Effect of adherence to primaquine on the risk of Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

BACKGROUND: Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of P. vivax recurrence. METHODS: Efficacy studies of patients with uncomplicated P. vivax malaria, including a treatment arm with daily primaquine, published between January 1999 and March 2020 were identified. Individual patient data from eligible studies were pooled using standardized methodology. Adherence to primaquine was inferred from i) the percentage of supervised doses and ii) the total mg/kg dose received compared to the target total mg/kg dose per protocol. The effect of adherence to primaquine on the incidence of P. vivax recurrence between days 7 and 90 was investigated by Cox regression analysis. RESULTS: Of 82 eligible studies, 32 were available including 6917 patients from 18 countries. For adherence assessed by percentage of supervised primaquine, 2790 patients (40.3%) had poor adherence (≤ 50%) and 4127 (59.7%) had complete adherence. The risk of recurrence by day 90 was 14.0% [95% confidence interval: 12.1-16.1] in patients with poor adherence compared to 5.8% [5.0-6.7] following full adherence; p = 0.014. After controlling for age, sex, baseline parasitaemia, and total primaquine dose per protocol, the rate of the first recurrence was higher following poor adherence compared to patients with full adherence (adjusted hazard ratio (AHR) = 2.3 [1.8-2.9]). When adherence was quantified by total mg/kg dose received among 3706 patients, 347 (9.4%) had poor adherence, 88 (2.4%) had moderate adherence, and 3271 (88.2%) had complete adherence to treatment. The risks of recurrence by day 90 were 8.2% [4.3-15.2] in patients with poor adherence and 4.9% [4.1-5.8] in patients with full adherence; p < 0.001. CONCLUSION: Reduced adherence, including less supervision, increases the risk of vivax recurrence.

Evaluation of the effect of supervised anti-malarial treatment on recurrences of Plasmodium vivax malaria.

BACKGROUND: Relapses in vivax malaria have posed great challenges for malaria control, and they also account for a great proportion of reported cases. Knowing the real effectiveness of a 7-day primaquine (PQ) scheme is crucial in order to evaluate not only the cost-effectiveness of implementing new anti-hypnozoite drugs, but also how health education strategies can guarantee better compliance and be reinforced. This study aimed to evaluate the effect of daily treatment with chloroquine and PQ supervised by health workers versus prescription without supervision. METHODS: The outcome was the passive detection of new positive thick blood smears up to 180 days, based on the official data records from the National Malaria Control Programme. The recurrences seen in the real life were, therefore, used as a surrogate for true relapses. RESULTS: Patients under supervised treatment had a lower risk of recurrence up to day 180 when compared to the unsupervised treatment (17.9% vs. 36.1%; p = 0.027). CONCLUSIONS: The lack of supervision in the non-supervised group (which followed standard of care in the real life) enabled proper comparison, as consent itself would have lead to greater compliance in this group. Future studies should scale such an analysis to different settings in the Brazilian Amazon.

Misperceptions of patients and health workers regarding malaria elimination in the Brazilian Amazon: a qualitative study.

BACKGROUND: Brazil has considerably reduced the number of cases of malaria in recent years and aims to eradicate the disease completely, however, vivax malaria continues to be a major challenge for the health system. In this context, the key to building a successful elimination programme may lie in the knowledge and the perceptions of the health agents, the patients affected by the disease and the personnel responsible for malaria diagnosis, treatment and control at the local level. METHODS: A qualitative study was undertaken in Manaus, capital of the state of Amazonas, Western Brazilian Amazon, using a sample of 33 patients who were being treated for malaria and 22 health agents who were working in malaria diagnosis, treatment and control at the local level. A semi-structured interview with a further thematic analysis was performed. RESULTS: There are still many myths regarding malaria transmission and treatment that may hinder the sensitization of the population of this region in relation to the use of current control tools and elimination strategies, such as mass drug administration (MDA). Most health professionals reported that the abandonment of treatment for malaria by the patient is related to poor social conditions, the high incidence of alcoholism and the low level of schooling of the affected population. One negative perception, observed in both groups with regard to the use of insecticide-treated nets, is that they may cause skin irritations and allergies. Most patients and health professionals have described malaria as an impossible disease to eliminate because it is intrinsically associated with forest landscapes, and according to them, elimination would only be possible if there were a vaccine against malaria. CONCLUSION: In the Amazon, cultural perceptions about the etiology of this disease can influence the behaviour and practices that social groups adopt in relation to the different forms of living in a malaria-endemic context. Negative perceptions about malaria elimination can act as a barrier when trying to reach proper coverage for control strategies such as mosquito nets and MDA.

Photobiomodulation Therapy to Treat Snakebites Caused by Bothrops atrox: A Randomized Clinical Trial.

Importance: Bothrops venom acts almost immediately at the bite site and causes tissue damage. Objective: To investigate the feasibility and explore the safety and efficacy of low-level laser therapy (LLLT) in reducing the local manifestations of B atrox envenomations. Design, Setting, and Participants: This was a double-blind randomized clinical trial conducted at Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, in Manaus, Brazil. A total of 60 adult participants were included from November 2020 to March 2022, with 30 in each group. Baseline characteristics on admission were similarly distributed between groups. Data analysis was performed from August to December 2022. Intervention: The intervention group received LLLT combined with regular antivenom treatment. The laser used was a gallium arsenide laser with 4 infrared laser emitters and 4 red laser emitters, 4 J/cm2 for 40 seconds at each application point. Main Outcomes and Measures: Feasibility was assessed by eligibility, recruitment, and retention rates; protocol fidelity; and patients' acceptability. The primary efficacy outcome of this study was myolysis estimated by the value of creatine kinase (U/L) on the third day of follow-up. Secondary efficacy outcomes were (1) pain intensity, (2) circumference measurement ratio, (3) extent of edema, (4) difference between the bite site temperature and that of the contralateral limb, (5) need for the use of analgesics, (6) frequency of secondary infections, and (7) necrosis. These outcomes were measured 48 hours after admission. Disability assessment was carried out from 4 to 6 months after patients' discharge. P values for outcomes were adjusted with Bonferroni correction. Results: A total of 60 patients (mean [SD] age, 43.2 [15.3] years; 8 female individuals [13%] and 52 male individuals [87%]) were included. The study was feasible, and patient retention and acceptability were high. Creatine kinase was significantly lower in the LLLT group (mean [SD], 163.7 [160.0] U/L) 48 hours after admission in relation to the comparator (412.4 [441.3] U/L) (P = .03). Mean (SD) pain intensity (2.9 [2.7] vs 5.0 [2.4]; P = .004), circumference measurement ratio (6.6% [6.6%] vs 17.1% [11.6%]; P < .001), and edema extent (25.8 [15.0] vs 40.1 [22.7] cm; P = .002) were significantly lower in the LLLT group in relation to the comparator. No difference was observed between the groups regarding the mean difference between the bite site temperature and the contralateral limb. Secondary infections, necrosis, disability outcomes, and the frequency of need for analgesics were similar in both groups. No adverse event was observed. Conclusions and Relevance: The data from this randomized clinical trial suggest that the use of LLLT was feasible and safe in a hospital setting and effective in reducing muscle damage and the local inflammatory process caused by B atrox envenomations. Trial Registration: Brazilian Registry of Clinical Trials Identifier: RBR-4qw4vf.

Providing Antivenom Treatment Access to All Brazilian Amazon Indigenous Areas: 'Every Life Has Equal Value'.

Snakebites are more frequent in the Brazilian Amazon than in other parts of Brazil, representing a high cost for the health system since antivenoms are only available through medical prescription from central municipal hospitals in most cases. The need for a cold chain and physicians usually restricts access to the only effective treatment of a snakebite, the antivenom. The complex topography of the rivers contributes to delays in treatment, and consequently increases the risk of severe complications, chronic sequelae and death. Thus, decentralization of antivenom treatment to primary healthcare facilities in the interior would increase access by indigenous population groups to proper healthcare. To standardize and evaluate the decentralization to low complexity indigenous healthcare units, we suggest the (i) development and validation of standardized operational procedures, (ii) training of professionals in the validated protocol in a referral health unit, (iii) implementation of the protocol in an indigenous healthcare unit, (iv) assessment of perceptions towards and acceptability of the protocol, and (v) estimation of the impact of the protocol's implementation. We expect that antivenom decentralization would shorten the time between diagnosis and treatment and, as such, improve the prognosis of snakebites. As health cosmology among indigenous populations has an important role in maintaining their way of life, the introduction of a new therapeutic strategy to their customs must take into account the beliefs of these peoples. Thus, antivenom administration would be inserted as a crucial therapeutic tool in a world of diverse social, natural and supernatural representations. The information presented here also serves as a basis to advocate for support and promotion of health policy initiatives focused on evidence-based care in snakebite management.

History and perspectives on how to ensure antivenom accessibility in the most remote areas in Brazil.

A plan to achieve self-sufficiency in manufacturing biologicals for public health has been structured for the last 40 years in Brazil, in the context of a reform in the health system. Industrial plants of the national public laboratories have been modernized, and a program for reducing morbidity and mortality of venomous snakebite has been created, as part of the National Epidemiological Surveillance System. The epidemiological data are essential to plan for the antivenom production of 400,000 vials of snake antivenoms per year, and the acquisition by the Ministry of Health, which is the exclusive purchaser in the country. Distribution is decentralized to reach hospitals in almost 3000 municipalities, and to provide free of charge antivenom treatment. The National Sanitary Surveillance Agency organized the regulatory environment to implement rules and supervise compliance of GMP procedures, elevating the quality of the biologicals that are produced, as well as reducing the costs in production. Despite all the advances in the health system, antivenom availability and accessibility is not uniform in regards to the most vulnerable parts of the populations, which inhabit remote areas in the Brazilian Amazon region. Better logistics and transportation of liquid form antivenoms is an issue to be addressed and realistic and comprehensive health programs for indigenous groups should be effectively structured, in order to reduce the high morbidity and mortality rates associated with snakebite envenoming.

River dataset as a potential fluvial transportation network for healthcare access in the amazon region

Remote areas, such as the Amazon Forest, face unique geographical challenges of transportation-based access to health services. As transportation to healthcare in most of the Amazon Forest is only possible by rivers routes, any travel time and travel distance estimation is limited by the lack of data sources containing rivers as potential transportation routes. Therefore, we developed an approach to convert the geographical representation of roads and rivers in the Amazon into a combined, interoperable, and reusable dataset. To build the dataset, we processed and combined data from three data sources: OpenStreetMap, HydroSHEDS, and GloRiC. The resulting dataset can consider distance metrics using the combination of streets and rivers as a transportation route network for the Amazon Forest. The created dataset followed the guidelines and attributes defined by OpenStreetMap to leverage its reusability and interoperability possibilities. This new data source can be used by policymakers, health authorities, and researchers to perform time-to-care analysis in the International Amazon region.

Stepping into a dangerous quagmire: Macroecological determinants of Bothrops envenomings, Brazilian Amazon.

Despite significant and successful efforts in Brazil regarding snakebites in the areas of research, antivenom manufacture and quality control, training of health professionals in the diagnosis and clinical management of bites, little is known about determinants of snakebites incidence in order to further plan interventions to reduce the impact of this medical condition. Understanding the complexity of ecological interactions in a geographical region is important for prediction, prevention and control measures of snakebites. This investigation aims to describe spatial distribution and identify environmental determinants of human envenoming by lancehead pit vipers (Bothrops genus), in the Brazilian Amazon. Aggregated data by the municipality was used to analyze the spatial distribution of Bothrops bites cases and its relationship with geographic and environmental factors. Eight geo-environmental factors were included in the analysis as independent variables: (1) tree canopy loss increase; (2) area with vegetation cover; (3) area covered by water bodies; (4) altitude; (5) precipitation; (6) air relative humidity; (7) soil moisture; and (8) air temperature. Human envenoming by lancehead pit vipers (Bothrops genus) in the Amazon region is more incident in lowlands [Adjusted regression coefficient [ARC] -0.0007 (IC95%: -0.001; -0.0006), p<0.0001], with high preserved original vegetation cover [ARC 0.0065 (IC95%: 0.0071; 0.0060), p<0.0001], with heaviest rainfall [ARC 0.0001 (IC95%: 0.00009; 0.0001), p<0.0001] and higher air relative humidity [ARC 0.0082 (IC95%: 0.0108; 0.0056), p<0.0001]. This association is interpreted as the result of the higher prey availability and further abundance of pit vipers in such landscapes.

[Evaluation of sandfly control measures in northern Paraná State, Brazil]. / Avaliação de medidas de controle de flebotomíneos no norte do Estado do Paraná, Brasil.

Sandfly captures from April 2001-September 2002 were compared to those from October 1996-September 1997 and October 1998-April 2000 in order to evaluate control procedures conducted in Recanto Marista in the county of Doutor Camargo, Paraná State, Brazil. Sandflies were captured with Falcão traps twice a month, both in the domiciles and henhouses, from 10 PM to 2 AM. In 2001-2002, 199,821 sandflies were captured, with an hourly average of 1,625.5 insects; average captures in 1996-1997 and 1997-1998 were 1,641.9 and 806.7, respectively. Nyssomyia neivai was the most abundant species (90.4%) in all habitats. This species, together N. whitmani, Migonemyia migonei, and Pintomyia fischeri, accounted for 99.9% of all the specimens captured. The total hourly average sandfly captures increased, but 85% of these insects were captured in henhouses built with the purpose of attracting sandfly specimens, while the density decreased in other environments, especially intradomiciliary.

Epidemiological and clinical aspects of snakebites in the upper Juruá River region, western Brazilian Amazonia / Aspectos clínicos e epidemiológicos de acidentes ofídicos na região do Alto Juruá, oeste da Amazônia brasileira

This study addresses the clinical and epidemiological aspects of envenoming cases resulting from snakebites treated at a hospital in Cruzeiro do Sul, in the upper Juruá River region, western Brazilian Amazonia. The specific identity of snakes that caused the envenomings was inferred (a) from the diagnosis of patient symptoms and signs upon hospital admission, (b) by enzyme immunoassay for detection of Bothrops atrox and Lachesis muta venom from serum samples taken from patients before antivenom therapy, or (c) by direct identification of the snake, when it was brought along to the hospital or photographed. There were 133 snakebites (76.2 cases per 100,000 inhabitants) registered during one year (July 2017 to June 2018). Most snakebites (88.7%) were caused by Bothrops spp., and the rest by non-venomous snakes or dry bites. Snakebites tended to occur more often during the rainy season, coinciding with the period of greater reproductive activity of the snakes and greater availability of their prey. In addition, the increase in the water level of rivers and lakes during the rainy season tends to concentrate snakes in dry places and, thus, to increase encounters with humans. Information campaigns on prevention and first aid, specially among the most vulnerable groups (indigenous people, farmers, and children and teenagers in rural areas), and the importance of using protective equipment (boots, leggings, leather gloves) in certain high risk activities (e.g. agriculture and extractivism in forests) are fundamental for the reduction of snakebite morbidity

Bee sting envenomation severe cases in Manaus, Brazilian Amazon: clinical characteristics and immune markers of case reports

Abstract Bee venom is a natural toxin composed of several peptides. Massive envenoming causes severe local and systemic reactions. We report two cases of severe bee envenomation, of which one was fatal. We also describe clinical characteristics and immune markers. Both victims suffered from respiratory distress, renal failure, rhabdomyolysis, and shock. They required invasive mechanical ventilation, vasoactive drugs, and renal replacement therapy. Moreover, serum levels of chemokines, cytokines, and cell-free circulating nucleic acids demonstrated an intense inflammatory process. Massive envenoming produced systemic injury in the victims, with an uncontrolled inflammatory response, and a more significant chemotactic response in the fatal case.

A painful journey to antivenom: the therapeutic itinerary of snakebite patients in the Brazilian Amazon

Access to antivenoms is not guarranteed for vulnerable populations that inhabit remote areas in the Amazon. The study of therapeutic itineraries (TI) for treatment of snakebites would support strategies to provide timely access to users. A TI is the set of processes by which individuals adhere to certain forms of treatment, and includes the path traveled in the search for healthcare, and practices to solve their health problems. This study aims to describe TIs of snakebite patients in the Brazilian Amazon. This study was carried out at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, in Manaus, state of Amazonas, Brazil. The itinerary from the moment of the bite to the patient’s admission to the reference unit was analyzed. Sample size was defined by saturation. After an exploratory survey to collect epidemiological variables, in-depth interviews were conducted following a semi-structured guide. Patients originated from rural areas of 11 different municipalities, including ones located >500 kilometers from Manaus. A great fragmentation was observed in the itineraries, marked by several changes of means of transport along the route. Four themes emerged from the analysis: exposure to snakebite during day-to-day activities, use of traditional therapeutic practices, and personal perception of the severity, as well as the route taken and its contingencies. Access to healthcare requires considerable effort on the part of snakebite patients. Major barriers were identified, such as the low number of hospitals that offer antivenom treatment, poor access to healthcare due to long distances and geographic barriers, low acceptability of healthcare offered in countryside, lack of use of personal protective equipment, common use of ineffective or deleterious self-care practices, late recognition of serious clinical signs and resistance to seeking medical assistance. Health education, promotion of immediate transport to health centers and decentralization of antivenom from reference hospitals to community healthcare centers in the Brazilian Amazon are more effective strategies that would to maximize access to antivenom treatment.

Scorpion envenoming caused by Tityus cf. silvestris evolving with severe muscle spasms in the Brazilian Amazon.

Scorpion stings are a public health problem in the Brazilian Amazon. However, detailed clinical characterization with the proper animal identification is scarce. Here we report a confirmed case of envenoming by Tityus cf. silvestris in the Brazilian Amazon. The case evolved with generalized muscle spasms and was treated with antivenom and supportive therapy, requiring intensive care unit admission. The patient evolved favourably and was discharged after 9 days of hospitalization.

Bothrops bilineatus: an arboreal pitviper in the Amazon and Atlantic forest / Bothrops bilineatus: uma víbora arbórea na Amazônia e na Mata Atlântica

The two-striped forest-pitviper (Bothrops bilineatus) is an arboreal snake that is currently represented by two subspecies (B. b. bilineatus and B. b. smaragdinus) that comprise a species complex, and its distribution is in the Amazon and the Atlantic Forest. The rarity of encounters with this snake is reflected in the low occurrence of cases of snakebites throughout its geographic distribution and the resulting low number of published clinical reports. However, in some areas, B. bilineatus proves to be more frequent and causes envenomations in a greater proportion. Herein, we review the main aspects of the species complex B. bilineatus, including its biology, ecology, taxonomy, morphology, genetic and molecular studies, geographic distribution, conservation status, venom, pathophysiology and clinical aspects, and epidemiology. In addition, the different antivenoms available for the treatment of envenomations caused by B. bilineatus are presented along with suggestions for future studies that are needed for a better understanding of the snakebites caused by this snake.

The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox)

Snake venoms are complex mixtures of proteins with toxic activities, with many distinct isoforms, affecting different physiological targets, comprised in a few protein families. It is currently accepted that this diversity in venom composition is an adaptive advantage for venom efficacy on a wide range of prey. However, on the other side, variability on isoforms expression has implications in the clinics of human victims of snakebites and in the efficacy of antivenoms. B. atrox snakes are responsible for most of the human accidents in Brazilian Amazon and the type and abundance of protein families on their venoms present individual variability. Thus, in this study we attempted to correlate the individual venom proteome of the snake brought to the hospital by the patient seeking for medical assistance with the clinical signs observed in the same patient. Individual variability was confirmed in venoms of the 14 snakes selected for the study. The abundance of each protein family was quite similar among the venom samples, while the isoforms composition was highly variable. Considering the protein families, the SVMP group presented the best correlation with bleeding disorders and edema. Considering individual isoforms, some isoforms of venom metalloproteinase (SVMP), C-type lectin-like toxins (CTL) and snake venom serine proteinases (SVSP) presented expression levels that with statistically significant positive correlation to signs and symptoms presented by the patients as bleeding disorders, edema, ecchymosis and blister formation. However, some unexpected data were also observed as the correlation between a CTL, CRISP or LAAO isoforms with blister formation, still to be confirmed with a larger number of samples. Although this is still a small number of patient samples, we were able to indicate that venom composition modulates clinical manifestations of snakebites, to confirm at the bedside the prominent role of SVMPs and to include new possible toxin candidates for the development of toxin inhibitors or to improve antivenom selectiveness, important actions for the next generation treatments of snakebites.

Bothrops atrox, the most important snake involved in human envenomings in the amazon: how venomics contributes to the knowledge of snake biology and clinical toxinology

Bothrops atrox snakes are mostly endemic of the Amazon rainforest and is certainly the South American pit viper responsible for most of the snakebites in the region. The composition of B. atrox venom is significantly known and has been used to trace the relevance of the venom phenotype for snake biology and for the impacts in the clinics of human patients involved in accidents by B. atrox. However, in spite of the wide distribution and the great medical relevance of B. atrox snakes, B. atrox taxonomy is not fully resolved and the impacts of the lack of taxonomic resolution on the studies focused on venom or envenoming are currently unknown. B. atrox venom presents different degrees of compositional variability and is generally coagulotoxic, inducing systemic hematological disturbances and local tissue damage in snakebite patients. Antivenoms are the effective therapy for attenuating the clinical signs. This review brings a comprehensive discussion of the literature concerning B. atrox snakes encompassing from snake taxonomy, diet and venom composition, towards clinical aspects of snakebite patients and efficacy of the antivenoms. This discussion is highly supported by the contributions that venomics and antivenomics added for the advancement of knowledge of B. atrox snakes, their venoms and the treatment of accidents they evoke

"Bad things come in small packages": predicting venom-induced coagulopathy in Bothrops atrox bites using snake ontogenetic parameters

Introduction: Snake venom composition shows significant inter- and intra-species variation. In the case of the viperid species Bothrops atrox, responsible for the majority of snakebites in the Amazon region, geographical and ontogenetic variables affect venom composition, with ecological and medical implications. Previous studies had shown that venom from neonate and juvenile Bothrops specimens have a higher in vitro coagulant activity. The aim of this investigation was to assess the association of clinical outcomes, such as venom-induced coagulopathy and local complications, with B. atrox ontogenetic variables. Methods: This study explored the relationship between some clinical parameters in patients suffering envenomations by B. atrox in the Amazon and several morphometric parameters of the snake specimens causing the bites.Results: There were 248 specimens confirmed as agents of envenomation, mostly female snakes (70.5%) and classified as juveniles (62.7%). Patients bitten by neonates compared to adult snakes [OR=2.70 (95%CI 1.15-6.37); p=.021] and by snakes with white tail tip [OR=1.98 (95%CI 1.15–3.41); p=.013] were more likely to develop coagulopathy. Time from patient admission to the unclottable blood reversion was not affected by the snake gender (p=.214) or age (p=.254). Patients bitten by neonate (p=.024) or juvenile snakes (p<.0001) presented a lower frequency of moderate to severe edema, as compared to those bitten by adult snakes. In agreement with experimental observations, patients bitten by neonates and by snakes with a white tail tip were more likely to develop coagulopathy than those bitten by adult snakes. In contrast, envenomations by adult snakes were associated with a higher incidence of severe local edema. Conclusion: Despite these variations, no difference was observed in the time needed to recover blood clotting in these patients after Bothrops antivenom administration.

Bothrops snakebites in the Amazon: recovery from hemostatic disorders after Brazilian antivenom therapy

Introduction: Bothrops atrox snakebites are a major public health problem in the Amazon region and also cause hemostatic disorders. In this study, we assessed the recovery from hemostatic disorders in Bothrops snakebite patients after being given antivenom therapy. Methods: This is a prospective study of Bothrops snakebite patients (n=100) treated at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazilian Amazon, between January 2016 and December 2017. Blood samples were taken for the measurement of venom concentrations, platelets, clotting time and factors of patients on admission, 12, 24 and 48h after antivenom therapy, and taken again on discharge. The presence of systemic bleeding was recorded during the follow-up. Results: On admission, systemic bleeding was observed in 14% of the patients. Thrombocytopenia was noted in 10% of the patients. A total of 54% of the patients presented unclottable blood with low levels of fibrinogen and alpha 2-antiplasmin, and high levels of fibrin/fibrinogen degradation product (FDP) and D-dimers. Unclottable blood and systemic bleeding were overcome in most patients 12h after the antivenom therapy. Three patients developed systemic bleeding 48h after antivenom therapy. Levels of fibrinogen and alpha 2-antiplasmin, FDP and D-dimer returned to normal around 48h after the treatment or on discharge. The frequency of thrombocytopenia with high mean platelet volume increased in the first 24h after antivenom therapy, and decreased on discharge. Bothrops venom levels in patients decreased 12h after antivenom therapy and were not correlated with coagulation and fibrinolytic parameters. There were no deaths. Conclusion: Laboratorial parameters of coagulopathy returned to normal values within 48h after the antivenom therapy until discharge. A few patients still presented bleeding signs within 48h after beginning antivenom therapy. However, the Brazilian antivenom was able to overcome the hemostatic disorders in these cases of envenomation.

Unsatisfactory long-term virological suppression in human immunodeficiency virus-infected children in the Amazonas State, Brazil

Abstract INTRODUCTION: Achieving viral suppression (VS) in children is challenging despite the exponential increase in access to antiretroviral therapy (ART). We evaluated VS in children >1 year of age and adolescents 5 years after they had begun ART, in Manaus, Amazonas state, Brazil. METHODS: HIV-infected, ART-naive children >1 year of age between 1999 and 2016 were eligible. Analysis was stratified by age at ART initiation: 1-5 y, >5-10 y, and >10-19 y. CD4+ T-cell count and viral load were assessed on arrival at the clinic, on ART initiation, and at 6 months, 1 year, 2 years, and 5 years after ART initiation. The primary outcome was a viral load <50 copies/mL 5 years after ART initiation. RESULTS: Ultimately, 121 patients were included. The mean age at diagnosis was 4.8 years (SD 3.5), mean CD4% was 17.9 (SD 9.8), and mean viral load was 4.6 log10 copies/ml (SD 0.8). Five years after ART initiation, the overall VS rate was 46.9%. VS by patient age group was as follows: 36.6% for 1-5 y, 53.3% for >5-10 y, and 30% for >10-19 y. Almost all children (90,4%) showed an increase in CD4%+ T cell count. There were no statistically significant predictors for detecting children who do not achieve VS with treatment. VS remained below 65% in all the evaluated periods. CONCLUSIONS: Considerable immunological improvement is seen in children after ART initiation. Further efforts are needed to maintain adequate long-term VS levels and improve the survival of this vulnerable population.

Snakebites in Rio Branco and surrounding region, Acre, Western Brazilian Amazon

Abstract INTRODUCTION Snakebites are considered a neglected tropical disease in many countries in Latin America, including Brazil. As few studies have assessed snakebites in the Amazon region and especially in the state of Acre, epidemiological studies are of great importance. The present study aimed to describe the epidemiological characteristics of snakebites in the Rio Branco region, observing their characteristics in rural and urban areas and their correlation with rainfall and river outflow. METHODS This retrospective, descriptive study analyzed epidemiological information obtained from snakebite notifications registered on the Information System for Notifiable Diseases that occurred from March, 2018 to February, 2019. The cases of snakebite were correlated with rainfall and flow. RESULTS A total of 165 cases of snakebite were registered in the period. Most cases were caused by Bothrops and affected mainly individuals of the male sex who were between 21 and 30 years old. Most of the snakebites occurred in Rio Branco (71.52%; 29 cases per 100,000 inhabitants). Of these, 60.2% occurred in the urban area and 39.8% in the rural area and the majority occurred during the rainy season. CONCLUSIONS Although studies have shown that a majority of cases occur in rural areas, in this study, urbanization of snakebites was observed. The Bothrops genus was responsible for the highest number of snakebites and, during the rainy season, bites occurred more frequently. Educational prevention campaigns, population advice, and first aid in case of snakebites for the population are thus suggested.