Clinical trial NCT03578133: Causes of Pneumonia in Yangon
Official title: A Cross-sectional Study Investigating the Causes of Pneumonia in Two Community Clinics in Two Yangon Townships, Myanmar
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Melioidosis Pneumonia
Keywords: pneumonia
melioidosis
Myanmar
diagnosis
Lead sponsor: Myanmar Oxford Clinical Research Unit
Sponsor class: OTHER
Collaborators: name: Medical Action Myanmar
name: Department of Medical Research, Myanmar
name: Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit
First posted: 2018-07-05
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: The population investigated will be patients attending two non-governmental organisation community clinics in the most deprived areas of Yangon, Myanmar

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients with a positive B.pseudomallei culture result
timeFrame: January 2019
measure: 1) Sensitivity, specificity, positive predictive value, negative predictive value of the RDT compared to culture
timeFrame: January 2019
Secondary outcomes:
measure: Proportion of patients diagnosed with tuberculosis (TB) including multidrug resistant TB
timeFrame: January 2019
measure: Proportion of patients diagnosed with Influenza A/B
timeFrame: March 2019
Other outcomes:
Locations:
city: Yangon
country: Myanmar
facility: Medical Action Myanmar Clinics
Study officials:
affiliation: Myanmar Oxford Clinical Research Unit
name: Elizabeth A Ashley, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Myanmar Oxford Clinical Research Unit and Medical Action Myanmar
name: Frank Smithuis, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Myanmar Oxford Clinical Research Unit and Medical Action Myanmar
name: Clare Warrell, Dr
role: STUDY_DIRECTOR
affiliation: Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit
name: David Dance, Prof
role: STUDY_DIRECTOR
affiliation: Medical Action Myanmar
name: Ni Ni Tun, Dr
role: STUDY_DIRECTOR
affiliation: Department of Medical Research, Myanmar
name: Mo Mo Win, Dr
role: STUDY_DIRECTOR
affiliation: Myanmar Oxford Clinical Research Unit
name: Alistair McLean, Dr
role: STUDY_DIRECTOR
affiliation: Myanmar Oxford Clinical Research Unit
name: Kyaw Soe
role: STUDY_DIRECTOR
References:
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.
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.
citation: 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.
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.
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):e02002-17. doi: 10.1128/JCM.02002-17. Print 2018 Jul.
citation: Wiersinga WJ, Currie BJ, Peacock SJ. Melioidosis. N Engl J Med. 2012 Sep 13;367(11):1035-44. doi: 10.1056/NEJMra1204699. No abstract available.