Inactivated influenza vaccine reduced proven influenza illness by 63% in infants up to 6 months of age and averted approximately a third of all febrile respiratory illnesses in mothers and young infants. Maternal influenza immunization is a strategy with substantial benefits for both mothers and infants. (ClinicalTrials.gov number, NCT00142389.)

BackgroundAntenatal immunization of mothers with influenza vaccine increases serum antibodies and reduces the rates of influenza illness in mothers and their infants. We report the effect of antenatal immunization on the levels of specific anti-influenza IgA levels in human breast milk. (ClinicalTrials.gov identifier NCT00142389; http://clinicaltrials.gov/ct2/show/NCT00142389).Methods and FindingsThe Mother's Gift study was a prospective, blinded, randomized controlled trial that assigned 340 pregnant Bangladeshi mothers to receive either trivalent inactivated influenza vaccine, or 23-valent pneumococcal polysaccharide vaccine during the third trimester. We evaluated breast milk at birth, 6 weeks, 6 months, and 12 months, and serum at 10 weeks and 12 months. Milk and serum specimens from 57 subjects were assayed for specific IgA antibody to influenza A/New Caledonia (H1N1) using an enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay, and for total IgA using ELISA. Influenza-specific IgA levels in breast milk were significantly higher in influenza vaccinees than in pneumococcal controls for at least 6 months postpartum (p = 0.04). Geometric mean concentrations ranged from 8.0 to 91.1 ELISA units/ml in vaccinees, versus 2.3 to 13.7 ELISA units/mL in controls. Virus neutralization titers in milk were 1.2 to 3 fold greater in vaccinees, and correlated with influenza-specific IgA levels (r = 0.86). Greater exclusivity of breastfeeding in the first 6 months of life significantly decreased the expected number of respiratory illness with fever episodes in infants of influenza-vaccinated mothers (p = 0.0042) but not in infants of pneumococcal-vaccinated mothers (p = 0.4154).ConclusionsThe sustained high levels of actively produced anti-influenza IgA in breast milk and the decreased infant episodes of respiratory illness with fever suggest that breastfeeding may provide local mucosal protection for the infant for at least 6 months. Studies are needed to determine the cellular and immunologic mechanisms of breast milk-mediated protection after antepartum immunization.Trial RegistrationClinicalTrials.gov NCT00142389

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T h e ne w e ngl a nd jou r na l o f m e dic i ne n engl j med 362;17 nejm.org april 29, 2010 1644 Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. Advisory Council on the Misuse of Drugs. Khat (qat): assess-1. ment of risk to the individual and communities in the UK. London: British Home Office, 2005. Al-Habori M. The potential adverse effects of habitual use of 2. Catha edulis (khat). Expert Opin Drug Saf 2005;4:1145-54. Al-Motarreb A, Briancon S, Al-Jaber N, et al. Khat chewing is 3. a risk factor for acute myocardial infarction: a case-control study. Br J Clin Pharmacol 2005;59:574-81. Al-Habori M, Al-Aghbari A, Al-Mamary M, Baker M. Toxico-4. logical evaluation of Catha edulis leaves: a long term feeding experiment in animals. J Ethnopharmacol 2002;83:209-17. Jones AL, Simpson KJ. Mechanisms and management of 5. hepatitis in ecstasy (MDMA) and amphetamine intoxication. Aliment Pharmacol Ther 1999;13:129-33.* Vaccinees were maternal recipients of the influenza vaccine, or their infants; results are presented for each vaccine type individually. Controls were mothers who received the control vaccine or their infants. Immunization occurred during the third trimester. Titers for infants at birth were measured in cord-serum samples. For all vaccine subtypes, the geometric mean titer was significantly lower in controls than in vaccinees (P<0.001) at delivery, birth, 10 weeks, and 20 to 26 weeks, unless otherwise indicated. CI denotes confidence interval. † The antibody titer for A/New Caledonia (H1N1) was greater among controls than among vaccinees (P = 0.03). ‡ The antibody titer for B/Hong Kong did not differ significantly between controls and vaccinees (P = 0.05).

Efficient transplacental transfer of RSV-specific antibody from mother to the fetus was documented in mother-infant pairs in Asia. Higher cord blood antibody titers were associated with protection from serologic infection.

Limited information is available on the etiology of acute lower respiratory infection (ALRI) particularly pneumonia in the rural community of developing countries since most etiological studies are carried out in the hospital settings. This study examined the etiology of pneumonia among young children in a rural community of Bangladesh. A cohort of 252 newborns was followed till 24 months of age during 1993-1996. Community health workers (CHWs) identified cases of ALRI during household surveillance and recommended hospitalization. On admission, nasopharyngeal aspirates (NPA) and blood were collected for bacterial and viral identification, and chest x-rays were done. Multiple regression analysis identified factors associated with a viral etiology. Physicians diagnosed 67 pneumonia; 45% of NPA were positive for viral agents of pneumonia, and respiratory syncytial virus (RSV) was predominant (81%); 6 of 48 blood cultures were positive. X-ray was done for 58 cases; 52% had pneumonic consolidation. Of the RSV cases, 33% were found in children without pneumonic consolidation. Children living in a one-room house were 3 times more likely to develop viral pneumonia (odds ratio (OR) = 3.67, CI 1.05-12.83) than children living in a larger house. Counseling on avoiding crowding where a newborn is accommodated might reduce pneumonia incidence.

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The burden of enterotoxigenic Bacteroides fragilis (ETBF)-related diarrhea was determined in a birth cohort of 252 children in rural Bangladesh. Isolation rates of ETBF in stool and risk factors for acquisition of ETBF and disease were established. Of 382 B. fragilis-positive specimens, 14.4% of the strains found in them produced enterotoxin, as determined by a tissue-culture assay. The overall isolation rate of ETBF was 2.3% (40/1750) from diarrheal specimens and 0.3% (15/5679) from nondiarrheal specimens collected throughout the 2 years of the study (P < .001). ETBF was isolated from 20.3% (40/197) of the B. fragilis-positive diarrheal specimens and from 8.1% (15/185) of the B. fragilis-positive nondiarrheal specimens (P < .001) and was significantly associated with acute diarrheal disease in children > or = 1 year of age (P = .0001). The diarrheal illness was mild in nature. In conditional multivariate analyses that examined environmental and host risk factors, the presence of livestock in the household area was linked to the acquisition of ETBF (chickens, P < .05; cows, P = .06). ETBF was found to be a small but significant contributor to diarrheal disease in this rural community. Improved management of livestock may be useful for the prevention of ETBF infection.