Hemophagocytic lymphohistiocytosis (HLH) is an unusual syndrome characterized by fever, splenomeg... more Hemophagocytic lymphohistiocytosis (HLH) is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis (phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors) in bone marrow and other tissues. HLH may be diagnosed in association with malignant, genetic, or autoimmune diseases but is also prominently linked with Epstein-Barr (EBV) virus infection. Hyperproduction of cytokines, including interferon-gamma and tumor necrosis factor-alpha, by EBV- infected T lymphocytes may play a role in the pathogenesis of HLH. EBV-associated HLH may mimic T-cell lymphoma and is treated with cytotoxic chemotherapy, while hemophagocytic syndromes associated with nonviral pathogens often respond to treatment of the underlying infection.
Hepatitis B vaccine is a key tool for the prevention of hepatitis B infection. Age-associated cha... more Hepatitis B vaccine is a key tool for the prevention of hepatitis B infection. Age-associated changes in immune function may contribute to decreased vaccine efficacy in older individuals, although research related to this topic has yielded contradictory findings. We performed a meta-analysis of 24 published trials and studies that evaluated the association of age with response to hepatitis B vaccine, using a random-effects model. Pooling of study results suggested a significantly increased risk of nonresponse to hepatitis B vaccine among older individuals (relative risk [RR], 1.76; 95% confidence interval [CI], 1.48-2.10). An elevated risk of nonresponse persisted even after exclusion of poor-quality studies (RR, 1.63; 95% CI, 1.23-2.15) and adjustment for publication bias (RR, 1.52; 95% CI, 1.26-1.83), and it was present even when "older" individuals were defined as being as young as 30 years. These findings have important implications for individuals at risk for hepatitis B infection, including health care workers and travelers.
Seasonality, a periodic surge in disease incidence corresponding to seasons or other calendar per... more Seasonality, a periodic surge in disease incidence corresponding to seasons or other calendar periods, characterizes many infectious diseases of public health importance. The recognition of seasonal patterns in infectious disease occurrence dates back at least as far as the Hippocratic era, but mechanisms underlying seasonality of person-to-person transmitted diseases are not well understood. Improved understanding will enhance understanding of host-pathogen interactions and will improve the accuracy of public health surveillance and forecasting systems. Insight into seasonal disease patterns may be gained through the use of autocorrelation methods or construction of periodograms, while seasonal oscillation of infectious diseases can be easily simulated using simple transmission models. Models demonstrate that small seasonal changes in host or pathogen factors may be sufficient to create large seasonal surges in disease incidence, which may be important particularly in the context of global climate change. Seasonality represents a rich area for future research.
Infection with herpes simplex virus type 2 (HSV-2) currently affects approximately 22% of adult A... more Infection with herpes simplex virus type 2 (HSV-2) currently affects approximately 22% of adult Americans and increased markedly in prevalence between the late 1970s and early 1990s. Although some estimates of the costs of prevalent disease due to HSV-2 are available, selection of interventions to prevent HSV-2 infection, as well as evaluation of their potential cost-effectiveness, should take into account projected future costs that will result if the epidemic is left unchecked. The goal was to estimate the future health and economic consequences attributable to the HSV-2 epidemic in the absence of interventions to slow the epidemic. A mathematical model was constructed to project future increases in HSV-2 seroprevalence in the United States. The probability of heterosexual transmission of HSV-2 was estimated from cross-sectional estimates of infection prevalence reported by the National Health and Nutrition Examination Survey (NHANES). Per-infection expected costs were calculated on the basis of data obtained from the published medical literature. RESULTS Without intervention, the prevalence of HSV-2 infection among individuals aged 15 to 39 years was projected to increase to 39% among men and 49% among women by 2025. Annual incidence was projected to increase steadily between 2000 and 2025, from 9 to 26 infections per 1,000 men and from 12 to 32 infections per 1,000 women in this age group. The cost of incident infections in the year 2000 were estimated to be $1.8 billion; the cost of incident infections was predicted to rise to $2.5 billion by 2015 and $2.7 billion by 2025. The projected cumulative cost of incident HSV-2 infections occurring over the next 25 years was estimated to be $61 billion; at a 3% discount rate, this sum has a present value of $43 billion. The costs of incident HSV-2 infection in the United States are substantial and can be expected to increase as both the incidence and prevalence of this disease increase in the first half of the century. The level of resource allocation for HSV-2 prevention strategies should reflect the economic benefits that would result from control of this epidemic.
Hemophagocytic lymphohistiocytosis (HLH) is an unusual syndrome characterized by fever, splenomeg... more Hemophagocytic lymphohistiocytosis (HLH) is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis (phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors) in bone marrow and other tissues. HLH may be diagnosed in association with malignant, genetic, or autoimmune diseases but is also prominently linked with Epstein-Barr (EBV) virus infection. Hyperproduction of cytokines, including interferon-gamma and tumor necrosis factor-alpha, by EBV- infected T lymphocytes may play a role in the pathogenesis of HLH. EBV-associated HLH may mimic T-cell lymphoma and is treated with cytotoxic chemotherapy, while hemophagocytic syndromes associated with nonviral pathogens often respond to treatment of the underlying infection.
Hepatitis B vaccine is a key tool for the prevention of hepatitis B infection. Age-associated cha... more Hepatitis B vaccine is a key tool for the prevention of hepatitis B infection. Age-associated changes in immune function may contribute to decreased vaccine efficacy in older individuals, although research related to this topic has yielded contradictory findings. We performed a meta-analysis of 24 published trials and studies that evaluated the association of age with response to hepatitis B vaccine, using a random-effects model. Pooling of study results suggested a significantly increased risk of nonresponse to hepatitis B vaccine among older individuals (relative risk [RR], 1.76; 95% confidence interval [CI], 1.48-2.10). An elevated risk of nonresponse persisted even after exclusion of poor-quality studies (RR, 1.63; 95% CI, 1.23-2.15) and adjustment for publication bias (RR, 1.52; 95% CI, 1.26-1.83), and it was present even when "older" individuals were defined as being as young as 30 years. These findings have important implications for individuals at risk for hepatitis B infection, including health care workers and travelers.
Seasonality, a periodic surge in disease incidence corresponding to seasons or other calendar per... more Seasonality, a periodic surge in disease incidence corresponding to seasons or other calendar periods, characterizes many infectious diseases of public health importance. The recognition of seasonal patterns in infectious disease occurrence dates back at least as far as the Hippocratic era, but mechanisms underlying seasonality of person-to-person transmitted diseases are not well understood. Improved understanding will enhance understanding of host-pathogen interactions and will improve the accuracy of public health surveillance and forecasting systems. Insight into seasonal disease patterns may be gained through the use of autocorrelation methods or construction of periodograms, while seasonal oscillation of infectious diseases can be easily simulated using simple transmission models. Models demonstrate that small seasonal changes in host or pathogen factors may be sufficient to create large seasonal surges in disease incidence, which may be important particularly in the context of global climate change. Seasonality represents a rich area for future research.
Infection with herpes simplex virus type 2 (HSV-2) currently affects approximately 22% of adult A... more Infection with herpes simplex virus type 2 (HSV-2) currently affects approximately 22% of adult Americans and increased markedly in prevalence between the late 1970s and early 1990s. Although some estimates of the costs of prevalent disease due to HSV-2 are available, selection of interventions to prevent HSV-2 infection, as well as evaluation of their potential cost-effectiveness, should take into account projected future costs that will result if the epidemic is left unchecked. The goal was to estimate the future health and economic consequences attributable to the HSV-2 epidemic in the absence of interventions to slow the epidemic. A mathematical model was constructed to project future increases in HSV-2 seroprevalence in the United States. The probability of heterosexual transmission of HSV-2 was estimated from cross-sectional estimates of infection prevalence reported by the National Health and Nutrition Examination Survey (NHANES). Per-infection expected costs were calculated on the basis of data obtained from the published medical literature. RESULTS Without intervention, the prevalence of HSV-2 infection among individuals aged 15 to 39 years was projected to increase to 39% among men and 49% among women by 2025. Annual incidence was projected to increase steadily between 2000 and 2025, from 9 to 26 infections per 1,000 men and from 12 to 32 infections per 1,000 women in this age group. The cost of incident infections in the year 2000 were estimated to be $1.8 billion; the cost of incident infections was predicted to rise to $2.5 billion by 2015 and $2.7 billion by 2025. The projected cumulative cost of incident HSV-2 infections occurring over the next 25 years was estimated to be $61 billion; at a 3% discount rate, this sum has a present value of $43 billion. The costs of incident HSV-2 infection in the United States are substantial and can be expected to increase as both the incidence and prevalence of this disease increase in the first half of the century. The level of resource allocation for HSV-2 prevention strategies should reflect the economic benefits that would result from control of this epidemic.
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Papers by David Fisman