Establishment of CD1b-restricted immunity to lipid antigens in the pulmonary response to infection.

CD1 is an antigen-presenting glycoprotein homologous to MHC I; however, CD1 proteins present lipid rather than peptide antigens. CD1 proteins are well established to present lipid antigens of (Mtb) to T cells, but understanding the role of CD1-restricted immunity in response to Mtb infection has been limited by the availability of animal models naturally expressing the CD1 proteins implicated in human response: CD1a, CD1b, and CD1c. Guinea pigs, in contrast to other rodent models, express four CD1b orthologs, and here we utilize the guinea pig to establish the kinetics of gene and protein expression of CD1b orthologs, as well as the Mtb lipid-antigen and CD1b-restricted immune response at the tissue level over the course of Mtb infection.

Establishment of CD1b-restricted immunity to lipid antigens in the pulmonary response to infection.

CD1 is an antigen presenting glycoprotein homologous to MHC I; however, CD1 proteins present lipid rather than peptide antigen. CD1 proteins are well established to present lipid antigens of (Mtb) to T cells, but understanding the role of CD1-restricted immunity in response to Mtb infection has been limited by availability of animal models naturally expressing the CD1 proteins implicated in human response: CD1a, CD1b and CD1c. Guinea pigs, in contrast to other rodent models, express four CD1b orthologs, and here we utilize the guinea pig to establish the kinetics of gene and protein expression of CD1b orthologs, as well as the Mtb lipid-antigen and CD1b-restricted immune response at the tissue level over the course of Mtb infection.

Preparation Strategies of the Anti-Mycobacterial Drug Bedaquiline for Intrapulmonary Routes of Administration.

() has infected one-quarter of the world's population and led to the deaths of 1.6 million individuals in 2021 according to estimates from the World Health Organization. The rise in prevalence of multidrug-resistant and extensively drug-resistant strains coupled with insufficient therapies to treat such strains has motivated the development of more effective treatments and/or delivery modalities.

Field Performance of Two Methods for Detection of Poliovirus in Wastewater Samples, Mexico 2016-2017.

To enhance our ability to monitor poliovirus circulation and certify eradication, we evaluated the performance of the bag-mediated filtration system (BMFS) against the two-phase separation (TPS) method for concentrating wastewater samples for poliovirus detection. Sequential samples were collected at two sites in Mexico; one L was collected by grab and ~ 5 L were collected and filtered in situ with the BMFS. In the laboratory, 500 mL collected by grab were concentrated using TPS and the sample contained in the filter of the BMFS was eluted without secondary concentration.

Use of the revised World Health Organization cluster survey methodology to classify measles-rubella vaccination campaign coverage in 47 counties in Kenya, 2016.

Introduction: To achieve measles elimination, two doses of measles-containing vaccine (MCV) are provided through routine immunization services or vaccination campaigns. In May 2016, Kenya conducted a measles-rubella (MR) vaccination campaign targeting 19 million children aged 9 months-14 years, with a goal of achieving ≥95% coverage. We conducted a post-campaign cluster survey to estimate national coverage and classify coverage in Kenya's 47 counties.

Immunogenicity of type 2 monovalent oral and inactivated poliovirus vaccines for type 2 poliovirus outbreak response: an open-label, randomised controlled trial.

Background: Monovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We aimed to assess the effect of two mOPV2 doses on the type 2 immune response by varying the time interval between mOPV2 doses and IPV co-administration with mOPV2.

Methods: We did a randomised, controlled, parallel, open-label, non-inferiority, inequality trial at two study clinics in Dhaka, Bangladesh.

Assessing the potency and immunogenicity of inactivated poliovirus vaccine after exposure to freezing temperatures.

According to manufacturers, inactivated poliovirus vaccines (IPVs) are freeze sensitive and require storage between 2°C and 8°C, whereas oral poliovirus vaccine requires storage at -20 °C. Introducing IPV into ongoing immunization services might result in accidental exposure to freezing temperatures and potential loss of vaccine potency. To better understand the effect of freezing IPVs, samples of single-dose vaccine vials from Statens Serum Institut (VeroPol) and multi-dose vaccine vials from Sanofi Pasteur (IPOL) were exposed to freezing temperatures mimicking what a vaccine vial might encounter in the field.

Effectiveness of a Third Dose of MMR Vaccine for Mumps Outbreak Control.

Background: The effect of a third dose of the measles-mumps-rubella (MMR) vaccine in stemming a mumps outbreak is unknown. During an outbreak among vaccinated students at the University of Iowa, health officials implemented a widespread MMR vaccine campaign. We evaluated the effectiveness of a third dose for outbreak control and assessed for waning immunity.

The role of supplementary environmental surveillance to complement acute flaccid paralysis surveillance for wild poliovirus in Pakistan - 2011-2013.

Background: More than 99% of poliovirus infections are non-paralytic and therefore, not detected by acute flaccid paralysis (AFP) surveillance. Environmental surveillance (ES) can detect circulating polioviruses from sewage without relying on clinical presentation. With extensive ES and continued circulation of polioviruses, Pakistan presents a unique opportunity to quantify the impact of ES as a supplement to AFP surveillance on overall completeness and timeliness of poliovirus detection.

Pathogen-Specific Burden of Outpatient Diarrhea in Infants in Nepal: A Multisite Prospective Case-Control Study.

Background: Nonsevere diarrheal disease in Nepal represents a large burden of illness. Identification of the specific disease-causing pathogens will help target the appropriate control measures.

Methods: Infants aged 6 weeks to 12 months were recruited from 5 health facilities in eastern, central, and western Nepal between August 2012 and August 2013.

Contribution of Contact Sampling in Increasing Sensitivity of Poliovirus Detection During A Polio Outbreak-Somalia, 2013.

Background.  In May 2013, a wild poliovirus type 1 (WPV1) outbreak reported in Somalia provided an opportunity to examine the contribution of testing contacts to WPV detection. Methods.

Measles immunity among pregnant women aged 15-44 years in Namibia, 2008 and 2010.

Background: Namibia experienced a large measles outbreak starting in 2009, with 38% of reported cases in adults, including women of reproductive age. Population immunity was assessed among pregnant women to determine whether immunization activities were needed in adults to achieve measles elimination in Namibia.

Methods: A total of 1708 and 2040 specimens sampled from Namibian pregnant women aged 15-44 years who were included in the 2008 and 2010 National HIV Sentinel Survey, respectively, were tested for measles immunoglobulin G antibody.

Rubella immunity among pregnant women aged 15-44 years, Namibia, 2010.

Background: The level of rubella susceptibility among women of reproductive age in Namibia is unknown. Documenting the risk of rubella will help estimate the potential burden of disease in Namibian women and the risk of congenital rubella syndrome (CRS) in infants, and will guide strategies for the introduction of rubella vaccine.

Methods: A total of 2044 serum samples from pregnant Namibian women aged 15-44 years were tested for rubella immunoglobulin G antibody; the samples were obtained during the 2010 National HIV Sentinel Survey.

The effect of diarrheal disease on bivalent oral polio vaccine (bOPV) immune response in infants in Nepal.

Background: A globally-coordinated phase out of all type 2 containing oral polio vaccine (OPV) is planned for April 2016 during which bivalent 1+3 OPV (bOPV) will replace trivalent OPV (tOPV) in routine immunization schedules and campaigns. Diarrhea impairs the immune response to tOPV, but the effect of diarrhea on bOPV is unknown.

Methods: Infants aged 6 weeks to 11 months, who had received <3 doses of OPV and had mild-moderate diarrhea or no diarrhea, were recruited at five health facilities in Nepal.

Early priming with inactivated poliovirus vaccine (IPV) and intradermal fractional dose IPV administered by a microneedle device: A randomized controlled trial.

Introduction: Inactivated poliovirus vaccine (IPV) introduction and phased oral poliovirus vaccine (OPV) cessation are essential for eradication of polio.

Methods: Healthy 6-week old infants in Bangladesh were randomized to one of five study arms: receipt of trivalent OPV (tOPV) or bivalent OPV (bOPV) at ages 6, 10 and 14 weeks, intramuscular IPV or intradermal one-fifth fractional dose IPV (f-IPV) at ages 6 and 14 weeks, or f-IPV at ages 6 and 14 weeks with bOPV at age 10 weeks (f-IPV/bOPV). All participants received tOPV at age 18 weeks.

Immunogenicity of three doses of bivalent, trivalent, or type 1 monovalent oral poliovirus vaccines with a 2 week interval between doses in Bangladesh: an open-label, non-inferiority, randomised, controlled trial.

Background: The provision of several doses of monovalent type 1 oral poliovirus vaccine (mOPV1) and bivalent OPV1 and 3 (bOPV) vaccines through campaigns is essential to stop the circulation of remaining wild polioviruses. Our study aimed to assess the shortening of intervals between campaigns with bOPV and mOPV1 and to assess the immunogenicity of bOPV in routine immunisation schedules.

Methods: We did an open-label, non-inferiority, five-arm, randomised controlled trial in Bangladesh.

Effect of time at temperature on wild poliovirus titers in stool specimens.

Background: The effect of transport temperature on the viability of poliovirus in stool specimens from paralyzed cases has not been tested. Quality assurance of programmatic indicators will be necessary in the final phase of polio eradication.

Objective: To estimate the effect of time at elevated temperatures on wild poliovirus titers in stool specimens.

Estimating the likely coverage of inactivated poliovirus vaccine in routine immunization: evidence from demographic and health surveys.

Background: The Strategic Advisory Group of Experts on Immunization (SAGE) has recommended introduction of at least 1 dose of inactivated poliovirus vaccine (IPV) at ≥14 weeks of age through the routine immunization program in countries currently not using IPV.

Methods: We analyzed all available unrestricted data obtained from the Demographic and Health Surveys since 2005 in sub-Saharan Africa (31 countries) and in South and Southeast Asia (9 countries) to determine coverage of the following injectable vaccines delivered through the routine immunization schedule: diphtheria-tetanus-pertussis vaccine dose 1 (DTP1), DTP2, DTP3, and measles vaccine. Coverage with these vaccines was used as a proxy measure of likely 1- and 2-dose IPV coverage.

An acute flaccid paralysis surveillance-based serosurvey of poliovirus antibodies in Western Uttar Pradesh, India.

Background: Despite intensified use of monovalent oral poliovirus type 1 vaccine and improved coverage of immunization campaigns, wild poliovirus type 1 persisted in Indian states of Uttar Pradesh and Bihar during 2006 to 2009.

Methods: A serosurvey was conducted among cases of acute flaccid paralysis in the 25 high-polio-incidence districts of western Uttar Pradesh. Children were recruited by age group (6-11 months, 12-24 months, and 25-69 months) from among cases reported through the acute flaccid paralysis surveillance system between November 2008 and August 2009.

Assessing population immunity in a persistently high-risk area for wild poliovirus transmission in India: a serological study in Moradabad, Western Uttar Pradesh.

Background: Moradabad district in Uttar Pradesh reported the highest number of paralytic polio cases in India during 2001-2007. We conducted a study in Moradabad in 2007 to assess seroprevalence against poliovirus types 1, 2, and 3 in children 6-12 and 36-59 months of age to guide future strategies to interrupt wild poliovirus transmission in high-risk areas.

Methods: Children attending 10 health facilities for minor illnesses who met criteria for study inclusion were eligible for enrollment.

Surveillance during an era of rapidly changing poliovirus epidemiology in India: the role of one vs. two stool specimens in poliovirus detection, 2000-2010.

Since 2004, efforts to improve poliovirus detection have significantly increased the volume of specimen testing from acute flaccid paralysis (AFP) patients in India. One option to decrease collection and testing burden would be collecting only a single stool specimen instead of two. We investigated stool specimen sensitivity for poliovirus detection in India to estimate the contribution of the second specimen.

When subatomic physics research meets clinical oncology.

New but costly forms of hadron therapy to treat certain cancers raise important questions about how much health systems can afford to pay, but for some cancers, including many child cancers, they are among the most promising treatments we have.

Limited duration of vaccine poliovirus and other enterovirus excretion among human immunodeficiency virus infected children in Kenya.

Background: Immunodeficient persons with persistent vaccine-related poliovirus infection may serve as a potential reservoir for reintroduction of polioviruses after wild poliovirus eradication, posing a risk of their further circulation in inadequately immunized populations.

Methods: To estimate the potential for vaccine-related poliovirus persistence among HIV-infected persons, we studied poliovirus excretion following vaccination among children at an orphanage in Kenya. For 12 months after national immunization days, we collected serial stool specimens from orphanage residents aged <5 years at enrollment and recorded their HIV status and demographic, clinical, immunological, and immunization data.

Uncertainty and sensitivity analyses of a decision analytic model for posteradication polio risk management.

Decision analytic modeling of polio risk management policies after eradication may help inform decisionmakers about the quantitative tradeoffs implied by various options. Given the significant dynamic complexity and uncertainty involving posteradication decisions, this article aims to clarify the structure of a decision analytic model developed to help characterize the risks, costs, and benefits of various options for polio risk management after eradication of wild polioviruses and analyze the implications of different sources of uncertainty. We provide an influence diagram of the model with a description of each component, explore the impact of different assumptions about model inputs, and present probability distributions of model outputs.

The risks, costs, and benefits of possible future global policies for managing polioviruses.

Objectives: We assessed the costs, risks, and benefits of possible future major policy decisions on vaccination, surveillance, response plans, and containment following global eradication of wild polioviruses.

Methods: We developed a decision analytic model to estimate the incremental cost-effectiveness ratios and net benefits of risk management options for polio for the 20-year period and stratified the world according to income level to capture important variability between nations.

Results: For low-, lower-middle-, and upper-middle-income groups currently using oral poliovirus vaccine (OPV), we found that after successful eradication of wild polioviruses, OPV cessation would save both costs and lives when compared with continued use of OPV without supplemental immunization activities.