guidelines for monitoring the impact of control programmes aimed at reducing morbidity caused by soil-transmitted helminths and schistosomes, with particular reference to school-age children. WHO/CDS/CPC/SIP/99.3.
WHO (2002). Report of the WHO informal consultation on the use of praziquantel during pregnancy/lactation and albendazole/mebendazole in children under 24 months. Geneva, 8–9 April 2002. WHO/CDS/CPE/PVC/2002.4.
WHO (2006). Report of the Scientific Working Group meeting on Schistosomiasis, Geneva, 14–16 November, 2005. TDR/SWG/07.
WHO (2010). Asthma Facts. World Health Organisation, Geneva.
Williams H. and Flohr C. (2006). How epidemiology has challenged 3 prevailing concepts about atopic dermatitis. Journal of Allergy and Clinical Immunology 118, 209213.
Woodburn P. W., Muhangi L., Hillier S., Ndibazza J., Namujju P. B., Kizza M., Ameke C., Omoding N. E., Booth M. and Elliott A. M. (2009). Risk Factors for Helminth, Malaria, and HIV Infection in Pregnancy in Entebbe, Uganda. PLoS Neglected Tropical Diseases 3(6), e473.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Parasitology
  • ISSN: 0031-1820
  • EISSN: 1469-8161
  • URL: /core/journals/parasitology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Full text views

Total number of HTML views: 9
Total number of PDF views: 145 *
Loading metrics...

Abstract views

Total abstract views: 217 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 22nd November 2017. This data will be updated every 24 hours.