Author
Andrea Meyerhoff
Bio: Andrea Meyerhoff is an academic researcher from Food and Drug Administration. The author has contributed to research in topics: Public health & Leishmaniasis. The author has an hindex of 4, co-authored 4 publications receiving 930 citations.
Papers
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Johns Hopkins University1, University of Texas at Austin2, United States Army Medical Research Institute of Infectious Diseases3, Centers for Disease Control and Prevention4, University of New Mexico5, Food and Drug Administration6, United States Department of Health and Human Services7, National Institutes of Health8, Nuclear Threat Initiative9, New York State Department of Health10, University of Minnesota11
TL;DR: Weapons disseminating a number of HFVs could cause an outbreak of an undifferentiated febrile illness 2 to 21 days later, associated with clinical manifestations that could include rash, hemorrhagic diathesis, and shock.
Abstract: ObjectiveTo develop consensus-based recommendations for measures to be taken
by medical and public health professionals if hemorrhagic fever viruses (HFVs)
are used as biological weapons against a civilian populationParticipantsThe Working Group on Civilian Biodefense included 26 representatives
from academic medical centers, public health, military services, governmental
agencies, and other emergency management institutionsEvidenceMEDLINE was searched from January 1966 to January 2002 Retrieved references,
relevant material published prior to 1966, and additional sources identified
by participants were reviewedConsensus ProcessThree formal drafts of the statement that synthesized information obtained
in the evidence-gathering process were reviewed by the working group Each
draft incorporated comments and judgments of the members All members approved
the final draftConclusionsWeapons disseminating a number of HFVs could cause an outbreak of an
undifferentiated febrile illness 2 to 21 days later, associated with clinical
manifestations that could include rash, hemorrhagic diathesis, and shock
The mode of transmission and clinical course would vary depending on the specific
pathogen Diagnosis may be delayed given clinicians' unfamiliarity with these
diseases, heterogeneous clinical presentation within an infected cohort, and
lack of widely available diagnostic tests Initiation of ribavirin therapy
in the early phases of illness may be useful in treatment of some of these
viruses, although extensive experience is lacking There are no licensed vaccines
to treat the diseases caused by HFVs
661 citations
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TL;DR: The following discussion of the data submitted in support of the New Drug Application for AmBisome shows the breadth of data from clinical trials that can be appropriate to support approval for drugs to treat tropical diseases.
Abstract: In August 1997, AmBisome (liposomal amphotericin B, Nexstar, San Dimas, CA) was the first drug approved for the treatment of visceral leishmaniasis by the U.S. Food and Drug Administration. The growing recognition of emerging and reemerging infections warrants that safe and effective agents to treat such infections be readily available in the United States. The following discussion of the data submitted in support of the New Drug Application for AmBisome for the treatment of visceral leishmaniasis shows the breadth of data from clinical trials that can be appropriate to support approval for drugs to treat tropical diseases.
256 citations
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TL;DR: The approval of ciprofloxacin hydrochloride, which was made on the basis of a surrogate human marker of efficacy, made extensive use of data from an animal model of disease and represents a new direction in the development of efficacy data in support of drug approval.
Abstract: In August 2000, the US Food and Drug Administration (FDA) approved ciprofloxacin hydrochloride (Cipro; Bayer) for management of postexposure inhalational anthrax. This was the first antimicrobial drug approved by the FDA for use in treating an infection due to a biological agent used intentionally. The terrorist attacks of 2001 involving anthrax underscore the imperative that safe and effective drugs to manage such infections be readily available in the United States. The approval of ciprofloxacin hydrochloride, which was made on the basis of a surrogate human marker of efficacy, made extensive use of data from an animal model of disease. This represents a new direction in the development of efficacy data in support of drug approval and facilitates the availability of those drugs for which there is an urgent need. This article presents the scientific data and regulatory mechanism that supported the approval of ciprofloxacin hydrochloride for management of postexposure of inhalational anthrax.
38 citations
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TL;DR: The ability of hospital ventilation systems to filter Aspergillus and other fungi following a building implosion and the impact of bedside design and furnishing on nosocomial infections are investigated.
2,632 citations
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TL;DR: The most recent version of the guidelines for the prevention and treatment of opportunistic infections (OI) in HIV-infected adults and adolescents was published in 2002 and 2004, respectively as mentioned in this paper.
Abstract: This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.
1,534 citations
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TL;DR: It is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy.
Abstract: Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. There are significant differences in the sensitivity of these species both to the standard drugs, for example, pentavalent antimonials and miltefosine, and those on clinical trial, for example, paromomycin. Over 60% of patients with visceral leishmaniasis in Bihar State, India, do not respond to treatment with pentavalent antimonials. This is now considered to be due to acquired resistance. Although this class of drugs has been used for over 60 years for leishmaniasis treatment, it is only in the past 2 years that the mechanisms of action and resistance have been identified, related to drug metabolism, thiol metabolism, and drug efflux. With the introduction of new therapies, including miltefosine in 2002 and paromomycin in 2005-2006, it is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy.
1,450 citations
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TL;DR: The majority of cases in the SARS outbreak in the greater Toronto area were related to hospital exposure, and several features of the clinical presentation will be useful in raising the suspicion of SARS.
Abstract: ContextSevere acute respiratory syndrome (SARS) is an emerging infectious disease
that first manifested in humans in China in November 2002 and has subsequently
spread worldwide.ObjectivesTo describe the clinical characteristics and short-term outcomes of
SARS in the first large group of patients in North America; to describe how
these patients were treated and the variables associated with poor outcome.Design, Setting, and PatientsRetrospective case series involving 144 adult patients admitted to 10
academic and community hospitals in the greater Toronto, Ontario, area between
March 7 and April 10, 2003, with a diagnosis of suspected or probable SARS.
Patients were included if they had fever, a known exposure to SARS, and respiratory
symptoms or infiltrates observed on chest radiograph. Patients were excluded
if an alternative diagnosis was determined.Main Outcome MeasuresLocation of exposure to SARS; features of the history, physical examination,
and laboratory tests at admission to the hospital; and 21-day outcomes such
as death or intensive care unit (ICU) admission with or without mechanical
ventilation.ResultsOf the 144 patients, 111 (77%) were exposed to SARS in the hospital
setting. Features of the clinical examination most commonly found in these
patients at admission were self-reported fever (99%), documented elevated
temperature (85%), nonproductive cough (69%), myalgia (49%), and dyspnea (42%).
Common laboratory features included elevated lactate dehydrogenase (87%),
hypocalcemia (60%), and lymphopenia (54%). Only 2% of patients had rhinorrhea.
A total of 126 patients (88%) were treated with ribavirin, although its use
was associated with significant toxicity, including hemolysis (in 76%) and
decrease in hemoglobin of 2 g/dL (in 49%). Twenty-nine patients (20%) were
admitted to the ICU with or without mechanical ventilation, and 8 patients
died (21-day mortality, 6.5%; 95% confidence interval [CI], 1.9%-11.8%). Multivariable
analysis showed that the presence of diabetes (relative risk [RR], 3.1; 95%
CI, 1.4-7.2; P = .01) or other comorbid conditions
(RR, 2.5; 95% CI, 1.1-5.8; P = .03) were independently
associated with poor outcome (death, ICU admission, or mechanical ventilation).ConclusionsThe majority of cases in the SARS outbreak in the greater Toronto area
were related to hospital exposure. In the event that contact history becomes
unreliable, several features of the clinical presentation will be useful in
raising the suspicion of SARS. Although SARS is associated with significant
morbidity and mortality, especially in patients with diabetes or other comorbid
conditions, the vast majority (93.5%) of patients in our cohort survived.Published online May 6, 2003 (doi:10.1001/jama.289.21.JOC30885).
1,269 citations
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TL;DR: SARS appears to be of viral origin, with patterns suggesting droplet or contact transmission, and the role of human metapneumovirus, a novel coronavirus, or both requires further investigation.
Abstract: background Severe acute respiratory syndrome (SARS) is a condition of unknown cause that has recently been recognized in patients in Asia, North America, and Europe. This report summarizes the initial epidemiologic findings, clinical description, and diagnostic findings that followed the identification of SARS in Canada. methods SARS was first identified in Canada in early March 2003. We collected epidemiologic, clinical, and diagnostic data from each of the first 10 cases prospectively as they were identified. Specimens from all cases were sent to local, provincial, national, and international laboratories for studies to identify an etiologic agent. results The patients ranged from 24 to 78 years old; 60 percent were men. Transmission occurred only after close contact. The most common presenting symptoms were fever (in 100 percent of cases) and malaise (in 70 percent), followed by nonproductive cough (in 100 percent) and dyspnea (in 80 percent) associated with infiltrates on chest radiography (in 100 percent). Lymphopenia (in 89 percent of those for whom data were available), elevated lactate dehydrogenase levels (in 80 percent), elevated aspartate aminotransferase levels (in 78 percent), and elevated creatinine kinase levels (in 56 percent) were common. Empirical therapy most commonly included antibiotics, oseltamivir, and intravenous ribavirin. Mechanical ventilation was required in five patients. Three patients died, and five have had clinical improvement. The results of laboratory investigations were negative or not clinically significant except for the amplification of human metapneumovirus from respiratory specimens from five of nine patients and the isolation and amplification of a novel coronavirus from five of nine patients. In four cases both pathogens were isolated. conclusions SARS is a condition associated with substantial morbidity and mortality. It appears to be of viral origin, with patterns suggesting droplet or contact transmission. The role of human metapneumovirus, a novel coronavirus, or both requires further investigation.
1,125 citations