The burden of respiratory syncytial virus in adults: a systematic review and meta-analysis.

Respiratory syncytial virus (RSV) is the most common pathogen associated with acute lower respiratory tract infections in young children. RSV is also a major viral pathogen causing severe lung disease in the adult population, particularly among the elderly. We conducted a review of adult RSV studies published from January 1970 to February 2017 to determine the burden of disease among adults worldwide. There were no restrictions on health care setting or definition of RSV infection. A total of 1530 published studies were identified, 95 of which were included in this review. The incidence rates of hospitalised RSV acute respiratory tract infection (ARI) in adults >65 years old ranged from 7.3 to 13.0/105 population in Africa and Asia and from 190 to 254/105 population in the USA. Higher incidence rates (195-1790/105 population) were observed in adults ≥50 years old for outpatient or emergency visits in the USA. Of all ARI patients, RSV accounted for 1-10% in adults and 2-14% in patients with chronic diseases or transplantation. Given the limitations in the existing data, significant efforts should be made to generate evidence on the burden of RSV infections in adults and to estimate the potential impact of future preventive interventions.

National patterns of Escherichia coli O157 infections, USA, 1996-2011.

US public health laboratories began reporting Escherichia coli O157 isolates to CDC in 1996. We describe temporal and geographical patterns of isolates reported from 1996 to 2011 and demographics of persons whose specimens yielded isolates. We calculated annual E. coli O157 isolation rates/100 000 persons by patient's state of residence, county of residence, age, and sex using census data. The average annual isolation rate was 0·84. The average isolation rate in northern states (1·52) was higher than in southern states (0·43). Counties with ⩾76% rural population had a lower isolation rate (0·67) than counties with ⩽25%, 26-50%, and 51-75% rural populations (0·81, 0·92, and 0·81, respectively). The highest isolation rate (3·19) was in children aged 1-4 years. Infections were seasonal with 49% of isolates collected during July to September. Research into reasons for higher incidence in northern states and for seasonality could guide strategies to prevent illnesses.

Outbreak of type A foodborne botulism at a boarding school, Uganda, 2008.

Botulism has rarely been reported in Africa. In October 2008, botulism was reported in three Ugandan boarding-school students. All were hospitalized and one died. A cohort study was performed to assess food exposures among students, and clinical specimens and available food samples were tested for botulinum toxin. Three case-patients were identified; a homemade, oil-based condiment was eaten by all three. In the cohort study, no foods were significantly associated with illness. Botulinum toxin type A was confirmed in clinical samples. This is the first confirmed outbreak of foodborne botulism in Uganda. A homemade, oil-based condiment was the probable source. Consumption of homemade oil-based condiments is widespread in Ugandan schools, putting children at risk. Clinicians and public health authorities in Uganda should consider botulism when clusters of acute flaccid paralysis are seen. Additionally, schools should be warned of the hazard of homemade oil-based condiments, and take steps to prevent their use.

Evidence of exposure to spotted fever group rickettsiae among Arizona dogs outside a previously documented outbreak area.

Since 2003, two communities in eastern Arizona have experienced a sustained outbreak of Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii, associated with transmission by Rhipicephalus sanguineus, the brown dog tick; 70 human cases, including eight deaths, were reported from these communities during 2003 through 2008. In both of the affected communities, antibodies to spotted fever group rickettsiae (SFGR) were present in dogs before the notice of the first human cases, suggesting that dogs may serve as useful sentinels for human risk of RMSF in this region. During 2005 and 2006, an exploratory serosurvey was conducted among stray and relinquished dogs presenting to animal control facilities in eastern Arizona located outside the area where human cases had been reported. Antibodies to SFGR were detected in 5.7% (14 of 247) dogs assessed outside the RMSF outbreak area. Animal shelters located in counties that either included or shared large borders with the outbreak area were significantly more likely to have seropositive dogs than facilities in more geographically separated counties (P = 0.01). In addition, stray dogs were significantly more likely to be antibody-positive than relinquished animals (P = 0.01), suggesting that control of stray dog populations should be considered as a means of limiting SFGR transmission in this region. The findings from this study may be extrapolated to suggest that the current risk for human RMSF infection may extend beyond the noted outbreak area. Heightened surveillance for human disease is needed in the region.

Human monocytic ehrlichiosis and human granulocytic anaplasmosis in the United States, 2001-2002.

The epidemiologic features are described of cases of human monocytic ehrlichiosis and human granulocytic anaplasmosis in the United States.

Precautions against biological and chemical terrorism directed at food and water supplies.

Deliberate food and water contamination remains the easiest way to distribute biological or chemical agents for the purpose of terrorism, despite the national focus on dissemination of these agents as small-particle aerosols or volatile liquids. Moreover, biological terrorism as a result of sabotage of our food supply has already occurred in the United States. A review of naturally occurring food- and waterborne outbreaks exposes this vulnerability and reaffirms that, depending on the site of contamination, a significant number of people could be infected or injured over a wide geographic area. Major knowledge gaps exist with regard to the feasibility of current disinfection and inspection methods to protect our food and water against contamination by a number of biological and chemical agents. However, a global increase in food and water safety initiatives combined with enhanced disease surveillance and response activities are our best hope to prevent and respond quickly to food- and waterborne bioterrorism.

Evaluation of methods for subtyping Campylobacter jejuni during an outbreak involving a food handler.

In October 1998, the Centers for Disease Control and Prevention (CDC) assisted in an investigation of an outbreak of campylobacteriosis at a school in Salina, Kansas. Twenty-two isolates were submitted from the Kansas state public health laboratory to CDC, 9 associated with the outbreak and 13 epidemiologically unrelated sporadic isolates. Pulsed-field gel electrophoresis (PFGE) using SmaI and SalI was initially used to validate the epidemiologic data. We then tested the ability of other subtyping techniques to distinguish the outbreak-associated isolates from unrelated sporadic isolates. The methods employed were somatic O serotyping, PCR-restriction fragment length polymorphism (RFLP) analysis of flaA, DNA sequence analysis of 582 bp of flaA that included the short variable region (SVR), and sequencing of the entire flaA gene. PFGE was the most discriminatory technique, yielding 11 SmaI and 10 SalI restriction profiles. All outbreak isolates were indistinguishable by PFGE, somatic O serotyping, and sequencing of the 582-bp region of the flaA gene. fla typing by PCR-RFLP grouped one sporadic isolate with the outbreak strain. Analysis of the DNA sequence of a 582-bp segment of flaA produced strain groupings similar to that generated by PCR-RFLP but further differentiated two flaA PCR-RFLP types (with a 1-bp difference in the 582-bp region). Two sporadic strains were distinct by flaA PCR-RFLP but differed only by a single base substitution in the 582-bp region. The entire flaA gene was sequenced from strains differing by a single base pair in the 582-bp region, and the data revealed that additional discrimination may in some cases be obtained by sequencing outside the SVR. PFGE was superior to all other typing methods tested for strain discrimination; it was crucial for understanding the Kansas outbreak and, when SmaI was used, provided adequate discrimination between unrelated isolates.

Botulinum toxin as a biological weapon: medical and public health management.

OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if botulinum toxin is used as a biological weapon against a civilian population. PARTICIPANTS: The working group included 23 representatives from academic, government, and private institutions with expertise in public health, emergency management, and clinical medicine. EVIDENCE: The primary authors (S.S.A. and R.S.) searched OLDMEDLINE and MEDLINE (1960-March 1999) and their professional collections for literature concerning use of botulinum toxin as a bioweapon. The literature was reviewed, and opinions were sought from the working group and other experts on diagnosis and management of botulism. Additional MEDLINE searches were conducted through April 2000 during the review and revisions of the consensus statement. CONSENSUS PROCESS: The first draft of the working group's consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group convened to review the first draft in May 1999. Working group members reviewed subsequent drafts and suggested additional revisions. The final statement incorporates all relevant evidence obtained in the literature search in conjunction with final consensus recommendations supported by all working group members. CONCLUSIONS: An aerosolized or foodborne botulinum toxin weapon would cause acute symmetric, descending flaccid paralysis with prominent bulbar palsies such as diplopia, dysarthria, dysphonia, and dysphagia that would typically present 12 to 72 hours after exposure. Effective response to a deliberate release of botulinum toxin will depend on timely clinical diagnosis, case reporting, and epidemiological investigation. Persons potentially exposed to botulinum toxin should be closely observed, and those with signs of botulism require prompt treatment with antitoxin and supportive care that may include assisted ventilation for weeks or months. Treatment with antitoxin should not be delayed for microbiological testing.

An outbreak of Campylobacter jejuni infections associated with food handler contamination: the use of pulsed-field gel electrophoresis.

In 1998, an outbreak of Campylobacter jejuni infections occurred in Kansas among persons attending a school luncheon; community cases were also reported. In a cohort study of luncheon attendees, 27 (17%) of 161 persons reported illness. Consuming gravy (relative risk [RR], 4.2; 95% confidence interval [CI], 1.5-11.7) or pineapple (RR, 2.4; 95% CI, 1.0-5.7) was associated with illness. Both foods were prepared in a kitchen that served 6 other schools where no illness was reported. A cafeteria worker at the luncheon had a diarrheal illness and was the likely source of the outbreak. The pulsed-field gel electrophoresis (PFGE) patterns of the isolates from the food handler and those of 8 lunch attendees were indistinguishable. Isolates from 4 community patients differed. This was the first use of PFGE in a Campylobacter outbreak in the United States; its use was critical in determining that community cases were not linked.

The pandemic of Salmonella enteritidis phage type 4 reaches Utah: a complex investigation confirms the need for continuing rigorous control measures.

In 1995, Salmonella Enteritidis (SE) cases in the state of Utah increased fivefold. Isolates were identified as phage type 4 (PT4). Risk factors and sources of infection were investigated in two case-control studies, a traceback of implicated foods, and environmental testing. Forty-three patients with sporadic infections and 86 controls were included in a case-control study of risk factors for infection. A follow-up case-control study of 25 case and 19 control restaurants patronized by case and control patients examined risks associated with restaurant practices. In the first case-control study, restaurant dining was associated with illness (P = 0.002). In the follow-up case-control study, case restaurants were likelier to use > 2000 eggs per week (P < 0.02), to pool eggs (P < 0.05), and to use eggs from cooperative 'A' (P < 0.009). Eggs implicated in separately investigated SE PT4 outbreaks were traced to cooperative 'A', and SE PT4 was cultured from one of the cooperative's five local farms. We conclude that SE PT4 transmitted by infected eggs from a single farm caused a fivefold increase in human infections in Utah.

Comparison of Escherichia coli O157:H7 antigen detection in stool and broth cultures to that in sorbitol-MacConkey agar stool cultures.

We evaluated the Meridian IC-STAT direct fecal and broth culture antigen detection methods with samples from children infected with Escherichia coli O157:H7 and correlated the antigen detection results with the culture results. Stools of 16 children who had recently had stool cultures positive for this pathogen (population A) and 102 children with diarrhea of unknown cause (population B) were tested with the IC-STAT device (direct testing). Fecal broth cultures were also tested with this device (broth testing). The results were correlated to a standard of the combined yield from direct culture of stools on sorbitol-MacConkey (SMAC) agar and culture of broth on SMAC agar. Eleven (69%) of the population A stool specimens yielded E. coli O157:H7 when plated directly on SMAC agar. Two more specimens yielded this pathogen when the broth culture was similarly plated. Of these 13 stool specimens, 8 and 13 were positive by direct and broth testing (respective sensitivities, 62 and 100%). Compared to the sensitivity of a simultaneously performed SMAC agar culture, the sensitivity of direct testing was 73%. Three (3%) of the population B stool specimens contained E. coli O157:H7 on SMAC agar culture; one and three of these stool specimens were positive by direct and broth testing, respectively. The direct and broth IC-STAT tests were 100% specific with samples from children from population B. Direct IC-STAT testing of stools is rapid, easily performed, and specific but is insufficiently sensitive to exclude the possibility of infection with E. coli O157:H7. Performing the IC-STAT test with a broth culture increases its sensitivity. However, attempts to recover E. coli O157:H7 by culture should not be abandoned but, rather, should be increased when the IC-STAT test result is positive.

Host-pathogen interactions in emerging and re-emerging infectious diseases: a genomic perspective of tuberculosis, malaria, human immunodeficiency virus infection, hepatitis B, and cholera.

On exposure to a pathogen, a host may resist infection, become subclinically infected, or progress through several stages from mild to severe infection. Chronic sequelae may or may not occur. Host factors, particularly host genes, influence many of these stages. We have used a model of the continuum of pathogenesis of infectious diseases to consider the effect of host genes on five pathogens of significant public health burden: Mycobacterium tuberculosis, Plasmodium species, human immunodeficiency virus, hepatitis B virus, and Vibrio cholerae. The relationships between these infections and polymorphisms in human leukocyte antigen, cytokines, other immune response, or pathogen receptor genes are reviewed. We discuss gene-gene interactions and their effects in complex settings, such as coinfections with several pathogens. Priorities for prevention and control of these pathogens include vaccines and antimicrobial drugs. Research on how host genes can influence vaccine responses and the efficacy of drugs or other interventions, as well as further research into the relationship of host genes to infectious disease outcomes, may lead to new strategies for prevention and control.

Helicobacter pylori and epidemic Vibrio cholerae O1 infection in Peru.

In a cross-sectional study of the 1991 Peruvian cholera epidemic, Vibrio cholerae O1 infection was associated with Helicobacter pylori infection, particularly in young children. These data support the hypothesis that hypochlorhydria induced by H. pylori is important in the pathogenesis of diarrhoeal disease.

Campylobacter jejuni.

Campylobacter jejuni is the most frequently diagnosed bacterial cause of human gastroenteritis in the United States. The emergence of antimicrobial-resistant and, in particular, of fluoroquinolone-resistant C. jejuni infections in Europe and the United States, temporally associated with the approval of use of fluoroquinolones in veterinary medicine, is an important public health concern. Recent research has provided strong evidence for an association between Campylobacter infection and Guillain-Barr Syndrome (GBS), and Campylobacter is the most frequent antecedent infection in GBS. The consumption of undercooked poultry and cross-contamination of other foods with uncooked meat products are leading risk factors for human campylobacteriosis. Reinforcing hygienic practices at each link in the food chain, from producer to consumer, is critical in preventing the disease.

Global burden of Shigella infections: implications for vaccine development and implementation of control strategies.

Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we report the results of a review of the literature published between 1966 and 1997 on Shigella infection. The data obtained permit calculation of the number of cases of Shigella infection and the associated mortality occurring worldwide each year, by age, and (as a proxy for disease severity) by clinical category, i.e. mild cases remaining at home, moderate cases requiring outpatient care, and severe cases demanding hospitalization. A sensitivity analysis was performed to estimate the high and low range of morbid and fatal cases in each category. Finally, the frequency distribution of Shigella infection, by serogroup and serotype and by region of the world, was determined. The annual number of Shigella episodes throughout the world was estimated to be 164.7 million, of which 163.2 million were in developing countries (with 1.1 million deaths) and 1.5 million in industrialized countries. A total of 69% of all episodes and 61% of all deaths attributable to shigellosis involved children under 5 years of age. The median percentages of isolates of S. flexneri, S. sonnei, S. boydii, and S. dysenteriae were, respectively, 60%, 15%, 6%, and 6% (30% of S. dysenteriae cases were type 1) in developing countries; and 16%, 77%, 2%, and 1% in industrialized countries. In developing countries, the predominant serotype of S. flexneri is 2a, followed by 1b, 3a, 4a, and 6. In industrialized countries, most isolates are S. flexneri 2a or other unspecified type 2 strains. Shigellosis, which continues to have an important global impact, cannot be adequately controlled with the existing prevention and treatment measures. Innovative strategies, including development of vaccines against the most common serotypes, could provide substantial benefits.

PIP: This article presents a review of the literature published between 1966 and 1997 on Shigella infection. The purpose of the review is to provide data on the global morbidity and mortality caused by the infection and to plan strategies of prevention and treatment. The data obtained from this literature were used to calculate the number of Shigella infection cases and the associated mortality occurring worldwide each year, by age and by clinical category. The burden of Shigella infection was also estimated by serogroup and serotype. A sensitivity analysis was performed to estimate the high and the low range of morbid and fatal cases in each category (mild cases remaining at home, moderate cases requiring outpatient care and severe cases demanding hospitalization). The result of the calculations and analysis revealed that the annual number of Shigella infections throughout the world was estimated to be 164.7 million. 163.2 million occurred in developing countries, with 1.1 million deaths, and 1.5 million occurred in industrialized countries. More than half of the episodes and death affects children under 5 years of age. In comparing developing countries against industrialized countries, the median of isolates are S. flexneri (60% vs. 16%), S. sonnei (15% vs. 77%), S. dysenteriae (6% vs. 1%), and S. boydii (6% vs. 2%). The predominant serotype of S. flexneri in developing countries is 2a, followed by 1b, 3a, 4a, and 6, while in industrialized countries most isolates are S. flexneri 2a and unspecified type 2 strains.

Clinical, epidemiological, and microbiological features of Vibrio vulnificus biogroup 3 causing outbreaks of wound infection and bacteraemia in Israel. Israel Vibrio Study Group.

BACKGROUND: Vibrio vulnificus is a gram-negative bacterium that causes septicaemia and wound infection. Cases occur sporadically, and no previous outbreaks due to a common source or a clonal strain have been reported. In the summer and autumn of 1996 and 1997, an outbreak of invasive V. vulnificus infection occurred in Israel in people who had recently handled fresh, whole fish purchased from artificial fish-ponds. METHODS: We reviewed clinical and epidemiological information, and undertook an environmental investigation to assess disease characteristics, modes of transmission, phenotypic characteristics of the bacterium, and fish-marketing policy. The clonal nature of 19 isolates was studied by biotyping, pulsed-field gel electrophoresis, and restriction-fragment length polymorphism (RFLP) analysis of a PCR fragment. FINDINGS: During 1996-97, 62 cases of wound infection and bacteraemia occurred. 57 patients developed cellulitis, four had necrotising fasciitis, and one developed osteomyelitis. In all cases, the fish were cultivated in inland fish-ponds. In the summer of 1996, fish-pond managers initiated a new marketing policy, in which fish were sold alive instead of being packed in ice. Phenotypically, the isolates had five atypical biochemical test results. The isolates were non-typeable by pulsed-field gel electrophoresis, and all had the same PCR-RFLP pattern which had not been seen previously. INTERPRETATION: The cause of the outbreak was a new strain of V. vulnificus, classified as biogroup 3. A new fish-marketing policy that began in 1996 may have exposed susceptible people to the organism.

Outbreak of type A botulism and development of a botulism surveillance and antitoxin release system in Argentina.

CONTEXT: Botulism is an important public health problem in Argentina, but obtaining antitoxin rapidly has been difficult because global supplies are limited. In January 1998, a botulism outbreak occurred in Buenos Aires. OBJECTIVES: To determine the source of the outbreak, improve botulism surveillance, and establish an antitoxin supply and release system in Argentina. DESIGN, SETTING, AND PARTICIPANTS: Cohort study in January 1998 of 21 drivers of a specific bus route in urban Buenos Aires. MAIN OUTCOME MEASURE: Occurrence of botulism and implication of a particular food as the vehicle causing this outbreak. RESULTS: Nine (43%) of 21 bus drivers developed botulism, presenting with gastroenteritis, symptoms of acute cranial nerve dysfunction including ptosis, dysphagia, blurred vision, and motor weakness. One driver experienced respiratory failure. Type A toxin was detected from 3 of 9 patients' serum samples. All drivers received botulism antitoxin; there were no fatalities. Consumption of matambre (Argentine meat roll) was significantly associated with illness. Among 11 persons who ate matambre, 9 developed illness, compared with none of those who did not eat it (P<.001). The matambre had been cooked in water at 78 degrees C to 80 degrees C for 4 hours, sealed in heat-shrinked plastic wrap, and stored in refrigerators that did not cool adequately. Subsequently, a botulism surveillance and antitoxin release system was established. CONCLUSIONS: Insufficient cooking time and temperatures, storage in heat-shrinked plastic wrap, and inadequate refrigeration likely contributed to Clostridium botulinum spore survival, germination, and toxin production. A rapid-response botulism surveillance and antitoxin release system in Argentina should provide more timely distribution of antitoxin to patients and may serve as a model for other nations.