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Find video protocols related to scientific articles indexed in Pubmed.
Loss and dysfunction of V?2? ?? T cells are associated with clinical tolerance to malaria.
Sci Transl Med
PUBLISHED: 08-29-2014
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Although clinical immunity to malaria eventually develops among children living in endemic settings, the underlying immunologic mechanisms are not known. The V?2(+) subset of ?? T cells have intrinsic reactivity to malaria antigens, can mediate killing of Plasmodium falciparum merozoites, and expand markedly in vivo after malaria infection in previously naïve hosts, but their role in mediating immunity in children repeatedly exposed to malaria is unclear. We evaluated ?? T cell responses to malaria among 4-year-old children enrolled in a longitudinal study in Uganda. We found that repeated malaria was associated with reduced percentages of V?2(+) ?? T cells in peripheral blood, decreased proliferation and cytokine production in response to malaria antigens, and increased expression of immunoregulatory genes. Further, loss and dysfunction of proinflammatory V?2(+) ?? T cells were associated with a reduced likelihood of symptoms upon subsequent P. falciparum infection. Together, these results suggest that repeated malaria infection during childhood results in progressive loss and dysfunction of V?2(+) ?? T cells that may facilitate immunological tolerance of the parasite.
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Longitudinal outcomes in a cohort of Ugandan children randomized to artemether-lumefantrine versus dihydroartemisinin-piperaquine for the treatment of malaria.
Clin. Infect. Dis.
PUBLISHED: 05-13-2014
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Artemisinin-based combination therapy (ACT) has become the standard of care for the treatment of uncomplicated Plasmodium falciparum malaria. Although several ACT regimens are approved, data guiding optimal choices of ACTs are limited. We compared short- and long-term outcomes in a cohort of young Ugandan children randomized to 2 leading ACTs.
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Temporal changes in prevalence of molecular markers mediating antimalarial drug resistance in a high malaria transmission setting in Uganda.
Am. J. Trop. Med. Hyg.
PUBLISHED: 05-05-2014
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Standard therapy for malaria in Uganda changed from chloroquine to chloroquine + sulfadoxine-pyrimethamine in 2000, and artemether-lumefantrine in 2004, although implementation of each change was slow. Plasmodium falciparum genetic polymorphisms are associated with alterations in drug sensitivity. We followed the prevalence of drug resistance-mediating P. falciparum polymorphisms in 982 samples from Tororo, a region of high transmission intensity, collected from three successive treatment trials conducted during 2003-2012, excluding samples with known recent prior treatment. Considering transporter mutations, prevalence of the mutant pfcrt 76T, pfmdr1 86Y, and pfmdr1 1246Y alleles decreased over time. Considering antifolate mutations, the prevalence of pfdhfr 51I, 59R, and 108N, and pfdhps 437G and 540E were consistently high; pfdhfr 164L and pfdhps 581G were uncommon, but most prevalent during 2008-2010. Our data suggest sequential selective pressures as different treatments were implemented, and they highlight the importance of genetic surveillance as treatment policies change over time.
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Artemisinin-based combination therapies are efficacious and safe for treatment of uncomplicated malaria in HIV-infected Ugandan children.
Clin. Infect. Dis.
PUBLISHED: 04-23-2014
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Artemisinin-based combination therapies (ACTs) are highly efficacious and safe, but data from human immunodeficiency virus (HIV)-infected children concurrently receiving antiretroviral therapy (ART) and ACTs are limited.
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Comparative impacts over 5 years of artemisinin-based combination therapies on Plasmodium falciparum polymorphisms that modulate drug sensitivity in Ugandan children.
J. Infect. Dis.
PUBLISHED: 03-08-2014
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Artemisinin-based combination therapies, including artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), are recommended to treat uncomplicated falciparum malaria. Sensitivities to components of AL and DP are impacted by polymorphisms in pfmdr1 and pfcrt. We monitored changes in prevalences of polymorphisms in Tororo, Uganda, from 2008 to 2012.
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Early parasite clearance following artemisinin-based combination therapy among Ugandan children with uncomplicated Plasmodium falciparum malaria.
Malar. J.
PUBLISHED: 01-21-2014
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Artemisinin-based combination therapy (ACT) is widely recommended as first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide. Artemisinin resistance has now been reported in Southeast Asia with a clinical phenotype manifested by slow parasite clearance. Although there are no reliable reports of artemisinin resistance in Africa, there is a need to better understand the dynamics of parasite clearance in African children treated with ACT in order to better detect the emergence of artemisinin resistance.
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IFN?/IL-10 co-producing cells dominate the CD4 response to malaria in highly exposed children.
PLoS Pathog.
PUBLISHED: 01-01-2014
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Although evidence suggests that T cells are critical for immunity to malaria, reliable T cell correlates of exposure to and protection from malaria among children living in endemic areas are lacking. We used multiparameter flow cytometry to perform a detailed functional characterization of malaria-specific T cells in 78 four-year-old children enrolled in a longitudinal cohort study in Tororo, Uganda, a highly malaria-endemic region. More than 1800 episodes of malaria were observed in this cohort, with no cases of severe malaria. We quantified production of IFN?, TNF?, and IL-10 (alone or in combination) by malaria-specific T cells, and analyzed the relationship of this response to past and future malaria incidence. CD4(+) T cell responses were measurable in nearly all children, with the majority of children having CD4(+) T cells producing both IFN? and IL-10 in response to malaria-infected red blood cells. Frequencies of IFN?/IL10 co-producing CD4(+) T cells, which express the Th1 transcription factor T-bet, were significantly higher in children with ?2 prior episodes/year compared to children with <2 episodes/year (P<0.001) and inversely correlated with duration since malaria (Rho?=?-0.39, P<0.001). Notably, frequencies of IFN?/IL10 co-producing cells were not associated with protection from future malaria after controlling for prior malaria incidence. In contrast, children with <2 prior episodes/year were significantly more likely to exhibit antigen-specific production of TNF? without IL-10 (P?=?0.003). While TNF?-producing CD4(+) T cells were not independently associated with future protection, the absence of cells producing this inflammatory cytokine was associated with the phenotype of asymptomatic infection. Together these data indicate that the functional phenotype of the malaria-specific T cell response is heavily influenced by malaria exposure intensity, with IFN?/IL10 co-producing CD4(+) T cells dominating this response among highly exposed children. These CD4(+) T cells may play important modulatory roles in the development of antimalarial immunity.
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Acceptability and feasibility of serial HIV antibody testing during pregnancy/postpartum and male partner testing in Tororo, Uganda.
AIDS Care
PUBLISHED: 08-02-2013
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Our objective was to determine whether serial HIV testing during pregnancy and the postpartum period as well as male partner testing are acceptable and feasible in Tororo, Uganda. This was a prospective study of pregnant women at the Tororo District Hospital (TDH) Antenatal Clinic. Patients presenting for routine antenatal care were asked to participate in a serial HIV testing integrated into standard antenatal and postpartum/child immunization visits, and to invite their male partners for HIV testing. Serial testing was defined as ?2 tests during pregnancy and ?2 tests within 24 weeks postpartum. Of the 214 enrolled women, 80 (37%) completed serial testing, 176 (82%) had ?2 tests, and 147 (69%) had ?3 tests during the study period. One hundred eighty-two women (85%) accepted male partner testing, but only 19 men (10%) participated. One woman seroconverted during the study, for a cumulative HIV incidence of 0.5% (1/214). In multivariable logistic regression analysis, longer distance between home and clinic (aOR 0.87 [95% CI 0.79-0.97]) and not knowing household income (aOR 0.30 [95% CI 0.11-0.84]) were predictive of not completing serial testing. Higher level of education was associated with completing serial testing (linear trend p value = 0.05). In conclusion, partial serial HIV testing was highly acceptable and feasible, but completion of serial testing and male partner testing had poor uptake.
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Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants.
J. Infect. Dis.
PUBLISHED: 02-27-2013
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Although dihydroartemisinin-piperaquine (DP) is used primarily in children, pharmacokinetic/pharmacodynamic (PK/PD) data on DP use in young children are lacking.
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The cost-effectiveness of repeat HIV testing during pregnancy in a resource-limited setting.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 02-09-2013
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To estimate the cost-effectiveness of HIV screening strategies for the prevention of perinatal transmission in Uganda, a resource-limited country with high HIV prevalence and incidence.
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The effects of ACT treatment and TS prophylaxis on Plasmodium falciparum gametocytemia in a cohort of young Ugandan children.
Am. J. Trop. Med. Hyg.
PUBLISHED: 02-04-2013
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Artemisinin-based combination therapies (ACTs) and trimethoprim-sulfamethoxazole (TS) prophylaxis are important tools for malaria control, but there are concerns about their effect on gametocytes, the stage of the parasite responsible for transmission. We conducted a longitudinal clinical trial in a cohort of HIV-infected and uninfected children living in an area of high malaria transmission intensity in Uganda. Study participants were randomized to artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) for all treatments of uncomplicated malaria (N = 4,380) as well as TS prophylaxis for different durations. The risks of gametocytemia detected by microscopy in the 28 days after antimalarial therapy were compared using multivariate analyses. The risk of gametocyte detection was significantly higher in patients treated with DP compared with AL (adjusted relative risk = 1.85, P < 0.001) and among children prescribed TS prophylaxis (adjusted relative risk = 1.76, P < 0.001). The risk of gametocytemia and its potential for increasing transmission should be considered when evaluating different ACTs and TS prophylaxis for malaria control.
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Intermittent preventive therapy with sulfadoxine-pyrimethamine for malaria in pregnancy: a cross-sectional study from Tororo, Uganda.
PLoS ONE
PUBLISHED: 01-01-2013
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Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is widely recommended in sub-Saharan Africa to reduce the risk of malaria and improve birth outcomes. However, there are reports that the efficacy of IPTp with SP is waning, especially in parts of Africa where antimalarial resistance to this drug has become widespread.
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Protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children in rural Uganda: a randomised clinical trial.
BMJ
PUBLISHED: 04-02-2011
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To evaluate the protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children (uninfected children born to HIV infected mothers) in Africa.
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Effect of nutritional status on response to treatment with artemisinin-based combination therapy in young Ugandan children with malaria.
Antimicrob. Agents Chemother.
PUBLISHED: 03-07-2011
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The relationship between malnutrition and malaria in young children is under debate, and no studies evaluating the association between malnutrition and response to artemisinin-based combination therapies (ACTs) have been published. We evaluated the association between malnutrition and response to antimalarial therapy in Ugandan children treated with ACTs for repeated episodes of malaria. Children aged 4 to 12 months diagnosed with uncomplicated malaria were randomized to dihydroartemisinin-piperaquine (DP) or artemether-lumefantrine (AL) and followed for up to 2 years. All HIV-exposed and HIV-infected children received trimethoprim-sulfamethoxazole prophylaxis (TS). The primary exposure variables included height-for-age and weight-for-age z scores. Outcomes included parasite clearance at days 2 and 3 and risk of recurrent parasitemia after 42 days of follow-up. Two hundred ninety-two children were randomized to DP or AL, resulting in 2,013 malaria treatments. Fewer than 1% of patients had a positive blood smear by day 3 (DP, 0.2%; AL, 0.6% [P = 0.18]). There was no significant association between height-for-age or weight-for-age z scores and a positive blood smear 2 days following treatment. For children treated with DP but not on TS, decreasing height-for-age z scores of <-1 were associated with a higher risk of recurrent parasitemia than a height-for-age z score of >0 (hazard ratio [HR] for height-for-age z score of <-1 and ?-2 = 2.89 [P = 0.039]; HR for height-for-age z score of <-2 = 3.18 [P = 0.022]). DP and AL are effective antimalarial therapies in chronically malnourished children in a high-transmission setting. However, children with mild to moderate chronic malnutrition not taking TS are at higher risk for recurrent parasitemia and may be considered a target for chemoprevention.
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Increased risk of early vomiting among infants and young children treated with dihydroartemisinin-piperaquine compared with artemether-lumefantrine for uncomplicated malaria.
Am. J. Trop. Med. Hyg.
PUBLISHED: 10-05-2010
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Artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are highly efficacious antimalarial therapies in Africa. However, there are limited data regarding the tolerability of these drugs in young children. We used data from a randomized control trial in rural Uganda to compare the risk of early vomiting (within one hour of dosing) for children 6-24 months of age randomized to receive DP (n = 240) or AL (n = 228) for treatment of uncomplicated malaria. Overall, DP was associated with a higher risk of early vomiting than AL (15.1% versus 7.1%; P = 0.007). The increased risk of early vomiting with DP was only present among breastfeeding children (relative risk [RR] = 3.35, P = 0.001) compared with children who were not breastfeeding (RR = 1.03, P = 0.94). Age less than 18 months was a risk factor for early vomiting independent of treatment (RR = 3.27, P = 0.02). Our findings indicate that AL may be better tolerated than DP among young breastfeeding children treated for uncomplicated malaria.
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Breastfeeding and the risk of malaria in children born to HIV-infected and uninfected mothers in rural Uganda.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-05-2010
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Early cessation of breastfeeding increases morbidity and mortality of children born to HIV-infected mothers in resource-limited settings. However, data on whether breastfeeding reduces the risk of malaria in HIV-exposed and HIV-infected children is limited.
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Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children.
Clin. Infect. Dis.
PUBLISHED: 11-03-2009
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Artemisinin-based combination therapies are now widely recommended as first-line treatment for uncomplicated malaria. However, which therapies are optimal is a matter of debate. We aimed to compare the short- and longer-term efficacy of 2 leading therapies in a cohort of young Ugandan children.
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Safety and tolerability of artemether-lumefantrine versus dihydroartemisinin-piperaquine for malaria in young HIV-infected and uninfected children.
Malar. J.
PUBLISHED: 08-28-2009
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Artemisinin combination therapy has become the standard of care for uncomplicated malaria in most of Africa. However, there is limited data on the safety and tolerability of these drugs, especially in young children and patients co-infected with HIV.
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Placental malaria among HIV-infected and uninfected women receiving anti-folates in a high transmission area of Uganda.
Malar. J.
PUBLISHED: 08-20-2009
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HIV infection increases the risk of placental malaria, which is associated with poor maternal and infant outcomes. Recommendations in Uganda are for HIV-infected pregnant women to receive daily trimethoprim-sulphamethoxazole (TS) and HIV-uninfected women to receive intermittent sulphadoxine-pyrimethamine (SP). TS decreases the risk of malaria in HIV-infected adults and children but has not been evaluated among pregnant women.
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Increasing incidence of malaria in children despite insecticide-treated bed nets and prompt anti-malarial therapy in Tororo, Uganda.
Malar. J.
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The burden of malaria has decreased in parts of Africa following the scaling up of control interventions. However, similar data are limited from high transmission settings.
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Maternal nutritional status predicts adverse birth outcomes among HIV-infected rural Ugandan women receiving combination antiretroviral therapy.
PLoS ONE
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Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda.
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The association between malnutrition and the incidence of malaria among young HIV-infected and -uninfected Ugandan children: a prospective study.
Malar. J.
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In sub-Saharan Africa, malnutrition and malaria remain major causes of morbidity and mortality in young children. There are conflicting data as to whether malnutrition is associated with an increased or decreased risk of malaria. In addition, data are limited on the potential interaction between HIV infection and the association between malnutrition and the risk of malaria.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.