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PubMed2002

Overview: cause and prevention in biowarfare and bioterrorism.

Bioweaponry is rooted in the ancient past. It became a science in the early 20th century following the breakthrough discoveries in microbiology and immunology of the late 1800s. The 20th century, with its major and minor wars, saw the research and development of biological weapons capable of immense destruction of life, which were used both by nations in preparation for military warfare and by individuals who engage in asymmetric warfare. Treaties, international agreements, and political pursuits have not been able either to control or to rid the world of bioweapons. The tools for specific defense against bioweapons consist of vaccines against both viruses and bacteria, and of antibiotics and drugs against bacteria. Vaccines and antimicrobials are of limited usefulness because of the large number of possible microbes that can be used for weapons, because of antimicrobial resistance to drugs and antibiotics, and because of limitations in technical feasibility for developing vaccines and antibacterials against certain of the agents. Induction of non-specific innate immunity by immunostimulatory vaccines (at one time licensed) needs to be explored for possible immunoprophylactic-therapeutic activity when administered immediately following exposure to bioweapon pathogens. The ideal solution to the bioweapons problem lies in measures to end their development and application throughout the world. Emphasis was made at the recent World Economic Forum of the need to end poverty and hunger in the world as a means to reduce the incentive to engage in warfare. Added to this is betterment of health, focused mainly on preventable diseases. A further solution to the problem may lie in the development of modern robotic systems for rapid forensic detection of development and production of bioweapons by "rogue" nations and even by individuals. This review deals with the specifics of the development of bioweapons and their control by vaccines, by therapy with antibacterials, by non-specific immunostimulants, by advanced systems for detection of development and deployment of biological agents of destruction, and by political and health-giving initiatives.

Adjuvants, Immunologic↗

PubMed1998

Risk scores to detect cervical infections in urban antenatal clinic attenders in Mwanza, Tanzania.

BACKGROUND: Detection and management of gonococcal and/or chlamydial infections in women is a challenge, particularly in developing countries where laboratory tests are not always available. The World Health Organisation (WHO) has developed a risk assessment approach to identify cervical infections among women complaining of vaginal discharge. We have evaluated this approach as a screening strategy among women attending an urban antenatal clinic (ANC) in Tanzania. OBJECTIVES: (i) To measure the prevalence of pathogens associated with sexually transmitted diseases (STD) and reproductive tract infections (RTI) in an urban population of ANC attenders in Tanzania; (ii) to examine characteristics of pregnant women associated with cervical infections; and (iii) to evaluate the performance of a WHO risk assessment algorithm and alternative risk scores for the detection of cervical infections in pregnant women. METHODS: A systematic sample of 660 pregnant women reporting for routine antenatal care at an urban clinic was enrolled. Women were interviewed by a nurse, who applied the WHO risk score. They were referred to a study room for interview about sociodemographic and behavioural factors, examination, and sampling for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Candida albicans, and bacterial vaginosis. Sensitivity, specificity, positive predictive value (PPV), and theoretical cost per true case treated were estimated for the diagnosis of cervical infection with N gonorrhoeae and/or C trachomatis for the WHO and other risk scores. RESULTS: The prevalence of any vaginal or cervical infection was 68%. Prevalence rates of various pathogens were: C albicans 39%, T vaginalis 16%, bacterial vaginosis 24%, N gonorrhoeae 2.3%, C trachomatis 5.9%, any cervical infection (N gonorrhoeae and/or C trachomatis) 7.4%. The WHO score identified only five of 49 women with N gonorrhoeae and/or C trachomatis (sensitivity 10.2%). The specificity and the PPV were 92% and 9.8% respectively. The theoretical cost per true case treated on the basis of the WHO score was over $18. Several risk factors were associated with cervical infection on univariate analysis, but only six remained significant at the 10% level after multivariate analysis. These were: never use of contraceptives (OR 3.09), more than one partner in the past 3 months (OR 3.32), partner with symptoms of genital discharge syndrome (GDS) (OR 7.55), frothy vaginal discharge (OR 1.88), 5-19 polymorphonucleocytes per high power field on cervical smear (OR 3.28), or more than 20 polymorphonucleocytes per high power field (OR 16.08), and wet preparation showing evidence of T vaginalis infection (OR 1.96). Scores based on these variables failed to attain high sensitivities or PPVs (all below 40%) although the costs per true case treated were cheaper than for the WHO score. CONCLUSION: Risk assessment for the screening and management of N gonorrhoeae and/or C trachomatis among women presenting at routine antenatal services appears feasible and acceptable, but of limited value in this population because of its low sensitivity. The optimal risk score may vary considerably from one place to another. The quest for simple, cheap, and reliable tests to diagnose N gonorrhoeae and C trachomatis infections still remains a high priority on the international STD technology research agenda.

Adult↗

PubMed2004

Work of the European Haemovigilance Network (EHN).

Haemovigilance has become a crucial part of the blood safety concept. In the Member States of the European Union, national haemovigilance systems are already in place or are developing. With the coming into force of the European Blood Directive 2002/98/EC, Community haemovigilance has become a priority: cooperation between the national haemovigilance systems will be of vital interest. The process of collaboration has already been initiated some years ago by the European Haemovigilance Network (EHN) with the following objectives: to favour the exchange of valid information between its members, to increase rapid alert/early warning between the members, to encourage joint activities between the members and to undertake educational activities relating to haemovigilance. This has been achieved by the EHN by developing and maintaining a website [http://www.ehn-org.net], by establishing a system for rapid alert and early warning (RAS), by discussing on all kinds of definitions relevant to haemovigilance, initiating standardisation of processes and forms (developing a common "mother matrix"), by starting with the compilation and analysis of European data (generated by the national haemovigilance systems in Europe) and by organising annual European Haemovigilance Seminars, where all these items are discussed. As in the past, the EHN will continue in the future to play a major role in promoting European haemovigilance.

Blood Banks↗

PubMed2005

Frequency of isolation and antimicrobial susceptibility of bacteria isolated from bloodstream infections at Children's Medical Center, Tehran, Iran, 1996-2000.

Antimicrobial susceptibility patterns of major bloodstream pathogens from Iran provide essential information regarding the selection of antibiotic therapy for patients with bloodstream infections (BSIs) living in Iran. Unfortunately, data regarding the isolation frequency and antimicrobial susceptibility patterns of endemic BSI pathogens are scarce in Iran. To shed some light on the susceptibility patterns of BSI pathogens endemic to Tehran, Iran, we investigated the antimicrobial susceptibility patterns of 2248 bloodstream isolates from patients in Children's Medical Center (CMC) Hospital in Tehran between January 1996 and December 2000. Microbiology reports of 24600 blood specimens collected from inpatients in CMC Hospital were retrospectively reviewed. Specimen culture, bacterial identification and disk diffusion susceptibility testing were performed according to National Committee for Clinical Laboratory Standards guidelines. Overall, Gram-positive bacteria comprised 72% (1627/2248) of recovered isolates and Gram-negative bacteria comprised 28% (621/2248). Coagulase-negative staphylococci (CoNS) comprised 48.4% of all isolates, followed by Staphylococcus aureus (16.7%) and Klebsiella spp. (8.5%). Among the 621 Gram-negative organisms, Klebsiella spp. (31%) were the most frequently isolated, followed by Escherichia coli (21%) and Pseudomonas aeruginosa (17%). The rates of oxacillin resistance for S. aureus and CoNS isolates were similar (60% versus 61%); however, the rate of S. aureus vancomycin resistance was almost twice that of CoNS resistance (21% versus 11%). Over 55% of S. pneumoniae were resistant to penicillin and co-trimoxazole. Although all isolates of enterococci were susceptible to vancomycin, only 21% were susceptible to gentamicin. Among Gram-negative isolates, amikacin was shown to be very effective, with susceptibility rates of 84%. The susceptibility of Klebsiella spp. to ampicillin and co-trimoxazole was 1% and 39%, respectively. The susceptibility of Klebsiella spp., E. coli and Enterobacter spp. to ceftriaxone was 47%, 86% and 67%, respectively. There were notable differences in the order of the five most common organisms isolated from blood cultures, which can help set priorities for focused control efforts. Our findings highlight the importance of a nationwide surveillance programme to monitor the trends in isolation frequency of bacteria and their antimicrobial resistance patterns throughout Iran.

Bacteremia↗

PubMed2006

Pandemic vaccines: promises and pitfalls.

Prototype vaccines against influenza A/H5N1 may be poorly immunogenic, and two or more doses may be required to induce levels of neutralising antibody that are deemed to be protective. The actual levels of antibody required to protect against a highly pathogenic virus that potentially can spread beyond the large airways is unknown. The global capacity for vaccine manufacture in eggs or tissue culture is considerable, but the number of doses that can theoretically be produced in a pandemic context will only be sufficient for a small fraction of the world's population, even less if a high antigen content is required. The safety of new pandemic vaccines should be addressed in an internationally coordinated way. Steps are underway through the Therapeutic Goods Administration to evaluate mock-up vaccines now, so that the time to registration of a new product can be minimised. It will be 3-6 months into the pandemic before an effective vaccine becomes available, so other control measures will be important in the early stages of a pandemic. The primary goal of a pandemic influenza vaccine must be to prevent death, and not necessarily to prevent infection.

Australia↗

PubMed2006

MannDB - a microbial database of automated protein sequence analyses and evidence integration for protein characterization.

BACKGROUND: MannDB was created to meet a need for rapid, comprehensive automated protein sequence analyses to support selection of proteins suitable as targets for driving the development of reagents for pathogen or protein toxin detection. Because a large number of open-source tools were needed, it was necessary to produce a software system to scale the computations for whole-proteome analysis. Thus, we built a fully automated system for executing software tools and for storage, integration, and display of automated protein sequence analysis and annotation data. DESCRIPTION: MannDB is a relational database that organizes data resulting from fully automated, high-throughput protein-sequence analyses using open-source tools. Types of analyses provided include predictions of cleavage, chemical properties, classification, features, functional assignment, post-translational modifications, motifs, antigenicity, and secondary structure. Proteomes (lists of hypothetical and known proteins) are downloaded and parsed from Genbank and then inserted into MannDB, and annotations from SwissProt are downloaded when identifiers are found in the Genbank entry or when identical sequences are identified. Currently 36 open-source tools are run against MannDB protein sequences either on local systems or by means of batch submission to external servers. In addition, BLAST against protein entries in MvirDB, our database of microbial virulence factors, is performed. A web client browser enables viewing of computational results and downloaded annotations, and a query tool enables structured and free-text search capabilities. When available, links to external databases, including MvirDB, are provided. MannDB contains whole-proteome analyses for at least one representative organism from each category of biological threat organism listed by APHIS, CDC, HHS, NIAID, USDA, USFDA, and WHO. CONCLUSION: MannDB comprises a large number of genomes and comprehensive protein sequence analyses representing organisms listed as high-priority agents on the websites of several governmental organizations concerned with bio-terrorism. MannDB provides the user with a BLAST interface for comparison of native and non-native sequences and a query tool for conveniently selecting proteins of interest. In addition, the user has access to a web-based browser that compiles comprehensive and extensive reports. Access to MannDB is freely available at http://manndb.llnl.gov/.

Algorithms↗

PubMed2006

An absence of reactive oxygen species improves the resolution of lung influenza infection.

Three influenza virus pandemics occurred in the last century, in 1918 killing 40-50 million people. In the absence of strain-specific vaccines, with potential resistance to antivirals and the threat of an imminent pandemic, strategies that alleviate symptoms are a priority. Reactive oxygen species are potent antimicrobial agents but cause immunopathology when produced in excess. Mice lacking a functional phagocyte NADPH oxidase (Cybb tm1 mice) or treated with the metalloporphyrin antioxidant manganese (III) tetrakis (N-ethyl pyridinium-2-yl) porpyhrin (MnTE-2-PyP) show heightened inflammatory infiltrates in their airways in response to pulmonary influenza infection, with augmented macrophage populations and a Th1-skewed T cell infiltrate. Underlying this exuberant macrophage response was a significant reduction in apoptosis and down-regulation of the myeloid inhibitory molecule CD200. Both, Cybb tm1 and MnTE-2-PyP-treated mice exhibited a reduced influenza titer in the lung parenchyma. Inflammatory infiltrate into the lung parenchyma was markedly reduced and lung function significantly improved. Manipulation of the homeostatic control of myeloid cells by inflammatory mediators therefore represents a novel therapeutic strategy in the treatment of influenza virus infection.

Animals↗

PubMed2002

Chromosomally-encoded resistance mechanisms of Pseudomonas aeruginosa: therapeutic implications.

Pseudomonas aeruginosa is an important nosocomial pathogen that presents a difficult therapeutic challenge. Although P. aeruginosa has been shown to acquire resistance mechanisms encoded on plasmids, this pathogen comes armed with multiple chromosomally-encoded mechanisms of resistance that can provide impressive intrinsic resistance, as well as the potential to mutate to high-level multi-drug resistance. Recent analysis of the sequenced genome of P. aeruginosa PAO1 suggested that we have just started to unlock the resistance potential of this pathogen. One of the most serious threats to the usefulness of beta-lactams against P. aeruginosa is the chromosomal AmpC cephalosporinase. When AmpC production increases through mutational events, overproduction of this cephalosporinase provides high-level resistance to all beta-lactams except the carbapenems. Carbapenem resistance typically requires down-regulation of the outer membrane protein (OprD), which serves as the primary route of entry for carbapenems. Perhaps the most threatening of the resistance mechanisms encoded on the P. aeruginosa chromosome are the multi-drug efflux pumps. These pumps have the ability to extrude multiple classes of antibiotics from the periplasmic space, as well as the cytoplasm. Natural expression of efflux pumps in 'wild-type' cells plays an important role in the relatively decreased susceptibility of P. aeruginosa to antibiotics. However, the greatest therapeutic problems occur when these pumps are overproduced in mutants and high-level, multi-drug resistance develops. Although the development of infections with highly resistant strains of P. aeruginosa can present serious therapeutic challenges, the most troublesome threat associated with the chromosomally-encoded resistance mechanisms is the potential for high-level resistance to emerge during the course of therapy. When resistance emerges during therapy, clinical failure can occur and the therapeutic options for second-line therapy can become severely limited. Unfortunately, the emergence of resistance during therapy is not a rare event with P. aeruginosa and these three resistance mechanisms. Therefore, clinicians must be mindful of this threat when choosing an appropriate therapy, and usually appropriate therapy includes a combination of drugs. Since the standard combination of an aminoglycoside and a beta-lactam has been shown to be ineffective in preventing the emergence of some resistance problems, the search for more effective combinations must be a priority.

Animals↗

PubMed2005

Aedes aegypti (L.) and Aedes polynesiensis Marks (Diptera: Culicidae) in Moorea, French Polynesia: a study of adult population structures and pathogen (Wuchereria bancrofti and Dirofilaria immitis) infection rates to indicate regional and seasonal epidemiological risk for dengue and filariasis.

Populations of Aedes aegypti (L.) and Aedes polynesiensis (Marks) on Moorea Island, French Polynesia, the local vectors of dengue and filariasis, respectively, were sampled by landing/biting collection at nine localities on the east, north, and west coasts, during the late dry season, early and late wet season (September-May) 2003 and 2004, to investigate epidemiologically important features of the populations and compare them between regions and months. Biting rates of both species tended to increase (but not always significantly) for each species in each region each month from the late dry season to the late wet season, and the north coast region had significantly higher biting rates of Ae. aegypti. Insemination rates of Ae. polynesiensis females (94.5-98.8%) were consistently greater than those of Ae. aegypti (87.5-93.5%) throughout the study, but there was no significant difference in the insemination rates of either species between months and regions. Parity rates were generally highest in north coast samples and lowest in west coast samples for both species and generally increased (albeit not always significantly) by month for each species, with a range of 52.9-88.8% for Ae. polynesiensis and 28.6-53.6% for Ae. aegypti, although the high gravid rate (15.8-45.9%) of Ae. aegypti samples (reflecting its feeding more than once in a gonotrophic cycle) confounded both intraspecific and interspecific comparisons. Filarial infection was rare in Ae. aegypti, although both W. bancrofti and D. immitis were recorded, and infection rates in Ae. polynesiensis increased through the study period in each region for both filarias, with up to 4.6% infected and 1.4% infective for W. bancrofti and up to 6.3% infected and 2.5% infective for D. immitis. For W. bancrofti, infection rates were significantly lower on the west coast and also in the dry season, whereas rates for infective stages were significantly greater in the late wet season. For D. immitis there was no significant difference in infection rates between regions, but rates were significantly greater in the late wet season. Rainfall in all months sustains populations of both vectors and explains the relatively few significant differences between seasons; however, the wet season may provide for increased vector abundance and longevity, and present a potentially increased risk for transmission. Although the differences shown between regions also were limited in a statistical sense, there were increased risks for the northern and eastern regions, where both locals and tourists are concentrated and where the seaports and airport are located, and these areas should be priority targets for disease surveillance and vector control.

Aedes↗

PubMed2004

Surveillance for waterborne-disease outbreaks associated with drinking water--United States, 2001-2002.

PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency, and the Council of State and Territorial Epidemiologists have maintained a collaborative surveillance system for collecting and periodically reporting data related to occurrences and causes of waterborne-disease outbreaks (WBDOs). This surveillance system is the primary source of data concerning the scope and effects of waterborne disease outbreaks on persons in the United States. REPORTING PERIOD COVERED: This summary includes data on WBDOs associated with drinking water that occurred during January 2001-December 2002 and on three previously unreported outbreaks that occurred during 2000. DESCRIPTION OF SYSTEM: Public health departments in the states, territories, localities, and the Freely Associated States are primarily responsible for detecting and investigating WBDOs and voluntarily reporting them to CDC on a standard form. The surveillance system includes data for outbreaks associated with both drinking water and recreational water; only outbreaks associated with drinking water are reported in this summary. RESULTS: During 2001-2002, a total of 31 WBDOs associated with drinking water were reported by 19 states. These 31 outbreaks caused illness among an estimated 1,020 persons and were linked to seven deaths. The microbe or chemical that caused the outbreak was identified for 24 (77.4%) of the 31 outbreaks. Of the 24 identified outbreaks, 19 (79.2%) were associated with pathogens, and five (20.8%) were associated with acute chemical poisonings. Five outbreaks were caused by norovirus, five by parasites, and three by non-Legionella bacteria. All seven outbreaks involving acute gastrointestinal illness of unknown etiology were suspected of having an infectious cause. For the first time, this MMWR Surveillance Summary includes drinking water-associated outbreaks of Legionnaires disease (LD); six outbreaks of LD occurred during 2001-2002. Of the 25 non-Legionella associated outbreaks, 23 (92.0%) were reported in systems that used groundwater sources; nine (39.1%) of these 23 groundwater outbreaks were associated with private noncommunity wells that were not regulated by EPA. INTERPRETATION: The number of drinking water-associated outbreaks decreased from 39 during 1999-2000 to 31 during 2001-2002. Two (8.0%) outbreaks associated with surface water occurred during 2001-2002; neither was associated with consumption of untreated water. The number of outbreaks associated with groundwater sources decreased from 28 during 1999-2000 to 23 during 2001-2002; however, the proportion of such outbreaks increased from 73.7% to 92.0%. The number of outbreaks associated with untreated groundwater decreased from 17 (44.7%) during 1999-2000 to 10 (40.0%) during 2001-2002. Outbreaks associated with private, unregulated wells remained relatively stable, although more outbreaks involving private, treated wells were reported during 2001-2002. Because the only groundwater systems that are required to disinfect their water supplies are public systems under the influence of surface water, these findings support EPA's development of a groundwater rule that specifies when corrective action (including disinfection) is required. PUBLIC HEALTH ACTION: CDC and EPA use surveillance data 1) to identify the types of water systems, their deficiencies, and the etiologic agents associated with outbreaks and 2) to evaluate the adequacy of technologies for providing safe drinking water. Surveillance data are used also to establish research priorities, which can lead to improved water-quality regulations. CDC and EPA recently completed epidemiologic studies that assess the level of waterborne illness attributable to municipal drinking water in nonoutbreak conditions. The decrease in outbreaks in surface water systems is attributable primarily to implementation of provisions of EPA rules enacted since the late 1980s. Rules under development by EPA are expected to protect the public further from microbial contaminants while addressing risk tradeoffs of disinfection byproducts in drinking water.

Disease Outbreaks↗

PubMed2004

Correlations between certain hearing changes and vegetative balance in miners.

This study responds to the priorities of the National Health Strategy aimed at control and mitigation of the hazardous effects of the workplace factors on cardio-vascular diseases of people in active working age from the branch "Mining industry". The aim of this work is to study the vegetative balance (by analysis of heart rate variability--AHRV) and the correlations with the state of miners' hearing functions. Sixty eight miners (diggers and mate-diggers) from mining industry were studied. This paper treats the results of AHRV examination of 25 miners who have no major and additional causes, leading to hearing injury--traumas, other diseases, medicines, etc. The analysis of heart rate variability was made by computer analysis of heart rate and variability. Standard ECG electrodes at bi-polar breast lead-off were used for recording ECG signals. The echo-cardiographic signal was converted by an ECG converter board into epochs of cardiac events (R-R intervals) for 10 minutes. The principal indices of heart rate variability were analysed. The obtained results provide the ground for further comprehensive studies on different workers contingents from other industries in order to detect workers with initial changes in the hearing analyser and to establish the corresponding pathogenetically based registration, monitoring, and treatment system. The studies conducted for monitoring the dynamic of vegetative equilibrium reflect the degree of disturbed heterostasis by chronically manifested sympatic activity in miners, diagnosed by AHRV indices. The revealed significant relationships between hearing changes and AHRV indices prove the presence of an extra-aural paraprofessional effect and statistically significant relations with the changes in the critical organ. The revealed highly significant correlations between AHRV indices and hearing show a significant relationship between the physiological vegetative level (assessed by AHRV) and the hearing status at chronic exposure to work-related stress factors in miners. The chronic sympathicotonia is an additional pathogenic factor (besides acoustic stress) manifested by spastic changes in the microcirculation of the cochlear neuroreceptor elements.

Adult↗

PubMed2006

Surveillance for waterborne disease and outbreaks associated with drinking water and water not intended for drinking--United States, 2003-2004.

PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency (EPA), and the Council of State and Territorial Epidemiologists have maintained a collaborative Waterborne Disease and Outbreaks Surveillance System for collecting and reporting data related to occurrences and causes of waterborne disease and outbreaks (WBDOs). This surveillance system is the primary source of data concerning the scope and effects of WBDOs in the United States. REPORTING PERIOD: Data presented summarize 36 WBDOs that occurred during January 2003-December 2004 and nine previously unreported WBDOs that occurred during 1982-2002. DESCRIPTION OF SYSTEM: The surveillance system includes data on WBDOs associated with drinking water, water not intended for drinking (excluding recreational water), and water of unknown intent. Public health departments in the states, territories, localities, and Freely Associated States (i.e., the Republic of the Marshall Islands, the Federated States of Micronesia, and the Republic of Palau, formerly parts of the U.S.-administered Trust Territory of the Pacific Islands) are primarily responsible for detecting and investigating WBDOs and voluntarily reporting them to CDC by using a standard form. RESULTS: During 2003-2004, a total of 36 WBDOs were reported by 19 states; 30 were associated with drinking water, three were associated with water not intended for drinking, and three were associated with water of unknown intent. The 30 drinking water-associated WBDOs caused illness among an estimated 2,760 persons and were linked to four deaths. Etiologic agents were identified in 25 (83.3%) of these WBDOs: 17 (68.0%) involved pathogens (i.e., 13 bacterial, one parasitic, one viral, one mixed bacterial/parasitic, and one mixed bacterial/parasitic/viral), and eight (32.0%) involved chemical/toxin poisonings. Gastroenteritis represented 67.7% of the illness related to drinking water-associated WBDOs; acute respiratory illness represented 25.8%, and dermatitis represented 6.5%. The classification of deficiencies contributing to WBDOs has been revised to reflect the categories of concerns associated with contamination at or in the source water, treatment facility, or distribution system (SWTD) that are under the jurisdiction of water utilities, versus those at points not under the jurisdiction of a water utility or at the point of water use (NWU/POU), which includes commercially bottled water. A total of 33 deficiencies were cited in the 30 WBDOs associated with drinking water: 17 (51.5%) NWU/POU, 14 (42.4%) SWTD, and two (6.1%) unknown. The most frequently cited NWU/POU deficiencies involved Legionella spp. in the drinking water system (n = eight [47.1%]). The most frequently cited SWTD deficiencies were associated with distribution system contamination (n = six [42.9%]). Contaminated ground water was a contributing factor in seven times as many WBDOs (n = seven) as contaminated surface water (n = one). INTERPRETATION: Approximately half (51.5%) of the drinking water deficiencies occurred outside the jurisdiction of a water utility in situations not currently regulated by EPA. The majority of the WBDOs in which deficiencies were not regulated by EPA were associated with Legionella spp. or chemicals/toxins. Problems in the distribution system were the most commonly identified deficiencies under the jurisdiction of a water utility, underscoring the importance of preventing contamination after water treatment. The substantial proportion of WBDOs involving contaminated ground water provides support for the Ground Water Rule (finalized in October 2006), which specifies when corrective action is required for public ground water systems. PUBLIC HEALTH ACTIONS: CDC and EPA use surveillance data to identify the types of water systems, deficiencies, and etiologic agents associated with WBDOs and to evaluate the adequacy of current technologies and practices for providing safe drinking water. Surveillance data also are used to establish research priorities, which can lead to improved water-quality regulation development. The growing proportion of drinking water deficiencies that are not addressed by current EPA rules emphasizes the need to address risk factors for water contamination in the distribution system and at points not under the jurisdiction of water utilities.

Communicable Diseases↗

PubMed1995

Cryptosporidia--who is at risk?

Cryptosporidium parvum is a coccidian parasite originally described a century ago and, until recently, not considered to be a human pathogen. It has a complex life cycle, including both sexual and asexual reproduction, an auto-infectious cycle, and the ability to complete its development within a single host. The transmission form is a robust, environmentally resistant oocyst, excreted in the stool, which can exist for long periods of time in the environment. Because animals, in particular domesticated livestock, are its primary host, human infection is usually zoonotic. Oocysts often find their way into water supplies, and it resists chlorination and is incompletely filtered from processed drinking water supplies, even when filtration is working optimally. Transmission via ingestion of fecally contaminated swimming pool water, food, fomites, and sexual activities facilitating fecal-oral inoculation have been demonstrated. The major target of C. parvum in the host is the intestinal epithelial cell, resulting in diarrhea, sometimes profuse and persistent, although it may also infect other organs such as the gall bladder and lungs. Pathogenesis involves attachment, probably via a sporozoite lectin, invasion, probably involving apical organelles, replication within a parasitophorous vacuole with the host cell membrane, causing cellular dysfunction. Diagnosis is generally made by visualization of the oocyst form in stool by staining methods, the best of which appears to be auramine and fluorescence microscopy. Those at greatest risk are immunocompromised adults and children, especially those with AIDS, children in day care, travelers to endemic regions, dairy or cattle farm workers of their families or contacts, household contacts of cases or carriers, and possibly owners of infected dogs or cats or their neighbors. There is no specific therapy available, however in the immunocompetent host the illness is self-limited, lasting from a few days to 3 weeks, and long term carriage is uncommon. In the immunocompromised host, infection is prolonged, sometimes asymptomatic, but may result in chronic debilitating diarrhea with dehydration, malabsorption and wasting. Public health measures to reduce contamination of water supplies and vigilant surveillance will reduce the risk to populations. Reducing behaviors favoring fecal-oral transmission, such as certain sexual activities, and scrupulous hygiene in the day care setting would also reduce the likelihood of transmission but not eliminate it. Given our lack of knowledge about Cryptosporidium biology and pathogenesis, high priority should be given to research designed to increase our understanding of the organism and improve the chance of developing useful therapeutic or preventative drugs or strategies.

Adult↗

PubMed2006

The Ponseti method for treatment of congenital club foot.

PURPOSE OF REVIEW: This review of the Ponseti technique for the treatment of congenital club foot covers a topic of recently renewed interest. Pediatric orthopedists and parents have become increasingly enthusiastic about the success of this technique, which has been practiced continuously at the University of Iowa since 1948 but only recently become widely utilized. RECENT FINDINGS: Current literature has emphasized the reproducibility of these excellent results among multiple centers throughout the world. In addition, the role of the Internet, and accessibility of medical information have been central elements in the development of this phenomenon. SUMMARY: The current research should convince physicians that all children should be managed by the Ponseti technique at the outset. This research should also reassure physicians and parents that the overwhelming majority of children with club feet can be successfully managed, without the need for major reconstructive surgery.

Braces↗

PubMed2002

Surveillance for waterborne-disease outbreaks--United States, 1999-2000.

PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency (EPA), and the Council of State and Territorial Epidemiologists (CSTE) have maintained a collaborative surveillance system for the occurrences and causes of waterborne-disease outbreaks (WBDOs).This surveillance system is the primary source of data concerning the scope and effects of waterborne diseases on persons in the United States. REPORTING PERIOD COVERED: This summary includes data regarding outbreaks occurring during January 1999-December 2000 and previously unreported outbreaks occurring in 1995 and 1997. DESCRIPTION OF THE SYSTEM: The surveillance system includes data for 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. The unit of analysis for the WBDO surveillance system is an outbreak, not an individual case of a waterborne disease. Two criteria must be met for an event to be defined as a WBDO. First, > or = 2 persons must have experienced a similar illness after either ingestion of drinking water or exposure to water encountered in recreational or occupational settings. This criterion is waived for single cases of laboratory-confirmed primary amebic meningoencephalitis and for single cases of chemical poisoning if water-quality data indicate contamination by the chemical. Second, epidemiologic evidence must implicate water as the probable source of the illness. RESULTS: During 1999-2000, a total of 39 outbreaks associated with drinking water was reported by 25 states. Included among these 39 outbreaks was one outbreak that spanned 10 states. These 39 outbreaks caused illness among an estimated 2,068 persons and were linked to two deaths. The microbe or chemical that caused the outbreak was identified for 22 (56.4%) of the 39 outbreaks; 20 of the 22 identified outbreaks were associated with pathogens, and two were associated with chemical poisoning. Of the 17 outbreaks involving acute gastroenteritis of unknown etiology, one was a suspected chemical poisoning, and the remaining 16 were suspected as having an infectious cause. Twenty-eight (71.8%) of 39 outbreaks were linked to groundwater sources; 18 (64.3%) of these 28 groundwater outbreaks were associated with private or noncommunity wells that were not regulated by EPA. Fifty-nine outbreaks from 23 states were attributed to recreational water exposure and affected an estimated 2,093 persons. Thirty-six (61.0%) of the 59 were outbreaks involving gastroenteritis. The etiologic agent was identified in 30 (83.3%) of 36 outbreaks involving gastroenteritis. Twenty-two (61.1%) of 36 gastroenteritis-related outbreaks were associated with pools or interactive fountains. Four (6.8%) of the 59 recreational water outbreaks were attributed to single cases of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri. All four cases were fatal. Fifteen (25.4%) of the 59 outbreaks were associated with dermatitis; 12 (80.0%) of 15 were associated with hot tubs or pools. In addition, recreational water outbreaks of leptospirosis, Pontiac fever, and chemical keratitis, as well as two outbreaks of leptospirosis and Pontiac fever associated with occupational exposure were also reported to CDC. INTERPRETATION: The proportion of drinking water outbreaks associated with surface water increased from 11.8% during 1997-1998 to 17.9% in 1999-2000. The proportion of outbreaks (28) associated with groundwater sources increased 87% from the previous reporting period (15 outbreaks), and these outbreaks were primarily associated (60.7%) with consumption of untreated groundwater. Recreational water outbreaks involving gastroenteritis doubled (36 outbreaks) from the number of outbreaks reported in the previous reporting period (18 outbreaks). These outbreaks were most frequently associated with Cryptosporidium parvum (68.2%) in treated water venues (e.g., swimming pools or interactive fountains) and by Escherichia coli O157:H7 (21.4%) in freshwater venues. The increase in the number of outbreaks probably reflects improved surveillance and reporting at the local and state level as well as a true increase in the number of WBDOs. PUBLIC HEALTH ACTION: CDC and others have used surveillance data to identify the types of water systems, their deficiencies, and the etiologic agents associated with outbreaks and evaluated current technologies for providing safe drinking water and safe recreational water. Surveillance data are used also to establish research priorities, which can lead to improved water-quality regulations. Only the groundwater systems under the influence of surface water are required to disinfect their water supplies, but EPA is developing a groundwater rule that specifies when corrective action (including disinfection) is required. CDC and EPA are conducting epidemiologic studies to assess the level of waterborne illness attributable to municipal drinking water in nonoutbreak conditions. Rules under development by EPA--the Ground Water Rule (GWR), the Long Term 2 Enhanced Surface Water Treatment Rule (LT2ESWTR), and Stage 2 Disinfection Byproduct Rules (DBPR)--are expected to further protect the public from contaminants and disinfection byproducts in drinking water. Efforts by EPA under the Beaches Environmental Assessment, Closure, and Health (BEACH) program are aimed at reducing the risks for infection attributed to ambient recreational water by strengthening beach standards and testing; providing faster laboratory test methods; predicting pollution; investing in health and methods research; and improving public access to information regarding both the quality of the water at beaches and information concerning health risks associated with swimming in polluted water. EPA's Beach Watch (available at http://www.epa.gov/waterscience/beaches) provides online information regarding water quality at U.S. beaches, local protection programs, and other beach-related programs. CDC partnered with a consortium of local and national pool associations to develop a series of health communication materials for the general public who attend treated recreational water venues and to staff who work at those venues. CDC has also developed a recreational water outbreak investigation toolkit that can be used by public health professionals. All of the CDC materials are accessible at the CDC Healthy Swimming website (http://www.cdc.gov/healthyswimming).

Communicable Diseases↗

PubMed2025

Global emergence and transmission dynamics of carbapenemase-producing Citrobacter freundii sequence type 22 high-risk international clone: a retrospective, genomic, epidemiological study.

BACKGROUND: Carbapenemase-producing Citrobacter (CPC) species have recently been recognised as emerging pathogens associated with nosocomial infections in humans. The increased rate of Citrobacter freundii infections is a public health concern and there is a paucity of genomic data regarding its global transmission dynamics. We aimed to characterise the genetic features of CPC species, and their associated carbapenemase-encoding plasmids, obtained from hospitalised patients in China and from publicly available global data, with a particular focus on high-risk clones. METHODS: This was a retrospective, genomic epidemiological study of CPC species obtained from a tertiary hospital in Zhejiang Province, China, from March 5, 2013, to March 5, 2023. We used antimicrobial susceptibility testing, short-read and long-read whole-genome sequencing, phylogenomic analysis, and plasmid structure analysis. A global dataset of complete plasmid sequences encoding blaKPC, blaNDM, and blaIMP was constructed from the National Center for Biotechnology Information (NCBI) RefSeq database to provide insights into their diversity and distribution. All carbapenemase-producing Citrobacter freundii genomes from the NCBI GenBank database were incorporated in the comparative genomic analyses. Bayesian phylogeographical analysis and growth rate assays were carried out to characterise the high-risk C freundii sequence type (ST) 22 clone. FINDINGS: 1724 Citrobacter species isolates were collected from diverse clinical specimens, with 48 identified as CPC species. Citrobacter koseri (22 [46%] of 48) and C freundii (20 [42%]) were the predominant CPC species. Comparative analysis found C freundii carried significantly higher median numbers of plasmid replicons (5·0 [IQR 3·3-6·0] vs 2·0 [2·0-3·0]; p<0·0001) and acquired antimicrobial resistance genes (12·0 [7·3-15·8] vs 3·0 [3·0-5·3]; p<0·0001) than did C koseri. Molecular characterisation identified Inc-type plasmids, In823::Kl.pn.I3/In1589-like/In837-like integrons, Tn6296/Tn125/Tn5060 transposons, and insertion sequences (eg, IS26, IS3000, IS5, ISAba125, ISCR1), collectively facilitating the dissemination of carbapenemase genes. Global analysis of 3126 carbapenemase-encoding plasmids found epidemic plasmids with broad host ranges and global diversity. Phylogenetic investigation of predominant carbapenemase-encoding plasmids showed their persistence across geographical regions, temporal spans, and Enterobacterales species, exhibiting high genetic similarity to our clinical plasmids. A phylogenetic tree of 726 global carbapenemase-producing C freundii genomes showed that ST22 (227 [31·3%]) represents the predominant multidrug-resistant clone across community, health-care, and environmental niches. Transmission across continents contributes to the global predominance of the ST22 clone, which carries a high load of resistance genes (median 15·0 [IQR 11·0-17·0] vs 12·0 [3·0-16·0]; p<0·0001) and enhanced plasmid maintenance capacity (median replicons 5·0 [IQR 4·0-7·0] vs 4·0 [3·0-6·0]; p<0·0001) relative to non-ST22 clones. INTERPRETATION: Our study provides evidence to suggest that Citrobacter species are emerging carriers of carbapenem-resistance genes. These findings provide insight into the population structure of CPC species and highlight C freundii ST22 as a prominent high-risk international clone. FUNDING: National Natural Science Foundation of China, National Health Commission Scientific Research Fund-Zhejiang Provincial Major Health Science and Technology Plan Project, Zhejiang Province Natural Science Foundation Project, Outstanding Youth Foundation of Jiangsu Province of China, the Priority Academic Program Development of Jiangsu Higher Education Institutions, and Postgraduate Research and Practice Innovation Program of Jiangsu Province.

Citrobacter freundii↗