Clinical Considerations for Anthrax in Pregnant and Postpartum Women

Dana Meaney-Delman, MD MPHAssistant Professor of Gynecology and ObstetricsEmory University School of MedicineConsultantDivision of Reproductive HealthCenters for Disease Control and Prevention

Overview• Review unique features of

pregnant women

• Comprehensive review of reported clinical experience with anthrax in pregnancy and the postpartum period

Pregnant and Postpartum Women

Approximately 7 million pregnancies/year Population that is not well studied

Recent H1N1 pandemic experience Complex clinical management decisions Pre-event planning essential to ensure an

efficient public health response and minimize the burden of disease

Ventura et al. National Vital Statistics Report 2009: 58(4): 1-13Cono et al. Emerg Infect Dis 2006;12:11 1631-1637.Pandemic and All-Hazards Preparedness Act. Public Law 109-417. December 19, 2006.

Considerations for Infectious Disease in Pregnancy

Maternal• Susceptibility• Severity• Obstetrical Issues• Access to

appropriate treatment

• Adherence

Fetal• Complications from

maternal infection• Congenital

infection• Risks from

diagnostic testing and treatments

Major Physiologic Characteristics of Pregnancy

Organ System Physiologic ChangeImmunologic shift away from cell-mediated immunity

and toward humoral immunityRespiratory increased tidal volume

decreased maternal oxygen reservedecreased lung compliance

Cardiovascular increased blood volumedecreased intravascular oncotic pressureincreased volume of distribution

Gastrointestinal decreased function and motilityRenal increased glomerular filtration

Increased renal secretionJamieson et al. Emerg Infect Dis ; 2006: 12:11Cono et al. Emerg Infect Dis; 2006: 12:11

Choice of Antimicrobial Agents in Pregnancy

Efficacy of drug Pharmacokinetics Maternal risks Fetal risks Other concerns

Availability Tolerability Adherence

Cono et al. Emerging Infectious Diseases; 2006: 12:11 1631-1637 Lagoy et al. J Women’s Health;2005:14: 104-110

What do we know about anthrax in

pregnancy?

Systematic Review of Worldwide Experience

• Extensive search dating back to 1886• 14 articles • 7 articles translated from Italian and

German• Submitted to Obstetrics & Gynecology

for publication

Findings• 20 cases total• 17 pregnant , 3 postpartum• 9/20 cases reported in the 19th century

• Anthrax reported in 8 countries– 1 in US– Poland, Iran, Iraq, Turkey, India, Italy – Greatest number in Germany

Location Author(Year) # of CasesTurkey Kadalani(2003) 2India Sujatha(2002) 1Poland Tomasiewicz(1998) 1Iran Handjani(1976), Dutz(1971),

Deneshbod (1970), Kohout(1964),

5

U.S. Regan(1923) 1Germany Rostowzew(1897), Eppinger

(1888), Paltauf(1888), Vogt (1927), Marchand (1886)

8

Italy Romano(1888), Morisani(1886)

2

Anthrax by Location

Anthrax Anthrax Form # of

casesSuspected Exposure

Inhalation (3) Unknown

Cutaneous 13 “flaying a dead cow”, “slaughtering a sick cow”, wool sorting, contact with infected “rags”

Gastrointestinal 2 Ingestion of spores, ingestion of improperly cooked beef

Uterine 1 Attempted abortion with contaminated instrument

Unknown 1 “Horse-hair sorting”

Clinical PresentationsCutaneous• Red painless papule black eschar• Significant edema including facial

and neck respiratory compromise• Fever, increased WBC• Enlarged regional lymph nodes• Difficulty swallowing• IUFD, labor

Clinical PresentationsGastrointestinal• Abdominal pain, vomiting, bloody

diarrhea, abdominal bloating, ascites, pallor, hypotension, vaginal bleeding, vulvar edema, anuria

Uterine• Endometritis, massive

hemorrhage, ascites

Case Author Age Gestational Age

Form Maternal Death

Fetal orNeonatal Death

1 Kadalani (2003) 33 32 weeks cutaneous N N

2 Kadalani (2003) 29 33 weeks cutaneous N N

3 Sujatha (2002) 44 NR gastrointestinal

Y Y*

4 Tomasiewicz (1998)

NR 31 weeks cutaneous N N

5 Handjani (1976) 20 16-20 weeks gastrointestinal

Y Y

6 Dutz (1971) NR NR uterine Y Y

7 Kohout (1964) 30 9 months cutaneous Y N

8 Regan (1923) 22 5-6 months cutaneous Y Y9 Rostowzew (1889) 34 8 months cutaneous Y Y

10 Rostowzew (1889) 36 7 months cutaneous Y Y

11 Rostowzew (1897) 35 4 months cutaneous Y Y

12 Eppinger (1888) NR NR (inhalation) Y Y

13 Eppinger (1888) NR NR (inhalation) Y Y

14 Paltauf (1888) NR 5 months (inhalation) Y Y

15 Romano (1888) 20 “full term” cutaneous Y Y

16 Morisani (1886) 40 “full term” cutaneous Y Y

17 Marchand (1886) 32 “full term” Unknown* Y Y

Postpartum CasesCase

Author Age

Time from Delivery ( at Presentation)

Maternal Death

Fetal/Neonatal Death

18 Daneshbod (1970)

NR 3 days Y N

19 Daneshbod (1970)

NR 3 days Y N

20 Vogt (1927) 32 5 months N N

Maternal Outcomes

Maternal Death Proportion = 80%

n=4

Case Year Form Gestational Age

Treatment Fetal Death

3 Sujatha (2002) GI unknown Cefotaximemetronidazole

Y

5 Handjani (1976) GI* 16-20 weeks

Penicillin/Streptomycin Y

6 Dutz (1971) U NR NR Y

7 Kohout (1964) C 9 months* Penicillin N (transient asphyxia)

8 Reagan (1923) C 5-6 months Antiserum in wound, disinfectants

Y

9 Rostowzew (1897)

C 8 months NR Y

10 Rostowzew (1897)

C 7 months NR Y

11 Rostowzew (1897)

C 4 months NR Y

12 Eppinger (1888) (I) NR NR Y13 Eppinger (1888) (I) NR NR Y14 Paltauf (1888) (I) 5 months NR Y

15 Romano (1888) C “full term”* Incision, cautery, disinfectants

N

16 Paltauf (1886) C “close to term”

Cautery Y

17 Marchand (1886) U “full term” NR Y

Fetal/Neonatal Deaths among Pregnancy Cases

Fetal Death Proportion = 64.7%

n=6

n=11

Preterm Deliveries (PTD)Author/Year Anthrax Gestational Age Clinical Kadalani/2003Turkey

Cutaneous(submandible)

32 weeks/34 weeks

Preterm delivery 13 days after presentation and 3 days after “infection resolved” with antibiotics

Kadalani/2003Turkey

Cutaneous (elbow)

33 weeks/34 weeks

Preterm delivery 7 days after presentation despite tocolysis, treated with antibiotics

Tomasiewicz/1998Poland

Cutaneous(eyelid)

31 weeks/34 weeks

Preterm delivery 3 weeks after presentation

Anthrax and Breastfeeding

• Vogt et al. 1927–Maternal case 5 months postpartum– Cutaneous anthrax on hand fever

debridement sepsis – Continued breastfeeding– No evidence of transmission despite

the lack of antibiotic treatment and severe disease

Anthrax in Fetal TissuesAuthor Maternal Anthrax Fetal TissuesRegan (1923) Cutaneous Placenta, amniotic

fluid, lungs, liver, heart

Rostowzew (1897) Cutaneous Placenta, umbilical vessels, liver

Rostowzew (1897) Cutaneous Placenta, umbilical cord liver, spleen, kidneys, adrenals

Rostowzew(1897) Cutaneous Placenta, liver, spleen adrenals

Paltauf (1888) (Inhalation) Placenta, lungs heart

Marchand (1886) Unknown* Blood, lungs, kidneys, adrenals, liver, spleen

Maternal & Neonatal Anthrax32 year old P2 experienced spontaneous labor, resulting in

the delivery of a male infant who appeared healthy at birth. Two hours after delivery, the patient developed weak pulse and lethargy, and experienced 1 episode of vomiting. Her respiratory status rapidly deteriorated and she expired 7 hours after delivery. Maternal autopsy revealed mesenteric edema, ascites and mesenteric lymph glands infiltrated with anthrax bacilli.

On day of life 3, infant developed “blue-red” rash over entire body, lethargy, a bloated abdomen and ultimately respiratory failure. Fetal autopsy revealed “enormous numbers of anthrax bacilli” in fetal blood, liver, spleen, kidneys adrenal glands and lungs.Marchand 1886

Results Summary• 20 cases of naturally-occurring anthrax in pregnant and

postpartum women• Most were cutaneous• High maternal mortality proportion overall and higher than

expected with cutaneous infections• Obstetrical complications

– High fetal/neonatal death proportion– PTD reported – Labor coincided with presentation in 3 cases– Delayed diagnosis may have contributed to disease

severity• Perinatal Transmission

– 6/11 fetal/neonatal deaths demonstrate anthrax in fetal tissues

– No evidence of passage of anthrax via in one case of anthrax sepsis

Limitations

• All naturally-occurring• Very old case reports• Few women received antibiotics• Delays (or failure) to make

diagnosis until autopsy

DiscussionAre pregnant and postpartum women more or less susceptible to anthrax than the

general population?• Unclear from this review

Is anthrax infection more severe in pregnant and postpartum women than in the general population?

• High proportion of maternal deaths but limited antibiotic use• Higher rate of death in cutaneous anthrax than reported for general population

Is there an increased risk of adverse obstetrical outcomes in women infected with anthrax?

• Deliveries- both preterm and full term• High proportion of fetal death

Is there a risk of congenital infection in infants whose mothers are infected with anthrax?

• Evidenced of anthrax in fetal tissues

Is there a risk of anthrax transmission through breast milk?• No evidence to date

Implications• Anthrax has substantial morbidity and

mortality in the obstetrical population • Medical countermeasures for pregnant

and postpartum women – should maximize maternal (and fetal)

survival– may involve the use of medications that are

not typically used this population – may need to include antimicrobials with

transplacental passage

Acknowledgements• Denise Jamieson• Marianne Zotti• Sonya Rasmussen• Tracee Treadwell• Reina Turcios-Ruiz• George Wendel• Sean Shadomy• Deborah Dee• Willie Bower• Etobssie Wako• Mirelys Rodriguez

Animal Data On Anthrax in Pregnancy

• Paucity of data• Reports of increased rates of

spontaneous abortions in cattle (F de Lalla 1992)

• Reports of maternal to fetal transmission in guinea-pigs, dogs, pigs (Regan 1923)

• Reports of anthrax detected in milk from dairy cattle (WHO 1993)

Anthrax in the 1880s• 1829 Regnier describes “anthrax”

transmissibility from mother to fetus• 1855 Pollender discovered bacilli• 1858 Brauell, Davaine & Koch 1867

innoculated pregnant animals--> no fetal infections

• 1882 Strauss/Chamberland & Koubassoff innoculated pregnant animals: fetal infections

• Other studies documenting perinatal transmission in animals– Perroncito, Walley 1889, Simon1889, Malvoz 1888,

Rosenblath 1889, Latis 1891, Lubarsch, Birch-Hirschfeld 1891