Management of Biohazardous Exposure in Pregnancy
At any point in time in the United States, 3 million women are pregnant. A biohazard exposure, deliberate or accidental, poses a unique challenge and requires careful assessment and prompt treatment to prevent harm to the woman or infant. Physiologic changes during pregnancy can change the safety and efficacy of medications and vaccines for pregnant women. In addition, the potential effect of many of these measures on the fetus is unknown (Cono, Cragan, Jamieson, & Rasmussen, 2006). This chapter discusses the five such biohazards in pregnancy—smallpox, Lassa fever, Ebola, plague, and anthrax—outlining symptomology and treatment options that may become necessary in the obstetric triage or emergency setting.
The working group on civilian biodefense has identified several biologic agents, including smallpox virus and some of the hemorrhagic fever viruses, which are more severe during pregnancy. These agents must be considered if exposure to bioterrorism is known or suspected.
Smallpox, a formerly eradicated disease, has become a bioterrorism threat. One confirmed case of smallpox is a public health emergency. An intense worldwide public health initiative resulted in no documented naturally occurring case of this highly infectious disease occurring since October 26, 1977. The World Health Organization (WHO) officially declared smallpox eradicated in 1980 (Hogan, Harchelroad, & McGovern, 2010). Only two laboratories in the world are known to house smallpox virus: the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the State Research Center of Virology and Biotechnology in Koltsovo, Russia. If these stores are weaponized, mass vaccination would be needed; for example, if a terrorism threat becomes real in the United States, more people, especially the military, will need to be vaccinated.
It is essential to plan for the needs of pregnant, postpartum, and lactating women during a biohazard event because of their unique immunology and physiology and the complexities of balancing maternal and fetal risks 254(Meaney-Delman et al., 2014). During pregnancy, the woman’s susceptibility to infections is altered. Hormonal, cellular, and humoral changes suppress the immune response (Blackburn, 2014). Circulating white cell count is slightly increased, whereas neutrophil chemotaxis and adherence, cell-mediated immunity, and natural killer cell activity decrease.
The virus starts attacking the lungs, then invades the bloodstream and spreads to the skin, intestines, lungs, kidneys, and brain. The virus activity creates a rash that starts as macules (flat, red lesions). The rash progresses to vesicles (raised blisters), then pustules (pus-filled pimples) appear about 12 to 17 days after being infected (Hogan, 2015). Clinical experience with smallpox (variola virus) indicates that pregnant women are more susceptible to variola infection and have more severe disease, resulting in an increased smallpox case-fatality rate. They are also more likely to have hemorrhagic smallpox (purpura variolosa; Jamieson, Theiler, & Rasmussen, 2006).
The CDC, the Department of Defense (DOD), and the Food and Drug Administration (FDA) monitor the outcomes of pregnancy in women exposed to smallpox vaccines in the National Smallpox Vaccine in Pregnancy Registry (Ryan & Seward, 2008). In this group, most (77%) were vaccinated near the time of conception, before pregnancy was confirmed. Outcome evaluations have not revealed higher-than-expected rates of pregnancy loss (11.9%), preterm birth (10.7%), or birth defects (2.8%). No cases of fetal vaccinia have been identified (Ryan & Seward, 2008).
Pregnant women are more susceptible to hemorrhagic smallpox or purpura variolosa. Symptoms include fever, backache, diffuse coppery-red rash, and a rapid decline in the health status of mother and infant. Information on the presentation and progression of smallpox is summarized in Exhibit 22.1.
Smallpox: Presentation and Progression
• Fever, chills
• Body aches, headache
• Rash appears 48–72 hours after initial symptoms
• Turns into virus-filled sores, later scabs over, process can take 2 weeks
• Virus enters respiratory tract
• Multiplies, spreads to regional lymph nodes
• Incubation period (12 days)
• Skin eruptions (lesions occur in the mouth, spread to the face, to the forearms and hands, and finally to lower limbs and trunk)
Source: Adapted from CDC (2009a, 2009b)
255Within 24 hours of the onset of symptoms, a woman will likely develop spontaneous ecchymosis, epistaxis, bleeding gums, an intense erythematous rash, and subconjunctival hemorrhages. Laboratory analysis during this period may demonstrate thrombocytopenia, increased capillary fragility, and depletion of coagulation factors and fibrinogen (CDC, 2009). Death would generally result from sepsis.
Variola virus can cross the placenta and infect the fetus. It is suggested that during pregnancy, there is an increased susceptibility of the fetus to the variola infection with greater severity of illness. Maternal mortality approaches 50%, compared with 30% for men and nonpregnant women (CDC, 2003a, 2007b, 2009).
HISTORY AND DATA COLLECTION
If infection occurs during the first trimester, it can result in high rates of fetal loss. Nishiura (2006) highlights three points about smallpox in pregnancy: Miscarriage and prematurity do not vary by trimester but case fatality is highest during the last trimester; mild cases were at high risk of causing miscarriage or premature birth; and vaccination or previous miscarriage were not associated with miscarriage and premature birth in the current pregnancy. During the latter half of pregnancy, infection is associated with increased rates of prematurity. For initial screening, the CDC has developed an interactive algorithm that can be quickly completed by the provider online. This algorithm indicates the risk of the current clinical condition being smallpox (CDC, 2007a).
Smallpox vaccine comes from a live virus related to smallpox called vaccinia, not smallpox virus (variola). The question remains whether to immunize pregnant women if a release of a biologic agent is confirmed or suspected (Jamieson et al., 2006). During a smallpox outbreak, recommendations for vaccination will change. Anyone exposed to smallpox should get vaccinated, because the risk from the disease is greater than the risk from the vaccine (CDC, 2007b). There is a rare, serious infection of the fetus, called fetal vaccinia, that can occur following vaccination for smallpox. Congenital variola ranges from 9% to 60% during epidemics of the disease. It is characterized by giant dermal pox and diffuse necrotic lesions of viscera and placenta. Fetal vaccinia typically results in stillbirth or death of the infant. There may be maternal immunity that protects the fetus. Smallpox vaccine is not known to cause congenital malformations but, if vaccinated, the woman ought to avoid pregnancy for a month, waiting until the vaccination site has completely healed and the scab has fallen off before trying to become pregnant.
Unvaccinated pregnant women are three times more likely to die from the disease. It is recommended that pregnant women receive the smallpox vaccine only when exposed to a diagnosed case of smallpox because there is a greater risk from the disease than from the vaccine. It is advised that pregnant women not come into contact with anyone who has been recently vaccinated.
If a breastfeeding mother (who has close contact with someone recently vaccinated) develops a rash, it is recommended that the health care provider be contacted to determine if the rash is related to the smallpox vaccine. If a vaccine-related rash occurs, the CDC recommends against breastfeeding until all scabs from the rash have healed. A woman who desires to maintain an adequate milk supply may continue to pump breast milk, but the milk must be discarded until scabs fully separate (CDC, 2009).
256Vaccinia immune globulin (VIG) is an alternate treatment for people who have serious reactions to smallpox vaccine. It is an immune globulin from the blood of people who have gotten the smallpox vaccine more than once (usually many times). Antibodies are removed, purified, and stored with the resulting product being VIG. It is administered intravenously and the licensed product is called “VIG-intravenous” (VIG-IV). VIG-IV is available from the CDC under the Investigational New Drug (IND) protocol that will have guidelines for dosage and administration.
It is recommended that women contact their health care provider regarding use of VIG. Currently, CDC’s Advisory Committee on Immunization Practices does not recommend preventive use of VIG for pregnant women. If a woman has another complication from smallpox vaccine that could be treated with VIG, it would be appropriate that it be given while the woman is pregnant. The few cases of reported fetal vaccinia infection have occurred after an accidental primary vaccination in early pregnancy, or the woman becoming pregnant within 28 days of vaccination. Smallpox vaccine is not known to cause congenital malformations (CDC, 2003).
Lassa fever is an arenavirus infection that occurs mostly in Africa and can be fatal. It may involve multiple organ systems but spares the central nervous system (CNS). The first reported case of Lassa fever was described in a pregnant woman. The mortality rate is higher for pregnant women and women who have given birth within a month. The mortality rate is 50% to 92% when women are pregnant or among those who have recently given birth (Mays, 2009). Recovery occurs within 7 to 31 days after becoming symptomatic or death may ensue. Evidence suggests that the placenta may be a preferred site for viral replication, which may explain why illness and death increase during the third trimester (Jamieson et al., 2006). Uterine evacuation may reduce maternal mortality. Most pregnant women will experience a pregnancy loss. Human cases of Lassa fever probably result from contamination of food with rodent urine, but human-to-human transmission can occur via urine, feces, saliva, vomitus, or blood.
PRESENTING SYMPTOMATOLOGY AND DATA COLLECTION
Lassa fever begins with a viral prodrome, followed by unexplained disease in any organ system except the CNS. Following laboratory test results, the provider may notice massive proteinuria and elevated liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels, which may be 10 times the normal level. Cell cultures are not routine and must be handled in a biosafety level IV laboratory. Lassa IgM antibodies or a four-fold rise in the IgG antibody titer may be detected using an indirect fluorescent antibody technique. Polymerase chain reaction (PCR) is the most rapid test. Chest x-rays may show basilar pneumonitis and pleural effusions (Mays, 2009).
Diagnosis and treatment within the first 6 days may reduce the mortality by up to 10-fold. Supportive treatment includes correction of fluid and electrolyte imbalances. Anti-Lassa fever plasma is helpful as an adjunctive therapy in very ill patients. Antibiotic treatment recommendations can be found in Exhibit 22.2 (Mays, 2009).
Lassa Fever: Treatment
• Ribavirin (Virazole)
• 30 mg/kg IV (maximum, 2 g) loading dose
• 16 mg/kg IV (maximum, 1 g/dose) every 6 hours for 4 days
• 8 mg/kg IV (maximum, 500 mg/dose) every 8 hours for 6 days
Source: Adapted from Mays (2009).
EBOLA HEMORRHAGIC FEVER
Many of the survivors of the 2014 to 2015 epidemic of Ebola virus disease (EVD) in West Africa were women of childbearing age. This epidemic of EVD, centered in West Africa, is the largest EVD epidemic in history. Vertical transmission of Ebola virus (EBOV) from mother to fetus occurs during acute Ebola infection, and can lead to intrauterine fetal death, stillbirth, or neonatal death. Little is known about the risk for transmission of the virus from women to infants outside of the acute infectious period. EBOV has been found in breast milk during acute disease (Kamali et al., 2016).
High amounts of Ebola viral nucleic acid persist in the amniotic fluid of acutely infected pregnant women following clearance of viremia. The question remains whether this amniotic fluid is infectious. Some theoretical concerns remain that interventions during labor and delivery or obstetric anesthetic procedures (e.g., spinal anesthesia) pose an infectious risk to care providers. Similar concerns exist when handling the products of conception or cerebrospinal fluid from EVD survivors. Initial studies following the recent epidemic suggest that women who become pregnant after recovery from EVD pose little risk for transmission of EBOV to the baby or others (Kamali et al., 2016).
PRESENTING SYMPTOMATOLOGY AND DATA COLLECTION
The Ebola virus (EBOV; Filoviridae group) is transmitted by direct contact with blood, secretions, or contaminated objects and is associated with high fatality rates. The EBOV begins to multiply within the body with symptoms beginning 4 to 6 days after infection. The incubation period can be as short as 2 days or as long as 21 days. Of health care workers contracting Ebola following caring for Ebola patients, all had inadequate personal protective equipment (PPE) or used it incorrectly (Beam, 2015; Bebell & Riley, 2015; Dunn et al., 2014).
Presenting symptoms include the sudden onset of flu-like symptoms, such as sore throat; dry, hacking cough; fever; weakness; severe headache; and joint and muscle aches. Diarrhea, dehydration, stomach pain, or vomiting may also occur, accompanied by a rash, hiccups, red eyes, and internal and external bleeding. In dark-skinned women, the rash may not be recognized until it begins to peel. Laboratory findings show low counts of white blood cells and platelets, and elevated liver enzymes (WHO, 2008).
When Ebola exposure has been documented, any woman presenting with fever, together with acute clinical symptoms, signs of hemorrhage such as bleeding of the gums or nose, conjunctival injection, red spots on the body, bloody stools and/or melena, or vomiting blood must be evaluated for possible Ebola. Pregnant women infected with Ebola more often have serious complications, such as hemorrhagic and neurologic sequelae. Pregnant women may not develop hemorrhagic symptoms, particularly in the earlier disease stage or with milder disease. In addition, as in this case, fever may be absent, underscoring the importance of obtaining a comprehensive clinical history and maintaining heightened vigilance for all signs and symptoms of EBOV infection in pregnant women (Oduyebo et al., 2015). Caring for pregnant women at high risk for EBOV disease or those with a diagnosis of EBOV disease based on laboratory confirmation is complex. The Society for Maternal-Fetal Medicine (SMFM) developed an EBOV disease pregnancy web page that links to several general guidance documents for clinicians (www.smfm.org/links/ebola; Riley & Ecker, 2015). Early, aggressive supportive care is the mainstay of management, and massive fluid resuscitation is the key management principle. Patients often may require 5 to 10 L or more per day of intravenous or oral fluid to maintain circulating blood volume. Fluid shifts warrant aggressive monitoring and correction of potassium levels and acid–base disturbances to prevent life-threatening arrhythmias and metabolic complications (Bebell & Riley, 2015; Jamieson et al. 2014).
The risk of death from Ebola is similar among all trimesters of pregnancy, 50% to 90% (Jamieson et al., 2006). Death usually occurs during the second week of symptoms from massive blood loss. The possibility of Ebola must be considered in the differential as a possible primary cause of bleeding (WHO, 2008).
Diagnosis is based on the enzyme-linked immunoassay (ELISA), or specific IgG and IgM antibodies or Ebola-specific antigen detection. These tests are not commercially available and must be sent to specially equipped regional laboratories or WHO collaborating centers. There is no recommended treatment or prophylaxis, and management is supportive therapies with antibiotics used for secondary infections (WHO, 2008).