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Journal of Tropical Pediatrics Advance Access originally published online on September 11, 2008
Journal of Tropical Pediatrics 2009 55(1):5-7; doi:10.1093/tropej/fmn073
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© The Author [2008]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Clinical Review

Evidence behind the WHO Guidelines: Hospital Care for Children: What is the most appropriate treatment for giardiasis?

Primary Reviewer: Edward Chandy

University of Edinburgh, Scotland

Secondary Reviewer: James McCarthy

Queensland Institute of Medical Research, University of Queensland, Australia

For more information on this project to evaluate the evidence behind the WHO Hospital Care for Children, see J Trop Pediatr 2006; 52: 1–2. If you would like suggest a topic or contribute a review, please contact Dr Julian Kelly. E-mail <julian.kelly{at}rch.org.au>.

The World Health Organization has produced guidelines for the management of common illnesses in hospitals with limited resources. This series reviews the scientific evidence behind WHO's recommendations. The WHO guidelines, and more reviews are available at: http://www.ichrc.org.

This review addresses the question: What is the most appropriate treatment for giardiasis?

The WHO Pocketbook of Hospital Care for Children recommends for giardiasis metronidazole 5 mg/kg 3 times a day for 5 days. (Pocketbook chapter 5.3.1, p. 123).


   Introduction
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Giardia Lamblia is the most commonly detected pathogenic protozoan in the human intestine [1]. Found in about 20% in patients with diarrhoea, its incidence may be as high as a billion cases, contributing to the 2.5 million annual deaths worldwide from diarrhoeal disease [2]. The most prominent symptoms, generally appearing 6–15 days after infection, are steatorrhoea, weakness, weight loss and abdominal pain.

Mostly these are self-limiting, though it is estimated that 30–50% of patients develop chronic disease. Steatorrhoea, iron deficiency anaemia, micronutrient deficiencies and malnutrition are among the long-term sequelae and can cause failure to thrive and psychomotor retardation in children [3].


   Methodology
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Search terms [Giardia$] AND [treatment OR therapeutics] AND [child$ OR paediat$ OR pediat$] were entered into MEDLINE, EMBASE and GLOBAL HEALTH with results limited to English language and 1990–2007. Only randomized controlled trials (RCTs) performed in low or middle income countries (according to the World Bank) were eligible for inclusion. Recent literature reviews [4] (http://www.sign.ac.uk/guidelines/fulltext/50/checklist2.html) were also searched to ensure that no pertinent RCTs had been overlooked. Aside from two exceptional cases [5, 6], only studies that featured both children with mono-infection and those who had presented symptomatically to health services were included. The exceptions were included due to their high quality. Fifteen trials met the inclusion criteria and depending on the number of SIGN 50 criteria [7] they met, were subclassified ‘1–’, ‘1+’ or ‘1++’.


   Results
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Discussion
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The literature on giardiasis since 1990 has concentrated on a relatively consistent set of pharmacological agents. In the RCTs included in this review metronidazole, currently the first line treatment, was shown to completely clear the protozoa on parasitological analysis with an efficacy ranging from 75% to 100% of patients [5, 8–15]. However, other nitroimidazoles (tinidazole, ornidazole and secnidazole), which have the advantage of requiring only a single dose, have demonstrated at least equivalent efficacy (100%, 79–100% and 82–93%, respectively) [6, 9, 13, 16–18]. The benzimidazoles, albendazole and mebendazole, were shown to be slightly less effective; results range from 50%–100% to 58.3–100%, respectively [5, 6, 8–12, 16–20].

No drug was reported to be unsafe, causing only mild to moderate and transient side effects (SEs). Whilst metronidazole was reported to produce SEs in up to approximately a quarter of patients (0–27%) [6, 12, 20]; tinidazole caused similar effects in nearly to two-thirds of children in one study (28–59%). Most common SEs included nausea and vomiting, metallic taste, headache and vertigo [5, 8–10, 11–15]. Various studies confirm the lower incidence of reported SEs with albendazole (0–8%) [5, 10, 16, 17, 19, 20].

Albendazole, mebendazole, metronidazole are on the WHO essential paediatric drug list [21]. Of the other drugs reviewed, only tinidazole is available cheaply in generic form large international pharmaceutical suppliers. Tinidazole is the cheapest of these at $40 per 1000 children treated compared with $45 for metronidazole. Albendazole and Mebendazole are more expensive at $52 and $86, respectively [22].


   Discussion
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Conclusion
 References
 
The nitroimidazoles appear to remain the most effective drugs available for treating giardiasis. The results of this review suggest that a single dose of tinidazole (50 mg/kg) has a similar efficacy to that of metronidazole, though the former has particular advantages in a resource poor setting. It is generally well tolerated and, because it requires only a single dose, has the potential to improve compliance. It is also slightly cheaper than metronidazole per treatment.

Therefore, it is suggested that the current WHO guidelines may no longer be the most appropriate; though this is mitigated by awareness that long-term safety data for tinidazole is not available in either adults or children. As cases of resistance to all anti-giardial agents have been reported, it is important that physicians have access to a range of medications and, in regions where the disease is prevalent, it is imperative to periodically audit local drug sensitivity patterns.


   Conclusion
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Decades of evidence confirm that giardiasis responds well to antimicrobial treatment, decreasing the length of the illness and reducing the possibility of long-term complications [1, 23]. Nitroimidazoles are the most effective drugs available, and considering compliance, side effects and cost, a single dose of tinidazole is the most appropriate treatment for children in resource poor settings.


   Notes
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Introduction
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Section Editors: Trevor Duke and Julian Kelly.


   References
Top
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 Introduction
 Methodology
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 References
 

  1. Wright JM, Dunn LA, Upcroft P, Upcroft JA. Efficacy of antigirdial drugs. Expert Opin Drug Saf (2003) 2:529–41.[CrossRef][Medline]
  2. Islam A. Giardiasis in developing countries. In. In: Human parasitic diseases—Meyer EA, ed. (1990) 3. Giardiasis: Amsterdam: Elsevier. 235–66.
  3. Gardner TB, Hill DR. Treatment of Giardiasis. Clin Microbiol Rev (2001) 14:114–28.[Abstract/Free Full Text]
  4. Escobedo AA, Cimerman S. Giardiasis: a pharmacotherapy review. Expert Opin Pharmacother (2007) 8(Pt 12):1885–19.[CrossRef][Web of Science][Medline]
  5. Hall A, Nahar Q. Albendazole as a treatment for infections with Giardia duodenalis in children in Bangladesh. Trans R Soc Trop Med Hyg (1993) 87:84–6.[CrossRef][Web of Science][Medline]
  6. Pengsaa K, Limkittikul K, Pojjaroen-anant C, et al. Single-dose therapy for giardiasis in school-age children. Southeast Asian J Trop Med Public Health (2002) 33:711–7.[Medline]
  7. SIGN 50: A guideline developer's handbook Guideline No. 50 ISBN 19781905813254 Revised edition January 2008.
  8. Dutta AK, Phadke MA, Bagade AC, et al. A randomised multicentre study to compare safety and efficacy of Albendazole and 70 Metronidazole in the treatment of giardiasis in children. Indian J Pediatr (1994) 61:689–93.[Medline]
  9. Misra PK, Kumar A, Agarwal V, Jagota SC. A comparative trial of albendazole versus metronidazole in children with giardiasis. Indian Pediatr (1995) 32:779–82.[Medline]
  10. Yereli K, Balcioglu C, Ertan P, et al. Albendazole as an alternative treatment for childhood giardiasis in Turkey. Clin Microbiol Infect (2004) 10:527–9.[CrossRef][Web of Science][Medline]
  11. Sadjjadi1 SM, Alborzi AW, Mostovfi H. Comparative clinical trial of Mebendazole and Metronidazole in giardiasis of children. J Trop Pediatr (2001) 47:176–8.[Abstract/Free Full Text]
  12. Bulut BU, Gulnar SB, Aysev D. Alternative treatment protocols in giardiasis: a pilot study. Scand J Infect Dis (1996) 28:493–5.[Web of Science][Medline]
  13. Rastegar-Lari A, Salek-Moghaddam A. Single-dose secnidazole versus 10-day metronidazole therapy of giardiasis in Iranian children. J Trop Pediatr (1996) 42:184–5.[Free Full Text]
  14. Ortiz JJ, Ayoub A, Gargala G, et al. Randomized clinical study of nitazoxanide compared to metronidazole in the treatment of symptomatic giardiasis in children from Northern Peru. Aliment Pharmacol Ther (2001) 15:1409–15.[CrossRef][Web of Science][Medline]
  15. Talari SA, Momtazmanesh N, Talebian A, et al. Comparison of Metronidazole and Furazolidone against giardia lamblia in children. J Med Sci (2006) 6:378–81.
  16. Escobedo AA, Nunez FA, Moreira I, et al. Comparison of chloroquine, albendazole and tinidazole in the treatment of children 100 with giardiasis. Ann Trop Med Parasitol (2003) 97:367–71.[CrossRef][Web of Science][Medline]
  17. Cañete R, Escobedo AA, González ME, et al. A randomized, controlled, open-label trial of a single day of mebendazole versus a single dose of tinidazole in the treatment of giardiasis in children. Curr Med Res Opin (2006) 22:2131–6.[CrossRef][Web of Science][Medline]
  18. Escobedo AA, Cañete R, Gonzalez ME, et al. A randomized trial comparing mebendazole and secnidazole for the treatment of giardiasis. Ann Trop Med Parasitol (2003) 97:499–504.[CrossRef][Web of Science][Medline]
  19. Canete R, Escobedo AA, Gonzalez ME, ALmirall P. Randomized clinical study of five days’ therapy with mebendazole compared to quinacrine in the treatment of symptomatic giardiasis in children. World J Gastroenterol (2006) 12:6366–70.[Web of Science][Medline]
  20. Al-Waili NSD, Hasan NU. Mebendazole in giardial infections: a comparative study with metronidazole. J Infect Dis (1992) 165:1170–1.[Web of Science][Medline]
  21. WHO Model List of Essential Medicines for Children (October 2007). 1 August 2008, date last accessed. http://www.who.int/childmedicines/publications/EMLc%20(2).pdf.
  22. Based upon a treating 1000 40kg children according to 5 cheapest 2006 prices quoted on International Drug Price Indicator Guide. In: Management Sciences for Health (2006) ISBN: 0-913723-05-3.
  23. Gardner TB, Hill DR. Treatment of giardiasis. Clin Microbiol Rev (2001) 14:114–28.[Abstract/Free Full Text]

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