Risk factors of infection-associated mortality in children with lupus nephritis in under-resourced areas.

INTRODUCTION: Treatment of lupus nephritis class III, IV and V with immunosuppressive therapy increases patient survival but poses a risk of infection-related mortality. This study was conducted to evaluate risk factors for fatal infection in children with lupus nephritis in under-resourced areas. METHODS: Medical records of patients, who were admitted to a tertiary-care university-based hospital from January 2002 to July 2018 with the diagnosis of systemic lupus erythematosus, were reviewed. Only patients aged less than 18 years with lupus nephritis and documented infection were included in the study. The primary outcome was infection-associated mortality. The logistic regression model was used to identify independent variables associated with fatal infection. Predicted probabilities of infection-related mortality adjusted for factors significant in multivariate analysis were calculated using marginal effects at representative values. RESULTS: Infection-related deaths occurred in 27 of 179 patients (15.1%). Hospital-acquired infections occurred in 72 of 375 episodes of hospital admissions (19.2%) and 13 hospital-acquired infections (18.1%) resulted in fatal infection. Invasive fungal infections were the leading cause of death (44.4%) and pulmonary infections were the predominant site (55.5%). Haemoglobin levels and glomerular filtration rates were significantly lower in deceased versus surviving patients. Percentages of patients with hospital-acquired infections, invasive fungal infections and pulmonary infections were significantly higher in deceased than surviving patients. Urine protein, the neutrophil-to-lymphocyte ratio, cumulative methylprednisolone dose and daily prednisolone dose were significantly higher in deceased than surviving patients. In multivariate analysis, a neutrophil-to-lymphocyte ratio more than 20, invasive fungal infections and high daily prednisolone dose were independently predictive of fatal infection with adjusted odds ratio of 3.02 (95% confidence interval 1.02-8.97, p = 0.04), 15.08 (95% confidence interval 4.72-48.24, p < 0.001) and 1.03 (95% confidence interval 1.01-1.06, p = 0.04), respectively. A high daily prednisolone dose intensified the impact of invasive fungal infections and high neutrophil-to-lymphocyte ratio on predicted probability of infection-associated mortality. CONCLUSIONS: Prevention of invasive fungal infections and minimization of daily prednisolone should be emphasized in routine clinical practice of children with lupus nephritis in under-resourced areas to achieve better survival. Children with lupus nephritis and a high neutrophil-to-lymphocyte ratio should be under cautious surveillance for infection.

Long-term growth in children with posterior urethral valves.

BACKGROUND: Posterior urethral valves (PUVs) are one of the leading causes of pediatric chronic kidney disease (CKD). Growth impairment is prevalent in pediatric CKD, and children with PUVs are at high risk for growth retardation. OBJECTIVE: The objective of this study was to describe growth profiles in PUVs and to identify risk factors for stunting, defined as age-specific height standard deviation score (SDS) below -2. PATIENTS AND METHODS: Medical records of 65 patients with PUVs and a minimum follow-up of two years were retrospectively reviewed. Chronic kidney disease stage 1-3 was considered mild CKD, whereas CKD stage 4-5 was considered advanced CKD. Age-specific height, weight, and body mass index (BMI) SDS were determined. Seven potential risk factors for stunting, namely timing of diagnosis, renal dysplasia, timing of surgery, requirement of urinary diversion, nadir serum creatinine after surgery, recurrent febrile urinary tract infection (UTI), and severity of CKD, were analyzed. RESULTS: Median age at diagnosis, at surgery, and at last follow-up was 0.51, 0.75, and 7.53 years, respectively. All patients underwent valve ablation, and 33.8% required urinary diversion. Median nadir serum creatinine after surgery was 0.40 mg/dL and was higher in patients who underwent urinary diversion (P < 0.001). Growth profiles by CKD stage are displayed in Fig. 1. Median height SDS was -0.40 and was lower in patients with advanced CKD (P = 0.03). Stunting was diagnosed in 15.4%. Advanced CKD was an independent risk factor for stunting, with the odds ratio of 12.7. Urinary diversion and nadir creatinine more than 0.80 mg/dL were weakly associated with stunting but not significant. Timing of diagnosis and surgery, unilateral renal dysplasia, and recurrent febrile UTI were not associated with stunting. Median SDS of weight and BMI was -0.64 and -0.19, respectively. Patients who were thin, of normal weight, overweight, and obese comprised 26.2%, 58.5%, 10.8%, and 4.6%, respectively. There was no significant difference of SDS of weight and BMI across CKD stages (Fig. 1). DISCUSSION: Deterioration in height began early in the course of disease and was worsening in relation to the decline of renal function. The impact of timing of diagnosis or surgery on height was controversial. Patients who underwent urinary diversion had high nadir creatinine and were likely to have severe PUVs. Although patients with severe baseline renal dysfunction may require urinary diversion, nadir serum creatinine and urinary diversion are not associated with stunting. Delaying progression of CKD could maximize linear growth potential in PUVs. A substantial proportion of patients were overweight or obese. Sufficient caloric intakes may be maintained in patients with PUVs.

Interleukin-10 promoter polymorphisms and expression in Thai children with juvenile systemic lupus erythematosus.

Interleukin (IL)-10 expression is regulated by its promoter and correlated with the activity of adult-onset lupus (systemic lupus erythematosus (SLE)). As the pathogenesis of adult-onset SLE may differ from SLE with the age at onset <18 years old (juvenile SLE or JSLE), we evaluated polymorphisms at positions -1082A/G, -819T/C and -592A/C of the IL-10 promoter and serum IL-10 levels in 71 patients with JSLE. Disease activity was determined by the SLE disease activity index (SLEDAI). Active SLE was defined by SLEDAI ≥ 6 and inactive SLE was defined by SLEDAI equal to zero. The mean age was 14.5 ± 2.8 years. Nephritis occurred in 57 patients. In JSLE patients, -592 CC and -819 CC were identified with a higher frequency than in controls with the odds ratio (OR) of 2.75 (95% confidence interval (CI) 1.11-6.81, p = 0.04). GCC increased the susceptibility to nephritis in patients with JSLE (OR 2.16, 95% CI 1.07-4.35, p = 0.03). Serum IL-10 levels were significantly higher in 20 JSLE patients with active disease than in 27 patients with inactive disease and in 15 healthy children (p < 0.001). In conclusion, IL-10 expression was upregulated in active JSLE. The -819 CC and -592 CC genotypes increased the susceptibility to JSLE and GCC increased the susceptibility to nephritis.

Association of CD247 with systemic lupus erythematosus in Asian populations.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. METHODS: In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. RESULTS: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. CONCLUSION: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.

Entire genome characterization of Chikungunya virus from the 2008-2009 outbreaks in Thailand.

The resurgence of Chikungunya virus (CHIKV) in the southern, northeastern and northern parts of Thailand, inflicting approximately 46,000 reported cases since October 2008 until December 2009, has raised public health concerns. In the present study, we characterized nearly complete genome sequences of four CHIKV isolates obtained from 2008 to 2009 outbreaks in Thailand. Phylogenetic analysis was performed to determine the relationships of the study viruses with previously reported isolates. Results showed that 2008-2009 Thailand isolates belonged to the East, Central and South African genotype and were most closely related to isolates detected in Malaysia and Singapore in 2008. This was in contrast to isolates from all previous outbreaks in Thailand which were caused by an Asian genotype. We describe several novel mutations in Thailand isolates that warrants further investigation on characterization of CHIKV from different parts of the country to better understand the molecular epidemiology of Chikungunya fever outbreaks in Thailand.

Hepatitis B virus infection in non-human primates.

Hepatitis B viruses (HBVs) represent a serious public health problem affecting 350 to 400 million HBV carriers worldwide. The virus does not exclusively infect humans, but can also be found in non-human primates as in the families Hominidae (chimpanzee, gorilla, orangutan) and Hylobatidae (gibbon), which are distributed over Africa (chimpanzee and gorilla) and Southeast Asia (orangutan and gibbon), the endemic areas of human HBV. The prevalence of asymptomatic HBV carriers reaches in gibbons 23-33% and in orangutans 15%. The genome organization of non-human primate HBVs is nearly identical to that of human HBVs. Because of this close similarity, the question of cross-transmission of HBV between species has arisen. There are many data on cross-transmission of human HBVs to the non-human primates. However, a cross-transmission of HBVs from non-human primates to humans has not been reported yet. Using more advanced diagnostic methods, the non-human primates have increasingly been identified as a reservoir of several viruses such as lymphocryptoviruses, Cercopithecine herpesvirus 1 (CeHV-1), Simian immunodeficiency virus (SIV), Simian foamy virus (SFV), and HBVs. Thus veterinarians, zookeepers, or people in close contact with non-human primates may potentially become infected with those viruses causing severe diseases. Enhanced awareness of prevalence, genetic relatedness and evolution of non-human primate HBVs will help prevent further spread and cross-transmission of these viruses between humans and non-human primates.

Molecular characterization of Hepatitis A virus causing an outbreak among Thai navy recruits.

Hepatitis A virus (HAV) infection is a communicable disease, typically transmitted by faecal-oral contamination. HAV outbreaks usually occur in endemic areas. We report an outbreak of HAV from June to July, 2008 among Thai navy recruits who had received training at the Sattahip Navy Base, Chonburi province, Thailand. Upon conclusion of the training, the recruits were deployed to serve at several navy bases across the country. Secondary cases of HAV infection were reported among military personnel from these navy bases. To elucidate origin and distribution of these outbreaks, we characterized the genome and genotype of HAV isolated from the different navy bases. Sera and stool from the subjects were tested for antiHAV IgM, antiHAV IgG and HAV RNA. Subsequently, molecular characterization of HAV was performed by nucleotide sequencing of the VP1-P2A region, BLAST/FASTA and phylogenetic analysis. HAV RNA was detected in specimens obtained from different areas. All isolated strains clustered in the same lineage and belonged to genotype 1A. They shared nearly 100% genome homology indicating a single point source of this outbreak. This study provides essential baseline data as a reference for genetic analysis of HAV strains causing future outbreaks. Early detection of HAV infection and identification of the source by using molecular characterization and prompt preventive measures will hopefully prevent further outbreaks.

Medication non-adherence in the adolescent renal transplant recipient: a clinician's viewpoint.

Recent advancements in immunosuppression and surgical techniques have significantly improved the outcome of kidney transplantation in the pediatric population. Adolescents enjoy the best 1-year graft survival of any age group. However, the long-term transplant outcome in adolescents is disappointing. Non-adherence with immunosuppressive medications is one of the most important contributing factors for graft rejection and loss in teenagers. The impact of non-adherence is perceived to be far more powerful in adolescent transplant recipients than in the transplant population as a whole. To better understand adolescent non-adherence, the process of transplantation must be placed in the context of adolescent development. Adolescents try to establish their identity and autonomy separately from the parents; however at the same time, adolescents with chronic illness require help, support and guidance from adults, including parents and medical personnel. Adolescents have limited ability to anticipate abstractly the long-term consequences of their immediate actions. This inconsistency can create frustration in both adolescents and in the supporting systems around them. Despite the significant consequences of adolescent non-adherence, research in this area is scarce. There are still no established definitions, standardized diagnostic methods and effective interventions to treat and prevent this problem. We propose the recommendations to approach the problems of adolescent transplant non-adherence from the transplant clinician's viewpoint. With early identification and appropriate interventions, significant improvement in adolescent graft survival is possible.