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Biomedical subjects

M J Beach

Publications and source records attributed to M J Beach.

At least 19 recordsLinked to original sources

Outbreak of norovirus illness associated with a swimming pool.

On 3 February 2004, the Vermont Department of Health received reports of acute gastroenteritis in persons who had recently visited a swimming facility. A retrospective cohort study was conducted among persons attending the facility between 30 January and 2 February. Fifty-three of 189 (28%) persons interviewed developed vomiting or diarrhoea within 72 h after visiting the facility. Five specimens tested positive for norovirus and three specimen sequences were identical. Entering the smaller of the two pools at the facility was significantly associated with illness (RR 5.67, 95% CI 1.5-22.0, P=0.012). The investigation identified several maintenance system failures: chlorine equipment failure, poorly trained operators, inadequate maintenance checks, failure to alert management, and insufficient record keeping. This study demonstrates the vulnerability of recreational water to norovirus contamination, even in the absence of any obvious vomiting or faecal accident. Our findings also suggest that norovirus is not as resistant to chlorine as previously reported in experimental studies. Appropriate regulations and enforcement, with adequate staff training, are necessary to ensure recreational water safety.

Acute Disease↗

An outbreak of Cryptosporidium hominis infection at an Illinois recreational waterpark.

Cryptosporidium has become increasingly recognized as a pathogen responsible for outbreaks of diarrhoeal illness in both immunocompetent and immunocompromised persons. In August 2001, an Illinois hospital reported a cryptosporidiosis cluster potentially linked to a local waterpark. There were 358 case-patients identified. We conducted community-based and waterpark-based case-control studies to examine potential sources of the outbreak. We collected stool specimens from ill persons and pool water samples for microscopy and molecular analysis. Laboratory-confirmed case-patients (n=77) were more likely to have attended the waterpark [odds ratio (OR) 16.0, 95% confidence interval (CI) 3.8-66.8], had pool water in the mouth (OR 6.0, 95% CI 1.3-26.8), and swallowed pool water (OR 4.5, 95% CI 1.5-13.3) than age-matched controls. Cryptosporidium was found in stool specimens and pool water samples. The chlorine resistance of oocysts, frequent swimming exposures, high bather densities, heavy usage by diaper-aged children, and increased recognition and reporting of outbreaks are likely to have contributed to the increasing trend in number of swimming pool-associated outbreaks of cryptosporidiosis. Recommendations for disease prevention include alteration of pool design to separate toddler pool filtration systems from other pools. Implementation of education programmes could reduce the risk of faecal contamination and disease transmission.

Adolescent↗

Factors associated with participation in a campaign of mass treatment against lymphatic filariasis, in Leogane, Haiti.

In October 2000, to interrupt transmission of Wuchereria bancrofti, an intense health-education campaign followed by a mass drug administration (MDA) with diethylcarbamazine and albendazole was undertaken in Leogane, Haiti. Three months after the MDA, which was the first in the study area, a knowledge-attitude-practice (KAP) survey, with a cluster-sample design and probability sampling, was undertaken, to determine the existing knowledge of the local residents, their attitudes toward the MDA, and the possible reasons for non-compliance. Questionnaire-based interviews were used to explore the KAP of 304 subjects (one randomly chosen resident aged > 14 years from each selected household) in 33 communities. Most (93%) of the interviewees were aware of filariasis and 72% knew at least one clinical sign of the disease. Awareness of the MDA was high (91%). The most frequently mentioned sources of information were other people (56%) and radio announcements (33%). More than 80% of the respondents encouraged other people to take the drugs distributed in the MDA and 63% had been treated. The primary reasons given for failing to take the drugs were absenteeism during the distribution (17%), use of contraceptive drugs (12%) and pregnancy (11%). In a multivariate analysis, being male [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 1.5-7.4], knowing that a mosquito transmits the disease (OR = 2.6; CI = 1.2-5.4), and having learned about the MDA through posters and banners (OR = 2.9; CI = 1.2-7.5) were found to be positively associated with taking the drugs. Information from such post-treatment surveys should be useful in developing better health communication for subsequent MDA.

Adolescent↗

Giardiasis surveillance--United States, 1992-1997.

PROBLEM/CONDITION: Giardia intestinalis, the organism that causes the gastrointestinal illness giardiasis, is the most commonly diagnosed intestinal parasite in public health laboratories in the United States. In 1992, the Council of State and Territorial Epidemiologists assigned giardiasis an event code that enabled states to begin voluntarily reporting surveillance data on giardiasis to CDC. REPORTING PERIOD: This report includes data that were reported from January 1992 through December 1997. DESCRIPTION OF THE SYSTEM: The National Giardiasis Surveillance System includes data about reported cases of giardiasis from participating states. Because most states were already collecting data on occurrence of giardiasis, the assignment of an event code to giardiasis has allowed voluntary reporting of these data to CDC via the National Electronic Telecommunications System for Surveillance. RESULTS: Since 1992, the number of states reporting cases of giardiasis to CDC has risen from 23 to 43. The annual number of giardiasis cases reported has ranged from 12,793 in 1992 to 27,778 in 1996. In 1997, cases per 100,000 state population ranged from 0.9 to 42.3, with 10 states reporting >20.0 cases per 100,000 population and a national average of 9.5 cases per 100,000 population. In 1997, New York State, including New York City, reported the highest number of cases (3,673, or 20.3 cases per 100,000 population), accounting for 14.5% of cases nationally; however, Vermont reported the highest incidence rate in 1997 (42.3 cases per 100,000 population). Both states have active surveillance systems in place for giardiasis. Cases have an approximately equal sex distribution. Nationally, rates were the highest among children aged 0-5 years, followed closely by persons aged 31-40 years. In these two age groups, most cases were reported during late summer and early fall--an indication that transmission occurred during the summer. INTERPRETATION: This report documents the first nationwide look at epidemiologic parameters and disease burden estimates for giardiasis in the United States. Transmission occurs in all major geographic areas of the country. The seasonal peak in age-specific case reports coincides with the summer recreational water season and might reflect the heavy use by young children of communal swimming venues (e.g., lakes, rivers, swimming pools, and water parks)--a finding consistent with Giardia's low infectious dose, the high prevalence of diaper-aged children in swimming venues, the extended periods of cyst shedding that can occur, and Giardia's environmental resistance. Estimates based on state surveillance data indicate that as many as 2.5 million cases of giardiasis occur annually in the United States. PUBLIC HEALTH ACTION: Giardiasis surveillance provides data to educate public health practitioners and health-care providers about the scope and magnitude of giardiasis in the United States. These data can be used to establish research priorities and to plan future prevention efforts.

Adolescent↗

Surveillance for waterborne-disease outbreaks--United States, 1997-1998.

PROBLEM/CONDITION: Since 1971, CDC and the U.S. Environmental Protection Agency (EPA) have maintained a collaborative surveillance system for collecting and periodically reporting data relating to occurrences and causes of waterborne-disease outbreaks (WBDOs). REPORTING PERIOD COVERED: This summary includes data from January 1997 through December 1998 and a previously unreported outbreak in 1996. DESCRIPTION OF THE SYSTEM: The surveillance system includes data regarding outbreaks associated with drinking water and recreational water. State, territorial, and local public health departments are primarily responsible for detecting and investigating WBDOs and voluntarily reporting them to CDC on a standard form. RESULTS: During 1997-1998, a total of 13 states reported 17 outbreaks associated with drinking water. These outbreaks caused an estimated 2,038 persons to become ill. No deaths were reported. The microbe or chemical that caused the outbreak was identified for 12 (70.6%) of the 17 outbreaks; 15 (88.2%) were linked to groundwater sources. Thirty-two outbreaks from 18 states were attributed to recreational water exposure and affected an estimated 2,128 persons. Eighteen (56.3%) of the 32 were outbreaks of gastroenteritis, and 4 (12.5%) were single cases of primary amebic meningoencephalitis caused by Naegleria fowleri, all of which were fatal. The etiologic agent was identified for 29 (90.6%) of the 32 outbreaks, with one death associated with an Escherichia coli O157:H7 outbreak. Ten (55.6%) of the 18 gastroenteritis outbreaks were associated with treated pools or ornamental fountains. Of the eight outbreaks of dermatitis, seven (87.5%) were associated with hot tubs, pools, or springs. INTERPRETATION: Drinking water outbreaks associated with surface water decreased from 31.8% during 1995-1996 to 11.8% during 1997-1998. This reduction could be caused by efforts by the drinking water industry (e.g., Partnership for Safe Water), efforts by public health officials to improve drinking water quality, and improved water treatment after the implementation of EPA's Surface Water Treatment Rule. In contrast, the proportion of outbreaks associated with systems supplied by a groundwater source increased from 59.1% (i.e., 13) during 1995-1996 to 88.2% (i.e., 15) during 1997-1998. Outbreaks caused by parasites increased for both drinking and recreational water. All outbreaks of gastroenteritis attributed to parasites in recreational water were caused by Cryptosporidium, 90% occurred in treated water venues (e.g., swimming pools and decorative fountains), and fecal accidents were usually suspected. The data in this surveillance summary probably underestimate the true incidence of WBDOs because not all WBDOs are recognized, investigated, and reported to CDC or EPA. ACTIONS TAKEN: To estimate the national prevalence of waterborne disease associated with drinking water, CDC and EPA are conducting a series of epidemiologic studies to better quantify the level of waterborne disease associated with drinking water in nonoutbreak conditions. The Information Collection Rule implemented by EPA in collaboration with the drinking water industry helped quantifythe level of pathogens in surface water. Efforts by CDC to address recreational water outbreaks have included meetings with the recreational water industry, focus groups to educate parents on prevention of waterborne disease transmission in recreational water settings, and publications with guidelines for parents and pool operators.

Communicable Diseases↗

An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis.

This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole + ivermectin or albendazole + diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90,635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n = 1538), ivermectin (9822), DEC (576), albendazole + ivermectin (7470), albendazole + DEC (69,020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80-90% of the 'at risk' populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin + albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.

Albendazole↗

The return of Cyclospora in 1997: another outbreak of cyclosporiasis in North America associated with imported raspberries. Cyclospora Working Group.

BACKGROUND: In the spring of 1996, an outbreak of cyclosporiasis associated with fresh Guatemalan raspberries occurred in the United States and Canada. Another multistate outbreak of cyclosporiasis occurred in North America in the spring of 1997. OBJECTIVE: To identify the vehicle of the outbreak that occurred in the spring of 1997. DESIGN: Retrospective cohort studies of clusters of cases associated with events (such as banquets) and traceback investigations of sources of implicated produce. SETTING: United States and Canada. PATIENTS: Persons who attended events associated with clusters of cases of cyclosporiasis. MEASUREMENTS: Identification of clinically defined or laboratory-confirmed cases of cyclosporiasis and risk factors for infection. RESULTS: 41 clusters of cases were reported in association with events held from 1 April through 26 May in 13 U.S. states, the District of Columbia, and 1 Canadian province. The clusters comprised 762 cases of cyclosporiasis, 192 (25.2%) of which were laboratory confirmed. In addition, 250 laboratory-confirmed sporadic cases were reported in persons who developed gastrointestinal symptoms from April through 15 June, for a total of 1012 cases. Fresh raspberries were the only food common to all 41 events and were the only type of berry served at 9 events (22.0%). Statistically significant associations between consumption of raspberry-containing items and cyclosporiasis were documented for 15 events (40.5% of 37). For 31 of the 33 events with well-documented traceback data, the raspberries either definitely came from Guatemala (8 events) or could have come from Guatemala (23 events). The mode of contamination of the raspberries remains unknown. The outbreak ended shortly after the exportation of fresh raspberries from Guatemala was voluntarily suspended at the end of May 1997. CONCLUSIONS: Similar multistate, multicluster outbreaks of cyclosporiasis associated with consumption of Guatemalan raspberries have occurred in consecutive years. These outbreaks highlight the need for better understanding of the biology and epidemiology of Cyclospora cayetanensis and for stronger prevention and control measures to ensure the safety of produce eaten raw.

Animals↗

Assessment of combined ivermectin and albendazole for treatment of intestinal helminth and Wuchereria bancrofti infections in Haitian schoolchildren.

This randomized, placebo-controlled trial investigated the efficacy and nutritional benefit of combining chemotherapeutic treatment for intestinal helminths (albendazole) and lymphatic filariasis (ivermectin). Children were infected with Ascaris (29.2%), Trichuris (42.2%), and hookworm (6.9%), with 54.7% of children having one or more of these parasites. Wuchereria bancrofti microfilaria were found in 13.3% of the children. Children were randomly assigned to treatment with placebo, albendazole, ivermectin, or combined therapy. Combination treatment reduced the prevalence of Trichuris infections significantly more than either drug alone. Combination therapy also significantly reduced the prevalence and density of W. bancrofti microfilaremia compared with placebo or ivermectin alone. Only combination therapy resulted in significantly greater gains in height (hookworm-infected children) or weight (Trichuris-infected children) compared with the placebo group. Combined albendazole and ivermectin was a more efficacious treatment for intestinal helminth and W. bancrofti infections in children and resulted in nutritional benefits not found with either drug alone.

Albendazole↗

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.

Albendazole↗

Viral specificity of hepatitis E virus antigens identified by fluorescent antibody assay using recombinant HEV proteins.

A fluorescent antibody (FA) assay for hepatitis E virus antigen (HEVAg) in infected liver tissue was used to confirm the presence of virus-specific antigens in hepatocytes during the course of infection. With the cloning of the HEV genome it is now possible to determine which viral antigens are recognized by this FA assay. Recombinant HEV proteins covering the carboxyl half of HEV open reading frame 2 (ORF2) were used in this study to demonstrate that some of the most immunoreactive virus-specific antigens detected by FA are contained within this region of ORF2 (nucleotides 6169-7126).

Animals↗

Molecular characterization of hepatitis C and E viruses.

The molecular features of each of the major viruses of non-A, non-B hepatitis, namely hepatitis C virus (HCV) and hepatitis E virus (HEV) are briefly described. The organization of the genome of each of these viruses is discussed and compared to those of other related or distantly related viruses that contain single-stranded, positive-sense RNA genomes. HCV has been tentatively classified as a separate genus within the Flaviviridae, whereas HEV has been loosely associated with caliciviruses and subsequently assigned to the Caliciviridae, although it does possess unique genetic features not found in other caliciviruses.

Animals↗

Interaction of immune sera with synthetic peptides corresponding to the structural protein region of hepatitis C virus.

Comparison of the deduced amino acid sequence from the structural region of the Hutchinson strain of hepatitis C virus (HCV-H) with four other HCV isolates clearly divides the five isolates into two groups based on sequence homology. The first group includes HCV-H, HCV-1, and HC-J1, while the second includes HCV-J1 and HC-J4. Among the five isolates the first 190 residues (putative nucleocapsid) are highly conserved whereas residues 196-513 exhibit significant diversity and include a hypervariable region encompassing residues 386-404. A series of overlapping decapeptides were synthesized by solid-phase pin technology according to sequence from HCV-H (amino acids 1-513), HC-J4 (amino acids 181-513), and regions from the three other isolates which exhibited sequence variation. A modified ELISA was used to measure immunoreactivity of sera from clinical posttransfusion cases and experimentally infected chimpanzees. Comparison of pre- and postinfection samples revealed 16 clusters of immunoreactive peptides within the structural region, none of which was found in the hypervariable region. Only one cluster (amino acids 73-89) was recognized by all human and chimpanzee sera. Clear variation in the immune response was observed between individuals, although no obvious difference in reactivity between acute and chronic cases was observed. Within individual profiles, the reactivity to each peptide cluster and the total number of reactive clusters increased over time.

Amino Acid Sequence↗

Temporal relationships of hepatitis C virus RNA and antibody responses following experimental infection of chimpanzees.

Liver enzyme levels, viral RNA, and the immune response against both structural and nonstructural hepatitis C virus (HCV) proteins have been studied in experimentally infected chimpanzees in order to further understand the natural history of HCV infection. An ELISA for measuring both IgG and IgM responses to core (c22), 33c (NS3), and c100 (NS4) was employed. The IgG response rates were 5/8 for core, and 8/8 for both 33c and c100. Utilizing this antigen combination, at least one antibody response is measureable at, or within 3 weeks of, the major ALT peak. Although no individual antibody response is universally associated with initial detection of seroconversion, the combination of all three recombinant proteins measures seroconversion an average of 54 days earlier than with c100 alone, in 6/8 of the animals. IgM responses were measureable in 5/8 of the chimpanzees, were of shorter duration, and usually arose concomitantly with IgG responses. IgM appears to be a good indicator of primary infection since neither boosting nor recrudescence of disease during the chronic phase of disease elicited a secondary IgM response. Viral RNA can be measured 4-7 days (average = 9 days) postinfection with the period preceding the ALT peak being characterized by several PCR positive segments interrupted by periods in which no viral RNA can be measured. Following the ALT peak, chronically infected animals with recurring ALT elevations are generally PCR positive with intercedent PCR negative periods. Those animals that appear to have biochemically resolved disease generally have PCR negative profiles, although they still may periodically exhibit PCR positive sera. This indicates that with the recent advent of new screening techniques, a more stringent definition of HCV resolution will be required.

Animals↗

Expression of a hepatitis E virus (HEV)-trpE fusion protein containing epitopes recognized by antibodies in sera from human cases and experimentally infected primates.

A 1700 base cDNA fragment coding for the putative structural gene(s) of hepatitis E virus (HEV) was inserted into the pATH 10 expression vector. The fusion protein (C2) expressed by this plasmid was found to contain epitopes recognized by anti-HEV antibodies. C2 protein was used in a Western blot format to examine its usefulness in detecting anti-HEV antibodies in well documented human cases of HEV and non-human primates infected with HEV. Both IgM and IgG anti-HEV could be detected in our Western blot assay. This Western blot assay was found not to detect antibodies from acute-phase sera from patients with either HAV or HBV. The C2 protein contains broadly cross-reactive epitopes, and the Western blot assay was able to detect anti-HEV antibodies in patient sera from Asia, Africa, and North America. The optimum serum dilution for the detection of both IgM and IgG was 1:25.

Animals↗

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.

Adult↗