scholarly journals Refugia and the evolutionary epidemiology of drug resistance

2015 ◽  
Vol 11 (11) ◽  
pp. 20150783 ◽  
Author(s):  
Andrew W. Park ◽  
James Haven ◽  
Ray Kaplan ◽  
Sylvain Gandon
Keyword(s):  
Drug Resistance ◽  
Disease Burden ◽  
Health Concern ◽  
Force Of Infection ◽  
Animal Populations ◽  
Prophylactic Drug ◽  
Evolutionary Epidemiology ◽  
Drug Treatments ◽  
Selection For ◽  
Multiple Drugs

Drug resistance is a long-standing economic, veterinary and human health concern in human and animal populations. Efficacy of prophylactic drug treatments targeting a particular pathogen is often short-lived, as drug-resistant pathogens evolve and reach high frequency in a treated population. Methods to combat drug resistance are usually costly, including use of multiple drugs that are applied jointly or sequentially, or development of novel classes of drugs. Alternatively, there is growing interest in exploiting untreated host populations, refugia , for the management of drug resistance. Refugia do not experience selection for resistance, and serve as a reservoir for native, drug-susceptible pathogens. The force of infection from refugia may dilute the frequency of resistant pathogens in the treated population, potentially at an acceptable cost in terms of overall disease burden. We examine this concept using a simple mathematical model that captures the core mechanisms of transmission and selection common to many host–pathogen systems. We identify the roles of selection and gene flow in determining the utility of refugia.

scholarly journals Functional Genomics Approaches to Elucidate Vulnerabilities of Intrinsic and Acquired Chemotherapy Resistance

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 260
Author(s):  
Ronay Cetin ◽  
Eva Quandt ◽  
Manuel Kaulich
Keyword(s):  
Drug Resistance ◽  
Acquired Resistance ◽  
Chemotherapy Resistance ◽  
Resistance Mechanisms ◽  
Therapy Failure ◽  
Tightly Coupled ◽  
Unbiased Gene ◽  
Multiple Drugs ◽  
Genome Scale ◽  
Gene Perturbations

Drug resistance is a commonly unavoidable consequence of cancer treatment that results in therapy failure and disease relapse. Intrinsic (pre-existing) or acquired resistance mechanisms can be drug-specific or be applicable to multiple drugs, resulting in multidrug resistance. The presence of drug resistance is, however, tightly coupled to changes in cellular homeostasis, which can lead to resistance-coupled vulnerabilities. Unbiased gene perturbations through RNAi and CRISPR technologies are invaluable tools to establish genotype-to-phenotype relationships at the genome scale. Moreover, their application to cancer cell lines can uncover new vulnerabilities that are associated with resistance mechanisms. Here, we discuss targeted and unbiased RNAi and CRISPR efforts in the discovery of drug resistance mechanisms by focusing on first-in-line chemotherapy and their enforced vulnerabilities, and we present a view forward on which measures should be taken to accelerate their clinical translation.

TREATMENT OF CARBAPENEM RESISTANT ENTEROBACTERIACEAE URINARY TRACT INFECTION WITH COMBINATION OF AMIKACIN AND MEROPENEM

2021 ◽  
pp. 54-55
Author(s):  
Jayesh Kalbhande ◽  
Vicky Kuldeep
Keyword(s):  
Drug Resistance ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
New Drugs ◽  
Resistant Organism ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
Multiple Drugs ◽  
Near Future

Drug resistance of bacteria is biggest challenge humanity is going to face in near future. Bacteria are rapidly developing resistant to multiple drugs and there are not many new drugs in pipeline. Infection because of drug resistant organism is a common cause of morbidity and mortality in intensive care unit. If acquisition of drug resistance by microorganism progresses at this rate, that time is not very far when we will be pushed in to preantibiotic era. We need to develop new strategies to combat drug resistant by microorganism. We report a case of highly drug resistant urinary tract infection caused by Klebsiella. This strain was resistant to both Inj. Meropenem and Inj. Amikacin. This case was successfully treated by combination of Inj. Meropenem and Inj. Amikacin and complete resolution of infection was observed.

Detection of Genetic markers associated with Plasmodium falciparum drug resistance among malaria patients in Kaduna State, Nigeria

2021 ◽  
Vol 42 (2) ◽  
pp. 206-213
Author(s):  
G.Y. Benjamin ◽  
H.I. Inabo ◽  
M.H.I. Doko ◽  
B.O. Olayinka
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Phylogenetic Tree ◽  
Genetic Markers ◽  
Cross Sectional Study ◽  
Sub Saharan Africa ◽  
Health Concern ◽  
Cross Sectional ◽  
Blood Samples ◽  
Test Kit

Malaria is a disease of public health concern in Nigeria and sub-Saharan Africa. It is caused by intracellular parasites of the genus Plasmodium. The aim of this study was to detect genetic markers associated with Plasmodium falciparum drug resistance among malaria patients in Kaduna State, Nigeria. The study was a cross-sectional study that lasted from May 2018 to October 2018. Three hundred blood samples were collected from consenting individuals attending selected hospitals, in the three senatorial districts of Kaduna State, Nigeria. Structured questionnaire were used to obtain relevant data from study participants. The blood samples were screened for malaria parasites using microscopy and rapid diagnostic test kit. Polymerase Chain Reaction was used for detection of the drug resistance genes. Pfcrt, pfmdr1, pfdhfr, pfdhps and pfatpase6 genes were detected at expected amplicon sizes from the malaria positive samples. The pfatpase6 PCR amplicons were sequenced and a phylogenetic tree was created to determine their relatedness. Result showed that Pfcrt (80%) had the highest prevalence, followed by pfdhfr (60%), pfmdr1 (36%) and pfdhps (8%). Pfatpase6 was also detected in 73.3% of the samples, and a phylogenetic tree showed relatedness between the pfatpase6  sequences in this study and those deposited in the GenBank. In conclusion, the study detected that Plasmodium falciparum genes were associated with drug resistance to commonly used antimalarials.

scholarly journals Evolution and Population Structure of Salmonella enterica Serovar Newport

2010 ◽  
Vol 192 (24) ◽  
pp. 6465-6476 ◽  
Author(s):  
Vartul Sangal ◽  
Heather Harbottle ◽  
Camila J. Mazzoni ◽  
Reiner Helmuth ◽  
Beatriz Guerra ◽  
...  
Keyword(s):  
Population Structure ◽  
North America ◽  
Salmonella Enterica ◽  
Health Concern ◽  
Global Public Health ◽  
Multiple Sequence ◽  
Monophyletic Lineage ◽  
Population Structures ◽  
Paratyphi B ◽  
Multiple Drugs

ABSTRACT Salmonellosis caused by Salmonella enterica serovar Newport is a major global public health concern, particularly because S. Newport isolates that are resistant to multiple drugs (MDR), including third-generation cephalosporins (MDR-AmpC phenotype), have been commonly isolated from food animals. We analyzed 384 S. Newport isolates from various sources by a multilocus sequence typing (MLST) scheme to study the evolution and population structure of the serovar. These were compared to the population structure of S. enterica serovars Enteritidis, Kentucky, Paratyphi B, and Typhimurium. Our S. Newport collection fell into three lineages, Newport-I, Newport-II, and Newport-III, each of which contained multiple sequence types (STs). Newport-I has only a few STs, unlike Newport-II or Newport-III, and has possibly emerged recently. Newport-I is more prevalent among humans in Europe than in North America, whereas Newport-II is preferentially associated with animals. Two STs of Newport-II encompassed all MDR-AmpC isolates, suggesting recent global spread after the acquisition of the bla CMY-2 gene. In contrast, most Newport-III isolates were from humans in North America and were pansusceptible to antibiotics. Newport was intermediate in population structure to the other serovars, which varied from a single monophyletic lineage in S. Enteritidis or S. Typhimurium to four discrete lineages within S. Paratyphi B. Both mutation and homologous recombination are responsible for diversification within each of these lineages, but the relative frequencies differed with the lineage. We conclude that serovars of S. enterica provide a variety of different population structures.

scholarly journals Recent advances in the contribution of noncoding RNAs to cisplatin resistance in cervical cancer

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9234
Author(s):  
Xin Wen ◽  
Shui Liu ◽  
Jiyao Sheng ◽  
Manhua Cui
Keyword(s):  
Cervical Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Treatment Option ◽  
Disease Burden ◽  
Cisplatin Resistance ◽  
Noncoding Rnas ◽  
Mechanisms Of Action ◽  
Female Population ◽  
Cellular Processes

Cervical cancer (CC) remains a major disease burden on the female population worldwide. Chemotherapy with cisplatin (cis-diamminedichloroplatinum (II); CDDP) and related drugs are the main treatment option for CC; however, their efficacy is limited by the development of drug resistance. Noncoding RNAs (ncRNAs) have been found to play critical roles in numerous physiological and pathological cellular processes, including drug resistance of cancer cells. In this review, we describe some of the ncRNAs, including miRNAs, lncRNAs and circRNAs, that are involved in the sensitivity/resistance of CC to CDDP-based chemotherapy and discuss their mechanisms of action. We also describe some ncRNAs that could be therapeutic targets to improve the sensitivity of CC to CDDP-based chemotherapy.

scholarly journals Adaptive Drug Resistance in Malaria Parasite: A Threat to Malaria Elimination Agenda?

2021 ◽  
Author(s):  
Moses Okpeku
Keyword(s):  
Drug Resistance ◽  
Malaria Elimination ◽  
Malaria Parasite ◽  
Disease Burden ◽  
Drug Application ◽  
African Region ◽  
Malaria Parasites ◽  
Sub Saharan ◽  
Host Development

Malaria is a global disease of importance, especially in the sub-Saharan African region, where malaria accounts for great losses economically and to life. Fight to eliminate this disease has resulted in reduced disease burden in many places where the diseases is endemic. Elimination strategies in most places is focus on the use of treated nets and drug application. Exposure of malaria parasites to anti-malaria drugs have led to the evolution of drug resistance in both parasites and host. Development of drug resistance vary but, studies on adaptive drug resistance has implications and consequences. Our knowledge of this consequences are limited but important for the pursuit of an uninterrupted malaria elimination agenda. This chapter draws our attention to this risks and recommends interventions.

scholarly journals Use of antipsychotic drugs and mood stabilizers in women of childbearing age with schizophrenia and bipolar disorder: epidemiological survey

2013 ◽  
Vol 22 (4) ◽  
pp. 355-361 ◽  
Author(s):  
C. Barbui ◽  
V. Conti ◽  
M. Purgato ◽  
A. Cipriani ◽  
I. Fortino ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Epidemiological Survey ◽  
Mood Stabilizers ◽  
Administrative Databases ◽  
Health Concern ◽  
Women Of Childbearing Age ◽  
Childbearing Age ◽  
Severe Mental Disorders ◽  
Normal Delivery ◽  
Drug Treatments

Aims.To determine the prevalence of women of childbearing age with schizophrenia and bipolar disorder exposed to antipsychotic (AP) drugs and mood stabilizers (MS) in Lombardy, a European region of 10 million inhabitants and 1 752 285 women of childbearing age.Methods.The data concerning psychiatric care, drug treatments and pregnancy outcomes were retrieved from local administrative databases during a 12-month census period.Results.During a 12-month census period, 2893 women of childbearing age with schizophrenia (74.8% of all women of childbearing age with schizophrenia) and 918 with bipolar disorder (80.1% of all women of childbearing age with bipolar disorder) were exposed to AP drugs or MS, yielding a prevalence of exposure for women with schizophrenia of 1.65 (95% confidence interval (CI) 1.59–1.71) per 1000 female inhabitants, and for women with bipolar disorder of 0.52 (95% CI 0.49–0.55) per 1000 female inhabitants. Persistent exposure to potentially teratogenic medications accounted for one in every 1000 women of childbearing age. Of the 57 pregnancies in women with schizophrenia, normal delivery was recorded in 23 (40%) cases; of the 26 pregnancies in women with bipolar disorder, normal delivery was recorded in 10 (38%) cases.Conclusions.In women of childbearing age with severe mental disorders, exposure to psychotropic drugs is substantial, which suggests that the issue of reproductive health is epidemiologically relevant and a major public health concern.

Evidence for selection for the tyrosine-86 allele of the pfmdr 1 gene of Plasmodium falciparum by chloroquine and amodiaquine

Parasitology ◽  
1997 ◽  
Vol 114 (3) ◽  
pp. 205-211 ◽  
Author(s):  
M. T. DURAISINGH ◽  
C. J. DRAKELEY ◽  
O. MULLER ◽  
R. BAILEY ◽  
G. SNOUNOU ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Genetic Basis ◽  
Drug Trial ◽  
Enzyme Digestion ◽  
Restriction Enzyme Digestion ◽  
Blood Samples ◽  
Allelic Status ◽  
Group A ◽  
Selection For

The 4-aminoquinolines chloroquine (CQ) and amodiaquine (AM) were used to treat Gambian children with uncomplicated falciparum malaria in a randomized drug trial. Blood samples were taken immediately before treatment (day 0), and at day 7 and day 28 after treatment. Samples from those parasitologically positive at day 7 following treatment (‘early positives’) and those positive at day 28 but negative at day 7 (‘late positives’) have been studied by PCR followed by restriction enzyme digestion to determine the allelic status of the pfmdr 1 locus at the codon-86 position (asparagine or tyrosine), previously associated with resistance to CQ. A significantly higher prevalence of the tyr-86 allele was observed in samples taken immediately before treatment (day 0) in the early positives group when compared with the late positives group. This suggests the tyr-86 allele contributes to drug resistance in the early positives group. This association remained significant for both CQ and AM groups, implying a common genetic basis of resistance. Predominance of the allele at day 7 is consistent with a strong selection in the first week following treatment. In the late positives group, a significantly higher prevalence of the tyr-86 allele was observed in the samples at day 28 when compared with those at day 0, suggestive of selection during the period day 7 to day 28. Differences were observed in the extent of this selection in the CQ and AM groups. The samples were genotyped at 3 unlinked polymorphic loci. These analyses suggested that most parasites observed at day 7 were probably recrudescences whereas most of those at day 28 were reinfections.

scholarly journals Efflux Pump-Mediated Intrinsic Drug Resistance in Mycobacterium smegmatis

2004 ◽  
Vol 48 (7) ◽  
pp. 2415-2423 ◽  
Author(s):  
Xian-Zhi Li ◽  
Li Zhang ◽  
Hiroshi Nikaido
Keyword(s):  
Drug Resistance ◽  
Ethidium Bromide ◽  
Mycobacterium Smegmatis ◽  
Efflux Pump ◽  
Upstream Region ◽  
Drug Efflux ◽  
Intact Cells ◽  
Intrinsic Drug Resistance ◽  
Multiple Drugs ◽  
Increased Susceptibility

ABSTRACT The Mycobacterium smegmatis genome contains many genes encoding putative drug efflux pumps. Yet with the exception of lfrA, it is not clear whether these genes contribute to the intrinsic drug resistance of this organism. We showed first by reverse transcription (RT)-PCR that several of these genes, including lfrA as well as the homologues of Mycobacterium tuberculosis Rv1145, Rv1146, Rv1877, Rv2846c (efpA), and Rv3065 (mmr and emrE), were expressed at detectable levels in the strain mc2155. Null mutants each carrying an in-frame deletion of these genes were then constructed in M. smegmatis. The deletions of the lfrA gene or mmr homologue rendered the mutant more susceptible to multiple drugs such as fluoroquinolones, ethidium bromide, and acriflavine (two- to eightfold decrease in MICs). The deletion of the efpA homologue also produced increased susceptibility to these agents but unexpectedly also resulted in decreased susceptibility to rifamycins, isoniazid, and chloramphenicol (two- to fourfold increase in MICs). Deletion of the Rv1877 homologue produced some increased susceptibility to ethidium bromide, acriflavine, and erythromycin. The upstream region of lfrA contained a gene encoding a putative TetR family transcriptional repressor, dubbed LfrR. The deletion of lfrR elevated the expression of lfrA and produced higher resistance to multiple drugs. Multidrug-resistant single-step mutants, independent of LfrA and attributed to a yet-unidentified drug efflux pump (here called LfrX), were selected in vitro and showed decreased accumulation of norfloxacin, ethidium bromide, and acriflavine in intact cells. Finally, use of isogenic β-lactamase-deficient strains showed the contribution of LfrA and LfrX to resistance to certain β-lactams in M. smegmatis.

Health impact assessment and burden of zoonotic diseases

2011 ◽  
Author(s):  
Christine M. Budke ◽  
Hélène Carabin ◽  
Paul R. Torgerson
Keyword(s):  
Disease Burden ◽  
Health Impact Assessment ◽  
Taenia Solium ◽  
Cost Benefit ◽  
Health Impact ◽  
Cost Utility ◽  
Zoonotic Diseases ◽  
Disease Assessment ◽  
Productivity Losses ◽  
Animal Populations

Numerous zoonotic diseases cause morbidity, mortality and productivity losses in both humans and animal populations. Recent studies suggest that these diseases can produce large societal impacts in endemic areas. Estimates of monetary impact and disease burden provide essential, evidence-based data for conducting cost-benefit and cost-utility analyses that can contribute to securing political will and financial and technical resources. To evaluate burden, monetary and non-monetary impacts of zoonoses on human health, agriculture and society should be comprehensively considered. This chapter reviews the framework used to assess the health impact and burden of zoonoses and the data needed to estimate the extent of the problem for societies. Case studies are presented to illustrate the use of burden of disease assessment for the zoonotic diseases cystic echinococcosis, Taenia solium cysticercosis, brucellosis and rabies.

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