Novel BTK mutation presenting with vaccine-associated paralytic poliomyelitis

Oral polio vaccine (OPV) has been used safely and efficiently for more than 40 years in preventive medicine. Vaccine-associated paralytic poliomyelitis (VAPP) is a rare adverse event of OPV due to reversion of the vaccine strain virus to a neurovirulent strain. VAPP can occur in healthy recipients or their close contacts. However, persons with primary humoral immunodeficiencies are at a much higher risk. X-linked agammaglobulinemia (XLA) is a prototypic humoral deficiency caused by mutations in the Bruton’s tyrosine kinase (BTK) gene. In addition to susceptibility to bacterial infections, patients with XLA are especially prone to enteroviruses. Here, we describe the occurrence of VAPP in a 15-month old Iranian boy. The child had received four doses of OPV, administered at birth, 2, 4, and 6 months of age. The patient’s infectious history was unremarkable. Laboratory evaluation revealed low levels of immunoglobulin G and CD19⁺ B cells of less than 1% of the lymphocyte population. A novel insertion (c.685_686insTTAC) in the SH3 domain of the BTK gene was detected as the underlying cause. Immunodeficient recipients of OPV can excrete poliovirus vaccine strains for a long period and are at risk of developing flaccid paralysis. They could also serve as a source of reverted virulent poliovirus to be reintroduced into the general population. This patient presented for the first time with VAPP, without any history of other major infections in 15 months. This suggests that a negative history for recurrent infections does not exclude the presence of a primary defect in the immune system.     

Graves' disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ

The role of genetic factors in the pathogenesis of Graves' disease (GD) is not clear. The purpose of this study was to investigate the association between single nucleotide polymorphisms in pro-inflammatory cytokine genes and GD in Iranian patients. A case-control hospital-based study was carried out on 107 GD patients and 140 healthy controls. Cytokine typing was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP) assay. The allele and genotype frequencies of the following cytokine genes were determined: TNF-α (-308A/G, -238A/G), IL-2 (-330T/G, +166G/T), IL-6 (-174C/G, A/G nt565), IL-12 (-1188A/C), and IFN-γ (UTR 5644A/T). The following alleles and genotypes were significantly overrepresented in patients: TNF-α -308A allele (P < 0.01) and AA genotype (P < 0.05), IL-2 -330G allele (P < 0.01) and GG genotype (P < 0.01), IL-6 -174C allele (P < 0.01) and CC genotype (P < 0.01), IL-12 -1188C allele (P < 0.01) and CC genotype (P < 0.01), IFN-γ UTR5644T allele (P < 0.01) and TT genotype (P < 0.01). In conclusion, this is the first study to show a significant association between GD and IL-2 -330G, IL-12 -1188C, and IFN-γ UTR 5644T alleles. Our results support the hypothesis that polymorphism in pro-inflammatory cytokines might be involved in predisposition to GD.     

Association between physical activity and metabolic syndrome in Iranian adults: national surveillance of risk factors of noncommunicable diseases (SuRFNCD-2007)

Metabolic syndrome (MetS) is a common health problem in developing countries. We aimed to assess the association between different aspects of physical activity and MetS in our country. A standardized international questionnaire (Global Physical Activity Questionnaire) recommended by the World Health Organization was used in the third national survey of risk factors of noncommunicable diseases (SuRFNCD-2007) to collect physical activity data from a nationally representative sample of Iranian adults. Physical activity was evaluated in 3 domains: work, commuting, and recreational activities. Both duration and intensity of activity were considered. Biochemical measurements were carried out, and MetS was defined by the International Diabetes Federation and the Adult Treatment Panel III criteria. The data collected from a total of 3296 individuals were analyzed. The national prevalence of MetS was estimated to be between 24% and 30%, depending on sex and the criteria used. The prevalence of MetS among individuals with high-, moderate-, and low-category activity was 18.7% ± 1.5%, 25.8% ± 2.0%, and 27.9% ± 2.0%, respectively (P < .001). These rates were 12.6% ± 1.6%, 26.0% ± 1.5%, and 34.1% ± 3.2% among individuals with vigorous activity, with nonvigorous activity, and without activity, respectively (P < .001). We demonstrated a significant linear association between the number of metabolic abnormalities and lower levels of various aspects of physical activity (total physical activity, duration of domain-specific activity, and duration of intensity-specific activity; P < .001 for all). Notably, the risk for MetS increased 1.28-fold with every 30-min/d reduction in vigorous-intensity activity (95% confidence interval = 1.15-1.42, P < .001). The results of the present study should be considered for future public health programs in Iran.     

HOMA-estimated insulin resistance is associated with hypertension in Iranian diabetic and non-diabetic subjects

The relationship between insulin resistance (IR) and essential hypertension (HTN) is controversial. The aim of this study was to determine the association of IR estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and HTN in a large sample of Iranian diabetic and non-diabetic population. A total of 2047 diabetic and non-diabetic individuals with or without HTN, aged 30-75 yrs, who were referred to a university general hospital between November 2004 and April 2007 were included in this study. Demographic data and anthropometric characteristics of participants were recorded. Fasting blood samples were collected, and fasting plasma glucose (FPG), serum creatinine, lipids, insulin, C-peptide and HbA1c were measured. HOMA-IR and HOMA derived Beta-cell function (HOMA-B) were also calculated. Age, sex and waist girth adjusted HOMA-IR values were compared between hypertensive and normotensive subjects. Hypertensive patients had significantly higher HOMA-IR than age-, sex-, and waist girth-adjusted normotensive individuals in both non-diabetic (2.163 +/- 0.08 and 1.75 +/- 0.03, p < 0.001) and diabetic (3.40 +/- 0.10 and 3.07 +/- 0.09, p < 0.05) groups. Multivariate logistic regression analysis showed that after adjustment for age, sex, waist girth, BMI, triglyceride, total cholesterol, FPG, and C-peptide, HOMA-IR was a significant independent predictor of HTN in all subjects (odds ratio = 1.117, CI 95% = 1.026-1.216, p < 0.05) and in diabetic and non-diabetic subjects separately (odds ratio = 1.102, CI 95% = 1.009-1.203, p < 0.05 and odds ratio = 1.328, CI 95% = 1.116-1.580, p < 0.01, respectively). In conclusion, this study showed that IR is associated with HTN in Iranian diabetic and non-diabetic subjects.     

Albuminuria and its correlates in an Iranian type 2 diabetic population

Objective  

To study the prevalence and correlates of increased urinary albumin excretion (UAE) in an Iranian type 2 diabetic population.     

Prevalence, awareness, treatment, and risk factors associated with hypertension in the Iranian population: the national survey of risk factors for noncommunicable diseases of Iran

BACKGROUND: The prevalence of hypertension in the Middle East is not well defined. We examined the prevalence, awareness, treatment, and control of hypertension in Iran. METHODS: The Survey of Risk Factors of Noncommunicable Diseases was conducted in 2005 and contains a representative sample of the Iranian adult population. Of 70,981 participants, the data of 68,250 adults aged 25-64 years who had two valid blood pressure (BP) readings were analyzed to estimate the total prevalence of hypertension (systolic BP >or= 140 mm Hg, diastolic BP >or= 90 mm Hg, or the concurrent use of antihypertensive agents) in the Iranian adult population. RESULTS: Approximately 25% or 6.6 million Iranians aged 25-64 years had hypertension; additionally 46% or 12 million Iranians aged 25-64 years had prehypertension. Among hypertensive patients, 34% were aware of their elevated BP; 25% were taking antihypertensive medications; and of these treated subjects, only 24% had BP values <140/90 mm Hg. Hypertension and prehypertension were associated with age, male gender, obesity, central obesity, hypercholesterolemia, and diabetes. CONCLUSIONS: The prevalence of hypertension and prehypertension is high, and the rates of awareness, treatment, and control are unacceptably low. These results underscore the urgent need to develop national strategies to improve prevention, detection, and treatment of hypertension in Iran.     

The interleukin-1 family gene polymorphisms and Graves’ disease

Genetic factors, including cytokine gene polymorphisms, are potential contributors to the pathogenesis of the Graves’ disease (GD). We attempted in this study to determine the association between GD and the following polymorphisms in the interleukin-1 (IL-1) family genes: IL-1α (−889C/T), IL-1ß (−511C/T), IL-1ß (+3962C/T), IL-1R (Pst-1 1970C/T) and IL-1RA (Mspa-I 11100 C/T). We studied 107 patients with an established diagnosis of GD and 140 healthy controls. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. Genotype distributions among patients were in Hardy-Weinberg equilibrium for all polymorphisms. The frequency of the IL-1α −889T allele was significantly higher in patients than in controls (51.9% vs. 31.6%, OR = 2.33, 95% CI = 1.61-3.38; p < 0.0001). The IL-1RA Msp-I 11100C allele was significantly more frequent in patients than in controls (50.0% vs. 22.9%, OR = 3.38, 95% CI = 2.29-4.97, p < 0.0001). No significant associations were found for other polymorphisms. Although the IL-1 family has well-known roles in GD pathogenesis, the contributions of their genetic variations to the disease are unclear. In this study, we documented a highly significant association between GD and polymorphism in IL-1α and IL-1RA genes. Further studies in other populations are necessary to confirm our results.     

Progress in measles and rubella elimination in Iran

BACKGROUND: Measles is a leading cause of death worldwide because of vaccine preventable diseases. Prevention and control of measles and rubella is a high priority for the Islamic Republic of Iran. In 2002, the Ministry of Health and Medical Education in Iran developed a comprehensive strategy to eliminate measles and rubella. This strategy included recommendations for a mass immunization campaign for all persons between the ages of 5-25 years with measles-rubella (MR) vaccine. This report reviews the results of this campaign and progress in the elimination of measles and rubella in Iran. METHODS: Measles vaccination coverage, supplemental immunization activities, surveillance data, and results from a nationwide serosurvey were reviewed. RESULTS: Between 1980 and 2005, vaccination coverage ranged from 38%-99% with sustained high coverage (> or =94-99%) for the past decade. Despite high coverage with the first dose of measles vaccine (MCV1) and the introduction of a second dose of measles in 1984, case counts remained high between 1980 and 2005 with a median case count of 4414. In December 2003, a nationwide immunization campaign was conducted targeting 33,579,082 people between the ages of 5 and 25 years with a combined measles and rubella vaccine; 98% of the target population was vaccinated. A postcampaign serosurvey conducted in 2004 revealed >97.4% of the population aged between 5 and 40 years had immunity to measles and rubella. Case-based surveillance for measles identified 3 children with laboratory confirmed disease in 2004, 35 in 2005, and 42 children in 2006. Most confirmed disease occurred in immigrant communities or communities with migrant populations from neighboring counties with ongoing measles outbreaks. Surveillance for rubella was established after the campaign and identified 37 patients with confirmed disease in the follow-up period. CONCLUSIONS: Implementation of a comprehensive strategy for measles elimination in Iran has remarkably reduced the incidence of measles and rubella to <1 case per 1,000,000. Sporadic transmission continues to occur, particularly in areas with immigrant and nomadic populations.     

Late complications of circumcision in Iran

Today, circumcision is the most commonly performed surgical procedure worldwide. Early and late complications may occur due to circumcision. To find the prevalence of late complications of circumcision, we studied 3,205 elementary-school boys aged 6–12 years in 2002. All of them were Iranian and Muslim. Nearly 3,125 of the boys have been circumcised. Most of the boys (2,214 boys) had been circumcised after 2 years of age. Moreover, most of them were operated by traditional circumcisers (43.49%). Late complications (7.39%) were reported in 231 boys. Excessive residual foreskin was seen in 113 children (3.6%). Excessive removal of skin was detected in 42 boys (1.3%), meatal stenosis in 29 boys (0.9%), granoloma in 22 boys (0.7%), penile rotation in 17 boys (0.5%), and 8 boys had secondary chordee (0.2%). The complication rate was not different between the neonatal circumcision and older groups. We suggested that circumcision should only be performed in medical institutions by suitably trained specialists.