Charles Edwards | Mercy Medical Center (original) (raw)

Papers by Charles Edwards

Research paper thumbnail of A Chapman-Layers Ionospheric Model for Mars

A numerical model (CLIMM) is developed that adopts functions of two Chapman layers to compute Mar... more A numerical model (CLIMM) is developed that adopts functions of two Chapman layers to compute Mars ionospheric electron densities at given local solar zenith angle and height. Electron density profiles derived from Mars Global Survey (MGS)-to-Earth radio occultation measurements collected during 1998 through 2005 are used to fit the model. The present model does not include variations with solar extreme

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Research paper thumbnail of Technical Brief Rapid Detection and Identification of Brettanomyces from Winery Air Samples Based on Peptide Nucleic Acid Analysis

A new filt e r-based chemiluminescent in s itu hybridiza tion method us ing peptide nucle ic a ci... more A new filt e r-based chemiluminescent in s itu hybridiza tion method us ing peptide nucle ic a cid probes for rapid and si mult a neous d e tectio n , identifi cati o n, a nd enumeration of Brettanomyces from a ir s a mples was develope d. Th e me thod a ls o a llows fo

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Research paper thumbnail of Leptospirosis

Leptospirosis in humans occurs globally(141) as an acute infection ranging in severity from unnot... more Leptospirosis in humans occurs globally(141) as an acute infection ranging in severity from unnoticed and subclinical to fatal. It is a zoonosis (strictly, an anthropozoonosis) acquired by humans from an animal source. The causal bacterium is a pathogenic spirochete of the genus Leptospira, of which there are several species and more than 250 serological varieties (serovars), each of which has

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Research paper thumbnail of Epidemiology of Helicobacter pylori infection in Barbados

The West Indian medical journal, 1997

The epidemiology of Helicobacter pylori infection in Barbadian patients and controls was studied.... more The epidemiology of Helicobacter pylori infection in Barbadian patients and controls was studied. H. pylori was isolated from biopsies from 50/100 (50%) adult patients undergoing endoscopy for investigation of upper gastrointestinal tract symptoms. Urease was detected in biopsies from 54 patients and gastritis was detected by histology in 71 patients. Serology was performed using a commercial ELISA method. Using an IgG concentration of 10 U/ml as a threshold, antibodies were detected in 78% of 100 patients undergoing endoscopy, 72% of 230 blood donors and 22% of 50 children. The mean antibody concentration was significantly higher in patients (92 U/ml) than in blood donors (49 U/ml) or in children (9.5 U/ml). Culture-positive patients (120 U/ml) had higher IgG concentrations than culture-negative patients (64 U/ml). Using isolation of H. pylori or a positive biopsy urease test as a measure of true prevalence of infection, the sensitivity of serology was 96%, the specificity 42%, pos...

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Research paper thumbnail of Leptospirosis in Barbados. A clinical study

The West Indian medical journal, 1990

A 39-month clinical study of leptospirosis was undertaken at the Queen Elizabeth Hospital, Barbad... more A 39-month clinical study of leptospirosis was undertaken at the Queen Elizabeth Hospital, Barbados. Eighty-eight patients had a confirmed diagnosis of the disease during the period. The major serogroups identified were autumnalis (including a new serovar bim), icterohaemorrhagiae, ballum and canicola. The majority of patients presented with jaundice (95%,) anorexia and headaches (85%), fever (76%) and conjunctival suffusion (54%). While abnormal creatinine levels were seen in 49% of patients on admission, only 16% were judged to have had renal failure. The urine to plasma urea ratio showed high sensitivity and specificity in the diagnosis of pre-renal azotemia. Cardiac arrhythmias and myocarditis occurred in 18% of patients and pericarditis in 6%. An elevated serum amylase was found in 65% of cases. The bilirubin level took 5.5 weeks to return to normal. Thrombocytopenia was shown not to be due to a disseminated intravascular coagulation, and a randomised trial of high dose penicil...

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Research paper thumbnail of Questionnaire detection of problem drinkers among acute medical admissions

The West Indian medical journal, 1991

The study was designed to determine the prevalence of alcoholism/problem drinking among emergency... more The study was designed to determine the prevalence of alcoholism/problem drinking among emergency medical admissions. Of 203 emergency admissions to two medical wards, 18% were found to be problem drinkers, using the brief Michigan alcoholic screening test (MAST) questionnaire. Problem drinking was found in 31% of males and 5% of females. Most drinking was done with friends (77%) and at the "rum shop" (62%). Fifty-one per cent of problem drinkers started between the ages of sixteen and twenty years. Seventy per cent of all problem drinkers had a first degree family relative who drank compared to 28% of non-drinkers. A high prevalence of alcoholism (48%) was found among smokers. Housestaff detected just over half of male (56%) and female (60%) alcoholics who were MAST-positive. Medical diagnoses among MAST-positive patients were gastrointestinal (cirrhosis, pancreatitis and hepatitis) in 32%, neurological (delirium tremens, seizures and subdural hematoma) in 27% and cardiov...

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Research paper thumbnail of Severe primary HIV-1 infection among black persons in Barbados

International Journal of STD and AIDS, 1997

ABSTRACT Descriptions of primary HIV-1 infection have so far been based on Caucasians living in i... more ABSTRACT Descriptions of primary HIV-1 infection have so far been based on Caucasians living in industrialized nations. Due to studies of leptospirosis in the predominantly black population of Barbados, serum was available for patients admitted with acute febrile illnesses to the Queen Elizabeth Hospital (QEH). By searching the medical records of 510 adult patients with known HIV-1 infection we identified 10 patients who had stored serum from an admission for an acute febrile illness that predated or coincided with their first HIV-1-positive test. Serological testing confirmed primary HIV-1 infection in 9 and was suggestive in the 10th patient. The clinical features of these 10 patients were in keeping with previous descriptions of primary HIV-1 infection but differed from leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. The findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established.

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Research paper thumbnail of As with many of the programs of the County of Albemarle, the development of the budget is a team effort. The County Executive's Office develops the final budget with the assistance of many other individuals in County government. This acknowledgement identifies those key individuals who shared in ...

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Research paper thumbnail of ABPN Congratulations Congratulations MOC C HILD AND ADOLESCENT PSYCHIATRY (167 D IPLOMATES )

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Research paper thumbnail of Cervical myelopathy

The Spine Journal, 2003

Cervical myelopathy is a varied clinical syndromes resulting from spinal cord dysfunction. Underl... more Cervical myelopathy is a varied clinical syndromes resulting from spinal cord dysfunction. Underlying causes are numerous, but spondylosis at one or more levels is the most common etiology. Natural history studies have demonstrated a variable clinical course with gradual neurologic deterioration in a majority of patients. While prospective clinical comparisons are limited, existing literature suggests that operative management reliably arrests

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Research paper thumbnail of Direct detection of leptospiral material in human postmortem samples

Research in Microbiology, 2003

Leptospiral culture, direct immunofluorescence, and the polymerase chain reaction (PCR) were used... more Leptospiral culture, direct immunofluorescence, and the polymerase chain reaction (PCR) were used to detect leptospiral material in postmortem specimens collected from eight patients who died of leptospirosis. Diagnosis of leptospiral infection was based on clinical summary (premortem) and confirmed by serological analysis and/or culture of leptospires. Leptospiral culture was the least sensitive technique, yielding two isolates (3%) from 65 samples. Both isolates were from the aqueous humour and cerebrospinal fluid of the same patient. Direct immunofluorescence was of intermediate sensitivity for detection of leptospires, confirming the presence of leptospires in 11% (2 of 18) of tissue samples from three patients. PCR analysis was the most sensitive technique for detection of leptospiral material in tissue samples, being positive in 20% (11 of 56) of samples from eight patients. Both samples (cerebellum and liver) positive by immunofluorescence were also positive by PCR. The sensitivity of the PCR assay was 1-10 leptospires ml(-1) sample, and the assay was specific for Leptospira pathogenic species. Multi-system involvement was indicated based on successful amplification of leptospiral DNA from more than one tissue sample, which corroborated with the clinical and pathologic findings. The results suggest that in acute and/or fatal leptospirosis, the pathogenesis of the pathologic features are related to the presence of the organisms in the tissues. In conclusion, PCR combined with serology appears to be a useful tool for diagnosis of leptospirosis and may be invaluable in epidemiological studies.

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Research paper thumbnail of Inefficient Cytotoxic T Lymphocyte–Mediated Killing of HIV-1–Infected Cells In Vivo

PLoS Biology, 2006

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Research paper thumbnail of LEPTOSPIROSIS AND PANCREATITIS

The Pediatric Infectious Disease Journal, 1999

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Research paper thumbnail of Sexual Transmission of Single Human Immunodeficiency Virus Type 1 Virions Encoding Highly Polymorphic Multisite Cytotoxic T-Lymphocyte Escape Variants

Journal of Virology, 2005

Antigenic variation inherent in human immunodeficiency virus type 1 (HIV-1) virions that successf... more Antigenic variation inherent in human immunodeficiency virus type 1 (HIV-1) virions that successfully instigate new infections transferred by sex has not been well defined. Yet this is the viral "challenge" which any vaccine-induced immunity must deal with. Closely timed comparisons of the virus circulating in the "donor" and that which initiates new infection are difficult to carry out rigorously, as suitable samples are very hard to get in the face of ethical hurdles. Here we investigate HIV-1 variation in four homosexual couples where we sampled blood from both parties within several weeks of the estimated transmission event. We analyzed variation within highly immunogenic HIV-1 internal proteins encoding epitopes recognized by cytotoxic T lymphocytes (CTLs). These responses are believed to be crucial as a means of containing viral replication. In the donors we detected virions capable of evading host CTL recognition at several linked epitopes of distinct HLA class I restriction. When a donor transmitted escape variants to a recipient with whom he had HLA class I molecules in common, the recipient's CTL response to those epitopes was prevented, thus impeding adequate viral control. In addition, we show that even when HLA class I alleles are disparate in the transmitting couple, a single polymorphism can abolish CTL recognition of an overlapping epitope of distinct restriction and so confer immune escape properties to the recipient's seroconversion virus. In donors who are themselves controlling an early, acute infection, the precise timing of onward transmission is a crucial determinant of the viral variants available to compose the inoculum.

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Research paper thumbnail of Passive Sexual Transmission of Human Immunodeficiency Virus Type 1 Variants and Adaptation in New Hosts

Journal of Virology, 2006

Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle for the design ... more Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle for the design of a successful vaccine. Certain viral polymorphisms encode human leukocyte antigen (HLA)-associated immune escape, potentially overcoming limited vaccine protection. Although transmission of immune escape variants has been reported, the overall extent to which this phenomenon occurs in populations and the degree to which it contributes to HIV-1 viral evolution are unknown. Selection on the HIV-1 env gene at transmission favors neutralization-sensitive variants, but it is not known to what degree selection acts on the internal HIV-1 proteins to restrict or enhance the transmission of immune escape variants. Studies have suggested that HLA class I may determine susceptibility to HIV-1 infection, but a definitive role for HLA at transmission remains unproven. Comparing populations of acute seroconverters and chronically infected patients, we found no evidence of selection acting to restrict transmission of HIV-1 variants. We found that statistical associations previously reported in chronic infection between viral polymorphisms and HLA class I alleles are not present in acute infection, suggesting that the majority of viral polymorphisms in these patients are the result of transmission rather than de novo adaptation. Using four episodes of HIV-1 transmission in which the donors and recipients were both sampled very close to the time of infection we found that, despite a transmission bottleneck, genetic variants of HIV-1 infection are transmitted in a frequency-dependent manner. As HIV-1 infections are seeded by unique donor-adapted viral variants, each episode is a highly individual antigenic challenge. Host-specific, idiosyncratic HIV-1 antigenic diversity will seriously tax the efficacy of immunization based on consensus sequences.

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Research paper thumbnail of Evaluation of the polymerase chain reaction for early diagnosis of leptospirosis

Journal of Medical Microbiology, 1995

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Research paper thumbnail of Loss of Viral Control in Early HIV‐1 Infection Is Temporally Associated with Sequential Escape from CD8 + T Cell Responses and Decrease in HIV–1–Specific CD4 + and CD8 + T Cell Frequencies

The Journal of Infectious Diseases, 2004

The outcome of human immunodeficiency virus type 1 (HIV-1) infection is related to the set-point ... more The outcome of human immunodeficiency virus type 1 (HIV-1) infection is related to the set-point plasma virus load (pVL) that emerges after primary HIV-1 infection (PHI). This set-point pVL generally remains stable but eventually increases with progression to disease. However, the events leading to loss of viremic control are poorly understood. Here, we describe an individual who presented with symptomatic PHI and subsequently progressed rapidly, after an initial period of 1 year during which viral replication was well controlled. Escalation of viral replication in this atypical case was preceded by the emergence of escape variants in many epitopes targeted by dominant CD8+ T cell responses and a marked decrease in HIV-1-specific CD4+ and CD8+ T cell frequencies. There were no changes in viral tropism, replication kinetics, or neutralizing antibody titers. These findings demonstrate the temporal relationship between viral escape from CD8+ T cell activity, decrease in HIV-1-specific T cell frequencies, and loss of control of viral replication.

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Research paper thumbnail of Serological Evidence of Hantavirus in Humans and Rodents in Barbados

Journal of Infection, 2002

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Research paper thumbnail of Mars dynamics from Earth-based tracking of the Mars Pathfinder lander

Journal of Geophysical Research, 1997

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Research paper thumbnail of Quality Retention in Strawberry and Carrot Purees Dried with Refractance WindowTM System

Journal of Food Science, 2002

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Research paper thumbnail of A Chapman-Layers Ionospheric Model for Mars

A numerical model (CLIMM) is developed that adopts functions of two Chapman layers to compute Mar... more A numerical model (CLIMM) is developed that adopts functions of two Chapman layers to compute Mars ionospheric electron densities at given local solar zenith angle and height. Electron density profiles derived from Mars Global Survey (MGS)-to-Earth radio occultation measurements collected during 1998 through 2005 are used to fit the model. The present model does not include variations with solar extreme

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Research paper thumbnail of Technical Brief Rapid Detection and Identification of Brettanomyces from Winery Air Samples Based on Peptide Nucleic Acid Analysis

A new filt e r-based chemiluminescent in s itu hybridiza tion method us ing peptide nucle ic a ci... more A new filt e r-based chemiluminescent in s itu hybridiza tion method us ing peptide nucle ic a cid probes for rapid and si mult a neous d e tectio n , identifi cati o n, a nd enumeration of Brettanomyces from a ir s a mples was develope d. Th e me thod a ls o a llows fo

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Research paper thumbnail of Leptospirosis

Leptospirosis in humans occurs globally(141) as an acute infection ranging in severity from unnot... more Leptospirosis in humans occurs globally(141) as an acute infection ranging in severity from unnoticed and subclinical to fatal. It is a zoonosis (strictly, an anthropozoonosis) acquired by humans from an animal source. The causal bacterium is a pathogenic spirochete of the genus Leptospira, of which there are several species and more than 250 serological varieties (serovars), each of which has

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Research paper thumbnail of Epidemiology of Helicobacter pylori infection in Barbados

The West Indian medical journal, 1997

The epidemiology of Helicobacter pylori infection in Barbadian patients and controls was studied.... more The epidemiology of Helicobacter pylori infection in Barbadian patients and controls was studied. H. pylori was isolated from biopsies from 50/100 (50%) adult patients undergoing endoscopy for investigation of upper gastrointestinal tract symptoms. Urease was detected in biopsies from 54 patients and gastritis was detected by histology in 71 patients. Serology was performed using a commercial ELISA method. Using an IgG concentration of 10 U/ml as a threshold, antibodies were detected in 78% of 100 patients undergoing endoscopy, 72% of 230 blood donors and 22% of 50 children. The mean antibody concentration was significantly higher in patients (92 U/ml) than in blood donors (49 U/ml) or in children (9.5 U/ml). Culture-positive patients (120 U/ml) had higher IgG concentrations than culture-negative patients (64 U/ml). Using isolation of H. pylori or a positive biopsy urease test as a measure of true prevalence of infection, the sensitivity of serology was 96%, the specificity 42%, pos...

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Research paper thumbnail of Leptospirosis in Barbados. A clinical study

The West Indian medical journal, 1990

A 39-month clinical study of leptospirosis was undertaken at the Queen Elizabeth Hospital, Barbad... more A 39-month clinical study of leptospirosis was undertaken at the Queen Elizabeth Hospital, Barbados. Eighty-eight patients had a confirmed diagnosis of the disease during the period. The major serogroups identified were autumnalis (including a new serovar bim), icterohaemorrhagiae, ballum and canicola. The majority of patients presented with jaundice (95%,) anorexia and headaches (85%), fever (76%) and conjunctival suffusion (54%). While abnormal creatinine levels were seen in 49% of patients on admission, only 16% were judged to have had renal failure. The urine to plasma urea ratio showed high sensitivity and specificity in the diagnosis of pre-renal azotemia. Cardiac arrhythmias and myocarditis occurred in 18% of patients and pericarditis in 6%. An elevated serum amylase was found in 65% of cases. The bilirubin level took 5.5 weeks to return to normal. Thrombocytopenia was shown not to be due to a disseminated intravascular coagulation, and a randomised trial of high dose penicil...

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Research paper thumbnail of Questionnaire detection of problem drinkers among acute medical admissions

The West Indian medical journal, 1991

The study was designed to determine the prevalence of alcoholism/problem drinking among emergency... more The study was designed to determine the prevalence of alcoholism/problem drinking among emergency medical admissions. Of 203 emergency admissions to two medical wards, 18% were found to be problem drinkers, using the brief Michigan alcoholic screening test (MAST) questionnaire. Problem drinking was found in 31% of males and 5% of females. Most drinking was done with friends (77%) and at the "rum shop" (62%). Fifty-one per cent of problem drinkers started between the ages of sixteen and twenty years. Seventy per cent of all problem drinkers had a first degree family relative who drank compared to 28% of non-drinkers. A high prevalence of alcoholism (48%) was found among smokers. Housestaff detected just over half of male (56%) and female (60%) alcoholics who were MAST-positive. Medical diagnoses among MAST-positive patients were gastrointestinal (cirrhosis, pancreatitis and hepatitis) in 32%, neurological (delirium tremens, seizures and subdural hematoma) in 27% and cardiov...

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Research paper thumbnail of Severe primary HIV-1 infection among black persons in Barbados

International Journal of STD and AIDS, 1997

ABSTRACT Descriptions of primary HIV-1 infection have so far been based on Caucasians living in i... more ABSTRACT Descriptions of primary HIV-1 infection have so far been based on Caucasians living in industrialized nations. Due to studies of leptospirosis in the predominantly black population of Barbados, serum was available for patients admitted with acute febrile illnesses to the Queen Elizabeth Hospital (QEH). By searching the medical records of 510 adult patients with known HIV-1 infection we identified 10 patients who had stored serum from an admission for an acute febrile illness that predated or coincided with their first HIV-1-positive test. Serological testing confirmed primary HIV-1 infection in 9 and was suggestive in the 10th patient. The clinical features of these 10 patients were in keeping with previous descriptions of primary HIV-1 infection but differed from leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. The findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established.

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Research paper thumbnail of As with many of the programs of the County of Albemarle, the development of the budget is a team effort. The County Executive's Office develops the final budget with the assistance of many other individuals in County government. This acknowledgement identifies those key individuals who shared in ...

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Research paper thumbnail of ABPN Congratulations Congratulations MOC C HILD AND ADOLESCENT PSYCHIATRY (167 D IPLOMATES )

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Cervical myelopathy

The Spine Journal, 2003

Cervical myelopathy is a varied clinical syndromes resulting from spinal cord dysfunction. Underl... more Cervical myelopathy is a varied clinical syndromes resulting from spinal cord dysfunction. Underlying causes are numerous, but spondylosis at one or more levels is the most common etiology. Natural history studies have demonstrated a variable clinical course with gradual neurologic deterioration in a majority of patients. While prospective clinical comparisons are limited, existing literature suggests that operative management reliably arrests

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Research paper thumbnail of Direct detection of leptospiral material in human postmortem samples

Research in Microbiology, 2003

Leptospiral culture, direct immunofluorescence, and the polymerase chain reaction (PCR) were used... more Leptospiral culture, direct immunofluorescence, and the polymerase chain reaction (PCR) were used to detect leptospiral material in postmortem specimens collected from eight patients who died of leptospirosis. Diagnosis of leptospiral infection was based on clinical summary (premortem) and confirmed by serological analysis and/or culture of leptospires. Leptospiral culture was the least sensitive technique, yielding two isolates (3%) from 65 samples. Both isolates were from the aqueous humour and cerebrospinal fluid of the same patient. Direct immunofluorescence was of intermediate sensitivity for detection of leptospires, confirming the presence of leptospires in 11% (2 of 18) of tissue samples from three patients. PCR analysis was the most sensitive technique for detection of leptospiral material in tissue samples, being positive in 20% (11 of 56) of samples from eight patients. Both samples (cerebellum and liver) positive by immunofluorescence were also positive by PCR. The sensitivity of the PCR assay was 1-10 leptospires ml(-1) sample, and the assay was specific for Leptospira pathogenic species. Multi-system involvement was indicated based on successful amplification of leptospiral DNA from more than one tissue sample, which corroborated with the clinical and pathologic findings. The results suggest that in acute and/or fatal leptospirosis, the pathogenesis of the pathologic features are related to the presence of the organisms in the tissues. In conclusion, PCR combined with serology appears to be a useful tool for diagnosis of leptospirosis and may be invaluable in epidemiological studies.

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Research paper thumbnail of Inefficient Cytotoxic T Lymphocyte–Mediated Killing of HIV-1–Infected Cells In Vivo

PLoS Biology, 2006

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Research paper thumbnail of LEPTOSPIROSIS AND PANCREATITIS

The Pediatric Infectious Disease Journal, 1999

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Research paper thumbnail of Sexual Transmission of Single Human Immunodeficiency Virus Type 1 Virions Encoding Highly Polymorphic Multisite Cytotoxic T-Lymphocyte Escape Variants

Journal of Virology, 2005

Antigenic variation inherent in human immunodeficiency virus type 1 (HIV-1) virions that successf... more Antigenic variation inherent in human immunodeficiency virus type 1 (HIV-1) virions that successfully instigate new infections transferred by sex has not been well defined. Yet this is the viral "challenge" which any vaccine-induced immunity must deal with. Closely timed comparisons of the virus circulating in the "donor" and that which initiates new infection are difficult to carry out rigorously, as suitable samples are very hard to get in the face of ethical hurdles. Here we investigate HIV-1 variation in four homosexual couples where we sampled blood from both parties within several weeks of the estimated transmission event. We analyzed variation within highly immunogenic HIV-1 internal proteins encoding epitopes recognized by cytotoxic T lymphocytes (CTLs). These responses are believed to be crucial as a means of containing viral replication. In the donors we detected virions capable of evading host CTL recognition at several linked epitopes of distinct HLA class I restriction. When a donor transmitted escape variants to a recipient with whom he had HLA class I molecules in common, the recipient's CTL response to those epitopes was prevented, thus impeding adequate viral control. In addition, we show that even when HLA class I alleles are disparate in the transmitting couple, a single polymorphism can abolish CTL recognition of an overlapping epitope of distinct restriction and so confer immune escape properties to the recipient's seroconversion virus. In donors who are themselves controlling an early, acute infection, the precise timing of onward transmission is a crucial determinant of the viral variants available to compose the inoculum.

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Research paper thumbnail of Passive Sexual Transmission of Human Immunodeficiency Virus Type 1 Variants and Adaptation in New Hosts

Journal of Virology, 2006

Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle for the design ... more Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle for the design of a successful vaccine. Certain viral polymorphisms encode human leukocyte antigen (HLA)-associated immune escape, potentially overcoming limited vaccine protection. Although transmission of immune escape variants has been reported, the overall extent to which this phenomenon occurs in populations and the degree to which it contributes to HIV-1 viral evolution are unknown. Selection on the HIV-1 env gene at transmission favors neutralization-sensitive variants, but it is not known to what degree selection acts on the internal HIV-1 proteins to restrict or enhance the transmission of immune escape variants. Studies have suggested that HLA class I may determine susceptibility to HIV-1 infection, but a definitive role for HLA at transmission remains unproven. Comparing populations of acute seroconverters and chronically infected patients, we found no evidence of selection acting to restrict transmission of HIV-1 variants. We found that statistical associations previously reported in chronic infection between viral polymorphisms and HLA class I alleles are not present in acute infection, suggesting that the majority of viral polymorphisms in these patients are the result of transmission rather than de novo adaptation. Using four episodes of HIV-1 transmission in which the donors and recipients were both sampled very close to the time of infection we found that, despite a transmission bottleneck, genetic variants of HIV-1 infection are transmitted in a frequency-dependent manner. As HIV-1 infections are seeded by unique donor-adapted viral variants, each episode is a highly individual antigenic challenge. Host-specific, idiosyncratic HIV-1 antigenic diversity will seriously tax the efficacy of immunization based on consensus sequences.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Evaluation of the polymerase chain reaction for early diagnosis of leptospirosis

Journal of Medical Microbiology, 1995

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Research paper thumbnail of Loss of Viral Control in Early HIV‐1 Infection Is Temporally Associated with Sequential Escape from CD8 + T Cell Responses and Decrease in HIV–1–Specific CD4 + and CD8 + T Cell Frequencies

The Journal of Infectious Diseases, 2004

The outcome of human immunodeficiency virus type 1 (HIV-1) infection is related to the set-point ... more The outcome of human immunodeficiency virus type 1 (HIV-1) infection is related to the set-point plasma virus load (pVL) that emerges after primary HIV-1 infection (PHI). This set-point pVL generally remains stable but eventually increases with progression to disease. However, the events leading to loss of viremic control are poorly understood. Here, we describe an individual who presented with symptomatic PHI and subsequently progressed rapidly, after an initial period of 1 year during which viral replication was well controlled. Escalation of viral replication in this atypical case was preceded by the emergence of escape variants in many epitopes targeted by dominant CD8+ T cell responses and a marked decrease in HIV-1-specific CD4+ and CD8+ T cell frequencies. There were no changes in viral tropism, replication kinetics, or neutralizing antibody titers. These findings demonstrate the temporal relationship between viral escape from CD8+ T cell activity, decrease in HIV-1-specific T cell frequencies, and loss of control of viral replication.

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Research paper thumbnail of Serological Evidence of Hantavirus in Humans and Rodents in Barbados

Journal of Infection, 2002

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Research paper thumbnail of Mars dynamics from Earth-based tracking of the Mars Pathfinder lander

Journal of Geophysical Research, 1997

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Research paper thumbnail of Quality Retention in Strawberry and Carrot Purees Dried with Refractance WindowTM System

Journal of Food Science, 2002

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