MyMedR

Fulltext Outcomes of human immunodeficiency virus-infected children after anti-retroviral therapy in Malaysia

Moy FS, Fahey P, Nik Yusoff NK, Razali KA, Nallusamy R, TREAT Asia Pediatric HIV Observational Database (TApHOD)

J Paediatr Child Health, 2015 Feb;51(2):204-8.

To describe outcome and examine factors associated with mortality among human immunodeficiency virus (HIV)-infected children in Malaysia after anti-retroviral therapy (ART).

Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial

Capeding MR, Tran NH, Hadinegoro SR, Ismail HI, Chotpitayasunondh T, Chua MN, et al.

Lancet, 2014 Oct 11;384(9951):1358-65.

PMID: 25018116 DOI: 10.1016/S0140-6736(14)61060-6

An estimated 100 million people have symptomatic dengue infection every year. This is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children.

Fulltext Weight as predictors of clinical progression and treatment failure: results from the TREAT Asia Pediatric HIV Observational Database

Kariminia A, Durier N, Jourdain G, Saghayam S, Do CV, Nguyen LV, et al.

J Acquir Immune Defic Syndr, 2014 Sep 01;67(1):71-6.

PMID: 24872132 DOI: 10.1097/QAI.0000000000000227

OBJECTIVE: To evaluate the value of time-updated weight and height in predicting clinical progression, and immunological and virological failure in children receiving combination antiretroviral therapy (cART).

METHODS: We used Cox regression to analyze data of a cohort of Asian children.

RESULTS: A total of 2608 children were included; median age at cART was 5.7 years. Time-updated weight for age z score < -3 was associated with mortality (P < 0.001) independent of CD4% and < -2 was associated with immunological failure (P ≤ 0.03) independent of age at cART.

CONCLUSIONS: Weight monitoring provides useful data to inform clinical management of children on cART in resource-limited settings.

Fulltext Characterizing HIV manifestations and treatment outcomes of perinatally infected adolescents in Asia

Chokephaibulkit K, Kariminia A, Oberdorfer P, Nallusamy R, Bunupuradah T, Hansudewechakul R, et al.

Pediatr Infect Dis J, 2014 Mar;33(3):291-4.

PMID: 23942457 DOI: 10.1097/INF.0b013e3182a18223

More perinatally HIV-infected children in Asia are reaching adolescence.

Fulltext X-linked chronic granulomatous disease in a male child with an X-CGD carrier, Klinefelter brother

Gill HK, Kumar HC, Cheng CK, Ming CC, Nallusamy R, Yusoff NM, et al.

Asian Pac J Allergy Immunol, 2013 Jun;31(2):167-72.

PMID: 23859418 DOI: 10.12932/AP0274.31.2.2013

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency (PID) caused by a dysfunctional respiratory burst enzyme NADPH-oxidase. The concurrence of Klinefelter’s Syndrome (KS) and CGD would be extremely rare.
OBJECTIVE: We describe the study of a family where the youngest male child had X-linked CGD (X-CGD) while his older brother was both an X-CGD carrier and a Klinefelter.
METHODS: Flow cytometry was used to study respiratory burst and gp91-phox expression, while genetic investigation was done by RT-PCR, PCR and X-chromosome short tandem repeat (X-STR) analysis.
RESULTS: The Dihydrorhodamine (DHR) assay showed the patient’s neutrophils failed to produce a respiratory burst, while both the mother and an older brother showed a bimodal response. gp91-phox expression was absent in the patient’s neutrophils, and bimodal in the mother’s and brother’s neutrophils. The patient’s cDNA showed a C>T change at nucleotide 676 of the CYBB gene. The same change was seen in the patient’s gDNA, while the brother and mother were heterozygous, with C and T, in this position. The c.676C>T is a nonsense mutation that leads to premature termination of the gp91-phox protein. The brother karyotyped as 47, XXY and X chromosome analysis showed that he had inherited both his mother’s X chromosomes.
CONCLUSIONS: This study showed that the patient had gp91-phox deficient CGD while his older brother was a CGD carrier and a Klinefelter, who had inherited both his mother’s X chromosomes. This is the first report of such a concurrence in an individual, and argues for family members to be included in PID studies.
Key words: Chronic granulomatous disease, CYBB, gp91-phox, Klinefelter’s syndrome NADPHoxidase

Fulltext Inherited IL-12p40 deficiency: genetic, immunologic, and clinical features of 49 patients from 30 kindreds

Prando C, Samarina A, Bustamante J, Boisson-Dupuis S, Cobat A, Picard C, et al.

Medicine (Baltimore), 2013 Mar;92(2):109-122.

PMID: 23429356 DOI: 10.1097/MD.0b013e31828a01f9

Autosomal recessive interleukin (IL)-12 p40 (IL-12p40) deficiency is a rare genetic etiology of mendelian susceptibility to mycobacterial disease (MSMD). We report the genetic, immunologic, and clinical features of 49 patients from 30 kindreds originating from 5 countries (India, Iran, Pakistan, Saudi Arabia, and Tunisia). There are only 9 different mutant alleles of the IL12B gene: 2 small insertions, 3 small deletions, 2 splice site mutations, and 1 large deletion, each causing a frameshift and leading to a premature stop codon, and 1 nonsense mutation. Four of these 9 variants are recurrent, affecting 25 of the 30 reported kindreds, due to founder effects in specific countries. All patients are homozygous and display complete IL-12p40 deficiency. As a result, the patients lack detectable IL-12p70 and IL-12p40 and have low levels of interferon gamma (IFN-γ). The clinical features are characterized by childhood onset of bacille Calmette-Guérin (attenuated Mycobacterium bovis strain) (BCG) and Salmonella infections, with recurrences of salmonellosis (36.4%) more common than recurrences of mycobacterial disease (25%). BCG vaccination led to BCG disease in 40 of the 41 patients vaccinated (97.5%). Multiple mycobacterial infections were rare, observed in only 3 patients, whereas the association of salmonellosis and mycobacteriosis was observed in 9 patients. A few other infections were diagnosed, including chronic mucocutaneous candidiasis (n = 3), nocardiosis (n = 2), and klebsiellosis (n = 1). IL-12p40 deficiency has a high but incomplete clinical penetrance, with 33.3% of genetically affected relatives of index cases showing no symptoms. However, the prognosis is poor, with mortality rates of up to 28.6%. Overall, the clinical phenotype of IL-12p40 deficiency closely resembles that of interleukin 12 receptor β1 (IL-12Rβ1) deficiency. In conclusion, IL-12p40 deficiency is more common than initially thought and should be considered worldwide in patients with MSMD and other intramacrophagic infectious diseases, salmonellosis in particular.

Fulltext Dengue and other common causes of acute febrile illness in Asia: an active surveillance study in children

Capeding MR, Chua MN, Hadinegoro SR, Hussain II, Nallusamy R, Pitisuttithum P, et al.

PLoS Negl Trop Dis, 2013;7(7):e2331.

PMID: 23936565 DOI: 10.1371/journal.pntd.0002331

Common causes of acute febrile illness in tropical countries have similar symptoms, which often mimic those of dengue. Accurate clinical diagnosis can be difficult without laboratory confirmation and disease burden is generally under-reported. Accurate, population-based, laboratory-confirmed incidence data on dengue and other causes of acute fever in dengue-endemic Asian countries are needed.

Epidemiology of intussusception in Malaysia: a three-year review

Giak CL, Singh HS, Nallusamy R, Leong TY, Ng TL, Bock HL

Southeast Asian J. Trop. Med. Public Health, 2008 Sep;39(5):848-55.

PMID: 19058579

This study aimed to document the baseline incidence and epidemiology of intussusception (IS) in Malaysia. This retrospective surveillance examined hospital discharge data from three hospitals in Malaysia to identify IS cases over a 3-year period (2000-2003) in children <5 years of age. Identification of definite cases of IS was done through a search of computerized hospital discharge records (ICD-9-CM code 560.0) followed by confirmation of diagnosis through medical record review. The definition of IS was based on the clinical guidelines from the IS Brighton Collaboration Working Group, version 2002. During the 3-year study period, there were 62 cases hospitalized due to IS, of which 74.2% were < 1 year of age. The incidences for hospitalization due to IS in children < 1 year old and < 5 years old averaged 17.8 and 4.8 per 100,000 person-years, respectively. No IS-associated deaths were recorded and all IS cases had a favorable outcome. No distinct seasonality with IS occurrence was observed.

Fulltext Fatal early-onset neonatal sepsis due to Streptococcus pneumoniae

Nallusamy R

Med J Malaysia, 1998 Dec;53(4):442-5.

PMID: 10971993

Two cases of invasive early-onset neonatal pneumococcal sepsis are reported. One neonate was born at term with no risk factors and the other preterm at 35 weeks. Sepsis was not detected at birth for either of these babies and diagnosis was made at the stage of severe sepsis. A fatal outcome resulted despite treatment. Pneumococcal sepsis was confirmed after death in both these cases. Although maternal carriage was not documented in either case, the ages at presentation and progression suggested perinatal acquisition of infection. Early onset neonatal pneumococcal sepsis presents similarly as early onset neonatal Group B streptococcal (GBS) sepsis. Vaginal carriage of pneumococcus is rare but the micro-organism may have a higher invasion to colonisation ratio (attack rate) than GBS. Risk factors for invasive disease are similar to GBS.

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