Evaluation of the Performance of a hsRDT Versus cRDT in Reactive Case Detection of Malaria Infections

Malaria,Falciparum Clinical Trial

Official title:

Evaluation of the Performance of a Highly-sensitive Rapid Diagnostic Test (RDT) Versus Conventional RDT, Compared With PCR as the Gold Standard, in Reactive Case Detection of Malaria Infections in Rakhine State, Myanmar

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03511443
• Other study ID #: HP-00076579
• Secondary ID: Pro00089928
• Status: Recruiting
• Phase: N/A
• First received: March 19, 2018
• Last updated: April 17, 2018
• Start date: October 2, 2017
• Est. completion date: October 1, 2018

Study information

• Verified date: April 2018
• Source: University Research Co, LLC
• Contact: San Kyawt Khine, MD
• Phone: 959450542076
• Email: skkhine.khine75[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A systematic review assessing the role, appropriateness and benefits of the active case detection strategy, both proactive and reactive, in low malaria transmission settings. A common indication is that more studies should be carried out to optimize the ACD strategy to the local context, or to provide evidence for the adoption of improved methods. One possible improved method is the use of more accurate diagnostic tools, such as the hsRDT proposed in this study, with an increased capacity to detect lower levels of parasitemia. It can provide a timely and relevant contribution for their development of national Standard Operating Procedures for a screening tool in the reactive case detection strategy.

Description:

The study is conducted in the areas under Sakhanmaw Rural Health Center, Ann Township in Southern Rakhine State, Myanmar.

General objective was to evaluate the performance of the new highly-sensitive rapid diagnostic test (RDT) developed by SD Bioline versus conventional RDT, compared with PCR as the gold standard, in reactive case detection of malaria infections in Rakhine State, Myanmar.

Specific objectives

• To evaluate the prevalence of malaria identified by the new hsRDT in comparison with that by cRDT and PCR

• To assess the diagnostic performance characteristics of hsRDT versus cRDT, using PCR as gold standard, in the detection of P.falciparum infections

• To evaluate correlation of detection capability between cRDT and hsRDT

• To identify risk factors associated with malaria infection, including but not limited to, socio-demographic factors and travel history related with malaria index cases

This is a prospective community-based single-center reactive case detection (RCD) study to assess the performance of hsRDT versus cRDT in identifying individuals with malaria infection ("Secondary case") in a population living and/or working in a close physical proximity to an "index case." All cases parasitologically confirmed by conventional RDT will be promptly notified to the study team and interviewed with a standardized case investigation form at their home, possibly within 3 days. All members of the primary case household and those of the nearest 10 households, aged 5 years and above, will be invited to participate in the study. A blood spot will be collected for subsequent PCR analysis. At least 50 index cases are targeted for investigation and reactive case detection and an estimated number of 1,980 persons will be involved in the study.

It is expected that this study will be an important input for the national malaria control program in Myanmar as they develop the strategies to conduct reactive case detection.

A suitable statistical software, e.g. STATA will be used to analyze the data resulting from the participant interviews and 3 parasitological tests. Logistic regression models will be developed to examine factors significantly associated with malaria infections.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1980
• Est. completion date: October 1, 2018
• Est. primary completion date: June 28, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years and older

Eligibility

Inclusion Criteria:

• Age at least 5 years old

• Resident of the villages, or temporary visitors, or co-workers or co-travelers of index case

• Willingness to participate in the study evident by informed consent

Exclusion Criteria:

• Presence of severe clinical illness including severe malaria

• Non-resident index cases

• Refusal to participate in the study

Related Conditions & MeSH terms

• Malaria
• Malaria Diagnosis
• Malaria, Falciparum
• Malaria,Falciparum

Intervention

Diagnostic Test:
• hsRDT
Testing highly sensitive RDT detection for low parasitemia

Locations

Country	Name	City	State
Myanmar	University Research Co., LLC (URC)	Yangon

Sponsors (5)

Lead Sponsor	Collaborator
University Research Co, LLC	Centers for Disease Control and Prevention, Department of Medical Research, Lower Myanmar, Duke University, United States Agency for International Development (USAID)

Country where clinical trial is conducted

Myanmar, 

References & Publications (10)

Adams M, Joshi SN, Mbambo G, Mu AZ, Roemmich SM, Shrestha B, Strauss KA, Johnson NE, Oo KZ, Hlaing TM, Han ZY, Han KT, Thura S, Richards AK, Huang F, Nyunt MM, Plowe CV. An ultrasensitive reverse transcription polymerase chain reaction assay to detect asymptomatic low-density Plasmodium falciparum and Plasmodium vivax infections in small volume blood samples. Malar J. 2015 Dec 23;14:520. doi: 10.1186/s12936-015-1038-z. — View Citation

Chen I, Clarke SE, Gosling R, Hamainza B, Killeen G, Magill A, O'Meara W, Price RN, Riley EM. "Asymptomatic" Malaria: A Chronic and Debilitating Infection That Should Be Treated. PLoS Med. 2016 Jan 19;13(1):e1001942. doi: 10.1371/journal.pmed.1001942. eCollection 2016 Jan. Review. — View Citation

Cheng Z, Wang D, Tian X, Sun Y, Sun X, Xiao N, Zheng Z. Capture and Ligation Probe-PCR (CLIP-PCR) for Molecular Screening, with Application to Active Malaria Surveillance for Elimination. Clin Chem. 2015 Jun;61(6):821-8. doi: 10.1373/clinchem.2014.237115. Epub 2015 May 11. — View Citation

Hustedt J, Canavati SE, Rang C, Ashton RA, Khim N, Berne L, Kim S, Sovannaroth S, Ly P, Ménard D, Cox J, Meek S, Roca-Feltrer A. Reactive case-detection of malaria in Pailin Province, Western Cambodia: lessons from a year-long evaluation in a pre-elimination setting. Malar J. 2016 Mar 1;15:132. doi: 10.1186/s12936-016-1191-z. — View Citation

Imwong M, Hanchana S, Malleret B, Rénia L, Day NP, Dondorp A, Nosten F, Snounou G, White NJ. High-throughput ultrasensitive molecular techniques for quantifying low-density malaria parasitemias. J Clin Microbiol. 2014 Sep;52(9):3303-9. doi: 10.1128/JCM.01057-14. Epub 2014 Jul 2. — View Citation

Imwong M, Nguyen TN, Tripura R, Peto TJ, Lee SJ, Lwin KM, Suangkanarat P, Jeeyapant A, Vihokhern B, Wongsaen K, Van Hue D, Dong le T, Nguyen TU, Lubell Y, von Seidlein L, Dhorda M, Promnarate C, Snounou G, Malleret B, Rénia L, Keereecharoen L, Singhasivanon P, Sirithiranont P, Chalk J, Nguon C, Hien TT, Day N, White NJ, Dondorp A, Nosten F. The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand-Myanmar border areas, Cambodia, and Vietnam. Malar J. 2015 Sep 30;14:381. doi: 10.1186/s12936-015-0906-x. — View Citation

malERA Consultative Group on Health Systems and Operational Research. A research agenda for malaria eradication: health systems and operational research. PLoS Med. 2011 Jan 25;8(1):e1000397. doi: 10.1371/journal.pmed.1000397. Review. — View Citation

Okell LC, Ghani AC, Lyons E, Drakeley CJ. Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. J Infect Dis. 2009 Nov 15;200(10):1509-17. doi: 10.1086/644781. Review. — View Citation

Searle KM, Shields T, Hamapumbu H, Kobayashi T, Mharakurwa S, Thuma PE, Smith DL, Glass G, Moss WJ. Efficiency of household reactive case detection for malaria in rural Southern Zambia: simulations based on cross-sectional surveys from two epidemiological settings. PLoS One. 2013 Aug 6;8(8):e70972. doi: 10.1371/journal.pone.0070972. Print 2013. — View Citation

van Eijk AM, Ramanathapuram L, Sutton PL, Kanagaraj D, Sri Lakshmi Priya G, Ravishankaran S, Asokan A, Tandel N, Patel A, Desai N, Singh R, Sullivan SA, Carlton JM, Srivastava HC, Eapen A. What is the value of reactive case detection in malaria control? A case-study in India and a systematic review. Malar J. 2016 Feb 6;15:67. doi: 10.1186/s12936-016-1120-1. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of malaria infections identified by the new hsRDT	Outcomes measured by malaria test positivity rate by cRDT, hsRDT and PCR, respectively	PCR diagnosis of samples will occur after 10 months of data collection.
Secondary	Diagnostic performance characteristics of hsRDT versus cRDT using PCR as gold standard, in the detection of P.falciparum infections	Outcomes measured between hsRDT and cRDT	Outcomes will be analyzed after 10 months of data collection
Secondary	Correlation of detection capability between cRDT and hsRDT	Outcomes measured by correlation of test positivity rates	PCR results will be analyzed during month 10
Secondary	Risk factors associated with malaria infection cases	Outcomes will be measured by relative risk of malaria in association with different risk factors identified	Outcome will be measured/analyzed in month 10, after PCR results are released