A neglected among the neglected: a review of cutaneous leishmaniasis in Guatemala.

Cutaneous leishmaniasis (CL) is a parasitic vector-borne disease affecting mostly low- and middle-income countries. CL is endemic in Guatemala, where an increase in the number of cases and incidence and a changing disease distribution in the past decade have been reported. Important research was conducted in Guatemala in the 1980s and 1990s to understand the epidemiology of CL and two Leishmania species were identified as the aetiologic agents. Several species of sand flies have been reported, five of which are naturally infected with Leishmania. Clinical trials conducted in the country evaluated different treatments against the disease and provided solid evidence for CL control strategies that are applicable worldwide. More recently, in the 2000s and 2010s, qualitative surveys were conducted to understand community perceptions of the disease and to highlight the challenges and enablers for disease control. However, limited recent data have been generated regarding the current CL situation in Guatemala, and key information necessary for effective disease control, such as incrimination of vectors and reservoirs, is still lacking. This review describes the current state of knowledge of CL in Guatemala, including the main parasite and sand fly species, disease reservoirs, diagnosis and control, as well as the perceptions of communities in endemic regions.

Optimización cardiopulmonar y de la calidad de vida en la fase de recuperación de la infección por COVID-19 a través de un programa de rehabilitación / Cardiopulmonary optimization and quality of life in the recovery phase of COVID-19 infection through a rehabilitation program

Introducción: la enfermedad por COVID-19 puede provocar una gran variedad de problemas de salud a largo plazo, como deterioro de la función pulmonar, reducción del rendimiento del ejercicio y disminución de la calidad de vida. Nuestro estudio tuvo como objetivo investigar la eficacia, viabilidad y seguridad de la rehabilitación pulmonar en pacientes con COVID-19 y comparar los resultados entre pacientes con un curso leve/moderado y grave/crítico de la enfermedad. Material y métodos: los pacientes en la fase posaguda de un curso leve a crítico de COVID-19 ingresados en un programa integral de rehabilitación pulmonar, se incluyeron en este estudio de cohorte prospectivo y observacional. Se evaluaron antes y después varias medidas de rendimiento del ejercicio, distancia de caminata de 6 minutos, función pulmonar (capacidad vital forzada (CVF)) y calidad de vida (encuesta de salud de formato corto de 36 preguntas (SF-36)). Se incluyeron 43 pacientes en el estudio (20 con COVID leve/moderado y 23 con COVID grave/crítico). Resultados: al ingreso los pacientes tenían una distancia de caminata reducida (leve: mediana 401 m, rango intercuartílico (IQR) 335-467 m; severo: 108 m, 84-132 m); una CVF deteriorada (leve: 72 %, severo: 35 %), y una puntuación baja de salud mental SF-36 (leve: 52 puntos, severo: 32 puntos. Los pacientes recibieron sesiones ajustadas a sus capacidades físicas y en ambos subgrupos mejoraron en la prueba de caminata de 6 minutos (leve/moderada: +54 m, severo/crítico: +117 m, ambos p <0.002), en CVF (leve/moderada: + 8.9 % , p = 0.004; severo/crítico: + 12.4 %, p <0.003) y en el componente mental SF-36 (leve / moderado: +6.8 puntos, p = 0.062; severo/crítico: +16.7 puntos, -p <0,005). Discusión y conclusiones: un programa de ejercicio bien estructurado resulta en un beneficio en las esferas de capacidad aeróbica, volúmenes pulmonares y calidad de vida; en tal sentido, se recomienda ampliar las muestras poblacionales para poder aplicar nuestro protocolo a otros centros encargados de la rehabilitación de pacientes con COVID-19.

Introduction: COVID-19 disease can cause a wide variety of long-term health problems, such as impaired lung function, reduced exercise performance, and decreased quality of life. Our study aimed to investigate the efficacy, feasibility, and safety of pulmonary rehabilitation in patients with COVID-19 and to compare the results between patients with a mild/moderate and severe/critical course of the disease. Materials and Methods: Patients in the post-acute phase of a mild to critical course of COVID-19 admitted to a comprehensive pulmonary rehabilitation program were included in this prospective, observational cohort study. Various measures of exercise performance, 6-minute walk distance, lung function (forced vital capacity (FVC)), and quality of life (36-question short-form health survey (SF-36)) were assessed before and after. We include 43 patients in this study (20 with mild/moderate COVID and 23 with severe/critical COVID-19). Results: At admission, patients had reduced walking distance (mild: median 401 m, interquartile range (IQR) 335-467 m; severe: 108 m, 84-132 m), impaired FVC (mild: 72%, severe: 35%,) and a low SF-36 mental health score (mild: 52 points, severe: 32 points). This patients received sessions adjusted to their physical abilities, and in both subgroups the patients improved on the walking test of 6 min (mild/moderate: +54m, severe/critical: +117m, both p < 0.002), FVC (mild/moderate: +8.9%, p=0.004; severe/critical: +12.4%, p <0.003) and mental component SF-36 (mild / moderate: +6.8 points, p = 0.062; severe / critical: +16.7 points, -p <0.005). Discussion and Conclusions: A well-structured exercise program results in a benefit in the patients' spheres of aerobic capacity, lung volumes and quality of life, in this sense it is recommended to expand population samples to be able to apply our protocol to other centers in charge of the rehabilitation of COVID 19 patients.

Púrpura trombocitopénica posterior a vacunación contra COVID-19 / Thrombocytopenic purpura following COVID-19 vaccination

Resumen Introducción: la pandemia por COVID-19 ha generado un costo inexorable a los gobiernos y una mortalidad elevada en términos generales, el proceso de vacunación es la única estrategia efectiva en disminuir la morbimortalidad en general, sin embargo, dicha administración no está exenta de riesgos. Presentación del caso: presentamos el caso clínico de una paciente de género femenino de la séptima década, quien es vacunada contra el COVID-19 y tras cuatro días posteriores a la segunda dosis de vacuna anti COVID-19, comienza a presentar lesiones purpúricas que inician en miembros inferiores y ascienden progresivamente hasta el tronco asociado a artralgias intensas, dolor abdominal y náuseas. Es ingresada encontrándose recuentos plaquetarios menores a 10 mil plaquetas y se hace el diagnóstico de una púrpura trombocitopénica inmune asociada a la vacuna de AstraZeneca contra COVID-19, iniciándose terapia inmunosupresora específica. Discusión: el presente caso constituye la aparición de una púrpura trombocitopénica idiopática, patología poco frecuente con un amplio repertorio de eventos desencadenantes encontrándose las infecciones y reacciones vacunales dentro de los principales detonantes. La presente reacción vacunal es poco frecuente siendo lo anecdótico en específico la presencia de púrpura trombocitopénica inmune, hasta el momento son muy escasas las descripciones en la literatura sobre este tipo de reacción vacunal razón por la cual se decide recopilar y publicar el mismo mencionando la evidencia científica disponible más reciente sobre el tema. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2268).

Abstract Introduction: the COVID-19 pandemic has generated an inexorable cost for governments and an elevated mortality overall. Vaccination is the only effective strategy for decreasing overall morbidity and mortality; however, this vaccination is not without risks. Case presentation: we present the clinical case of a female patient in her seventies who was vaccinated against COVID-19 and four days after the second dose of the COVID-19 vaccine developed purpuric lesions beginning on her lower limbs and ascending progressively towards the trunk, associated with intense arthralgias, abdominal pain and nausea. She was admitted with platelet counts of less than 10,000, was diagnosed with immune thrombocytopenic purpura associated with the AstraZeneca COVID-19 vaccine, and was started on specific immunosuppressive therapy. Discussion: this is a case of idiopathic thrombocytopenic purpura, a rare pathology with a broad repertoire of triggering events, with infections and vaccine reactions among the main triggers. This vaccine reaction is rare, with the specific anecdotal point being the presence of immune thrombocytopenic purpura. To date, there are very few descriptions of this type of vaccine reaction in the literature, which is why we chose to compile and publish it, mentioning the most recent scientific evidence available on the subject. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2268).

Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis.

Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they negatively impact the environment and reduce populations of insect pollinator species. Here we present a promising, environment-friendly alternative to current insecticides that targets the insect tyrosine metabolism pathway. A bloodmeal contains high levels of tyrosine, which is toxic to haematophagous insects if it is not degraded and eliminated. RNA interference (RNAi) of either the first two enzymes in the tyrosine degradation pathway (tyrosine aminotransferase (TAT) and 4-hydroxyphenylpyruvate dioxygenase (HPPD)) was lethal to tsetse. Furthermore, nitisinone (NTBC), an FDA-approved tyrosine catabolism inhibitor, killed tsetse regardless if the drug was orally or topically applied. However, oral administration of NTBC to bumblebees did not affect their survival. Using a novel mathematical model, we show that NTBC could reduce the transmission of African trypanosomiasis in sub-Saharan Africa, thus accelerating current disease elimination programmes.

Venezuela's humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region.

In the past 5-10 years, Venezuela has faced a severe economic crisis, precipitated by political instability and declining oil revenue. Public health provision has been affected particularly. In this Review, we assess the impact of Venezuela's health-care crisis on vector-borne diseases, and the spillover into neighbouring countries. Between 2000 and 2015, Venezuela witnessed a 359% increase in malaria cases, followed by a 71% increase in 2017 (411 586 cases) compared with 2016 (240 613). Neighbouring countries, such as Brazil, have reported an escalating trend of imported malaria cases from Venezuela, from 1538 in 2014 to 3129 in 2017. In Venezuela, active Chagas disease transmission has been reported, with seroprevalence in children (<10 years), estimated to be as high as 12·5% in one community tested (n=64). Dengue incidence increased by more than four times between 1990 and 2016. The estimated incidence of chikungunya during its epidemic peak is 6975 cases per 100 000 people and that of Zika virus is 2057 cases per 100 000 people. The re-emergence of many vector-borne diseases represents a public health crisis in Venezuela and has the possibility of severely undermining regional disease elimination efforts. National, regional, and global authorities must take action to address these worsening epidemics and prevent their expansion beyond Venezuelan borders.

Identification of potential protein partners that bind to the variant surface glycoprotein in Trypanosoma equiperdum.

Trypanosoma equiperdum possesses a dense coat of a variant surface glycoprotein (VSG) that is used to evade the host immune response by a process known as antigenic variation. Soluble and membrane forms of the predominant VSG from the Venezuelan T. equiperdum TeAp-N/D1 strain (sVSG and mVSG, respectively) were purified to homogeneity; and antibodies against sVSG and mVSG were raised, isolated, and employed to produce anti-idiotypic antibodies that structurally mimic the VSG surface. Prospective VSG-binding partners were initially detected by far-Western blots, and then by immunoblots using the generated anti-idiotypic antibodies. Polypeptides of ~80 and 55 kDa were isolated when anti-idiotypic antibodies-Sepharose affinity matrixes were used as baits. Mass spectrometry sequencing yielded hits with various proteins from Trypanosoma brucei such as heat-shock protein 70, tryparedoxin peroxidase, VSG variants, expression site associated gene product 6, and two hypothetical proteins. In addition, a possible interaction with a protein homologous to the glutamic acid/alanine-rich protein from Trypanosoma congolense was also found. These results indicate that the corresponding orthologous gene products are candidates for VSG-interacting proteins in T. equiperdum.

Proline Metabolism is Essential for Trypanosoma brucei brucei Survival in the Tsetse Vector.

Adaptation to different nutritional environments is essential for life cycle completion by all Trypanosoma brucei sub-species. In the tsetse fly vector, L-proline is among the most abundant amino acids and is mainly used by the fly for lactation and to fuel flight muscle. The procyclic (insect) stage of T. b. brucei uses L-proline as its main carbon source, relying on an efficient catabolic pathway to convert it to glutamate, and then to succinate, acetate and alanine as the main secreted end products. Here we investigated the essentiality of an undisrupted proline catabolic pathway in T. b. brucei by studying mitochondrial Δ1-pyrroline-5-carboxylate dehydrogenase (TbP5CDH), which catalyzes the irreversible conversion of gamma-glutamate semialdehyde (γGS) into L-glutamate and NADH. In addition, we provided evidence for the absence of a functional proline biosynthetic pathway. TbP5CDH expression is developmentally regulated in the insect stages of the parasite, but absent in bloodstream forms grown in vitro. RNAi down-regulation of TbP5CDH severely affected the growth of procyclic trypanosomes in vitro in the absence of glucose, and altered the metabolic flux when proline was the sole carbon source. Furthermore, TbP5CDH knocked-down cells exhibited alterations in the mitochondrial inner membrane potential (ΔΨm), respiratory control ratio and ATP production. Also, changes in the proline-glutamate oxidative capacity slightly affected the surface expression of the major surface glycoprotein EP-procyclin. In the tsetse, TbP5CDH knocked-down cells were impaired and thus unable to colonize the fly's midgut, probably due to the lack of glucose between bloodmeals. Altogether, our data show that the regulated expression of the proline metabolism pathway in T. b. brucei allows this parasite to adapt to the nutritional environment of the tsetse midgut.

Variant surface glycoproteins from Venezuelan trypanosome isolates are recognized by sera from animals infected with either Trypanosoma evansi or Trypanosoma vivax.

Salivarian trypanosomes sequentially express only one variant surface glycoprotein (VSG) on their cell surface from a large repertoire of VSG genes. Seven cryopreserved animal trypanosome isolates known as TeAp-ElFrio01, TEVA1 (or TeAp-N/D1), TeGu-N/D1, TeAp-Mantecal01, TeGu-TerecayTrino, TeGu-Terecay03 and TeGu-Terecay323, which had been isolated from different hosts identified in several geographical areas of Venezuela were expanded using adult albino rats. Soluble forms of predominant VSGs expressed during the early infection stages were purified and corresponded to concanavalin A-binding proteins with molecular masses of 48-67 kDa by sodium dodecyl sulfate-polyacrylamide gel electropohoresis, and pI values between 6.1 and 7.5. The biochemical characterization of all purified soluble VSGs revealed that they were dimers in their native form and represented different gene products. Sequencing of some of these proteins yielded peptides homologous to VSGs from Trypanosoma (Trypanozoon) brucei and Trypanosoma (Trypanozoon) evansi and established that they most likely are mosaics generated by homologous recombination. Western blot analysis showed that all purified VSGs were cross-reacting antigens that were recognized by sera from animals infected with either T. evansi or Trypanosoma (Dutonella) vivax. The VSG glycosyl-phosphatidylinositol cross-reacting determinant epitope was only partially responsible for the cross-reactivity of the purified proteins, and antibodies appeared to recognize cross-reacting conformational epitopes from the various soluble VSGs. ELISA experiments were performed using infected bovine sera collected from cattle in a Venezuelan trypanosome-endemic area. In particular, soluble VSGs from two trypanosome isolates, TeGu-N/D1 and TeGu-TeracayTrino, were recognized by 93.38% and 73.55% of naturally T. vivax-infected bovine sera, respectively. However, approximately 70% of the sera samples did not recognize all seven purified proteins. Hence, the use of a combination of various VSGs for the diagnosis of animal trypanosomosis is recommended.

Physiological androgen insensitivity of the fetal, neonatal, and early infantile testis is explained by the ontogeny of the androgen receptor expression in Sertoli cells.

CONTEXT: Although gonadotropins and testosterone are high in the fetal/early postnatal periods, Sertoli cells remain immature and spermatogenesis does not progress. We hypothesized that Sertoli cells do not respond to testosterone because they do not express the androgen receptor. OBJECTIVE: The objective of the study was to describe the precise ontogeny of androgen receptor expression in the human testis from fetal life through adulthood. DESIGN: This was an immunohistochemical study on testicular biopsies from fetal, neonatal, prepubertal, pubertal, and adult human testes. MAIN OUTCOME MEASURES: Quantification of androgen receptor expression in Sertoli cells was measured. Evaluation of androgen receptor expression in peritubular and interstitial cells as well as anti-Müllerian hormone and inhibin-alpha was also performed. RESULTS: Androgen receptor expression was first observed in the nuclei of few Sertoli cells at the age of 5 months. Labeling was weak in 2-15% of Sertoli cells until 4 yr of age and progressively increased thereafter. High levels of androgen receptor expression were observed in more than 90% from the age of 8 yr through adulthood. Androgen receptor was positive in peritubular cells and variable in interstitial cells. Anti-Müllerian hormone immunolabeling was strong in all Sertoli cells from fetal life throughout prepuberty and weakened progressively as spermatogenesis developed. Inhibin-alpha expression was detected in all Sertoli cells from fetal life through adulthood. CONCLUSIONS: A lack of androgen receptor expression could explain a physiological Sertoli cell androgen insensitivity during fetal and early postnatal life, which may serve to protect the testis from precocious Sertoli cell maturation, resulting in proliferation arrest and spermatogenic development.