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Resumen Antecedentes La histoplasmosis diseminada (HD) es una infeccion fungica oportunista en pacientes con infeccion por VIH gravemente inmunocomprometidos. El sindrome hemofagocitico (SHF), que puede presentarse en estos pacientes coinfectados cuando la respuesta inmunitaria esta significativamente alterada, suele estar asociado a una elevada mortalidad. Objetivos Describir las caracteristicas epidemiologicas, clinicas, analiticas y microbiologicas, asi como evaluar la presencia de SHF, en pacientes con HD-VIH. Metodos Estudio retrospectivo de serie de casos, consistente en la revision de registros clinicos de pacientes con diagnostico de HD e infeccion VIH, durante los anos 2014 y 2015. Resultados El 1,3% (8/597) de los pacientes VIH presentaron HD. El 100% se hallaban en estadio C3 y el 75% (6/8) no se encontraban en terapia antirretroviral combinada (TARVc). Los dos pacientes restantes habian comenzado recientemente el tratamiento con TARVc (posible sindrome de reconstitucion inmunologica). El 62,5% (5/8) cumplieron con criterios diagnosticos de SHF. Las manifestaciones clinicas mas frecuentes fueron el sindrome linfoproliferativo y consuntivo, el compromiso respiratorio y la citopenia. En el 75% (6/8) de los pacientes se aislo Histoplasma en ganglios, en el 25% (2/8) en muestras hematicas y en uno adicionalmente en tejido intestinal. La terapia antifungica fue anfotericina B desoxicolato; no se emplearon adyuvantes. La mortalidad global fue del 50%. Conclusiones En nuestra serie la coinfeccion HD-VIH progreso en la mayoria de los casos a SHF con elevada mortalidad. El cuadro clinico puede asemejarse al de otras enfermedades sistemicas, como la tuberculosis, o presentarse simultaneamente a ellas. Con el fin de obtener un diagnostico precoz y poder prescribir la terapia especifica oportuna es importante poseer un adecuado indice de sospecha en pacientes con sindrome linfoproliferativo y consuntivo asociado a citopenia grave.

Summary Background Delamanid is one of two recently approved drugs for the treatment of multidrug-resistant tuberculosis. We aimed to evaluate the safety and efficacy of delamanid in the first 6 months of treatment. Methods This randomised, double-blind, placebo-controlled, phase 3 trial was done at 17 sites in seven countries (Estonia, Latvia, Lithuania, Moldova, Peru, the Philippines, and South Africa). We enrolled eligible adults (>18 years) with pulmonary multidrug-resistant tuberculosis to receive, in combination with an optimised background regimen developed according to WHO and national guidelines, either oral delamanid (100 mg twice daily) for 2 months followed by 200 mg once daily for 4 months or placebo (same regimen). Patients were centrally randomised (2:1) and stratified by risk category for delayed sputum culture conversion. Primary outcomes were the time to sputum culture conversion over 6 months and the difference in the distribution of time to sputum culture conversion over 6 months between the two groups, as assessed in the modified intention-to-treat population. The trial is registered at ClinicalTrials.gov, number NCT01424670. Findings Between Sept 2, 2011, and Nov 27, 2013, we screened 714 patients, of whom 511 were randomly assigned (341 to delamanid plus optimised background regimen [delamanid group] and 170 to placebo plus optimised background regimen [placebo group]) and formed the safety analysis population. 327 patients were culture-positive for multidrug-resistant tuberculosis at baseline and comprised the efficacy analysis population (226 in the delamanid group and 101 in the placebo group). Median time to sputum culture conversion did not differ between the two groups (p=0·0562; modified Peto-Peto), with 51 days (IQR 29–98) in the delamanid group and 57 days (43–85) in the placebo group; the hazard ratio was 1·17 (95% CI 0·91–1·51, p=0·2157). 501 (98·0%) of 511 patients had at least one treatment-emergent adverse event. 136 (26·6%) of 511 patients had at least one serious treatment-emergent adverse event; the incidence was similar between treatment groups (89 [26·1%] of 341 patients for delamanid and 47 [27·6%] of 170 for placebo). Deaths related to treatment-emergent adverse events were similar between groups (15 [4·4%] of 341 for delamanid and six [3·5%] of 170 for placebo). No deaths were considered to be related to delamanid. Interpretation The reduction in median time to sputum culture conversion over 6 months was not significant in the primary analysis. Delamanid was well tolerated with a highly characterised safety profile. Further evaluation of delamanid is needed to determine its role in a rapidly evolving standard of care. Funding Otsuka Pharmaceutical.

Animal sacrifice has played an important role as a material expression of the ritual behavior practiced by different societies around the world. In the South American Andes, the ceremonial immolation of llamas is well documented by both ethnohistoric and ethnographic sources. Nevertheless, archaeological evidence of animal sacrifice remains poorly documented. In this paper, we report the burial of two young camelids from El Pacifico, a Formative Period ceremonial site located on the central coast of Peru. AMS radiocarbon dates suggest the ritual sacrifice occurred when the architecture of the site was no longer in use, around the time of the Inca conquest. Based on the presence of cut marks and fly pupae, we suggest that one of the camelids, a yearling llama, was sacrificed by removal of its heart and buried shortly thereafter. Similarly, given the location of cut marks and representation of skeletal parts, we infer that the second camelid was slaughtered for human consumption prior to burial. In accordance with documented Andean rites, archaeological evidence from El Pacifico suggests that practitioners of camelid sacrifice followed a behavioral script following the selection of the animal to its final interment. We hypothesize the costly performance of this ceremony at an ancestral sacred site was part of a social and political strategy for promoting intergroup social cohesion during the arrival of the Incas to the region.

Chikungunya is an arthropod-borne virus transmitted by Aedes mosquito bites. A viral mutation has allowed Aedes albopictus to become the preferred vector extending the geographic spread of the condition. The virus causes an acute febrile illness occasionally followed by a chronic rheumatic condition causing severe impairment. The diagnosis is usually confirmed with serology. No specific treatment is currently available. This article reviews the condition with emphasis on his dissemination in the Americas. Keywords: Chikungunya, Alphavirus, Epidemics

Background: Concurrent treatment of tuberculosis and HIV is challenging owing to drug interactions, overlapping toxicities, and immune reconstitution inflammatory syndrome (IRIS). The efficacy and safety of dolutegravir were assessed in adults with HIV and drug-susceptible tuberculosis. Methods: INSPIRING (NCT02178592) is a Phase 3b, non-comparative, active-control, randomised, open-label study in HIV-1-infected ARTcells/mm3). Participants on rifampicin-based tuberculosis treatment ≤8 weeks were randomised (3:2) to receive dolutegravir (50mg twice-daily during and 2 weeks post-tuberculosis therapy, then 50mg once-daily) or efavirenz (600mg once-daily), with two NRTI for 52 weeks. The primary endpoint was the proportion of dolutegravir-arm participants with plasma HIV-1-RNA 100,000 c/mL in 64%, with median CD4 208 c/µL; for efavirenz (N=44), 55% had HIV-1-RNA >100,000 c/mL, median CD4 count was 202 c/µL. Week 48 response rate was 75% (52/69) (95%CI: 65%, 86%) for dolutegravir and 82% (36/44) (70%, 93%) for efavirenz. Dolutegravir non-response was driven by non-treatmentrelated discontinuations, mostly loss-to-follow-up following initial virologic suppression. There were no deaths or study drug switches in either arm; there were two discontinuations for toxicity (efavirenz).There were three protocol-defined virological failures (2 dolutegravir with no emergence of resistance, 1 efavirenz with NRTI and NNRTI emergent resistance detected). Tuberculosis treatment success was high. TBassociated IRIS was uncommon, with no discontinuations for IRIS. Interpretation: Among adults with HIV receiving rifampicin-based tuberculosis treatment, twice-daily dolutegravir was effective and well-tolerated. Clinical Trial Number: NCT02178592 Funding Statement: This study was funded by ViiV Healthcare. Declaration of Interests: MAK, MA, RS, CLT, KA, AT, DB and MRK are employed by and own shares in GSK. KED received salary support through her university for research effort devoted to this study. Ethics Approval Statement: The trial was approved by local ethics committees at each site, and participants gave written informed consent.

Summary Objectives To describe the mycologic and clinical outcomes and factors associated with failure in Peruvian patients with AIDS-associated cryptococcal meningitis (CM) treated with amphotericin B deoxycholate (Amph B) followed by fluconazole. Methods Patients were treated with intravenous Amph B 0.7mg/kg/day for 2 or 3 weeks followed by oral fluconazole 400mg/day for 7 or 8 weeks. Clinical and laboratory evaluations including cerebrospinal fluid (CSF) studies were performed at baseline and at weeks 2 and 10. Results The CSF cultures were negative in 25% and 68% of 47 patients at weeks 2 and 10, respectively. In the univariate analysis, baseline low body mass index (BMI), hyponatremia, low serum albumin, positive blood culture and CSF antigen titers ≥1024 were associated with a positive CSF culture at week 2. Baseline positive urine culture, positive blood culture, any positive extraneural culture and CSF opening pressure at week 2 ≥300mm H2O were associated with a positive CSF culture at week 10. In the multivariate analysis no association was found. Conclusions Therapy with Amph B and fluconazole, combined with aggressive management of elevated intracranial pressure (ICP), results in low CSF sterilization rates at week 2 and acceptable CSF sterilization rates at week 10 when compared with other series.