“…During the acute phase, which lasts about six to eight weeks, there is positive parasitemia but the symptoms are generally mild and/or flu‐like. Therefore, this stage often passes without diagnosis of the disease . Due to the host immune response, the parasite load is controlled, and the majority of patients move to a chronic stage after two months, which is generally asymptomatic: i.e., the patient is infected and able to transmit, but without clear clinical pathological signs of the disease .…”
Section: Introductionmentioning
confidence: 99%
“…Therefore, this stage often passes without diagnosis of the disease. [6] Due to the host immune response, the parasite load is controlled, and the majority of patientsm ove to ac hronic stage after two months, which is generally asymptomatic:i.e.,the patient is infected anda ble to transmit, but withoutc lear clinicalp athological signs of the disease. [1] However,a fter years or even decades, approximately 30 %o fi nfected patients develop progressive chronic cardiomyopathy, whilea nother 10 %d evelop digestive, neurological, or mixed clinical symptoms.…”
Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in‐house library led to the identification of 2,2′‐methylenebis(5‐(4‐bromophenyl)‐4,4‐dimethyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC50 value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′‐methylenebis(5‐(3‐bromo‐4‐methoxyphenyl)‐4,4‐dimethyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one (NPD‐0228) as the most potent analogue. NPD‐0228 has an in vitro pIC50 value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC‐5 cell line and murine cardiac cells.
“…During the acute phase, which lasts about six to eight weeks, there is positive parasitemia but the symptoms are generally mild and/or flu‐like. Therefore, this stage often passes without diagnosis of the disease . Due to the host immune response, the parasite load is controlled, and the majority of patients move to a chronic stage after two months, which is generally asymptomatic: i.e., the patient is infected and able to transmit, but without clear clinical pathological signs of the disease .…”
Section: Introductionmentioning
confidence: 99%
“…Therefore, this stage often passes without diagnosis of the disease. [6] Due to the host immune response, the parasite load is controlled, and the majority of patientsm ove to ac hronic stage after two months, which is generally asymptomatic:i.e.,the patient is infected anda ble to transmit, but withoutc lear clinicalp athological signs of the disease. [1] However,a fter years or even decades, approximately 30 %o fi nfected patients develop progressive chronic cardiomyopathy, whilea nother 10 %d evelop digestive, neurological, or mixed clinical symptoms.…”
Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in‐house library led to the identification of 2,2′‐methylenebis(5‐(4‐bromophenyl)‐4,4‐dimethyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC50 value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′‐methylenebis(5‐(3‐bromo‐4‐methoxyphenyl)‐4,4‐dimethyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one (NPD‐0228) as the most potent analogue. NPD‐0228 has an in vitro pIC50 value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC‐5 cell line and murine cardiac cells.
“…Clinically, ChD exhibits a primary acute phase characterized by variable signs and symptoms ranging from mild to severe, and patent parasitemia is detected in direct blood tests. This phase progresses to the chronic phase, which persists throughout the patient's life 2,3 . In this phase, detection of the parasite is rare due to subpatent and transient parasitemia.…”
Introduction:In order to detect Trypanosoma cruzi and determine the genetic profiles of the parasite during the chronic phase of Chagas disease (ChD), parasitological and molecular diagnostic methods were used to assess the blood of 91 patients without specific prior treatment. Methods: Blood samples were collected from 68 patients with cardiac ChD and 23 patients with an indeterminate form of ChD, followed by evaluation using blood culture and polymerase chain reaction. T. cruzi isolates were genotyped using three different genetic markers. Results: Blood culture was positive in 54.9% of all patients, among which 60.3% had the cardiac form of ChD, and 39.1% the indeterminate form of ChD. There were no significant differences in blood culture positivity among patients with cardiac and indeterminate forms. Additionally, patient age and clinical forms did not influence blood culture results. Polymerase chain reaction (PCR) was positive in 98.9% of patients, although comparisons between blood culture and PCR results showed that the two techniques did not agree. Forty-two T. cruzi stocks were isolated, and TcII was detected in 95.2% of isolates. Additionally, one isolate corresponded to TcIII or TcIV, and another corresponded to TcV or TcVI. Conclusions: Blood culture and PCR were both effective for identifying T. cruzi using a single blood sample, and their association did not improve parasite detection. However, we were not able to establish an association between the clinical form of ChD and the genetic profile of the parasite.
“…The acute phase is characterized by an active infection, inflammation and myocardial damage [2,3]. Myocarditis is characterized by tachycardia, prolongation of the PR interval, low-voltage QRS complexes, nonspecific T wave changes, cardiomegaly and heart failure [4,5]. This phase also features the presence of parasites in the circulating blood and several other tissues, including myocardium, and usually results in the appearance of antibodies [6].…”
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