Scrub typhus in South India: clinical and laboratory manifestations, genetic variability, and outcome

SummaryObjectivesThis study sought to document the clinical and laboratory manifestations, genetic variability, and outcomes of scrub typhus, an often severe infection caused by Orientia tsutsugamushi, in South India.MethodsPatients admitted to a large teaching hospital with IgM ELISA-confirmed scrub typhus were evaluated. Clinical examination with a thorough search for an eschar, laboratory testing, chest X-ray, and outcome were documented and analyzed. Additionally, a 410-bp region of the 56-kDa type-specific antigen gene of O. tsutsugamushi was sequenced and compared with isolates from other regions of Asia.ResultsMost of the 154 patients evaluated presented with fever and non-specific symptoms. An eschar was found in 86 (55%) patients. Mild hepatic involvement was seen in most, with other organ involvement including respiratory, cardiovascular, and renal. Multi-organ dysfunction was noted in 59 (38.3%), and the fatality rate was 7.8%. Hypotension requiring vasoactive agents was found to be an independent predictor of mortality (p<0.001). The phylogeny of 26 samples showed 17 (65%) clustering with the Kato-like group and eight (31%) with the Karp-like group.ConclusionsThe presentation of scrub typhus can be variable, often non-specific, but with potentially severe multi-organ dysfunction. Prompt recognition is key to specific treatment and good outcomes. Further study of the circulating strains is essential for the development of a successful vaccine and sensitive point-of-care testing

HBV Infection in Relation to Consistent Condom Use: A Population-Based Study in Peru

Data on hepatitis B virus (HBV) prevalence are limited in developing countries. There is also limited information of consistent condom use efficacy for reducing HBV transmission at the population level. The study goal was to evaluate the prevalence and factors associated with HBV infection in Peru, and the relationship between anti-HBc positivity and consistent condom use.Data from two different surveys performed in 28 mid-sized Peruvian cities were analyzed. Participants aged 18-29 years were selected using a multistage cluster sampling. Information was collected through a validated two-part questionnaire. The first part (face-to-face) concerned demographic data, while the second part (self-administered using handheld computers) concerned sexual behavior. Hepatitis B core antibody (anti-HBc) was tested in 7,000 blood samples. Prevalences and associations were adjusted for sample strata, primary sampling units and population weights. Anti-HBc prevalence was 5.0% (95%CI 4.1%-5.9%), with the highest prevalence among jungle cities: 16.3% (95%CI 13.8%-19.1%). In the multivariable analysis, Anti-HBc positivity was directly associated with geographic region (highlands OR = 2.05; 95%CI 1.28-3.27, and jungle OR = 4.86; 95%CI 3.05-7.74; compared to coastal region); and inversely associated with age at sexual debut (OR = 0.90; 95%CI 0.85-0.97). Consistent condom use, evaluated in about 40% of participants, was associated with reduced prevalence (OR = 0.34; 95%CI 0.15-0.79) after adjusting for gender, geographic region, education level, lifetime number of sex partners, age at sexual debut and year of survey.Residence in highlands or jungle cities is associated with higher anti-HBc prevalences, whereas increasing age at sexual debut were associated with lower prevalences. Consistent condom use was associated with decreased risk of anti-HBc. Findings from this study emphasize the need of primary prevention programs (vaccination) especially in the jungle population, and imply that condom use promotion might be a potential strategy to prevent HBV infection

Rare X chromosome abnormalities in systemic lupus erythematosus and Sjögren's syndrome

Objective: Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are related by clinical and serologic manifestations as well as genetic risks. Both diseases are more commonly found in women than in men, at a ratio of ~10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease, suggesting a dose effect on the X chromosome. Methods: We examined cohorts of SS and SLE patients by constructing intensity plots of X chromosome single-nucleotide polymorphism alleles, along with determining the karyotype of selected patients. Results: Among ~2,500 women with SLE, we found 3 patients with a triple mosaic, consisting of 45,X/46,XX/47,XXX. Among ~2,100 women with SS, 1 patient had 45,X/46,XX/47,XXX, with a triplication of the distal p arm of the X chromosome in the 47,XXX cells. Neither the triple mosaic nor the partial triplication was found among the controls. In another SS cohort, we found a mother/daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in ~1 in 25,000–50,000 live female births, while partial triplications are even rarer. Conclusion: Very rare X chromosome abnormalities are present among patients with either SS or SLE and may inform the location of a gene(s) that mediates an X dose effect, as well as critical cell types in which such an effect is operative. © 2017, American College of Rheumatolog

Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma

High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8+ cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs. [18F]FHBG imaging was safe and enabled the longitudinal imaging of T cells stably transfected with a PET reporter gene in patients. Further optimization of this imaging approach for monitoring in vivo cell trafficking should greatly benefit various cell-based therapies for cancer