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Breastfeeding protective against Hib

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Pediatr Res. 2009 Nov;66(5):565-70.

Breast-feeding is associated with a reduced frequency of acute otitis media and high serum antibody levels against NTHi and outer membrane protein vaccine antigen candidate P6.

Sabirov A, Casey JR, Murphy TF, Pichichero ME.

Department of Microbiology/Immunology, University of Rochester, Rochester, New York 14627, USA.


Nontypeable Haemophilus influenzae (NTHi) causes acute otitis media (AOM) in infants. Breast-feeding protects against AOM and/or nasopharyngeal (NP) colonization; however, the mechanism of protection is incompletely understood. Children with AOM and healthy children were studied according to feeding status: breastfed,breast/formula fed, or formula fed. Cumulative episodes of AOM, ELISA titers of serum IgG antibodies to whole-cell NTHi and vaccine candidate outer membrane protein P6, bactericidal titers of serum and NP colonization by NTHi were assessed. A lower incidence of AOM was found in breast- versus formula-fed children. Levels of specific serum IgG antibody to NTHi and P6 were highest in breast-fed, intermediate in breast/formula fed, and lowest in formula-fed infants. Serum IgG antibody to P6 correlated with bactericidal activity against NTHi. Among children with AOM, the prevalence of NTHi in the NP was lower in breast- versus nonbreast-fed infants. We conclude that breast-feeding shows an association with higher levels of antibodies to NTHi and P6, suggesting that breast-feeding modulates the serum immune response to NTHi and P6. Higher serum IgG might facilitate protection against AOM and NP colonization in breast-fed children.

PMID: 19581824 [PubMed - indexed for MEDLINE]PMCID: PMC2783794 Free PMC Article


Bull World Health Organ. 2008 May;86(5):408-16.

Epidemiology and etiology of childhood pneumonia.

Rudan I, Boschi-Pinto C, Biloglav Z, Mulholland K, Campbell H.

Croatian Centre for Global Health, University of Split Medical School, Split, Croatia.


Childhood pneumonia is the leading single cause of mortality in children aged less than 5 years. The incidence in this age group is estimated to be 0.29 episodes per child-year in developing and 0.05 episodes per child-year in developed countries. This translates into about 156 million new episodes each year worldwide, of which 151 million episodes are in the developing world. Most cases occur in India (43 million), China (21 million) and Pakistan (10 million), with additional high numbers in Bangladesh, Indonesia and Nigeria (6 million each). Of all community cases, 7-13% are severe enough to be life-threatening and require hospitalization. Substantial evidence revealed that the leading risk factors contributing to pneumonia incidence are lack of exclusive breastfeeding, undernutrition, indoor air pollution, low birth weight, crowding and lack of measles immunization. Pneumonia is responsible for about 19% of all deaths in children aged less than 5 years, of which more than 70% take place in sub-Saharan Africa and south-east Asia. Although based on limited available evidence, recent studies have identified Streptococcus pneumoniae, Haemophilus influenzae and respiratory syncytial virus as the main pathogens associated with childhood pneumonia.

PMID: 18545744 [PubMed - indexed for MEDLINE]PMCID: PMC2647437Free PMC Article


Vaccine. 2007 Feb 9;25(8):1497-502. Epub 2006 Oct 30.

Breastfeeding enhances the antibody response to Hib and Pneumococcal serotype 6B and 14 after vaccination with conjugate vaccines.

Silfverdal SA, Ekholm L, Bodin L.

Department of Paediatrics, Orebro University Hospital, Orebro, Sweden.


BACKGROUND: This study was performed in order to investigate the relationship between breastfeeding and the antibody response after vaccination with conjugate vaccines against Hib and pneumococcal diseases.

METHODS: This was an open non-randomised multi-centre study enrolling 101 healthy Swedish infants. PncCRM was administered concomitantly with DTaP/IPV/Hib at 3, 5, and 12 months at separate site. Duration of breastfeeding was calculated for days of almost exclusive as well as of total (any form of) breastfeeding.

RESULTS: At 13 months of age 6 out of 83 children did not reach 0.2mug/ml against serotype 6B, and five of these were breastfed less than 90 days (Fisher's Exact test, P=0.011). Four children did not reach 1mug/ml against Hib and all those were breastfed less than 90 days (Fisher's Exact test, P=0.008). One month after the second dose, at 6 months of age, children breastfed 90 days or more showed significantly higher GMC against serotype 14 (P=0.003).

CONCLUSION: This study indicates that children exclusively breastfed 90 days or more might get a better serological protection against Hib, and the pneumococcal serotypes 6B and 14 after vaccination, compared to children less breastfed.

PMID: 17097198 [PubMed - indexed for MEDLINE]


Paediatr Respir Rev. 2005 Jun;6(2):88-93.

The burden of pneumonia in children: an Asian perspective.

Singh V.

Lady Hardinge Medical College, Associated K S Children's Hospital, Bangla Sahib Lane, New Delhi, India.


Pneumonia results in two million deaths each year among children worldwide (20% of all child deaths), 70% of them in Africa and South-east Asia. Most countries in Africa and Asia record 2-10 times more children with pneumonia (7-40/100 annually) than in the USA. Apart from resource constraints and an overburdened health system, there is lack of uniformity in defining pneumonia. Most nations employ a WHO standard case management protocol using age-specific cut-offs for increased respiratory rates and chest in-drawing for a clinical definition of pneumonia. The limited data available on the causative organisms have identified Streptococcus pneumoniae, Haemophilus influenzae and viruses such as respiratory syncytial virus (RSV), influenza, para influenza and adenoviruses as the major pathogens. Measles infection increases pneumonia morbidity and mortality. Low birth weight, under-nutrition, hypovitaminosis A, zinc deficiency, lack of breastfeeding, air pollution (including environmental tobacco smoke) and over-crowding increase the risk for pneumonias in children. Standard case management protocols used for acute respiratory infections (ARIs) in these countries have brought down the disease burden but an improvement in the diagnostic algorithm is needed to appropriately recognise those with associated wheeze. Research is needed to find effective and affordable preventive strategies.

PMID: 15911453 [PubMed - indexed for MEDLINE]


Eur J Epidemiol. 2003;18(9):917-22.

Risk of Haemophilus influenzae type b meningitis in Polish children varies directly with number of siblings: possible implications for vaccination strategies.

Zielinski A, Kwon CB, Tomaszunas-Blaszczyk J, Magdzik W, Bennett JV.

National Research Center of Public Health, National Institute of Hygiene, Warsaw, Poland.


BACKGROUND: In the absence of an effective vaccine, Haemophilus influenzae type b (Hib) meningitis has frequently been found to be the most common bacterial meningitis among children less than or equal to 5 years of age. This study was conducted prior to the introduction of Hib vaccine in Poland, and is the first case-control study of Hib meningitis in this country.

METHODS: A 1:3 matched case-control study was nested within a population-based surveillance study of Hib meningitis in children less than or equal to 5 years old in Poland. Controls were matched on the case's age at onset of disease and immunization center.

RESULTS: Having one or more siblings is a highly significant risk factor for Hib meningitis and, under the rare disease assumption, risk increases linearly with the increase in the number of siblings. The size of the living area of the home was not itself a significant risk factor for disease. Breast-feeding was not protective in contrast to previous studies. Childcare outside of the home was a significant risk factor for Hib meningitis especially among children greater than 16 months of age, whereas the effect of sibling number on Hib meningitis was much greater among the younger children.

CONCLUSION: Risk of Hib meningitis approximately doubles for every unit increase in the number of siblings. Routine vaccination of Polish infants who have two or more siblings could potentially prevent half of the Hib meningitis cases.

PMID: 14561054 [PubMed - indexed for MEDLINE]

Contrary results


Pediatr Infect Dis J. 2002 Sep;21(9):816-21.

Long term enhancement of the IgG2 antibody response to Haemophilus influenzae type b by breast-feeding.

Silfverdal SA, Bodin L, Ulanova M, Hahn-Zoric M, Hanson LA, Olcen P.

Department of Pediatric, Orebro University Hospital, Orebro, Sweden.


SUBJECTS: Sets of sera were obtained from 30 children <6 years of age with invasive type b (Hib) infection and their mothers. Duration and mode of breast-feeding were monitored. Titers of IgG1, IgG2, IgA and IgM antibodies against Hib capsular polysaccharide were determined in sera taken during the acute illness and during early and late convalescence.

RESULTS: Children 18 months or older with longer durations of exclusive breast-feeding (13 weeks or more; mean, 19.3 weeks) had higher Hib antibody concentrations of the IgG1, IgG2, IgA and IgM isotypes than those with a shorter duration of exclusive breast-feeding (<13 weeks; mean, 5.4 weeks). The difference was greatest for the IgG2 isotype. In regression analyses the association between the duration of exclusive breast-feeding and the anti-Hib IgG2 concentration was significant when breast-feeding, type of Hib infection, maternal Hib antibody titer and age were used as explanatory factors. In the group of 14 children <18 months of age no significant differences were noted.

DISCUSSION: This study indicates the presence of a long lasting enhancing effect of breast-feeding on the antibody response to Hib in children, in particular on IgG2 Hib antibody production. This may result from the content in the milk of IFN-gamma and IFN-gamma-producing cells and possibly other factors, which can support IgG2 antibody production.

PMID: 12352801 [PubMed - indexed for MEDLINE]


Acta Paediatr Suppl. 1999 Aug;88(430):42-6.

Human milk and host defence: immediate and long-term effects.

Hanson LA.

Department of Clinical Immunology, Göteborg University, Sweden.


Convincing studies demonstrate significant protection during breastfeeding against diarrhoea, respiratory tract infections, otitis media, bacteraemia, bacterial meningitis, botulism, urinary tract infections and necrotizing enterocolitis. There is also good evidence for enhanced protection for years after the termination of breastfeeding against Haemophilus influenzae type b infections, otitis media, diarrhoea, respiratory tract infections and wheezing bronchitis. In some reports breastfeeding has also improved vaccine responses. Several studies show that milk may actively stimulate the immune system of the offspring via transfer of anti-idiotypic antibodies and lymphocytes. This may explain why breastfeeding diminishes the risk of developing coeliac disease. Some investigations suggest that there may also be a similar effect on allergic diseases and autoimmune diseases, as well as inflammatory bowel diseases and certain tumours. This needs to be confirmed.

PMID: 10569222 [PubMed - indexed for MEDLINE]


Int J Epidemiol. 1999 Feb;28(1):152-6.

Protective effect of breastfeeding: an ecologic study of Haemophilus influenzae meningitis and breastfeeding in a Swedish population.

Silfverdal SA, Bodin L, Olcén P.

Department of Paediatrics, Orebro Medical Center Hospital, Sweden.


BACKGROUND: In Orebro County, Sweden, a 2.5-fold increase in the incidence of Haemophilus influenzae (HI) meningitis was found between 1970 and 1980. In a case-control study of possible risk factors for invasive HI infection conducted in the same area, 1987-1992, breastfeeding was found to be a strong protective factor.

MATERIAL AND METHODS: In order to study the relation between incidence rates of HI meningitis between 1956-1992 and breastfeeding rates in the population an ecologic study was performed.

RESULTS: A strong (negative) correlation between breastfeeding and incidence of HI infection 5 to 10 years later (rho(xy) (s) approximately -0.6) was seen, whereas no relation seems to exist for the time lag 15 years and beyond. The correlation for contemporary data was intermediate. There were similar results for the breastfeeding proportions at 2, 4 as well as 6 months of age.

DISCUSSION: Our ecologic data are consistent with results from our case-control study. The time-lag for the delayed effect on the population level could be estimated although sparse data make the estimates vulnerable to sampling fluctuations. Limitations with ecologic studies are discussed.

CONCLUSION: There seems to be an association between high breastfeeding rate in the population and a reduced incidence of HI meningitis 5 to 10 years later. These results do have implications on strategies for breastfeeding promotion, especially in countries where Hib vaccination is too costly and not yet implemented.

PMID: 10195681 [PubMed - indexed for MEDLINE]Free Article


J Trop Pediatr. 1999 Jun;45(3):173-6.

Isolation of respiratory bacterial pathogens from the throats of healthy infants fed by different methods.

Hokama T, Yara A, Hirayama K, Takamine F.

Maternal and Child Health Department, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.


Most bacterial infections are caused by organisms that have already colonized the host. Bacterial attachment to pharyngeal cells and proliferation may be necessary to infect the lower respiratory tract or middle ear. We investigated the incidence of pathogenic bacteria isolated from the throat of healthy infants with different feeding methods. The protecting role of breastmilk is also discussed. The incidence of respiratory bacterial pathogens isolated from the oropharynx of 113 normal infants with different feeding methods was investigated. Group A beta haemolytic Streptococcus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were selected as respiratory bacterial pathogens. No respiratory bacterial pathogens were detected in breastfed and mixed-fed infants. Haemophilus influenzae and Moraxella catarrhalis were isolated from the oropharynx of formula-fed infants. The incidence of respiratory bacterial pathogens did differ among infants with different feeding methods. These results suggest that breastmilk may inhibit the colonization by respiratory bacterial pathogens of the throat of infants, by enhancing mucosal immunity against respiratory tract infection.

PMID: 10401200 [PubMed - indexed for MEDLINE]


Ann Allergy Asthma Immunol. 1998 Dec;81(6):523-33; quiz 533-4, 537.

Breastfeeding provides passive and likely long-lasting active immunity.

Hanson LA.

Department of Clinical Immunology, Göteborg University, Sweden.

Erratum in:

  • Ann Allergy Asthma Immunol 1999 May;82(5):478.


OBJECTIVES: The reader of this review will learn about the mechanisms through which breastfeeding protects against infections during and most likely after lactation, as well as possibly against certain immunologic diseases, including allergy.

DATA SOURCES: I have followed the literature in the area closely for the last 30 to 40 years and have made repeated literature searches through MEDLINE, most recently in 1998. Textbooks and peer-reviewed journals have been sought for, as well as books representing meeting reports in English, French, German, and Spanish.

RESULTS: Human milk protects against infections in the breastfed offspring mainly via the secretory IgA antibodies, but also most likely via several other factors like the bactericidal lactoferrin. It is striking that the defense factors of human milk function without causing inflammation, some components are even directly anti-inflammatory. Protection against infections has been well evidenced during lactation against, e.g., acute and prolonged diarrhea, respiratory tract infections, otitis media, urinary tract infection, neonatal septicemia, and necrotizing enterocolitis. There is also interesting evidence for an enhanced protection remaining for years after lactation against diarrhea, respiratory tract infections, otitis media, Haemophilus influenzae type b infections, and wheezing illness. In several instances the protection seems to improve with the duration of breastfeeding. Some, but not all studies have shown better vaccine responses among breastfed than non-breastfed infants. A few factors in milk like anti-antibodies (anti-idiotypic antibodies) and T and B lymphocytes have in some experimental models been able to transfer priming of the breastfed offspring. This together with transfer of numerous cytokines and growth factors via milk may add to an active stimulation of the infant's immune system. Consequently, the infant might respond better to both infections and vaccines. Such an enhanced function could also explain why breastfeeding may protect against immunologic diseases like coeliac disease and possibly allergy. Suggestions of protection against autoimmune diseases and tumors have also been published, but need confirmation.

CONCLUSIONS: Breastfeeding may, in addition to the well-known passive protection against infections during lactation, have a unique capacity to stimulate the immune system of the offspring possibly with several long-term positive effects.

PMID: 9892025 [PubMed - indexed for MEDLINE]


Int J Epidemiol. 1997 Apr;26(2):443-50.

Protective effect of breastfeeding on invasive Haemophilus influenzae infection: a case-control study in Swedish preschool children.

Silfverdal SA, Bodin L, Hugosson S, Garpenholt O, Werner B, Esbjörner E, Lindquist B, Olcén P.

Department of Pediatrics, Orebro Medical Centre Hospital, Sweden.


BACKGROUND: In Orebro County a 2.5-fold increase in the incidence of Haemophilus influenzae (HI) meningitis was found between 1970 and 1980, an observation that initiated the present study.

MATERIALS AND METHODS: In order to search for associations between morbidity in invasive HI infection and possible risk factors, a case-control study was conducted over a 6-year period from 1987 to 1992, before general Hib vaccination was introduced in Sweden. Fifty-four cases with invasive HI infection 139 matched controls were studied for possible risk factors such as day-care outside the home, short duration of breastfeeding, passive smoking, low socioeconomic level of the household, many siblings in the family, allergy, frequent, infections, repeated antibiotic treatments and immunoglobulin deficiency.

RESULTS: Multivariate analysis showed a significant association between invasive HI infection and two independent factors, i.e. short duration (< 13 weeks) of exclusive breastfeeding, odds ratio (OR) 3.79 (95% confidence interval [CI] 1.6-8.8) and history of frequent infections, OR 4.49 (95% CI : 1.0-21.0). For the age at onset 12 months or older, the associations were stronger, OR 7.79 (95% CI : 2.4-26.6) and 5.86 (95% CI : 1.1-30.6), respectively. When breastfeeding duration in weeks was analysed as a continuous variable the OR was 0.95 (95% CI : 0.92-0.99), indicating a decreased risk with each additional week. Increased OR were observed for other risk factors as well but not of the magnitude found for short duration of breastfeeding.

DISCUSSION: The association of decreased risk for invasive HI infection and long duration of breastfeeding was persisting beyond the period of breastfeeding itself. This finding supports the hypothesis of a long-lasting protective effect of breastfeeding on the risk for invasive HI infection.

CONCLUSION: A decreased risk for invasive HI infection with long duration of breastfeeding was found. Our results do have implications for strategies in breastfeeding promotion, especially in countries where Hib vaccination is too costly and not yet implemented.

PMID: 9169183 [PubMed - indexed for MEDLINE]Free Article


J Pediatr. 1994 Feb;124(2):193-8.

Human milk secretory IgA antibody to nontypeable Haemophilus influenzae: possible protective effects against nasopharyngeal colonization.

Harabuchi Y, Faden H, Yamanaka N, Duffy L, Wolf J, Krystofik D.

Department of Pediatrics, School of Medicine, State University of New York at Buffalo.


Sixty-eight children fed human milk were followed prospectively from birth to 12 months of age to assess the effect of milk antibody on nasopharyngeal colonization. Human milk secretory IgA antibody to P6, a highly conserved outer membrane protein of nontypeable Haemophilus influenzae, was measured with the use of an enzyme-linked immunosorbent assay. Nasopharyngeal colonization with nontypeable H. influenzae and the occurrence of otitis media were determined. Nasopharyngeal colonization was found in 22 children (32%), and 39 children (57%) had otitis media. Frequency of isolation of nontypeable H. influenzae was directly related to episodes of otitis media (r = 0.35; p = 0.001). The level of human milk anti-P6 secretory IgA antibody was inversely related to frequency of isolation of the organism (r = -0.27; p = 0.026). The average antibody level, expressed as nanograms per 0.1 mg total secretory IgA, in human milk fed to children with no colonization of nontypeable H. influenzae was significantly higher than in milk fed to children in whom colonization occurred on multiple occasions (156 +/- 120 vs 69 +/- 50; p = 0.013). Prevention of colonization was most evident during breast-feeding. These data suggest that the protective effects of human milk against otitis media may be due in part to inhibition of nasopharyngeal colonization with nontypeable H. influenzae by specific secretory IgA antibody.

PMID: 8301421 [PubMed - indexed for MEDLINE]


Pediatr Infect Dis J. 1994 Mar;13(3):183-8.

A prospective cohort study on breast-feeding and otitis media in Swedish infants.

Aniansson G, Alm B, Andersson B, Håkansson A, Larsson P, Nylén O, Peterson H, Rignér P, Svanborg M, Sabharwal H, et al.

Department of Medical Microbiology, Lund University, Sweden.


This study analyzed the effect of breast-feeding on the frequency of acute otitis media. The protocol was designed to examine each child at 2, 6 and 10 months of age. At each visit nasopharyngeal cultures were obtained, the feeding pattern was recorded and the acute otitis media (AOM) episodes were documented. The analysis was based on 400 children from whom complete information was obtained. They represented 83% of the newborns in the study areas. By 1 year of age 85 (21%) children had experienced 111 AOM episodes; 63 (16%) had 1 and 22 (6%) had 2 or more episodes. The AOM frequency was significantly lower in the breast-fed than in the non-breast-fed children in each age group (P < 0.05). The first AOM episode occurred significantly earlier in children who were weaned before 6 months of age than in the remaining groups. The frequency of nasopharyngeal cultures positive for Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was significantly higher in children with AOM. At 4 to 7 and 8 to 12 months of age, the AOM frequency was significantly higher in children with day-care contact and siblings (P < 0.05 and < 0.01, respectively). The frequency of upper respiratory tract infections was increased in children with AOM but significantly reduced in the breast-fed group.

PMID: 8177624 [PubMed - indexed for MEDLINE]


Acta Paediatr Jpn. 1994 Oct;36(5):557-61.

Breast feeding: overview and breast milk immunology.

Hanson LA, Hahn-Zoric M, Berndes M, Ashraf R, Herias V, Jalil F, Bhutta TI, Laeeq A, Mattsby-Baltzer I.

Department of Clinical Immunology, University of Göteborg, Sweden.


The transfer of host defence capacity to the human offspring provides a remarkable model of passive transfer of immunity. In fact it may also provide an example of active immunization. The transfer of mucosal protection via breast feeding offers many additional advantages for the mother and infant. Through its contraceptive effects it increases the spacing between births, thus diminshing the infant mortality and the burden on the mother. It also enhances bonding between mother and child, it seems to increase the IQ and school result of the infant and might decrease the risk of certain malignancies and perhaps of juvenile diabetes. A fully breast-fed infant receives as much as 0.5-1 g of secretory immunoglobulin A (SIgA) antibodies daily, the predominant antibody of human milk. This can be compared to the production of some 2.5 g of SIgA per day for a 60 kg adult. These SIgA antibodies have been shown to protect against Vibrio cholerae, ETEC, Campylobacter, Shigella and Giardia. Furthermore, milk is rich in receptor analogues for certain epithelial structures which microbes need for attachment to host tissues as an initial step in infections. Thus the adherence of Haemophilus influenzae and pneumococci for example to retropharyngeal cells is efficiently inhibited by human milk. This may be one explanation for the fact that breast-fed babies have less otitis media than the non-breast-fed. Other milk factors like lysozyme and lactoferin may contribute to the host defence, but this has not yet been well defined. However, human milk also supports the well-being of the infant by being anti-inflammatory.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 7825463 [PubMed - indexed for MEDLINE]


J Clin Microbiol. 1993 Oct;31(10):2674-8.

Prevalence of bacterial respiratory pathogens in the nasopharynx in breast-fed versus formula-fed infants.

Kaleida PH, Nativio DG, Chao HP, Cowden SN.

Department of Pediatrics, University of Pittsburgh School of Medicine, Pennsylvania.


In several studies, breast-feeding has been associated with decreased frequency or duration of otitis media episodes. If a causal relationship exists, the mechanism of protection of breast-feeding has not been established. We hypothesized that infants who are breast-fed, compared with infants who are formula-fed, have a lower prevalence of nasopharyngeal colonization with the bacterial respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes) commonly isolated from the middle ear effusions of children with acute otitis media. In two private pediatric practices, we obtained specimens from the nasopharynx for culture from 211 infants at 1 month of age and from 173 of these infants at 2 months of age. A swab was left in place in the nasopharynx for 45 s and was then immediately transferred onto appropriate culture media. Exclusively breast-fed (n = 84) and exclusively formula-fed (n = 76) infants were similar regarding the number of persons in the household, the number of children in the household, the number of siblings in day care, and the proportion with a recent upper respiratory tract infection. The two groups did not differ significantly in the proportions found to have one or more respiratory pathogens at 1 month of age (10.7 versus 18.4%; P = 0.12) or 2 months of age (34.8 versus 35.1%; P = 0.57). We conclude that during the first 2 months after birth, the exclusive receipt of breast milk appears not to substantially influence the prevalence of nasopharyngeal colonization with common bacterial respiratory pathogens.

PMID: 8253964 [PubMed - indexed for MEDLINE]PMCID: PMC265971Free PMC Article

Contrary results