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1.
PLoS Med ; 16(5): e1002784, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31100064

RESUMO

BACKGROUND: In Vietnam, the importance of vivax malaria relative to falciparum during the past decade has steadily increased to 50%. This, together with the spread of multidrug-resistant Plasmodium falciparum, is a major challenge for malaria elimination. A 2-year prospective cohort study to assess P. vivax morbidity after radical cure treatment and related risk factors was conducted in Central Vietnam. METHODS AND FINDINGS: The study was implemented between April 2009 and December 2011 in four neighboring villages in a remote forested area of Quang Nam province. P. vivax-infected patients were treated radically with chloroquine (CQ; 25 mg/kg over 3 days) and primaquine (PQ; 0.5 mg/kg/day for 10 days) and visited monthly (malaria symptoms and blood sampling) for up to 2 years. Time to first vivax recurrence was estimated by Kaplan-Meier survival analysis, and risk factors for first and recurrent infections were identified by Cox regression models. Among the 260 P. vivax patients (61% males [159/260]; age range 3-60) recruited, 240 completed the 10-day treatment, 223 entered the second month of follow-up, and 219 were followed for at least 12 months. Most individuals (76.78%, 171/223) had recurrent vivax infections identified by molecular methods (polymerase chain reaction [PCR]); in about half of them (55.61%, 124/223), infection was detected by microscopy, and 84 individuals (37.67%) had symptomatic recurrences. Median time to first recurrence by PCR was 118 days (IQR 59-208). The estimated probability of remaining free of recurrence by month 24 was 20.40% (95% CI [14.42; 27.13]) by PCR, 42.52% (95% CI [35.41; 49.44]) by microscopy, and 60.69% (95% CI [53.51; 67.11]) for symptomatic recurrences. The main risk factor for recurrence (first or recurrent) was prior P. falciparum infection. The main limitations of this study are the age of the results and the absence of a comparator arm, which does not allow estimating the proportion of vivax relapses among recurrent infections. CONCLUSION: A substantial number of P. vivax recurrences, mainly submicroscopic (SM) and asymptomatic, were observed after high-dose PQ treatment (5.0 mg/kg). Prior P. falciparum infection was an important risk factor for all types of vivax recurrences. Malaria elimination efforts need to address this largely undetected P. vivax transmission by simultaneously tackling the reservoir of P. falciparum and P. vivax infections.


Assuntos
Antimaláricos/administração & dosagem , Cloroquina/administração & dosagem , Malária Vivax/tratamento farmacológico , Plasmodium vivax/efeitos dos fármacos , Primaquina/administração & dosagem , Adolescente , Adulto , Antimaláricos/efeitos adversos , Criança , Pré-Escolar , Cloroquina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Incidência , Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Malária Vivax/transmissão , Masculino , Pessoa de Meia-Idade , Plasmodium vivax/patogenicidade , Primaquina/efeitos adversos , Intervalo Livre de Progressão , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Vietnã/epidemiologia , Adulto Jovem
2.
Pediatr Res ; 82(1): 155-163, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28376078

RESUMO

BackgroundPropranolol's mechanism of action for controlling infantile hemangioma (IH) remains unclear. We hypothesize that this nonselective beta antagonist downregulates renin-angiotensin-aldosterone (RAA) axis components, preventing angiogenic substrate induction of IH.MethodsIH tissue and serum were collected from children with propranolol-treated or -untreated IH during surgery. Normal skin and serum from demographically matched children were used as controls. Real-time PCR and western blot quantified RAA components in proliferative (n=10), involuting (n=10), propranolol-treated (n=12) IH, and normal specimens (n=11). Serum was analyzed by enzyme-linked immunosorbent assay (ELISA).ResultsThere were significantly greater messenger RNA (mRNA) levels of angiotensinogen (AGT) in proliferating IH, but not in involuting or treated IH, when compared with controls (P<0.05). Angiotensin-converting enzyme (ACE) and angiotensin II receptor 1 (AGTR1) mRNA expression was higher in all IH specimens when comparedwith controls (P<0.05). ACE and AGTR1 protein expression was greater in proliferating IH tissue compared with that in controls and in involuting and treated IH tissue (P<0.05). ELISA showed no significant difference in ACE serum levels but did show a significant reduction in renin in involuting compared with proliferating IH (P<0.05).ConclusionsThe protein and mRNA expression of several RAA pathway constituents is elevated in IH tissue when compared with that in normal tissue. The action of propranolol on IH may be the result of reductions in ACE and AGTR1.


Assuntos
Hemangioma Capilar/metabolismo , Propranolol/uso terapêutico , Sistema Renina-Angiotensina , Angiotensinogênio/metabolismo , Proliferação de Células , Pré-Escolar , Feminino , Hemangioma Capilar/tratamento farmacológico , Humanos , Lactente , Fígado/metabolismo , Masculino , Peptidil Dipeptidase A/metabolismo , RNA Mensageiro/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Pele/metabolismo
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