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  1. Abd Hamid IJ, Azman NA, Gennery AR, Mangantig E, Hashim IF, Zainudeen ZT
    Front Immunol, 2020;11:1923.
    PMID: 32983118 DOI: 10.3389/fimmu.2020.01923
    Introduction: Primary immunodeficiency diseases (PIDs) are under-reported in Malaysia. The actual disease frequency of PID in this country is unknown due to the absence of a national patient registry for PID. Objective: This systematic review aimed to determine the prevalence rates of PID cases diagnosed and published in Malaysia from 1st of January 1979 until 1st of March 2020. It also aimed to describe the various types of PIDs reported in Malaysia. Method: Following the development of a comprehensive search strategy, all published literature of PID cases from Malaysia was identified and collated. All cases that fulfilled the International Union of Immunological Societies (IUIS) classification diagnosis were included in the systematic review. Data were retrieved and collated into a proforma. Results: A total of 4,838 articles were identified and screened, with 34 publications and 119 patients fulfilling the criteria and being included in the systematic review. The prevalence rate was 0.37 per 100,000 population. In accordance with the IUIS, the distribution of diagnostic classifications was immunodeficiencies affecting cellular and humoral immunities (36 patients, 30.3%), combined immunodeficiencies with associated or syndromic features (21 patients, 17.6%), predominant antibody deficiencies (24 patients, 20.2%), diseases of immune dysregulation (13 patients, 10.9%), congenital defects in phagocyte number or function (20 patients, 16.8%), defects in intrinsic and innate immunity (4 patients, 3.4%), and autoinflammatory disorders (1 patient, 0.8%). Parental consanguinity was 2.5%. Thirteen different gene mutations were available in 21.8% of the cases. Conclusion: PIDs are underdiagnosed and under-reported in Malaysia. Developing PID healthcare and a national patient registry is much needed to enhance the outcome of PID patient care.
  2. Cinicola BL, Ottaviano G, Hashim IF, Zainudeen ZT, Hamid IJA, Elfeky R
    J Clin Immunol, 2023 Dec 22;44(1):23.
    PMID: 38129624 DOI: 10.1007/s10875-023-01615-3
    PURPOSE: Non-tuberculous mycobacteria (NTM) infections in hematopoietic stem cell transplantation (HSCT) recipients represent a diagnostic and therapeutic challenge. Here, we aimed to review and analyze current literature on incidence, clinical presentation, and outcome of NTM infection after allogeneic HSCT.

    METHODS: We performed a systematic review and meta-analysis of available literature regarding NTM infection in children and adults receiving allogeneic HSCT.

    RESULTS: We identified 56 articles eligible for the analysis. Among 15 studies, describing 15,798 allogeneic HSCT, we estimated a prevalence of 1.26% (95% CI 0.72, 1.93) of NTM after transplant. Analysis of 175 patients with NTM infection showed a median time of diagnosis of 318 days after HSCT, an increased prevalence in adults (82.9%), and a most frequent pulmonary involvement (44%). Comparison between children and adults revealed an earlier post-transplant disease onset (median 130 days vs 287 days) and most frequent non-pulmonary presentation in children. A vast heterogeneity of therapeutic approach reflected the lack of universal recommendations regarding drug combination and duration of therapy. Overall, NTM-related mortality accounted for 33% in this systematic review.

    CONCLUSION: Although rare, NTM infections can complicate post-transplant course with a high mortality rate in children and adults. The lack of prospective studies and guidelines prevents identification of risk factors and therapeutic recommendations.

  3. Zainudeen ZT, Abd Hamid IJ, Azizuddin MNA, Abu Bakar FF, Sany S, Zolkepli IA, et al.
    BMJ Open, 2021 08 11;11(8):e050523.
    PMID: 34380732 DOI: 10.1136/bmjopen-2021-050523
    OBJECTIVE: To investigate the psychosocial impact of COVID-19 on Malaysian families.

    DESIGN: A cross-sectional study performed using an anonymous online questionnaire distributed through social media, email and the Department of Social Welfare.

    SETTING: Malaysian families were invited to answer the questionnaires. The sampling was performed between 12 May 2020 and 9 June 2020.

    INTERVENTION: The psychological impact was assessed using the Impact of Event Scale-Revised (IES-R) and Children's Revised Impact of Event Scale (CRIES). The mental health status was assessed using the Depression, Anxiety and Stress Scale (DASS) 21.

    MAIN OUTCOME MEASURE: (1) Psychological impact on Malaysian families. (2) Prevalence of mental health status of Malaysian families during COVID-19 pandemic.

    RESULT: A total of 409 Malaysian families have responded (409 parents and 348 children), 154 respondents (38%) reported high psychological impact (score 14) for psychological construct and 189 respondents (46%) reported high psychological impact (score 6) for behavioural construct. A significantly higher proportion of respondents with not permanent employment status of the family lead reported high psychological impact. The prevalence of anxiety reported from family respondents was 23%. Forty-five children answered the DASS-21 questionnaire; 28.5% reported anxiety, 31.4% reported depression and 13.3% reported stress. The job security status of the family lead was found to be the predictive factor for the mean total IES-R score (psychological construct) and ethnicity for mean total CRIES-8 and CRIES-13.

    CONCLUSION: Rates of depression and anxiety during the COVID-19 pandemic were high. Findings suggest that urgent measures to ensure job security among Malaysian families are important to reduce the impact of the COVID-19 pandemic on psychosocial and mental health outcomes.

  4. Zahari NH, Abd Hamid IJ, Tuan Din SA, Hashim IF, Zainudeen ZT, Mohd Shariff N, et al.
    Malays J Med Sci, 2023 Jun;30(3):112-121.
    PMID: 37425378 DOI: 10.21315/mjms2023.30.3.10
    BACKGROUND: Intravenous immunoglobulin (IVIG) replacement therapy is increasingly in demand. This study focused on the characteristics of IVIG usage and associated factors toward the frequency status of IVIG among patients in Hospital Kuala Lumpur.

    METHODS: A retrospective cross-sectional study was performed on patients who received IVIG in Hospital Kuala Lumpur. Data were extracted from the request forms for IVIG recorded in the Pharmacy Department from January 2018 until December 2019. Chi-squared test and t-test analysis were used for statistical analysis, and a P-value of < 0.05 was considered significant.

    RESULTS: A total of 482 patients received IVIG in Hospital Kuala Lumpur. There were 243 (50.4%) females and 228 (47.3%) males with median age of the patients was 27 years old. The highest indications for IVIG among all patients were hypogammaglobulinemia and other deficiency states in 127 patients (26.3%). The most common indication for one-off treatment in adults was hypogammaglobulinemia and other deficiency states, 35%; whereas in paediatrics, it was Kawasaki disease, 20.3%. The highest indication for regular therapy among adult patients was chronic inflammatory demyelinating polyneuropathy (23.4%), while in paediatrics it was sepsis (31.1%). The clinical category was associated with the frequency status of IVIG usage in both adult and paediatric cohorts with P = 0.004 and P = 0.017, respectively.

    CONCLUSION: There were significant differences between the indication of one-off treatment and regular therapy among adult and paediatric patients. A national guideline on the prescription of IVIG for patients is instantly needed to help clinicians in prescribing IVIG appropriately.

  5. Ahmed Meelad R, Abd Hamid IJ, Zainudeen ZT, Hashim IF, Azizuddin MNA, Mangantig E, et al.
    J Clin Immunol, 2023 Jul;43(5):999-1006.
    PMID: 36882668 DOI: 10.1007/s10875-023-01463-1
    PURPOSE: Primary immunodeficiency disease (PID) affects various aspects of a patient's life. However, the health-related quality of life (HRQOL) of PID among Malaysian patients is poorly described. This study aimed to determine the quality of life of PID patients and their respective parents.

    METHOD: This cross-sectional study was performed from August 2020 to November 2020. Patients with PID and their families were invited to answer the PedsQL Malay version (4.0) questionnaire, the tool used to assess the HRQOL. A total of 41 families and 33 patients with PID answered the questionnaire. A comparison was performed with the previously published value of healthy Malaysian children.

    RESULT: Parents of respondents recorded a lower mean of total score than the parents of healthy children (67.26 ± 16.73 vs. 79.51 ± 11.90, p-value = 0.001, respectively). PID patients reported lower mean total score to healthy children (73.68 ± 16.38 vs. 79.51 ± 11.90, p-value = 0.04), including the psychosocial domain (71.67 ± 16.82 vs. 77.58 ± 12.63, p-value = 0.05) and school functioning (63.94 ± 20.87 vs. 80.00 ± 14.40, p-value = 0.007). No significant difference of reported HRQOL when comparing between subgroup of PID on immunoglobulin replacement therapy and those without immunoglobulin replacement (56.96 ± 23.58 vs. 65.83 ± 23.82, p-value 0.28). Socioeconomic status was found to be predictive of the lower total score of PedsQL in both parent and children reports.

    CONCLUSION: Parents and children with PID, especially those from middle socioeconomic status, have lower HRQOL and school function impairment than healthy children.

  6. Habib Dzulkarnain SM, Hashim IF, Zainudeen ZT, Taib F, Mohamad N, Nasir A, et al.
    J Clin Immunol, 2023 Oct;43(7):1623-1639.
    PMID: 37328647 DOI: 10.1007/s10875-023-01532-5
    Purine nucleoside phosphorylase deficient severe combined immunodeficiency (PNP SCID) is one of the rare autosomal recessive primary immunodeficiency disease, and the data on epidemiology and outcome are limited. We report the successful management of a child with PNP SCID and present a systematic literature review of published case reports, case series, and cohort studies on PNP SCID listed in PubMed, Web of Science, and Scopus from 1975 until March 2022. Forty-one articles were included from the 2432 articles retrieved and included 100 PNP SCID patients worldwide. Most patients presented with recurrent infections, hypogammaglobulinaemia, autoimmune manifestations, and neurological deficits. There were six reported cases of associated malignancies, mainly lymphomas. Twenty-two patients had undergone allogeneic hematopoietic stem cell transplantation with full donor chimerism seen mainly in those receiving matched sibling donors and/or conditioning chemotherapy before the transplant. This research provides a contemporary, comprehensive overview on clinical manifestations, epidemiology, genotype mutations, and transplant outcome of PNP SCID. These data highlight the importance of screening for PNP SCID in cases presented with recurrent infections, hypogammaglobulinaemia, and neurological deficits.
  7. Ahmed Meelad R, Abd Hamid IJ, Hashim IF, Zainudeen ZT, Abu Bakar FF, Taib F, et al.
    Front Pediatr, 2022;10:846393.
    PMID: 35433547 DOI: 10.3389/fped.2022.846393
    INTRODUCTION: Primary immunodeficiency diseases (PIDs) are chronic diseases that affect the various aspects of a patient's life. However, the impact of living with PIDs is poorly described.

    OBJECTIVE: This study aimed to explore the living experience challenges among the Malaysian caregivers of the patients with PID who underwent a follow-up in the Universiti Sains Malaysia or those registered members of the Malaysian PIDs Society.

    METHODOLOGY: The study was conducted from March 1 to May 30, 2021. The parents of children with PIDs were invited to participate for a semi-structured in-depth interview at the PID clinics in the USM. The estimated time of each interview was 30 min. The semi-structured interview was performed via a telephone call because of COVID-19 pandemic restrictions. The audio recording of each interview was transcribed and translated from Malay to English. Subsequently, a thematic analysis utilizing the ATLAS.ti software was performed.

    RESULTS: The thematic analysis revealed five main themes, which are living with fear and anxiety with four sub-themes (sickness, psychological issues, fear of infections and hereditary issues), PID healthcare support struggles with four sub-themes (PID health system, treatment, diagnosis and financial issues), knowledge with two sub-themes (educational issues and disease understanding), social constraint with two sub-themes (relationships and social isolations) and coping with three sub-themes (acceptance, child health improvement and emotional hygiene).

    CONCLUSION: Living with fear and anxiety is a major theme impacting the living experiences of Malaysian patients with PIDs. Improvements in healthcare delivery and disease education are needed to ensure optimal quality of life.

  8. Noh LM, Latiff AHA, Ismail IH, Noah RM, Wahab AA, Hamid IJA, et al.
    Allergy Asthma Clin Immunol, 2021 May 17;17(1):50.
    PMID: 34001231 DOI: 10.1186/s13223-021-00551-4
    BACKGROUND: A retrospective review of clinical manifestations and demographic pattern of patients diagnosed as chronic granulomatous disease (CGD) from 7 hospitals in Malaysia. An analysis of the available database would establish clinical characteristics, diagnoses and outcome including microbiologic pattern. Studying the demography allows us to document the occurrence of CGD amongst multiethnic groups and its geographical distribution for Malaysia.

    METHODS: Data from the Malaysia Primary Immunodeficiency Network (MyPIN) with cases of CGD diagnosed from 1991 until 2016 were collated and analysed.

    RESULTS: Twenty patients were diagnosed as CGD. Males (N = 13, 65%) outnumber females (N = 7, 35%). CGD is commonest amongst the Malays (65%) followed by the Chinese (15.0%), Indians (10.0%) and natives of Borneo (10.0%), reflecting the ethnic composition of the country. The mean age of diagnosis was 3.7 years. There was a positive family history in 40% of the cases. Abscess was the main presenting feature in 16 patients (80%) with one involving the brain. Pneumonia occurred in 10 (50%) and one with complicated bronchiectasis. Catalase-positive bacteria were the most commonly isolated pathogen with Chromobacterium violaceum predominating (N = 5, 25%) with consequent high mortality (N = 4, 80%). All CGD patients with C. violaceum infection displayed CD4 + (T helper cells) lymphopenia.

    CONCLUSION: This study has shown CGD occurs in the major ethnic groups of Malaysia. To the best of our knowledge, this is the first and the largest series of chronic granulomatous disease in South East Asia which may be reflective of similar clinical pattern in the region. C. violaceum infection is associated with a higher mortality in CGD patients in Malaysia. All the CGD patients with C. violaceum infection in this patient series displayed CD4 + (T helper) lymphopenia. We recorded rare clinical manifestation of CGD viz. brain abscess and bronchiectasis.

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