Impact of Legionella Urine Antigen Testing (LUAT) on the Local Epidemiology and Diagnosis of Legionella Pneumonia

The Impact of Legionella Urine Antigen Testing (LUAT) on the Local Epidemiology and Diagnosis of Legionella Pneumonia - A Hospital Based Study in Malaysia

There has never been a paper published or research done to determine the rate of Legionella species as a cause of community or nosocomial acquired pneumonia requiring hospitalization in Malaysia. Anecdotally, Legionnaires' disease is thought to be uncommon in Malaysia. This is one of the first prospective hospital-based studies to comprehensively evaluate the epidemiological and demographical factors of patients hospitalized with Legionella infection in Malaysia.

Study Overview

• Status: Completed
• Conditions: Legionella Pneumophila Pneumonia
• Intervention / Treatment: Diagnostic test: Immunocatch™ Legionella Urine Antigen Test

Detailed Description

Legionellosis is an environment-related, acute gram negative bacterial respiratory infection and is caused primarily by the species Legionella pneumophila, an atypical pulmonary pathogen, in the likes of mycoplasma and chlamydia species. Potentially all Legionella spp. may cause human disease, however, the majority (92%) of clinical cases are caused by L. pneumophila and the predominant serogroup is serogroup 1.

Globally, 1-5% of community acquired pneumonia patients is caused by Legionella spp. and is a challenge to public health authorities. The incidence of Legionella Pneumonia in the US has exceeded expectations and is increasing, with at least 13,000 cases occurring annually. In Singapore, Legionella spp. is responsible for 2-7% of cases of hospitalized community-acquired pneumonia.

Legionella pneumophila is being increasingly recognized as a common pathogen causing both community-acquired and nosocomial pneumonia that is responsible for significant morbidity and mortality. It is also one of the most common aetiology discovered when pneumonia is sufficiently severe to require admission to an intensive care unit. It's likely to cause a severe form of pneumonia with high likelihood of adverse medical outcomes which includes rapid deterioration, respiratory failure and the need for intensive care unit (ICU) admission.

It will be impossible to distinguish patients with Legionnaires' disease from patients with other types of pneumonia clinically. The key to diagnosis is to perform microbiologic testing when a patient is stratified into a high-risk category. Rapid diagnosis of these pneumonias is desired as delayed diagnosis and institution of appropriate antibiotics is associated with poor outcomes.

In routine clinical practice, legionellosis is rarely proven by culture whereas detection of urinary antigen is now common. In US and Europe, case detection rates were revolutionized with the usage of urine antigen test at 97% and 79% respectively. Urine antigen testing has a reported sensitivity that ranges between 76% and 86% for cases of Legionella pneumonia serogroup 1 and a specificity that approaches 100%.

In this region, urine antigen test is rarely done due to lack of clinical awareness, a perception that Legionella infection is uncommon and due to the lack of availability of this test regionally. The introduction of the immunochromatographic (ICT) membrane assay to detect antigenuria has revolutionized the usage of UAT to diagnose Legionella infections. The ICT assay is similar to a home pregnancy test and is commercially available. The test is simple to perform and does not require special laboratory equipment, and results can be obtained within 15 minutes. The investigators wish to utilize this innovation to test patients whom are hospitalized with pneumonia and determine the incidence of Legionella infection in the local setting.

• Study Type: Observational
• Enrollment (Actual): 505

Contacts and Locations

Study Locations

• Malaysia
  • Perak
    • Taiping, Perak, Malaysia, 34000
      • Hospital Taiping

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A total of 503 patients who are consecutively hospitalised with pneumonia in Hospital Taiping from date of commencement of study.

Description

Inclusion Criteria:

1. More than 18 years of age,
2. Hospitalized consecutively for pneumonia irrespective of it being community or hospital acquired.

3. Acute symptoms of less than 2 weeks and radiological features which are compatible to pneumonia.

   -

Exclusion Criteria:

1. Under 18 years of age
2. Suspected/confirmed case of active tuberculosis
3. Patients who refused to give consent -

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

HOSPITALISED PNEUMONIA PATIENTS; All patients of more than 18 years of age, hospitalized consecutively for pneumonia irrespective of it being community or hospital acquired. All the patients included in this study will need to have acute symptoms of less than 2 weeks and radiological features which are compatible to pneumonia. They will undergo testing for Legionella pneumophila serogroup 1 urine antigen using a qualitative rapid assay following manufacturer's instructions at baseline. The diagnosis of Legionella pneumonia is made if the Immunocatch™ Legionella Urine Antigen Test is positive.

Diagnostic test: Immunocatch™ Legionella Urine Antigen Test; A total number of 503 urine specimens from study participants will be tested with LUAT - Immunocatch™. This test utilises the immunochromatographic (ICT) membrane assay to detect antigenuria which has revolutionized the usage of UAT to diagnose Legionella infections. The results can be obtained within minutes and the test does not require any sophisticated laboratory support. A comparison of the ICT with the Enzyme Immuno Assay (EIA) test showed comparable performance characteristics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Legionella Pneumonia	The diagnosis of Legionella pneumonia is made if the Legionella Urine Antigen Test is positive. The LUAT test kit utilized in this study will not be compared to the gold standard test for Legionellosis which would be the culture on specialised media/buffered-charcoal yeast extract (BCYE) plates, as this test is not available nationwide	15 months

Collaborators and Investigators

• Sponsor: Ministry of Health, Malaysia
• Investigators: Principal Investigator: ALBERT IRUTHIARAJ L ANTHONY, MBBS, Hospital Taiping

Publications and helpful links

General Publications

• Touray S, Newstein MC, Lui JK, Harris M, Knox K. Legionella pneumophila cases in a community hospital: A 12-month retrospective review. SAGE Open Med. 2014 Oct 10;2:2050312114554673. doi: 10.1177/2050312114554673. eCollection 2014.
• Diederen BM, Kluytmans JA, Vandenbroucke-Grauls CM, Peeters MF. Utility of real-time PCR for diagnosis of Legionnaires' disease in routine clinical practice. J Clin Microbiol. 2008 Feb;46(2):671-7. doi: 10.1128/JCM.01196-07. Epub 2007 Dec 19.
• Farnham A, Alleyne L, Cimini D, Balter S. Legionnaires' disease incidence and risk factors, New York, New York, USA, 2002-2011. Emerg Infect Dis. 2014 Nov;20(11):1795-1802. doi: 10.3201/eid2011.131872.
• Helbig JH, Uldum SA, Bernander S, Luck PC, Wewalka G, Abraham B, Gaia V, Harrison TG. Clinical utility of urinary antigen detection for diagnosis of community-acquired, travel-associated, and nosocomial legionnaires' disease. J Clin Microbiol. 2003 Feb;41(2):838-40. doi: 10.1128/JCM.41.2.838-840.2003.
• Fiumefreddo R, Zaborsky R, Haeuptle J, Christ-Crain M, Trampuz A, Steffen I, Frei R, Muller B, Schuetz P. Clinical predictors for Legionella in patients presenting with community-acquired pneumonia to the emergency department. BMC Pulm Med. 2009 Jan 19;9:4. doi: 10.1186/1471-2466-9-4.
• Levcovich A, Lazarovitch T, Moran-Gilad J, Peretz C, Yakunin E, Valinsky L, Weinberger M. Complex clinical and microbiological effects on Legionnaires' disease outcone; A retrospective cohort study. BMC Infect Dis. 2016 Feb 10;16:75. doi: 10.1186/s12879-016-1374-9.
• Hollenbeck B, Dupont I, Mermel LA. How often is a work-up for Legionella pursued in patients with pneumonia? a retrospective study. BMC Infect Dis. 2011 Sep 7;11:237. doi: 10.1186/1471-2334-11-237.

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2017
• Primary Completion (Actual): May 15, 2019
• Study Completion (Actual): May 15, 2019

Study Registration Dates

• First Submitted: June 24, 2017
• First Submitted That Met QC Criteria: June 24, 2017
• First Posted (Actual): June 27, 2017

Study Record Updates

• Last Update Posted (Actual): July 30, 2019
• Last Update Submitted That Met QC Criteria: July 27, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Legionella urine antigen test
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Legionellosis; Pneumonia; Legionnaires' Disease
• Other Study ID Numbers: NMRR-17-50-34002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No