Correction: A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model.

[This corrects the article DOI: 10.1371/journal.pntd.0010611.].

A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model.

BACKGROUND: Scrub typhus is a vector-borne febrile illness caused by Orientia tsutsugamushi transmitted by the bite of Trombiculid mites. O. tsutsugamushi has a high genetic diversity and is increasingly recognized to have a wider global distribution than previously assumed. METHODOLOGY/PRINCIPLE FINDINGS: We evaluated the clinical outcomes and host immune responses of the two most relevant human pathogenic strains of O. tsutsugamushi; Karp (n = 4) and Gilliam (n = 4) in a time-course study over 80 days post infection (dpi) in a standardized scrub typhus non-human primate rhesus macaque model. We observed distinct features in clinical progression and immune response between the two strains; Gilliam-infected macaques developed more pronounced systemic infection characterized by an earlier onset of bacteremia, lymph node enlargement, eschar lesions and higher inflammatory markers during the acute phase of infection, when compared to the Karp strain. C-reactive protein (CRP) plasma levels, interferon gamma (IFN-γ, interleukin-1 receptor antagonist (IL-1ra), IL-15 serum concentrations, CRP/IL10- and IFN-γ/IL-10 ratios correlated positively with bacterial load in blood, implying activation of the innate immune response and preferential development of a T helper-type 1 immune response. The O. tsutsugamushi-specific immune memory responses in cells isolated from skin and lymph nodes at 80 dpi were more markedly elevated in the Gilliam-infected macaques than in the Karp-infected group. The comparative cytokine response dynamics of both strains revealed significant up-regulation of IFN-γ, tumor necrosis factor (TNF), IL-15, IL-6, IL-18, regulatory IL-1ra, IL-10, IL-8 and granulocyte-colony-stimulating factor (G-CSF). These data suggest that the clinical outcomes and host immune responses to scrub typhus could be associated with counter balancing effects of pro- and anti-inflammatory cytokine-mediated responses. Currently, no data on characterized time-course comparisons of O. tsutsugamushi strains regarding measures of disease severity and immune response is available. Our study provides evidence for the strain-specificity of host responses in scrub typhus, which supports our understanding of processes at the initial inoculation site (eschar), systemic disease progression, protective and/or pathogenic host immune mechanisms and cellular immune memory function. CONCLUSIONS/SIGNIFICANCE: This study characterised an improved intradermal rhesus macaque challenge model for scrub typhus, whereby the Gilliam strain infection associated with higher disease severity in the rhesus macaque model than the previous Karp strain infection. Difficulties associated with inoculum quantitation for obligate-intracellular bacteria were overcome by using functional inoculum titrations in outbred mice. The Gilliam-based rhesus macaque model provides improved endpoint measurements and contributes towards the identification of correlates of protection for future vaccine development.

Type 2 diabetes mellitus among youth in Puerto Rico, 2003.

AIMS: To describe the clinical characteristics, and estimate the prevalence of type 2 diabetes mellitus among Puerto Rican youth, 1995-2003. METHODS: All patients aged less than 20 years with a confirmed diagnosis of type 2 diabetes were identified from pediatric endocrinologists' medical practices. Medical records of each patient were reviewed to confirm the diagnosis, classify the type of diabetes, and gather sociodemographic and clinical characteristics. From 1995 to 2003 a total of 32,444 records were reviewed. A total of 2,800 children with diabetes were identified, of which 2,702 were type 1 and 93 type 2; typel/type 2 ratio was 29:1. Frequency distributions were obtained for categorical variables, and summary measures (mean +/- standard deviation) for quantitative measure were computed. RESULTS: Mean age at first visit was 14 years. The majority of cases were females (69%), for a female/ male ratio of 2.2:1. 78.5% had a family history of the disease, 74.2% were overweight, and 48% had acanthosis nigricans. 64.5% of the cases were receiving some type of hypoglycemic therapy. 18.5% of the cases had severe hypertension while 17.5% had cholesterol levels considered at increased risk (e"200). The overall prevalence was 13.5 per 100,000 population. CONCLUSIONS: This study is the first that describes the frequency and clinical presentation of type 2 diabetes in children and adolescents in a sample of Puerto Ricans. Further investigations must be conducted to obtain a more precise estimate of the burden of type 2 diabetes in youth and to raise awareness of this condition among health care professionals.

Diabetes, obesity and non-optimum blood pressure levels in a group of employees of the University of Puerto Rico, Medical Sciences Campus, 2003.

OBJECTIVE: To estimate the proportion of diabetes, obesity and non-optimum blood pressure levels in a group of employees of the University of Puerto Rico Medical Sciences Campus that participated in a diabetes health fair at the "Centro de Diabetes para Puerto Rico". METHODS: A total of 113 participants of the diabetes health fair completed a questionnaire to obtain demographic characteristics and the frequency of self-reported diabetes. The nursing staff examined the participants in order to obtain the following clinical characteristics: body mass index, blood pressure and blood glucose levels. RESULTS: The proportion of self-reported diabetes, obesity (> or = 30 kg/m2) and non-optimum blood pressure levels (systolic > or = 20 mm/Hg or diastolic > or = 80 mm/Hg) were 15.4% (95% CI: 8.5% - 25.7%), 80.0% (95% CI: 70.8%-86.9%) and 70.5% (95% CI: 61.1%-78.6%), respectively. Although it was not statistically significant, diabetes was higher among females (15.4%) compared to males (12.0%). All participants with self-reported diabetes were overweight or obese, and 91.7% showed non-optimum blood pressure levels. A significant positive correlation (p < 0.001) was observed between blood pressure levels and body mass index (r = 0.3). CONCLUSIONS: The percentage of persons with diabetes, obesity, and non-optimum blood pressure levels in this sample of Medical Sciences Campus employees underscores the need for confirming these results in a larger study and developing strategies focused on reducing health risks in this population.

The public health burden of diabetes: a comprehensive review

The review of several diabetes epidemiological studies confirms that diabetes is one of the most prevalent non-communicable diseases globally, and it is the fourth or fifth leading cause of death in most developed countries. Diabetes prevalence ranges from nearly 0 in New Guinea to 50 in the Indians of Arizona. No modifiable risk factors have been clearly established in persons with type 1 diabetes, but major environmental determinants have been suggested. Impaired glucose tolerance, gestational diabetes, insulin resistance, obesity and lack of physical activity have been consistently identified as risk factors for type 2 diabetes. The prevalence of diabetes increases with age, but a sex-specific tendency has not been consistent. In addition, the prevalence of diabetes is higher in African-Americans and Hispanics when compared to other ethnic groups. Diabetes affects almost all organs of the body and is the leading cause of blindness and amputations of legs, imposing both clinical and economic costs to patients and society.