Comparison Between Numeric Parameters From Acute and Chronic Venous Leg Ulcers: Identification of Potential Objective Nonhealing Parameters.

BACKGROUND: Some authors claim that the clinical methods often employed to assess chronic venous leg ulcers (CVLU) are based on subjective interpretation. The treatments based on a subjective characterization could become a trial-and-error therapy, resulting in longer evolutions and high recurrence rates. PURPOSE: The aim of this work was to compare numeric parameters from acute and chronic venous leg ulcers to identify potential objective nonhealing parameters. METHODS: The study was performed with hospital outpatients from 2016 to 2019. Cohorts were established according to the ulcer evolution time. Data collected related to ulcer characteristics included exudate pH, lactate and glucose concentrations, temperatures, microbiology findings, and imaging study results. RESULTS: Approximately 83% of the examined ulcers were chronic. Seventy-one percent of CVLUs and 59% of the acute ulcers had a pH ≥8. A high variability was found for the concentration of glucose and lactate in exudates of both acute and chronic ulcers. Variations of temperatures of normal skin (ΔT1) and periulcer zone (ΔT2) in reference to the wound bed temperature with values above 1 could indicate the presence of an inflammatory process and be used as a new potential marker of inflammation. All the acute ulcers and 88% of CVLUs showed <80% of granulation tissue in the imaging study. Finally, more than 105 organisms per gram of tissuewere found in 100% of the analyzed samples. CONCLUSIONS: Whereas there were not significant differences among the clinical measured parameters between acute and chronic ulcers, further research on the use of objective measurable parameters is needed to establish cutoff points to differentiate the "chronic state" of an ulcer as a "nonhealing state" regardless of the evolution time. Also, the use of these easily obtainable and low-cost nonhealing parameters would be a new approach to accurately monitor this pathology.

Case-fatality From Orally-transmitted Acute Chagas Disease: A Systematic Review and Meta-analysis.

Orally-transmitted acute Chagas disease (CD) is emerging as an important public health problem. The prognosis of acute infection following oral transmission is unknown. The aim of this study was to analyze and summarize data on orally-transmitted acute CD. We searched for publications from 1968 to 31 January 2018. We included studies and unpublished data from government sources that reported patients with acute orally-transmitted CD. We identified 41 papers and we added 932 unpublished cases. In all, our study covered 2470 cases and occurrence of 97 deaths. Our meta-analysis estimated that the case-fatality rate was 1.0% (95% CI 0.0-4.0%). Lethality rates have declined over time (P = .02). In conclusion, orally-transmitted acute CD has considerable lethality in the first year after infection. The lethality in symptomatic cases is similar to that from other routes of infection. The lethality rate of orally-acquired disease has declined over the years.

Acute Chagas disease in Brazil from 2001 to 2018: A nationwide spatiotemporal analysis.

BACKGROUND: In Brazil, acute Chagas disease (ACD) surveillance involves mandatory notification, which allows for population-based epidemiological studies. We conducted a nationwide population-based ecological analysis of the spatiotemporal patterns of ACD notifications in Brazil using secondary surveillance data obtained from the Notifiable Diseases Information System (SINAN) maintained by Brazilian Ministry of Health. METHODOLOGY/PRINCIPAL FINDINGS: In this nationwide population-based ecological all cases of ACD reported in Brazil between 2001 and 2018 were included. Epidemiological characteristics and time trends were analyzed through joinpoint regression models and spatial distribution using microregions as the unit of analysis. A total of 5,184 cases of ACD were recorded during the period under study. The annual incidence rate in Brazil was 0.16 per 100,000 inhabitants/year. Three statistically significant changes in time trends were identified: a rapid increase prior to 2005 (Period 1), a stable drop from 2005 to 2009 (Period 2), followed by another increasing trend after 2009 (Period 3). Higher frequencies were noted in males and females in the North (all three periods) and in females in Northeast (Periods 1 and 2) macroregions, as well as in individuals aged between 20-64 years in the Northeast, and children, adolescents and the elderly in the North macroregion. Vectorial transmission was the main route reported during Period 1, while oral transmission was found to increase significantly in the North during the other periods. Spatiotemporal distribution was heterogeneous in Brazil over time. Despite regional differences, over time cases of ACD decreased significantly nationwide. An increasing trend was noted in the North (especially after 2007), and significant decreases occurred after 2008 among all microregions other than those in the North, especially those in the Northeast and Central-West macroregions. CONCLUSIONS/SIGNIFICANCE: In light of the newly identified epidemiological profile of CD transmission in Brazil, we emphasize the need for strategically integrated entomological and health surveillance actions.

FTIR spectroscopy of chronic venous leg ulcer exudates: an approach to spectral healing marker identification.

Chronic venous leg ulcer (CVLU) arises as a chronic venous insufficiency complication and is a major cause of morbidity throughout the world. Our hypothesis is that the CVLU exudate composition is a biochemical representation of the wound clinical state. Then, Fourier Transform Infrared (FTIR) spectroscopy could be a useful and less-invasive technique to study the clinical state of the ulcer. For this, the aim of this work was to perform a spectral characterization of the exudate from CVLU using FTIR spectroscopy to identify potential healing markers. 45 exudate samples from CVLU, 95% of the strains isolated from CVLU in planktonic and biofilm phenotypes and other related biological samples such as human plasma, serum, urine, blood cells, urea, creatinine, glucose and albumin were studied by FTIR spectroscopy. According to the vibration frequency of biomolecules' (lipids, proteins, nucleic acids and carbohydrates) characteristic bonds in the infrared region, different spectral windows were selected and spectral areas of each window were measured. Besides, Savitzky-Golay second derivatives were obtained for all spectra and peaks from each standardized window were detected. FTIR spectroscopy allowed identification of sample types (exudate, plasma, serum, urine) as each one presents a unique relative composition and ratios range. Also, this technique could be useful to identify bacteria in the phenotypic-ulcer state and allows differentiation of whether bacteria are in the biofilm or planktonic form which is unlikely by conventional methods. In this work we found some spectral markers (areas, peaks) that allow identification of several parameters in the exudate such as (a) total cellularity, (b) inflammatory cell load, (c) bacterial load, (d) fibrin amount, and (e) inflammatory proteins. Because the measured areas or founded peaks are concentration-dependent this method could also serve to measure them. Therefore, FTIR spectroscopy could be useful to evaluate patient evolution as all these exudate parameters represent critical negative markers for wound healing.

Community-Based Entomological Surveillance Reveals Urban Foci of Chagas Disease Vectors in Sobral, State of Ceará, Northeastern Brazil.

BACKGROUND: The aim of this work was to explore the potential risk of vector-borne Chagas disease in urban districts in northeastern Brazil, by analyzing the spatiotemporal distributions and natural infection rates with Trypanosoma cruzi of triatomine species captured in recent years. The main motivation of this work was an acute human case of Chagas disease reported in 2008 in the municipality of Sobral. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed data from community-based entomological surveillance carried out from 2010 to 2014. Triatomine natural T. cruzi infection was assessed by examination of insect feces by optical microscopy. Sites of triatomine capture were georeferenced through Google Earth and analyzed with ArcGIS. A total of 191 triatomines were collected, consisting of 82.2% Triatoma pseudomaculata, 7.9% Rhodnius nasutus, 5.8% T. brasiliensis, 3.7% Panstrongylus lutzi, and 0.5% P. megistus, with an overall natural infection index of 17.8%. Most infestations were reported in the districts of Dom José (36.2%), Padre Palhano (24.7%), and Alto do Cristo (10.6%). The overwhelming majority of insects (185/96.9%) were captured inside houses, and most insects tended to be collected in intermittent peaks. Moreover, captured triatomines tended to constitute colonies. The acute case reported in 2008 was found to be situated within a T. pseudomaculata hotspot. CONCLUSION: The triatomine collection events carried out by dwellers were aggregated in time and space into distinct foci, suggesting that insects are intermittently and artificially introduced into the city, possibly via accidental migration from their natural reservoirs. The relatively high T. cruzi infection rate indicates considerable circulation of the parasite in these areas, increasing the risk of vector-borne Chagas disease infection. These data suggest a need to strengthen epidemiological surveillance and integrate appropriate control actions targeting triatomines, T. cruzi reservoirs, and human populations. Our data also identify Chagas disease transmission as a hazard in urban areas of Sobral.

Epidemiology of soil-transmitted helminthiases-related mortality in Brazil.

Soil-transmitted helminth (STH) infections are widely distributed in tropical and subtropical areas, including Brazil. We performed a nationwide population-based study including all deaths in Brazil from 2000 to 2011, in which STHs (ascariasis, trichuriasis and/or hookworm infection) were mentioned on death certificates, either as underlying or as associated causes of death. Epidemiological characteristics, time trends and spatial analysis of STH-related mortality were analysed. STHs was identified on 853/12 491 280 death certificates: 827 (97·0%) deaths related to ascariasis, 25 (2·9%) to hookworm infections, and 1 (0·1%) to trichuriasis. The average annual age-adjusted mortality rate was 0·34/1 000 000 inhabitants (95% confidence interval: 0·27-0·44). Females, children <10 years of age, indigenous ethnic groups and residents in the Northeast region had highest STH-related mortality rates. Nationwide mortality decreased significantly over time (annual percent change: -5·7%; 95% CI: -6·9 to -4·4), with regional differences. We identified spatial high-risk clusters for STH-related mortality mainly in the North, Northeast and South regions. Diseases of the digestive system and infectious/parasitic diseases were the most commonly associated causes of death mentioned in the STH-related deaths. Despite decreasing mortality in Brazil, a considerable number of deaths is caused by STHs, with ascariasis responsible for the vast majority. There were marked regional differences, affecting mainly children and vulnerable populations.

Towards a toolkit for cross-neglected tropical disease morbidity and disability assessment.

BACKGROUND: Neglected tropical diseases (NTDs) are a group of often chronic and disabling infectious conditions, closely related to poverty and inequities. While it is estimated that millions of people are affected, accurate and internationally comparable data about NTD-related morbidity and disability are lacking. Therefore we aimed to develop and pilot a toolkit to assess and monitor morbidity and disability across NTDs. METHODS: A cross-sectional, non-random survey design with a mixed methods approach was used. We conducted a literature review on existing tools to assess and monitor disability, followed by a Delphi study with NTD experts to compile a prototype toolkit. A first-phase validation study was conducted in Northeast Brazil among people with Chagas disease, leishmaniasis, leprosy and schistosomiasis. RESULTS: Instruments included were the clinical profile, WHODAS, P-scale, SRQ, WHOQOL-BREF and WHOQOL-DIS. Most questions in the various instruments were readily understood with the exception of the WHOQOL-BREF, where additional explanations and examples were often needed. The respondents were very appreciative of the instruments and found it valuable to have the opportunity to talk about these aspects of their condition. CONCLUSIONS: Our findings support the acceptability and relevance of five of the six instruments tested and the concept of a cross-NTD toolkit.

Compounds from Lactobacillus plantarum culture supernatants with potential pro-healing and anti-pathogenic properties in skin chronic wounds.

CONTEXT: It is necessary to advance the field of alternative treatments for chronic wounds that are financially accessible to the least economically developed countries. Previously we demonstrated that topical applications of Lactobacillus plantarum culture supernatants (LAPS) on human-infected chronic wounds reduce the pathogenic bioburden, the amount of necrotic tissue, and the wound area, as well as promote debridement, granulation tissue, and wound healing. OBJECTIVE: To study LAPS chemically and biologically and to find potential molecules responsible for its pro-healing and anti-pathogenic properties in chronic wounds. MATERIALS AND METHODS: (1) Chemical analysis: extracts were subjected to a column chromatography and the fractions obtained were studied by GCMS. (2) Quantification: dl-lactic acid (commercial kit), phenolic compounds (Folin-Ciocalteu), H2O2 (micro-titration), and cations (flame photometry). (3) Biological analysis: autoinducers type 2 (AI-2) (Vibrio harveyi BB170 bioassay), DNAase activity (Agar DNAase), and Pseudomonas aeruginosa biofilm inhibition (crystal violet technique). RESULTS: According to its biological activity, the most significant molecules found by GCMS were the following: antimicrobials (mevalonolactone, 5-methyl-hydantoine, benzoic acid, etc.); surfactants (di-palmitin, distearin, and 1,5-monolinolein); anesthetics (barbituric acid derivatives), and AI-2 precursors (4,5-dihydroxy-2,3-pentanedione and 2-methyl-2,3,3,4-tetrahydroxytetrahydrofurane). Concentrations measured (µg/mL): DL-lactic acid (11.71 ± 1.53) and H2O2 (36 ± 2.0); phenolic compounds (485.2 ± 15.20); sodium (370 ± 17); potassium 920 ± 24); calcium (20 ± 4); and magnesium (15 ± 3). DNAase from LAPS had activity on genomic DNA from PMNs and P. aeruginosa. DISCUSSION AND CONCLUSION: The molecules and biological activities found in LAPS could explain the observed effects in human chronic wounds.

Antipathogenic properties of Lactobacillus plantarum on Pseudomonas aeruginosa: the potential use of its supernatants in the treatment of infected chronic wounds.

Pathogenic bacteria delay wound healing through several different mechanisms such as persistent production of inflammatory mediators or maintenance of necrotic neutrophils, which release cytolytic enzymes and free oxygen radicals. One of the most frequent pathogens isolated from infections in chronic wounds is Pseudomonas aeruginosa. This bacterium is extremely refractory to therapy and to host immune attack when it forms biofilms. Therefore, antibiotics and antiseptics are becoming useless in the treatment of these infections. In previous works, we demonstrated that Lactobacillus plantarum has an important antipathogenic capacity on P. aeruginosa. The aim of the present work was to elucidate the mechanism involved in the control of growth of P. aeruginosa on different surfaces by L. plantarum. For this purpose, we investigated the effects of L. plantarum supernatants on pathogenic properties of P. aeruginosa, such as adhesion, viability, virulence factors, biofilm formation, and quorum sensing signal expression. L. plantarum supernatants were able to inhibit pathogenic properties of P. aeruginosa by a quorum quenching mechanism. The antipathogenic properties mentioned above, together with the immunomodulatory, tissue repair, and angiogenesis properties in the supernatants of L. plantarum, make them an attractive option in infected chronic wound treatment.

Clusters of leprosy transmission and of late diagnosis in a highly endemic area in Brazil: focus on different spatial analysis approaches.

OBJECTIVE: The Brazilian National Hansen's Disease Control Program recently identified clusters with high disease transmission. Herein, we present different spatial analytical approaches to define highly vulnerable areas in one of these clusters. METHOD: The study area included 373 municipalities in the four Brazilian states Maranhão, Pará, Tocantins and Piauí. Spatial analysis was based on municipalities as the observation unit, considering the following disease indicators: (i) rate of new cases/100,000 population, (ii) rate of cases <15 years/100,000 population, (iii) new cases with grade-2 disability/100,000 population and (iv) proportion of new cases with grade-2 disabilities. We performed descriptive spatial analysis, local empirical Bayesian analysis and spatial scan statistic. RESULTS: A total of 254 (68.0%) municipalities were classified as hyperendemic (mean annual detection rates >40 cases/100,000 inhabitants). There was a concentration of municipalities with higher detection rates in Pará and in the center of Maranhão. Spatial scan statistic identified 23 likely clusters of new leprosy case detection rates, most of them localized in these two states. These clusters included only 32% of the total population, but 55.4% of new leprosy cases. We also identified 16 significant clusters for the detection rate <15 years and 11 likely clusters of new cases with grade-2. Several clusters of new cases with grade-2/population overlap with those of new cases detection and detection of children <15 years of age. The proportion of new cases with grade-2 did not reveal any significant clusters. CONCLUSIONS: Several municipality clusters for high leprosy transmission and late diagnosis were identified in an endemic area using different statistical approaches. Spatial scan statistic is adequate to validate and confirm high-risk leprosy areas for transmission and late diagnosis, identified using descriptive spatial analysis and using local empirical Bayesian method. National and State leprosy control programs urgently need to intensify control actions in these highly vulnerable municipalities.

Persisting leprosy transmission despite increased control measures in an endemic cluster in Brazil: the unfinished agenda.

OBJECTIVE: To provide an evidence base for improvement of leprosy control in Brazil's high transmission areas. DESIGN: We obtained data from municipalities in a major disease cluster from databases for notifiable diseases of four states (Maranhão, Parâ, Tocantins, Piauí), including notifications from 2001 to 2009. Indicators for monitoring and evaluation of leprosy according to the World Health Organization were evaluated with emphasis on the rates of new cases presenting grade-2 disabilities and among children < 15 years of age, indicating late diagnosis and active transmission, respectively. RESULTS: A total of 82,463 leprosy cases were detected in the area (mean annual case detection rate: 95.9/100,000; RR = 4.56 as compared to the rest of Brazil; 95% CI: 4.45-4.66, P < 0.0001). There was a steady decrease of detection rates in the study period, from 100.8 to 75.6/100,000 inhabitants. In children <15 years of age, 9,009 cases of leprosy were detected (28.40/100,000), significantly more than in the rest of Brazil (RR = 5.80; 95% CI: 5.39-6.25, P < 0.0001). New cases with grade-2 disabilities/100,000 population maintained a stable trend at a high level (4.43 cluster vs. 1.28 rest of country; RR = 3.46; 95% CI: 3.11-3.84, P < 0.0001), whereas the proportion of new cases with grade-2 was slightly lower than the country's average (5.51% vs. 6.75%; RR = 0.84; 95% CI: 0.81-0.86, P < 0.0001). CONCLUSIONS: Despite recently improved leprosy control measures, there is still major active transmission and late diagnosis in the cluster. Further specific actions are needed to improve early case detection and prompt treatment with the aim to reduce disease burden in the population, considering social inequities.

High occurrence of HIV-positive siblings due to repeated mother-to-child transmission in Brazil.

Pregnancies in women without knowledge of their HIV-positive status increase the risk of mother-to-child transmission, and of disease progression. This study aimed to characterize the frequency of multiple pregnancies and of HIV-positive children in the family, during HAART era. We analyzed data of a national multicenter cohort study among Brazilian children with AIDS diagnosed between 1999 and 2002. In total, 945 children and their 928 mothers were included. Five hundred and ninety (64.6%) women had a history of multiple pregnancies, and 49.5% attended prenatal care (mean: 3.5 consultations; SD 3.6). In 483 child cases, HIV status of the sibling was known; 130 (26.9%) of these were infected with HIV. In 38.5% of cases, the child with AIDS included in the cohort study was the first case in the family. Despite the overall positive results of the Brazilian control policy of HIV/AIDS, our study shows that HIV infection in pregnant women was often undetected and that consequently there was a high frequency of repeated HIV-infected children. There is a need to improve comprehensive prenatal and postnatal care of Brazilian women. HIV-affected families are most vulnerable and should be targeted by specific control programs, preventing additional HIV infections in other children.

Opportunistic illnesses in Brazilian children with AIDS: results from two national cohort studies, 1983-2007.

BACKGROUND: HAART has significantly reduced AIDS-related morbidity in children. However, limited evidence is available from developing countries regarding patterns of opportunistic illnesses. We describe these events and their associated factors in children with AIDS in Brazil. METHODS: This study is based on two representative retrospective multi-center cohorts including a total 1,859 children with AIDS, infected via mother-to-child transmission (MTCT), between 1983-2002. Opportunistic illnesses were described and analyzed over time. The association of demographic, clinical and operational data with the occurrence of opportunistic diseases was assessed. RESULTS: In total, 1,218 (65.5%) had at least one event of an opportunistic disease. Variables significantly associated with occurrence of these events included: region of residence (OR 2.68-11.33, as compared to the Northern region), age < 1 year at diagnosis (OR 2.56, 95% CI 1.81-3.61, p < 0.001), and non-performance of MTCT prevention measures (OR 1.58, 95% CI 1.21-2.07, p < 0.001). Protective factors included year of HIV diagnosis in the HAART era (OR 0.34, 95% CI 0.15-0.76, p = 0.009) and ART use (OR 0.58, 95% CI 0.44-0.77, p < 0.001). In both periods bacterial infections represented the most common opportunistic events (58.6 vs. 34.7%; p < 0.001), followed by Pneumocystis jirovecii pneumonia (21.9 vs. 13.2%; p < 0.001), and bacterial meningitis/sepsis (16.8 vs. 7.4%; p < 0.001). CONCLUSIONS: Despite the significant reduction in recent years, opportunistic illnesses are still common in Brazilian children with AIDS in the HAART era, especially bacterial diseases. The data reinforce the need for scaling up prevention of MTCT, early diagnosis of infection, and improvement of comprehensive pediatric care.

Bioactive sesqui- and diterpenoids from the Argentine liverwort Porella chilensis.

Four fusicoccane-type diterpenoids (1-4), including the new 1 and 2; four pinguisane-type sesquiterpenoids (5-8); and two aromadendrane-type sesquiterpenoids (9 and 10) were isolated from an Argentine collection of the endemic liverwort Porella chilensis. The biofilm formation of the human pathogen Pseudomonas aeruginosa was inhibited by compounds 3 (53 and 47%), 9 (45 and 41%), and 10 (48 and 37%) at 50 and 5 µg/mL, respectively. Compounds 3, 9, and 10 also produced a slight decrease in bacterial growth and interfere with the process of quorum sensing at the same doses.

Continuing improvement in survival for children with acquired immunodeficiency syndrome in Brazil.

This retrospective cohort study examined a nationally representative sample of 945 Brazilian children (ages 0-12 years) diagnosed with AIDS in 1999 to 2002 and followed through 2007. The probability of survival to 60 months was 86.3% (95% CI, 84.1%-88.5%). This compares with 52.8% (95% CI, 41.9%-60.8%) in a study of cases diagnosed in 1983 to 1998. These results demonstrate substantial improvement in survival for children with AIDS in Brazil.