Causes of Pneumonia in Yangon

• Sponsor: Myanmar Oxford Clinical Research Unit (Other)
• Overall Status: Completed
• CT.gov ID: NCT03578133
• Collaborator: Medical Action Myanmar (Other), Department of Medical Research, Myanmar (Other), Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit (Other)
• Enrollment: 300
• Location: 1
• Actual Duration (Months): 8.8
• Patients Per Site Per Month: 33.9

Study Details

Study Description

Brief Summary

This study will evaluate a new point of care diagnostic test for the diagnosis of melioidosis pneumonia in patients attending outpatient clinics in Yangon, Myanmar

Condition or Disease	Intervention/Treatment	Phase
Melioidosis Pneumonia	Diagnostic Test: InBios® Active Melioidosis DetectTM-Lateral Flow Assay

Detailed Description

Melioidosis is caused by Burkholderia pseudomallei, a Gram-negative saprophytic environmental bacterium that is an important emerging tropical infection. There are an estimated 165,000 cases and 89,000 deaths world-wide each year. Eighty-four percent of cases are in SE Asia where mortality is 40%; far exceeding most recognised neglected tropical diseases. Pneumonia, secondary to either inhalation of B.pseudomallei or to bacteraemic spread to the lung is the commonest presentation (51%). Annually the highest burden (75%) of infection occurs in the rainy season in (75% in Thailand). Up to 80% patients have at least one recognised risk factor for melioidosis including; diabetes, alcohol-dependence, glucocorticoid therapy, chronic obstructive pulmonary disease (COPD), chronic renal disease and cancer. COPD and diabetes mellitus are amongst the top ten causes of death in Myanmar (2018). Patients with HIV have not been shown to have greater risk of B. pseudomallei than immunocompetent patients.

Melioidosis was discovered in Myanmar in 1911 by British pathologist Alfred Whitmore and his assistant CS Krishnaswami. Yet since 1949 there have been few published cases. Under-reporting is partly due to difficulty in diagnosing melioidosis. Clinical and radiological findings are indistinguishable from tuberculosis. Laboratory diagnosis is challenging, lack of facilities, expertise and awareness of B.pseudomallei results in missed diagnostic opportunities.

Culture is the gold-standard diagnostic method but requires appropriate facilities and expertise which are not readily available in many developing countries like Myanmar. A rapid diagnostic (RDT) test has been developed for low resource settings that has been evaluated in Laos and India. The InBios® Active Melioidosis DetectTM-Lateral Flow Assay (AMD-LFA) detects B.pseudomallei 6-deoxyheptan capsular polysaccharide antigen. Shaw et al demonstrated sensitivity 85.71% (CI:74.61% to 93.25%) and specificity 93.62% (CI:88.23% to 97.04%), with positive predictive value of 85.71% (CI: 75.98% to 91.92%) compared to culture. We propose to evaluate this test for the diagnosis of melioidosis pneumonia in Myanmar.

Study Design

• Study Type: Observational
• Actual Enrollment: 300 participants
• Observational Model: Other
• Time Perspective: Cross-Sectional
• Official Title: A Cross-sectional Study Investigating the Causes of Pneumonia in Two Community Clinics in Two Yangon Townships, Myanmar
• Actual Study Start Date: Jul 9, 2018
• Actual Primary Completion Date: Apr 4, 2019
• Actual Study Completion Date: Apr 4, 2019

Outcome Measures

Primary Outcome Measures

1. Proportion of patients with a positive B.pseudomallei culture result [January 2019]

   Number of patients with a positive sputum culture for B.pseudomallei expressed as a proportion of all patients

2. 1) Sensitivity, specificity, positive predictive value, negative predictive value of the RDT compared to culture [January 2019]

   Using culture as the gold-standard the performance of the lateral flow assay will be assessed

Secondary Outcome Measures

1. Proportion of patients diagnosed with tuberculosis (TB) including multidrug resistant TB [January 2019]

   Proportion of enrolled participants with a positive GeneXpert MTB/RIF test on sputum

2. Proportion of patients diagnosed with Influenza A/B [March 2019]

   Proportion of enrolled participants with a positive Xpert Flu test on nasopharyngeal swab

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 18 years old

2. Reported fever or axillary temperature > 37.5 °C

3. Productive cough

4. Written informed consent

Exclusion Criteria:

1. Inability to provide a sputum specimen

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Action Myanmar Clinics	Yangon		Myanmar

Sponsors and Collaborators

• Myanmar Oxford Clinical Research Unit
• Medical Action Myanmar
• Department of Medical Research, Myanmar
• Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit

Investigators

• Principal Investigator: Elizabeth A Ashley, Dr, Myanmar Oxford Clinical Research Unit
• Principal Investigator: Frank Smithuis, Prof, Myanmar Oxford Clinical Research Unit and Medical Action Myanmar
• Study Director: Clare Warrell, Dr, Myanmar Oxford Clinical Research Unit and Medical Action Myanmar
• Study Director: David Dance, Prof, Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit
• Study Director: Ni Ni Tun, Dr, Medical Action Myanmar
• Study Director: Mo Mo Win, Dr, Department of Medical Research, Myanmar
• Study Director: Alistair McLean, Dr, Myanmar Oxford Clinical Research Unit
• Study Director: Kyaw Soe, Myanmar Oxford Clinical Research Unit

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chierakul W, Wuthiekanun V, Chaowagul W, Amornchai P, Cheng AC, White NJ, Day NP, Peacock SJ. Short report: disease severity and outcome of melioidosis in HIV coinfected individuals. Am J Trop Med Hyg. 2005 Dec;73(6):1165-6.
• Houghton RL, Reed DE, Hubbard MA, Dillon MJ, Chen H, Currie BJ, Mayo M, Sarovich DS, Theobald V, Limmathurotsakul D, Wongsuvan G, Chantratita N, Peacock SJ, Hoffmaster AR, Duval B, Brett PJ, Burtnick MN, Aucoin DP. Development of a prototype lateral flow immunoassay (LFI) for the rapid diagnosis of melioidosis. PLoS Negl Trop Dis. 2014 Mar 20;8(3):e2727. doi: 10.1371/journal.pntd.0002727. eCollection 2014 Mar.
• Limmathurotsakul D, Golding N, Dance DA, Messina JP, Pigott DM, Moyes CL, Rolim DB, Bertherat E, Day NP, Peacock SJ, Hay SI. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol. 2016 Jan 11;1:15008. doi: 10.1038/nmicrobiol.2015.8.
• Shaw T, Tellapragada C, Ke V, AuCoin DP, Mukhopadhyay C. Performance evaluation of Active Melioidosis Detect-Lateral Flow Assay (AMD-LFA) for diagnosis of melioidosis in endemic settings with limited resources. PLoS One. 2018 Mar 26;13(3):e0194595. doi: 10.1371/journal.pone.0194595. eCollection 2018.
• Wiersinga WJ, Currie BJ, Peacock SJ. Melioidosis. N Engl J Med. 2012 Sep 13;367(11):1035-44. doi: 10.1056/NEJMra1204699. Review.
• Woods KL, Boutthasavong L, NicFhogartaigh C, Lee SJ, Davong V, AuCoin DP, Dance DAB. Evaluation of a Rapid Diagnostic Test for Detection of Burkholderia pseudomallei in the Lao People's Democratic Republic. J Clin Microbiol. 2018 Jun 25;56(7). pii: e02002-17. doi: 10.1128/JCM.02002-17. Print 2018 Jul.

• Responsible Party: Myanmar Oxford Clinical Research Unit
• ClinicalTrials.gov Identifier: NCT03578133
• Other Study ID Numbers: OXTREC 19-18
• First Posted: Jul 5, 2018
• Last Update Posted: Jan 13, 2020
• Last Verified: Jan 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Myanmar Oxford Clinical Research Unit: pneumonia; melioidosis; Myanmar; diagnosis
• Additional relevant MeSH terms: Pneumonia; Melioidosis

Study Results

No Results Posted as of Jan 13, 2020