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The first use of combination of Intrapleural Fibrinolytics (Alteplase & DNAse) for pleural infection in Malaysia

Muhammad Redzwan SRA

Med J Malaysia, 2019 04;74(2):176-178.
PMID: 31079131

The use of a combination of intrapleural fibrinolytics or tissue plasminogen activator(tPA) Alteplase and deoxyribonuclease (Dnase) has been increasing for cases of complicated pleural infection/parapneumonic effusion worldwide. Its efficacy and success rate in selected cases of complicated parapneumonic effusion unresponsive to antibiotics and chest drainage are well documented. This case report demonstrates the first use of combination intrapleural fibrinolytic (Alteplase) and DNAse (Pulmozyme) in Malaysia for a case of pleural infection/parapneumonic effusion.
Fulltext Individualised second line anti-tuberculous therapy for an extensively resistant pulmonary tuberculosis (XDR PTB) in East Malaysia

Muhammad Redzwan SR, Ralph AP, Sivaraman Kannan KK, William T

Med J Malaysia, 2015 Jun;70(3):200-4.
PMID: 26248785 MyJurnal

Clinical experience with extensively Drug Resistant tuberculosis (XDR-TB) has not been reported in Malaysia before. We describe the clinical characteristics, risk factors, progress and therapeutic regimen for a healthcare worker with XDR-TB, who had failed therapy for multidrug resistant TB (MDR TB) in our institution. This case illustrates the risk of TB among healthcare workers in high TB-burden settings, the importance of obtaining upfront culture and susceptibility results in all new TB cases, the problem of acquired drug resistance developing during MDR-TB treatment, the challenges associated with XDR-TB treatment regimens, the value of surgical resection in refractory cases, and the major quality of life impact this disease can have on young, economically productive individuals.
A prospective study of mycobacterial viability in refrigerated, unpreserved sputum batched for up to 8 weeks

Rashid Ali MR, Parameswaran U, William T, Bird E, Wilkes CS, Lee WK, et al.

Int J Tuberc Lung Dis, 2015 May;19(5):620-1.
PMID: 25868033 DOI: 10.5588/ijtld.14.0938
Fulltext A prospective study of tuberculosis drug susceptibility in Sabah, Malaysia, and an algorithm for management of isoniazid resistance

Rashid Ali MR, Parameswaran U, William T, Bird E, Wilkes CS, Lee WK, et al.

J Trop Med, 2015;2015:261925.
PMID: 25838829 DOI: 10.1155/2015/261925

Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium tuberculosis drug resistance are poorly defined. Our objectives were to determine M. tuberculosis susceptibility and document management after receipt of susceptibility results.
Methods. Prospective study of adult outpatients with smear-positive pulmonary tuberculosis (PTB) in Sabah, Malaysia. Additionally, hospital clinicians accessed the reference laboratory for clinical purposes during the study.
Results. 176 outpatients were enrolled; 173 provided sputum samples. Mycobacterial culture yielded M. tuberculosis in 159 (91.9%) and nontuberculous Mycobacterium (NTM) in three (1.7%). Among outpatients there were no instances of multidrug resistant M. tuberculosis (MDR-TB). Seven people (4.5%) had isoniazid resistance (INH-R); all were switched to an appropriate second-line regimen for varying durations (4.5-9 months). Median delay to commencement of the second-line regimen was 13 weeks. Among 15 inpatients with suspected TB, 2 had multidrug resistant TB (one extensively drug resistant), 2 had INH-R, and 4 had NTM.
Conclusions. Current community rates of MDR-TB in Sabah are low. However, INH-resistance poses challenges, and NTM is an important differential diagnosis in this setting, where smear microscopy is the usual diagnostic modality. To address INH-R management issues in our setting, we propose an algorithm for the treatment of isoniazid-resistant PTB.
Study site: Tuberculosis clinic, Klinik Kesihatan Luyang, Kota Kinabalu, Sabah, Malaysia
Fulltext Vitamin D and activated vitamin D in tuberculosis in equatorial Malaysia: a prospective clinical study

Ralph AP, Rashid Ali MRS, William T, Piera K, Parameswaran U, Bird E, et al.

BMC Infect Dis, 2017 04 27;17(1):312.
PMID: 28449659 DOI: 10.1186/s12879-017-2314-z

BACKGROUND: Vitamin D deficiency (low plasma 25-hydroxyvitamin D [25D] concentration) is often reported in tuberculosis. Adjunctive vitamin D has been tested for its potential to improve treatment outcomes, but has proven largely ineffective. To better understand vitamin D in tuberculosis, we investigated determinants of 25D and its immunologically active form, 1,25-dihydroxyvitamin D (1,25D), their inter-relationship in tuberculosis, longitudinal changes and association with outcome.
METHODS: In a prospective observational study of adults with smear-positive pulmonary tuberculosis in Sabah, Malaysia, we measured serial 25D, 1,25D, vitamin D-binding protein (VDBP), albumin, calcium, parathyroid hormone, chest x-ray, week 8 sputum smear/culture and end-of-treatment outcome. Healthy control subjects were enrolled for comparison.
RESULTS: 1,25D was elevated in 172 adults with tuberculosis (mean 229.0 pmol/L, 95% confidence interval: 215.4 - 242.6) compared with 95 controls (153.9, 138.4-169.4, p
Identification of Newcastle Disease Virus sub-genotype VII 1.1 isolated from chickens in Sabah, Malaysia

Syamsiah Aini S, Leow BL, Faizul Fikri MY, Muhammad Redzwan S, Faizah Hanim MS

Trop Biomed, 2022 Dec 01;39(4):579-586.
PMID: 36602219 DOI: 10.47665/tb.39.4.015

Newcastle disease (ND) is an extremely contagious and fatal viral disease causing huge economic losses to the poultry industry. Following recent ND outbreaks in Sabah in commercial poultry and backyard farms, it was speculated that this could be due to a new introduction of Newcastle Disease Virus (NDV) genotype/sub-genotype. Here we report the genetic characterization of NDVs isolated from Sabah during early 2021. All isolates were amplified and sequenced with primers specific to the viral fusion (F) gene using reverse transcription-polymerase chain reaction (RT-PCR). Nucleotide sequence analysis of the F gene showed that all isolates shared similar homology of 99.4% with NDV strain from Iran isolated in 2018. Amino acid sequences of the F protein cleavage site revealed the motif of 112RRQKRF117 indicating all isolates were of virulent strain. Phylogenetic analysis demonstrated that all isolates were clustered under sub-genotype VII 1.1 and clustered together with isolates from Iran (previously known as subgenotype VIIl). The present findings suggested that there is an emerging of a new sub-genotype into the poultry population in Sabah and this sub-genotype has never been reported before in Malaysia. Therefore, transboundary monitoring and continuous surveillance should be implemented for proper control and prevention of the disease. A further molecular epidemiological analysis of NDV is needed to well understand the circulatory patterns of virulent strains of NDV in the country to prevent future outbreaks.
Molecular Characterization of Avian Infectious Bronchitis Virus Isolated in Malaysia during 2014-2016

Leow BL, Syamsiah Aini S, Faizul Fikri MY, Muhammad Redzwan S, Khoo CK, Ong GH, et al.

Trop Biomed, 2018 Dec 01;35(4):1092-1106.
PMID: 33601856

Avian Infectious Bronchitis (IB) is a highly contagious disease which can cause huge economic losses to the poultry industry. Forty five IB viruses (IBV) were isolated from poultry in Malaysia during 2014-2016. Phylogenetic analysis of the spike glycoprotein 1 (S1) gene revealed that all isolates were clustered into five distinct groups. The predominant type of IBV isolated was QX strains (47%), second was 4/91 type (27%), followed by Malaysian strain MH5365/95 (13%), Massachusetts type (11%) and finally Taiwanese strains (2%). Four types of S1 protein cleavage recognition motifs were found among the isolates which includes HRRRR, RRSRR, RRFRR and RRVRR. To our knowledge, this is the first report describing the motif RRVRR and are unique to Malaysian strains. Six IBVs were grouped in Malaysian MH5365/95 strains. Among these, one isolate was different from others where it only shared 82% identity with MH5365/95 and to others. It formed its own branch in the Malaysian cluster suggesting it may be a variant unique to Malaysia. Alignment analysis of the S1 amino acid sequences indicated that point mutations, insertions and deletions contribute to the divergence of IB variants. This study indicated at least five groups of IBV are circulating in Malaysia with most of the isolates belonged to QX strains. As new IBV variants continue to emerge, further study need to be carried out to determine whether the current available vaccine is able to give protection against the circulating virus.
Aggressive versus symptom-guided drainage of malignant pleural effusion via indwelling pleural catheters (AMPLE-2): an open-label randomised trial

Muruganandan S, Azzopardi M, Fitzgerald DB, Shrestha R, Kwan BCH, Lam DCL, et al.

Lancet Respir Med, 2018 09;6(9):671-680.
PMID: 30037711 DOI: 10.1016/S2213-2600(18)30288-1

BACKGROUND: Indwelling pleural catheters are an established management option for malignant pleural effusion and have advantages over talc slurry pleurodesis. The optimal regimen of drainage after indwelling pleural catheter insertion is debated and ranges from aggressive (daily) drainage to drainage only when symptomatic.
METHODS: AMPLE-2 was an open-label randomised trial involving 11 centres in Australia, New Zealand, Hong Kong, and Malaysia. Patients with symptomatic malignant pleural effusions were randomly assigned (1:1) to the aggressive (daily) or symptom-guided drainage groups for 60 days and minimised by cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group [ECOG] score 0-1 vs ≥2), presence of trapped lung, and prior pleurodesis. Patients were followed up for 6 months. The primary outcome was mean daily breathlessness score, measured by use of a 100 mm visual analogue scale during the first 60 days. Secondary outcomes included rates of spontaneous pleurodesis and self-reported quality-of-life measures. Results were analysed by an intention-to-treat approach. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12615000963527.
FINDINGS: Between July 20, 2015, and Jan 26, 2017, 87 patients were recruited and randomly assigned to the aggressive (n=43) or symptom-guided (n=44) drainage groups. The mean daily breathlessness scores did not differ significantly between the aggressive and symptom-guided drainage groups (geometric means 13·1 mm [95% CI 9·8-17·4] vs 17·3 mm [13·0-22·0]; ratio of geometric means 1·32 [95% CI 0·88-1·97]; p=0·18). More patients in the aggressive group developed spontaneous pleurodesis than in the symptom-guided group in the first 60 days (16 [37·2%] of 43 vs five [11·4%] of 44, p=0·0049) and at 6 months (19 [44·2%] vs seven [15·9%], p=0·004; hazard ratio 3·287 [95% CI 1·396-7·740]; p=0·0065). Patient-reported quality-of-life measures, assessed with EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L), were better in the aggressive group than in the symptom-guided group (estimated means 0·713 [95% CI 0·647-0·779] vs 0·601 [0·536-0·667]). The estimated difference in means was 0·112 (95% CI 0·0198-0·204; p=0·0174). Pain scores, total days spent in hospital, and mortality did not differ significantly between groups. Serious adverse events occurred in 11 (25·6%) of 43 patients in the aggressive drainage group and in 12 (27·3%) of 44 patients in the symptom-guided drainage group, including 11 episodes of pleural infection in nine patients (five in the aggressive group and six in the symptom-guided drainage group).
INTERPRETATION: We found no differences between the aggressive (daily) and the symptom-guided drainage regimens for indwelling pleural catheters in providing breathlessness control. These data indicate that daily indwelling pleural catheter drainage is more effective in promoting spontaneous pleurodesis and might improve quality of life.
FUNDING: Cancer Council of Western Australia and the Sir Charles Gairdner Research Advisory Group.
Fulltext Protocol of the Australasian Malignant Pleural Effusion-2 (AMPLE-2) trial: a multicentre randomised study of aggressive versus symptom-guided drainage via indwelling pleural catheters

Azzopardi M, Thomas R, Muruganandan S, Lam DC, Garske LA, Kwan BC, et al.

BMJ Open, 2016 07 05;6(7):e011480.
PMID: 27381209 DOI: 10.1136/bmjopen-2016-011480

INTRODUCTION: Malignant pleural effusions (MPEs) can complicate most cancers, causing dyspnoea and impairing quality of life (QoL). Indwelling pleural catheters (IPCs) are a novel management approach allowing ambulatory fluid drainage and are increasingly used as an alternative to pleurodesis. IPC drainage approaches vary greatly between centres. Some advocate aggressive (usually daily) removal of fluid to provide best symptom control and chance of spontaneous pleurodesis. Daily drainages however demand considerably more resources and may increase risks of complications. Others believe that MPE care is palliative and drainage should be performed only when patients become symptomatic (often weekly to monthly). Identifying the best drainage approach will optimise patient care and healthcare resource utilisation.
METHODS AND ANALYSIS: A multicentre, open-label randomised trial. Patients with MPE will be randomised 1:1 to daily or symptom-guided drainage regimes after IPC insertion. Patient allocation to groups will be stratified for the cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group status 0-1 vs ≥2), presence of trapped lung (vs not) and prior pleurodesis (vs not). The primary outcome is the mean daily dyspnoea score, measured by a 100 mm visual analogue scale (VAS) over the first 60 days. Secondary outcomes include benefits on physical activity levels, rate of spontaneous pleurodesis, complications, hospital admission days, healthcare costs and QoL measures. Enrolment of 86 participants will detect a mean difference of VAS score of 14 mm between the treatment arms (5% significance, 90% power) assuming a common between-group SD of 18.9 mm and a 10% lost to follow-up rate.
ETHICS AND DISSEMINATION: The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study (number 2015-043). Results will be published in peer-reviewed journals and presented at scientific meetings.
TRIAL REGISTRATION NUMBER: ACTRN12615000963527; Pre-results.