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Abstract From the arrival of Chikungunya virus in the Americas in 2013 until March 2016, approximately two million cases of the disease have been reported. In Brazil, the virus was identified in 2014 and thousands of people have been affected. The disease has high attack rates, infecting 50% of a population within a few months. Approximately 50% of infected people develop chronic symptoms lasting for months or years. Joint involvement is the main clinical manifestation of Chikungunya. It is characterized by swelling and intense pain that is poorly responsive to analgesics, both in the acute and chronic phase of the disease. This significantly compromises quality of life and may have immeasurable psychosocial and economic repercussions, constituting therefore, a serious public health problem requiring a targeted approach. Physicians are often not familiar with how to approach the management of pain, frequently prescribing limited analgesics, such as dipyrone, in sub-therapeutic doses. In addition, there are few published studies or guidelines on the approach to the treatment of pain in patients with Chikungunya. Some groups of specialists from different fields have thus developed a protocol for the pharmacologic treatment of Chikungunya-associated acute and chronic joint pain; this will be presented in this review.

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Abstract This review discusses studies on the venom of Bothrops erythromelas published over the past 36 years. During this period, many contributions have been made to understand the venomous snake, its venom, and its experimental and clinical effects better. The following chronological overview is based on 29 articles that were published between 1979 and 2015, with emphasis on diverse areas. The complexity of this task demands an integration of multidisciplinary research tools to study toxinology. This science is in need of renewed conceptual and experimental platforms aimed at obtaining a profound understanding of the highly complex pathophysiology of snakebite envenoming and toxins isolated from snakes.

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Abstract: INTRODUCTION: The significant increase in dengue, Zika, and chikungunya and the resistance of the Aedes aegypti mosquito to major insecticides emphasize the importance of studying alternatives to control this vector. The aim of this study was to develop a controlled-release device containing Piper nigrum extract and to study its larvicidal activity against Aedes aegypti. METHODS: Piper nigrum extract was produced by maceration, standardized in piperine, and incorporated into cotton threads, which were inserted into hydrogel cylinders manufactured by the extrusion of carrageenan and carob. The piperine content of the extract and thread reservoirs was quantified by chromatography. The release profile from the device was assessed in aqueous medium and the larvicidal and residual activities of the standardized extract as well as of the controlled-release device were examined in Aedes aegypti larvae. RESULTS The standardized extract contained 580mg/g of piperine and an LC50 value of 5.35ppm (24h) and the 3 cm thread reservoirs contained 13.83 ± 1.81mg of piperine. The device showed zero-order release of piperine for 16 days. The P. nigrum extract (25ppm) showed maximum residual larvicidal activity for 10 days, decreasing progressively thereafter. The device had a residual larvicidal activity for up to 37 days. CONCLUSIONS: The device provided controlled release of Piper nigrum extract with residual activity for 37 days. The device is easy to manufacture and may represent an effective alternative for the control of Aedes aegypti larvae in small water containers.

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Abstract: INTRODUCTION: Dengue fever is a viral disease transmitted by the Aedes aegypti Linn. (1792) (Diptera: Culicidae) mosquito, which is endemic in several regions of Brazil. Alternative methods for the control of the vector include botanical insecticides, which offer advantages such as lower environmental contamination levels and less likelihood of resistant populations. Thus, in this study, the ability of botanical insecticide formulations to inhibit the activity of the liver enzymes serum cholinesterase and malate dehydrogenase was evaluated. METHODS: Inhibition profiles were assessed using in vitro assays for cholinesterase and malate dehydrogenase activity and quantitated by ultraviolet-visible spectroscopy at 410nm to 340nm. RESULTS Insecticide products formulated from cashew nutshell liquid [A] and ricinoleic acid [B] showed cholinesterase activity levels of 6.26IU/mL and 6.61IU/mL, respectively, while the control level for cholinesterase was 5-12IU/mL. The products did not affect the level of 0.44IU/mL established for malate dehydrogenase, as the levels produced by [A] and [B] were 0.43IU/mL and 0.45IU/mL, respectively. CONCLUSIONS Our findings show that in vitro testing of the formulated products at concentrations lethal to A. aegypti did not affect the activity of cholinesterase and malate dehydrogenase, indicating the safety of these products.

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Abstract INTRODUCTION: The sandfly fauna is well studied globally. In Brazil, sandfly fauna is very diverse in the Northeast region, especially in states such as Maranhão, Ceará, and Bahia. However, in the State of Pernambuco, the distribution of these insects is still not well known. Therefore, the objective of this study was to identify the different species that constitute the sandfly fauna in an urban area in the Northeast region of Brazil, where an outbreak of visceral leishmaniasis (VL) was recently reported. METHODS: The sandflies were collected from an urban area endemic for VL, at five collection points. The collection of samples was carried out from November 2014 to December 2015, using CDC light traps installed in intradomiciliary and peridomiciliary fashion. RESULTS: The collected sandflies (n = 297) belonged to eight species: Lutzomyia lenti, Lutzomyia longipalpis, Lutzomyia sallesi, Lutzomyia migonei, Lutzomyia walkeri, Lutzomyia capixaba, Lutzomyia carmelinoi, and Lutzomyia whitmani. Most of the specimens collected were peridomiciliary (247/297, 83%). L. lenti (154/297, 52%) was the most frequently sampled species, followed by L. longipalpis (88/297, 29.6%), and L. sallesi (42/297, 14.1%), which together accounted for over 90% of the collected sandfly specimens. CONCLUSIONS: The continued presence of L. longipalpis in urban areas, including that in intradomiciliary areas, with a predominance of females, is crucial because of the high possibility of them causing VL outbreaks, since this species is the main vector of Leishmania infantum in Brazil.

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Abstract: INTRODUCTION: Plants have been commonly used in popular medicine of most cultures for the treatment of disease. The in vitro antimicrobial activity of certain Argentine plants used in traditional medicine has been reported. The aim of this study was to investigate the antimicrobial, anti-biofilm, and anti-cell adherence activities of native plants (Larrea divaricata, Tagetes minuta, Tessaria absinthioides, Lycium chilense, and Schinus fasciculatus) collected in northwestern Argentina. METHODS: The activities of the five plant species were evaluated in Bacillus strains and clinical strains of coagulase-negative Staphylococcus isolated from northwestern Argentina and identified by 16S rDNA. RESULT: Lycium chilense and Schinus fasciculatus were the most effective antimicrobial plant extracts (15.62µg/ml and 62.50µg/ml for Staphylococcus sp. Mcr1 and Bacillus sp. Mcn4, respectively). The highest (66%) anti-biofilm activity against Bacillus sp. Mcn4 was observed with T. absinthioides and L. divaricate extracts. The highest (68%) anti-biofilm activity against Staphylococcus sp. Mcr1 was observed with L. chilense extract. T. minuta, T. absinthioides, and L. divaricata showed percentages of anti-biofilm activity of between 55% and 62%. The anti-adherence effects of T. minuta and L. chilense observed in Bacillus sp. Mcn4 reflected a difference of only 22% and 10%, respectively, between anti-adherence and biofilm inhibition. Thus, the inhibition of biofilm could be related to cell adherence. In Staphylococcus sp. Mcr1, all plant extracts produced low anti-adherence percentages. CONCLUSION: These five species may represent a source of alternative drugs derived from plant extracts, based on ethnobotanical knowledge from northwest Argentina.

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Abstract: INTRODUCTION: Chagas disease currently affects 5.7 million people in Latin America and is emerging in non-endemic countries. There is no consensus concerning the efficacy of trypanocidal therapy for patients with the chronic form of the disease. We evaluated cardiac function and sociodemographic, clinical, and serologic characteristics of a group of asymptomatic Trypanosoma cruzi-seropositive former blood donors, and compared the effects of benznidazole treatment applied for different lengths of time. METHODS: Blood donors who screened positive for T. cruzi between 1998 and 2002 were recruited 10 years later for follow-up (n = 244); 46 individuals had received treatment. Three subjects had terminated treatment prematurely. The remaining 43 individuals were divided into two groups: individuals who had received benznidazole therapy for 50-60 days (n = 28; BT ≤60 group) or more than 60 days (n = 15; BT >60). Serologic assays, biochemical tests, electrocardiographic, echocardiographic, and clinical examinations were performed on all participants. Parasite loads were determined by qualitative and quantitative polymerase chain reaction. RESULTS: Parasitemia was significantly reduced in the BT ≤60 and BT >60 groups compared with the untreated group. There were no differences in epidemiologic profiles or clinical, biochemical, electrocardiographic, or echocardiographic data between any of the groups. CONCLUSIONS: Despite elimination or significant reduction in parasitemia in patients with chronic Chagas disease who received benznidazole, there was no clinical difference between those who were treated for >60 days and those treated for a shorter duration. Furthermore, the adverse effects of benznidazole appear to be less severe than previous reports would suggest.

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Abstract INTRODUCTION: Geographical, epidemiological, and environmental differences associated with therapeutic response to Chagas etiological treatment have been previously discussed. This study describes high seroconversion rates 72 months after benznidazole treatment in patients under 16 years from a project implemented by Doctors without Borders in Guatemala. METHODS: An enzyme-linked immunosorbent assay was used to detect Trypanosoma cruzi IgG antibodies in capillary blood samples from patients 72 months after treatment. Fisher's exact test was used to establish association between characteristics, such as sex, age, and origin of patients, and final seroconversion. Kappa index determined concordance between laboratory tests. The level of significance was set to 5%. RESULTS: Ninety-eight patients, aged 6 months to 16 years, were available for follow-up. Sex and origin were not associated with seroconversion. Individuals older than 13 were more prone to maintain a positive result 72 months after treatment, although results were not highly significant. Laboratory tests presented elevated Kappa concordance (95% CI) = 0.8290 (0.4955-1), as well as high (97%) seroconversion rates. CONCLUSIONS: The high seroconversion rate found in this study emphasizes the importance of access to diagnosis, treatment, and follow-up of individuals affected by Chagas disease. Moreover, it contradicts the idea that it is not possible to achieve a cure with the currently available drugs. This study strongly supports expanding programs for patients infected with T. cruzi in endemic and non-endemic countries.

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Abstract INTRODUCTION Early identification of patients at higher risk of progressing to severe disease and death is crucial for implementing therapeutic and preventive measures; this could reduce the morbidity and mortality from kala-azar. We describe a score set composed of four scales in addition to software for quick assessment of the probability of death from kala-azar at the point of care. METHODS: Data from 883 patients diagnosed between September 2005 and August 2008 were used to derive the score set, and data from 1,031 patients diagnosed between September 2008 and November 2013 were used to validate the models. Stepwise logistic regression analyses were used to derive the optimal multivariate prediction models. Model performance was assessed by its discriminatory accuracy. A computational specialist system (Kala-Cal(r)) was developed to speed up the calculation of the probability of death based on clinical scores. RESULTS: The clinical prediction score showed high discrimination (area under the curve [AUC] 0.90) for distinguishing death from survival for children ≤2 years old. Performance improved after adding laboratory variables (AUC 0.93). The clinical score showed equivalent discrimination (AUC 0.89) for older children and adults, which also improved after including laboratory data (AUC 0.92). The score set also showed a high, although lower, discrimination when applied to the validation cohort. CONCLUSIONS: This score set and Kala-Cal(r) software may help identify individuals with the greatest probability of death. The associated software may speed up the calculation of the probability of death based on clinical scores and assist physicians in decision-making.

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Abstract INTRODUCTION: The occurrence of leprosy reactions, a common event during treatment, may be mostly related to the action of multidrug therapy on Mycobacterium leprae. The clinical and laboratory monitoring of patients with reactions is important, since collecting data that assists in predicting the risk of reactions may help to prevent disability. METHODS: This was a sectional study, in order to correlate clinical and laboratory diagnosis with the number of reactions during treatment. Spearman's correlation was used to verify the degree of association between the assessed variables. RESULTS: This study was conducted with 211 patients with leprosy reactions during treatment of M. leprae. The borderline tuberculoid group was the most prevalent clinical form (74/211; 35.1%) and the type one reaction showed the highest frequency (136/211; 64.5%). It was observed that 73.5% (155/211) of reactions occurred within 3 months of the initiation of multidrug therapy. The diagnostic values, including the bacterial indices (BIs) of dermal smears (r = 0.21, p < 0.05) and skin biopsies (r = 0.20; p < 0.05), showed a positive correlation with the number of reactions during treatment. CONCLUSIONS: This research showed a positive correlation between bacillary load markers and the number of leprosy reactions. This study provided scientific support to future research aiming to elucidate the influence of antigenic load on the number of leprosy reactions during treatment.

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Abstract INTRODUCTION: Mycolactones, secreted by Mycobacterium ulcerans, were previously believed to prevent super infection in Buruli ulcer lesions. However, little is known about secondary bacterial infections in these lesions. This study evaluated contaminating bacterial flora and their antibiotic susceptibility patterns in cases of previously untreated Buruli ulcer disease from three states in Southern Nigeria. METHODS A prospective analysis was conducted between January and June of 2015 using wound swabs from eligible patients with Buruli ulcer disease, confirmed by quantitative-polymerase chain reaction, with active ulcers. Microbiological analyses including isolation of bacteria, species identification of isolates, and drug susceptibility tests were performed. RESULTS Of 51 patients, 27 (52.9%) were female. One or more bacterial species of clinical importance was isolated from each patient. A total of 17 different microbial species were isolated; 76.4% were Gram-negative and 23.6% were Gram-positive isolates. The most common bacterial species detected was Staphylococcus aureus (24%), followed by Aeromonas hydrophila (13%), Pseudomonas aeruginosa (13%), and Klebsiella pneumoniae (11%). Drug susceptibility tests showed a particularly high frequency of resistance to commonly used antimicrobials in Nigeria for Staphylococcus aureus. CONCLUSIONS Super bacterial infections occur in Buruli ulcer lesions in Nigeria, and these infections are associated with high rates of resistance to commonly used antibiotics in the country.

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Abstract INTRODUCTION: We studied the potential in vitro antischistosomal activity of Cerastes cerastes venom on adult Schistosoma mansoni worms. METHODS: Live specimens of the horned viper snake, C. cerastes were collected from the Aswan Governorate (Egypt). Venom was collected from snakes by manual milking. Worms of S. mansoni were obtained from infected hamsters by perfusion and isolated from blood using phosphate buffer. Mortality rates of worms were monitored after 3 days of exposure to snake venom at LC50 and various sublethal concentrations (10, 5, 2.5µg/ml). Scanning electron microscopy was used to investigate tegumental changes in treated worms after exposure to LC50 doses of venom. RESULTS: The LC50 of C. cerastes venom was 21.5µg/ml. The effect of C. cerastes venom on Schistosoma worms varied according to their sex. The mortality rate of male and female worms after 48-h exposure was 83.3% and 50%, respectively. LC50 of C. cerastes venom induced mild to severe tegumental damage in Schistosoma worms in the form of destruction of the oral sucker, shrinkage and erosion of the tegument, and loss of some tubercle spines. CONCLUSIONS: The present study demonstrated that C. cerastes venom exerts potential in vitro antischistosomal activity in a time and dose-dependent manner. These results may warrant further investigations to develop novel schistosomicidal agents from C. cerastes snake venom.

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Abstract INTRODUCTION: Hypertriglyceridemia incidence should be estimated in HIV-infected patients after antiretroviral therapy (ART) initiation. METHODS: We retrospectively analyzed clinical data of HIV-infected adults at 3 public referral centers. Cumulative and person-time incidences were estimated for patients without hypertriglyceridemia. Survival time and hazard ratio (HR) were estimated by Kaplan-Meier analysis and Cox proportional regression, respectively. RESULTS: Cumulative and person-time incidences were 40.4% and 1.4 cases/100 person-months, respectively. The median period for hypertriglyceridemia occurrence was 47 months. Men and patients with switched ART regimens had increased hypertriglyceridemia risk (HR=3.05 and 3.34, respectively). CONCLUSIONS: Hypertriglyceridemia incidence is high in HIV-infected patients undergoing ART.

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Abstract INTRODUCTION: Despite the therapeutic benefits of drugs, adverse drug reactions (ADRs) occur. Method: We assessed a series of suspected ADRs identified from notifications and intensive monitoring of inpatients from March 2013 to March 2014. RESULTS: Skin reactions predominated (31%). Systemic anti-infective agents were implicated in 16 (72%) reactions. Fifteen (68%) ADRs were classified as possible. The implicated drug was not correctly identified by the healthcare team in 12 cases. CONCLUSIONS: Some reactions were not correctly attributed to the causative drug(s), suggesting that the use of a validated evaluation method can promote successful identification of causal links between ADRs and drugs.

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Abstract: INTRODUCTION: The aim of this study was to investigate the prevalence of Chagas disease in patients treated at a Public Oncology Service in the City of Pelotas, Southern Brazil. METHODS: This study included 200 individuals undergoing cancer treatment and involved the use of a questionnaire and venous blood collection for the detection of anti-Trypanosoma cruzi antibody. RESULTS: The study found a 5% prevalence of patient seropositivity. Significant variables are presented and discussed in the article. CONCLUSIONS: Serological T. cruzi checks are recommended in cancer patients, especially individuals from endemic areas in Brazil and other Latin American countries.

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Abstract: INTRODUCTION: The present note discusses some evidence on the increasing potential risk for American visceral leishmaniasis (AVL) transmission in the Northern Brazilian State of Amapá, the Guianan-Amazon biome. METHODS Early and present data about AVL were collected, including our recent entomological findings. RESULTS: The spread of the sand fly vector Lutzomyia longipalpis, and a sylvatic reservoir host, the crab-eating fox Cerdocyon thous in that region represents important findings related to the epidemiology of AVL in the Guianan-Amazon biome. CONCLUSIONS: These observations suggest that Brazilian authorities need to develop surveillance strategies in these risk areas.

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Abstract INTRODUCTION: Intralesional treatment for cutaneous leishmaniasis has been applied for over 30 years at the Oswaldo Cruz Foundation, Rio de Janeiro, with good therapeutic results and without relevant systemic toxicity. METHODS Meglumine antimoniate was injected subcutaneously, using a long medium-caliber needle (for example, 30mm × 0.8mm); patients received 1-3 injections, with 15-day intervals. RESULTS The technique is described in detail sufficient to enable replication. CONCLUSIONS: The treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate is a simple, effective, and safe technique, which may be used in basic healthcare settings.

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Abstract: INTRODUCTION: The incidence of Hansen's disease is high in overlooked populations. METHODS: Data of Hansen's disease cases reported in the information system of the Department of Informatics, Brazilian Unified Health System, from 2013 to 2014 were analyzed. RESULTS: Among 434 studied cases of Hansen's disease, the female sex (52.5%), adult age (73.7%), low educational level (61.8%), and multibacillary form were associated with higher prevalence rates. CONCLUSIONS: Hansen's disease is more frequent among female adults with a low educational level, and the prevalence of multibacillary leprosy reflects disease detection at late stages.

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Abstract INTRODUCTION: We evaluated the associations between interleukin-10 (IL-10) gene polymorphisms -G1082A/-C819T/-C592A and periportal fibrosis regression after specific treatment for schistosomiasis. METHODS: This retrospective cohort study involved 125 Brazilian patients infected with Schistosomiasis mansoni, who were followed up for 2 years after specific treatment to estimate the probability of periportal fibrosis regression. RESULTS: There was no evidence of associations between IL-10 polymorphisms and periportal fibrosis regression after treatment. CONCLUSIONS: There was no evidence of associations between gene promoter polymorphisms of IL-10 and the regression of periportal fibrosis in this Brazilian population.

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Abstract: INTRODUCTION This retrospective study shows the profile of arachnidism, ophidism, and scorpionism in the Ouro Preto Municipality, Brazil, from January 2007 to December 2013. METHODS The data were gathered from forms of the Epidemiological Surveillance Sector of the town's Health's Municipal Secretary. RESULTS Of the 412 envenomations, 308 were caused by spiders, 78 by scorpions, and 26 by snakes. The highest number of incidents involved people aged 20-34 years. Females were more affected than males. There were no reports of death. CONCLUSIONS The results show that envenomations caused by spiders, scorpions and snakes have decreased in recent years.

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Abstract: Chikungunya virus (CHIKV) is a mosquito-borne arthritogenic alphavirus that has recently been introduced to Brazil. We report the case of a 36-year-old male patient from the City of Rio de Janeiro who developed molecularly-confirmed CHIKV disease and whose clinical picture was remarkable because of acute arthritis of an interphalangeal joint that had been damaged by trauma 8 years previously. This case illustrates that acute CHIKV disease may preferentially target previously damaged joints. Careful study of individual cases may provide valuable information on the presentation and management of this emerging zoonosis in Brazil.

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Abstract Candida arthritis is an unusual manifestation that usually affects the knees. A 35-year-old man presented with a 2-month history of pain and swelling in the right knee. Swelling persisted after anti-inflammatory treatment. Peripheric spondyloarthritis was considered, but methotrexate, sulfasalazine, and methylprednisolone did not reduce the swelling. Direct examination of synovial fluid and a culture were positive for Candida albicans. Intravenous and intra-articular amphotericin-B were administered. The arthritis regressed and a culture and direct staining showed negative results. Candida arthritis should be considered in patients with arthritis that is resistant to treatment and prolonged, even if risk factors are absent.

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Abstract A 2-year-old Brazilian female child from the countryside in Bahia State presented with pain in the right flank of the abdomen, accompanied by a daily fever for about 2 weeks before admission. A large mass in the abdomen was resected by the surgical team. The biopsies revealed the mass was an intra-abdominal mucormycosis. However, the diagnosis was late, and despite treatment (amphotericin B) initiation, the patient eventually died.

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Abstract: Dermatitis caused by bombardier beetles is rarely reported. Here, we report a case of beetle-caused dermatitis that occurred in Pará State, the Brazilian Amazon. A female patient while putting on her shoes, felt a burning pain in the right hallux and noticed a beetle inside the shoe. During medical consultation, the physician observed that the injury site was brown and discolored. The patient complained of localized burning pain and blurred vision. The beetle responsible for the injury was identified as Pheropsophus sp. Administered treatment included cleaning with saline, analgesics, and topical hydrocortisone acetate and the patient was discharged without complaints.