Impaired immune responsiveness in Plasmodium berghei immune mice

Mice immunized against Plasmodium berghei parasites by drug-controlled infection exhibited decreased immunoresponsiveness against rabbit red blood cells (RRBC). Increasing RRBC antigen dose increased responsiveness, but agglutinating anti-RRBC antibodies of the IgG class remained undetectable. Clearance of colloidal carbon from the bloodstream of malaria-immunized mice was not different from controls. Removal of all the persistent parasites from immune mice did not restore responsiveness until 140 days after treatment, suggesting that the parasite per se did not influence responsiveness directly. Because of this, and because of the fact that priming of mice with RRBC before P. berghei immunization was not more effective than priming after immunization, it was concluded that antigen uptake and subsequent presentation were not impaired in P. berghei immune mice, in contrast to infected mice. Anti-RRBC antibodies were detected in serum of P. berghei immune mice, but regulation of responsiveness to RRBC by transfer of such immune mouse serum was not found. Immunoglobulin levels, especially of the IgG2 and IgG3 subclass were elevated in sera of P. berghei immune mice, which indicated an LPS-like polyclonal activation. The results also suggest that during drug-controlled infection, which leads to immunity against infection, a state of B-cell tolerance is induced.     

Hepatitis C Seroprevalence Among Prison Inmates Since 2001: Still High but Declining

Objectives

Although the hepatitis C epidemic in the United States disproportionately affects correctional populations, the last national estimates of seroprevalence and disease burden among these populations are more than a decade old. We investigated routine hepatitis C surveillance conducted in state prison systems and updated previous estimates.

Methods

We surveyed all U.S. state correctional departments to determine which state prison systems had performed routine hepatitis C screening since 2001. Using seroprevalence data for these prison systems, we estimated the national hepatitis C seroprevalence among prisoners in 2006 and the share of the epidemic borne by correctional populations.

Results

Of at least 12 states performing routine testing from 2001 to 2012, seroprevalences of hepatitis C ranged from 9.6% to 41.1%. All but one state with multiple measurements demonstrated declining seroprevalence. We estimated the national state prisoner seroprevalence at 17.4% in 2006. Based on the estimated total U.S. correctional population size, we projected that 1,857,629 people with hepatitis C antibody were incarcerated that year. We estimated that correctional populations represented 28.5%–32.8% of the total U.S. hepatitis C cases in 2006, down from 39% in 2003.

Conclusions

Our results provide an important updated estimate of hepatitis C seroprevalence and suggest that correctional populations bear a declining but still sizable share of the epidemic. Correctional facilities remain important sites for hepatitis C case finding and therapy implementation. These results may also assist future studies in projecting the societal costs and benefits of providing new treatment options in prison systems.Hepatitis C virus (HCV) is the most common chronic bloodborne pathogen in the United States, both in the general population and among prisoners. National Health and Nutrition Examination Survey (NHANES) data from 2003–2006 suggested an overall anti-HCV serum antibody prevalence (seroprevalence) of 1.3% among household-dwelling populations.¹ Others have suggested that the national seroprevalence may be closer to 2.0% after adding prisoners, homeless people, and other populations not sampled by NHANES.² However, enrollment in NHANES requires several months of housing stability,³ so people with unstable or intermittent housing at any time during a given year are unlikely to participate. Thus, the number of infected people not in households during a period of time, rather than at a single point, should be added to the national seroprevalence estimate.Unsafe injection practices, including injection drug use, are the primary risk factors for HCV infection in the general population.⁴ National HCV prevalence is greater among men than women, and among non-Hispanic black people compared with non-Hispanic white people.¹ Prevalence peaks among individuals born between 1945 and 1965.⁵HCV infection disproportionately affects those who have been in jails and prisons. Although men (compared with women) and black people (compared with white people) are disproportionately incarcerated, the most likely cause for this infection rate disparity is injection drug use, which is both a risk factor for the disease and a criminal behavior.⁶ Hammett et al. estimated that correctional populations in 1997 accounted for 29.4%–43.2% of the total U.S. hepatitis C case burden.⁷ In 2003, the Centers for Disease Control and Prevention (CDC) reported that 16%–41% of inmates had serological evidence of prior HCV exposure, based on data derived from eight states. CDC also estimated that correctional populations bore 39% of the disease burden.⁸The 1976–1980 birth cohort currently comprises the largest proportion of state prison, federal prison, and local jail populations.⁹ As the birth cohort with peak HCV prevalence (1945–1965) ages out of crime-prone years, its contact with the criminal justice system will decline. Hence, the prevalence of HCV among correctional populations should fall. Two states included in the 2003 CDC analysis have since updated their seroprevalence estimates and both demonstrated declines. In Rhode Island, a sampling of prisoners in the mid-1990s showed an HCV seroprevalence of 37%,¹⁰ but seroprevalence dropped to 23% from 1998 to 2000.¹¹ In California, seroprevalence dropped from 41% of entering inmates in 1994¹² to 34% among a small cohort of entrants tested in 2001.¹³It has been estimated that 65%–75% of people with viral hepatitis are unaware of their status.¹⁴ Inmates are likely to be at the upper end of this range.¹⁵ Correctional facilities have represented rich sources for case finding. Once identified, new cases can be directed to treatment programs either in prison or the community. The need to initiate treatment before release for each case is contingent upon multiple factors. One determinant is whether the expected duration of incarceration is longer than the time required for treatment, which is currently one year but becoming shorter.¹⁶Prison health-care planners would benefit from up-to-date information regarding the number of hepatitis C infections in their systems. Currently, the U.S. lacks data on the prevalence of HCV among prisoners and the share of the epidemic borne by incarcerated individuals since the last national estimates were derived a decade ago.^7,8 We investigated routine HCV surveillance conducted in state prison systems to update estimates of the national prison HCV seroprevalence and the share of the epidemic borne by inmates and releasees. We hypothesized that HCV prevalence was falling nationwide among prisoners and that imprisoned populations represented a reduced share of the hepatitis C epidemic.     

Pseudopapilledema and association with idiopathic intracranial hypertension

Purpose

Diagnosing idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, can be challenging in children. Diagnosis is based on lumbar puncture, opening pressures, and appearance of the optic disk. Misdiagnosis of papilledema, a typical finding, may lead to unnecessary treatments and procedures. We report 52 children over a 6-year period to better identify the true incidence of pseudopapilledema and other factors that may confound the diagnosis of IIH.

Methods

A retrospective chart review approved by the Institutional Review Board was performed. Fifty-two children under the age of 21 referred to us based on suspected IIH or papilledema from 2007 to 2013 are included in this study. Patients were assessed by a pediatric ophthalmologist and a neurosurgeon.

Results

Fifty-two children were initially diagnosed with IIH and/or papilledema; 26 diagnoses were revised to pseudopapilledema after pediatric ophthalmological review. Out of those 26 patients with pseudopapilledema, 14 had undergone lumbar punctures, 19 had MRIs, 9 had CTs, and 12 were taking medications—these medications were discontinued upon revision of the diagnoses. The difference in the CSF opening pressure between children diagnosed with true IIH (32.7 cm H₂O) and children diagnosed with pseudopapilledema (24.7 cm H₂O) was statistically significant.

Conclusions

IIH diagnosis is heavily reliant on the appearance of the optic disk. Pediatric ophthalmological assessment is essential to carefully examine the optic disk and prevent further unnecessary investigation and treatments. Close communication between pediatricians, ophthalmologists, and neurosurgeons can avoid invasive procedures for children who do have pseudopapilledema, and not IIH or associated papilledema.     

Interdependent Citizens: The Ethics of Care in Pandemic Recovery

The crisis of Covid-19 has forced us to notice two things: our human interdependence and American society's tolerance for what Nancy Krieger has called “inequalities embodied in health inequities,” reflected in data on Covid-19 mortality and geographies. Care is integral to our recovery from this catastrophe and to the development of sustainable public health policies and practices that promote societal resilience and reduce the vulnerabilities of our citizens. Drawing on the insights of Joan Tronto and Eva Feder Kittay, we argue that the ethics of care offers a critical alternative to utilitarian and deontological approaches and provides a street-ready framework for integration into public health deliberations to anchor public policy and investments concerning the recovery and future well-being of America's citizens and society.     

Associations of perceived prenatal stress and adverse pregnancy outcomes with perceived stress years after delivery

Archives of Women's Mental Health - Maternal stress is a risk factor for adverse pregnancy outcomes (APOs). This study evaluates the associations of prenatal stress and APOs with maternal...     

Point-of-care testing versus standard practice for chlamydia: a new approach to assessing the public health effect of rapid testing and treatment at local level

BackgroundChlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection in Britain. Present standards specify treatment within 14 days of testing positive; point-of-care testing (POCT) can eliminate this delay and potentially reduce loss to follow-up; its greater convenience might increase testing. 90-min nucleic acid amplification tests are the best available POCTs for chlamydia, with alternatives under development. However, cost-effectiveness depends on cost-per-test, sensitivity and specificity, and the effect of POCT on transmission.MethodsWe developed a user-friendly web-based method, based on a transmission-dynamic model for chlamydia, to assess the epidemiological impact and cost-effectiveness of introducing POCT in different local settings. The model uses behavioural and prevalence data from the National Survey of Sexual Attitudes and Lifestyles, and Public Health England surveillance data; these data inform on local-level variation, which is represented by sampling parameter values from within their ranges of uncertainty and selecting parameter sets that reproduce local coverage and diagnosis rates. The user can select different local settings, and vary sensitivity and specificity for the tests, specify costs (fixed and unit costs, including staff time), and then assess the effect of introducing POCT in different clinical services by comparison with a situation with no POCT. In the model, presumptive treatment is represented, which we expect to be reduced with the introduction of POCT because test results would be rapidly available to guide treatment.FindingsChanges in numbers of infections and diagnoses occurring under different scenarios (including conventional testing) were estimated, with uncertainty ranges, allowing calculation of total costs, and cost per infection (and serious sequelae) averted, while accommodating the considerable variation in chlamydia testing coverage, positivity, and diagnosis rates. Potential changes in sexual behaviour between test and treatment could determine the relative contribution of increased treatment rates and reduced treatment delay to the reduction in prevalence as a consequence of POCT.InterpretationThe effect of POCT was dependent on both the test performance characteristics and the assumptions about the implementation of the test across local services. Exploration of many uncertainties surrounding chlamydia epidemiology and screening implementation is possible with this model. This method can complement local and national knowledge, and contribute to local-level management of chlamydia infection.FundingInnovate UK (Technology Strategy Board), UK Medical Research Council, and the National Institute for Health Research. The Electronic Self-Testing Instruments for Sexually Transmitted Infection (eSTI2) Consortium eSTI2 is Funded under the UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council (Grant Number G0901608) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, the Chief Scientist Office of the Scottish Government Health Directorates, and the Wellcome Trust