Causes of Pneumonia in Yangon

Study Overview
=================
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.

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

Conditions
-----------------
Melioidosis Pneumonia

Intervention / Treatment
-----------------
* Diagnostic Test: InBios® Active Melioidosis DetectTM-Lateral Flow Assay


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: >18 years old Reported fever or axillary temperature > 37.5 °C Productive cough Written informed consent Exclusion Criteria: 1. Inability to provide a sputum specimen

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|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|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Proportion of patients diagnosed with Influenza A/B | Proportion of enrolled participants with a positive Xpert Flu test on nasopharyngeal swab | March 2019 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pneumonia, melioidosis, Myanmar, diagnosis