Infections in Migrants in Sweden - the Importance of Malaria and Other Parasitic Infections

Malaria Clinical Trial

— MMS  

Official title:

Infections in Migrants in Sweden - the Importance of Malaria and Other Parasitic Infections

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05086887
• Other study ID #: MMS2019
• Status: Recruiting
• Start date: April 15, 2019
• Est. completion date: June 30, 2023

Study information

• Verified date: October 2021
• Source: Region Stockholm
• Contact: Andreas Wangdahl, MD
• Phone: +46731512904
• Email: andreas.wangdahl[@]ki.se
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Malaria is a parasitic disease causing substantial morbidity and mortality globally. Malaria is a potentially severe and fatal disease in non-immune individuals. In areas of intense transmission infections individuals acquired immunity that protect against clinical disease. Nonetheless, immunity is not regarding sterilizing and repeated infections often result in an asymptomatic carriage of malaria parasites. These chronic apparently asymptomatic infections have been associated with anemia, cognitive dysfunction and adverse events during pregnancy. Global migration has increased over the last decade and has resulted in an increasing number of migrants from malaria endemic regions arriving in non-endemic countries. Migrants from malaria endemic countries may carry asymptomatic infections with malaria parasites, as well as other parasitic infections such as strongyloides and schistosomiasis, with a possible negative impact on health in this group. The prevalence of asymptomatic malaria and other parasites is not fully elucidated in migrants from different regions. Moreover, the longevity of asymptomatic carriage of malaria parasites in absence of re-exposure is not known. The aim of this study is to assess the prevalence of malaria parasites and other parasitic infections in migrants in Sweden, both newly arrived and migrants with longer residency, and intend to evaluate the need for screening for various parasitic infections in migrants arriving in Sweden. Moreover, this study will also assess antibody responses to malaria and other parasitic diseases.

Description:

Study participants are recruited in different ways, participation in the study is offered when attending an asylum health clinic at several sites in the Stockholm county. Secondly, patients attending the Infectious Disease outpatient clinic for non-febrile diseases (e.g. follow up of hepatitis, treatment for latent tuberculosis). Thirdly, quota refugees from Democratic Republic of the Congo or Uganda with arrival in Sweden in the years 2015-2019 with postal address in Stockholm, will be invited by letter to participate in the study . A venous blood sample (EDTA tube) is collected from study participants at one occasion and a questionnaire including questions about patient origin and previous malaria are completed with the aid of a translator. Blood samples are analysed in the research laboratory, where a malaria rapid diagnostic test (RDT) is performed and haemoglobin concentrations are measured (using Hemocue, point of care test) the same day as sample collection. The samples are then centrifuged, aliquoted, and stored frozen at the research laboratory. Presence of malaria parasites are analysed by realtime-PCR of the species specific 18SRNA gene in a multiplex assay. Serologic markers for other parasitic diseases (eg. schistosomiasis and strongyloides) are analysed in plasma. These analyses are performed at the reference laboratory at the Public Health Agency of Sweden. Projected sample size is estimated using the formula n=(Z^2xP(1-P))/d^2 where P is the expected prevalence based on previous studies (5%) and d is the precision (1.5%) and Z is the confidence interval (95%). Based on these assumptions, the required sample size is n=715. All RDT or PCR positive individuals are referred to the Department of Infectious Diseases or the Department of Pediatrics at the regional hospital for further investigations and treatment. Results from complete blood count are assessed and followed up according to clinical routine at each centre where samples were collected. Contact information to the study participant are included as part of the recruitment and consent procedures in order to be able to contact the study participants for referral. Moreover, antibody responses to crude parasite extracts and specific antigens are assessed by ELISA and Luminex. In a subset of participants peripheral blood mononuclear cells, PBMC, are prepared in follow up samples to assess the cellular immune response. The magnitude and breadth of antibody and cellular responses are assessed in relation to duration of residency in a malaria free country. An estimation of the long- term decay kinetics using a sero-epidemiological mathematical model is performed. All data will be handled according to the EU GDPR (General Data Protection Regulation) superseded all EU member states' data protection laws based on the 1995 Data Protection Directive (DPD), (GDPR, EU 2016/679 and SFS 2018:218). The patient register, containing all collected data and analysis results, is kept pseudonymizised and stored in a secure server at Karolinska University Hospital. The key to pseudonumization is kept in a secure locker at the institution. Collected blood specimens are stored in Stockholm Medical Biobank located at Karolinska University Hospital in Solna. Handling of these stored samples is governed by the Act on Biobanks in Health Care (SFS 2002: 297).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 715
• Est. completion date: June 30, 2023
• Est. primary completion date: January 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Born in a malaria endemic country (a country with reported indigenous spread of malaria according to World Malaria Report 2019)

Exclusion Criteria:

• Inability to understand study information or sign informed consent, except for children where legal guardian is asked for consent.

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Malaria
• Parasitic Diseases
• Parasitic Infection

Intervention

Diagnostic Test:
• Malaria diagnostic tests (RDT and PCR) and serology for malaria and other parasitic diseases
All individuals are tested. Individuals with demonstrated parasitic disease are referred to the Infectious diseases or Pediatric clinic for evaluation and treatment.

Locations

Country	Name	City	State
Sweden	Asylum Health Care Facilities in SLSO and Karolinska University Hospital	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Region Stockholm

Country where clinical trial is conducted

Sweden, 

References & Publications (23)

Asghar M, Hasselquist D, Hansson B, Zehtindjiev P, Westerdahl H, Bensch S. Chronic infection. Hidden costs of infection: chronic malaria accelerates telomere degradation and senescence in wild birds. Science. 2015 Jan 23;347(6220):436-8. doi: 10.1126/science.1261121. — View Citation

Babiker HA, Abdel-Muhsin AM, Ranford-Cartwright LC, Satti G, Walliker D. Characteristics of Plasmodium falciparum parasites that survive the lengthy dry season in eastern Sudan where malaria transmission is markedly seasonal. Am J Trop Med Hyg. 1998 Oct;59(4):582-90. — View Citation

Chaves NJ, Paxton GA, Biggs BA, Thambiran A, Gardiner J, Williams J, Smith MM, Davis JS. The Australasian Society for Infectious Diseases and Refugee Health Network of Australia recommendations for health assessment for people from refugee-like backgrounds: an abridged outline. Med J Aust. 2017 Apr 17;206(7):310-315. — View Citation

Cowman AF, Healer J, Marapana D, Marsh K. Malaria: Biology and Disease. Cell. 2016 Oct 20;167(3):610-624. doi: 10.1016/j.cell.2016.07.055. Review. — View Citation

Doolan DL, Dobaño C, Baird JK. Acquired immunity to malaria. Clin Microbiol Rev. 2009 Jan;22(1):13-36, Table of Contents. doi: 10.1128/CMR.00025-08. Review. — View Citation

Färnert A, Wyss K, Dashti S, Naucler P. Duration of residency in a non-endemic area and risk of severe malaria in African immigrants. Clin Microbiol Infect. 2015 May;21(5):494-501. doi: 10.1016/j.cmi.2014.12.011. Epub 2014 Dec 26. — View Citation

Fernando SD, Rodrigo C, Rajapakse S. The 'hidden' burden of malaria: cognitive impairment following infection. Malar J. 2010 Dec 20;9:366. doi: 10.1186/1475-2875-9-366. Review. — View Citation

Kärki T, Napoli C, Riccardo F, Fabiani M, Dente MG, Carballo M, Noori T, Declich S. Screening for infectious diseases among newly arrived migrants in EU/EEA countries--varying practices but consensus on the utility of screening. Int J Environ Res Public Health. 2014 Oct 21;11(10):11004-14. doi: 10.3390/ijerph111011004. — View Citation

Langhorne J, Ndungu FM, Sponaas AM, Marsh K. Immunity to malaria: more questions than answers. Nat Immunol. 2008 Jul;9(7):725-32. doi: 10.1038/ni.f.205. Review. — View Citation

Marangi M, Di Tullio R, Mens PF, Martinelli D, Fazio V, Angarano G, Schallig HD, Giangaspero A, Scotto G. Prevalence of Plasmodium spp. in malaria asymptomatic African migrants assessed by nucleic acid sequence based amplification. Malar J. 2009 Jan 12;8:12. doi: 10.1186/1475-2875-8-12. — View Citation

Maroushek SR, Aguilar EF, Stauffer W, Abd-Alla MD. Malaria among refugee children at arrival in the United States. Pediatr Infect Dis J. 2005 May;24(5):450-2. — View Citation

Matisz CE, Naidu P, Shokoples SE, Grice D, Krinke V, Brown SZ, Kowalewska-Grochowska K, Houston S, Yanow SK. Post-arrival screening for malaria in asymptomatic refugees using real-time PCR. Am J Trop Med Hyg. 2011 Jan;84(1):161-5. doi: 10.4269/ajtmh.2011.10-0494. Erratum in: Am J Trop Med Hyg. 2011 Oct;85(4):790. — View Citation

Monge-Maillo B, López-Vélez R. Is screening for malaria necessary among asymptomatic refugees and immigrants coming from endemic countries? Expert Rev Anti Infect Ther. 2011 May;9(5):521-4. doi: 10.1586/eri.11.37. — View Citation

Monge-Maillo B, López-Vélez R. Migration and malaria in europe. Mediterr J Hematol Infect Dis. 2012;4(1):e2012014. doi: 10.4084/MJHID.2012.014. Epub 2012 Mar 10. — View Citation

Njama-Meya D, Kamya MR, Dorsey G. Asymptomatic parasitaemia as a risk factor for symptomatic malaria in a cohort of Ugandan children. Trop Med Int Health. 2004 Aug;9(8):862-8. — View Citation

Okell LC, Bousema T, Griffin JT, Ouédraogo AL, Ghani AC, Drakeley CJ. Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nat Commun. 2012;3:1237. doi: 10.1038/ncomms2241. — View Citation

Rono J, Osier FH, Olsson D, Montgomery S, Mhoja L, Rooth I, Marsh K, Färnert A. Breadth of anti-merozoite antibody responses is associated with the genetic diversity of asymptomatic Plasmodium falciparum infections and protection against clinical malaria. Clin Infect Dis. 2013 Nov;57(10):1409-16. doi: 10.1093/cid/cit556. Epub 2013 Aug 27. — View Citation

Shokoples SE, Ndao M, Kowalewska-Grochowska K, Yanow SK. Multiplexed real-time PCR assay for discrimination of Plasmodium species with improved sensitivity for mixed infections. J Clin Microbiol. 2009 Apr;47(4):975-80. doi: 10.1128/JCM.01858-08. Epub 2009 Feb 25. — View Citation

Sifft KC, Geus D, Mukampunga C, Mugisha JC, Habarugira F, Fraundorfer K, Bayingana C, Ndoli J, Umulisa I, Karema C, von Samson-Himmelstjerna G, Aebischer T, Martus P, Sendegeya A, Gahutu JB, Mockenhaupt FP. Asymptomatic only at first sight: malaria infection among schoolchildren in highland Rwanda. Malar J. 2016 Nov 14;15(1):553. — View Citation

Stauffer WM, Weinberg M, Newman RD, Causer LM, Hamel MJ, Slutsker L, Cetron MS. Pre-departure and post-arrival management of P. falciparum malaria in refugees relocating from sub-Saharan Africa to the United States. Am J Trop Med Hyg. 2008 Aug;79(2):141-6. — View Citation

Szmitko PE, Kohn ML, Simor AE. Plasmodium falciparum malaria occurring 8 years after leaving an endemic area. Diagn Microbiol Infect Dis. 2009 Jan;63(1):105-7. doi: 10.1016/j.diagmicrobio.2008.08.017. Epub 2008 Oct 21. — View Citation

White NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM. Malaria. Lancet. 2014 Feb 22;383(9918):723-35. doi: 10.1016/S0140-6736(13)60024-0. Epub 2013 Aug 15. Review. — View Citation

Yman V, White MT, Rono J, Arcà B, Osier FH, Troye-Blomberg M, Boström S, Ronca R, Rooth I, Färnert A. Antibody acquisition models: A new tool for serological surveillance of malaria transmission intensity. Sci Rep. 2016 Feb 5;6:19472. doi: 10.1038/srep19472. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parasite prevalence	Number of participants with ongoing malaria infection	Measured at one occasion within 10 years from arrival in Sweden
Primary	Prevalence of other parasites focusing on strongyloides and schistosomiasis	Number of participants showing serological response to strongyloides and schistosomiasis	Measured at one occasion within 10 years from arrival in Sweden
Secondary	Immune responses to malaria and other parasites	Levels and breadth of P. falciparum specific antibody and memory B cell responses.	A blood specimen will be collected from participants upon inclusion, and a subset of volunteers will be asked to contribute with a second blood sample after 6-12 months