Biomedical subjects

Christopher D Paddock

Publications and source records attributed to Christopher D Paddock.

At least 37 records · Page 2Linked to original sources

PubMed2005

Tick-borne rickettsioses around the world: emerging diseases challenging old concepts.

During most of the 20th century, the epidemiology of tick-borne rickettsioses could be summarized as the occurrence of a single pathogenic rickettsia on each continent. An element of this paradigm suggested that the many other characterized and noncharacterized rickettsiae isolated from ticks were not pathogenic to humans. In this context, it was considered that relatively few tick-borne rickettsiae caused human disease. This concept was modified extensively from 1984 through 2005 by the identification of at least 11 additional rickettsial species or subspecies that cause tick-borne rickettsioses around the world. Of these agents, seven were initially isolated from ticks, often years or decades before a definitive association with human disease was established. We present here the tick-borne rickettsioses described through 2005 and focus on the epidemiological circumstances that have played a role in the emergence of the newly recognized diseases.

Animals↗

PubMed2005

Rickettsia parkeri as a paradigm for multiple causes of tick-borne spotted fever in the western hemisphere.

Among the many contributions made to rickettsiology by entomologist and rickettsiologist Ralph R. Parker was his discovery in 1937 of a novel rickettsia isolated from the Gulf Coast tick, Amblyomma maculatum. This bacterium was subsequently characterized as a unique rickettsial species in 1965 and named Rickettsia parkeri in honor of its discoverer. During the next several decades R. parkeri was generally considered as one of several "nonpathogenic" spotted fever group (SFG) rickettsiae that resided in ticks of the United States. The identification of novel rickettsioses on other continents during the last two decades of the twentieth century provided important evidence of the frequent coexistence of multiple and unique tick-borne SFG rickettsiae sharing common geographic regions. Surprisingly, this paradigm, which was repeatedly demonstrated in Europe, Africa, and Australia during the last 10 years, had no confirmed correlate in the United States until 2002, when R. parkeri was isolated from a patient from the state of Virginia. Several pieces of epidemiologic, laboratory, and clinical evidence are compelling enough to suggest that this infection has occurred in other U.S. patients who reside within the range of the Gulf Coast tick. Just as important are new data indicating relatively high infection rates of A. maculatum ticks with R. parkeri, documenting the occurrence of R. parkeri in Amblyomma triste ticks from Uruguay, and providing evidence that other Amblyomma species might serve as efficient vectors of R. parkeri. The recognition of R. parkeri as a cause of disease in humans will hopefully encourage a closer examination for specific etiologies of tick-borne spotted fever rickettsioses in the United States and other countries of the Western Hemisphere.

Animals↗

PubMed2004

Human monkeypox infection: a family cluster in the midwestern United States.

BACKGROUND: The outbreak of monkeypox in the Midwestern United States during June 2003 marks the first documented human infection in the Western Hemisphere. Consistent with those in outbreaks in Africa, most cases in this outbreak were associated with febrile rash illness. We describe a cluster of monkeypox in a family with a spectrum of clinical illness, including encephalitis, and outline the laboratory confirmation of monkeypox. METHODS: Standardized patient information was collected by questionnaire and medical chart review; all cases described were laboratory confirmed. Laboratory methods included nucleic acid detection, viral culture, serologic testing, histopathologic evaluation, and immunohistochemical testing. RESULTS: Of 3 family members with monkeypox, 2 had rash illness only, and 1 required hospitalization for severe encephalitis. The family member with the mildest clinical course had previously received smallpox vaccination. Diagnostic testing by both polymerase chain reaction and culture revealed infectious monkeypox virus in skin lesions of all 3 patients; 2 patients had orthopoxvirus detected by immunohistochemistry in skin lesions. The patient with encephalitis had orthopoxvirus-reactive immunoglobulin M (IgM) in cerebrospinal fluid. All patients had detectable IgM responses to orthopoxvirus antigens. CONCLUSIONS: These 3 patients illustrate a spectrum of clinical illness with monkeypox despite a common source of exposure; manifestation and severity of illness may be affected by age and prior smallpox vaccination. We report that monkeypox, in addition to causing febrile rash illness, causes severe neurologic infection, and we discuss the use of novel laboratory tests for its diagnosis.

Adult↗

PubMed2004

Rickettsia parkeri: a newly recognized cause of spotted fever rickettsiosis in the United States.

Ticks, including many that bite humans, are hosts to several obligate intracellular bacteria in the spotted fever group (SFG) of the genus Rickettsia. Only Rickettsia rickettsii, the agent of Rocky Mountain spotted fever, has been definitively associated with disease in humans in the United States. Herein we describe disease in a human caused by Rickettsia parkeri, an SFG rickettsia first identified >60 years ago in Gulf Coast ticks (Amblyomma maculatum) collected from the southern United States. Confirmation of the infection was accomplished using serological testing, immunohistochemical staining, cell culture isolation, and molecular methods. Application of specific laboratory assays to clinical specimens obtained from patients with febrile, eschar-associated illnesses following a tick bite may identify additional cases of R. parkeri rickettsiosis and possibly other novel SFG rickettsioses in the United States.

Adult↗

PubMed2004

Clinicopathologic study and laboratory diagnosis of 23 cases with West Nile virus encephalomyelitis.

The differences in pathologic findings of fatal cases of West Nile virus (WNV) encephalitis in the context of underlying conditions and illness duration are not well known. During 2002, we studied central nervous system (CNS) tissue samples from 23 patients who had serologic and immunohistochemical (IHC) evidence of a recent WNV infection. Fifteen patients had underlying medical conditions (5 malignancies, 3 renal transplants, 3 with diabetes or on dialysis, 2 with AIDS, and 2 receiving steroids). WNV serology was positive for 18 patients, negative for 2, and not available for 3. Perivascular lymphocytic infiltrates, microglial nodules, and loss of neurons were predominantly observed in the brainstem and anterior horns in the spinal cord. IHC using antibodies against flaviviruses and WNV showed viral antigens in 12 (52%) of 23 patients. Viral antigens were found inside neurons and neuronal processes predominantly in the brainstem and anterior horns. In general, the antigens were focal and sparse; however, in 4 severely immunosuppressed patients, extensive viral antigens were seen throughout the CNS. Positive IHC staining was observed in tissues of 7 of 8 patients who died within 1 week after illness onset, compared with 4 of 14 with more than 2 weeks' illness duration. WNV causes an encephalomyelitis by primarily affecting brainstem and spinal cord. Differences in the amount of viral antigen may be related to underlying medical conditions and length of survival. IHC can be an important diagnostic method, particularly during the 1st week of illness, when antigen levels are high.

Adult↗

PubMed2004

Pseudoepidemic of Q fever at an animal research facility.

Serum samples from people exposed to sheep at a research facility were evaluated by a commercial laboratory and resulted in an overall Coxiella burnetii seroprevalence of 75%. We interviewed individuals to determine exposure history and compatible illness, and retested their sera. Analysis indicated that the commercial laboratory was misinterpreting its results; when corrected, the seroprevalence dropped to 27%. Test kits of the brand used by the commercial laboratory gave equivalent results to the in-house CDC assay when tested in parallel at CDC. Upon final analysis, only the attending veterinarian was confirmed as a Q fever case. This event resulted in increased risk reduction protocols at the research facility and improved public health communication among health authorities. This pseudoepidemic resulted from a lapse in laboratory quality control for testing. Similar errors can be avoided through standardization and improved review of laboratory procedures.

Animals↗

PubMed2004

Detection of Ehrlichia chaffeensis in adult and nymphal Amblyomma americanum (Acari: Ixodidae) ticks from Long Island, New York.

The lone star tick, Amblyomma americanum (L.), has increased in abundance in several regions of the northeastern United States, including areas of Long Island, NY. Adult and nymphal stage A. americanum collected from several sites on Long Island were evaluated for infection with Ehrlichia chaffeensis, the causative agent of human monocytic ehrlichiosis (HME), by using a nested polymerase chain reaction assay. Fifty-nine (12.5%) of 473 adults and eight of 113 pools of five nymphs each (estimated minimum prevalence of infection 1.4%) contained DNA of E. chaffeensis. These data, coupled with the documented expansion of lone star tick populations in the northeastern United States, confirm that E. chaffeensis is endemic to many areas of Long Island and that HME should be considered among the differential diagnoses of the many distinct tick-borne diseases that occur in this region.

Animals↗

PubMed2004

Monkeypox transmission and pathogenesis in prairie dogs.

During May and June 2003, the first cluster of human monkeypox cases in the United States was reported. Most patients with this febrile vesicular rash illness presumably acquired the infection from prairie dogs. Monkeypox virus was demonstrated by using polymerase chain reaction in two prairie dogs in which pathologic studies showed necrotizing bronchopneumonia, conjunctivitis, and tongue ulceration. Immunohistochemical assays for orthopoxviruses demonstrated abundant viral antigens in surface epithelial cells of lesions in conjunctiva and tongue, with less amounts in adjacent macrophages, fibroblasts, and connective tissues. Viral antigens in the lung were abundant in bronchial epithelial cells, macrophages, and fibroblasts. Virus isolation and electron microscopy demonstrated active viral replication in lungs and tongue. These findings indicate that both respiratory and direct mucocutaneous exposures are potentially important routes of transmission of monkeypox virus between rodents and to humans. Prairie dogs offer insights into transmission, pathogenesis, and new vaccine and treatment trials because they are susceptible to severe monkeypox infection.

Animals↗

PubMed2004

Q fever endocarditis in HIV-infected patient.

We describe a case of Q fever endocarditis in an HIV-infected patient. The case was treated successfully with valvular replacement and a combination of doxycycline and hydroxychloroquine. We review the current literature on Q fever endocarditis, with an emphasis on the co-infection of HIV and Coxiella burnetii.

Anti-Infective Agents↗

PubMed2004

Fatal spotted fever rickettsiosis, Kenya.

We report a fatal case of rickettsiosis in a woman from the United States living in Kenya, who had a history of tick exposure. Immunohistochemical staining of skin, kidney, and liver demonstrated spotted fever group rickettsiae. The clinical findings, severity, and fatal outcome are most consistent with Rickettsia conorii infection.

Adult↗

PubMed2004

Imported spotted fever rickettsioses in United States travelers returning from Africa: a summary of cases confirmed by laboratory testing at the Centers for Disease Control and Prevention, 1999-2002.

The increasing popularity of foreign travel and ecotourism places travelers at increased risk for certain tick-borne diseases. From 1999 through 2002, 31 cases of imported spotted fever-group rickettsioses (SFGR) in United States residents reporting travel to Africa were confirmed by laboratory testing at the Centers for Disease Control and Prevention. Nineteen patients (61%) reported visiting South Africa prior to illness onset. Most patients reported fever and one or more eschars; rash was reported for only 26% of the patients. Twelve patients had an initial non-reactive acute-phase serum sample obtained a median of three days after illness onset, and were confirmed by testing a second convalescent-phase serum sample obtained a median of 32 days after illness onset. Five patients were confirmed positive through immunohistochemical staining of skin biopsies, including three patients with acute-phase serum samples that tested negative for SFGR. This study emphasizes the importance of evaluating convalescent-phase serum specimens 28 days or more after illness onset or examining skin biopsies by immunohistochemical staining during early infection to confirm a diagnosis of imported SFGR.

Africa↗

PubMed2003

Rocky Mountain spotted fever: a clinician's dilemma.

Rocky Mountain spotted fever is still the most lethal tick-vectored illness in the United States. We examine the dilemmas facing the clinician who is evaluating the patient with possible Rocky Mountain spotted fever, with particular attention to the following 8 pitfalls in diagnosis and treatment: (1) waiting for a petechial rash to develop before diagnosis; (2) misdiagnosing as gastroenteritis; (3) discounting a diagnosis when there is no history of a tick bite; (4) using an inappropriate geographic exclusion; (5) using an inappropriate seasonal exclusion; (6) failing to treat on clinical suspicion; (7) failing to elicit an appropriate history; and (8) failing to treat with doxycycline. Early diagnosis and proper treatment save lives.

Anti-Bacterial Agents↗

PubMed2003

A novel coronavirus associated with severe acute respiratory syndrome.

BACKGROUND: A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak. METHODS: We received clinical specimens from patients in seven countries and tested them, using virus-isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens. RESULTS: None of the previously described respiratory pathogens were consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription-polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point-source outbreak. Indirect fluorescence antibody tests and enzyme-linked immunosorbent assays made with the new isolate have been used to demonstrate a virus-specific serologic response. This virus may never before have circulated in the U.S. population. CONCLUSIONS: A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. Because of the death of Dr. Carlo Urbani, we propose that our first isolate be named the Urbani strain of SARS-associated coronavirus.

Adult↗

PubMed2003

Increased detection of rickettsialpox in a New York City hospital following the anthrax outbreak of 2001: use of immunohistochemistry for the rapid confirmation of cases in an era of bioterrorism.

BACKGROUND: Rickettsialpox is a self-limited febrile illness with skin lesions that may be mistaken for signs of potentially more serious diseases, such as cutaneous anthrax or chickenpox. The cluster of cutaneous anthrax cases from bioterrorism in October 2001 likely heightened awareness of and concern for cutaneous eschars. OBJECTIVES: To apply an immunohistochemical technique on paraffin-embedded skin biopsy specimens for diagnosing rickettsialpox, and to compare the reported incidence of rickettsialpox before, during, and after the cluster of cutaneous anthrax cases. DESIGN: Case series. SETTING: Dermatology department in a large tertiary care hospital in New York City. PATIENTS: Eighteen consecutive patients with the clinical diagnosis of rickettsialpox from February 23, 2001, through October 31, 2002. MAIN OUTCOME MEASURES: Results of immunohistochemical testing of skin biopsy specimens and of serological testing. RESULTS: Immunohistochemical testing revealed spotted fever group rickettsiae in all 16 eschars and in 5 of the 9 papulovesicles tested. A 4-fold or greater increase in IgG antibody titers reactive with Rickettsia akari was observed in all 9 patients for whom acute and convalescent phase samples were available; 6 patients had single titers indicative of rickettsialpox infection (> or =1:64). Of the 18 patients, 9 (50%) presented in the 5 months following the bioterrorism attacks. CONCLUSIONS: Rickettsialpox remains endemic in New York City, and the bioterrorism attacks of October 2001 may have led to increased awareness and detection of this disease. Because rickettsialpox may be confused with more serious diseases, such as cutaneous anthrax or chickenpox, clinicians should be familiar with its clinical presentation and diagnostic features. Immunohistochemical staining of skin biopsy specimens, particularly from eschars, is a sensitive technique for confirming the clinical diagnosis.

Adolescent↗

PubMed2003

Rickettsialpox in a patient with HIV infection.

We describe the first case of rickettsialpox in a patient infected with HIV. Immunohistochemical staining of biopsied lesions showed a relatively large number of rickettsiae within the papulovesicular rash. Rickettsialpox is easily treated and may resemble more serious cutaneous eruptions in patients infected with HIV. This diagnosis should be considered in immunocompromised city-dwellers, with fever and a papulovesicular rash.

Anti-Bacterial Agents↗

PubMed2003

Rickettsialpox in New York City: a persistent urban zoonosis.

Rickettsialpox, a spotted fever rickettsiosis, was first identified in New York City (NYC) in 1946. During the next five years, approximately 540 additional cases were identified in NYC. However, during the subsequent five decades, rickettsialpox received relatively little attention from clinicians and public health professionals, and reporting of the disease diminished markedly. During February 2001 through August 2002, 34 cases of rickettsialpox in NYC were confirmed at CDC from cutaneous biopsy specimens tested by using immunohistochemical (IHC) staining, PCR analysis, and isolation of Rickettsia akari in cell culture, as well as an indirect immunofluorescence assay of serum specimens. Samples were collected from patients with febrile illnesses accompanied by an eschar, a papulovesicular rash, or both. Patients originated predominantly from two boroughs (Manhattan and the Bronx). Only 8 (24%) of the cases were identified prior to the reports of bioterrorism-associated anthrax in the United States during October 2001, and lesions of several patients evaluated during and subsequent to this episode were suspected initially to be cutaneous anthrax. IHC staining of biopsy specimens of eschars and papular lesions were positive for spotted fever group rickettsiae for 32 patients. Of the eleven patients for whom paired serum samples were obtained, all demonstrated fourfold or greater increases in antibody titers reactive with R. akari. The 17-kDa protein gene sequence of R. akari was amplified from eschars of five patients. Four isolates of R. akari were obtained from cutaneous lesions. Possible factors responsible for the increase in clinical samples evaluated for rickettsialpox during this interval include renewed clinical interest in the disease, improved diagnostic methods, epizootiological influences, and factors associated with the recent specter of bioterrorism.

Animals↗

PubMed2003

Ehrlichia chaffeensis: a prototypical emerging pathogen.

Ehrlichia chaffeensis is an obligately intracellular, tick-transmitted bacterium that is maintained in nature in a cycle involving at least one and perhaps several vertebrate reservoir hosts. The moderate to severe disease caused by E. chaffeensis in humans, first identified in 1986 and reported for more than 1,000 patients through 2000, represents a prototypical "emerging infection." Knowledge of the biology and natural history of E. chaffeensis, and of the epidemiology, clinical features, and laboratory diagnosis of the zoonotic disease it causes (commonly referred to as human monocytic ehrlichiosis [HME]) has expanded considerably in the period since its discovery. In this review, we summarize briefly the current understanding of the microbiology, pathogenesis, and clinical manifestations associated with this pathogen but focus primarily on discussing various ecological factors responsible for the recent recognition of this important and potentially life-threatening tick-borne disease. Perhaps the most pivotal element in the emergence of HME has been the staggering increases in white-tailed deer populations in the eastern United States during the 20th century. This animal serves as a keystone host for all life stages of the principal tick vector (Amblyomma americanum) and is perhaps the most important vertebrate reservoir host for E. chaffeensis. The contributions of other components, including expansion of susceptible human populations, growth and broadening geographical distributions of other potential reservoir species and A. americanum, and improvements in confirmatory diagnostic methods, are also explored.

Animals↗

PubMed2003

Molecular heterogeneity of Ehrlichia chaffeensis isolates determined by sequence analysis of the 28-kilodalton outer membrane protein genes and other regions of the genome.

Ehrlichia chaffeensis, a tick-transmitted rickettsial agent, is responsible for human monocytic ehrlichiosis (HME). In this study, we genetically mapped 10 isolates obtained from HME patients. Sequence analysis of the 28-kDa outer membrane protein (OMP) multigene locus spanning 6 of the 22 tandemly arranged genes identified three distinct genetic groups with shared homology among isolates within each group. Isolates in Groups I and III contained six genes each, while Group II isolates had a gene deletion. There were two regions on the locus where novel gene deletion or insertion mutations occurred, resulting in the net loss of one gene in Group II isolates. Numerous nucleotide differences among genes in isolates of each group also were detected. The shared homology among isolates in each group for the 28-kDa OMP locus suggests the derivation of clonal lineages. Transcription and translation analysis of the locus revealed differences in the expressed genes of different group isolates. Analysis of the 120-kDa OMP gene and variable-length PCR target gene showed size variations resulting from loss or gain of long, direct repeats within the protein coding sequences. To our knowledge this is the first study that looked at several regions of the genome simultaneously, and we provide the first evidence of heterogeneity resulting from gene deletion and insertion mutations in the E. chaffeensis genome. Diversity in different genomic regions could be the result of a selection process or of independently evolved genes.

Amino Acid Sequence↗