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The prevalence of soil-transmitted helminths (STH) is high in communities within the Peruvian Amazon despite repeated mass-drug administration, demanding alternative strategies of control. Smartphone-attached microscopy (SAM) permits visualization of STH from a small portable microscope through a smartphone screen, potentially providing an inexpensive and rapid method of STH visualization in communities where diagnostic laboratories with microscopes are inaccessible. In this study, a total of 45 community health workers who work within the health systems of Loreto, Peru, attended a 1-day training session with lectures and practicums on STH and SAM. Participants received a pre- and post-intervention questionnaire. Post-intervention, participants were significantly more confident using SAM and identifying parasite images, symptoms, transmission, and treatment (P ≤ 0.0045). Post-intervention, participants correctly labeled a median of five of seven SAM apparatus components and five of eight steps of Kato-Katz technique, were less likely to choose taking medicine to prevent parasite infection (P = 0.0075), and were more likely to select Kato-Katz technique as a type of diagnostic test (P < 0.0001). Most participants felt ready to use SAM in their communities and stated that it could help rural communities far from health centers or laboratories (24%); provide faster identification, results, diagnosis (19%); permit at-home or on-the-spot visualization (14%); and save money (14%). Results show that community health workers show a high level of willingness and competency to learn about both STH and SAM and may be a yet-unexplored practical method of augmenting STH visualization, bringing healthcare to communities in Loreto with poor access to diagnostic laboratories and clinics.

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OBJECTIVE: The aim of the study was to describe the clinicopathological profile of patients diagnosed with liver, bile ducts or gallbladder cancer. MATERIALS AND METHODS: Between 2006 and 2017, 89 patients (57% female; mean age: 62 years-old) with these cancers were diagnosed at two national hospitals in Lima, Peru. RESULTS: Most patients (64%) had advanced stages of disease. Anemia was more frequent in patients with bile duct and liver cancer and in advanced stages. Hypertension (HTN) was frequent among liver cancer patients (32%). The analysis by age showed that HTN was more frequent in patients over 50 years. Likewise, people under 50 years had more frequent history of previous infections (50%), Hepatitis B (HBV) being the most common. CONCLUSIONS: This study describes the baseline clinicopathological characteristics of a malignancy poorly studied in Peru.

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RESUMEN Objetivo: El objetivo del estudio fue describir las características clínico-patológicas de individuos diagnosticados de cáncer de hígado, vías biliares o vesícula. Materiales y métodos: Entre el 2006 y 2017, se diagnosticaron 89 pacientes (57% mujeres; media: 62 años) con estos canceres en dos hospitales nacionales de Lima, Perú. Resultados: Los resultados mostraron que, independientemente del tipo de cáncer, 64% de los participantes habían sido diagnosticados en estadios avanzados. La anemia fue más frecuente en los pacientes con cáncer de vías biliares e hígado y en estadios avanzados. Se observó mayor frecuencia (32%) de hipertensión arterial (HTA) en el grupo con cáncer de hígado. El análisis por edad mostró que en los pacientes mayores de 50 años la HTA fue más frecuente. Asimismo, sujetos menores de 50 años reportaron antecedentes de infecciones previas en mayor frecuencia (50%), siendo Hepatitis B (HBV) la más común. Conclusiones: Este estudio describe las características clínico-patológicas de base de una neoplasia poco estudiada en el ámbito nacional.

ABSTRACT Objective: The aim of the study was to describe the clinicopathological profile of patients diagnosed with liver, bile ducts or gallbladder cancer. Materials and methods: Between 2006 and 2017, 89 patients (57% female; mean age: 62 years-old) with these cancers were diagnosed at two national hospitals in Lima, Peru. Results: Most patients (64%) had advanced stages of disease. Anemia was more frequent in patients with bile duct and liver cancer and in advanced stages. Hypertension (HTN) was frequent among liver cancer patients (32%). The analysis by age showed that HTN was more frequent in patients over 50 years. Likewise, people under 50 years had more frequent history of previous infections (50%), Hepatitis B (HBV) being the most common. Conclusions: This study describes the baseline clinicopathological characteristics of a malignancy poorly studied in Peru.

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Liver flukes Fasciola hepatica, Opisthorchis viverrini and Clonorchis sinensis are causing agents of liver and hepatobiliary diseases. A remarkable difference between such worms is the fact that O. viverrini and C. sinensis are carcinogenic organisms whereas F. hepatica is not carcinogenic. The release of secretory factors by carcinogenic flukes seems to contribute to cancer development however if some of these target the host cell nuclei is unknown. We investigated the existence of O. viverrini and C. sinensis secretory proteins that target the nucleus of host cells and compared these with the corresponding proteins predicted in F. hepatica. Here we applied an algorithm composed by in silico approaches that screened and analyzed the potential genes predicted from genomes of liver flukes. We found 31 and 22 secretory proteins that target the nucleus of host cells in O. viverrini and C. sinensis, respectively, and that have no homologs in F. hepatica. These polypeptides have enriched the transcription initiation process and nucleic acid binding in O. viverrini and C. sinensis, respectively. In addition, other 11 secretory proteins of O. viverrini and C. sinensis, that target the nucleus of host cells, had F. hepatica homologs, have enriched RNA processing function. In conclusion, O. viverrini and C. sinensis have 31 and 22 genes, respectively, that may be involved in their carcinogenic action through a direct targeting on the host cell nuclei.

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OBJECTIVES: Triclabendazole (TCBZ) is the recommended anthelmintic against Fasciola hepatica at a dose of 10 mg/kg body weight administered as a single or double dose. However, treatment failures to TCBZ standard-of-care (SOC) doses have been reported in humans. The aim of this study was to describe the effectiveness and tolerability of alternative TCBZ regimens in those patients who failed the SOC regimen for fascioliasis in Peru. METHODS: A retrospective study was conducted at a major referral centre for fascioliasis in Peru between 2002 and 2018. Inclusion criteria were cases with chronic F. hepatica infection who failed the SOC regimen for human fascioliasis with TCBZ at 10 mg/kg orally as single dose with food. RESULTS: A total of 27 cases (59% female; mean age 39.4 years, range 6-71 years) with chronic fascioliasis failed at least once the current SOC regimen of TCBZ. Of 27 cases, 21 failed a second treatment regimen. Multiple regimens of TCBZ were given to these patients until three consecutive stool examinations were negative for Fasciola eggs. The overall cure rate was 74%. TCBZ was well tolerated with minimal side effects. CONCLUSION: According to the results of this study, patients labelled as having 'TCBZ resistance' may respond to multiple regimens of TCBZ with a cure rate of 74%. Thus, the term 'TCBZ resistance' should be re-evaluated using biomarkers.

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BACKGROUND: Previous studies suggest that medical students may have higher rates of irritable bowel syndrome as compared to the general population. We hypothesized lifestyle characteristics may be associated to irritable bowel syndrome. METHODS: A cross-sectional survey was conducted in 2015 among students in their fourth, fifth, sixth and seven years of a medical school in Peru. Volunteer participants responded to questions pertaining to demographics, surveys including the Rome III criteria and the Self-reported Stress questionnaire. Regression models were performed to establish variables independently associated with irritable bowel syndrome. RESULTS: Out of 452 students, 346 responded the survey (response rate: 76.5%; female rate: 47%; median age: 22 years). The irritable bowel syndrome prevalence in respondents was 9.5% (95% confidence interval: 6.7%-13.1%). On univariate analysis, being a senior medical student (odds ratio: 2.8; 95% confidence interval: 1.3-5.9; P < 0.01), mental illness (odds ratio: 3.3; 95% confidence interval: 1.6-6.8; P = 0.002), psychiatric medication use (odds ratio: 2.8; 95% confidence interval: 1.4-5.9; P = 0.005), sedentary lifestyle (odds ratio: 4.4; 95% confidence interval: 1.8-11; P = 0.001) and stress (odds ratio: 4.4; 95% confidence interval: 2.1-9.3; P < 0.001) were associated to irritable bowel syndrome. On a multivariate analysis, a sedentary lifestyle (odds ratio: 3.2; 95% confidence interval: 1.25-8.20; P = 0.01) and stress (odds ratio: 3.0; 95% confidence interval: 1.35-6.67; P < 0.01) were independently associated with irritable bowel syndrome. CONCLUSION: The prevalence of irritable bowel syndrome in medical students from Peru is slightly lower compared to the global prevalence of irritable bowel syndrome. Stress and a sedentary lifestyle were independent risk factors associated with irritable bowel syndrome. Our study suggests that lifestyle modifications and stress coping techniques could have an impact to reduce the rates of irritable bowel syndrome in medical students.

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Children in the Peruvian Amazon Basin are at risk of soil-transmitted helminths (STH) infections. This study aimed to determine the prevalence of STH infection in children from a rural Amazonian community of Peru and to elucidate epidemiological risk factors associated with its perpetuation while on a school-based deworming program with mebendazole. Stool samples of children aged 2-14 years and their mothers were analyzed through direct smear analysis, Kato-Katz, spontaneous sedimentation in tube, Baermann's method, and agar plate culture. A questionnaire was administered to collect epidemiological information of interest. Among 124 children, 25.8% had one or more STH. Individual prevalence rates were as follows: Ascaris lumbricoides, 16.1%; Strongyloides stercoralis, 10.5%; hookworm, 1.6%; and Trichuris trichiura, (1.6%). The prevalence of common STH (A. lumbricoides, T. trichiura, and hookworm) was higher among children aged 2-5 years than older children (31.6% versus 12.8%; P = 0.01). In terms of sanitation deficits, walking barefoot was significantly associated with STH infection (OR = 3.28; CI 95% = 1.11-12.07). Furthermore, STH-infected children more frequently had a mother who was concomitantly infected by STH than the non-STH-infected counterpart (36.4% versus 14.1%, P = 0.02). In conclusion, STH infection is highly prevalent in children from this Amazonian community despite routine deworming. Institutional health policies may include hygiene and sanitation improvements and screening/deworming of mothers to limit the dissemination of STH. Further studies are needed to address the social and epidemiological mechanics perpetuating these infections.

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Fascioliasis is an infectious parasitic disease distributed globally and caused by the liver fluke Fasciola hepatica or F. gigantica This neglected tropical disease affects both animals and humans, and it represents a latent public health problem due to the significant economic losses related to its effects on animal husbandry. For decades, triclabendazole has been the unique anti-Fasciola drug that can effectively treat this disease. However, triclabendazole resistance in fascioliasis has more recently been reported around the world, and thus, the discovery of novel drugs is an urgent need. The aim of this study was to investigate the fasciocidal properties of 400 compounds contained in the Pathogen Box. The first stage of the screening was carried out by measuring the fasciocidal activity on metacercariae at a concentration of 33 µM each compound (the standard dose). Subsequently, the activities of the most active compounds (n = 33) at their 50% inhibitory concentration (IC50) values against metacercariae were assayed, and the results showed that 13 compounds had IC50s of ≤10 µM. The second stage queried the activities of these compounds at 33 µM against adult flukes, with seven of the compounds producing high mortality rates of >50%. Four hit compounds were selected on the basis of their predicted nontoxic properties, and the IC50 values obtained for adult worms were <10 µM; thus, these compounds represented the best fasciocidal compounds tested here. A cytotoxicity assay on four types of cell lines demonstrated that three compounds were nontoxic at their most active concentration. In conclusion, three hit compounds identified in this proof-of-concept study are potential candidates in the discovery of new fasciocidal drugs. Further studies are warranted.

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Humans encounter mycobacterial species due to their ubiquity in different environmental niches. In many individuals, pathogenic mycobacterial species may breach our first-line barrier defenses of the innate immune system and modulate the activation of phagocytes to cause disease of the respiratory tract or the skin and soft tissues, sometimes resulting in disseminated infection. Cutaneous mycobacterial infections may cause a wide range of clinical manifestations, which are divided into four main disease categories: (i) cutaneous manifestations of Mycobacterium tuberculosis infection, (ii) Buruli ulcer caused by Mycobacterium ulcerans and other related slowly growing mycobacteria, (iii) leprosy caused by Mycobacterium leprae and Mycobacterium lepromatosis, and (iv) cutaneous infections caused by rapidly growing mycobacteria. Clinically, cutaneous mycobacterial infections present with widely different clinical presentations, including cellulitis, nonhealing ulcers, subacute or chronic nodular lesions, abscesses, superficial lymphadenitis, verrucous lesions, and other types of findings. Mycobacterial infections of the skin and subcutaneous tissue are associated with important stigma, deformity, and disability. Geography-based environmental exposures influence the epidemiology of cutaneous mycobacterial infections. Cutaneous tuberculosis exhibits different clinical phenotypes acquired through different routes, including via extrinsic inoculation of the tuberculous bacilli and dissemination to the skin from other sites, or represents hypersensitivity reactions to M. tuberculosis infection. In many settings, leprosy remains an important cause of neurological impairment, deformity, limb loss, and stigma. Mycobacterium lepromatosis, a mycobacterial species related to M. leprae, is linked to diffuse lepromatous leprosy of Lucio and Latapí. Mycobacterium ulcerans produces a mycolactone toxin that leads to subcutaneous tissue destruction and immunosuppression, resulting in deep ulcerations that often produce substantial disfigurement and disability. Mycobacterium marinum, a close relative of M. ulcerans, is an important cause of cutaneous sporotrichoid nodular lymphangitic lesions. Among patients with advanced immunosuppression, Mycobacterium kansasii, the Mycobacterium avium-intracellulare complex, and Mycobacterium haemophilum may cause cutaneous or disseminated disease. Rapidly growing mycobacteria, including the Mycobacterium abscessus group, Mycobacterium chelonei, and Mycobacterium fortuitum, are increasingly recognized pathogens in cutaneous infections associated particularly with plastic surgery and cosmetic procedures. Skin biopsies of cutaneous lesions to identify acid-fast staining bacilli and cultures represent the cornerstone of diagnosis. Additionally, histopathological evaluation of skin biopsy specimens may be useful in identifying leprosy, Buruli ulcer, and cutaneous tuberculosis. Molecular assays are useful in some cases. The treatment for cutaneous mycobacterial infections depends on the specific pathogen and therefore requires a careful consideration of antimicrobial choices based on official treatment guidelines.

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The human macrophage migration inhibitory factor 1 (Hu-MIF-1) is a protein involved in the inflammatory and immunology response to parasite infection. In the present study, the existence of Hu-MIF-1 from parasites have been explored by mining WormBase. A total of 35 helminths were found to have Hu-MIF-1 homologs, including some parasites of importance for public health. Physicochemical, structural, and biological properties of Hu-MIF-1 were compared with its orthologs in parasites showing that most of these are secretory proteins, with positive net charge and presence of the Cys-Xaa-Xaa-Cys motif that is critical for its oxidoreductase activity. The inhibitor-binding site present in Hu-MIF-1 is well conserved among parasite MIFs suggesting that Hu-MIF inhibitors may target orthologs in pathogens. The binding of Hu-MIF-1 to its cognate receptor CD74 was predicted by computer-assisted docking, and it resulted to be very similar to the predicted complexes formed by parasite MIFs and human CD74. More than 1 plausible conformation of MIFs in the extracellular loops of CD74 may be possible as demonstrated by the different predicted conformations of MIF orthologs in complex with CD74. Parasite MIFs in complex with CD74 resulted with some charged residues oriented to CD74, which was not observed in the Hu-MIF-1/CD74 complex. Our findings predict the binding mode of Hu-MIF-1 and orthologs with CD74, which can assist in the design of novel MIF inhibitors. Whether the parasite MIFs function specifically subvert host immune responses to suit the parasite is an open question that needs to be further investigated. Future research should lead to a better understanding of parasite MIF action in the parasite biology.

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BACKGROUND: Fascioliasis has been sporadically associated with chronic liver disease on previous studies. In order to describe the current evidence, we carried out a systematic review to assess the association between fascioliasis with liver fibrosis, cirrhosis and cancer. METHODOLOGY AND PRINCIPAL FINDINGS: A systematic search of electronic databases (PubMed, LILACS, Scopus, Embase, Cochrane, and Scielo) was conducted from June to July 2015 and yielded 1,557 published studies. Among 21 studies that met inclusion and exclusion criteria, 12 studies explored the association of F. hepatica with liver fibrosis, 4 with liver cirrhosis, and 5 with cancer. Globally these studies suggested the ability of F. hepatica to promote liver fibrosis and cirrhosis. The role of F. hepatica in cancer is unknown. Given the heterogeneity of the studies, a meta-analysis could not be performed. CONCLUSIONS: Future high-quality studies are needed to determine the role of F. hepatica on the development of liver fibrosis, liver cirrhosis, and cancer in humans.

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Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder of uncertain etiology. Several studies have proposed the possible role of intestinal parasites in the pathogenesis of IBS. We aimed to summarize the epidemiological studies that describe a possible link between intestinal parasites and IBS, with special interest in endemic areas for intestinal parasitism such as South America. A comprehensive review of the literature was conducted by using the keywords: irritable bowel syndrome, intestinal parasites, protozoan infection, soil-transmitted helminths and South America. Giardia lamblia may cause IBS symptoms that can persist several years after effective treatment. Dientamoeba fragilis can cause IBS-like symptoms, but low sensitive parasitological techniques may fail to detect it. Entamoeba histolytica can cause a chronic non-dysenteric colitis, but several studies have failed to find an association with IBS. The role of Blastocystis hominis in IBS remains controversial. In addition, epidemiological studies evaluating the effect of soil-transmitted helminths in IBS are scant. Symptoms elicited by intestinal parasites may resemble to those in IBS, especially in endemic areas such as South America, where both the prevalence of IBS and intestinal parasitism are high. Whether these organisms are the cause or contributing factors in IBS remains a subject of study. Routine parasitologicalexamination of stools in individuals who full-fit the criteria for IBS should be included upon initial assessment in endemic countries.

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La fasciolosis humana es prevalente en zonas ganaderas del Perú. La única droga efectiva para tratar a la infección por Fasciola hepatica en la práctica clínica es el triclabendazole (TCBZ). Sin embargo, se ha reportado recientemente resistencia de la F. hepatica al TCBZ en Perú tanto en humanos como en animales. Este problema ya se sospechaba anteriormente en vista que una dosis única de triclabendazole no curaba (eliminación de huevos de Fasciola en heces) en algunos pacientes. Aquí reportamos 11 de 12 casos humanos infectados por F. hepatica que no respondieron a dosis única de TCBZ 10 mg/kg vía oral. En vista de estos resultados observados en la práctica clínica, recomendamos considerar por lo menos dos dosis de TCBZ para los infectados. Creemos que el tratamiento de fasciolosis se ha convertido en un problema emergente desde el punto de vista farmacológico. Se necesitan nuevos regímenes de terapia o drogas contra F. hepática

Human fascioliasis is prevalent in cattle raising areas in Peru. The only effective drug against Fasciola hepatica infections in clinical practice is triclabendazole (TCBZ). However, the occurrence of TCBZ-resistant F. hepatica both in humans and animals has recently been reported in Peru. This issue was previously suspected, due to treatment failure (presence of Fasciola eggs after treatment) in some patients receiving a single dose of TCBZ. Here, we report 11 of 12 human cases infected by F. hepatica who did not respond to TCBZ administered in a single 10 mg/Kg oral dose. Given these results observed in clinical practice, we recommend the use of at least two doses of TCBZ for human fascioliasis. Nowadays, the treatment for fascioliasis has become an emergent problem from the pharmacological point of view. New therapies against Fasciola are urgently needed

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Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder of uncertain etiology. Several studies have proposed the possible role of intestinal parasites in the pathogenesis of IBS. We aimed to summarize the epidemiological studies that describe a possible link between intestinal parasites and IBS, with special interest in endemic areas for intestinal parasitism such as South America. A comprehensive review of the literature was conducted by using the keywords: irritable bowel syndrome, intestinal parasites, protozoan infection, soil-transmitted helminths and South America. Giardia lamblia may cause IBS symptoms that can persist several years after effective treatment. Dientamoeba fragilis can cause IBS-like symptoms, but low sensitive parasitological techniques may fail to detect it. Entamoeba histolytica can cause a chronic non-dysenteric colitis, but several studies have failed to find an association with IBS. The role of Blastocystis hominis in IBS remains controversial. In addition, epidemiological studies evaluating the effect of soil-transmitted helminths in IBS are scant. Symptoms elicited by intestinal parasites may resemble to those in IBS, especially in endemic areas such as South America, where both the prevalence of IBS and intestinal parasitism are high. Whether these organisms are the cause or contributing factors in IBS remains a subject of study. Routine parasitological examination of stools in individuals who full-fit the criteria for IBS should be included upon initial assessment in endemic countries...

El Síndrome de intestino irritable (SII) es un desorden gastrointestinal funcional de etiología incierta. Muchos estudios han propuesto que los parásitos intestinales pueden tener un rol en la patogénesis del SII. Se sintetizó estudios epidemiológicos que describen una relación posible entre el parasitismo intestinal y el SII, con especial interés en aquellos estudios que fueron realizados en zonas endémicas para dichos organismos. Se realizó una revisión extensa de la literatura por medio de las siguientes palabras clave: síndrome de intestino irritable; parásitos intestinales; protozoarios; helmintos y Sud-América. Giardia lamblia puede causar síntomas similares al SII que pueden persistir por muchos años, después de tratamiento efectivo. Dientamoeba fragilis puede causar un cuadro similar al SII, pero al emplearse técnicas de baja sensibilidad, se puede fallar en detectar su presencia. Entamoeba histolytica puede causar un cuadro de colitis no disentérica, pero varios estudios no han podido encontrar una relacion con el SII. El rol del Blastocystis hominis en el SII sigue siendo controversial. Adicionalmente, los estudios epidemiológicos evaluando el efecto de los helmintos en el SII son escazos. Los parásitos intestinales pueden causar síntomas que pueden parecerse a los que se encuentran en pacientes con SII. Ésta observación merece especial atención en regiones como Sud-América, donde las prevalencias del SII y del parasitismo intestinal han sido estimadas como altas. Si es que éstos organismos son la causa o un factor contributor en el SII, aún es materia de estudio. En la evaluación inicial de un probable caso de SII, los estudios parasitológicos pueden ser necesarios, especialmente en áreas endémicas...

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Only three helminths (Schistosoma haematobium, Opisthorchis viverrini and Clonorchis sinensis) are directly associated with carcinogenesis in humans whereas the role of other parasites in cancer remains unclear. This study aimed to perform a systematic review to identify recent insights in the role of other parasite infections in carcinogenesis. We conducted systematic searches of MEDLINE and EMBASE on July 2015. Our primary outcome was the association between parasitic infections and carcinogenesis. Out of 1,266 studies, 19 were selected for detailed evaluation (eight for helminths and 11 for protozoa). The mechanisms of helminth-induced cancer included chronic inflammation, sustained proliferation, modulation of the host immune system, reprogramming of glucose metabolism and redox signaling, induction of genomic instability and destabilization of suppressor tumor proteins, stimulation of angiogenesis, resisting cell death, and activation of invasion and metastasis. In addition to the current knowledge, the following parasites were found in cancers or tumors: Echinococcus, Strongyloides, Fasciola, Heterakis, Platynosomum and Trichuris. Additional parasites were found in this systematic review that could potentially be associated with cancers or tumors but further evidence is needed to elaborate a cause-effect relationship.

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In developing countries, education to health-care professionals is a cornerstone in the battle against neglected tropical diseases (NTD). Studies evaluating the level of knowledge of medical students in clinical and socio-demographic aspects of NTD are lacking. Therefore, a cross-sectional study was conducted among students from a 7 year-curriculum medical school in Peru to assess their knowledge of NTD by using a pilot survey comprised by two blocks of 10 short questions. Block I consisted of socio-demographic and epidemiological questions whereas block II included clinical vignettes. Each correct answer had the value of 1 point. Out of 597 responders (response rate: 68.4%), 583 were considered to have valid surveys (male:female ratio: 1:1.01; mean age 21 years, SD ± 2.42). Total knowledge showed a raising trend through the 7-year curriculum. Clinical knowledge seemed to improve towards the end of medical school whereas socio-demographic and epidemiological concepts only showed progress the first 4 years of medical school, remaining static for the rest of the curricular years (p = 0.66). Higher mean scores in socio-demographic and epidemiological knowledge compared to clinical knowledge were seen in the first two years (p<0.001) whereas the last three years showed higher scores in clinical knowledge (p<0.001). In conclusion, students from this private medical school gained substantial knowledge in NTD throughout the career which seems to be related to improvement in clinical knowledge rather than to socio-demographic and epidemiological concepts. This study assures the feasibility of measuring the level of knowledge of NTD in medical students and stresses the importance of evaluating education on NTD as it may need more emphasis in epidemiological concepts, especially at developing countries such as Peru where many people are affected by these preventable and treatable diseases.

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