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Aim Households are a significant venue for the transmission of SARS-CoV-2. We conducted a study to characterise the transmission dynamics and identify risk factors for household transmission of SARS-CoV-2 in Negeri Sembilan, Malaysia. Methods This retrospective observational study included 185 families of paediatric COVID-19 cases from 1 February 2020 to 31 December 2020. We identified the index case for each household and gathered the socio-demographic, epidemiological investigation results and risk factors for household transmission from medical case records. The secondary attack rate was calculated, and logistic regression analyses were used to identify risk factors associated with secondary household transmission of SARS-CoV-2. Results Of the 848 household contacts, 466 acquired secondary infections, resulting in a secondary attack rate of 55%. The median age of the secondary cases was 12 years. Female household contacts and household contacts who slept in the same room with the index case were significantly associated with increased risk for COVID-19. Other independent risk factors associated with higher transmission risk in the household included an index case who was symptomatic, a household index case aged greater than 18 years and a male household index case. Conclusions High rates of household transmission of COVID-19 were found, indicating households were a major setting of transmission of SARS-CoV-2. Our data provide insight into the risk factors for household transmission of SARS-CoV-2 in Malaysia.

Pneumococcal disease is a potentially fatal bacterial infection that is vaccine-preventable. Malaysia has yet to adopt a pneumococcal conjugate vaccine (PCV) into its national immunization program (NIP). In 2016, pneumonia was the 3rd leading cause of death in children under five in Malaysia, accounting for 3.8% of under-five deaths. Introducing a pneumococcal conjugate vaccine (PCV) is an effective strategy to reduce the disease burden. This study used a decision-analytic model to assess the potential impacts of introducing the available PCVs (13-valent and 10-valent) in Malaysia. Epidemiological and costs inputs were sourced from published literature. For each vaccination program, health outcomes and associated healthcare costs were estimated. The scenarios of initiating PCV13 vs. PCV10 and the status quo (no pneumococcal vaccine) were compared. Serotype trends of Finland and the U.K. were used to model the clinical impacts of PCV10 and PCV13 respectively. The base-case analysis used a societal perspective over a 5-year time horizon. Compared with PCV10, PCV13 was projected to avert an additional 190,628 cases of pneumococcal disease and 1126 cases of death. The acquisition of PCV13 was estimated to cost an incremental US$89,904,777, offset by a cost reduction of -US$250,219,914 on pneumococcal disease-related medical care and lost productivity. PCV13 demonstrated a higher cost-saving potential over PCV10. Compared with no vaccination, PCV13 was estimated as cost-saving. Results were robust across a series of sensitivity analyses. The introduction of PCV13 in a NIP was estimated to reduce a significant burden of disease and to be a cost-saving for the Malaysian health system.

Background: Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infection, with a high global health burden. There are no effective treatments available. ALX- 0171 is a novel trivalent Nanobody with antiviral properties against RSV. We aimed to assess the safety and antiviral activity of nebulised ALX- 0171 in children admitted to hospital with RSV lower respiratory tract infection. Methods: This double-blind, randomised, placebo- controlled, phase 2b trial was done in 50 hospital paediatric departments across 16 countries. Previously healthy children aged between 28 days to younger than 24 months who were admitted to hospital with RSV acute severe lower respiratory tract infection were randomly assigned in three sequential safety cohorts (3:1) to receive nebulised ALX-0171 (cohort 1 received 3 mg/kg, cohort 2 received 6 mg/kg, and cohort 3 received 9 mg/kg) or placebo once daily for 3 days using web- based randomisation in the sequential safety part (first block size 12, subsequently four). In a parallel part of the study, participants (cohort 4) were randomly assigned (parallel 1:1:1:1) to receive nebulised ALX-0171 3 mg/kg, 6 mg/kg, 9 mg/kg, or placebo (blocks of eight by restricted randomisation). Study drug masking was by two consecutive nebulisations (each either ALX-0171 or placebo) depending on assigned treatment group. The primary outcome was to evaluate time for the RSV viral load to drop to below quantifiable limit, measured by plaque assay on mid-turbinate nasal swabs. Safety, clinical efficacy, pharmacokinetics, viral load by RT-qPCR, and immunogenicity were secondary outcomes. Analysis, including of the primary outcome, was by modified intention to treat (participants receiving at least one dose of study drug as assigned), and safety was assessed in all children who received at least one administration of study drug, as treated. This trial is registered with EudraCT, 2016-001651-49. Findings: Between Jan 10, 2017, and April 26, 2018, 175 children (median age 4·8 months [IQR 2·0-10·8]), received at least one dose of study drug (45 received 3 mg/kg of ALX-0171, 43 received 6 mg/kg of ALX-0171, 45 received 9 mg/kg of ALX- 0171, and 42 received placebo ; the modified intention-to-treat population) commencing at a mean 3·3 days (SD 1·1) from symptom onset. Median time for the viral load to drop to below quantifiable limit on plaque assay was significantly faster for the 3 mg/kg group (median 14·2 h [IQR 5·0-28·0]), 6 mg/kg group (5·1 h [4·7- 28·5]), and 9 mg/kg group (5·1 h [4·6-5·9]) than the placebo group (46·1 h [25·2-116·7] ; hazard ratio [HR] all ALX-0171 groups vs placebo 2·6 [1·7-3·9] ; p92% for 4 h in room air and adequate oral feeding) in ALX-0171 groups and the placebo group (median 43·8 h [IQR 21·7-68·5] vs 47·9 h [22·5-76·4] ; HR 1·1 [95% CI 0·8-1·6]) or change in the global severity score from baseline to 5 h post-dose on day 2 (-4 [IQR -6 to -2] vs -4 [-6 to -1] ; difference in least- squares mean -0·45 [95% CI -1·39 to 0·49]). Serum concentrations of ALX-0171 on day 2 exceeded the concentration estimated to give full RSV neutralisation in the lung at 6 mg/kg and 9 mg/kg doses. Treatment-emergent antidrug antibodies were detected at day 14 in 46 (34%) of 135 patients who received ALX-0171 and ten (26%) of 39 patients who received placebo. Serious adverse events were reported in five (13%) of 40 children in the placebo group and ten (7%) of 135 children in all ALX-0171 groups, leading to study drug discontinuation in three children (two in the 3 mg/kg group and one in the 6 mg/kg group). 13 of 15 serious adverse events (three of four in the 3 mg/kg group, two of three in the 6 mg/kg group, three of three in the 9 mg/kg group, and five of five in the placebo group) were related to worsening respiratory status, and none were considered to be related to the study drug. Interpretation: Antivirals against RSV might be unable to improve clinical course once RSV lower respiratory tract infection is established. Future studies of RSV antivirals should focus on earlier intervention and more precise measurement of objective outcomes before the onset of significant lower respiratory tract inflammation.

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

This prospective observational study aims to determine the incidence, predictors and clinical features of Mycoplasma hominis (MH), Ureaplasma urealyticum (UU) and Chlamydia trachomatis (CT) respiratory colonization in infants

Background There is scarcity of data regarding epidemiology and clinical aspects of human adenovirus acute respiratory infection (ARI) among children in developing countries. Methods Retrospective data on demographics, clinical presentation, outcomes and laboratory findings of 116 children admitted into Tuanku Jaafar Hospital in Seremban, Malaysia from 2012 to 2013 with documented diagnosis of community-acquired adenovirus ARI were collected and analyzed. Results Male to female ratio was 1.70. Median age was 14 (1-107) months. The commonest symptoms were fever (94.8%; 110/116), cough (82.8%, 96), rhinorrhea (63.8%; 74), interrupted feeding (66.4%; 77), diarrhea (33.6%; 39) and conjunctivitis (21.6%; 25). Mean temperature on admission was 38.4°C±0.9°C. Among all 116 subjects, 20.7% (24) needed oxygen supplementation, 57.8% (67) required intravenous hydration, 11.2% (13) were admitted into the pediatric intensive care unit and 6.9% (8) required mechanical ventilation. Only 1% (1/87) had positive blood culture (Streptococcus pneumoniae) among 87 who received antibiotic treatment. Case fatality rate was 2.6% (3/116) and 1.7% (2/116) developed bronchiolitis obliterans. Median length of hospital stay was 4 (1-50) days. Conclusion Adenovirus ARI caused significant morbidity and substantial resource utilization among hospitalized Malaysian children. It should be considered in the differential diagnosis of infants below two years presenting with ARI associated with high fever. Antibiotics should not be prescribed as secondary bacterial infections are uncommon.

Pneumococcal disease causes large morbidity, mortality and health care utilization and medical and non-medical costs, which can all be reduced by effective infant universal routine immunization programs with pneumococcal conjugate vaccines (PCV). We evaluated the clinical and economic benefits of such programs with either 10- or 13-valent PCVs in Malaysia and Hong Kong by using an age-stratified Markov cohort model with many country-specific inputs. The incremental cost per quality-adjusted life year (QALY) was calculated to compare PCV10 or PCV13 against no vaccination and PCV13 against PCV10 over a 10-year birth cohort's vaccination. Both payer and societal perspectives were used. PCV13 had better public health and economic outcomes than a PCV10 program across all scenarios considered. For example, in the base case scenario in Malaysia, PCV13 would reduce more cases of IPD (+2,296), pneumonia (+705,281), and acute otitis media (+376,967) and save more lives (+6,122) than PCV10. Similarly, in Hong Kong, PCV13 would reduce more cases of IPD cases (+529), pneumonia (+172,185), and acute otitis media (+37,727) and save more lives (+2,688) than PCV10. During the same time horizon, PCV13 would gain over 74,000 and 21,600 additional QALYs than PCV10 in Malaysia and Hong Kong, respectively. PCV13 would be cost saving when compared against similar program with PCV10, under both payer and societal perspective in both countries. PCV13 remained a better choice over PCV10 in multiple sensitivity, scenario, and probabilistic analyses. PCV13s broader serotype coverage in its formulation and herd effect compared against PCV10 were important drivers of differences in outcomes.

Efficient separation of sub-micrometer synthetic or biological components is imperative in particle-based drug delivery systems and purification of extracellular vesicles for point-of-care diagnostics. Herein, we report a novel phenomenon in spiral inertial microfluidics, in which the particle transient innermost distance (Dinner) varies with size during Dean vortices-induced migration and can be utilized for small microparticle (MP) separation; aptly termed as high-resolution Dean flow fractionation (HiDFF). The developed technology was optimized using binary bead mixtures (1–3 μm) to achieve ~100- to 1000-fold enrichment of smaller particles. We demonstrated tunable size fractionation of polydispersed drug-loaded poly(lactic-co-glycolic acid) particles for enhanced drug release and anti-tumor effects. As a proof-of-concept for microvesicles studies, circulating extracellular vesicles/MPs were isolated directly from whole blood using HiDFF. Purified MPs exhibited well-preserved surface morphology with efficient isolation within minutes as compared with multi-step centrifugation. In a cohort of type 2 diabetes mellitus subjects, we observed strong associations of immune cell-derived MPs with cardiovascular risk factors including body mass index, carotid intima-media thickness and triglyceride levels (P

To determine effects of pandemic (H1N1) 2009 on children in the tropics, we examined characteristics of children hospitalized for this disease in Malaysia. Of 1,362 children, 51 (3.7%) died, 46 of whom were in an intensive care unit. Although disease was usually mild, >1 concurrent conditions were associated with higher death rates. T ransmission of pandemic (H1N1) 2009 in the Northern and Southern Hemispheres has been well documented (1–12). These reports described a relatively mild and selflimited clinical illness for most cases. However, data on disease prevalence and severity in children in the tropics are scarce. Malaysia has 132 public and 214 private hospitals. We examined the demographics, clinical presentation, and outcomes of children hospitalized for pandemic (H1N1) 2009 in 68 Ministry of Health–affi liated public hospitals in Malaysia that offered pediatric services. These 68 hospitals provide 3,757 beds for children and 101 beds in pediatric intensive care units; each year they serve ≈7,898,700 children

OBJECTIVES: To evaluate the role of routine stool examination for all pathogens in paediatric nosocomial diarrhea (NAD) and community-acquired diarrhea (CAD) over a two-year period at Alberta Children’s Hospital and current practices in other Canadian hospitals. A secondary objective was to characterize features that may predict NAD or CAD etiology.STUDY DESIGN: Retrospective cohort study and telephone survey.SETTING: Alberta Children’s Hospital (retrospective review) and Canadian tertiary care paediatric centres (telephone survey).METHODS: The health and microbiological records of all children with an admission or discharge diagnosis of diarrhea were reviewed using a standardized data collection form. In addition, a telephone survey of laboratories serving all paediatric hospitals in Canada was conducted using a standard questionnaire to obtain information about practices for screening for pathogens related to NAD.RESULTS: Four hundred and thirty-four CAD episodes and 89 NAD episodes were identified. Overall, rotavirus andClostridium difficilewere the most commonly identified pathogens. Bacterial culture was positive in 10.6% CAD episodes tested, withEscherichia coliO157:H7 identified as the most common non-C difficileorganism. In NAD, no bacteria were identified other thanC difficile(toxin). Screening for ova and parasites had negligible yield. Viruses were more frequent in the winter months, while bacterial pathogens were more common in the summer and fall months. Over 50% of Canadian paediatric hospitals still routinely process NAD specimens similarly to CAD specimens.CONCLUSIONS: There is a need for the re-evaluation of routine ova and parasite screening, and bacterial culture in nonoutbreak episodes of NAD in children.

Flip Chip Ball Grid Array (FCBGA) package with large silicon chip and package size typically exhibits high warpage and coplanarity. Many percieved that such package design faced surface mount technology (SMT) challenges. In this study, the warpage characteristic and the SMT validation for such large package was investigated. A hybrid methodology utilizing both numerical and empirical data to predict the coplanarity of this package is presented. SMT validation was performed on range of coplanarity to demonstrate the process robustness together with solder joint reliability (SJR) data. With all the studies, the correlation between package room temperature coplanarity and reflow warpage has been established without comprising SMT quality and SJR performance. In the end, an improved FCBGA coplanarity specification limit has been defined and aligned with the Alternate Warpage Specification in JEDEC standard.

Children aged 11 to

Scrub typhus is a common cause of febrile illness among children from rural regions in tropical countries. We described 2 cases of scrub typhus with an eschar localized in the genitalia that was missed during the routine medical examination of a febrile child.

Scrub typhus is a common cause of febrile illness among children from rural regions in tropical countries. We described 2 cases of scrub typhus with an eschar localized in the genitalia that was missed during the routine medical examination of a febrile child.

A three day old male, term infant with hemothorax due to hemorrhagic disease of the newborn was treated successfully with vitamin K and thoracocentesis. Exclusive breast feeding and absence of vitamin K prophylaxis were important diagnostic clues, although hemothorax as a sole manifestation of hemorrhagic disease of the newborn is rare. This case highlighted the good prognosis of an uncommon complication when prompt diagnosis and appropriate treatment are instituted. The importance of vitamin K prophylaxis to all newborns is emphasized.

a b s t r a c t Background: Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia. Methods: In this observer-blind, placebo-controlled, Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD-TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs) reported throughout the study, and immunogenicity expressed as geometric mean titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody titres. Results: 250 participants enrolled in the study (CYD-TDV: n = 199; placebo: n = 51). There was a trend for reactogenicity to be higher with CYD-TDV than with placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in frequency with each subsequent dose and were similar overall between groups (CYD-TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV and placebo groups, respectively. No deaths were reported. Baseline seropositivity against each of the four DENV serotypes was similar between groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8 (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post- dose 3 for DENV-1 and DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold (DENV-1) to 7.96-fold (DENV-3). Conclusions: This study demonstrated a satisfactory safety profile and a balanced humoral immune response against all four DENV serotypes for CYD-TDV administered via a three-dose regimen to children in Malaysia.

We reported a case of amoebic liver abscess (ALA) in a 6-year-old Malaysian boy who presented with fever, lethargy, diarrhoea and right hypochondriac pain. On admission he was diagnosed with perforated acute appendicitis and a laparotomy was done. After surgery he developed acute respiratory distress. Ultrasonography, chest X-Ray and CT scan revealed two ALAs in the posterior segment of right lobe of liver, pleural effusion and collapsed consolidation of lungs bilaterally. Percutaneous liver abscesses drainage was done and intravenous Metronidazole was started. PCR carried out on the pus from the abscess was positive for Entamoeba histolytica. Patient however succumbed to the infection one week after admission.

Background The immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia, where PHiD-CV has been licensed. Methods In the primary vaccination phase, 298 infants from Singapore and 168 infants from Malaysia were randomised to receive the Phase III Clinical (Clin) or the Commercial (Com) lot of PHiD-CV at 2, 3, and 5 months of age. In the booster vaccination phase, 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18–21 months of age. Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and functional opsonophagocytic activity (OPA) assay and to protein D, using ELISA. Results Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjusted antibody geometric mean concentration (GMC) ratios for each vaccine pneumococcal serotype and protein D. For each vaccine pneumococcal serotype, ≥93.6% and ≥88.5% of infants from Malaysia and Singapore had post-primary vaccination antibody concentrations ≥0.2 μg/mL and OPA titres ≥8, in the Clin and Com groups, respectively. For each vaccine pneumococcal serotype, ≥60.8% and ≥98.2% of toddlers from Singapore had pre- and post-booster antibody concentrations ≥0.2 μg/mL, in the Clin and Com groups, respectively. All children, except one, had measurable anti-protein D antibodies and the primary and booster doses of the co-administered vaccines were immunogenic. The incidence of each grade 3 solicited symptom was ≤11.1% in both study phases. No serious adverse events considered causally related to vaccination were reported throughout the study. Conclusions PHiD-CV given as three-dose primary vaccination to infants in Singapore and Malaysia and booster vaccination to toddlers in Singapore was shown to be immunogenic with a clinically acceptable-safety profile. This study has been registered at http://www.clinicaltrials.govNCT00808444 and NCT01119625. Electronic supplementary material The online version of this article (doi:10.1186/1471-2334-14-530) contains supplementary material, which is available to authorized users.