Assessing seroprevalence and associated risk factors for multiple infectious diseases in Sabah, Malaysia using serological multiplex bead assays.

Background: Infectious diseases continue to burden populations in Malaysia, especially among rural communities where resources are limited and access to health care is difficult. Current epidemiological trends of several neglected tropical diseases in these populations are at present absent due to the lack of habitual and efficient surveillance. To date, various studies have explored the utility of serological multiplex beads to monitor numerous diseases simultaneously. We therefore applied this platform to assess population level exposure to six infectious diseases in Sabah, Malaysia. Furthermore, we concurrently investigated demographic and spatial risk factors that may be associated with exposure for each disease. Methods: This study was conducted in four districts of Northern Sabah in Malaysian Borneo, using an environmentally stratified, population-based cross-sectional serological survey targeted to determine risk factors for malaria. Samples were collected between September to December 2015, from 919 villages totaling 10,100 persons. IgG responses to twelve antigens of six diseases (lymphatic filariasis- Bm33, Bm14, BmR1, Wb123; strongyloides- NIE; toxoplasmosis-SAG2A; yaws- Rp17 and TmpA; trachoma- Pgp3, Ct694; and giardiasis- VSP3, VSP5) were measured using serological multiplex bead assays. Eight demographic risk factors and twelve environmental covariates were included in this study to better understand transmission in this community. Results: Seroprevalence of LF antigens included Bm33 (10.9%), Bm14+ BmR1 (3.5%), and Wb123 (1.7%). Seroprevalence of Strongyloides antigen NIE was 16.8%, for Toxoplasma antigen SAG2A was 29.9%, and Giardia antigens GVSP3 + GVSP5 was 23.2%. Seroprevalence estimates for yaws Rp17 was 4.91%, for TmpA was 4.81%, and for combined seropositivity to both antigens was 1.2%. Seroprevalence estimates for trachoma Pgp3 + Ct694 were 4.5%. Age was a significant risk factors consistent among all antigens assessed, while other risk factors varied among the different antigens. Spatial heterogeneity of seroprevalence was observed more prominently in lymphatic filariasis and toxoplasmosis. Conclusions: Multiplex bead assays can be used to assess serological responses to numerous pathogens simultaneously to support infectious disease surveillance in rural communities, especially where prevalences estimates are lacking for neglected tropical diseases. Demographic and spatial data collected alongside serosurveys can prove useful in identifying risk factors associated with exposure and geographic distribution of transmission.

Adaptation to a Multiplex Bead Assay and Seroprevalence to Rift Valley Fever N Protein: Nampula Province, Mozambique, 2013-2014.

Rift Valley fever virus (RVFV) is endemic in sub-Saharan Africa (SSA), with outbreaks reported in the Arabian Peninsula and throughout SSA. The natural reservoir for RVFV are ruminants, with livestock populations exceeding 50% exposure rates in some areas of SSA. Transmission to humans can occur through exposure to infected livestock products or multiple species of mosquito vectors. In 2013 and 2014, cross-sectional surveys occurred in two districts of Nacala-a-Velha and Mecubúri in northern Mozambique, and participants provided blood samples for later serological assays. IgG against the N protein of RVFV was detected through multiplex bead assay (MBA). Of the 2,278 persons enrolled between the two surveys and study sites, 181 (7.9%, 95% confidence interval (CI): 6.9%-9.1%) were found to be IgG seropositive with increasing seroprevalence with older age and significantly higher seroprevalence in Nacala-a-Velha (10.5%, 8.8%-12.5%) versus Mecubúri (5.7%, 4.5%-7.1%). Seroprevalence estimates were not significantly different between the 2013 and 2014 surveys. Significant spatial clustering of IgG positive persons were consistent among surveys and within the two districts, pointing toward the consistency of serology data for making population-level assumptions regarding RVFV seroprevalence. A subset of persons (n = 539) provided samples for both the 2013 and 2014 surveys, and a low percentage (0.81%) of these were found to seroconvert between these two surveys. Including the RVFV N protein in an MBA antigen panel could assist elucidate RVFV exposure in SSA. IMPORTANCE Due to sporadic transmission, human contact with Rift Valley Fever Virus (RVFV) is difficult to ascertain at a population level. Detection of antibodies against RVFV antigens assist in estimating exposure as antibodies remain in the host long after the virus has been cleared. In this study, we show that antibodies against RVFV N protein can be detected from dried blood spot (DBS) samples being assayed by multiplex bead assay. DBS from two districts in northern Mozambique were tested for IgG against the N protein, and 7.9% of all enrolled persons were seropositive. Older persons, males, and persons residing closer to the coast had higher RVFV N protein seroprevalence. Spatial clustering of IgG positive persons was noted in both districts. These results show low exposure rates to RVFV in these two northern districts in Mozambique, and the ability to perform serology for the RVFV N protein from dried blood samples.

Multiplex Serology for Measurement of IgG Antibodies Against Eleven Infectious Diseases in a National Serosurvey: Haiti 2014-2015.

Background: Integrated surveillance for multiple diseases can be an efficient use of resources and advantageous for national public health programs. Detection of IgG antibodies typically indicates previous exposure to a pathogen but can potentially also serve to assess active infection status. Serological multiplex bead assays have recently been developed to simultaneously evaluate exposure to multiple antigenic targets. Haiti is an island nation in the Caribbean region with multiple endemic infectious diseases, many of which have a paucity of data for population-level prevalence or exposure. Methods: A nationwide serosurvey occurred in Haiti from December 2014 to February 2015. Filter paper blood samples (n = 4,438) were collected from participants in 117 locations and assayed for IgG antibodies on a multiplex bead assay containing 15 different antigens from 11 pathogens: Plasmodium falciparum, Toxoplasma gondii, lymphatic filariasis roundworms, Strongyloides stercoralis, chikungunya virus, dengue virus, Chlamydia trachomatis, Treponema pallidum, enterotoxigenic Escherichia coli, Entamoeba histolytica, and Cryptosporidium parvum. Results: Different proportions of the Haiti study population were IgG seropositive to the different targets, with antigens from T. gondii, C. parvum, dengue virus, chikungunya virus, and C. trachomatis showing the highest rates of seroprevalence. Antibody responses to T. pallidum and lymphatic filariasis were the lowest, with <5% of all samples IgG seropositive to antigens from these pathogens. Clear trends of increasing seropositivity and IgG levels with age were seen for all antigens except those from chikungunya virus and E. histolytica. Parametric models were able to estimate the rate of seroconversion and IgG acquisition per year for residents of Haiti. Conclusions: Multiplex serological assays can provide a wealth of information about population exposure to different infectious diseases. This current Haitian study included IgG targets for arboviral, parasitic, and bacterial infectious diseases representing multiple different modes of host transmission. Some of these infectious diseases had a paucity or complete absence of published serological studies in Haiti. Clear trends of disease burden with respect to age and location in Haiti can be used by national programs and partners for follow-up studies, resource allocation, and intervention planning.

Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger.

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.

Young Adults' Knowledge of State Cannabis Policy: Implications for Studying the Effects of Legalization in Vermont.

Objectives: Cannabis policy evaluations commonly assume equal policy exposure across a state's population using date of implementation as the key independent variable. This study aimed to explore policy knowledge as another measure of exposure and describe the sociodemographic, cognitive, and behavioral correlates of cannabis policy knowledge in young adults in Vermont. Methods: Data are from the PACE Vermont Study (Spring 2019), an online cohort study of Vermonters (12-25). Bivariate and multivariable analyses estimated prevalence ratios (PR) for correlations between knowledge of Vermont's cannabis policy (allowed possession for adults 21 and older) and sociodemographics, cannabis use, and harm perceptions in 1,037 young adults (18-25). Results: Overall, 60.1% of participants correctly described the state's cannabis policy. Being younger, Hispanic, non-White race, and less educated were inversely correlated with policy knowledge. Ever (PR=1.37; 95% CI 1.16-1.63) and past-30-day cannabis use (PR=1.27; 95% CI 1.12-1.45) were positively correlated with policy knowledge. Policy knowledge was more prevalent among young adults who perceived slight risk of harm from weekly cannabis use (vs. no risk; aPR=1.28; 95% CI 1.11-1.48) or agreed that regular cannabis use early in life can negatively affect attention (vs. disagree; aPR=1.55; 95% CI 1.22-1.97). Conclusion: Findings suggest that 40% of Vermont young adults in the study were unaware of current state cannabis policy and that policy knowledge was lower in younger, less educated, Hispanic, and non-White young adults. Future research should explore using a measure of policy knowledge as an exposure or moderator variable to better quantify the effects of changes in cannabis legal status on perceptions and use in young people.

The Association of Patient Educational Attainment With Cardiac Rehabilitation Adherence and Health Outcomes.

PURPOSE: Participating in cardiac rehabilitation (CR) after a cardiac event provides many clinical benefits. Patients of lower socioeconomic status (SES) are less likely to attend CR. It is unclear whether they attain similar clinical benefits as patients with higher SES. This study examines how educational attainment (one measure of SES) predicts both adherence to and improvements during CR. METHODS: This was a prospective observational study of 1407 patients enrolled between January 2016 and December 2019 in a CR program located in Burlington, VT. Years of education, smoking status (self-reported and objectively measured), depression symptom level (Patient Health Questionnaire), self-reported physical function (Medical Outcomes Survey), level of fitness (peak metabolic equivalent, peak oxygen uptake, and handgrip strength), and body composition (body mass index and waist circumference) were obtained at entry to, and for a subset (n = 917), at exit from CR. Associations of educational attainment with baseline characteristics were examined using Kruskal-Wallis or Pearson's χ 2 tests as appropriate. Associations of educational attainment with improvements during CR were examined using analysis of covariance or logistic regression as appropriate. RESULTS: Educational attainment was significantly associated with most patient characteristics examined at intake and was a significant predictor of the number of CR sessions completed. Lower educational attainment was associated with less improvement in cardiorespiratory fitness, even when controlling for other variables. CONCLUSIONS: Patients with lower SES attend fewer sessions of CR than their higher SES counterparts and may not attain the same level of benefit from attending. Programs need to increase attendance within this population and consider program modifications that further support behavioral changes during CR.

Multiplex Bead Assay for the Detection of Human IgG Antibody Responses to African Trypanosomes.

The recent introduction of large-scale, population-based serologic surveys in several nations where human African trypanosomiasis (HAT) remains endemic could provide an opportunity to better map the remaining disease foci and to identify asymptomatic, seropositive individuals who are infected with the more chronic form of the parasite, Trypanosoma brucei gambiense (gHAT). We have incorporated a soluble form of variant surface glycoprotein 117 and a recombinant invariant surface glycoprotein 65.1 into a multiplex bead assay (MBA) method that is commonly used for the detection of IgG antibody responses to other neglected tropical diseases. A positive result was defined as reactivity to both antigens. MBA sensitivity and specificity for gHAT infection were 92% and 96%, respectively. Assay specificity for the acute form of disease caused by T.b. rhodesiense (rHAT) was 94%, but the sensitivity was only 63.6%. In the future, additional antigens could be incorporated into the multiplex assay to improve rHAT sensitivity.

Determining seropositivity-A review of approaches to define population seroprevalence when using multiplex bead assays to assess burden of tropical diseases.

BACKGROUND: Serological surveys with multiplex bead assays can be used to assess seroprevalence to multiple pathogens simultaneously. However, multiple methods have been used to generate cut-off values for seropositivity and these may lead to inconsistent interpretation of results. A literature review was conducted to describe the methods used to determine cut-off values for data generated by multiplex bead assays. METHODOLOGY/PRINCIPAL FINDINGS: A search was conducted in PubMed that included articles published from January 2010 to January 2020, and 308 relevant articles were identified that included the terms "serology", "cut-offs", and "multiplex bead assays". After application of exclusion of articles not relevant to neglected tropical diseases (NTD), vaccine preventable diseases (VPD), or malaria, 55 articles were examined based on their relevance to NTD or VPD. The most frequently applied approaches to determine seropositivity included the use of presumed unexposed populations, mixture models, receiver operating curves (ROC), and international standards. Other methods included the use of quantiles, pre-exposed endemic cohorts, and visual inflection points. CONCLUSIONS/SIGNIFICANCE: For disease control programmes, seropositivity is a practical and easily interpretable health metric but determining appropriate cut-offs for positivity can be challenging. Considerations for optimal cut-off approaches should include factors such as methods recommended by previous research, transmission dynamics, and the immunological backgrounds of the population. In the absence of international standards for estimating seropositivity in a population, the use of consistent methods that align with individual disease epidemiological data will improve comparability between settings and enable the assessment of changes over time.

Validation of a diphtheria toxoid multiplex bead assay for serosurveys.

We validated a multiplex bead assay for diphtheria toxoid IgG antibodies against the Vero cell toxin neutralization test using 1300 specimens (correlation = 0.88). At the ≥0.01 IU/mL cutoff for minimal seroprotection, sensitivity was 95% and specificity was 83%. Agreement for three categories (<0.01, 0.01-<0.1, ≥0.1 IU/mL) was 81% (kappa = 0.71).

Development of a Measles and Rubella Multiplex Bead Serological Assay for Assessing Population Immunity.

Serosurveys are important tools for estimating population immunity and providing immunization activity guidance. The measles and rubella multiplex bead assay (MBA) offers multiple advantages over standard serological assays and was validated by comparison with the enzyme-linked immunosorbent assay (ELISA) and the measles plaque reduction neutralization (PRN) assay. Results from a laboratory-produced purified measles virus whole-virus antigen MBA (MeV WVAL) correlated better with ELISA and PRN than results from the baculovirus-expressed measles nucleoprotein (N) MBA. Therefore, a commercially produced whole-virus antigen (MeV WVAC) was evaluated. Serum IgG antibody concentrations correlated significantly with a strong linear relationship between the MeV WVAC and MeV WVAL MBAs (R = 0.962 and R2 = 0.926). IgG concentrations from the MeV WVAC MBA showed strong correlation with PRN titers (R = 0.846), with a linear relationship comparable to values obtained with the MeV WVAL MBA and PRN assay (R2 = 0.716 and R2 = 0.768, respectively). Receiver operating characteristic (ROC) curve analysis of the MeV WVAC using PRN titer as the comparator resulted in a seroprotection cutoff of 153 mIU/ml, similar to the established correlate of protection of 120 mIU/ml, with a sensitivity of 98% and a specificity of 83%. IgG concentrations correlated strongly between the rubella WVA MBA and ELISA (R = 0.959 and R2 = 0.919). ROC analysis of the rubella MBA using ELISA as the comparator yielded a cutoff of 9.36 IU/ml, similar to the accepted cutoff of 10 IU/ml for seroprotection, with a sensitivity of 99% and a specificity of 100%. These results support use of the MBA for multiantigen serosurveys assessing measles and rubella population immunity.

Development of a Multiplex Bead Assay for the Detection of Canine IgG4 Antibody Responses to Guinea Worm.

Increased levels of guinea worm (GW) disease transmission among dogs in villages along the Chari River in Chad threaten the gains made by the GW Eradication Program. Infected dogs with preemergent worm blisters are difficult to proactively identify. If these dogs are not contained, blisters can burst upon submersion in water, leading to the contamination of the water supply with L1 larvae. Guinea worm antigens previously identified using sera from human dracunculiasis patients were coupled to polystyrene beads for multiplex bead assay analysis of 41 non-endemic (presumed negative) dog sera and 39 sera from GW-positive dogs from Chad. Because commercially available anti-dog IgG secondary antibodies did not perform well in the multiplex assay, dog IgGs were partially purified, and a new anti-dog IgG monoclonal antibody was developed. Using the new 4E3D9 monoclonal secondary antibody, the thioredoxin-like protein 1-glutathione-S-transferase (GST), heat shock protein (HSP1)-GST, and HSP2-GST antigen multiplex assays had sensitivities of 69-74% and specificities of 73-83%. The domain of unknown function protein 148 (DUF148)-GST antigen multiplex assay had a sensitivity of 89.7% and a specificity of 85.4%. When testing samples collected within 1 year of GW emergence (n = 20), the DUF148-GST assay had a sensitivity of 90.0% and a specificity of 97.6% with a receiver-operating characteristic area under the curve of 0.94. Using sera from two experimentally infected dogs, antibodies to GW antigens were detected within 6 months of exposure. Our results suggest that, when used to analyze paired, longitudinal samples collected 1-2 months apart, the DUF148/GST multiplex assay could identify infected dogs 4-8 months before GW emergence.

Fine-scale heterogeneity in Schistosoma mansoni force of infection measured through antibody response.

Schistosomiasis is among the most common parasitic diseases in the world, with over 142 million people infected in low- and middle-income countries. Measuring population-level transmission is centrally important in guiding schistosomiasis control programs. Traditionally, human Schistosoma mansoni infections have been detected using stool microscopy, which is logistically difficult at program scale and has low sensitivity when people have low infection burdens. We compared serological measures of transmission based on antibody response to S. mansoni soluble egg antigen (SEA) with stool-based measures of infection among 3,663 preschool-age children in an area endemic for S. mansoni in western Kenya. We estimated force of infection among children using the seroconversion rate and examined how it varied geographically and by age. At the community level, serological measures of transmission aligned with stool-based measures of infection (ρ = 0.94), and serological measures provided more resolution for between-community differences at lower levels of infection. Force of infection showed a clear gradient of transmission with distance from Lake Victoria, with 94% of infections and 93% of seropositive children in communities <1.5 km from the lake. Force of infection increased through age 3 y, by which time 65% (95% CI: 53%, 75%) of children were SEA positive in high-transmission communities-2 y before they would be reached by school-based deworming programs. Our results show that serologic surveillance platforms represent an important opportunity to guide and monitor schistosomiasis control programs, and that in high-transmission settings preschool-age children represent a key population missed by school-based deworming programs.

Development of a Multiplex Bead Assay for the Detection of IgG Antibody Responses to Guinea Worm.

The success of the Guinea Worm (GW) Eradication Program over the past three decades has been tempered by the persistence of GW disease in a few African nations and the potential for a future resurgence in cases. Domestic dogs are now a major concern as a disease reservoir as large numbers of cases of canine GW disease are now reported each year, mainly along the Chari River in Chad. As a first step toward the development of a serologic assay for dogs, archived human plasma samples from dracunculiasis-positive donors from Togo were used to select adult female GW antigens for peptide sequencing and cloning. Eight protein sequences of interest were expressed as recombinant glutathione-S-transferase (GST) fusion proteins, and the most promising proteins were coupled to carboxylated microspheres for use in multiplex assays. A thioredoxin-like protein (TRXL1) and a domain of unknown function (DUF148) were assessed for total IgG and IgG4 reactivities using a panel of specimens from GW cases, uninfected donors, and individuals infected with various nematode worms, including Onchocerca volvulus. Both the DUF148-GST and the TRXL1-GST assays cross-reacted with O. volvulus sera, but the latter assay was always the more specific. The IgG4 and total IgG TRXL1-GST assays both had sensitivities > 87% and specificities > 90%. Maximum specificity (> 96%) was obtained with the total IgG assay when reactivity to both antigens was used to define a positive case. Given the good performance of the human assay, we are now working to modify the assay for dog assessments.

Current smoking as a marker of a high-risk behavioral profile after myocardial infarction.

Continued smoking following myocardial infarction (MI) is strongly associated with increased morbidity and mortality. Patients who continue to smoke may also engage in other behaviors that exacerbate risk. This study sought to characterize the risk profile of a national sample of individuals with previous MI who currently smoke. Data were taken from the 2017 Behavioral Risk Factor Surveillance Survey (United States), with 4.2% of the sample reporting a past MI (N = 26,004). Participants were classified by smoking status (current/former/never) and compared on medical comorbidities and the clustering of modifiable behaviors relevant for secondary prevention (smoking, poor nutrition, problematic alcohol use, physical inactivity, medication adherence). Current smokers were more likely to report other comorbidities including stroke, chronic obstructive pulmonary disease, physical limitations, and poor mental health. Smokers were also less likely to report taking blood pressure and cholesterol medications, and less likely to attend cardiac rehabilitation (examined in a subset of the sample, N = 2181). Current smoking remained an independent predictor of other health-related behaviors even when controlling for age, sex, race, educational attainment, and other comorbidities. In the modifiable risk-factor behavior cluster analysis, the most common pattern among current smokers was having two risk factors, smoking plus one additional risk factor, whereas the most common pattern was zero risk factors among never or former-smokers. Physical inactivity was the most common additional risk factor across smoking statuses. Current smoking is associated with multiple comorbidities and should be considered a marker for a high-risk behavioral profile among patients with a history of MI.

Recruiting and Retaining Youth and Young Adults in the Policy and Communication Evaluation (PACE) Vermont Study: Randomized Controlled Trial of Participant Compensation.

BACKGROUND: The standard approach for evaluating the effects of population-level substance use prevention efforts on youth and young adult perceptions and behaviors has been to compare outcomes across states using national surveillance data. Novel surveillance methods that follow individuals over shorter time intervals and capture awareness of substance use prevention policy and communication efforts may provide a stronger basis for their evaluation than annual cross-sectional studies. OBJECTIVE: This study aimed to identify a combination of strategies to recruit a sample of youth and young adults sufficiently representative of the Vermont population and determine how best to retain a web-based panel of youth and young adults over a 6-month period. METHODS: Eligible participants were Vermont residents aged 12 to 25 years who were willing to complete three 10 to 15-minute web-based surveys over a 6-month period. Recruitment was conducted via the following three main mechanisms: (1) web-based recruitment (paid and unpaid), (2) community-based recruitment through partners, and (3) participant referrals via a personalized link. Upon completion of the baseline survey, participants were randomly assigned to one of the following three retention incentive conditions: (1) guaranteed incentive (US $10), (2) lottery incentive (US $50 weekly lottery drawing), and (3) preferred method (guaranteed or lottery). Analyses examined cost per survey start by recruitment source, distribution of demographic characteristics across incentive conditions, and retention by study condition at 3-month and 6-month follow-ups. RESULTS: Over a 10-week period in 2019, we recruited 480 eligible youth (aged 12-17 years) and 1037 eligible young adults (aged 18-25 years) to the Policy and Communication Evaluation (PACE) Vermont Study. Facebook and Instagram advertising produced the greatest number of survey starts (n=2013), followed by posts to a state-wide web-based neighborhood forum (n=822) and Google advertisements (n=749). Retention was 78.11% (1185/1517) at 3 months and 72.18% (1095/1517) at 6 months. Retention was equivalent across all incentive study conditions at both waves, despite a strong stated preference among study participants for the guaranteed payment at baseline. Youth had greater retention than young adults at both waves (wave 2: 395/480, 82.3% vs 790/1037, 76.18%; wave 3: 366/480, 76.3% vs 729/1037, 70.30%). Substance use prevalence in this cohort was similar to national and state-level surveillance estimates for young adults, but was lower than state-level surveillance estimates for youth. Most participants retained at wave 3 provided positive qualitative feedback on their experience. CONCLUSIONS: Our study supports the feasibility of recruiting a web-based cohort of youth and young adults with representation across an entire state to evaluate substance use prevention efforts. Findings suggest that a guaranteed payment immediately upon survey completion coupled with a bonus for completing all survey waves and weekly survey reminders may facilitate retention in a cohort of youth and young adults.

Seroprevalence of Measles, Rubella, Tetanus, and Diphtheria Antibodies among Children in Haiti, 2017.

In Haiti, measles, rubella, and maternal and neonatal tetanus have been eliminated, but a diphtheria outbreak is ongoing as of 2019. We conducted a nationally representative, household-based, two-stage cluster survey among children aged 5-7 years in 2017 to assess progress toward maintenance of control and elimination of selected vaccine-preventable diseases (VPDs). We stratified Haiti into West region (West department, including the capital city) and non-West region (all other departments). We obtained vaccination history and dried blood spots, and measured antibody concentrations to VPDs on a multiplex bead assay. Among 1,146 children, national seropositivity was 83% (95% CI: 80-86%) for tetanus, 83% (95% CI: 81-85%) for diphtheria, 87% (95% CI: 85-89%) for measles, and 84% (95% CI: 81-87%) for rubella. None of the children had long-term immunity to tetanus or diphtheria (IgG concentration ≥ 1 international unit/mL). Seropositivity in the West region was lower than that in the non-West region. Vaccination coverage was 68% (95% CI: 61-74%) for ≥ 3 doses of tetanus- and diphtheria-containing vaccine (DTP3), 84% (95% CI: 80-87%) for one dose of measles-rubella vaccine (MR1), and 20% (95% CI: 16-24%) for MR2. The seroprevalence of measles, rubella, and diphtheria antibodies is lower than population immunity levels needed to prevent disease transmission, particularly in the West region; reintroduction of these diseases could lead to an outbreak. To maintain VPD control and elimination, Haiti should achieve DTP3 and MR2 coverage ≥ 95%, and include tetanus and diphtheria booster doses in the routine immunization schedule.

Investigating tobacco withdrawal in response to reduced nicotine cigarettes among smokers with opioid use disorder and other vulnerabilities.

Individuals with opioid use disorder (OUD) have high prevalence of smoking and poor cessation outcomes. Data suggest that smokers with OUD may experience heightened nicotine reinforcement and more severe tobacco withdrawal compared to smokers without OUD. The Food and Drug Administration is currently considering reducing the nicotine content of cigarettes to reduce smoking prevalence and smoking-related disease. It is critical to understand the effects of reduced nicotine content cigarettes (RNCCs) on tobacco withdrawal in this subgroup. In this secondary analysis, we investigated the ability of RNCCs to attenuate acute tobacco withdrawal and craving severity in smokers with OUD versus those without substance use disorders (SUDs). Smokers maintained on methadone or buprenorphine (opioid-maintained [OM]; n = 65) versus without other SUDs (i.e., non-SUD; n = 135) completed 5 laboratory sessions wherein they smoked their usual brand (UB) or a research cigarette varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g of tobacco) under double-blind, acute abstinence conditions. Participants completed the Minnesota Tobacco Withdrawal Scale, including a desire to smoke (craving) item, before and every 15 min for 1 hr following smoking each cigarette. Tobacco withdrawal and craving did not differ significantly by OM status in response to UB or RNCCs. In addition to the Dose × Time interaction, greater depression and cigarette dependence consistently predicted withdrawal and craving (ps < .05). Across all cigarettes, tobacco withdrawal and craving did not significantly differ by OM status, suggesting that smokers receiving opioid agonist treatment may respond favorably to RNCCs. Additional studies with larger and more diverse samples are needed to address this question more definitively. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Measuring Cryptosporidium Serologic Responses by Multiplex Bead Assay.

For more than 35 years, various assay formats have been used to detect Cryptosporidium-specific antibodies in human and animal sera. Cryptosporidium parvum 17- and 27-kDa antigens, identified from invasive sporozoites, have been used in serologic antibody assays to identify individuals infected in outbreaks of diarrheal disease caused by this protozoan parasite and to monitor exposures in communities. During infection, immunoglobulin (Ig) A, IgM, and IgG responses are elicited by these immunodominant antigens, and the parasite-specific Ig responses diminish following the resolution of infection. Using the recombinant forms of the 17- and 27-kDa C. parvum antigens and the relatively recently developed multiplex bead assay (MBA), data from serologic antibody responses can be economically and efficiently acquired, especially when the Cryptosporidium assays are integrated with assays for antibody responses to antigens from other pathogens monitored in community-wide or nation-wide serosurveys. Here we describe the coupling of the C. parvum recombinant antigens to carboxylated polystyrene beads, the data acquisition and analysis of IgG antibodies bound to the coupled beads, and the quality control methods required for data validation using the Luminex/MBA system.

Fecal Immunoglobulin A Against a Sporozoite Antigen at 12 Months Is Associated With Delayed Time to Subsequent Cryptosporidiosis in Urban Bangladesh: A Prospective Cohort Study.

In this prospective cohort study of Bangladeshi children, greater fecal immunoglobulin A, but not plasma immunoglobulin G, directed against the Cryptosporidium sporozoite-expressed antigen Cp23 at 12 months of age was associated with delayed time to subsequent cryptosporidiosis. This finding suggests a protective role for mucosal antibody-mediated immunity in naturally exposed children.

Risk of Readmission and Mortality Following Hospitalization with Hypercapnic Respiratory Failure.

PURPOSE: Hypercapnic respiratory failure (HRF) is a frequent cause of hospitalization and a common comorbidity in hospitalized patients. There are few studies addressing what factors might predict poor outcomes in this patient population. The purpose of the current study was to investigate characteristics and outcomes of patients hospitalized with HRF. METHODS: A study of patients ≥ 18 years admitted with HRF in a 1-year period. Patients with limited life expectancy related to other conditions, and those with a non-respiratory cause of HRF, were excluded. RESULTS: 202 subjects met eligibility criteria: 24% had a diagnosis of obstructive sleep apnea, 6% obesity hypoventilation, 46% chronic obstructive pulmonary disease, and 10% asthma. Fifteen (7%) died during the index admission. Forty-one patients (23%) were readmitted within 30 days: peripheral vascular disease [adjusted odds ratio (aOR) 4.78, CI 1.45-15.74] and tachycardia (aOR 2.97, CI 1.22-7.26) were associated with an increased risk of readmission. Sixty-six patients (36%) died after discharge. Risk of death was increased in older patients (aOR 1.32, CI 1.13-1.54 per 5 years), those with peripheral vascular disease (aOR 12.56, CI 2.35-67.21), higher Charlson co-morbidity index (aOR 1.39, CI 1.09-1.76), use of home oxygen (aOR 4.03, CI 1.89-8.57), and those who had been readmitted (aOR 3.07, CI 1.46-6.43). CONCLUSIONS: Hospitalization for HRF is associated with a high morbidity and mortality. Our observation that home oxygen use was associated with increased mortality suggests that oxygen use could be a risk factor for death in patients with HRF.