Randomized Trial of Vitamin D Supplementation and Risk of Acute Respiratory Infection in Mongolia Immune function in rural Gambian children is not related to season of birth, birth size, or maternal supplementation status. Undernutrition as an underlying cause of child deaths associated with diarrhea, pneumonia, malaria, and measles. Antibody-response to three recombinant hepatitis B vaccines: comparative evaluation of multicenter travel-clinic based experience. Effect of recent diarrhoeal episodes on risk of pneumonia in children under the age of 5 years in Karachi, Pakistan. Seasonal variation of paediatric diseases in The Gambia, west Africa. Nasopharyngeal carriage of Streptococcus pneumoniae shortly before vaccination with a pneumococcal conjugate vaccine causes serotype-specific hyporesponsiveness in early infancy. Factors affecting the immunogenicity of oral poliovirus vaccine: a prospective evaluation in Brazil and the Gambia. World Health Organization Collaborative Study Group on Oral Poliovirus Vaccine. BCG vaccination among West African infants is associated with less anergy to tuberculin and diphtheria-tetanus antigens. Epidemiology of respiratory syncytial virus in children ≤2 years of age hospitalized with lower respiratory tract infections in the Russian Federation: a prospective, multicenter study Seasonal variation of maternally derived respiratory syncytial virus antibodies and association with infant hospitalizations for respiratory syncytial virus. The evaluation of delayed-type hypersensitivity responsiveness and nutritional status as predictors of gastro-intestinal and acute respiratory infection: a prospective field study among traditional nomadic Kenyan children. Influence of host related factors on the antibody response to trivalent oral polio vaccine in Tunisian infants. Cord Blood Vitamin D Deficiency Is Associated With Respiratory Syncytial Virus Bronchiolitis Malnutrition, cell‐mediated immune deficiency and acute upper respiratory infections in rural Bangladeshi children
OBJECTIVE : Observational studies suggest that serum levels of 25-hydroxyvitamin D ( 25[OH]D ) are inversely associated with acute respiratory infections ( ARIs ) . We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs . METHODS : By using cluster r and omization , classrooms of 744 Mongolian schoolchildren were r and omly assigned to different treatments in winter ( January – March ) . This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk ( control ; n = 104 ) or milk fortified with 300 IU of vitamin D3 ( n = 143 ) . This comparison was double-blinded . The primary outcome was the number of parent-reported ARIs over the past 3 months . RESULTS : At baseline , the median serum 25(OH)D level was 7 ng/mL ( interquartile range : 5–10 ng/mL ) . At the end of the trial , follow-up was 99 % ( n = 244 ) , and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different ( 7 vs 19 ng/mL ; P < .001 ) . Compared with controls , children receiving vitamin D reported significantly fewer ARIs during the study period ( mean : 0.80 vs 0.45 ; P = .047 ) , with a rate ratio of 0.52 ( 95 % confidence interval : 0.31–0.89 ) . Adjusting for age , gender , and history of wheezing , vitamin D continued to halve the risk of ARI ( rate ratio : 0.50 [ 95 % confidence interval : 0.28–0.88 ] ) . Similar results were found among children either below or above the median 25(OH)D level at baseline ( rate ratio : 0.41 vs 0.57 ; Pinteraction = .27 ) . CONCLUSIONS : Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency BACKGROUND We previously showed that mortality from infectious diseases among young adults in rural Gambia is strongly correlated with the season of their birth . This suggests that early life insults that involve fetal malnutrition , exposure to natural toxins , or highly seasonal infections affecting the infant or pregnant mother cause permanent damage to the immune system . Excess mortality begins after puberty and has a maximal odds ratio of > 10 for deaths between ages 25 and 50 y. OBJECTIVE We investigated the immune function of children according to birth weight , season of birth , and exposure to maternal dietary supplementation during pregnancy . DESIGN Immune function was measured in 472 prepubertal children aged 6.5 - 9.5 y from 28 villages in rural Gambia . The mothers of these children had been r and omly assigned to a high-energy prenatal supplementation program , which significantly increased birth weight . This permitted supplementation status , birth weight , and season of birth to be investigated as exposure variables . The outcome variables tested were naive responses to rabies and pneumococcus vaccines , delayed-type hypersensitivity skin reactions , and mucosal defense ( secretory immunoglobulin A and dual-sugar permeability ) . RESULTS Immune responses were strongly related to current age and sex , suggesting a high level of sensitivity , but were not consistently related to birth weight , season of birth , or maternal supplementation ( control compared with intervention ) . CONCLUSION Events in early life did not predict a measurable defect in immune response within this cohort of rural Gambian children . It is possible that the early programming of immune function may be mediated through a defect in immunologic memory or early senescence rather than through impairment of early responses BACKGROUND Previous analyses derived the relative risk ( RR ) of dying as a result of low weight-for-age and calculated the proportion of child deaths worldwide attributable to underweight . OBJECTIVES The objectives were to examine whether the risk of dying because of underweight varies by cause of death and to estimate the fraction of deaths by cause attributable to underweight . DESIGN Data were obtained from investigators of 10 cohort studies with both weight-for-age category ( < -3 SDs , -3 to < -2 SDs , -2 to < -1 SD , and > -1 SD ) and cause of death information . All 10 studies contributed information on weight-for-age and risk of diarrhea , pneumonia , and all-cause mortality ; however , only 6 studies contributed information on deaths because of measles , and only 3 studies contributed information on deaths because of malaria or fever . With use of weighted r and om effects models , we related the log mortality rate by cause and anthropometric status in each study to derive cause-specific RRs of dying because of undernutrition . Prevalences of each weight-for-age category were obtained from analyses of 310 national nutrition surveys . With use of the RR and prevalence information , we then calculated the fraction of deaths by cause attributable to undernutrition . RESULTS The RR of mortality because of low weight-for-age was elevated for each cause of death and for all-cause mortality . Overall , 52.5 % of all deaths in young children were attributable to undernutrition , varying from 44.8 % for deaths because of measles to 60.7 % for deaths because of diarrhea . CONCLUSION A significant proportion of deaths in young children worldwide is attributable to low weight-for-age , and efforts to reduce malnutrition should be a policy priority The immunogenicity of three currently used hepatitis B vaccines was compared in an unselected study population in an every day travel clinical setting . Five hundred and eighteen vaccinees received Engerix-B ( EB ) , 990 received Twinrix ( TWX ) , and  366 were immunised with Gen-HB-Vax ( GHB ) . Overall , 88.6 % of the vaccinees , tested within the first 6 months after completion of the vaccination series , developed protective levels of anti-HBs ( > or = 10 mIU/ml ) . However , GHB recipients showed significantly lower seroprotection rates ( SPR ) than EB and TWX recipients ( 79.3 % vs. 87.7 % vs. 92.3 % , P < 0.000001 ) . GMTs for anti-HBs , tested within 6 months after the third vaccination , showed the lowest results in the GHB group , followed by EB and TWX ( 142 vs. 523 vs. 1008 mIU/ml , P < 0.000001 ) . TWX vaccinees , however , showing a higher antibody decline rate than EB recipients within the first years after completion of the full immunisation course ( 30 % vs. 25 % ; P = 0.0538 ) . This study confirms an overall good immune response to the 20 microg-dose vaccine , in the course of a regular clinical setting . The significant difference in SPRs and GMTs to the 10 microg-dose vaccine , however , may influence future immunisation practice s for the elderly BACKGROUND We assessed the association between the duration of diarrhoea and the risk ofpneumonia incidence  among children < 5 years of age . METHODS We analysed data from a cluster r and omized controlled trial in Karachi , Pakistan , which assessed the effect of promoting h and washing with soap ( antibacterial and plain ) on child health . Field workers visited households with children < 5 years of age weekly and asked primary caregivers if their child had diarrhoea , cough or difficulty breathing in the preceding week . We used the WHO clinical case definitions for diarrhoea and pneumonia . We used adjusted time-to-event analyses with cumulative diarrhoea prevalence over the previous 2 and 4 weeks as exposure and pneumonia as outcome . We calculated the attributable risk of pneumonia due to recent diarrhoea across the intervention groups . RESULTS 873 households with children < 5 years were visited . Children had an increased risk of pneumonia for every additional day of diarrhoea in the 2 weeks ( 1.06 , 95 % CI : 1.03 - 1.09 ) and 4 weeks ( 1.04 , 95 % CI : 1.03 - 1.06 ) prior to the week of pneumonia onset . The attributable risk of pneumonia cases due to recent exposure to diarrhoea was 6 % . A lower associated pneumonia risk following diarrhoea was found in the control group : ( 3 % ) compared with soap groups ( 6 % in antibacterial soap , 9 % in plain soap ) . CONCLUSION Children < 5 years of age are at an increased risk of pneumonia following recent diarrhoeal illness . Public health programmes that prevent diarrhoea may also reduce the burden of respiratory illnesses In a 3-year prospect i ve study of 9584 consecutive paediatric admissions to the Royal Victoria Hospital in Banjul , The Gambia , we examined the impact of seasonal variations in childhood diseases . The four principal diseases ( falciparum malaria , pneumonia , gastro-enteritis and malnutrition ) all peaked in September to October following the rainy season . The mortality rate was also higher in the rainy season than in the dry season . Of the 1525 children with cerebral malaria , 83 % were admitted during the extended rainy season from July to December . With the emergence of chloroquine-resistant malaria over the 3 years , there was a 27 % annual increase in severe anaemia owing to malaria . The median age of malarial anaemia ( 23 months ) was significantly younger than that of cerebral malaria ( 42 months ) . Malnutrition peaked immediately following the annual rainy season epidemics of bacterial gastro-enteritis but was not associated with the cool dry season rotavirus outbreaks . Rainy season diarrhoea was also associated with more persistent diarrhoea , an older mean age and a higher mortality . Meningitis was caused by either pneumococcus or Haemophilus influenzae in 64 % of cases , of whom 19 % were 0 - 2 months of age . Causes of death in hospital showed good agreement with Gambian community studies . We conclude that analysis of hospital data in a developing country can give accurate information on childhood morbidity and mortality patterns which can be used to set priorities for health care interventions . Seasonal variation is a cardinal feature of paediatric diseases in this part of Africa , and accentuates the vulnerability of children in poor families BACKGROUND The antibody response to pneumococcal conjugate vaccines ( PCVs ) in infants is variable . Factors responsible for this variability have not been fully eluci date d. The objective of this study was to investigate whether pneumococcal carriage around the time of the first dose of 7-valent PCV ( PCV7 ) affects serotype-specific immunologic response . METHODS Healthy 2-month old infants were r and omized to receive 2 ( at the ages of 4 and 6 months ) or 3 ( at the ages of 2 , 4 , and 6 months ) PCV7 doses and a booster dose ( at the age of 12 months ) . Nasopharyngeal or oropharyngeal specimens were obtained for culture shortly before the first PCV7 dose . Serotype-specific immunoglobulin ( Ig ) G levels were measured at ages 2 , 7 , and 13 months . RESULTS Of 545 children studied , 332 received a booster dose . The most common serotypes carried around the time of the first PCV7 dose were 6B ( n = 37 ) , 19F ( n = 22 ) , and 23F ( n = 14 ) . In carriers before the first dose , the IgG response to the carried serotype after 2 or 3 doses was significantly lower than in noncarriers . In contrast , response to the noncarried serotypes was not affected . Although all children responded to the booster dose , the response to the originally carried serotype was generally lower . CONCLUSIONS Serotype-specific hyporesponsiveness to PCV7 after pneumococcal carriage in infants is demonstrated for the first time . This phenomenon was common , lasted for at least several months , and was only partially overcome by the 12-month booster . TRIAL REGISTRATION is rct n.org identifier : IS RCT N28445844 To assess factors that may influence the immunogenicity of oral poliovirus vaccine ( OPV ) , neutralizing antibody responses were measured in 1409 infants in Brazil and the Gambia who were r and omized to receive one of four different formulations of OPV at approximately birth and at 6 , 10 , and 14 weeks .  Overall seroconversion rates at the end of the trial were 85 % for poliovirus type 1 ( P1 ) , 94 % for type 2 ( P2 ) , and 68 % for type 3 ( P3 ) . Factors associated with vaccine failure included high levels of maternal antibody ( P1 , P2 , and P3 ) , vaccination during the rainy season ( P1 , P2 , and P3 ) , diarrhea at the time of vaccination ( P2 and P3 ) , household exposure to other OPV recipients ( P1 ) , and breast-feeding ( P3 ) ( P < .05 for each factor , logistic regression analysis ) . OPV containing twice the st and ard potency of Sabin type 1 virus increased seroconversion rates to P1 by 8 % in Brazil ( P < .05 ) and 15 % in the Gambia ( P < .001 ) . Suboptimal responses to OPV in developing countries are determined by a complex array of factors related to the vaccine , host , and environment To examine risk factors for anergy , delayed-type hypersensitivity was assessed among 884 infants participating in a vaccine trial in Guinea-Bissau . The infants were skin-tested at 7.5 months of age with a panel of seven intradermal antigens . Risk factors for anergy to tuberculin or anergy to both the diphtheria and tetanus antigens were determined in relation to Bacillus Calmette-Guérin ( BCG ) vaccination , diphtheria-tetanus-pertussis ( DTP ) vaccination , and measles vaccination . We found sick children to be more anergic to tuberculin and diphtheria-tetanus antigens than healthy children ( OR=2.49 ( 95 % confidence interval 1.40 - 4.55 ) ) . There was a higher prevalence of anergy to tuberculin in the rainy season than in the dry season ( OR=1.67 ( 1.25 - 2.23 ) ) . Children who had taken antimalarials within the last week had a higher prevalence of anergy to tuberculin ( OR=1.41 ( 1.02 - 1.92 ) ) . BCG vaccination was significantly associated with less anergy to tuberculin and diphtheria-tetanus antigens ( OR=0.42 ( 0.28 - 0.63 ) , OR=0.77 ( 0.60 - 0.99 ) , respectively ) . Children vaccinated with BCG before 1 month of age were more anergic to tuberculin than children vaccinated after 1 month ( OR=1.61 ( 1.19 - 2.19 ) ) . DTP vaccination  was associated with less anergy to diphtheria-tetanus antigens ( OR=0.40 ( 0.32 - 0.49 ) ) , but not to tuberculin . Children with a positive reaction to tuberculin were less likely to be anergic to diphtheria-tetanus antigens ( OR=0.36 ( 0.26 - 0.49 ) ) than children with a negative tuberculin reaction . Children who were vaccinated with BCG before they received their last DTP vaccine were less anergic to diphtheria-tetanus antigens ( OR=0.40 ( 0.16 - 0.88 ) ) than other DTP-vaccinated children . In conclusion , current disease , rainy season , age below 1 month of age at the time of BCG vaccination , and administration of chloroquine or quinimax within the last 7 days were risk factors for anergy to tuberculin among 7.5-month-old infants .  BCG vaccination and a positive tuberculin reaction were associated with a lower prevalence of anergy to both tuberculin and diphtheria-tetanus . Thus , BCG vaccination may contribute to better cell-mediated immune responses among infants Background Respiratory syncytial virus ( RSV ) is the leading cause of severe lower respiratory tract infections among infants and young children , and is responsible for an estimated four million deaths per year globally . A monthly injection of palivizumab has been used for prophylaxis of serious RSV infections among high-risk children in 71 countries since 1998 and approval for use in the Russian Federation was obtained in February 2010 . A recommendation for RSV prophylaxis in the Russian Federation would require knowledge of the prevalence and seasonality of RSV in that country . Methods In a prospect i ve , multicenter , epidemiological study of the prevalence , seasonality , and peak occurrence of RSV infection , children aged ≤2 years hospitalized for lower respiratory tract infections in three regions of the Russian Federation , from September 2008 through April 2009 , were screened and tested for RSV using rapid immunochromatography of nasopharyngeal lavage . For subjects who were tested positive , hospitalization data were collected . Results Of 519 children aged ≤2 years enrolled from September 11 , 2008 through April 26 , 2009 , 197 tested positive for RSV ( 38.0 % , 95 % CI : 33.8 , 42.3 ) . The onset of the 2008–2009 RSV season in the Russian Federation occurred in late October 2008 , similar to what is observed in other northern temperate zones . Peak activity occurred in early April 2009 , when 62 % of children enrolled tested positive for RSV . Conclusion The prevalence of serious RSV infections in the Russian Federation is similar to the prevalence previously identified in other temperate zones of the northern hemisphere . The seasonality of disease shifted towards early spring , with peak activity later in the season , within a range reported in other countries . These data provide further evidence of serious RSV infection in children in the Russian Federation , as well as guidance for timing of seasonal RSV prophylaxis , especially among individuals at high risk for serious RSV infection This study used 459 prospect ively sample d cord blood sample s  to examine the association between maternally derived respiratory syncytial virus (RSV)-neutralizing antibodies and the RSV hospitalization season in Denmark . We found a clear temporal association and suggest that RSV-neutralizing antibody level plays a role in the RSV seasonal pattern A 10-month prospect i ve study of children from a nomadic pastoralist community in northwest Kenya was conducted to examine the relationship between nutritional status , cell-mediated immunity ( CMI ) , and morbidity due to gastroenteritis and acute respiratory infection ( ARI ) . In children ages 6 months to 10 years , nutritional status and cellular immunocompetence , determined by delayed-type hypersensitivity ( DTH ) , were related to individual attack rates of diarrhoea and ARI over two 5-month observation periods , one each in the wet and dry season . While no association was found between premorbid nutritional status and gastroenteritis , DTH responsiveness was a significant predictor of diarrhoeal disease , with anergic children experiencing , on average , 20 per cent higher attack rates than immunocompetent children . When examined separately , both nutritional status and DTH responsiveness were significant predictors of individual attack rates of ARI in the wet season . However , when the effects of nutritional and immunological status were simultaneously tested , only DTH responsiveness was significant . Anergic children experienced 34 per cent excess ARI , compared to immunocompetent children . These results indicate that cellular immunocompetence is a sensitive predictor of gastrointestinal and respiratory infection , and that the effect of nutritional status on the occurrence of ARI may be mediated by cellular immune function The low efficiency of trivalent oral polio vaccine ( TOPV ) in inducing protective antibody titres to polio3 is a problem of great importance in many regions of the world . A prospect i ve study was conducted in 121 Tunisian infants aged 3 months during routine immunization with TOPV under carefully controlled conditions .  Seroconversion rates to  polio1 , polio2 and polio3  , one month after the third dose , were 94.7 , 100 and 89.5 % , respectively . The kinetics of the antibody response showed delayed and more difficult responses to polio3 compared to polio2 and polio1 . The following host related factors , previously suggested to interfere with the immune response , were assessed : maternal antibodies ; breast-feeding ; concurrent enteric infections ; and other illnesses . The main factor associated with the lack of seroconversion was concurrent infection with non-polio enteroviruses ( NPE ) which was found in 50 % of non-responders to polio1 and /or to polio3 during the vaccination protocol whereas no NPE was isolated in vaccine responders . The other studied factors seemed not to interfere in the infants according to the locally adopted vaccination schedule and to the specific socio-economic conditions BACKGROUND : Respiratory syncytial virus ( RSV ) is the most important pathogen causing severe lower respiratory tract infection ( LRTI ) in infants . Epidemiologic and basic studies suggest that vitamin D may protect against RSV LRTI . OBJECTIVE : To determine the association between plasma vitamin D concentrations at birth and the subsequent risk of RSV LRTI . DESIGN : A prospect i ve birth cohort study was performed in healthy term neonates . Concentrations of 25-hydroxyvitamin D ( 25-OHD ) in cord blood plasma were related to RSV LRTI in the first year of life , defined as parent-reported LRTI symptoms in a daily log and simultaneous presence of RSV RNA in a nose-throat specimen . RESULTS : The study population included 156 neonates . Eighteen ( 12 % ) developed RSV LRTI . The mean plasma 25-OHD concentration was 82 nmol/L. Overall , 27 % of neonates had 25-OHD concentrations < 50 nmol/L , 27 % had 50 - 74 nmol/L and only 46 % had 25-OHD 75 nmol/L. Cord blood 25-OHD concentrations were strongly associated with maternal vitamin D3 supplementation during pregnancy . Concentrations of 25-OHD were lower in neonates who subsequently developed RSV LRTI compared with those who did not ( 65 nmol/L versus 84 nmol/L , P = .009 ) . Neonates born with 25-OHD concentrations < 50 nmol/L had a sixfold ( 95 % confidence interval : 1.6 - 24.9 ; P = .01 ) increased risk of RSV LRTI in the first year of life compared with those with 25-OHD concentrations ≥75 nmol/L. CONCLUSIONS : Vitamin D deficiency in healthy neonates is associated with increased risk of RSV LRTI in the first year of life . Intensified routine vitamin D supplementation during pregnancy may be a useful strategy to prevent RSV LRTI during infancy A community‐based longitudinal study conducted in rural Bangladesh investigated the association between nutritional status , cell‐mediated immune status and acute upper respiratory infections ( URI ) .  A total of 696 children aged 0–59 months was followed prospect ively for 1 y yielding 183 865 child‐days ' observation . Trained field workers visited each child every 4th d and collected morbidity data on symptoms suggesting URI ( cough , fever , nasal discharge ) for the preceding 3 d by recall . On the day of visit they examined each child reporting cough and /or fever to record the temperature , presence of nasal discharge , rate of respiration and presence of chest indrawing . Anthropometry for all children was conducted monthly . Cell‐mediated immune competence was assessed by a multiple antigen skin test at baseline and thereafter every 3 months . The incidence of URI was 5 . 3 episodes per child‐year observed . Approximately three‐quarters of the study children were below ‐2 Z‐score weight for age and height for age , and a quarter below ‐2 Z‐score weight for height . During different test periods 9–21 % of the study children did not respond to any of the test antigens . In a regression model children < ‐2 Z‐score for weight for height had 16 % [ odds ratio ( OR ) 1 . 16 , 95 % confidence interval ( CI ) 1 . 03–1 . 31 , p= 0 . 01 ] higher risk of developing URI . Anergic children had 20 % higher risk ( OR 1 . 20 , CI 1 . 05–1 . 38 , p= 0 . 009 ) of URI than immunocompetent children . The study demonstrated that wasting and depressed cell‐mediated immunity ( CMI ) , but not stunting , were associated with the incidence of URI among rural Bangladeshi children
INTRODUCTION Cyclical fluctuations in host immunity have been proposed as a driver of respiratory infection seasonality , however few studies have attempted to directly assess whether or not seasonal immune modulation occurs in humans .