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Clinical Considerations for Anthrax in Pregnant and Postpartum Women Dana Meaney-Delman, MD MPH Assistant Professor of Gynecology and Obstetrics Emory.

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Presentation on theme: "Clinical Considerations for Anthrax in Pregnant and Postpartum Women Dana Meaney-Delman, MD MPH Assistant Professor of Gynecology and Obstetrics Emory."— Presentation transcript:

1 Clinical Considerations for Anthrax in Pregnant and Postpartum Women Dana Meaney-Delman, MD MPH Assistant Professor of Gynecology and Obstetrics Emory University School of Medicine Consultant Division of Reproductive Health Centers for Disease Control and Prevention Dana Meaney-Delman, MD MPH Assistant Professor of Gynecology and Obstetrics Emory University School of Medicine Consultant Division of Reproductive Health Centers for Disease Control and Prevention

2 Overview Review unique features of pregnant women Comprehensive review of reported clinical experience with anthrax in pregnancy and the postpartum period

3 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): 1-13 Cono et al. Emerg Infect Dis 2006;12:11 1631-1637. Pandemic and All-Hazards Preparedness Act. Public Law 109-417. December 19, 2006.

4 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

5 Major Physiologic Characteristics of Pregnancy Organ SystemPhysiologic Change Immunologicshift away from cell-mediated immunity and toward humoral immunity Respiratoryincreased tidal volume decreased maternal oxygen reserve decreased lung compliance Cardiovascularincreased blood volume decreased intravascular oncotic pressure increased volume of distribution Gastrointestinaldecreased function and motility Renalincreased glomerular filtration Increased renal secretion Jamieson et al. Emerg Infect Dis ; 2006: 12:11 Cono et al. Emerg Infect Dis; 2006: 12:11

6 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

7 What do we know about anthrax in pregnancy?

8 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

9 Findings 20 cases total 17 pregnant, 3 postpartum 9/20 cases reported in the 19 th century Anthrax reported in 8 countries –1 in US –Poland, Iran, Iraq, Turkey, India, Italy –Greatest number in Germany

10 LocationAuthor(Year)# of Cases TurkeyKadalani(2003)2 IndiaSujatha(2002)1 PolandTomasiewicz(1998)1 IranHandjani(1976), Dutz(1971), Deneshbod (1970), Kohout(1964), 5 U.S.Regan(1923)1 GermanyRostowzew(1897), Eppinger (1888), Paltauf(1888), Vogt (1927), Marchand (1886) 8 ItalyRomano(1888), Morisani(1886)2 Anthrax by Location

11 Anthrax Anthrax Form# of casesSuspected Exposure Inhalation(3)Unknown Cutaneous13“flaying a dead cow”, “slaughtering a sick cow”, wool sorting, contact with infected “rags” Gastrointestinal2Ingestion of spores, ingestion of improperly cooked beef Uterine1Attempted abortion with contaminated instrument Unknown1“Horse-hair sorting”

12 Clinical Presentations Cutaneous Red painless papule  black eschar Significant edema including facial and neck  respiratory compromise Fever, increased WBC Enlarged regional lymph nodes Difficulty swallowing IUFD, labor

13 Clinical Presentations Gastrointestinal Abdominal pain, vomiting, bloody diarrhea, abdominal bloating, ascites, pallor, hypotension, vaginal bleeding, vulvar edema, anuria Uterine Endometritis, massive hemorrhage, ascites

14 CaseAuthorAgeGestational AgeFormMaternal Death Fetal or Neonatal Death 1Kadalani (2003)3332 weekscutaneousNN 2Kadalani (2003)2933 weekscutaneousNN 3Sujatha (2002)44NRgastrointestinalYY* 4Tomasiewicz (1998)NR31 weekscutaneousNN 5Handjani (1976)2016-20 weeksgastrointestinalYY 6Dutz (1971)NR uterineYY 7Kohout (1964)309 monthscutaneousYN 8Regan (1923)225-6 monthscutaneousYY 9Rostowzew (1889)348 monthscutaneousYY 10Rostowzew (1889)367 monthscutaneousYY 11Rostowzew (1897)354 monthscutaneousYY 12Eppinger (1888)NR (inhalation)YY 13Eppinger (1888)NR (inhalation)YY 14Paltauf (1888)NR5 months(inhalation)YY 15Romano (1888)20“full term”cutaneousYY 16Morisani (1886)40“full term”cutaneousYY 17Marchand (1886)32“full term”Unknown*YY

15 Postpartum Cases CaseAuthorAgeTime from Delivery ( at Presentation) Maternal Death Fetal/Neonatal Death 18Daneshbod (1970) NR3 daysYN 19Daneshbod (1970) NR3 daysYN 20Vogt (1927)325 monthsNN

16 Maternal Outcomes Maternal Death Proportion = 80% n=4

17 CaseYearFormGestational Age TreatmentFetal Death 3Sujatha (2002)GIunknownCefotaxime metronidazole Y 5Handjani (1976)GI*16-20 weeksPenicillin/StreptomycinY 6Dutz (1971)UNR Y 7Kohout (1964)C9 months*PenicillinN (transient asphyxia) 8Reagan (1923)C5-6 months Antiserum in wound, disinfectants Y 9Rostowzew (1897)C8 monthsNRY 10Rostowzew (1897)C7 monthsNRY 11Rostowzew (1897)C4 monthsNRY 12Eppinger (1888)(I)NR Y 13Eppinger (1888)(I)NR Y 14Paltauf (1888)(I)5 monthsNRY 15Romano (1888)C“full term”*Incision, cautery, disinfectants N 16Paltauf (1886)C“close to term” CauteryY 17Marchand (1886)U“full term”NRY

18 Fetal/Neonatal Deaths among Pregnancy Cases Fetal Death Proportion = 64.7% n=6 n=11

19 Preterm Deliveries (PTD) Author/YearAnthraxGestational AgeClinical Kadalani/2003 Turkey Cutaneous (submandible) 32 weeks/34 weeksPreterm delivery 13 days after presentation and 3 days after “infection resolved” with antibiotics Kadalani/2003 Turkey Cutaneous (elbow) 33 weeks/34 weeksPreterm delivery 7 days after presentation despite tocolysis, treated with antibiotics Tomasiewicz/1998 Poland Cutaneous (eyelid) 31 weeks/34 weeksPreterm delivery 3 weeks after presentation

20 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

21 Anthrax in Fetal Tissues AuthorMaternal AnthraxFetal Tissues Regan (1923)CutaneousPlacenta, amniotic fluid, lungs, liver, heart Rostowzew (1897)CutaneousPlacenta, umbilical vessels, liver Rostowzew (1897)CutaneousPlacenta, umbilical cord liver, spleen, kidneys, adrenals Rostowzew(1897)CutaneousPlacenta, liver, spleen adrenals Paltauf (1888)(Inhalation)Placenta, lungs heart Marchand (1886)Unknown*Blood, lungs, kidneys, adrenals, liver, spleen

22 Maternal & Neonatal Anthrax 32 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

23 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 tiss ues –No evidence of passage of anthrax via in one case of anthrax sepsis

24 Limitations All naturally-occurring Very old case reports Few women received antibiotics Delays (or failure) to make diagnosis until autopsy

25 Discussion Are 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

26 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

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

28 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)

29 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

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