CONCLUSION: Ex-prematurity and the presence of an underlying illness results in escalation of the direct treatment cost of RSV chest infection. Current guidelines for use of passive RSV immunization do not appear to be cost-effective if adopted for Malaysian infants.
METHODS: We developed mouse models representing three different phenotypes of allergic airway inflammation-eosinophilic, mixed, and neutrophilic asthma via different methods of house dust mite sensitization and challenge. Transcriptomic analysis of the lungs, followed by the RT-PCR, western blot, and confocal microscopy, was performed. Primary human bronchial epithelial cells cultured in air-liquid interface were used to study the mechanisms revealed in the in vivo models.
RESULTS: By whole-genome transcriptome profiling of the lung, we found that airway tight junction (TJ), mucin, and inflammasome-related genes are differentially expressed in these distinct phenotypes. Further analysis of proteins from these families revealed that Zo-1 and Cldn18 were downregulated in all phenotypes, while increased Cldn4 expression was characteristic for neutrophilic airway inflammation. Mucins Clca1 (Gob5) and Muc5ac were upregulated in eosinophilic and even more in neutrophilic phenotype. Increased expression of inflammasome-related molecules such as Nlrp3, Nlrc4, Casp-1, and IL-1β was characteristic for neutrophilic asthma. In addition, we showed that inflammasome/Th17/neutrophilic axis cytokine-IL-1β-may transiently impair epithelial barrier function, while IL-1β and IL-17 increase mucin expressions in primary human bronchial epithelial cells.
CONCLUSION: Our findings suggest that differential expression of TJ, mucin, and inflammasome-related molecules in distinct inflammatory phenotypes of asthma may be linked to pathophysiology and might reflect the differences observed in the clinic.
OBJECTIVES: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis.
METHODS: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles ("immunoallertypes"), were determined.
MEASUREMENTS AND MAIN RESULTS: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. "Sensitized bronchiectasis" was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome.
CONCLUSIONS: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a "treatable trait" permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.
DESIGN AND SETTINGS: A prospective cohort study of vaccinated undergraduate students of University Putra Malaysia.
PATIENTS AND METHODS: A total of 408 undergraduate students who received infant hepatitis B vaccination volunteered for this study; 5 mL of venous blood was taken from the volunteers. Hepatitis B surface antigen (HBsAg) and core antibodies were tested using a commercially available enzyme-linked immunosorbent assay kit according to the manufacturer's instructions (DRG international Inc., USA). Molecular detection of hepatitis B viral DNA was performed using nested polymerase chain reaction.
RESULTS: The prevalence of isolated anti-HBc among the vaccinated cohort was found to be 5.0%, out of which 80% had a hepatitis B surface antibodies (anti-HBs) titer higher than 10 IU/L, while 20% had less than 10 IU/L anti-HBs titer. All the anti-HBc positivesubjects had detectable hepatitis B viral DNA in their serum. Anamnestic response was found to be 100% among isolated anti-HBc with negative antibody.
CONCLUSION: Isolated anti-HBc developed protective levels of anti-HBs after a single dose of recombinant hepatitis B vaccination. HBV DNA was detected in all isolated anti-HBc indicating occult chronic HBV infection with undetectable HBsAg.
METHOD: A cross-sectional study was conducted from September to November 2020 among the guardians of 243 Rohingya refugee children studying under the sponsorship of the King Salman Humanitarian Aid and Relief Center, Malaysia.
RESULTS: Among the 243 children, 90 (37%) were unimmunised, 147 (60.5%) were partially immunised and only 6 (2.5%) were fully immunised. The country of child's birth, the child's age and access to healthcare services were significantly associated with unimmunisation (all P<0.05).
DISCUSSION: This study found low immunisation coverage among Rohingya refugee children in Malaysia. Given the low level of coverage, a public health intervention, such as a vaccination program, for this refugee population is necessary.
RESULTS: A novel approach of utilizing an in-trans protein surface display system of Lactobacillus plantarum carrying and displaying combination of Mycobacterium tuberculosis subunit epitope antigens (Ag85B, CFP-10, ESAT-6, Rv0475 and Rv2031c) fused with LysM anchor motif designated as ACERL was constructed, cloned and expressed in Esherichia coli Rossetta expression host. Subsequently the binding capability of ACERL to the cell wall of L. plantarum was examined via the immunofluorescence microscopy and whole cell ELISA where successful attachment and consistent stability of cell wall binding up to 4 days was determined. The immunization of the developed vaccine of L. plantarum surface displaying ACERL (Lp ACERL) via the oral route was studied in mice for its immunogenicity effects. Lp ACERL immunization was able to invoke significant immune responses that favor the Th1 type cytokine response of IFN-γ, IL-12 and IL-2 as indicated by the outcome from the cytokine profiling of spleen, lung, gastrointestinal tract (GIT), and the re-stimulation of the splenocytes from the immunized mice. Co-administration of an adjuvant consisting of Lactococcus lactis secreting mouse IL-12 (LcIL-12) with Lp ACERL was also investigated. It was shown that the addition of LcIL-12 was able to further generate significant Th1 type cytokines immune responses, similar or better than that of Lp ACERL alone which can be observed from the cytokine profiling of the immunized mice's spleen, lung and GIT.
CONCLUSIONS: This study represents a proof of concept in the development of L. plantarum as a carrier for a non-genetically modified organism (GMO) tuberculosis vaccine, which may be the strategy in the future for tuberculosis vaccine development.
METHODS: In this economic evaluation study, 22 primary healthcare centers were randomly selected in Malaysia between December 2019 and July 2020. The baseline immunization schedule includes switching from Pentaxim® (four doses) and hepatitis B (three doses) to Hexaxim® (four doses), whereas the alternative scheme includes switching from Pentaxim® (four doses) and hepatitis B (three doses) to Hexaxim® (four doses) and hepatitis B (one dose) administered at birth. Direct medical costs were extracted using a costing questionnaire and an observational time and motion chart. Direct non-medical (cost for transportation) and indirect costs (loss of productivity) were derived from parents'/caregivers' questionnaire. Also, HCPs' and parent's/caregivers' perceptions were investigated using structured questionnaires.
RESULTS: The cost per dose of Pentaxim® plus hepatitis B vs. Hexaxim® for the baseline scheme was Malaysian ringgit (RM) 31.90 (7.7 United States dollar [USD]) vs. 17.10 (4.1 USD) for direct medical cost, RM 54.40 (13.1 USD) vs. RM 27.20 (6.6 USD) for direct non-medical cost, RM 221.33 (53.3 USD) vs. RM 110.66 (26.7 USD) for indirect cost, and RM 307.63 (74.2 USD) vs. RM 155.00 (37.4 USD) for societal (total) cost. A similar trend was observed for the alternative scheme. Compared with Pentaxim® plus hepatitis B, total cost savings per dose of Hexaxim® were RM 137.20 (33.1 USD) and RM 104.70 (25.2 USD) in the baseline and alternative scheme, respectively. Eighty-four percent of physicians and 95% of nurses supported the use of Hexaxim® in the NIP. The majority of parents/caregivers had a positive perception regarding Hexaxim® vaccine in various aspects.
CONCLUSIONS: Incorporation of Hexaxim® within Malaysian NIP is highly recommended because the use of Hexaxim® has demonstrated substantial direct and indirect cost savings for healthcare providers and parents/caregivers with a high percentage of positive perceptions, compared with Pentaxim® plus hepatitis B.
TRIAL REGISTRATION: Not applicable.