Luis A. Marcos

Carcinogenesis associated with parasites other than Schistosoma, Opisthorchis and Clonorchis: A systematic review.

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.

Association of Fasciola hepatica Infection with Liver Fibrosis, Cirrhosis, and Cancer: A Systematic Review

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.

Cryptococcal meningoencephalitis in HIV/AIDS: when to start antiretroviral therapy?

© The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The institution of antiretroviral therapy (ART) in HIVinfected individuals with the goal of achieving virologic control and restoring immunity has led to substantial declines in AIDS-related complications, non-AIDS related morbidity, and improved survival [1]. In addition to the benefit provided at the individual level, it is also a crucial intervention to reduce HIV-transmission. Current treatment guidelines continue to emphasize early initiation of ART among individuals presenting at any stage of HIV-infection regardless of their CD4 cell count [1]. There is also an overall consensus that ART should be initiated within the first 2 weeks in individuals with advanced HIV-infection presenting with an AIDS-defining opportunistic infection with the possible exception of cryptococcal meningoencephalitis. However, the most recent update of the treatment guidelines of the International Antiviral Society-USA recommend considering ART within 2 weeks of diagnosis of cryptococcal meningoencephalitis in resource-rich settings where there is increased availability of optimal antifungal therapy (amphotericin B formulations and flucytosine); and means to monitor and aggressively treat increased intracranial pressure [1]. Worldwide, the highest burden of CNS cryptococcosis occurs in Sub-Saharan Africa and Southeast Asia, however, a substantial burden of disease occurs in highincome settings [2–4]. In the US, the Southeast has the highest rates of AIDS-associated hospitalization and mortality due to cryptococcosis [5]. Restoring immune function by the institution of ART is a crucial intervention in HIV-associated cryptococcal meningoencephalitis [2, 3]. We suggest that the timing of ART initiation should be individualized in every case considering host and fungal-related ones.

Hypothetical granulin-like molecule from Fasciola hepatica identified by bioinformatics analysis

Fasciola hepatica is considered an emergent human pathogen, causing liver fibrosis or cirrhosis, conditions that are known to be direct causes of cancer. Some parasites have been categorized by WHO as carcinogenic agents such as Opisthorchis viverrini, a relative of F. hepatica. Although these two parasites are from the same class (Trematoda), the role of F. hepatica in carcinogenesis is unclear. We hypothesized that F. hepatica might share some features with O. viverrini and to be responsible to induce proliferation of host cells. We analyzed the recently released genome of F. hepatica looking for a gene coding a granulin-like growth factor, a protein secreted by O. viverrini (Ov-GRN-1), which is a potent stimulator of proliferation of host cells. Using computational biology tools, we identified a granulin-like molecule in F. hepatica, here termed FhGLM, which has high sequence identity level to Ov-GRN-1 and human progranulin. We found evidence of an upstream promoter compatible with the expression of FhGLM. The FhGLM architecture showed to have five granulin domains, one of them, the domain 3, was homologue to Ov-GRN-1 and human GRNC. The structure of the FhGLM granulin domain 3 resulted to have the overall folding of its homologue the human GRNC. Our findings show the presence of a homologue of a potent modulator of cell growth in F. hepatica that might have, as other granulins, a proliferative action on host cells during fascioliasis. Future experimental assays to demonstrate the presence of FhGLM in F. hepatica are needed to confirm our hypothesis.

Negative serology of Fasciola hepatica infection in patients with liver cancer in Peru: a preliminary report

INTRODUCTION The etiology of several hepatocellular carcinoma (HCC) cases remains largely unknown. Although Fasciola hepatica has been associated with liver fibrosis in Latin America, it has not yet been associated with HCC. This study aimed to determine the existence of specific IgG antibodies against F. hepatica in the serum samples of HCC patients. METHODS In total, 13 serum samples from 13 HCC patients were screened using Fas2-ELISA. RESULTS Fas2-ELISA demonstrated negative results in all HCC patients included in this study. CONCLUSIONS The pre-existence of F. hepatica infection in HCC patients needs to be further investigated in epidemiological and experimental studies.

Manifestations of Mycobacterium marinum in the Immunocompromised Host

Purpose of ReviewAtypical Mycobacterium infections are occasionally encountered in clinical practice. As a result of immune function modulation in some particular populations (i.e., transplant, immunotherapies for chronic rheumatological diseases, chronic steroid therapy), there has been an increase in the number of diagnosed cases with atypical Mycobacterium, in particular M. marinum, associated with a history of exposure to natural or artificial water systems. The aim of this study is to review recent clinical presentations, risk factors, and management of M. marinum infections in immunocompromised individuals.Recent FindingsM. marinum exposure may potentially cause skin and soft tissue infections leading to important morbidity with sometimes life-threatening complications among immunocompromised hosts. The diagnosis of this infection is frequently delayed by months due to the often-atypical clinical presentations. A common immunosuppression associated with infection is TNF inhibition secondary to novel TNF inhibitors. These patients often present with infection within the nose. This atypical clinical presentation, in contrast to the classic “fish tank granuloma” hand lesion, may be related to immunosuppressive factors.SummaryIncreasing awareness of this particular nontuberculous mycobacterial infection among physicians caring for patients with potential exposure to aquatic environments may reduce the time of diagnosis to treatment and avoid further complications.

A computational assessment of the predicted structures of Human Macrophage Migration Inhibitory Factor 1 orthologs in parasites and its affinity to human CD74 receptor

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.

Historical Aspects of Endemic Trachoma in Peru: 1895–2000

Trachoma, a chronic keratoconjunctivitis caused by the intracellular bacterium Chlamydia trachomatis, is the leading infectious cause of blindness and affects the most underprivileged populations worldwide. An estimated 1.3 million people have been blinded, and there are more than 50 trachoma-endemic countries, mainly in Africa, the Middle East, and Asia [1,2]. In Latin America, countries such as Brazil, Guatemala, and Mexico have targeted the areas where trachoma has been identified, according to the Report on the Sixteenth Meeting of World Health Organization (WHO) Alliance for the Global Elimination of Trachoma by 2020 (GET 2020) [3]. Recently, Colombia has reported pockets of trachoma among indigenous populations in Vaupes, [4] San Joaquin, and Santa Catalina, and it is identifying additional areas for completeness of the data [5]. Other countries, such as Peru, Bolivia, and Venezuela, which are likely to be endemic, according to these sources, have not reported population-based estimates. This lack of trachoma assessment at the population level was noted and put on the agenda of the WHO GET 2020, a target that could not be reached without recent and well-designed studies in suspected countries. Regarding Peru, the current status of trachoma is unknown. A search of the two main e-libraries, the Medical Literature Analysis and Retrieval System Online (MEDLINE) and the Scientific Electronic Library Online (ScIELO), using keywords such as trachoma, trichiasis, and Peru, produced no articles. Only one database considered as gray literature, the Latin American Literature in the Health Sciences (Literatura Latinoamericana en Ciencias de la Salud, or LILACS), produced seven articles, all in Spanish and not referenced in any large recent reviews on blindness, trachoma, or other neglected tropical diseases in Latin America and the Caribbean. Moreover, the full versions of these articles were not available, even after institutional request. To fill this gap, we have conducted an extensive and critical historical review of the local literature and have searched all available sources of early written documentation and pictorial evidence of trachoma in Peru.

Medical Student Knowledge of Neglected Tropical Diseases in Peru: A Cross-Sectional Study.

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.