Biomedical subjects

Anthony A Marfin

Publications and source records attributed to Anthony A Marfin.

At least 19 recordsLinked to original sources

PubMed2006

Detection of West Nile virus in formalin-fixed, paraffin-embedded human tissues by RT-PCR: a useful adjunct to conventional tissue-based diagnostic methods.

BACKGROUND: West Nile virus (WNV), a member of genus Flavivirus, causes febrile illness, encephalitis, meningitis, myelitis, and occasional deaths in humans. Although several reverse transcription-polymerase chain reaction (RT-PCR) assays have been developed for detection of WNV in serum, cerebrospinal fluid, and fresh tissues, the usefulness of WNV RT-PCR assays for RNA extracted from formalin-fixed human tissues has not previously been demonstrated. OBJECTIVE: The objective of this study was to evaluate the application of a RT-PCR technique for the detection of WNV in routinely processed, formalin-fixed, paraffin-embedded (FFPE) human tissues, and to compare it with conventional serology and immunohistochemistry (IHC). STUDY DESIGN: We performed two WNV-specific nested RT-PCR assays targeting the viral capsid, premembrane, and envelope genes in FFPE central nervous system tissue samples from 27 patients with fatal WNV encephalitis, as confirmed by serology or IHC, and compared the results. The presence of WNV in RT-PCR-positive samples was confirmed by amplicon sequencing. RESULTS: Twenty (74%) patients were WNV RT-PCR positive while 24 (89%) were seropositive. WNV IHC staining of neurons and neuronal processes was positive in fourteen (52%) patients. The concordance between IHC and serology was 41% (11/27) and between RT-PCR and serology was 63% (17/27). All 11 seropositive/IHC-positive patients and 6 (46%) of 13 seropositive/IHC-negative patients were RT-PCR positive while all 3 seronegatives were positive by both IHC and RT-PCR. CONCLUSIONS: In this study, RT-PCR was significantly more sensitive than IHC in detecting WNV infections and provided specific sequence information about the infecting virus. RT-PCR on FFPE tissues may be a particularly useful diagnostic tool in patients who die relatively soon after disease onset and for whom serology may be negative. Combined use of serology, IHC, and RT-PCR would be expected to have the best overall sensitivity and improve detection of fatal WNV infection.

Adult↗

PubMed2006

West Nile virus disease: a descriptive study of 228 patients hospitalized in a 4-county region of Colorado in 2003.

BACKGROUND: Risk factors for complications of West Nile virus disease and prognosis in hospitalized patients are incompletely understood. METHODS: Demographic characteristics and data regarding potential risk factors, hospitalization, and dispositions were abstracted from medical records for residents of 4 Colorado counties who were hospitalized in 2003 with West Nile virus disease. Univariate and multivariate analyses were used to identify factors associated with West Nile encephalitis (WNE), limb weakness, or death by comparing factors among persons with the outcome of interest with factors among those without the outcome of interest. RESULTS: Medical records of 221 patients were reviewed; 103 had West Nile meningitis, 65 had WNE, and 53 had West Nile fever. Respiratory failure, limb weakness, and cardiac arrhythmia occurred in all groups, with significantly more cases of each in the WNE group. Age, alcohol abuse, and diabetes were associated with WNE. Age and WNE were associated with limb weakness. The mortality rate in the WNE group was 18%; age, immunosuppression, requirement of mechanical ventilation, and history of stroke were associated with death. Only 21% of patients with WNE who survived returned to a prehospitalization level of function. The estimated incidence of West Nile fever cases that required hospitalization was 6.0 cases per 100,000 persons; West Nile fever was associated with arrhythmia, limb weakness, and respiratory failure. CONCLUSIONS: Persons with diabetes and a reported history of alcohol abuse and older persons appear to be at increased risk of developing WNE. Patients with WNE who have a history of stroke, who require mechanical ventilation, or who are immunosuppressed appear to be more likely to die. Respiratory failure, limb weakness, and arrhythmia occurred in all 3 categories, but there were significantly more cases of all in the WNE group.

Adolescent↗

PubMed2006

Transfusion-associated transmission of West Nile virus, United States 2003 through 2005.

BACKGROUND: National blood donation screening for West Nile virus (WNV) started in June 2003, after the documentation of WNV transfusion-associated transmission (TAT) in 2002. STUDY DESIGN AND METHODS: Blood donations were screened with investigational nucleic acid amplification assays in minipool formats. Blood collection agencies (BCAs) reported screening results to state and local public health authorities. Donor test results and demographic information were forwarded to CDC via ArboNET, the national electronic arbovirus surveillance system. State health departments and BCAs also reported suspect WNV TATs to CDC, which investigated these reports to confirm WNV infection in blood transfusion recipients in the absence of likely mosquito exposure. RESULTS: During 2003 to 2005, a total of 1,425 presumptive viremic donors were reported to CDC from 41 states. Of 36 investigations of suspected WNV TAT in 2003, 6 cases were documented. Estimated viremia levels were available for donations implicated in four TAT cases; the median estimated viremia was 0.1 plaque-forming units (PFUs) per mL (range, 0.06-0.50 PFU/mL; 1 PFU equals approximately 400 copies/mL). CONCLUSIONS: National blood screening for WNV identified and removed more than 1,400 potentially infectious blood donations in 2003 through 2005. Despite the success of screening in 2003, some residual WNV TAT risk remained due to donations containing very low levels of virus. Screening algorithms employing selected individual-donation testing were designed to address this residual risk and were fully implemented in 2004 and 2005. Continued vigilance for TAT will evaluate the effectiveness of these strategies.

Adolescent↗

PubMed2006

West Nile Virus-associated flaccid paralysis outcome.

We report 1-year follow-up data from a longitudinal prospective cohort study of patients with West Nile virus-associated paralysis. As in the 4-month follow-up, a variety of recovery patterns were observed, but persistent weakness was frequent. Respiratory involvement was associated with considerable illness and death.

Follow-Up Studies↗

PubMed2005

The cost-effectiveness of screening the U.S. blood supply for West Nile virus.

BACKGROUND: The spread of West Nile virus across North America and evidence of transmission by transfusion prompted the U.S. Food and Drug Administration to encourage the development of methods to screen the blood supply. OBJECTIVE: To assess the cost-effectiveness of nucleic acid amplification testing for West Nile virus in the U.S. blood supply. DESIGN: Markov cohort simulation. DATA SOURCES: Outcome probabilities estimated from nucleic acid testing done for West Nile virus in 2003, data from the Centers for Disease Control and Prevention, and published literature. Costs were taken from an economic study of West Nile virus infection and from estimated test costs. TARGET POPULATIONS: Transfusion recipients, 60 years of age or older, with and without underlying immunocompromise. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: The authors compared 6 strategies, taking into consideration minipool (pools of 6 to 16 donations) versus individual donation testing, and the geographic and seasonal nature of West Nile virus activity. OUTCOME MEASURES: Costs and effects of each strategy based on the prevention of transfusion-transmitted West Nile virus. RESULTS OF BASE-CASE ANALYSIS: The cost-effectiveness of annual, national minipool testing was 483,000 dollars per quality-adjusted life-year (QALY), whereas the cost-effectiveness of annual, national individual donation testing was 897,000 dollars/QALY. The cost-effectiveness of targeted individual donation testing in an area experiencing an outbreak coupled with minipool testing elsewhere was 520,000 dollars/QALY. RESULTS OF SENSITIVITY ANALYSIS: In 1-way analyses, the most important influences were the prevalence of West Nile virus and the cost of minipool testing and individual donation testing. The 95% range of results from probabilistic sensitivity analysis for targeted individual donation testing was 256,000 dollars to 1,044,000 dollars/QALY. LIMITATIONS: The outcomes of West Nile virus infection were based on data from the general population rather than from the population who received transfusions. The results are most useful in the context of geographically focused outbreaks of West Nile virus infection. CONCLUSIONS: Using targeted individual donation testing to interdict blood donations that are positive for the West Nile virus is relatively cost-effective but is highly dependent on West Nile virus prevalence.

Blood Transfusion↗

PubMed2005

Yellow fever and Japanese encephalitis vaccines: indications and complications.

Appropriate administration of yellow fever or Japanese encephalitis vaccines to travelers requires an assessment of the traveler's risk for infection with these vector-borne flaviviruses during their travels and the presence of risk factors for adverse events following immunization. Japanese encephalitis and yellow fever vaccines have been more frequently associated with serious adverse events following immunization since the early 1980s and the late 1990s, respectively. This article describes the adverse events, the magnitude of their risk, and associated risk factors.

Encephalitis, Japanese↗

PubMed2005

Rhabdomyolysis in patients with west nile encephalitis and meningitis.

Since 1999, more than 6,500 cases of West Nile virus neuroinvasive disease (WNND) have been reported in the United States. Patients with WNND can present with muscle weakness that is often assumed to be of neurological origin. During 2002, nearly 3,000 persons with WNV meningitis or encephalitis (or both) were reported in the United States; in suburban Cook County, Illinois, with 244 persons were hospitalized for WNV illnesses. The objective of this investigation was to describe the clinical and epidemiological features of identified cases of WNV neuroinvasive disease and rhabdomyolysis. Public health officials investigated patients hospitalized in Cook County, and identified a subset of WNV neuroinvasive disease patients with elevated creatine kinase levels. Cases were defined as hospitalized persons with a WNV infection, encephalitis or meningitis, and rhabdomyolysis. Retrospective medical record reviews were conducted and data was abstracted with a standardized data collection instrument. Eight patients with West Nile encephalitis and one with West Nile meningitis were identified with rhabdomyolysis. Median age of the nine patients was 70 years (range, 45-85 years), and eight were men. For all nine patients, the peak CK level was documented a median of 2 days after hospitalization (range, 1-24 days). Median CK level during hospitalization for all case-patients was 3,037 IU (range, 1,153-42,113 IU). Six patients had history of recent falls prior to admission. Although the temporal relationship of rhabdomyolysis and neurological WNV illness suggested a common etiology, these patients presented with complex clinical conditions which may have led to development of rhabdomyolysis from other causes. The spectrum of WNV disease requires further investigation to describe this and other clinical conditions associated with WNV infection.

Aged↗

PubMed2005

Molecular subtyping of Treponema pallidum from North and South Carolina.

Patients from five clinics in North and South Carolina who had lesions suggestive of primary or secondary syphilis were evaluated using molecular techniques that allow the differentiation of Treponema pallidum strains on the basis of two variable genes, tpr and arp. Lesion samples were screened for the presence of T. pallidum DNA using PCR for polA, which represents a segment of the polymerase I gene that is unique to the spirochete. Twenty-seven of 154 lesion samples were found to contain T. pallidum, 23 of which had typeable DNA. Seven molecular subtypes were found (10f, 12f, 13f, 14f, 14g, 15f, and 16f); one to four subtypes were identified at each clinic. Subtype 14f was found in 52% of the typeable specimens and was distributed in four of the five clinics. Subtype 16f was found in 22% of specimens and was concentrated at one clinic. Further data are needed to define the role of this technique in examining the epidemiology of syphilis.

Adult↗

PubMed2005

Shifting epidemiology of Flaviviridae.

The dengue, West Nile, Japanese encephalitis and yellow fever viruses are important mosquito-borne viruses whose epidemiology is shifting in response to changing societal factors, such as increasing commerce, urbanization of rural areas, and population growth. All four viruses are expanding geographically, as exemplified by the emergence of West Nile virus in the Americas and Japanese encephalitis virus in Australasia. The large, recent global outbreaks of severe neurological disease caused by West Nile virus, the increasing frequency of dengue hemorrhagic fever outbreaks in the Americas, and the emergence of yellow fever virus vaccination-associated viscerotropic disease, are new clinical epidemiologic trends. These worrisome epidemiologic trends will probably continue in coming decades, as a reversal of their societal and biological drivers is not in sight. Nevertheless, the substantial reductions in Japanese encephalitis virus incidence resulting from vaccination programs and economic development in some Asian countries provide some encouragement within this overall guarded outlook.

Animals↗

PubMed2005

West Nile virus-associated flaccid paralysis.

The causes and frequency of acute paralysis and respiratory failure with West Nile virus (WNV) infection are incompletely understood. During the summer and fall of 2003, we conducted a prospective, population-based study among residents of a 3-county area in Colorado, United States, with developing WNV-associated paralysis. Thirty-two patients with developing paralysis and acute WNV infection were identified. Causes included a poliomyelitislike syndrome in 27 (84%) patients and a Guillain-Barré-like syndrome in 4 (13%); 1 had brachial plexus involvement alone. The incidence of poliomyelitislike syndrome was 3.7/100,000. Twelve patients (38%), including 1 with Guillain-Barré-like syndrome, had acute respiratory failure that required endotracheal intubation. At 4 months, 3 patients with respiratory failure died, 2 remained intubated, 25 showed various degrees of improvement, and 2 were lost to followup. A poliomyelitislike syndrome likely involving spinal anterior horn cells is the most common mechanism of WNV-associated paralysis and is associated with significant short- and long-term illness and death.

Adolescent↗

PubMed2005

West Nile virus epidemic, northeast Ohio, 2002.

Serum samples and sociodemographic data were obtained from 1,209 Ohio residents. West Nile virus immunoglobulin M (IgM) and IgG antibodies were detected by enzyme-linked immunosorbent assay and confirmed. Children were 4.5 times more likely to become infected yet 110 times less likely to have neuroinvasive disease develop.

Adolescent↗

PubMed2004

Post-infectious encephalomyelitis associated with St. Louis encephalitis virus infection.

Neurologic illness associated with acute St. Louis encephalitis, West Nile, and Japanese encephalitis virus infection includes acute aseptic meningitis, encephalomyelitis, and a poliomyelitis-like syndrome. Few post-infectious immune-mediated neurologic events associated with flaviviral infection have been reported. The authors report on a woman with apparent post-infectious encephalomyelitis associated with recent St. Louis encephalitis virus infection, suggesting that neurologic illness from flaviviruses may also be seen in the post-infectious period following mild clinical illness.

Brain↗

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

The epidemic of West Nile virus in the United States, 2002.

Since 1999, health officials have documented the spread of West Nile virus across the eastern and southern states and into the central United States. In 2002, a large, multi-state, epidemic of neuroinvasive West Nile illness occurred. Using standardized guidelines, health departments conducted surveillance for West Nile virus illness in humans, and West Nile virus infection and illness in non-human species. Illnesses were reported to the Centers for Disease Control and Prevention (CDC) through the ArboNET system. In 2002, 39 states and the District of Columbia reported 4,156 human West Nile virus illness cases. Of these, 2,942 (71%) were neuroinvasive illnesses (i.e., meningitis, encephalitis, or meningoencephalitis) with onset dates from May 19 through December 14; 1,157 (28%) were uncomplicated West Nile fever cases, and 47 (1%) were clinically unspecified. Over 80% of neuroinvasive illnesses occurred in the central United States. Among meningitis cases, median age was 46 years (range, 3 months to 91 years), and the fatality-to-case ratio was 2%; for encephalitis cases (with or without meningitis), median age was 64 years (range, 1 month to 99 years) and the fatality-to-case ratio was 12%. Neuroinvasive illness incidence and mortality, respectively, were significantly associated with advanced age (p = 0.02; p = 0.01) and being male (p < 0.001; p = 0.002). In 89% of counties reporting neuroinvasive human illnesses, West Nile virus infections were first noted in non-human species, but no human illnesses were reported from 77% of counties in which non-human infections were detected. In 2002, West Nile virus caused the largest recognized epidemic of neuroinvasive arboviral illness in the Western Hemisphere and the largest epidemic of neuroinvasive West Nile virus ever recorded. It is unknown why males appeared to have higher risk of severe illness and death, but possibilities include higher prevalence of co-morbid conditions or behavioral factors leading to increased infection rates. Several observations, including major, multi-state West Nile virus epidemics in 2002 and 2003, suggest that major epidemics may annually reoccur in the United States. Non-human surveillance can warn of early West Nile virus activity and needs continued emphasis, along with control of Culex mosquitoes.

Adolescent↗

PubMed2003

Transmission of West Nile virus through blood transfusion in the United States in 2002.

BACKGROUND: During the 2002 West Nile virus epidemic in the United States, patients were identified whose West Nile virus illness was temporally associated with the receipt of transfused blood and blood components. METHODS: Patients with laboratory evidence of recent West Nile virus infection within four weeks after receipt of a blood component from a donor with viremia were considered to have a confirmed transfusion-related infection. We interviewed the donors of these components, asking them whether they had had symptoms compatible with the presence of a viral illness before or after their donation; blood specimens retained from the time of donation and collected at follow-up were tested for West Nile virus. RESULTS: Twenty-three patients were confirmed to have acquired West Nile virus through transfused leukoreduced and nonleukoreduced red cells, platelets, or fresh-frozen plasma. Of the 23 recipients, 10 (43 percent) were immunocompromised owing to transplantation or cancer and 8 (35 percent) were at least 70 years of age. Immunocompromised recipients tended to have longer incubation periods than nonimmunocompromised recipients and infected persons in mosquito-borne community outbreaks. Sixteen donors with evidence of viremia at donation were linked to the 23 infected recipients; of these donors, 9 reported viral symptoms before or after donation, 5 were asymptomatic, and 2 were lost to follow-up. Fever, new rash, and painful eyes were independently associated with being an implicated donor with viremia rather than a donor without viremia. All 16 donors were negative for West Nile virus-specific IgM antibody at donation. CONCLUSIONS: Transfused red cells, platelets, and fresh-frozen plasma can transmit West Nile virus. Screening of potential donors with the use of nucleic acid-based assays for West Nile virus may reduce this risk.

Adolescent↗

PubMed2003

Neurologic manifestations and outcome of West Nile virus infection.

CONTEXT: The neurologic manifestations, laboratory findings, and outcome of patients with West Nile virus (WNV) infection have not been prospectively characterized. OBJECTIVE: To describe prospectively the clinical and laboratory features and long-term outcome of patients with neurologic manifestations of WNV infection. DESIGN, SETTING, AND PARTICIPANTS: From August 1 to September 2, 2002, a community-based, prospective case series was conducted in St Tammany Parish, La. Standardized clinical data were collected on patients with suspected WNV infection. Confirmed WNV-seropositive patients were reassessed at 8 months. MAIN OUTCOME MEASURES: Clinical, neurologic, and laboratory features at initial presentation, and long-term neurologic outcome. RESULTS: Sixteen (37%) of 39 suspected cases had antibodies against WNV; 5 had meningitis, 8 had encephalitis, and 3 had poliomyelitis-like acute flaccid paralysis. Movement disorders, including tremor (15 [94%]), myoclonus (5 [31%]), and parkinsonism (11 [69%]), were common among WNV-seropositive patients. One patient died. At 8-month follow-up, fatigue, headache, and myalgias were persistent symptoms; gait and movement disorders persisted in 6 patients. Patients with WNV meningitis or encephalitis had favorable outcomes, although patients with acute flaccid paralysis did not recover limb strength. CONCLUSIONS: Movement disorders, including tremor, myoclonus, and parkinsonism, may be present during acute illness with WNV infection. Some patients with WNV infection and meningitis or encephalitis ultimately may have good long-term outcome, although an irreversible poliomyelitis-like syndrome may result.

Activities of Daily Living↗

PubMed2003

West Nile virus.

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Animals↗

PubMed2003

Transmission of West Nile virus from an organ donor to four transplant recipients.

BACKGROUND: In August 2002, fever and mental-status changes developed in recipients of organs from a common donor. Transmission of West Nile virus through organ transplantation was suspected. METHODS: We reviewed medical records, conducted interviews, and collected blood and tissue samples for testing with a variety of assays. Persons who donated blood to the organ donor and associated blood components were identified and tested for West Nile virus. RESULTS: We identified West Nile virus infection in the organ donor and in all four organ recipients. Encephalitis developed in three of the organ recipients, and febrile illness developed in one. Three recipients became seropositive for West Nile virus IgM antibody; the fourth recipient had brain tissue that was positive for West Nile virus by isolation and nucleic acid and antigen assays. Serum specimens obtained from the organ donor before and immediately after blood transfusions showed no evidence of West Nile virus; however, serum and plasma samples obtained at the time of organ recovery were positive on viral nucleic acid testing and viral culture. The organ donor had received blood transfusions from 63 donors. A review of blood donors and follow-up testing identified one donor who had viremia at the time of donation and who became seropositive for West Nile virus IgM antibodies during the next two months. CONCLUSIONS: Our investigation of this cluster documents the transmission of West Nile virus by organ transplantation. Organ recipients receiving immunosuppressive drugs may be at high risk for severe disease after West Nile virus infection. Blood transfusion was the probable source of the West Nile virus viremia in the organ donor.

Adult↗