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1.
PLoS Negl Trop Dis ; 14(1): e0007901, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31999690

RESUMO

BACKGROUND: Large-scale deworming programs have, to date, mostly targeted preschool- and school-age children. As community-based deworming programs become more common, deworming will be offered to women of reproductive age. The World Health Organization recommends preventive chemotherapy be administered to pregnant women only after the first trimester. It is therefore important for deworming programs to be able to identify women in early pregnancy. Our objective was to validate a short questionnaire which could be used by deworming program managers to identify and screen out women in early pregnancy. METHODOLOGY/PRINCIPAL FINDINGS: In May and June 2018, interviewers administered a questionnaire, followed by a pregnancy test, to 1,203 adult women living in the Peruvian Amazon. Regression analyses were performed to identify questions with high predictive properties (using the pregnancy test as the gold standard). Test parameters were computed at different decision tree nodes (where nodes represented questions). With 106 women confirmed to be pregnant, the positive predictive value of asking the single question 'Are you pregnant?' was 100%, at a 'cost' of a false negative rate of 1.9% (i.e. 21 women were incorrectly identified as not pregnant when they were truly pregnant). Additional questions reduced the false negative rate, but increased the false positive rate. Rates were dependent on both the combination and the order of questions. CONCLUSIONS/SIGNIFICANCE: To identify women in early pregnancy when deworming programs are community-based, both the number and order of questions are important. The local context and cultural acceptability of different questions should inform this decision. When numbers are manageable and resources are available, pregnancy tests can be considered at different decision tree nodes to confirm pregnancy status. Trade-offs in terms of efficiency and misclassification rates will need to be considered to optimize deworming coverage in women of reproductive age.


Assuntos
Gravidez , Inquéritos e Questionários , Adulto , Feminino , Helmintíase/tratamento farmacológico , Helmintíase/prevenção & controle , Humanos , Pessoa de Meia-Idade , Peru , Testes de Gravidez
2.
Sci Transl Med ; 11(519)2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748227

RESUMO

T cell responses have been implicated in reduced risk of HIV acquisition in uninfected persons and control of viral replication in HIV-infected individuals. HIV Gag-specific T cells have been predominantly associated with post-infection control, whereas Env antigens are the target for protective antibodies; therefore, inclusion of both antigens is common in HIV vaccine design. However, inclusion of multiple antigens may provoke antigenic competition, reducing the potential effectiveness of the vaccine. HVTN 084 was a randomized, multicenter, double-blind phase 1 trial to investigate whether adding Env to a Gag/Pol vaccine decreases the magnitude or breadth of Gag/Pol-specific T cell responses. Fifty volunteers each received one intramuscular injection of 1 × 1010 particle units (PU) of rAd5 Gag/Pol and EnvA/B/C (3:1:1:1 mixture) or 5 × 109 PU of rAd5 Gag/Pol. CD4+ T cell responses to Gag/Pol measured 4 weeks after vaccination by cytokine expression were significantly higher in the group vaccinated without Env, whereas CD8+ T cell responses did not differ significantly between the two groups. Mapping of individual epitopes revealed greater breadth of the Gag/Pol-specific T cell response in the absence of Env compared to Env coimmunization. Addition of an Env component to a Gag/Pol vaccine led to reduced Gag/Pol CD4+ T cell response rate and magnitude as well as reduced epitope breadth, confirming the presence of antigenic competition. Therefore, T cell-based vaccine strategies should aim at choosing a minimalist set of antigens to reduce interference of individual vaccine components with the induction of the maximally achievable immune response.

3.
PLoS One ; 14(9): e0222183, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31536518

RESUMO

INTRODUCTION: Developing guidelines to inform the use of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention in resource-limited settings must necessarily be informed by considering the resources and infrastructure needed for PrEP delivery. We describe an approach that identifies subpopulations of cisgender men who have sex with men (MSM) and transgender women (TGW) to prioritize for the rollout of PrEP in resource-limited settings. METHODS: We use data from the iPrEx study, a multi-national phase III study of PrEP for HIV prevention in MSM/TGW, to build statistical models that identify subpopulations at high risk of HIV acquisition without PrEP, and with high expected PrEP benefit. We then evaluate empirically the population impact of policies recommending PrEP to these subpopulations, and contrast these with existing policies. RESULTS: A policy recommending PrEP to a high risk subpopulation of MSM/TGW reporting condomless receptive anal intercourse over the last 3 months (estimated 3.3% 1-year HIV incidence) yields an estimated 1.95% absolute reduction in 1-year HIV incidence at the population level, and 3.83% reduction over 2 years. Importantly, such a policy requires rolling PrEP out to just 59.7% of MSM/TGW in the iPrEx population. We find that this policy is identical to that which prioritizes MSM/TGW with high expected PrEP benefit. It is estimated to achieve nearly the same reduction in HIV incidence as the PrEP guideline put forth by the US Centers for Disease Control, which relies on the measurement of more behavioral risk factors and which would recommend PrEP to a larger subset of the MSM/TGW population (86% vs. 60%). CONCLUSIONS: These findings may be used to focus future mathematical modelling studies of PrEP in resource-limited settings on prioritizing PrEP for high-risk subpopulations of MSM/TGW. The statistical approach we took could be employed to develop PrEP policies for other at-risk populations and resource-limited settings.

5.
Epidemiology ; 30(5): 659-668, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31205289

RESUMO

BACKGROUND: Soil-transmitted helminth infections have been found to be associated with child development. The objective was to investigate hemoglobin levels and malnutrition as mediators of the association between Ascaris infection and intelligence quotient (IQ) scores in children. METHODS: We conducted a longitudinal cohort study in Iquitos, Peru, between September 2011 and July 2016. A total of 1760 children were recruited at 1 year of age and followed up annually to 5 years. We measured Ascaris infection and malnutrition at each study visit, and hemoglobin levels were measured as of age 3. The exposure was defined as the number of detected Ascaris infections between age 1 and 5. We measured IQ scores at age 5 and used Bayesian models to correct exposure misclassification. RESULTS: We included a sample of 781 children in the analysis. In results adjusted for Ascaris misclassification, mean hemoglobin levels mediated the association between Ascaris infection and IQ scores. The natural direct effects (not mediated by hemoglobin) (95% CrI) and natural indirect effects (mediated by hemoglobin) (95% CrI) were compared with no or one infection: -0.9 (-4.6, 2.8) and -4.3 (-6.9, -1.6) for the effect of two infections; -1.4 (-3.8, 1.0) and -1.2 (-2.0, -0.4) for three infections; and -0.4 (-3.2, 2.4) and -2.7 (-4.3, -1.0) for four or five infections. CONCLUSION: Our results are consistent with the hypothesis that hemoglobin levels mediate the association between Ascaris infection and IQ scores. Additional research investigating the effect of including iron supplements in STH control programs is warranted.

7.
N Engl J Med ; 380(3): 215-228, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30650322

RESUMO

BACKGROUND: Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed "radical cure"). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax. METHODS: This multicenter, double-blind, double-dummy, parallel group, randomized, placebo-controlled trial was conducted in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. We enrolled 522 patients with microscopically confirmed P. vivax infection (>100 to <100,000 parasites per microliter) and normal glucose-6-phosphate dehydrogenase (G6PD) activity (with normal activity defined as ≥70% of the median value determined at each trial site among 36 healthy male volunteers who were otherwise not involved in the trial). All patients received a 3-day course of chloroquine (total dose of 1500 mg). In addition, patients were assigned to receive a single 300-mg dose of tafenoquine on day 1 or 2 (260 patients), placebo (133 patients), or a 15-mg dose of primaquine once daily for 14 days (129 patients). The primary outcome was the Kaplan-Meier estimated percentage of patients who were free from recurrence at 6 months, defined as P. vivax clearance without recurrent parasitemia. RESULTS: In the intention-to-treat population, the percentage of patients who were free from recurrence at 6 months was 62.4% in the tafenoquine group (95% confidence interval [CI], 54.9 to 69.0), 27.7% in the placebo group (95% CI, 19.6 to 36.6), and 69.6% in the primaquine group (95% CI, 60.2 to 77.1). The hazard ratio for the risk of recurrence was 0.30 (95% CI, 0.22 to 0.40) with tafenoquine as compared with placebo (P<0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P<0.001). Tafenoquine was associated with asymptomatic declines in hemoglobin levels, which resolved without intervention. CONCLUSIONS: Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; DETECTIVE ClinicalTrials.gov number, NCT01376167 .).


Assuntos
Aminoquinolinas/administração & dosagem , Antimaláricos/administração & dosagem , Malária Vivax/tratamento farmacológico , Plasmodium vivax , Prevenção Secundária/métodos , Adolescente , Adulto , Aminoquinolinas/efeitos adversos , Antimaláricos/efeitos adversos , Cloroquina/administração & dosagem , Citocromo P-450 CYP2D6/metabolismo , Intervalo Livre de Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucosefosfato Desidrogenase/metabolismo , Hemoglobinas/análise , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Modelos Logísticos , Malária Vivax/metabolismo , Masculino , Parasitemia/tratamento farmacológico , Plasmodium vivax/isolamento & purificação , Primaquina/administração & dosagem
8.
N Engl J Med ; 380(3): 229-241, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30650326

RESUMO

BACKGROUND: Tafenoquine, a single-dose therapy for Plasmodium vivax malaria, has been associated with relapse prevention through the clearance of P. vivax parasitemia and hypnozoites, termed "radical cure." METHODS: We performed a phase 3, prospective, double-blind, double-dummy, randomized, controlled trial to compare tafenoquine with primaquine in terms of safety and efficacy. The trial was conducted at seven hospitals or clinics in Peru, Brazil, Colombia, Vietnam, and Thailand and involved patients with normal glucose-6-phosphate dehydrogenase (G6PD) enzyme activity and female patients with moderate G6PD enzyme deficiency; all patients had confirmed P. vivax parasitemia. The patients were randomly assigned, in a 2:1 ratio, to receive a single 300-mg dose of tafenoquine or 15 mg of primaquine once daily for 14 days (administered under supervision); all patients received a 3-day course of chloroquine and were followed for 180 days. The primary safety outcome was a protocol-defined decrease in the hemoglobin level (>3.0 g per deciliter or ≥30% from baseline or to a level of <6.0 g per deciliter). Freedom from recurrence of P. vivax parasitemia at 6 months was the primary efficacy outcome in a planned patient-level meta-analysis of the current trial and another phase 3 trial of tafenoquine and primaquine (per-protocol populations), and an odds ratio for recurrence of 1.45 (tafenoquine vs. primaquine) was used as a noninferiority margin. RESULTS: A protocol-defined decrease in the hemoglobin level occurred in 4 of 166 patients (2.4%; 95% confidence interval [CI], 0.9 to 6.0) in the tafenoquine group and in 1 of 85 patients (1.2%; 95% CI, 0.2 to 6.4) in the primaquine group, for a between-group difference of 1.2 percentage points (95% CI, -4.2 to 5.0). In the patient-level meta-analysis, the percentage of patients who were free from recurrence at 6 months was 67.0% (95% CI, 61.0 to 72.3) among the 426 patients in the tafenoquine group and 72.8% (95% CI, 65.6 to 78.8) among the 214 patients in the primaquine group. The efficacy of tafenoquine was not shown to be noninferior to that of primaquine (odds ratio for recurrence, 1.81; 95% CI, 0.82 to 3.96). CONCLUSIONS: Among patients with normal G6PD enzyme activity, the decline in hemoglobin level with tafenoquine did not differ significantly from that with primaquine. Tafenoquine showed efficacy for the radical cure of P. vivax malaria, although tafenoquine was not shown to be noninferior to primaquine. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; GATHER ClinicalTrials.gov number, NCT02216123 .).


Assuntos
Aminoquinolinas/administração & dosagem , Antimaláricos/administração & dosagem , Malária Vivax/tratamento farmacológico , Plasmodium vivax , Primaquina/administração & dosagem , Prevenção Secundária/métodos , Adolescente , Adulto , Aminoquinolinas/efeitos adversos , Antimaláricos/efeitos adversos , Cloroquina/uso terapêutico , Intervalo Livre de Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/complicações , Hemoglobinas/análise , Humanos , Estimativa de Kaplan-Meier , Malária Vivax/complicações , Masculino , Parasitemia/tratamento farmacológico , Plasmodium vivax/isolamento & purificação , Primaquina/efeitos adversos , Estudos Prospectivos
10.
Am J Clin Nutr ; 108(6): 1238-1248, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30351381

RESUMO

Background: Anemia is a term that describes low hemoglobin concentrations and can result from micronutrient deficiencies, infection, or low birth weight. Early-life anemia, particularly iron-deficiency anemia (IDA) is associated with several negative metabolic, developmental, and cognitive outcomes, some of which persist into adulthood. Objective: The aim of this study was to investigate alterations in systemic metabolism and fecal microbial diversity and functionality associated with anemia and IDA in male and female infants from Iquitos, Peru. Design: Cross-sectional stool and serum samples were collected from 95 infants (53 boys and 42 girls) at 12 mo of age. The fecal microbiome was assessed by using 16S ribosomal RNA gene sequencing, and the fecal and serum metabolomes were quantified using 1H-nuclear magnetic resonance. Results: The prevalence of anemia was 64%, with a greater proportion of anemia in male infants attributed to iron deficiency. Metabolically, anemia was associated with decreased concentrations of tricarboxylic acid cycle metabolites in both sexes (males: succinate, P = 0.031; females: fumarate, P = 0.028). In addition, anemic male infants exhibited significantly lower serum concentrations of several amino acids compared with nonanemic male infants. Although no specific structural or functional differences in the microbiota were observed with anemia in general, likely due the heterogeneity of its etiology, IDA affected the microbiome both structurally and functionally. Specifically, the abundance of butyrate-producing bacteria was lower in IDA subjects of both sexes than in nonanemic, non-iron-deficient subjects of the same sex (females: Butyricicoccus, P = 0.041; males: Coprococcus, P = 0.010; Roseburia, P = 0.027). IDA male infants had higher concentrations of 4-hydroxyphenyllactate (P < 0.001) and putrescine (P = 0.042) than those without IDA, whereas IDA female infants exhibited higher concentrations of leucine (P = 0.011) and valine (P = 0.003). Conclusions: Sexually dimorphic differences associated with anemia and IDA are suggestive of greater mitochondrial dysfunction and oxidative stress in male infants compared with female infants, and alterations in microbial structure and function may further contribute. Differences in metabolic pathways associated with anemia and IDA in each sex point to potential mechanisms for the associated lasting cognitive deficits. This trial is registered at clinicaltrials.gov as NCT03377777.


Assuntos
Anemia Ferropriva/sangue , Anemia Ferropriva/microbiologia , Microbioma Gastrointestinal/fisiologia , Fatores Sexuais , Aminoácidos/sangue , Ciclo do Ácido Cítrico , Estudos Transversais , Fezes/química , Fezes/microbiologia , Feminino , Humanos , Lactente , Leucina/análise , Masculino , Metaboloma/fisiologia , Mitocôndrias/fisiologia , Estresse Oxidativo , Peru , Fenilpropionatos/análise , Putrescina/análise , Valina/análise
11.
PLoS Negl Trop Dis ; 12(7): e0006688, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30052640

RESUMO

BACKGROUND: Soil-transmitted helminth (STH) infection leads to malnutrition and anemia, and has been linked to impaired child development. Previous research on this topic is limited and mostly conducted in school-age children. The goal of this study was to determine the effect of the number of detected STH infections between one and two years of age on subsequent cognitive and verbal abilities, in a cohort of preschool children. METHODOLOGY/PRINCIPAL FINDINGS: A longitudinal cohort study was conducted in 880 children in Iquitos, Peru between September 2011 and July 2016. Children were recruited at one year of age and followed up at 18 months and then annually between two and five years of age. STH infection was measured with the Kato-Katz technique or the direct smear technique. Child development was measured with the Bayley Scales of Infant and Toddler Development-III at the one to three-year visits and with the Wechsler Preschool and Primary Scale of Intelligence-III at the four and five-year visits. Hierarchical multivariable linear regression models were used to account for the repeated outcome measures for each child and Bayesian latent class analysis was used to adjust for STH misclassification. Children found infected with any STH infection between one and two years of age had lower cognitive scores between two and five years of age (between group score differences (95% credible intervals) for infected once, and infected two or three times, compared to never infected: -4.31 (-10.64, -0.14) and -3.70 (-10.11, -0.11), respectively). Similar results were found for Ascaris infection and for verbal scores. CONCLUSIONS/SIGNIFICANCE: An association was found between having been infected with Ascaris or any STH between one and two years of age and lower cognitive and verbal abilities later in childhood. These results suggest that targeting children for STH control as of one year of age is particularly important.


Assuntos
Cognição , Helmintíase/parasitologia , Helmintíase/psicologia , Helmintos/fisiologia , Solo/parasitologia , Aprendizagem Verbal , Animais , Desenvolvimento Infantil , Pré-Escolar , Estudos de Coortes , Feminino , Helmintos/genética , Helmintos/isolamento & purificação , Humanos , Lactente , Estudos Longitudinais , Masculino , Peru , Fala
12.
Int J Epidemiol ; 47(4): 1180-1194, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30010794

RESUMO

Background: Limited research has documented an association between soil-transmitted helminth (STH) infections and child development. This has recently been identified as an important knowledge gap. Methods: A longitudinal cohort study was conducted in Iquitos, Peru, between September 2011 and July 2016. A cohort of 880 children, recruited at 1 year of age, was followed up to 5 years. STH infection was measured annually and child development was measured with the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) at 5 years. Linear-regression models were used to investigate the effect of the number of detected STH infections between 1 and 5 years of age on WPPSI-III scores at 5 years of age. Bayesian latent class analysis was used to adjust for exposure misclassification. Results: A total of 781 (88.8%) children were included in the analysis. In multivariable analysis, adjusted for STH misclassification, increasing numbers of Ascaris, Trichuris, hookworm and any STH infections were associated with lower WPPSI-III scores. Among the largest observed effects were those for the effect of Ascaris infection on verbal IQ scores [difference in IQ (95% CrI) for two, three, and four or five detected infections compared with zero or one infection: -8.27 (-13.85, -3.10), -6.69 (-12.05, -2.05) and -5.06 (-10.75, 0.05), respectively]. Misclassification of STH infection generally led to a bias towards the null. Conclusions: These results document an association between STH infection and child development. The results highlight the importance of adjusting for STH misclassification; however, future research is needed to accurately determine the sensitivity of STH diagnostic techniques. STH control in preschool children may contribute to lowering the disease burden associated with poor child development.


Assuntos
Desenvolvimento Infantil , Helmintíase/epidemiologia , Solo/parasitologia , Animais , Teorema de Bayes , Pré-Escolar , Feminino , Helmintos , Humanos , Lactente , Modelos Lineares , Estudos Longitudinais , Masculino , Análise Multivariada , Peru/epidemiologia
13.
Lancet Infect Dis ; 18(8): 874-883, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29909069

RESUMO

BACKGROUND: DSM265 is a novel, long-duration inhibitor of plasmodium dihydroorotate dehydrogenase (DHODH) with excellent selectivity over human DHODH and activity against blood and liver stages of Plasmodium falciparum. This study aimed to assess the efficacy of DSM265 in patients with P falciparum or Plasmodium vivax malaria infection. METHODS: This proof-of-concept, open-label, phase 2a study was conducted at the Asociación Civil Selva Amazónica in Iquitos, Peru. Patients aged 18-70 years, weighing 45-90 kg, who had clinical malaria (P falciparum or P vivax monoinfection) and fever within the previous 24 h were eligible. Exclusion criteria were clinical or laboratory signs of severe malaria, inability to take oral medicine, and use of other antimalarial treatment in the preceding 14 days. Patients were divided into cohorts of those with P falciparum (cohort a) or P vivax (cohort b) infection. Two initial cohorts received single oral doses of 400 mg DSM265. Patients were followed up for efficacy for 28 days and safety for 35 days. Further cohorts received escalated or de-escalated doses of DSM265, after safety and efficacy assessment of the initial dose. The primary endpoints were the proportion of patients achieving PCR-adjusted adequate clinical and parasitological response (ACPR) by day 14 for patients infected with P falciparum and the proportion of patients achieving a crude cure by day 14 for those infected with P vivax. Cohort success, the criteria for dose escalation, was defined as ACPR (P falciparum) or crude cure (P vivax) in at least 80% of patients in the cohort. The primary analysis was done in the intention-to-treat population (ITT) and the per-protocol population, and safety analyses were done in all patients who received the study drug. This study is registered at ClinicalTrials.gov (NCT02123290). FINDINGS: Between Jan 12, 2015, and Dec 2, 2015, 45 Peruvian patients (24 with P falciparum [cohort a] and 21 with P vivax [cohort b] infection) were sequentially enrolled. For patients with P falciparum malaria in the per-protocol population, all 11 (100%) in the 400 mg group and eight (80%) of ten in the 250 mg group achieved ACPR on day 14. In the ITT analysis, 11 (85%) of 13 in the 400 mg group and eight (73%) of 11 in the 250 mg group achieved ACPR at day 14. For the patients with P vivax malaria, the primary endpoint was not met. In the per-protocol analysis, none of four patients who had 400 mg, three (50%) of six who had 600 mg, and one (25%) of four who had 800 mg DSM265 achieved crude cure at day 14. In the ITT analysis, none of five in the 400 mg group, three (33%) of nine in the 600 mg group, and one (14%) of seven in the 800 mg group achieved crude cure at day 14. During the 28-day extended observation of P falciparum patients, a resistance-associated mutation in the gene encoding the DSM265 target DHODH was observed in two of four recurring patients. DSM265 was well tolerated. The most common adverse events were pyrexia (20 [44%] of 45) and headache (18 [40%] of 45), which are both common symptoms of malaria, and no patients had any treatment-related serious adverse events or adverse events leading to study discontinuation. INTERPRETATION: After a single dose of DSM265, P falciparum parasitaemia was rapidly cleared, whereas against P vivax, DSM265 showed less effective clearance kinetics. Its long duration of action provides the potential to prevent recurrence of P falciparum after treatment with a single dose, which should be further assessed in future combination studies. FUNDING: The Global Health Innovative Technology Fund, the Bill & Melinda Gates Foundation, the National Institutes of Health (R01 AI103058), the Wellcome Trust, and the UK Department of International Development.


Assuntos
Antimaláricos/administração & dosagem , Malária Falciparum/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Plasmodium falciparum/imunologia , Pirimidinas/administração & dosagem , Triazóis/administração & dosagem , Adulto , Estudos de Coortes , Feminino , Humanos , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Malária Vivax/imunologia , Malária Vivax/parasitologia , Masculino , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Peru
14.
Emerg Infect Dis ; 23(11): 1929-1930, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29048291

RESUMO

Diffuse multibacillary leprosy of Lucio and Latapí is mainly reported in Mexico and Central America. We report a case in a 65-year-old man in Peru. He also had Lucio's phenomenon, characterized by vascular thrombosis and invasion of blood vessel walls by leprosy bacilli, causing extensive skin ulcers.


Assuntos
Hanseníase Multibacilar/diagnóstico , Mycobacterium leprae/isolamento & purificação , Idoso , Humanos , Hanseníase Multibacilar/microbiologia , Hanseníase Multibacilar/patologia , Masculino , Peru , Pele/microbiologia , Pele/patologia
15.
Sex Transm Dis ; 44(5): 306-309, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28407648

RESUMO

Exchange sex and higher education were associated with an increased likelihood of international sexual partnerships (ISPs). Exchange sex and older age were associated with an increased likelihood of condomless sex in ISPs. Educational and socioeconomic factors may create unbalanced power dynamics that influence exchange sex and condomless sex in ISPs.


Assuntos
Infecções por HIV/transmissão , Comportamento Sexual , Parceiros Sexuais , Adulto , Preservativos/estatística & dados numéricos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Assunção de Riscos , Classe Social , Fatores Socioeconômicos , Sexo sem Proteção , Adulto Jovem
16.
PLoS One ; 12(2): e0171136, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28207749

RESUMO

OBJECTIVE: To identify determinants which influence the timing of the first antenatal care (ANC) visit in pregnant women. DESIGN: Retrospective matched nested case-control study. SETTING: Two health centres, Belén and 6 de Octubre, in the Peruvian Amazon. POPULATION: All pregnant women who had attended ANC during the years 2010, 2011, and 2012. METHODS: All cases (819 women initiating ANC in their first trimester) were selected from ANC registries from 2010 to 2012. A random sample of controls (819 women initiating ANC in their second or third trimester) was matched 1:1 to cases on health centre and date of first ANC visit. Data were obtained from ANC registries. Conditional logistic regression analyses were performed. MAIN OUTCOME MEASURE: Case-control status of each woman determined by the gestational age at first ANC visit. RESULTS: Cases had higher odds of: 1) being married or cohabiting (aOR = 1.69; 95% CI: 1.19, 2.41); 2) completing secondary school or attending post-secondary school (aOR = 1.45; 95% CI: 1.02, 2.06); 3) living in an urban environment (aOR = 1.79; 95% CI: 1.04, 3.10) and 4) having had a previous miscarriage (aOR = 1.56; 95% CI: 1.13, 2.15), compared to controls. No statistically significant difference in odds was found for parity (aOR = 1.08; 95% CI: 0.85, 1.36). CONCLUSIONS: This study provides empirical evidence of determinants of first ANC attendance. These findings are crucial to the planning and timing of local interventions, like deworming, aimed at pregnant women so that they can access and benefit fully from all government-provided ANC services.


Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Primeiro Trimestre da Gravidez , Cuidado Pré-Natal/estatística & dados numéricos , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Humanos , Paridade , Aceitação pelo Paciente de Cuidados de Saúde , Peru , Gravidez , Gestantes , Estudos Retrospectivos , Adulto Jovem
17.
PLoS Negl Trop Dis ; 11(1): e0005098, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28056024

RESUMO

BACKGROUND: Nutritional interventions targeting the critical growth and development period before two years of age can have the greatest impact on health trajectories over the life course. Compelling evidence has demonstrated that interventions investing in maternal health in the first 1000 days of life are beneficial for both mothers and their children. One such potential intervention is deworming integrated into maternal postpartum care in areas where soil-transmitted helminth (STH) infections are endemic. METHODOLOGY/PRINCIPAL FINDINGS: From February to August 2014, 1010 mother-infant pairs were recruited into a trial aimed at assessing the effectiveness of maternal postpartum deworming on infant and maternal health outcomes. Following delivery, mothers were randomly assigned to receive either single-dose 400 mg albendazole or placebo. Participants were followed-up at 1 and 6 months postpartum. There was no statistically significant difference in mean weight gain between infants in the experimental and control groups (mean difference: -0.02; 95% CI: -0.1, 0.08) at 6 months of age. Further, deworming had no effect on measured infant morbidity indicators. However, ad hoc analyses restricted to mothers who tested positive for STHs at baseline suggest that infants of mothers in the experimental group had greater mean length gain in cm (mean difference: 0.8; 95% CI: 0.1, 1.4) and length-for-age z-score (mean difference: 0.5; 95% CI: 0.2, 0.8) at 6 months of age. CONCLUSIONS/SIGNIFICANCE: In a study population composed of both STH-infected and uninfected mothers, maternal postpartum deworming was insufficient to impact infant growth and morbidity indicators up to 6 months postpartum. Among STH-infected mothers, however, important improvements in infant length gain and length-for-age were observed. The benefits of maternal postpartum deworming should be further investigated in study populations having higher overall prevalences and intensities of STH infections and, in particular, where whipworm and hookworm infections are of public health concern. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01748929).


Assuntos
Albendazol/administração & dosagem , Anti-Helmínticos/administração & dosagem , Helmintíase/tratamento farmacológico , Doenças do Recém-Nascido/tratamento farmacológico , Ganho de Peso/efeitos dos fármacos , Adulto , Método Duplo-Cego , Feminino , Seguimentos , Helmintíase/parasitologia , Helmintíase/fisiopatologia , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/parasitologia , Doenças do Recém-Nascido/fisiopatologia , Masculino , Mães , Peru , Período Pós-Parto , Adulto Jovem
18.
Health Promot Perspect ; 6(4): 174-179, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27766233

RESUMO

Background: In Peru, 11% of deaths are due to trauma. Iquitos is a large underserved Peruvian city isolated from central resources by its geography. Our objective was to implement a locally driven trauma registry to sustainably improve trauma healthcare in this region. Methods: All trauma patients presenting to the main regional referral hospital were included in the trauma registry. A pilot study retrospectively analyzed data from the first two months after implementation. Results: From March to April 2013, 572 trauma patients were entered into the database. Average age was 26.9 years. Ten percent of patients presented more than 24 hours after injury. Most common mechanisms of injury were falls (25.5%), motor vehicle collisions (23.3%), and blunt assault (10.5%). Interim analysis revealed that 99% of patients were entered into the database. However, documentation of vital signs was poor: 42% of patients had temperature, 26% had oxygen saturation documented. After reporting to registry staff, a significant increase in temperature (42 to 97%, P < 0.001) and oxygen saturation (26 to 92%, P < 0.001) documentation was observed. Conclusion: A trauma registry is possible to implement in a resource-poor setting. Future efforts will focus on analysis of data to enhance prevention and treatment of injuries in Iquitos.

19.
Lancet HIV ; 3(11): e521-e528, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27658870

RESUMO

BACKGROUND: As pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine for the prevention of HIV infection is rolled out internationally, strategies to maintain effectiveness and to minimise adverse effects merit consideration. In this study, we aimed to assess reductions in renal function and predictors of renal toxicity in a large open-label study of PrEP. METHODS: As part of the iPrEx open-label extension (OLE) study, men who have sex with men or transgender women aged 18-70 years who were HIV negative and had participated in three previous PrEP trials from Brazil, Ecuador, Peru, South Africa, Thailand, and the USA were enrolled into an open-label PrEP study. There were no restrictions on current renal function for enrolment into iPrEx OLE, in which participants were given combination tablets of tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) and advised to take one tablet per day. At follow-up sessions every 12 weeks, participants' creatinine clearance on PrEP was estimated and in a subset of participants, hair samples were collected to measure tenofovir and emtricitabine concentrations (a measure of adherence and exposure) via liquid-chromatography-tandem-mass-spectrometry. Reductions in creatinine clearance from baseline were calculated and predictors of decline were identified by use of multivariate models. iPrEx is registered with ClinicalTrials.com, number NCT00458393. FINDINGS: Baseline characteristics were similar between all participants in iPrEx-OLE (1224 participants with 7475 person-visits) and those participating in the hair substudy (220 participants with 1114 person-visits). During a median of 72 weeks, the mean decline in creatinine clearance was -2·9% (95% CI -2·4 to -3·4; ptrend<0·0001), but declines were greater for those who started PrEP at older ages: participants aged 40-50 years at baseline had declines of -4·2% (95% CI -2·8 to -5·5) and participants older than 50 years at baseline had declines of -4·9% (-3·1 to -6·8). In multivariate models, age and baseline creatinine clearance less than 90 mL/min predicted declines in renal function. We identified a monotonic association between percentage decrease in creatinine clearance and the number of doses of tenofovir disoproxil fumarate and emtricitabine taken per week, as estimated by hair concentrations of tenofovir and emtricitabine (ptrend=0·008). INTERPRETATION: Our data suggest that the frequency of safety monitoring for PrEP might need to be different between age groups and that pharmacological measures can monitor for toxic effects as well as adherence. FUNDING: National Institutes of Health.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Creatinina/sangue , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição , Adulto , Fatores Etários , Fármacos Anti-HIV/análise , Fármacos Anti-HIV/uso terapêutico , Brasil/epidemiologia , Estudos de Coortes , Equador/epidemiologia , Emtricitabina/efeitos adversos , Emtricitabina/análise , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/virologia , Cabelo/química , Humanos , Testes de Função Renal , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Peru/epidemiologia , África do Sul , Tenofovir/efeitos adversos , Tenofovir/análise , Tenofovir/uso terapêutico , Tailândia/epidemiologia
20.
Am J Trop Med Hyg ; 95(1): 83-7, 2016 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-27139441

RESUMO

Large-scale deworming interventions, using anthelminthic drugs, are recommended in areas where the prevalence of soil-transmitted helminth infection is high. Anthelminthic safety has been established primarily in school-age children. Our objective was to provide evidence on adverse events from anthelminthic use in early childhood. A randomized multi-arm, placebo-controlled trial of mebendazole, administered at different times and frequencies, was conducted in children 12 months of age living in Iquitos, Peru. Children were followed up to 24 months of age. The association between mebendazole administration and the occurrence of a serious or minor adverse event was determined using logistic regression. There was a total of 1,686 administrations of mebendazole and 1,676 administrations of placebo to 1,760 children. Eighteen serious adverse events (i.e., 11 deaths and seven hospitalizations) and 31 minor adverse events were reported. There was no association between mebendazole and the occurrence of a serious adverse event (odds ratio [OR] = 1.21; 95% confidence interval [CI] = 0.47, 3.09) or a minor adverse event (OR = 0.84; 95% CI = 0.41, 1.72). Results from our trial support evidence of safety in administering mebendazole during early childhood. These results support World Health Organization deworming policy and the scaling up of interventions to reach children as of 12 months of age in endemic areas.


Assuntos
Anti-Helmínticos/efeitos adversos , Helmintíase/tratamento farmacológico , Mebendazol/efeitos adversos , Anti-Helmínticos/uso terapêutico , Pré-Escolar , Método Duplo-Cego , Estudos de Viabilidade , Humanos , Lactente , Modelos Logísticos , Mebendazol/uso terapêutico , Análise Multivariada , Peru , Prevalência , Fatores Socioeconômicos , Solo/parasitologia
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