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Possible Child-to-Mother Transmission of HIV by Breastfeeding
To the Editor: In 1998, an outbreak of human immunodeficiency virus (HIV) infection involving 402 children and 18 mothers of these children occurred at Benghazi Children’s Hospital in Libya. In 2001, 118 of these children and all 18 of the mothers (who were diagnosed as HIV infected in 1999) were referred to the National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome, Italy. The outbreak had been caused by a single monophyletic strain,1 and transmission to the children was likely nosocomial.2 Because the transmission mode for the mothers remained unknown, we investigated the possibility of child-to-mother transmission through breastfeeding.
Methods
The 118 infected children were members of 113 families. A total of 102 of their mothers (including the 18 who were HIV infected) and 75 of their fathers (including 15 of the 18 husbands of the infected mothers) accompanied the children to Rome and provided written informed consent for a medical protocol including HIV antibody testing and clinical follow-up. In the context of a standardized medical history, the mothers were asked about breastfeeding, sexual contacts, prior medical care (including blood transfusions and parenteral treatment), and mucocutaneous exposure to their children’s body fluids. Laboratory personnel (but not interviewers) were blinded to HIV status. The ethics committee waived requirements for informed consent because data were collected for clinical practice without additional intervention and were presented without individually identifying features.
Wilcoxon rank-sum test and Fisher exact test were used for comparison of continuous and categorical variables, respectively. Statistical significance was defined as P<.05. Analyses were performed using STATA 8.0 (Stata Corporation, College Station, Tex).
Results
Infection with HIV was confirmed in all 118 children and in the 18 mothers and excluded in the remaining mothers and in all of the fathers. The only known risk factors for the HIV-positive mothers were intravenous treatment (parenteral antibiotics or asthma medications) at Benghazi Children’s Hospital during the outbreak (n = 3) and nonintact skin contamination with the child’s blood (n = 1). Breastfeeding at the time of the child’s first admission to the hospital during the outbreak was reported by 15 of 16 (93.8%) HIV-infected mothers and 23 of 77 (29.9%) uninfected mothers (odds ratio, 35.2; 95% confidence interval, 4.7-1508.8) (Table).
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Table. Characteristics of 102 Mothers of Children Infected With HIV During the 1998 Nosocomial Outbreak in Benghazi, Libya
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To assess the robustness of this association, we repeated the analysis under worst case assumptions. The 4 HIV-infected mothers who had other possible risk factors and the 27 mothers whose husbands were not tested at our institute were excluded, and for the mothers with information missing for breastfeeding, the 2 who were HIV infected were classified as non-breastfeeding and the 7 who were not HIV infected as breastfeeding. The association remained significant (proportion of breastfeeding women: 10/11 among HIV-infected and 24/60 among uninfected) (odds ratio, 15.0; 95% confidence interval, 1.9-668.5; P = .002). In contrast to breastfeeding during the outbreak, the association between maternal HIV status and breastfeeding at any time was not significant.
HIV-positive mothers reported a nonsignificant longer duration of breastfeeding during the outbreak. More infected mothers reported nipple fissures during breastfeeding and had significantly younger HIV-infected children (Table).
Comment
Although the association with breastfeeding could indicate mother-to-child transmission, we believe that child-to-mother transmission through breastfeeding is the most plausible explanation. First, although not all husbands of the seropositive mothers were tested, all fathers who were tested were seronegative. Second, all mothers and children were infected by the same strain in a limited time period,1 indicating that the mothers did not acquire the virus outside of the nosocomial outbreak. Third, this mode is biologically plausible, since the children may have had mucositis (characteristic of acute HIV infection) and traces of blood in the oral cavity. Transmission may have been facilitated by the presence of nipple fissures, which showed a strong association with HIV infection. Finally, possible child-to-mother transmission through breastfeeding was reported in 1990 for HIV-positive mothers of children infected during a nosocomial epidemic in Russia.3 Although the mothers could have acquired HIV infection from their children through close personal contact, the risk posed by close contact with HIV-infected preschool-aged children appears to be extremely small, at least in developed countries.4
As a case-control study, conclusions are limited to association rather than causation. The wide confidence intervals are also a reflection of the small sample size and limited accuracy of these estimates of effect size. However, the potential for child-to-mother transmission of HIV infection through breastfeeding is of great importance, particularly because wet nursing is widespread in countries with limited resources and has been indicated among the possible alternatives to bottle-feeding when the mother is HIV infected.5
Access to Data: Dr Visco-Comandini had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Financial Disclosures: None reported.
Funding/Support: This work was supported by research grant RF 2001.101 and Ricerca Corrente from the "Ministero della Salute," Rome, Italy.
Role of the Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.
Acknowledgment: We thank Guido Castelli Gattinara, MD (Bambino Gesù Children’s Hospital) for clinical information and the Lybia Project Task Force for supporting this study. We also thank Andrea Stoler, PhD (National Institute for Infectious Diseases, Rome) for editorial assistance and Mark Kanieff (Istituto Superiore di Sanità, Rome) and Douglas Horejsh, PhD (National Institute for Infectious Diseases) for critical suggestions.
Ubaldo Visco-Comandini, MD, PhD
viscocomandini{at}inmi.it
Benedetta Longo, MD;
Paola Perinelli, MD;
Giuseppina Liuzzi, MD;
Valerio Tozzi, MD;
Gianfranco Anzidei, MD;
Andrea Antinori, MD, PhD;
Giuseppe Ippolito, MD;
Enrico Girardi, MD
National Institute for Infectious Diseases "Lazzaro Spallanzani"
Rome, Italy
Mohammed A. Budabbus, MD
Embassy of the Popular Jamajria of Libya
Rome, Italy
Osama A. Eljhawi, MD;
Mahadi Mehabresh, MD
El Fath Children’s Hospital
Benghazi, Libya
1. Visco-Comandini U, Cappiello G, Liuzzi G, et al. Monophyletic HIV type 1 CRF02-AG in a nosocomial outbreak in Benghazi, Libya. AIDS Res Hum Retroviruses. 2002;18:727-732.
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2. Yerly S, Quadri R, Negro F, et al. Nosocomial outbreak of multiple bloodborne viral infections. J Infect Dis. 2001;184:369-372.
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3. Pokrovskii VV, Eramov II, Kuznetsova II, Sliusareva LA, Lipetikov VV. HIV transmission from child to mother during breast feeding. Zh Mikrobiol Epidemiol Immunobiol. 1990;3:23-26.
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4. Rogers MF, White CR, Sanders R, et al. Lack of transmission of human immunodeficiency virus from infected children to their household contacts. Pediatrics. 1990;85:210-214.
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5. UNICEF. Infant feeding and HIV. Available at: http://www.unicef.org/nutrition/23964_infantfeeding.html. Accessed September 6, 2005.
Letters Section Editor: Robert M. Golub, MD, Senior Editor.
JAMA. 2005;294:2301-2302.
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