INTRODUCTION: An estimated 800 000 children (<15 years) globally living with HIV remain undiagnosed. To reach these children with timely HIV testing services during infancy, we implemented a community-based differentiated care model using mobile point-of-care (POC) technology for early infant diagnosis (EID) of HIV, and assessed its effects on EID positivity, antiretroviral therapy (ART) initiation and 3-month retention in care. METHODS: Between 1 June 2019 and 31 May 2020 at six health facilities in Lusaka, Zambia, we enrolled mother-infant pairs (MIPs) at high risk for vertical transmission of HIV based on missing or late infant EID testing or other maternal risk factors. We offered these MIPs community POC EID testing (post-intervention), and compared their outcomes to historical high-risk controls at the same sites (1 June 2017-31 May 2018; pre-intervention). We used propensity score matched weighting and mixed effects regression modelling to estimate outcome differences pre-intervention and post-intervention, and to identify MIP characteristics predictive of vertical transmission of HIV. RESULTS: 2577 MIPs were included in the analysis: 1763 and 814 high-risk MIPs from the pre-intervention and post-intervention periods, respectively. Infant HIV positivity was significantly higher in the post-intervention (2.2%) vs pre-intervention (1.1%) period (p=0.038), however this difference was attenuated (0.83%, 95% CI: -0.50%, 2.15%) after adjusting for differences in maternal age, maternal antenatal care visits, infant birth month and facility. During the post-intervention period, MIPs where the mother disengaged from care were 12.97 (95% CI: 2.41, 69.98) times as likely to have an infant diagnosed with HIV vs those in which the infant received late EID testing without maternal care disengagement. Among 18 infants diagnosed with HIV by the intervention, 16 (88.9%) initiated same-day ART and all continued ART at 3-month follow-up. CONCLUSION: Community-based differentiated care employing POC EID technology increased testing positivity in unadjusted analyses, and resulted in high ART initiation and early care retention, suggesting it may be a promising approach for reaching infants and young children living with HIV being missed by current facility-based approaches. TRIAL REGISTRATION NUMBER: This trial is registered under the following Clinicaltrials.gov Identifier: NCT03133728.

IMPORTANCE: During the 2023-2024 respiratory syncytial virus (RSV) season in the United States, 2 new RSV prevention products were recommended to protect infants in their first RSV season: nirsevimab and Pfizer's maternal RSV vaccine. Postlicensure studies are needed to assess prevention product impact and effectiveness. OBJECTIVE: To compare the epidemiology and disease burden of medically attended RSV-associated acute respiratory illness (ARI) among children younger than 5 years during the 2023-2024 RSV season with 3 prepandemic RSV seasons (2017-2020), estimate nirsevimab effectiveness against medically attended RSV-associated ARI, and compare nirsevimab binding site mutations among circulating RSV in infants with and without nirsevimab receipt. DESIGN, SETTING, AND PARTICIPANTS: This study included a prospective population-based surveillance for medically attended ARI with systematic molecular testing for RSV and whole-genome sequencing of RSV positive samples, as well as a test-negative case-control design to estimate nirsevimab effectiveness. The study was conducted in 7 academic pediatric medical centers in the United States with data from RSV seasons (September 1 through April 30) in 2017 through 2024. Participants were children younger than 5 years with medically attended ARI. EXPOSURE: For the nirsevimab effectiveness analyses, nirsevimab receipt among infants younger than 8 months as of or born after October 1, 2023. MAIN OUTCOME AND MEASURE: Medically attended RSV-associated ARI. RESULTS: Overall, 28 689 children younger than 5 years with medically attended ARI were enrolled, including 9536 during September 1, 2023, through April 30, 2024, and 19 153 during the same calendar period of 2017-2020. Of these children, 16 196 (57%) were male, and 12 444 (43.4) were female; the median (IQR) age was 15 (6-29) months. During 2023-2024, the proportion of children with RSV was 23% (2199/9490) among all medically attended episodes, similar to 2017-2020. RSV-associated hospitalization rates in 2023-2024 were similar to average 2017-2020 seasonal rates with 5.0 (95% CI, 4.6-5.3) per 1000 among children younger than 5 years; the highest rates were among children aged 0 to 2 months (26.6; 95% CI, 23.0-30.2). Low maternal RSV vaccine uptake precluded assessment of effectiveness. Overall, 10 of 765 case patients (1%) who were RSV positive and 126 of 851 control patients (15%) who were RSV negative received nirsevimab. Nirsevimab effectiveness was 89% (95% CI, 79%-94%) against medically attended RSV-associated ARI and 93% (95% CI, 82%-97%) against RSV-associated hospitalization. Among 229 sequenced specimens, there were no differences in nirsevimab binding site mutations by infant nirsevimab receipt status. CONCLUSIONS AND RELEVANCE: This analysis documented the continued high burden of medically attended RSV-associated ARI among young children in the US. There is a potential for substantial public health impact with increased and equitable prevention product coverage in future seasons.

A better understanding of risk factors and the predictive capability of water management program (WMP) data in detecting Legionella are needed to inform the efforts aimed at reducing Legionella growth and preventing outbreaks of Legionnaires' disease. Using WMPs and Legionella testing data from a national lodging organization in the United States, we aimed to (1) identify factors associated with Legionella detection and (2) assess the ability of WMP disinfectant and temperature metrics to predict Legionella detection. We conducted a logistic regression analysis to identify WMP metrics associated with Legionella serogroup 1 (SG1) detection. We also estimated the predictive values for each of the WMP metrics and SG1 detection. Of 5435 testing observations from 2018 to 2020, 411 (7.6%) had SG1 detection, and 1606 (29.5%) had either SG1 or non-SG1 detection. We found failures in commonly collected WMP metrics, particularly at the primary test point for total disinfectant levels in hot water, to be associated with SG1 detection. These findings highlight that establishing and regularly monitoring water quality parameters for WMPs may be important for preventing Legionella growth and subsequent disease. However, while unsuitable water quality parameter results are associated with Legionella detection, this study found that they had poor predictive value, due in part to the low prevalence of SG1 detection in this dataset. These findings suggest that Legionella testing provides critical information to validate if a WMP is working, which cannot be obtained through water quality parameter measurements alone.

Background Identification of risk factors for COVID-19-associated hospitalization is needed to guide prevention and clinical care.Objective To examine if age, sex, race/ethnicity, and underlying medical conditions is independently associated with COVID-19-associated hospitalizations.Design Cross-sectional.Setting 70 counties within 12 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET) and a population-based sample of non-hospitalized adults residing in the COVID-NET catchment area from the Behavioral Risk Factor Surveillance System.Participants U.S. community-dwelling adults (≥18 years) with laboratory-confirmed COVID-19-associated hospitalizations, March 1- June 23, 2020.Measurements Adjusted rate ratios (aRR) of hospitalization by age, sex, race/ethnicity and underlying medical conditions (hypertension, coronary artery disease, history of stroke, diabetes, obesity [BMI ≥30 kg/m2], severe obesity [BMI≥40 kg/m2], chronic kidney disease, asthma, and chronic obstructive pulmonary disease).Results Our sample included 5,416 adults with COVID-19-associated hospitalizations. Adults with (versus without) severe obesity (aRR:4.4; 95%CI: 3.4, 5.7), chronic kidney disease (aRR:4.0; 95%CI: 3.0, 5.2), diabetes (aRR:3.2; 95%CI: 2.5, 4.1), obesity (aRR:2.9; 95%CI: 2.3, 3.5), hypertension (aRR:2.8; 95%CI: 2.3, 3.4), and asthma (aRR:1.4; 95%CI: 1.1, 1.7) had higher rates of hospitalization, after adjusting for age, sex, and race/ethnicity. In models adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults ≥65 years, 45-64 years (versus 18-44 years), males (versus females), and non-Hispanic black and other race/ethnicities (versus non-Hispanic whites).Limitations Interim analysis limited to hospitalizations with underlying medical condition data.Conclusion Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.Competing Interest StatementDr. Anderson reports personal fees from AbbVie, personal fees from Pfizer, grants from Pfizer, grants from Merck, grants from Micron, grants from Paxvax, grants from Sanofi Pasteur, grants from Novavax, grants from MedImmune, grants from Regeneron, grants from GSK, outside the submitted work. Mr. Henderson, Ms. Kim, Ms. George, and Ms. Hill report grants from Council of State and Territorial Epidemiologists (CSTE), during the conduct of the study. Dr. Lynfield reports grants from CDC- Emerging Infections Program, during the conduct of the study; and Royalties from a book on infectious disease surveillance and compensation for AAP Red Book (Report from Committee on Infectious Disease) donated to Minnesota Dept of Health. Dr. Schaffner reports grants from CDC, during the conduct of the study; personal fees from VBI Vaccines, outside the submitted work. Dr. Talbot reports other from Seqirus, outside the submitted work.Funding StatementThis work was supported by the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement (grant CK17-1701) and through a Council of State and Territorial Epidemiologists cooperative agreement (grant NU38OT000297-02-00).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This analysis was exempt from CDC's Institutional Review Board, as it was considered part of public health surveillance and emergency response. Participating sites obtained approval for the COVID-NET surveillance protocol from their respective state and local IRBs, as required.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved regi try, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData is not publically available at this time.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2/BA.2.12.1 and BA.4/BA.5 subvariants have mutations associated with increased capacity to evade immunity when compared with prior variants. We evaluated mRNA monovalent booster dose effectiveness among persons ≥5 years old during BA.2/BA.2.12.1 and BA.4/BA.5 predominance. METHODS: A test-negative, case-control analysis included data from 12 148 pharmacy SARS-CoV-2 testing sites nationwide for persons aged ≥5 years with ≥1 coronavirus disease-2019 (COVID-19)-like symptoms and a SARS-CoV-2 nucleic acid amplification test from April 2 to August 31, 2022. Relative vaccine effectiveness (rVE) was estimated comparing 3 doses of COVID-19 mRNA monovalent vaccine to 2 doses; for tests among persons ≥50 years, rVE estimates also compared 4 doses to 3 doses (≥4 months since third dose). RESULTS: A total of 760 986 test-positive cases and 817 876 test-negative controls were included. Among individuals ≥12 years, rVE of 3 versus 2 doses ranged by age group from 45% to 74% at 1-month post vaccination and waned to 0% by 5-7 months post vaccination during the BA.4/BA.5 period.Adults aged ≥50 years (fourth dose eligible) who received 4 doses were less likely to have symptomatic SARS-CoV-2 infection compared with those with 3 doses; this rVE remained >0% through at least 3 months since last dose. For those aged ≥65 years, rVE of 4 versus 3 doses 1-month post vaccination was higher during BA.2/BA.2.12.1 (rVE = 49%; 95% confidence interval [CI], 43%-53%) than BA.4/BA.5 (rVE = 40%; 95% CI, 36%-44%). In 50- to 64-year-olds, rVE estimates were similar. CONCLUSIONS: Monovalent mRNA booster doses provided additional protection against symptomatic SARS-CoV-2 infection during BA.2/BA.2.12.1 and BA.4/BA.5 subvariant circulation, but protection waned over time.

The SARS-CoV-2 Omicron sublineage XBB was first detected in the United States in August 2022.* XBB together with a sublineage, XBB.1.5, accounted for >50% of sequenced lineages in the Northeast by December 31, 2022, and 52% of sequenced lineages nationwide as of January 21, 2023. COVID-19 vaccine effectiveness (VE) can vary by SARS-CoV-2 variant; reduced VE has been observed against some variants, although this is dependent on the health outcome of interest. The goal of the U.S. COVID-19 vaccination program is to prevent severe disease, including hospitalization and death (1); however, VE against symptomatic infection can provide useful insight into vaccine protection against emerging variants in advance of VE estimates against more severe disease. Data from the Increasing Community Access to Testing (ICATT) national pharmacy program for SARS-CoV-2 testing were analyzed to estimate VE of updated (bivalent) mRNA COVID-19 vaccines against symptomatic infection caused by BA.5-related and XBB/XBB.1.5-related sublineages among immunocompetent adults during December 1, 2022–January 13, 2023. Reduction or failure of spike gene (S-gene) amplification (SGTF) in real-time reverse transcription–polymerase chain reaction (RT-PCR) was used as a proxy indicator of infection with likely BA.5-related sublineages and S-gene target presence (SGTP) of infection with likely XBB/XBB.1.5-related sublineages (2). Among 29,175 nucleic acid amplification tests (NAATs) with SGTF or SGTP results available from adults who had previously received 2–4 monovalent COVID-19 vaccine doses, the relative VE of a bivalent booster dose given 2–3 months earlier compared with no bivalent booster in persons aged 18–49 years was 52% against symptomatic BA.5 infection and 48% against symptomatic XBB/XBB.1.5 infection. As new SARS-CoV-2 variants emerge, continued vaccine effectiveness monitoring is important. Bivalent vaccines appear to provide additional protection against symptomatic BA.5-related sublineage and XBB/XBB.1.5-related sublineage infections in persons who had previously received 2, 3, or 4 monovalent vaccine doses. All persons should stay up to date with recommended COVID-19 vaccines, including receiving a bivalent booster dose when they are eligible.

On June 18, 2022, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for use of the 2-dose monovalent Moderna COVID-19 vaccine as a primary series for children aged 6 months-5 years* and the 3-dose monovalent Pfizer-BioNTech COVID-19 vaccine as a primary series for children aged 6 months-4 years,(†) based on safety, immunobridging, and limited efficacy data from clinical trials (1-3). Monovalent mRNA vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection was evaluated using the Increasing Community Access to Testing (ICATT) program, which provides SARS-CoV-2 testing to persons aged ≥3 years at pharmacy and community-based testing sites nationwide(§) (4,5). Among children aged 3-5 years with one or more COVID-19-like illness symptoms(¶) for whom a nucleic acid amplification test (NAAT) was performed during August 1, 2022-February 5, 2023, VE of 2 monovalent Moderna doses (complete primary series) against symptomatic infection was 60% (95% CI = 49% to 68%) 2 weeks-2 months after receipt of the second dose and 36% (95% CI = 15% to 52%) 3-4 months after receipt of the second dose. Among symptomatic children aged 3-4 years with NAATs performed during September 19, 2022-February 5, 2023, VE of 3 monovalent Pfizer-BioNTech doses (complete primary series) against symptomatic infection was 31% (95% CI = 7% to 49%) 2 weeks-4 months after receipt of the third dose; statistical power was not sufficient to estimate VE stratified by time since receipt of the third dose. Complete monovalent Moderna and Pfizer-BioNTech primary series vaccination provides protection for children aged 3-5 and 3-4 years, respectively, against symptomatic infection for at least the first 4 months after vaccination. CDC expanded recommendations for use of updated bivalent vaccines to children aged ≥6 months on December 9, 2022 (6), which might provide increased protection against currently circulating SARS-CoV-2 variants (7,8). Children should stay up to date with recommended COVID-19 vaccines, including completing the primary series; those who are eligible should receive a bivalent vaccine dose.

On September 1, 2022, bivalent COVID-19 mRNA vaccines, composed of components from the SARS-CoV-2 ancestral and Omicron BA.4/BA.5 strains, were recommended by the Advisory Committee on Immunization Practices (ACIP) to address reduced effectiveness of COVID-19 monovalent vaccines during SARS-CoV-2 Omicron variant predominance (1). Initial recommendations included persons aged ≥12 years (Pfizer-BioNTech) and ≥18 years (Moderna) who had completed at least a primary series of any Food and Drug Administration-authorized or -approved monovalent vaccine ≥2 months earlier (1). On October 12, 2022, the recommendation was expanded to include children aged 5-11 years. At the time of recommendation, immunogenicity data were available from clinical trials of bivalent vaccines composed of ancestral and Omicron BA.1 strains; however, no clinical efficacy data were available. In this study, effectiveness of the bivalent (Omicron BA.4/BA.5-containing) booster formulation against symptomatic SARS-CoV-2 infection was examined using data from the Increasing Community Access to Testing (ICATT) national SARS-CoV-2 testing program.* During September 14-November 11, 2022, a total of 360,626 nucleic acid amplification tests (NAATs) performed at 9,995 retail pharmacies for adults aged ≥18 years, who reported symptoms consistent with COVID-19 at the time of testing and no immunocompromising conditions, were included in the analysis. Relative vaccine effectiveness (rVE) of a bivalent booster dose compared with that of ≥2 monovalent vaccine doses among persons for whom 2-3 months and ≥8 months had elapsed since last monovalent dose was 30% and 56% among persons aged 18-49 years, 31% and 48% among persons aged 50-64 years, and 28% and 43% among persons aged ≥65 years, respectively. Bivalent mRNA booster doses provide additional protection against symptomatic SARS-CoV-2 in immunocompetent persons who previously received monovalent vaccine only, with relative benefits increasing with time since receipt of the most recent monovalent vaccine dose. Staying up to date with COVID-19 vaccination, including getting a bivalent booster dose when eligible, is critical to maximizing protection against COVID-19 (1).

To the Editor: For persons who received a single dose of the Ad26.COV2.S vaccine (Johnson & Johnson–Janssen) against coronavirus disease 2019 (Covid-19), a booster dose of a messenger RNA (mRNA) vaccine at least 2 months after the primary dose is recommended. Recipients of Ad26.COV2.S for both the primary and booster doses may receive a second booster dose of an mRNA Covid-19 vaccine at least 4 months after the first Ad26.COV2.S booster dose.1 Immunogenicity data from a phase 1–2 clinical trial conducted before B.1.1.529 and the BA sublineages of omicron emerged showed that increases in the titers of binding and neutralizing antibodies with heterologous boosting were similar to or greater than the increases with homologous boosting.2 In a study involving U.S. veterans, data that were obtained during a period in which omicron was the predominant circulating variant also showed that among Ad26.COV2.S recipients, vaccine effectiveness against omicron infection was higher with heterologous boosting than with homologous boosting3; however, data from the general adult population and on vaccine effectiveness over time are lacking. More than 18 million doses of the Ad26.COV2.S vaccine have been administered in the United States alone4; therefore, data are needed on boosting strategies that are effective over time.

IMPORTANCE: Efficacy of 2 doses of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) against COVID-19 was high in pediatric trials conducted before the SARS-CoV-2 Omicron variant emerged. Among adults, estimated vaccine effectiveness (VE) of 2 BNT162b2 doses against symptomatic Omicron infection was reduced compared with prior variants, waned rapidly, and increased with a booster. OBJECTIVE: To evaluate the association of symptomatic infection with prior vaccination with BNT162b2 to estimate VE among children and adolescents during Omicron variant predominance. DESIGN, SETTING, AND PARTICIPANTS: A test-negative, case-control analysis was conducted using data from 6897 pharmacy-based, drive-through SARS-CoV-2 testing sites across the US from a single pharmacy chain in the Increasing Community Access to Testing platform. This analysis included 74208 tests from children 5 to 11 years of age and 47744 tests from adolescents 12 to 15 years of age with COVID-19-like illness who underwent SARS-CoV-2 nucleic acid amplification testing from December 26, 2021, to February 21, 2022. EXPOSURES: Two BNT162b2 doses 2 weeks or more before SARS-CoV-2 testing vs no vaccination for children; 2 or 3 doses 2 weeks or more before testing vs no vaccination for adolescents (who are recommended to receive a booster dose). MAIN OUTCOMES AND MEASURES: Symptomatic infection. The adjusted odds ratio (OR) for the association of prior vaccination and symptomatic SARS-CoV-2 infection was used to estimate VE: VE=(1-OR)100%. RESULTS: A total of 30999 test-positive cases and 43209 test-negative controls were included from children 5 to 11 years of age, as well as 22273 test-positive cases and 25471 test-negative controls from adolescents 12 to 15 years of age. The median age among those with included tests was 10 years (IQR, 7-13); 61189 (50.2%) were female, 75758 (70.1%) were White, and 29034 (25.7%) were Hispanic/Latino. At 2 to 4 weeks after dose 2, among children, the adjusted OR was 0.40 (95% CI, 0.35-0.45; estimated VE, 60.1% [95% CI, 54.7%-64.8%]) and among adolescents, the OR was 0.40 (95% CI, 0.29-0.56; estimated VE, 59.5% [95% CI, 44.3%-70.6%]). During month 2 after dose 2, among children, the OR was 0.71 (95% CI, 0.67-0.76; estimated VE, 28.9% [95% CI, 24.5%-33.1%]) and among adolescents, the OR was 0.83 (95% CI, 0.76-0.92; estimated VE, 16.6% [95% CI, 8.1%-24.3%]). Among adolescents, the booster dose OR 2 to 6.5 weeks after the dose was 0.29 (95% CI, 0.24-0.35; estimated VE, 71.1% [95% CI, 65.5%-75.7%]). CONCLUSIONS AND RELEVANCE: Among children and adolescents, estimated VE for 2 doses of BNT162b2 against symptomatic infection was modest and decreased rapidly. Among adolescents, the estimated effectiveness increased after a booster dose.

Nursing home residents have experienced disproportionally high levels of COVID-19-associated morbidity and mortality and were prioritized for early COVID-19 vaccination (1). Following reported declines in vaccine-induced immunity after primary series vaccination, defined as receipt of 2 primary doses of an mRNA vaccine (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) or 1 primary dose of Ad26.COV2 (Johnson & Johnson [Janssen]) vaccine (2), CDC recommended that all persons aged ≥12 years receive a COVID-19 booster vaccine dose.* Moderately to severely immunocompromised persons, a group that includes many nursing home residents, are also recommended to receive an additional primary COVID-19 vaccine dose.(†) Data on vaccine effectiveness (VE) of an additional primary or booster dose against infection with SARS-CoV-2 (the virus that causes COVID-19) among nursing home residents are limited, especially against the highly transmissible B.1.1.529 and BA.2 (Omicron) variants. Weekly COVID-19 surveillance and vaccination coverage data among nursing home residents, reported by skilled nursing facilities (SNFs) to CDC's National Healthcare Safety Network (NHSN)(§) during February 14-March 27, 2022, when the Omicron variant accounted for >99% of sequenced isolates, were analyzed to estimate relative VE against infection for any COVID-19 additional primary or booster dose compared with primary series vaccination. After adjusting for calendar week and variability across SNFs, relative VE of a COVID-19 additional primary or booster dose was 46.9% (95% CI = 44.8%-48.9%). These findings indicate that among nursing home residents, COVID-19 additional primary or booster doses provide greater protection against Omicron variant infection than does primary series vaccination alone. All immunocompromised nursing home residents should receive an additional primary dose, and all nursing home residents should receive a booster dose, when eligible, to protect against COVID-19. Efforts to keep nursing home residents up to date with vaccination should be implemented in conjunction with other COVID-19 prevention strategies, including testing and vaccination of nursing home staff members and visitors.

Reported Legionnaires' disease (LD) cases began increasing in the United States in 2003 after relatively stable numbers for >10 years; reasons for the rise are unclear. We compared epidemiologic patterns associated with cases reported to the Centers for Disease Control and Prevention before and during the rise. The age-standardized average incidence was 0.48 cases/100,000 population during 1992-2002 compared with 2.71 cases/100,000 in 2018. Reported LD incidence increased in nearly every demographic, but increases tended to be larger in demographic groups with higher incidence. During both periods, the largest number of cases occurred among White persons, but the highest incidence was in Black or African American persons. Incidence and increases in incidence were generally largest in the East North Central, Middle Atlantic, and New England divisions. Seasonality was more pronounced during 2003-2018, especially in the Northeast and Midwest. Rising incidence was most notably associated with increasing racial disparities, geographic focus, and seasonality.

IMPORTANCE: Monitoring COVID-19 vaccine performance over time since vaccination and against emerging variants informs control measures and vaccine policies. OBJECTIVE: To estimate the associations between symptomatic SARS-CoV-2 infection and receipt of BNT162b2, mRNA-1273, and Ad26.COV2.S by day since vaccination before and during Delta variant predominance (pre-Delta period: March 13-May 29, 2021; Delta period: July 18-October 17, 2021). DESIGN, SETTING, AND PARTICIPANTS: Test-negative, case-control design with data from 6884 US COVID-19 testing sites in the pharmacy-based Increasing Community Access to Testing platform. This study included 1634271 laboratory-based SARS-CoV-2 nucleic acid amplification tests (NAATs) from adults 20 years and older and 180112 NAATs from adolescents 12 to 19 years old with COVID-19-like illness from March 13 to October 17, 2021. EXPOSURES: COVID-19 vaccination (1 Ad26.COV2.S dose or 2 mRNA doses) 14 or more days prior. MAIN OUTCOMES AND MEASURES: Association between symptomatic infection and prior vaccination measured using the odds ratio (OR) from spline-based multivariable logistic regression. RESULTS: The analysis included 390762 test-positive cases (21.5%) and 1423621 test-negative controls (78.5%) (59.9% were 20-44 years old; 9.9% were 12-19 years old; 58.9% were female; 71.8% were White). Among adults 20 years and older, the BNT162b2 mean OR for days 14 to 60 after a second dose (initial OR) was lower during the pre-Delta period (0.10 [95% CI, 0.09-0.11]) than during the Delta period (0.16 [95% CI, 0.16-0.17]) and increased with time since vaccination (per-month change in OR, pre-Delta: 0.04 [95% CI, 0.02-0.05]; Delta: 0.03 [95% CI, 0.02-0.03]). The initial mRNA-1273 OR was 0.05 (95% CI, 0.04-0.05) during the pre-Delta period, 0.10 (95% CI, 0.10-0.11) during the Delta period, and increased with time (per-month change in OR, pre-Delta: 0.02 [95% CI, 0.005-0.03]; Delta: 0.03 [95% CI, 0.03-0.04]). The Ad26.COV2.S initial OR was 0.42 (95% CI, 0.37-0.47) during the pre-Delta period and 0.62 (95% CI, 0.58-0.65) during the Delta period and did not significantly increase with time since vaccination. Among adolescents, the BNT162b2 initial OR during the Delta period was 0.06 (95% CI, 0.05-0.06) among 12- to 15-year-olds, increasing by 0.02 (95% CI, 0.01-0.03) per month, and 0.10 (95% CI, 0.09-0.11) among 16- to 19-year-olds, increasing by 0.04 (95% CI, 0.03-0.06) per month. CONCLUSIONS AND RELEVANCE: Among adults, the OR for the association between symptomatic SARS-CoV-2 infection and COVID-19 vaccination (as an estimate of vaccine effectiveness) was higher during Delta variant predominance, suggesting lower protection. For mRNA vaccination, the steady increase in OR by month since vaccination was consistent with attenuation of estimated effectiveness over time; attenuation related to time was greater than that related to variant.

IMPORTANCE: Assessing COVID-19 vaccine performance against the rapidly spreading SARS-CoV-2 Omicron variant is critical to inform public health guidance. OBJECTIVE: To estimate the association between receipt of 3 doses of Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccine and symptomatic SARS-CoV-2 infection, stratified by variant (Omicron and Delta). DESIGN, SETTING, AND PARTICIPANTS: A test-negative case-control analysis among adults 18 years or older with COVID-like illness tested December 10, 2021, through January 1, 2022, by a national pharmacy-based testing program (4666 COVID-19 testing sites across 49 US states). EXPOSURES: Three doses of mRNA COVID-19 vaccine (third dose 14 days before test and 6 months after second dose) vs unvaccinated and vs 2 doses 6 months or more before test (ie, eligible for a booster dose). MAIN OUTCOMES AND MEASURES: Association between symptomatic SARS-CoV-2 infection (stratified by Omicron or Delta variants defined using S-gene target failure) and vaccination (3 doses vs unvaccinated and 3 doses vs 2 doses). Associations were measured with multivariable multinomial regression. Among cases, a secondary outcome was median cycle threshold values (inversely proportional to the amount of target nucleic acid present) for 3 viral genes, stratified by variant and vaccination status. RESULTS: Overall, 23391 cases (13098 Omicron; 10293 Delta) and 46764 controls were included (mean age, 40.3 [SD, 15.6] years; 42050 [60.1%] women). Prior receipt of 3 mRNA vaccine doses was reported for 18.6% (n=2441) of Omicron cases, 6.6% (n=679) of Delta cases, and 39.7% (n=18587) of controls; prior receipt of 2 mRNA vaccine doses was reported for 55.3% (n=7245), 44.4% (n=4570), and 41.6% (n=19456), respectively; and being unvaccinated was reported for 26.0% (n=3412), 49.0% (n=5044), and 18.6% (n=8721), respectively. The adjusted odds ratio for 3 doses vs unvaccinated was 0.33 (95% CI, 0.31-0.35) for Omicron and 0.065 (95% CI, 0.059-0.071) for Delta; for 3 vaccine doses vs 2 doses the adjusted odds ratio was 0.34 (95% CI, 0.32-0.36) for Omicron and 0.16 (95% CI, 0.14-0.17) for Delta. Median cycle threshold values were significantly higher in cases with 3 doses vs 2 doses for both Omicron and Delta (Omicron N gene: 19.35 vs 18.52; Omicron ORF1ab gene: 19.25 vs 18.40; Delta N gene: 19.07 vs 17.52; Delta ORF1ab gene: 18.70 vs 17.28; Delta S gene: 23.62 vs 20.24). CONCLUSIONS AND RELEVANCE: Among individuals seeking testing for COVID-like illness in the US in December 2021, receipt of 3 doses of mRNA COVID-19 vaccine (compared with unvaccinated and with receipt of 2 doses) was less likely among cases with symptomatic SARS-CoV-2 infection compared with test-negative controls. These findings suggest that receipt of 3 doses of mRNA vaccine, relative to being unvaccinated and to receipt of 2 doses, was associated with protection against both the Omicron and Delta variants, although the higher odds ratios for Omicron suggest less protection for Omicron than for Delta.

Lesotho is a small, landlocked country in southern Africa with a population of approximately 2 million persons, approximately two thirds of whom live in rural areas (1). Lesotho has the second highest prevalence of HIV infection in the world (2). In 2017, 25.6% of persons aged 15-59 years living in Lesotho were HIV-positive (3). Strategies implemented in recent years to control HIV include efforts to reduce mother-to-child transmission and improve coverage with antiretroviral therapy, as well as increasing testing for HIV. Among persons aged 15-24 years, the HIV prevalence among females in 2017 (11.1%) was approximately three times that among males (3.4%) (3). The Determined, Resilient, Empowered, AIDS-Free, Mentored, and Safe (DREAMS)* program in Lesotho was started during October 2016 in two districts. DREAMS comprises a package of biomedical, behavioral, and structural interventions to address factors that make adolescent girls and young women vulnerable to HIV acquisition (4). The goal of the DREAMS program was to decrease HIV incidence among adolescent girls and young women by 25% after 1 year and by 40% after 2 years (4). After 3.5 years of program implementation in Lesotho, new HIV diagnoses among adolescent girls and young women attending antenatal care (ANC) decreased 71.4% in the two districts that implemented DREAMS compared with a reduction of 48.4% in three comparison districts without the program (p = 0.002). During 2016-2020, reductions in new HIV diagnoses among adolescent girls and young women attending ANC in Lesotho have been substantial, both in districts that have and have not implemented the DREAMS program (DREAMS and non-DREAMS districts). Apart from the DREAMS program, the decrease in new HIV diagnoses might be a result of the reduction in viral load in the population because more persons living with HIV infection became virally suppressed while on antiviral therapy, as well as other interventions such as preexposure prophylaxis, voluntary medical male circumcision, behavior change, and increased HIV diagnostic coverage.

Soil-transmitted helminth (STH) infections and diarrheal illness affect billions of people yearly. We conducted a cross-sectional survey in Nueva Santa Rosa, Guatemala to identify factors associated with STH infections and diarrhea using univariable and multivariable logistic regression models. On multivariable analyses, we found associations between STH infections and two factors: school-aged children (odds ratio (OR) vs. adults: 2.35, 95% CI 1.10–4.99) and household drinking water supply classified as ‘other improved’ (OR vs. ‘improved’: 7.00, CI 1.22–40.14). Finished floors in the household vs. natural floors were highly protective (OR 0.16, CI 0.05–0.50) for STH infection. In crowded households (>2.5 people/bedroom), observing water present at handwashing stations was also protective (OR 0.32, CI 0.11–0.98). When adjusted for drying hands, diarrhea was associated with preschool-age children (OR vs. adults: 3.33, CI 1.83–6.04), spending >10 min per round trip collecting water (OR 1.90, CI 1.02–3.56), and having a handwashing station ≤10 m near a sanitation facility (OR 3.69, CI 1.33–10.21). Our study indicates that familiar WASH interventions, such as increasing drinking water quantity and water at handwashing stations in crowded homes, coupled with a hygiene intervention like finished flooring may hold promise for STH and diarrhea control programs. © 2021 The Authors.

Nursing home and long-term care facility residents live in congregate settings and are often elderly and frail, putting them at high risk for infection with SARS-CoV-2, the virus that causes COVID-19, and severe COVID-19-associated outcomes; therefore, this population was prioritized for early vaccination in the United States (1). Following rapid distribution and administration of the mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) under an Emergency Use Authorization by the Food and Drug Administration (2), observational studies among nursing home residents demonstrated vaccine effectiveness (VE) ranging from 53% to 92% against SARS-CoV-2 infection (3-6). However, concerns about the potential for waning vaccine-induced immunity and the recent emergence of the highly transmissible SARS-CoV-2 B.1.617.2 (Delta) variant(†) highlight the need to continue to monitor VE (7). Weekly data reported by the Centers for Medicaid & Medicare (CMS)-certified skilled nursing facilities or nursing homes to CDC's National Healthcare Safety Network (NHSN)(§) were analyzed to evaluate effectiveness of full vaccination (2 doses received ≥14 days earlier) with any of the two currently authorized mRNA COVID-19 vaccines during the period soon after vaccine introduction and before the Delta variant was circulating (pre-Delta [March 1-May 9, 2021]), and when the Delta variant predominated(¶) (Delta [June 21-August 1, 2021]). Using 17,407 weekly reports from 3,862 facilities from the pre-Delta period, adjusted effectiveness against infection for any mRNA vaccine was 74.7% (95% confidence interval [CI] = 70.0%-78.8%). Analysis using 33,160 weekly reports from 11,581 facilities during an intermediate period (May 10-June 20) found that the adjusted effectiveness was 67.5% (95% CI = 60.1%-73.5%). Analysis using 85,593 weekly reports from 14,917 facilities during the Delta period found that the adjusted effectiveness was 53.1% (95% CI = 49.1%-56.7%). Effectiveness estimates were similar for Pfizer-BioNTech and Moderna vaccines. These findings indicate that mRNA vaccines provide protection against SARS-CoV-2 infection among nursing home residents; however, VE was lower after the Delta variant became the predominant circulating strain in the United States. This analysis assessed VE against any infection, without being able to distinguish between asymptomatic and symptomatic presentations. Additional evaluations are needed to understand protection against severe disease in nursing home residents over time. Because nursing home residents might remain at some risk for SARS-CoV-2 infection despite vaccination, multiple COVID-19 prevention strategies, including infection control, testing, and vaccination of nursing home staff members, residents, and visitors, are critical. An additional dose of COVID-19 vaccine might be considered for nursing home and long-term care facility residents to optimize a protective immune response.

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that contaminates healthcare environments causing healthcare-associated outbreaks. The mechanisms facilitating contamination are not established. METHODS: C. auris was quantified in residents' bilateral axillary/inguinal composite skin swabs and environmental samples during a point-prevalence survey at a ventilator-capable skilled-nursing facility (vSNF A) with documented high colonization prevalence. Environmental samples were collected from all doorknobs, windowsills and handrails of each bed in 12 rooms. C. auris concentrations were measured using culture and C. auris-specific qPCR. The relationship between C. auris concentrations in residents' swabs and associated environmental samples were evaluated using Kendall's tau-b (τb) correlation coefficient. RESULTS: C. auris was detected in 70 /100 tested environmental samples and 31/ 57 tested resident skin swabs. The mean C. auris concentration in skin swabs was 1.22 x 10 5 cells/mL by culture and 1.08 x 10 6 cells/mL by qPCR. C. auris was detected on all handrails of beds occupied by colonized residents, as well as 10/24 doorknobs and 9/12 windowsills. A positive correlation was identified between the concentrations of C. auris in skin swabs and associated handrail samples based on culture (τb = 0.54, p = 0.0004) and qPCR (τb = 0.66, p = 3.83e -6). Two uncolonized residents resided in beds contaminated with C. auris. CONCLUSIONS: Colonized residents can have high C. auris burdens on their skin, which was positively related with contamination of their surrounding healthcare environment. These findings underscore the importance of hand hygiene, transmission-based precautions, and particularly environmental disinfection in preventing spread in healthcare facilities.

Residents of long-term care facilities (LTCFs), particularly those in skilled nursing facilities (SNFs), have experienced disproportionately high levels of COVID-19-associated morbidity and mortality and were prioritized for early COVID-19 vaccination (1,2). However, this group was not included in COVID-19 vaccine clinical trials, and limited postauthorization vaccine effectiveness (VE) data are available for this critical population (3). It is not known how well COVID-19 vaccines protect SNF residents, who typically are more medically frail, are older, and have more underlying medical conditions than the general population (1). In addition, immunogenicity of the Pfizer-BioNTech vaccine was found to be lower in adults aged 65-85 years than in younger adults (4). Through the CDC Pharmacy Partnership for Long-Term Care Program, SNF residents and staff members in Connecticut began receiving the Pfizer-BioNTech COVID-19 vaccine on December 18, 2020 (5). Administration of the vaccine was conducted during several on-site pharmacy clinics. In late January 2021, the Connecticut Department of Public Health (CT DPH) identified two SNFs experiencing COVID-19 outbreaks among residents and staff members that occurred after each facility's first vaccination clinic. CT DPH, in partnership with CDC, performed electronic chart review in these facilities to obtain information on resident vaccination status and infection with SARS-CoV-2, the virus that causes COVID-19. Partial vaccination, defined as the period from >14 days after the first dose through 7 days after the second dose, had an estimated effectiveness of 63% (95% confidence interval [CI] = 33%-79%) against SARS-CoV-2 infection (regardless of symptoms) among residents within these SNFs. This is similar to estimated effectiveness for a single dose of the Pfizer-BioNTech COVID-19 vaccine in adults across a range of age groups in noncongregate settings (6) and suggests that to optimize vaccine impact among this population, high coverage with the complete 2-dose series should be recommended for SNF residents and staff members.

Provision of safe drinking water in the United States is a great public health achievement. However, new waterborne disease challenges have emerged (e.g., aging infrastructure, chlorine-tolerant and biofilm-related pathogens, increased recreational water use). Comprehensive estimates of the health burden for all water exposure routes (ingestion, contact, inhalation) and sources (drinking, recreational, environmental) are needed. We estimated total illnesses, emergency department (ED) visits, hospitalizations, deaths, and direct healthcare costs for 17 waterborne infectious diseases. About 7.15 million waterborne illnesses occur annually (95% credible interval [CrI] 3.88 million-12.0 million), results in 601,000 ED visits (95% CrI 364,000-866,000), 118,000 hospitalizations (95% CrI 86,800-150,000), and 6,630 deaths (95% CrI 4,520-8,870) and incurring US $3.33 billion (95% CrI 1.37 billion-8.77 billion) in direct healthcare costs. Otitis externa and norovirus infection were the most common illnesses. Most hospitalizations and deaths were caused by biofilm-associated pathogens (nontuberculous mycobacteria, Pseudomonas, Legionella), costing US $2.39 billion annually.

BACKGROUND: Typhoid fever in the United States is acquired primarily through international travel by unvaccinated travelers. There is currently no typhoid vaccine licensed in the United States for use in children <2 years. METHODS: We reviewed Salmonella enterica serotype Typhi infections reported to the Centers for Disease Control and Prevention (CDC) and antimicrobial-resistance data on Typhi isolates in CDC's National Antimicrobial Resistance Monitoring System from 1999 through 2015. RESULTS: 5131 cases of typhoid fever were diagnosed and 5004 Typhi isolates tested for antimicrobial susceptibility. Among 1992 pediatric typhoid fever patients, 1616 (81%) had traveled internationally within 30 days of illness onset, 1544 (81%) of 1906 were hospitalized (median duration, 6 days; range, 0-50), and none died. Forty percent (799) were <6 years old; 12% were <2 years old. Based on age and travel destination, 1435 (83%) of 1722 pediatric patients were vaccine-eligible; only 68 (5%) of 1361 were known to be vaccinated. Of 2003 isolates tested for antimicrobial susceptibility, 1216 (61%) were fluoroquinolone-nonsusceptible, of which 272 (22%) were also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant [MDR]). All were susceptible to ceftriaxone and azithromycin. MDR and fluoroquinolone-nonsusceptible isolates were more common in children than adults (16% vs 9%, P < .001, and 61% vs 54%, P < .001, respectively). Fluoroquinolone nonsusceptibility was more common among travel-associated than domestically acquired cases (70% vs 17%, P < .001). CONCLUSIONS: Approximately 95% of currently vaccine-eligible pediatric travelers were unvaccinated, and antimicrobial-resistant infections were common. New public health strategies are needed to improve coverage with currently licensed vaccines. Introduction of an effective pretravel typhoid vaccine for children <2 years could reduce disease burden and prevent drug-resistant infections.

BACKGROUND: Data on risk factors for COVID-19-associated hospitalization are needed to guide prevention efforts and clinical care. We sought to identify factors independently associated with COVID-19-associated hospitalizations. METHODS: U.S. community-dwelling adults (≥18 years) hospitalized with laboratory-confirmed COVID-19 during March 1-June 23, 2020 were identified from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a multi-state surveillance system. To calculate hospitalization rates by age, sex, and race/ethnicity strata, COVID-NET data served as the numerator and Behavioral Risk Factor Surveillance System estimates served as the population denominator for characteristics of interest. Underlying medical conditions examined included hypertension, coronary artery disease, history of stroke, diabetes, obesity [BMI ≥30 kg/m 2], severe obesity [BMI≥40 kg/m 2], chronic kidney disease, asthma, and chronic obstructive pulmonary disease. Generalized Poisson regression models were used to calculate adjusted rate ratios (aRR) for hospitalization. RESULTS: Among 5,416 adults, hospitalization rates were higher among those with ≥3 underlying conditions (versus without)(aRR: 5.0; 95%CI: 3.9, 6.3), severe obesity (aRR:4.4; 95%CI: 3.4, 5.7), chronic kidney disease (aRR:4.0; 95%CI: 3.0, 5.2), diabetes (aRR:3.2; 95%CI: 2.5, 4.1), obesity (aRR:2.9; 95%CI: 2.3, 3.5), hypertension (aRR:2.8; 95%CI: 2.3, 3.4), and asthma (aRR:1.4; 95%CI: 1.1, 1.7), after adjusting for age, sex, and race/ethnicity. Adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults aged ≥65, 45-64 (versus 18-44 years), males (versus females), and non-Hispanic black and other race/ethnicities (versus non-Hispanic whites). CONCLUSION: Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that causes outbreaks in healthcare settings around the world. In 2016, clinicians and public health officials identified patients with C. auris bloodstream infections (BSI) in Colombian healthcare facilities. To evaluate potential risk factors and outcomes for these infections, we investigated epidemiologic and clinical features of patients with C. auris and other Candida species BSI. METHODS: We performed a retrospective case-case investigation in four Colombian acute care hospitals, defining a case as Candida spp. isolated from blood culture during January 2015-September 2016. C. auris BSI cases were compared to other Candida species BSI cases. Odds ratio (OR), estimated using logistic regression, was used to assess the association between risk factors and outcomes. RESULTS: We analyzed 90 patients with BSI, including 40 with C. auris and 50 with other Candida species. All had been admitted to the intensive care unit (ICU). No significant demographic differences existed between the two groups. The following variables were independently associated with C. auris BSI: ≥ 15 days of pre-infection ICU stay (OR: 5.62, CI: 2.04-15.5), evidence of severe sepsis (OR: 3.70, CI 1.19-11.48), and diabetes mellitus (OR 5.69, CI 1.01-31.9). CONCLUSION: Patients with C. auris BSI had longer lengths of ICU stay than those with other candidemias, suggesting that infections are acquired during hospitalization. This is different from other Candida infections, which are usually thought to result from autoinfection with host flora.

In Zambia limited access to adequate water and sanitation is a key developmental challenge, particularly for rapidly expanding peri-urban areas. During 20162017, a cross-sectional household survey was conducted among 12,500 households representing ~60,000 individuals to assess the burden of household diarrheal and respiratory disease and to measure water, sanitation, and hygiene (WASH) characteristics in Lusaka, Zambia. We found that socio-economic factors, including having an additional household member, having children <5 years old in the household, living in a rental home, and higher annual household expenditure were associated with diarrhea and respiratory illness. We also found an increased risk for diarrhea associated with a number of WASH-related factorssuch as not covering all water storage containers, not using soap for handwashing, having an unimproved sanitation facility, and utilizing a heavily shared toilet (18 people). Detectable free chlorine residual in household stored water and more hours of water availability per day were associated with reduced odds of waterborne illness. In all, 75% of household stored water was contaminated with E. coli and households consuming less water (<20 L/day per person) for all purposes had lower odds of diarrhea than households consuming more waterthese findings highlight the need for enhanced WASH services within densely populated peri-urban areas and the importance of achieving universal access to safely managed water and sanitation services.

Histoplasmosis is an important cause of mortality in people with advanced HIV, especially in countries with limited access to diagnostic assays. Histoplasmosis can be diagnosed using culture, histopathology, and antibody, antigen, and molecular assays. Several factors may affect the analytical performance of these laboratory assays, including sample type, clinical stage of the disease, and previous use of antifungal treatment, among others. Here we describe the results of a systematic literature review, followed by a meta-analysis of the analytical performances of the diagnostic laboratory assays employed. Our initial search identified 1631 references, of which 1559 references were excluded after title and abstract screening, leaving 72 references identified as studies relevant to the validation of histoplasmosis diagnostic assays. After evaluating the full text, 30 studies were selected for final review, including one paper not identified in the initial search. The meta-analysis for assay analytical performance shows the following results for the overall sensitivity (Sen) and specificity (Spe) of the various methods evaluated: Culture, Sen 77% (no data for specificity calculation); antibody detection assays, Sen 58%/Spe 100%; antigen detection assays, Sen 95%/Spe 97%; and DNA detection assays (molecular), Sen 95%/Spe 99%. Of the 30 studies reviewed, nearly half (n = 13) evaluated Histoplasma antigen assays, which were determined to be the most accurate methodology for diagnosis of progressive disseminated histoplasmosis in advanced HIV (inverse of the negative likelihood ratio was 13.2). Molecular assays appear promising for accurate diagnosis of histoplasmosis, but consensus on exact techniques is needed. Cultures showed variable sensitivity related to sample type and laboratory handling. Finally, antibody assays presented high specificity but low sensitivity. This poor sensitivity is most likely due the highly immunosuppressed state of this patient population. Diagnostic assays are crucial for accurate diagnosis of progressive disseminated histoplasmosis (PDH) with advanced HIV disease.

Shigella is a leading cause of human diarrheal disease worldwide with S. flexneri being the most frequently isolated in developing countries. This serogroup is presently classified into 19 serotypes worldwide. We report here a Multicenter Validation of a Multiplex PCR based-strategy previously developed by Sun et al. (doi: 10.1128/JCM.01259-11) for molecular serotyping of S. flexneri This study was performed by seven international laboratories, with a panel of 71 blinded strains as well as 279 strains collected from each own local culture collections. This collaborative work found high extent of agreement among laboratories, calculated through IRR measures for PCR test, proven its robustness. It was also observed agreement with traditional method (serology) in all laboratories for 14 serotypes studied, while specific genetic events could be responsible for the discrepancies among methodologies in other five serotypes as determined by PCR product sequencing in most of the cases. This work provided an empirical frame that allowed the use of this molecular method to serotype S. flexneri, and showed several advantages over the traditional method of serological typing. These included overcoming the problem of availability of suitable antisera in testing laboratories, as well as facilitated the analysis of multiple samples at the same time. The method is also less time consuming for completion, and easier to implement in routine laboratories. We recommend that this PCR be adopted, as it is a reliable diagnostic and characterization methodology that can be used globally for laboratory-based shigellae surveillance.

Improved water quality reduces diarrhea, but the impact of improved water quality on Ascaris and Trichuris, soil-transmitted helminths (STH) conveyed by the fecal-oral route, is less well described. To assess water quality associations with diarrhea and STH, we conducted a cross-sectional survey in households of south-eastern Guatemala. Diarrhea was self-reported in the past week and month. STH was diagnosed by stool testing using a fecal parasite concentrator method. We explored associations between Escherichia coli-positive source water (water quality) and disease outcomes using survey logistic regression models. Overall, 732 persons lived in 167 households where water was tested. Of these, 79.4% (581/732) had E. coli-positive water, 7.9% (58/732) had diarrhea within the week, 14.1% (103/732) had diarrhea within the month, and 6.6% (36/545) tested positive for Ascaris or Trichuris, including 1% (6/536) who also reported diarrhea. Univariable analysis found a statistically significant association between water quality and STH (odds ratio [OR] = 5.1, 95% confidence interval [CI] = 1.1-24.5) but no association between water quality and diarrhea. Waterborne transmission and effects of water treatment on STH prevalence should be investigated further. If a causal relationship is found, practices such as household water treatment including filtration might be useful adjuncts to sanitation, hygiene, and deworming in STH control programs.

BACKGROUND: Fungal infections remain a major contributor to the opportunistic infections that affect people living with HIV. Among them, histoplasmosis is considered neglected, often being misdiagnosed as tuberculosis, and is responsible for numerous deaths in Latin America. The objective of this study was to estimate the burden of HIV-associated histoplasmosis compared with tuberculosis in Latin American countries. METHODS: For this modelling study, we estimated prevalence of previous exposure to Histoplasma capsulatum, HIV-associated histoplasmosis annual incidence, and number of deaths in 2012 in Latin American countries based on historical histoplasmin skin test studies in the general population, with an antigen dilution level of more than 1/10. Studies were identified in a literature search. Data on HIV-associated tuberculosis were extracted from the WHO notifications and outcomes tables and data on people living with HIV were extracted from the UNAIDS report for the year 2012. We systematically propagated uncertainty throughout all the steps of the estimation process. FINDINGS: Among 1310 articles identified as of June 1, 2015, 24 articles were included in the study, representing 129 histoplasmin skin test studies led in the general population of Latin American countries. For the year 2012, we estimated a range of 6710 (95% CI 5680-7867) to 15 657 (13 254-18 357) cases of symptomatic HIV-associated histoplasmosis in Latin America. Hotspot areas for histoplasmosis prevalence (>30%) and incidence (>1.5 cases per 100 people living with HIV) were Central America, the northernmost part of South America, and Argentina. According to realistic scenarios, we estimated a range of 671 (95% CI 568-787) to 9394 (7952-11 014) deaths related to histoplasmosis, compared with 5062 (3777-6405) deaths related to tuberculosis reported in Latin America. INTERPRETATION: Our estimates of histoplasmosis incidence and deaths are high and consistent with published data. For the first time, the burden of histoplasmosis is estimated to be equivalent in incidence and even higher in deaths when compared with tuberculosis among people living with HIV in Latin America. FUNDING: None.

Two California state prisons (A and B) have very high rates of coccidioidomycosis (Valley Fever). The prison health care service sought to improve their prevention strategy by risk stratification with a newly available spherulin-based Coccidioides delayed-type hypersensitivity test. Of the 36,789 voluntarily screened inmates, 4.7% experienced adverse reactions. A positive test (8.6% of those tested) was independently associated with (1) incarceration at prisons A and B, (2) admission to prison from a Coccidioides-endemic county, (3) length of stay at prisons A and B, and (4) increasing age. These findings suggest that the test is safe and performing well at risk stratification; the prison system now restricts inmates with negative tests from prisons A and B. This novel use of the test might benefit other coccidioidomycosis prevention programs.

On October 6, 2017, an outbreak of cholera was declared in Zambia after laboratory confirmation of Vibrio cholerae O1, biotype El Tor, serotype Ogawa, from stool specimens from two patients with acute watery diarrhea. The two patients had gone to a clinic in Lusaka, the capital city, on October 4. Cholera cases increased rapidly, from several hundred cases in early December 2017 to approximately 2,000 by early January 2018 (Figure). In collaboration with partners, the Zambia Ministry of Health (MoH) launched a multifaceted public health response that included increased chlorination of the Lusaka municipal water supply, provision of emergency water supplies, water quality monitoring and testing, enhanced surveillance, epidemiologic investigations, a cholera vaccination campaign, aggressive case management and health care worker training, and laboratory testing of clinical samples. In late December 2017, a number of water-related preventive actions were initiated, including increasing chlorine levels throughout the city's water distribution system and placing emergency tanks of chlorinated water in the most affected neighborhoods; cholera cases declined sharply in January 2018. During January 10-February 14, 2018, approximately 2 million doses of oral cholera vaccine were administered to Lusaka residents aged >/=1 year. However, in mid-March, heavy flooding and widespread water shortages occurred, leading to a resurgence of cholera. As of May 12, 2018, the outbreak had affected seven of the 10 provinces in Zambia, with 5,905 suspected cases and a case fatality rate (CFR) of 1.9%. Among the suspected cases, 5,414 (91.7%), including 98 deaths (CFR = 1.8%), occurred in Lusaka residents.