Titis Widowati

Burden of Severe Rotavirus Diarrhea in Indonesia

Globally, rotavirus is the leading cause of diarrhea-related hospitalizations and deaths among young children, but the burden of rotavirus disease in Indonesia is poorly documented. From January through December 2006, we conducted prospective surveillance (inpatient and outpatient) among children aged <5 years at 6 hospitals in 6 provinces of Indonesia, using standardized methodology. Of 2240 enrolled children hospitalized for diarrhea, 1345 (60%) were rotavirus positive. Of 176 children enrolled in outpatient clinics in 3 hospitals, 73 (41%) were rotavirus positive. Among children hospitalized for diarrhea, dehydration was more common among those who tested positive for rotavirus than among those who did not (91% vs 82%; P < .05), as was vomiting (86% vs 67%; P < .05). Children aged 6-23 months experienced 72% of all rotavirus episodes. Rotavirus prevalence increased slightly in the cool, dry season. The most commonly detected genotypes were G9 (30%) and P[6] (56%). G1P[6] and G9P[6] accounted for 34% and 21% of strains, respectively. A high proportion of genotype P[6] was detected, in combination with the common G types G1 and G9. Available rotavirus vaccines would likely be efficacious against the most common circulating strains, but continued monitoring of uncommon genotypes is needed.

RET and EDNRB mutation screening in patients with Hirschsprung disease: Functional studies and its implications for genetic counseling

Hirschsprung disease (HSCR) is a major cause of chronic constipation in children. HSCR can be caused by germline mutations in RET and EDNRB. Defining causality of the mutations identified is difficult and almost exclusively based on in silico predictions. Therefore, the reported frequency of pathogenic mutations might be overestimated. We combined mutation analysis with functional assays to determine the frequencies of proven pathogenic RET and EDNRB mutations in HSCR. We sequenced RET and EDNRB in 57 HSCR patients. The identified RET-coding variants were introduced into RET constructs and these were transfected into HEK293 cells to determine RET phosphorylation and activation via ERK. An exon trap experiment was performed to check a possible splice-site mutation. We identified eight rare RET-coding variants, one possible splice-site variant, but no rare EDNRB variants. Western blotting showed that three coding variants p.(Pr270Leu), p.(Ala756Val) and p.(Tyr1062Cys) resulted in lower activation of RET. Moreover, only two RET variants (p.(Ala756Val) and p.(Tyr1062Cys)) resulted in reduced ERK activation. Splice-site assays on c.1880-11A>G could not confirm its pathogenicity. Our data suggest that indeed almost half of the identified rare variants are proven pathogenic and that, hence, functional studies are essential for proper genetic counseling.

Profil dan temuan klinis pasien perdarahan saluran cerna di Departemen Kesehatan Anak RSUP Dr. Sardjito 2009 - 2015

Latar belakang . Perdarahan saluran cerna pada anak merupakan salah satu tanda bahaya sehingga diagnosis dan pengobatan dini sangat penting. Tujuan . Mengetahui etiologi dan temuan klinis perdarahan saluran cerna anak yang dirawat di RSUP Dr. Sardjito. Metode . Penelitian retrospektif menggunakan rekam medis pasien anak berusia kurang dari 18 tahun yang menjalani endoskopi dan kolonoskopi karena perdarahan saluran cerna dari Januari 2009 hingga Juni 2015. Data rekam medis yang tidak lengkap tidak diikutkan sertakan dalam penelitian. Hasil . Dari 55 pasien yang memenuhi syarat, terdapat 27 (49%) pasien perdarahan saluran cerna atas dan 28 (51%) pasien perdarahan saluran cerna bawah. Varises esofagus adalah etiologi terbanyak perdarahan saluran cerna atas 10 (37%), sedangkan untuk perdarahan saluran cerna bawah adalah kolitis 17 (60%). Perdarahan saluran pada anak lebih sering terjadi pada perempuan usia 1-6 tahun 29 (53%). Gejala yang lebih sering terjadi yaitu hematemesis 13 (24%) dan hematokezia 27 (49%). Keluhan perdarahan saluran cerna atas terbanyak adalah nyeri perut 13 (48%) sedangkan saluran cerna bawah adalah diare 8 (29%). Anemia berat ditemukan pada 5 (19%) pasien perdarahan saluran cerna atas dan 1 (4%) pasien perdarahan saluran cerna bawah. Kesimpulan . Varises esofagus merupakan penyebab tersering perdarahan saluran cerna atas sedangkan saluran cerna bawah adalah kolitis. Anak yang datang dengan keluhan nyeri perut dan diare harus dipikirkan salah satu penyebabnya adalah perdarahan saluran cerna.