Daniel Lucey - Academia.edu (original) (raw)
Papers by Daniel Lucey
Proceedings of the National Academy of Sciences of the United States of America, Feb 1, 1989
Medical research archives, 2023
BMJ, Jan 7, 2020
Lessons from two contrasting outbreaks
JAMA network open, Jul 13, 2023
The COVID-19 pandemic, caused by SARS-CoV-2, has had many society-wide health, economic, educatio... more The COVID-19 pandemic, caused by SARS-CoV-2, has had many society-wide health, economic, educational, and political impacts. According to the World Health Organization, as of June 2023, approximately 7 million COVID-19 deaths have occurred globally. The identification of risk factors for SARS-CoV-2 infection and COVID-19 can play a key role in treating individuals or groups at higher risk of severe disease. Such risk factors can help guide interventions to prevent infection, severe disease,
AIDS Research and Human Retroviruses, Apr 1, 1990
Except for IgE, serum immunoglobulin abnormalities in persons with human immunodeficiency virus (... more Except for IgE, serum immunoglobulin abnormalities in persons with human immunodeficiency virus (HIV-1) infection have been well described.1_3 The mechanisms of B-cell dysfunction secondary to HIV infection are complex and multifactorial.4,5 In a series of 622 patients with HIV infection, we have found that mean serum IgE levels are normal until CD4+ lymphocyte counts decrease below 200 cells/mm3, whereupon a striking elevation in mean serum IgE occurs. By Department of Defense mandate, all HIV-positive Air Force (USAF) personnel undergo a staging evaluation at Wilford Hall USAF Medical Center.6 As part of their initial evaluation, serum IgE levels (normal 6-182 IU/ml RIA, Hybritech, San Diego, CA) and absolute CD4+ lymphocyte counts (OKT4-FITC or OKT4A-FITC, Ortho-mune, Ortho Diagnostics Systems, Inc., Raritan, NJ) were routinely measured on 622 patients between 1985 and 1988. IgE levels were not always obtained on patients undergoing therapy for life-threatening opportunistic infections. Flow cytometry analysis of T cells was performed using a Coulter Epics Profile or Epics C instrument (Coulter, Hialeah, FL). We divided the 622 patients into five groups based on absolute CD4+ lymphocyte counts (Table 1). Mean serum IgE levels were compared between these groups by an analysis of variance (F = 6.69, p < .0001). Subsequent analysis by the Tukey B-test7 confirmed that mean IgE values for the 0-200 CD4+ lymphocyte group are significantly (p < .05) increased compared with each of the other CD4 groups. A wide range of serum IgE concentrations was noted in all CD4+ T-cell groups. Within the 0-200 CD4+ T-cell group, 13 of 26 patients without AIDS-defining opportunistic infections (Walter Reed Stages 3-5)8 and 4 of 15 patients with AIDS-defining infections (Walter Reed Stage 6) had elevated serum IgE levels. Thus, 17 of 41 patients (41%) in the 0-200 CD4+ T-cell group had elevated serum IgE values. Of these 17 persons, 13 did not have
Vaccine, Mar 1, 1993
Human immunodeficiency virus (HIV) infection in US Air Force personnel between 1985 and 1989 was ... more Human immunodeficiency virus (HIV) infection in US Air Force personnel between 1985 and 1989 was examined through a mandatory serological survey, and through annual examination of infected patients. CD4+ cell counts were determined by flow cytometry; beta 2 microglobulin and neopterin were measured by immunoassay. During this period 933 cases were found, of which 161 were documented seroconversions, giving an incidence rate of 15.6/100,000 person-years. For patients with > 400 CD4 cells microliters-1, the rate of initial occurrence of opportunistic infection was 1 and 4% at 1 and 2 years, respectively. HIV-infected persons with < 400 CD4+ cells microliters-1, in contrast, had rates of 21% at 1 year and 36% at 2 years. In a cross-sectional study, beta 2 microglobulin concentration was shown to increase in both the serum and spinal fluid of patients infected with HIV as their blood CD4 numbers declined. Neopterin levels in serum and spinal fluid showed a similar trend, with significantly lower neopterin concentrations in the group that had > 1000 CD4+ T cells compared to the 0-600 CD4+ cell group. Longitudinal studies included correlation of HIV p24 antigen with CD4 counts over a 1 year period. The p24 antigen-positive group had a 21% decline in CD4+ T cells, while the antigen-negative group had a 14% decline. Specific helper T-cell subsets were also examined over a 6 month period. A significant decline was seen in the CD4+/CD29+, CD4+/CD45R+, and overall CD4+ subsets which was not seen in AZT-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
One health & implementation research, Mar 31, 2024
American Journal of Tropical Medicine and Hygiene, Apr 1, 2003
Strongyloides hyperinfection syndrome may be complicated by paralytic ileus that interferes with ... more Strongyloides hyperinfection syndrome may be complicated by paralytic ileus that interferes with the absorption of oral anti-helminthics. We report on the administration of ivermectin as a rectal enema preparation to a renal transplant recipient with Strongyloides hyperinfection syndrome and progressive ileus. Attempts at treatment using nasogastric albendazole and ivermectin were unsuccessful despite clamping the nasogastric tube after drug administration. Ivermectin tablets were ground to a powder, resuspended in a commercially available suspending agent, and administered per rectum. The suspending agent was chosen for its near-physiologic osmolality to allow longer retention, in contrast to many enema preparations that have a laxative effect. The patient improved markedly within 72 hours of initiation of the therapy per rectum and recovered fully. Ivermectin administered as an enema may be beneficial in patients with severe strongyloidiasis who are unable to absorb or tolerate oral therapy.
Viral Immunology, 1993
Monocytes and brain macrophage-microglial cells are thought to play a crucial role in the neurolo... more Monocytes and brain macrophage-microglial cells are thought to play a crucial role in the neurologic dysfunction associated with HIV-1 disease. Since neopterin is produced by monocytes-macrophages, we asked whether cerebrospinal fluid (CSF) neopterin levels increase before the onset of HIV-1 neurologic disease and whether they correlate with other CSF and peripheral blood immunologie parameters. In this study, CSF neopterin levels from 159 neurologically asymptomatic HIV-positive persons were found to increase as the blood CD4+ T-cell count decreased and as CSF IgG, IgG synthesis, IgG index, and ß2-microglobulin increased. Neopterin levels in the CSF exceeded those in the serum in 32% of patients, while 25% had CSF levels >13.5 nmol/liter. CSF neopterin levels vary with immune status, may reflect intrathecal production, and can be elevated in asymptomatic HIV-positive patients with normal neurologic examinations. Long-term follow-up of this patient population should be able to define the clinical correlation between CSF neopterin levels during the asymptomatic phase of HIV-1 disease and the risk of subsequent neurologic disease.
American Heart Journal, Oct 1, 2001
Native valve endocarditis caused by coagulase-negative staphylococci is uncommon and the diagnosi... more Native valve endocarditis caused by coagulase-negative staphylococci is uncommon and the diagnosis is infrequently considered. The disease, however, appears to be increasing in frequency and can pursue an aggressive clinical course. We report the clinical features of 7 cases of coagulase-negative staphylococcal native valve endocarditis (CNS-NVE) seen at 1 institution with a large cardiovascular referral base over a 10-month period. All cases required valve replacement surgery. Clinical history, echocardiograms, and microbiologic and histopathologic data were reviewed for 7 patients with surgical CNS-NVE. Four patients had intravenous central catheters, and 1 had recent surgery, whereas the remaining 2 had no identifiable risk factors. Presentations ranged from subacute (4 cases) to acute with complications (3 cases). Complications included congestive heart failure, stroke, and heart block. Echocardiography demonstrated valvular lesions in all 7 cases. Valve pathologic study demonstrated gram-positive cocci in all 7 cases; blood cultures grew coagulase-negative staphylococci in 6 cases and valve cultures grew Staphylococcus epidermidis in 5 cases. Coagulase-negative staphylococci, including S epidermidis, can cause severe native valve endocarditis requiring valve replacement. The increasing use of intravascular access devices in the community may herald an increase in the incidence of CNS-NVE. A high index of diagnostic suspicion in the appropriate clinical setting is critical for optimal management.
Infectious Diseases in Clinical Practice, Dec 1, 2001
Instructive Cases FIGURE 2. Caseating granulomas with multinucleated giant cells (hematoxylin and... more Instructive Cases FIGURE 2. Caseating granulomas with multinucleated giant cells (hematoxylin and eosin, original magnification ϫ40).
Annals of Internal Medicine, Sep 26, 2017
Yellow fever (YF) virus, a flavivirus that infects the liver, causes a self-limited febrile syndr... more Yellow fever (YF) virus, a flavivirus that infects the liver, causes a self-limited febrile syndrome in 85% of patients. In the other 15%, however, it causes jaundice, bleeding, and renal damage, and half of these patients die. No antiviral therapy exists. In urban settings, YF virus is transmitted between humans by Aedes aegypti mosquitoes, as are Zika, dengue, and other viruses. Outside urban settings, in the jungle or forest (sylvatic cycle), YF transmission occurs between monkeys and from monkeys to humans via non-Aedes mosquitoes (1). The United States had YF epidemics in the 18th and 19th centuries. In the 20th century, epidemics occurred in sub-Saharan Africa, Latin America, and the Caribbean. The first cases in Asia were reported in 2016, when 11 workers returned home to China after having been infected in Angola (1). A live attenuated YF vaccine was developed 80 years ago; it is grown in special pathogen-free eggs, currently the only production platform (2). In most immunocompetent persons aged 9 months to 60 years who are not allergic to eggs, this vaccine is considered safe and highly effective. It is the only vaccine that some countries require travelers to show proof of having received, as documented by the International Certificate of Vaccination or Prophylaxis. In 2016, the World Health Organization (WHO) concluded that a single dose of YF vaccine confers lifelong immunitythus, revaccination is no longer needed (3). Despite this positive finding, recent vaccine shortages have caused great concern, and catastrophic shortages could occur if the virus ever spreads in Asia (4). Therefore, an accelerated, prolonged increase in the global stockpile of YF vaccines is needed, as well as the development of new cell culturebased or DNA vaccines in addition to the egg-based ones available now. Shortage in the Democratic Republic of Congo, 2016 An epidemic of YF spread from Angola to the Democratic Republic of Congo in 2016, creating a serious vaccine shortage when it became necessary to vaccinate the entire population of Kinshasa, the capital city. The Democratic Republic of Congo Ministry of Health and several partners coordinated a campaign from 17 to 26 August 2016, vaccinating about 7.5 million persons using only one fifth of the normal dose per person. The duration of protection with this dose is unknown but is believed to be at least 1 year (5). Fractional dosing, as it is termed by the WHO, does not allow the recipient to receive the International Certificate of Vaccination or Prophylaxis required for international travel (5). A one-fifth dose had never been used in a YF vaccination campaign. Shortage in the United States, 2017 to 2018 In the United States, only 1 YF vaccine (YF-VAX [Sanofi Pasteur]) is licensed by the U.S. Food and Drug Administration and is produced at only 1 domestic location. Each year, approximately 500000 doses are provided for civilian and military travelers (6). A manufacturing complication that resulted in the loss of many doses has contributed to a shortage that is projected to last from mid-2017 to mid-2018 (6). A list of U.S. clinics where an imported YF vaccine (Stamaril [Sanofi Pasteur]) can be obtained is available at wwwnc.cdc.gov/travel/page/search-for-stamaril-clinics. Vaccine Supply Challenges in Brazil, 2017 In Brazil, an ongoing outbreak of sylvatic, nonurban YF from December 2016 to 31 May 2017 included 792 laboratory-confirmed human cases reported from 8 states and resulting in 435 deaths. At the time of writing, no confirmed human cases have occurred since May 2017 (7). Of note, the virus was not found in A aegypti, the mosquito that transmits YF virus between humans in urban settings (1, 2). Should the virus infect A aegypti, the YF epidemic would likely spread to 1 or more cities in Brazil, a prospect that causes concern. Thus, at least 26.3 million doses of YF vaccine have been distributed in Brazil between January and May 2017 (7). Plans to vaccinate the residents of Rio de Janeiro have been made, and the large Brazilian YF vaccine manufacturer has accelerated production. Even so, Brazil imported at least 3.5 million doses from the international emergency stockpile in March 2017 (8). A Risk for Catastrophic Shortage if Epidemics Occur in Asia In September 2016, the WHO issued its Global Strategy to Eliminate Yellow fever Epidemics, estimating that 1.38 billion doses of vaccine would be needed from 2017 to 2026 to eliminate YF epidemics in Africa, Latin America, and the Caribbean. The WHO also noted the potential for Asian outbreaks in countries such as India and China, which harbour Aedes mosquitoes and are home to 2 billion people who are immunologically naive for YF (9). It stated, In the mid to long term, WHO will also work with vaccine manufacturers to explore and encourage novel vaccine production technologies, such as YF vaccine production based cell-culture or a DNA vaccine (9). In 2016, Wasserman and colleagues described the potential…
International Journal of Infectious Diseases, Nov 1, 2017
We propose the term "pan-epidemic Anthropocene" to refer to multifocal infectious disease epidemi... more We propose the term "pan-epidemic Anthropocene" to refer to multifocal infectious disease epidemics related to human-caused (anthropogenic) forces such as urbanization, globalization, industrialization and the growing populations of humans and animals. The integrated framework of One Health (human, animal, and environmental health) helps both to understand why epidemics occur when and where they do, and also how to respond, mitigate, and sometimes prevent them. We suggest a collaborative mechanism for increasing One Health in medical education to create a synergy of strengths between the growing number of contributing One Health organizations in the US and internationally.
International Journal of Infectious Diseases, 2021
The coronavirus disease-2019 (COVID-19) pandemic is an ongoing devastating threat to human lives ... more The coronavirus disease-2019 (COVID-19) pandemic is an ongoing devastating threat to human lives and livelihoods around the world. Healthcare workers (HCW) are part of the frontline in the struggle against the pandemic. Many HCWs have been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have lost their lives worldwide during the pandemic.
Social Science Research Network, May 9, 2016
The worst yellow fever epidemic in Angola since 1986 is rapidly spreading, including the capital,... more The worst yellow fever epidemic in Angola since 1986 is rapidly spreading, including the capital, Luanda. In Angola, the epidemic began in December 2015 and the laboratory-confirmed outbreak was reported to the World Health Organization (WHO) on January 21, 2016. 1 Angola has had 2023 suspected cases and 258 deaths as of April 26, 2016. 1 China, the Democratic Republic of Congo, and Kenya also have reported cases arising from infected travelers from Angola. Namibia and Zambia also share a long border with Angola, with considerable population movement between the countries. Similar to other recent epidemics, quick and effective action to stop the spread of yellow fever is the responsibility of the world's health community. More than 7 million Angolans have been vaccinated, but supply shortages could potentially lead to a health security crisis if yellow fever spreads within Africa, Asia (which has never experienced a yellow fever epidemic), or the Americas (where Aedes mosquito vectors transmit yellow fever as well as Zika, dengue, and chikungunya). The Pan American Health Organization declared an epidemiological alert on April 22, 2016, for yellow fever in Latin America. 2 The WHO should urgently convene an emergency committee to mobilize funds, coordinate an international response, and spearhead a surge in vaccine production.
Vaccine, Mar 1, 1993
The results of HIV screening between early 1986 and February 1991 in the United States Air Force ... more The results of HIV screening between early 1986 and February 1991 in the United States Air Force are presented. In this period, two total-force screenings were conducted. HIV incidence estimates are presented by age, ethnicity/race, sex and occupational category.
Advances in Experimental Medicine and Biology, 1991
We have previously reported the identification of highly conserved homologous regions located in ... more We have previously reported the identification of highly conserved homologous regions located in the carboxy terminus of the HIV 1 gp41 (aa 837-844), and the amino-terminal of the beta chain of all human HLA class II antigens (aa 19-25). Murine monoclonal antibodies raised against synthetic peptides from these homologous regions bound not only to the isolated peptides, but also to "native" HLA class II molecules on cells. Screening of sera from HIV 1 infected individuals revealed high frequency of sera (35%) containing anti-class II crossreactive antibodies (CRAb), not only in AIDS patients, but also in early, asymptomatic patients. The CRAb containing sera caused potent inhibition of normal CD4-bearing cells' proliferative responses to tetanus toxoid in vitro. They could also kill class II bearing cells by ADCC. The possible contribution of these antibodies to the establishment of immunodeficiency state in HIV 1 infected individuals and/or to disease progression, was examined in two clinical studies: I. Asymptomatic patients were tested in parallel for their PBL responses to flu/tetanus, HLA alloantigens, and PHA (proliferation and IL2 production), and for the presence of anti-class II CRAb. About 50% of these patients showed a selective loss of their in vitro responses to recall antigens (flu/tetanus), which depend on CD4+ cells, while still responding to PHA and ALLO. Interestingly, positive correlation was found (P less than 0.001) between patients' lack of responsiveness to flu/tetanus and the presence in their sera of anti-class II CRAb. II. Retrospective study of HIV 1-infected hemophiliacs, suggest that patients with high titers of CRAb early in the disease progressed faster to full blown disease.
IntroductionIn the early parts of the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) ... more IntroductionIn the early parts of the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) were implemented worldwide, including in sub-Saharan Africa, to prevent and control SARS-CoV-2 transmission. This mixed-methods study examines adherence to and enforcement of NPIs implemented to curb COVID-19 in Nigeria, Rwanda, and Zambia, leading up to the 10,000th case of laboratory-confirmed COVID-19 in each country. Additionally, we aim to evaluate the relationship between levels and changes of NPIs over time and changes in COVID-19 cases and deaths.MethodsThis mixed-methods analysis utilized semi-structured interviews and a quantitative dataset constructed using multiple open data sources, including the Oxford COVID-19 Government Response Tracker. To understand potential barriers and facilitators in implementing and enforcing NPIs qualitative data were collected from those involved in the COVID-19 response and analyzed using NVivo. Quantitative results were analyzed using descripti...
HIV infection is characterized by rapid and error-prone viral replication resulting in geneticall... more HIV infection is characterized by rapid and error-prone viral replication resulting in genetically diverse virus populations. The rate of accumulation of diversity and the mechanisms involved are under intense study to provide useful information to understand immune evasion and the development of drug resistance. To characterize the development of viral diversity after infection, we carried out an in-depth analysis of single genome sequences of HIV pro-pol to assess diversity and divergence, and to estimate replicating population sizes in a group of treatment naive HIV-infected individuals sampled at single (N=22) or multiple, longitudinal time points (N=11). Analysis of single genome sequences (SGS) revealed non-linear accumulation of sequence diversity during the course of infection. Diversity accumulated in recently infected individuals at rates 30-fold higher than in patients with chronic infection. Accumulation of synonymous changes accounted for most of the diversity during chronic infection. Accumulation of diversity resulted in population shifts, but the rates of change were slow relative to estimated replication cycle times, consistent with relatively large population sizes. Analysis of changes in allele frequencies revealed effective population sizes that are substantially higher than previous estimates of approximately 1000 infectious particles/infected individual. Taken together, these observations indicate that HIV populations are large, diverse, and slow to change in chronic infection and that the emergence of new mutations, including drug resistance mutations, is governed by both selection forces and drift.
Proceedings of the National Academy of Sciences of the United States of America, Feb 1, 1989
Medical research archives, 2023
BMJ, Jan 7, 2020
Lessons from two contrasting outbreaks
JAMA network open, Jul 13, 2023
The COVID-19 pandemic, caused by SARS-CoV-2, has had many society-wide health, economic, educatio... more The COVID-19 pandemic, caused by SARS-CoV-2, has had many society-wide health, economic, educational, and political impacts. According to the World Health Organization, as of June 2023, approximately 7 million COVID-19 deaths have occurred globally. The identification of risk factors for SARS-CoV-2 infection and COVID-19 can play a key role in treating individuals or groups at higher risk of severe disease. Such risk factors can help guide interventions to prevent infection, severe disease,
AIDS Research and Human Retroviruses, Apr 1, 1990
Except for IgE, serum immunoglobulin abnormalities in persons with human immunodeficiency virus (... more Except for IgE, serum immunoglobulin abnormalities in persons with human immunodeficiency virus (HIV-1) infection have been well described.1_3 The mechanisms of B-cell dysfunction secondary to HIV infection are complex and multifactorial.4,5 In a series of 622 patients with HIV infection, we have found that mean serum IgE levels are normal until CD4+ lymphocyte counts decrease below 200 cells/mm3, whereupon a striking elevation in mean serum IgE occurs. By Department of Defense mandate, all HIV-positive Air Force (USAF) personnel undergo a staging evaluation at Wilford Hall USAF Medical Center.6 As part of their initial evaluation, serum IgE levels (normal 6-182 IU/ml RIA, Hybritech, San Diego, CA) and absolute CD4+ lymphocyte counts (OKT4-FITC or OKT4A-FITC, Ortho-mune, Ortho Diagnostics Systems, Inc., Raritan, NJ) were routinely measured on 622 patients between 1985 and 1988. IgE levels were not always obtained on patients undergoing therapy for life-threatening opportunistic infections. Flow cytometry analysis of T cells was performed using a Coulter Epics Profile or Epics C instrument (Coulter, Hialeah, FL). We divided the 622 patients into five groups based on absolute CD4+ lymphocyte counts (Table 1). Mean serum IgE levels were compared between these groups by an analysis of variance (F = 6.69, p < .0001). Subsequent analysis by the Tukey B-test7 confirmed that mean IgE values for the 0-200 CD4+ lymphocyte group are significantly (p < .05) increased compared with each of the other CD4 groups. A wide range of serum IgE concentrations was noted in all CD4+ T-cell groups. Within the 0-200 CD4+ T-cell group, 13 of 26 patients without AIDS-defining opportunistic infections (Walter Reed Stages 3-5)8 and 4 of 15 patients with AIDS-defining infections (Walter Reed Stage 6) had elevated serum IgE levels. Thus, 17 of 41 patients (41%) in the 0-200 CD4+ T-cell group had elevated serum IgE values. Of these 17 persons, 13 did not have
Vaccine, Mar 1, 1993
Human immunodeficiency virus (HIV) infection in US Air Force personnel between 1985 and 1989 was ... more Human immunodeficiency virus (HIV) infection in US Air Force personnel between 1985 and 1989 was examined through a mandatory serological survey, and through annual examination of infected patients. CD4+ cell counts were determined by flow cytometry; beta 2 microglobulin and neopterin were measured by immunoassay. During this period 933 cases were found, of which 161 were documented seroconversions, giving an incidence rate of 15.6/100,000 person-years. For patients with > 400 CD4 cells microliters-1, the rate of initial occurrence of opportunistic infection was 1 and 4% at 1 and 2 years, respectively. HIV-infected persons with < 400 CD4+ cells microliters-1, in contrast, had rates of 21% at 1 year and 36% at 2 years. In a cross-sectional study, beta 2 microglobulin concentration was shown to increase in both the serum and spinal fluid of patients infected with HIV as their blood CD4 numbers declined. Neopterin levels in serum and spinal fluid showed a similar trend, with significantly lower neopterin concentrations in the group that had > 1000 CD4+ T cells compared to the 0-600 CD4+ cell group. Longitudinal studies included correlation of HIV p24 antigen with CD4 counts over a 1 year period. The p24 antigen-positive group had a 21% decline in CD4+ T cells, while the antigen-negative group had a 14% decline. Specific helper T-cell subsets were also examined over a 6 month period. A significant decline was seen in the CD4+/CD29+, CD4+/CD45R+, and overall CD4+ subsets which was not seen in AZT-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
One health & implementation research, Mar 31, 2024
American Journal of Tropical Medicine and Hygiene, Apr 1, 2003
Strongyloides hyperinfection syndrome may be complicated by paralytic ileus that interferes with ... more Strongyloides hyperinfection syndrome may be complicated by paralytic ileus that interferes with the absorption of oral anti-helminthics. We report on the administration of ivermectin as a rectal enema preparation to a renal transplant recipient with Strongyloides hyperinfection syndrome and progressive ileus. Attempts at treatment using nasogastric albendazole and ivermectin were unsuccessful despite clamping the nasogastric tube after drug administration. Ivermectin tablets were ground to a powder, resuspended in a commercially available suspending agent, and administered per rectum. The suspending agent was chosen for its near-physiologic osmolality to allow longer retention, in contrast to many enema preparations that have a laxative effect. The patient improved markedly within 72 hours of initiation of the therapy per rectum and recovered fully. Ivermectin administered as an enema may be beneficial in patients with severe strongyloidiasis who are unable to absorb or tolerate oral therapy.
Viral Immunology, 1993
Monocytes and brain macrophage-microglial cells are thought to play a crucial role in the neurolo... more Monocytes and brain macrophage-microglial cells are thought to play a crucial role in the neurologic dysfunction associated with HIV-1 disease. Since neopterin is produced by monocytes-macrophages, we asked whether cerebrospinal fluid (CSF) neopterin levels increase before the onset of HIV-1 neurologic disease and whether they correlate with other CSF and peripheral blood immunologie parameters. In this study, CSF neopterin levels from 159 neurologically asymptomatic HIV-positive persons were found to increase as the blood CD4+ T-cell count decreased and as CSF IgG, IgG synthesis, IgG index, and ß2-microglobulin increased. Neopterin levels in the CSF exceeded those in the serum in 32% of patients, while 25% had CSF levels >13.5 nmol/liter. CSF neopterin levels vary with immune status, may reflect intrathecal production, and can be elevated in asymptomatic HIV-positive patients with normal neurologic examinations. Long-term follow-up of this patient population should be able to define the clinical correlation between CSF neopterin levels during the asymptomatic phase of HIV-1 disease and the risk of subsequent neurologic disease.
American Heart Journal, Oct 1, 2001
Native valve endocarditis caused by coagulase-negative staphylococci is uncommon and the diagnosi... more Native valve endocarditis caused by coagulase-negative staphylococci is uncommon and the diagnosis is infrequently considered. The disease, however, appears to be increasing in frequency and can pursue an aggressive clinical course. We report the clinical features of 7 cases of coagulase-negative staphylococcal native valve endocarditis (CNS-NVE) seen at 1 institution with a large cardiovascular referral base over a 10-month period. All cases required valve replacement surgery. Clinical history, echocardiograms, and microbiologic and histopathologic data were reviewed for 7 patients with surgical CNS-NVE. Four patients had intravenous central catheters, and 1 had recent surgery, whereas the remaining 2 had no identifiable risk factors. Presentations ranged from subacute (4 cases) to acute with complications (3 cases). Complications included congestive heart failure, stroke, and heart block. Echocardiography demonstrated valvular lesions in all 7 cases. Valve pathologic study demonstrated gram-positive cocci in all 7 cases; blood cultures grew coagulase-negative staphylococci in 6 cases and valve cultures grew Staphylococcus epidermidis in 5 cases. Coagulase-negative staphylococci, including S epidermidis, can cause severe native valve endocarditis requiring valve replacement. The increasing use of intravascular access devices in the community may herald an increase in the incidence of CNS-NVE. A high index of diagnostic suspicion in the appropriate clinical setting is critical for optimal management.
Infectious Diseases in Clinical Practice, Dec 1, 2001
Instructive Cases FIGURE 2. Caseating granulomas with multinucleated giant cells (hematoxylin and... more Instructive Cases FIGURE 2. Caseating granulomas with multinucleated giant cells (hematoxylin and eosin, original magnification ϫ40).
Annals of Internal Medicine, Sep 26, 2017
Yellow fever (YF) virus, a flavivirus that infects the liver, causes a self-limited febrile syndr... more Yellow fever (YF) virus, a flavivirus that infects the liver, causes a self-limited febrile syndrome in 85% of patients. In the other 15%, however, it causes jaundice, bleeding, and renal damage, and half of these patients die. No antiviral therapy exists. In urban settings, YF virus is transmitted between humans by Aedes aegypti mosquitoes, as are Zika, dengue, and other viruses. Outside urban settings, in the jungle or forest (sylvatic cycle), YF transmission occurs between monkeys and from monkeys to humans via non-Aedes mosquitoes (1). The United States had YF epidemics in the 18th and 19th centuries. In the 20th century, epidemics occurred in sub-Saharan Africa, Latin America, and the Caribbean. The first cases in Asia were reported in 2016, when 11 workers returned home to China after having been infected in Angola (1). A live attenuated YF vaccine was developed 80 years ago; it is grown in special pathogen-free eggs, currently the only production platform (2). In most immunocompetent persons aged 9 months to 60 years who are not allergic to eggs, this vaccine is considered safe and highly effective. It is the only vaccine that some countries require travelers to show proof of having received, as documented by the International Certificate of Vaccination or Prophylaxis. In 2016, the World Health Organization (WHO) concluded that a single dose of YF vaccine confers lifelong immunitythus, revaccination is no longer needed (3). Despite this positive finding, recent vaccine shortages have caused great concern, and catastrophic shortages could occur if the virus ever spreads in Asia (4). Therefore, an accelerated, prolonged increase in the global stockpile of YF vaccines is needed, as well as the development of new cell culturebased or DNA vaccines in addition to the egg-based ones available now. Shortage in the Democratic Republic of Congo, 2016 An epidemic of YF spread from Angola to the Democratic Republic of Congo in 2016, creating a serious vaccine shortage when it became necessary to vaccinate the entire population of Kinshasa, the capital city. The Democratic Republic of Congo Ministry of Health and several partners coordinated a campaign from 17 to 26 August 2016, vaccinating about 7.5 million persons using only one fifth of the normal dose per person. The duration of protection with this dose is unknown but is believed to be at least 1 year (5). Fractional dosing, as it is termed by the WHO, does not allow the recipient to receive the International Certificate of Vaccination or Prophylaxis required for international travel (5). A one-fifth dose had never been used in a YF vaccination campaign. Shortage in the United States, 2017 to 2018 In the United States, only 1 YF vaccine (YF-VAX [Sanofi Pasteur]) is licensed by the U.S. Food and Drug Administration and is produced at only 1 domestic location. Each year, approximately 500000 doses are provided for civilian and military travelers (6). A manufacturing complication that resulted in the loss of many doses has contributed to a shortage that is projected to last from mid-2017 to mid-2018 (6). A list of U.S. clinics where an imported YF vaccine (Stamaril [Sanofi Pasteur]) can be obtained is available at wwwnc.cdc.gov/travel/page/search-for-stamaril-clinics. Vaccine Supply Challenges in Brazil, 2017 In Brazil, an ongoing outbreak of sylvatic, nonurban YF from December 2016 to 31 May 2017 included 792 laboratory-confirmed human cases reported from 8 states and resulting in 435 deaths. At the time of writing, no confirmed human cases have occurred since May 2017 (7). Of note, the virus was not found in A aegypti, the mosquito that transmits YF virus between humans in urban settings (1, 2). Should the virus infect A aegypti, the YF epidemic would likely spread to 1 or more cities in Brazil, a prospect that causes concern. Thus, at least 26.3 million doses of YF vaccine have been distributed in Brazil between January and May 2017 (7). Plans to vaccinate the residents of Rio de Janeiro have been made, and the large Brazilian YF vaccine manufacturer has accelerated production. Even so, Brazil imported at least 3.5 million doses from the international emergency stockpile in March 2017 (8). A Risk for Catastrophic Shortage if Epidemics Occur in Asia In September 2016, the WHO issued its Global Strategy to Eliminate Yellow fever Epidemics, estimating that 1.38 billion doses of vaccine would be needed from 2017 to 2026 to eliminate YF epidemics in Africa, Latin America, and the Caribbean. The WHO also noted the potential for Asian outbreaks in countries such as India and China, which harbour Aedes mosquitoes and are home to 2 billion people who are immunologically naive for YF (9). It stated, In the mid to long term, WHO will also work with vaccine manufacturers to explore and encourage novel vaccine production technologies, such as YF vaccine production based cell-culture or a DNA vaccine (9). In 2016, Wasserman and colleagues described the potential…
International Journal of Infectious Diseases, Nov 1, 2017
We propose the term "pan-epidemic Anthropocene" to refer to multifocal infectious disease epidemi... more We propose the term "pan-epidemic Anthropocene" to refer to multifocal infectious disease epidemics related to human-caused (anthropogenic) forces such as urbanization, globalization, industrialization and the growing populations of humans and animals. The integrated framework of One Health (human, animal, and environmental health) helps both to understand why epidemics occur when and where they do, and also how to respond, mitigate, and sometimes prevent them. We suggest a collaborative mechanism for increasing One Health in medical education to create a synergy of strengths between the growing number of contributing One Health organizations in the US and internationally.
International Journal of Infectious Diseases, 2021
The coronavirus disease-2019 (COVID-19) pandemic is an ongoing devastating threat to human lives ... more The coronavirus disease-2019 (COVID-19) pandemic is an ongoing devastating threat to human lives and livelihoods around the world. Healthcare workers (HCW) are part of the frontline in the struggle against the pandemic. Many HCWs have been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have lost their lives worldwide during the pandemic.
Social Science Research Network, May 9, 2016
The worst yellow fever epidemic in Angola since 1986 is rapidly spreading, including the capital,... more The worst yellow fever epidemic in Angola since 1986 is rapidly spreading, including the capital, Luanda. In Angola, the epidemic began in December 2015 and the laboratory-confirmed outbreak was reported to the World Health Organization (WHO) on January 21, 2016. 1 Angola has had 2023 suspected cases and 258 deaths as of April 26, 2016. 1 China, the Democratic Republic of Congo, and Kenya also have reported cases arising from infected travelers from Angola. Namibia and Zambia also share a long border with Angola, with considerable population movement between the countries. Similar to other recent epidemics, quick and effective action to stop the spread of yellow fever is the responsibility of the world's health community. More than 7 million Angolans have been vaccinated, but supply shortages could potentially lead to a health security crisis if yellow fever spreads within Africa, Asia (which has never experienced a yellow fever epidemic), or the Americas (where Aedes mosquito vectors transmit yellow fever as well as Zika, dengue, and chikungunya). The Pan American Health Organization declared an epidemiological alert on April 22, 2016, for yellow fever in Latin America. 2 The WHO should urgently convene an emergency committee to mobilize funds, coordinate an international response, and spearhead a surge in vaccine production.
Vaccine, Mar 1, 1993
The results of HIV screening between early 1986 and February 1991 in the United States Air Force ... more The results of HIV screening between early 1986 and February 1991 in the United States Air Force are presented. In this period, two total-force screenings were conducted. HIV incidence estimates are presented by age, ethnicity/race, sex and occupational category.
Advances in Experimental Medicine and Biology, 1991
We have previously reported the identification of highly conserved homologous regions located in ... more We have previously reported the identification of highly conserved homologous regions located in the carboxy terminus of the HIV 1 gp41 (aa 837-844), and the amino-terminal of the beta chain of all human HLA class II antigens (aa 19-25). Murine monoclonal antibodies raised against synthetic peptides from these homologous regions bound not only to the isolated peptides, but also to "native" HLA class II molecules on cells. Screening of sera from HIV 1 infected individuals revealed high frequency of sera (35%) containing anti-class II crossreactive antibodies (CRAb), not only in AIDS patients, but also in early, asymptomatic patients. The CRAb containing sera caused potent inhibition of normal CD4-bearing cells' proliferative responses to tetanus toxoid in vitro. They could also kill class II bearing cells by ADCC. The possible contribution of these antibodies to the establishment of immunodeficiency state in HIV 1 infected individuals and/or to disease progression, was examined in two clinical studies: I. Asymptomatic patients were tested in parallel for their PBL responses to flu/tetanus, HLA alloantigens, and PHA (proliferation and IL2 production), and for the presence of anti-class II CRAb. About 50% of these patients showed a selective loss of their in vitro responses to recall antigens (flu/tetanus), which depend on CD4+ cells, while still responding to PHA and ALLO. Interestingly, positive correlation was found (P less than 0.001) between patients' lack of responsiveness to flu/tetanus and the presence in their sera of anti-class II CRAb. II. Retrospective study of HIV 1-infected hemophiliacs, suggest that patients with high titers of CRAb early in the disease progressed faster to full blown disease.
IntroductionIn the early parts of the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) ... more IntroductionIn the early parts of the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) were implemented worldwide, including in sub-Saharan Africa, to prevent and control SARS-CoV-2 transmission. This mixed-methods study examines adherence to and enforcement of NPIs implemented to curb COVID-19 in Nigeria, Rwanda, and Zambia, leading up to the 10,000th case of laboratory-confirmed COVID-19 in each country. Additionally, we aim to evaluate the relationship between levels and changes of NPIs over time and changes in COVID-19 cases and deaths.MethodsThis mixed-methods analysis utilized semi-structured interviews and a quantitative dataset constructed using multiple open data sources, including the Oxford COVID-19 Government Response Tracker. To understand potential barriers and facilitators in implementing and enforcing NPIs qualitative data were collected from those involved in the COVID-19 response and analyzed using NVivo. Quantitative results were analyzed using descripti...
HIV infection is characterized by rapid and error-prone viral replication resulting in geneticall... more HIV infection is characterized by rapid and error-prone viral replication resulting in genetically diverse virus populations. The rate of accumulation of diversity and the mechanisms involved are under intense study to provide useful information to understand immune evasion and the development of drug resistance. To characterize the development of viral diversity after infection, we carried out an in-depth analysis of single genome sequences of HIV pro-pol to assess diversity and divergence, and to estimate replicating population sizes in a group of treatment naive HIV-infected individuals sampled at single (N=22) or multiple, longitudinal time points (N=11). Analysis of single genome sequences (SGS) revealed non-linear accumulation of sequence diversity during the course of infection. Diversity accumulated in recently infected individuals at rates 30-fold higher than in patients with chronic infection. Accumulation of synonymous changes accounted for most of the diversity during chronic infection. Accumulation of diversity resulted in population shifts, but the rates of change were slow relative to estimated replication cycle times, consistent with relatively large population sizes. Analysis of changes in allele frequencies revealed effective population sizes that are substantially higher than previous estimates of approximately 1000 infectious particles/infected individual. Taken together, these observations indicate that HIV populations are large, diverse, and slow to change in chronic infection and that the emergence of new mutations, including drug resistance mutations, is governed by both selection forces and drift.