BACKGROUND: Indoor residual spraying (IRS) using neonicotinoid-based insecticides (clothianidin and combined clothianidin with deltamethrin) was deployed in two previously unsprayed districts of Côte d'Ivoire in 2020 and 2021 to complement standard pyrethroid insecticide-treated nets. This retrospective observational study uses health facility register data to assess the impact of IRS on clinically reported malaria case incidence. METHODS: Health facility data were abstracted from consultation registers for the period September 2018 to April 2022 in two IRS districts and two control districts that did not receive IRS. Malaria cases reported by community health workers (CHWs) were obtained from district reports and District Health Information Systems 2. Facilities missing complete data were excluded. Controlled interrupted time series models were used to estimate the effect of IRS on monthly all-ages population-adjusted confirmed malaria cases and cases averted by IRS. Models controlled for transmission season, precipitation, vegetation, temperature, proportion of cases reported by CHWs, proportion of tested out of suspected cases and non-malaria outpatient visits. RESULTS: An estimated 10 988 (95% CI 5694 to 18 188) malaria cases were averted in IRS districts the year following the 2020 IRS campaign, representing a 15.9% reduction compared with if IRS had not been deployed. Case incidence in IRS districts dropped by 27.7% (incidence rate ratio (IRR) 0.723, 95% CI 0.592 to 0.885) the month after the campaign. In the 8 months after the 2021 campaign, 14 170 (95% CI 13 133 to 15 025) estimated cases were averted, a 24.7% reduction, and incidence in IRS districts dropped by 37.9% (IRR 0.621, 95% CI 0.462 to 0.835) immediately after IRS. Case incidence in control districts did not change following IRS either year (p>0.05) and the difference in incidence level change between IRS and control districts was significant both years (p<0.05). CONCLUSION: Deployment of clothianidin-based IRS was associated with a reduction in malaria case rates in two districts of Côte d'Ivoire following IRS deployment in 2020 and 2021.

During the COVID-19 vaccination rollout from March 2021- December 2022, the Centers for Disease Control and Prevention funded 110 primary and 1051 subrecipient partners at the national, state, local, and community-based level to improve COVID-19 vaccination access, confidence, demand, delivery, and equity in the United States. The partners implemented evidence-based strategies among racial and ethnic minority populations, rural populations, older adults, people with disabilities, people with chronic illness, people experiencing homelessness, and other groups disproportionately impacted by COVID-19. CDC also expanded existing partnerships with healthcare professional societies and other core public health partners, as well as developed innovative partnerships with organizations new to vaccination, including museums and libraries. Partners brought COVID-19 vaccine education into farm fields, local fairs, churches, community centers, barber and beauty shops, and, when possible, partnered with local healthcare providers to administer COVID-19 vaccines. Inclusive, hyper-localized outreach through partnerships with community-based organizations, faith-based organizations, vaccination providers, and local health departments was critical to increasing COVID-19 vaccine access and building a broad network of trusted messengers that promoted vaccine confidence. Data from monthly and quarterly REDCap reports and monthly partner calls showed that through these partnerships, more than 295,000 community-level spokespersons were trained as trusted messengers and more than 2.1 million COVID-19 vaccinations were administered at new or existing vaccination sites. More than 535,035 healthcare personnel were reached through outreach strategies. Quality improvement interventions were implemented in healthcare systems, long-term care settings, and community health centers resulting in changes to the clinical workflow to incorporate COVID-19 vaccine assessments, recommendations, and administration or referrals into routine office visits. Funded partners' activities improved COVID-19 vaccine access and addressed community concerns among racial and ethnic minority groups, as well as among people with barriers to vaccination due to chronic illness or disability, older age, lower income, or other factors.

ABSTRACTDespite the human immunodeficiency virus (HIV) pandemic continuing worldwide for 40 years, no vaccine to combat the disease has been licensed for use in at risk populations. Here, we describe a novel recombinant vesicular stomatitis virus (rVSV) vector vaccine expressing modified HIV envelope glycoproteins and Ebola virus glycoprotein. Three heterologous immunizations successfully prevented infection by a different clade SHIV in 60% of nonhuman primates (NHPs). No trend was observed between resistance and antibody interactions. Resistance to infection was associated with high proportions of central memory T cell CD69 and CD154 marker upregulation, increased IL-2 production, and a reduced IFN-γ response, offering insight into correlates of protection.

OBJECTIVE: to conduct a systematic review of the observational studies analyzing the association between ultra-processed food (UPF) intake and the risk of depression. DESIGN: the search adhered to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); a search for observational studies published until June 2020 was performed in PubMed, Embase, Cochrane Library, and Web of Science databases, followed by additional manual searches. Eight reviewers, working independently in teams of two, screened studies for eligibility, extracted data, and assessed risk of bias. We resolved disagreements through discussion or, if necessary, through adjudication by a third (LH). And the study assessed cross-sectional studies using the Agency for Healthcare Research and Quality (AHRQ) methodological checklist and cohort and case-control studies using the Newcastle-Ottawa Scale (NOS) for quality. We used a tabular format to summarize the articles. RESULTS: twenty-eight studies evaluating UPF intake and risk of depression were finally selected, 21 of which had a cross-sectional design, 6 studies had a cohort design, and 1 had a case-control design. Of these, 4 cohort studies and 17 cross-sectional studies found that consumption of UPF were positively associated with depression or depressive symptoms. CONCLUSIONS: our review demonstrated that most studies included in the systematic review showed that UPF consumption is associated with the risk of depression. Future studies should consider the use of validated food intake assessments and standardized depression assessment methods to promote comparability between studies.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (73%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (07%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (914%), moxifloxacin (916%) and ethambutol (933%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation. 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Understanding the ecological and epidemiological roles of pets in the transmission of SARS-CoV-2 is critical for animal and human health, identifying household reservoirs, and predicting the potential enzootic maintenance of the virus. We conducted a longitudinal household transmission study of 76 dogs and cats living with at least one SARS-CoV-2-infected human in Texas and found that 17 pets from 25.6% of 39 households met the national case definition for SARS-CoV-2 infections in animals. This includes three out of seventeen (17.6%) cats and one out of fifty-nine (1.7%) dogs that were positive by RT-PCR and sequencing, with the virus successfully isolated from the respiratory swabs of one cat and one dog. Whole-genome sequences of SARS-CoV-2 obtained from all four PCR-positive animals were unique variants grouping with genomes circulating among people with COVID-19 in Texas. Re-sampling showed persistence of viral RNA for at least 25 d-post initial test. Additionally, seven out of sixteen (43.8%) cats and seven out of fifty-nine (11.9%) dogs harbored SARS-CoV-2 neutralizing antibodies upon initial sampling, with relatively stable or increasing titers over the 2-3 months of follow-up and no evidence of seroreversion. The majority (82.4%) of infected pets were asymptomatic. 'Reverse zoonotic' transmission of SARS-CoV-2 from infected people to animals may occur more frequently than recognized.

Asthma is one of the most common underlying diseases in women of reproductive age that can lead to potentially serious medical problems during pregnancy and lactation. A group of key stakeholders across multiple relevant disciplines was invited to take part in an effort to prioritize, strategize, and mobilize action steps to fill important gaps in knowledge regarding asthma medication safety in pregnancy and lactation. The stakeholders identified substantial gaps in the literature on the safety of asthma medications used during pregnancy and lactation and prioritized strategies to fill those gaps. Short-term action steps included linking data from existing complementary study designs (US and international claims data, single drug pregnancy registries, case-control studies, and coordinated systematic data systems). Long-term action steps included creating an asthma disease registry, incorporating the disease registry into electronic health record systems, and coordinating care across disciplines. The stakeholders also prioritized establishing new infrastructures/collaborations to perform research in pregnant and lactating women and to include patient perspectives throughout the process. To address the evidence gaps, and aid in populating product labels with data that inform clinical decision making, the consortium developed a plan to systematically obtain necessary data in the most efficient and timely manner.

As part of a longitudinal household transmission study of pets living with persons with COVID-19 in Texas, two pets were confirmed to be infected with the SARS-CoV-2 B.1.1.7 variant of concern (VOC). The pets were a dog and a cat from the same household, sampled two days after their owner tested positive for COVID-19. The oral, nasal, and fur swabs for both pets tested positive for SARS-CoV-2 by qRT-PCR and consensus whole genome sequences from the dog and cat were 100 % identical and matched the B.1.1.7 VOC. Virus was isolated from the cat's nasal swab. One month after initial detection of infection, the pets were re-tested twice at which time only the fur swabs (both pets) and oral swab (dog only) remained positive, and neutralizing antibodies for SARS-CoV-2 were present in both animals. Sneezing by both pets was noted by the owner in the weeks between initial and follow-up testing. This study documents the first detection of B.1.1.7. in companion animals in the United States, and the first genome recovery and isolation of B.1.1.7 variant of concern globally in any animal.

From 2008 to 2017, the city of Abidjan, Côte d'Ivoire experienced several Aedes-borne disease epidemics which required control of the vector mosquito population based on the reduction of larval habitats and insecticidal sprays for adult mosquitoes. This study was undertaken to assess the insecticide susceptibility status of Aedes aegypti (Linnaeus) in the city of Abidjan. Immature Ae. aegypti were sampled from several larval habitats within seven communes of Abidjan and reared to adults. Three to five days old F1 emerged adults were tested for susceptibility using insecticide-impregnated papers and the synergist piperonyl butoxide (PBO) following WHO bioassay guidelines. The results showed that Ae. aegypti populations from Abidjan were resistant to 0.1% propoxur, and 1% fenitrothion, with mortality rates ranging from 0% to 54.2%. Reduced susceptibility (93.4-97.5% mortality) was observed to 0.05% deltamethrin, 0.75% permethrin, 0.05% lambda-cyhalothrin, 5% malathion, and 0.8% chlorpyrifos-methyl. This reduced susceptibility varied depending on the insecticide and the collection site. The restoration of mortality when the mosquitoes were pre-exposed to the synergist PBO suggests that increased activity of oxidases could be contributing to resistance. Three kdr mutations (V410L, V1016I, and F1534C) were present in populations tested, with low frequencies for the Leu410 (0.28) and Ile1016 (0.32) alleles and high frequencies for the Cys1534 allele (0.96). These findings will be used to inform future arbovirus vector control activities in Abidjan.

We present the Progression and Transmission of HIV (PATH 4.0), a simulation tool for analyses of cluster detection and intervention strategies. Molecular clusters are groups of HIV infections that are genetically similar, indicating rapid HIV transmission where HIV prevention resources are needed to improve health outcomes and prevent new infections. PATH 4.0 was constructed using a newly developed agent-based evolving network modeling (ABENM) technique and evolving contact network algorithm (ECNA) for generating scale-free networks. ABENM and ECNA were developed to facilitate simulation of transmission networks for low-prevalence diseases, such as HIV, which creates computational challenges for current network simulation techniques. Simulating transmission networks is essential for studying network dynamics, including clusters. We validated PATH 4.0 by comparing simulated projections of HIV diagnoses with estimates from the National HIV Surveillance System (NHSS) for 2010-2017. We also applied a cluster generation algorithm to PATH 4.0 to estimate cluster features, including the distribution of persons with diagnosed HIV infection by cluster status and size and the size distribution of clusters. Simulated features matched well with NHSS estimates, which used molecular methods to detect clusters among HIV nucleotide sequences of persons with HIV diagnosed during 2015-2017. Cluster detection and response is a component of the U.S. Ending the HIV Epidemic strategy. While surveillance is critical for detecting clusters, a model in conjunction with surveillance can allow us to refine cluster detection methods, understand factors associated with cluster growth, and assess interventions to inform effective response strategies. As surveillance data are only available for cases that are diagnosed and reported, a model is a critical tool to understand the true size of clusters and assess key questions, such as the relative contributions of clusters to onward transmissions. We believe PATH 4.0 is the first modeling tool available to assess cluster detection and response at the national-level and could help inform the national strategic plan. © 2021 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)

Feng Shuren, Mei Joanne, Yang Lu, Luo Ping, Wang Xiaonan, Wang Yuan, Yao Jingyi, Cui Lan, Pan Lei, Wang Zefang, Xin Li. International journal of neonatal screening 2020 Feb 6(1)

Accurate laboratory reporting is crucial to patient diagnosis and treatment. This study identified critical success factors (CSF) for implementing a laboratory quality management system (QMS). This descriptive research used qualitative and quantitative methods to collect and analyze data from laboratory managers and staff employed in Vietnamese hospital laboratories implementing a QMS. The top five CSFs identified were: (1) staff QMS knowledge, (2) manager leadership, (3) staff commitment, (4) mentorship, and (5) hospital administration support. Identifying CSFs is critical to successful planning and implementation of QMS.

Since their discovery in the United States in 1963, outbreaks of infection with equine influenza virus (H3N8) have been associated with serious respiratory disease in horses worldwide. Genomic analysis suggests that equine H3 viruses are of an avian lineage, likely originating in wild birds. Equine-like internal genes have been identified in avian influenza viruses isolated from wild birds in the Southern Cone of South America. However, an equine-like H3 hemagglutinin has not been identified. We isolated 6 distinct H3 viruses from wild birds in Chile that have hemagglutinin, nucleoprotein, nonstructural protein 1, and polymerase acidic genes with high nucleotide homology to the 1963 H3N8 equine influenza virus lineage. Despite the nucleotide similarity, viruses from Chile were antigenically more closely related to avian viruses and transmitted effectively in chickens, suggesting adaptation to the avian host. These studies provide the initial demonstration that equine-like H3 hemagglutinin continues to circulate in a wild bird reservoir.

BACKGROUND: Increased Attalea butyracea palm propagation, notable for its role as key habitat for the primary Chagas disease vector in Panama, has been linked to landscape disturbance in single-palm observations in this region. Close proximity of these palms to human dwellings is proposed to increase risk of Chagas disease transmission from sylvatic transmission cycles to domestic transmission involving human populations. This study examines the relationship between landscape disturbance and mature A. butyracea spatial distribution, density, and proximity to human populations and vector and reservoir species' movement corridors at a regional scale in a 300 km(2) heterogeneous tropical landscape in central Panama. METHODS: We remotely identified the locations of over 50,000 mature A. butyracea palms using high-resolution WorldView2 satellite imagery. A local Getis-Ord Gi* spatial analysis identified significant clusters of aggregated palms. Associations between palm and cluster abundance and a landscape disturbance gradient, derived from official Panama land cover data, were tested using Chi-square tests for Homogeneity and Z-test for proportions. Kruskall-Wallis non-parametric analysis of variance tests were run to assess whether palm cluster area varied by disturbance level, or whether disturbance was associated with proximity of palms and palm clusters to susceptible populations or vector movement corridors. RESULTS: Our findings indicate a regional relationship between landscape disturbance and A. butyracea occurrence. We observe a significant increase in both individual and clustered A. butyracea in secondary forest, but a reduction of palms in agricultural settings. We do not detect evidence of any reduction in abundance of palms in residential settings. The majority of residential and commercial buildings in our study area are within vector flight distance of potential vector habitat in palm crowns. CONCLUSIONS: We observe probable anthropogenic elimination of A. butyracea palms in agricultural, but not residential, settings. Even in heavily deforested regions, significant concentrations of mature palms remain in close proximity to human establishments.

During August 7-16, 2020, a motorcycle rally was held in western South Dakota that attracted approximately 460,000 persons from across the United States to numerous indoor and outdoor events over a 10-day period. During August-September 2020, the Minnesota Department of Health (MDH) investigated a coronavirus disease 2019 (COVID-19) outbreak associated with the rally in Minnesota residents. Fifty-one primary event-associated cases were identified, and 35 secondary or tertiary cases occurred among household, social, and workplace contacts, for a total of 86 cases; four patients were hospitalized, and one died. Approximately one third (34%) of 87 counties in Minnesota had at least one primary, secondary, or tertiary case associated with this rally. Genomic sequencing supported the associations with the motorcycle rally. These findings support current recommendations for mask use, physical distancing, reducing the number of attendees at gatherings, isolation for patients with COVID-19, and quarantine for close contacts to slow the spread of SARS-CoV-2 (1). Furthermore, although these findings did not capture the impact of the motorcycle rally on residents of other states, they demonstrate the rationale for consistent mitigation measures across states.

Ninhydrin-based fluorometric quantification of phenylalanine is one of the most widely used methods for hyperphenylalaninemia (HPA) screening in neonates due to its high sensitivity, high accuracy, and low cost. Here we report an increase of false positive cases in neonatal HPA screening with this method, caused by contamination of blood specimen collection devices during the printing process. Through multiple steps of verification, the contaminants were identified from ink circles printed on the collection devices to indicate the positions and sizes of blood drops. Blood specimens from HPA-negative persons collected on these contaminated collection devices showed positive results in the fluorometric tests, but negative results in tandem mass spectroscopy (MS/MS) experiments. Contaminants on the collection devices could be extracted by 80% ethanol and showed an absorption peak around 245 nm, suggesting that these contaminants may contain benzene derivatives with similar structure to phenylalanine. High-performance liquid chromatography (HPLC) analysis of the ethanol extracts from contaminated collection devices identified two prominent peaks specifically from the devices. Methyl-2-benzoylbenzoate (MBB, CAS#606-28-0) was found as one of the major chemicals from contaminated collection devices. This report aims to remind colleagues in the field of this potential contamination and call for tighter regulation and quality control of specimen collection devices.

Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis and sepsis worldwide and an occasional cause of meningococcal urethritis. When isolates are unavailable for surveillance or outbreak investigations, molecular characterization of pathogens needs to be performed directly from clinical specimens such as cerebrospinal fluid (CSF), blood, or urine. However, genome sequencing of specimens is challenging because of low bacterial and high human DNA abundances. We developed selective whole genome amplification (SWGA), an isothermal multiple displacement amplification-based method, to efficiently enrich, sequence and de novo assemble Nm DNA from clinical specimens with low bacterial loads. SWGA was validated with 12 CSF specimens from invasive meningococcal disease cases and 12 urine specimens from meningococcal urethritis cases. SWGA increased the mean proportion of Nm reads by 2-3 orders of magnitude enabling identification of at least 90% of the 1605 Nm core genome loci for 50% of the specimens. The validated method was used to investigate two meningitis outbreaks recently reported in Togo and Burkina Faso. Twenty-seven specimens with low bacterial load were processed by SWGA before sequencing and 12 of 27 were successfully assembled to obtain the full molecular typing and vaccine antigen profile of the Nm pathogen, therefore enabling thorough characterization of outbreaks. This method is particularly important for enhancing molecular surveillance in regions with low culture rate. SWGA produces enough reads for phylogenetic and allelic analysis with a low cost. More importantly, the procedure can be extended to enrich other important human bacterial pathogens.

BACKGROUND: Geenius HIV 1/2 Supplemental Assay (Geenius; Bio-Rad Laboratories) is the only Food and Drug Administration-approved HIV-1/HIV-2 antibody differentiation test for the second step in the HIV laboratory testing algorithm. We characterized the occurrence of true HIV-1 and HIV-2 infections as well as false results in 6 US clinical laboratories using Geenius. METHODS: We examined routine HIV testing outcome data from the time the laboratories began using the algorithm with Geenius until September 30, 2017. We calculated the positive predictive value for Geenius HIV-1 and HIV-2 reactivity separately. RESULTS: Of 5,046,684 specimens tested, 41,791 had reactive antigen/antibody test results. Most specimens with reactive antigen/antibody results were HIV-1 antibody-positive established infections (n = 32,421), 1,865 of which also had indeterminate HIV-2 bands present. Ninety-three specimens were HIV-2 antibody positive or untypable for HIV-1/HIV-2 antibody. Acute HIV-1 infections were found in 528 specimens; 881 specimens lacked the nucleic acid test to determine the possibility of acute HIV-1 infection. False-positive antigen/antibody test results were present in 7505 specimens. Few specimens (n = 363) had false-positive antigen/antibody results with indeterminate Geenius and negative HIV-1 nucleic acid test results. The positive predictive values of Geenius reactivity were 99.4% for HIV-1 and 4.3% for HIV-2. CONCLUSIONS: Routine testing using the laboratory testing algorithm with Geenius resulted in most specimens resolving as HIV negative or HIV-1 positive. The occurrence of indeterminate HIV-2 bands with a Geenius final assay interpretation of HIV-1 positive was more common than true HIV-2 infections. Reporting indeterminate HIV-2 results in this situation may cause confusion with interpreting HIV infection status.

BACKGROUND: At least 13-20% of all Tuberculosis (TB) cases are recurrent TB. Recurrent TB has critical public health importance because recurrent TB patients have high risk of Multi-Drug Resistant TB (MDR-TB). It is critical to understand variations in the prevalence and treatment outcomes of recurrent TB between different geographical settings. The objective of our study was to estimate the prevalence of recurrent TB among TB cases and compare risk of unfavorable treatment outcomes between rural and urban settings. METHODS: In a retrospective cohort study conducted in southern province of Zambia, we used mixed effects logistic regression to asses associations between explanatory and outcome variables. Primary outcome was all-cause mortality and exposure was setting (rural/urban). Data was abstracted from the facility TB registers. RESULTS: Overall 3566 recurrent TB cases were diagnosed among 25,533 TB patients. The prevalence of recurrent TB was 15.3% (95% CI: 14.8 15.9) in urban and 11.3% (95% CI: 10.7 12.0) in rural areas. Death occurred in 197 (5.5%), 103 (2.9%) were lost to follow-up, and 113 (3.2%) failed treatment. Rural settings had 70% higher risk of death (adjusted OR: 1.7; 95% CI: 1.2 2.7). Risk of lost to follow-up was twice higher in rural than urban (adjusted OR: 2.0 95% CI: 1.3 3.0). Compared to HIV-uninfected, HIV-infected individuals on Antiretroviral Treatment (ART) were 70% more likely to die (adjusted OR: 1.7; 95% CI: 1.2 3.1). CONCLUSION: Recurrent TB prevalence was generally high in both urban and rural settings. The risk of mortality and lost to follow-up was higher among rural patients. We recommend a well-organized Directly Observed Therapy strategy adapted to setting where heightened TB control activities are focused on areas with poor treatment outcomes.

Objective: Our objective was to improve understanding of the differences in cigarette use behavior and exposure for participants smoking their own brand of cigarettes in a clinical setting versus smoking under natural conditions. Methods: Adult daily smokers (N = 163) attended 2 clinic visits where they smoked through a CReSS topography device. Participants collected cigarette butts smoked without a CReSS device and completed a diary of location, mood, and activity for each cigarette smoked. Cigarette butts were used to determine mouth level nicotine (MLN). Least square means (LSMs) were estimated from mixed effects models. Results: The LSM for MLN was higher among participants who smoked cigarettes in the clinical setting. LSM MLN was 1.589 [95% CI: 1.312, 1.924] mg/cig for cigarettes smoked in the clinic and 1.087 [95% CI: 0.902, 1.310] mg/cig for cigarettes smoked outside of the clinic; we found differences between race and sex. Conclusions: Our results show nicotine intake and some smoking behavior are significantly biased upwards when studied in a clinical setting. Therefore, tobacco smoke exposure determinations in a clinical setting may not be completely generalizable to smoke exposure determinations in naturalistic settings.

OBJECTIVES: To describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China. DESIGN: This was a multicentre, retrospective, observational study. SETTING: 13 teaching hospitals in northern, central and southern China from 1 January 2014 to 31 December 2014 PARTICIPANTS: Information on hospitalised patients aged >/=14 years with radiographically confirmed pneumonia with illness onset in the community was collected using standard case report forms. PRIMARY AND SECONDARY OUTCOME MEASURES: Resource use for CAP management. RESULTS: Of 14 793 patients screened, 5828 with radiographically confirmed CAP were included in the final analysis. Low mortality risk patients with a CURB-65 score 0-1 and Pneumonia Severity Index risk class I-II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients, respectively. 21.7% (1111/5130) patients had already achieved clinical stability on admission. A definite or probable pathogen was identified only in 12.7% (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection risk factors received antimicrobial overtreatment regimens. The median duration between clinical stability to discharge was 5.0 days with 30-day mortality of 4.2%. CONCLUSIONS: These data demonstrated the overuse of health resources in CAP management, indicating that there is potential for improvement and substantial savings to healthcare systems in China. TRIAL REGISTRATION NUMBER: NCT02489578; Results.

The Maputo Declaration of 2008 advocated for commitment from global stakeholders and national governments to prioritise support and harmonisation of laboratory systems through development of comprehensive national laboratory strategies and policies in sub-Saharan Africa. As a result, HIV laboratory medicine in Africa has undergone a transformation, and substantial improvements have been made in diagnostic services, networks, and institutions, including the development of a competent workforce, introduction of point-of-care diagnostics, and innovative quality improvement programmes that saw more than 1100 laboratories enrolled and 44 accredited to international standards. These improved HIV laboratories can now be used to combat emerging continental and global health threats in the decades to come. For instance, the unprecedented Ebola virus disease outbreak in west Africa exposed the severe weaknesses in the overall national health systems in affected countries. It is now possible to build robust health-care systems in Africa and to combat emerging continental and global health threats in the future. In this Personal View, we aim to describe the remarkable transformation that has occurred in laboratory medicine to combat HIV/AIDS and improve global health in sub-Saharan Africa since 2008.

Background: Data are limited on the impact of neuraminidase inhibitor (NAI) treatment on avian influenza A(H7N9) virus RNA shedding. Methods: In this multicenter, retrospective study, data were collected from adults hospitalized with A(H7N9) infection during 2013-2017 in China. We compared clinical features and A(H7N9) shedding among patients with different NAI doses and combination therapies and evaluated factors associated with A(H7N9) shedding, using Cox proportional hazards regression. Results: Among 478 patients, the median age was 56 years, 71% were male, and 37% died. The median time from illness onset to NAI treatment initiation was 8 days (interquartile range [IQR], 6-10 days), and the median duration of A(H7N9) RNA detection from onset was 15.5 days (IQR, 12-20 days). A(H7N9) RNA shedding was shorter in survivors than in patients who died (P < .001). Corticosteroid administration (hazard ratio [HR], 0.62 [95% confidence interval {CI}, .50-.77]) and delayed NAI treatment (HR, 0.90 [95% CI, .91-.96]) were independent risk factors for prolonged A(H7N9) shedding. There was no significant difference in A(H7N9) shedding duration between NAI combination treatment and monotherapy (P = .65) or between standard-dose and double-dose oseltamivir treatment (P = .70). Conclusions: Corticosteroid therapy and delayed NAI treatment were associated with prolonged A(H7N9) RNA shedding. NAI combination therapy and double-dose oseltamivir treatment were not associated with a reduced A(H7N9) shedding duration as compared to standard-dose oseltamivir.

Laboratory medicine is essential for disease detection, surveillance, control, and management.1 However, access to quality-assured laboratory diagnosis has been a challenge in low-income and middle-income countries (LMICs) resulting in delayed or inaccurate diagnosis and ineffective treatment with consequences for patient safety.1 In the new Lancet Series2–4 on pathology and laboratory medicine (PALM) in LMICs, Michael Wilson and colleagues2 provide a comprehensive analysis of the challenges and gaps that limit access to PALM services. Some of the challenges include the absence of essential infrastructure, laboratory supplies, basic equipment, skilled personnel, supply chain management, and equipment maintenance; reliance on empirical treatment; inadequate quality management systems; and no government standards for laboratory testing. In their Series paper, Shahin Sayed and colleagues3 provide a roadmap to solutions for improving laboratory medicine, and Susan Horton and colleagues4 call for all stakeholders to ensure the effective provision of PALM services in resource-limited settings.

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950 Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each lab using a different lipidomics workflow. A total of 1527 unique lipids were measured across all laboratories, and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and inter-laboratory quality control and method validation. These analyses were performed using non-standardized laboratory-independent workflows. The consensus locations were also compared to a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

BACKGROUND: HIV transmission is the result of complex dynamics in the risk behaviors, partnership choices, disease stage and position along the HIV care continuum-individual characteristics that themselves can change over time. Capturing these dynamics and simulating transmissions to understand the chief sources of transmission remain important for prevention. METHODS: The Progression and Transmission of HIV/AIDS (PATH 2.0) is an agent-based model of a sample of 10,000 people living with HIV (PLWH), who represent all men who have sex with men (MSM) and heterosexuals living with HIV in the U.S.A. Persons uninfected were modeled as populations, stratified by risk and gender. The model included detailed individual-level data from several large national surveillance databases. The outcomes focused on average annual transmission rates from 2008 through 2011 by disease stage, HIV care continuum, and sexual risk group. RESULTS: The relative risk of transmission of those in the acute phase was nine-times [5th and 95th percentile simulation interval (SI): 7, 12] that of those in the non-acute phase, although, on average, those with acute infections comprised 1% of all PLWH. The relative risk of transmission was 24- to 50-times as high for those in the non-acute phase who had not achieved viral load suppression as compared with those who had. The relative risk of transmission among MSM was 3.2-times [SI: 2.7, 4.0] that of heterosexuals. Men who have sex with men and women generated 46% of sexually acquired transmissions among heterosexuals. CONCLUSIONS: The model results support a continued focus on early diagnosis, treatment and adherence to ART, with an emphasis on prevention efforts for MSM, a subgroup of whom appear to play a role in transmission to heterosexuals.

OBJECTIVE: To evaluate the expected cost-effectiveness and net benefit of the recent implementation of newborn screening (NBS) for severe combined immunodeficiency (SCID) in Washington State. STUDY DESIGN: We constructed a decision analysis model to estimate the costs and benefits of NBS in an annual birth cohort of 86 600 infants based on projections of avoided infant deaths. Point estimates and ranges for input variables, including the birth prevalence of SCID, proportion detected asymptomatically without screening through family history, screening test characteristics, survival rates, and costs of screening, diagnosis, and treatment were derived from published estimates, expert opinion, and the Washington NBS program. We estimated treatment costs stratified by age of identification and SCID type (with or without adenosine deaminase deficiency). Economic benefit was estimated using values of $4.2 and $9.0 million per death averted. We performed sensitivity analyses to evaluate the influence of key variables on the incremental cost-effectiveness ratio (ICER) of net direct cost per life-year saved. RESULTS: Our model predicts an additional 1.19 newborn infants with SCID detected preclinically through screening, in addition to those who would have been detected early through family history, and 0.40 deaths averted annually. Our base-case model suggests an ICER of $35 311 per life-year saved, and a benefit-cost ratio of either 5.31 or 2.71. Sensitivity analyses found ICER values <$100 000 and positive net benefit for plausible assumptions on all variables. CONCLUSIONS: Our model suggests that NBS for SCID in Washington is likely to be cost-effective and to show positive net economic benefit.

BACKGROUND: Two doses of live-attenuated varicella-zoster vaccine are recommended for human immunodeficiency virus 1 (HIV-1)-infected children with CD4% ≥15%. We determined the prevalence and persistence of antibody in immunized children with perinatal HIV (PHIV) and their association with number of vaccinations, combination antiretroviral therapy (cART), and HIV status. METHODS: The Adolescent Master Protocol is an observational study of children with PHIV and perinatally HIV-exposed but uninfected (PHEU) children conducted at 15 US sites. In a cross-sectional analysis, we tested participants' most recent stored sera for varicella antibody using whole-cell and glycoprotein enzyme-linked immunosorbent assay. Seropositivity predictors were identified using multivariable logistic regression models and C statistics. RESULTS: Samples were available for 432 children with PHIV and 221 PHEU children; 82% of children with PHIV and 97% of PHEU children were seropositive (P < .001). Seropositivity after 1 vaccine dose among children with PHIV and PHEU children was 100% at <3 years (both), 73% and 100% at 3-<7 years (P < .05), and 77% and 97% at ≥7 years (P < .01), respectively. Seropositivity among recipients of 2 vaccine doses was >94% at all intervals. Independent predictors of seropositivity among children with PHIV were receipt of 2 vaccine doses, receipt of 1 dose while on ≥3 months of cART, compared with none (adjusted odds ratio [aOR]: 14.0 and 2.8, respectively; P < .001 for overall dose effect), and in those vaccinated ≥3 years previously, duration of cART (aOR: 1.29 per year increase, P = .02). CONCLUSIONS: Humoral immune responses to varicella vaccine are best achieved when children with PHIV receive their first dose ≥3 months after cART initiation and maintained by completion of the 2-dose series and long-term cART use.

BACKGROUND: Telomeres provide a key mechanism for protecting the integrity of chromosomes and their attrition after cell division and during aging are evident in lymphocytes. However, the significance of telomere shortening in age-associated decline of immune function is unknown. METHODS: We selected 22 HLA-A2+ healthy older adults who have relatively short or long telomere lengths to compare their antibody response against the influenza vaccine, and their CD8+ T cell response against an influenza antigen. RESULTS: B cells from individuals with a robust antibody response to the influenza vaccine had significantly longer telomeres than those with a poor antibody response. Monocyte-derived antigen-presenting cells of both short and long telomere groups induced similar expansions of influenza M1-specific CD8+ T cells. Vaccination did not increase M1-specific CD8+ T cells in blood, however, M1-specific CD8+ T cells from the long telomere group exhibited significantly better expansion in vitro compared to those from the short telomere group. Finally, M1-specific CD8+ T cells that underwent more expansions had significantly longer telomeres compared to cells with fewer divisions. CONCLUSIONS: Telomere length is positively associated with a robust lymphocyte response and telomere attrition may contribute to the age-associated decline of adaptive immunity.

BACKGROUND: In 2010, a National Laboratory Strategic Plan was set forth in Ethiopia to strengthen laboratory quality systems and set the stage for laboratory accreditation. As a result, the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme was initiated in 45 Ethiopian laboratories. OBJECTIVES: This article discusses the implementation of the programme, the findings from the evaluation process and key challenges. METHODS: The 45 laboratories were divided into two consecutive cohorts and staff from each laboratory participated in SLMTA training and improvement projects. The average amount of supportive supervision conducted in the laboratories was 68 hours for cohort I and two hours for cohort II. Baseline and exit audits were conducted in 44 of the laboratories and percent compliance was determined using a checklist with scores divided into zero- to five-star rating levels. RESULTS: Improvements, ranging from < 1 to 51 percentage points, were noted in 42 laboratories, whilst decreases were recorded in two. The average scores at the baseline and exit audits were 40% and 58% for cohort I (p < 0.01); and 42% and 53% for cohort II (p < 0.01), respectively. The p-value for difference between cohorts was 0.07. At the exit audit, 61% of the first and 48% of the second cohort laboratories achieved an increase in star rating. Poor awareness, lack of harmonisation with other facility activities and the absence of a quality manual were challenges identified. CONCLUSION: Improvements resulting from SLMTA implementation are encouraging. Continuous advocacy at all levels of the health system is needed to ensure involvement of stakeholders and integration with other improvement initiatives and routine activities.