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2.
J Matern Fetal Neonatal Med ; 33(1): 92-95, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29886762

RESUMO

Background: Malaria in pregnancy carries a proven huge health burden; however, the economic challenges have not been properly evaluated in Nigeria.Methodology: The study was a descriptive cross-sectional hospital-based approach. A structured questionnaire was used to collect microeconomic data from pregnant women, on the medical and nonmedical cost of malaria to them.Results: A total of 371 questionnaires were analyzed (93%; 371/400), of 400 respondents interviewed. The average direct medical cost was N3581.78 naira (N) (US$11.86) with SD of N177.9 and mean direct nonmedical cost of N5741.5 (US$18.97). Of the patients, 86.8% received artemisinin-based combination therapy (ACTs) for the treatment of malaria. Nigeria has an estimated population of women of child-bearing age of 40 million and, the fertility rate of 124 per 1000. On the basis of estimation of 56.5% of pregnant women receiving at least one intermittent preventive therapy (IPT), will approximate to 22.8 billion naira (US$75.5 million) national annual expenditure for malaria in pregnancy. This approximates to 0.016% of the Nigerian gross domestic product of 481 billion USD of 2015. The major mechanism that was used to pay for treatment was out-of-pocket (OOP).Conclusions: Malaria carries high-economic burden both on individual and national levels, especially in Nigeria where OOPs is the major payment mechanism. Scaling up malaria control measures will not only improve the lives of pregnant women but will also improve the economy of the nation.


Assuntos
Antimaláricos/economia , Malária/tratamento farmacológico , Malária/economia , Complicações Parasitárias na Gravidez/tratamento farmacológico , Complicações Parasitárias na Gravidez/economia , Adulto , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/economia , Efeitos Psicossociais da Doença , Estudos Transversais , Quimioterapia Combinada/economia , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Custos de Cuidados de Saúde , Humanos , Recém-Nascido , Malária/epidemiologia , Nigéria/epidemiologia , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Inquéritos e Questionários , Adulto Jovem
3.
PLoS Negl Trop Dis ; 13(6): e0007371, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31188820

RESUMO

BACKGROUND: The objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other helminths on the inflammatory micro environment. METHODS/FINDINGS: This was a secondary analysis of samples from 369 mother-infant pairs participating in a randomized controlled trial of praziquantel given at 12-16 weeks' gestation. We performed regression analysis to address our study objectives. In maternal peripheral blood, the concentrations of CXCL8, and TNF receptor I and II decreased from 12 to 32 weeks' gestation, while IL-13 increased. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Hookworm infection was associated with elevated placental IL-1, CXCL8 and IFN-γ. The risk of small-for-gestational age increased with elevated IL-6, IL-10, and CXCL8 in cord blood. The risk of prematurity was increased when cord blood sTNFRI and placental IL-5 were elevated. CONCLUSIONS: Our study suggests that fetal cytokines, which may be related to infectious disease exposures, contribute to poor intrauterine growth. Additionally, hookworm infection influences cytokine concentrations at the maternal-fetal interface. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: ClinicalTrials.gov (NCT00486863).


Assuntos
Anti-Helmínticos/administração & dosagem , Citocinas/sangue , Sangue Fetal/química , Placenta/patologia , Praziquantel/administração & dosagem , Complicações Parasitárias na Gravidez/patologia , Esquistossomose Japônica/patologia , Adulto , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Masculino , Filipinas , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Esquistossomose Japônica/complicações , Esquistossomose Japônica/tratamento farmacológico , Adulto Jovem
4.
PLoS Negl Trop Dis ; 13(5): e0007406, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31083673

RESUMO

BACKGROUND: The World Health Organization has recently reemphasized the importance of providing preventive chemotherapy to women of reproductive age in countries endemic for soil-transmitted helminthiasis as they are at heightened risk of associated morbidity. The Demographic and Health Surveys (DHS) Program is responsible for collecting and disseminating accurate, nationally representative data on health and population in developing countries. Our study aims to estimate the number of pregnant women at risk of soil-transmitted helminthiasis that self-reported deworming by antenatal services in endemic countries that conducted Demographic and Health Surveys. METHODOLOGY/PRINCIPAL FINDINGS: The number of pregnant women living in endemic countries was extrapolated from the United Nations World Population Prospects 2015. National deworming coverage among pregnant women were extracted from Demographic and Health Surveys and applied to total numbers of pregnant women in the country. Sub-national DHS with data on self-reported deworming were available from 49 of the 102 endemic countries. In some regions more than 73% of STH endemic countries had a DHS. The DHS report an average deworming coverage of 23% (CI 19-28), ranging from 2% (CI 1-3) to 35% (CI 29-40) in the different regions, meaning more than 16 million pregnant women were dewormed in countries surveyed by DHS. The deworming rates amongst the 43 million pregnant women in STH endemic countries not surveyed by DHS remains unknown. CONCLUSIONS/SIGNIFICANCE: These estimates will serve to establish baseline numbers of deworming coverage among pregnant women, monitor progress, and urge endemic countries to continue working toward reducing the burden of soil-transmitted helminthiasis. The DHS program should be extended to STH-endemic countries currently not covering the topic of deworming during pregnancy.


Assuntos
Anti-Helmínticos/uso terapêutico , Helmintíase/tratamento farmacológico , Helmintos/isolamento & purificação , Complicações Parasitárias na Gravidez/tratamento farmacológico , Solo/parasitologia , Adulto , África/epidemiologia , Animais , Ásia/epidemiologia , Doenças Endêmicas/prevenção & controle , Feminino , Helmintíase/epidemiologia , Helmintos/classificação , Helmintos/genética , Humanos , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Autorrelato , América do Sul/epidemiologia , Organização Mundial da Saúde , Adulto Jovem
5.
J Infect Dis ; 220(3): 457-466, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-30891605

RESUMO

BACKGROUND: Placental malaria is a major cause of adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of parasitemia during pregnancy and placental malaria. METHODS: Data came from 637 women enrolled in a randomized controlled trial of intermittent preventive treatment of malaria in pregnancy (IPTp) from Uganda. Plasmodium falciparum parasitemia was assessed using microscopy and ultrasensitive quantitative PCR at intervals of 28 days from 12 to 20 weeks gestation through delivery. Multivariate analysis was used to measure associations between characteristics of parasitemia during pregnancy and the risk of placental malaria based on histopathology. RESULTS: Overall risk of placental malaria was 44.6%. None of the 34 women without parasitemia detected during pregnancy had evidence of placental malaria. Increasing proportion of interval assessments with parasitemia and higher parasite densities were independently associated with an increased risk of placental malaria. Higher gravidity and more effective IPTp were associated with a decreased risk of placental malaria. Women with parasitemia only detected before the third trimester still had an increased risk of placental malaria. CONCLUSIONS: The frequency, density, and timing of parasitemia are all important risk factors for placental malaria. Interventions should target the prevention of all levels of parasitemia throughout pregnancy.


Assuntos
Malária Falciparum/complicações , Malária Falciparum/parasitologia , Parasitemia/etiologia , Placenta/parasitologia , Complicações Infecciosas na Gravidez/parasitologia , Complicações Parasitárias na Gravidez/parasitologia , Adulto , Antimaláricos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Estudos Longitudinais , Malária Falciparum/tratamento farmacológico , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Parasitárias na Gravidez/tratamento farmacológico , Uganda , Adulto Jovem
6.
Parasite ; 26: 13, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30838974

RESUMO

We assessed clinical and serologic findings in 25 infants with congenital toxoplasmosis born to mothers treated during pregnancy in the United States. Results indicate a lower prevalence of eye findings and hydrocephalus in the group of infants born to treated mothers (62.5% and 38.5%, respectively) compared to results on the same pathologies reported in our previous cohort of infants born to untreated mothers (92.2% and 67.7%, respectively). The sensitivity of the IgM ISAGA and IgA ELISA in the present study were lower (44% and 60%, respectively) compared to sensitivity of these methods in our previously studied group of infants born to untreated mothers (86.6% and 76.5%, respectively). These findings provide further evidence that anti-parasitic treatment if administered during pregnancy can contribute to better clinical outcomes, even in countries where systematic screening and treatment have not been routinely implemented.


Assuntos
Anticorpos Antiprotozoários/sangue , Complicações Parasitárias na Gravidez/tratamento farmacológico , Toxoplasmose Congênita/sangue , Toxoplasmose Congênita/epidemiologia , Técnicas de Laboratório Clínico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hidrocefalia/epidemiologia , Hidrocefalia/etiologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Masculino , Mães , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Testes Sorológicos , Toxoplasmose Congênita/tratamento farmacológico , Estados Unidos/epidemiologia
7.
Therapie ; 74(4): 487-494, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-30904318

RESUMO

In 2006, because of the chloroquine-resistance and following the World Health Organization (WHO) recommendations, Côte d'Ivoire adopted a new policy for the prevention of malaria during pregnancy by intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). However, its implementation remains limited. Objectives of this study were to evaluate the knowledge of the TPIp-SP regimen and prescribers opinion concerning this protocol. It was a knowledge attitude and pratices (KAP) cross-sectional descriptive study. We used a two-stage stratified sounding. The study took place in 12 health facilities in the health region of Abidjan 2 from march to august 2016 and involved 187 health professionals. We performed descriptive analysis, univariate and bivariate comparative analysis. The study found that half of the prescribers surveyed actually knew the ITPp program (SP - 3 doses - 2nd and 3rd trimesters). Knowledge was better among practitioners with more than 5 years of exercise (P=0.011) and at the level of first contact of health institution (P=0.001). Half of the prescribers were in favor of applying the protocol. The level of knowledge of prescribers has changed little in 2016 compared to 2008 for physicians (Pr (|Z|<|z|)=0.4861) or midwives Pr (|Z|<|z|)=0.4786). Prescribers remained faithful to the old 2-dose protocol. The opinion on the protocol was better in 2016 compared to 2008 Pr (Z

Assuntos
Antimaláricos/administração & dosagem , Conhecimentos, Atitudes e Prática em Saúde , Malária/tratamento farmacológico , Complicações Parasitárias na Gravidez/tratamento farmacológico , Pirimetamina/administração & dosagem , Sulfadoxina/administração & dosagem , Adulto , Competência Clínica/estatística & dados numéricos , Costa do Marfim/epidemiologia , Estudos Transversais , Esquema de Medicação , Combinação de Medicamentos , Escolaridade , Feminino , Humanos , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Malária/epidemiologia , Masculino , Corpo Clínico/educação , Corpo Clínico/normas , Corpo Clínico/estatística & dados numéricos , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Medicina Preventiva/educação , Medicina Preventiva/métodos , Medicina Preventiva/estatística & dados numéricos , Adulto Jovem
8.
J Infect Chemother ; 25(6): 427-430, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30824301

RESUMO

Primary infection with Toxoplasma gondii (T. gondii) during pregnancy may cause congenital infection of the infant. This study evaluated whether screening using IgG avidity and multiplex-nested polymerase chain reaction (PCR) methods was effective for detecting a high-risk pregnancy for congenital T. gondii infection. In a prospective cohort study serum T. gondii IgG avidity was measured in 469 pregnant women who had a positive test for T. gondii antibody plus a positive or equivocal test for IgM. Multiplex-nested PCR for T. gondii DNA on amniotic fluid, maternal blood, and neonatal blood was performed with informed consent. Low (<30%), borderline (30-35%), and high (>35%) IgG avidity indices were found in 104 (22.2%), 30 (6.4%), and 305 (71.4%), respectively. A total of 12 cases had a positive PCR test for amniotic fluids of the prenatal amniocentesis or at birth, or neonatal blood. Seven of the 12 cases were diagnosed as having congenital T. gondii infection, and they had low IgG avidity indices. Congenital T. gondii infection screening using of IgG avidity and multiplex-nested PCR methods for pregnant women with a positive test for T. gondii antibody plus a positive or equivocal test for T. gondii IgM was useful for detecting a high-risk pregnancy and diagnosing congenital T. gondii infection.


Assuntos
Anticorpos Antiprotozoários/isolamento & purificação , DNA de Protozoário/isolamento & purificação , Complicações Parasitárias na Gravidez/diagnóstico , Toxoplasma/isolamento & purificação , Toxoplasmose Congênita/diagnóstico , Adulto , Amniocentese , Líquido Amniótico/parasitologia , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Antiprotozoários , Criança , Pré-Escolar , DNA de Protozoário/sangue , Feminino , Seguimentos , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Imunoglobulina M/isolamento & purificação , Lactente , Recém-Nascido , Gravidez , Complicações Parasitárias na Gravidez/sangue , Complicações Parasitárias na Gravidez/tratamento farmacológico , Complicações Parasitárias na Gravidez/parasitologia , Gravidez de Alto Risco , Estudos Prospectivos , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasmose Congênita/sangue , Toxoplasmose Congênita/tratamento farmacológico , Toxoplasmose Congênita/parasitologia , Resultado do Tratamento
9.
PLoS Negl Trop Dis ; 13(2): e0007172, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30818339

RESUMO

BACKGROUND: Globally, vaccine-preventable diseases remain a significant cause of early childhood mortality despite concerted efforts to improve vaccine coverage. One reason for impaired protection may be the influence of prenatal exposure to parasitic antigens on the developing immune system. Prior research had shown a decrease in infant vaccine response after in utero parasite exposure among a maternal cohort without aggressive preventive treatment. This study investigated the effect of maternal parasitic infections on infant vaccination in a more recent setting of active anti-parasitic therapy. METHODOLOGY/PRINCIPAL FINDINGS: From 2013-2015, 576 Kenyan women were tested in pregnancy for malaria, soil-transmitted helminths, filaria, and S. haematobium, with both acute and prophylactic antiparasitic therapies given. After birth, 567 infants received 10-valent S. pneumoniae conjugate vaccine and pentavalent vaccine for hepatitis B, pertussis, tetanus, H. influenzae type B (Hib) and C. diphtheriae toxoid (Dp-t) at 6, 10, and 14 weeks. Infant serum samples from birth, 10 and 14 weeks, and every six months until age three years, were analyzed using a multiplex bead assay to quantify IgG for Hib, Dp-t, and the ten pneumococcal serotypes. Antenatal parasitic prevalence was high; 461 women (80%) had at least one and 252 (43.6%) had two or more infections during their pregnancy, with the most common being malaria (44.6%), S. haematobium (43.9%), and hookworm (29.2%). Mixed models comparing influence of infection on antibody concentration revealed no effect of prenatal infection status for most vaccine outcomes. Prevalences of protective antibody concentrations after vaccination were similar among the prenatal exposure groups. CONCLUSIONS/SIGNIFICANCE: These findings are in contrast with results from our prior cohort study performed when preventive anti-parasite treatment was less frequently given. The results suggest that the treatment of maternal infections in pregnancy may be able to moderate the previously observed effect of antenatal maternal infections on infant vaccine responses.


Assuntos
Anticorpos Antibacterianos/sangue , Doenças Parasitárias/imunologia , Complicações Parasitárias na Gravidez/patologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Adulto , Formação de Anticorpos , Antígenos de Bactérias/imunologia , Estudos de Coortes , Difteria/prevenção & controle , Vacina contra Difteria, Tétano e Coqueluche/uso terapêutico , Feminino , Vacinas Anti-Haemophilus/uso terapêutico , Haemophilus influenzae tipo b , Vacinas contra Hepatite B/uso terapêutico , Humanos , Lactente , Doenças Parasitárias/tratamento farmacológico , Vacinas Pneumocócicas/uso terapêutico , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/parasitologia , Estudos Prospectivos , Streptococcus pneumoniae , Tétano/prevenção & controle , Vacinação , Coqueluche/prevenção & controle , Adulto Jovem
10.
Int J Risk Saf Med ; 30(2): 73-89, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30714973

RESUMO

BACKGROUND: Data regarding the relative safety profile of anti-malarial drugs in pregnancy is sparse mainly limited by the absence of head-to-head clinical trials. The present study is a network meta-analysis of safety of anti-malarial drugs used to treat malaria in pregnant women. METHODS: A thorough literature search using the search strategy "Malaria [tiab] AND (Pregnant [tiab] OR Pregnancy [tiab])" was carried out for either randomized controlled trials or prospective cohort studies in pregnant malarial women prescribed any of the recommended anti-malarial drugs by World Health Organization (WHO) and that have reported adverse pregnancy outcomes such as miscarriage, still birth, and neonatal deaths. Odds ratio with 95% confidence interval was used as the effect estimate. Random-effects model and Markov Chain Monte Carlo simulation method was used to generate pooled estimates. Sensitivity analysis was performed excluding data from first trimester and GRADE approach was used to categorize the quality of evidence. RESULTS: A total of 1242 papers were obtained with the search strategy, of which seven evaluating 10 treatment arms in a total of 5510 participants were included in the present meta-analysis. The pooled estimates revealed significantly lower risks of abortion with quinine and artemisinin-lumefantrine compared to dihydroartemisinin-piperaquine, artesunate with mefloquine and artesunate with amodiaquine. But when a cohort study that was conducted in the first trimester of pregnancy was excluded, no significant differences were observed in the risk of abortion between the anti-malarial drugs. No significant differences in the risk of either stillbirths or neonatal deaths were observed with any of the drugs. The quality of evidence was found to be very low due to serious limitations in both the precision and indirectness. CONCLUSION: WHO recommended anti-malarials in pregnancy have similar risk profiles with regard to abortion, stillbirth and neonatal deaths.


Assuntos
Antimaláricos/farmacologia , Malária/tratamento farmacológico , Complicações Parasitárias na Gravidez/tratamento farmacológico , Feminino , Humanos , Metanálise em Rede , Gravidez , Resultado da Gravidez , Medição de Risco
11.
Rev Soc Bras Med Trop ; 52: e20180233, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30810655

RESUMO

Visceral leishmaniasis (VL) in pregnant is considered rare. We present the case of a woman with 24 gestational weeks presenting fever, hepatosplenomegaly, pancytopenia, and inversion of albumin/globulin ratio. Anti-rK39 was positive and amastigotes were visualized on myelogram. Treatment with LAmB showed disease improvement. The newborn was born healthy at term, with delivery performed without complications. As VL in pregnancy can progress to death and complications for the mother-fetus binomial, inclusion of VL in the differential diagnosis of patients from endemic areas with compatible clinical picture is mandatory. Treatment with LAmB demonstrates safety and high cure rates in pregnancy.


Assuntos
Leishmaniose Visceral/diagnóstico , Complicações Parasitárias na Gravidez/diagnóstico , Adolescente , Brasil , Feminino , Humanos , Leishmaniose Visceral/tratamento farmacológico , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Resultado da Gravidez
12.
Travel Med Infect Dis ; 27: 20-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30654041

RESUMO

BACKGROUND: Malaria infection poses a significant risk in pregnancy, yet chemoprophylaxis for pregnant women is limited. A systematic review was conducted to evaluate the incidence of adverse outcomes after atovaquone-proguanil (AP) exposure during pregnancy. METHODS: Following PRISMA guidelines, the authors searched PubMed, MEDLINE, and the Malaria in Pregnancy Consortium Library to identify relevant literature including infant outcomes after exposure to atovaquone, proguanil, or AP in pregnancy. Two authors independently screened the titles, abstracts, and full texts, and extracted data into an EpiInfo database. Overall proportions and 95% confidence intervals of adverse outcomes were determined by pooling data across studies. RESULTS: Of 455 records identified, 16 studies were included: ten AP studies and six proguanil studies. The overall proportions and 95% confidence intervals (CI) of adverse outcomes reported for the 446 women exposed to AP include miscarriage (8.08% CI: 5.07, 12.08%), stillbirth (1.05% CI: 0.03, 5.73%), early neonatal death (0% CI: 0, 7.4%), and congenital anomalies (2.56% CI: 1.28, 4.53%). CONCLUSIONS: The limited available data suggest that outcomes following AP exposure during pregnancy are similar to expected rates in similar populations. AP may be a promising option for pregnant women, but further data are needed on its safety in pregnancy.


Assuntos
Antimaláricos/efeitos adversos , Atovaquona/uso terapêutico , Malária/tratamento farmacológico , Malária/prevenção & controle , Complicações Parasitárias na Gravidez/tratamento farmacológico , Complicações Parasitárias na Gravidez/prevenção & controle , Proguanil/uso terapêutico , Aborto Espontâneo/induzido quimicamente , Antimaláricos/uso terapêutico , Atovaquona/efeitos adversos , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Recém-Nascido , Malária Falciparum/tratamento farmacológico , Gravidez , Proguanil/efeitos adversos , Natimorto , Viagem
13.
Mol Cell Proteomics ; 18(2): 182-199, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30242111

RESUMO

Malaria in pregnancy is a public health concern in malaria-endemic areas. Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction. Little is known about the molecular changes occurring in a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection). We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria. A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas. This study showed apoptosis-related mechanisms associated with placental malaria that can be further explored as therapeutic target against adverse pregnancy outcomes.


Assuntos
Malária Falciparum/metabolismo , Placenta/metabolismo , Complicações Parasitárias na Gravidez/metabolismo , Proteômica/métodos , Animais , Modelos Animais de Doenças , Feminino , Glicosilação , Humanos , Sistema de Sinalização das MAP Quinases , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Camundongos , Fosforilação , Placenta/parasitologia , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Mapas de Interação de Proteínas
14.
Artigo em Inglês | MEDLINE | ID: mdl-30530597

RESUMO

Dihydroartemisinin-piperaquine (DHA-PQ) is under study for intermittent preventive treatment during pregnancy (IPTp), but it may accelerate selection for drug resistance. Understanding the relationships between piperaquine concentration, prevention of parasitemia, and selection for decreased drug sensitivity can inform control policies and optimization of DHA-PQ dosing. Piperaquine concentrations, measures of parasitemia, and Plasmodium falciparum genotypes associated with decreased aminoquinoline sensitivity in Africa (pfmdr1 86Y, pfcrt 76T) were obtained from pregnant Ugandan women randomized to IPTp with sulfadoxine-pyrimethamine (SP) or DHA-PQ. Joint pharmacokinetic/pharmacodynamic models described relationships between piperaquine concentration and the probability of genotypes of interest using nonlinear mixed effects modeling. An increase in the piperaquine plasma concentration was associated with a log-linear decrease in risk of parasitemia. Our models predicted that higher median piperaquine concentrations would be required to provide 99% protection against mutant infections than against wild-type infections (pfmdr1: N86, 9.6 ng/ml; 86Y, 19.6 ng/ml; pfcrt: K76, 6.5 ng/ml; 76T, 19.6 ng/ml). Comparing monthly, weekly, and daily dosing, daily low-dose DHA-PQ was predicted to result in the fewest infections and the fewest mutant infections per 1,000 pregnancies (predicted mutant infections for pfmdr1 86Y: SP monthly, 607; DHA-PQ monthly, 198; DHA-PQ daily, 1; for pfcrt 76T: SP monthly, 1,564; DHA-PQ monthly, 283; DHA-PQ daily, 1). Our models predict that higher piperaquine concentrations are needed to prevent infections with the pfmdr1/pfcrt mutant compared to those with wild-type parasites and that, despite selection for mutants by DHA-PQ, the overall burden of mutant infections is lower for IPTp with DHA-PQ than for IPTp with SP. (This study has been registered at ClinicalTrials.gov under identifier NCT02282293.).


Assuntos
Antimaláricos/farmacocinética , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária/prevenção & controle , Complicações Parasitárias na Gravidez/prevenção & controle , Quinolinas/uso terapêutico , Artemisininas/farmacocinética , Resistência a Medicamentos/fisiologia , Quimioterapia Combinada , Feminino , Humanos , Malária/tratamento farmacológico , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Quinolinas/farmacocinética , Uganda , Adulto Jovem
15.
Sex Transm Dis ; 46(1): 2-8, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30067546

RESUMO

BACKGROUND: Our primary objective was to determine the rate of persistent Trichomonas infection among pregnant women posttreatment. The secondary objective was to determine if oral multidose metronidazole was associated with fewer cases of persistent Trichomonas compared with single-dose treatment. METHODS: This is a retrospective cohort study of women diagnosed with genital Trichomonas vaginalis from 2008 to 2017. We calculated the rate of persistent Trichomonas by dividing the number of positive Trichomonas tests collected 21 days or longer posttreatment by the total number of women treated and retested. Bivariate analysis was performed to compare the rates of positive tests after single and multidose metronidazole. Multivariate logistic regression was used to evaluate factors associated with persistent infection. RESULTS: Five hundred forty-two women with 565 pregnancies were diagnosed with Trichomonas infection. The majority of subjects were prescribed either single-dose (n = 352) or multidose metronidazole (n = 74). Posttreatment Trichomonas tests were collected 21 days or longer in 326 subjects and 44% (143) were positive. Rates of positive Trichomonas tests among women receiving single-dose and multidose regimens were similar (45% vs. 40%, P = 0.50). Women who had ≥1 pregnancy affected by Trichomonas infection were more likely to have a positive test posttreatment (adjusted odds ratio, 20.1; 95% confidence interval, 1.9-215.3). Obese women were less likely to have a positive test posttreatment (adjusted odds ratio, 0.3; 95% confidence interval, 0.1-0.9). CONCLUSIONS: Given high rates of positive Trichomonas tests and increased detection with nucleic acid amplification tests (NAATs), all pregnant women should be retested with NAATs approximately 3 weeks posttreatment. Further studies are needed to determine the most effective treatment of Trichomonas infection in pregnant women.


Assuntos
Metronidazol/uso terapêutico , Complicações Parasitárias na Gravidez/tratamento farmacológico , Vaginite por Trichomonas/tratamento farmacológico , Trichomonas vaginalis/efeitos dos fármacos , Administração Oral , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Modelos Logísticos , North Carolina , Gravidez , Complicações Parasitárias na Gravidez/diagnóstico , Estudos Retrospectivos , Vaginite por Trichomonas/diagnóstico , Trichomonas vaginalis/isolamento & purificação
16.
Expert Opin Drug Saf ; 17(11): 1129-1144, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30351243

RESUMO

INTRODUCTION: Malaria in pregnancy and postpartum cause maternal mortality and adverse fetal outcomes. Efficacious and safe antimalarials are needed to treat and prevent such serious consequences. However, because of the lack of evidence on fetal safety, quinine, an old and less efficacious drug has long been recommended for pregnant women. Uncertainty about safety in relation to breastfeeding leads to withholding of efficacious treatments postpartum or cessation of breastfeeding. Areas covered: A search identified literature on humans in three databases (MEDLINE, Embase and Global health) using pregnancy or lactation, and the names of antimalarial drugs as search terms. Adverse reactions to the mother, fetus or breastfed infant were summarized together with efficacies. Expert opinion: Artemisinins are more efficacious and well-tolerated than quinine in pregnancy. Furthermore, the risks of miscarriage, stillbirth or congenital abnormality were not higher in pregnancies exposed to artemisinin derivatives for treatment of malaria than in pregnancies exposed to quinine or in the comparable background population unexposed to any antimalarials, and this was true for treatment in any trimester. Assessment of safety and efficacy of antimalarials including dose optimization for pregnant women is incomplete. Resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum and long unprotected intervals between intermittent treatment doses begs reconsideration of current preventative recommendations in pregnancy. Data remain limited on antimalarials during breastfeeding; while most first-line drugs appear safe, further research is needed.


Assuntos
Antimaláricos/administração & dosagem , Malária/tratamento farmacológico , Complicações Parasitárias na Gravidez/tratamento farmacológico , Antimaláricos/efeitos adversos , Artemisininas/administração & dosagem , Artemisininas/efeitos adversos , Aleitamento Materno , Feminino , Humanos , Recém-Nascido , Lactação , Malária/complicações , Malária/prevenção & controle , Gravidez , Quinina/administração & dosagem , Quinina/efeitos adversos
17.
Expert Opin Pharmacother ; 19(16): 1779-1796, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30289730

RESUMO

INTRODUCTION: Malaria in pregnancy continues to be a significant public health burden globally, with over 100 million women at risk each year. Sulfadoxine-pyrimethamine (SP) is the only antimalarial recommended for intermittent preventive therapy in pregnancy (IPTp) but increasing parasite resistance threatens its viability. There are few other available antimalarial therapies that currently have sufficient evidence of tolerability, safety, and efficacy to replace SP. AREAS COVERED: Novel antimalarial combinations are under investigation for potential use as chemoprophylaxis and in IPTp regimens. The present review summarizes currently available therapies, emerging candidate combination therapies, and the potential challenges to integrating these into mainstream policy. EXPERT OPINION: Alternative drugs or combination therapies to SP for IPTp are desperately required. Dihydroartemisinin-piperaquine and azithromycin-based combinations are showing great promise as potential candidates for IPTp but pharmacokinetic data suggest that dose modification may be required to ensure adequate prophylactic efficacy. If a suitable candidate regimen is not identified in the near future, the success of chemopreventive strategies such as IPTp may be in jeopardy.


Assuntos
Antimaláricos/uso terapêutico , Tratamento Farmacológico/métodos , Malária/tratamento farmacológico , Complicações Parasitárias na Gravidez/tratamento farmacológico , Adulto , Antimaláricos/farmacologia , Feminino , Humanos , Malária/patologia , Gravidez , Complicações Parasitárias na Gravidez/patologia
18.
Parasitol Int ; 67(6): 715-721, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30041005

RESUMO

Toxoplasma gondii is an obligate intracellular parasite which is known to infect one-third of the total world population chronically though it is asymptomatic in immunocompetent patients. However, in an immunocompromised patient or an infected fetus, it may cause devastating effects. The parasite may cross the placenta of an infected pregnant woman and probably infect the fetus congenitally. The severity of the infection depends on the gestational age at which the infection has occurred i.e., if it has occurred in the early phase, the rate of transmission is low but the severity is high if the fetus is infected and if it has occurred in the later phase then transmission rate is higher while the severity would be low. Congenital toxoplasmosis may result in non-specific consequences like abortion, intra-uterine growth restriction, jaundice, hepatosplenomegaly or even intra-uterine death. It may also result in neurological or ocular manifestations like intracranial calcifications, hydrocephalus or retinochoroiditis. The diagnosis may be done by serological screening of anti-Toxoplasma antibodies (IgM and IgG) while PCR of the amniotic fluid or the placenta is the confirmatory test. Acute or chronic infections may be differentiated by IgG avidity tests. The treatment regimens include spiramycin to prevent congenital transmission from an infected mother, pyrimethamine, sulfadoxine and folinic acid to treat the infected fetus, CSF shunting for the treatment of hydrocephalus and a combination of pyrimethamine, azithromycin, and corticosteroids for treating ocular toxoplasmosis.


Assuntos
Toxoplasma/fisiologia , Toxoplasmose Cerebral , Toxoplasmose Congênita , Toxoplasmose Ocular , Antiprotozoários/administração & dosagem , Feminino , Humanos , Gravidez , Complicações Parasitárias na Gravidez/diagnóstico , Complicações Parasitárias na Gravidez/tratamento farmacológico , Complicações Parasitárias na Gravidez/epidemiologia , Complicações Parasitárias na Gravidez/parasitologia , Prevalência , Estudos Soroepidemiológicos , Toxoplasmose Cerebral/diagnóstico , Toxoplasmose Cerebral/tratamento farmacológico , Toxoplasmose Cerebral/epidemiologia , Toxoplasmose Cerebral/parasitologia , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/tratamento farmacológico , Toxoplasmose Congênita/epidemiologia , Toxoplasmose Congênita/parasitologia , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/tratamento farmacológico , Toxoplasmose Ocular/epidemiologia , Toxoplasmose Ocular/parasitologia
19.
J Infect Dis ; 217(12): 1967-1976, 2018 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-29659897

RESUMO

Background: Although consensus exists that malaria in pregnancy (MiP) increases the risk of malaria in infancy, and eventually nonmalarial fevers (NMFs), there is a lack of conclusive evidence of benefits of MiP preventive strategies in infants. Methods: In Burkina Faso, a birth cohort study was nested to a clinical trial assessing the effectiveness of a community-based scheduled screening and treatment of malaria in combination with intermittent preventive treatment with sulfadoxine-pyrimethamine (CSST/IPTp-SP) to prevent placental malaria. Clinical episodes and asymptomatic infections were monitored over 1 year of follow-up to compare the effect of CSST/IPTp-SP and standard IPTp-SP on malaria and NMFs. Results: Infants born during low-transmission season from mothers receiving CSST/IPTp-SP had a 26% decreased risk of experiencing a first clinical episode (hazard ratio, 0.74 [95% confidence interval, .55-0.99]; P = .047). CSST/IPTp-SP interacted with birth season and gravidity to reduce the incidence of NMFs. No significant effects of CSST/IPTp-SP on the incidence of clinical episodes, parasite density, and Plasmodium falciparum infections were observed. Conclusions: Our findings indicate that CSST/IPTp-SP strategy may provide additional protection against both malaria and NMFs in infants during the first year of life, and suggest that malaria control interventions during pregnancy could have long-term benefits in infants.


Assuntos
Antimaláricos/uso terapêutico , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Adulto , Burkina Faso , Estudos de Coortes , Combinação de Medicamentos , Feminino , Humanos , Incidência , Lactente , Masculino , Programas de Rastreamento/métodos , Plasmodium falciparum/efeitos dos fármacos , Gravidez , Complicações Parasitárias na Gravidez/diagnóstico , Complicações Parasitárias na Gravidez/tratamento farmacológico , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico
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