Therapeutic monitoring of antimicrobial agents in pediatrics. Review based on Latin American experiences

This review summarizes recommendations of therapeutic monitoring of three antimicrobials based in regional data: vancomycin, amikacin and voriconazole in pediatric population. Regional evidence agrees with international literature regarding the requirement of higher daily doses than 40 mg/kg/day of vancomycin, as well as with the possibility of use one daily doses of amikacin and to recommend higher doses of voriconazole compared to the initially recommended doses of 8 mg/kg/day. Local data on the pharmacokinetic/pharmacodynamic behavior of various antimicrobials in pediatrics are of great value for dosing adjustment in our pediatric population. More studies in therapeutic monitoring in the use of antimicrobials in pediatrics should be performed in order to allow the generation of adequate treatment guidelines for this age group

Acute retinal necrosis in an acute leukemia pediatric patient Necrosis retinal aguda en un paciente pediátrico con leucemia aguda

Acute retinal necrosis (ARN) is a serious condition that can impair vision. It mostly occurs in adult patients, especially those severely immunocompromised, in association with a reactivation of a herpes virus infection. We present a 4 years old patient with high risk acute leukemia, whom during a course of intense chemotherapy acquired chickenpox with visceral involvement that affected the retina, causing unilateral blindness. Varicella-zoster virus was detected by PCR in the vitreous humor, in spite of previous acyclovir treatment. The contralateral vision remained undamaged

Meningomyelitis associated with infection by human herpes virus 7. Report of two cases Meningomielitis asociadas a infección por herpes virus humano 7. Comunicación de dos casos

Human herpesvirus 7 (HHV-7) may cause encephalomyelitis in immunocompetent adults. We report two patients infected by the virus. A 34-year-old male presenting with paraparesis and a sensitive deficiency located in D6 dermatome. Cerebrospinal fluid had 35 white blood cells per mm 3 and 75 mg protein per dl. A PCR-microarray examination was positive for HHV-7. The patient was treated with prednisolone and ganciclovir with full recovery. A 27-year-old male presenting with headache, fever and diarrhea. Cerebrospinal fluid analysis showed 160 cells per mm 3 and 75 mg protein per dl. Viral RNA detection was positive for HHV-7. The patient was managed with analgesia and rest and was discharged with the diagnosis of viral meningitis. Our comunication supports the notion that HHV-7 may be considered as pathogen factor in humans, even in immunocompetent ones

Gastric Damage and Cancer-Associated Biomarkers in Helicobacter pylori-Infected Children

Helicobacter pylori (H. pylori) is well-known to be involved in gastric carcinogenesis, associated with deregulation of cell proliferation and epigenetic changes in cancer-related genes. H. pylori infection is largely acquired during childhood, persisting long-term in about half of infected individuals, a subset of whom will go on to develop peptic ulcer disease and eventually gastric cancer, however, the sequence of events leading to disease is not completely understood. Knowledge on carcinogenesis and gastric damage-related biomarkers is abundant in adult populations, but scarce in children. We performed an extensive literature review focusing on gastric cancer related biomarkers identified in adult populations, which have been detected in children infected with H. pylori. Biomarkers were related to expression levels (RNA or protein) and/or methylation levels (DNA) in gastric tissue or blood of infected children as compared to non-infected controls. In this review, we identified 37 biomarkers of which 24 are over expressed, three are under expressed, and ten genes are significantly hypermethylated in H. pylori-infected children compared to healthy controls in at least 1 study. Only four of these biomarkers (pepsinogen I, pepsinogen II, gastrin, and SLC5A8) have been studied in asymptomatically infected children. Importantly, 13 of these biomarkers (beta-catenin, C-MYC, GATA-4, DAPK1, CXCL13, DC-SIGN, TIMP3, EGFR, GRIN2B, PIM2, SLC5A8, CDH1, and VCAM-1.) are consistently deregulated in infected children and in adults with gastric cancer. Future studies should be designed to determine the clinical significance of these changes in infection-associated biomarkers in children and their persistence over time. The effect of eradication therapy over these biomarkers in children if proven significant, could lead to modifications in treatment guidelines for younger populations, and eventually promote the development of preventive strategies, such as vaccination, in the near future.Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 117045

Optimizing RT-PCR detection of SARS-CoV-2 for developing countries using pool testing

The global shortage of reagents and kits for nucleic acid extraction and molecular detection of SARS-CoV-2 requires new cost-effective strategies for the diagnosis of suspected COVID-19 cases, especially in countries that need to increase detection capacity. Pooled nucleic acid testing has been extensively used as a cost-effective strategy for HIV HepB, HepC and influenza. Also, protocols dispensing of RNA extraction appears as an attractive option for detection of SARS-CoV-2. In this study, we found that pooling of 5 samples showed that C-T variations were in the range of 1.0-4,5 units, with less likelihood of a false negative result. Results of the sample without nucleic acid extraction, was unsatisfactory, with a significant increase in C-T values, and thus for risk of a false negative result. In conclusion, pooling nasopharyngeal samples with both automated and manual extraction proved reliable, and thus a potential efficient alternative for the diagnosis of suspected COVID-19 in developing countries.La escasez mundial de reactivos para la extracción de ácidos nucleicos y la detección molecular de SARS-CoV-2 requiere de nuevas estrategias de mayor rendimiento para el diagnóstico de casos sospechosos de COVID-19, especialmente en países que necesitan aumentar su capacidad diagnóstica. La detección de ácidos nucleicos en muestras agrupadas o pool testing se ha utilizado ampliamente como una estrategia costo-efectiva para el VIH, hepatitis B, hepatitis C e influenza. Adicionalmente, los protocolos que no requieren extracción de ARN aparecen como una opción para la detección de SARS-CoV-2. En este trabajo, presentamos los resultados de una estrategia detección de SARS-CoV-2 en muestras agrupadas, que incluye diferentes métodos de extracción de ARN que puede ser una estrategia atractiva para los países en desarrollo. La agrupación de 5 muestras mostró variaciones CT en el rango de 1,0 a 4,5 unidades, con una baja probabilidad de obtener falsos negativos, a diferencias de los resultados agregando muestras agrupadas directamente en la reacción de amplificación de SARS-CoV-2. En conclusión, la agrupación de muestras nasofaríngeas, demostró ser un método confiable y, por lo tanto, una alternativa para aumentar el rendimiento en el diagnóstico de COVID-19 para países en desarrollo

Intravenous palivizumab in respiratory syncytial virus infection after hematopoietic stem cell transplant in children

Respiratory syncytial virus (RSV) infection can cause lower respiratory tract disease and mortality in pediatric hematopoietic stem cell transplant (HSCT) recipients. We report two children who underwent HSCT and developed RSV infection simultaneously at the Bone Marrow Transplant Unit. The treatment with intravenous palivizumab was provided and sequential viral loads were measured in nasopharyngeal (NP) and whole blood samples. To our knowledge, this is the first report where RSV loads were measured in parallel (NP and blood), before and after palivizumab, in correlation with a favorable clinical outcome in both cases.FONDECYT 1130911 1112153

Valuing the cost of improving chilean primary vaccination: a cost minimization analysis of a hexavalent vaccine

Background: The phased withdrawal of oral polio vaccine (OPV) and the introduction of inactivated poliovirus vaccine (IPV) is central to the polio ‘end-game’ strategy. Methods: We analyzed the cost implications in Chile of a switch from the vaccination scheme consisting of a pentavalent vaccine with whole-cell pertussis component (wP) plus IPV/OPV vaccines to a scheme with a hexavalent vaccine with acellular pertussis component (aP) and IPV (Hexaxim®) from a societal perspective. Cost data were collected from a variety of sources including national estimates and previous vaccine studies. All costs were expressed in 2017 prices (US$1.00=$Ch 666.26). Results: The overall costs associated with the vaccination scheme (4 doses of pentavalent vaccine plus 1 dose IPV and 3 doses OPV) from a societal perspective was estimated to be US$12.70 million, of which US$ 8.84 million were associated with the management of adverse events related to wP. In comparison, the cost associated with the 4-dose scheme with a hexavalent vaccine (based upon the PAHO reference price) was US$19.76 million. The cost of switching to the hexavalent vaccine would be an additional US$ 6.45 million. Overall, depending on the scenario, the costs of switching to the hexavalent scheme would range from an additional US$2.62 million to US$ 6.45 million compared with the current vaccination scheme. Conclusions: The switch to the hexavalent vaccine schedule in Chile would lead to additional acquisition costs, which would be partially offset by improved logistics, and a reduction in adverse events associated with the current vaccines

Prevalence of TPMT and ITPA gene polymorphisms and effect on mercaptopurine dosage in Chilean children with acute lymphoblastic leukemia

Artículo de publicación ISIBackground: Mercaptopurine (6-MP) plays a pivotal role in treatment of childhood acute lymphoblastic leukemia (ALL); however, interindividual variability in toxicity of this drug due to genetic polymorphism in 6-MP metabolizing enzymes has been described. We determined the prevalence of the major genetic polymorphisms in 6-MP metabolizing enzymes in Chilean children with ALL. Methods: 103 Chilean pediatric patients with a confirmed diagnosis of ALL were enrolled. DNA was isolated from whole blood and genetic polymorphism in thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) coding genes were detected by polymorphism chain reaction-restriction fragment length (PCR-RFLP) assay. Results: The total frequency of variant TPMT alleles was 8%. TPMT*2, TPMT*3A and TPMT*3B alleles were found in 0%, 7%, and 1% of patients, respectively. For ITPA, the frequency of P32T allele was 3%. We did not observe any homozygous variant for TPMT and ITPA alleles. We also analyzed a subgroup of 40 patients who completed the maintenance phase of ALL treatment, and we found that patients carrying a TPMT gene variant allele required a significantly lower median cumulative dosage and median daily dosage of 6-MP than patients carrying wild type alleles. Conclusion: TMPT genotyping appears an important tool to further optimize 6-MP treatment design in Chilean patients with ALL.This work was supported by grants from Fundación Nuestros Hijos (JM and MJF) and FONDECYT 1120809 (MJF). We are indebted to and pleased to acknowledge Drs. Mary V. Relling and Cristine Crews for TPMT activity measurement