Severe combined immunodeficiency: a cohort of 40 patients.

Severe Combined Immunodeficiency (SCID) consists of a heterogeneous group of genetic disorders characterized by an arrest in T lymphocyte development which is variably associated with an abnormal differentiation of B and NK cells. In order to depict the clinical state of Iranian patients with SCID, records of forty patients were reviewed. Patients were classified based on the flow cytometry data in two groups of B- and B+. In thirty two families (80%) parents were consanguine and in 17 families (50%) there were affected members other than proband. We showed that autosomal forms of SCID might be more frequent due to higher rate of consanguineous marriages. Alongside several infective complications, complicated Bacillus Calmette-Guérin (BCG) vaccination was documented in 18 cases (45%) following the routine vaccination at birth. BCG immunization is still a part of standard vaccination for newborns in developing countries; whereas in communities with a better health condition it could be held for a few months and performed for kids whose immune system sounds intact. We discuss where consanguine mating is common, a test of screening should be run timely. A complete blood count of cord blood could reveal lymphocytopenia at birth; this helps early diagnosis. Genetic consultation would help the families with affected members preventing new SCID offspring.     

Tuberculin Conversion Following BCG Vaccination in Preterm Infants

ABSTRACT. Tuberculin conversion following BCG vaccination was evaluated in 3 groups of infants. Group I consisted of 12 preterm appropriate-for-gestational-age (AGA) infants given BCG vaccination at birth; Group II was made up of 15 term AGA infants similarly immunized while 8 preterm AGA infants (Group III) received BCG about the time estimated to be their normal birth-date. The tuberculin conversion rates of 83 %, 93 % and 88 % in groups I, II and III respectively were not significantly different ( p ±0.5). The results suggest that the preterm AGA infants born at 32-36 weeks of gestation can be effectively immunized with BCG at birth.     

Tuberculin conversion following BCG vaccination in preterm infants

Tuberculin conversion following BCG vaccination was evaluated in 3 groups of infants. Group I consisted of 12 preterm appropriate-for-gestational-age (AGA) infants given BCG vaccination at birth; Group II was made up of 15 term AGA infants similarly immunized while 8 preterm AGA infants (Group III) received BCG about the time estimated to be their normal birth-date. The tuberculin conversion rates of 83%, 93% and 88% in groups I, II and III respectively were not significantly different (p greater than 0.5). The results suggest that the preterm AGA infants born at 32-36 weeks of gestation can be effectively immunized with BCG at birth.     

Low birth weight infants and Calmette-Guérin bacillus vaccination at birth: community study from Guinea-Bissau

BACKGROUND: In developing countries, low birth weight (LBW) children are often not vaccinated with Calmette-Guérin bacillus (BCG) at birth. Recent studies have suggested that BCG may have a nonspecific beneficial effect on infant mortality. We evaluated the consequences of not vaccinating LBW children at birth in Guinea-Bissau. METHODS: Between 1989 and 1999, 7138 children born at the central hospital had a birth weight registered. We assessed BCG coverage until 3 years of age. Data on tuberculin skin test (TST) for 297 children and BCG scar for 1319 children in the study population were reanalyzed for differences between normal birth weight (NBW) children and LBW children. We assessed the effect of early BCG vaccination on mortality to 12 months of age. RESULTS: Among LBW children there were 1.5- to 3-fold more unvaccinated individuals than among NBW children up to 4 months of age. There was no overall difference between LBW and NBW children in TST or BCG scarring; LBW children vaccinated early may have had slightly reduced reactions to tuberculin. Among 845 LBW children, 182 had received BCG within the first week of life. Controlling for background factors and censoring at first diphtheria-tetanuspertussis vaccination, measles vaccination or at 6 months of age (whichever came first), the mortality rate ratio for BCG-vaccinated versus -unvaccinated LBW children was 0.17 (95% confidence interval, 0.06-0.49), with an even stronger effect for LBW children vaccinated in the first week of life (mortality rate ratio, 0.07; 95% confidence interval, 0.01-0.62). CONCLUSIONS: The policy of not vaccinating with BCG at birth had a negative impact on vaccination coverage for LBW children. Early BCG vaccination had no large negative impact on TST and BCG scarring. Mortality was lower for BCG-vaccinated than for unvaccinated LBW children controlling for available background factors. BCG vaccination of LBW children may have a beneficial effect on survival that cannot be explained by protection against tuberculosis. Future studies should examine possible adverse effects from equalizing BCG policy for LBW and NBW children.     

Disseminated BCG as a unique feature of an infant with severe combined immunodeficiency

Severe combined immunodeficiency (SCID) is a rare primary immunodeficiency disease, which renders patients prone to recurrent severe infections in early childhood. Herein, we present a five-month-old boy with SCID who was referred to our center with recurrent diarrhea, respiratory infection and lymphadenopathy. Immunological studies showed hypogammaglobulinemia and low number of T-cells, which was compatible with the diagnosis of T- B+ SCID. An advanced cytomegalovirus pneumonitis was detected based on the results of lung necropsy. Cultures and polymerase chain reaction studies of bone marrow aspirates and spleen specimen were indicative of Mycobacterium bovis. This report emphasizes the importance of lymphadenopathy as a sentinel sign of immunological disorders. Underlying immunodeficiency diseases such as SCID should be considered in the differential diagnosis of an infant with infections and lymphadenopathy, particularly in the regions with routine national Bacillus Calmette-Guérin (BCG) vaccination.     

Successful bone marrow transplantation and treatment of BCG infection in two patients with severe combined immunodeficiency

We report successful bone marrow transplantation (BMT) in two patients with severe combined immunodeficiency (SCID), who had developed BCG infection following neonatal vaccination. Patient 1 had Omenn Syndrome, associated with hypertrophic nonobstructive cardiomyopathy. Patient 2 had SCID due to adenosine deaminase deficiency. This communication demonstrates that with appropriate anti-mycobacterial cover, immunological reconstitution together with full recovery from BCG infection can be achieved by BMT. As demonstrated by persistant negative Mantoux tests, specific cell-mediated immunity to BCG was not acquired following BMT. We suggest that these children may continue to be at risk from mycobacterial infection.     

Influence of Bacillus Calmette-Guèrin vaccination at birth and 2 months old age on the peripheral blood T-cell subpopulations [gamma/delta (γδ) and alpha-beta (αβ) T cell]

The neonatal immune system is immature and may be affected by Bacillus Calmette-Guèrin (BCG) vaccine. We investigated the influence of BCG given at two different ages on the peripheral blood (PB) T-cell subpopulations. Forty full term healthy newborns were randomly chosen. Twenty of them were vaccinated with BCG at birth (group I) and the remaining at the age of 2 months (group II). The cell analysis were carried out before (pre-BCGI and pre-BCGII), and 2 months after (post-BCGI and post-BCGII) the vaccination. The analysis of the gamma/delta and alpha/beta T-cell receptor (TCR) antigens was done by two-colour flowcytometer. The purified protein derivative (PPD) response was investigated 2 months after vaccination. The results showed that although T-cell (TCR+ cell) counts showed no difference in PB before and after vaccination in both study groups, the total lymphocyte and non-T cell (TCR- cell) populations increased significantly whereas alphabetaT-cell population significantly decreased after vaccination. On the contrary, gammadeltaT-cell counts in PB increased significantly 2 months after vaccination in group I but not in group II. Total lymphocyte and non-T cell counts in vaccinated infants at 2 months of age (post-BCGI) were significantly higher than in unvaccinated infants of the same age whereas alphabetaT-cell count in vaccinated infants was significantly low. However, total T-cell and gammadeltaT-cell counts showed no difference. PPD positivity was similar in both study groups (61% in group I, 66% in group II). Neither alphabetaT- nor gammadeltaT-cell counts were different in PPD positive and PPD negative infants. Our study shows that BCG causes marked quantitative changes in the PB T-cell subpopulations in young infants.     

Disseminated Bacillus Calmette-Guerin infection after BCG vaccination

The BCG is administered to all the newborns at birth in Iran. Systemic adverse reactions to BCG vaccine such as osteomyelitis and disseminated BCG infection are rare. This is a retrospective study of 15 cases <72 months who were admitted with systemic syndrome compatible with disseminated mycobacterial disease during 2004-07. Disseminated BCG disease occurred in eight children younger than 6-months old and 12 patient younger than 12-months old. Twelve patients were male. Nine of 15 patients had well known primary immune deficiency disorders including severe combined immunodeficiency, chronic granulomatous disease; cell mediated immune defect and HIV infection. Nine (60%) cases had good response to four anti-mycobacterial drug therapy and interferon gamma. Disseminated BCG disease is a rare but devastating complication of BCG vaccination that should be considered in the appropriate clinical setting. Severe immune-compromised infants are at greatest risk and they respond poorly to standard therapies.     

PREVENTION OF CHILDHOOD LEUKEMIA BY BCG VACCINATION IN NEWBORNS? A POPULATION-BASED CASE-CONTROL STUDY IN LOWER SAXONY,GERMANY

Data from a case-control study in Lower Saxony, Germany, were used to assess whether the risk for childhood cancer may be reduced by bacille Calmette-Guerin (BCG) vaccination in the neonatal period. There were 420 newly diagnosed childhood cancer cases from the German cancer registry and 613 controls eligible for this study. A mailed questionnaire was completed during a telephone interview with parents. Details on the perinatal history were abstracted from the birth charts by nurses blinded to the children's case-control status. Complete information was available for 259 cases and for 323 controls. A total of 85% of the controls had been BCG vaccinated in the newborn period. The adjusted odds ratios for BCG vaccination were 0.90 (95% confidence interval; 0.51-1.61) for leukemia and 0.61 (95% confidence interval; 0.25-1.50) for other cancers. Based on these data the probability of a 50% or more reduction of more reduction of the cancer risk by BCG vaccination in the newborn period is small. The statistical power of this study, however, was not high enough to rule out a smaller, still relevant reduction in cancer risk.     

Prevention of childhood leukemia by BCG vaccination in newborns? A population-based case-control study in Lower Saxony, Germany

Data from a case-control study in Lower Saxony, Germany, were used to assess whether the risk for childhood cancer may be reduced by bacille Calmette-Guerin (BCG) vaccination in the neonatal period. There were 420 newly diagnosed childhood cancer cases from the German cancer registry and 613 controls eligible for this study. A mailed questionnaire was completed during a telephone interview with parents. Details on the perinatal history were abstracted from the birth charts by nurses blinded to the children's case-control status. Complete information was available for 259 cases and for 323 controls. A total of 85% of the controls had been BCG vaccinated in the newborn period. The adjusted odds ratios for BCG vaccination were 0.90 (95% confidence interval; 0.51-1.61) for leukemia and 0.61 (95% confidence interval; 0.25-1.50) for other cancers. Based on these data the probability of a 50% or more reduction of more reduction of the cancer risk by BCG vaccination in the newborn period is small. The statistical power of this study, however, was not high enough to rule out a smaller, still relevant reduction in cancer risk.     

Protective effect of BCG vaccination in infant Asians: a case-control study.

BCG vaccination has been routinely offered to infant Asian children in Birmingham since 1965. We conducted a case-control study to assess the protective effect of this scheme. Altogether 108 Asian children aged under 13 years, born since 1965, received treatment for tuberculosis. For each case four controls were selected; they were matched to the case by month and year of birth, sex, and ethnic origin. Cases and controls were all born in Birmingham. Of the cases, 62 out of 108 (57%) had received BCG, and of the controls, 336 out of 432 (78%) had received BCG. The estimated protective efficacy of vaccination was 64% (95% confidence limits, 43% and 77%). Routine BCG vaccination in infant Asians confers useful protection against the development of tuberculosis in childhood.     

Couverture vaccinale BCG en médecine libérale : premières données chez le nourrisson,sept mois après la levée de l’obligation vaccinale en France

ObjectivesIn July 2007, compulsory BCG vaccination for all children was replaced by a strong recommendation to vaccinate children at high risk of tuberculosis (children who live in Île-de-France [IDF] or Guyana regions, who were born or whose parents were born in tuberculosis endemic countries, with a family history of tuberculosis or living in conditions defined as at risk by the doctor). In the absence of tools to detect an early decrease in vaccine coverage (VC) in this specific group, we conducted a survey with the main objective of measuring BCG VC in high risk children for which BCG is now recommended and who were born after the change in BCG vaccine policy.MethodsCross-sectional survey performed amongst physicians registered at “Infovac-France”, a network of general practitioners and paediatricians particularly aware of recent changes in the field of vaccinations. Each doctor was asked to recruit, during his medical consultation, between six and 12 children aged 2–7 months (born after the end of compulsory BCG vaccination in July 2007) and 8–23 months (born after the withdrawal from the market of the multipuncture form of BCG [Monovax^®] in January 2006 and before the end of compulsory BCG vaccination in July 2007). Doctors were asked to fill in a structured online questionnaire. Data were standardized and analysed with Stata 9.2.ResultsA total of 2536 children, recruited by 279 general practitioners and paediatricians (6.5% of all contacted doctors), were included. VC in the target group of high risk children for who BCG is still recommended and who were seen by doctors working in a private medical practice was: overall 68%; 58% in children born after the end of compulsory BCG vaccination (68% in IDF, 48% outside IDF); 77% in those born after the withdrawal of Monovax^® from the market and before the end of compulsory BCG vaccination; 90% in children living in IDF born after the end of compulsory vaccination and considered as particularly at risk of tuberculosis (presence of vaccination criteria other than residing in IDF) and 60% in the same category of children whose sole criteria for vaccination was residing in IDF. Of doctors who worked in a private medical practice: 75% used to perform the BCG vaccination themselves and 58% had recommended or suggested vaccination to children at risk who were not yet vaccinated. Seventy-six percent of parents of children at risk of tuberculosis not yet vaccinated accepted BCG vaccination when recommended by their doctor.ConclusionOur survey showed, on the one hand, insufficient VC in children seen in a private medical practice and born after the end of compulsory vaccination for whom BCG is still recommended. This should encourage the Ministry of Health to reinforce its communication concerning this new policy. On the other hand, the survey showed encouraging results concerning both the coverage of children at particularly high risk in IDF and the adherence of doctors and families to the new vaccine policy. These results should be interpreted with caution, taking into account the methodological limitations of this survey.     

BCG reaction in twin newborns: effect of zygosity and chorionicity

OBJECTIVE: To study local response to BCG vaccination in twin babies and find out the effect of zygosity andchorionicity on BCG uptake. DESIGN: Analytical observational study. SETTING: Tertiary hospital. METHODS: Twin pairs born in the hospital were evaluated for zygosity and chorionicity. BCG vaccination was given within 48 hours of birth to babies >/=33 weeks of gestation and birth weight >/= 1500 g. Follow-up was done at 6,10 and 14 weeks. Local response to BCG vaccination was recorded in the form of no reaction, abortive reaction, papule, pustule, ulcer, scab or scar. RESULTS: One hundred thirty three twin pairs were delivered (16 monochorionic, 117 dichorionic); of which zygosity was determined in 110 pairs (81 dizygotic, 29 monozygotic). Two hundred four twin babies qualified for BCG vaccination. After 14 weeks, local reaction was seen in 84.3% babies and scar formed in 41.2% cases. Five abortive reactors and 20 'true non-reactors' were also found. Intra-pair agreement for local BCG reaction was highly significant in both monozygotic/dizygotic, as well as monochorionic/dichorionic twins (P<0.01). However, monozygotic and monochorionic intrapair agreements were not significantly larger than the dizygotic and dichorionic intrapair agreements(P >/= 0.05), respectively. CONCLUSION: Local response to BCG vaccination in twin newborn babies follows same pattern as singletons and there is no effect of zygosity or chorionicity on the uptake.     

新生儿接种卡介苗在结核病控制中的作用

为了解新生儿卡介苗接种在结核病控制中的作用,分析前期（1984年－1989年）3010例新生儿与后期（1994年－1999年）2575例新生儿接种卡介苗后PPD试验的结果,前期接种者阳转率85．12％,阴性率14．88％,未种者阳性率0,后期接种者阳转率87．57％,阴性率12．43％,后期未接种者例数增多,阴性率91．67％,阳性率增至8．33％,两期合计,已接种者阳转率86．24％,阴性率13．76％,未种者阴性率92．19％,阳性率为7．81％,已种者阳转率显著高于未种者,资料显示新生儿应尽早接种卡介苗,在未取得新的菌苗代替前,对控制结核病有应用价值,当前面临的问题是如何提高接种的作用及效果。     

Familial occurrence of Kawasaki syndrome in North America

OBJECTIVE: To describe families with multiple members affected with Kawasaki syndrome (KS) to increase awareness of the familial occurrence of KS among practitioners who care for these patients. DESIGN: Retrospective review of medical records at 2 medical centers and data collection from remote KS families who contacted the KS Research Program at the University of California, San Diego. RESULTS: Eighteen families with multiple affected members were identified. There were 9 families with 2 affected siblings. In San Diego, 3 (0.7%) of 424 KS families had sibling cases. Nine families were identified with KS in 2 generations or in multiple affected members, yielding a total of 24 KS-affected children. No clear pattern of inheritance could be deduced from these pedigrees, and it is likely that multiple polymorphic alleles influence KS susceptibility. CONCLUSION: Physicians should counsel affected families and make them aware of the potential increased risk of KS among family members.     

DISSEMINATED BCG INFECTION RESEMBLING LANGERHANS CELL HISTIOCYTOSIS IN AN INFANT WITH SEVERE COMBINED IMMUNODEFICIENCY: A Case Report

We present a very rare congenital immunologic disease, severe combined immunodeficiency syndrome (SCID) in 6-months-old-boy with prolonged mucocutaneous candidiasis, severe anaemia, skin rash similar to the infiltrative eczema of Langerhans cell histiocytosis (LCH) and subcutaneous nodules with histiocytic infiltration. Laboratory findings show profound absence of humoral and cell-mediated immunity. Pathology specimens analysis of subcutaneous nodule revealed numerous S-100 protein and Cd1a negative histiocytes, occupied by BCG intracellular growth. Histopathology and immunohistochemistry confirmed the diagnosis of BCG dissemination. BCG vaccination in infants with SCID can lead to life threatening dissemination, resembling to the infiltrative eczema of LCH and may mislead the clinician.     

Disseminated BCG infection resembling langerhans cell histiocytosis in an infant with severe combined immunodeficiency: a case report

We present a very rare congenital immunologic disease, severe combined immunodeficiency syndrome (SCID) in 6-months-old-boy with prolonged mucocutaneous candidiasis, severe anaemia, skin rash similar to the infiltrative eczema of Langerhans cell histiocytosis (LCH) and subcutaneous nodules with histiocytic infiltration. Laboratory findings show profound absence of humoral and cell-mediated immunity. Pathology specimens analysis of subcutaneous nodule revealed numerous S-100 protein and Cd1a negative histiocytes, occupied by BCG intracellular growth. Histopathology and immunohistochemistry confirmed the diagnosis of BCG dissemination. BCG vaccination in infants with SCID can lead to life threatening dissemination, resembling to the infiltrative eczema of LCH and may mislead the clinician.     

Tuberculin sensitivity in rural Gambian children

A tuberculin survey was undertaken in 480 Gambian children under the age of 10 years, resident in a group of villages where BCG vaccination, shortly after birth, has been widely practised for about 5 years. Ten tuberculin units of purified protein derivative were given by needle and syringe; reactions of 3 mm or greater were considered positive. An overall tuberculin positivity rate of 59% was found which varied little with age, sex or village size. Among children who had probably not had BCG vaccination the positivity rate was about 20% with an annual increase of approximately 5%. Among children who had probably been vaccinated with BCG the positivity rate was between 60% and 80%. There was a fall in the prevalence of positivity of about 10-20% during the first year after vaccination. Thereafter, positivity rates were well maintained for at least another 5 years.     

Angiotensin-converting enzyme genotype distribution in familial vesicoureteral reflux

 Vesicoureteric reflux (VUR) is known to occur in families. In siblings of index patients with VUR, there is a much higher incidence (16% to 46%) than in the general population. The renin-angiotensin system plays an important role in renal development. Recently, it has been reported that angiotensin-converting enzyme (ACE) I/D gene polymorphism is a risk factor for renal parenchymal damage in patients with congenital urological abnormalities. The aim of this study was to investigate the ACE I/D genotype pattern in familial VUR patients. Blood samples were obtained from 86 families in which two or more members had VUR. Samples of DNA were extracted from 407 blood samples (183 affected patients and 224 non-affected family members). To detect ACE I/D polymorphism, polymerase chain reaction (PCR) amplification was performed using specific primers for the ACE gene. PCR products were electrophoresed with 2% agarose gel containing ethidium bromide. Among 224 non-affected family members the ACE genotype distribution of DD, ID, and II was 23%; 56% and 21%, respectively. The ACE genotype distribution of 183 affected patients was 28%, 47% and 25%, respectively. There was no significant difference in ACE I/D distribution between affected patients and their non-affected families. Both the ACE genotype distribution of affected patients and that of non-affected family members were not significantly different from the previously reported genotype distribution of the normal Caucasian population. This study demonstrates that ACE genotype frequencies are similar in index patients with VUR and their unaffected siblings, thus suggesting that the ACE gene is not involved in the development of familial VUR.     

Clinical presentation of Bacillus Calmette-Guérin infections in patients with immunodeficiency syndromes

Nine children with immunodeficiency syndromes who developed persistent or disseminated Bacillus Calmette-Guérin (BCG) infections after BCG vaccination at birth were observed in Santiago, Chile, over a period of 10 years. This represents a risk for persistent or disseminated BCG infections of 3.4/1,000,000 vaccinated newborns. This may closely reflect the incidence of severe combined immunodeficiency syndromes, cellular immunodeficiency syndromes and chronic granulomatous disease in the study area. The clinical presentation and course of the infection varied considerably depending on the underlying immunodeficiency syndrome. Two patients with severe combined immunodeficiency presented with cutaneous nodules in the absence of any local reaction at the site of BCG vaccination. Both patients died of disseminated BCG infection within the first year of life. Four patients with cellular immunodeficiency syndromes presented with regional lymphadenitis resistant to treatment after the fifth month of life. Three of these patients had specific unresponsiveness to tuberculin and survived from 5 to 6 years of age. Two boys with X-linked chronic granulomatous disease presented with regional lymphadenitis in the first 3 months of life. A girl with autosomal recessive chronic granulomatous disease presented at 18 months of age with regional lymphadenitis. All three patients with chronic granulomatous disease had positive tuberculin reactions and died from infections other than BCG.