Non-Coding RNAs in the Etiology and Control of Major and Neglected Human Tropical Diseases.

Non-coding RNAs (ncRNAs) including microRNAs (miRs) and long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in immune cells development and function. Their expression is altered in different physiological and disease conditions, hence making them attractive targets for the understanding of disease etiology and the development of adjunctive control strategies, especially within the current context of mitigated success of control measures deployed to eradicate these diseases. In this review, we summarize our current understanding of the role of ncRNAs in the etiology and control of major human tropical diseases including tuberculosis, HIV/AIDS and malaria, as well as neglected tropical diseases including leishmaniasis, African trypanosomiasis and leprosy. We highlight that several ncRNAs are involved at different stages of development of these diseases, for example miR-26-5p, miR-132-3p, miR-155-5p, miR-29-3p, miR-21-5p, miR-27b-3p, miR-99b-5p, miR-125-5p, miR-146a-5p, miR-223-3p, miR-20b-5p, miR-142-3p, miR-27a-5p, miR-144-5p, miR-889-5p and miR-582-5p in tuberculosis; miR-873, MALAT1, HEAL, LINC01426, LINC00173, NEAT1, NRON, GAS5 and lincRNA-p21 in HIV/AIDS; miR-451a, miR-let-7b and miR-106b in malaria; miR-210, miR-30A-5P, miR-294, miR-721 and lncRNA 7SL RNA in leishmaniasis; and miR-21, miR-181a, miR-146a in leprosy. We further report that several ncRNAs were investigated as diseases biomarkers and a number of them showed good potential for disease diagnosis, including miR-769-5p, miR-320a, miR-22-3p, miR-423-5p, miR-17-5p, miR-20b-5p and lncRNA LOC152742 in tuberculosis; miR-146b-5p, miR-223, miR-150, miR-16, miR-191 and lncRNA NEAT1 in HIV/AIDS; miR-451 and miR-16 in malaria; miR-361-3p, miR-193b, miR-671, lncRNA 7SL in leishmaniasis; miR-101, miR-196b, miR-27b and miR-29c in leprosy. Furthermore, some ncRNAs have emerged as potential therapeutic targets, some of which include lncRNAs NEAT1, NEAT2 and lnr6RNA, 152742 in tuberculosis; MALAT1, HEAL, SAF, lincRNA-p21, NEAT1, GAS5, NRON, LINC00173 in HIV/AIDS; miRNA-146a in malaria. Finally, miR-135 and miR-126 were proposed as potential targets for the development of therapeutic vaccine against leishmaniasis. We also identify and discuss knowledge gaps that warrant for increased research work. These include investigation of the role of ncRNAs in the etiology of African trypanosomiasis and the assessment of the diagnostic potential of ncRNAs for malaria, and African trypanosomiasis. The potential targeting of ncRNAs for adjunctive therapy against tuberculosis, leishmaniasis, African trypanosomiasis and leprosy, as well as their targeting in vaccine development against tuberculosis, HIV/AIDS, malaria, African trypanosomiasis and leprosy are also new avenues to explore.

Identificación de especies micobacterianas ambientales u oportunistas en pacientes sintomáticos y con VIH/sida / Identification of environmental or opportunistic mycobacterial species in symptomatic symptomatic and HIV/AIDS patients

El aumento de las infecciones por micobacterias ambientales u oportunistas (MAO) coincide mundialmente con el declive de la infección tuberculosa e incremento de la infección por el virus de inmunodeficiencia humana (VIH). El presente trabajo es un estudio retrospectivo realizado en el Laboratorio Nacional de Referencia-Investigaciones de Tuberculosis/Micobacterias/Lepra (LNRI-TB/Lepra/Micobacterias), del Instituto de Medicina Tropical Pedro Kourí (IPK), La Habana, Cuba, durante el período enero 2014-diciembre 2018. El objetivo de nuestro estudio fue conocer la variabilidad de especies aisladas para establecer un referente actualizado sobre las infecciones causadas por estas. En este trabajo se clasificaron-identificaron 413 cepas procedentes de pacientes sintomáticos; 162 (39.22%) eran aislamientos de pacientes con VIH/sida atendidos en nuestro Hospital Nacional de Referencia a Atención al paciente VIH/sida (IPK), y el resto (n = 251 [60.77%]), procedentes de pacientes inmunocompetentes, incluyendo aislamientos recibidos de los Centros Provinciales de Higiene, Epidemiología, y Microbiología (CPHEM). Las muestras fueron analizadas con las técnicas convencionales establecidas: las pulmonares fueron descontaminadas por el método de Petroff modificado; las extrapulmonares, por el método del ácido sulfúrico al 4%; el cultivo se realizó en medio de Löwenstein-Jensen modificado. Posteriormente se realizó la clasificación-identificación de especies según el esquema fenotípico-bioquímico establecido. Las especies con mayor porcentaje de aislamiento pertenecieron a los Grupos III y IV, complejo Mycobacterium avium-intracellulare (34.14%) y complejo M. fortuitum (20.82%), respectivamente. Estos resultados permitirán conocer la prevalencia de estas especies en nuestro país, reafirmando la importancia diagnóstica de estos microorganismos para aplicar tratamiento específico, sobre todo en pacientes con factores de riesgo, en quienes es más probable la diseminación de la infección.

The increase in infections by environmental or opportunistic mycobacteria (MAO) coincides worldwide with the decline in tuberculosis infection and an increase in infection by the human immunodeficiency virus (HIV). The present work is a retrospective study carried out at the National Reference Laboratory-Tuberculosis/Mycobacterial/Leprosy Research (LNRI-TB / Leprosy / Mycobacteria), of the Pedro Kourí Institute of Tropical Medicine (IPK), La Habana, Cuba, during the period January 2014-December 2018. The objective of our study was to know the variability of isolated species to establish an updated reference on the infections caused by MAO. In this study, 413 strains from symptomatic patients were classified and identified; 162 (39.22%) were isolates from patients with HIV/AIDS treated at our National Hospital of Reference for Attention to HIV/AIDS patients (IPK), and the remaining (n=251 [60.77%]), from immunocompetent patients, including isolates received from the Provincial Centers of Hygiene, Epidemiology, and Microbiology (CPHEM). The samples were analyzed with the established conventional techniques: the lung samples were decontaminated by the modified Petroff method; the extrapulmonary, by the 4% sulfuric acid method; the culture was carried out in modified Löwenstein-Jensen medium. Subsequently, the classification-identification of species was carried out according to the established phenotypic-biochemical scheme. The species with the highest percentage of isolation belonged to Groups III and IV, Mycobacterium avium-intracellulare complex (34.14%), and M. fortuitum complex (20.82%), respectively. These results will allow us to know the prevalence of these species in our country, emphasizing the diagnostic importance of these microorganisms and thus apply a specific treatment, especially in patients with risk factors, in whom the spread of the infection is more likely

Using a clinic based creativity initiative to reduce HIV related stigma at the Infectious Diseases Institute, Mulago National Referral Hospital, Uganda.

BACKGROUND: Stigma has been associated with chronic health conditions such as HIV/AIDS, leprosy, tuberculosis, Mental illness and Epilepsy. Different forms of stigma have been identified: enacted stigma, perceived stigma, and self stigma. Stigma is increasingly regarded as a key driver of the HIV/AIDS epidemic and has a major impact on public health interventions. OBJECTIVES: The initiative was to provide activities in the clinic while patients waited to be seen by healthcare professionals. It was envisaged this would contribute to reduction of clinic based stigma felt by clients. METHODS: This was a repeated cross-sectional survey (October-November 2005 and March-April 2007) that was conducted at the Infectious Diseases Institute clinic (IDC) at Mulago, the national referral hospital in Uganda. We utilized quantitative (survey) and qualitative (key informants, focus group discussions) methods to collect the data. Data were collected on stigma before the creativity initiative intervention was implemented, and a second phase survey was conducted to assess effectiveness of the interventions. RESULTS: Clients who attended the IDC before the creativity intervention were about twice as likely to fear catching an infection as those who came after the intervention. The proportion that had fears to be seen by a friend or relative at the clinic decreased. Thus during the implementation of the Creativity intervention, HIV related stigma was reduced in this clinic setting. CONCLUSIONS: The creativity intervention helped to build self esteem and improved communication among those attending the clinic; there was observed ambiance at the clinic and clients became empowered, with creative, communication and networking skills. Improved knowledge and communication are key in addressing self stigma among HIV positive individuals.

Medical rehabilitation of leprosy patients discharged home in abia and ebonyi States of Nigeria.

OBJECTIVES: To examine the extent to which medical coverage is available to discharged leprosy patients in communities. Evidence has shown that after care services, follow-up visits and national disease prevention programs are important components of medical rehabilitation to leprosy patients discharged home after treatment. Denying them accessibility to these services could expose them to multiple disabilities as well as several disease conditions including HIV/AIDS. These adverse health conditions could be averted if health workers extend healthcare services to discharged leprosy patients. This study was conducted to examine the extent to which discharged leprosy patients have access to healthcare services in the communities. METHODS: All 33 leprosy patients who were fully treated with multi-drug therapy (MDT) and discharged home in the two leprosy settlements in Abia and Ebonyi States of Nigeria were included in this study. The list of discharged leprosy patients studied and their addresses were provided by the leprosy settlements where they were treated. Also, snowball-sampling method was used to identify some of the leprosy patients whose addresses were difficult to locate in the communities. Instruments for data collection were questionnaire, interview guide and checklist. These were administered because respondents were essentially those with no formal education. Analysis of data was done quantitatively and qualitatively. RESULTS: Findings showed that 20 (60.6%) of discharged patients did not receive health programs like HIV/AIDS prevention or family planning. Also, follow-up visits and after-care services were poor. About 14 (42.4%) of the patients live in dirty and overcrowded houses. On the whole, discharged patients were poorly medically rehabilitated (mean score: 4.7±1.1 out of total score of 7). CONCLUSION: Denying discharged leprosy patients opportunity of accessing health care services could increase prevalence of infectious diseases including HIV/AIDS among them. There is need to extend national prevention programs, follow-up visits, after-care services and free treatment to discharged patients in the communities.

Bases genéticas de la susceptibilidad a enfermedades infecciosas humanas / Genetic Basis of Susceptibility to Human Infectious Diseases

Los diferentes componentes genéticos juegan un papel importante en la determinación diferencial de la susceptibilidad a las principales enfermedades infecciosas de los humanos, tales como la malaria, la lepra, VIH/SIDA, tuberculosis y enfermedades por micobacterias, entre otras. La genética epidemiológica, incluyendo los estudios de gemelos, proporciona evidencia fuerte de que la variación genética en las poblaciones humanas contribuye a la susceptibilidad a dichas enfermedades. La genética humana de las enfermedades infecciosas ha postulado que un raro grupo de inmunodeficiencias primarias confiere vulnerabilidad a múltiples enfermedades infecciosas (un gen, múltiples infecciones), mientras que las enfermedades infecciosas comunes están asociadas con la herencia poligénica de múltiples genes de susceptibilidad (una infección, múltiples genes). Simultáneamente, se ha determinado, en varias infecciones comunes, la herencia de un gen principal de susceptibilidad, al menos en algunas poblaciones. Este nuevo paradigma (un gen, una infección) desdibuja la distinción entre la genética mendeliana basada en pacientes, y la genética de enfermedades complejas basadas en estudios de población, lo cual nos da una nueva forma de abordaje conceptual para explorar las bases moleculares de la genética de enfermedades infecciosas en los humanos.

Several genetic factors play an important role in determining differential susceptibility to major infectious diseases in human populations, such as malaria, leprosy, HIV/AIDS, tuberculosis and mycobacterial infections. Genetic epidemiology, including twin studies, provides robust evidence that genetic variation in human populations contributes to susceptibility to infectious disease. The dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). In parallel, several common infections have been shown to reflect the inheritance of one major susceptibility gene, at least in some populations. This new point of view (one gene, one infection), distort the distinction between patient-based Mendelian genetics and population-based complex genetics, and provides a unified conceptual frame for exploring the molecular genetic basis of infectious diseases in humans.