Michael J. Beach

The Natural History of Community-Acquired Hepatitis C in the United States

BACKGROUND Chronic liver disease develops in more than half of patients with post-transfusion hepatitis C, but little is known about the natural history of community-acquired hepatitis C. METHODS In 1985 and 1986 we identified adults with acute non-A, non-B hepatitis in four counties in the United States and followed them prospectively. We used three markers to detect hepatitis C virus (HCV) infection in stored samples of serum: antibody to HCV (anti-HCV) detected by second-generation serologic assays; HCV RNA detected by polymerase-chain-reaction assay; and antibody to HCV antigen (anti-HCVAg) detected by fluorescent-antibody-blocking assay. RESULTS Of 130 patients with non-A, non-B hepatitis, 106 (82 percent) had HCV infection, 93 were positive for anti-HCV, and 13 were positive only for HCV RNA or anti-HCVAg. Chronic hepatitis developed in 60 (62 percent) of 97 HCV-infected patients followed for 9 to 48 months, with no relation to the risk factors for infection. Ten of the 30 patients who had liver biopsies had chronic active hepatitis. In samples collected 42 to 48 months after the onset of hepatitis, HCV RNA was detected in 12 of 13 tested patients with chronic hepatitis and in all 15 tested patients with hepatitis that had resolved. Anti-HCV persisted in all but two of the initially positive patients, for a rate of antibody loss of 0.6 per 100 person-years. CONCLUSIONS Patients with community-acquired hepatitis C have a high rate of chronic hepatitis. HCV may be a major cause of chronic liver disease in the United States, and in most patients HCV infection seems to persist for at least several years, even in the absence of active liver disease.

Causes of Outbreaks Associated with Drinking Water in the United States from 1971 to 2006

SUMMARY Since 1971, the CDC, EPA, and Council of State and Territorial Epidemiologists (CSTE) have maintained the collaborative national Waterborne Disease and Outbreak Surveillance System (WBDOSS) to document waterborne disease outbreaks (WBDOs) reported by local, state, and territorial health departments. WBDOs were recently reclassified to better characterize water system deficiencies and risk factors; data were analyzed for trends in outbreak occurrence, etiologies, and deficiencies during 1971 to 2006. A total of 833 WBDOs, 577,991 cases of illness, and 106 deaths were reported during 1971 to 2006. Trends of public health significance include (i) a decrease in the number of reported outbreaks over time and in the annual proportion of outbreaks reported in public water systems, (ii) an increase in the annual proportion of outbreaks reported in individual water systems and in the proportion of outbreaks associated with premise plumbing deficiencies in public water systems, (iii) no change in the annual proportion of outbreaks associated with distribution system deficiencies or the use of untreated and improperly treated groundwater in public water systems, and (iv) the increasing importance of Legionella since its inclusion in WBDOSS in 2001. Data from WBDOSS have helped inform public health and regulatory responses. Additional resources for waterborne disease surveillance and outbreak detection are essential to improve our ability to monitor, detect, and prevent waterborne disease in the United States.

High sensitivity of children to swimming-associated gastrointestinal illness: results using a rapid assay of recreational water quality.

Background: Culture-based methods of monitoring fecal pollution in recreational waters require 24 to 48 hours to obtain results. This delay leads to potentially inaccurate management decisions regarding beach safety. We evaluated the quantitative polymerase chain reaction (QPCR) as a faster method to assess recreational water quality and predict swimming-associated illnesses. Methods: We enrolled visitors at 4 freshwater Great Lakes beaches, and contacted them 10 to 12 days later to ask about health symptoms experienced since the visit. Water at the beaches was polluted by point sources that carried treated sewage. We tested water samples daily for Enterococcus using QPCR and membrane filtration (EPA Method 1600). Results: We completed 21,015 interviews and tested 1359 water samples. Enterococcus QPCR cell equivalents (CEs) were positively associated with swimming-associated gastrointestinal (GI) illness (adjusted odds ratio per 1 log10 QPCR CE =1.26; 95% confidence interval = 1.06–1.51). The association between GI illness and QPCR CE was stronger among children aged 10 years and below (1.69; 1.24–2.30). Nonenteric illnesses were not consistently associated with Enterococcus QPCR CE exposure, although rash and earache occurred more frequently among swimmers. Enterococcus QPCR CE exposure was more strongly associated with GI illness than Enterococcus measured by membrane filtration. Conclusions: Measurement of the indicator bacteria Enterococci in recreational water using a rapid QPCR method predicted swimming-associated GI illness at freshwater beaches polluted by sewage discharge. Children at 10 years or younger were at greater risk for GI illness following exposure.

Evaluation of Three Commercial Assays for Detection of Giardia and Cryptosporidium Organisms in Fecal Specimens

ABSTRACT There is an increasing demand for diagnostic testing for Giardia intestinalis (G. lamblia) and Cryptosporidium parvum, with a priority being placed on obtaining diagnostic results in an efficient and timely manner. Several commercial companies have developed rapid diagnostic tests that are simple to perform and can be completed in less time than traditional methods for detecting Giardia and Cryptosporidium. We compared one of these rapid tests, the ImmunoCard STAT! (Meridian Bioscience, Inc.) lateral-flow immunoassay, with the MERIFLUOR direct fluorescent-antibody (DFA) test, the ProSpecT EZ microplate assay for Giardia and the ProSpecT microplate assay for Cryptosporidium, and modified Kinyouns acid-fast stained smears for the detection of Cryptosporidium using 246 specimens. The MERIFLUOR DFA (Meridian Bioscience, Inc.) test detected the largest number of cases (32 Giardia and 37 Cryptosporidium) infections and was used to calculate the sensitivity and specificity of the other tests. For Giardia, the sensitivities of the ImmunoCard STAT! and the ProSpecT Giardia EZ microplate assay (Alexon-Trend, Inc.) were 81 and 91%, respectively. For detection of Cryptosporidium, the sensitivities of the ImmunoCard STAT!, the ProSpecT Cryptosporidium microplate assay (Alexon-Trend, Inc.), and modified Kinyouns acid-fast stained smears were 68, 70, and 78%, respectively. Test specificities were equal to or greater than 99%. Specimens with very small numbers of organisms were not detected by the ImmunoCard STAT!, the ProSpecT microplate assay or modified Kinyouns acid-fast stained smears.

Hepatitis C virus antigen in hepatocytes: immunomorphologic detection and identification.

Hepatitis C virus (HCV) antigen was detected immunohistochemically using fluorescein isothiocyanate-labeled immunoglobulin G fractions from chimpanzee and human sera strongly reactive with recombinant hepatitis C virus structural and non-structural proteins. The antigen was localized in the cytoplasm of hepatocytes in all 9 chimpanzees with acute hepatitis C, in 5 of 10 chimpanzees with chronic HCV infection, and in 11 of 12 patients with chronic hepatitis C. The specificity of the hepatocellular HCV and FITC-labeled probes for HCV was ascertained by blocking studies with paired serum samples obtained from 8 infected and uninfected chimpanzees or from 14 patients during the acute and chronic phases of HCV infection. Absorption experiments on FITC-labeled probes with selected host proteins (normal liver homogenate, plasma proteins, red blood cells) did not indicate cross reactivity of the probes with these antigens. Direct immunomorphologic evidence for the HCV specificity of hepatocellular HCV antigen deposits and the FITC-labeled polyclonal anti-HCVAg probe was established in absorption experiments using recombinant HCV nonstructural proteins. The putative HCV NS3 protein was the most prominent component of hepatocellular HCV antigen.

Rapidly measured indicators of recreational water quality and swimming-associated illness at marine beaches: a prospective cohort study.

IntroductionIn the United States and elsewhere, recreational water quality is monitored for fecal indicator bacteria to help prevent swimming-associated illnesses. Standard methods to measure these bacteria take at least 24 hours to obtain results. Molecular approaches such as quantitative polymerase chain reaction (qPCR) can estimate these bacteria faster, in under 3 hours. Previously, we demonstrated that measurements of the fecal indicator bacteria Enterococcus using qPCR were associated with gastrointestinal (GI) illness among swimmers at freshwater beaches. In this paper, we report on results from three marine beach sites.MethodsWe interviewed beach-goers and collected water samples at marine beaches affected by treated sewage discharges in Mississippi in 2005, and Rhode Island and Alabama in 2007. Ten to twelve days later, we obtained information about gastrointestinal, respiratory, eye, ear and skin symptoms by telephone. We tested water samples for fecal indicator organisms using qPCR and other methods.ResultsWe enrolled 6,350 beach-goers. The occurrence of GI illness among swimmers was associated with a log10-increase in exposure to qPCR-determined estimates of fecal indicator organisms in the genus Enterococcus (AOR = 2.6, 95% CI 1.3-5.1) and order Bacteroidales (AOR = 1.9, 95% CI 1.3-2.9). Estimates of organisms related to Clostridium perfringens and a subgroup of organisms in the genus Bacteroides were also determined by qPCR in 2007, as was F+ coliphage, but relationships between these indicators and illness were not statistically significant.ConclusionsThis study provides the first evidence of a relationship between gastrointestinal illness and estimates of fecal indicator organisms determined by qPCR at marine beaches.

Risk Factors for Sporadic Cryptosporidiosis among Immunocompetent Persons in the United States from 1999 to 2001

ABSTRACT Many studies have evaluated the role of Cryptosporidium spp. in outbreaks of enteric illness, but few studies have evaluated sporadic cryptosporidiosis in the United States. To assess the risk factors for sporadic cryptosporidiosis among immunocompetent persons, a matched case-control study was conducted in seven sites of the Foodborne Diseases Active Surveillance Network (FoodNet) involving 282 persons with laboratory-identified cryptosporidiosis and 490 age-matched and geographically matched controls. Risk factors included international travel (odds ratio [OR] = 7.7; 95% confidence interval [95% CI] = 2.7 to 22.0), contact with cattle (OR = 3.5; 95% CI = 1.8 to 6.8), contact with persons >2 to 11 years of age with diarrhea (OR = 3.0; 95% CI = 1.5 to 6.2), and freshwater swimming (OR = 1.9; 95% CI = 1.049 to 3.5). Eating raw vegetables was protective (OR = 0.5; 95% CI = 0.3 to 0.7). This study underscores the need for ongoing public health education to prevent cryptosporidiosis, particularly among travelers, animal handlers, child caregivers, and swimmers, and the need for further assessment of the role of raw vegetables in cryptosporidiosis.

National Outbreak of Acanthamoeba Keratitis Associated with Use of a Contact Lens Solution, United States

Premarket standardized testing for Acanthamoeba spp. is warranted.

Cryptosporidium surveillance and risk factors in the United States.

Surveillance for Cryptosporidium in the United States indicates that the reported incidence of infection has increased dramatically since 2004. The reasons for this increase are unclear but might be caused by an actual increase in incidence, improved surveillance, improved awareness about cryptosporidiosis, and/or increases in testing practices resulting from the licensing of the first-ever treatment for cryptosporidiosis. While regional differences remain, the incidence of cryptosporidiosis appears to be increasing across the United States. Onset of illness is most common during the summer, particularly among younger children. Cryptosporidiosis case reporting also influences outbreak detection and reporting; the recent rise in cases coincides with an increase in the number of reported cryptosporidiosis outbreaks, particularly in treated recreational water venues. Risk factors include ingesting contaminated recreational or drinking water, exposure to infected animals, having close contacts with cryptosporidiosis, travel to disease-endemic areas, and ingestion of contaminated food. Advances in molecular characterization of clinical specimens have improved our understanding of the changing epidemiology and risk factors. Prevention and control of cryptosporidiosis requires continued efforts to interrupt the transmission of Cryptosporidium through water, food, and contact with infected persons or animals. Of particular importance is continued improvement and monitoring of drinking water treatment and advances in the design, operation, and management of recreational water venues coupled with behavioral changes among the swimming public.

Randomised placebo-controlled comparison of ivermectin and albendazole alone and in combination for Wuchereria bancrofti microfilaraemia in Haitian children.

BACKGROUND Lymphatic filariasis and intestinal helminth infections are important disorders in tropical areas. Periodic treatment with albendazole is now used in many school-based intestinal helminth-control programmes. However, few such programmes exist for lymphatic filariasis, despite evidence that single-dose treatment with ivermectin can greatly reduce the concentration of Wuchereria bancrofti microfilariae in the blood for months to years. We aimed to assess the potential for school-based control of lymphatic filariasis by investigating the efficacy and tolerability or combined ivermectin and albendazole in Haitian schoolchildren. METHODS In January, 1996, we collected 832 20 microL capillary blood samples for inclusion in a randomised controlled study from children aged 5-11 years, and examined them by microscopy for W bancrofti microfilariae. Infected children were randomly assigned treatment with placebo (n = 29), a single 200-400 micrograms/kg dose of ivermectin (mean, 273 micrograms/kg, n = 28), 400 mg albendazole (n = 29), or a combination of 200-400 micrograms/kg ivermectin and 400 mg albendazole (n = 24). Children with high concentrations of microfilariae in the blood were admitted to hospital and adverse reactions were monitored for 3-5 days, otherwise children were examined at school or during a visit to their home. 4 months after treatment, we examined blood samples again for microfilariae. FINDINGS 113 microfilaraemic children were enrolled (mean age 7.8 years). 4 months after treatment, the proportion of children who remained positive for microfilariae was significantly lower in the ivermectin plus albendazole group (four [17%]), but there were no significant changes in the other three groups (20 [69%] placebo, 22 [76%] albendazole alone, 17 [61%] ivermectin alone remained positive; p = 0.004). Geometric mean microfilarial concentration decreased from 9.3 to 5.3 per 20 microL blood among children who received placebo; from 15.5 to 1.5 per 20 microL blood among those who received ivermectin only (p = 0.032); from 14.1 to 5.1 per 20 microL blood among those who received albendazole alone; and from 13.7 to 0.3 per 20 microL blood among those who received both ivermectin and albendazole (p = 0.0001). Systemic adverse reactions did not differ significantly between children who received ivermectin alone and those who were treated with ivermectin and albendazole [corrected]. INTERPRETATION For children with W bancrofti microfilaraemia, combined treatment with ivermectin and albendazole was more effective than treatment with ivermectin only, with no measurable increase in severity of adverse reactions.