A Randomized, Controlled, Noninferiority, Multicenter Trial of Systemic vs Intralesional Treatment With Meglumine Antimoniate for Cutaneous Leishmaniasis in Brazil.

BACKGROUND: Meglumine antimoniate (MA) remains the main treatment for cutaneous leishmaniasis (CL). Uncontrolled studies suggest that intralesional MA (IL-MA) may be noninferior and safer than systemic MA (S-MA). METHODS: Multicenter, randomized, controlled, open-label, phase 3 clinical trial to evaluate the efficacy and toxicity of IL-MA in 3 infiltrations at 14-day intervals compared with S-MA (10-20 mg Sb5+/kg/day, 20 days) for CL, with noninferiority margin of 20%. Primary and secondary outcomes were definitive cure at day 180 and epithelialization rate at day 90 of treatment, respectively. A 2-year follow-up was performed to assess relapses and emergence of mucosal lesions. Adverse events (AEs) were monitored according to the Division of AIDS AE grading system. RESULTS: We evaluated 135 patients. The cure rates (95% confidence interval) for IL-MA and S-MA treatment were, respectively, 82.8% (70.5-91.4) and 67.8% (53.3-78.3) per protocol (PP) and 70.6% (58.3-81.0) and 59.7% (47.0-71.5) per intention to treat (ITT). The epithelialization rates of the IL-MA and S-MA treatment were, respectively, 79.3% (66.6-88 + 8) and 71.2% (57.9-82.2) PP and 69.1% (55.2-78.5) and 64.2% (50.0-74.2) ITT. AEs in the IL-MA and S-MA groups were, respectively, clinical, 45.6% and 80.6%; laboratory, 26.5% and 73.1%; and electrocardiogram, 8.8% and 25.4%. Ten participants in the S-MA group and 1 in the IL-MA group were discontinued due to severe or persistent AEs. CONCLUSIONS: IL-MA provides a similar cure rate and results in less toxicity compared with S-MA and may be used as first-line therapy for CL patients. CLINICAL TRIALS REGISTRATION: REBEC: RBR-6mk5n4.

Detection of Zika Virus in April 2013 Patient Samples, Rio de Janeiro, Brazil.

We tested 210 dengue virus‒negative samples collected from febrile patients during a dengue virus type 4 outbreak in Rio de Janeiro in April 2013 and found 3 samples positive for Zika virus. Our findings support previously published entomological data suggesting Zika virus was introduced into Brazil during October 2012-May 2013.

Sensitivity and specificity of in situ hybridization for diagnosis of cutaneous infection by Leishmania infantum in dogs.

An accurate diagnosis of infection by Leishmania infantum in dogs is fundamental for the control of zoonotic visceral leishmaniasis (VL). Histopathology (HP) and immunohistochemistry (IHC) are frequently used for the histological diagnosis of L. infantum in dogs but have shown limited accuracy. To improve the sensitivity and specificity of the histological diagnosis of VL, we evaluated automated in situ hybridization (ISH) using a generic probe for Leishmania and a specific probe for L. infantum in surgical skin biopsy specimens of dogs. The ISH results were compared with those of HP and IHC, using parasitological culture as the reference standard. Skin samples from 51 dogs with cutaneous L. infantum infection and 51 noninfected dogs were randomly selected from samples of dogs from various cities in Brazil where canine VL is endemic. These samples were processed for parasitological culture, HP, IHC, and ISH using both probes. The sensitivities of ISH using the specific probe, ISH using the generic probe, IHC, and HP were, respectively, 74.5%, 70.6%, 69.5%, and 57.6%. The specificity of both ISH probes tested was 100%, and there was no cross-hybridization of the generic and specific probes with selected pathogenic fungi and protozoa. The specific probe discriminated L. infantum from the other species of Leishmania that infect dogs in the New World. ISH is highly sensitive and specific for the diagnosis of L. infantum in histologic samples of skin from infected dogs and can be used on routine biopsy material to make a diagnosis of leishmaniasis.

Clinical and laboratory features that discriminate dengue from other febrile illnesses: a diagnostic accuracy study in Rio de Janeiro, Brazil.

BACKGROUND: Dengue is an acute febrile illness caused by an arbovirus that is endemic in more than 100 countries. Early diagnosis and adequate management are critical to reduce mortality. This study aims to identify clinical and hematological features that could be useful to discriminate dengue from other febrile illnesses (OFI) up to the third day of disease. METHODS: We conducted a sectional diagnostic study with patients aged 12 years or older who reported fever lasting up to three days, without any evident focus of infection, attending an outpatient clinic in the city of Rio de Janeiro, Brazil, between the years 2005 and 2008. Logistic regression analysis was used to identify symptoms, physical signs, and hematological features valid for dengue diagnosis. Receiver-operating characteristic (ROC) curve analyses were used to define the best cut-off and to compare the accuracy of generated models with the World Health Organization (WHO) criteria for probable dengue. RESULTS: Based on serological tests and virus genome detection by polymerase chain reaction (PCR), 69 patients were classified as dengue and 73 as non-dengue. Among clinical features, conjunctival redness and history of rash were independent predictors of dengue infection. A model including clinical and laboratory features (conjunctival redness and leukocyte counts) achieved a sensitivity of 81% and specificity of 71% and showed greater accuracy than the WHO criteria for probable dengue. CONCLUSIONS: We constructed a predictive model for early dengue diagnosis that was moderately accurate and performed better than the current WHO criteria for suspected dengue. Validation of this model in larger samples and in other sites should be attempted before it can be applied in endemic areas.

Ocular Manifestations of Sporotrichosis in a Hyperendemic Region in Brazil: Description of a Series of 120 Cases.

PURPOSE: To describe 120 cases of ocular sporotrichosis. METHODS: Review of medical records of patients with culture-proven (from eye specimen) ocular sporotrichosis, in Rio de Janeiro, from 2007 to 2017. RESULTS: Women were more affected (61.7%) and median age was 24 years. The isolated ocular form was more frequent (75.8%). Fixed cutaneous sporotrichosis was the most commonly associated form (48.3%). Hypersensitivity reactions were observed in 10% of patients. Ocular involvement was unilateral in 98.3% of the cases, and the most frequent clinical presentation was granulomatous conjunctivitis (86.7%), followed by eyelid lesion (25%). Dacryocystitis represented 7.5% of the cases, predominantly in children (55.6%). Itraconazole was the first choice treatment (95.8%). Sequelae were observed in 23 patients (22.5%), and surgical treatment was required for most of them. CONCLUSION: Ocular sporotrichosis can be considered a characteristic form of the zoonotic transmission, with high morbidity. Delay in initiating specific treatment is likely to increase the risk of progression to more severe forms of the disease, and development of ocular sequelae.

Meningeal Sporotrichosis Due to Sporothrix brasiliensis: A 21-Year Cohort Study from a Brazilian Reference Center.

Meningeal sporotrichosis is rare and occurs predominantly in immunosuppressed individuals. This retrospective study explored clinical and laboratory characteristics, treatment, and prognosis of patients with disseminated sporotrichosis who underwent lumbar puncture (LP) at a Brazilian reference center from 1999 to 2020. Kaplan-Meier and Cox regression models were used to estimate overall survival and hazard ratios. Among 57 enrolled patients, 17 had meningitis. Fifteen (88.2%) had HIV infection, and in 6 of them, neurological manifestations occurred because of the immune reconstitution inflammatory syndrome (IRIS). The most frequent symptom was headache (88.2%). Meningeal symptoms at first LP were absent in 7/17 (41.2%) patients. Sporothrix was diagnosed in cerebrospinal fluid either by culture or by polymerase chain reaction in seven and four patients, respectively. All but one patient received prolonged courses of amphotericin B formulations, and seven received posaconazole, but relapses were frequent. Lethality among patients with meningitis was 64.7%, with a higher chance of death compared to those without meningitis (HR = 3.87; IC95% = 1.23;12.17). Meningeal sporotrichosis occurs mostly in people with HIV and can be associated with IRIS. Screening LP is indicated in patients with disseminated disease despite the absence of neurological complaints. Meningitis is associated with poor prognosis, and better treatment strategies are needed.

Smell dysfunction in COVID-19 patients: More than a yes-no question.

Anosmia has been recognized as a prevalent and early symptom by many COVID-19 patients. However, most researchers have recorded smell dysfunction solely as present or absent and based on subjective evaluation by patients. We described the results of 57 consecutive COVID-19 patients seen at FIOCRUZ, Rio de Janeiro, Brazil, from April to May 2020. Data about the presence of smell loss, the onset of smell loss and other COVID-19 symptoms such as ageusia and nasal congestion or rhinorrhea were recorded. All patients at the initial consultation and 34 healthy controls underwent the Q-SIT, which is a quick disposable three-item smell identification test, by a trained physician. We compared three groups: healthy controls, COVID+ patients with reported smell loss (COVID w/ SL) and COVID+ patients without smell loss (COVID+ w/o SL). The mean age of patients was 41.4 years (SD ± 10.4), and 54.4% were women. Smell loss was reported by 40.4% of COVID-19 patients. We observed a gradual effect with higher Q-SIT scores in healthy controls, followed by COVID+ w/o SL and COVID+ w/ SL (medians = 3, 2 and 0; respectively, p < 0.001). Anosmia or severe microsmia (Q-SIT≤1) was present in 11.1% (CI: 3.1%-26.1%) of controls, 32.4% (CI: 17.4%-50.5%) of COVID-19 w/o SL and 87% (CI: 66.4%-97.2%) of COVID+ w/ SL (p < 0.001). This study provides evidence that olfactory dysfunction in COVID-19 is common and more prevalent than what is perceived by patients. Q-SIT is a quick and reliable screening test for the detection of smell dysfunction during the pandemics.

Cardiac findings in infants with in utero exposure to Zika virus- a cross sectional study.

BACKGROUND: Antenatal exposure to Zika virus (ZIKV) is related to severe neurological manifestations. A previous study in Brazil reported an increased incidence of non-severe congenital heart defects in infants with diagnosis of congenital Zika syndrome but without laboratory confirmation of ZIKV infection in the mother or infant. The objective of this study is to report echocardiographic (ECHO) findings in infants with laboratory confirmed antenatal exposure to ZIKV. METHODOLOGY: Cross sectional study of cardiologic assessments of infants born between November 2015 and January 2017 with confirmed vertical exposure to ZIKV in Rio de Janeiro, Brazil. RESULTS: The study enrolled 120 children with a median age of 97 days (1 to 376 days). In utero exposure to ZIKV was confirmed in 97 children (80,8%) through positive maternal polymerase chain reaction (PCR) results during pregnancy or a positive PCR result at birth; 23 additional children (19.2%) had maternal positive PCR results during pregnancy and postnatally. Forty- eight infants (40%) had cardiac defects noted on ECHO. Thirteen infants (10.8%) had major cardiac defects (atrial septal defect, ventricular septal defect, patent ductus arteriosus). None of the defects were severe. The frequency of major defects was higher in infants whose mothers had a rash in the 2nd trimester of pregnancy, or who had altered Central Nervous System (CNS) imaging postnatally or were preterm. CONCLUSIONS: Infants with in utero ZIKV exposure have a higher prevalence of major cardiac defects, however none were severe enough to require immediate intervention. For this reason, guidelines for performance of postnatal ECHO in this population should follow general newborn screening guidelines, which significantly reduces the burden of performing emergent fetal or neonatal ECHOs in a setting where resources are not available, such as most Brazilian municipalities.

Comparative study of in situ hybridization, immunohistochemistry and parasitological culture for the diagnosis of canine leishmaniosis.

BACKGROUND: The establishment of an accurate diagnostic protocol for canine visceral leishmaniosis (CanL) is a significant laboratory challenge and the lack of a reliable reference standard is one of the major problems. The aim of this study was to compare in situ hybridization (ISH), immunohistochemistry (IHC) and parasitological culture (PC) for detection of L. infantum in skin, spleen, lymph node and bone marrow of clinically healthy and sick seropositive dogs. FINDINGS: The study included 65 dogs positive with both DPP® and ELISA for anti-Leishmania antibodies. In situ hybridization of spleen or lymph node had the highest positivity rates of L. infantum detection. The total positivity rates for IHC, ISH and PC were 70%, 68.1% and 65.8%, respectively. When combining techniques, the positivity rates were 81.5% in the spleen, 79.0% in lymph nodes, 59.0% in bone marrow and 52.3% in the skin. The highest percentage of infected dogs (87.7%) was detected by using lymph node samples. When examining only skin, positivity was significantly higher in sick dogs than in the clinically healthy dogs. Infection with L. infantum was confirmed in 95.8% of sick dogs and in 82.4% of healthy dogs. CONCLUSIONS: Considering the advantages of accurately diagnosing different Leishmania species and of being more sensitive than PC, ISH should be considered as reference standard test for the diagnosis of CanL. Spleen and lymph node are the most suitable tissues to confirm infection with L. infantum in seropositive dogs. The testing of only skin from clinically healthy dogs may result in a high percentage of false negative results.

Detection of serum antibodies against Bartonella species in cats with sporotrichosis from Rio de Janeiro, Brazil.

Cat scratch disease is a zoonosis caused by Bartonella species, transmitted to humans through scratches or bites from infected cats and via direct contact with infected feces. Sporotrichosis, caused by the fungal complex Sporothrix, is transmitted by traumatic inoculation of the fungus. Cats are important in zoonotic transmission. Serum samples from 112 domestic cats with sporotrichosis and 77 samples from healthy cats were analyzed by indirect immunofluorescence assay (IFA), using the commercial kit Bartonella henselae IFA IgG (Bion). The presence of antibodies against feline leukemia virus (FeLV) and of feline immunodeficiency virus (FIV) core antigens was detected using the commercial kit Snap Combo FIV-FeLV (Idexx). The group of animals with sporotrichosis contained 93 males with a median age of 22 months, eight (7.1%) of which were positive for FIV and 15 (13.4%) for FeLV. The group of animals without sporotrichosis contained 36 males with a median age 48 months, 10 (13.0%) of which were positive for FIV and eight (10.4%) for FeLV. Of the 112 cats with sporotrichosis and 77 cats without mycosis, 72 (64.3%) and 35 (45.5%), respectively, were IFA reactive. No association was found between age, sex, FIV/FeLV and the presence of antibodies to Bartonella species. The results suggest that the study population can be considered a potential source of zoonotic infection for both diseases.

Home-based exercise program in TSP/HAM individuals: a feasibility and effectiveness study / Programa de exercícios domiciliares em indivíduos com PET/MAH: um estudo de viabilidade e efetividade

Objetivo: Investigar a viabilidade e eficácia de um programa de exercícios domiciliares (PED) em indivíduos com PET/MAH. Métodos: 23 indivíduos com PET/MAH divididos em dois grupos conforme teste Timed Up and Go - TUG (<20s vs ≥20s) realizaram o PED durante 20 semanas. Desfechos primários ­ adesão aos exercícios, contração isométrica voluntária máxima dos membros inferiores (CIVM), Índice de Barthel e SF-36. Desfechos secundários ­ ocorrência de eventos adversos e presença de barreiras à prática de exercícios. Resultados: CIVM e componente "Aspectos Sociais" da SF-36 aumentaram significativamente no grupo TUG <20s. Os indivíduos do grupo TUG ≥20s aumentaram significativamente componente "Capacidade Funcional" da SF-36. A adesão ao PED foi de 90%. Foram observados eventos adversos de intensidade leve a moderada relacionados ao PED. Não foram encontrados eventos adversos relacionados à CIVM. Conclusões: O PED é viável e eficaz em melhorar a incapacidade e a qualidade de vida de indivíduos com PET/MAH.

Socioeconomic development, family income, and psychosocial risk factors: a study of families with children in public elementary school.

This article aims to evaluate the effects of Brazil's recent economic growth on the monetary income, consumption patterns, and risk exposures of families with children enrolled in the public elementary school system in São Gonçalo, Rio de Janeiro State, Brazil. The article analyzes the following information on families of 447 children that participated in two waves in a longitudinal study: social stratum, per capita family income, evolution in income over a three-year period, and psychosocial factors. The findings showed a 74.8% increase in the families' income, accompanied by an increase in the consumption of material assets and access to health services. This increase should not be interpreted as a guarantee of improved living and health conditions, since it was spent on basic products and needs that do not substantially affect the families' form of social inclusion. Psychosocial risk factors were frequent among the families, but decreased during the study period, which may either reflect the improved family situation or result from the later stage in child development.

Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World.

Pentavalent antimonials are first-line drugs for the treatment of the cutaneous form of American tegumentary leishmaniasis. Second-line drugs include amphotericin B and pentamidine. Although these drugs have been used for decades, there are no systematic reviews about their safety. The objective of this review was to identify and classify the main adverse effects associated with these drugs and to estimate the frequency of these effects, whenever possible. Intervention studies, case series and case reports containing information regarding clinical, laboratory or electrocardiographic adverse effects of drugs used for the treatment of cutaneous leishmaniasis were systematically retrieved from 10 databases searched between August 13, 2008 and March 31, 2009. The 65 studies included in this review had treated a total of 4359 patients from 12 countries infected with eight different Leishmania species. Despite the small number of drugs used in these studies, a wide variability in the therapeutic regimens was observed. As a consequence, the adverse effects of pentavalent antimonials and pentamidine needed to be classified jointly according to system, irrespective of formulation, daily dose, duration of treatment, and route of administration. The frequencies of adverse effects were calculated based on the data of 32 articles involving 1866 patients. The most frequently reported clinical adverse effects of pentavalent antimonials and pentamidine were musculoskeletal pain, gastrointestinal disturbances, and mild to moderate headache. Electrocardiographic QTc interval prolongation and a mild to moderate increase in liver and pancreatic enzymes were additional adverse effects of pentavalent antimonials. Patients treated with liposomal amphotericin B had mild dyspnea and erythema. The adverse effects associated with miltefosine were vomiting, nausea, kinetosis, headache, diarrhea, and a mild to moderate increase in aminotransferases and creatinine. Although closer surveillance is needed for the treatment of cutaneous leishmaniasis, antileishmanial drugs are basically safe and severe side effects requiring the discontinuation of treatment are relatively uncommon.

Evaluation of immunohistochemistry for the diagnosis of sporotrichosis in dogs.

The aim of this study was to apply immunohistochemistry (IHC) for the diagnosis of canine sporotrichosis and to compare this method with the Grocott's silver stain (GSS) and periodic acid Schiff (PAS) techniques. Eighty-seven dogs with sporotrichosis (group 1) and 35 with American tegumentary leishmaniosis (ATL) (group 2) were studied. The fungus was detected in group 1 by GSS, PAS and IHC. IHC was also applied to group 2 to evaluate the occurrence of cross-reactions. PAS, GSS and IHC detected yeast cells in 19.5%, 43.7% and 65.5% of the group 1 cases, respectively. The detection of intracellular antigens of Sporothrix schenckii by IHC increased the sensitivity of the histological diagnosis to 80.5%. No positive reaction was observed in ATL lesions. The results suggest that IHC may be indicated for the diagnosis of sporotrichosis because of its higher diagnostic sensitivity.

The influence of breastfeeding on children’s health, well-being and development: A theoretical and empirical review / La influencia de la lactancia materna en la salud infantil, el bienestar y el desarrollo: una revisión teórica y empírica

El objetivo fue examinar el efecto de la lactancia materna en la salud infantil, el bienestar y el desarrollo. La revisión de la literatura se acercó a varias dimensiones de la salud del niño y el desarrollo, a fin de evaluar en cuáles hay realmente beneficios de la leche materna y en cuáles no se encuentra una asociación positiva con la lactancia. La hipótesis general de la Organización Mundial de la Salud (oms) de recomendar la lactancia materna durante los primeros seis meses de vida del niño no parece estar confirmada por la literatura, ya que los estudios disponibles se centran en los efectos benéficos muy específicos de la lactancia materna. Por otra parte, las limitaciones de la literatura incluyen la existencia de resultados incongruentes y aspectos metodológicos menos sólidos que deben ser resueltos en futuras investigaciones. Dadas las implicaciones clínicas, sociales y culturales de las políticas referentes a la lactancia materna, es necesario explicar las discrepancias encontradas entre los estudios, y confirmar si la lactancia materna se correlaciona significativamente con la salud de los niños y su bienestar o si en realidad son creencias de salud.

The objective was to examine the impact of breastfeeding on children's health, well-being and development. This literature review approached several dimensions of the child's health and development, in order to assess which ones actually benefit from the maternal milk, and which dimensions do not support a positive association with breastfeeding. The general assumption of the World Health Organization (WHO) of recommending breastfeeding during the first six months of the child's life does not seem to be confirmed by the literature, since the available studies are centred in very specific beneficial effects of maternal breastfeeding. Furthermore, the limitations of the literature include the existence of incongruent results and less solid methodological aspects that should be solved in future research. Given the clinical, social and cultural implications of the politics regarding maternal breast feeding, it is necessary to explain the discrepancies found between studies, and to confirm if maternal breastfeeding is significantly correlated with the children’s health and well-being or if they actually are health beliefs.