BACKGROUND: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages. METHODS: Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%. Annual incidence rate ratios (IRRs) were estimated comparing the incidence before any PCV with each year post-PCV10 or post-PCV13 introduction using Bayesian multi-level, mixed-effects Poisson regressions, by site and age group. All site-weighted average IRRs were estimated using linear mixed-effects regression, stratified by product and previous seven-valent PCV (PCV7) effect (none, moderate, or substantial). FINDINGS: Analyses included 32 PCV13 sites (488 758 cases) and 15 PCV10 sites (46 386 cases) in 30 countries, primarily high income (39 sites), using booster dose schedules (41 sites). By 6 years after PCV10 or PCV13 introduction, IPD due to PCV10-type serotypes and PCV10-related serotype 6A declined substantially for both products (age <5 years: 83-99% decline; ≥65 years: 54-96% decline). PCV7-related serotype 19A increases before PCV10 or PCV13 introduction were reversed at PCV13 sites (age <5 years: 61-79% decline relative to before any PCV; age ≥65 years: 7-26% decline) but increased at PCV10 sites (age <5 years: 1·6-2·3-fold; age ≥65 years: 3·6-4·9-fold). Serotype 3 IRRs had no consistent trends for either product or age group. Non-PCV13-type IPD increased similarly for both products (age <5 years: 2·3-3·3-fold; age ≥65 years: 1·7-2·3-fold). Despite different serotype 19A trends, all-serotype IPD declined similarly between products among children younger than 5 years (58-74%); among adults aged 65 years or older, declines were greater at PCV13 (25-29%) than PCV10 (4-14%) sites, but other differences between sites precluded attribution to product. INTERPRETATION: Long-term use of PCV10 or PCV13 reduced IPD substantially in young children and more moderately in older ages. Non-vaccine-type serotypes increased approximately two-fold to three-fold by 6 years after introduction of PCV10 or PCV13. Continuing serotype 19A increases at PCV10 sites and declines at PCV13 sites suggest that PCV13 use would further reduce IPD at PCV10 sites. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

OBJECTIVE: To describe maternal demographics and compare clinical characteristics of infants with congenital cytomegalovirus (cCMV) identified through diagnostic codes and laboratory data in the United States during 2018-2023. METHODS: We used a CDC-licensed subset of HealthVerity data, which contained linked pregnant people-infant claims data from publicly and privately insured individuals during 2018-2023 (2023 Quarter 3 HealthVerity Maternal Outcomes Masterset data). We identified infants with cCMV using diagnostic codes or positive laboratory test results within 45 days of birth. RESULTS: Among 744 (4.6 per 10,000 live births) infants with cCMV during 2018-2023, 599 (81%) were identified by a diagnostic code only. Among 732 linked pregnant people, 91 (12%) had a diagnosis of CMV infection during pregnancy, with a similar distribution by age group and insurance type, but a lower proportion were Black as compared to those without CMV infection during pregnancy (14% vs. 29%, respectively). Overall, 452 (61%) infants had ≥1 cCMV-related clinical sign at birth and 185 (25%) had valganciclovir prescriptions. Eighty-eight (68%) infants identified by a positive laboratory test only had no cCMV-related signs and none had valganciclovir prescriptions. CONCLUSIONS: Using healthcare claims data, we found a minimal overlap of cCMV identified by diagnostic codes and laboratory test results. A minority of linked pregnant people with infants with cCMV had a CMV diagnosis during pregnancy. cCMV surveillance will help better understand the validity of ICD codes to identify infants with cCMV, describe the spectrum of disease, and monitor use of antivirals.

INTRODUCTION: Testing for immunity to measles, mumps, and rubella should include only IgG; IgM testing is appropriate only if acute illness is suspected. The appropriateness of measles, mumps, and rubella IgM testing was evaluated in a national administrative dataset. METHODS: Laboratory testing for measles, mumps, and rubella during 2019-2022 was analyzed in 2024 using HealthVerity administrative claims and laboratory data. IgG, IgM, and reverse-transcriptase polymerase chain reaction (RT-PCR) testing are described by year, demographics, and region. IgM testing was examined for appropriateness, defined as an IgM test combined with diagnostic codes indicative of acute illness. RESULTS: During 2019-2022, IgM testing represented a small proportion of serologic testing (measles: 3.3%, mumps: 2.4%, rubella: 2.1%) but appeared to be appropriately performed in only 15.4% of cases for measles, 32.8% of cases for mumps, and 10.2% of cases for rubella. IgM testing was more commonly performed for female patients, with the largest discrepancy seen for rubella (90.5% female vs 9.5% male). IgM for measles and mumps was more often performed appropriately for persons aged 0-19 years (37.6% and 60.1%) compared with persons aged 20-49 years (11.8% and 22.0%) and 50+ years (16.5% and 33.8%). CONCLUSIONS: The majority of IgM testing for measles, mumps, and rubella during this period appeared inappropriate. Clinicians and health systems could ensure that IgG testing alone is performed when evaluating for immunity through modifications to electronic medical records and commercial laboratories could ensure that providers are able to test for IgG alone when evaluating immunity.

We assessed tuberculosis (TB) diagnostic delays among patients with TB and COVID-19 in California, USA. Among 58 persons, 43% experienced TB diagnostic delays, and a high proportion (83%) required hospitalization for TB. Even when viral respiratory pathogens circulate widely, timely TB diagnostic workup for at-risk persons remains critical for reducing TB-related illness.

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]). | Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium’s analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps. | eng

INTRODUCTION: Coronavirus disease 2019 (COVID-19) may be associated with gestational diabetes mellitus (GDM); however, evidence is limited by sample sizes and lack of control groups. METHODS: To assess the GDM risk after COVID-19 in pregnancy, we constructed a retrospective cohort of pregnancies ending March 2020-October 2022 using medical claims. People with COVID-19 diagnosis claims from conception to 21 gestational weeks (n = 57,675) were matched 1:2 to those without COVID-19 during pregnancy (n =115,350) by age-range, pregnancy start month, and encounter year-month. GDM (claim ≥23 gestational weeks) relative risk and risk difference overall, by race and ethnicity, and variant period were estimated using log-binomial models. RESULTS: GDM risk was higher among those with COVID-19 during pregnancy compared to those without (adjusted risk ratio, aRR = 1.12, 95% CI: 1.08-1.15). GDM risk was significantly associated with COVID-19 in non-Hispanic (NH) White (aRR = 1.08, 95% CI: 1.04-1.14), NH Black (aRR=1.15, 95% CI: 1.07-1.24), and Hispanic (aRR = 1.17, 95% CI: 1.10-1.24) groups. GDM risk was significantly higher during pre-Delta (aRR = 1.17, 95% CI: 1.11-1.24) as compared to Omicron (aRR = 1.07, 95% CI: 1.02-1.13) periods, but neither differed from the Delta period (aRR = 1.10, 95% CI: 1.04-1.17). The adjusted risk difference was 0-2% for all models. CONCLUSIONS: COVID-19 during pregnancy was modestly associated with GDM in claims-based data, especially during earlier SARS-CoV-2 variant periods. As these associations are based on COVID-19 in claims data, studies employing systematic testing are warranted.

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, with >52,000 cases in California as of May 4, 2020. Here we investigate the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning 9 counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least 7 different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington State, with lack of a predominant lineage and limited transmission between communities. Lineages associated with outbreak clusters in 2 counties were defined by a single base substitution in the viral genome. These findings support contact tracing, social distancing, and travel restrictions to contain SARS-CoV-2 spread in California and other states.

Reports are emerging at a rapid pace that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the nervous system in various ways. Preliminary data from Wuhan, China, suggest that neurological manifestations are present in more than 30% of patients presenting with coronavirus disease 2019 (COVID-19).1 Neurological features range from quite diffuse neurological signs and symptoms like headache, dizziness, reduced level of consciousness, confusion, diffuse corticospinal tract signs, and paraesthesia, to more specific manifestations, such as seizures, stroke, encephalitis, or meningoencephalitis, and myopathy.1, 2 To date, SARS-CoV-2 has not been detected in the neural tissue directly, although it has been isolated from the CSF of some patients.3 The hypothesis of neurotropism with subsequent neuronal injury, either directly or indirectly (through immune mechanisms), is supported by previous findings from other infections with severe acute respiratory syndrome CoV and Middle East respiratory syndrome CoV.3

Health navigation is increasingly being used to support people living with HIV, but timely monitoring of navigation is challenging due to the burden of reporting a high volume of diverse activities. We designed a mobile application (app) for navigators to report their interactions with men who have sex with men living with HIV (n = 374), including: (1) mode of support; (2) content; and (3) duration. We assessed sociodemographic and behavioral characteristics of the study sample and calculated monitoring system indicators. We also conducted qualitative interviews with navigators (n = 7) and used thematic analysis to assess app acceptability and usability. From January 2017 to June 2018, 95.3% of participants interacted with their navigator at least one time and 4281 reports were recorded by nine navigators. The median number of interactions per participant was 10 (range: 1-46). The majority of interactions (71.6%) occurred remotely. Most frequently covered topics included: appointment reminders (36.9%), employment (19.9%), and family (15.5%). Navigators indicated that the system was easy to use, but some did not use it in real time as intended. Timely access to navigator data enabled feedback and continuous training. These data can also facilitate analysis of intensity and content of interactions to improve tailoring and sustainability.

Dengue virus (DENV) affects more than 100 countries worldwide. Dengue virus infection has been increasing in the southern Peruvian Amazon city of Puerto Maldonado since 2000. We designed this study to describe the prevalence of past DENV infection and to evaluate risk factors. In 2012, we conducted a cross-sectional serosurvey and administered a knowledge, attitudes, and practices (KAP) questionnaire to members of randomly selected households. Sera were screened for antibodies to DENV by ELISA and confirmed by plaque reduction neutralization test. We created indices for KAP (KAPi). We used SaTScan to detect clustering and created a multivariate model introducing the distance of households to potential vector and infection sources. A total of 505 participants from 307 households provided a blood sample and completed a questionnaire. Fifty-four percent of participants (95% CI: 49.6; 58.5) had neutralizing antibodies to DENV. Higher values of KAPi were positively associated with having DENV antibodies in the multivariate analysis (odds ratio [ORII]: 1.6, 95% CI: 0.6, 2.4; ORIII: 2.7, 95% CI: 1.3, 5.5; and ORIV: 2.4, 95% CI: 1.2, 5.0). Older groups had lower chances of having been exposed to DENV than younger people (OR20-30: 0.5, 95% CI: 0.2, 0.8; OR31-45: 0.5, 95% CI: 0.3, 0.9; and OR>45: 0.6, 95% CI: 0.3, 1.3). Multivariate data analysis from the 270 households with location information showed male gender to have lower risk of past DENV infection (OR: 0.6, 95% CI: 0.4, 0.9). We conclude that risk of DENV infection in Puerto Maldonado is related to gender, age of the population, and location.

Scientific evidence showing the benefits of early initiation of antiretroviral therapy (ART) prompted World Health organization (WHO) to recommend that all persons diagnosed HIV-positive should commence ART irrespective of CD4 count and disease progression. Based on this recommendation, countries should adopt and implement the HIV "Treat All" policy to achieve the UNAIDS 90-90-90 targets and ultimately reach epidemic control. Attaining this goal along the HIV treatment cascade depends on the laboratory to monitor progress and measure impact. The laboratory plays an important role in HIV diagnosis to attain the first 90 and in viral load (VL) and HIV drug resistance testing to reinforce adherence, improve viral suppression, and measure the third 90. Countries in the Caribbean region have endorsed the WHO HIV "Treat all" recommendation; however, they are faced with diminishing financial resources to support laboratory testing, seen as a rate-limiting factor to achieving this goal. To improve laboratory coverage with fewer resources in the Caribbean there is the need to optimise laboratory operations to ensure the implementation of high quality, less expensive, evidence-based approaches that will result in more efficient and effective service delivery. Suggested practical and innovative approaches to achieve this include: 1) targeted testing within HIV hotspots; 2) strengthening sample referral systems for VL; 3) better laboratory data collection systems; and 4) use of treatment cascade data for programmatic decision making. Furthermore, strengthening quality improvement and procurement systems will minimize diagnostic errors and guarantee a continuum of uninterrupted testing which is critical for routine monitoring of patients to meet the stated goal.

Despite the lack of evidence for symptomatic human infection with Maguari virus (MAGV), its close relation to Cache Valley virus (CVV), which does infect humans, remains a concern. We sequenced the complete genome of a MAGV-like isolate (OBS6657) obtained from a febrile patient in Pucallpa, Ucayali, Peru, in 1998. To facilitate its classification, we generated additional full-length sequences for the MAGV prototype strain, 3 additional MAGV-like isolates, and the closely related CVV (7 strains), Tlacotalpan (1 strain), Playas (3 strains), and Fort Sherman (1 strain) viruses. The OBS6657 isolate is similar to the MAGV prototype, whereas 2 of the other MAGV-like isolates are located on a distinct branch and most likely warrant classification as a separate virus species and 1 is, in fact, a misclassified CVV strain. Our findings provide clear evidence that MAGV can cause human disease.

Background: Implementing quality management systems and accrediting laboratories in the Caribbean has been a challenge. Objectives: We report the development of a stepwise process for quality systems improvement in the Caribbean Region. Methods: The Caribbean Laboratory Stakeholders met under a joint Pan American Health Organization/US Centers for Disease Control and Prevention initiative and developed a userfriendly framework called 'Laboratory Quality Management System - Stepwise Improvement Process (LQMS-SIP) Towards Accreditation' to support countries in strengthening laboratory services through a stepwise approach toward fulfilling the ISO 15189: 2012 requirements. Results: This approach consists of a three-tiered framework. Tier 1 represents the minimum requirements corresponding to the mandatory criteria for obtaining a licence from the Ministry of Health of the participating country. The next two tiers are quality improvement milestones that are achieved through the implementation of specific quality management system requirements. Laboratories that meet the requirements of the three tiers will be encouraged to apply for accreditation. The Caribbean Regional Organisation for Standards and Quality hosts the LQMS-SIP Secretariat and will work with countries, including the Ministry of Health and stakeholders, including laboratory staff, to coordinate and implement LQMS-SIP activities. The Caribbean Public Health Agency will coordinate and advocate for the LQMS-SIP implementation. Conclusion: This article presents the Caribbean LQMS-SIP framework and describes how it will be implemented among various countries in the region to achieve quality improvement.

The transmission dynamics of many arboviruses in the Amazon Basin region have not been fully elucidated, including the vectors and natural reservoir hosts. Identification of blood meal sources in field-caught mosquitoes could yield information for identifying potential arbovirus vertebrate hosts. We identified blood meal sources in 131 mosquitoes collected from areas endemic for arboviruses in the Peruvian Department of Loreto by sequencing polymerase chain reaction amplicons of the cytochrome b gene. Psorophora (Janthinosoma) albigenu, Psorophora (Grabhamia) cingulata, Mansonia humeralis, Anopheles oswaldoi s.l., and Anopheles benarrochi s.l. had mainly anthropophilic feeding preferences; Aedes (Ochlerotatus) serratus, and Aedes (Ochlerotatus) fulvus had feeding preferences for peridomestic animals; and Culex (Melanoconion) spp. fed on a variety of vertebrates, mainly rodents (spiny rats), birds, and amphibians. On the basis of these feeding preferences, many mosquitoes could be considered as potential enzootic and bridge arbovirus vectors in the Amazon Basin of Peru.

In 2008 HIV rapid testing (HIV RT) was only minimally used in the Caribbean region. Collaboration with countries and international partners since then has resulted in greater availability and use of HIV RT services. Surveys were conducted in 2012 and 2014 among 11 selected Caribbean countries to inform stakeholders of progress made since 2008 and to identify strategies to further improve access and uptake of high-quality HIV RT in community- and facility-based settings in support of the UNAIDS 90-90-90 targets. Key accomplishments during this period include: 1) presence of in-country national HIV RT algorithms; 2) use of the dried tube specimen (DTS) as an external quality assessment (EQA) program; 3) use of standardized logbooks for data collection and monitoring; and, 4) use of oral fluid for HIV RT, particularly for key population surveys. Although progress has been made since 2008 to increase access and improve the quality of HIV RT among countries in the Caribbean some work remains to be done. This includes the development of new policies and implementation of existing ones, task shifting, quality and access to testing, testing strategies, and integration of HIV RT into HIV Testing Services (HTS).

BACKGROUND: In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was licensed and recommended in the USA for prevention of invasive pneumococcal disease in children. Licensure was based on immunogenicity data comparing PCV13 with the earlier seven-valent formulation. Because clinical endpoints were not assessed for the new antigens, we did a postlicensure matched case-control study to assess vaccine effectiveness. METHODS: Cases in children aged 2-59 months were identified through active surveillance in 13 sites. Controls were identified via birth registries and matched to cases by age and postal (zip) code. The primary objective was the vaccine effectiveness of at least one dose against the 13 serotypes included in PCV13. Secondary objectives included vaccine effectiveness against all-cause invasive pneumococcal disease, against antibiotic non-susceptible invasive pneumococcal disease, and among children with and without underlying conditions. Vaccine effectiveness was calculated as (1 - matched odds ratio) x 100%. FINDINGS: We enrolled 722 children with invasive pneumococcal disease and 2991 controls; PCV13 serotype cases (217 [30%]) included most commonly serotypes 19A (128 [18%]), 7F (32 [4%]), and 3 (43 [6%]). Vaccine effectiveness against PCV13 serotypes was 86.0% (95% CI 75.5 to 92.3), driven by serotypes 19A and 7F, for which vaccine effectiveness was 85.6% (95% CI 70.6 to 93.5) and 96.5% (82.7 to 100), respectively. We also identified statistically significant effectiveness against serotype 3 (79.5%, 95% CI 30.3 to 94.8) and against antibiotic non-susceptible invasive pneumococcal disease (65.6%, 44.9 to 78.7). Vaccine effectiveness against all-cause invasive pneumococcal disease was 60.2% (95% CI 46.8 to 70.3). Vaccine effectiveness was similar among children with (81.4%, 95% CI 45.4 to 93.6) and without (85.8%, 74.9 to 91.9) underlying conditions. INTERPRETATION: PCV13 appears highly effective against invasive pneumococcal disease among children in the USA in the context of routine and catch-up schedules, although some new vaccine antigens could not be assessed. PCV13 immunisation provides a robust strategy for combating pneumococcal antimicrobial resistance. FUNDING: Centers for Disease Control and Prevention.

BACKGROUND: Monitoring influenza virus susceptibility to neuraminidase (NA) inhibitors (NAIs) is vital for detecting drug-resistant variants, and is primarily assessed using NA inhibition (NI) assays, supplemented by NA sequence analysis. However, differences in NI testing methodologies between surveillance laboratories results in variability of 50% inhibitory concentration (IC50) values, which impacts data sharing, reporting and interpretation. In 2011, the Centers for Disease Control and Prevention (CDC), in collaboration with the Association for Public Health Laboratories (APHL) spearheaded efforts to standardize fluorescence-based NI assay testing in the United States (U.S.), with the goal of achieving consistency of IC50 data. METHODS: For the standardization process, three participating state public health laboratories (PHLs), designated as National Surveillance Reference Centers for Influenza (NSRC-Is), assessed the NAI susceptibility of the 2011-12 CDC reference virus panel using stepwise procedures with support from the CDC reference laboratory. Next, the NSRC-Is assessed the NAI susceptibility of season 2011-12 U.S. influenza surveillance isolates (n=940), with a large subset (n=742) tested in parallel by CDC. Subsequently, U.S. influenza surveillance isolates (n=9629) circulating during the next three influenza seasons (2012-15), were independently tested by the three NSRC-Is (n=7331) and CDC (n=2298). RESULTS: The NI assay IC50s generated by respective NSRC-Is using viruses and drugs prepared by CDC were similar to those obtained with viruses and drugs prepared in-house, and were uniform between laboratories. IC50s for U.S. surveillance isolates tested during four consecutive influenza seasons (2011-15) were consistent from season to season, within and between laboratories. CONCLUSION: These results show that the NI assay is robust enough to be standardized, marking the first time IC50 data have been normalized across multiple laboratories, and used for U.S. national NAI susceptibility surveillance.

BACKGROUND: Past efforts to improve laboratory quality systems and to achieve accreditation for better patient care in the Caribbean Region have been slow. OBJECTIVE: To describe the impact of the Strengthening of Laboratory Management Toward Accreditation (SLMTA) training programme and mentorship amongst five clinical laboratories in the Caribbean after 18 months. METHOD: Five national reference laboratories from four countries participated in the SLMTA programme that incorporated classroom teaching and implementation of improvement projects. Mentors were assigned to the laboratories to guide trainees on their improvement projects and to assist in the development of Quality Management Systems (QMS). Audits were conducted at baseline, six months, exit (at 12 months) and post-SLMTA (at 18 months) using the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) checklist to measure changes in implementation of the QMS during the period. At the end of each audit, a comprehensive implementation plan was developed in order to address gaps. RESULTS: Baseline audit scores ranged from 19% to 52%, corresponding to 0 stars on the SLIPTA five-star scale. After 18 months, one laboratory reached four stars, two reached three stars and two reached two stars. There was a corresponding decrease in nonconformities and development of over 100 management and technical standard operating procedures in each of the five laboratories. CONCLUSION: The tremendous improvement in these five Caribbean laboratories shows that SLMTA coupled with mentorship is an effective, user-friendly, flexible and customisable approach to the implementation of laboratory QMS. It is recommended that other laboratories in the region consider using the SLMTA training programme as they engage in quality systems improvement and preparation for accreditation.

Environmental odor concerns are commonly reported to environmental health units at the local and state levels. Many U.S. Environmental Protection Agency program sites (Superfund and Resource Conservation and Recovery Act) and approximately 25% of Agency for Toxic Substances and Disease Registry (ATSDR) petition requests involve an odor concern component (e.g., industries, landfills, and confined animal feeding operations [CAFOs]). Increasing numbers of scientific studies are finding associations between environmental odors and health effects. Despite this need for information on environmental odors, no comprehensive electronic source or Web site existed that covered this topic and provided resources for the many parties that face environmental odor issues. Assessing the possible health impacts of odors is also complex. Even if the chemical or chemical mixture is identified, little to no regulations exist at the state and local levels. The lack of an effective odor response framework makes odor problems difficult to resolve. | In an effort to improve this situation, ATSDR collaborated with the National Center for Environmental Health at the Centers for Disease Control and Prevention to develop a comprehensive Web site that provides communities, health care providers, policy makers, health officials, municipalities, industries, and other stakeholders with actionable steps to deal with environmental odors in their communities.

Airborne silica dust (quartz) is common in coal mines and represents a respiratory hazard that can lead to silicosis, a potentially fatal lung disease. With an eye toward developing a portable monitoring device for rapid analysis of silica dust, laser-induced breakdown spectroscopy (LIBS) was used to quantify quartz in coal dust samples collected on filter media. Pure silica (Min-U-Sil(TM) 5), Georgia kaolin, and Pittsburgh-4 and Illinois-6 coal dusts were deposited separately and at multiple mass loadings onto 37-mm polyvinylchloride (PVC) filters. LIBS-generated silicon emission was monitored at 288.16 nm, and non-silica contributions to that signal from kaolinite were removed by simultaneously detecting aluminum. Measurements of the four samples were used to calculate limits of detection (LOD) for silicon and aluminum of approximately 0.08 mug/cm(2) and 0.05 mug/cm(2), respectively (corresponding to 0.16 mug/cm(2) and 0.20 mug/cm(2) for silica and kaolinite, respectively). Relative errors of prediction are around 10%. Results demonstrate that LIBS can dependably quantify silica on filter samples of coal dust and confirm that accurate quantification can be achieved for very lightly loaded samples, which supports the potential application of LIBS for rapid, in-field monitoring.

BACKGROUND: Neuraminidase inhibitor (NAI) antiviral drugs can shorten the duration of uncomplicated influenza when administered early (<48 hours after illness onset) to otherwise healthy outpatients, but the optimal timing of effective therapy for critically ill patients is not well established. METHODS: We analyzed California surveillance data to characterize the outcomes of patients in intensive care units (ICUs) treated with NAIs for influenza A(H1N1)pdm09 (pH1N1). Demographic and clinical data were abstracted from medical records, using standardized case report forms. RESULTS: From 3 April 2009 through 10 August 2010, 1950 pH1N1 cases hospitalized in ICUs were reported. Of 1859 (95%) with information available, 1676 (90%) received NAI treatment, and 183 (10%) did not. The median age was 37 years (range, 1 week-93 years), 1473 (79%) had ≥1 comorbidity, and 492 (26%) died. The median time from symptom onset to starting NAI treatment was 4 days (range, 0-52 days). NAI treatment was associated with survival: 107 of 183 untreated case patients (58%) survived, compared with 1260 of 1676 treated case patients (75%; P ≤ .0001). There was a trend toward improved survival for those treated earliest (P < .0001). Treatment initiated within 5 days after symptom onset was associated with improved survival compared to those never treated (P < .05). CONCLUSIONS: NAI treatment of critically ill pH1N1 patients improves survival. While earlier treatment conveyed the most benefit, patients who started treatment up to 5 days after symptom onset also were more likely to survive. Further research is needed about whether starting NAI treatment >5 days after symptom onset may also convey benefit.

After a human rabies outbreak in southeastern Peru, we collected bats to estimate the prevalence of rabies in various species. Among 165 bats from 6 genera and 10 species, 10.3% were antibody positive; antibody prevalence was similar in vampire and nonvampire bats. Thus, nonvampire bats may also be a source for human rabies in Peru.

Since its identification in April 2009, an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity suggests that the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predictive of adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting that previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).