Burden of pertussis among young infants in Malaysia: A hospital-based surveillance study.

BACKGROUND: The case fatality rate and the risk of complications due to pertussis is very high in infants. Asia has the second highest childhood pertussis burden. The study aimed to assess the prevalence, clinical complications, and mortality rates of pertussis disease requiring hospitalization among young infants in Malaysia. METHODS: The study was a one-year, hospital-based, multi-site surveillance of infants less than six months of age with symptoms consistent with pertussis and a cross-sectional analysis of their mothers for recent pertussis infection. Information was obtained from medical records and interviews with the parents. Pertussis diagnosis was confirmed for all infants through serum anti-PT titration test or PCR test. RESULTS: 441 possible cases of pertussis were included in this study. Of these, 12.7 % had laboratory confirmation of pertussis. Infants with confirmed pertussis had significantly higher rates of cyanosis (37.5 % vs 8.6 %; p < 0.0001) and apnea (12.5 % vs 3.9 %; p = 0.027) than test-negative infants. Most infants from both groups were in recovery/recovered at discharge. Those with confirmed pertussis had higher case fatality rate than test-negative cases (5.4 % vs 1.0 %; p = 0.094), but the difference did not reach significance. The majority of confirmed pertussis cases (89.3 %) occurred in infants too young to be fully vaccinated or under-vaccinated for their age. Both test-negative and confirmed pertussis resulted in work-day losses and incurred costs for both parents. CONCLUSIONS: A high pertussis disease burden persists in infants less than six months of age, especially among those un- and under-vaccinated. Maternal and complete, on-time infant vaccination is important to reduce disease burden.

A single-center pilot study in Malaysia on the clinical utility of whole-exome sequencing for inborn errors of immunity.

Primary immunodeficiency diseases refer to inborn errors of immunity (IEI) that affect the normal development and function of the immune system. The phenotypical and genetic heterogeneity of IEI have made their diagnosis challenging. Hence, whole-exome sequencing (WES) was employed in this pilot study to identify the genetic etiology of 30 pediatric patients clinically diagnosed with IEI. The potential causative variants identified by WES were validated using Sanger sequencing. Genetic diagnosis was attained in 46.7% (14 of 30) of the patients and categorized into autoinflammatory disorders (n = 3), diseases of immune dysregulation (n = 3), defects in intrinsic and innate immunity (n = 3), predominantly antibody deficiencies (n = 2), combined immunodeficiencies with associated and syndromic features (n = 2) and immunodeficiencies affecting cellular and humoral immunity (n = 1). Of the 15 genetic variants identified, two were novel variants. Genetic findings differed from the provisional clinical diagnoses in seven cases (50.0%). This study showed that WES enhances the capacity to diagnose IEI, allowing more patients to receive appropriate therapy and disease management.

Feasibility of case-control and test-negative designs to evaluate dengue vaccine effectiveness in Malaysia.

BACKGROUND: The world's first dengue vaccine [Dengvaxia; Sanofi Pasteur] was licensed in 2015 and others are in development. Real-world evaluations of dengue vaccines will therefore soon be needed. We assessed feasibility of case control (CC) and test-negative (TN) design studies for dengue vaccine effectiveness by measuring associations between socio-demographic risk factors, and hospitalized dengue outcomes, in Malaysia. METHODS: Following ethical approval, we conducted hospital-based dengue surveillance for one year in three referral hospitals. Suspected cases aged 9-25 years underwent dengue virological confirmation by RT-PCR and/or NS1 Ag ELISA at a central laboratory. Two age- and geography-matched hospitalized non-dengue case-controls were recruited for a traditional CC study. Suspected cases testing negative were test-negative controls. Socio-demographic, risk factor and routine laboratory data were collected. Logistic regression models were used to estimate associations between confirmed dengue and risk factors. RESULTS: We recruited 327 subjects; 155 were suspected of dengue. The planned sample size was not met. 124 (80%) of suspected cases were dengue-confirmed; seven were assessed as severe. Three had missing RT-PCR results; the study recruited 28 test-negative controls. Only 172 matched controls could be recruited; 90 cases were matched with ≥1 controls. Characteristics of cases and controls were mostly similar. By CC design, two variables were significant risk factors for hospitalized dengue: recent household dengue contact (OR: 54, 95% CI: 7.3-397) and recent neighbourhood insecticidal fogging (OR: 2.1; 95% CI: 1.3-3.6). In the TN design, no risk factors were identified. In comparison with gold-standard diagnostics, routine tests performed poorly. CONCLUSIONS: The CC design may be more appropriate than the TN design for hospitalized dengue vaccine effectiveness studies. Selection bias in case control selection could be minimized by protocol changes more easily than increasing TN design control numbers, because early-stage dengue diagnosis in endemic countries is highly specific. MREC study approval: (39)KKM/NIHSEC/P16-1334.

Incidence rates of neurotropic-like and viscerotropic-like disease in three dengue-endemic countries: Mexico, Brazil, and Malaysia.

BACKGROUND: The background incidence of viscerotropic- (VLD) and neurotropic-like disease (NLD) unrelated to immunization in dengue-endemic countries is currently unknown. METHODS: This retrospective population-based analysis estimated crude and standardized incidences of VLD and NLD in twelve hospitals in Brazil (n = 3), Mexico (n = 3), and Malaysia (n = 6) over a 1-year period before the introduction of the tetravalent dengue vaccine. Catchment areas were estimated using publicly available population census information and administrative data. The denominator population for incidence rates was calculated, and sensitivity analyses assessed the impact of important assumptions. RESULTS: Total cases adjudicated as definite VLD were 5, 57, and 56 in Brazil, Mexico, and Malaysia, respectively. Total cases adjudicated as definite NLD were 103, 29, and 26 in Brazil, Mexico, and Malaysia, respectively. Crude incidence rates of cases adjudicated as definite VLD in Brazil, Mexico, and Malaysia were 1.17, 2.60, and 1.48 per 100,000 person-years, respectively. Crude incidence rates of cases adjudicated as definite NLD in Brazil, Mexico, and Malaysia were 4.45, 1.32, and 0.69 per 100,000 person-years, respectively. CONCLUSIONS: Background incidence estimates of VLD and NLD obtained in Mexico, Brazil, and Malaysia could provide context for cases occurring after the introduction of the tetravalent dengue vaccine.