Ex vivo innate immune cytokine signature of enhanced risk of relapsing brucellosis.

BackgroundBrucellosis, a zoonotic infection caused by one of the Gram-negative intracellular bacteria of the Brucella genus, is an ongoing public health problem in Perú. While most patients who receive standard antibiotic treatment recover, 5-40% suffer a brucellosis relapse. In this study, we examined the ex vivo immune cytokine profiles of recovered patients with a history of acute and relapsing brucellosis.Methodology/principal findingsBlood was taken from healthy control donors, patients with a history of acute brucellosis, or patients with a history of relapsing brucellosis. Peripheral blood mononuclear cells were isolated and remained in culture without stimulation or were stimulated with a panel of toll-like receptor agonists or heat-killed Brucella melitensis (HKBM) isolates. Innate immune cytokine gene expression and protein secretion were measured by quantitative real-time polymerase chain reaction and a multiplex bead-based immunoassay, respectively. Acute and relapse patients demonstrated consistently elevated cytokine gene expression and secretion levels compared to controls. Notably, these include: basal and stimulus-induced expression of GM-CSF, TNF-α, and IFN-γ in response to LPS and HKBM; basal secretion of IL-6, IL-8, and TNF-α; and HKBM or Rev1-induced secretion of IL-1β, IL-2, GM-CSF, IFN-Υ, and TNF-α. Although acute and relapse patients were largely indistinguishable by their cytokine gene expression profiles, we identified a robust cytokine secretion signature that accurately discriminates acute from relapse patients. This signature consists of basal IL-6 secretion, IL-1β, IL-2, and TNF-α secretion in response to LPS and HKBM, and IFN-γ secretion in response to HKBM.Conclusions/significanceThis work demonstrates that informative cytokine variations in brucellosis patients can be detected using an ex vivo assay system and used to identify patients with differing infection histories. Targeted diagnosis of this signature may allow for better follow-up care of brucellosis patients through improved identification of patients at risk for relapse

Fecal contamination of drinking water within peri-urban households, Lima, Peru.

We assessed fecal contamination of drinking water in households in 2 peri-urban communities of Lima, Peru. We measured Escherichia coli counts in municipal source water and, within households, water from principal storage containers, stored boiled drinking water, and water in a serving cup. Source water was microbiologically clean, but 26 (28%) of 93 samples of water stored for cooking had fecal contamination. Twenty-seven (30%) of 91 stored boiled drinking water samples grew E. coli. Boiled water was more frequently contaminated when served in a drinking cup than when stored (P < 0.01). Post-source contamination increased successively through the steps of usage from source water to the point of consumption. Boiling failed to ensure safe drinking water at the point of consumption because of easily contaminated containers and poor domestic hygiene. Hygiene education, better point-of-use treatment and storage options, and in-house water connections are urgently needed

Molecular Diagnosis of TB in the HIV Positive Population

Background: Tuberculosis (TB) remains a major contributor to morbidity and mortality in HIV-positive individuals, causing 1.1 million incident cases and 0.32 million deaths in 2012. Diagnosis of TB is particularly challenging in HIV-coinfected individuals, due to a high frequency of smear-negative disease, atypical presentations, and extrapulmonary TB. Objective: The aim of this article was to review the current literature on molecular diagnostics for TB with an emphasis on the performance of these diagnostic tests in the HIV-positive population. Methods: We searched the PubMed database using at least one of the terms TB, HIV, diagnostics, Xpert MTB/RIF, 'nucleic acid amplification tests', drug susceptibility testing, RNA transcription, and drew on World Health Organization publications. Findings: With increased focus on reducing TB prevalence worldwide, a new set of tools for diagnosing the disease have emerged. Molecular tools such as Xpert MTB/RIF and line-probe assays are now in use or are being rolled out in many regions. The diagnostic performance of these and other molecular assays are discussed here as they pertain to the HIV-positive population. ConclusionsMolecular diagnostics offer a useful addition and at times, alternative, to traditional culture methods for the diagnosis of TB. However, most of these tests suffer from decreased accuracy in the HIV-positive population

A Comprehensive Safety Trial of Chimeric Antibody 14.18 With GM-CSF, IL-2, and Isotretinoin in High-Risk Neuroblastoma Patients Following Myeloablative Therapy: Children\u27s Oncology Group Study ANBL0931

Purpose: A phase 3 randomized study (COG ANBL0032) demonstrated significantly improved outcome by adding immunotherapy with ch14.18 antibody to isotretinoin as post-consolidation therapy for high-risk neuroblastoma (NB). This study, ANBL0931, was designed to collect FDA-required safety/toxicity data to support FDA registration of ch14.18. Experimental design: Newly diagnosed high-risk NB patients who achieved at least a partial response to induction therapy and received myeloablative consolidation with stem cell rescue were enrolled to receive six courses of isotretinoin with five concomitant cycles of ch14.18 combined with GM-CSF or IL2. Ch14.18 infusion time was 10-20 h per dose. Blood was collected for cytokine analysis and its association with toxicities and outcome. Results: Of 105 patients enrolled, five patients developed protocol-defined unacceptable toxicities. The most common grade \u3e/= 3 non-hematologic toxicities of immunotherapy for cycles 1-5, respectively, were neuropathic pain (41, 28, 22, 31, 24%), hypotension (10, 17, 4, 14, 8%), allergic reactions (ARs) (3, 10, 5, 7, 2%), capillary leak syndrome (1, 4, 0, 2, 0%), and fever (21, 59, 6, 32, 5%). The 3-year event-free survival and overall survival were 67.6 +/- 4.8% and 79.1 +/- 4.2%, respectively. AR during course 1 was associated with elevated serum levels of IL-1Ra and IFNgamma, while severe hypotension during this course was associated with low IL5 and nitrate. Higher pretreatment CXCL9 level was associated with poorer event-free survival (EFS). Conclusion: This study has confirmed the significant, but manageable treatment-related toxicities of this immunotherapy and identified possible cytokine biomarkers associated with select toxicities and outcome. EFS and OS appear similar to that previously reported on ANBL0032

Skinfold thickness and the incidence of type 2 diabetes mellitus and hypertension: an analysis of the PERU MIGRANT study.

OBJECTIVE: To determine the association between excess body fat, assessed by skinfold thickness, and the incidence of type 2 diabetes mellitus (T2DM) and hypertension (HT). DESIGN: Data from the ongoing PERU MIGRANT Study were analysed. The outcomes were T2DM and HT, and the exposure was skinfold thickness measured in bicipital, tricipital, subscapular and suprailiac areas. The Durnin-Womersley formula and SIRI equation were used for body fat percentage estimation. Risk ratios and population attributable fractions (PAF) were calculated using Poisson regression. SETTING: Rural (Ayacucho) and urban shantytown district (San Juan de Miraflores, Lima) in Peru. PARTICIPANTS: Adults (n 988) aged ≥30 years (rural, rural-to-urban migrants, urban) completed the baseline study. A total of 785 and 690 were included in T2DM and HT incidence analysis, respectively. RESULTS: At baseline, age mean was 48·0 (sd 12·0) years and 47 % were males. For T2DM, in 7·6 (sd 1·3) years, sixty-one new cases were identified, overall incidence of 1·0 (95 % CI 0·8, 1·3) per 100 person-years. Bicipital and subscapular skinfolds were associated with 2·8-fold and 6·4-fold risk of developing T2DM. On the other hand, in 6·5 (sd 2·5) years, overall incidence of HT was 2·6 (95 % CI 2·2, 3·1) per 100 person-years. Subscapular and overall fat obesity were associated with 2·4- and 2·9-fold risk for developing HT. The PAF for subscapular skinfold was 73·6 and 39·2 % for T2DM and HT, respectively. CONCLUSIONS: We found a strong association between subscapular skinfold thickness and developing T2DM and HT. Skinfold assessment can be a laboratory-free strategy to identify high-risk HT and T2DM cases

Epidemiologic Differences Between Cyclosporiasis and Cryptosporidiosis in Peruvian Children

We compared the epidemiologic characteristics of cyclosporiasis and cryptosporidiosis in data from a cohort study of diarrhea in a periurban community near Lima, Peru. Children had an average of 0.20 episodes of cyclosporiasis/year and 0.22 episodes of cryptosporidiosis/year of follow-up. The incidence of cryptosporidiosis peaked at 0.42 for 1-year-old children and declined to 0.06 episodes/child-year for 5- to 9-year-old children. In contrast, the incidence of cyclosporiasis was fairly constant among 1- to 9-year-old children (0.21 to 0.28 episodes/child-year). Likelihood of diarrhea decreased significantly with each episode of cyclosporiasis; for cryptosporidiosis, this trend was not statistically significant. Both infections were more frequent during the warm season (December to May) than the cooler season (June to November). Cryptosporidiosis was more frequent in children from houses without a latrine or toilet. Cyclosporiasis was associated with ownership of domestic animals, especially birds, guinea pigs, and rabbits

Contribution of modifiable risk factors for hypertension and type-2 diabetes in Peruvian resource-limited settings.

BACKGROUND: It is important to understand the local burden of non-communicable diseases including within-country heterogeneity. The aim of this study was to characterise hypertension and type-2 diabetes profiles across different Peruvian geographical settings emphasising the assessment of modifiable risk factors. METHODS: Analysis of the CRONICAS Cohort Study baseline assessment was conducted. Cardiometabolic outcomes were blood pressure categories (hypertension, prehypertension, normal) and glucose metabolism disorder status (diabetes, prediabetes, normal). Exposures were study setting and six modifiable factors (smoking, alcohol drinking, leisure time and transport-related physical activity levels, TV watching, fruit/vegetables intake and obesity). Poisson regression models were used to report prevalence ratios (PR). Population attributable risks (PAR) were also estimated. RESULTS: Data from 3238 participants, 48.3% male, mean age 45.3 years, were analysed. Age-standardised (WHO population) prevalence of prehypertension and hypertension was 24% and 16%, whereas for prediabetes and type-2 diabetes it was 18% and 6%, respectively. Outcomes varied according to study setting (p<0.001). In multivariable model, hypertension was higher among daily smokers (PR 1.76), heavy alcohol drinkers (PR 1.61) and the obese (PR 2.06); whereas only obesity (PR 2.26) increased the prevalence of diabetes. PAR showed that obesity was an important determinant for hypertension (15.7%) and type-2 diabetes (23.9%). CONCLUSIONS: There is an evident heterogeneity in the prevalence of and risk factors for hypertension and diabetes within Peru. Prehypertension and prediabetes are highly prevalent across settings. Our results emphasise the need of understanding the epidemiology of cardiometabolic conditions to appropriately implement interventions to tackle the burden of non-communicable diseases

Sodium and Potassium Consumption in a Semi-Urban Area in Peru: Evaluation of a Population-Based 24-Hour Urine Collection.

Despite the negative effects of high sodium and low potassium consumption on cardiovascular health, their consumption has not been quantified in sites undergoing urbanization. We aimed to determine the sodium and potassium consumption in a semi-urban area in Peru with a cross-sectional study. 24-h urine samples were collected. The outcomes were mean consumption of sodium and potassium, as well as adherence to their consumption recommendation: <2 g/day and ≥3.51 g/day, respectively. Bivariate analyses were conducted to identify socio-economic and clinical variables associated with the consumption recommendations of 602 participants, complete urine samples were found in 409: mean age of participants was 45.7 (standard deviation (SD): 16.2) years and 56% were women. The mean sodium and potassium consumption was 4.4 (SD: 2.1) and 2.0 (SD: 1.2) g/day. The sodium and potassium recommendation was met by 7.1% and 13.7% of the study sample; none of the participants met both recommendations. People not adherent to the sodium recommendation had higher diastolic (73.1 mmHg vs. 68.2 mmHg, p = 0.015) and systolic (113.1 mmHg vs. 106.3 mmHg, p = 0.047) blood pressure than those who comply with the recommendation. Public health actions ought to be implemented in areas undergoing urbanization to improve sodium and potassium consumption at the population level

Impact of urbanisation and altitude on the incidence of, and risk factors for, hypertension.

BACKGROUND: Most of the data regarding the burden of hypertension in low-income and middle-income countries comes from cross-sectional surveys instead of longitudinal studies. We estimated the incidence of, and risk factors for, hypertension in four study sites with different degree of urbanisation and altitude. METHODS: Data from the CRONICAS Cohort Study, conducted in urban, semiurban and rural areas in Peru, was used. An age-stratified and sex-stratified random sample of participants was taken from the most updated census available in each site. Hypertension was defined as systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥90 mm Hg, or self-report physician diagnosis and current treatment. The exposures were study site and altitude as well as modifiable risk factors. Incidence, incidence rate ratios (IRRs), 95% CIs and population-attributable fractions (PAFs) were estimated using generalised linear models. RESULTS: Information from 3237 participants, mean age 55.8 (SD±12.7) years, 48.4% males, was analysed. Overall baseline prevalence of hypertension was 19.7% (95% CI 18.4% to 21.1%). A total of 375 new cases of hypertension were recorded, including 5266 person-years of follow-up, with an incidence of 7.12 (95% CI 6.44 to 7.88) per 100 person-years. Individuals from semiurban site were at higher risk of hypertension compared with highly urbanised areas (IRR=1.76; 95% CI 1.39 to 2.23); however, those from high-altitude sites had a reduced risk (IRR=0.74; 95% CI 0.58 to 0.95). Obesity was the leading risk factor for hypertension with a great variation according to study site with PAF ranging from 12.5% to 42.4%. CONCLUSIONS: Our results suggest heterogeneity in the progression towards hypertension depending on urbanisation and site altitude