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  1. Akhter A, Mughal MK, Elyamany G, Sinclair G, Azma RZ, Masir N, et al.
    Diagn Pathol, 2016 Sep 15;11(1):89.
    PMID: 27632978 DOI: 10.1186/s13000-016-0541-z
    The World Health Organization (WHO) classification system defines recurrent chromosomal translocations as the sole diagnostic and prognostic criteria for acute leukemia (AL). These fusion transcripts are pivotal in the pathogenesis of AL. Clinical laboratories universally employ conventional karyotype/FISH to detect these chromosomal translocations, which is complex, labour intensive and lacks multiplexing capacity. Hence, it is imperative to explore and evaluate some newer automated, cost-efficient multiplexed technologies to accommodate the expanding genetic landscape in AL.
    Matched MeSH terms: Child, Preschool
  2. Miyake N, Fukai R, Ohba C, Chihara T, Miura M, Shimizu H, et al.
    Am J Hum Genet, 2016 Oct 06;99(4):950-961.
    PMID: 27666374 DOI: 10.1016/j.ajhg.2016.08.005
    We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and β-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy.
    Matched MeSH terms: Child, Preschool
  3. Sreeramareddy CT, Low YP, Forsberg BC
    BMC Pediatr, 2017 03 21;17(1):83.
    PMID: 28320354 DOI: 10.1186/s12887-017-0836-6
    BACKGROUND: Diarrhea remains to be a main cause of childhood mortality. Diarrhea case management indicators reflect the effectiveness of child survival interventions. We aimed to assess time trends and country-wise changes in diarrhea case management indicators among under-5 children in low-and-middle-income countries.

    METHODS: We analyzed aggregate data from Demographic and Health Surveys and Multiple Indicator Cluster Surveys done from 1986 to 2012 in low-and-middle-income countries. Two-week prevalence rates of diarrhea, caregiver's care seeking behavior and three case management indicators were analyzed. We assessed overall time trends across the countries using panel data analyses and country-level changes between two sequential surveys.

    RESULTS: Overall, yearly increase in case management indicators ranged from 1 · 3 to 2 · 5%. In the year 2012, <50% of the children were given correct treatment (received oral rehydration and increased fluids) for diarrhea. Annually, an estimated 300 to 350 million children were not given oral rehydration solutions, or recommended home fluids or 'increased fluids' and 304 million children not taken to a healthcare provider during an episode of diarrhea. Overall, care seeking for diarrhea, increased from pre-2000 to post-2000, i.e. from 35 to 45%; oral rehydration rates increased by about 7% but the rate of 'increased fluids' decreased by 14%. Country-level trends showed that care seeking had decreased in 15 countries but increased in 33 countries. Care seeking from a healthcare provider increased by ≥10% in about 23 countries. Oral rehydration rates had increased by ≥10% in 15 countries and in 30 countries oral rehydration rates increased by <10%.

    CONCLUSIONS: Very limited progress has been made in the case management of childhood diarrhea. A better understanding of caregiver's care seeking behavior and health care provider's case management practices is needed to improve diarrhea case management in low- and-middle-income countries.

    Matched MeSH terms: Child, Preschool
  4. Mohd Azizi FS, Kew Y, Moy FM
    Vaccine, 2017 05 19;35(22):2955-2961.
    PMID: 28434687 DOI: 10.1016/j.vaccine.2017.04.010
    BACKGROUND: Vaccine hesitancy is a threat in combating vaccine-preventable diseases. It has been studied extensively in the Western countries but not so among Asian countries.

    OBJECTIVES: To assess the test-retest reliability of the Parent Attitudes about Childhood Vaccines (PACV) questionnaire in Malay language; to determine the prevalence of vaccine hesitancy among parents and its associations with parents' socio-demographic characteristics.

    METHODS: Forward and backward translation of PACV in Malay language was carried out. The reliability of the Malay-PACV questionnaire was tested among parents with children. The same questionnaire was used to study vaccine hesitancy among parents in a tertiary hospital in Kuala Lumpur. Information pertaining to socio-demographic characteristics, sources of information regarding vaccination and vaccine hesitancy were collected. Associations between vaccine hesitancy with socio-demographic factors were tested using Multivariable Logistic Regression.

    RESULTS: The Spearman correlation coefficient and Cronbach alpha for total PACV was 0.79 (p<0.001) and 0.79 respectively. The intra-class correlation coefficients of the subscales ranged from 0.54 to 0.90 demonstrating fair to excellent reliability. A total of 63 (11.6%) parents were noted to be vaccine hesitant. In the univariate analyses, vaccine hesitancy was associated with unemployed parents, parents who were younger, had fewer children and non-Muslim. In the multivariate model, pregnant mothers expecting their first child were four times more likely to be vaccine hesitant compared to those who already had one or more children (aOR: 3.91, 95% CI: 1.74-8.79) and unemployed parents were also more likely to be vaccine hesitant (aOR: 1.97, 95% CI: 1.08-3.59). The internet (65.6%) was the main source of information on vaccination followed by brochures (56.9%).

    CONCLUSION: The Malay-PACV questionnaire is reliable to be used. The prevalence of vaccine hesitancy among the multi-ethnic Malaysians was comparable with other populations. Pregnant mothers expecting their first child and unemployed parents were found to be more vaccine hesitant.

    Matched MeSH terms: Child, Preschool
  5. Kruszka P, Addissie YA, McGinn DE, Porras AR, Biggs E, Share M, et al.
    Am J Med Genet A, 2017 Apr;173(4):879-888.
    PMID: 28328118 DOI: 10.1002/ajmg.a.38199
    22q11.2 deletion syndrome (22q11.2 DS) is the most common microdeletion syndrome and is underdiagnosed in diverse populations. This syndrome has a variable phenotype and affects multiple systems, making early recognition imperative. In this study, individuals from diverse populations with 22q11.2 DS were evaluated clinically and by facial analysis technology. Clinical information from 106 individuals and images from 101 were collected from individuals with 22q11.2 DS from 11 countries; average age was 11.7 and 47% were male. Individuals were grouped into categories of African descent (African), Asian, and Latin American. We found that the phenotype of 22q11.2 DS varied across population groups. Only two findings, congenital heart disease and learning problems, were found in greater than 50% of participants. When comparing the clinical features of 22q11.2 DS in each population, the proportion of individuals within each clinical category was statistically different except for learning problems and ear anomalies (P 
    Matched MeSH terms: Child, Preschool
  6. Al-Absi B, Razif MFM, Noor SM, Saif-Ali R, Aqlan M, Salem SD, et al.
    Genet Test Mol Biomarkers, 2017 Oct;21(10):592-599.
    PMID: 28768142 DOI: 10.1089/gtmb.2017.0084
    BACKGROUND: Genome-wide and candidate gene association studies have previously revealed links between a predisposition to acute lymphoblastic leukemia (ALL) and genetic polymorphisms in the following genes: IKZF1 (7p12.2; ID: 10320), DDC (7p12.2; ID: 1644), CDKN2A (9p21.3; ID: 1029), CEBPE (14q11.2; ID: 1053), and LMO1 (11p15; ID: 4004). In this study, we aimed to conduct an investigation into the possible association between polymorphisms in these genes and ALL within a sample of Yemeni children of Arab-Asian descent.

    METHODS: Seven single-nucleotide polymorphisms (SNPs) in IKZF1, three SNPs in DDC, two SNPs in CDKN2A, two SNPs in CEBPE, and three SNPs in LMO1 were genotyped in 289 Yemeni children (136 cases and 153 controls), using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Logistic regression analyses were used to estimate ALL risk, and the strength of association was expressed as odds ratios with 95% confidence intervals.

    RESULTS: We found that the IKZF1 SNP rs10235796 C allele (p = 0.002), the IKZF1 rs6964969 A>G polymorphism (p = 0.048, GG vs. AA), the CDKN2A rs3731246 G>C polymorphism (p = 0.047, GC+CC vs. GG), and the CDKN2A SNP rs3731246 C allele (p = 0.007) were significantly associated with ALL in Yemenis of Arab-Asian descent. In addition, a borderline association was found between IKZF1 rs4132601 T>G variant and ALL risk. No associations were found between the IKZF1 SNPs (rs11978267; rs7789635), DDC SNPs (rs3779084; rs880028; rs7809758), CDKN2A SNP (rs3731217), the CEBPE SNPs (rs2239633; rs12434881) and LMO1 SNPs (rs442264; rs3794012; rs4237770) with ALL in Yemeni children.

    CONCLUSION: The IKZF1 SNPs, rs10235796 and rs6964969, and the CDKN2A SNP rs3731246 (previously unreported) could serve as risk markers for ALL susceptibility in Yemeni children.

    Matched MeSH terms: Child, Preschool
  7. Nguyen Bao KL, Sandjaja S, Poh BK, Rojroongwasinkul N, Huu CN, Sumedi E, et al.
    Nutrients, 2018 Jun 13;10(6).
    PMID: 29899251 DOI: 10.3390/nu10060759
    Despite a major decrease in undernutrition worldwide over the last 25 years, underweight and stunting in children still persist as public health issues especially in Africa and Asia. Adequate nutrition is one of the key factors for healthy growth and development of children. In this study, the associations between dairy consumption and nutritional status in the South East Asian Nutrition Survey (SEANUTS) were investigated. National representative data of 12,376 children in Indonesia, Malaysia, Thailand, and Vietnam aged between 1 and 12 years were pooled, representing nearly 88 million children in this age category. It was found that the prevalence of stunting and underweight was lower in children who consumed dairy on a daily basis (10.0% and 12.0%, respectively) compared to children who did not use dairy (21.4% and 18.0%, respectively) (p < 0.05). The prevalence of vitamin A deficiency and vitamin D insufficiency was lower in the group of dairy users (3.9% and 39.4%, respectively) compared to non-dairy consumers (7.5% and 53.8%, respectively) (p < 0.05). This study suggests that dairy as part of a daily diet plays an important role in growth and supports a healthy vitamin A and vitamin D status.
    Matched MeSH terms: Child, Preschool
  8. Global Burden of Disease Study 2013 Collaborators
    Lancet, 2015 Aug 22;386(9995):743-800.
    PMID: 26063472 DOI: 10.1016/S0140-6736(15)60692-4
    BACKGROUND: Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.
    METHODS: Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries.
    FINDINGS: Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2·4 billion and 1·6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537·6 million in 1990 to 764·8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114·87 per 1000 people to 110·31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21·1% in 1990 to 31·2% in 2013.
    INTERPRETATION: Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
    FUNDING: Bill & Melinda Gates Foundation.
    Malaysian collaborators: Department of Medicine, Universiti Kebangsaan Malaysia Medical Center, Kuala Lampur, Malaysia (Prof N Mohamed Ibrahim MBBch); Universiti Kebangsaan Malaysia Medical Centre, Bangi, Selangor, Malaysia (R Sahathevan PhD); Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman, Selangor, Malaysia (C T Sreeramareddy MD); WorldFish, Penang, Malaysia (A L Thorne-Lyman ScD); TCM Medical TK SDN BHD TCM, Nusajaya, Johor Bahru, Malaysia (K Yun Kin PhD)
    Matched MeSH terms: Child, Preschool
  9. Munkongdee T, Tongsima S, Ngamphiw C, Wangkumhang P, Peerapittayamongkol C, Hashim HB, et al.
    Sci Rep, 2021 05 14;11(1):10352.
    PMID: 33990643 DOI: 10.1038/s41598-021-89641-2
    β-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. A thalassemia severity score has been developed from Mediterranean β-thalassemia patients. However, different ethnic groups may have different allele frequency and linkage disequilibrium structures. Here, Thai β0-thalassemia/HbE disease genome-wild association studies (GWAS) data of 487 patients were analyzed by SNP interaction prioritization algorithm, interacting Loci (iLoci), to find predictive SNPs for disease severity. Three SNPs from two SNP interaction pairs associated with disease severity were identifies. The three-SNP disease severity risk score composed of rs766432 in BCL11A, rs9399137 in HBS1L-MYB and rs72872548 in HBE1 showed more than 85% specificity and 75% accuracy. The three-SNP predictive score was then validated in two independent cohorts of Thai and Malaysian β0-thalassemia/HbE patients with comparable specificity and accuracy. The SNP risk score could be used for prediction of clinical severity for Southeast Asia β0-thalassemia/HbE population.
    Matched MeSH terms: Child, Preschool
  10. Griffiths MJ, Ooi MH, Wong SC, Mohan A, Podin Y, Perera D, et al.
    J Infect Dis, 2012 Sep 15;206(6):881-92.
    PMID: 22829643 DOI: 10.1093/infdis/jis446
    BACKGROUND: Enterovirus 71 (EV71) causes large outbreaks of hand, foot, and mouth disease (HFMD), with severe neurological complications and cardio-respiratory compromise, but the pathogenesis is poorly understood.

    METHODS: We measured levels of 30 chemokines and cytokines in serum and cerebrospinal fluid (CSF) samples from Malaysian children hospitalized with EV71 infection (n = 88), comprising uncomplicated HFMD (n = 47), meningitis (n = 8), acute flaccid paralysis (n = 1), encephalitis (n = 21), and encephalitis with cardiorespiratory compromise (n = 11). Four of the latter patients died.

    RESULTS: Both pro-inflammatory and anti-inflammatory mediator levels were elevated, with different patterns of mediator abundance in the CSF and vascular compartments. Serum concentrations of interleukin 1β (IL-1β), interleukin 1 receptor antagonist (IL-1Ra), and granulocyte colony-stimulating factor (G-CSF) were raised significantly in patients who developed cardio-respiratory compromise (P = .013, P = .004, and P < .001, respectively). Serum IL-1Ra and G-CSF levels were also significantly elevated in patients who died, with a serum G-CSF to interleukin 5 ratio of >100 at admission being the most accurate prognostic marker for death (P < .001; accuracy, 85.5%; sensitivity, 100%; specificity, 84.7%).

    CONCLUSIONS: Given that IL-1β has a negative inotropic action on the heart, and that both its natural antagonist, IL-1Ra, and G-CSF are being assessed as treatments for acute cardiac impairment, the findings suggest we have identified functional markers of EV71-related cardiac dysfunction and potential treatment options.

    Matched MeSH terms: Child, Preschool
  11. Fong CY, Kong AN, Noordin M, Poh BK, Ong LC, Ng CC
    Eur. J. Paediatr. Neurol., 2018 Jan;22(1):155-163.
    PMID: 29122496 DOI: 10.1016/j.ejpn.2017.10.007
    INTRODUCTION: Children with epilepsy on long-term antiepileptic drugs (AEDs) are at risk of low bone mineral density (BMD). The aims of our study were to evaluate the prevalence and determinants of low BMD among Malaysian children with epilepsy.

    METHOD: Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in a tertiary hospital in Malaysia from 2014 to 2015. Detailed assessment of anthropometric measurements; environmental lifestyle risk factors; serum vitamin D, calcium and parathyroid hormone levels; genotyping of single nucleotide polymorphisms of genes in vitamin D and calcium metabolism; and lumbar spine BMD were obtained. Low BMD was defined as BMD Z-score ≤ -2.0 SD.

    RESULTS: Eighty-seven children with mean age of 11.9 years (56 males) participated in the study. The prevalence of low lumbar BMD was 21.8% (19 patients). Multivariate logistic regression analysis identified polytherapy >2 AEDs (OR: 7.86; 95% CI 1.03-59.96), small frame size with wrist breadth of <15th centile (OR 14.73; 95% CI 2.21-98.40), and body mass index Z-score 2 AEDs, underweight or with small frame size as they are at higher risk of having low BMD.

    Matched MeSH terms: Child, Preschool
  12. Tan KK, Dang DA, Kim KH, Kartasasmita C, Kim HM, Zhang XH, et al.
    Hum Vaccin Immunother, 2018 01 02;14(1):95-105.
    PMID: 29125809 DOI: 10.1080/21645515.2017.1375073
    BACKGROUND: Few studies describe the community-acquired pneumonia (CAP) burden in children in Asia. We estimated the proportion of all CAP hospitalizations in children from nine hospitals across the Republic of Korea (high-income), Indonesia, Malaysia (middle-income), and Vietnam (low/middle-income).

    METHODS: Over a one or two-year period, children <5 years hospitalized with CAP were identified using ICD-10 discharge codes. Cases were matched to standardized definitions of suspected (S-CAP), confirmed (C-CAP), or bacterial CAP (B-CAP) used in a pneumococcal conjugate vaccine efficacy study (COMPAS). Median total direct medical costs of CAP-related hospitalizations were calculated.

    RESULTS: Vietnam (three centers): 7591 CAP episodes were identified with 4.3% (95% confidence interval 4.2;4.4) S-CAP, 3.3% (3.2;3.4) C-CAP and 1.4% (1.3;1.4) B-CAP episodes of all-cause hospitalization in children aged <5 years. The B-CAP case fatality rate (CFR) was 1.3%. Malaysia (two centers): 1027 CAP episodes were identified with 2.7% (2.6;2.9); 2.6% (2.4;2.8); 0.04% (0.04;0.1) due to S-CAP, C-CAP, and B-CAP, respectively. One child with B-CAP died. Indonesia (one center): 960 CAP episodes identified with 18.0% (17.0;19.1); 16.8% (15.8;17.9); 0.3% (0.2;0.4) due to S-CAP, C-CAP, and B-CAP, respectively. The B-CAP CFR was 20%. Korea (three centers): 3151 CAP episodes were identified with 21.1% (20.4;21.7); 11.8% (11.2;12.3); 2.4% (2.1;2.7) due to S-CAP, C-CAP, and B-CAP, respectively. There were no deaths.

    COSTS: CAP-related hospitalization costs were highest for B-CAP episodes: 145.00 (Vietnam) to 1013.3 USD (Korea) per episode.

    CONCLUSION: CAP hospitalization causes an important health and cost burden in all four countries studied (NMRR-12-50-10793).

    Matched MeSH terms: Child, Preschool
  13. Mat Ariffin N, Islahudin F, Kumolosasi E, Makmor-Bakry M
    BMC Infect Dis, 2017 12 08;17(1):759.
    PMID: 29216842 DOI: 10.1186/s12879-017-2868-9
    BACKGROUND: Recurrence rates of Plasmodium vivax infections differ across various geographic regions. Interestingly, South-East Asia and the Asia-Pacific region are documented to exhibit the most frequent recurrence incidences. Identifying patients at a higher risk for recurrences gives valuable information in strengthening the efforts to control P. vivax infections. The aim of the study was to develop a tool to identify P. vivax- infected patients that are at a higher risk of recurrence in Malaysia.

    METHODS: Patient data was obtained retrospectively through the Ministry of Health, Malaysia, from 2011 to 2016. Patients with incomplete data were excluded. A total of 2044 clinical P. vivax malaria cases treated with primaquine were included. Data collected were patient, disease, and treatment characteristics. Two-thirds of the cases (n = 1362) were used to develop a clinical risk score, while the remaining third (n = 682) was used for validation.

    RESULTS: Using multivariate analysis, age (p = 0.03), gametocyte sexual count (p = 0.04), indigenous transmission (p = 0.04), type of treatment (p = 0.12), and incomplete primaquine treatment (p = 0.14) were found to be predictors of recurrence after controlling for other confounding factors; these predictors were then used in developing the final model. The beta-coefficient values were used to develop a clinical scoring tool to predict possible recurrence. The total scores ranged between 0 and 8. A higher score indicated a higher risk for recurrence (odds ratio [OR]: 1.971; 95% confidence interval [CI]: 1.562-2.487; p ≤ 0.001). The area under the receiver operating characteristic (ROC) curve of the developed (n = 1362) and validated model (n = 682) was of good accuracy (ROC: 0.728, 95% CI: 0.670-0.785, p value 

    Matched MeSH terms: Child, Preschool
  14. Dhanoa A, Hassan SS, Ngim CF, Lau CF, Chan TS, Adnan NA, et al.
    BMC Infect Dis, 2016 08 11;16(1):406.
    PMID: 27514512 DOI: 10.1186/s12879-016-1731-8
    BACKGROUND: The co-circulation of 4 DENV serotypes in geographically expanding area, has resulted in increasing occurrence of DENV co-infections. However, studies assessing the clinical impact of DENV co-infections have been scarce and have involved small number of patients. This study explores the impact of DENV co-infection on clinical manifestations and laboratory parameters.

    METHODS: This retrospective study involved consecutive hospitalized patients with non-structural protein 1 (NS1) antigen positivity during an outbreak (Jan to April 2014). Multiplex RT-PCR was performed directly on NS1 positive serum samples to detect and determine the DENV serotypes. All PCR-positive serum samples were inoculated onto C6/36 cells. Multiplex PCR was repeated on the supernatant of the first blind passage of the serum-infected cells. Random samples of supernatant from the first passage of C6/36 infected cells were subjected to whole genome sequencing. Clinical and laboratory variables were compared between patients with and without DENV co-infections.

    RESULTS: Of the 290 NS1 positive serum samples, 280 were PCR positive for DENV. Medical notes of 262 patients were available for analysis. All 4 DENV serotypes were identified. Of the 262 patients, forty patients (15.3 %) had DENV co-infections: DENV-1/DENV-2(85 %), DENV-1/DENV-3 (12.5 %) and DENV-2/DENV-3 (2.5 %). Another 222 patients (84.7 %) were infected with single DENV serotype (mono-infection), with DENV- 1 (76.6 %) and DENV- 2 (19.8 %) predominating. Secondary dengue infections occurred in 31.3 % patients. Whole genome sequences of random samples representing DENV-1 and DENV-2 showed heterogeneity amongst the DENVs. Multivariate analysis revealed that pleural effusion and the presence of warning signs were significantly higher in the co-infected group, both in the overall and subgroup analysis. Diarrhoea was negatively associated with co-infection. Additionally, DENV-2 co-infected patients had higher frequency of patients with severe thrombocytopenia (platelet count < 50,000/mm(3)), whereas DENV-2 mono-infections presented more commonly with myalgia. Elevated creatinine levels were more frequent amongst the co-infected patients in univariate analysis. Haemoconcentration and haemorrhagic manifestations were not higher amongst the co-infected patients. Serotypes associated with severe dengue were: DENV-1 (n = 9), DENV-2 (n = 1), DENV-3 (n = 1) in mono-infected patients and DENV-1/DENV-2 (n = 5) and DENV-1/DENV-3 (n = 1) amongst the co-infected patients.

    CONCLUSION: DENV co-infections are not uncommon in a hyperendemic region and co-infected patients are skewed towards more severe clinical manifestations compared to mono-infected patients.

    Matched MeSH terms: Child, Preschool
  15. Al-Talib H, Latif B, Mohd-Zain Z
    J Clin Microbiol, 2014 Sep;52(9):3244-9.
    PMID: 24958797 DOI: 10.1128/JCM.00891-14
    Diarrheal diseases cause illness and death among children younger than 10 years in developing countries. Conventional testing for the detection of hemorrhagic bacteria takes 2 to 5 days to yield complete information on the organism and its antibiotic sensitivity pattern. Hence, in the present study, we developed a molecular-based diagnostic assay that identifies common hemorrhagic bacteria in stool samples. A set of specific primers were designed for the detection of Salmonella spp., Shigella spp., enterohemorrhagic Escherichia coli (EHEC), and Campylobacter spp., suitable for use in a one-tube PCR assay. The assay in the present study simultaneously detected five genes, namely, ompC for the Salmonella genus, virA for the Shigella genus, eaeA for EHEC, 16S rRNA for the Campylobacter genus, and hemA for an internal control. Specific primer pairs were successfully designed and simultaneously amplified the targeted genes. Validation with 20 Gram-negative and 17 Gram-positive strains yielded 100% specificity. The limit of detection of the multiplex PCR assay was 1 × 10(3) CFU at the bacterial cell level and 100 pg at the genomic DNA level. Further evaluation of the multiplex PCR with 223 bacterium-spiked stool specimens revealed 100% sensitivity and specificity. We conclude that the developed multiplex PCR assay was rapid, giving results within 4 h, which is essential for the identification of hemorrhagic bacteria, and it might be useful as an additional diagnostic tool whenever time is important in the diagnosis of hemorrhagic bacteria that cause diarrhea. In addition, the presence of an internal control in the multiplex PCR assay is important for excluding false-negative cases.
    Matched MeSH terms: Child, Preschool
  16. Saleem Z, Godman B, Hassali MA, Hashmi FK, Azhar F, Rehman IU
    Pathog Glob Health, 2019 Jun;113(4):191-205.
    PMID: 31215326 DOI: 10.1080/20477724.2019.1632070
    Health-care-associated infections (HAIs) are considered a serious public health issues that contribute substantially to the global burden of mortality and morbidity with respect to infectious diseases. The aim is to assess the burden of health-care-associated infections by collation of available data from published point prevalence surveys (PPS) on HAIs to give future guidance. Study protocol and methodology were designed according to preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Published research papers that conducted a point prevalence survey of HAIs in hospital settings by following the structured survey methodology employed by European Centre of Disease Prevention and Control (ECDC) were included. Of 1212 articles, 67 studies were included in the final analysis conducted across different countries. Overall, 35 studies were conducted in Europe, 21 in Asia, 9 in America, and 2 in Africa. The highest prevalence of HAIs was recorded in a study conducted in adult ICU settings of 75 regions of Europe (51.3%). The majority of the studies included HAI data on urinary tract infections, respiratory tract infections, and bloodstream infections. Klebsiella pneumonia, Pseudomonas aeruginosa and E. coli were the most frequent pathogens responsible for HAIs. PPS is an useful tool to quantify HAIs and provides a robust baseline data for policymakers. However, a standardize surveillance method is required. In order to minimize the burden of HAIs, infection prevention and control programs and antibiotic stewardship may be effective strategies to minimize the risk of HAIs.
    Matched MeSH terms: Child, Preschool
  17. Jiram AI, Ooi CH, Rubio JM, Hisam S, Karnan G, Sukor NM, et al.
    Malar J, 2019 May 02;18(1):156.
    PMID: 31046769 DOI: 10.1186/s12936-019-2786-y
    BACKGROUND: Malaysia has declared its aim to eliminate malaria with a goal of achieving zero local transmission by the year 2020. However, targeting the human reservoir of infection, including those with asymptomatic infection is required to achieve malaria elimination. Diagnosing asymptomatic malaria is not as straightforward due to the obvious lack of clinical manifestations and often subpatent level of parasites. Accurate diagnosis of malaria is important for providing realistic estimates of malaria burden and preventing misinformed interventions. Low levels of parasitaemia acts as silent reservoir of transmission thus remains infectious to susceptible mosquito vectors. Hence, the aim of this study is to investigate the prevalence of asymptomatic submicroscopic malaria (SMM) in the District of Belaga, Sarawak.

    METHODS: In 2013, a total of 1744 dried blood spots (DBS) were obtained from residents of 8 longhouses who appeared healthy. Subsequently, 251 venous blood samples were collected from residents of 2 localities in 2014 based on the highest number of submicroscopic cases from prior findings. Thin and thick blood films were prepared from blood obtained from all participants in this study. Microscopic examination were carried out on all samples and a nested and nested multiplex PCR were performed on samples collected in 2013 and 2014 respectively.

    RESULTS: No malaria parasites were detected in all the Giemsa-stained blood films. However, of the 1744 samples, 29 (1.7%) were positive for Plasmodium vivax by PCR. Additionally, of the 251 samples, the most prevalent mono-infection detected by PCR was Plasmodium falciparum 50 (20%), followed by P. vivax 39 (16%), P. knowlesi 9 (4%), and mixed infections 20 (8%).

    CONCLUSIONS: This research findings conclude evidence of Plasmodium by PCR, among samples previously undetectable by routine blood film microscopic examination, in local ethnic minority who are clinically healthy. SMM in Belaga district is attributed not only to P. vivax, but also to P. falciparum and P. knowlesi. In complementing efforts of programme managers, there is a need to increase surveillance for SMM nationwide to estimate the degree of SMM that warrant measures to block new transmission of malaria.

    Matched MeSH terms: Child, Preschool
  18. Lim LL, Fu AWC, Lau ESH, Ozaki R, Cheung KKT, Ma RCW, et al.
    Nephrol Dial Transplant, 2019 Aug 01;34(8):1320-1328.
    PMID: 29939305 DOI: 10.1093/ndt/gfy154
    BACKGROUND: Early detection and risk factor control prevent chronic kidney disease (CKD) progression. Evaluation of peripheral autonomic dysfunction may detect incident cardiovascular-renal events in type 2 diabetes (T2D).

    METHODS: SUDOSCAN, a non-invasive tool, provides an age-adjusted electrochemical skin conductance (ESC) composite score incorporating hands/feet ESC measurements, with a score ≤53 indicating sudomotor dysfunction. A consecutive cohort of 2833 Chinese adults underwent structured diabetes assessment in 2012-13; 2028 participants without preexisting cardiovascular disease (CVD) and CKD were monitored for incident cardiovascular-renal events until 2015.

    RESULTS: In this prospective cohort {mean age 57.0 [standard deviation (SD) 10.0] years; median T2D duration 7.0 [interquartile range (IQR) 3.0-13.0] years; 56.1% men; 72.5% never-smokers; baseline ESC composite score 60.7 (SD 14.5)}, 163 (8.0%) and 25 (1.2%) participants developed incident CKD and CVD, respectively, after 2.3 years of follow-up. The adjusted hazard ratios (aHRs) per 1-unit decrease in the ESC composite score for incident CKD, CVD and all-cause death were 1.02 [95% confidence interval (CI) 1.01-1.04], 1.04 (1.00-1.07) and 1.04 (1.00-1.08), respectively. Compared with participants with an ESC composite score >53, those with a score ≤53 had an aHR of 1.56 (95% CI 1.09-2.23) for CKD and 3.11 (95% CI 1.27-7.62) for CVD, independent of common risk markers. When added to clinical variables (sex and duration of diabetes), the ESC composite score improved discrimination of all outcomes with appropriate reclassification of CKD risk.

    CONCLUSIONS: A low ESC composite score independently predicts incident cardiovascular-renal events and death in T2D, which may improve the screening strategy for early intervention.

    Matched MeSH terms: Child, Preschool
  19. Muhammad EN, Abdul Mutalip MH, Hasim MH, Paiwai F, Pan S, Mahmud MAF, et al.
    BMC Infect Dis, 2020 Nov 16;20(1):843.
    PMID: 33198646 DOI: 10.1186/s12879-020-05500-x
    BACKGROUND: Typhoid fever causes global morbidity and mortality and is a significant health burden, particularly in low- and middle-income countries. The direct fecal-oral route is the main transmission mode, but indirect environmental transmission could occur, particularly in urban settings. This study aimed to investigate the burden and trend of typhoid fever, reporting the coverage system between government and private practice and pattern of multidrug-resistant (MDR) typhoid cases in the urban Klang Valley area from 2011 to 2015.

    METHODS: The data from a cross-sectional study retrieved from the e-Notifikasi System, a national reporting system for communicable diseases provided by the Disease Control Division, Ministry of Health Malaysia and secondary data of all the typhoid cases were obtained from the public and private hospitals and laboratories in Klang Valley. Descriptive analysis was performed to examine the sociodemographic characteristics, spatial mapping was conducted to examine trends, and the crude incidence rates of confirmed typhoid cases and percentage of reporting coverage were calculated. Significant differences between MDR and non-MDR Salmonella typhi were determined in the patient's sociodemographic characteristics, which were analyzed using χ2 test. P values

    Matched MeSH terms: Child, Preschool
  20. Jamal R, Fadzillah G, Zulkifli SZ, Yasmin M
    PMID: 10772566
    Regular blood transfusions for patients with thalassemia have improved their overall survival although these transfusions carry a definite risk of the transmission of certain viruses. Infection with hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) leads to complications which contribute to the morbidity and mortality of patients with thalassemia. We analyzed the blood samples taken from 85 transfusion dependent thalassemics receiving treatment at the day care center in Hospital Universiti Kebangsaan Malaysia and found that the seroprevalence rates for HBV, HCV and CMV were 2.4%, 22.4% and 91.8% respectively. None of the patients tested positive for HIV. Those positive for HBV and HCV will require further tests and treatment if chronic hepatitis is confirmed.
    Matched MeSH terms: Child, Preschool
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