How did "flatten the curve" become "flatten the economy?" A perspective from the United States of America.

The coronavirus SARS-CoV-2 (COVID-19) pandemic offers many medical, economic, societal, and cultural challenges. The response by individual states in the United States of America varies, but with the common initial impetus for all being to "flatten the curve," which was intended to delay infections and spread the burden and impact on hospitals and medical systems. Starting with that intention, the responses by states has included many major steps not taken in prior pandemics. Those steps have significantly adversely affected hospitals rather than support them, and the overall impact has been to "flatten the economy" rather than just to "flatten the curve." Many state governors have stated that their decisions are "science-led" and "data driven" but the reality is that there is not relevant experimental data. The progression of decisions during the early pandemic decisions is traced, and the basis of decisions based in science or herd mentality is discussed. Experiences are not experiments, and experiences are not founded in the scientific process. Medical and government leaders must be vigilant to recognize the limitations of available data in responding to unique circumstances.

Systemic and mucosal differences in HIV burden, immune, and therapeutic responses.

BACKGROUND: Mucosal tissues represent major targets for HIV transmission but differ in susceptibility and reservoir function by unknown mechanisms. METHODS: In a cross-sectional study, HIV RNA and infectious virus were compared between oral and genital compartments and blood in HIV-infected women, in association with clinical parameters, copathogens, and putative innate and adaptive HIV inhibitors. RESULTS: HIV RNA was detectable in 24.5% of women from all 3 compartments, whereas 45% had RNA in only 1 or 2 sites. By comparison, infectious HIV, present in blood of the majority, was rare in mucosal sites. Innate mediators, secretory leukocyte protease inhibitor and thrombospondin, were highest in mucosae. Highly active antiretroviral therapy was associated with an 80% decreased probability of shedding. Multivariate logistic regression models revealed that mucosal HIV RNA was associated with higher plasma RNA, infectious virus, and total mucosal IgA, but not IgG. There was a 37-fold increased probability of detecting RNA in both genital and oral specimens (P = 0.008; P = 0.02, respectively) among women in highest versus lowest IgA tertiles. CONCLUSIONS: Mucosal sites exhibit distinct characteristics of infectious HIV, viral shedding, and responses to therapy, dependent upon both systemic and local factors. Of the putative innate and adaptive mucosal defense factors examined, only IgA was associated with HIV RNA shedding. However, rather than being protective, there was a striking increase in probability of detectable HIV RNA shedding in women with highest total IgA.

Integrating quality improvement and residency education: insights from the AIAMC National Initiative about the roles of the designated institutional official and program director.

Active engagement of both the designated institutional official (DIO) and the program director (PD) is essential to implement any change in graduate medical education (GME). Strategies that are established by the Accreditation Council for Graduate Medical Education or other entities are, in the end, effective only as implemented at the individual program level. The interpretation of national standards or guidelines, and the specific adaptation to the vagaries of individual institutions and programs, can lead to significant variability in implementation and potentially in outcomes. Variability occurs between programs within the same institution and between some specialty programs at different institutions. The National Initiative, sponsored by the Alliance of Independent Academic Medical Centers, was launched in 2007 to demonstrate the effectiveness of GME as a key driver to improve quality, patient safety, and cost-effectiveness of care. This report addresses (1) the key roles of both the DIO and the PD in achieving the goals of the National Initiative, (2) the challenges these goals presented to each role, and (3) some of the tactics drawn from the experiences of the National Initiative in overcoming those challenges. The experience of the National Initiative underscored the synergies of the DIO and PD roles to improve patient care while simultaneously fulfilling their critical responsibilities as institutional and program leaders in GME with even greater effectiveness.

Human papillomavirus vaccine: a paradigm shift for pediatricians.

PURPOSE OF REVIEW: Recommendations for human papillomavirus (HPV) vaccination during adolescence primarily for a disease, cancer, that occurs only during adulthood is a paradigm shift for pediatricians. Additional postlicensure data and guidelines about HPV biology and epidemiology, disease association, adverse effects, vaccination during pregnancy, and cost-benefit analyses are now available to inform pediatricians and guide HPV vaccination recommendations. RECENT FINDINGS: The prespecified, end-of-study combined analysis of HPV vaccine efficacy studies for prevention of cervical cancer, and now also for prevention of vulvar and vaginal cancers, confirmed 98-100% vaccine efficacy. Postlicensure surveillance identified a new association of vaccine administration with syncope, and provides assurance of the safety of inadvertent vaccination during pregnancy. Several cost-effectiveness analyses consistently demonstrated that HPV vaccination of 12-year-old girls and catch-up vaccination through 18 years of age, and possibly to 26 years of age, is cost-effective, although the thresholds of affordability vary by study. The downward trend in age of initial HPV infection and the need to educate parents and patients about HPV disease and vaccination underscore the essential role of pediatricians in managing HPV illness. SUMMARY: It is critical for pediatricians to thoroughly understand HPV biology and disease and champion HPV vaccination to prevent cervical, vulvar, and vaginal cancers, even though these benefits accrue during adulthood and will likely require 2-4 decades to realize the financial and public health benefits. Several new developments are expected in the near future, including licensure for use in boys and men and the approval of a second, bivalent HPV vaccine.

Virologic Diagnosis, Viral Monitoring, and Treatment of Epstein-Barr Virus Infectious Mononucleosis.

Epstein-Barr virus (EBV) is the cause of infectious mononucleosis and is associated with severe infections in immunocompromised patients. EBV is also causally linked with several human malignancies. The heterophile antibody test and EBV-specific antibody tests remain the principal means of diagnosis of initial infection in otherwise healthy patients. Enzyme-linked immunosorbent assays have replaced the traditional immunofluorescence assays for EBV-specific antibodies. Several newer molecular diagnostic tests have become available that facilitate accurate monitoring of infection. The role of these tests for patients with uncomplicated infectious mononucleosis is limited, although these tests are being increasingly used to monitor the state and level of EBV replication for severe infections and among immunocompromised patients. Antiviral therapy has a limited, short-term effect on oropharyngeal shedding but has proven ineffective for the clinical manifestations of infectious mononucleosis. Patients with selected complications frequently benefit from short-term corticosteroid therapy.

Impact of pneumococcal and influenza vaccines on otitis media.

PURPOSE OF REVIEW: The pneumococcal conjugate vaccine and influenza virus vaccines have the potential to reduce the risk of acute otitis media. Several recent studies have evaluated the impact of each of these vaccines on the incidence of acute otitis media. RECENT FINDINGS: In controlled studies, pneumococcal conjugate vaccine has resulted in a reduction in the incidence of acute otitis media of approximately 6%. Inactivated influenza vaccine does not appear to reduce the incidence of acute otitis media in children 6-24 months of age, but a few studies, each with design or methodological limitations, suggest that it may reduce the incidence among older children. One study reported that the live-attenuated, cold-adapted trivalent influenza vaccine reduced the incidence of febrile otitis media by 30%. Additional studies are needed to clarify the value of influenza vaccines to prevent acute otitis media. SUMMARY: The pneumococcal conjugate vaccine and the influenza vaccines may have a limited beneficial impact on the incidence of acute otitis media. Nevertheless, at this time, these vaccines should be promoted because of their primary benefits, which are reduced serious pulmonary and invasive infections, and not because they may reduce the incidence of acute otitis media.

The changing picture of hepatitis A in the United States.

PURPOSE OF REVIEW: Hepatitis A causes approximately half of the cases of viral hepatitis in the United States. Since 1999, routine hepatitis A immunization of children in areas of the United States with high rates of hepatitis A has been recommended. RECENT FINDINGS: There has been an increasing appreciation of the role of young children with asymptomatic or inapparent infection as the community reservoir of hepatitis A virus. Epidemiologic studies have demonstrated striking geographic variations in the incidence of hepatitis A in the United States. On the basis of this understanding, recommendations for control of hepatitis A were updated in 1999 to include routine vaccination of children living in states, counties, and communities with high rates of hepatitis A. Routine hepatitis A vaccination of children in areas with high rates of hepatitis A is a cost-effective strategy to reduce the incidence of hepatitis A. SUMMARY: Improved understanding of the epidemiology and transmission of hepatitis A combined with the availability of effective hepatitis A vaccines have dramatically reduced the burden of hepatitis A in the United States.

Should smallpox vaccine be tested in children?

Following the terrorist attacks on 11 September 2001 there has been increased concern about bioterrorism, much of it focused on smallpox. Routine smallpox vaccination in the USA was discontinued in 1972 and most US citizens are susceptible to smallpox. The last natural case of smallpox occurred in 1978 but the virus has been stocked in freezers. If a terrorist had access to stored smallpox virus a release could produce a chaotic situation. In response the USA has developed a program for vaccinating adults but children have been left out. The only available vaccine has recently been tested in adults but a proposal for testing children was not approved. We need to know if available vaccines are safe for children so children can be safely and effectively vaccinated in an emergency situation.

Risk factors for pediatric human immunodeficiency virus-related malignancy.

CONTEXT: Although cancers occur with increased frequency in children with human immunodeficiency virus (HIV) infection, the specific clinical, immunological, and viral risk factors for malignancy have not been identified. OBJECTIVE: To identify risk factors for malignancy among HIV-infected children. DESIGN, SETTING, AND PATIENTS: A multicenter case-control study of children with HIV at 26 institutions participating in the Pediatric Oncology Group. Forty-three case patients with a new malignancy and 74 control patients without a malignancy were matched based on the duration of their infection. Patients were enrolled between January 1992 and July 1998. MAIN OUTCOME MEASURES: Clinical and laboratory factors assessed as putative risk factors included demographic characteristics, HIV characteristics, prior antiretroviral treatment, and CD4 cell count. Coviral infections with Epstein-Barr virus (EBV), cytomegalovirus, and human herpesvirus 6 were assessed by semiquantitative polymerase chain reaction assays and serological testing. RESULTS: Case malignancy diagnoses included 28 non-Hodgkin lymphoma, 4 B-cell acute lymphoblastic leukemia, 1 Hodgkin disease, 8 leiomyosarcoma, 1 hepatoblastoma, and 1 schwannoma. Epstein-Barr virus viral load of more than 50 viral genome copies per 105 peripheral blood mononuclear cells was strongly associated with cancer risk but only for children with CD4 cell counts of at least 200/ microL (odds ratio [OR], 11.33; 95% confidence interval [CI], 2.09-65.66, P<.001). High EBV viral load was not associated with cancer for children with CD4 cell counts of less than 200/ microL (OR, 1.12; 95% CI, 0.13-9.62; P =.99). Zidovudine antiretroviral therapy did not confer a significant protective effect for either the high (OR, 0.81; 95% CI, 0.22-3.09; P =.77) or the low CD4 cell count groups (OR, 0.27; 95% CI, 0.04-1.46; P =.16). The route of HIV infection was not associated with increased cancer risk. CONCLUSIONS: Route of infection, demographic characteristics, and zidovudine use were not associated with the development of malignancy in HIV-infected children. High viral burden with EBV was associated with the development of malignancy in HIV-infected children although the effect was modified by CD4 cell count. The pathogenesis of HIV-related pediatric malignancies remains unclear and other contributing risk factors can be elucidated only through further study.

New recommendations for influenza vaccination for children and pregnant women.

This year the Advisory Committee on Immunization Practices of the United States Centers for Disease Control and Prevention has updated recommendations for use of influenza vaccine. Previously, use of influenza vaccine focused primarily on the elderly as well as younger persons with underlying conditions that place them at high risk for severe disease and complications from influenza infection. The new recommendations also emphasize the benefits of influenza vaccination for young, healthy children who are at high risk for hospitalization with influenza infection. These changes are the result of recent reports demonstrating that otherwise healthy young children aged 6 to 24 months are hospitalized for influenza and its complications at rates comparable to those for whom influenza vaccination is already recommended, including the elderly.

Human herpesvirus 8 infection.

Human herpesvirus 8, also known as Kaposi sarcoma-associated herpesvirus, is etiologically associated with Kaposi sarcoma and other rare malignancies. Human herpesvirus 8 infection is common in certain areas of Africa and Italy, but occurs in only 0% to 15% of adult populations in North America and Europe. Reports of human herpesvirus 8 prevalence of 3% to over 50% among children in Central Africa, Brazil, and South Texas suggest that horizontal transmission of human herpesvirus 8 occurs among children. Primary human herpesvirus 8 infection in immunocompetent children is associated with a fever and maculopapular rash.

Performance of two commercial glycoprotein G-based enzyme immunoassays for detecting antibodies to herpes simplex viruses 1 and 2 in children and young adolescents.

In 61 patients 1 to 14 years of age, the Gull/Meridian enzyme-linked immunosorbent assay (ELISA) had a sensitivity of 100% for herpes simplex virus type 1 (HSV-1) and specificities of 74% for HSV-1 and 48% for HSV-2. In 128 similarly aged patients, the HerpeSelect ELISA (Focus Technologies) showed sensitivities of 80% for HSV-1 and 88% for HSV-2, and specificities of 97% for HSV-1 and 100% for HSV-2.

High prevalence of human herpesvirus 8 (HHV-8) infection in south Texas children.

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, is etiologically associated with Kaposi's sarcoma and other rare malignancies. HHV-8 infection is common in certain areas of Africa and Italy, but occurs in only 0-15% of populations in North America and Europe. The epidemiology and prevalence of HHV-8 infection among children in the United States has not been determined, but is assumed to be low based on limited studies. The objective of this study was to determine the seroprevalence and possible risk factors of HHV-8 infection in children living in south Texas. Questionnaire data were collected and HHV-8 serologic tests were performed from a consecutive, non-probability sample of 123 healthy children (ages 4-13 years) attending general pediatric clinics in south Texas. Serum was tested for HHV-8 antibodies by latent immunofluorescence assay and ORF65 enzyme-linked immunosorbent assay confirmed by immunoblot. HHV-8 prevalence and 95 percent confidence intervals were calculated using standard epidemiologic methods. Logistic regression was used to assess independent risk factors associated with HHV-8 seropositivity. The overall prevalence of HHV-8 infection was 26%. No statistically significant associations were exhibited between HHV-8 prevalence and the variables under study. The prevalence of HHV-8 infection among children in south Texas, particularly among those under the age of 12 years, indicates that non-sexual transmission of this virus is likely to occur among this population. Future investigations of larger study samples will be necessary to develop an understanding of specific routes and risk factors of HHV-8 transmission among children in south Texas.

Epstein-Barr virus and human immunodeficiency virus serological responses and viral burdens in HIV-infected patients treated with HAART.

Epstein-Barr virus (EBV) associated non-Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV- and HIV-specific serological responses together with EBV DNA levels in a cohort of HIV-infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12-month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNA at some point over the follow-up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four-fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA-IgG in 4/29 (14%); four-fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti-HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV-specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months.

Characterization of an Epstein-Barr virus-related gammaherpesvirus from common marmoset (Callithrix jacchus).

A gammaherpesvirus related to Epstein-Barr virus (EBV; Human herpesvirus 4) infects otherwise healthy common marmosets (Callithrix jacchus). Long-term culture of common marmoset peripheral blood lymphocytes resulted in outgrowth of spontaneously immortalized lymphoblastoid cell lines, primarily of B cell lineage. Electron microscopy of cells and supernatants showed herpesvirus particles. There were high rates of serological cross-reactivity to other herpesviruses (68-86%), but with very low geometric mean antibody titres [1:12 to human herpesvirus 6 and 1:14 to Herpesvirus papio (Cercopithecine herpesvirus 12)]. Sequence analysis of the conserved herpesvirus DNA polymerase gene showed that the virus is a member of the lymphocryptovirus subgroup and is most closely related to a lymphocryptovirus from rhesus macaques and is closely related to EBV and Herpesvirus papio. High seroprevalence (79%, with geometric mean antibody titre of 1:110) among 28 common marmosets from two geographically distinct colonies indicated that the virus is likely present in many common marmosets in captivity. A New World primate harbouring a lymphocryptovirus suggests that this subgroup arose much earlier than previously thought.