Jaime Altcheh - Academia.edu (original) (raw)

Papers by Jaime Altcheh

Birkhäuser advances in infectious diseases, 2019

Congenital infection with Trypanosoma cruzi is a global problem, occurring on average in 5% of ch... more Congenital infection with Trypanosoma cruzi is a global problem, occurring on average in 5% of children born from chronically infected mothers, with variations depending on the region. In endemic areas with inadequate vector control, Chagas disease, also known as American trypanosomiasis, is usually a vector-borne disease. In areas with effective vector control and in urban areas, the main route of new cases of CD is through mother-to-child transmission. The estimated number of new cases of congenital T. cruzi infection is 8668 cases/year [2]. This is also the case of non-endemic countries where, due to population migration, CD is increasingly becoming a public health problem in non-endemic settings. The majority of infected infants are asymptomatic, and the diagnosis is based on the microscopic observation of the parasite in the blood of newborns and by serology in infants older than 8 months of age when maternal transplacental antibodies have waned. Two drugs are available for treatment, benznidazole and nifurtimox. Treatment should be implemented immediately after diagnosis since the sooner the infection is treated, the better the prognosis. The treatment efficacy is around 95% in different cohorts with a good drug safety profile. Recent studies have shown that its transmission can be prevented through treatment of infected women before they become pregnant. Considering that etiological treatment of the child is highly effective if performed before 1 year of age, the diagnosis of infection in pregnant women and their newborns has to become the standard of care and integrated into the surveillance programs of syphilis and human immunodeficiency virus.

Pharmacology & Pharmacy, 2021

Infection with Toxoplasma gondii, is one of the most widespread zoonoses in the world. Congenital... more Infection with Toxoplasma gondii, is one of the most widespread zoonoses in the world. Congenital Toxoplasmosis (CT) is particularly risky due to its fetal complications. Sulfadiazine (SDZ) and Pyrimethamine (PYR) are usually used for CT treatment in Argentina, to prevent morbidity. Due to the lack of commercial pediatric formulations, these must be prepared in the hospital pharmacy. This is the first report of serum concentrations measures in pediatric CT therapy for this combination of drugs. A bioanalytical method was developed for identification and simultaneous quantification of SDZ and PYR by High Performance Liquid Chromatography (HPLC) with UV detection. The validated method was applied to residual serum samples obtained from 6 pediatric patients undergoing treatment with SDZ 42.20 a 93.70 mg/kg/day and PYR 0.77 a 2.70 mg/kg/day. Sample pretreatment consisted on a deproteinization step followed by centrifugation and then injection of supernatant. Limit of Detection (LOD) and Quantification (LOQ) were (0.17 ± 0.02 and 0.13 ± 0.02) µg/mL and (0.46 ± 0.

Archivos Argentinos de Pediatria, 2020

Presentación de casos clínicos RESUMEN La toxocariosis es una parasitosis generada por la larva d... more Presentación de casos clínicos RESUMEN La toxocariosis es una parasitosis generada por la larva del género Toxocara sp., que causa dos síndromes clásicamente definidos: larva migrans visceral o larva migrans ocular, dependiendo de la localización de la larva. Sin embargo, la mayor parte de los niños presenta una infección asintomática. El ser humano se comporta como un hospedador paraténico, en el que Toxocara sp. no llega a completar su ciclo biológico. Las manifestaciones clínicas pueden ser diversas y dependen del número y de la localización de las larvas enquistadas, así como de la respuesta inmune del huésped. En los últimos años, se ha descrito una relación entre Toxocara sp. y ciertas manifestaciones cutáneas. Se describe el caso clínico de un lactante de 19 meses con toxocariosis visceral y manifestaciones cutáneas de vasculitis. Se detalla su forma de presentación, evolución clínica, metodología diagnóstica y terapéutica empleada.

Archivos Argentinos de Pediatria

Reporte de casos RESUMEN Existen numerosas entidades en la población pediátrica que pueden presen... more Reporte de casos RESUMEN Existen numerosas entidades en la población pediátrica que pueden presentarse en forma de quistes o como lesiones de similares características. De estas patologías, las infecciosas son las más frecuentes. Se presenta el caso de una paciente oriunda de Bolivia con migración reciente a la Argentina que presentó una coinfección con tuberculosis e hidatidosis pulmonar. Ambas infecciones se pueden presentar con signos y síntomas similares y, aunque la asociación citada es poco frecuente en la bibliografía, ciertos mecanismos inmunitarios podrían intervenir en la coinfección de parásitos helmintos y micobacterias. Ambas patologías son infecciones prevalentes en nuestra región y deben ser tenidas en cuenta entre los diagnósticos diferenciales ante pacientes con imágenes quísticas o cavitarias pulmonares.

Revista Da Sociedade Brasileira De Medicina Tropical, 2005

medRxiv (Cold Spring Harbor Laboratory), Sep 29, 2022

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Diagnostic Microbiology and Infectious Disease, Mar 1, 2022

The performance of Toxoplasma rGra8, rMic1, and the chimeric rGra4-Gra7 antigens for early congen... more The performance of Toxoplasma rGra8, rMic1, and the chimeric rGra4-Gra7 antigens for early congenital toxoplasmosis (CT) diagnosis was evaluated. Sera from CT patients showed high IgG reactivity to rMic1, rGra8, and rGra4-Gra7. The seroreactivity of samples from uninfected infants was lost within 2 months of age.

Chagas disease (CD) caused by the parasite Trypanosoma cruzi, belongs to the so-called neglected ... more Chagas disease (CD) caused by the parasite Trypanosoma cruzi, belongs to the so-called neglected diseases group. In Argentina about 1,500 children are born with congenital Chagas disease per year. The diagnosis of CD in the newborn relies on the ability to detect parasites in the blood by microscopic observation, as the serological tests are ruled out because of the presence of maternal antibodies. CD treatment is more effective during the acute phase of infection. Early diagnosis and treatment of the disease is thus very important. The Argentinian National Program for early detection of metabolic diseases uses Whatman903 filter paper for blood sampling. This type of sample collection presents many advantages as the use of low blood volumes, minimal biological risk, and easy storage and transportation. The objective of the study was to evaluate the conservation efficiency of blood samples on filter paper in order to access good sensitivity on qPCR results for the detection of T. cruzi. To standardize the procedure, negative samples of blood were infected artificially with serial dilutions of trypomastigotes forms of T. cruzi from the TcVI strain obtained by cell culture in Vero cells. Concentrations between 50000 and 5 parasites/mL were prepared and loaded in filter paper for analysis. DNA extraction was conducted by the QIAamp DNA Mini Kit from QIAGEN. For qPCR, a method based on TaqMan technology was used, with a multiplex reaction for quantification of T. cruzi satellite DNA and an internal amplification control (IAC). The detection limit found from our results was 400 parasites/mL, demonstrating that this method could be a reliable option for the diagnosis of congenital CD by the detection of T.

PLOS Neglected Tropical Diseases, Aug 29, 2019

Archives of Disease in Childhood, Nov 29, 2009

Women with Chagas disease receiving treatment with nifurtimox are discouraged from breast feeding... more Women with Chagas disease receiving treatment with nifurtimox are discouraged from breast feeding. Many patients who would receive treatment with nifurtimox live in extreme poverty, have limited access to resources such as clean water and baby formula and may not have safe alternatives to breast milk. We aimed to estimate, using limited available pharmacokinetics data, potential infant exposure to nifurtimox through breast milk. Original nifurtimox plasma concentrations were obtained from published studies. Pharmacokinetic parameters were estimated using non-linear mixed-effect modelling with NONMEM V.VI. A total of 1000 nifurtimox plasma-concentration profiles were simulated and used to calculate the amount of drug that an infant would be exposed to, if breast fed 150 ml/kg/day. Breast milk concentrations on the basis of peak plasma levels (1361 ng/ml) and milk-plasma ratio were estimated. We calculated infant nifurtimox exposure of a breastfed infant of a mother treated with this drug to be below 10% of the maternal weight-adjusted dose, even if milk-plasma ratio were overestimated. Simulation led to similar estimates. Risk for significant infant exposure to nifurtimox through breast milk seems small and below the level of exposure of infants with Chagas disease receiving nifurtimox treatment. This potential degree of exposure may not justify discontinuation of breast feeding.

Annals of Tropical Medicine and Parasitology, Sep 1, 2010

Little is known about the immune responses of newborns with congenital Chagas disease (CCD) or co... more Little is known about the immune responses of newborns with congenital Chagas disease (CCD) or congenital toxoplasmosis (CT) but they probably differ to those seen in adults with Chagas disease or toxoplasmosis, leading to differences in pathology. The concentrations of interleukin-18 (IL-18), interferon-γ (IFN-γ) and interleukin 10 (IL-10) in the sera of infants with CCD or CT were determined and compared with those in the sera of uninfected controls (born to mothers who were seropositive or seronegative for Trypanosoma cruzi). The infants with CCD or CT were found to have lower IL-18 and IFN-γ concentrations but higher IL-10 concentrations than the uninfected controls. The IL-18 and IFN-γ concentrations were also significantly lower in the infants with CCD than in those with CT. Although the infants with symptomatic CT had significantly higher serum concentrations of IL-18 than those with asymptomatic infection with Toxoplasma, the infants with symptomatic CCD had similar serum concentrations of IL-18 to the infants with asymptomatic Tr. cruzi infection. Taken together, these results indicate that IL-10 contributes to the suppression of pro-inflammatory immune responses and therefore, perhaps, to clinically overt CCD and CT.

Archives of Disease in Childhood, May 17, 2019

dk), where midazolam dose is adjusted to total body weight or age, may lead to both supra-and sub... more dk), where midazolam dose is adjusted to total body weight or age, may lead to both supra-and subtherapeutic doses respectively, in children with obesity. However, confirmatory studies are needed.

Antimicrobial Agents and Chemotherapy, Apr 18, 2023

Nifurtimox is recommended for the treatment of Chagas disease; however, long-term follow-up data ... more Nifurtimox is recommended for the treatment of Chagas disease; however, long-term follow-up data are scarce. This prolonged follow-up phase of the prospective, historically controlled, CHICO clinical trial evaluated seronegative conversion in pediatric patients aged <18 years with Chagas disease who were followed for 4 years after nifurtimox treatment.

Antimicrobial Agents and Chemotherapy, May 17, 2022

Chagas disease (ChD), caused by Trypanosoma cruzi , has a global prevalence due to patient migrat... more Chagas disease (ChD), caused by Trypanosoma cruzi , has a global prevalence due to patient migration. However, despite its worldwide distribution, long-term follow-up efficacy studies with nifurtimox (NF) are scarce and have been conducted with only small numbers of patients. A retrospective study of a large cohort of ChD treated children and adults with NF.

PLOS Neglected Tropical Diseases

Background Measurement of the success of antitrypanosomal treatment for Chagas disease is difficu... more Background Measurement of the success of antitrypanosomal treatment for Chagas disease is difficult, particularly in the chronic phase of the disease, because anti-Trypanosoma cruzi antibodies persist in serum for prolonged periods. We studied the effects of nifurtimox administered by two different treatment regimens on the T. cruzi calcium-binding flagellar protein F29 in children diagnosed with Chagas disease measured using an enzyme-linked immunosorbent assay (ELISA) technique (ELISA F29). Methods and principal findings In a phase 3, randomized, double-blind, parallel-group, historically controlled study (ClinicalTrials.gov NCT02625974), blood samples obtained from children diagnosed with Chagas disease and treated with nifurtimox for either 60 days or 30 days were analyzed using an ELISA with an F29 recombinant protein as the antigen, as well as conventional serological tests (recombinant ELISA and indirect hemagglutination assay). In an exploratory approach, serological respons...

Nature Communications

During an infection the immune system produces pathogen-specific antibodies. These antibody reper... more During an infection the immune system produces pathogen-specific antibodies. These antibody repertoires become specific to the history of infections and represent a rich source of diagnostic markers. However, the specificities of these antibodies are mostly unknown. Here, using high-density peptide arrays we examined the human antibody repertoires of Chagas disease patients. Chagas disease is a neglected disease caused by Trypanosoma cruzi, a protozoan parasite that evades immune mediated elimination and mounts long-lasting chronic infections. We describe a proteome-wide search for antigens, characterised their linear epitopes, and show their reactivity on 71 individuals from diverse human populations. Using single-residue mutagenesis we revealed the core functional residues for 232 of these epitopes. Finally, we show the diagnostic performance of identified antigens on challenging samples. These datasets enable the study of the Chagas antibody repertoire at an unprecedented depth a...

Antimicrobial Agents and Chemotherapy