Posts filed under ‘Antiparasitarios’

Clinical and epidemiological features of chronic Trypanosoma cruzi infection in patients with HIV/AIDS in Buenos Aires, Argentina

International Journal of Infectious Diseases February 2018 V.67 P.118–121

Andrés Guillermo Benchetrit, Marisa Fernández, Amadeo Javier Bava, Marcelo Corti, Norma Porteiro, Liliana Martínez Peralta

Highlights

  • Chagas disease reactivation is an AIDS-defining illness with a high mortality rate.
  • Besides the vector-borne route, other means of T. cruzi infection acquisition must be assessed.
  • HIV-infected patients with lower CD4 T-cell counts are at higher risk of Chagas disease reactivation.
  • Severely immunecompromised patients infected with T. cruzi may have negative serological assay results.
  • Direct parasitological techniques should be performed in the diagnosis of patients for whom there is a suspicion of T. cruzi reactivation.

Objectives

Trypanosoma cruzi reactivation in HIV patients is considered an opportunistic infection, usually with a fatal outcome. The aim of this study was to describe the epidemiological and clinical features of T. cruzi infection in HIV patients and to compare these findings between patients with and without Chagas disease reactivation.

Methods

The medical records of T. cruzi–HIV co-infected patients treated at the Muñiz Infectious Diseases Hospital from January 2005 to December 2014 were reviewed retrospectively. Epidemiological and clinical features were assessed and compared between patients with and without Chagas disease reactivation.

Results

The medical records of 80 T. cruzi–HIV co-infected patients were reviewed. The most likely route of T. cruzi infection was vector-borne (32/80 patients), followed by intravenous drug use (12/80). Nine of 80 patients had reactivation. Patients without reactivation had a significantly higher CD4 T-cell count at diagnosis of T. cruzi infection (144 cells/μl vs. 30 cells/μl, p = 0.026). Chagas disease serology was negative in two of nine patients with reactivation.

Conclusions

Serological assays for T. cruzi infection may be negative in severely immunocompromised patients. Direct parasitological techniques should be performed in the diagnosis of patients for whom there is a suspicion of T. cruzi reactivation. HIV patients with a lower CD4 count are at higher risk of reactivation.

abstract

http://www.ijidonline.com/article/S1201-9712(17)30309-0/fulltext

PDF

http://www.ijidonline.com/article/S1201-9712(17)30309-0/pdf

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February 18, 2018 at 4:05 pm

Treating malaria: new drugs for a new era

Lancet Infectious Diseases December 2017 V.17 N.12 P.1223–1224

COMMENT

Treating malaria: new drugs for a new era

G Dennis Shanks, Jörg J Möhrle

In The Lancet Infectious Diseases, Ousmane Koita and colleagues1 reported the results of a randomised, phase 2, non-inferiority clinical trial. They compared AQ-13, a next generation 4-aminoquinoline (4-AQ) compound, with artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in 66 Malian men.

The per-protocol analysis of this well executed trial showed that both groups had similar proportions cured (28 [100%] of 28 for AQ-13 vs 31 [93·9%] of 33 for artemether plus lumefantrine; p=0·50) and non-inferiority of AQ-13 to artemether plus lumefantrine (difference −6·1%, 95% CI −14·7 to 2·4). The intention-to-treat analysis also showed that proportions cured were also similar between the groups (28 [84·8%] of 33 for AQ-13 vs 31 [93·9%] of 33 for artemether plus lumefantrine; p=0·43); however, this analysis did not show non-inferiority of AQ-13 to artemether plus lumefantrine (difference 9·1%, 95% CI −5·6 to 23·8). The study’s suboptimal number of participants was possibly due to civil military disturbances in Mali or improving malaria control in the Sahel. The data presented show AQ-13 to be efficacious in this relatively easy-to-treat population. The next challenge is to understand how well AQ-13 will treat patients who have lower or no immunity to malaria, such as African children….

FULL TEXT

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30475-9/fulltext?elsca1=etoc

PDF

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(17)30475-9.pdf

 

 

Lancet Infectious Diseases December 2017 V.17 N.12 P.1266–1275

AQ-13, an investigational antimalarial, versus artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria: a randomised, phase 2, non-inferiority clinical trial

Prof Ousmane A Koita, PhD, Lansana Sangaré, PhD, Haiyan D Miller, BS, Aliou Sissako, MD, Moctar Coulibaly, MD, Trevor A Thompson, BS, Prof Saharé Fongoro, MD, Youssouf Diarra, PharmD, Mamadou Ba, PhD, Prof Ababacar Maiga, PhD, Prof Boubakar Diallo, MD, David M Mushatt, MD, Frances J Mather, PhD, Jeffrey G Shaffer, PhD, Asif H Anwar, MD, Prof Donald J Krogstad

Background

Chloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria.

Methods

We did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per μL of blood). Eligible participants were randomly assigned to either the artemether plus lumefantrine group or AQ-13 group by permuting blocks of four with a random number generator. Physicians and others caring for the participants were masked, except for participants who received treatment and the research pharmacist who implemented the randomisation and provided treatment. Participants received either 80 mg of oral artemether and 480 mg of oral lumefantrine twice daily for 3 days or 638·50 mg of AQ-13 base (two oral capsules) on days 1 and 2, and 319·25 mg base (one oral capsule) on day 3. Participants were monitored for parasite clearance (50 μL blood samples twice daily at 12 h intervals until two consecutive negative samples were obtained) and interviewed for adverse events (once every day) as inpatients during week 1. During the 5-week outpatient follow-up, participants were examined for adverse events and recurrent infection twice per week. All participants were included in the intention-to-treat analysis and per-protocol analysis, except for those who dropped out in the per-protocol analysis. The composite primary outcome was clearance of asexual parasites and fever by day 7, and absence of recrudescent infection by parasites with the same molecular markers from days 8 to 42 (defined as cure). Non-inferiority was considered established if the proportion of patients who were cured was higher for artemether plus lumefantrine than for AQ-13 and the upper limit of the 95% CI was less than the non-inferiority margin of 15%. This trial is registered at ClinicalTrials.gov, number NCT01614964.

Findings

Between Aug 6 and Nov 18, 2013, and between Sept 18 and Nov 20, 2015, 66 Malian men with uncomplicated malaria were enrolled. 33 participants were randomly assigned to each group. There were no serious adverse events (grade 2–4) and asexual parasites were cleared by day 7 in both groups. 453 less-severe adverse events (≤grade 1) were reported: 214 in the combination group and 239 in the AQ-13 group. Two participants withdrew from the AQ-13 group after parasite clearance and three were lost to follow-up. In the artemether plus lumefantrine group, two participants had late treatment failures (same markers as original isolates). On the basis of the per-protocol analysis, the AQ-13 and artemether plus lumefantrine groups had similar proportions cured (28 [100%] of 28 vs 31 [93·9%] of 33; p=0·50) and AQ-13 was not inferior to artemether plus lumefantrine (difference −6·1%, 95% CI −14·7 to 2·4). Proportions cured were also similar between the groups in the intention-to-treat analysis (28 of 33, 84·8% for AQ-13 vs 31 of 33, 93·9% for artemether and lumefantrine; p=0·43) but the upper bound of the 95% CI exceeded the 15% non-inferiority margin (difference 9·1%, 95% CI −5·6 to 23·8).

Interpretation

The per-protocol analysis suggested non-inferiority of AQ-13 to artemether plus lumefantrine. By contrast, the intention-to-treat analysis, which included two participants who withdrew and three who were lost to follow-up from the AQ-13 group, did not meet the criterion for non-inferiority of AQ-13, although there were no AQ-13 treatment failures. Studies with more participants (and non-immune participants) are needed to decide whether widespread use of modified 4-aminoquinolones should be recommended.

Funding

US Food and Drug Administration Orphan Product Development, National Institutes of Health, US Centers for Disease Control and Prevention, Burroughs-Wellcome Fund, US State Department, and WHO.

FULL TEXT

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30365-1/fulltext?elsca1=etoc

PDF

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(17)30365-1.pdf

 

November 24, 2017 at 8:35 am

False-Positive Rapid Malaria Antigen Test Result in a Returned Traveler

Journal of Clinical Microbiology August 2017 V.55 N.8 P.2294-2297

The Brief Case

Kristle L. Haberichter, Paul C. Johnson, Paul J. Chittick, Peter Millward, Barbara Robinson-Dunn, and Bobby L. Boyanton Jr.

A previously healthy 43-year-old female presented to her primary care physician with a 13-day history of recurrent nightly fevers (100°F to 101°F), nonproductive cough, and respiratory congestion. She was prescribed azithromycin, albuterol, and benzonatate. She presented to the emergency center 2 days later without improvement and at that time reported night sweats. She had recently traveled to Thailand, Laos, Cambodia, and the United Arab Emirates. The nightly fevers began 11 days after returning home. She acknowledged being bitten by mosquitoes throughout her travels and did not take malaria prophylaxis.

A previously healthy 43-year-old female presented to her primary care physician with a 13-day history of recurrent nightly fevers (100°F to 101°F), nonproductive cough, and respiratory congestion. She was prescribed azithromycin, albuterol, and benzonatate. She presented to the emergency center 2 days later without improvement and at that time reported night sweats. She had recently traveled to Thailand, Laos, Cambodia, and the United Arab Emirates. The nightly fevers began 11 days after returning home. She acknowledged being bitten by mosquitoes throughout her travels and did not take malaria prophylaxis….

PDF

http://jcm.asm.org/content/55/8/2294.full.pdf+html

 

 

Journal of Clinical Microbiology August 2017 V.55 N.8 P.2560-2561

Closing the Brief Case: False-Positive Rapid Malaria Antigen Test Result in a Returned Traveler

Kristle L. Haberichter, Paul C. Johnson, Paul J. Chittick, Peter Millward, Barbara Robinson-Dunn, and Bobby L. Boyanton Jr.

aDepartment of Pathology and Laboratory Medicine, Beaumont Health, Royal Oak, Michigan, USA

bDepartment of Infectious Disease, Beaumont Health, Royal Oak, Michigan, USA

cOakland University William Beaumont School of Medicine, Rochester, Michigan, USA

ANSWERS TO SELF-ASSESSMENT QUESTIONS

PDF

http://jcm.asm.org/content/55/8/2560.full.pdf+html

July 26, 2017 at 9:23 am

Sexual transmission of American trypanosomiasis in humans: a new potential pandemic route for Chagas parasites

Memórias do Instituto Oswaldo Cruz June 2017 V.112 N.6

Perla F Araujo1, Adriana B Almeida1, Carlos F Pimentel1, Adriano R Silva1, Alessandro Sousa1, Sebastião A Valente2,

Vera C Valente2, Manuela M Britto1, Ana C Rosa1, Rozeneide M Alves1, Luciana Hagström1, Antonio RL Teixeira1  *  +

1Universidade de Brasília, Faculdade de Medicina, Laboratório Multidisciplinar de Pesquisa em Doença de Chagas, Brasília, DF, Brasil

2Instituto Evandro Chagas, Belém, PA, Brasil

BACKGROUND

The Trypanosoma cruzi infection endemic in Latin America has now spread to several countries across four continents; this endemic involves triatomine vector-free protists. We hypothesised that the sexual transmission of T. cruzi contributes to the ongoing spread of Chagas disease.

OBJECTIVES

A short-term longitudinal study was conducted to evaluate this hypothesis.

METHODS

The study population comprised 109 subjects from four families, among whom 21 had been diagnosed with acute Chagas disease by direct parasitological analysis. Blood mononuclear cells and serum samples were obtained from each study subject once per year for three consecutive years. Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence serological examinations were used to detect specific T. cruzi antibodies. Polymerase chain reaction of T. cruzi DNA revealed 188-nucleotide bands, which hybridised to a specific radiolabelled probe and were confirmed by cloning and sequencing.

RESULTS

Three independent assessments at different time points revealed T. cruzi nuclear DNA footprints in 76% (83/109) of the study population with active infection. In contrast, the ELISA and indirect immunofluorescence assays detected the T. cruzi antibody in 28.4% (31/109) of the study samples. Moreover, the semen from 82.6% (19/23) of subjects people revealed harboured the 188- bp base pair T. cruzi footprint. Interestingly, the ejaculates of nuclear DNA-positive Chagas patient transmitted the T. cruzi upon peritoneal injection or infusion in the vagina of mice, and amastigotes were detected in the skeletal muscle, myocardium, vas deferens, and uterine tube.

MAIN CONCLUSIONS

T. cruzi infections can be transmitted from females or males to naïve mates through intercourse, and progeny showed discrepancies between the ratios of nuclear DNA footprints and specific antibody that can be explained by the tolerance attained during early embryo growth. Additional studies are needed to develop drugs to eradicate the infections. Additionally, the importance of a vigorous education, information, and communication program to prevent sexually transmitted Chagas disease in humans cannot be underemphasised.

PDF

http://www.scielo.br/pdf/mioc/v112n6/0074-0276-mioc-112-6-0437.pdf

July 14, 2017 at 8:23 am

Abordaje terapéutico actual de la malaria grave importada

Revista Española de Quimioterapia Septiembre 2016 V.29 Supl.1

EMMANUELE VENANZI, ROGELIO LÓPEZ-VÉLEZ

PDF

http://www.seq.es/seq/0214-3429/29/sup1/15venanzi.pdf

 

Resistencia a los antimaláricos

EMMANUELE VENANZI, ROGELIO LÓPEZ-VÉLEZ

PDF

http://www.seq.es/seq/0214-3429/29/sup1/16venanzi.pdf

 

April 9, 2017 at 12:44 pm

A New Development in Trypanosoma cruzi Detection

Journal of Clinical Microbiology March 2017 V.55 N.3 P.690-692

Herbert B. Tanowitz and Louis M. Weiss

Department of Pathology, Division of Tropical Medicine and Parasitology, and Department of Medicine, Division of Infectious Disease, Albert Einstein College of Medicine, Bronx, New York, USA

Chagas disease is caused by the parasite Trypanosoma cruzi and is an important cause of morbidity and mortality in areas of Latin America where Chagas disease is endemic and among infected individuals who have migrated to nonendemic areas of North America and Europe.

There are many diagnostic tests that are employed in the serological diagnosis of this infection. In this issue of the Journal of Clinical Microbiology, Bautista-López et al. provide characterization of excretory vesicles (EVs) from Vero cells infected with T. cruzi and provide data on the EVs produced by trypomastigotes and amastigotes (N. L. Bautista-López et al., J Clin Microbiol 55:744–758, 2017, https://doi.org/10.1128/JCM.01649-16).

Their proteomic study defines potential targets to evaluate for improved diagnostic tests, effects on host cell biology that contribute to the pathogenesis of infection, and vaccine candidates. If any of the EV-associated proteins identified were to be correlated to cure of infection, this would be a major advance….

PDF

http://jcm.asm.org/content/55/3/690.full.pdf+html

February 24, 2017 at 8:01 am

Safety, tolerability, and efficacy of repeated doses of dihydroartemisinin-piperaquine for prevention and treatment of malaria: a systematic review and meta-analysis

Lancet Infectious Diseases February 2017 V.17 N.2 P.184–193

Julie Gutman, MD,  Stephanie Kovacs, PhD, Prof Grant Dorsey, MD, Prof Andy Stergachis, PhD, Prof Feiko O ter Kuile, MD

Background

Intermittent preventive treatment (IPT) for malaria is used in infants, children, adults, and pregnant women. Dihydroartemisinin-piperaquine (DP) is an effective, well tolerated artemisinin-based combination therapy. The long half-life of piperaquine makes it attractive for IPT. We conducted a systematic review and meta-analysis to establish the efficacy and safety of repeated treatment with DP.

Methods

Following PRISMA guidelines, we searched multiple databases on Sept 1, 2016, with the terms: “human” AND “dihydroartemisinin-piperaquine” OR “DHA-PPQ”. Studies were eligible if they were randomised controlled trials (RCTs) or prospective cohort studies involving repeat exposures to standard 3-day courses of DP for either seasonal malaria chemoprevention, mass drug administration, or treatment of clinical malaria, conducted at any time and in any geographic location. Random-effects meta-analysis was used to generate pooled incidence rate ratios and relative risks, or risk differences.

Findings

11 studies were included: two repeat treatment studies (one in children younger than 5 years and one in pregnant women), and nine IPT trials (five in children younger than 5 years, one in schoolchildren, one in adults, two in pregnant women). Comparator interventions included placebo, artemether-lumefantrine, sulfadoxine-pyrimethamine (SP), SP+amodiaquine, SP+piperaquine, SP+chloroquine, and co-trimoxazole. Of 14 628 participants, 3935 received multiple DP courses (2–18). Monthly IPT-DP was associated with an 84% reduction in the incidence of malaria parasitaemia measured by microscopy compared with placebo. Monthly IPT-DP was associated with fewer serious adverse events than placebo, daily co-trimoxazole, or monthly SP. Among 56 IPT-DP recipients (26 children, 30 pregnant women) with cardiac parameters, all QTc intervals were within normal limits, with no significant increase in QTc prolongation with increasing courses of DP.

Interpretation

Monthly DP appears well tolerated and effective for IPT. Additional data are needed in pregnancy and to further explore the cardiac safety with monthly dosing.

Funding

Bill & Melinda Gates Foundation and NIH.

FULL TEXT

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(16)30378-4/fulltext?elsca1=etoc

PDF

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(16)30378-4.pdf

February 1, 2017 at 2:09 pm

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