We describe a case of botulism infection in a patient who had undergone laparoscopic appendectomy, an occurrence not previously described in the literature. This case exemplifies the need for coordination between clinical and public health personnel to ensure the immediate recognition and treatment of suspected botulism cases.
Objectives. We examined the association between Helicobacter pylori infection and the incidence of diarrheal diseases.
Methods. In a nested case-control study participants were sampled from cohorts of male Israeli soldiers aged 18–21 years, serving in field units and followed up for diarrheal diseases. Case patients (n = 177) were subjects who visited the base clinic because diarrhea and were positive for Shigella sonnei (n = 66), enterotoxigenic Escherichia coli (ETEC) (n = 31) or negative for bacterial pathogens (n = 80; diarrhea of unknown etiology). Controls (n = 418) were subjects who did not suffer from a diarrheal disease during the follow-up. They were matched to case patients by training unit and period. Serum samples were obtained from participants at the beginning of their field training and were tested for anti–H. pylori immunoglobulin (Ig) G and preexisting Shigella sonnei lipopolysaccharide IgG and IgA antibodies using enzyme-linked immunosorbent assay.
Results. The proportion of H. pylori–infected subjects was significantly lower among case patients with infection of unknown etiology (36.3%) than among controls (56.0%) (adjusted odds ratio [OR], 0.43; 95% confidence interval [CI], .24–.77; P = .005). The proportion of H. pylori–infected subjects among case patients with S. sonnei shigellosis was also significantly lower than in the control group: 36.3% versus 56.0%. The association persisted after adjusting for sociodemographic variables and preexisting S. sonnei serum IgA antibodies (adjusted OR, 0.37; 95% CI, .14–.95; P = .03) and IgG antibodies (adjusted OR, 0.38; 95% CI, .14–.99; P = .04). The direction of the association between H. pylori infection and ETEC diarrhea was similar, albeit not statistically significant.
Conclusions. Our findings suggest an active role of H. pylori in protection against diarrheal diseases.
Background. International travel poses a risk of destination-specific illness and may contribute to the global spread of infectious diseases. Despite this, little is known about the health characteristics and pretravel healthcare of US international travelers, particularly those at higher risk of travel-associated illness.
Methods. We formed a national consortium (Global TravEpiNet) of 18 US clinics registered to administer yellow fever vaccination. We collected data regarding demographic and health characteristics, destinations, purpose of travel, and pretravel healthcare from 13235 international travelers who sought pretravel consultation at these sites from January 2009 through January 2011.
Results. The destinations and itineraries of Global TravEpiNet travelers differed from those of the overall population of US international travelers. The majority of Global TravEpiNet travelers were visiting low- or lower-middle-income countries, and Africa was the most frequently visited region. Seventy-five percent of travelers were visiting malaria-endemic countries, and 38% were visiting countries endemic for yellow fever. Fifty-nine percent of travelers reported ≥1 medical condition. Atovaquone/proguanil was the most commonly prescribed antimalarial drug, and most travelers received an antibiotic for self-treatment of travelers’ diarrhea. Hepatitis A and typhoid were the most frequently administered vaccines.
Conclusions. Data from Global TravEpiNet provide insight into the characteristics and pretravel healthcare of US international travelers who are at increased risk of travel-associated illness due to itinerary, purpose of travel, or existing medical conditions. Improved understanding of this epidemiologically significant population may help target risk-reduction strategies and interventions to limit the spread of infections related to global travel.
Background. Google Flu Trends (GFT) is a novel Internet-based influenza surveillance system that uses search engine query data to estimate influenza activity and is available in near real time. This study assesses the temporal correlation of city GFT data to cases of influenza and standard crowding indices from an inner-city emergency department (ED).
Methods. This study was performed during a 21-month period (from January 2009 through October 2010) at an urban academic hospital with physically and administratively separate adult and pediatric EDs. We collected weekly data from GFT for Baltimore, Maryland; ED Centers for Disease Control and Prevention–reported standardized influenzalike illness (ILI) data; laboratory-confirmed influenza data; and ED crowding indices (patient volume, number of patients who left without being seen, waiting room time, and length of stay for admitted and discharged patients). Pediatric and adult data were analyzed separately using cross-correlation with GFT.
Results. GFT correlated with both number of positive influenza test results (adult ED, r = 0.876; pediatric ED, r = 0.718) and number of ED patients presenting with ILI (adult ED, r = 0.885; pediatric ED, r = 0.652). Pediatric but not adult crowding measures, such as total ED volume (r = 0.649) and leaving without being seen (r = 0.641), also had good correlation with GFT. Adult crowding measures for low-acuity patients, such as waiting room time (r = 0.421) and length of stay for discharged patients (r = 0.548), had moderate correlation with GFT.
Conclusions. City-level GFT shows strong correlation with influenza cases and ED ILI visits, validating its use as an ED surveillance tool. GFT correlated with several pediatric ED crowding measures and those for low-acuity adult patients.
(See the Editorial Commentary by Kollef, on pages
Background. Not all risk factors for acquiring multidrug-resistant (MDR) organisms are equivalent in predicting pneumonia caused by resistant pathogens in the community. We evaluated risk factors for acquiring MDR bacteria in patients coming from the community who were hospitalized with pneumonia. Our evaluation was based on actual infection with a resistant pathogen and clinical outcome during hospitalization.
Methods. An observational, prospective study was conducted on consecutive patients coming from the community who were hospitalized with pneumonia. Data on admission and during hospitalization were collected. Logistic regression models were used to evaluate risk factors for acquiring MDR bacteria independently associated with the actual presence of a resistant pathogen and in-hospital mortality.
Results. Among the 935 patients enrolled in the study, 473 (51%) had at least 1 risk factor for acquiring MDR bacteria on admission. Of all risk factors, hospitalization in the preceding 90 days (odds ratio [OR], 4.87 95% confidence interval {CI}, 1.90–12.4]; P = .001) and residency in a nursing home (OR, 3.55 [95% CI, 1.12–11.24]; P = .031) were independent predictors for an actual infection with a resistant pathogen. A score able to predict pneumonia caused by a resistant pathogen was computed, including comorbidities and risk factors for MDR. Hospitalization in the preceding 90 days and residency in a nursing home were also independent predictors for in-hospital mortality.
Conclusions. Risk factors for acquiring MDR bacteria should be weighted differently, and a probabilistic approach to identifying resistant pathogens among patients coming from the community with pneumonia should be embraced.
Background. Antibiotic-resistant Staphylococcus aureus is a globally emerging pathogen. Exchangeable virulence factors, such as Panton-Valentine leukocidin (PVL), have been proposed to drive this epidemic. We investigated whether skin infections and nasal colonization in travelers contribute to the global spread of such strains.
Methods. We conducted a case-control study of 38 returnees from the tropics and subtropics with S. aureus–positive skin and soft tissue infections (SSTIs) and 124 control patients with other travel-associated disorders. We collected information on travel characteristics, clinical outcomes of SSTIs, antibiotic sensitivity patterns, and genotypes of S. aureus strains isolated from skin lesions and the nares.
Results. S. aureus–positive SSTIs were associated with travel duration and purpose and were most common in returnees from Africa (odds ratio, 4.2; P = .005). PVL-positive (PVL+) S. aureus was frequent in the lesional and nasal isolates from travelers with SSTIs but could not be found in the nares of the control patients. The presence of PVL in S. aureus in travelers was associated with complicated disease, reduced antibiotic susceptibility, and secondary spread. The genotypes of PVL+ S. aureus in returnees were reported to be endemic to the visited destination but rarely observed in Europe.
Conclusions. Geographic variation in the risk of SSTIs in travelers supports a globally heterogeneous distribution of virulent S. aureus. Complicated SSTIs in returnees from nontemperate climates are associated with PVL+ S. aureus and promote the emergence and spread of virulent and antibiotic-resistant strains. We propose a network for the surveillance of imported S. aureus (www.staphtrav.eu).
Background. Definition of clinical trial end points for childhood tuberculosis is hindered by lack of a standard case definition. We aimed to identify areas of consensus or debate on potential end points for tuberculosis vaccine trials among human immunodeficiency virus–uninfected children.
Methods. Thirty-eight opinion leaders participated in a Consensus Workshop at the Second Global Forum on TB Vaccines (Estonia, 2010). Outcomes were categorized as unanimity, modified consensus, or lack of consensus. Individual reservations were noted.
Results. Modified consensus was achieved on 3 issues: (1) unsuitability of historical BCG trial end points as sole primary end points for modern infant trials; (2) symptomatic, complicated intrathoracic tuberculosis as an uncommon but clinically relevant disease phenotype; (3) primary complex tuberculosis in younger children as a common, high-risk phenotype, with a high rate of spontaneous resolution. Participants agreed that radiologic diagnosis of intrathoracic tuberculosis would be based primarily on hilar lymphadenopathy. Lack of consensus was noted for (1) significance of isolated culture of Mycobacterium tuberculosis and (2) the need for evidence of prior tuberculosis exposure to support a diagnosis of tuberculosis disease. Reservations were expressed regarding use of interferon- release assays and the clinical relevance, and potential for misclassification, of primary complex tuberculosis.
Conclusions. The Workshop did not achieve consensus on a single primary end-point definition. Tuberculosis disease phenotypes with optimal diagnostic certainty will be uncommon in the study population. Criteria for composite or multiple end points were identified, and we propose a hierarchy of end-point criteria, based on rate of occurrence, clinical relevance, and diagnostic certainty.
Background. Candida bloodstream infections cause significant morbidity and mortality among hospitalized patients. Although clinical and microbiological factors affecting prognosis have been identified, the impact of genetic variation in the innate immune responses mediated by cytokines on outcomes of infection remains to be studied.
Methods. A cohort of 338 candidemia patients and 351 noninfected controls were genotyped for single-nucleotide polymorphisms (SNPs) in 6 cytokine genes (IFNG, IL10, IL12B, IL18, IL1β, IL8) and 1 cytokine receptor gene (IL12RB1). The association of SNPs with both candidemia susceptibility and outcome were assessed. Concentrations of pro- and antiinflammatory cytokines were measured in in vitro peripheral blood mononuclear cell stimulation assays and in serum from infected patients.
Results. None of the cytokine SNPs studied were associated with susceptibility to candidemia. Persistent fungemia occurred in 13% of cases. In the multivariable model, persistent candidemia was significantly associated with (odds ratio [95% confidence interval]): total parenteral nutrition (2.79 [1.26–6.17]), dialysis dependence (3.76 [1.46–8.64]), and the SNPs IL10 rs1800896 (3.45 [1.33–8.93]) and IL12B rs41292470 (5.36 [1.51–19.0]). In vitro production capacity of interleukin-10 and interferon- was influenced by these polymorphisms, and significantly lower proinflammatory cytokine concentrations were measured in serum from patients with persistent fungemia.
Conclusions. Polymorphisms in IL10 and IL12B that result in low production of proinflammatory cytokines are associated with persistent fungemia in candidemia patients. This provides insights for future targeted management strategies for patients with Candida bloodstream infections.
Background. Escherichia coli O157:H7 is a Shiga toxin–producing E. coli (STEC) associated with numerous foodborne outbreaks in the United States and is an important cause of bacterial gastrointestinal illness. In May 2009, we investigated a multistate outbreak of E. coli O157:H7 infections.
Methods. Outbreak-associated cases were identified using serotyping and molecular subtyping procedures. Traceback investigation and product testing were performed. A matched case-control study was conducted to identify exposures associated with illness using age-, sex-, and state-matched controls.
Results. Seventy-seven patients with illnesses during the period 16 March–8 July 2009 were identified from 30 states; 35 were hospitalized, 10 developed hemolytic-uremic syndrome, and none died. Sixty-six percent of patients were <19 years; 71% were female. In the case-control study, 33 of 35 case patients (94%) consumed ready-to-bake commercial prepackaged cookie dough, compared with 4 of 36 controls (11%) (matched odds ratio = 41.3; P < .001); no other reported exposures were significantly associated with illness. Among case patients consuming cookie dough, 94% reported brand A. Three nonoutbreak STEC strains were isolated from brand A cookie dough. The investigation led to a recall of 3.6 million packages of brand A cookie dough and a product reformulation.
Conclusions. This is the first reported STEC outbreak associated with consuming ready-to-bake commercial prepackaged cookie dough. Despite instructions to bake brand A cookie dough before eating, case patients consumed the product uncooked. Manufacturers should consider formulating ready-to-bake commercial prepackaged cookie dough to be as safe as a ready-to-eat product. More effective consumer education about the risks of eating unbaked cookie dough is needed.
Background. Antimicrobial killing in mycobacterial infections may be accompanied by (transient) clinical deterioration, known as paradoxical reaction. To search for patterns reflecting such reactions in the treatment of Buruli ulcer (Mycobacterium ulcerans infection), the evolution of lesions of patients treated with antimicrobials was prospectively assessed.
Methods. The lesion size of participants of the BURULICO antimicrobial trial (with lesions ≤10 cm cross-sectional diameter) was assessed by careful palpation and recorded by serial acetate sheet tracings. Patients were treated with antimicrobials for 8 weeks. For the size analysis, participants whose treatment had failed, had skin grafting, or were coinfected with human immunodeficiency virus were excluded. For every time point, surface area was compared with the previous assessment. A generalized additive mixed model was used to study lesion evolution. Nonulcerative lesions were studied using digital images recording possible subsequent ulceration.
Results. Of 151 participants, 134 were included in the lesion size analysis. Peak paradoxical response occurred at week 8; >30% of participants showed an increase in lesion size as compared with the previous (week 6) assessment. Seventy-five of 90 (83%) of nonulcerative lesions ulcerated after start of treatment. Nine participants developed new lesions during or after treatment. All lesions subsequently healed.
Conclusions. After start of antimicrobial treatment for Buruli ulcer, new or progressive ulceration is common before healing sets in. This paradoxical response, most prominent at the end of the 8-week antimicrobial treatment, should not be misinterpreted as failure to respond to treatment.
Clinical Trials Registration. ClinicalTrials.gov, NCT00321178.
Background. Hemorrhagic fever–like illness caused by a novel Bunyavirus, Huaiyangshan virus (HYSV, also known as Severe Fever with Thrombocytopenia virus [SFTSV] and Fever, Thrombocytopenia and Leukopenia Syndrome [FTLS]), has recently been described in China.
Methods. Patients with laboratory-confirmed HYSV infection who were admitted to Union Hospital or Zhongnan Hospital between April 2010 and October 2010 were included in this study. Clinical and routine laboratory data were collected and blood, throat swab, urine, or feces were obtained when possible. Viral RNA was quantified by real-time reverse-transcriptase polymerase chain reaction. Blood levels of a range of cytokines, chemokines, and acute phase proteins were assayed.
Results. A total of 49 patients with hemorrhagic fever caused by HYSV were included; 8 (16.3%) patients died. A fatal outcome was associated with high viral RNA load in blood at admission, as well as higher serum liver transaminase levels, more pronounced coagulation disturbances (activated partial thromboplastin time, thrombin time), and higher levels of acute phase proteins (phospholipase A, fibrinogen, hepcidin), cytokines (interleukin [IL]–6, IL-10, interferon-), and chemokines (IL-8, monocyte chemotactic protein 1, macrophage inflammatory protein 1b). The levels of these host parameters correlated with viral RNA levels. Blood viral RNA levels gradually declined over 3–4 weeks after illness onset, accompanied by resolution of symptoms and laboratory abnormalities. Viral RNA was also detectable in throat, urine, and fecal specimens of a substantial proportion of patients, including all fatal cases assayed.
Conclusions. Viral replication and host immune responses play an important role in determining the severity and clinical outcome in patients with infection by HYSV.
Clinical specimens from 9 states during 2008–2010 were tested by PCR for Bordetella pertussis and Bordetella parapertussis. Of the positive samples, 13.99% were identified as B. parapertussis. It was concluded that B. parapertussis infections are more common than previously realized and contribute to cases thought to be vaccine failures.
Background. In vitro, animal, and mathematical models suggest that human immunodeficiency virus (HIV) co- or superinfection would result in increased fitness of the pathogen and, possibly, increased virulence. However, in patients, the impact of dual HIV type 1 (HIV-1) infection on disease progression is unclear, because parameters relevant for disease progression have not been strictly analyzed. The objective of the present study is to analyze the effect of dual HIV-1 infections on disease progression in a well-defined cohort of men who have sex with men.
Methods. Between 2000 and 2009, 37 men who had primary infection with HIV-1 subtype B, no indication for immediate need of combination antiretroviral therapy (cART), and sufficient follow-up were characterized with regard to dual infection or single infection and to coreceptor use. Patients were followed to estimate the effect of these parameters on clinical disease progression, as defined by the rate of CD4+ T-cell decline and the time to initiation of cART.
Results. Four patients presented with HIV-1 coinfection; 6 patients acquired HIV-1 superinfection, on average 8.5 months from their primary infection; and 27 patients remained infected with a single strain. Slopes of longitudinal CD4+ T-cell counts and time-weighted changes from baseline were significantly steeper for patients with dual infection compared with patients with single infection. Multivariate analysis showed that the most important parameter associated with CD4+ T-cell decline over time was dual infection (P = .001). Additionally, patients with HIV-1 coinfection had a significantly earlier start of cART (P < .0001).
Conclusions. Dual HIV-1 infection is the main factor associated with CD4+ T-cell decline in men who have untreated primary infection with HIV-1 subtype B.
Background. The impact of hepatitis B virus (HBV) genotypes B and C on the clinical, immunologic, and virologic outcomes of human immunodeficiency virus (HIV)–infected patients with chronic HBV infection remains largely unknown.
Methods. Between January 1997 and December 2008, we enrolled 96 HIV-infected patients with HBV genotype B coinfection and 49 with genotype C coinfection; the patients were followed prospectively until December 2010. Clinical and immunologic outcomes in the context of HBV genotypes as well as the emergence of HBV DNA mutations conferring lamivudine resistance (rtM204I/V) were determined.
Results. The median duration of lamivudine-containing highly active antiretroviral therapy (HAART) was 2.80 years (interquartile range, 1.73–5.92 years). The 2 groups of HIV-infected patients were comparable in age, sex, baseline HIV profiles, and liver function profiles. Compared with HIV-infected patients with HBV genotype C coinfection, those with genotype B coinfection had a higher risk of hepatitis flares (43.8% vs 26.5%; P = .04), liver disease-related death (9.4% vs 0%; P = .03), hepatitis B e antigen (HBeAg) seroconversion (61.5% vs 25.0%, P = .03), and development of lamivudine resistance (31.3% vs 12.2%; P < .0001). No differences were observed between the 2 groups in terms of the development of hyperbilirubinemia, cirrhosis, or virologic and immunologic responses to HAART.
Conclusions. Although therapeutic responses to long-term lamivudine-containing HAART were comparable between HIV-infected patients with HBV genotypes B and C coinfection, patients with genotype B coinfection were more likely to experience acute exacerbations of hepatitis, HBeAg seroconversion, lamivudine resistance, and liver disease–related death than those with genotype C coinfection.
Fibrosis progression after acute hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)–infected patients with follow-up >9 months became similar to reported rates from studies in chronic HIV/HCV coinfection, as measured with transient elastometry. The duration of follow-up and serum alanine transaminase correlated with liver stiffness, and short follow-up resulted in high fibrosis progression rates.
High attack rates and the ability of Staphylococcus aureus to develop resistance to all antibiotics in medical practice heightens the urgency for vaccine development. S. aureus causes many disease syndromes, including invasive disease, pneumonia, and skin and soft tissue infections. It remains unclear whether a single vaccine could protect against all of these. Vaccine composition is also challenging. Active immunization with conjugated types 5 and 8 capsular polysaccharides, an iron scavenging protein, isdB, and passive immunization against clumping factor A and lipoteichoic acid have all proven unsuccessful in clinical trials. Many experts advocate an approach using multiple antigens and have suggested that the right combination of antigens has not yet been identified. Others advocate that a successful vaccine will require antigens that work by multiple immunologic mechanisms. Targeting staphylococcal protein A and stimulating the T-helper 17 lymphocyte pathway have each received recent attention as alternative approaches to vaccination in addition to the more traditional identification of opsonophagocytic antibodies. Many questions remain as to how to successfully formulate a successful vaccine and to whom it should be deployed.
Fidaxomicin, a nonabsorbed macrocyclic compound, is the first antimicrobial agent approved by the FDA for the treatment of Clostridium difficile infection (CDI) in adults over the last 25 years. It is bactericidal, and its mechanism of action relates to inhibition of a RNA polymerase at a site distinct from where rifamycins interact. Fidaxomicin, 200 milligrams by mouth twice daily, is not inferior to vancomycin, 125 milligrams by mouth 4 times daily, for treatment of CDI as determined by clinical response after 10 days of treatment and is superior to vancomycin for sustained response without recurrence 25 days after treatment completion. These results are a significant advance in the treatment of CDI and herald the development of narrow-spectrum anti–C. difficile agents that relatively spare the indigenous fecal microbiota. Continued vigilance for the development of resistance and unanticipated side affects will be important as the drug is introduced into clinical practice.
