BACKGROUND: In October 2013, Burkina Faso introduced 13-valent pneumococcal conjugate vaccine (PCV13) into the routine childhood immunization program using 3 primary doses with no booster. Previous pneumococcal carriage studies showed reductions in vaccine-type (VT) carriage in children aged <5 years but not in older age groups. METHODS: We conducted a cross-sectional, age-stratified pneumococcal carriage study among healthy persons aged ≥1 month in Bobo-Dioulasso in March 2020. Pneumococci isolated by culture from nasopharyngeal swabs (all participants) and oropharyngeal swabs (participants aged ≥5 years) were serotyped by polymerase chain reaction; a subset was serotyped by Quellung. Using data from a study with the same design from March 2017, we examined changes in pneumococcal carriage by age group. RESULTS: Among 1005 (2017) and 1002 (2020) enrolled participants, VT carriage decreased (21.6% to 15.9%; adjusted prevalence ratio [aPR], 0.76 [95% confidence interval {CI}, .63-.92]). By age group, decline in VT carriage was significant among children aged 5-14 years (28.9% to 16.3%; aPR, 0.57 [95% CI, .39-.84]) but not among children aged <5 years (22.4% to 19.1%; aPR, 0.87 [95% CI, .70-1.09]) or adults aged ≥15 years (12.0% to 5.5%; aPR, 0.52 [95% CI, .26-1.05]). CONCLUSIONS: Between 3 and 6 years after PCV13 introduction, significant declines in VT carriage were observed in older children, possibly reflecting indirect effects of PCV13 use. VT carriage in children aged <5 years remained stable with almost 1 in 5 carrying VT pneumococci, suggesting limitations to a PCV schedule without a booster dose.

BackgroundPublic health guidance recommending isolation of individuals with group A streptococcal (GAS) infection or carriage for 12-24 h from antibiotic initiation to prevent onward transmission requires a strong evidence base.AimTo estimate the pooled proportion of individuals who remain GAS culture-positive at set intervals after initiation of antibiotics through a systematic literature review (PROSPERO CRD42021290364) and meta-analysis.MethodsWe searched Ovid MEDLINE (1946-), EMBASE (1974-) and Cochrane library. We included interventional or observational studies with ≥ 10 participants reporting rates of GAS throat culture positivity during antibiotic treatment for culture-confirmed GAS pharyngitis, scarlet fever and asymptomatic pharyngeal GAS carriage. We did not apply age, language or geographical restrictions.ResultsOf 5,058 unique records, 43 were included (37 randomised controlled studies, three non-randomised controlled trials and three before-and-after studies). The proportion of individuals remaining culture-positive on day 1, day 2 and days 3-9 were 6.9% (95% CI: 2.7-16.8%), 5.4% (95% CI: 2.1-13.3%) and 2.6% (95% CI: 1.6-4.2%). For penicillins and cephalosporins, day 1 positivity was 6.5% (95% CI: 2.5-16.1%) and 1.6% (95% CI: 0.04-42.9%), respectively. Overall, for 9.1% (95% CI: 7.3-11.3), throat swabs collected after completion of therapy were GAS culture-positive. Only six studies had low risk of bias.ConclusionsOur review provides evidence that antibiotics for pharyngeal GAS achieve a high rate of culture conversion within 24 h but highlights the need for further research given methodological limitations of published studies and imprecision of pooled estimates. Further evidence is needed for non-beta-lactam antibiotics and asymptomatic individuals.

Background: Public health guidance recommending isolation of individuals with group A streptococcal (GAS) infection or carriage for 12-24 hours from antibiotic initiation to prevent onward transmission requires a strong evidence-base. Method(s): We conducted a systematic review (PROSPERO CRD42021290364) and meta-analysis to estimate the pooled proportion of individuals who remain GAS culture-positive at set intervals after initiation of antibiotics. We searched Ovid MEDLINE (1946-), EMBASE (1974-) and the Cochrane library. We included interventional or observational studies with ten or more participants reporting rates of GAS throat culture during antibiotics for culture confirmed GAS pharyngitis, scarlet fever, and asymptomatic pharyngeal GAS carriage. We did not apply age, language, or geographical restrictions. Finding(s): Of 5,058 unique records identified, 43 were included; 37 (86%) randomised controlled studies, three (7%) non-randomised controlled trials and three (7%) before-and-after studies. The proportion of individuals who remained culture-positive at day 1, day 2, and day 3-9 were 6.9% (95% CI 2.7-16.8%), 5.4% (95% CI 2.1-13.3%) and 2.6% (95% CI 1.6-4.2%). For penicillins and cephalosporins, day 1 positivity was 6.5% (95% CI 2.5-16.1%) and 1.6% (95% CI 0.04-42.9%) respectively. Overall, for 9.1% (95% CI 7.3-11.3), throat swabs collected after completion of therapy were GAS culture-positive. Interpretation(s): Our review provides evidence that antibiotics for pharyngeal GAS achieve a high rate of culture conversion within 24 hours but highlights the need for further research given the methodological limitations of published studies and imprecision of pooled estimates. Further evidence is needed for non-beta-lactam antibiotics and for asymptomatic individuals. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

BACKGROUND: The incidence of invasive disease caused by group A streptococcus (GAS) has increased in multiple countries in the past 15 years. However, despite these reports, to the best of our knowledge, no systematic reviews and combined estimates of the incidence of invasive GAS have been done in key high-risk groups. To address this, we estimated the incidence of invasive GAS disease, including death and disability outcomes, among two high-risk groups-namely, pregnant women and children younger than 5 years. METHODS: We did a systematic review and meta-analyses on invasive GAS outcomes, including incidence, case fatality risks, and neurodevelopmental impairment risk, among pregnant women, neonates (younger than 28 days), infants (younger than 1 year), and children (younger than 5 years) worldwide and by income region. We searched several databases for articles published from Jan 1, 2000, to June 3, 2020, for publications that reported invasive GAS outcomes, and we sought unpublished data from an investigator group of collaborators. We included studies with data on invasive GAS cases, defined as laboratory isolation of Streptococcus pyogenes from any normally sterile site, or isolation of S pyogenes from a non-sterile site in a patient with necrotising fasciitis or streptococcal toxic shock syndrome. For inclusion in pooled incidence estimates, studies had to report a population denominator, and for inclusion in pooled estimates of case fatality risk, studies had to report aggregate data on the outcome of interest and the total number of cases included as a denominator. We excluded studies focusing on groups at very high risk (eg, only preterm infants). We assessed heterogeneity with I(2). FINDINGS: Of the 950 published articles and 29 unpublished datasets identified, 20 studies (seven unpublished; 3829 cases of invasive GAS) from 12 countries provided sufficient data to be included in pooled estimates of outcomes. We did not identify studies reporting invasive GAS incidence among pregnant women in low-income and middle-income countries (LMICs) nor any reporting neurodevelopmental impairment after invasive GAS in LMICs. In nine studies from high-income countries (HICs) that reported invasive GAS in pregnancy and the post-partum period, invasive GAS incidence was 0·12 per 1000 livebirths (95% CI 0·11 to 0·14; I(2)=100%). Invasive GAS incidence was 0·04 per 1000 livebirths (0·03 to 0·05; I(2)=100%; 11 studies) for neonates, 0·13 per 1000 livebirths (0·10 to 0·16; I(2)=100%; ten studies) for infants, and 0·09 per 1000 person-years (95% CI 0·07 to 0·10; I(2)=100%; nine studies) for children worldwide; 0·12 per 1000 livebirths (95% CI 0·00 to 0·24; I(2)=100%; three studies) in neonates, 0·33 per 1000 livebirths (-0·22 to 0·88; I(2)=100%; two studies) in infants, and 0·22 per 1000 person-years (0·13 to 0·31; I(2)=100%; two studies) in children in LMICs; and 0·02 per 1000 livebirths (0·00 to 0·03; I(2)=100%; eight studies) in neonates, 0·08 per 1000 livebirths (0·05 to 0·11; I(2)=100%; eight studies) in infants, and 0·05 per 1000 person-years (0·03 to 0·06; I(2)=100%; seven studies) in children for HICs. Case fatality risks were high, particularly among neonates in LMICs (61% [95% CI 33 to 89]; I(2)=54%; two studies). INTERPRETATION: We found a substantial burden of invasive GAS among young children. In LMICs, little data were available for neonates and children and no data were available for pregnant women. Incidences of invasive GAS are likely to be underestimates, particularly in LMICs, due to low GAS surveillance. It is essential to improve available data to inform development of prevention and management strategies for invasive GAS. FUNDING: Wellcome Trust.

BACKGROUND: The genomic features and transmission link of circulating Group A streptococcus (GAS) strains causing different disease types, such as pharyngitis and invasive disease, are not well understood. METHODS: We used whole-genome sequencing (WGS) to characterize GAS isolates recovered from persons with pharyngitis and invasive disease in the Denver metropolitan area from June 2016 to April 2017. RESULTS: GAS isolates were cultured from 236 invasive and 417 pharyngitis infections. WGS identified 34 emm types. Compared to pharyngitis isolates, invasive isolates were more likely to carry the erm family genes (23% vs. 7.4%, p<0.001), which confer resistance to erythromycin and clindamycin (including inducible resistance), and covS gene inactivation (7% vs. 0.5%, p<0.001). WGS identified 97 genomic clusters (433 isolates; 2-65 isolates per cluster) that consisted of genomically closely related isolates (median SNP (IQR) = 3 (1-4) within cluster). Thirty genomic clusters (200 isolates; 31% of all isolates) contained both pharyngitis and invasive isolates and were found in 11 emm types. CONCLUSIONS: In the Denver metropolitan population, mixed disease types were commonly seen in clusters of closely related isolates, indicative of overlapping transmission networks. Antibiotic-resistance and covS inactivation was disproportionally associated with invasive disease.

Background Rheumatic heart disease (RHD) is a severe, chronic complication of acute rheumatic fever, triggered by group A streptococcal pharyngitis. Centralized patient registries are recommended for RHD prevention and control, but none exists in American Samoa. Using existing RHD tracking systems, we estimated RHD period prevalence and the proportion of people with RHD documented in the electronic health record. Methods and Results RHD cases were identified from a centralized electronic health record system, which retrieved clinical encounters with RHD International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, clinical problem lists referencing RHD, and antibiotic prophylaxis administration records; 3 RHD patient tracking spreadsheets; and an all-cause mortality database. RHD cases had ≥1 clinical encounter with RHD ICD-10-CM codes, a diagnostic echocardiogram, or RHD as a cause of death, or were included in RHD patient tracking spreadsheets. Period prevalence per 1000 population among children aged <18 years and adults aged ≥18 years from 2016 to 2018 and the proportion of people with RHD with ≥1 clinical encounter with an RHD ICD-10-CM code were estimated. From 2016 to 2018, RHD was documented in 327 people (57.2%: children aged <18 years). Overall RHD period prevalence was 6.3 cases per 1000 and varied by age (10.0 pediatric cases and 4.3 adult cases per 1000). Only 67% of people with RHD had ≥1 clinical encounter with an RHD ICD-10-CM code. Conclusions RHD remains a serious public health problem in American Samoa, and the existing electronic health record does not include all cases. A centralized patient registry could improve tracking people with RHD to ensure they receive necessary care.

BACKGROUND: Streptococcus pneumoniae, or pneumococcus, is a leading cause of morbidity and mortality in children worldwide. Pneumococcal conjugate vaccines (PCV) reduce carriage in the nasopharynx, preventing disease. We conducted a pneumococcal carriage study to estimate the prevalence of pneumococcal colonization, identify risk factors for colonization, and describe antimicrobial susceptibility patterns among pneumococci colonizing young children in Port-au-Prince, Haiti, before introduction of 13-valent PCV (PCV13). METHODS: We conducted a cross-sectional study of children aged 6-24 months at an immunization clinic in Port-au-Prince between September 2015 and January 2016. Consenting parents were interviewed about factors associated with pneumococcal carriage; nasopharyngeal swabs were collected from each child and cultured for pneumococcus after broth enrichment. Pneumococcal isolates were serotyped and underwent antimicrobial susceptibility testing. We compared frequency of demographic, clinical, and environmental factors among pneumococcus-colonized children (carriers) to those who were not colonized (noncarriers) using unadjusted bivariate analysis and multivariate logistic regression. RESULTS: Pneumococcus was isolated from 308 of the 685 (45.0%) children enrolled. Overall, 157 isolates (50.8%) were PCV13 vaccine-type serotypes; most common were 6A (13.3%), 19F (12.6%), 6B (9.7%), and 23F (6.1%). Vaccine-type isolates were significantly more likely to be nonsusceptible to ≥1 antimicrobial (63.1% vs 45.4%, P = .002). On bivariate analysis, carriers were significantly more likely than noncarriers to live in a household without electricity or running water, to share a bedroom with ≥3 people, to have a mother or father who did not complete secondary education, and to have respiratory symptoms in the 24 hours before enrollment (P < .05 for all comparisons). On multivariable analysis, completion of the pentavalent vaccination series (targeting diphtheria, pertussis, tetanus, hepatitis B, and Haemophilus influenzae type b) remained significantly more common among noncarriers. CONCLUSIONS: Nearly a quarter of healthy children surveyed in Haiti were colonized with vaccine-type pneumococcal serotypes. This baseline carriage study will enable estimation of vaccine impact following nationwide introduction of PCV13.

BACKGROUND: Burkina Faso, a country in Africa's meningitis belt, introduced 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013, with 3 primary doses given at 8, 12 and 16 weeks of age. To assess whether the new PCV13 program controlled pneumococcal carriage, we evaluated overall and serotype-specific colonization among children and adults during the first 3 years after introduction. METHODS: We conducted 2 population-based, cross-sectional, age-stratified surveys in 2015 and 2017 in the city of Bobo-Dioulasso. We used standardized questionnaires to collect sociodemographic, epidemiologic, and vaccination data. Consenting eligible participants provided nasopharyngeal (all ages) and oropharyngeal (≥5 years only) swab specimens. Swab specimens were plated onto blood agar either directly (2015) or after broth enrichment (2017). Pneumococci were serotyped by conventional multiplex polymerase chain reaction. We assessed vaccine effect by comparing the proportion of vaccine-type (VT) carriage among colonized individuals from a published baseline survey (2008) with each post-PCV survey. RESULTS: We recruited 992 (2015) and 1005 (2017) participants. Among children aged <5 years, 42.8% (2015) and 74.0% (2017) received ≥2 PCV13 doses. Among pneumococcal carriers aged <1 year, VT carriage declined from 55.8% in 2008 to 36.9% in 2017 (difference, 18.9%; 95% confidence interval, 1.9%-35.9%; P = .03); among carriers aged 1-4 years, VT carriage declined from 55.3% to 31.8% (difference, 23.5%; 6.8%-40.2%; P = .004); and among participants aged ≥5 years, no significant change was observed. CONCLUSION: Within 3 years of PCV13 implementation in Burkina Faso, we documented substantial reductions in the percentage of pneumococcal carriers with a VT among children aged <5 years, but not among persons aged ≥5 years. More time, a change in the PCV13 schedule, or both, may be needed to better control pneumococcal carriage in this setting.

BACKGROUND: The World Health Organization (WHO) coordinates the Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Surveillance Network to support vaccine introduction decisions and use. The network was established to strengthen surveillance and laboratory confirmation of meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. METHODS: Sentinel hospitals report cases of children <5 years of age hospitalized for suspected meningitis. Laboratories report confirmatory testing results and strain characterization tested by polymerase chain reaction. In 2019, the network included 123 laboratories that follow validated, standardized testing and reporting strategies. RESULTS: From 2014 through 2019, >137 000 suspected meningitis cases were reported by 58 participating countries, with 44.6% (n = 61 386) reported from countries in the WHO African Region. More than half (56.6%, n = 77 873) were among children <1 year of age, and 4.0% (n = 4010) died among those with reported disease outcome. Among suspected meningitis cases, 8.6% (n = 11 798) were classified as probable bacterial meningitis. One of 3 bacterial pathogens was identified in 30.3% (n = 3576) of these cases, namely S. pneumoniae (n = 2177 [60.9%]), H. influenzae (n = 633 [17.7%]), and N. meningitidis (n = 766 [21.4%]). Among confirmed bacterial meningitis cases with outcome reported, 11.0% died; case fatality ratio varied by pathogen (S. pneumoniae, 12.2%; H. influenzae, 6.1%; N. meningitidis, 11.0%). Among the 277 children who died with confirmed bacterial meningitis, 189 (68.2%) had confirmed S. pneumoniae. The proportion of pneumococcal cases with pneumococcal conjugate vaccine (PCV) serotypes decreased as the number of countries implementing PCV increased, from 77.8% (n = 273) to 47.5% (n = 248). Of 397 H. influenzae specimens serotyped, 49.1% (n = 195) were type b. Predominant N. meningitidis serogroups varied by region. CONCLUSIONS: This multitier, global surveillance network has supported countries in detecting and serotyping the 3 principal invasive bacterial pathogens that cause pediatric meningitis. Streptococcus pneumoniae was the most common bacterial pathogen detected globally despite the growing number of countries that have nationally introduced PCV. The large proportions of deaths due to S. pneumoniae reflect the high proportion of meningitis cases caused by this pathogen. This global network demonstrated a strong correlation between PCV introduction status and reduction in the proportion of pneumococcal meningitis infections caused by vaccine serotypes. Maintaining case-based, active surveillance with laboratory confirmation for prioritized vaccine-preventable diseases remains a critical component of the global agenda in public health.The World Health Organization (WHO)-coordinated Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network reported data from 2014 to 2019, contributing to the estimates of the disease burden and serotypes of pediatric meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

BACKGROUND: Treatment of severe group A streptococcal infections requires timely and appropriate antibiotic therapy. We describe the epidemiology of antimicrobial-resistant invasive group A streptococcal (iGAS) infections in the U.S. METHODS: We analyzed population-based iGAS surveillance data at 10 U.S. sites from 2006-2017. Cases were defined as infection with GAS isolated from normally sterile sites or wounds in patients with necrotizing fasciitis or streptococcal toxic shock syndrome. GAS isolates were emm typed. Antimicrobial susceptibility was determined using broth microdilution or whole genome sequencing. We compared characteristics among patients infected with erythromycin nonsusceptible (EryNS) and clindamycin nonsusceptible (CliNS) strains to those with susceptible infections. We analyzed proportions of EryNS and CliNS among isolates by site, year, risk factors and emm type. RESULTS: Overall, 17,179 iGAS cases were reported; 14.5% were EryNS. Among isolates tested for both inducible and constitutive CliNS (2011-2017), 14.6% were CliNS. Most (99.8%) CliNS isolates were EryNS. Resistance was highest in 2017 (EryNS: 22.8%; CliNS: 22.0%). All isolates were susceptible to beta-lactams. EryNS and CliNS infections were most frequent among persons aged 18-34 years and in persons residing in long-term care facilities, experiencing homelessness, incarcerated, or who injected drugs. Patterns varied by site. Patients with nonsusceptible infections were significantly less likely to die. Emm types with >30% EryNS or CliNS included: 77, 58, 11, 83, 92. CONCLUSION: Increasing prevalence of EryNS and CliNS iGAS infections in the U.S. is predominantly due to expansion of several emm types. Clinicians should consider local resistance patterns when treating iGAS infections.

OBJECTIVES: Routine surveillance for streptococcal toxic shock syndrome (STSS), a severe manifestation of invasive group A Streptococcus (GAS) infections, likely underestimates its true incidence. The objective of our study was to evaluate routine identification of STSS in a national surveillance system for invasive GAS infections. METHODS: Active Bacterial Core surveillance (ABCs) conducts active population-based surveillance for invasive GAS disease in selected US counties in 10 states. We categorized invasive GAS cases with a diagnosis of STSS made by a physician as STSS-physician and cases that met the Council of State and Territorial Epidemiologists (CSTE) clinical criteria for STSS based on data in the medical record as STSS-CSTE. We evaluated agreement between the 2 methods for identifying STSS and compared the estimated national incidence of STSS when applying proportions of STSS-CSTE and STSS-physician among invasive GAS cases from this study with national invasive GAS estimates for 2017. RESULTS: During 2014-2017, of 7572 invasive GAS cases in ABCs, we identified 1094 (14.4%) as STSS-CSTE and 203 (2.7%) as STSS-physician, a 5.3-fold difference. Of 1094 STSS-CSTE cases, we identified only 132 (12.1%) as STSS-physician cases. Agreement between the 2 methods for identifying STSS was low (κ = 0.17; 95% CI, 0.14-0.19). Using ABCs data, we estimated 591 cases of STSS-physician and 3618 cases of STSS-CSTE occurred nationally in 2017. CONCLUSIONS: We found a large difference in estimates of incidence of STSS when applying different surveillance methods and definitions. These results should help with better use of currently available surveillance data to estimate the incidence of STSS and to evaluate disease prevention efforts, in addition to guiding future surveillance efforts for STSS.

BACKGROUND: Multiple case definitions are used to identify hospitalized patients with community-acquired acute respiratory infections (ARI). We evaluated several commonly used hospitalized ARI case definitions to identify influenza cases. METHODS: The study included all patients from a population-based surveillance site in Damanhour, Egypt hospitalized for a broad set of criteria consistent with community acquired ARIs. Naso- and oropharyngeal (NP/OP) swabs were tested for influenza using RT-PCR. Sensitivity, specificity and PPV for influenza identification was compared between the 2014 WHO Severe Acute Respiratory Infection (SARI) definition (fever ≥38°C and cough with onset within 10 days), the 2011 WHO SARI definition (fever ≥38°C and cough with onset within 7 days), the 2006 PAHO SARI definition, the International Emerging Infections Program (IEIP) pneumonia case definition, and the International Management of Childhood Illness (IMCI) case definitions for moderate and severe pneumonia. RESULTS: From June 2009-December 2012, 5768 NP/OP swabs were obtained from 6113 hospitalized ARI patients; 799 (13.9%) were influenza positive. The 2014 WHO SARI case definition captured the greatest number of ARI patients, influenza positive patients and ARI deaths compared to the other case definitions examined. Sensitivity for influenza detection was highest for the 2014 WHO SARI definition with 88.6%, compared to the 2011 WHO SARI (78.2%) the 2006 PAHO SARI (15.8%) the IEIP pneumonia (61.0%) and the IMCI moderate and severe pneumonia (33.8% and 38.9%) case definitions (IMCI applies to <5 only). CONCLUSIONS: Our results support use of the 2014 WHO SARI definition for identifying influenza positive hospitalized SARI cases as it captures the highest proportion of ARI deaths and influenza positive cases. Routine use of this case definition for hospital-based surveillance will provide a solid, globally comparable foundation on which to build needed response efforts for novel pandemic viruses.

In April 2017, surveillance detected a surge in severe acute respiratory infections (SARI) in Bangladesh. We collected specimens from SARI patients and asymptomatic controls for analysis with multipathogen diagnostic tests. Influenza A(H1N1)pdm09 was associated with the SARI epidemic, suggesting that introducing vaccines and empiric antiviral drugs could be beneficial.

INTRODUCTION: Etiology studies of severe acute respiratory infections (SARI) in adults are limited. We studied potential etiologies of SARI among adults in six countries using multi-pathogen diagnostics. METHODS: We enrolled both adults with SARI (acute respiratory illness onset with fever and cough requiring hospitalization) and asymptomatic adults (adults hospitalized with non-infectious illnesses, non-household members accompanying SARI patients, adults enrolled from outpatient departments, and community members) in each country. Demographics, clinical data, and nasopharyngeal and oropharyngeal specimens were collected from both SARI patients and asymptomatic adults. Specimens were tested for presence of 29 pathogens utilizing the Taqman® Array Card platform. We applied a non-parametric Bayesian regression extension of a partially latent class model approach to estimate proportions of SARI caused by specific pathogens. RESULTS: We enrolled 2,388 SARI patients and 1,135 asymptomatic adults from October 2013 through October 2015. We detected ≥1 pathogen in 76% of SARI patients and 67% of asymptomatic adults. Haemophilus influenzae and Streptococcus pneumoniae were most commonly detected (≥23% of SARI patients and asymptomatic adults). Through modeling, etiology was attributed to a pathogen in most SARI patients (range among countries: 57.3-93.2%); pathogens commonly attributed to SARI etiology included influenza A (14.4-54.4%), influenza B (1.9-19.1%), rhino/enterovirus (1.8-42.6%), and RSV (3.6-14.6%). CONCLUSIONS: Use of multi-pathogen diagnostics and modeling enabled attribution of etiology in most adult SARI patients, despite frequent detection of multiple pathogens in the upper respiratory tract. Seasonal flu vaccination and development of RSV vaccine would likely reduce the burden of SARI in these populations.

Background: Streptococcus pyogenes is a major cause of severe, invasive infections in humans. The bacterial pathogen harbors a wide array of virulence factors and exhibits high genomic diversity. Rapid changes of circulating strains in a community are common. Understanding the current prevalence and dynamics of S. pyogenes lineages could inform vaccine development and disease control strategies. Methods: We used whole-genome sequencing (WGS) to characterize all invasive S. pyogenes isolates obtained through the United States Center for Disease Control and Prevention’s Active Bacterial Core surveillance (ABCs) in 2016 and 2017. We determined the distribution of strain features, including emm type, antibiotic resistance determinants, and selected virulence factors. Changes in strain feature distribution between years 2016 and 2017 were evaluated. Phylogenetic analysis was used to identify expanding lineages within emm type. Results: Seventy-one emm types were identified from 3873 isolates characterized. The emm types targeted by a 30-valent M protein-based vaccine accounted for 3230 (89%) isolates. The relative frequencies of emm types collected during the 2 years were similar. While all isolates were penicillin-susceptible, erythromycin-resistant isolates increased from 273 (16% of 2016 isolates) to 432 (23% of 2017 isolates), mainly driven by increase of the erm-positive emm types 92 and 83. The prevalence of 24 virulence factors, including 11 streptococcal pyrogenic toxins, ranged from 6 to 90%. In each of three emm types (emm 49, 82, and 92), a subgroup of isolates significantly expanded between 2016 and 2017 compared to isolates outside of the subgroup (P-values < 0.0001). Specific genomic sequence changes were associated with these expanded lineages. Conclusions: While the overall population structure of invasive S. pyogenes isolates in the United States remained stable, some lineages, including several that were antibiotic-resistant, increased between 2016 and 2017. Continued genomic surveillance can help monitor and characterize bacterial features associated with emerging strains from invasive infections.

BACKGROUND: Reported outbreaks of invasive group A Streptococcus (iGAS) infections among people who inject drugs (PWID) and people experiencing homelessness (PEH) have increased, concurrent with rising US iGAS rates. We describe epidemiology among iGAS patients with these risk factors. METHODS: We analyzed iGAS infections from population-based Active Bacterial Core surveillance (ABCs) at 10 US sites from 2010 to 2017. Cases were defined as GAS isolated from a normally sterile site or from a wound in patients with necrotizing fasciitis or streptococcal toxic shock syndrome. GAS isolates were emm typed. We categorized iGAS patients into four categories: injection drug use (IDU) only, homelessness only, both, and neither. We calculated annual change in prevalence of these risk factors using log binomial regression models. We estimated national iGAS infection rates among PWID and PEH. RESULTS: We identified 12 386 iGAS cases; IDU, homelessness, or both were documented in ~13%. Skin infections and acute skin breakdown were common among iGAS patients with documented IDU or homelessness. Endocarditis was 10-fold more frequent among iGAS patients with documented IDU only versus those with neither risk factor. Average percentage yearly increase in prevalence of IDU and homelessness among iGAS patients was 17.5% and 20.0%, respectively. iGAS infection rates among people with documented IDU or homelessness were ~14-fold and 17- to 80-fold higher, respectively, than among people without those risks. CONCLUSIONS: IDU and homelessness likely contribute to increases in US incidence of iGAS infections. Improving management of skin breakdown and early recognition of skin infection could prevent iGAS infections in these patients.

BACKGROUND: To better understand how to prevent and respond to pneumococcal meningitis outbreaks in the meningitis belt, we retrospectively examined Burkina Faso's case-based meningitis surveillance data for pneumococcal meningitis clusters and assessed potential usefulness of response strategies. METHODS: Demographic and clinical information, and cerebrospinal fluid laboratory results for meningitis cases were collected through nationwide surveillance. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination; strains were serotyped using PCR. We reviewed data from 2011 to 2017 to identify and describe clusters of >/= 5 confirmed pneumococcal meningitis cases per week in a single district. We assessed whether identified clusters met the 2016 WHO provisional pneumococcal meningitis outbreak definition: a district with a weekly incidence of >5 suspected meningitis cases/100,000 persons, >60% of confirmed meningitis cases caused by Streptococcus pneumoniae, and >10 confirmed pneumococcal meningitis cases. RESULTS: Twenty pneumococcal meningitis clusters were identified, with a maximum weekly incidence of 7 cases and a maximum duration of 4 weeks. Most identified clusters (15/20; 75%) occurred before nationwide introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013. Most cases were due to serotype 1 (74%), 10% were due to PCV13 serotypes besides serotype 1, and 8 clusters had >1 serotype. While 6 identified clusters had a weekly incidence of >5 suspected cases/100,000 and all 20 clusters had >60% of confirmed meningitis cases due to S. pneumoniae, no cluster had >10 confirmed pneumococcal meningitis cases in a single week. CONCLUSIONS: Following PCV13 introduction, pneumococcal meningitis clusters were rarely detected, and none met the WHO provisional pneumococcal outbreak definition. Due to the limited cluster size and duration, there were no clear instances where reactive vaccination could have been useful. More data are needed to inform potential response strategies.

Respiratory pathogens, such as novel influenza A viruses, Middle East respiratory syndrome coronavirus (MERS-CoV), and now, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are of particular concern because of their high transmissibility and history of global spread (1). Clusters of severe respiratory disease are challenging to investigate, especially in resource-limited settings, and disease etiology often is not well understood. In 2014, endorsed by the Group of Seven (G7),* the Global Health Security Agenda (GHSA) was established to help build country capacity to prevent, detect, and respond to infectious disease threats.(dagger) GHSA is a multinational, multisectoral collaboration to support countries towards full implementation of the World Health Organization's International Health Regulations (IHR).( section sign) Initially, 11 technical areas for collaborator participation were identified to meet GHSA goals. CDC developed the Detection and Response to Respiratory Events (DaRRE) strategy in 2014 to enhance country capacity to identify and control respiratory disease outbreaks. DaRRE initiatives support the four of 11 GHSA technical areas that CDC focuses on: surveillance, laboratory capacity, emergency operations, and workforce development.( paragraph sign) In 2016, Kenya was selected to pilot DaRRE because of its existing respiratory disease surveillance and laboratory platforms and well-developed Field Epidemiology and Laboratory Training Program (FELTP) (2). During 2016-2020, Kenya's DaRRE partners (CDC, the Kenya Ministry of Health [MoH], and Kenya's county public health officials) conceptualized, planned, and implemented key components of DaRRE. Activities were selected based on existing capacity and determined by the Kenya MoH and included 1) expansion of severe acute respiratory illness (SARI) surveillance sites; 2) piloting of community event-based surveillance; 3) expansion of laboratory diagnostic capacity; 4) training of public health practitioners in detection, investigation, and response to respiratory threats; and 5) improvement of response capacity by the national emergency operations center (EOC). Progress on DaRRE activity implementation was assessed throughout the process. This pilot in Kenya demonstrated that DaRRE can support IHR requirements and can capitalize on a country's existing resources by tailoring tools to improve public health preparedness based on countries' needs.

Nicola N Lynskey and colleagues1 reported that a hypertoxigenic clone of emm1 group A streptococcus (M1UK), characterised by increased streptococcal pyrogenic exotoxin A (SpeA) production, has rapidly emerged in the UK since 2014. Large-scale genomic examinations of this M1UK clade indicated a single lineage in the global group A streptococcus genomic databases, with only one isolate identified in the USA in 2015.1,2 We investigated whether the M1UK lineage has expanded in the USA since 2015 using data from the Active Bacterial Core surveillance (ABCs) system of the US Centers for Disease Control and Prevention.

BACKGROUND: Group A Streptococcus (GAS) is a leading cause of acute respiratory infections frequently resulting in antibiotic prescribing. Vaccines against GAS are currently in development. METHODS: We estimated the incidence of healthcare visits and antibiotic prescribing for pharyngitis, sinusitis, and acute otitis media (AOM) in the United States using nationally-representative surveys of outpatient care provision, supplemented by insurance claims data. We estimated the proportion of these episodes attributable to GAS, and to GAS emm types included in a proposed 30-valent vaccine. We used these outputs to estimate the incidence of outpatient visits and antibiotic prescribing preventable by GAS vaccines with various efficacy profiles under infant and school-age dosing schedules. RESULTS: GAS pharyngitis causes 19.1 (95%CI: 17.3-21.1) outpatient visits and 10.2 (9.0-11.5) antibiotic prescriptions per 1,000 US persons aged 0-64 years, annually. GAS pharyngitis causes 93.2 (82.3-105.3) visits and 53.2 (45.2-62.5) antibiotic prescriptions per 1,000 children ages 3-9 years, annually, representing 5.9% (5.1-7.0%) of all outpatient antibiotic prescribing in this age group. Collectively, GAS-attributable pharyngitis, sinusitis, and AOM cause 26.9 (23.9-30.8) and 16.1 (14.0-18.7) outpatient visits and antibiotic prescriptions per 1,000 population, annually. A 30-valent GAS vaccine meeting the WHO 80% efficacy target could prevent 5.4% (4.6-6.4%) of outpatient antibiotic prescriptions among children aged 3-9 years. If vaccine prevention of GAS pharyngitis made routine antibiotic treatment of pharyngitis unnecessary, up to 17.1% (15.0-19.6%) of outpatient antibiotic prescriptions among children aged 3-9 years could be prevented. CONCLUSIONS: An efficacious GAS vaccine could prevent substantial incidence of pharyngitis infections and associated antibiotic prescribing in the United States.

Nearly 140 years after the initial culture of Streptococcus pyogenes or group A Streptococcus (GAS) from human skin lesions [1], the natural history of GAS colonization, transmission, and susceptibility to disease and subsequent immune response in the human host is incompletely understood. Vast differences in the distribution of genetically distinct categories of circulating GAS strains within different geographic regions and climates contribute significantly to the challenge of designing a global GAS vaccine. In this issue of The Journal of Infectious Diseases, Campbell and colleagues describe a 10-month, prospective, longitudinal study of group A streptococcal strains obtained from school children with impetigo and pharyngitis infections in Fiji, a tropical country in the South Pacific [2]. Impetigo infections were much more common than pharyngitis and causal strains represented many diverse M protein gene (emm) types.

BACKGROUND: In 2013, Burkina Faso introduced 13-valent pneumococcal conjugate vaccine (PCV13) into the routine childhood immunization program, to be administered to children at 8, 12, and 16 weeks of age. We evaluated the impact of PCV13 on pneumococcal meningitis. METHODS: Using nationwide surveillance, we gathered demographic/clinical information and cerebrospinal fluid (CSF) results for meningitis cases. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination; strains were serotyped using PCR. We compared annual incidence (cases per 100 000) 4 years after PCV13's introduction (2017) to average pre-PCV13 incidence (2011-2013). We adjusted incidence for age and proportion of cases with CSF tested at national laboratories. RESULTS: In 2017, pneumococcal meningitis incidence was 2.7 overall and 10.5 (<1 year), 3.8 (1-4 years), 3.5 (5-14 years), and 1.4 (>/=15 years) by age group. Compared to 2011-2013, PCV13-serotype incidence was significantly lower among all age groups, with the greatest decline among children aged <1 year (77%; 95% confidence interval [CI], 65%-84%). Among all ages, the drop in incidence was larger for PCV13 serotypes excluding serotype 1 (79%; 95% CI, 72%-84%) than for serotype 1 (52%; 95% CI, 44%-59%); incidence of non-PCV13 serotypes also declined (53%; 95% CI, 37%-65%). In 2017, 45% of serotyped cases among all ages were serotype 1 and 12% were other PCV13 serotypes. CONCLUSIONS: In Burkina Faso, meningitis caused by PCV13 serotypes continues to decrease, especially among young children. However, the concurrent decline in non-PCV13 serotypes and short pre-PCV13 observation period complicate evaluation of PCV13's impact. Efforts to improve control of serotype 1, such as switching from a 3 + 0 schedule to a 2 + 1 schedule, may improve overall control of pneumococcal meningitis in this setting.

Two near-identical clinical Streptococcus pyogenes isolates of emm subtype emm43.4 with a pbp2x missense mutation (T553K) were detected. Minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin were 8-fold higher, and the MIC for cefotaxime was 3-fold higher than for near-isogenic control isolates, consistent with a first-step in developing beta-lactam resistance.

The risk for invasive streptococcal infection has not been clearly quantified among persons experiencing homelessness (PEH). We compared the incidence of detected cases of invasive group A Streptococcus infection, group B Streptococcus infection, and Streptococcus pneumoniae (pneumococcal) infection among PEH with that among the general population in Anchorage, Alaska, USA, during 2002-2015. We used data from the Centers for Disease Control and Prevention's Arctic Investigations Program surveillance system, the US Census, and the Anchorage Point-in-Time count (a yearly census of PEH). We detected a disproportionately high incidence of invasive streptococcal disease in Anchorage among PEH. Compared with the general population, PEH were 53.3 times as likely to have invasive group A Streptococcus infection, 6.9 times as likely to have invasive group B Streptococcus infection, and 36.3 times as likely to have invasive pneumococcal infection. Infection control in shelters, pneumococcal vaccination, and infection monitoring could help protect the health of this vulnerable group.

An immunocompetent adult with asthma developed severe human metapneumovirus (HMPV) illness complicated by group A Streptococcus coinfection, progressing to ARDS and shock. Several coworkers had less severe HMPV infection. HMPV can cause severe respiratory illness in healthy adults and should be considered as a potential cause of community respiratory outbreaks.

BACKGROUND: Bacterial meningitis is a major cause of morbidity and mortality in sub-Saharan Africa. We analyzed data from the World Health Organization's (WHO) Invasive Bacterial Vaccine-preventable Diseases Surveillance Network (2011-2016) to describe the epidemiology of laboratory-confirmed Streptococcus pneumoniae (Spn), Neisseria meningitidis, and Haemophilus influenzae meningitis within the WHO African Region. We also evaluated declines in vaccine-type pneumococcal meningitis following pneumococcal conjugate vaccine (PCV) introduction. METHODS: Reports of meningitis in children <5 years old from sentinel surveillance hospitals in 26 countries were classified as suspected, probable, or confirmed. Confirmed meningitis cases were analyzed by age group and subregion (South-East and West-Central). We described case fatality ratios (CFRs), pathogen distribution, and annual changes in serotype and serogroup, including changes in vaccine-type Spn meningitis following PCV introduction. RESULTS: Among 49 844 reported meningitis cases, 1670 (3.3%) were laboratory-confirmed. Spn (1007/1670 [60.3%]) was the most commonly detected pathogen; vaccine-type Spn meningitis cases declined over time. CFR was the highest for Spn meningitis: 12.9% (46/357) in the South-East subregion and 30.9% (89/288) in the West-Central subregion. Meningitis caused by N. meningitidis was more common in West-Central than South-East Africa (321/954 [33.6%] vs 110/716 [15.4%]; P < .0001). Haemophilus influenzae (232/1670 [13.9%]) was the least prevalent organism. CONCLUSIONS: Spn was the most common cause of pediatric bacterial meningitis in the African region even after reported cases declined following PCV introduction. Sustaining robust surveillance is essential to monitor changes in pathogen distribution and to inform and guide vaccination policies.

Using population-based surveillance data, we quantified secondary invasive group A Streptococcus (iGAS) disease risk among household contacts. Disease risk in the 30 days post-exposure to an index case-patient was highest among individuals aged >/=65 years (4,122 cases/100,000 person-years) versus the annual background incidence of 4.0 cases/100,000 population of all ages.

The term group A Streptococcus is considered synonymous for the species Streptococcus pyogenes. We describe an emergent invasive S. dysgalactiae subspecies equisimilis lineage that obtained the group A antigen through a single ancestral recombination event between a group C S. dysgalactiae subsp. equisimilis strain and a group A S. pyogenes strain.

During 2014-2017, CDC Emerging Infections Program surveillance data reported that the occurrence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections associated with injection drug use doubled among persons aged 18-49 years residing in Monroe County in western New York.* Unpublished surveillance data also indicate that an increasing proportion of all Candida spp. bloodstream infections in Monroe County and invasive group A Streptococcus (GAS) infections in 15 New York counties are also occurring among persons who inject drugs. In addition, across six surveillance sites nationwide, the proportion of invasive MRSA infections that occurred in persons who inject drugs increased from 4.1% of invasive MRSA cases in 2011 to 9.2% in 2016 (1). To better understand the types and frequency of these infections and identify prevention opportunities, CDC and public health partners conducted a rapid assessment of bacterial and fungal infections among persons who inject drugs in western New York. The goals were to assess which bacterial and fungal pathogens most often cause infections in persons who inject drugs, what proportion of persons who inject use opioids, and of these, how many were offered medication-assisted treatment for opioid use disorder. Medication-assisted treatment, which includes use of medications such as buprenorphine, methadone, and naltrexone, reduces cravings and has been reported to lower the risk for overdose death and all-cause mortality in persons who use opioids (2,3). In this assessment, nearly all persons with infections who injected drugs used opioids (97%), but half of inpatients (22 of 44) and 12 of 13 patients seen only in the emergency department (ED) were not offered medication-assisted treatment. The most commonly identified pathogen was S. aureus (80%), which is frequently found on skin. Health care visits for bacterial and fungal infections associated with injection opioid use are an opportunity to treat the underlying opioid use disorder with medication-assisted treatment. Routine care for patients who continue to inject should include advice on hand hygiene and not injecting into skin that has not been cleaned or to use any equipment contaminated by reuse, saliva, soil, or water (4,5).

BACKGROUND: Determining the etiology of pneumonia is essential to guide public health interventions. Diagnostic test results, including from polymerase chain reaction (PCR) assays of upper respiratory tract specimens, have been used to estimate prevalence of pneumococcal pneumonia. However limitations in test sensitivity and specificity and the specimen types available make establishing a definitive diagnosis challenging. Prevalence estimates for pneumococcal pneumonia could be biased in the absence of a true gold standard reference test for detecting Streptococcus pneumoniae. METHODS: We conducted a case control study to identify etiologies of community acquired pneumonia (CAP) from April 2014 through August 2015 in Thailand. We estimated the prevalence of pneumococcal pneumonia among adults hospitalized for CAP using Bayesian latent class models (BLCMs) incorporating results of real-time polymerase chain reaction (qPCR) testing of upper respiratory tract specimens and a urine antigen test (UAT) from cases and controls. We compared the prevalence estimate to conventional analyses using only UAT as a reference test. RESULTS: The estimated prevalence of pneumococcal pneumonia was 8% (95% CI: 5-11%) by conventional analyses. By BLCM, we estimated the prevalence to be 10% (95% CrI: 7-16%) using binary qPCR and UAT results, and 11% (95% CrI: 7-17%) using binary UAT results and qPCR cycle threshold (Ct) values. CONCLUSIONS: BLCM suggests a > 25% higher prevalence of pneumococcal pneumonia than estimated by a conventional approach assuming UAT as a gold standard reference test. Higher quantities of pneumococcal DNA in the upper respiratory tract were associated with pneumococcal pneumonia in adults but the addition of a second specific pneumococcal test was required to accurately estimate disease status and prevalence. By incorporating the inherent uncertainty of diagnostic tests, BLCM can obtain more reliable estimates of disease status and improve understanding of underlying etiology.