Transmission of Infectious Diseases Through Breast Milk and Breastfeeding

Documenting Transmission

Documenting the transmission of infection from mother to infant by breastfeeding requires the demonstration of the infectious agent in the breast milk and a subsequent clinically significant infection in an infant that was caused by a plausible infectious process. The first step is to establish the occurrence of a specific infection (clinically or immunologically evident) in a mother and demonstrate the persistence of the infectious agent, such that it could be transmitted to the infant. Isolation or identification of the infectious agent from the colostrum, the breast milk, or an infectious lesion of the breast is important, but it is not necessarily proof of transmission to an infant. The identification of the infectious agent simply demonstrates that transmission via breast milk is possible but says nothing about the likelihood or probability of an infection occurring via human breast milk. Other mechanisms of transmission may dominate the natural history of infection by the specific agent (e.g., measles is transmitted predominately via airborne transmission). Demonstration of a clinical or subclinical infection in the infant after exposure to human breast milk is also necessary.

Exclusion of Other Mechanisms of Transmission

Exclusion of other possible mechanisms of transmission (exposure to mother or other persons/animals/environmental sources via airborne, droplet, arthropod, or vector modes of transmission or through direct contact with other infectious fluids) would complete the confirmation of transmission of infection via breastfeeding. It is also essential to exclude prenatal or perinatal transmission of infection to a fetus or infant. Exclusion of all the other possible mechanisms of transmission is very difficult to do.

Epidemiologic Evidence of Transmission

Epidemiologic evidence of transmission can include information from public health surveillance, field investigations, and analytic studies. ¹ Descriptive epidemiology may provide information on the chain of infection (agent, reservoir, portal of exit, mode[s] of transmission, portal of entry and susceptible host); disease incidence; and distribution of illness by person, place, and time. Infection via breast milk or breastfeeding can occur by direct contact with an infectious lesion on the mother’s breast, the infectious agent persisting in the fluid component of or cells in human milk, or contamination of the milk at the time of expression or during storage and later administration. Analytic epidemiology commonly utilizes an appropriate group for comparison to provide information on rates of infection and calculations of association (e.g., odds ratios or risk ratios). To determine a reasonable estimate of the risk for infection via breast milk, larger analytical epidemiologic studies are needed to compare infection rates in breastfed infants versus formula-fed infants. Other appropriate comparison groups could be breastfeeding mothers with and without the specific infection, or the different timing of maternal infection and the exposure of the infant to a potential pathogen in the colostrum or breast milk. The amount, frequency, and duration of breastfeeding, equivalent to an estimated “dose” of the potential infectious agent, are other important variables to consider in the estimate of risk. (See Chapter 5 regarding additional discussion of “dose” related to breastfeeding.)

These considerations are only some of the variables to consider, in general, to assess the risk for transmission of an infectious agent from mother to infant via breast milk or breastfeeding. Efforts to prove transmission of infection in a specific maternal–infant dyad can be just as difficult and must consider many of the same factors.

This chapter focuses on a discussion of specific, clinically relevant infectious agents and diseases, with reasonable estimates of the risk for infection to infants from breastfeeding. The basic tenet concerning breastfeeding and infection is that breastfeeding is rarely contraindicated in maternal infection. The few exceptions relate to specific infectious agents with strong evidence of transmission and to the association of an infant’s illness with significant morbidity and mortality. ² , ³

The risk or benefit of breastfeeding relative to the immunization of a mother or infant is discussed for certain microorganisms. Appendix D addresses precautions and breastfeeding recommendations for maternal infections. Chapter 5 reviews how breastfeeding may protect against infection. Chapter 22 addresses specific concerns relating to banked breast milk and includes standards developed by the Human Milk Banking Association of North America (HMBANA) to guide the appropriate handling of banked human milk relative to possible infectious agents.

Standard Precautions

Standard precautions include preventing contact with blood, all body fluids, secretions and excretions, nonintact skin, and mucous membranes by (1) careful handwashing before and after every patient contact; (2) use of gloves when touching body fluids, nonintact skin, mucous membranes, or any items contaminated with body fluids (linens, equipment, devices, etc.); (3) use of nonsterile gowns to prevent contact of clothing with body fluids; (4) use of masks, eye protection, or face shields when splashing with body fluids is possible; and (5) appropriate disposal of these materials. Standard precautions should be applied to all patients regardless of actual or perceived risks. The Centers for Disease Control and Prevention (CDC) does not consider breast milk to be a body fluid with infectious risks, and thus these policies do not apply to breast milk. (See section on misadministration of breast milk later in this chapter as a possible exception to this concept.)

In considering breastfeeding infant–mother dyads and standard precautions, body fluids other than breast milk should be avoided, and only in specified situations should breast milk also be avoided. In general, clothing or a gown for the mother, and bandages if necessary, should prevent direct contact with nonintact skin, potential infectious lesions, or secretions. Avoiding infant contact with maternal mucous membranes requires mothers to be aware of and understand the risks and to make a conscious effort to avoid this type of contact. The use of gloves, gowns, and masks on infants for protection is neither practical nor appropriate. The recommendations concerning the appropriateness of breastfeeding and breast milk are addressed for specific infectious agents throughout this chapter. Human immunodeficiency virus (HIV) infection is an example of one infection that can be prevented using standard precautions, including avoiding breast milk and breastfeeding. The recommendations concerning breastfeeding and HIV and the various variables and considerations involved are discussed later in the chapter.

Airborne Precautions

Airborne precautions are intended to prevent transmission via droplet nuclei (dried respiratory particles smaller than 5 μm that contain microorganisms and can remain suspended in the air for long periods) or dust particles containing microorganisms. Airborne precautions include the use of a private room with negative-air-pressure ventilation and designated respiratory protective devices at all times. In the case of pulmonary tuberculosis (TB), respiratory protective devices (requiring personal fitting and seal testing before use) should be worn. Airborne precautions are recommended with measles, varicella or disseminated zoster, and TB. Breastfeeding in the presence of these maternal infections is prohibited during the infectious period. This is to protect against airborne transmission of the infection from the mother and to allow the infant to be fed the mother’s expressed breast milk by another individual. The exception to allowing breast milk would be local involvement of the breast by varicella-zoster lesions or Mycobacterium tuberculosis , such that the milk becomes contaminated by the infectious agent.

Droplet Precautions

Transmission via droplets occurs when an individual produces droplets that travel only a short distance in the air and then contact a new host’s eyes, nose, mouth, or skin. The common mechanisms for producing droplets include coughing, sneezing, talking (singing or yelling), suctioning, intubation, nasogastric tube placement, and bronchoscopy. In addition to standard precautions applied to all patients, droplet precautions include the use of a private room (preferred) and a mask if within 3 feet (0.9 m) of the patient. Droplet precautions are recommended for adenovirus, diphtheria, respiratory infections, Hemophilus influenzae, Neisseria meningitidis or invasive infection, influenza, mumps, mycoplasma, parvovirus, pertussis, plague (pneumonic), and rubella, as well as streptococcal pharyngitis, pneumonia, or scarlet fever. The institution of droplet precautions with a breastfeeding mother who has these infections should be specified for each infection. This may require some period of separation for the infant and mother (for the duration of the illness, for the short term, during treatment of the mother, or for the standard infectious period for that organism) with the use of the mother’s fresh expressed breast milk for nutrition in the interim. Prophylactic treatment of the infant and maternal use of a mask during breastfeeding or close contact, combined with meticulous handwashing and the mother’s avoidance of touching her mucous membranes, may be adequate and reasonable for certain infections.

Contact Precautions

Contact precautions are meant to prevent the transmission of an infectious agent via direct contact (contact between the body surfaces of one individual and another) and indirect contact (contact of a susceptible host with an object contaminated with microorganisms from another individual). Contact precautions include cohorting or use of a private room, gloves and gowns at all times, and handwashing after removal of gown and gloves. Contact precautions are recommended for a long list of infections, such as diarrhea in diapered or incontinent patients with Clostridium difficile infection, Escherichia coli O157:H7, Shigella , rotavirus, hepatitis A, respiratory illness with parainfluenza virus or respiratory syncytial virus (RSV), multidrug-resistant (MDR) bacteria (e.g., enterococci, staphylococci, gram-negative organisms), enteroviral infections, cutaneous diphtheria, impetigo, herpes simplex virus (HSV) infection, herpes zoster (disseminated or in immunocompromised individuals), pediculosis, scabies, Staphylococcus aureus skin infection, viral hemorrhagic fevers (e.g., Ebola, Lassa), conjunctivitis and abscesses, cellulitis, and decubitus that cannot be contained by dressings. ⁶ For a breastfeeding mother–infant dyad, the implementation of precautions for each of these infections in a mother requires meticulous attention to gowning and handwashing by the mother and a specialized plan for each situation. This is particularly true for uncommon but potentially serious or fatal infections, such as viral hemorrhagic fevers, including Ebola virus disease (EVD), or exposure.

Each of these transmission-based precautions can be used in combination for organisms or illnesses that can be transmitted by more than one route. Within health care settings, they should always be used in conjunction with standard precautions, which are recommended for all patients. The Red Book: 2018 Report of the Committee on Infectious Diseases by the American Academy of Pediatrics (AAP) ⁶ and the CDC website ( www.cdc.gov/infectioncontrol/guidelines/index.html ) remain excellent resources for infection-control guidelines and recommendations to prevent transmission in specific situations and infections ( Box 12.1 ).

Culturing Breast Milk

The routine culturing of breast milk or the culturing of breast milk to screen for infectious agents is not recommended, except when the milk is intended as donor milk for another mother’s child directly or through human milk banks. Most milk banks culture donor milk after pasteurization routinely as quality and safety control. See Chapter 22 for specific bacterial-count standards for raw donor milk and related to pasteurized donor milk. Breastfeeding and the expression or pumping of breast milk (referred to as expressed breast milk ) for later use are not sterile activities. An emerging practice related to an increase in the use of donor human milk is milk sharing. (This is addressed in the next section and Chapter 22 ).

Bacterial Isolates From Human Breast Milk

In general, expressed breast milk should not contain large numbers of microorganisms (less than 10 ⁴ for raw milk and less than 10 ⁶ for milk to be pasteurized), nor should it contain large numbers of potential pathogens, such as S. aureus , β-hemolytic streptococci, Pseudomonas species, Proteus species, or Streptococcus faecalis or faecium . Few studies have examined the “routine” culturing of milk and the significance of specific bacterial colony counts relative to illness in infants. ² Schanler et al. identified Staphylococcus epidermidis as the most frequent bacterial isolate from human breast milk, with a variety of other organisms identified (1963 microbial isolates from 813 milk samples). ⁷ Other isolates they identified included Enterococcus faecalis , Acinetobacter sp., Stenotrophomonas maltophilia , Coagulase-negative Staphylococcus , S. aureus , Pseudomonas sp., Klebsiella sp., and other less common organisms. In this study, initial milk cultures did not predict later milk-culture isolates, and individual milk cultures did not predict subsequent infection in premature infants. ⁷ Other studies have been primarily concerned with premature or low-birth-weight (LBW) infants who remain hospitalized and are commonly fed via enteral tubes. A study from Canada tested 7610 samples of milk for use in 98 preterm infants. ⁸ This study also did not identify any adverse events in the infants attributed to organisms growing in the milk samples. A study from Chicago also examined gram-negative bacilli in the milk used for premature infants. ⁹ Samples were tested before feeding and from the nasogastric tubes during feeding. Milk samples from before feeding were less likely to contain gram-negative bacilli (36%) than milk samples from the nasogastric tubing (60%). Feeding intolerance was observed when there were more than 10 ³ colony-forming units per milliliter (CFU/mL), and episodes of sepsis were identified when the bacterial counts in the milk were greater than or equal to 10 ⁶ CFU/mL. Another study from Arkansas focused on the contamination of feeding tubes during the administration of expressed breast milk or formula. ¹⁰ Ten infants in the neonatal intensive care unit (NICU) were exposed to greater than 10 ⁵ gram-negative bacteria in their feeding tubes. The three infants who were fed expressed breast milk with contamination at greater than 10 ⁵ organisms remained well, but the seven formula-fed infants with high levels of bacterial contamination in the feeding tubes developed necrotizing enterocolitis. The gram-negative bacteria with high-level contamination in the feeding tubes were either Enterobacter or Klebsiella in all cases. Many NICUs still consider 10 ⁵ to 10 ⁶ CFU/mL as the significant bacterial count for gram-negative bacilli in breast milk that places premature and LBW infants at greater risk for infection. Even fewer data are available concerning specific bacterial colony counts for gram-positive organisms and the risk to the infant. Generally, less than 10 ³ gram-positive organisms per milliliter of milk is considered acceptable, with only case reports and no controlled trials to support this cutoff.

Collection Methods for Culturing Milk

Many small reports comment on the contamination of breast milk with different collection methods. Relative comparisons suggest decreasing contamination of expressed breast milk when collected by the following methods: drip milk, hand-pumped milk, manual expression, modern electric-pumped milk. One group from Malaysia published results showing no difference in contamination between milk collected by electric pump versus manual expression when collected in the hospital. Expressed breast milk collected at home by breast pump had higher rates of contamination with staphylococci and gram-negative bacteria, ¹¹ and in another study, bacterial contamination of expressed breast milk was more common in samples from home. ¹² In a more recent study from Brazil, there was no significant difference in culture results of breast milk collected at home versus at a milk bank. ¹³ Discussion continues about the need to discard the first few milliliters of milk to lower the bacteria numbers in expressed breast milk, without any evidence to suggest if this is truly necessary. ¹⁴ , ¹⁵ No evidence shows that cleansing the breast with anything other than tap water decreases the bacterial counts in cultured expressed breast milk. ¹⁶

Routine Breast-Milk Cultures

Routine breast-milk cultures are not useful in the clinical setting. When the presence of an infectious illness occurs in an infant and breast milk is seriously considered as a possible mechanism of transmission to the infant, culturing breast milk to identify the organism may be warranted and useful. Routine culturing of breast milk from a mother with mastitis or a breast abscess is unlikely to be useful in most situations. With recurrent infection, persistent mastitis, or breast abscess in the mother despite empiric antibiotic therapy, milk cultures with speciation and sensitivity testing of the isolated organisms can guide definitive therapy. Drainage of a breast abscess is often essential for definitive therapy of an abscess. More important than hurrying to culture breast milk is the careful instruction of mothers on the proper technique for collecting expressed breast milk, storing it, and cleaning the collection unit. This reinforcement of proper technique from time to time, especially when a question of contamination arises, is important.

If an infant is directly breastfeeding, collecting milk for culture by manual expression and trying to obtain a “midstream” sample (as is done with “midstream” urine collection for culture) is appropriate. If an infant is being fed expressed breast milk, collecting and culturing the milk at different points during collection (utilizing the same technique the mother uses [manual expression, hand pump, or electric pump]) and administration are appropriate. This can include a sample from immediately after collection, another of stored expressed breast milk, and a sample of milk from the most recent infant feeding at the time the decision to culture is made to identify a point of possible contamination in the handling process. See Box 12.2 for the basic steps in culturing expressed breast milk.

The interpretation of the results of breast-milk cultures can be difficult. When faced with concern for infection via breast milk given to a hospitalized infant, involving a pediatric infectious disease expert, a microbiologist, and a hospital epidemiologist may be appropriate. Additional organism identification is often required, utilizing antibiogram patterns or molecular fingerprinting by various techniques, to correlate a bacterial isolate from breast milk with an isolate causing disease in infant or mother.

Donor Human Milk

The World Health Organization (WHO), the United Nations Children’s Fund (UNICEF), and the AAP recommend the use of donor human milk when the infant’s own mother’s milk is unavailable. The AAP recommends pasteurized donor milk. ³ Possible sources of donor human milk include wet nursing, cross-nursing, milk sharing, and human milk banks. Milk sharing is a more informal process compared with human milk banks, which have guidelines and procedures to maintain the safety and quality of the donated milk. Milk sharing occurs more directly among family and friends or now at greater distances between unknown donors and recipients via the Internet. Human milk banks are either not-for-profit banks (e.g., HMBANA, European Milk Bank Association [EMBA]) or established milk banks in numerous other countries or commercial entities (e.g., Prolacta and Medolac).

Milk Safety

The federal government in the United States does not regulate or oversee milk banking, but the HMBANA and EMBA maintain milk-banking guidelines and procedures for banks within their associations. Prolacta Bioscience, Inc. follows US Food and Drug Administration (FDA) guidelines for both food and pharmaceuticals in the production of its human milk products. Medolac Laboratories does so as well but uses a high-temperature pasteurization process. Donor selection, screening, exclusion, and education; Holder pasteurization (HP) or high-temperature short-time (HTST) pasteurization; and postpasteurization bacterial culture testing are the main components utilized to maintain the safety and quality of donor milk from human milk banks (see Chapter 22 ). ¹⁷

The proper pasteurization of donor human milk virtually eliminates any infectious risks from donor human milk. Medolac reports that its process also eliminates Bacillus cereus (personal communication with Elena Medo). The risk of drug exposure through donor milk is primarily addressed through donor selection and exclusion. In one study from Spain of donor milk from a nonprofit human milk bank, the breast milk from 36 donors did not contain drugs of abuse, but 50% of them had caffeine detected. ¹⁸ In a separate study, 400 milk samples from 63 donors were again tested for drugs and compared with results from the milk bank’s required screening questionnaire. No drugs of abuse were identified in any donor milk, nicotine and cotinine were found in one donor’s milk who did not report tobacco use, and caffeine was detected in 45% of the donor milk samples. The sensitivity and specificity of the questionnaire to detect caffeine in donor milk were both low; sensitivity was 46%, and specificity was 77%. ¹⁹ Prolacta includes donor milk drug testing as part of its screening process.

Milk Sharing

The notable increase in donor human milk sharing via Internet sites has raised concerns about the safety and quality of milk obtained in this manner. Although several of the larger Internet organizations (e.g., Human Milk for Human Babies [HM4HB]. The website for Human Milk for Human Babies is currently under construction as of October 2020, with a statement that it will be reinstated, http://www.hm4hb.net ], and Eats on Feets [ http://www.eatsonfeets.org ] promote the concepts of safe and ethical milk sharing; informed consent; “informal donor screening”; safe collection, storage, shipment, and handling; and home pasteurization, there are many other avenues on the Internet for milk sharing, and the safety of milk sharing via the Internet requires ongoing study.

Two publications by the same group have looked at the process of purchasing human milk on the Internet in terms of the ease and reliability of the process, shipping, costs, delays, the condition of packaging and milk containers, the temperature of the milk samples on arrival, and microbial contamination. Geraghty et al. ²⁰ and Keim et al. ²¹ reported receiving 50% of the packages on the day after shipment and 37% on the second day after shipment. Nine percent of these shipping boxes were rated as severely damaged, 15% of the milk containers had evidence of leaking milk, and 45% of the milk samples arrived with a surface temperature of the milk >4°C, the recommended refrigerator temperature for the storage of human milk. The surface milk temperature was noted to correlate with the cost of shipping, time in transit, and rating of milk-container condition. The authors also compared the bacteriologic culture results of milk obtained via the Internet and milk obtained from a human milk bank. The Internet samples were colonized with gram-negative bacteria 74% of the time or had colony counts of >10 ⁴ CFU/mL. Compared with samples from a human milk bank, the Internet samples had higher mean total aerobic counts, total gram-negative counts, coliform counts, and Staphylococcus sp. counts. Milk bank samples were cytomegalovirus (CMV) DNA positive 5% of the time, with 21% of Internet samples being CMV DNA positive. None of the samples tested positive for HIV ribonucleic acid (RNA). ²⁰ , ²¹ Keim and Geraghty and others have also looked at drugs of abuse and cow’s milk contamination of human milk purchased from the Internet. Sellers of human milk in these studies reported abstinence from drugs 71% of the time and made no statement about it in 29% of the advertisements. One hundred and two milk samples were tested for 13 groups of drugs of abuse, and none of the samples tested positive. The same 102 samples were tested for bovine DNA, and 10 of the samples contained amounts consistent with at least 10% of the fluid sample being made up of cow’s milk. ²² , ²³ Testing for tobacco metabolites and caffeine, the same authors found that 4% of the milk samples contained levels of nicotine or cotinine consistent with active smoking, and 97% of the same samples contained detectable amounts of caffeine. ²⁴ Even though the larger milk-sharing websites recommend guidelines for hygienic collection, appropriate storage, and shipping, the quality and safety of human milk obtained via milk sharing on the Internet fall short of expected standards for donor human milk. Further study is needed with larger numbers of donor human milk samples to provide accurate information on the risk of transmission of infection or contamination with drugs of abuse or cow’s milk. This highlights the importance of ethical milk sharing, informed consent, “informal donor screening,” and proper and effective home pasteurization of donor human milk by the receiving mother before giving it to an infant.

Collection and use of donor human milk via milk banks are increasing, and human milk-sharing practices in the United States continue to evolve. The Academy of Breastfeeding Medicine (ABM) has published a statement in support of informed and enhanced milk-safety practices for milk sharing. ²⁵ Various studies suggest that milk sharing is a “complex practice,” with donors and recipients exchanging roles over time with and without “cross-nursing,” and that exchanges were most often face to face or with individuals they knew. ²⁶ , ²⁷ Participants report milk sharing on the Internet through milk-sharing websites and through their own personal networks. Totally anonymous milk sharing or selling and shipping of breast milk are less commonly reported. Practices of “screening” donors occurred but varied between donor–recipient pairs with greater or less familiarity with the other. Practices for the safe handling and storage of milk are known to most participants, but it is difficult to tell how well they are followed in all situations. ²⁸ Clearly, more study of the safety and quality of donor human milk obtained via the Internet is needed, with a focus on obtaining outcome data on the infants receiving this milk. Additionally, increasing the availability and decreasing the cost of donor human milk from not-for-profit and commercial milk banks while maintaining quality and safety are essential to providing for the needs of an increasing number of infants who have an inadequate supply of their own mother’s milk.

Anthrax

Bacillus anthracis , a gram-positive, spore-forming rod, causes zoonotic disease worldwide. Human infection typically occurs as a result of contact with animals or their products. Three forms of human disease occur: cutaneous anthrax (the most common), inhalation anthrax, and gastrointestinal (GI) anthrax (rare). Person-to-person transmission can occur as a result of discharge from cutaneous lesions, but no evidence of human-to-human transmission of inhalational anthrax is available. No evidence of transmission of anthrax via breast milk exists. ³⁷ , ³⁸ Standard contact isolation is appropriate for hospitalized patients or patients with draining skin lesions.

The issue of anthrax as a biologic weapon has exaggerated its importance as a cause of human disease. The primary concerns regarding anthrax and breastfeeding are antimicrobial therapy or prophylaxis in breastfeeding mothers and the possibility that the infant and mother were exposed by intentional aerosolization of anthrax spores. The AAP Committee on Infectious Diseases and Disaster Preparedness Advisory Council published recommendations for treatment and prophylaxis in infants, children, and breastfeeding mothers. ³⁹ The recommendations include the use of a range of antibiotics, often in combination, including amoxicillin, ampicillin, chloramphenicol, ciprofloxacin, clindamycin, doxycycline, imipenem, levofloxacin, linezolid, meropenem, moxifloxacin, penicillin, and rifampin. Amoxicillin, ampicillin clindamycin, imipenem, linezolid, meropenem, and penicillin are acceptable for use with breastfeeding. ³⁹ Little information is available on ciprofloxacin, levofloxacin, moxifloxacin, and doxycycline in breast milk for prolonged periods of therapy or prophylaxis (60 days) and possible effects on infants’ teeth and bone or cartilage growth during that time period. ⁴⁰ , ⁴¹ , ⁴² Short-term use is acceptable while breastfeeding for those four drugs, but alternative drugs are preferred for longer-term use in place of chloramphenicol and clindamycin. ⁴³ , ⁴⁴ Depending on the clinical situation and sensitivity testing of the identified anthrax strain, specific agents can be chosen to complete the 60-day course of therapy. Guidelines are also given for the use of the adsorbed anthrax vaccine and/or raxibacumab antitoxin, although vaccine use in children is available through an investigational new-drug protocol. ³⁹

The simultaneous exposure of infant and mother could occur from primary aerosolization or from spores “contaminating” the local environment. In either case, decontamination of the mother–infant dyad’s environment should be considered.

Breastfeeding can continue during a mother’s therapy for anthrax if she is physically well. Open cutaneous lesions should be carefully covered, and depending on the situation, simultaneous prophylaxis for the infant may be appropriate. If there is no likelihood of contamination of the breast milk from a local skin lesion, breastfeeding or the use of breast milk can continue.

Botulism

Considerable justifiable concern has been expressed because of the reports of sudden infant death from botulism. Infant botulism is distinguished from foodborne botulism from improperly preserved food containing the preformed toxin and from wound botulism caused by spores entering a wound.

Bacillus cereus

Bacillus cereus is a gram-positive, spore-forming aerobic rod that grows well under anaerobic conditions. It causes at least two kinds of food poisoning: diarrhea and emesis, produced by different toxins. This organism is ubiquitous in the environment, and food-poisoning outbreaks are associated with many types of foods: plant derived, meat, eggs, and dairy. B. cereus –related disease is not a reportable illness, so the true incidence is unknown. The foods commonly associated with diarrheal disease are meats, soups, vegetables, puddings, sauces, milk, and milk products, and those associated with emetic disease are fried and cooked rice, pasta, pastry, and noodles. The emetic syndrome has a relatively short incubation period, usually less than 6 hours, and lasts 6 to 24 hours, suggesting it is a result of “intoxication” from food containing the emetic toxin cereulide. The infective dose is estimated to be 10 ⁵ to 10 ⁸ cells per g ⁻¹ of the suspected offending food or toxin present in the suspected food equivalent to 8 to 10 μgkg ⁻¹ body weight (estimated from animal studies). For the diarrhea syndrome, the incubation is approximately 8 to 16 hours, and it lasts from 12 to 24 hours, up to days. The infective dose is 10 ⁵ to 10 ⁸ cells or spores, although there are reports of diarrheal disease with as low as 10 ³ B. cereu s CFUg ⁻¹ of food. Diarrheal disease is more likely a result of the ingestion of cells or spores that produce one of several enterotoxins during the vegetative phase of growth within the intestine. ⁵²

Previously, B. cereus was noted for being found in dried milk products, including powdered infant formulas. More recently, B. cereus has been identified in donor human milk even after Holder pasteurization, which may relate to Bacillus spore temperature resistance and the ability to form biofilms. ⁵³ , ⁵⁴ A couple of reports contend that human milk could have played a role in B. cereus infection in premature infants, even though the strain of B. cereus causing disease was not found in milk and contaminated donor human milk was not identified. This has led to new tests to quantify the Bacillus toxins by PCR testing or liquid chromatography-tandem mass spectrometry. New techniques for processing donor human milk are being tested, including HTST, high-pressure processing (HPP), ultraviolet irradiation (UV-C), and thermo-ultrasonic processing, with the intent of ensuring the safety and quality of donor human milk. ⁵⁵ Other processing methods utilizing heat and pressure that eradicate B. cereus and other pathogens have been reported. ⁵⁶

New research assessing the risk of B. cereus infection resulting from pasteurized donor human milk ⁵⁷ , ⁵⁸ and discussion of updated recommendations for quality improvement and processing of human donor milk by milk banks are ongoing. ⁵⁹ , ⁶⁰ With the use of a Monte Carlo simulation, Lewin et al. estimated that the risk of infection from donor human milk to premature infants was very low and that additional precautions in postpasteurization culture testing made little difference in diminishing the apparent risk to exposed infants. ⁵⁷ To optimize the safety, accessibility, affordability, and quality of donor human milk for neonates, a significant amount of research into B. cereus and quality control/improvement is still needed.

Brucellosis

Brucella melitensis has been isolated in the milk of animals. Foods and animals represent the primary sources of infection in humans. Human-to-human transmission is rare, with less than 50 cases reported in the last 49 years, as reported in a recent systematic review. ⁶¹ Eleven of those cases were likely via transplacental transmission, and 7 cases were reportedly via breastfeeding based on timing. Only two of the seven cases reported as breastfeeding related were associated with a positive human milk culture. There are no reports of isolation of Brucella from human milk on routine culturing. ⁶¹ Brucellosis demonstrates a broad spectrum of illness in humans, from subclinical to subacute to chronic illness with nonspecific signs of weakness, fever, malaise, body aches, fatigue, sweats, arthralgia, and lymphadenitis. In areas where the disease is enzootic, childhood illness has been described more frequently. The clinical manifestations in children are similar to those in adults. In infants, the dominant symptoms include respiratory distress, hyperbilirubinemia, fever, hepatomegaly, and arthralgia. ⁶² Infection can occur during pregnancy, leading to abortion (infrequently), and can produce transplacental spread, causing neonatal infection (rarely). Neonatal brucellosis has been reported rarely, even in endemic areas. ⁶³

The transmission of B. melitensis through breast milk has been implicated in neonatal infection, but the data are circumstantial, at best, for this rare infection in newborns and infants. ⁶⁴ , ⁶⁵ , ⁶⁶

Separately, B. melitensis has been cultured from women with breast lumps and abscesses. ⁶⁷ Only one of six women described in this report was lactating at the time of diagnosis, and no information about the infant was given. Brucellosis mastitis or abscess should be considered in women presenting with appropriate symptoms and occupational exposure to animals, contact with domestic animals in their environment, or exposure to animal milk or milk products (especially unpasteurized products). The breast inflammation tends to be granulomatous in nature (without caseation). It is often associated with axillary adenopathy, and occasionally, systemic illness in the woman is evident. Brucellosis mastitis or abscess should be treated with surgery or fine-needle aspiration, as indicated, accompanied by 4 to 6 weeks of combination antibiotic therapy with two or three medications. Acceptable medications for treating the mother, while continuing breastfeeding, include gentamicin, streptomycin, trimethoprim-sulfamethoxazole, and rifampin for the longer period of therapy (4 to 6 weeks). Doxycycline should be used with caution in the lactating woman for this longer period. ⁴²

By the time the diagnosis of Brucella mastitis is made, the infant has already been exposed. There is no reason to interrupt breastfeeding or the use of the mother’s milk.

Chlamydial Infections

Chlamydial infection is the most frequent sexually transmitted disease (STD) in the United States and is a frequent cause of conjunctivitis and pneumonitis in an infant from perinatal infection. The major determinant of whether chlamydial infection occurs in a newborn is the prevalence rate of chlamydial infection of the cervix. ⁶⁸ Specific chlamydial immunoglobulin A (IgA) has been found in colostrum and breast milk in a small number of postpartum women who were seropositive for Chlamydia . No information is available on the role of milk antibodies in protecting against infection in infants. ⁶⁹ It is not believed that Chlamydia is transmitted via breast milk. The use of erythromycin or tetracycline to treat mothers and oral erythromycin or azithromycin and ophthalmic preparations of tetracyclines, erythromycin, or sulfonamides to treat suspected infection in infants (with a risk-benefit assessment for the use of the specific antibiotic in the specific infant) is appropriate during continued breastfeeding. Separating infants from mothers with chlamydial infections or stopping breastfeeding is not indicated. The simultaneous treatment of mothers and infants may be appropriate in some situations.

Clostridium difficile

C. difficile is a spore-forming, obligate anaerobic, gram-positive bacillus with Toxins A and B causing intestinal infection. It is acquired via the fecal-oral route from other individuals or the environment. Its increasing incidence in adults and children relates to its relative importance. ⁷⁰ Infants can readily be colonized (most often asymptomatic carriage), with reported C. difficile colonization at approximately 30% to 40% before 1 month of age, 20% to 30% at 1 to 6 months of age, 10% to 20% at 12 months of age, and continuing to decline to about 3 years of age, when the colonization rate approaches the same rate as in adults, 3% to 5%. ⁷¹ Various studies show that colonization with C. difficile in breastfed infants is almost half of the colonization rate in formula-fed infants. ⁷² , ⁷³ , ⁷⁴ Proposed explanations for this include competition with bacteria common in the microbiome in breastfed infants, secretory IgA, and neutralizing antibodies against the C. difficile toxins in colostrum. The AAP has advised against routinely testing infants less than 1 year of age because of the high rate of asymptomatic colonization. The AAP recommends testing for alternative etiologies of diarrhea or intestinal disease in children less than 3 years of age.

If a mother is infected with C. difficile and hospitalized, standard and contact precautions are likely to be instituted within the hospital. There is no reason to separate the mother and child, except the severity of the mother’s illness. Breastfeeding can continue, including during antimicrobial therapy in the mother for C. difficile . Vancomycin, rifaximin, and nitazoxanide can be readily utilized in infants, and their very limited absorption from the intestine limits the systemic exposure to the infant. Metronidazole can also be used in the mother or infant with their first episode of C. difficile infection, with precaution regarding dosing when the infant is <2 kg in weight and <7 days old. ⁷⁵ There are limited data on the use of fidaxomicin in infants. ⁷⁶

Diphtheria

Corynebacterium diphtheriae causes several forms of clinical disease, including membranous nasopharyngitis, obstructive laryngotracheitis, and cutaneous infection. Complications can include airway obstruction from membrane formation and toxin-mediated central nervous system (CNS) disease or myocarditis. The overall incidence of diphtheria has declined, even though immunization does not prevent infection but does prevent severe disease from toxin production. Fewer than five cases are reported annually in the United States, whereas thousands of cases are reported worldwide (the WHO documented 7097 diphtheria cases reported in 2016), and many more go unreported. ⁷⁷

Transmission occurs via droplets or direct contact with contaminated secretions from the nose, throat, eye, or skin. Infection occurs in individuals whether they have been immunized or not, but infection in the nonimmunized is more severe and prolonged. If the skin of the breast is not involved, no risk for transmission exists via breast milk. No toxin-mediated disease from a toxin transmitted through breast milk has been reported in an infant.

Breastfeeding, along with chemoprophylaxis and the immunization of affected infants, is appropriate in the absence of cutaneous breast involvement (see Appendix D ).

Gonococcal Infections

Maternal infection with N. gonorrhoeae can produce a large spectrum of illness, ranging from uncomplicated vulvovaginitis, proctitis, pharyngitis, and conjunctivitis to more severe and invasive disease, including pelvic inflammatory disease, meningitis, endocarditis, and disseminated gonococcal infection. The risk for transmission from mother to infant occurs mainly during delivery in the passage through the infected birth canal and occasionally from postpartum contact with the mother (or her partner). The risk for transmission from breast milk is negligible, and N. gonorrhoeae does not seem to cause local infection of the breasts. Infection in neonates is most often ophthalmia neonatorum and less often a scalp abscess or disseminated infection. Mothers with presumed or documented gonorrhea should be reevaluated for other STDs, especially Chlamydia trachomatis and syphilis, because some therapies for gonorrhea are not adequate for either of these infections.

With the definitive identification of gonorrhea in a mother, empiric therapy should begin immediately for the infant. Treatment of the mother with ceftriaxone, cefixime, penicillin, or erythromycin is without significant risk for the infant. Single-dose treatment with spectinomycin, ciprofloxacin, ofloxacin, or azithromycin has not been adequately studied to recommend their use during lactation. Doxycycline use in a nursing mother is not routinely recommended.

Careful preventive therapy for ophthalmia neonatorum should be provided, and close observation of the infant should continue for 2 to 7 days, the usual incubation period. Empiric or definitive therapy against N. gonorrhoeae may be necessary, depending on an infant’s clinical status, and it should be chosen based on the maternal isolate’s sensitivity pattern. The mother should not handle other infants until after 24 hours of adequate therapy. The infant should be separated from the rest of the nursery population, with or without breastfeeding. There is no reason to separate the mother and infant because the infant has already been exposed, and there is no reason to interrupt breastfeeding or hold breast milk.

Hemophilus influenzae

H. influenzae type B can cause severe invasive disease, such as meningitis, sinusitis, pneumonia, epiglottitis, septic arthritis, pericarditis, and bacteremia. Shock can also occur. Because of the increased utilization of the H. influenzae type B conjugate vaccines, invasive disease caused by Hemophilus has decreased dramatically, with a greater than 95% reduction in the United States. Most invasive disease occurs in children 3 months to 3 years of age. Older children and adults rarely experience severe disease but do serve as sources of infection for young children. Children younger than 3 months of age seem to be protected because of passively acquired antibodies from the mothers, and some additional benefits may be received from breast milk.

Transmission occurs through contact with respiratory secretions, and droplet precautions are protective. No evidence suggests transmission through breast milk or breastfeeding. Evidence supports that breast milk limits the colonization of H. influenzae in the throat. ⁷⁸

In the rare case of maternal infection, an inadequately immunized infant in a household is an indication to provide rifampin prophylaxis and close observation for all household contacts, including the breastfeeding infant. Breastfeeding or the use of expressed breast milk can continue if the mother is well enough.

Leprosy

Although uncommon in the United States, leprosy occurs throughout the world despite ongoing efforts for eradication with contact testing, postexposure chemoprophylaxis, and ongoing trials of postexposure vaccination with several vaccine formulations. This chronic disease presents with a spectrum of symptoms depending on the tissues involved (typically the skin, peripheral nerves, and mucous membranes of the upper respiratory tract) and the cellular immune response to the causative organism, Mycobacterium leprae . Transmission occurs through long-term contact with individuals with untreated or multibacillary (large numbers of organisms in the tissues) disease. Leprosy is believed to be transmitted primarily through the respiratory tract.

Although leprosy can be transmitted to the fetus during pregnancy and young children can manifest with leprosy, there is no evidence of transmission of M. leprae via breast milk or breastfeeding. Leprosy is not a contraindication to breastfeeding, according to Jelliffe and Jelliffe. ⁷⁹ The importance of breastfeeding and the urgency of treatment are recognized by experts who treat infants and mothers early and simultaneously. There are data concerning infants born to mothers with leprosy during pregnancy and the occurrence of smaller placentas and lower birth weights. There is only one long-term study of the growth of children born to mothers with leprosy, which demonstrated slower growth (catch-up by 3.6 years), more childhood infections, and higher infant mortality in comparison to healthy controls. ⁸⁰ The authors suggested that this could be a result of immunologic factors associated with leprosy, but support of breastfeeding and maternal and infant nutrition during therapy should be included as part of the antimicrobial therapy. Additionally, contact testing within the household and family and postexposure prophylaxis are being studied for their ability to interrupt the cycle of transmission. Breastfeeding and the use of breast milk can continue during maternal therapy and infant prophylaxis. Dapsone, rifampin, and clofazimine are typically and safely used for infant and mother, regardless of the method of feeding (see Appendix D ). ⁸¹

Listeriosis

Listeriosis is a relatively uncommon infection that can have a broad range of manifestations. In immunocompetent individuals, including pregnant women, the infection can vary from being asymptomatic to presenting as an influenza-like illness, occasionally with GI symptoms or back pain. Severe disease occurs more frequently in immunodeficient individuals or infants infected in the perinatal period (pneumonia, sepsis, meningitis, and granulomatosis infantisepticum).

Although listeriosis during pregnancy may manifest as mild disease in a mother and is often difficult to recognize and diagnose, it is typically associated with stillbirth, abortion, and premature delivery. Neonatal infection occurs as either early- or late-onset infection from transplacental spread late in pregnancy, ascending infection during labor and delivery, infection during passage through the birth canal, or rarely, during postnatal exposure.

No evidence in the literature suggests that Listeria is transmitted through breast milk. There are rare reports of Listeria infecting the breast. ⁸² Treatment of the mother with ampicillin, penicillin, or trimethoprim-sulfamethoxazole is not a contraindication to breastfeeding as long as the mother is well enough. Expressed colostrum or breast milk can also be given if the infant is able to feed orally. The management of lactation and feeding in neonatal listeriosis is conducted supportively, as it is in any situation in which an infant is extremely ill, beginning feeding with expressed breast milk or directly breastfeeding as soon as reasonable.

Meningococcal Infections

N. meningitidis most often causes severe invasive infections, including meningococcemia or meningitis, often associated with fever and a rash and progressing to purpura, disseminated intravascular coagulation, shock, coma, and death.

Transmission occurs via respiratory droplets. Spread can occur from an infected, ill individual or from an asymptomatic carrier. Droplet precautions are recommended until 24 hours after the initiation of effective therapy. Despite the frequent occurrence of bacteremia, no evidence indicates breast involvement or transmission through breast milk.

The risk for transmission of infection from a mother to an infant after birth is from droplet exposure and exists whether the infant is breastfeeding or bottle-feeding. In either case, the exposed infant should receive chemoprophylaxis with rifampin, 10 mg/kg per dose every 12 hours for 2 days (5 mg/kg per dose for infants younger than 1 month of age), or ceftriaxone, 125 mg intramuscularly (IM) once, for children younger than 15 years of age. Close observation of the infant should continue for 7 days, and breastfeeding during and after prophylaxis is appropriate. The severity of maternal illness may prevent breastfeeding, but it can continue if the mother is able.

Pertussis

Respiratory illness caused by Bordetella pertussis evolves in three stages: catarrhal (nasal discharge, congestion, increasing cough), paroxysmal (severe paroxysms of cough sometimes ending in an inspiratory whoop, i.e., whooping cough), and convalescent (gradual improvement in symptoms).

Transmission is via respiratory droplets. The greatest risk for transmission occurs in the catarrhal phase, often before the diagnosis of pertussis. The nasopharyngeal culture usually becomes negative after 5 days of antibiotic therapy. Chemoprophylaxis for all household contacts is routinely recommended. No evidence indicates transmission through breast milk, with similar risk to breastfed and bottle-fed infants.

In the case of maternal infection with pertussis, chemoprophylaxis for all household contacts, regardless of age or immunization status, is indicated. In addition to chemoprophylaxis of the infant, close observation and subsequent immunization (in infants older than 6 weeks of age) are appropriate. Prophylaxis for the infant should be azithromycin or erythromycin, although trimethoprim-sulfamethoxazole can be used when the infant is 6 weeks or older. Standard and droplet precautions are recommended for 5 days after the initiation of effective therapy. There are no trials assessing the protection to the infant while utilizing infant prophylaxis and ongoing breastfeeding. Maternal immunization in the third trimester has demonstrated increased passive transfer of antipertussis antibodies to the infant at birth. ⁸³ , ⁸⁴ , ⁸⁵ Prenatal maternal immunization is more effective than postnatal immunization at preventing pertussis disease and decreasing the severity of pertussis infection in infants less than 8 weeks of age. ⁸⁶ Although antipertussis antibodies have been demonstrated in colostrum and breast milk, protection directly from breast milk against pertussis infection in infancy has been difficult to prove. ⁸⁴ Breastfeeding or the use of mother’s milk can continue because exposure has already occurred by the time the diagnosis is made in the mother. There are clear benefits to prenatal maternal immunization, chemoprophylaxis, and immunizing adult caregivers against pertussis in protecting infants.

Methicillin-Resistant Staphylococcus aureus

MRSA is an important pathogen worldwide. Community-acquired MRSA is different from hospital-acquired MRSA. Community-acquired MRSA is usually defined as occurring in an individual without the common predisposing variables associated with hospital-acquired MRSA. Community-acquired MRSA also lacks a multidrug resistance (MDR) phenotype (common with hospital-acquired MRSA) and frequently carries multiple exotoxin virulence factors (e.g., Panton-Valentine leukocidin toxin), as well as the smaller type IV staphylococcal cassette cartridge for the MecA gene on a chromosome (hospital-acquired MRSA carries the types I to III staphylococcal cassette cartridge). This is molecularly distinct from the common nosocomial strains of hospital-acquired MRSA. Community-acquired MRSA is most commonly associated with skin and soft tissue infections and necrotizing pneumonia and less frequently associated with endocarditis, bacteremia, necrotizing fasciitis, myositis, osteomyelitis, or parapneumonic effusions. Community-acquired MRSA is so common that it is now being observed in hospital outbreaks. ⁹⁴ , ¹⁰³ , ¹⁰⁴ , ¹⁰⁵

Community-acquired MRSA transmission to infants via breast milk has been reported. ⁹³ , ⁹⁴ , ⁹⁵ , ⁹⁶ , ⁹⁷ Premature or small-for-gestational-age infants are more susceptible to and at increased risk for significant morbidity and mortality as a result of MRSA, in part because of prolonged hospitalization, multiple courses of antibiotics, invasive procedures and intravenous (IV) lines, their relative immune deficiency related to prematurity and illness, and altered GI tract as a result of different flora and decreased gastric acidity. Therefore colonization with MRSA may pose a greater risk to infants in NICUs in the long run. Full-term infants develop pustulosis, cellulitis, and soft tissue infections, but invasive disease has rarely been reported. ⁹¹ , ¹⁰⁶ , ¹⁰⁷ Fortunov et al. ¹⁰⁷ from Texas reported 126 infections in term or late-preterm previously well infants, including 43 with pustulosis, 68 with cellulitis or abscesses, and 15 invasive infections. A family history of soft tissue skin infections and male sex were the only variables associated with risk for infection; cesarean delivery, breastfeeding, and circumcision were not. ¹⁰⁷ Nguyen et al. ⁹¹ reported MRSA infections in a well-infant nursery from California. The 11 cases were all in full-term boys with pustular-vesicular lesions in the groin. The infections were associated with longer length of stay, lidocaine injection use in infants, maternal age older than 30 years, and circumcision. Breastfeeding was not an associated risk factor for MRSA infection. ⁹¹ The question of the role of circumcision in MRSA outbreaks was addressed by Van Howe and Robson. ¹⁰⁸ They reported that circumcised boys are at greater risk for staphylococcal colonization and infection. ¹⁰⁸

Others report that S. aureus carriage in infants (and subsequent infection) is most likely affected by multiple variables, including infant factors (antibiotics, surgical procedures [circumcision being the most common], duration of hospital stay as a newborn), maternal factors (previous colonization, previous antibiotic usage, mode of delivery, length of stay), and environmental factors (MRSA in the family or hospital, nursery stay versus rooming-in, hand hygiene). ⁹⁸ , ¹⁰⁵ , ¹⁰⁹ , ¹¹⁰ , ¹¹¹ , ¹¹² , ¹¹³ Gerber et al. ¹⁰¹ from the Chicago area published a consensus statement for the management of MRSA outbreaks in the NICU. The recommendations, which were strongly supported by experimental, clinical, and epidemiologic data, included using a waterless, alcohol-based hand-hygiene product, monitoring and enforcing hand hygiene, placing MRSA-positive infants in contact precautions with cohorting if possible, using gloves and gowns for direct contact and masks for aerosol-generating procedures, cohorting nurses for the care of MRSA-positive infants when possible, periodic screening of infants for MRSA using nares or nasopharyngeal cultures, clarifying the MRSA status of infants being transferred into the NICU, limiting overcrowding, and maintaining ongoing instruction and monitoring of health care workers in their compliance with infection-control and hand-hygiene procedures. The evaluation of the outbreak could include screening of health care workers and environmental surfaces to corroborate epidemiologic data and laboratory molecular analysis of the MRSA strains if indicated epidemiologically. The use of mupirocin or other decolonizing procedures should be determined on an individual basis for each NICU.

S. aureus is the most common cause of mastitis in lactating women. ¹¹⁴ , ¹¹⁵ , ¹¹⁶ , ¹¹⁷ Recurrence or persistence of symptoms of mastitis is a well-described occurrence and an important issue in the management of mastitis. Community-acquired MRSA has been associated with mastitis as well ¹⁰⁵ , ¹¹⁶ , ¹¹⁸ (see Chapter 16 for a complete discussion of mastitis).

Two studies, one from France and one from Brazil, investigated the occurrence of MRSA in expressed breast milk. ¹¹⁹ , ¹²⁰ Barbe et al. ¹¹⁹ cultured 9171 expressed breast-milk samples from 378 women and tested 2351 samples before pasteurization and 6820 samples after pasteurization. MRSA and methicillin-susceptible S. aureus were identified, respectively, in 8 samples (0.8%) from 3 mothers and 281 samples (19.3%) from 73 mothers, using the tested expressed breast milk before pasteurization. After pasteurization, S. aureus was not detected in any of the 6820 samples of expressed breast milk. Colonization of one infant with MRSA was identified, but no MRSA infections were identified in any of the hospitalized infants in the NICU during the 18 months of the study. ¹¹⁹ Novak et al. ¹²⁰ identified MRSA in 57 of 500 samples (11%) of expressed fresh-frozen milk from 500 different donors from five Brazilian milk banks. Only 3 of the 57 samples were positive with high-level bacterial counts of MRSA (greater than 10,000 CFU/mL). These were the only samples that would not have been acceptable by bacteriologic criteria according to Brazilian or American criteria for raw milk use. They did not investigate other epidemiologic data to identify possible variables associated with low- or high-level contamination of expressed breast milk with MRSA. ¹²⁰

The management of an infant and/or mother with MRSA infection, relative to breastfeeding or the use of breast milk, should be based on the severity of disease and whether the infant is premature, LBW, very low-birth-weight (VLBW), previously ill, or full term.

When full-term infants or their mothers develop mild to moderate infections (impetigo, pustulosis, cellulitis/abscess, mastitis/breast abscess, or soft tissue infection), those infants can continue breastfeeding. An initial evaluation for other evidence of infection should be done in the maternal–infant dyad, the infected child and/or mother should be placed on “commonly” effective therapy for the MRSA infection, and ongoing observation for clinical disease should continue. The mother and infant can “room-in” together in the hospital, if necessary, with standard and contact precautions. Culturing the breast milk is not necessary. Empiric therapy for the infant may be chosen based on medical concerns for the infant and the known sensitivity testing of the MRSA isolate. Appropriate antibiotic choices include short-term use of azithromycin (erythromycin use during infancy [younger than 6 weeks of age] is associated with an increased risk for hypertrophic pyloric stenosis), sulfamethoxazole-trimethoprim (in the absence of G6PD deficiency and older than 30 days of age), clindamycin (short course, 3 to 5 days), and perhaps linezolid for mild to moderate infections.

When infants in NICUs (premature, LBW, VLBW, and/or previously ill) or their mothers have an MRSA infection, those infants should have the breast milk cultured and suspend breastfeeding or receiving breast milk from their mothers until the breast milk is shown to be culture-negative for MRSA. The infant should be treated as indicated for infection or empirically treated if symptomatic (with pending culture results) and closely observed for the development of new signs or symptoms of infection. Pumping to maintain the milk supply and the use of banked breast milk are appropriate. The infant should be placed on contact precautions, in addition to the routine standard precautions. The infant can be cohorted with other MRSA-positive infants, with nursing care cohorted as well. The mother with MRSA infection should be instructed concerning hand hygiene; the careful collection, handling, and storage of breast milk; contact precautions to be used with her infant; and the avoidance of contact with any other infants. The mother can receive several possible antibiotics for MRSA that are compatible with breastfeeding when used for a short period. If the mother remains clinically well, including without evidence of mastitis, but her breast milk is positive for MRSA greater than 10 ⁴ CFU/mL, empiric therapy to diminish or eradicate colonization would be appropriate. Various regimens have been proposed to “eradicate” MRSA colonization, but no single one has been proven to be highly efficacious. These regimens usually include systemic antibiotics with one or two medications (rifampin added as the second medication), as well as nasal mupirocin to the nares twice daily for 1 to 2 weeks with routine hygiene, with or without the usage of hexachlorophene (or similar topical agent or cleanser) for bathing during the 1- to 2-week treatment period. There is no clear information concerning the efficacy of using similar colonization-eradication regimens for other household members or pets in preventing recolonization of the mother or infant. Before reintroducing the use of the mother’s breast milk to the infant, at least one negative breast-milk culture should be obtained after the completion of therapy.

The routine screening of breast milk provided by mothers for their infants in NICUs for the presence of MRSA is not indicated in the absence of MRSA illness in the maternal–infant dyad, an MRSA outbreak in NICUs, or a high frequency of MRSA infection in a specific NICU.

Toxin-Mediated Staphylococcus Disease

One case of staphylococcal scalded skin syndrome (SSSS) was reported by Katzman and Wald ¹²¹ in an infant breastfed by a mother with a lesion on her areola that did not respond to ampicillin therapy for 14 days. Subsequently, the infant developed conjunctivitis with S. aureus , which produced an exfoliative toxin, and a confluent erythematous rash without mucous membrane involvement or Nikolsky sign. No attempt to identify the exfoliative toxin in the breast milk was made, and the breast milk was not cultured for S. aureus . The child responded to IV therapy with nafcillin. This emphasizes the importance of evaluating the mother and infant at the time of a suspected infection and the need for continued observation of the infant for evidence of a pyogenic infection or toxin-mediated disease, especially with maternal mastitis or breast lesions.

This case also raises the issue of when and how infants and their mothers become colonized with S. aureus and what factors lead to infection and illness in each. The concern is that Staphylococcus can be easily transmitted through skin-to-skin contact, colonization readily occurs, and potentially serious illness can occur later, long after colonization. In the case of staphylococcal scalded skin syndrome or toxic shock syndrome (TSS), the primary site of infection can be insignificant (e.g., conjunctivitis, infection of a circumcision, or simple pustulosis), but a clinically significant amount of toxin can be produced and lead to serious disease.

TSS can result from S. aureus or Streptococcus pyogenes infection and probably from a variety of antigens produced by other organisms. TSS-1 has been identified as a “superantigen” that affects the T lymphocytes and other components of the immune response, producing an unregulated and excessive immune response and resulting in an overwhelming systemic clinical response. TSS has been reported in association with vaginal delivery, cesarean delivery, mastitis, and other local infections in mothers. Mortality rates in mothers may be as high as 5%.

The case definition of staphylococcal TSS includes meeting all four major criteria: fever greater than 38.9°C, rash (diffuse macular erythroderma), hypotension, and desquamation (associated with subepidermal separation seen on skin biopsy). The definition also includes the involvement of three or more organ systems (GI, muscular, mucous membrane, renal, hepatic, hematologic, or CNS); negative titers for Rocky Mountain spotted fever, leptospirosis, and rubeola; and lack of isolation of S. pyogenes from any source or S. aureus from the cerebrospinal fluid (CSF). ¹²² A similar case definition has been proposed for streptococcal TSS. ¹²³ Aggressive empiric antibiotic therapy against staphylococci and streptococci and careful supportive therapy are essential for decreasing illness and death. Oxacillin, nafcillin, first-generation cephalosporins, clindamycin, erythromycin, and vancomycin are acceptable antibiotics, even for a breastfeeding mother. The severity of illness in the mother may preclude breastfeeding, but it can be reinitiated when the mother is improving and wants to restart. Standard precautions, with breastfeeding, are recommended.

Staphylococcal enterotoxin F has been identified in breast-milk specimens collected on days 5, 8, and 11 from a mother who developed TSS at 22 hours postpartum. ¹²⁴ S. aureus that produced staphylococcal enterotoxin F was isolated from the mother’s vagina but not from breast milk. The infant and mother lacked significant levels of antibodies against staphylococcal enterotoxin F in their sera. The infant remained healthy after 60 days of follow-up. Staphylococcal enterotoxin F is pepsin inactivated at pH 4.5 and therefore is probably destroyed in the stomach environment, presenting little or no risk to the breastfeeding infant. ¹²⁵ Breastfeeding can continue if the mother is able.

Coagulase-Negative Staphylococcus

Coagulase-negative staphylococcal infection ( S. epidermidis is the predominant isolate) produces minimal disease in healthy, full-term infants but is a significant problem in hospitalized or premature infants. Factors associated with increased risk for this infection include prematurity, high colonization rates in specific nurseries, invasive therapies (e.g., IV lines, chest tubes, intubation), and antibiotic use. Illness produced by coagulase-negative staphylococci can be invasive and severe in high-risk neonates but rarely in mothers. There are reports of necrotizing enterocolitis associated with coagulase-negative Staphylococcus . At 2 weeks of age, for infants still in the nursery, S. epidermidis is a frequent colonizing organism at multiple sites, with colonization rates as high as 75% to 100%. Serious infections with coagulase-negative staphylococci (e.g., abscesses, IV-line infection, bacteremia/sepsis, endocarditis, osteomyelitis) require effective IV therapy. Many strains are resistant to penicillin and the semisynthetic penicillins, so sensitivity testing is essential. Empiric or definitive therapy may require treatment with vancomycin, gentamicin, rifampin, teicoplanin, linezolid, or combinations of these for synergistic activity. Transmission of infection in association with breastfeeding appears to be no more common than with bottle-feeding. As with S. aureus , infection control includes contact and standard precautions. Occasionally, during presumed outbreaks, careful epidemiologic surveillance may be required, including cohorting, limiting overcrowding and understaffing, surveillance cultures of infants and nursery personnel, reemphasis on meticulous infection-control techniques for all individuals entering the nursery, and rarely, removal of colonized personnel from direct infant contact.

S. epidermidis is one of the most common organisms identified by molecular studies in human breast milk. ¹²⁶ It has been identified as part of the fecal microbiota of thriving breast-fed infants. ¹²⁷ S. epidermidis has also been identified in the breast milk of women with clinical evidence of mastitis. ¹²⁸ Nevertheless, S. epidermidis is rarely associated with infection in full-term infants. Conceivably, breast milk for premature infants could be a source of S. epidermidis colonization in the NICUs. The benefits of early full human milk feeding potentially outweigh the risk for colonization with S. epidermidis via breast milk. ¹²⁹ Ongoing education and assistance should be provided to mothers about the careful collection, storage, and delivery of human breast milk for their premature infants. ¹³⁰

Group A Streptococcus

S. pyogenes (β-hemolytic group A Streptococcus [GAS]) is a common cause of skin and throat infections in children, producing pharyngitis, cellulitis, and impetigo. Illnesses produced by GAS can be classified into three categories: (1) impetigo, cellulitis, or pharyngitis without invasion or complication; (2) severe invasive infection with bacteremia, necrotizing fasciitis, myositis, or systemic illness (e.g., streptococcal TSS); and (3) autoimmune-mediated phenomena, including acute rheumatic fever and acute glomerulonephritis. GAS can also cause puerperal sepsis, endometritis, and neonatal omphalitis. Significant morbidity and mortality rates are associated with invasive GAS infection; the mortality rate is 20% to 50%, with almost half the survivors requiring extensive tissue debridement or amputation. ¹³¹ Infants are not at risk for the autoimmune sequelae of GAS (rheumatic fever or poststreptococcal glomerulonephritis). Transmission is through direct contact (rarely indirect contact) and droplet spread. Outbreaks of GAS in the nursery are rare, unlike with staphylococcal infections. Either the mother or infant can be initially colonized with GAS and transmit it to the other.

In the situation of maternal illness (extensive cellulitis, necrotizing fasciitis, myositis, pneumonia, TSS, and mastitis), it is appropriate to continue breastfeeding and use breast milk. The mother can readily receive effective therapy (penicillin, ampicillin, cephalosporins, and erythromycin), the infant can be observed expectantly, and breastfeeding can continue.

Group B Streptococcus

Group B Streptococcus (GBS, Streptococcus agalactiae ) is a significant cause of perinatal bacterial infection. In parturient women, infection can lead to asymptomatic bacteriuria, urinary tract infection (often associated with premature birth), endometritis, or amnionitis. In infants, infection usually occurs between birth and 3 months of age (1 to 4 cases per 1000 live births). It is routinely classified by the time of onset of illness in the infant: early onset (0 to 7 days, majority less than 24 hours) and late onset (7 to 90 days, generally less than 4 weeks). Infants may develop sepsis, pneumonia, meningitis, osteomyelitis, arthritis, or cellulitis.

Early-Onset GBS Disease

Early-onset GBS disease (EOD) is often fulminant, presenting as sepsis or pneumonia with respiratory failure; three-quarters of neonatal disease is early onset. A recent review showed that the estimated pooled incidence of invasive GBS disease in infants was 0.49 per 1000 live births (95% CI 0.43 to 0.56). The rate was highest in Africa (1.12) and lowest in Asia (0.30). EOD incidence was 0.41 (95% CI 0.36 to 0.47); late-onset disease incidence was 0.26 (95% CI 0.21 to 0.30). The estimated case-fatality rate (CFR) was 8.4% (95% CI 6.6% to 10.2%). Serotype III (61.5%) dominated, with 97% of cases caused by serotypes Ia, Ib, II, III, and V. ¹³²

Transmission is believed to occur in utero and during delivery. Colonization rates of mothers and infants vary between 5% and 35%. Postpartum transmission is thought to be uncommon, although it has been documented. Risk factors for EOD include delivery before 37 weeks of gestation, rupture of membranes for longer than 18 hours before delivery, intrapartum fever, heavy maternal colonization with GBS, or low concentrations of anti-GBS capsular antibody in maternal sera. ¹³³ The common occurrence of severe GBS disease before 24 hours of age in neonates has led to prevention strategies. Revised guidelines developed by the AAP Committees on Infectious Diseases and on the Fetus and Newborn have tried to combine various variables for increased risk for GBS infection (prenatal colonization with GBS, obstetric and neonatal risk factors for EOD) and provide intrapartum antibiotic prophylaxis (IAP) to those at high risk ¹³³ , ¹³⁴ ( Fig. 12.1 ). The utilization of these guidelines, universal culture-based screening, and IAP across the United States have decreased the incidence of EOD by approximately 80% from an estimated 1.4 cases of EOD per 1000 live births in 1990 to 0.28 cases per 1000 live births in 2009. ¹³⁵ Within the United Kingdom, additional variables and interventions are being identified to further decrease EOD, including giving intrapartum antibiotics to the mother whenever there is prolonged rupture of membranes, regardless of gestational age, ¹³⁶ and utilizing rapid PCR testing for GBS at presentation for delivery to identify additional infants exposed to GBS and initiate IAP. ¹³⁷ Researchers in Hong Kong have also noted that the implementation of “universal GBS screening” and improved GBS testing could allow enhanced IAP and decrease EOD in full-term infants. ¹³⁸ However, there is no clear international consensus, and research is ongoing to develop an optimal evidence-based guideline. ¹³⁹ , ¹⁴⁰

Tuberculosis

The face of TB is changing throughout the world but is still driven by poverty, HIV coinfection, multidrug-resistant TB (MDR-TB), and migration. In the United States, the incidence of TB rose from 1986 through 1993 and has been declining since then. ¹⁶⁴ In 2017 the incidence rate was 2.8 cases per 100,000 population, which represents a decrease of 2.5% from 2016 to 2017. In 2017 the WHO reported an estimated 10 million new cases of TB (133 cases per 100,000 population), which was a 1.8% decline from 2016. The number of deaths resulting from TB also declined by 3.9% from 2016 to 2017, but the case fatality was still 15.7%. ¹⁶⁵

TB During Pregnancy

TB during pregnancy has always been a significant concern for patients and physicians alike. ¹⁶⁶ It is now clear that the course and prognosis of TB in pregnancy are less affected by the pregnancy and more determined by HIV coinfection, MDR-TB, the location and extent of disease (as defined primarily by chest radiograph), and the susceptibility of the individual patient. Historically, untreated TB in pregnancy was associated with maternal and infant mortality rates of 30% to 40%. ¹⁶⁷ More recent studies have not supported the idea that pregnancy predisposes to worse outcomes of TB. ¹⁶⁸ A recent systematic review and meta-analysis also did not show increased maternal mortality compared with pregnant women without TB. There was an increase in maternal and neonatal morbidity, including anemia, cesarean delivery, miscarriage, preterm birth, LBW, acute fetal distress, asphyxia, and perinatal death compared with pregnancies without TB in the mother. ¹⁶⁹ Effective therapy is crucial to the clinical outcome in both pregnant and nonpregnant women. TB during pregnancy rarely results in congenital TB, although congenital TB has a mortality rate as high as 50%. ¹⁷⁰ A case review and review of the literature from 2011 reported that before 1994, the mortality of congenital TB was 52.6%, and after 1994, the mortality was 33.9%. Data on morbidity in congenital TB was associated with earlier age at the onset of symptoms and the existence of intracranial lesions. ¹⁷¹ Any individual in a high-risk group for TB should be screened with a tuberculin skin test (TST). No contraindication or altered responsiveness to the TST exists during pregnancy or breastfeeding. Interpretation of the TST should follow the most recent guidelines, using different sizes of induration in different-risk populations as cutoffs for a positive test, as proposed by the CDC. ¹⁷² Fig. 12.2 outlines the evaluation and treatment of a pregnant woman with a positive TST. ¹⁷³

Treatment of active TB should begin as soon as the diagnosis is made, regardless of the fetus’s gestational age, because the risk for disease to mother and fetus clearly outweighs the risks of treatment. Isoniazid, rifampin, and ethambutol have been used safely in all three trimesters. Isoniazid and pyridoxine therapy during breastfeeding is safe. ¹⁷⁴ , ¹⁷⁵ There is a low risk for hepatotoxicity in the mother during the first 2 to 3 months postpartum. ¹⁷⁶ , ¹⁷⁷

Congenital TB is extremely rare, if one considers that 9 to 10 million new cases of TB occur each year worldwide and that less than 300 cases of congenital TB have been reported in the literature. As with other infectious diseases presenting in the perinatal period, distinguishing congenital infection from perinatal or postnatal TB in infants can be difficult. The Spanish Society for Pediatric Infectious Diseases has published guidelines for the diagnosis of congenital TB. ¹⁷⁸

Postnatal TB infection in infancy typically presents with severe disease and extrapulmonary extension (meningitis; lymphadenopathy; and bone, liver, spleen involvement). Airborne transmission of TB to infants is the major mode of postnatal infection because of close and prolonged exposure in enclosed spaces, especially in their own household, to any adult with infectious pulmonary TB. Potential infectious sources could be the mother or any adult caregiver, such as babysitters, daycare workers, relatives, friends, neighbors, and even health care workers. Mittal et al. recently reviewed the management of the newborn infant exposed to the mother with TB. ¹⁷⁹

TB Exposure for a Neonate or Infant

The suspicion of TB infection or disease in a household with possible exposure of an infant is a highly anxiety-provoking situation ( Fig. 12.3 ). Although protecting an infant from infection is foremost in everyone’s mind, separation of the infant from the mother should be avoided when reasonable. Every situation is unique, and the best approach will vary according to the specifics of the case and accepted principles of TB management. The first step in caring for the potentially exposed infant is to determine accurately the true TB status of the suspected case (mother or household contact). This prompt evaluation should include a complete history (previous TB infection or disease; previous or ongoing TB treatment; TST status; symptoms suggestive of active TB; results of most recent chest radiograph, sputum smears, or cultures), physical examination, a TST if indicated, a new chest radiograph, and mycobacterial cultures and smears of any suspected sites of infection. All household contacts should be evaluated promptly, including history and TST, with further evaluation as indicated. ¹⁷² Continued risk to the infant can occur from infectious household contacts who have not been effectively evaluated and treated.

When the mother and infant are hospitalized at the initiation of concern for maternal TB, the infant should be temporarily separated from the mother or other adult as the suspected source if symptoms suggest active disease or a recent TST documents conversion, and separation should continue until the results of the chest radiograph of the possible source are seen. Because of considerable variability in the course of illness and the concomitant infectious period, debate continues without adequate data about the appropriate period of separation. ¹⁸⁰ , ¹⁸¹ This should be individualized given the specific situation. HIV testing and assessment of the risk for MDR-TB should be done in every case of active TB. Sensitivity testing should be done on every M. tuberculosis isolate from a pregnant or lactating woman. Table 12.1 summarizes the management of the newborn infant whose mother (or other household contact) has TB.

Table 12.1

Management of a Newborn Whose Mother (or Other Household Contact) Has Tuberculosis (TB) Infection

Data from the Committee on Infectious Diseases, American Academy of Pediatrics. Red Book: Report of the Committee on Infectious Diseases . 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003.

Mother–Infant Status	Additional Workup Recommended a	Therapy for Mother or Contact	Therapy for Infant	Separation b	Breast Milk c	Breastfeeding d
1. TB infection, no disease d	None for mother/contact	Prophylactic e	None	No	Yes	Yes
2. TB infection: Abnormal CXR not suggestive of active disease		Decide active vs. inactive disease
a. Symptoms or physical findings suggestive of active TB	Aerosolized sputum (culture, smears) f	Active disease: Empiric e	Isoniazid g	Yes	Yes	No h
		Inactive disease: Prophylactic e	None	No	Yes	Yes
b. No symptoms or physical findings suggestive of active TB	Aerosolized sputum in select cases	Prophylactic e	None	No	Yes	Yes
3. TB infection: Abnormal CXR suggestive of active disease	Aerosolized sputum (culture, smears) f	Empiric therapy e	Isoniazid g	Yes	Yes	No h
4. Active pulmonary TB: Suspected MDR TB	Aerosolized sputum (culture, smears) f	Consult TB specialist for best regimen i	Consult pediatric TB specialist i	Yes	Yes	No
			Consider bacille Calmette-Guérin vaccine
5. TB disease: Suspected mastitis j	Aerosolized sputum (culture, smears) f	Empiric e	Isoniazid g	Yes	No k	No
6. TB infection: Status undertermined l	Perform/interpret CXR within 24 hours			Yes, until CXR interpreted (see a and b)	Yes	No
a. Abnormal CXR not suggestive of active disease	Proceed as in 2		As in 2	As in 2	As in 2
b. Abnormal CXR suggestive of active disease	Proceed as in 3		As in 3	As in 3	As in 3

CXR , Chest x-ray; MDR , multidrug resistant.

a Further workup should always include the evaluation of the TB status of all other household (or close) contacts by tuberculin skin testing (TST), review of symptoms, physical examination, and CXR. Sputum smears and cultures should be done as indicated.

b Separation should occur until interpretation of CXR confirms the absence of active disease, or with active disease, separation should continue until the individual is no longer considered infectious: three negative consecutive sputum smears; adequate ongoing empiric therapy; and decreased fever, cough, and sputum production. Separation means movement to a different house or location, not simply separate rooms in a household. The duration of separation should be individualized for each case, in consultation with the TB specialist.

c This assumes no evidence of breast involvement, suspected TB mastitis, or lesions (except in status 5, when breast involvement is considered). The risk to the infant is via aerosolized bacteria in the sputum from the lung. Expressed breast milk can be given even if separation of mother and infant is advised.

d TST positive, no symptoms or physical findings suggestive of TB, negative CXR.

e Prophylactic therapy: isoniazid 10 mg/kg per day, maximum 300 mg for 6 months; pyridoxine 25 to 50 mg/day for 6 months. Empiric therapy: standard three- or four-drug regimens for 2 months, and treatment should continue for total of 6 months with isoniazid and rifampin when the organism is shown to be sensitive. Suspected MDR TB requires consultation with a TB specialist to select the optimum empiric regimen and for ongoing monitoring of therapy and clinical response.

f Sensitivity testing should be done on any positive culture.

g Isoniazid 10 mg/kg per day for 3 to 9 months, depending on the mother’s or contact’s status; repeat TST at 3 months and obtain a normal CXR in the infant before stopping isoniazid. Before beginning therapy, a workup of the infant for congenital or active TB may be appropriate. This workup should be determined based on the clinical status of the infant and the suspected potential risk, and it may include TST after 4 weeks of age, with CXR, complete blood count, and erythrocyte sedimentation rate; liver function tests; cerebrospinal fluid analysis; gastric aspirates; and sonography or computed tomography of the liver, spleen, and chest if congenital TB is suspected.

h Breastfeeding is proscribed when the separation of the mother and infant is indicated because of the risk for aerosolized transmission of bacteria. Expressed breast milk given to the infant via bottle is acceptable in the absence of mastitis or breast lesions.

i Consult with a TB specialist about MDR TB. Empiric therapy will be chosen based on the most recent culture sensitivities of the index patient or perhaps the suspected source case, if known, as well as medication toxicities and other factors.

j TB mastitis usually involves a single breast, with associated axillary lymph node swelling and, infrequently, a draining sinus tract. It can also present as a painless mass or edema of the breast.

k With suspected mastitis or breast lesions caused by TB, even breast milk is contraindicated until the lesion or mastitis heals, usually after 2 weeks or more.

l Patient has a documented, recent TST conversion but has not been completely evaluated. Evaluation should begin, and CXR should be done and evaluated in less than 24 hours to minimize the separation of this person from the infant. Further workup should proceed as indicated by symptoms, physical findings, and CXR results.

Initiation of prophylactic isoniazid therapy in the infant has been demonstrated to be effective in preventing TB infection and disease in the infant. Therefore continued separation of the infant and mother is unnecessary after therapy in both mother and child has begun. ¹⁸² The AAP recommends isoniazid (INH) prophylaxis for all infants whose mothers have been diagnosed with active pulmonary TB in the postpartum period. The real risk requiring infant separation is airborne transmission. Separation of the infant from a mother with active pulmonary TB is appropriate, regardless of the method of feeding. However, in many parts of the world, when effective antituberculous therapy in the mother and prophylaxis with isoniazid in the infant have begun, the infant and mother are not separated. ¹⁷⁸ With or without separation, the mother and infant should continue to be closely observed throughout the course of maternal therapy to ensure good compliance with medication by both mother and infant and to identify, early on, any symptoms in the infant suggestive of TB. The mother should be followed to confirm that she is no longer considered infectious, with negative smears and cultures within 2 to 4 weeks of beginning TB therapy.

Tuberculous mastitis occurs rarely in the United States, and it is uncommon even in other parts of the world. ¹⁸³ , ¹⁸⁴ , ¹⁸⁵ , ¹⁸⁶ , ¹⁸⁷ , ¹⁸⁸ , ¹⁸⁹ , ¹⁹⁰ , ¹⁹¹ , ¹⁹² Tuberculosis mastitis can lead to infection in infants, frequently involving the tonsils. A mother usually has a single breast mass and associated axillary lymph node swelling and infrequently develops a draining sinus. TB of the breast can also present as a painless mass or edema. Involvement of the breast can occur with or without evidence of disease at other sites. Evaluation of the extent of the disease is appropriate, including lesion cultures by needle aspiration, biopsy, or wedge resection and milk cultures. Therapy should be with multiple anti-TB medications, but surgery should supplement this, as needed, to remove extensive necrotic tissue or a persistently draining sinus. ¹⁹³ Neither breastfeeding nor breast-milk feeding should be done until the lesion is healed, usually after 2 weeks or more of appropriate antituberculous medications. Continued anti-TB therapy for 6 months in the mother and prophylactic isoniazid for the infant for 3 to 6 months is indicated.

In the absence of tuberculous breast infection in the mother, the transmission of TB through breast milk has not been documented. Thus, even though temporary separation of the infant and mother may occur pending complete evaluation and initiation of adequate therapy in the mother and prophylactic isoniazid therapy (10 mg/kg per day as a single daily dose) in the infant, breast milk can be expressed and given to the infant during the short separation. Breastfeeding can safely continue when the mother, infant, or both are receiving anti-TB therapy. Anti-TB medications (isoniazid, rifampin, pyrazinamide, aminoglycosides, ethambutol, ethionamide, p -aminosalicylic acid) have been safely used in infancy, and therefore, the presence of these medications in smaller amounts in breast milk is not a contraindication to breastfeeding.

Arboviruses

The term arboviruses describes a large collection of viruses grouped together because of the common mode of transmission through arthropods. They have now been reclassified into several different families: Bunyaviridae, Togaviridae, Flaviviridae, Reoviridae , and others. They include more than 30 human pathogens.

These organisms primarily produce either CNS infections (encephalitis, meningoencephalitis) or undifferentiated illnesses associated with fever and rash, severe hemorrhagic manifestations, and involvement of other organs (hepatitis, myalgia, polyarthritis). Infection with one of these viruses may also be asymptomatic and subclinical, although how often this occurs is uncertain. Some of the notable human pathogens include Bunyaviridae (California serogroup viruses), hantavirus, Hantaan virus, phlebovirus (Rift Valley fever), nairovirus (Crimean-Congo hemorrhagic fever), alphavirus (western, eastern, and Venezuelan equine encephalomyelitis viruses, chikungunya virus [CHIKV]), flavivirus (St. Louis encephalitis virus, Japanese encephalitis virus, dengue viruses, yellow fever virus, tick-borne encephalitis viruses, WNV), and orbivirus (Colorado tick fever). Other than for Crimean-Congo hemorrhagic fever and for reported cases of Colorado tick fever associated with transfusion, direct person-to-person spread has rarely been described. Outbreaks in 2005 and 2007 of CHIKV infection on Reunion Island and in India appear to have involved infection in young infants probably secondary to vertical spread from mother to infant transplacentally. ¹⁹⁸ , ¹⁹⁹ , ²⁰⁰ A few cases of early fetal deaths were associated with infection in pregnant women. The cases of vertical transmission occurred with near-term infection in the mothers, and the infants developed illness within 3 to 7 days of delivery. ¹⁹⁸ , ¹⁹⁹ No evidence for transmission via breast milk or breastfeeding is available.

Overall, little evidence indicates that these organisms can be transmitted through breast milk. The exceptions to this include evidence of transmission of three flaviviruses via breast milk: dengue virus, WNV, and yellow fever vaccine virus. Standard precautions are generally sufficient. With any of these infections in a breastfeeding mother, the severity of the illness may determine the mother’s ability to continue breastfeeding. Providing the infant with expressed breast milk is acceptable. (See the discussion of dengue virus, WNV, and yellow fever vaccine virus later in this chapter.)

In general, treatment for these illnesses is supportive. However, ribavirin appears to decrease the severity of and mortality from hantavirus pulmonary syndrome, hemorrhagic fever with renal failure, and Crimean-Congo hemorrhagic fever. Ribavirin has been described as teratogenic in various animal species and is contraindicated in pregnant women. No information is available concerning ribavirin in breast milk, with limited information available on the use of IV or oral ribavirin in infants. ²⁰¹

Arenaviruses

Arenaviruses are single-stranded RNA viruses that infect rodents and are acquired by humans through the rodents. The six major human pathogens in this group are (1) lymphocytic choriomeningitis virus, (2) Lassa fever virus, (3) Junin virus (Argentine hemorrhagic fever), (4) Machupo virus (Bolivian hemorrhagic fever), (5) Guanarito virus (Venezuelan hemorrhagic fever), and (6) Sabia virus. The geographic distribution of these viruses and the illness they cause are determined by the living range of the host rodent (reservoir). ²⁰² The exact mechanism of transmission to humans is unknown and hotly debated. ²⁰³ , ²⁰⁴ , ²⁰⁵ Direct contact and aerosolization of rodent excretions and secretions are probable mechanisms.

Lymphocytic choriomeningitis virus is well recognized in Europe, the Americas, and other areas. Perinatal maternal infection can lead to severe disease in the newborn, but no evidence suggests transmission through breast milk. ²⁰⁶ , ²⁰⁷ Standard precautions with breastfeeding are appropriate.

Lassa fever (West Africa) and Argentine hemorrhagic fever (Argentine pampas) are usually more severe illnesses, with dramatic bleeding and involvement of other organs, including the brain. These fevers more frequently lead to shock and death than do the forms of hemorrhagic fever caused by the other viruses in this group. Person-to-person spread of Lassa fever virus does occur, including transmission within households. ²⁰⁸ The possibility of persistent virus in human urine, semen, and blood after infection exists for each of the arenaviruses. The possibility of airborne transmission is undecided. Current recommendations by the CDC and others ²⁰⁴ , ²⁰⁹ are to use contact precautions for the duration of the illness in situations of suspected viral hemorrhagic fever. No substantial information describes the infectivity of various body fluids, including breast milk, for these different viral hemorrhagic fevers. Considering the severity of the illness in mothers and the risk to the infants, it is reasonable to avoid breastfeeding in these situations if alternative forms of infant nutrition can be provided for the short term.

As more information becomes available, reassessment of these recommendations is advisable. A vaccine is in trials in endemic areas for Junin virus and Argentine hemorrhagic fever. ²¹⁰ Preliminary studies suggest it will be effective, but data are still being accumulated concerning the vaccine’s use in children and pregnant or breastfeeding women.

Chikungunya Virus

CHIKV is an alphavirus transmitted most commonly through mosquitoes. Humans are the primary host of the virus during epidemics, but there is limited evidence of transmission from person to person. ²¹¹ Bloodborne transmission and intrapartum transmission have been documented. Disease varies from asymptomatic in 10% to 15% of people to symptomatic infection, which most commonly includes fever, polyarthralgia, headache, myalgia, hemorrhage, myelitis, conjunctivitis, nausea/vomiting, and maculopapular rash. Reports from around the world document vertical maternal-fetal transmission, both congenital and perinatal. Data from the epidemic on Reunion Island in 2005 to 2006 show varied results. Lenglet et al. described 160 pregnant women with CHIKV infection during pregnancy. Of these women, 151 had documented infection, 118 did not have viremia at delivery, and none showed congenital disease. Thirty-three mothers were viremic at delivery, and 16 infants demonstrated neonatal chikungunya infection. ²¹² Fritel et al. compared 658 women infected during pregnancy with 628 uninfected pregnant women in the prolonged epidemic on Reunion Island. Infection was reported to occur in the first trimester for 15% of women, in the second trimester for 59%, and in the third trimester for 26%. ²¹³ There were more frequent hospitalizations in the infected group of women but no reported difference in cesarean deliveries, preterm birth, stillbirths after 22 weeks’ gestational age, LBW, or congenital malformations after maternal infection compared with the uninfected women. ²¹³ Separately, Ramful et al. retrospectively described 38 infected neonates from the same epidemic whose mothers presented with evidence of chikungunya infection at delivery or the infant themselves presented with illness within the first days of life. Neonatal symptomatology included pain (in 100% of cases), rash (82%), fever (79%), and peripheral edema (58%). Laboratory abnormalities included elevation of aspartate aminotransferase (77%), thrombocytopenia (76%), decreased prothrombin time (65%), and lymphopenia (47%) of infants. Neonatal complications included seizures, hemorrhage/hemorrhagic disorders, and cardiac involvement (myocardial hypertrophy, ventricular dysfunction, coronary artery dilatation, and pericarditis). CSF was positive for real-time PCR (RT-PCR) testing in 22 of 24 cases, and magnetic resonance imaging (MRI) results were abnormal in 14 of 25 infants, with white-matter lesions or intraparenchymal hemorrhages noted. ¹⁹⁹ Torres et al. reviewed congenital and perinatal complications of chikungunya fever (CHIKF) in Latin America. They described 169 symptomatic infants with CHIKF in four large maternity hospitals in three countries. The reported maternal-to-infant transmission rate ranged from 27.7% to 48.29%. Seventy-nine infected newborns were followed prospectively. The onset of illness was between 3 and 9 days after birth, and the CFR was 5.1% compared with reported CFRs from Reunion Island and Sri Lanka data ranging from 0 to 2.6%. ²¹⁴ Gérardin et al. reported persistent disabilities in 30% to 45% of the children with apparent clinical CNS involvement. ²¹⁵

CHIKV has been detected once in a breastfeeding mother during CHIKV infection, but the infant was not ill and remained PCR and serology negative. ²¹⁶ There is little other information to suggest CHIKV transmission is common or significant during breastfeeding. The benefits of continuing breastfeeding outweigh the possible protection from stopping breastfeeding with maternal CHIKV infection before delivery or during lactation in most situations.

Cytomegalovirus

CMV is one of the human herpesviruses. Congenital infection of infants, postnatal infection of premature infants, and infection of immune-deficient individuals represent the most serious forms of this infection in children. The gestational age or postconceptual age when the virus infects the fetus or infant, the presence of CMV in the breast milk (virolactia), the infant’s immune susceptibility, and the presence or absence of antibodies against CMV provided to the infant by the mother (transplacentally acquired or in colostrum and breast milk) ²¹⁷ are important determinants of the severity of infection and the likelihood of significant sequelae (congenital infection syndrome, deafness, chorioretinitis, abnormal neurodevelopment, learning disabilities). ²¹⁸ , ²¹⁹ About 1% of all infants are born excreting CMV at birth, and approximately 5% of these congenitally infected infants will demonstrate evidence of infection at birth (approximately 5 symptomatic cases per 10,000 live births). Approximately 15% of infants born after primary infection in a pregnant woman will manifest at least one sequela of prenatal infection. ²²⁰

Various studies have detected that 3% to 28% of pregnant women have CMV in cervical cultures and that 4% to 5% of pregnant women have CMV in their urine. ²²¹ , ²²² Perinatal infection certainly occurs through contact with the virus in these fluids, but it is not usually associated with clinical illness in full-term infants. The lack of illness is thought to result from the transplacental passive transfer of protective antibodies from the mother.

Postnatal infection later in infancy occurs via breastfeeding or contact with infected fluids (e.g., saliva, urine), but again, it rarely causes clinical illness in full-term infants. Seroepidemiologic studies have documented the transmission of infection in infancy, with higher rates of transmission occurring in daycare centers, especially when the prevalence of CMV in the urine and saliva is high.