Neglected infectious diseases in the geriatrics

Infectious diseases in the elderly population pose a significant threat to their lives. Neglected tropical diseases significantly impact the health of the affected patients and populations at risk. Reports show that many of these disorders are among the highest ten most typical causes of disability-adjusted life years. In the present literature review, we have discussed the most common neglected tropical infections in geriatrics based on data from the current studies in the literature. Different infections can affect the geriatric population. However, evidence shows that this population is susceptible to developing severe disease-related conditions. This has been reported with dengue infection, onchocerciasis, and cholera. It has been demonstrated that ocular lesions and other clinical manifestations are highest among the elderly population with onchocerciasis. Severe dengue and dengue hemorrhagic fever are also reported at a high rate in this age group. Concurrent infections and disorders were documented with many of these infections, probably due to reduced immunity. Socioeconomic factors, co-morbidities, access to healthcare settings, environmental factors, sanitation, clustering, and overcrowding contribute to the frequency of neglected tropical diseases in the elderly. Further studies are still needed because the current report is scarce, which might underestimate the current evidence.

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Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease

Viruses ◽

10.3390/v13081540 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1540

Author(s):

Beatriz Sierra ◽

Ana Cristina Magalhães ◽

Daniel Soares ◽

Bruno Cavadas ◽

Ana B. Perez ◽

...

Keyword(s):

Receptor Antagonist ◽

Dengue Fever ◽

In Silico ◽

Serotonin Receptor ◽

Neglected Tropical Diseases ◽

Dengue Infection ◽

Severe Dengue ◽

Functional Evaluation ◽

Atpase Inhibitor ◽

Serotonin Receptor Antagonist

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico–informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, “Adrenergic receptor antagonist”, “ATPase inhibitor”, “NF-kB pathway inhibitor” and “Serotonin receptor antagonist”, were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.

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Genomic and phenotypic characterization of experimentally selected resistant Leishmania donovani reveals a role for dynamin-1 like protein in the mechanism of resistance to a novel anti-leishmanial compound

10.1101/2021.01.05.425522 ◽

2021 ◽

Author(s):

Aya Hefnawy ◽

Gabriel Negreira ◽

Marlene Jara ◽

James A. Cotton ◽

Ilse Maes ◽

...

Keyword(s):

Drug Resistance ◽

Visceral Leishmaniasis ◽

Infectious Diseases ◽

Leishmania Donovani ◽

Neglected Tropical Diseases ◽

Arms Race ◽

Etiological Agent ◽

Phenotypic Characterization ◽

Tropical Diseases

AbstractThe implementation of prospective drug resistance (DR) studies in the R&D pipelines is a common practice for many infectious diseases, but not for Neglected Tropical Diseases. Here, we explored and demonstrated the importance of this approach, using as paradigms Leishmania donovani, the etiological agent of Visceral Leishmaniasis (VL), and TCMDC-143345, a promising compound of the GSK ‘Leishbox’ to treat VL. We experimentally selected resistance to TCMDC-143345 in vitro and characterized resistant parasites at genomic and phenotypic levels. We found that it took more time to develop resistance to TCMDC-143345 than to other drugs in clinical use and that there was no cross resistance to these drugs, suggesting a new and unique mechanism. By whole genome sequencing, we found two mutations in the gene encoding the L. donovani dynamin-1-like protein (LdoDLP1) that were fixed at highest drug pressure. Through phylogenetic analysis, we identified LdoDLP1 as a family member of the dynamin-related proteins, a group of proteins that impacts the shapes of biological membranes by mediating fusion and fission events, with a putative role in mitochondrial fission. We found that L. donovani lines genetically engineered to harbor the two identified LdoDLP1 mutations were resistant to TCMDC-143345 and displayed altered mitochondrial properties. By homology modeling, we showed how the two LdoDLP1 mutations may influence protein structure and function. Taken together, our data reveal a clear involvement of LdoDLP1 in the adaptation/resistance of L. donovani to TCMDC-143345.ImportanceHumans and their pathogens are continuously locked in a molecular arms race during which the eventual emergence of pathogen drug resistance (DR) seems inevitable. For neglected tropical diseases (NTDs), DR is generally studied retrospectively, once it has already been established in clinical settings. We previously recommended to keep one step ahead in the host-pathogen arms race and implement prospective DR studies in the R&D pipeline, a common practice for many infectious diseases, but not for NTDs. Here, using Leishmania donovani, the etiological agent of Visceral Leishmaniasis (VL), and TCMDC-143345, a promising compound of the GSK ‘Leishbox’ to treat VL, as paradigms, we experimentally selected resistance to the compound and proceeded to genomic and phenotypic characterization of DR parasites. The results gathered in the present study suggest a new DR mechanism involving the L. donovani dynamin-1 like protein (LdoDLP1) and demonstrate the practical relevance of prospective DR studies.

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How can monoclonal antibodies be harnessed against neglected tropical diseases and other infectious diseases?

Expert Opinion on Drug Discovery ◽

10.1080/17460441.2019.1646723 ◽

2019 ◽

Vol 14 (11) ◽

pp. 1103-1112 ◽

Cited By ~ 4

Author(s):

Andreas H. Laustsen

Keyword(s):

Monoclonal Antibodies ◽

Infectious Diseases ◽

Neglected Tropical Diseases ◽

Tropical Diseases

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Community acquired infections in elderly population

Open Medicine ◽

10.2478/s11536-008-0072-4 ◽

2009 ◽

Vol 4 (2) ◽

pp. 171-178

Author(s):

Yasar Kucukardali ◽

Oral Oncul ◽

Erdogan Kunter ◽

Vedat Turhan ◽

Emrullah Solmazgul ◽

...

Keyword(s):

Infectious Diseases ◽

Elderly Population ◽

Average Length ◽

Bloodstream Infections ◽

The Elderly ◽

Urinary System ◽

Central Nervous System Infections ◽

Wbc Count ◽

Length Of Hospitalization ◽

Common Infections

AbstractIn geriatric practice, data regarding infections including the epidemiology, morbidity, and mortality are lacking. Our aim was to evaluate the frequency, location, microbiological and laboratory characteristics of infectious diseases in elderly population admitted to a training hospital. The patients were included total of 330 patients, aged over 65 with infection, seen between January 1, 2005 and January 1, 2006. In the result, of patients 136 (41%) had respiratory system infection, 90 (27%) urinary system infection, 39 (12%) gastrointestinal system infection, 34 (10%) bloodstream infections, 17 (5%) soft tissue infection, 8 (2%) central nervous system infections, and 6 (2%) others. Average length of hospitalization was 8.6±7.7 days. Mortality rate from all causes was 57 (17%). The most common infections in elderly patients were respiratory tract and urinary system infections, and there were no fever, leukocytes and high CRP levels in approximately 1/3 of cases. Infectious diseases may occur even in the absence of such infection indicators as fever, raised WBC count and high CRP level in the elderly population.

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Decomposition of Ethiopian life expectancy by age and cause of mortality; 1990-2010

10.7287/peerj.preprints.1925v1 ◽

2016 ◽

Author(s):

Gizachew Balew ◽

Youngtae Cho

Keyword(s):

Life Expectancy ◽

Respiratory Infection ◽

Burden Of Disease ◽

Neglected Tropical Diseases ◽

World Health ◽

Tropical Diseases ◽

Lower Respiratory Infection ◽

Diarrheal Diseases ◽

Life Years ◽

Tract Infections

Background: Ethiopia, a sub-Saharan country with over 94 million populations growing at a rate of 2.6 percent is showing a fast socio-economic improvement. According to World Health Organization 2014, life expectancy in the country has increased by about 19 years with in the last two decades. It has also reduced child mortality by 2/3rd; two years ahead of millennium development goal deadline. This research will focus in decomposing the improvement in life expectancy in the country from 1990 to 2010. Methods: We used a secondary data on cause and age specific mortality estimate of Ethiopia from institute of health metrics and evaluation. Burden of disease is measured using potential life years lost and potential life years gained using survival 6 program and compared across time. Further improvement in life expectancy is decomposed across age and specific causes using Pollard’s life expectancy decomposition method. Results: Burden of disease measured in weighted years of life lost (YLL) shows that lower respiratory infection at a value of 5.35, neonatal disorders [4.058], diarrheal diseases [3.6], neglected tropical diseases [2.4], meningitis [1.49] and tuberculosis [1.19] are the top causes of burden in 1990 which showed a slight shift in 2010. Lower respiratory tract infections showed the highest reduction in YLL by about 41.27%, followed by diarrheal disease (32.8%) and meningitis (26.46%). Decomposition of life expectancy shows among the total 15.25 years increase in life expectancy from 1990 to 2010, about 5.8 (35.78%) years of increase in life expectancy is achieved through improved longevity in children’s aged 1- 4 year. On the other hand diarrheal diseases reduction contributes about 3.12 [15.96%] followed by lower respiratory infection about 2.54 [12.98%], neglected tropical diseases by 1.45 [7.43%] and tuberculosis by 1.2 [6.25%] years. Conclusions and recommendation: Burden of disease in Ethiopia has declined dramatically which has contributed to the improvement in life expectancy, with the highest reduction already recorded in major communicable diseases. Though it is encouraging that mortality from children has reduced in the country, the slow change in mortality and burden of disease in the general adult population needs future public attention.

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Causes of Acute Abdominal Pain in Geriatrics: A Review

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i52b33594 ◽

2021 ◽

pp. 20-28

Author(s):

Abdullah Saed Albalawi ◽

Mohammed Omar Amer ◽

Mohammed Ghannam Alharbi ◽

Etizaz Ayed Alshaleikhi

Keyword(s):

Abdominal Pain ◽

Elderly Population ◽

Renal Colic ◽

Acute Abdominal Pain ◽

The Elderly ◽

Current Evidence ◽

Biliary Disease ◽

Timely Manner ◽

Cross Sectional ◽

Common Causes

Background: Aging affects all functions of the gastrointestinal system (GIS). The elderly commonly has atypical presentation of a disease with more subtle symptoms; hence physicians who are not familiar with these might miss the opportunity to make a diagnosis of abdominal pain in timely manner. The main objective of our study is to summarize the current evidence regarding causes and management of acute abdominal pain in elderly. Methodology: MEDLINE, Embolic, CINAHL, PsycInfo, and ASSIA were searched from 2000 until April 2021, and reference lists of included studies were searched. Studies were included that described causes and management of abdominal pain in elderly. No software has been utilized to analyze the data. The data was extracted based on specific form that contains (Author’s name, publication year, country, methodology and results). Results: The study included 7 papers. 2 cross sectional, 2 prospective and 3 retrospective studies all reporting causes and management of acute abdominal pain in elderly. Conclusion: The most common causes of abdominal pain in elderly population were biliary disease, appendicitis and bowel obstruction. Renal colic, hernia and ischemia were also reported in different rates. Diagnosis and management of abdominal pain especially in elderly should be immediate to avoid potential complications.

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Infections and the elderly

Medicinski pregled ◽

10.2298/mpns0306243v ◽

2003 ◽

Vol 56 (5-6) ◽

pp. 243-246 ◽

Cited By ~ 2

Author(s):

Jovan Vukadinov ◽

Sinisa Sevic ◽

Grozdana Canak ◽

Nadezda Madle-Samardzija ◽

Vesna Turkulov ◽

...

Keyword(s):

Infectious Diseases ◽

Older Persons ◽

Elderly Population ◽

Poor Response ◽

The Elderly ◽

Geriatric Population ◽

Delay In Diagnosis ◽

Immunization Rates ◽

Life Threatening ◽

Health Care Associated Infections

Epidemiology Aging is a natural process and a part of our lives, but nowadays there is an increase in the number of persons aged 65 and over. Today infectious diseases are still responsible for one-third of all deaths in the world. The elderly population is most vulnerable to serious infections and at greatest risk for death and complications. Among geriatric population pneumonia and influenza are the fourth most common cause of death Vaccination One of the goals of preventive medicine is to reduce the rate of complications and mortality from infectious diseases by increasing immunization rates. Influenza and pneumococcal vaccines are indicated for persons aged 65 and over. Despite well-recognized benefit of such vaccination, less than 50% of eligible patients receive the vaccine each year. Infections Older persons generally have increased susceptibility to infections because of multiple risk factors and they are the most vulnerable population to nosocomial and health-care associated infections. Older persons may manifest infectious diseases atypically, with acute confusion or delirium which can lead into delay in diagnosis and therapy. It is important to know that the older present with delayed or poor response to antimicrobial therapy and high rates of adverse reactions to drugs, including antibiotics Conclusion As elderly population is rapidly growing, majority of patients with serious or life-threatening infections are old. Geriatric issues have not typically been a focus of training in infectious diseases, but we must become aware of and knowledgeable about special and unique aspects of infections in this population.

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Association of Hypothyroidism and Mortality in the Elderly Population: A Systematic Review and Meta-Analysis

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz186 ◽

2019 ◽

Vol 105 (6) ◽

pp. 2068-2080 ◽

Cited By ~ 3

Author(s):

Tou-Yuan Tsai ◽

Yu-Kang Tu ◽

Kashif M Munir ◽

Shu-Man Lin ◽

Rachel Huai-En Chang ◽

...

Keyword(s):

Cardiovascular Mortality ◽

Elderly Population ◽

Meta Analysis ◽

The Elderly ◽

Current Evidence ◽

Cochrane Library ◽

Overt Hypothyroidism ◽

Significant Difference ◽

All Cause Mortality ◽

The Impact

Abstract Context The evidence of whether hypothyroidism increases mortality in the elderly population is currently inconsistent and conflicting. Objective The objective of this meta-analysis is to determine the impact of hypothyroidism on mortality in the elderly population. Data Sources PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched from inception until May 10, 2019. Study Selection Studies evaluating the association between hypothyroidism and all-cause and/or cardiovascular mortality in the elderly population (ages ≥ 60 years) were eligible. Data Extraction Two reviewers independently extracted data and assessed the quality of the studies. Relative risk (RR) was retrieved for synthesis. A random-effects model for meta-analyses was used. Data Synthesis A total of 27 cohort studies with 1 114 638 participants met the inclusion criteria. Overall, patients with hypothyroidism experienced a higher risk of all-cause mortality than those with euthyroidism (pooled RR = 1.26, 95% CI: 1.15-1.37); meanwhile, no significant difference in cardiovascular mortality was found between patients with hypothyroidism and those with euthyroidism (pooled RR = 1.10, 95% CI: 0.84-1.43). Subgroup analyses revealed that overt hypothyroidism (pooled RR = 1.10, 95% CI: 1.01-1.20) rather than subclinical hypothyroidism (pooled RR = 1.14, 95% CI: 0.92-1.41) was associated with increased all-cause mortality. The heterogeneity primarily originated from different study designs (prospective and retrospective) and geographic locations (Europe, North America, Asia, and Oceania). Conclusions Based on the current evidence, hypothyroidism is significantly associated with increased all-cause mortality instead of cardiovascular mortality among the elderly. We observed considerable heterogeneity, so caution is needed when interpreting the results. Further prospective, large-scale, high-quality studies are warranted to confirm these findings.

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Analysis of research intensity on infectious disease by disease burden reveals which infectious diseases are neglected by researchers

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1814484116 ◽

2018 ◽

Vol 116 (2) ◽

pp. 478-483 ◽

Cited By ~ 18

Author(s):

Yuki Furuse

Keyword(s):

Infectious Disease ◽

Infectious Diseases ◽

Disease Burden ◽

Neglected Tropical Diseases ◽

Research Activity ◽

Country Level ◽

Life Years ◽

Considerable Morbidity ◽

Immunodeficiency Syndrome ◽

Research Intensity

Infectious diseases are associated with considerable morbidity and mortality worldwide. Although human, financial, substantial, and time resources are limited, it is unknown whether such resources are used effectively in research to manage diseases. The correlation between the disability-adjusted life years to represent disease burden and number of publications as a surrogate for research activity was investigated to measure burden-adjusted research intensity for 52 infectious diseases at global and country levels. There was significantly low research intensity for paratyphoid fever and high intensity for influenza, HIV/acquired immunodeficiency syndrome, hepatitis C, and tuberculosis considering their disease burden. We identified the infectious diseases that have received the most attention from researchers and those that have been relatively disregarded. Interestingly, not all so-called neglected tropical diseases were subject to low burden-adjusted research intensity. Analysis of the intensity of infectious disease research at a country level revealed characteristic patterns. These findings provided a basis for further discussion of the more appropriate allocation of resources for research into infectious diseases.

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