1. 25 July 2003School of Public Health & Tropical Medicine Role of Strongyloides serology Rick Speare and David Durrheim School of Public Health and Tropical Medicine James Cook University Townsville 4811 25 July 2003

2. School of Public Health & Tropical Medicine How is strongyloidiasis diagnosed? Larvae in faeces –Direct exam –Agar plate technique Serology –ELISA using sonicated S. ratti antigen –Detects anti- Strongyloides IgG

3. 25 July 2003School of Public Health & Tropical Medicine Current “status” of tests Detection of larvae in faeces –High specificity (~ 100%) –In severe strongyloidiasis, sensitivity high (>90%) –In chronic strongyloidiasis, sensitivity moderate / low (50% or less)

4. 25 July 2003School of Public Health & Tropical Medicine Relationship between severity of strongyloidiasis and number of larvae in faeces From Rawlins et al (1983)

5. 25 July 2003School of Public Health & Tropical Medicine How much searching effort is required to make a diagnosis using faeces in chronic strongyloidiasis? Grove DI. Strongyloidiasis: a major roundworm infection of man. 1989 67% of cases detected from one faecal specimen

6. 25 July 2003School of Public Health & Tropical Medicine Australian Strongyloides ELISA No commercial strongyloides test kit Test in Australia developed by David Grove and Ian Sampson using POWs in WA Measures anti-Strongyloides (genus) IgG In chronic strongyloidiasis: (Grove 1980) –Sensitivity 93% –Specificity 95% In under 5s with acute strongyloidiasis, test has very low sensitivity (Kukuruzovic et al 2002)

7. 25 July 2003School of Public Health & Tropical Medicine Antigen is S. ratti whole larvae Since the antigen is not standardised, and test protocols reported in the literature vary in detail, the validity of extrapolating results obtained for tests in other countries is questionable. Sensitivity and specificity for the test in Australia has to be based on the Australian test.

8. 25 July 2003School of Public Health & Tropical Medicine What is the strongyloides ELISA currently used for? Diagnosis of strongyloidiasis in chronic strongyloidiasis Monitoring of efficacy of therapy

9. 25 July 2003School of Public Health & Tropical Medicine Sensitivity / specificity >90% Yes, it is a useful test for current infection in chronic strongyloidiasis –Adults (Grove 1989) –Children >5y (Sampson & Grove 1987) Not a useful test in acute strongyloidiasis since IgG has not been generated –Under 5s recently infected (Kukuruzovic et al 2002) Time to positive serology after infection is unknown Does a positive ELISA in chronic strongyloidiasis indicate current infection?

10. 25 July 2003School of Public Health & Tropical Medicine Is the strongyloides ELISA a useful tool in monitoring success of therapy? Widely used by clinicians in Australia for this purpose –If strongyloides ELISA is still positive at 6 mo, retreat No published longitudinal case series on Australian strongyloides ELISA –Page’s preliminary data from East Arnhem Land shows >90% of cases decline to negative after “adequate” therapy Longitudinal case series in literature show: –ELISA does decline after effective treatment, but –Series are small –Further research is needed

11. 25 July 2003School of Public Health & Tropical Medicine Should the strongyloides ELISA be the first choice to diagnose suspect chronic cases? Higher sensitivity than faecal test For Australian adults venipuncture is usually more acceptable than provision of faeces Cheaper per test ($16 vs $23 or $40 for OCP plus agar plate); More cost effective per positive case. More useful baseline for long-term post- therapy monitoring than faecal tests.

12. 25 July 2003School of Public Health & Tropical Medicine Recommend In clinical situation, do serological test and regard positive serology as sufficient proof to initiate treatment and follow-up

13. 25 July 2003School of Public Health & Tropical Medicine Essential Testing Recommended testing in strongyloides endemic communities of persons about to receive immuno-suppressive therapy These people are at high risk of severe strongyloidiasis

14. 25 July 2003School of Public Health & Tropical Medicine Role of Strongyloides ELISA in screening? Any screening test should: –Have high sensitivity –Cause minimal inconvenience and harm to patient –Be less costly than confirmatory tests Of the available tests, the ELISA is a more appropriate screening test

15. 25 July 2003School of Public Health & Tropical Medicine Strongyloidiasis: a fight we can win! Only in marginalised groups in Australia –Probably fewer than 40,000 cases Cycle of transmission easily broken –Faeces in toilets not on soil –Treatment of cases 100% effective Effective and cheap diagnostic tools available Effective cheap treatment available Needs establishment of official guidelines for diagnosis, therapy and monitoring Once eliminated from Australia it will not return

16. 25 July 2003School of Public Health & Tropical Medicine Thank you! References de Silva S, Saykao P, Kelly H, MacIntyre CR, Ryan N, Leydon J, Biggs BA. Chronic Strongyloides stercoralis infection in Laotian immigrants and refugees 7-20 years after resettlement in Australia. Epidemiology and Infection 2002;128(3):439-444. Grove DI. Diagnosis. In: Grove DI (ed). Strongyloidiasis: a major roundworm infection of man. London: Taylor Francis. 1989;175-197. Kukuruzovic R, Robins-Browne RM, Anstey NM, Brewster DR. Intestinal pathogens, intestinal permeability and nitric oxide production in acute gastroenteritis. Pediatric Infectious Diseases Journal 2002;21(8):730-739. Meloni BP, Thompson RC, Hopkins RM, Reynoldson JA, Gracey M. The prevalence of Giardia and other intestinal parasites in children, dogs and cats from aboriginal communities in the Kimberley. Medical Journal of Australia 1993;158(3):157-159. Oliver NW, Rowbottom DJ, Sexton P, Goldsmid JM, Byard R, Tooth M, Thomson KS. Chronic strongyloidiasis in Tasmanian veterans--clinical diagnosis by the use of a screening index. Australian and New Zealand Journal of Medicine 1989;19(5):458-462. Pathology and Scientific Services. MDWP Instruction 02/12. Management of requests for “strongyloides serology”. Brisbane: Queensland Health. 2002. Rawlins SC, Terry SI, Chen WN. Some laboratory, epidemiological and clinical features of Strongyloides stercoralis infection in a focus of low endemicity. West Indies Medical Journal 1983;32:212-218. Reynoldson JA, Behnke JM, Pallant LJ, Macnish MG, Gilbert F, Giles S, Spargo RJ, Thompson RC. Failure of pyrantel in treatment of human hookworm infections (Ancylostoma duodenale) in the Kimberley region of north west Australia. Acta Tropica 1997;68(3):301-312. Sampson IA, Grove DI. Strongyloidiasis is endemic in another Australian population group: Indochinese immigrants. Medical Journal of Australia 1987;146(11):580-582.