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Eighty-five samples of shellfish (50 soft shell clams, 21 hard shell clams and 14 oysters) were examined for the presence of human enteric viruses. In addition, bacterial contamination levels, both fecal coliform and standard plate count, were determined. Seventy-five samples were harvested from open shellfish areas and 10 samples from restricted shellfish areas during seasonal opening. Enteroviruses were not detected in any of the samples tested. In contrast, 33 (30 from open beds and 3 from restricted areas) of 82 shellfish samples had levels of bacterial contamination that exceed current regulatory limits for shellfish.

Background The rate of cytomegalovirus (CMV) viral load increase and peak viral loads are associated with CMV disease in kidney and liver transplant recipients, but relationships to disease severity or mortality have not been shown. Methods Using stored serial serum specimens from renal (n = 59) and liver (n = 35) transplant recipients (D+R-; CMV-seropositive donors, CMV-seronegative recipients) from 2 prospective, randomized, controlled, interventional prophylaxis trials of CMV immune globulin (CMVIG), CMV viral load was measured using the COBAS quantitative polymerase chain reaction assay and the World Health Organization CMV standard. Patients with severe CMV-associated disease were classified according to trial definitions. Pairwise comparisons of mean viral load among deceased, surviving diseased, and nondiseased patients were analyzed by 2-way analysis of variance. To determine if viral load could predict mortality, receiver operating characteristic (ROC) curves were constructed using area under the curve (AUC) of the viral load and peak viral concentration (Vmax). Results Viral load (mean log10 [AUC], peak viral load [Vmax]) for patients with severe CMV disease was significantly higher compared with nondiseased patients (P < .001). Similarly, higher viral burden was significantly associated with mortality (P < .001). Viral load AUC and Vmax AUROCs for predicting mortality were 0.796 and 0.824, respectively, for renal patients, and 0.769 and 0.807, respectively, for liver patients. Conclusions Using specimens from studies preceding the antiviral prophylaxis era, CMV viral load was associated with severe CMV disease and death, supporting CMV viral load quantification as a proxy for CMV disease severity and disease-associated mortality end points in solid organ transplantation.

Background: Many public health laboratories adopting the U.S. HIV laboratory testing algorithm do not have a nucleic acid test (NAT), which is needed when the third- or fourth-generation HIV screening immunoassay is reactive and the antibody-based supplemental test is non-reactive or indeterminate. Objectives: Among public health laboratories utilizing public health referral laboratories for NAT conducted as part of the algorithm, we evaluated the percentage of screening immunoassays needing NAT, the number of specimens not meeting APTIMA (NAT) specifications, time to APTIMA result, the proportion of acute infections (i.e., reactive APTIMA) among total infections, and screening immunoassay specificity. Study design: From August 2012 to April 2013, 22 laboratories enrolled to receive free APTIMA (NAT) at New York or Florida public health referral laboratories. Data were analyzed for testing conducted until June 2013. Results: Submitting laboratories conducted a median of 4778 screening immunoassays; 0–1.3% (median 0.2%) needed NAT. Of 140 specimens received, 9 (6.4%) did not meet NAT specifications. The median time from specimen collection to reporting the 11 reactive NAT results was ten days, including six days from receipt in the submitting laboratory to shipment to the referral laboratory. Acute infections ranged from 0 to 12.5% (median 0%) of total infections. Third- and fourth-generation immunoassays met package insert specificity values. Conclusions: Public health referral laboratories provide a feasible option for conducting NAT. Reducing the time from specimen collection to submission of specimens for NAT is an important step toward maximizing the public health impact of identifying acute infections. Published by Elsevier B.V.

Background The Massachusetts Department of Public Health's (MDPH) Office of HIV/AIDS (OHA) and Hinton State Laboratory Institute (HSLI) have offered HIV screening since 1985. Point-of-care screening and serum collection for laboratory-based testing is conducted at clinic and non-clinic-based sites across Massachusetts as part of an integrated communicable disease screening intervention. Objectives and project design MDPH aimed to transition to a 4th generation HIV screening-based algorithm for testing all serum specimens collected at OHA-funded programs and submitted to the HSLI to detect acute HIV infections, detect and differentiate HIV-1 and HIV-2 infections, eliminate indeterminate results, reduce cost and turnaround time, and link newly diagnosed HIV+ individuals to care. The HSLI and OHA created a joint project management team to plan and lead the transition. Results The laboratory transitioned successfully to a 4th generation screening assay as part of a revised diagnostic algorithm. In the 12 months since implementation, a total of 7984 serum specimens were tested with 258 (3.2%) positive for HIV-1 and one positive for HIV-2. Eight were reported as acute HIV-1 infections. These individuals were linked to medical care and partner services in a timely manner. Turnaround time was reduced and the laboratory realized an overall cost savings of approximately 15%. Conclusions The identification of eight acute HIV infections in the first year underscores the importance of using the most sensitive screening tests available. A multi-disciplinary program and laboratory team was critical to the success of the transition, and the lessons learned may be useful for other jurisdictions.

Summary Objective In three U.S. State Public Health Laboratories (PHLs) using a fourth-generation immunoassay (IA), an HIV-1/HIV-2 differentiation antibody IA and a nucleic acid test (NAT), we characterized the yield and time to reporting of acute infections, and cost per positive specimen. Methods Routine HIV testing data were collected from July 1, 2012–June 30, 2013 for Massachusetts and Maryland PHLs, and from November 27, 2012–June 30, 2013 for Michigan PHL. Massachusetts and Michigan used fourth-generation and differentiation IAs with NAT conducted by a referral laboratory. In Maryland, fourth-generation IA repeatedly reactive specimens were followed by a Western blot (WB), and those with negative or indeterminate results were tested with a differentiation IA and HIV-1 NAT, and if positive by NAT, confirmed by a different HIV-1 NAT. Specimens from WB-positive persons at risk for HIV-2 were tested with a differentiation IA and, if positive, with an HIV-2 WB and/or differential HIV-1/HIV-2 proviral DNA polymerase chain reaction. Results Among 7914 specimens from Massachusetts PHL, 6069 from Michigan PHL, and 36,266 from Maryland PHL, 0.10%, 0.02% and 0.05% acute infections were identified, respectively. Massachusetts and Maryland PHLs each had 1 HIV-2 positive specimen. The median time from specimen receipt to laboratory reporting of results for acute infections at Massachusetts, Michigan and Maryland PHLs was 8, 11, and 7 days respectively. The laboratory cost per HIV positive specimen was $336 (Massachusetts), $263 (Michigan) and $210 (Maryland). Conclusions Acute and established infections were found by PHLs using fourth-generation IA in conjunction with antibody tests and NAT. Time to reporting of acute HIV test results to clients was suboptimal, and needs to be streamlined to expedite treatment and interrupt transmission.

Background Elevated serum iron levels have been associated with infectious outcomes in various patient populations but, to our knowledge, have never been studied after liver transplantation. Methods The relationship between serum iron levels and infectious outcomes after liver transplantation was evaluated in a nested case-control study using prospectively collected data and serum samples. Unadjusted and adjusted hazard ratios were calculated for each iron marker predictor variable (iron level, unsaturated iron-binding capacity, total iron-binding capacity, transferrin saturation, and ferritin level) and time to development of each of 6 outcomes (cytomegalovirus [CMV] disease, invasive fungal infection, bacteremia, invasive fungal infection or bacteremia, any infection, and 1-year mortality rate). Results Serum measurements (n = 109) corresponding to increased levels of serum iron were independently associated with an increased risk of any infection and death. After adjusting for the number of red blood cell transfusions, donor CMV-seropositive status, and fungal colonization, ferritin level was independently associated with the development of any infection (hazard ratio, 1.09; 95% confidence interval, 1.04-1.14). After adjusting for the number of red blood cell transfusions, development of CMV disease, and administration of intravenous steroids for treatment of rejection, ferritin level was also was independently associated with death (hazard ratio, 1.11; 95% confidence interval, 1.04-1.18). Similar results were found for unsaturated iron binding capacity for the same 2 outcomes. Conclusions A better understanding of iron metabolism and its relationship to infection could help guide future infection prognosis, prevention, and management efforts in this high-risk population.

In this study, we review annual rabies data from Massachusetts from 1985 to 2006, spanning the introduction of raccoon strain rabies in 1992. Of 52,034 animals tested, 9.7% (5,049/52,034) were rabid, representing 26 of over 67 species submitted. Bats were the most common rabid animals prior to 1992 (50 of 52), but raccoons (Procyon lotor) became the most common rabies-positive species upon arrival of raccoon strain rabies virus (38.2%, 2,728 of 7,138 tested), followed by striped skunks (Mephitis mephitis, 34.4%, 1,489 of 4,332), bats (5.3%, 427 of 8,053), foxes (red fox, Vulpes vulpes, and gray fox, Urocyon cinereoargenteus, 16.3%, 135 of 827), cats (0.8%, 136 of 18,050), and woodchucks (Marmota monax, 5.7%, 82 of 1,446). Cats were the most frequently tested animal (34.7%). Raccoon strain rabies spread from two foci of introduction with an initial epizootic phase of 4 yr, by which time most of the state was affected. In 1992, there was a transition from enzootic bat rabies, with little spillover to other animals, to terrestrial rabies associated with raccoon strain virus. Although raccoons were most affected by the raccoon strain virus, there was spillover to other species, particularly to skunks. The eastern United States raccoon rabies epizootic led to a marked increase in submissions for rabies testing and the number of positive animals detected; however, bat rabies cases remained at their previous levels. Wild animal rabies presents a significant threat to humans and domestic/companion animals and increased costs related to increased demand for rabies testing, postexposure prophylaxis as well as euthanasia of valuable domestic animals.

Background. To improve clinical and public health outcomes through early human immunodeficiency virus (HIV) detection, fourth-generation antigen/antibody immunoassay (4IA) and supplemental testing results must be returned rapidly. Methods. We examined HIV testing data at Harborview Medical Center (HMC), Massachusetts General Hospital (MGH), and the Medical University of South Carolina (MUSC), which used 4IA and supplemental antibody and nucleic acid tests (NATs). At MGH and MUSC, HIV-1 Western blot (WB) and HIV-2 testing were conducted at a reference laboratory. We compared time from specimen collection to laboratory result for established (positive WB) and acute infections (reactive 4IA, negative/indeterminate WB, detectable NAT), and we calculated testing cost per positive-test result. Results. From 3731 (MUSC) to 19 774 (MGH) tests were conducted; 0.01% (MGH) to 0.05% (HMC) were acute infections. Each laboratory had reactive 4IA, WB-negative, or indeterminate specimens without NAT (ie, potential acute infections). Time to result was 1.5 (HMC) to 5.2 days (MGH) for acute and 1.0 (HMC) to 5.2 days (MGH) for established infections. Costs were $1054 (MGH) to $1521 (MUSC). Conclusions. Conducting supplemental testing in-house lowered turnaround times, which may be further reduced with rapid HIV-1/HIV-2 differentiation tests. Hospitals may benefit from quantitative NATs not requiring physician orders, so all potential acute infections receive NAT.

BACKGROUND Recent studies suggest a substantial incidence of posttransplant hypogammaglobulinemia and an association with infection. METHODS We conducted a retrospective analysis of immunoglobulin (Ig) G levels from blood prospectively collected during a randomized double-blind placebo-controlled trial of cytomegalovirus (CMV) immune globulin that included 146 patients who underwent liver transplantation between December 1987 and June 1990. Serum samples collected at baseline and approximately weeks 4, 8, 12, 16, 24, and 32 posttransplant were analyzed. Hypogammaglobulinemia was defined as having at least one IgG level below 560 mg/dl. A variety of variables were analyzed as potential risk factors and outcomes of hypogammaglobulinemia. RESULTS A total of 613 samples from 112 patients were analyzed. Twenty-nine (26%) patients had posttransplant hypogammaglobulinemia. Fourteen (12.5%) had hypogammaglobulinemia at the time of their baseline measurement. There was a strong association between hypogammaglobulinemia and both one-year (P=0.0490) and five-year mortality (P=0.0187), even when adjusted for variables known to be associated with mortality (HR for one-year mortality 3.08, confidence interval 1.20, 7.91). Risk factors for hypogammaglobulinemia included only non A/non B hepatitis and "other diagnosis" (a category made up of rare causes of liver disease). None of the infectious outcomes examined, including CMV infection, CMV disease, bacteremia or invasive fungal disease, or rejection were significantly associated with hypogammaglobulinemia. CONCLUSIONS In orthotopic liver transplant recipients we found a 26% incidence of posttransplant hypogammaglobulinemia. Approximately half of these patients were hypogammaglobulinemic at baseline. A strong association between hypogammaglobulinemia and mortality was seen. Prospective studies are needed to further elucidate the risk factors and outcomes of posttransplant hypogammaglobulinemia.

The prevalence of human immunodeficiency virus (HIV) type 1 antiretroviral resistance is expected to be higher in recently infected antiretroviral-naive individuals than in those who have been infected longer. Antiretroviral-naive HIV-1-infected adults who presented to an outpatient clinic in an urban hospital in Boston for initial evaluation in 1999 were screened for drug-selected resistance mutations and phylogenetic subtype. Drug-selected mutations were identified in 16 (18%) of 88 subjects. Twelve (14%) included mutations associated with nucleoside reverse-transcriptase inhibitors, 4 (5%) included mutations associated with nonnucleoside reverse-transcriptase inhibitors, and 3 (3%) included mutations associated with protease inhibitors. Two (2%) had resistance mutations associated with multiple classes of drugs. Nine (10%) subjects had infection with non-B subtype HIV-1 and did not have drug-selected mutations. Serological results indicated infection for >/=6 months. Drug-selected mutations or non-B subtypes were detected in a substantial portion of antiretroviral-naive adults who had been infected for at least 6 months.

Presentation of Case A 38-year-old woman was admitted to the hospital in early August 2002 because of fever and confusion. The patient had been well until four days earlier, when a headache gradually developed and increased in intensity, accompanied by mild photophobia and stiffness of the neck. Two days before admission, she believed that she was mildly febrile. The day before admission, she was examined at another facility, where she was told she had a “viral illness.” She was given fluids intravenously and was discharged. On the morning of admission, she awoke with shaking chills and a temperature of 40°C. . . .

Background. Cytomegalovirus (CMV) infection and disease has been found to be associated with decreased graft and patient survival among heart transplant recipients. We sought to explore the effect of CMV infection and disease on long-term survival in orthotopic liver transplant (OLT) recipients using a derivation and validation cohort. Methods. For derivation-validation modeling, we used data collected from two prospectively followed cohorts as the basis for multivariate analyses: 167 OLT recipients from the Boston Center for Liver Transplantation (the derivation set; median follow-up: 5.5 years, mortality: 40%) and an independent cohort of 294 OLT recipients from the Mayo Clinic (the validation set; median follow-up: 4.8 years, mortality: 27%). Results. Underlying liver disease other than primary biliary cirrhosis or sclerosing cholangitis, number of units of red blood cells administered during transplantation, and donor CMV seropositivity were the pre- and intratransplant variables independently associated (P

Predictors of recurrent cytomegalovirus (CMV) disease after the first episode of successfully treated CMV disease in orthotopic liver transplant recipients were studied. Recurrent CMV disease was defined as disease diagnosed > 14 days after the end of a minimum 8-day course of ganciclovir therapy for the first episode and was classified as early or late if it occurred within or after 90 days, respectively, after completion of ganciclovir treatment. Eleven (27%) of 41 patients had recurrent CMV disease (nine early recurrences and two late recurrences). Death was more likely to occur in patients with recurrent CMV disease than in those without it (55% vs. 13%, respectively; P = .006). Initial episodes of multiorgan CMV disease (P = .001) and CMV pneumonia (P = .012) were associated with early recurrence. Multivariate analysis showed that multiorgan CMV disease was independently associated with early recurrence (P = .003; odds ratio, 13.5; 95% confidence interval, 2.4-76.8). Recognition of risk factors for recurrent CMV disease may help identify patients for whom a more intensive therapeutic or diagnostic approach is needed.

Cytomegalovirus (CMV) is a cause of considerable morbidity and mortality among orthotopic liver transplant (OLT) recipients. To study the impact of CMV on cost and hospital length of stay in this population, we undertook an analysis of a cohort of OLT recipients from four transplant centers in Boston who participated in a CMV prophylaxis trial. First posttransplant year hospital length of stay (including the hospital stay after transplantation and readmissions within 1 year after transplantation) was available for all 141 patients included in the study. In a multiple linear regression model bacteremia (P=0.0001), CMV disease (P=0.0007), abdominal reexploration (excluding retransplantation) (P=0.0070), recipient age < or = 16 years (P=0.0352), and the number of units of blood products (red blood cells, platelets, or fresh frozen plasma) administered during transplantation (P=0.0523) were shown to be independently associated with longer first posttransplant year hospital length of stay. Cost data for in-hospital care for the year beginning with admission for liver transplantation were available for 66 OLT recipients. Using a multiple linear regression model, development of CMV disease (P=0.0001), the number of units of blood products administered during transplantation (P=0.0001), bacteremia (P=0.0002), decreased pretransplant renal function (estimated by creatinine clearance) (P=0.0109), and need for retransplantation (P=0.0619) were shown to be independently associated with higher cost. These data strongly suggest that CMV disease has a direct impact on cost and hospital length of stay in liver transplantation.

The role of markers of cytomegalovirus (CMV) infection, such as the isolation of CMV, the presence of CMV antigenemia, or detection of viral DNA by polymerase chain reaction (PCR) assay, as predictors of subsequent CMV disease has been examined in recent studies. We studied the value of performing surveillance cultures of blood, urine, and throat specimens in a cohort of 156 liver transplant recipients who had participated in clinical trials and had received ganciclovir only for documented CMV disease. Cultures of urine and throat specimens for detection of CMV were performed every week, and cultures of blood specimens were performed every other week for the first 2 months after transplantation, then monthly for 6 months. Eighty-nine (57%) of 156 patients developed CMV infection, 41 (46%) of whom developed clinical CMV disease (36 had organ involvement and five had CMV syndrome). Fifty (32%) of 156 patients had positive blood cultures, 35 (22%) had positive urine cultures, and 41 (26%) had positive throat cultures. The positive and negative predictive values of surveillance cultures for predicting CMV disease were as follows: blood cultures, 46% and 83%, respectively; urine cultures, 26% and 74%, respectively; and throat cultures, 32% and 76%, respectively. These data indicate that such cultures are not useful in predicting CMV disease in liver transplant recipients. Future studies should examine the value of alternative markers, such as CMV antigenemia or the detection of viral DNA by PCR, for predicting CMV disease in this setting.

To define predictors of bacteremia and to assess the potential role of exposure to cytomegalovirus (CMV) as a risk factor for bacteremia in liver transplant recipients, an intention-to-treat analysis of data for 146 orthotopic liver transplant recipients who participated in a multicenter, randomized, intervention trial was undertaken. Fifty-eight episodes of bacteremia occurred in 40 (27.4%) of 146 patients within 1 year after transplantation. Bacteremia was diagnosed a median of 39.5 days (range, 1-325 days) after transplantation. One-year mortality rates were higher among patients with bacteremia than among those without bacteremia (47.5% [19 of 40] vs. 18% [19 of 106], respectively; P = .001). A time-dependent multivariate analysis of variables that were significantly (P < or = .05) associated with bacteremia in the univariate analysis showed that donor CMV seropositivity (relative risk [RR], 3.4; 95% confidence interval [CI], 1.6-6.6; P = .0005), age of younger than 16 years (RR, 2.6; 95% CI, 1.3-5.2; P < .0059), and a major abdominal operation after transplantation excluding retransplantation (RR, 3.8; 95% CI, 1.8-8.0; P = .0004) were independently associated with bacteremia. These epidemiologic data suggest that exposure to CMV from the donated organ is an independent risk factor for bacteremia in orthotopic liver transplant recipients.

Primary cytomegalovirus (CMV) infection in liver transplant recipients generally occurs following transmission via a CMV-seropositive donor organ. Occasionally primary infection arises in recipients of CMV-seronegative donor organs through blood transfusions. We studied the differences in clinical manifestations of primary CMV infection associated with these two modes of transmission, among 40 liver transplant recipients who had documented primary CMV infection post-transplantation. Thirty-one of 40 patients received a CMV-seropositive donor organ; CMV infection in the other nine patients was transfusion related. Symptomatic CMV disease (22 of 31 vs. 4 of 9; P = .06), CMV hepatitis (20 of 31 vs. 1 of 9; P = .007), invasive fungal disease (13 of 31 vs. 0 of 9; P = .03), and death (16 of 31 vs. 1 of 9; P = .06) were more likely to occur in patients with donor organ-associated primary CMV infection. The incubation period between transplantation and onset of CMV infection, a possible marker for viral load, was shorter in recipients of donor organ-transmitted CMV infection (median, 44 vs. 137 days; P = .004). Controlling for potential confounders such as immunosuppression did not alter these associations. Primary CMV infection associated with the donor organ has a more profound impact than primary infection associated with transfusion. These differences may be due to dissimilarities in the viral load associated with donated livers and transfused blood products.

Influenza and related pneumonia continue to cause significant amounts of morbidity and mortality despite the availability of effective vaccines. Two comparable counties in Massachusetts served as project areas of a national trial to see if reimbursement for immunizing Medicare-B eligible recipients against influenza would increase the use of the vaccine and reduce the costs attributed to related morbidity. Providers of health and social services to elders were recruited to participate in one county. A variety of professional and public education campaigns and media were used to promote influenza immunizations. Laboratory-based surveillance was instituted in both counties to assess the extent of circulating virus in each. Vaccine was made available to medical providers in both counties. While the amount of vaccine used in the comparison county increased by 6% from pre-project time (16,000 to 17,000 doses administered), vaccine use increased 219% in the intervention county (21,250 to 46,494 doses administered). In a post-project survey of participating physicians, 88% of 238 respondents reported administering less than 100 doses of influenza vaccine per year prior to the project. By the end of the project, only 32% administered less than 100 in the previous year. This project demonstrated the need for educating both the provider and the public in order to successfully promote immunizations. It was not clear, however, if reimbursement was a more important factor for promoting influenza immunizations than was universal distribution of free vaccine.

The incidence, predictors, and outcome of cytomegalovirus pneumonia in OLT recipients have not been well defined. We conducted an analysis of prospectively collected data from 141 OLT recipients who were included as part of a randomized, placebo-controlled trial of CMV immune globulin prophylaxis. Cytomegalovirus pneumonia was diagnosed in 13 of 141 (9.2%) OLT recipients during the first year posttransplant and was associated with a higher 1-year mortality compared with those recipients without CMV pneumonia (84.6 vs. 17.2%, P=0.0001). Univariate analysis demonstrated that CMV viremia (P=0.001), invasive fungal disease (P=0.0001), donor(+)/pretransplant recipient(-) CMV serologic status (P=0.013), abdominal operation (excluding retransplantation) after liver transplantation (P=0.0027), bacteremia (P=0.0105), and advanced United Network of Organ Sharing status (P=0.023) were associated with CMV pneumonia. Cytomegalovirus viremia was diagnosed in 11 of 13 patients with CMV pneumonia at a median of 11 days (range 1-66 days) before diagnosis of CMV pneumonia. In a multivariate analysis using a time-dependent, Cox proportional hazards model, CMV viremia (RR=8.6, 95% CI 1.8-39.7, P=0.0012), invasive fungal disease (RR=6.5, 95% CI 2.1-20.3, P=0.0001), and abdominal reoperation (RR=4.4, 95% CI 1.4-13.1, P=0.0043) were found to be independent predictors of CMV pneumonia. The attributable mortality associated with CMV pneumonia within the first year after liver transplantation for the patients with CMV pneumonia was 67.4%. Intensified measures for prevention of CMV should be considered for patients at high risk of developing CMV pneumonia.

Existing protocols for the detection of Mycobacterium tuberculosis Direct Test (MDT) inhibitors require substantial quantities of specimen and cannot distinguish Mycobacterium tuberculosis complex from other mycobacteria if inhibitors are present. We describe a preliminary evaluation of a simple and practical protocol for MTD inhibitor testing that circumvents these difficulties.

Passively acquired antibody may interfere with the active antibody response to live viral vaccines such as measles and rubella. To evaluate the duration of this inhibitory effect, we measured the measles and rubella antibody responses of Apache children immunized with measles, mumps, and rubella vaccine at varying intervals after administration of an immune globulin termed bacterial polysaccharide immune globulin (BPIG). This specific immune globulin contained measles and rubella antibody titers similar to those in standard intramuscularly and intravenously administered immune globulins. Antibody responses to measles vaccine were inhibited for up to 5 months after a BPIG dose of 80 mg IgG per kilogram of body weight, but responses to rubella vaccine were inhibited for only 2 months. Most children who had a decreased measles antibody response to primary measles, mumps, and rubella immunization given 1 1/2 to 4 months after BPIG administration responded to a booster immunization given 6 months after their last BPIG dose. We conclude that high doses of immune globulin (10 mg/kg) may inhibit the antibody response to measles for more than 3 months. We propose that the interval between administration of immune globulin and measles and rubella immunization be adjusted on the basis of the dose of immune globulin.

OBJECTIVE: We measured the seroprevalence of human immunodeficiency virus in women seeking reproductive services. STUDY dESIGN: Demographic and risk behavior data from women were linked anonymously to human immunodeficiency virus antibody results. RESULTS: The overall human immunodeficiency virus seropositivity rate of cord blood was 22 per 1000. Crude seroprevalence rates were higher for black women versus white women (25/1000 vs 22/1000) but lower for black Americans versus white Americans (21/1000 vs 29/1000). Human immunodeficiency virus infection was significantly higher for those women who acknowledged intravenous drug use (odds ratio 12.9, 95% confidence interval 7.3 to 22.7), were born in Haiti (odds ratio 2.6, 95% confidence interval 1.6 to 4.1), lacked prenatal care (odds ratio 2.2, 95% confidence interval 1.1 to 4.2), or received prenatal care at the hospital clinic versus a neighborhood health center (odds ratio 3.0, 95% confidence interval 1.7 to 5.3). The seroprevalence rates were 18/1000 for women seeking abortion and 16/1000 for women seeking family-planning services. CONCLUSION: Intravenous drug use and country of origin are major risk factors for human immunodeficiency virus infection in women, which may explain differences in seroprevalence rates in various racial or ethnic groups. Hospital-specific data on human immunodeficiency virus infection may be useful for monitoring the epidemic and allocating resources for education, counseling, testing, and prevention.

Human eastern equine encephalitis (EEE) is a life-threatening mosquito-borne disease. To determine whether mosquito abundance and EEE virus infection rates are associated with human EEE disease, we evaluated retrospectively a total of 592,637 mosquitoes and onset dates for 20 confirmed human cases over 26 years in Massachusetts. Annual Culiseta melanura populations at 10 defined sites decreased over the study period (P = 0.002). Weekly infection rates and number of infected Culiseta melanura captured per trap night were positively associated EEE cases (P < 0.023 and P < 0.001, respectively), whereas abundance was not (P = 0.077). The infection rate for Culiseta melanura of 0.39 per 1,000 tested mosquitoes identified human cases with a sensitivity of 0.87, a specificity of 0.82, a positive predictive value of 0.14, and a negative predictive value of 0.995. Timely mosquito testing and infection rate calculation are critical for disease risk estimation and outbreak control efforts.

Although U.S. prison inmates have higher rates of HIV infection than the general population, most inmates are not routinely tested for HIV infection at prison entry. The study objective was to implement a routine, voluntary HIV testing program in a Massachusetts county prison. During admission, inmates were given group HIV pre-test counseling and were subsequently offered private HIV testing. This intervention was compared to a control period during which HIV testing was provided only upon inmate or physician request. Between November 2004 and April 2005, 1,004 inmates met inclusion criteria and were offered routine, voluntary HIV testing. Of these, 734 (73.1%) accepted, 2 (0.3%) were HIV-infected, and 457 (45.5%) had been tested for HIV in the previous year. The testing rate of 73.1% was significantly increased from the rate of 18.0% (318 of 1,723) during the control period (p

In many developing countries and outside hospital settings, the characteristics of endemic Mycobacterium tuberculosis strains resistant to multiple drugs remain unknown. In a community-based referral and therapy program in northern Lima, Peru, beginning in 1996, patients found to be failures on standard regimens were referred for drug-susceptibility testing of their isolates, and those found to be infected with M. tuberculosis isolates resistant to at least rifampin were treated with individualized regimens based on their infecting strains. Isolates from 42 of these patients were subjected to DNA sequencing of the rpoB gene region responsible for rifampin resistance. We determined the frequency of types of mutations in the rpoB gene among these Peruvian isolates.

The enhanced Gen-Probe Amplified Mycobacterium Tuberculosis Direct (MTD) test was evaluated using a combined set of 338 acid-fast smear-positive and smear-negative, respiratory and nonrespiratory clinical specimens received by the Massachusetts State Tuberculosis Laboratory from September 1999 through March 2002. Microbiological culture was used as the reference method; therefore, the sensitivity and specificity of the MTD test were calculated for culture-positive specimens only. The initial assessment indicated that the overall sensitivity, specificity, and positive and negative predictive values of the MTD test for all specimens grouped together were 62, 98, 99, and 68%, respectively. A detailed discrepancy analysis revealed that two major factors causing negative MTD results in specimens that were culture positive for M. tuberculosis complex were patient treatment with antituberculosis drugs prior to testing and the presence of inhibitory substances in the specimen. Based on these findings, a protocol for optimizing MTD test performance in this setting is proposed in which (i) specimens from patients taking antituberculosis medications are excluded from testing and (ii) all initially MTD-negative or MTD-equivocal specimens are subjected to testing for inhibitors. If this strategy was followed, the MTD test sensitivity would be at least 91%, a significant improvement over the initial sensitivity of 62%. Accordingly, the negative predictive value would increase from 68 to 91%.

Recent electrophysiological and histopathological reports point to motor neurons in the anterior horn of the spinal cord and the brainstem as targets of severe West Nile virus (WNV) infection. We report histopathological confirmation of this poliomyelitis-like syndrome in a patient with WNV infection in Massachusetts.

To explore the possible interaction between human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) in patients who have undergone organ transplantation, stored serum samples from 139 orthotopic liver transplant recipients were tested for HHV-6 immunoglobulin (Ig) G and IgM antibodies. HHV-6 reactivation occurred in 87 patients (62.6%) and was associated with CMV disease (P = .01), severe CMV-associated disease (P = .01), older age (P = .005), and use of muromonab-CD3 (Orthoclone; Orthobiotech) as treatment for rejection (P = .02). Trends for an association between HHV-6 reactivation and invasive fungal disease (P = .12), bacteremia (P = .10), and graft loss (P = .12) were seen. In a multivariate analysis of risk factors for severe CMV-associated disease, HHV-6 reactivation (relative risk [RR], 3.5; 95% confidence interval [CI], 1.2-10.2; P = .02), CMV donor-positive-recipient-negative match (RR, 5.7; 95% CI, 2.5-13.2; P

Screening and confirmatory testing of cadaver organ donors for hepatitis C virus infection: A U.S. National Collaborative Study. Hepatitis C virus (HCV) can be transmitted by organ transplantation. Cadaver organ donors are screened for HCV infection by testing for antibodies to HCV (anti-HCV). The prevalence of HCV infection and performance of anti-HCV tests in detecting HCV infection in organ donors are unknown. Sera from 3078 cadaver organ donors were tested for anti-HCV by a first generation enzyme-linked immunosorbent assay (ELISA1). Sera from all 137 ELISA1 positive donors and a random sample of 92 ELISA1 negative donors were tested for anti-HCV by a second generation ELISA (ELISA2) and for HCV RNA by the polymerase chain reaction. Organ bank records were reviewed for risk factors associated with HCV infection. Follow-up was available on 70 recipients of organs from 42 ELISA2 positive donors. The prevalence of HCV RNA, extrapolated to all 3078 donors, was 2.4%. Liver disease, anti-HCV and HCV RNA were detected more frequently among recipients of organs from ELISA2 positive donors with HCV RNA than from ELISA2 positive donors without HCV RNA. Among donors, the sensitivity and negative predictive value of the ELISA2 for HCV RNA were 100%. However, despite a specificity of 98.1%, the positive predictive value was only 55.1%. Clinical and laboratory characteristics did not distinguish ELISA2 positive donors with and without HCV RNA. The presence of serum HCV RNA in organ donors predicts the risk of transmission of HCV infection. Discarding organs from ELISA2 positive donors would eliminate transmission, but organs from 1.88 percent of donors would be wasted. To reduce waste, it is necessary to develop confirmatory tests with a higher specificity for HCV RNA than those that are currently available.

Objective To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants. Design Randomized, multicenter, placebo-controlled, double-blind trial. Setting Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). Patients One hundred forty-one liver transplant recipients completed the study. Intervention CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16. Measurements Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness. Results Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group). Conclusion CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.

The use of CMVIG, approved in 1990 for prophylactic administration in seronegative recipients of kidneys from seropositive donors, has been shown to be extremely effective in preventing the considerable morbidity and mortality associated with CMV disease. While the complex interactions between CMV and the immune system, including the effects of immunosuppressive therapy, are still under investigation, passive immunization with CMVIG offers a practical, safe, and cost-effective means of clinical intervention in renal transplant patients known to be at risk for CMV disease. Further clinical studies will need to explore the mechanisms of interaction of CMVIG with reactivation of latent infection and superinfection and with allograft dysfunction and antirejection therapy. Studies that evaluate the use of CMVIG in combination with other pharmacologic and immunologic interventions, both for prevention and treatment of CMV disease, will guide the use of the drug. CMVIG promises to be most helpful in reducing morbidity and mortality in transplant recipients and other particularly at-risk populations such as those who are immunosuppressed iatrogenically.

Our study objective was to determine the cost-effectiveness of prophylaxis with cytomegalovirus immune globulin for preventing CMV-associated disease in renal transplant patients. We used a decision analytic model applied to 5 groups of renal transplant recipients at varying risks of developing CMV-associated disease. We obtained the rates of developing CMV-associated disease, graft rejection, and mortality, and the effectiveness of CMV-IG from the published literature. We used actual variable costs of CMV-IG, hospitalization, dialysis, and outpatient follow-up. The incremental cost of administering CMV-IG compared with withholding it ranged from $29,800 per life saved for the highest risk group, CMV-seronegative recipients of kidneys from CMV-seropositive cadaveric donors, to $1.68 million per additional life saved for the lowest risk group, CMV-seronegative recipients of grafts from CMV-seronegative donors. The outcome was somewhat sensitive to the effectiveness of CMV-IG in preventing CMV-associated disease but not sensitive to wide variations in CMV-IG costs, dialysis costs, outpatient costs, and the probability of graft rejection. Our conclusion is that prophylaxis with CMV-IG is very worthwhile for renal transplant recipients at high risk of CMV-associated disease and is possibly worthwhile for some patients at lower risk. The cost-effectiveness of other strategies for preventing CMV-associated disease, such as prophylaxis with acyclovir, CMV vaccine, or unselected immune globulin, should be compared with CMV-IG.

To assess the occupational risk of hepatitis B infection in emergency medical personnel, a seroepidemiologic survey of 87 emergency medical technicians and paramedics was conducted. Serologic markers indicating exposure to hepatitis B virus were detected in 18 percent. The prevalence of markers was associated with race (p = 0.006), with a relative risk of 3.5 (95 percent confidence interval 1.42 to 8.63) for nonwhites. Seropositivity was not associated with age, sex, previous clinical hepatitis, or blood transfusion. There was a suggestion that duration of employment as an emergency medical technician was related to the prevalence of hepatitis B markers (p = 0.11). Efforts to control the risk of hepatitis B infection in this profession are complicated by unique problems with postexposure prophylaxis and uncontrolled exposure to blood. Immunization with hepatitis B vaccine would be the optimal strategy to reduce infection in this high-risk occupation.

The seroprevalence of hepatitis B virus (HBV) markers and antibody to the delta agent (anti-delta) was determined for 112 parenteral drug abusers entering a methadone maintenance program. Markers of HBV infection were found in 87.5 percent of the group, and seropositivity was significantly associated with duration of drug abuse (p = 0.02). Antibody to the hepatitis B core antigen (anti-HBc) was present in all seropositive subjects; three (2.7 percent) were hepatitis B surface antigen-positive, and 16 (14.2 percent) had only anti-HBc. Five (10.6 percent) of 47 subjects with HBV markers had anti-delta. Anti-delta was more common in subjects who reported multiple symptomatic episodes of hepatitis (p = 0.02) and fewer than three daily drug injections (p = 0.05). Ten susceptible subjects received hepatitis B vaccine, and seroconversion rates at one, three, and six months were 20.0, 88.8, and 100 percent, respectively. The data indicate that hepatitis B vaccine is immunogenic in this population, and that anti-HBc is the optimal prevaccination screening test. Recent outbreaks of fulminant HBV and delta co-infection among drug abusers emphasize the need for early immunization in this group.

Host responses to hepatitis B infection in patients in a chronic hemodialysis unit. Host responses to hepatitis B infection were studied in 222 patients in a chronic hemodialysis unit. From 1970 to 1976, patients were monitored monthly for development of hepatitis B surface antigen (HB S Ag), antibody to hepatitis B surface antigen (anti-HB S ), and serum transaminase (SGPT) elevations. Five categories of patients were identified as: 1) chronic carriers of HB S Ag; 2) transiently HB S Ag(+), who developed anti HB S ; 3) HB S Ag(-) on admission, who developed anti-HB S without becoming HB S Ag(+); 4) anti-HB S (+) on admission; 5) uninfected, who remained HB S Ag(-) and anti-HB S (-). For a patient who became HB S Ag(+) in this clinic, the probability of becoming a chronic carrier was 62.8% and rose to 88.5% if he or she had been HB S Ag(+) for five consecutive months. Males were more likely to become chronic carriers, and females were more likely to develop anti-HB S . Neither age, race, nor type of underlying kidney disease was associated with particular host responses to hepatitis B virus. No effect of hepatitis B infection on mortality was detected. Variation in host response to hepatitis B infection among renal dialysis patients may affect the usefulness of hepatitis B hyperimmune globulin and hepatitis B vaccine and be related to the outcome of kidney transplantation. Reponse de l'hote a l'infection par le virus de l'hepatite B chez les malades d'une unite d'hemodialyse chronique. La reponse de l'hote a l'infection par le virus de l'hepatite B a ete etudiee chez 222 malades d'une unite d'hemodialyse chronique. De 1970 a 1976, une surveillance mensuelle a ete exercee chez ces malades pour detecter l'antigene de surface de l'hepatite B (HB S Ag), de l'anticorps dirige contre l'antigene de surface de l'hepatite B (anti-HB S ), et l'elevation des transaminases seriques. Cinq categories de malades ont ete identifiees: 1) des porteurs chroniques de HB S Ag, 2) des sujets transitoriment HB S Ag(+) qui ont developpe l'anti-HB S , 3) des sujets initialement HB S AG(-) qui ont developpe l'anti-HB S sans devenir HB S AG(+), 4) des anti-HB S (+) des l'admission, 5) des sujets non infectes qui sont restes HB S Ag(-) et anti-HB S (-). La probabilite qu'un malade qui est devenu HB S A(+) dans ce centre d'hemodialyse devienne un porteur chronique est de 62,8% et augmente a 88,5% s'il a ete HB S Ag(+) pendant cinq mois consecutifs. Les hommes ont une plus grande probabilite de devenir des porteurs chroniques et les femmes ont une plus grande probabilite d'apparition de l'anti-HB S . Ni l'âge, ni la race, ni la variete de la maladie renale sous-jacente ne sont associees a une reponse particuliere de l'hote au virus de l'hepatite B. Aucun effet de l'hepatite B sur la mortalite n'a ete observe. La variation de la reponse de l'hote a l'infection par le virus de l'hepatite B peut affecter l'utilite de la globuline hyperimmune specifique et du vaccin contre l'hepatite B et peut etre influencee par l'issue de la transplantation renale.

Experimentation dans 4 cas. 2 des 4 malades ont recu un rein d'un donneur positif pour le virus ; un seul a presente peut-etre une infection symptomatique

The structure of an hypothesized hybrid or “Lepore-type” IgG contained in the serum of donor 2904 was investigated. Previous immunological studies suggested that this serum contained IgG with aγ3-γ1 hybrid heavy chain consisting of aγ3 Fd portion and aγ1 Fc. Structural studies have now shown that the carboxyl terminal end of the 2904 hybrid IgG, including much of the Fc fragment, isγ1 in character. However, the fingerprints of the Fc tryptic peptides at both pH 3.6 and pH 6.4 included a peptide, possibly from the hinge region, in peptide maps of Fc from aγG3 Gm (5) myeloma protein, but absent from maps of Fc peptides fromγG1 proteins. Gel filtration of the CNBr fragments of Fc from 2904 suggested that the hinge region isγ3-like. Papain cleavage experiments indicated an elevated level of resistant IgG, which agrees with immunological findings of an increasedγG2 subclass level. Our data confirm previous reports that theγ chain C-terminal octadecapeptides fromγG3 proteins have a subclass specific residue of arginine and indicate that within this subclass there is an allotypic variation related to the Gm type of the protein.

Antibody to hepatitis-B core antigen (anti-HB c ) was assayed in the serum of patients with primary hepatic carcinoma (P.H.C.) and controls from Hong Kong, West Africa, and the United States. In each region the prevalence of anti-HB c was higher in P.H.C. patients than in controls, ranging from 70 to 95 % in the patients and from 20 to 68% in the controls from Asia and Africa; 24% of P.H.C. patients and 4% of controls from the U.S. had anti-HB c . These data support the hypothesis that chronic infection with hepatitis-B virus is aetiologically related to P.H.C., especially in Asia and Africa, although other factors must also be involved.

Sera containing hepatitis B surface antigen from 30 asymptomatic blood donors were assayed for e antigen (HBeAg) and antibody to e antigen (anti-HBe) by rheophoresis,. Fourteen samples (47%) had detectable HBeAg, ten (33%) had anti-HBe, and six (20%) had neither. DNA was extracted from 26 of these sera and assayed for its ability to anneal to a [32P]-DNA probe that is a copy of Dane particle DNA. All 10 HBeAg-positive samples tested contained DNA that formed specific hybrids with the DNA probe, as did one of 10 anti HBe-positive samples. Hybridization was not detected in nine sera containing anti-HBe and six sera without HBeAg or anti-HBe. Because the Dane particle is thought to be the hepatitis B virus, this association between HBeAg positivity and Dane particle DNA strongly supports the hypothesis that e antigen is a marker of the presence of the virus and, consequently, potential infectivity.

The variable patterns of clinical and serologic responses following exposure to hepatitis B virus (HBV) have been well documented (1,2,3,4). The common serologic profiles are charted using the markers listed in Table 1.

Twenty-eight health care workers who had a poor antibody response when initially vaccinated with hepatitis B vaccine were revaccinated with three additional 20-microgram doses. Eight of the twenty nonresponders, who had levels of antibody to hepatitis B surface antigen (anti-HBs) of less than 8 estimated radioimmunoassay (RIA) units, and all 8 of the hyporesponders, who had anti-HBs levels of 8 or 16 RIA units, attained anti-HBs levels of 36 RIA units or more after revaccination. Tests for HLA-A, B, C, and DR; for complement proteins C2, C4A, C4B, and BF; and for the erythrocyte enzyme glyoxalase I were done in 17 nonresponders and 3 hyporesponders. Nine (45%) had HLA-DR7 and 8 (40%) had HLA-DR3, compared with an expected rate of 23% in the general population. At least one of two extended haplotypes (B44, DR7, FC31 or B8, DR3, SCO1) were detected in 6 of the 9 who did not respond to revaccination, compared with 2 of 11 who responded to a second course of vaccine. Poor responders to vaccine may benefit from revaccination, and genetic factors may modulate the immune response to vaccination.

Recently a new virus has been described which infects woodchucks, Marmota monax. This virus, named woodchuck hepatitis virus (WHV) is closely related to human hepatitis virus (HBV). The virions have the same principal antigenic system involving surface and core determinants and a serological relationship has been found. WHV has also a DNA polymerase associated with the core. It has previously been reported that trisodium phosphonoformate (PFA) but not phosphonoacetic acid (PAA) inhibits DNA polymerase associated with HBV. This investigation shows the same type of inhibition pattern by PFA and PAA on WHV DNA polymerase.

We assessed the ability of radioimmunoassay for hepatitis B e antigen (HBeAg) to predict infectivity in exposed medical personnel by analyzing 390 samples of sera positive for hepatitis B surface antigen (HBsAg) that were implicated in accidental inoculations of known outcome. The radioimmunoassay detected HBeAg or its antibody (anti-HBe) in 91% of the donor sera. The incidence of hepatitis B was 19% (44 of 234) in recipients of HBeAg-positive sera but was only 2.5% (three of 121) in recipients of sera positive for anti-HBe, and nil (none of 35) in recipients of sera negative for HBeAg and anti-HBe. The known relation of HBeAg and infectivity was quantified by radioimmunoassay as a risk ratio of 10:1 (HBeAg-positive to HBeAg-negative) for this type of exposure. The sensitivity of the radioimmunoassay also showed that a large proportion (55%) of donor sera not producing hepatitis were positive for HBeAg; therefore, even the most flagrant needlestick exposures to HBsAg-positive sera often must involve subthreshold amounts of infective material.

In a double-blind trial, we randomly assigned 1330 high-risk health care personnel to receive three 20-micrograms doses of hepatitis B vaccine or placebo. Among vaccine recipients 58% responded within 1 month and 97% within 9 months; there was no difference in immune response to the vaccine between men and women. Efficacy was evaluated after a mean follow-up of only 13.2 months, just before the vaccine was released commercially. Five hepatitis B infections were identified in placebo recipients and one in a vaccine recipient. Although the number of infections was too small to allow confident conclusions about protective efficacy of the vaccine, we saw a 67% reduction in the need for hepatitis B immune globulin after accidental hepatitis B inoculation in the vaccine group (relative risk, 5.08; 95% confidence intervals, 1.3 to 19.9). Minor side effects occurred with equal frequency after vaccine (28.7%) and placebo (27.2%) injections; no participant had a severe adverse reaction. Vaccination with the 20-micrograms hepatitis B vaccine was highly immunogenic and safe in health care workers.