BlaB-15, a new BlaB metallo-β-lactamase variant found in an Elizabethkingia miricola clinical isolate

A multidrug-resistant strain of Elizabethkingia miricola was isolated from the urine of a 2-year-old boy hospitalized for severe clinical conditions. The strain produces 2 metallo-β-lactamases belonging to subclasses B1 and B3: a new BlaB variant (BlaB-15) and a GOB-7–like enzyme.

Dose-dependent effects of experimental infection with the virulent Neospora caninum Nc-Spain7 isolate in a pregnant mouse model.

Pregnant BALB/c mice have been widely used as an in vivo model to study Neospora caninum infection biology and to provide proof-of-concept for assessments of drugs and vaccines against neosporosis. The fact that this model has been used with different isolates of variable virulence, varying infection routes and differing methods to prepare the parasites for infection, has rendered the comparison of results from different laboratories impossible. In most studies, mice were infected with similar number of parasites (2 × 10(6)) as employed in ruminant models (10(7) for cows and 10(6) for sheep), which seems inappropriate considering the enormous differences in the weight of these species. Thus, for achieving meaningful results in vaccination and drug efficacy experiments, a refinement and standardization of this experimental model is necessary. Thus, 2 × 10(6), 10(5), 10(4), 10(3) and 10(2) tachyzoites of the highly virulent and well-characterised Nc-Spain7 isolate were subcutaneously inoculated into mice at day 7 of pregnancy, and clinical outcome, vertical transmission, parasite burden and antibody responses were compared. Dams from all infected groups presented nervous signs and the percentage of surviving pups at day 30 postpartum was surprisingly low (24%) in mice infected with only 10(2) tachyzoites. Importantly, infection with 10(5) tachyzoites resulted in antibody levels, cerebral parasite burden in dams and 100% mortality rate in pups, which was identical to infection with 2 × 10(6) tachyzoites. Considering these results, it is reasonable to lower the challenge dose to 10(5) tachyzoites in further experiments when assessing drugs or vaccine candidates.

A vaccine formulation combining rhoptry proteins NcROP40 and NcROP2 improves pup survival in a pregnant mouse model of neosporosis.

Currently there are no effective vaccines for the control of bovine neosporosis. During the last years several subunit vaccines based on immunodominant antigens and other proteins involved in adhesion, invasion and intracellular proliferation of Neospora caninum have been evaluated as targets for vaccine development in experimental mouse infection models. Among them, the rhoptry antigen NcROP2 and the immunodominant NcGRA7 protein have been assessed with varying results. Recent studies have shown that another rhoptry component, NcROP40, and NcNTPase, a putative dense granule antigen, exhibit higher expression levels in tachyzoites of virulent N. caninum isolates, suggesting that these could be potential vaccine candidates to limit the effects of infection. In the present work, the safety and efficacy of these recombinant antigens formulated in Quil-A adjuvant as monovalent vaccines or pair-wise combinations (rNcROP40+rNcROP2 and rNcGRA7+rNcNTPase) were evaluated in a pregnant mouse model of neosporosis. All the vaccine formulations elicited a specific immune response against their respective native proteins after immunization. Mice vaccinated with rNcROP40 and rNcROP2 alone or in combination produced the highest levels of IFN-γ and exhibited low parasite burdens and low IgG antibody levels after the challenge. In addition, most of the vaccine formulations were able to increase the median survival time in the offspring. However, pup survival only ensued in the groups vaccinated with rNcROP40+rNcROP2 (16.2%) and rNcROP2 (6.3%). Interestingly, vertical transmission was not observed in those survivor pups immunized with rNcROP40+rNcROP2, as shown by PCR analyses. These results show a partial protection against N. caninum infection after vaccination with rNcROP40+rNcROP2, suggesting a synergistic effect of the two recombinant rhoptry antigens.

Rhinovirus Infections and Associated Respiratory Morbidity in Infants: A Prospective Cohort Study.

BACKGROUND Risk factors promoting rhinovirus (RV) infections are inadequately described in healthy populations, especially infants. OBJECTIVES To determine the frequency of symptomatic and asymptomatic RV infections and identify possible risk factors from host and environment among otherwise healthy infants. METHODS In a prospective birth cohort, respiratory health was assessed in 41 term-born infants by weekly telephone interviews during the first year of life, and weekly nasal swabs were collected to determine RV prevalence. In a multilevel logistic regression model, associations between prevalence and respiratory symptoms during RV infections and host/environmental factors were determined. RESULTS 27% of nasal swabs in 41 infants tested positive for RVs. Risk factors for RV prevalence were autumn months (OR=1.71, p=0.01, 95% CI 1.13-2.61), outdoor temperatures between 5-10 °C (OR=2.33, p=0.001, 95% CI 1.41-3.86), older siblings (OR=2.60, p=0.001, 95% CI 1.50-4.51) and childcare attendance (OR=1.53, p=0.07, 95% CI 0.96-2.44). 51% of RV-positive samples were asymptomatic. Respiratory symptoms during RV infections were less likely during the first three months of life (OR=0.34, p=0.003, 95% CI 0.17-0.69) and in infants with atopic mothers (OR=0.44, p=0.008, 95% CI 0.24-0.80). Increased tidal volume (OR=1.67, p=0.03, 95% CI 1.04-2.68) and outdoor temperatures between 2-5 °C (OR=2.79, p=0.02, 95% CI 1.17-6.61) were associated with more symptoms. CONCLUSIONS RVs are highly prevalent during the first year of life, and most infections are asymptomatic. Frequency of RV infections is associated with environmental factors, while respiratory symptoms during RV infections are linked to host determinants like infant age, maternal atopy, or premorbid lung function.

In Utero Exposure to Antiretroviral Drugs: Effect on Birth Weight and Growth Among HIV-exposed Uninfected Children in Brazil.

BACKGROUND There are concerns about the effects of in utero exposure to antiretroviral drugs (ARVs) on the development of HIV-exposed but uninfected (HEU) children. The aim of this study was to evaluate whether in utero exposure to ARVs is associated with lower birth weight/height and reduced growth during the first 2 years of life. METHODS This cohort study was conducted among HEU infants born between 1996 and 2010 in Tertiary children's hospital in Rio de Janeiro, Brazil. Weight was measured by mechanical scale, and height was measured by measuring board. Z-scores for weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length were calculated. We modeled trajectories by mixed-effects models and adjusted for mother's age, CD4 cell count, viral load, year of birth and family income. RESULTS A total of 588 HEU infants were included of whom 155 (26%) were not exposed to ARVs, 114 (19%) were exposed early (first trimester) and 319 (54%) later. WAZ were lower among infants exposed early compared with infants exposed later: adjusted differences were -0.52 (95% confidence interval [CI]: -0.99 to -0.04, P = 0.02) at birth and -0.22 (95% CI: -0.47 to 0.04, P = 0.10) during follow-up. LAZ were lower during follow-up: -0.35 (95% CI: -0.63 to -0.08, P = 0.01). There were no differences in weight-for-length scores. Z-scores of infants exposed late during pregnancy were similar to unexposed infants. CONCLUSIONS In HEU children, early exposure to ARVs was associated with lower WAZ at birth and lower LAZ up to 2 years of life. Growth of HEU children needs to be monitored closely.

Environmental and behavioral risk factors for moderate or severe rotavirus diarrhea in children less than 24 months

On a global basis rotaviruses are the most important agents involved in childhood diarrhea. In developing countries they account for 6% of all diarrheas and 20% of all diarrhea related deaths of children under 5 years of age, with over 1 billion episodes and over 4 million deaths annually. Given the disease burden, there is a need for better understanding the risk factors involved in rotavirus disease, to identify areas of intervention. In order to provide this information, two areas were developed: a review of the literature, examining the causal evidence for rotavirus diarrhea and a case comparison study. The case comparison study analyzed two areas: identifying climate factors and, identifying environmental and behavioral risk factors. The literature review showed that few analytical studies have identified specific risk factors such as home environment, and a winter seasonal trend for temperate areas, but in key areas evidence is contradictory. The case comparison study for climate factors demonstrated that seasonality occurs in a tropical country like Venezuela and that a complex interplay between weather conditions contribute to the seasonal pattern. A positive association between rain fall (OR 4.1); dew point (OR 2.3) and temperature differential during the day (OR 1.4) and, an inverse association with temperature (OR 0.5) and relative humidity (OR 0.8) was found. This information is useful in understanding the seasonal pattern of rotavirus and for planning health care needs. The second analysis demonstrated that environmental variables such as crowding (OR 14.3), contact with someone with an infectious disease (OR 4.9) and animal ownership (OR 2.3) were important. Restricting the analysis to animal owners demonstrated that living In a rural settling (OR 13.8), defecating in inappropriate places (OR 7.2), crowding(4.2) and indoor animals (4.0) are of importance. Behavioral variables identified were: lack of breast feeding (OR 4.0) and visiting when someone was sick (OR 3.4). Biological and demographic variables of importance were: age, with a dose response relationship; undernurishment (OR 11.3) and household per capita monthly income less than US $ 16.30 (OR 8.5). Using a diarrhea compeer group we found that, although some of the previous variables were of importance, no major differences were found. These findings are important in identifying paths for prevention and further research. ^

Case control study identifying the maternal risk factors for congenital syphilis in Texas: 1998--2001

Background. Congenital syphilis (CS) is the oldest recognized congenital infection in the world. CS infection can affect multiple organs and can even cause neonatal death. CS is largely preventable when maternal syphilis is treated in an adequate and timely manner. During the decade of the nineties, rates of CS in Texas have often exceeded the overall US rate. Few studies, with adequate sample sizes, have been conducted to determine the risk factors associated with CS while controlling for factors associated with adult (maternal) syphilis infection. Objective. To determine the current maternal risk factors for CS infection in Texas from 1998–2001. Methods. A total of 1083 women with positive serological tests for syphilis during pregnancy or at delivery were reported to, and assessed by, health department surveillance staff. Mothers delivering infants in Texas between January 1, 1998 and June 30, 2001 comprised the study population. Mothers of infants diagnosed with confirmed or presumptive CS (N = 291) were compared to mothers of infants diagnosed as non-cases (N = 792) to determine the risk factors for vertical transmission (while controlling for risk factors of horizontal transmission). Logistic regression analyses were conducted to determine the associated odds between selected maternal variables and the outcome of CS. Results. Among 291 case infants, 5 (1.7%), 12 (4.1%), 274 (94.2%) were classified as confirmed cases, syphilitic stillbirths, and presumptive cases, respectively. Lack of maternal syphilis treatment was the strongest predictor of CS: odds ratio (OR) = 199.57 (95% CI 83.45–477.25) compared to those receiving treatment before pregnancy, while women treated during their pregnancies were also at increased risk (OR = 6.67, 95% CI 4.01–11.08). Women receiving no prenatal care were more likely (OR = 2.77, 95% CI 1.60–4.79) to have CS infants than those receiving prenatal care. Single women had higher odds (OR = 1.90, 95% CI 1.10–3.26) than ever-married women. African-Americans (OR 0.91, 95% CI 0.37–2.23) and Hispanics (OR = 1.66, 95% CI 0.68–4.05) may be more likely to have a CS infant than non-Hispanic Whites. Conclusions. The burden of CS in Texas can be alleviated through the provision of quality health care services, particularly prenatal care and treatment for sexually transmitted diseases. ^

Clinical factors associated with growth and mortality of pediatric patients on HAART at Mulago PIDC, Uganda, 2003--2006

The global social and economic burden of HIV/AIDS is great, with over forty million people reported to be living with HIV/AIDS at the end of 2005; two million of these are children from birth to 15 years of age. Antiretroviral therapy has been shown to improve growth and survival of HIV-infected individuals. The purpose of this study is to describe a cohort of HIV-infected pediatric patients and assess the association between clinical factors, with growth and mortality outcomes. ^ This was a historical cohort study. Medical records of infants and children receiving HIV care at Mulago Pediatric Infectious Disease Clinic (PIDC) in Uganda between July 2003 and March 2006 were analyzed. Height and weight measurements were age and sex standardized to Centers for Disease Control and prevention (CDC) 2000 reference. Descriptive and logistic regression analyses were performed to identify covariates associated with risk of stunting or being underweight, and mortality. Longitudinal regression analysis with a mixed model using autoregressive covariance structure was used to compare change in height and weight before and after initiation of highly active antiretroviral therapy (HAART). ^ The study population was comprised of 1059 patients 0-20 years of age, the majority of whom were aged thirteen years and below (74.6%). Mean height-for-age before initiation of HAART was in the 10th percentile, mean weight-for-age was in the 8th percentile, and the mean weight-for-height was in the 23rd percentile. Initiation of HAART resulted in improvement in both the mean standardized weight-for-age Z score and weight-for-age percentiles (p <0.001). Baseline age, and weight-for-age Z score were associated with stunting (p <0.001). A negative weight-for-age Z score was associated with stunting (OR 4.60, CI 3.04-5.49). Risk of death decreased from 84% in the >2-8 years age category to 21% in the >13 years age category respectively, compared to the 0-2 years of age (p <0.05). ^ This pediatric population gained weight significantly more rapidly than height after starting HAART. A low weight-for-age Z score was associated with poor survival in children. These findings suggest that age, weight, and height measurements be monitored closely at Mulago PIDC. ^

Maternal nutrition and oral health factors in early childhood caries

Background. Early Childhood Caries (ECC) is the most common chronic infectious disease of childhood worldwide. Seven of ten American children have one or more decayed or filled primary teeth by age five. ECC prevalence is especially high in lower socio-economic ethnic populations. Commonly recognized as a diet-induced disease, focal etiological factors include cariogenic bacteria, fermentable carbohydrates, and a susceptible newly erupted tooth. Sequencing of breast and/or bottle feeding and introduction of beikost come at a time when children's defense mechanisms and, perhaps maternal direction of children's dietary patterns, are not yet fully developed or mature. To date, most research has examined biological factors, while maternal factors, especially psychosocial ones, have received scant attention. Objective. To examine the association of psychosocial factors in terms of maternal nutrition and oral health knowledge, attitudes, and beliefs, as well as social support and self-efficacy (KABS2) in a population of socio-economically disadvantaged infants and young children. A secondary aim was to describe ECC prevalence in this population. Methods. This study examined cross-sectionally the relationship between selected maternal psychosocial variables and ECC in a convenience sample of Mexican-American women and very young children participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in San Antonio, Texas. Mothers were surveyed by use of a criteria- and content-valid, reliable questionnaire, and dental examinations were conducted on 191 children, aged 5 to 47 months old. Results. Thirty-nine percent of the children had ECC. As assessed on a 30-question scale, women in whose children were diagnosed with ECC were found to demonstrate lower Knowledge ( p=0.03), Attitudes (p=0.02), Beliefs (p=0.04), and Social Support (p<0.01) scores, compared to women whose children were found to be caries-free. No differences in Self-Efficacy scores were found between the groups. Conclusions. These data indicate that current etiological model depicting relevant factors associated with ECC in Mexican-American infants and children of low socio-economic status should be broadened to include consideration of maternal psychosocial factors such as nutrition and oral health knowledge, attitudes, beliefs, and social support, and that these factors should be considered when planning educational approaches to reduce the occurrence of ECC. ^

Differences in health status of HIV infected children cared for by parents as compared to those cared for by grandparents

Purpose. The purpose of the study was to use measures of an HIV positive child's health to examine whether or not there is a difference in their health status according to caretaker and household economic status. ^ Study design. This was a case comparison study between HIV infected children living with parents and those living with grandparents. ^ Study setting. The study was conducted at the Pediatric Infectious Disease Clinic (PIDC) in Mulago, Kampala, Uganda. ^ Participants. 369 HIV-infected children aged seven months to 15 years attending the PIDC between June 13th and August 15th 2007 as well as their caretakers. ^ Method. Patients were recruited during their clinic visits after they had seen the health care providers and waited to receive their medication. Methods used included a survey of all the 369 caregiver participants and abstraction of data from the 369 patient charts. ^ Results. There was no significant association between staging and caretaker status (OR: 0.73 95%CI 0.44–1.21 p=0.09). Children taken care of by grandparents were more likely to have low height for age z-scores and higher weight for height z-scores (OR: 0.32, 95%CI: 0.14–0.74, p = 0.005). There was no difference is social support seeking behavior between parents and grandparents. ^ Conclusion. There was no statistically significant association observed between caretaker status and presenting in advanced stages. This implies that the stage at which HIV-infected children present for care is not determined by the type of caretaker. Caretakers for HIV-infected children need a lot of support beyond medical care. ^

Diffusely adherent Escherichia coli (DAEC) as a cause of acute diarrhea

Acute diarrhea is the most common medical problem in the developing countries. Infectious agents are responsible for a majority of cases of acute diarrhea. Knowing the cause of acute diarrhea is important to developing plans for disease prevention, control and therapy. Acute diarrhea is caused by many viruses, bacteria and parasites. ^ Travelers to developing countries of the world commonly develop diarrhea as a result of eating contaminated food or drinking contaminated water. About 30-50% of travelers who travel from industrialized countries like United States to the developing countries are at risk of developing diarrhea. High risk areas for travelers' diarrhea are Mexico, Latin America and Southeast Asia. Public restaurants are the common sites for exposure to this type of food-borne infectious disease in travelers. Food becomes contaminated when they are handled by people with fecal content on their hands. ^ The importance of Diffusely Adherent Escherichia Coli (DAEC) in travelers to these areas has not been well studied. Some of the studies looking at DAEC have shown the organism to be present in children without symptoms. Other studies have shown a relationship between DAEC infection and presence of symptoms. I have selected this topic because the patho-physiological processes in DAEC infection that allow intestinal and extra-intestinal infections to develop are not fully understood. DAEC related acute diarrhea is a relatively new topic of public health significance. There is a limited number of studies regarding the virulence and pathogenic mechanisms of DAEC. The presumed virulence factor of the organism is diffuse attachment to the intestinal lining of the infected host. However more research needs to be done to identify the pathogenic mechanisms and virulence factors associated with DAEC infection for better treatment planning and diarrhea prevention. ^

A retrospective analysis of patients referred for tuberculosis testing at Parkland Hospital, Dallas, TX

Tuberculosis (TB) is an infectious disease of great public health importance, particularly to institutions that provide health care to large numbers of TB patients such as Parkland Hospital in Dallas, TX. The purpose of this retrospective chart review was to analyze differences in TB positive and TB negative patients to better understand whether or not there were variables that could be utilized to develop a predictive model for use in the emergency department to reduce the overall number of suspected TB patients being sent to respiratory isolation for TB testing. This study included patients who presented to the Parkland Hospital emergency department between November 2006 and December 2007 and were isolated and tested for TB. Outcome of TB was defined as a positive sputum AFB test or a positive M. tuberculosis culture result. Data were collected utilizing the UT Southwestern Medical Center computerized database OACIS and included demographic information, TB risk factors, physical symptoms, and clinical results. Only two variables were significantly (P<0.05) related to TB outcome: dyspnea (shortness of breath) (P<0.001) and abnormal x-ray (P<0.001). Marginally significant variables included hemoptysis (P=0.06), weight loss (P=0.11), night sweats (P=0.20), history of homelessness or incarceration (P=0.15), and history of positive skin PPD (P=0.19). Using a combination of significant and marginally significant variables, a predictive model was designed which demonstrated a specificity of 24% and a sensitivity of 70%. In conclusion, a predictive model for TB outcome based on patients who presented to the Parkland Hospital emergency department between November 2006 and December 2007 was unsuccessful given the limited number of variables that differed significantly between TB positive and TB negative patients. It is suggested that a future prospective cohort study should be implemented to collect data on TB positive and TB negative patients. It may be possible that a more thorough prospective collection of data may lead to clearer comparisons between TB positive and TB negative patients and ultimately to the design of a more sensitive predictive model for TB outcome. ^

Syndromic surveillance at a long term shelter for persons displaced by hurricanes Katrina and Rita conducted by the San Antonio Metropolitan Health District

Background. Beginning September 2, 2005, San Antonio area shelters received approximately 12,700 evacuees from Hurricane Katrina. Two weeks later, another 12,000 evacuees from Hurricane Rita arrived. By mid-October, 2005, the in-shelter population was 1,000 people. There was concern regarding the potential for spread of infectious diseases in the shelter. San Antonio Metropolitan Health District (SAMHD) established a syndromic surveillance system with Comprehensive Health Services (CHS) who provided on-site health care. CHS was in daily contact with SAMHD to report symptoms of concern until the shelter closed December 23, 2005. ^ Study type. The objective of this study was to assess the methods used and describe the practical considerations involved in establishing and managing a syndromic surveillance system, as established by the SAMHD in the long-term shelter clinic maintained by CHS for the hurricane evacuees. ^ Methods. Information and descriptive data used in this study was collected from multiple sources, primarily from the San Antonio Metropolitan Health District’s 2006 Report on Syndromic Surveillance of a Long-Term Shelter by Hausler & Rohr-Allegrini. SAMHD and CHS staff ensured that each clinic visit was recorded by date, demographic information, chief complaint and medical disposition. Logs were obtained daily and subsequently entered into a Microsoft Access database and analyzed in Excel. ^ Results. During a nine week period, 4,913 clinic visits were recorded, reviewed and later analyzed. Repeat visits comprised 93.0% of encounters. Chronic illnesses contributed to 21.7% of the visits. Approximately 54.0% were acute care encounters. Of all encounters, 17.3% had infectious disease potential as primarily gastrointestinal and respiratory syndromes. Evacuees accounted for 86% and staff 14% of all visits to the shelter clinic. There were 782 unduplicated individuals who sought services at the clinic, comprised of 63% (496) evacuees and 36% (278) staff members. Staff were more likely to frequent the clinic but for fewer visits each. ^ Conclusion. The presence of health care services and syndromic surveillance provided the opportunity to recognize, document and intervene in any disease outbreak at this long-term shelter. Constant vigilance allowed SAMHD to inform and reassure concerned people living and working in the shelter and living outside the shelter.^

Targeted immunization to protect infants against pertussis in the United States

Pertussis is an infectious disease caused by the bacteria Bordetella pertussis, and is associated with a serious respiratory infection, a prolonged cough, and can require hospitalization. A vaccine for adolescents and adults has been available since 2005. This paper examines one recommended immunization strategy to prevent pertussis among infants, called “cocooning.” The strategy focuses on creating immunity among adult caregivers so they serve as a protective cocoon to the newborns, who are too young to be vaccinated. This paper looks at relevant studies summarizing implementation of cocooning strategies and addresses the question – Does the research literature support the view of using cocooning as an effective strategy to prevent pertussis in infants? After exclusions, 8 studies remained for synthesis. The evidence shows that cocooning is complex strategy and the evidence is mixed when it comes to ensuring an increase in immunization of caregivers. ^

THE SHORT- AND LONG-TERM EFFECTS OF A HANDBOOK ON THE ANTIMICROBIAL PRESCRIBING PATTERNS OF HOSPITAL PHYSICIANS

This study evaluates the effect of a specially designed, physician-oriented handbook of antimicrobial use on the prescribing patterns of a group of fifty doctors at a university hospital. Data were evaluated over a peroid of one-and-one-half years, before and after the distribution of the handbook. For the purposes of this study, antimicrobial therapy was classified: (1) inappropriate if it violated one of a number of recognized principles of antimicrobial therapy, (2) appropriate if it agreed with specific recommendations or alternatives given in the distributed reference handbook, and (3) acceptable if it was neither inappropriate nor appropriate as defined by the handbook. An initial survey of antimicrobial prescribing patterns was made. Five months later the handbook was distributed and a two-week orientation program, consisting of the distribution and promotion of the problem-oriented, pocket-size handbook of appropriate antimicrobial therapy, was conducted. The handbook, which was developed by the authors and reviewed and approved by a panel of infectious disease specialists, presented guidelines for appropriate and efficacious usage of antimicrobial agents as most currently accepted in common clinical infections. Subsequent surveys were then conducted two weeks, three months, and six months after distribution of the handbook. A statistically significant difference (p < 0.01) in antimicrobial prescribing patterns was noted between the survey conducted two weeks after the introduction of the handbook and the other surveys. In this survey, while therapy classified inappropriate decreased from 44% to 28%, therapy appropriate as recommended increased from 31% to 53%. The findings of this study demonstrate that the introduction and promotion of the handbook decreases abuse and increases proper use of antimicrobial therapy, although the effect is sustainable for only a short duration--no longer than three months. These results indicate the need for a vigorous, updated program to achieve and maintain current appropriate antibotic therapy in clinical medicine. ^