BACKGROUND: Several U.S. hospitals had surges in COVID-19 caseload, but their effect on COVID-19 survival rates remains unclear, especially independent of temporal changes in survival. OBJECTIVE: To determine the association between hospitals' severity-weighted COVID-19 caseload and COVID-19 mortality risk and identify effect modifiers of this relationship. DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT04688372). SETTING: 558 U.S. hospitals in the Premier Healthcare Database. PARTICIPANTS: Adult COVID-19-coded inpatients admitted from March to August 2020 with discharge dispositions by October 2020. MEASUREMENTS: Each hospital-month was stratified by percentile rank on a surge index (a severity-weighted measure of COVID-19 caseload relative to pre-COVID-19 bed capacity). The effect of surge index on risk-adjusted odds ratio (aOR) of in-hospital mortality or discharge to hospice was calculated using hierarchical modeling; interaction by surge attributes was assessed. RESULTS: Of 144 116 inpatients with COVID-19 at 558 U.S. hospitals, 78 144 (54.2%) were admitted to hospitals in the top surge index decile. Overall, 25 344 (17.6%) died; crude COVID-19 mortality decreased over time across all surge index strata. However, compared with nonsurging (<50th surge index percentile) hospital-months, aORs in the 50th to 75th, 75th to 90th, 90th to 95th, 95th to 99th, and greater than 99th percentiles were 1.11 (95% CI, 1.01 to 1.23), 1.24 (CI, 1.12 to 1.38), 1.42 (CI, 1.27 to 1.60), 1.59 (CI, 1.41 to 1.80), and 2.00 (CI, 1.69 to 2.38), respectively. The surge index was associated with mortality across ward, intensive care unit, and intubated patients. The surge-mortality relationship was stronger in June to August than in March to May (slope difference, 0.10 [CI, 0.033 to 0.16]) despite greater corticosteroid use and more judicious intubation during later and higher-surging months. Nearly 1 in 4 COVID-19 deaths (5868 [CI, 3584 to 8171]; 23.2%) was potentially attributable to hospitals strained by surging caseload. LIMITATION: Residual confounding. CONCLUSION: Despite improvements in COVID-19 survival between March and August 2020, surges in hospital COVID-19 caseload remained detrimental to survival and potentially eroded benefits gained from emerging treatments. Bolstering preventive measures and supporting surging hospitals will save many lives. PRIMARY FUNDING SOURCE: Intramural Research Program of the National Institutes of Health Clinical Center, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute.

Ivermectin is an antiparasitic medication approved by the US Food and Drug Administration (FDA) for use in humans. Ivermectin oral tablets are used worldwide for treatment of certain parasitic infections. An in vitro study has shown that ivermectin inhibits the replication of SARS-CoV-2 in tissue cell cultures.1 Some observational studies and clinical trials have evaluated ivermectin for the treatment and prevention of COVID-19 in humans; however, most had incomplete information and methodological limitations.2 Human data from well-designed and well-conducted clinical trials with robust sample sizes are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment or prevention of COVID-19.

BACKGROUND: Late sequelae of COVID-19 have been reported; however, few studies have investigated the time-course or incidence of late new COVID-19-related health conditions (post-COVID conditions) after COVID-19 diagnosis. Studies distinguishing post-COVID conditions from late conditions caused by other etiologies are lacking. Using data from a large administrative all-payer database, we assessed the type, association, and timing of post-COVID conditions following COVID-19 diagnosis. METHODS: Using the Premier Healthcare Database Special COVID-19 Release (PHD-SR) (release date, October 20, 2020) data, during March-June 2020, 27,589 inpatients and 46,857 outpatients diagnosed with COVID-19 (case-patients) were 1:1 matched with patients without COVID-19 through the 4-month follow-up period (control-patients) by using propensity score matching. In this matched-cohort study, adjusted odds ratios were calculated to assess for late conditions that were more common in case-patients compared with control-patients. Incidence proportion was calculated for conditions that were more common in case-patients than control-patients during 31-120 days following a COVID-19 encounter. RESULTS: During 31-120 days after an initial COVID-19 inpatient hospitalization, 7.0% of adults experienced at least one of five post-COVID conditions. Among adult outpatients with COVID-19, 7.7% experienced at least one of ten post-COVID conditions. During 31-60 days after an initial outpatient encounter, adults with COVID-19 were 2.8 times as likely to experience acute pulmonary embolism as outpatient control-patients and were also more likely to experience a range of conditions affecting multiple body systems (e.g. nonspecific chest pain, fatigue, headache, and respiratory, nervous, circulatory, and gastrointestinal system symptoms) than outpatient control-patients. Children with COVID-19 were not more likely to experience late conditions than children without COVID-19. CONCLUSIONS: These findings add to the evidence of late health conditions possibly related to COVID-19 in adults following COVID-19 diagnosis and can inform health care practice and resource planning for follow-up COVID-19 care.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a newly identified and serious health condition associated with SARS-CoV-2 infection. Clinical manifestations vary widely among patients with MIS-C, and the aim of this study was to investigate factors associated with severe outcomes. METHODS: In this retrospective surveillance study, patients who met the US Centers for Disease Control and Prevention (CDC) case definition for MIS-C (younger than 21 years, fever, laboratory evidence of inflammation, admitted to hospital, multisystem [≥2] organ involvement [cardiac, renal, respiratory, haematological, gastrointestinal, dermatological, or neurological], no alternative plausible diagnosis, and either laboratory confirmation of SARS-CoV-2 infection by RT-PCR, serology, or antigen test, or known COVID-19 exposure within 4 weeks before symptom onset) were reported from state and local health departments to the CDC using standard case-report forms. Factors assessed for potential links to severe outcomes included pre-existing patient factors (sex, age, race or ethnicity, obesity, and MIS-C symptom onset date before June 1, 2020) and clinical findings (signs or symptoms and laboratory markers). Logistic regression models, adjusted for all pre-existing factors, were used to estimate odds ratios between potential explanatory factors and the following outcomes: intensive care unit (ICU) admission, shock, decreased cardiac function, myocarditis, and coronary artery abnormalities. FINDINGS: 1080 patients met the CDC case definition for MIS-C and had symptom onset between March 11 and Oct 10, 2020. ICU admission was more likely in patients aged 6-12 years (adjusted odds ratio 1·9 [95% CI 1·4-2·6) and patients aged 13-20 years (2·6 [1·8-3·8]), compared with patients aged 0-5 years, and more likely in non-Hispanic Black patients, compared with non-Hispanic White patients (1·6 [1·0-2·4]). ICU admission was more likely for patients with shortness of breath (1·9 [1·2-2·9]), abdominal pain (1·7 [1·2-2·7]), and patients with increased concentrations of C-reactive protein, troponin, ferritin, D-dimer, brain natriuretic peptide (BNP), N-terminal pro B-type BNP, or interleukin-6, or reduced platelet or lymphocyte counts. We found similar associations for decreased cardiac function, shock, and myocarditis. Coronary artery abnormalities were more common in male patients (1·5 [1·1-2·1]) than in female patients and patients with mucocutaneous lesions (2·2 [1·3-3·5]) or conjunctival injection (2·3 [1·4-3·7]). INTERPRETATION: Identification of important demographic and clinical characteristics could aid in early recognition and prompt management of severe outcomes for patients with MIS-C. FUNDING: None.

This cross-sectional study examines changes in the outpatient retail dispensing frequency of proposed treatments for coronavirus disease 2019 after the March 13, 2020, declaration of a national emergency due to the pandemic.

Although much of the response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has focused on acute coronavirus disease 2019 (COVID-19) illness, accumulating evidence demonstrates morbidity beyond acute SARS-CoV-2 infection.1-4 At least 2 other periods of illness appear to be temporally associated with SARS-CoV-2 infection: a rare postacute hyperinflammatory illness and late inflammatory and virological sequelae. These 3 illness periods not only define the temporal course of SARS-CoV-2 infection at the population level but also capture distinct phases of host-viral interaction.

Coronavirus disease 2019 (COVID-19) is a complex clinical illness with potential complications that might require ongoing clinical care (1-3). Few studies have investigated discharge patterns and hospital readmissions among large groups of patients after an initial COVID-19 hospitalization (4-7). Using electronic health record and administrative data from the Premier Healthcare Database,* CDC assessed patterns of hospital discharge, readmission, and demographic and clinical characteristics associated with hospital readmission after a patient's initial COVID-19 hospitalization (index hospitalization). Among 126,137 unique patients with an index COVID-19 admission during March-July 2020, 15% died during the index hospitalization. Among the 106,543 (85%) surviving patients, 9% (9,504) were readmitted to the same hospital within 2 months of discharge through August 2020. More than a single readmission occurred among 1.6% of patients discharged after the index hospitalization. Readmissions occurred more often among patients discharged to a skilled nursing facility (SNF) (15%) or those needing home health care (12%) than among patients discharged to home or self-care (7%). The odds of hospital readmission increased with age among persons aged ≥65 years, presence of certain chronic conditions, hospitalization within the 3 months preceding the index hospitalization, and if discharge from the index hospitalization was to a SNF or to home with health care assistance. These results support recent analyses that found chronic conditions to be significantly associated with hospital readmission (6,7) and could be explained by the complications of underlying conditions in the presence of COVID-19 (8), COVID-19 sequelae (3), or indirect effects of the COVID-19 pandemic (9). Understanding the frequency of, and risk factors for, readmission can inform clinical practice, discharge disposition decisions, and public health priorities such as health care planning to ensure availability of resources needed for acute and follow-up care of COVID-19 patients. With the recent increases in cases nationwide, hospital planning can account for these increasing numbers along with the potential for at least 9% of patients to be readmitted, requiring additional beds and resources.

BACKGROUND: Countries are transitioning assets and functions from polio eradication to integrated immunization and surveillance activities. We assessed the extent of linkages between and perceptions of National Immunization Technical Advisory Groups (NITAGs) and National Certification Committees (NCCs) for polio eradication to understand how linkages can be leveraged to improve efficiencies of these expert bodies. METHODS: During May 2017 to May 2018, we administered a 15-question survey to a NITAG chair or member and an NCC counterpart in all countries of the WHO Regions for Africa (AFR) and for the Eastern Mediterranean (EMR) that had both a NITAG and an NCC. Data were analysed using frequency distributions. RESULTS: Of countries with both a NITAG and an NCC (n = 44), the response rate was 92% (22/24) in AFR and 75% (15/20) in EMR. Some respondents reported being very familiar with the functions of the other technical bodies, 36% (8/22) for NITAG members and 38% (14/37) for NCC members. Over 85% (51/59) of respondents felt it was somewhat useful or very useful to strengthen ties between bodies. Nearly all respondents (98%, 58/59) felt that NCC expertise could inform measles and rubella elimination programmes. CONCLUSIONS: We observed a broad consensus that human resource assets of NCCs may serve an important technical role to support national immunization policy-making. At this stage of the polio eradication initiative, countries should consider how to integrate the technical expertise of NCC members to reinforce NITAGs and maintain the polio essential functions, beginning in countries that have been polio-free for several years.

Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED).(†) These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 infections, deaths, and other severe outcomes among persons aged <21 years remains particularly important as schools reopen in the United States. Ongoing evaluation of effectiveness of prevention and control strategies will also be important to inform public health guidance for schools and parents and other caregivers.

Alcohol-based hand sanitizer is a liquid, gel, or foam that contains ethanol or isopropanol used to disinfect hands. Hand hygiene is an important component of the U.S. response to the emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). If soap and water are not readily available, CDC recommends the use of alcohol-based hand sanitizer products that contain at least 60% ethyl alcohol (ethanol) or 70% isopropyl alcohol (isopropanol) in community settings (1); in health care settings, CDC recommendations specify that alcohol-based hand sanitizer products should contain 60%-95% alcohol (≥60% ethanol or ≥70% isopropanol) (2). According to the Food and Drug Administration (FDA), which regulates alcohol-based hand sanitizers as an over-the-counter drug, methanol (methyl alcohol) is not an acceptable ingredient. Cases of ethanol toxicity following ingestion of alcohol-based hand sanitizer products have been reported in persons with alcohol use disorder (3,4). On June 30, 2020, CDC received notification from public health partners in Arizona and New Mexico of cases of methanol poisoning associated with ingestion of alcohol-based hand sanitizers. The case reports followed an FDA consumer alert issued on June 19, 2020, warning about specific hand sanitizers that contain methanol. Whereas early clinical effects of methanol and ethanol poisoning are similar (e.g., headache, blurred vision, nausea, vomiting, abdominal pain, loss of coordination, and decreased level of consciousness), persons with methanol poisoning might develop severe anion-gap metabolic acidosis, seizures, and blindness. If left untreated methanol poisoning can be fatal (5). Survivors of methanol poisoning might have permanent visual impairment, including complete vision loss; data suggest that vision loss results from the direct toxic effect of formate, a toxic anion metabolite of methanol, on the optic nerve (6). CDC and state partners established a case definition of alcohol-based hand sanitizer-associated methanol poisoning and reviewed 62 poison center call records from May 1 through June 30, 2020, to characterize reported cases. Medical records were reviewed to abstract details missing from poison center call records. During this period, 15 adult patients met the case definition, including persons who were American Indian/Alaska Native (AI/AN). All had ingested an alcohol-based hand sanitizer and were subsequently admitted to a hospital. Four patients died and three were discharged with vision impairment. Persons should never ingest alcohol-based hand sanitizer, avoid use of specific imported products found to contain methanol, and continue to monitor FDA guidance (7). Clinicians should maintain a high index of suspicion for methanol poisoning when evaluating adult or pediatric patients with reported swallowing of an alcohol-based hand sanitizer product or with symptoms, signs, and laboratory findings (e.g., elevated anion-gap metabolic acidosis) compatible with methanol poisoning. Treatment of methanol poisoning includes supportive care, correction of acidosis, administration of an alcohol dehydrogenase inhibitor (e.g., fomepizole), and frequently, hemodialysis.

Since the Global Polio Eradication Initiative (GPEI) was established in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been eradicated.* Transmission of WPV type 1 (WPV1) remains uninterrupted only in Afghanistan and Pakistan. This report summarizes progress toward global polio eradication during January 1, 2018-March 31, 2020 and updates previous reports (1,2). In 2019, Afghanistan and Pakistan reported the highest number of WPV1 cases (176) since 2014. During January 1-March 31, 2020 (as of June 19), 54 WPV1 cases were reported, an approximate fourfold increase from 12 cases during the corresponding period in 2019. Paralytic poliomyelitis can also be caused by circulating vaccine-derived poliovirus (cVDPV), which emerges when attenuated oral poliovirus vaccine (OPV) virus reverts to neurovirulence following prolonged circulation in underimmunized populations (3). Since the global withdrawal of type 2-containing OPV (OPV2) in April 2016, cVDPV type 2 (cVDPV2) outbreaks have increased in number and geographic extent (4). During January 2018-March 2020, 21 countries reported 547 cVDPV2 cases. Complicating increased poliovirus transmission during 2020, the coronavirus disease 2019 (COVID-19) pandemic and mitigation efforts have resulted in suspension of immunization activities and disruptions to poliovirus surveillance. When the COVID-19 emergency subsides, enhanced support will be needed to resume polio eradication field activities.

Since the Global Polio Eradication Initiative (GPEI) began in 1988, transmission of wild poliovirus (WPV) has been interrupted in all countries except Afghanistan, Nigeria, and Pakistan. WPV type 2 (WPV2) was declared eradicated in 2015; WPV type 3 has not been detected since 2012 (1). After the certification of the eradication of WPV2, a global switch from trivalent oral poliovirus vaccine (tOPV, containing vaccine virus types 1, 2, and 3) to bivalent oral poliovirus vaccine (bOPV, containing types 1 and 3) was completed in April 2016. Nigeria last reported WPV type 1 (WPV1) cases in 2016. This report describes global progress toward poliomyelitis eradication during January 1, 2017-March 31, 2019, and updates previous reports (1,2). Afghanistan and Pakistan reported their lowest annual number of WPV cases (22) in 2017; however, 33 WPV1 cases were reported in 2018. During January-March 2019 (as of May 3), 12 WPV1 cases had been reported worldwide, four more than the eight reported during the corresponding period in 2018. The occurrence of polio cases caused by circulating vaccine-derived poliovirus (cVDPV) is rare and occurs where oral poliovirus vaccine (OPV) coverage has been low and vaccine virus reverts to neurovirulence (3). Eight countries (Democratic Republic of the Congo [DRC], Indonesia, Mozambique, Niger, Nigeria, Papua New Guinea, Somalia, and Syria) reported 210 cVDPV cases during 2017-2019 (as of May 3). Reaching children during supplemental immunization activities (SIAs), accessing mobile populations at high risk, and variations in surveillance performance represent ongoing challenges. Innovative efforts to vaccinate every child and strengthen coordination efforts between Afghanistan and Pakistan will help achieve eradication. For cVDPV outbreak responses to promptly stop transmission, intensified programmatic improvements are needed to make the responses more effective and limit the risk for generating future outbreaks.

This report describes global progress towards polio eradication between January 2016 and March 2018 and updates previous reports. In 2017, 22 cases of polio due to WPV1 were reported, a 41% decrease from the 37 cases reported in 2016. As of 24 April 2018, 8 WPV1 cases had been reported (7 in Afghanistan and 1 in Pakistan), as compared with 5 cases during the same period in 2017. In Pakistan, continuing WPV1 transmission was confirmed in many areas in 2018 in samples isolated from wastewater. In Nigeria, ongoing endemic WPV1 transmission was confirmed in 2016;3 although WPV was not detected in 2017 and has not been detected in 2018 to date, limited access for vaccination and surveillance in insurgent-held areas in northeast Nigeria might result in continued undetected transmission of poliovirus. Substantial progress towards polio eradication has continued in recent years; however, WPV transmission can be interrupted only by overcoming the remaining challenges in reaching and vaccinating every missed child. Until poliovirus eradication is achieved, all countries must remain vigilant by maintaining high population immunity and sensitive poliovirus surveillance.

In 1988, when an estimated 350,000 cases of poliomyelitis occurred in 125 countries, the World Health Assembly resolved to eradicate polio globally. Transmission of wild poliovirus (WPV) continues uninterrupted in only three countries (Afghanistan, Nigeria, and Pakistan) (1), and among the three serotypes, WPV type 1 (WPV1) remains the only confirmed circulating type. This report describes global progress toward polio eradication during January 2016-March 2018, and updates previous reports (2). In 2017, 22 WPV1 cases were reported, a 41% decrease from the 37 WPV1 cases reported in 2016. As of April 24, 2018, eight WPV1 cases have been reported (seven in Afghanistan and one in Pakistan), compared with five cases during the same period in 2017. In Pakistan, continuing WPV1 transmission has been confirmed in multiple areas in 2018 by isolation from wastewater samples. In Nigeria, ongoing endemic WPV1 transmission was confirmed in 2016 (3); although WPV was not detected in 2017 or in 2018 to date, limitations in access for vaccination and surveillance in insurgent-held areas in northeastern Nigeria might permit continued undetected poliovirus transmission. Substantial progress toward polio eradication has continued in recent years; however, interruption of WPV transmission will require overcoming remaining challenges to reaching and vaccinating every missed child. Until poliovirus eradication is achieved, all countries must remain vigilant by maintaining high population immunity and sensitive poliovirus surveillance.

State immunization and cancer registries contain data that, if linked, could be used to monitor the impact of human papillomavirus (HPV) vaccine on cervical cancer and precancer. Michigan is uniquely positioned to examine these outcomes using two population-based resources: the state-wide cancer registry and immunization information system (IIS). We assessed the feasibility of identifying females in the IIS who had continuous Michigan residence and linking them to the cancer registry. We considered continuous residence necessary for future studies of vaccine impact to avoid misclassifying those who may have been immunized while residing out-of-state and whose immunization therefore may not have been reported in Michigan. We identified females with 1976-1996 birthdates in the IIS and used probabilistic linkage software to match them with Michigan birth records. A stratified random sample of IIS-birth matches was provided to a commercial locator service to identify females with continuous Michigan residence. Cervical carcinoma in situ cases diagnosed in 2006 among females aged 10 through 30 years were also matched with the birth records; cancer registry-birth matches were merged with the IIS-birth matches using the birth record identifier. Overall, 68% of the 1274,282 IIS and 61% of the 1358 cancer registry records could be matched with birth records. Among the sample of IIS-birth matches, most (86%) were continuous residents. Seventy percent or more of cancer registry-birth matches merged with IIS-birth matches for cases born after 1984. This is the first effort in the U.S. to show that linking records across IIS and cancer registries is practical and reasonably efficient. The increasing proportion of matches between the registries and live birth file with birth year, and the use of population-based data, strengthen the utility of this approach. Future steps include use of this method to examine incidence of cervical cancer precursors in HPV immunization-eligible females.

PURPOSE: The USA has a well-established network of central cancer registries (CCRs) that collect data using standardized definitions and protocols to provide population-based estimates of cancer incidence. The addition of cervical cancer precursors in select CCR operations would facilitate future studies measuring the population-level impact of human papillomavirus (HPV) vaccine. To assess the feasibility of collecting data on cervical cancer precursors, we conducted a multi-site surveillance study in three state-wide CCRs, to obtain annual case counts and compare rates of precursor lesions to those for invasive cervical cancer. METHODS: We developed standardized methods for case identification, data collection and transmission, training and quality assurance, while allowing for registry-specific strategies to accomplish surveillance objectives. We then conducted population-based surveillance for precancerous cervical lesions in three states using the protocols. RESULTS: We identified 5,718 cases of cervical cancer precursors during 2009. Age-adjusted incidence of cervical cancer precursors was 77 (Kentucky), 60 (Michigan), and 54 (Louisiana) per 100,000 women. Highest rates were observed in those aged 20-29 years: 274 (Kentucky), 202 (Michigan), and 196 (Louisiana) per 100,000. The variable with the most missing data was race/ethnicity, which was missing for 13 % of cases in Kentucky, 18 % in Michigan, and 1 % in Louisiana. Overall rates of cervical cancer precursors were over sixfold higher than invasive cervical cancer rates [rate ratios: 8.6 (Kentucky), 8.3 (Michigan), and 6.2 (Louisiana)]. CONCLUSIONS: Incorporating surveillance of cervical cancer precursors using existing CCR infrastructure is feasible and results in collection of population-based incidence data. Standardized collection of these data in high-quality registry systems will be useful in future activities monitoring the impact of HPV vaccination across states. As a result of this study, ongoing surveillance of these lesions has now been conducted in four CCRs since 2010.

BACKGROUND: We present data on Pap test results and HPV prevalence from the HPV Sentinel Surveillance project, a multiyear surveillance project enrolling women from a diverse set of 26 clinics throughout the US from 2003 to 2005. We use mathematical modeling to illustrate the potential timing and magnitude of decreases in Pap test abnormalities in sexually transmitted disease (STD), family planning, and primary care clinics in the US as a result of HPV vaccination. METHODS: The probability of an abnormal Pap result was based on three factors: (1) infection with HPV 16/18, or both; (2) infection with high-risk HPV types other than HPV 16/18; and (3) infection with HPV 6/11, or both. We estimated the relative reduction in the probability of an abnormal Pap result over the first 25 years of a female-only, quadrivalent HPV vaccination program, compared to a scenario of no HPV vaccination in which the probability of abnormal Pap results was assumed constant. RESULTS: The probability of an abnormal Pap result ranged from 7.0% for the lowest risk group (those without any high-risk HPV types and without HPV 6/11) to 45.2% for the highest risk group (those with HPV 16/18 and at least one other high-risk HPV type). Estimated reductions in abnormal Pap results among women in the 21- to 29-year age group were 0.8%, 10.2%, and 11.3% in years 5, 15, and 25 of the vaccine program respectively, in the lower vaccine coverage scenario, and 7.4%, 21.4%, and 22.2%, respectively, in the higher coverage scenario. CONCLUSIONS: Our results suggest that HPV vaccination will have a discernable impact on the probability of Pap abnormalities, but the timing and magnitude of the reduction will depend substantially on vaccine coverage and the degree of cross-protection against high risk HPV types other than HPV 16/18.

INTRODUCTION: From August to December 2011, a multidisciplinary group with expertise in mathematical modeling was constituted by the GAVI Alliance and the Bill & Melinda Gates Foundation to estimate the impact of vaccination in 73 countries supported by the GAVI Alliance. METHODS: The number of deaths averted in persons projected to be vaccinated during 2011-2020 was estimated for ten antigens: hepatitis B, yellow fever, Haemophilus influenzae type B (Hib), Streptococcus pneumoniae, rotavirus, Neisseria meningitidis serogroup A, Japanese encephalitis, human papillomavirus, measles, and rubella. Impact was calculated as the difference in the number of deaths expected over the lifetime of vaccinated cohorts compared to the number of deaths expected in those cohorts with no vaccination. Numbers of persons vaccinated were based on 2011 GAVI Strategic Demand Forecasts with projected dates of vaccine introductions, vaccination coverage, and target population size in each country. RESULTS: By 2020, nearly all GAVI-supported countries with endemic disease are projected to have introduced hepatitis B, Hib, pneumococcal, rotavirus, rubella, yellow fever, N. meningitidis serogroup A, and Japanese encephalitis-containing vaccines; 55 (75 percent) countries are projected to have introduced human papillomavirus vaccine. Projected use of these vaccines during 2011-2020 is expected to avert an estimated 9.9 million deaths. Routine and supplementary immunization activities with measles vaccine are expected to avert an additional 13.4 million deaths. Estimated numbers of deaths averted per 1000 persons vaccinated were highest for first-dose measles (16.5), human papillomavirus (15.1), and hepatitis B (8.3) vaccination. Approximately 52 percent of the expected deaths averted will be in Africa, 27 percent in Southeast Asia, and 13 percent in the Eastern Mediterranean. CONCLUSION: Vaccination of persons during 2011-2020 in 73 GAVI-eligible countries is expected to have substantial public health impact, particularly in Africa and Southeast Asia, two regions with high mortality. The actual impact of vaccination in these countries may be higher than our estimates because several widely used antigens were not included in the analysis. The quality of our estimates is limited by lack of data on underlying disease burden and vaccine effectiveness against fatal disease outcomes in developing countries. We plan to update the estimates annually to reflect updated demand forecasts, to refine model assumptions based on results of new information, and to extend the analysis to include morbidity and economic benefits.

BACKGROUND: Prevalence estimates from population-based surveys do not suffer from the same biases as case-report and clinic positivity data and may be better to monitor sexually transmitted disease morbidity over time. METHODS: We estimated the prevalence of Neisseria gonorrhoeae in a nationally representative sample of persons aged 14 to 39 years participating in the National Health and Nutrition Examination Survey. RESULTS: From 1999 to 2008, the overall prevalence of gonorrhea was 0.27% (95% confidence interval, 0.13%-0.47%). In the 2005 to 2006 and 2007 to 2008 cycles, prevalence approached 0% and was based on too few positive sample persons to obtain reliable estimates. In 2004, most infections were found in 1 survey location. DISCUSSION: Given the low prevalence and geographic clustering of disease, gonorrhea estimates from national probability surveys are often imprecise and unstable. In 2008, gonorrhea testing in National Health and Nutrition Examination Survey was discontinued. Continued surveillance of gonorrhea should include case reporting and prevalence estimates from local surveys and sentinel surveillance systems.

We investigated the feasibility of monitoring trends in prevalence of vaccine-preventable human papillomavirus (HPV) types in different clinic populations. We collected cervical specimens from women presenting to family planning, primary care, and sexually transmitted disease (STD) clinics for routine pap smears in five US cities during 2003-2005. We performed HPV genotyping and calculated annual type-specific prevalences; pre-vaccine era prevalence was highest for HPV 16 (6.0; 95% confidence interval [CI] 5.5-6.6%) and annual prevalences for vaccine-preventable types were stable, with few exceptions, after controlling for clinic type, age group, and city. With sufficient sample size and stable population characteristics, clinic-based surveillance systems can contribute to monitoring HPV vaccine impact in the cervical screening population.

BACKGROUND: We report the first population-based assessment of national trends in chlamydia prevalence in the United States. METHODS: We investigated trends in chlamydia prevalence in representative samples of the US population aged 14 to 39 years using data from five 2-year survey cycles of the National Health and Nutrition Examination Survey from 1999 to 2008. Prevalence estimates and 95% confidence intervals (CI) are reported stratified by age, gender, and race/ethnicity. Percent change in prevalence over this time period was estimated from regression models. RESULTS: In the 2007-2008 cycle, chlamydia prevalence among participants aged 14 to 39 years was 1.6% (95% CI: 1.1%-2.4%). Prevalence was higher among females (2.2%, 95% CI: 1.4%-3.4%) than males (1.1%, 95% CI: 0.7%-1.7%). Prevalence among non-Hispanic black persons was 6.7% (95% CI: 4.6%-9.9%) and was 2.5% (95% CI: 1.6%-3.8%) among adolescents aged 14 to 19 years. Over the five 2-year cycles, there was an estimated 40% reduction (95% CI: 8%-61%) in prevalence among participants aged 14 to 39 years. Decreases in prevalence were notable in men (53% reduction, 95% CI: 19%-72%), adolescents aged 14 to 19 years (48% reduction, 95% CI: 11%-70%), and adolescent non-Hispanic black persons (45%, reduction, 95% CI: 4%-70%). There was no change in prevalence among females aged 14 to 25 years, the population targeted for routine annual screening. CONCLUSIONS: On the basis of population estimates of chlamydia prevalence, the overall chlamydia burden in the United States decreased from 1999 to 2008. However, there remains a need to reduce prevalence in populations most at risk and to reduce racial disparities.

BACKGROUND: In April 2009, experts on sexually transmitted diseases (STDs) were convened to review updates on STD prevention and treatment in preparation for the revision of the Centers for Disease Control and Prevention (CDC) STD Treatment Guidelines. At this meeting, there was a discussion of important updates on human papillomavirus (HPV), genital warts, and cervical cancer screening. METHODS: Key questions were identified with assistance from an expert panel, and systematic reviews of the literature were conducted searching the English-language literature of the PubMed computerized database (US National Library of Medicine). The available evidence was reviewed, and new information was incorporated in the 2010 CDC STD Treatment Guidelines. RESULTS: Two HPV vaccines are now available, the quadrivalent HPV vaccine and the bivalent HPV vaccine; either vaccine is recommended routinely for girls aged 11 or 12 years. The quadrivalent HPV vaccine may be given to boys and men aged 9-26 years. A new patient-applied treatment option for genital warts, sinecatechins 15% ointment, is available and recommended for treatment of external genital warts. This product is a mixture of active ingredients (catechins) from green tea. Finally, updated counseling guidelines and messages about HPV, genital warts, and cervical cancer are included. CONCLUSIONS: This manuscript highlights updates to the 2010 CDC STD Treatment Guidelines for HPV and genital warts. Important additions to the 2010 STD Treatment Guidelines include information on prophylactic HPV vaccine recommendations, new patient-applied treatment options for genital warts, and counseling messages for patients on HPV, genital warts, cervical cancer screening, and HPV tests.

BACKGROUND: In April 2008, experts reviewed updates on sexually transmitted disease (STD) prevention and treatment in preparation for the revision of the Centers for Disease Control and Prevention (CDC) STD Treatment Guidelines. This included a review of cervical cancer screening in the STD clinical setting. METHODS: Key questions were identified with assistance from an expert panel. Reviews of the literature were conducted using the PubMed computerized database and shared with the panel. Updated information was incorporated in the 2010 CDC STD Treatment Guidelines. RESULTS: We recommend that STD clinics offering cervical screening services screen and treat women according to guidelines by the American College of Obstetrics and Gynecology, the American Cancer Society, the US Preventive Services Task Force, and the American Society for Colposcopists and Cervical Pathologists. New to the 2010 guidelines are higher age for initiating cervical screening (age >=21 years) and less frequent intervals of screening (at least every 3 years). New recommendations include new technologies, such as liquid-based cytology and high-risk human papillomavirus (HPV) DNA tests. Liquid-based technologies are not recommended over conventional testing. HPV DNA tests are recommended as adjunct tests and with new indications for use in cervical screening and management. Stronger recommendations were issued for STD clinics offering cervical screening services to have protocols in place for follow-up of test results and referral (eg, colposcopy). CONCLUSIONS: Important additions to the 2010 STD Treatment Guidelines include information on updated algorithms for screening and management of women and recommendations for use of liquid-based cytology and high-risk HPV testing.

BACKGROUND: Increased duration of hormonal contraceptive (HC) use may be positively associated with the risk of invasive cervical cancer. METHODS: This is a secondary analysis from the HPV Sentinel Surveillance Study. The authors examined the association between type-specific human papillomavirus (HPV) detection and current HC use among 7718 women attending 26 sexually transmitted disease, family planning and primary care clinics in the USA. RESULTS: There was an association between HC use and HPV-16 detection (adjusted prevalence rate ratio 1.34 (95% CI 1.05 to 1.71) for oral contraceptive users and 1.41 (1.01 to 2.04) for depot-medroxyprogesterone acetate users); there was no association between HC use and detection of other HPV types or any HPV overall. CONCLUSIONS: Longitudinal studies are needed to better define this type-specific association and its clinical significance.

Post-licensure evaluation of vaccines plays an important role in monitoring the progress of immunization programs, demonstrating population impact of vaccines, and providing data for ongoing policy decisions. Two human papillomovirus (HPV) vaccines are licensed and recommended for use in females in the United States, a quadrivalent human HPV vaccine, licensed in 2006 and a bivalent vaccine HPV vaccine licensed in 2009. HPV vaccination is recommended for females 11 or 12 years of age with catch-up vaccination through age 26 years. Post-licensure monitoring of the HPV vaccine program has included some of the same systems established for other vaccines, such as those for vaccine safety and coverage monitoring. However, monitoring HPV vaccine impact on infection and disease outcomes has required new efforts. While there are well established cancer registries in the United States, it will take decades before the impact of vaccine on cervical cancer is observed. More proximal measures of vaccine impact include outcomes such as prevalence of HPV vaccine types, incidence of cervical precancers and genital warts. We review systems in place or being established for post-licensure monitoring of HPV vaccine in the United States.

OBJECTIVE: Most young women initiate sexual activity during adolescence; risk for sexually transmitted infections (STIs) accompanies this initiation. In this study we estimated the prevalence of the most common STIs among a representative sample of female adolescents in the United States. METHODS: Data were analyzed from 838 females who were aged 14 to 19 and participating in the nationally representative National Health and Nutrition Examination Survey 2003-2004. After interview and examination, survey participants provided biological specimens for laboratory testing. The main outcome was weighted prevalence of at least 1 of 5 STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, herpes simplex virus type 2, and human papillomavirus (HPV) (any of 23 high-risk types or type 6 or 11). RESULTS: Prevalence of any of the 5 STIs was 24.1% among all and 37.7% among sexually experienced female adolescents. HPV (23 high-risk types or type 6 or 11) was the most common STI among all female adolescents (prevalence: 18.3%), followed by C trachomatis infection (prevalence: 3.9%). Prevalence of any of the STIs was 25.6% among those whose age was the same or 1 year greater than their age at sexual initiation and 19.7% among those who reported only 1 lifetime sex partner. CONCLUSIONS: The prevalence of STIs among female adolescents is substantial, and STIs begin to be acquired soon after sexual initiation and with few sex partners. These findings support early and comprehensive sex education, routine HPV vaccination at the age of 11 to 12 years, and C trachomatis screening of sexually active female adolescents.

BACKGROUND: Although the role of concurrent sexual partnerships (i.e., having sexual activity with another partner after a current partnership has been established) has been most strongly associated with the transmission of bacterial sexually transmitted infections, its role in the transmission of viral sexually transmitted infections, specifically human papillomavirus (HPV) is less clear. METHODS: Analysis of risk behavior data collected from 812 women screened for HPV as part of a sentinel surveillance project conducted in a family planning clinic, a primary care clinic, and 2 sexually transmitted disease clinics in Los Angeles, CA. RESULTS: The mean age of participants was 34.2 years (range: 18-65), with 31.8% identifying as African American 32.8% as Asian, and 28.4% as Hispanic. The overall prevalence of high-risk HPV (HR-HPV) was 21.7% and was higher among women who reported a concurrent partnership (25.7%) as compared to those who reported no concurrency (17.1%; P = 0.004). In multivariate analysis, concurrency was associated with HR-HPV and this relationship varied by race/ethnicity. Among Hispanic women those reporting a concurrent partnership were nearly twice as likely to have HR-HPV as compared to those who did not report concurrency (adjusted odds ration [AOR] = 1.71; 95% confidence interval [CI]: 1.13-2.58). However, among African American women those who reported a concurrent partnership were less likely to be diagnosed with HR-HPV (AOR = 0.60; 95% CI: 0.37-0.98). CONCLUSIONS: This study demonstrates that concurrency is associated with HR-HPV and that there may be differences by race/ethnicity in the individual or partnership characteristics of those who report concurrency.