Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Transmission Through Solid Organ Transplantation and Outcomes of Coronavirus Disease 2019 Among Recent Transplant Recipients.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmissible through lung transplantation, and outcomes among infected organ recipients may be severe. Transmission risk to extrapulmonary organ recipients and recent (within 30 days of transplantation) SARS-CoV-2-infected recipient outcomes are unclear. Methods: During March 2020-March 2021, potential SARS-CoV-2 transmissions through solid organ transplantation were investigated. Assessments included SARS-CoV-2 testing, medical record review, determination of likely transmission route, and recent recipient outcomes. Results: During March 2020-March 2021, approximately 42 740 organs were transplanted in the United States. Forty donors, who donated 140 organs to 125 recipients, were investigated. Nine (23%) donors and 25 (20%) recipients were SARS-CoV-2 positive by nucleic acid amplification test (NAAT). Most (22/25 [88%]) SARS-CoV-2-infected recipients had healthcare or community exposures. Nine SARS-CoV-2-infected donors donated 21 organs to 19 recipients. Of these, 3 lung recipients acquired SARS-CoV-2 infections from donors with negative SARS-CoV-2 testing of pretransplant upper respiratory tract specimens but from whom posttransplant lower respiratory tract (LRT) specimens were SARS-CoV-2 positive. Sixteen recipients of extrapulmonary organs from SARS-CoV-2-infected donors had no evidence of posttransplant COVID-19. All-cause mortality within 45 days after transplantation was 6-fold higher among SARS-CoV-2-infected recipients (9/25 [36%]) than those without (6/100 [6%]). Conclusions: Transplant-transmission of SARS-CoV-2 is uncommon. Pretransplant NAAT of lung donor LRT specimens may prevent transmission of SARS-CoV-2 through transplantation. Extrapulmonary organs from SARS-CoV-2-infected donors may be safely usable, although further study is needed. Reducing recent recipient exposures to SARS-CoV-2 should remain a focus of prevention.

Analysis of the initial lot of the CDC 2019-Novel Coronavirus (2019-nCoV) real-time RT-PCR diagnostic panel.

At the start of the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) designed, manufactured, and distributed the CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel for SARS-CoV-2 detection. The diagnostic panel targeted three viral nucleocapsid gene loci (N1, N2, and N3 primers and probes) to maximize sensitivity and to provide redundancy for virus detection if mutations occurred. After the first distribution of the diagnostic panel, state public health laboratories reported fluorescent signal in the absence of viral template (false-positive reactivity) for the N3 component and to a lesser extent for N1. This report describes the findings of an internal investigation conducted by the CDC to identify the cause(s) of the N1 and N3 false-positive reactivity. For N1, results demonstrate that contamination with a synthetic template, that occurred while the "bulk" manufactured materials were located in a research lab for quality assessment, was the cause of false reactivity in the first lot. Base pairing between the 3' end of the N3 probe and the 3' end of the N3 reverse primer led to amplification of duplex and larger molecules resulting in false reactivity in the N3 assay component. We conclude that flaws in both assay design and handling of the "bulk" material, caused the problems with the first lot of the 2019-nCoV Real-Time RT-PCR Diagnostic Panel. In addition, within this study, we found that the age of the examined diagnostic panel reagents increases the frequency of false positive results for N3. We discuss these findings in the context of improvements to quality control, quality assurance, and assay validation practices that have since been improved at the CDC.

SARS-CoV-2 Infections among Recent Organ Recipients, March-May 2020, United States.

We conducted public health investigations of 8 organ transplant recipients who tested positive for severe acute respiratory syndrome coronavirus 2 infection. Findings suggest the most likely source of transmission was community or healthcare exposure, not the organ donor. Transplant centers should educate transplant candidates and recipients about infection prevention recommendations.

Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020.

In the 10 months since the first confirmed case of coronavirus disease 2019 (COVID-19) was reported in the United States on January 20, 2020 (1), approximately 13.8 million cases and 272,525 deaths have been reported in the United States. On October 30, the number of new cases reported in the United States in a single day exceeded 100,000 for the first time, and by December 2 had reached a daily high of 196,227.* With colder weather, more time spent indoors, the ongoing U.S. holiday season, and silent spread of disease, with approximately 50% of transmission from asymptomatic persons (2), the United States has entered a phase of high-level transmission where a multipronged approach to implementing all evidence-based public health strategies at both the individual and community levels is essential. This summary guidance highlights critical evidence-based CDC recommendations and sustainable strategies to reduce COVID-19 transmission. These strategies include 1) universal face mask use, 2) maintaining physical distance from other persons and limiting in-person contacts, 3) avoiding nonessential indoor spaces and crowded outdoor spaces, 4) increasing testing to rapidly identify and isolate infected persons, 5) promptly identifying, quarantining, and testing close contacts of persons with known COVID-19, 6) safeguarding persons most at risk for severe illness or death from infection with SARS-CoV-2, the virus that causes COVID-19, 7) protecting essential workers with provision of adequate personal protective equipment and safe work practices, 8) postponing travel, 9) increasing room air ventilation and enhancing hand hygiene and environmental disinfection, and 10) achieving widespread availability and high community coverage with effective COVID-19 vaccines. In combination, these strategies can reduce SARS-CoV-2 transmission, long-term sequelae or disability, and death, and mitigate the pandemic's economic impact. Consistent implementation of these strategies improves health equity, preserves health care capacity, maintains the function of essential businesses, and supports the availability of in-person instruction for kindergarten through grade 12 schools and preschool. Individual persons, households, and communities should take these actions now to reduce SARS-CoV-2 transmission from its current high level. These actions will provide a bridge to a future with wide availability and high community coverage of effective vaccines, when safe return to more everyday activities in a range of settings will be possible.

Seroprevalence of hepatitis A virus antibodies in the U.S.: results from the National Health and Nutrition Examination Survey.

OBJECTIVES: We described seroprevalence of antibody to hepatitis A virus (anti-HAV) in the United States during 1999-2006 and compared it with seroprevalence before the availability of vaccine. METHODS: We analyzed data from the 1988-1994 and 1999-2006 National Health and Nutrition Examination Survey (NHANES) to obtain estimates of anti-HAV seroprevalence for the U.S. household population. We grouped region of residence based on the 1999 Advisory Committee on Immunization Practices recommendations into 17 states with any recommendation (vaccinating) and 33 states without any recommendation (non-vaccinating). RESULTS: During 1999-2006, the overall seroprevalence of anti-HAV was 34.9% (95% confidence interval [CI] 33.1, 36.7). During 1999-2006, U.S.-born children living in vaccinating states (33.8%, 95% CI 26.2, 42.2) had a higher seroprevalence than children in non-vaccinating states (11.0%, 95% CI 9.4, 12.8; p < 0.001). Seroprevalence among children increased from 8.0% (95% CI 6.3, 10.1) during 1988-1994 to 20.2% (95% CI 16.0, 24.8) during 1999-2006 (p < 0.001). For U.S.-born children aged 6-19 years, the strongest factor associated with seroprevalence was residence in vaccinating states. Among U.S.-born adults aged > 19 years, the overall age-adjusted seroprevalence of anti-HAV was 29.9% (95% CI 28.3, 31.5) during 1999-2006, which was not significantly different from the seroprevalence during 1988-1994 (32.2%, 95% CI 30.1, 34.4). CONCLUSIONS: Increases in seroprevalence among children in vaccinating states suggest a positive effect of the 1999 vaccination recommendations.

Incidence and transmission patterns of acute hepatitis C in the United States, 1982-2006.

BACKGROUND: Monitoring disease incidence and transmission patterns is important to characterize groups at risk for hepatitis C virus (HCV) infection. Clinical cases generally represent about 20% to 30% of all newly acquired infections. METHODS: We used sentinel surveillance to determine incidence and transmission patterns for acute hepatitis C in the United States using data from 25 years of population-based surveillance in the general community. Acute cases of hepatitis C were identified from 1982 through 2006 by a stimulated passive surveillance system in 4 to 6 US counties. Cases were defined by a discrete onset of symptoms, alanine aminotransferase (ALT) levels greater than 2.5 times the upper limit of normal (×ULN), negative findings for serologic markers for acute hepatitis A and B, and positive findings for antibody to HCV or HCV RNA. Incidence and frequency of reported risk factors were the main outcome measures. RESULTS: Of 2075 patients identified, the median age was 31 years, 91.5% had ALT values greater than 7×ULN, 77.3% were jaundiced, 22.5% were hospitalized, and 1.2% died. Incidence averaged 7.4 per 100,000 individuals (95% confidence interval [CI], 6.4-8.5 per 100,000) during 1982 to 1989 then declined averaging 0.7 per 100,000 (95% CI, 0.5-1.0 per 100,000) during 1994 to 2006. Among 1748 patients interviewed (84.2%), injection drug use (IDU) was the most commonly reported risk factor. The average number of IDU-related cases declined paralleling the decline in incidence, but the proportion of IDU-related cases rose from 31.8% (402 of 1266) during 1982 to 1989 to 45.6% (103 of 226) during 1994 to 2006. Among IDU-related cases reported during 1994 to 2006, 56 of 61 individuals (91.8%) had been in a drug treatment program and/or incarcerated. CONCLUSIONS: The incidence of acute HCV declined substantially over the 25 years of population-based surveillance. Despite declines, IDU is the most common risk factor for new HCV infection.

The prevalence of hepatitis B virus infection in the United States in the era of vaccination.

BACKGROUND: Our objective was to assess trends in the prevalence of hepatitis B virus (HBV) infection in the United States after widespread hepatitis B vaccination. METHODS: The prevalence of HBV infection and immunity was determined in a representative sample of the US population for the periods 1999-2006 and 1988-1994. National Health and Nutrition Examination Surveys participants 6 years of age were tested for antibody to hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg), and antibody to hepatitis B surface antigen (anti-HBs). Prevalence estimates were weighted and age-adjusted. RESULTS: During the period 1999-2006, age-adjusted prevalences of anti-HBc (4.7%) and HBsAg (0.27%) were not statistically different from what they were during 1988-1994 (5.4% and 0.38%, respectively). The prevalence of anti-HBc decreased among persons 6-19 years of age (from 1.9% to 0.6%; P < .01) and 20-49 years of age (from 5.9% to 4.6%; P < .01) but not among persons 50 years of age (7.2% vs 7.7%). During 1999-2006, the prevalence of anti-HBc was higher among non-Hispanic blacks (12.2%) and persons of "Other" race (13.3%) than it was among non-Hispanic whites (2.8%) or Mexican Americans (2.9%), and it was higher among foreign-born participants (12.2%) than it was among US-born participants (3.5%). Prevalence among US-born children 6-19 years of age (0.5%) did not differ by race or ethnicity. Disparities between US-born and foreign-born children were smaller during 1999-1996 (0.5% vs 2.0%) than during 1988-1994 (1.0% vs 12.8%). Among children 6-19 years of age, 56.7% had markers of vaccine-induced immunity. CONCLUSIONS: HBV prevalence decreased among US children, which reflected the impact of global and domestic vaccination, but it changed little among adults, and approximately 730,000 US residents (95% confidence interval, 550,000-940,000) are chronically infected.

Reduction in hepatitis B virus seroprevalence among U.S.-born children of foreign-born Asian parents -- benefit of universal infant hepatitis B vaccination.

We demonstrate that after implementation of recommendations for universal infant hepatitis B vaccination, HBV infection prevalence among children of foreign-born Asian parents in Georgia declined dramatically; horizontal transmission of infection within households has occurred infrequently; and the vast majority of infants and children have received the recommended hepatitis B vaccinations. These results provide evidence of the success of the hepatitis B infant vaccination program and highlight its potential impact on reducing chronic HBV infection morbidity and mortality among U.S. populations at high risk.

Infection with hepatitis C virus among HIV-infected pregnant women in Thailand.

OBJECTIVE: The purpose of this study was to describe the epidemiology of coinfection with hepatitis C virus (HCV) and HIV among a cohort of pregnant Thai women. METHODS: Samples from 1771 pregnant women enrolled in three vertical transmission of HIV studies in Bangkok, Thailand, were tested for HCV. RESULTS: Among HIV-infected pregnant women, HCV seroprevelance was 3.8% and the active HCV infection rate was 3.0%. Among HIV-uninfected pregnant women, 0.3% were HCV-infected. Intravenous drug use by the woman was the factor most strongly associated with HCV seropositivity. Among 48 infants tested for HCV who were born to HIV/HCV coinfected women, two infants were HCV infected for an HCV transmission rate of 4.2% (95% 0.51-14.25%). CONCLUSIONS: HCV seroprevalence and perinatal transmission rates were low among this Thai cohort of HIV-infected pregnant women.

Differences in response to a hepatitis B vaccine booster dose among Alaskan children and adolescents vaccinated during infancy.

BACKGROUND: The duration of protection provided by hepatitis B vaccination is unknown, but the presence of immune memory can be evaluated indirectly by measuring the immune response to a booster dose of vaccine. METHODS: Participants included 74 adolescents (aged 11.7-14.9 years) who had received a plasma-derived 3-dose primary vaccine series and 138 adolescents (aged 10.0-14.7 years) and 166 children (aged 5.0-7.0 years) who received a recombinant 3-dose primary vaccine series. All were born to hepatitis B surface antigen-negative mothers and had received the first dose of hepatitis B vaccine within 7 days of birth. The proportion of participants with serologic evidence of protective immunity (antibody to hepatitis B surface antigen > or = 10 mIU/mL) at baseline (prebooster), the proportion who developed an anamnestic response (increase to > or = 10 mIU/mL or at or more than fourfold increase in antibody to hepatitis B surface antigen to > 10 mIU/mL), and the geometric mean concentration by 1, 2, and 4 weeks after a 5-microg recombinant vaccine booster dose were determined. RESULTS: No participant had evidence of chronic hepatitis B virus infection. Overall, 99% of the group of children who received recombinant hepatitis B vaccine, 83% of the group of adolescents who received recombinant hepatitis B vaccine, and 69% of the group of adolescents who received the plasma-derived vaccine had an anamnestic response to a booster dose; among responders, the geometric mean concentration at 2 weeks postbooster was 3360 and 128 mIU/mL among adolescents who received plasma-derived vaccine with antibodies to hepatitis B surface antigen > or = 10 and < 10 mIU/mL at baseline, respectively, compared with 1283 and 369 mIU/mL among adolescents who received recombinant hepatitis B vaccine and 5091 and 696 mIU/mL for children who received recombinant hepatitis B vaccine. The anamnestic response rate at 2 weeks postbooster among participants with antibodies to hepatitis B surface antigen < 10 mIU/mL at baseline was inversely associated with age; 97% of 5-year-olds responded compared with 60% of 14-year-olds. CONCLUSIONS: Although most participants responded to a booster dose of hepatitis B vaccine, the significance of the increased proportion of nonresponses among older adolescents might indicate waning immune memory.

Near elimination of hepatitis B virus infections among Hawaii elementary school children after universal infant hepatitis B vaccination.

OBJECTIVES: Hawaii implemented routine infant hepatitis B vaccination in 1992 and required it for school entry in 1997. Previously, in 1989, a serologic survey among Hawaii school children in grades 1 to 3 indicated that 1.6% had chronic hepatitis B virus infection, and 2.1% had resolved infection. We conducted a follow-up survey to examine changes in hepatitis B virus infection rates. PATIENTS AND METHODS: This study was performed in Oahu, Hawaii, during the 2001-2002 school year among children in grades 2 and 3. Consenting parents/guardians provided demographic information including place of birth. Participants were tested for serologic evidence of hepatitis B virus infection and their vaccination status was determined by reviewing school records. Rates of symptomatic acute hepatitis B among persons aged < or = 19 years were calculated from cases reported from Hawaii to the Centers for Disease Control and Prevention between 1990 and 2004. RESULTS: Completed hepatitis B vaccination series were documented for 83% of the 2469 participants by age 18 months and for 97% by age 5 years. Past or present hepatitis B virus infection was detected among 6 participants (0.24%), including 1 (0.04%) with chronic infection and 5 (0.20%) with resolved infections. Compared with the 1989 survey, these prevalences represent declines of 97% and 90% in chronic and resolved hepatitis B virus infections, respectively. The incidence of symptomatic acute hepatitis B in Hawaii children and adolescents aged < or = 19 years decreased from 4.5 cases per 100,000 in 1990 to 0.0 during 2002-2004. To date, the last reported case in a child aged < 15 years in Hawaii occurred in 1996. CONCLUSIONS: Hepatitis B virus infection has nearly been eliminated in Hawaii children born after universal infant hepatitis B vaccination was implemented. These findings suggest that hepatitis B prevention goals are being met through routine immunization and related prevention programs among US children.

Changes in hepatitis C virus (HCV) viral load and interferon-alpha levels in HIV/HCV-coinfected patients treated with highly active antiretroviral therapy.

BACKGROUND: Reports are mixed as to whether highly active antiretroviral therapy (HAART) increases liver transaminase levels or hepatitis C virus (HCV) titers in HIV/HCV-coinfected individuals. It is hypothesized that increases in HCV RNA titers may result from changes in endogenous interferon-alpha (IFN-alpha) production. METHODS: HIV/HCV-coinfected patients receiving HAART were tested at baseline, 1, 2, 3, 6, and 9 months for liver transaminase levels, HIV and HCV viral loads, and IFN-alpha. Linear regression analysis was used to determine the effect of HAART on liver transaminase levels, HCV viral load, and IFN-alpha. RESULTS: Initiating HAART did not increase liver transaminase levels in majority of cases. In patients (n = 30) with baseline HIV titer >10,000 copies/mL, HCV titers increased 0.69 log10 and IFN-alpha decreased -0.96 log10 during HAART, in association with a > or =0.5 log10 decrease in HIV titer. As HIV titers reached their nadir approximately 4 months after initiation of HAART, HCV titers remained 0.54 log10 and IFN-alpha -0.71 log10 above and below baseline levels, respectively. HCV titers and IFN-alpha levels did not change from baseline in patients with baseline HIV titer < or =10,000 copies/mL. CONCLUSIONS: Coinfected patients did not have evidence of hepatoxicity HAART. In patients with baseline HIV titer >10,000 copies/mL, suppression of HIV replication by HAART was associated with an increase in HCV titer and a decrease in endogenous IFN-alpha levels.

The prevalence of hepatitis C virus infection in the United States, 1999 through 2002.

BACKGROUND: Defining the primary characteristics of persons infected with hepatitis C virus (HCV) enables physicians to more easily identify persons who are most likely to benefit from testing for the disease. OBJECTIVE: To describe the HCV-infected population in the United States. DESIGN: Nationally representative household survey. SETTING: U.S. civilian, noninstitutionalized population. PARTICIPANTS: 15,079 participants in the National Health and Nutrition Examination Survey between 1999 and 2002. MEASUREMENTS: All participants provided medical histories, and those who were 20 to 59 years of age provided histories of drug use and sexual practices. Participants were tested for antibodies to HCV (anti-HCV) and HCV RNA, and their serum alanine aminotransferase (ALT) levels were measured. RESULTS: The prevalence of anti-HCV in the United States was 1.6% (95% CI, 1.3% to 1.9%), equating to an estimated 4.1 million (CI, 3.4 million to 4.9 million) anti-HCV-positive persons nationwide; 1.3% or 3.2 million (CI, 2.7 million to 3.9 million) persons had chronic HCV infection. Peak prevalence of anti-HCV (4.3%) was observed among persons 40 to 49 years of age. A total of 48.4% of anti-HCV-positive persons between 20 and 59 years of age reported a history of injection drug use, the strongest risk factor for HCV infection. Of all persons reporting such a history, 83.3% had not used injection drugs for at least 1 year before the survey. Other significant risk factors included 20 or more lifetime sex partners and blood transfusion before 1992. Abnormal serum ALT levels were found in 58.7% of HCV RNA-positive persons. Three characteristics (abnormal serum ALT level, any history of injection drug use, and history of blood transfusion before 1992) identified 85.1% of HCV RNA-positive participants between 20 and 59 years of age. LIMITATIONS: Incarcerated and homeless persons were not included in the survey. CONCLUSIONS: Many Americans are infected with HCV. Most were born between 1945 and 1964 and can be identified with current screening criteria. History of injection drug use is the strongest risk factor for infection.

Hepatitis C virus infection in Samoa and American Samoa.

Little is known about the prevalence of hepatitis C virus (HCV) in Pacific islands. In this study, serum specimens collected in 1985 and 2002 among the general populations of Samoa and American Samoa were tested for antibody to HCV by a third-generation enzyme immunoassay and a recombinant immunoblot assay. Of the 3,466 specimens tested, 8 (0.2%; 95% confidence interval = 0.07-0.4%) were positive for antibody to HCV. Prevalence did not vary by location or demographic characteristic. Thus, HCV is present in the Samoas but at a low prevalence.

Molecular epidemiology of foodborne hepatitis a outbreaks in the United States, 2003.

BACKGROUND: Molecular epidemiologic investigations can link geographically separate foodborne hepatitis A outbreaks but have not been used while field investigations are in progress. In 2003, outbreaks of foodborne hepatitis A were reported in multiple states. METHODS: Case-control studies were conducted in 3 states. Hepatitis A virus was sequenced from serologic specimens from individuals associated with outbreaks and from individuals concurrently ill with hepatitis A in non-outbreak settings in the United States and Mexico. RESULTS: Case-control studies in Tennessee (TN), North Carolina (NC), and Georgia (GA) found green onions to be associated with illness among restaurant patrons (TN: odds ratio [OR], 65.5 [95% confidence interval {CI}, 8.9-482.5; NC: OR, 2.4 [95% CI, 0.3-21.9]; GA: OR, 20.9 [95% CI, 3.9-110.3]). Viral sequences from TN case patients differed by 2 nt, compared with those from case patients in NC and GA. A third sequence, differing from the TN and GA/NC sequences by 1 nt, was identified among case patients in a subsequent outbreak in Pennsylvania. Each outbreak sequence was identical to > or =1 sequence isolated from northern Mexican resident(s) with hepatitis A. The sources of green onions served in restaurants in TN and GA were 3 farms in northern Mexico. CONCLUSIONS: Ongoing viral strain surveillance facilitated the rapid implementation of control measures. Incorporation of molecular epidemiologic methods into routine hepatitis A surveillance would improve the detection of hepatitis A outbreaks and increase our understanding of hepatitis A epidemiology in the United States.

Vaccination in the county jail as a strategy to reach high risk adults during a community-based hepatitis A outbreak among methamphetamine drug users.

Illicit drug use (IDU) is an important risk factor for hepatitis A, but implementing vaccination programs among drug users is difficult. During January 2001-July 2002, 403 hepatitis A cases were reported in Polk County, Florida; 48% were drug users and of these, 80% were recently in jail. To assess the county jail as a potential vaccination venue, we interviewed 280 inmates and conducted a serologic survey during July--August 2002. Of these, 227 (81%) reported a past IDU history. Previous HAV infection was found in 33%. In communities with illicit drug users at risk for hepatitis A and who are frequently jailed, vaccination programs in jails could be an important component of a community-based strategy to control hepatitis A outbreaks among illicit drug users.

The F-ATPase operon promoter of Streptococcus mutans is transcriptionally regulated in response to external pH.

Streptococcus mutans F-ATPase, the major component of the acid-adaptive response of the organism, is transcriptionally upregulated at low pH. Fusions of the F-ATPase promoter to chloramphenicol acetyltransferase indicated that pH-dependent expression is still observed with a short promoter that contains a domain conserved between streptococcal ATPase operons.

Guidelines for laboratory testing and result reporting of antibody to hepatitis C virus. Centers for Disease Control and Prevention.

Testing for the presence of antibody to hepatitis C virus (anti-HCV) is recommended for initially identifying persons with hepatitis C virus (HCV) infection (CDC. Recommendations for prevention and control of hepatitis C virus [HCV] infection and HCV-related chronic disease. MMWR 1998;47[No. RR-19] :1-33). Testing for anti-HCV should include use of an antibody screening assay, and for screening test-positive results, a more specific supplemental assay. Verifying the presence of anti-HCV minimizes unnecessary medical visits and psychological harm for persons who test falsely positive by screening assays and ensures that counseling, medical referral, and evaluation are targeted for patients serologically confirmed as having been infected with HCV. However, substantial variation in reflex supplemental testing practices exists among laboratories, and an anti-HCV-positive laboratory report does not uniformly represent a confirmed positive result. These guidelines expand recommendations for anti-HCV testing to include an option for reflex supplemental testing based on screening-test-positive signal-to-cut-off (s/co) ratios. Use of s/co ratios minimizes the amount of supplemental testing that needs to be performed while improving the reliability of reported test results. These guidelines were developed on the basis of available knowledge of CDC staff in consultation with representatives from the Food and Drug Administration and public health, hospital, and independent laboratories. Adoption of these guidelines by all public and private laboratories that perform in vitro diagnostic anti-HCV testing will improve the accuracy and utility of reported anti-HCV test results for counseling and medical evaluation of patients by health-care professionals and for surveillance by public health departments.

Genetic and biochemical characterization of the F-ATPase operon from Streptococcus sanguis 10904.

Oral streptococci utilize an F-ATPase to regulate cytoplasmic pH. Previous studies have shown that this enzyme is a principal determinant of aciduricity in the oral streptococcal species Streptococcus sanguis and Streptococcus mutans. Differences in the pH optima of the respective ATPases appears to be the main reason that S. mutans is more tolerant of low pH values than S. sanguis and hence pathogenic. We have recently reported the genetic arrangement for the S. mutans operon. For purposes of comparative structural biology we have also investigated the F-ATPase from S. sanguis. Here, we report the genetic characterization and expression in Escherichia coli of the S. sanguis ATPase operon. Sequence analysis showed a gene order of atpEBFHAGDC and that a large intergenic space existed upstream of the structural genes. Activity data demonstrate that ATPase activity is induced under acidic conditions in both S. sanguis and S. mutans; however, it is not induced to the same extent in the nonpathogenic S. sanguis. Expression studies with an atpD deletion strain of E. coli showed that S. sanguis-E. coli hybrid enzymes were able to degrade ATP but were not sufficiently functional to permit growth on succinate minimal media. Hybrid enzymes were found to be relatively insensitive to inhibition by dicyclohexylcarbodiimide, indicating loss of productive coupling between the membrane and catalytic subunits.