scholarly journals Pathogenicity of trypanosomes in relation to 1 drug sensitivity: comparative studies between a drug-sensitive and drug-resistant Trypanosoma congolense strain in murine-and bovine model

2020 ◽  
Author(s):  
Anna Ngumbi ◽  
Ladslaus Mnyone
Keyword(s):  
Rectal Temperature ◽  
Resistant Strain ◽  
Drug Sensitivity ◽  
Clinical Manifestations ◽  
Trypanosoma Congolense ◽  
Prepatent Period ◽  
Sensitive Strain ◽  
Drug Resistant ◽  
Highly Pathogenic ◽  
Field Situation

Abstract Background: Indiscriminate exposure of Trypanosoma congolense and other trypanosomes to trypanocides have led to emergence of resistant strains, which increasingly undermine the control efforts against tsetse transmitted animal trypanosomosis. Despite the increasing trend of resistance, no studies have conducted to assess whether or not drug sensitivity affects the pathogenicity of T. congolense and other predominant species. Methods: We compared the pathogenicity of two strains of trypanosomes: drug-sensitive Trypanosoma congolense -Mikese and drug-resistant T. congolense Mbagala. These strains were isolated from cattle at Mikese, Morogoro region and Mbagala, Dar es Salaam region, Tanzania, respectively. Experimental mice and cattle were infected with either tryapnosomes and monitored for rectal temperature, prepatent period, parasitemia, packed cell volume (PCV), survival and clinical manifestations. Drug sensitivity status of either strains was re-confirmed before pathogenicity testing. Results: Mean rectal temperature was higher in mice infected with T. congolense -sensitive strain (p=0.049, 95% CI= 0.003-1.13). Mean prepatent period of resistant strain in mice and cattle was shorter than that of sensitive strain. The mean level of parasitemia was significantly higher in resistant- (7.5±0.8) than in sensitive-strain (6.5±0.8) (p<0.001, 95% CI= -1.28 to -0.68). Mice infected with resistant strain were relatively dull and lethargic compared to those infected with sensitive strain. The decline PCV was higher in cattle infected with sensitive- strain than resistant-strain (p=0.041, 95% CI, -6.97 to -0.17). Conclusion: Pathogenicity of the two Trypanosoma congolense strains varied significantly across host species. The resistant strain was highly pathogenic in mice and less so in cattle. Contrarily, the sensitive strain was highly pathogenic to cattle and less so to mice. As such, this study emphasizes variations on the pathways by which different trypanosomes act upon the host; thus warranting subsequent studies using large number of experimental animals, preferentially cattle, in view of reflecting the field situation.

Immunity in trypanosomiasis

Parasitology ◽  
1959 ◽  
Vol 49 (1-2) ◽  
pp. 143-152 ◽  
Author(s):  
M. A. Soltys
Keyword(s):  
Resistant Strain ◽  
Therapeutic Dose ◽  
Sensitive Strain ◽  
Drug Resistant ◽  
Chemotherapeutic Drugs ◽  
Natural Conditions ◽  
Resistant Strains ◽  
Drug Resistant Strains

Antibody-resistant strains are less sensitive to suramin and antrycide than antibody-sensitive strains. When living trypanosomes were exposed to suramin and antrycide in vitro, antibody-resistant strains needed 50 times more drugs than antibody-sensitive trypanosomes in order to make them non-infectious to mice. In therapeutic experiments in mice the minimal therapeutic dose of drugs for antibody-sensitive strains was 0·1 mg. but for resistant strains it was 0·3 mg./20 g. mice. Rabbits treated prophylactically with suramin resisted infection with the antibody-sensitive strain for a period of 4 months, but failed to resist infection with the antibody-resistant strain after 2 months.Rabbits treated prophylactically with antrycide pro-salt, resisted infection with antibody-sensitive strains for a period of 2 months, but failed to resist infection with the antibody-resistant strain even 1 month after injection with the drug. Although trypanosomes can become drug resistant without being antibody resistant it is suggested that, under natural conditions, drug-resistant strains in animals and man develop from antibody-resistant strains, particularly when trypanostatic drugs are used. It is suggested in conclusion from these experiments that strains of trypanosomes which are exposed for some time to antibodies and become antibody resistant after passage through animals like rabbits, as well as those strains frequently passaged through mice, should be used in all tests for the efficiency of chemotherapeutic drugs.

Emerging of a highly pathogenic and multi-drug resistant strain of Escherichia coli causing an outbreak of colibacillosis in chickens

2018 ◽  
Vol 65 ◽  
pp. 392-398 ◽  
Author(s):  
Junfeng Gao ◽  
Xueyan Duan ◽  
Xiaoqi Li ◽  
Hong Cao ◽  
Yongqiang Wang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Resistant Strain ◽  
Drug Resistant ◽  
Highly Pathogenic

Dynamic analysis of conversion from a drug-sensitivity strain to a drug-resistant strain

2018 ◽  
Vol 11 (08) ◽  
pp. 1850113
Author(s):  
Zhong Zhao ◽  
Fengmei Tao ◽  
Qiuying Li
Keyword(s):  
Periodic Solution ◽  
Resistant Strain ◽  
Drug Sensitivity ◽  
Sufficient Conditions ◽  
Continuous System ◽  
State Feedback Control ◽  
Drug Resistant ◽  
Qualitative Properties ◽  
Optimal Criterion ◽  
The Stability

In this paper, a mathematical model of conversion from a drug-sensitivity strain to a drug-resistant strain is given to investigate how antibiotic usage may be optimized to preserve or restore antibiotic effectiveness. This novel theoretical framework could result in an optimal criterion on how to reduce the drug resistance to a reasonable range by using the antibiotic dressing strategy. The sufficient conditions of existence of order-1 periodic solution are obtained in view of the geometrical theory of the semi-continuous dynamical system and the qualitative properties of the corresponding continuous system. The stability of the order-1 periodic solution is proved by means of [H. J. Guo, L. S. Chen and X. Y. Song, Qualitative analysis of impulsive state feedback control to an algae-fish system with bistable property, Appl. Math. Comput. 271 (2015) 905–922]. Finally, our results are confirmed by means of numerical simulations.

scholarly journals Pathobiology of A/Chicken/Hong Kong/220/97 (H5N1) Avian Influenza Virus in Seven Gallinaceous Species

2001 ◽  
Vol 38 (2) ◽  
pp. 149-164 ◽  
Author(s):  
L. E. L. Perkins ◽  
D. E. Swayne
Keyword(s):  
Hong Kong ◽  
Avian Influenza ◽  
Pulmonary Edema ◽  
Multiorgan Failure ◽  
Clinical Manifestations ◽  
Highly Pathogenic ◽  
H5n1 Avian Influenza Virus ◽  
Multiple Organs ◽  
H5n1 Avian Influenza ◽  
Virus Localization

Direct bird-to-human transmission, with the production of severe respiratory disease and human mortality, is unique to the Hong Kong-origin H5N1 highly pathogenic avian influenza (HPAI) virus, which was originally isolated from a disease outbreak in chickens. The pathobiology of the A/chicken/Hong Kong/ 220/97 (H5N1) (HK/220) HPAI virus was investigated in chickens, turkeys, Japanese and Bobwhite quail, guinea fowl, pheasants, and partridges, where it produced 75-100% mortality within 10 days. Depression, mucoid diarrhea, and neurologic dysfunction were common clinical manifestations of disease. Grossly, the most severe and consistent lesions included splenomegaly, pulmonary edema and congestion, and hemorrhages in enteric lymphoid areas, on serosal surfaces, and in skeletal muscle. Histologic lesions were observed in multiple organs and were characterized by exudation, hemorrhage, necrosis, inflammation, or a combination of these features. The lung, heart, brain, spleen, and adrenal glands were the most consistently affected, and viral antigen was most often detected by immunohistochemistry in the parenchyma of these organs. The pathogenesis of infection with the HK/220 HPAI virus in these species was twofold. Early mortality occurring at 1-2 days postinoculation (DPI) corresponded to severe pulmonary edema and congestion and virus localization within the vascular endothelium. Mortality occurring after 2 DPI was related to systemic biochemical imbalance, multiorgan failure, or a combination of these factors. The pathobiologic features were analogous to those experimentally induced with other HPAI viruses in domestic poultry.

scholarly journals The Potential Impact of Up-Front Drug Sensitivity Testing on India’s Epidemic of Multi-Drug Resistant Tuberculosis

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0131438 ◽  
Author(s):  
Kuldeep Singh Sachdeva ◽  
Neeraj Raizada ◽  
Radhey Shyam Gupta ◽  
Sreenivas Achuthan Nair ◽  
Claudia Denkinger ◽  
...  
Keyword(s):  
Drug Sensitivity ◽  
Drug Resistant ◽  
Sensitivity Testing ◽  
Drug Resistant Tuberculosis ◽  
Drug Sensitivity Testing ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Potential Impact

scholarly journals New Threats from H7N9 Influenza Virus: Spread and Evolution of High- and Low-Pathogenicity Variants with High Genomic Diversity in Wave Five

2018 ◽  
Vol 92 (11) ◽  
pp. e00301-18 ◽  
Author(s):  
Chuansong Quan ◽  
Weifeng Shi ◽  
Yang Yang ◽  
Yongchun Yang ◽  
Xiaoqing Liu ◽  
...  
Keyword(s):  
Geographical Distribution ◽  
Pearl River Delta ◽  
River Delta ◽  
Genomic Diversity ◽  
Pearl River ◽  
Distribution Analysis ◽  
Drug Resistant ◽  
Highly Pathogenic ◽  
Genetic Characteristics ◽  
Human Infections

ABSTRACT H7N9 virus has caused five infection waves since it emerged in 2013. The highest number of human cases was seen in wave 5; however, the underlying reasons have not been thoroughly elucidated. In this study, the geographical distribution, phylogeny, and genetic evolution of 240 H7N9 viruses in wave 5, including 35 new isolates from patients and poultry in nine provinces, were comprehensively analyzed together with strains from first four waves. Geographical distribution analysis indicated that the newly emerging highly pathogenic (HP) and low-pathogenicity (LP) H7N9 viruses were cocirculating, causing human and poultry infections across China. Genetic analysis indicated that dynamic reassortment of the internal genes among LP-H7N9/H9N2/H6Ny and HP-H7N9, as well as of the surface genes, between the Yangtze and Pearl River Delta lineages resulted in at least 36 genotypes, with three major genotypes (G1 [A/chicken/Jiangsu/SC537/2013-like], G3 [A/Chicken/Zhongshan/ZS/2017-like], and G11 [A/Anhui/40094/2015-like]). The HP-H7N9 genotype likely evolved from G1 LP-H7N9 by the insertion of a KRTA motif at the cleavage site (CS) and then evolved into 15 genotypes with four different CS motifs, including PKGKRTAR/G, PKGKRIAR/G, PKRKRAAR/G, and PKRKRTAR/G. Approximately 46% (28/61) of HP strains belonged to G3. Importantly, neuraminidase (NA) inhibitor (NAI) resistance (R292K in NA) and mammalian adaptation (e.g., E627K and A588V in PB2) mutations were found in a few non-human-derived HP-H7N9 strains. In summary, the enhanced prevalence and diverse genetic characteristics that occurred with mammalian-adapted and NAI-resistant mutations may have contributed to increased numbers of human infections in wave 5. IMPORTANCE The highest numbers of human H7N9 infections were observed during wave 5 from October 2016 to September 2017. Our results showed that HP-H7N9 and LP-H7N9 had spread virtually throughout China and underwent dynamic reassortment with different subtypes (H7N9/H9N2 and H6Ny) and lineages (Yangtze and Pearl River Delta lineages), resulting in totals of 36 and 3 major genotypes, respectively. Notably, the NAI drug-resistant (R292K in NA) and mammalian-adapted (e.g., E627K in PB2) mutations were found in HP-H7N9 not only from human isolates but also from poultry and environmental isolates, indicating increased risks for human infections. The broad dissemination of LP- and HP-H7N9 with high levels of genetic diversity and host adaptation and drug-resistant mutations likely accounted for the sharp increases in the number of human infections during wave 5. Therefore, more strategies are needed against the further spread and damage of H7N9 in the world.

Total synthesis and antimalarial activity of mortiamides A–D

2019 ◽  
Vol 55 (52) ◽  
pp. 7434-7437 ◽  
Author(s):  
Christopher Bérubé ◽  
Dominic Gagnon ◽  
Alexandre Borgia ◽  
Dave Richard ◽  
Normand Voyer
Keyword(s):  
Plasmodium Falciparum ◽  
Total Synthesis ◽  
Resistant Strain ◽  
Antimalarial Activity ◽  
Drug Resistant

This work describes the first total synthesis of mortiamides and their anti-malarial activity against a multi-drug resistant strain of Plasmodium falciparum.

scholarly journals Carbapenemases: Transforming Acinetobacter baumannii into a Yet More Dangerous Menace

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 720 ◽  
Author(s):  
Maria Soledad Ramirez ◽  
Robert A. Bonomo ◽  
Marcelo E. Tolmasky
Keyword(s):  
Acinetobacter Baumannii ◽  
Nosocomial Infections ◽  
Acquired Resistance ◽  
Clinical Manifestations ◽  
High Capacity ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Wound Infections ◽  
Extensively Drug Resistant

Acinetobacter baumannii is a common cause of serious nosocomial infections. Although community-acquired infections are observed, the vast majority occur in people with preexisting comorbidities. A. baumannii emerged as a problematic pathogen in the 1980s when an increase in virulence, difficulty in treatment due to drug resistance, and opportunities for infection turned it into one of the most important threats to human health. Some of the clinical manifestations of A. baumannii nosocomial infection are pneumonia; bloodstream infections; lower respiratory tract, urinary tract, and wound infections; burn infections; skin and soft tissue infections (including necrotizing fasciitis); meningitis; osteomyelitis; and endocarditis. A. baumannii has an extraordinary genetic plasticity that results in a high capacity to acquire antimicrobial resistance traits. In particular, acquisition of resistance to carbapenems, which are among the antimicrobials of last resort for treatment of multidrug infections, is increasing among A. baumannii strains compounding the problem of nosocomial infections caused by this pathogen. It is not uncommon to find multidrug-resistant (MDR, resistance to at least three classes of antimicrobials), extensively drug-resistant (XDR, MDR plus resistance to carbapenems), and pan-drug-resistant (PDR, XDR plus resistance to polymyxins) nosocomial isolates that are hard to treat with the currently available drugs. In this article we review the acquired resistance to carbapenems by A. baumannii. We describe the enzymes within the OXA, NDM, VIM, IMP, and KPC groups of carbapenemases and the coding genes found in A. baumannii clinical isolates.

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