Soluble interleukin-2 receptor (sCD25) and interleukin-10 plasma concentrations are associated with severity of primary respiratory syncytial virus (RSV) infection

The role of the immune response in the severity of RSV infection was examined by determining plasma concentrations of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), interleukin-2 receptor (sCD25) and soluble tumor necrosis factor receptor II (sTNFR-II) in 196, previously healthy infants, during acute and convalescence phases of primary RSV infection. The results were analyzed separately for days 1-4 (early) and days 5-7 (late) of symptoms before sample collection and according to disease severity (105 hypoxic, 91 non-hypoxic). Significant associations between plasma levels and severity were found in early samples only. IL-10 and sCD25 concentrations were higher (p=0.01, each) in hypoxic compared with non-hypoxic infants, whereas no differences were observed in IFN-gamma and sTNFR-II levels between the groups. Early sCD25 levels correlated positively with IL-10 concentrations (p= 0.0003; r= 0,401). Amongst the hypoxic infants, the number of days of oxygen supplementation correlated positively with early IL-10 levels (p=0.009; r=0.495) and negatively with the IFN-gamma/IL-10 ratio (p=0.007; r=0.495). IFN-gamma levels were significantly higher in the acute phase than during convalescence for hypoxic and non-hypoxic infants, while IL-10 levels were significantly higher in the acute phase only in hypoxic infants for days 1-4 (early; p=0.0007). sCD25 concentrations were elevated only in hypoxic infants at days 1-4 of the acute phase (p=0.002), whereas sTNFR-II levels did not vary between acute and convalescence phases, independent of severity and time point of sampling. We found no association between plasma levels during the convalescence phase and the severity of the RSV infection.     

Plasma interferon-gamma, interleukin-10 and soluble markers of immune activation in infants with primary adenovirus (ADV) and respiratory syncytial virus (RSV) infection

Adenovirus (ADV) and respiratory syncytial virus (RSV) are etiological agents of acute respiratory tract infection in infants. Long-term prognosis of ADV infection includes severe lung damage, bronchiectasis and hyperlucent lung, while RSV infection is associated with development of recurrent wheezing and subsequent asthma. These differences may be related to differences in the primary immune responses elicited by these viruses. In this paper, we investigated the type of cytokine responses and the magnitude of immune activation in ADV and RSV infections in infants. We examined plasma concentrations of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), soluble interleukin-2 receptor (sCD25) and soluble tumor necrosis factor receptor II (sTNFR-II) in previously healthy infants during the acute phase of primary ADV infection (n = 21) and RSV infection (n = 68), and in uninfected controls (n = 44). In ADV-infected infants, IFN-gamma plasma levels were significantly higher than those observed in RSV cases and the control group (p < 0.05). RSV cases did not show any differences in IFN-gamma plasma levels compared to the other groups. sCD25 levels were significantly higher in ADV- and RSV-infected infants than in controls (p < 0.0001), and higher in ADV than in RSV cases (p < 0.05). sTNFR-II levels were significantly higher in RSV- and ADV-infected infants than in controls (p < 0.0001, p < 0.05, respectively), and higher in RSV than in ADV infection (p < 0.05). No significant differences were observed in IL-10 plasma concentrations between the three groups. These results indicate that ADV and RSV infections in infants differ significantly with regard to the magnitude of production of interferon-gamma and soluble immune activation markers sCD25 and sTNFR-II. These immunological differences may be involved in the different clinical outcomes associated with these viral infections.     

Association between infant feeding patterns and diarrhoeal and respiratory illness: A cohort study in Chittagong, Bangladesh

Background

In developing countries, infectious diseases such as diarrhoea and acute respiratory infections are the main cause of mortality and morbidity in infants aged less than one year. The importance of exclusive breastfeeding in the prevention of infectious diseases during infancy is well known. Although breastfeeding is almost universal in Bangladesh, the rates of exclusive breastfeeding remain low. This cohort study was designed to compare the prevalence of diarrhoea and acute respiratory infection (ARI) in infants according to their breastfeeding status in a prospective cohort of infants from birth to six months of age.

Methods

A total of 351 pregnant women were recruited in the Anowara subdistrict of Chittagong. Breastfeeding practices and the 7-day prevalence of diarrhoea and ARI were recorded at monthly home visits. Prevalences were compared using chi-squared tests and logistic regression.

Results

A total of 272 mother-infant pairs completed the study to six months. Infants who were exclusively breastfed for six months had a significantly lower 7-day prevalence of diarrhoea [AOR for lack of EBF = 2.50 (95%CI 1.10, 5.69), p = 0.03] and a significantly lower 7-day prevalence of ARI [AOR for lack of EBF = 2.31 (95%CI 1.33, 4.00), p < 0.01] than infants who were not exclusively breastfed. However, when the association between patterns of infant feeding (exclusive, predominant and partial breastfeeding) and illness was investigated in more detail, there was no significant difference in the prevalence of diarrhoea between exclusively [6.6% (95% CI 2.8, 10.4)] and predominantly breastfed infants [3.7% (95% CI 0.09, 18.3), (p = 0.56)]. Partially breastfed infants had a higher prevalence of diarrhoea than the others [19.2% (95% CI 10.4, 27.9), (p = 0.01)]. Similarly, although there was a large difference in prevalence in acute respiratory illness between exclusively [54.2% (95%CI 46.6, 61.8)] and predominantly breastfed infants [70.4% (95%CI 53.2, 87.6)] there was no significant difference in the prevalence (p = 0.17).

Conclusion

The findings suggest that exclusive or predominant breastfeeding can reduce rates of morbidity significantly in this region of rural Bangladesh.     

Systemic T-helper and T-regulatory cell type cytokine responses in rhinovirus vs. respiratory syncytial virus induced early wheezing: an observational study

Background

Rhinovirus (RV) associated early wheezing has been recognized as an independent risk factor for asthma. The risk is more important than that associated with respiratory syncytial virus (RSV) disease. No comparative data are available on the immune responses of these diseases.

Objective

To compare T-helper₁ (Th₁), Th₂ and T-regulatory (T_reg) cell type cytokine responses between RV and RSV induced early wheezing.

Methods

Systemic Th₁-type (interferon [IFN] -gamma, interleukin [IL] -2, IL-12), Th₂-type (IL-4, IL-5, IL-13) and T_reg-type (IL-10) cytokine responses were studied from acute and convalescence phase serum samples of sole RV (n = 23) and RSV affected hospitalized wheezing children (n = 27). The pre-defined inclusion criteria were age of 3-35 months and first or second wheezing episode. Analysis was adjusted for baseline differences. Asymptomatic children with comparable demographics (n = 11) served as controls for RV-group.

Results

RV-group was older and had more atopic characteristics than RSV-group. At acute phase, RV-group had higher (fold change) IL-13 (39-fold), IL-12 (7.5-fold), IFN-gamma (6.0-fold) and IL-5 (2.8-fold) concentrations than RSV-group and higher IFN-gamma (27-fold), IL-2 (8.9-fold), IL-5 (5.6-fold) and IL-10 (2.6-fold) than the controls. 2-3 weeks later, RV-group had higher IFN-gamma (>100-fold), IL-13 (33-fold) and IL-10 (6.5-fold) concentrations than RSV-group and higher IFN-gamma (15-fold) and IL-2 (9.4-fold) than the controls. IL-10 levels were higher in acute phase compared to convalescence phase in both infections (p < 0.05 for all).

Conclusion

Our results support a hypothesis that RV is likely to trigger wheezing mainly in children with a predisposition. IL-10 may have important regulatory function in acute viral wheeze.     

Cytokine patterns during dengue shock syndrome

OBJECTIVE: To investigate the patterns of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, interferon-gamma (IFN-gamma) and interleukin-1 receptor antagonist (IL-1Ra) during the course of dengue shock syndrome. DESIGN: Prospective clinical study. SETTING: Pediatric Intensive Care Unit, Dr. Kariadi Hospital, the university hospital of Diponegoro University, Semarang, Indonesia. PATIENTS: Fifty children with dengue shock syndrome. MEASUREMENTS: The plasma concentration and the ex vivo production, with and without lipopolysaccharide (LPS), of TNF-alpha, IL-1beta and IL-1Ra were measured in duplicate by nonequilibrium radioimmunoassay (RIA); IFN-gamma and IL-6 were measured by ELISA. RESULTS: During the acute phase, the plasma concentrations and the ex vivo production without LPS of IL-1Ra were considerably elevated and returned to normal on recovery. However, the ex vivo LPS-stimulated production of the proinflammatory cytokines TNF-alpha and IL-1beta were considerably depressed. Also, these concentrations returned towards normal on recovery. In non-survivors, the plasma concentrations of IL-6 and IL-1Ra were significantly higher than in survivors (p = 0.00001 and p = 0.0005, respectively). In addition, the ex vivo production of IL-1Ra in non-survivors was significantly higher than in survivors, both without LPS stimulation (p = 0.0008) and with LPS (p < 0.004). IL-1Ra was significantly associated with mortality (p = 0.007). CONCLUSION: Since IL-1Ra was significantly associated with mortality, this measurement may be used as an index of disease severity in dengue shock syndrome.     

Suboptimal breastfeeding practices are associated with infant illness in Vietnam

Background

Despite evidence supporting the importance of breastfeeding to child health, breastfeeding practices remain suboptimal in Vietnam. There is currently little evidence on the importance of breastfeeding in the prevention of morbidity during infancy in Vietnam. In order to provide country specific data for policy makers to support breastfeeding friendly policies and programs, analysis was undertaken on a cross-sectional dataset to investigate the association between breastfeeding practices and prevalence of diarrhea and acute respiratory infection (ARI) among infants aged 0–5 months.

Methods

Data on socio-demographic characteristics, infant feeding practices and prevalence of diarrhea and ARI were obtained from 6,068 mother-child dyads in 11 provinces of Vietnam in 2011. Multivariate logistic regression was used to examine the associations between breastfeeding practices and child illnesses.

Results

On average, the prevalence of diarrhea and ARI among infants 0–5 months was 5.3% and 24.5%, respectively. Though half of all infants were breastfed within one hour of birth, 73.3% were given prelacteal foods in the first three days after birth. Only 20.2% of children 0–5 months old were exclusively breastfed, while 32.4% were predominantly breastfed and 47.4% partially breastfed. After adjusting for confounders, early initiation of breastfeeding was associated with lower prevalence of diarrhea [adjusted odds ratio (AOR)?=?0.74 (95% CI 0.58, 0.93)], while prelacteal feeding was associated with higher prevalence [AOR?=?1.53 (95% CI 1.15, 2.03)]. Compared to infants who were exclusively breastfed, infants who were predominantly [AOR?=?1.52 (95% CI 1.05, 2.21)] or partially breastfed [AOR?=?1.55 (95% CI 1.07, 2.24)] were more likely to have diarrhea. Prelacteal feeding [AOR?=?1.16 (95% CI 1.01, 1.33)] and partial breastfeeding [AOR relative to exclusive breastfeeding?=?1.24 (95% CI 1.03, 1.48)] were associated with higher prevalence of ARI. While the protective effects of exclusive breastfeeding against diarrhea declined with child age, this effect for ARI appears to have remained constant.

Conclusions

Early initiation and exclusive breastfeeding protects against diarrhea and ARI. Results confirm that interventions to improve early and exclusive breastfeeding would contribute to improving child health and nutrition in Vietnam.

     

The role of bacteria in lactational mastitis and some considerations of the use of antibiotic treatment

Background

The proportion of mothers in Japan who breastfeed exclusively has been low since the 1970s. The purpose of this study was to examine the association between the time of first breastfeed after birth and the proportion of mothers fully breastfeeding up to four months postpartum.

Methods

A survey was conducted using a self-administered questionnaire. The participants were 318 mothers who participated in a physical examination of their four month old infants in Nagasaki City, Japan in 2003.

Results

The time of first breastfeeding up to 120 minutes was significantly associated with the proportion of mothers fully breastfeeding during their stay in the clinic/hospital (p = 0.006), at one month (p = 0.004) and at four months after birth (p = 0.003). There was no significant difference in the proportion of full breastfeeding in mothers who first breastfed between the period of less 30 minutes after birth and that of between 31 and 120 minutes after birth. Logistic regression analysis indicated that the proportion of mothers who continued full breastfeeding at four months was significantly higher in those who breastfed their baby within 120 minutes compared with more than 120 minutes (OR 2.5, p = 0.01), but was not significantly different in those who breastfed within 30 minutes compared with more than 30 minutes (OR 1.8, p = 0.06). Early breastfeeding was affected by caesarean section, premature delivery and severe bleeding during delivery.

Conclusion

Commencement of early breastfeeding was associated with the proportion of mothers who fully breastfed their infants up to four months. Early breastfeeding, especially within two hours, is recommended for child and maternal health.     

Breastfeeding Progression in Preterm Infants Is Influenced by Factors in Infants,Mothers and Clinical Practice: The Results of a National Cohort Study with High Breastfeeding Initiation Rates

Background and Aim

Many preterm infants are not capable of exclusive breastfeeding from birth. To guide mothers in breastfeeding, it is important to know when preterm infants can initiate breastfeeding and progress. The aim was to analyse postmenstrual age (PMA) at breastfeeding milestones in different preterm gestational age (GA) groups, to describe rates of breastfeeding duration at pre-defined times, as well as analyse factors associated with PMA at the establishment of exclusive breastfeeding.

Methods

The study was part of a prospective survey of a national Danish cohort of preterm infants based on questionnaires and structured telephone interviews, including 1,221 mothers and their 1,488 preterm infants with GA of 24–36 weeks.

Results

Of the preterm infants, 99% initiated breastfeeding and 68% were discharged exclusively breastfed. Breastfeeding milestones were generally reached at different PMAs for different GA groups, but preterm infants were able to initiate breastfeeding at early times, with some delay in infants less than GA 32 weeks. Very preterm infants had lowest mean PMA (35.5 weeks) at first complete breastfeed, and moderate preterm infants had lowest mean PMA at the establishment of exclusive breastfeeding (36.4 weeks). Admitting mothers to the NICU together with the infant and minimising the use of a pacifier during breastfeeding transition were associated with 1.6 (95% CI 0.4–2.8) and 1.2 days (95% CI 0.1–2.3) earlier establishment of exclusive breastfeeding respectively. Infants that were small for gestational age were associated with 5.6 days (95% CI 4.1–7.0) later establishment of exclusive breastfeeding.

Conclusion

Breastfeeding competence is not developed at a fixed PMA, but is influenced by multiple factors in infants, mothers and clinical practice. Admitting mothers together with their infants to the NICU and minimising the use of pacifiers may contribute to earlier establishment of exclusive breastfeeding.     

IL-12, IFN-gamma, and T cell proliferation to measles in immunized infants

Measles infection in infants is associated with severe complications, and secondary infections are attributed to generalized immunosuppression. Measles binding to its monocyte receptor down-regulates IL-12 which is expected to diminish Th1-like cytokine responses, including IFN-gamma. Whether young infants can be immunized effectively against measles is an important public health issue. We evaluated Ag-specific IL-12, IFN-gamma, and T cell responses of infants at 6 (n = 60), 9 (n = 46), or 12 mo (n = 56) of age and 29 vaccinated adults. IL-12 and IFN-gamma release by PBMC stimulated with measles Ag increased significantly after measles immunization in infants. IL-12 and IFN-gamma concentrations were equivalent in younger and older infants, but IL-12 concentrations were significantly lower in infants than in adults (p = 0.04). IL-12 production by monocytes was down-regulated by measles; the addition of recombinant human IL-12 enhanced IFN-gamma production by PBMC stimulated with measles Ag, but infant T cells released significantly less IFN-gamma than adult T cells under this condition. Of particular interest, the presence of passive Abs to measles had no effect on the specific T cell proliferation or IFN-gamma production after measles stimulation. Cellular immunity to measles infection and vaccination may be limited in infants compared with adults as a result of less effective IFN-gamma and IL-12 production in response to measles Ags. These effects were not exaggerated in younger infants compared with effects in infants who were immunized at 12 mo. In summary, infant T cells were primed with measles Ag despite the presence of passive Abs, but their adaptive immune responses were limited compared with those of adults.     

Duration,Pattern of Breastfeeding and Postnatal Transmission of HIV: Pooled Analysis of Individual Data from West and South African Cohorts

Background

Both breastfeeding pattern and duration are associated with postnatal HIV acquisition; their relative contribution has not been reliably quantified.

Methodology and Principal Findings

Pooled data from 2 cohorts: in urban West Africa where breastfeeding cessation at 4 months was recommended but exclusive breastfeeding was rare (Ditrame Plus, DP); in rural South Africa where high rates of exclusive breastfeeding were achieved, but with longer duration (Vertical Transmission Study, VTS). 18-months HIV postnatal transmission (PT) was estimated by Kaplan-Meier in infants who were HIV negative, and assumed uninfected, at age >1 month. Censoring with (to assess impact of mode of breastfeeding) and without (to assess effect of breastfeeding duration) breastfeeding cessation considered as a competing event. Of 1195 breastfed infants, not HIV-infected perinatally, 38% DP and 83% VTS children were still breastfed at age 6 months. By age 3 months, 66% of VTS children were exclusively breastfed since birth and 55% of DP infants predominantly breastfed (breastmilk+water-based drinks). 18-month PT risk (95%CI) in VTS was double that in DP: 9% (7–11) and 5% (3–8), respectively (p = 0.03). However, once duration of breastfeeding was allowed for in a competing risk analysis assuming that all children would have been breastfed for 18-month, the estimated PT risk was 16% (8–28) in DP and 14% (10–18) in VTS (p = 0.32). 18-months PT risk was 3.9% (2.3–6.5) among infants breastfed for less than 6 months, and 8.7% (6.8–11.0) among children breastfed for more than 6 months; crude hazard ratio (HR): 2.1 (1.2–3.7), p = 0.02; adjusted HR 1.8 (0.9–3.4), p = 0.06. In individual analyses of PT rates for specific breastfeeding durations, risks among children exclusively breastfed were very similar to those in children predominantly breastfed for the same period. Children exposed to solid foods during the first 2 months of life were 2.9 (1.1–8.0) times more likely to be infected postnatally than children never exposed to solids this early (adjusted competing risk analysis, p = 0.04).

Conclusions

Breastfeeding duration is a major determinant of postnatal HIV transmission. The PT risk did not differ between exclusively and predominantly breastfed children; the negative effect of mixed breastfeeding with solids on PT were confirmed.     

Determinants of breastfeeding initiation among mothers in Kuwait

Background

Exclusive breastfeeding is recommended as the optimal way to feed infants for the first six months of life. While overall breastfeeding rates are high, exclusive breastfeeding is relatively uncommon among Middle Eastern women. The objective of this study was to identify the incidence of breastfeeding amongst women in the six governorates of Kuwait and the factors associated with the initiation of breastfeeding.

Methods

A sample of 373 women (aged 17-47 years), recruited shortly after delivery from four hospitals in Kuwait, completed a structured, interviewer-administered questionnaire. Multivariate logistic regression analysis was used to identify those factors independently associated with the initiation of breastfeeding.

Results

In total, 92.5% of mothers initiated breastfeeding and at discharge from hospital the majority of mothers were partially breastfeeding (55%), with only 30% of mothers fully breastfeeding. Prelacteal feeding was the norm (81.8%) and less than 1 in 5 infants (18.2%) received colostrum as their first feed. Only 10.5% of infants had been exclusively breastfed since birth, the remainder of the breastfed infants having received either prelacteal or supplementary infant formula feeds at some time during their hospital stay. Of the mothers who attempted to breastfeed, the majority of women (55.4%) delayed their first attempt to breastfeed until 24 hours or more after delivery. Breastfeeding at discharge from hospital was positively associated with paternal support for breastfeeding and negatively associated with delivery by caesarean section and with the infant having spent time in the Special Care Nursery.

Conclusions

The reasons for the high use of prelacteal and supplementary formula feeding warrant investigation. Hospital policies and staff training are needed to promote the early initiation of breastfeeding and to discourage the unnecessary use of infant formula in hospital, in order to support the establishment of exclusive breastfeeding by mothers in Kuwait.     

Increased synovial fluid levels of interleukin-12, sCD25 and sTNF-RII/sTNF-RI ratio delineate a cytokine pattern characteristic of immune arthropathies

The assessment of cytokines and their soluble receptors in the synovial fluid (SF) of inflammatory arthropathies may be useful in studying pathogenetic and immunoregulatory mechanisms underlying different diseases. The aim of this work was to study the cytokine network occurring in inflammatory arthropathies and to identify a cytokine profile which is characteristic of an immune-mediated synovitis. Levels of IL-12, as well as IL-4, IL-8, IL-10, IFN-gamma, sCD25, TNF-alpha and its soluble receptors were measured in the SF of various arthropathies, i.e. non-inflammatory arthropathies: "control" meniscus pathology (n = 21), osteoarthritis (n = 22) and chronic crystal arthritis (n = 9); a non-immune inflammatory arthropathy: acute crystal arthritis (n = 11); 2 immune inflammatory arthropathies: reactive arthritis (ReA) (n = 23) and rheumatoid arthritis (RA) (n = 44). SF levels of IL-10, TNF-alpha and sTNF-RII were found to be increased in the three inflammatory arthropathies compared to the "control" meniscus group. Within the inflammatory group, acute crystal arthritis was characterized by a significantly higher sTNF-RI/TNF-alpha ratio and ReA by a significantly lower sTNF-RII/TNF-alpha ratio compared to the two other diseases. The two immune arthropathies, RA and ReA, were characterized by increased SF levels of IL-12, sCD25 and of the sTNF-RII/sTNF-RI ratio. ReA differed however from RA by showing lower IL-8 and IL-4 levels, higher IFN-gamma levels and a higher IL-12/IL-10 ratio, suggesting a more prevalent Th1 profile in ReA SF. Our data indicate that the measurement of SF cytokines and soluble receptors may discriminate between each inflammatory arthropathy and might be useful in clinical practice.     

Factors associated with exclusive breastfeeding practices among mothers in Goba district,south east Ethiopia: a cross-sectional study

Background

Exclusive breastfeeding is defined as feeding infants only breast milk, be it directly from breast or expressed, with no addition of any liquid or solids apart from drops or syrups consisting of vitamins, mineral supplements or medicine, and nothing else. Several studies have shown that exclusive breastfeeding for the first six months plays a great role in preventing morbidity and mortality. However, in Ethiopia a large portion of infants are not exclusively breastfed according to the infant feeding recommendations. Understanding the factors that influence exclusive breastfeeding is crucial to promoting the practice. This study was carried out to identify factors predicting exclusive breastfeeding among mothers in Bale Goba district, south east Ethiopia.

Methods

A community-based cross-sectional study was conducted from March to February 2010 involving both quantitative and qualitative data. A total of 608 mothers were selected randomly. A convenience sampling technique was used to generate the qualitative data. The qualitative data were analyzed using thematic frameworks. A multivariable logistic regression analysis was used to identify independent predictors of exclusive breastfeeding after controlling for background variables.

Results

The prevalence of exclusive breastfeeding in the last 24?hours preceding the survey was 71.3%. The median duration of exclusive breastfeeding was three months and mean frequency of breastfeeding was six times per day. Being unemployed [AOR: 10.4 (95% CI: 1.51, 71.50)] and age of infants of less than two months [AOR: 5.6 (95% CI: 2.28, 13.60)] were independently associated with exclusive breastfeeding.

Conclusions

A large proportion of infants are not exclusively breastfed during the first 6?months, despite what is recommended in the national and global infant and young child feeding (IYCF) guidelines. Employed mothers were less likely to practice exclusive breastfeeding, implying the need for promoting workplace breastfeeding practices and creating an enabling environment for exclusive breastfeeding. Extensions of maternity leave up to the first six month of child’s age to achieve optimal level of exclusive breastfeeding practices should also be looked into as an alternative solution.

     

Local interleukin-10 production during respiratory syncytial virus bronchiolitis is associated with post-bronchiolitis wheeze

Background

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Following RSV bronchiolitis, 50% of children develop post-bronchiolitis wheeze (PBW). Animal studies have suggested that interleukin (IL)-10 plays a critical role in the pathogenesis of RSV bronchiolitis and subsequent airway hyperresponsiveness. Previously, we showed that ex vivo monocyte IL-10 production is a predictor of PBW. Additionally, heterozygosity of the single-nucleotide polymorphism (SNP) rs1800872 in the IL10 promoter region was associated with protection against RSV bronchiolitis.

Methods

This study aimed to determine the in vivo role of IL-10 in RSV pathogenesis and recurrent wheeze in a new cohort of 235 infants hospitalized for RSV bronchiolitis. IL-10 levels in nasopharyngeal aspirates (NPAs) were measured at the time of hospitalization and the IL10 SNP rs1800872 genotype was determined. Follow-up data were available for 185 children (79%).

Results

Local IL-10 levels during RSV infection turned out to be higher in infants that later developed physician diagnosed PBW as compared to infants without PBW in the first year after RSV infection (958 vs 692 pg/ml, p = 0.02). The IL10 promoter SNP rs1800872 was not associated with IL-10 concentration in NPAs.

Conclusion

The relationship between high local IL-10 levels during the initial RSV infection and physician diagnosed PBW provides further evidence of the importance of the IL-10 response during RSV bronchiolitis.     

Exclusive Breastfeeding,Diarrhoeal Morbidity and All-Cause Mortality in Infants of HIV-Infected and HIV Uninfected Mothers: An Intervention Cohort Study in KwaZulu Natal,South Africa

Introduction

Antiretroviral drug interventions significantly reduce the risk of HIV transmission to infants through breastfeeding. We report diarrhoea prevalence and all-cause mortality at 12 months of age according to infant feeding practices, among infants born to HIV-infected and uninfected mothers in South Africa.

Methods

A non-randomised intervention cohort study that followed both HIV-infected and HIV-uninfected mothers and their infants until 18 months of age. Mothers were supported in their infant feeding choice. Detailed morbidity and vital status data were collected over the first year. At the time, only single dose nevirapine was available to prevent mother-to-child transmission of HIV.

Results

Among 2,589 infants, detailed feeding data and vital status were available for 1,082 HIV-exposed infants and 1,155 HIV non-exposed infants. Among exclusively breastfed (EBF) infants there were 9.4 diarrhoeal days per 1,000 child days (95%CI. 9.12-9.82) while among infants who were never breastfed there were 15.6 diarrhoeal days per 1,000 child days (95%CI. 14.62-16.59). Exclusive breastfeeding was associated with fewer acute, persistent and total diarrhoeal events than mixed or no breastfeeding in both HIV-exposed infants and also infants of HIV uninfected mothers. In an adjusted cox regression analysis, the risk of death among all infants by 12 months of age was significantly greater in those who were never breastfed (aHR 3.5, p<0.001) or mixed fed (aHR 2.65, p<0.001) compared with those who were EBF. In separate multivariable analyses, infants who were EBF for shorter durations had an increased risk of death compared to those EBF for 5-6 months [aHR 2.18 (95% CI, 1.56-3.01); p<0.001].

Discussion

In the context of antiretroviral drugs being scaled-up to eliminate new HIV infections among children, there is strong justification for financial and human resource investment to promote and support exclusive breastfeeding to improve HIV-free survival of HIV-exposed and non-exposed infants. Trial Registration: ClinicalTrials.gov NCT01948557; http://clinicaltrials.gov/     

Impact of Withholding Breastfeeding at the Time of Vaccination on the Immunogenicity of Oral Rotavirus Vaccine—A Randomized Trial

BackgroundBreast milk contains anti-rotavirus IgA antibodies and other innate immune factors that inhibit rotavirus replication in vitro. These factors could diminish the immunogenicity of oral rotavirus vaccines, particularly if breastfeeding occurs close to the time of vaccine administration.MethodsBetween April 2011 and November 2012, we conducted an open label, randomized trial to compare the immunogenicity of Rotarix (RV1) in infants whose breastfeeding was withheld one hour before through one hour after vaccination with that in infants breastfed at the time of vaccination. The trial was conducted in the peri-urban area of Ibrahim Hyderi in Karachi, Pakistan. Both groups received three doses of RV1 at 6, 10 and 14 weeks of age. Seroconversion (anti-rotavirus IgA antibodies ≥20 U/mL in subjects seronegative at 6 weeks of age) following three vaccine doses (6, 10 and 14 weeks) was determined at 18 weeks of age (primary objective) and seroconversion following two doses (6 and 10 weeks) was determined at 14 weeks of age (secondary objective).ResultsFour hundred eligible infants were randomly assigned in a 1:1 ratio between the withholding breastfeeding and immediate breastfeeding arms. Overall, 353 (88.3%) infants completed the study according to protocol; 181 in the withholding breastfeeding group and 172 in the immediate breastfeeding group. After three RV1 doses, anti-rotavirus IgA antibody seroconversion was 28.2% (95% CI: 22.1; 35.1) in the withholding arm and 37.8% (95% CI: 30.9; 45.2) in the immediate breastfeeding arm (difference: -9.6% [95% CI: -19.2; 0.2] p=0.07). After two doses of RV1, seroconversion was 16.6% (95% CI: 11.9; 22.7) in the withholding arm and 29.1% (95% CI: 22.8, 36.3) in the immediate breastfeeding arm (difference: -12.5% [95% CI: -21.2,-3.8] p=0.005).ConclusionsWithholding breastfeeding around the time of RV1 vaccine administration did not lead to increased anti-rotavirus IgA seroconversion compared with that seen with a breastfeed at the time of vaccination. On the contrary, IgA seroconversion in infants immediately breastfed tended to be higher than in those withheld from a feeding. Our findings suggest that breastfeeding should be continued adlib around the time of rotavirus vaccination and withholding breastfeeding at that time is unlikely to improve the vaccine immunogenicity.

Trial Registration

ClinicalTrials.gov NCT01199874     

Enhanced pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of interleukin-4 (IL-4) and IL-10.

In previous studies, children immunized with a formalin-inactivated respiratory syncytial virus vaccine (FI-RSV) developed severe pulmonary disease with greater frequency than did controls during subsequent natural RSV infection. In earlier efforts to develop an animal model for this phenomenon, extensive pulmonary histopathology developed in FI-RSV-immunized cotton rats and mice subsequently challenged with RSV. In mice, depletion of CD4+ T cells at the time of RSV challenge completely abrogated this histopathology. Furthermore, the predominant cytokine mRNA present in lungs of FI-RSV-immunized mice during subsequent infection with RSV was that characteristically secreted by Th2 T cells, namely interleukin-4 (IL-4). In the present studies, we sought to determine the relative contributions of gamma interferon (IFN-gamma), IL-2, IL-4, and IL-10 to the lymphocytic infiltration into the lungs observed following RSV challenge of mice previously immunized with FI-RSV. Mice previously immunized with FI-RSV or infected with RSV were depleted of IFN-gamma, IL-2, IL-4, or IL-10 immediately before RSV challenge, and the magnitude of inflammatory cell infiltration around bronchioles and pulmonary blood vessels was quantified. The phenomenon of pulmonary-histopathology potentiation by FI-RSV was reproduced in the present study, thereby allowing us to investigate the effect of cytokine depletion on the process. Simultaneous depletion of both IL-4 and IL-10 completely abrogated pulmonary histopathology in FI-RSV-immunized mice. Depletion of IL-4 alone significantly reduced bronchiolar, though not perivascular, histopathology. Depletion of IL-10 alone had no effect. Depletion of IFN-gamma, IL-2, or both together had no effect on the observed histopathology. These data indicate that FI-RSV immunization primes for a Th2-, IL-4-, and IL-10-dependent inflammatory response to subsequent RSV infection. It is possible that this process played a role in enhanced disease observed in infants and children immunized with FI-RSV.     

Reasons given by mothers for discontinuing breastfeeding in Iran

Background

We have previously shown that in Iran, only 28% of infants were exclusively breastfed at six months, despite a high prevalence of breastfeeding at two years of age. The primary aim of this study was to investigate the reasons women discontinued exclusive breastfeeding.

Method

This retrospective study was based on questionnaires and interviews with 63,071 mothers of infants up to 24?months of age, divided into two populations: infants younger than six months and six months or older. The data were collected in 2005?C2006 from all 30 provinces of Iran.

Results

Only 5.3% of infants less than six months of age stopped breastfeeding (mean age of 3.2?months); more commonly in urban than rural areas. The most frequently cited reasons mothers gave for discontinuing exclusive breastfeeding were physicians?? recommendation (54%) and insufficient breast milk (self-perceived or true, 28%). Breastfeeding was common after six months of age: only 11% of infants discontinued breastfeeding, at a mean of 13.8?months. The most common reason for discontinuation at this age was insufficient breast milk (self-perceived or true, 45%). Maternal illness or medication (10%), infant illness (6%), and return to work (3%) were uncommon causes. Use of a pacifier was correlated with breastfeeding discontinuation. Maternal age and education was not associated with duration of breastfeeding. Multivariate analysis showed that using a pacifier and formula or other bottle feeding increased the risk of early cessation of breastfeeding.

Conclusions

Physicians and other health professionals have an important role to play in encouraging and supporting mothers to maintain breastfeeding.     

Autocrine regulation of pulmonary inflammation by effector T-cell derived IL-10 during infection with respiratory syncytial virus

Respiratory syncytial virus (RSV) infection is the leading viral cause of severe lower respiratory tract illness in young infants. Clinical studies have documented that certain polymorphisms in the gene encoding the regulatory cytokine IL-10 are associated with the development of severe bronchiolitis in RSV infected infants. Here, we examined the role of IL-10 in a murine model of primary RSV infection and found that high levels of IL-10 are produced in the respiratory tract by anti-viral effector T cells at the onset of the adaptive immune response. We demonstrated that the function of the effector T cell -derived IL-10 in vivo is to limit the excess pulmonary inflammation and thereby to maintain critical lung function. We further identify a novel mechanism by which effector T cell-derived IL-10 controls excess inflammation by feedback inhibition through engagement of the IL-10 receptor on the antiviral effector T cells. Our findings suggest a potentially critical role of effector T cell-derived IL-10 in controlling disease severity in clinical RSV infection.