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

Knowledge and practices of tour guides in Cuzco on the prevention and treatment of traveler's diarrhea

Objectives: To describe the knowledge and practices among tour guides in Cuzco, Peru regarding prevention and treatment of traveler's diarrhea. Methods: The main tour guide association in Cuzco organized a mandatory re-certification course for tour guides in February 2004. We invited tour guides attending this course to participate in the study. Those aged 18 to 50 who had worked as a tour guide for at least one year were asked to complete a brief anonymous questionnaire. Results: A total of 173 questionnaires were returned; 137 met the inclusion criteria and were included in the analysis. The median age was 31 years (interquartile range (IQR): 28-34 years), and 56.7% were male. The median number of foreign languages spoken by subjects included was 1, being English (91.9%) the most common, followed by French (17.9%) and Italian (16.8%). The median time working as a tour guide was 4 years (IQR: 2-8 years). Tour guidance was a full-time job for 47.1% of the subjects, and for 82.4% Inca Trail was the most commonly covered route. Traveler's diarrhea was considered a food-borne disease by 85.4%, but only 60.6% considered it a water-borne disease. The majority of subjects identified raw salads (84.4%), cold sauces (81.5%) and tap water (81.1%) as risky products whereas hot soups (77 8%) and bread (75.0%) were mainly considered as safe. Most of the tour guides considered bloody stools (84.8%) and fever (60.6%) as indications to seek medical attention. The medications most frequently recommended by tour guides were oral re-hydration solutions ( 85.1%), trimethoprim-sulphamethoxazole (26.1%) and loperamide (20.1%). Conclusions: Tour guides have a basic knowledge about traveler's diarrhea. However, more training is necessary to improve management while trekking outside of Cuzco The recommendation to seek pharmacists should be particularly addressed

Testing for Network and Spatial Autocorrelation

Testing for dependence has been a well-established component of spatial statistical analyses for decades. In particular, several popular test statistics have desirable properties for testing for the presence of spatial autocorrelation in continuous variables. In this paper we propose two contributions to the literature on tests for autocorrelation. First, we propose a new test for autocorrelation in categorical variables. While some methods currently exist for assessing spatial autocorrelation in categorical variables, the most popular method is unwieldy, somewhat ad hoc, and fails to provide grounds for a single omnibus test. Second, we discuss the importance of testing for autocorrelation in network, rather than spatial, data, motivated by applications in social network data. We demonstrate that existing tests for autocorrelation in spatial data for continuous variables and our new test for categorical variables can both be used in the network setting

Ántrax cutáneo en Lima, Perú: análisis retrospectivo de 71 casos, incluyendo cuatro con complicación meningoencefálica

Anthrax is a zoonosis produced by Bacillus anthracis, and as an human infection is endemic in several areas in the world, including Peru. More than 95% of the reported naturally acquired infections are cutaneous, and approximately 5% of them can progress to meningoencephalitis. In this study we review the clinical and epidemiological characteristics of the patients with diagnosis of cutaneous anthrax evaluated between 1969 and 2002 at the Hospital Nacional Cayetano Heredia (HNCH) and the Instituto de Medicina Tropical Alexander von Humboldt in Lima, Peru. Seventy one patients were included [49/71 (69%) of them men], with a mean age of 37 years. The diagnoses were classified as definitive (44%) or probable (56%). The most common occupation of the patients was agriculture (39%). The source of infection was found in 63 (88.7%) patients. All the patients had ulcerative lesions, with a central necrosis. Most of the patients (65%) had several lesions, mainly located in the upper limbs (80%). Four patients (5.6%) developed meningoencephalitis, and three of them eventually died. In conclusion, considering its clinical and epidemiological characteristics, cutaneous anthrax must be included in the differential diagnosis of skin ulcers. A patient with clinical suspicion of the disease should receive effective treatment soon, in order to avoid neurological complications which carry a high fatality rate.El ántrax es una zoonosis producida por el Bacillus anthracis y la infección humana es endémica en diversas partes del mundo, incluyendo el Perú. Más del 95% de las infecciones adquiridas naturalmente son cutáneas y aproximadamente 5% de ellas pueden evolucionar para meningoencefalitis. En este estudio revisamos las características clínicas y epidemiológicas de los pacientes con diagnóstico de ántrax cutáneo evaluados entre 1969 y 2002 en el Hospital Nacional Cayetano Heredia (HNCH) y en el Instituto de Medicina Tropical Alexander von Humboldt, en Lima, Perú. Se incluyeron 71 pacientes [49/71 (69%) del sexo masculino], con edad media de 37 años. Los diagnósticos fueron clasificados como definitivos (44%) o probables (56%). La ocupación más frecuente fue la agricultura (39%). La fuente de infección fue identificada en 63 (88.7%) pacientes. Todos presentaron lesiones ulcerativas con necrosis central. La mayoría de ellos (65%) tuvieron lesiones múltiples, principalmente localizadas en miembros superiores (80%). Cuatro pacientes (5.6%) desarrollaron meningoencefalitis y tres de ellos fallecieron. En conclusión, considerando sus particulares características clínicas y epidemiológicas, el ántrax cutáneo debe ser siempre incluido en el diagnóstico diferencial de las lesiones cutáneas ulcerativas. Los pacientes con sospecha clínica de la enfermedad deben recibir tratamiento precoz con el objetivo de evitar complicaciones neurológicas, las cuales presentan elevados índices de fatalidad

High prevalence of clustered tuberculosis cases in peruvian migrants in Florence, Italy.

Tuberculosis is a leading cause of morbidity for Peruvian migrants in Florence, Italy, where they account for about 20% of yearly diagnosed cases. A retrospective study on cases notified in Peruvian residents in Florence in the period 2001-2010 was carried out and available Mycobacterium tuberculosis strains were genotyped (MIRU-VNTR-24 and Spoligotyping). One hundred thirty eight cases were retrieved. Genotyping performed in 87 strains revealed that 39 (44.8%) belonged to 12 clusters. Assuming that in each cluster the transmission of tuberculosis from the index case took place in Florence, a large proportion of cases could be preventable by improving early diagnosis of contagious cases and contact tracing

Exportation of MDR TB to europe from setting with actively transmitted persistent strains in peru

We performed a cross-border molecular epidemiology analysis of multidrug-resistant tuberculosis in Peru, Spain, and Italy. This analysis revealed frequent transmission in Peru and exportation of a strain that recreated similar levels of transmission in Europe during 2007–2017. Transnational efforts are needed to control transmission of multidrug-resistant tuberculosis globally

High prevalence of bronchiectasis is linked to HTLV-1-associated inflammatory disease.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus, is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia/lymphoma (ATLL). The reported association with pulmonary disease such as bronchiectasis is less certain. METHODS: A retrospective case review of a HTLV-1 seropositive cohort attending a national referral centre. The cohort was categorised into HTLV-1 symptomatic patients (SPs) (ATLL, HAM/TSP, Strongyloidiasis and HTLV associated inflammatory disease (HAID)) and HTLV-1 asymptomatic carriers (ACs). The cohort was reviewed for diagnosis of bronchiectasis. RESULT: 34/246 ACs and 30/167 SPs had been investigated for respiratory symptoms by computer tomography (CT) with productive cough +/- recurrent chest infections the predominant indications. Bronchiectasis was diagnosed in one AC (1/246) and 13 SPs (2 HAID, 1 ATLL, 10 HAM/TSP) (13/167, RR 19.2 95 % CI 2.5-14.5, p = 0.004) with high resolution CT. In the multivariate analysis ethnicity (p = 0.02) and disease state (p < 0.001) were independent predictors for bronchiectasis. The relative risk of bronchiectasis in SPs was 19.2 (95 % CI 2.5-14.5, p = 0.004) and in HAM/TSP patients compared with all other categories 8.4 (95 % CI 2.7-26.1, p = 0.0002). Subjects not of African/Afro-Caribbean ethnicity had an increased prevalence of bronchiectasis (RR 3.45 95 % 1.2-9.7, p = 0.02). CONCLUSIONS: Bronchiectasis was common in the cohort (3.4 %). Risk factors were a prior diagnosis of HAM/TSP and ethnicity but not HTLV-1 viral load, age and gender. The spectrum of HTLV-associated disease should now include bronchiectasis and HTLV serology should be considered in patients with unexplained bronchiectasis

Rates and Reasons for Early Change of First HAART in HIV-1-Infected Patients in 7 Sites throughout the Caribbean and Latin America

BACKGROUND: HAART rollout in Latin America and the Caribbean has increased from approximately 210,000 in 2003 to 390,000 patients in 2007, covering 62% (51%-70%) of eligible patients, with considerable variation among countries. No multi-cohort study has examined rates of and reasons for change of initial HAART in this region. METHODOLOGY: Antiretroviral-naïve patients >or= 18 years who started HAART between 1996 and 2007 and had at least one follow-up visit from sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Time from HAART initiation to change (stopping or switching any antiretrovirals) was estimated using Kaplan-Meier techniques. Cox proportional hazards modeled the associations between change and demographics, initial regimen, baseline CD4 count, and clinical stage. PRINCIPAL FINDINGS: Of 5026 HIV-infected patients, 35% were female, median age at HAART initiation was 37 years (interquartile range [IQR], 31-44), and median CD4 count was 105 cells/uL (IQR, 38-200). Estimated probabilities of changing within 3 months and one year of HAART initiation were 16% (95% confidence interval (CI) 15-17%) and 28% (95% CI 27-29%), respectively. Efavirenz-based regimens and no clinical AIDS at HAART initiation were associated with lower risk of change (hazard ratio (HR) = 1.7 (95% CI 1.1-2.6) and 2.1 (95% CI 1.7-2.5) comparing neverapine-based regimens and other regimens to efavirenz, respectively; HR = 1.3 (95% CI 1.1-1.5) for clinical AIDS at HAART initiation). The primary reason for change among HAART initiators were adverse events (14%), death (5.7%) and failure (1.3%) with specific toxicities varying among sites. After change, most patients remained in first line regimens. CONCLUSIONS: Adverse events were the leading cause for changing initial HAART. Predictors for change due to any reason were AIDS at baseline and the use of a non-efavirenz containing regimen. Differences between participant sites were observed and require further investigation

Antiretroviral resistance after first-line antiretroviral therapy failure in diverse HIV-1 subtypes in the SECOND-LINE study

We investigate mutations and correlates according to HIV-1 subtype after virological failure (VF) of standard first-line antiretroviral therapy (ART) (non-nucleoside/nucleotide reverse transcriptase inhibitor [NNRTI] +2 nucleoside/nucleotide reverse transcriptase inhibitor [N(t)RTI]). SECOND-LINE study participants were assessed at baseline for HIV-1 subtype, demographics, HIV-1 history, ART exposure, viral load (VL), CD4(+) count, and genotypic ART resistance. We used backward stepwise multivariate regression (MVR) to assess associations between baseline variables and presence of ≥3 N(t)RTI mutations, ≥1 NNRTI mutation, ≥3 thymidine analog-N(t)RTI [ta-N(t)RTI] mutations (TAMs), the K65/K70 mutation, and predicted etravirine (ETV)/rilpivirine (RPV) activity. The inclusion p-value for MVR was p  .05. Of 541 participants, 491 (91%) had successfully characterized baseline viral isolates. Subtype distribution: B (n = 123, 25%), C (n = 202, 41%), CRF01_AE (n = 109, 22%), G (n = 25, 5%), and CRF02_AG (n = 27, 5%). Baseline CD4(+) 200-394 cells/mm(3) were associated with <3 N(t)RTI mutations (OR = 0.47; 95% CI 0.29-0.77; p = .003), absence of the K65/K70 mutation (OR = 0.43; 95% CI 0.26-0.73; p = .002), and higher ETV sensitivity (OR = 0.52; 95% CI 0.35-0.78; p = .002). Recent tenofovir (TDF) use was associated with K65/K70 mutations (OR = 8.91; 95% CI 5.00-15.85; p < .001). Subtype CRF01_AE was associated with ≥3 N(t)RTI mutations (OR = 2.34; 95% CI 1.31-4.17; p = .004) and higher RPV resistance (OR = 2.13; 95% CI 1.30-3.49; p = .003), and subtype C was associated with <3 TAMs (OR = 0.45; 95% CI 0.21-0.99; p = .015). Subtypes CRF01_AE (OR = 2.46; 95% CI 1.26-4.78; p = .008) and G (OR = 4.77; 95% CI 1.44-15.76; p = .01) were associated with K65/K70 mutations. Higher VL at confirmed first-line VF was associated with ≥3 N(t)RTI mutations (OR = 1.39; 95% CI 1.07-1.78; p = .013) and ≥3 TAMs (OR = 1.62; 95% CI 1.15-2.29; p = .006). The associations of first-line resistance mutations across the HIV-1 subtypes in this study are consistent with knowledge derived from subtype B, with some exceptions. Patterns of resistance after failure of a first-line ta-N(t)RTI regimen support using TDF in N(t)RTI-containing second-line regimens, or using N(t)RTI-sparing regimens.Edward P. Lam, Cecilia L. Moore, Eduardo Gotuzzo, Chidi Nwizu, Adeeba Kamarulzaman, Ploenchan Chetchotisakd, Jean van Wyk, Hedy Teppler, Nagalingeswaran Kumarasamy, Jean-Michel Molina, Sean Emery, David A. Cooper, and Mark A. Boyd, for the SECOND-LINE study grou