Causes of Pneumonia in Yangon

Melioidosis Pneumonia Clinical Trial

Official title:

A Cross-sectional Study Investigating the Causes of Pneumonia in Two Community Clinics in Two Yangon Townships, Myanmar

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03578133
• Other study ID #: OXTREC 19-18
• Status: Completed
• Start date: July 9, 2018
• Est. completion date: April 4, 2019

Study information

• Verified date: January 2020
• Source: Myanmar Oxford Clinical Research Unit
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: April 4, 2019
• Est. primary completion date: April 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melioidosis
• Melioidosis Pneumonia
• Pneumonia

Intervention

Diagnostic Test:
• InBios® Active Melioidosis DetectTM-Lateral Flow Assay
Evaluation of a lateral flow assay for the detection of B.pseudomallei 6-deoxyheptan capsular polysaccharide antigen from sputum

Locations

Country	Name	City	State
Myanmar	Medical Action Myanmar Clinics	Yangon

Sponsors (4)

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

Country where clinical trial is conducted

Myanmar, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Wiersinga WJ, Currie BJ, Peacock SJ. Melioidosis. N Engl J Med. 2012 Sep 13;367(11):1035-44. doi: 10.1056/NEJMra1204699. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with a positive B.pseudomallei culture result	Number of patients with a positive sputum culture for B.pseudomallei expressed as a proportion of all patients	January 2019
Primary	1) Sensitivity, specificity, positive predictive value, negative predictive value of the RDT compared to culture	Using culture as the gold-standard the performance of the lateral flow assay will be assessed	January 2019
Secondary	Proportion of patients diagnosed with tuberculosis (TB) including multidrug resistant TB	Proportion of enrolled participants with a positive GeneXpert MTB/RIF test on sputum	January 2019
Secondary	Proportion of patients diagnosed with Influenza A/B	Proportion of enrolled participants with a positive Xpert Flu test on nasopharyngeal swab	March 2019