Interleukin-12 (IL12) is a cytokine that is secreted by activated phagocytes and dendritic cells and that induces interferon-gamma production by natural-killer and T lymphocytes. It consists of two subunits, p35 and p40, which are encoded by IL12A and IL12B, respectively. The first reported patient with a genetic cytokine disorder was a Pakistani child, who was homozygous for a large loss-of-function deletion (g.482+82_856-854del) in IL12B. This IL12-deficient child suffered from infections caused by bacille Calmette-Guérin (BCG) and Salmonella enteritidis. We herein report 12 additional patients from five other kindreds. In one kindred from India, the same large deletion that was described elsewhere (g.482+82_856-854del) was identified. In four kindreds from Saudi Arabia, a recessive loss-of-function frameshift insertion (g.315_316insA) was found. A conserved haplotype encompassing the IL12B gene suggested that a founder effect accounted for the recurrence of each mutation. The two founder mutational events-g.482+82_856-854del and g.315_316insA-were estimated to have occurred approximately 700 and approximately 1,100 years ago, respectively. Among a total of 13 patients with IL12 deficiency, 1 child had salmonellosis only and 12 suffered from clinical disease due to BCG or environmental nontuberculous mycobacteria. One patient also had clinical disease caused by virulent Mycobacterium tuberculosis, five patients had clinical disease caused by Salmonella serotypes, and one patient had clinical disease caused by Nocardia asteroides. The clinical outcome varies from case to case, since five patients (aged 2-11 years) died of overwhelming infection, whereas eight patients (aged 3-12 years) are still in good health and are not currently taking antibiotics. In conclusion, IL12 deficiency is not limited to a single kindred, shows significant variability of outcome, and should be considered in the genetic diagnosis of patients with mycobacteriosis and/or salmonellosis. To date, two founder IL12B mutations have been identified, accounting for the recurrence of a large deletion and a small insertion within populations from the Indian subcontinent and from the Arabian Peninsula, respectively.

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Highlights MMR vaccine uptake rates have dropped between 25.64% - 73.55% during COVID-19. A measles epidemic is a possibility due to reduction in community herd immunity. Urgent public health efforts are needed to maintain efficacious vaccine coverage.

This study reviewed the 18-year experience of acute dialysis in the pediatric intensive care unit, in order to identify factors that could predict outcome, and to determine whether newer modalities of acute dialysis have influenced this outcome. Sixty-six children (ages 1 day to 19 years) received acute dialysis from May 1980 to April 1998. Factors predicting outcome were analyzed using univariate and Cox regression analysis. Modality of dialysis in the first 15 years was exclusively peritoneal dialysis. with a mortality of 63.9%. However, in the last 3 years, with increasing patient numbers, continuous hemodiafiltration (CHDF) was the modality of choice (56.7%), with a mortality of 73.3%. Univariate analysis showed that age <1 year, coma, acute tubular necrosis, disseminated intravascular coagulopathy, assisted ventilation, and hypotension were associated significantly with poor outcome (P<0.05). Cox regression analysis revealed that mortality was significantly higher in patients on mechanical ventilation (RR 5.96, 95% CI 1.82-19.50), or with age <1 year (RR 2.00, 95% CI 1.08-3.73). In conclusion, despite the increasing use of CHDF over the last 3 years, there was no significant improvement in mortality, probably related to the fact that more critically ill patients were dialyzed.

This study compared the pattern of acute glomerulonephritis (AGN), a disease known to be influenced by socioeconomic and environmental factors, in children 12 years and under, for the years 1971 and 1985. All children admitted to the four major paediatric departments with haematuria and at least two of the following (oedema, hypertension or oliguria) had an initial diagnosis of AGN. A sample population from one unit from 1980 to 1984 showed that over 70% of these children had evidence of a post-streptococcal aetiology. In 1971, 411 children were admitted with AGN, as compared with only 58 in 1985. The age-sex-race standardized rates for 1971 and 1985 were 0.632 and 0.023/1,000 children 12 years and under, respectively (P less than 0.001). The mean age of presentation was lower in 1971. Over this period, Singapore saw a threefold rise in the gross national product, accompanied by rapid urbanization. On analysis of the housing pattern, only 31% of the children lived in high-rise apartments in 1971, in contrast with 86% in 1985 (P less than 0.001). The majority of non-apartment dwellers had homes in rural districts. From an epidemiological perspective, factors which could have led to the highly significant decline in prevalence of AGN in Singapore children included improvement in the socioeconomic status and health care system, and urbanization of the country.