Effect of fluralaner on the biology, survival, and reproductive fitness of the neotropical malaria vector Anopheles aquasalis.

BACKGROUND: Reducing mosquito abundance or interfering with its ability to support the parasite cycle can help to interrupt malaria in areas of significant risk of malaria transmission. Fluralaner is a safe and effective drug for veterinary use indicated for the treatment against fleas and ticks which acts as an antagonist of chloride ion channels mediated by γ-aminobutyric acid (GABA), preventing the entry of these ions into the postsynaptic neuron, leading to hyperexcitability of the postsynaptic neuron of the central nervous system of arthropods. Fluralaner demonstrated insecticidal activity against different insect species. METHODS: The study aimed to evaluate the effects of fluralaner on the biology, survival, and reproductive fitness of Anopheles aquasalis. The following lethal concentrations (LC) were determined for An. aquasalis: LC5 = 0.511 µM; LC25 = 1.625 µM; LC50 = 3.237 µM. RESULTS: A significant decrease (P < 0.001) was evident in the number of eggs, larvae, and pupae in the group exposed to a sublethal dose of fluralaner when compared to a control group (without the drug). Using blood from dogs after administration of fluralaner, it was observed that the drug causes 100% mortality in An. aquasalis in less than 24 h after feeding; this effect remains even after 90 days in all samples. DISCUSSION: Fluralaner showed the same result for up to 60 days, and after that, there was a slight reduction in its effect, evidenced by a decrease in the percentage of dead females; however, still significant when compared to the control group. CONCLUSION: Fluralaner affects the biology and reduction of survival in An. aquasalis in a lasting and prolonged period, and its fecundity with lower dosages, is a strong candidate for controlling disease vectors.

Treatment of a Snakebite Injury With Secondary Bacterial Infection: A Case Study.

BACKGROUND: Pit viper snakebites are challenging as they often cause tissue injury and secondary bacterial infection that may impair full recovery of the affected limb. We describe the evolution of a snakebite injury with secondary infection and the use of specialized dressings to achieve tissue repair and complete closure of the wound. CASE: Ms E., a 45-year-old woman, was bitten by a pit viper that began as a small lesion and progressed to necrosis, cellulitis, edema, and hyperemia of the perilesional skin, local inflammation, and infection. We implemented a combination of topical hydrogel therapy with calcium alginate and hydrofiber with 1.2% silver to promote autolytic debridement, combat local infection, and provide a moist wound environment. The wound required daily local treatment for 2 months due to extensive tissue damage, combined with the proteolytic action of the bothropic venom. CONCLUSION: The care of wounds caused by snakebites is a challenge for the health care team due to tissue loss resulting from the action of the venom and secondary bacterial infection. Close follow-up with the use of systemic antibiotics and topical therapies proved effective in minimizing tissue loss in this case.

Vector Competence for Zika Virus Changes Depending on the Aedes aegypti's Region of Origin in Manaus: A Study of an Endemic Brazilian Amazonian City.

Zika virus (ZIKV) is transmitted to humans by the infectious bite of mosquitoes such as Aedes aegypti. In a city, the population control of mosquitoes is carried out according to alerts generated by different districts via the analysis of the mosquito index. However, we do not know whether, besides mosquito abundance, the susceptibility of mosquitoes could also diverge among districts and thus impact the dissemination and transmission of arboviruses. After a viremic blood meal, the virus must infect the midgut, disseminate to tissues, and reach the salivary gland to be transmitted to a vertebrate host. This study evaluated the patterns of ZIKV infection in the Ae. aegypti field populations of a city. The disseminated infection rate, viral transmission rate, and transmission efficiency were measured using quantitative PCR at 14 days post-infection. The results showed that all Ae. aegypti populations had individuals susceptible to ZIKV infection and able to transmit the virus. The infection parameters showed that the geographical area of origin of the Ae. aegypti influences its vector competence for ZIKV transmission.

Validation of a Culturally Relevant Snakebite Envenomation Clinical Practice Guideline in Brazil.

Snakebite envenoming (SBE) is a neglected tropical disease with significant global morbidity and mortality. Even when antivenom is available in low-resource areas, health workers do not receive adequate training to manage SBEs. This study aims to develop and validate a clinical practice guideline (CPG) for SBE management across Brazil. A panel of expert judges with academic and/or technical expertise in SBE management performed content validation. The content validity index (CVI) score was 90% for CPG objectives, 89% for structure and presentation and 92% for relevance and classified the CPG as valid. A semantic validation was performed by analyzing focus group discussions with doctors and nurses from three municipalities of the Brazilian Amazon, after a 5-day meeting during which the CPG was presented. Two central themes emerged: knowledge acquired during the meeting and recommendations for improving the CPG. Based on these results, the CPG was revised into a final version. This study presents the successful development and validation process of a CPG for SBE management, which is targeted to a specific low-resource, high-burden setting. This development and validation process can be adapted to other settings and/or other neglected tropical diseases.

Snakebites in "Invisible Populations": A cross-sectional survey in riverine populations in the remote western Brazilian Amazon.

In the Brazilian Amazon, long distances, low healthcare coverage, common use of ineffective or deleterious self-care practices, and resistance to seeking medical assistance have an impact on access to antivenom treatment. This study aimed to estimate snakebite underreporting, and analyze barriers that prevent victims from obtaining healthcare in communities located in 15 municipalities on the banks of the Solimões, Juruá and Purus Rivers, in the remote Western Brazilian Amazon. Information on the participants' demographics, previous snakebites, access to healthcare, time taken to reach medical assistance, use of self-care practices, and the reason for not accessing healthcare were collected through semi-structured interviews. In the case of deaths, information was collected by interviewing parents, relatives or acquaintances. A total of 172 participants who reported having suffered snakebites during their lifetime were interviewed. A total of 73 different treatment procedures was reported by 65.1% of the participants. Participants living in different river basins share few self-care procedures that use traditional medicine, and 91 (52.9%) participants reported that they had access to healthcare. Living in communities along the Juruá River [OR = 12.6 (95% CI = 3.2-49.7; p<0.001)] and the use of traditional medicine [OR = 11.6 (95% CI = 3.4-39.8; p<0.001)] were variables that were independently associated to the lack of access to healthcare. The main reasons for not accessing healthcare were the pprioritization of traditional treatments (70.4%), and the failure to recognize the situation as being potentially severe (50.6%). Four deaths from complications arising from the snakebite were reported, and three of these were from communities on the banks of the Juruá River. Only one of these received medical assistance. We found an unexpectedly high underreporting of snakebite cases and associated deaths. Snakebite victims utilized three main different healing systems: 1) self-care using miscellaneous techniques; 2) official medical healthcare generally combined with traditional practices; and 3) self-care using traditional practices combined with Western medicines. To mitigate snakebite burden in the Brazilian Amazon, an innovative intervention that would optimize timely delivery of care, including antivenom distribution among existing community healthcare centers, is needed.

Coral snake bites in Brazilian Amazonia: Perpetrating species, epidemiology and clinical aspects.

Coral snakes constitute a relatively diverse and little known group of venomous snakes. So far, data for this kind of snakebite in the Amazon region are based only on case reports. This study takes advantage of novel data from the Brazilian Health Ministry database from 2010 to 2015 and presents a review of the cases reported in the literature regarding the Amazonian biome both from Brazil and nearby countries. Thirty-four cases reported in the database were used in the study, representing 0.05% of the snakebites in Brazilian Amazonia for that period. The incidence rate was 0.123 cases/100,000 inhabitants/year. The most affected group is that of working age men, suggesting occupational risk. Most of bites were on lower limbs. Pain, edema and paresthesia were the most common symptoms. Systemic symptoms not usually associated with coral snakes envenomings, such as coagulopathy and thrombocytopenia, have been reported in Amazonia. Five patients received less antivenom than indicated by the Health Ministry. Based on these results, we recommend the execution of educational programs to avoid such accidents and to teach both the general public and health professionals the correct treatment for the bites. We also suggest that the covering of Intensive Care Units in the region needs to be improved to avoid deaths.

Snakebites as cause of deaths in the Western Brazilian Amazon: Why and who dies? Deaths from snakebites in the Amazon.

Snake envenoming represents a major burden for public health worldwide. In the Amazon, the official number of cases and deaths detected is probably underestimated because of the difficulty riverine and indigenous populations have reaching health centers in order to receive medical assistance. Thus, integrated analysis of health information systems must be used in order to improve adequate health policies. The aim of this work is to describe a series of deaths and identify risk factors for lethality from snakebites in the state of Amazonas, Brazil. All deaths from snakebites reported to the Brazilian Notifiable Diseases Surveillance System (SINAN) and to the Mortality Information System (SIM; ICD10-10th revision, X.29), from 2007 to 2015, were included. Variables were assessed by blocks with distal (ecological variables), intermediate (demographics) and proximal (clinical variables) components to identify predictors of case fatality. A total of 127 deaths from snakebites were recorded, with 58 pairs found through linkage of the SINAN and SIM databases (45.7%), 37 (29.1%) deaths found only in SINAN and 32 (25.2%) found only in the SIM. Deaths occurred mostly in males (95 cases; 74.8%) living in rural areas (78.6%). The most affected age group was the ≥61 years old (36 cases; 28.4%). Snakebites were presumably due to Bothrops snakes in 68.5% of the cases and Lachesis in 29.5% based on clinico-epidemiological diagnosis. A proportion of 26.2% of the cases received treatment over 24 h after the bite ocurred. On admission, cases were mostly classified as severe (65.6%). Overall, 28 patients (22.0%). Deceased without any medical assistance Antivenom was given to 53.5%. In the multivariate analysis, a distance from Manaus >300 km [OR = 3.40 (95%CI = 1.99-5.79); (p < 0.001)]; age ≥61 years [OR = 4.31 (95%CI = 1.22-15.21); (p = 0.023)] and Indigenous status [OR = 5.47 (95%CI = 2.37-12.66); (p < 0.001)] were independently associated with case fatality from snakebites. Severe snakebites [OR = 16.24 (95%CI = 4.37-60.39); (p < 0.001)] and a lack of antivenom administration [OR = 4.21 (95%CI = 1.30-13.19); (p = 0.014)] were also independently associated with case fatality. Respiratory failure/dyspnea, systemic bleeding, sepsis and shock were recorded only among fatal cases. In conclusion, i) death from snakebites was underreported in the mortality surveillance system; ii) older age groups living in remote municipalities and indigenous peoples were the population groups most prone to death; iii) lack or underdosage of antivenom resulted in higher case fatality and iv) systemic bleeding, circulatory shock, sepsis and acute respiratory failure were strongly associated to fatal outcome.

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.

Validation of a culturally relevant snakebite envenomation clinical practice guideline in Brazil

Snakebite envenoming (SBE) is a neglected tropical disease with significant global morbidity and mortality. Even when antivenom is available in low-resource areas, health workers do not receive adequate training to manage SBEs. This study aims to develop and validate a clinical practice guideline (CPG) for SBE management across Brazil. A panel of expert judges with academic and/or technical expertise in SBE management performed content validation. The content validity index (CVI) score was 90% for CPG objectives, 89% for structure and presentation and 92% for relevance and classified the CPG as valid. A semantic validation was performed by analyzing focus group discussions with doctors and nurses from three municipalities of the Brazilian Amazon, after a 5-day meeting during which the CPG was presented. Two central themes emerged: knowledge acquired during the meeting and recommendations for improving the CPG. Based on these results, the CPG was revised into a final version. This study presents the successful development and validation process of a CPG for SBE management, which is targeted to a specific low-resource, high-burden setting. This development and validation process can be adapted to other settings and/or other neglected tropical diseases

Snakebites in “invisible populations”: a cross-sectional survey in riverine populations in the remote western Brazilian Amazon

In the Brazilian Amazon, long distances, low healthcare coverage, common use of ineffective or deleterious self-care practices, and resistance to seeking medical assistance have an impact on access to antivenom treatment. This study aimed to estimate snakebite underreporting, and analyze barriers that prevent victims from obtaining healthcare in communities located in 15 municipalities on the banks of the Solimões, Juruá and Purus Rivers, in the remote Western Brazilian Amazon. Information on the participants’ demographics, previous snakebites, access to healthcare, time taken to reach medical assistance, use of self-care practices, and the reason for not accessing healthcare were collected through semi-structured interviews. In the case of deaths, information was collected by interviewing parents, relatives or acquaintances. A total of 172 participants who reported having suffered snakebites during their lifetime were interviewed. A total of 73 different treatment procedures was reported by 65.1% of the participants. Participants living in different river basins share few self-care procedures that use traditional medicine, and 91 (52.9%) participants reported that they had access to healthcare. Living in communities along the Juruá River [OR = 12.6 (95% CI = 3.2–49.7; p<0.001)] and the use of traditional medicine [OR = 11.6 (95% CI = 3.4–39.8; p<0.001)] were variables that were independently associated to the lack of access to healthcare. The main reasons for not accessing healthcare were the pprioritization of traditional treatments (70.4%), and the failure to recognize the situation as being potentially severe (50.6%). Four deaths from complications arising from the snakebite were reported, and three of these were from communities on the banks of the Juruá River. Only one of these received medical assistance. We found an unexpectedly high underreporting of snakebite cases and associated deaths. Snakebite victims utilized three main different healing systems: 1) self-care using miscellaneous techniques; 2) official medical healthcare generally combined with traditional practices; and 3) self-care using traditional practices combined with Western medicines. To mitigate snakebite burden in the Brazilian Amazon, an innovative intervention that would optimize timely delivery of care, including antivenom distribution among existing community healthcare centers, is needed.

Snakebites as cause of deaths in the Western Brazilian Amazon: Why and who dies? Deaths from snakebites in the Amazon

Snake envenoming represents a major burden for public health worldwide. In the Amazon, the official number of cases and deaths detected is probably underestimated because of the difficulty riverine and indigenous populations have reaching health centers in order to receive medical assistance. Thus, integrated analysis of health information systems must be used in order to improve adequate health policies. The aim of this work is to describe a series of deaths and identify risk factors for lethality from snakebites in the state of Amazonas, Brazil. All deaths from snakebites reported to the Brazilian Notifiable Diseases Surveillance System (SINAN) and to the Mortality Information System (SIM; ICD10-10th revision, X.29), from 2007 to 2015, were included. Variables were assessed by blocks with distal (ecological variables), intermediate (demographics) and proximal (clinical variables) components to identify predictors of case fatality. A total of 127 deaths from snakebites were recorded, with 58 pairs found through linkage of the SINAN and SIM databases (45.7%), 37 (29.1%) deaths found only in SINAN and 32 (25.2%) found only in the SIM. Deaths occurred mostly in males (95 cases; 74.8%) living in rural areas (78.6%). The most affected age group was the >= 61 years old (36 cases; 28.4%). Snakebites were presumably due to Bothrops snakes in 68.5% of the cases and Lachesis in 29.5% based on clinico-epidemiological diagnosis. A proportion of 26.2% of the cases received treatment over 24 h after the bite ocurred. On admission, cases were mostly classified as severe (65.6%). Overall, 28 patients (22.0%). Deceased without any medical assistance Antivenom was given to 53.5%. In the multivariate analysis, a distance from Manaus >300 km [OR = 3.40 (95%Cl = 1.99-5.79); (p < 0.001)1; age >= 61 years [OR = 431 (95%Cl = 1.22-1521); (p = 0.023)] and Indigenous status [OR = 5.47 (95%Cl = 237-12.66); (p < 0.001)1 were independently associated with case fatality from snakebites. Severe snakebites [OR = 16.24 (95%Cl = 4.37-6039); (p < 0.001)] and a lack of antivenom administration [OR = 4.21 (95%Cl = 1.30-13.19); (p = 0.014)] were also independently associated with case fatality. Respiratory failureklyspnea, systemic bleeding, sepsis and shock were recorded only among fatal cases. In conclusion, i) death from snakebites was under-reported in the mortality surveillance system; ii) older age groups living in remote municipalities and indigenous peoples were the population groups most prone to death; iii) lack or underdosage of anti venom resulted in higher case fatality and iv) systemic bleeding, circulatory shock, sepsis and acute respiratory failure were strongly associated to fatal outcome.