Browsing by Subject "malaria"
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Item Assessing Knowledge and Perceptions Related to Preventive Methods and Treatment of Malaria in the Local Endemic Area of Trujillo, Honduras(Springer, 2015) Campodonico, Joanna; Sevilla-Martir, Javier; Arrizabalaga, Gustavo; Kochhar, Komal; Department of Family Medicine, IU School of MedicineMalaria in Honduras is endemic and accounts for 40% of the total cases in Central America. Our goal was to assess knowledge of preventive methods and current treatment of malaria among the affected community of Trujillo, Honduras. A cross-sectional survey was administered to 71 individuals. Most respondents had a good understanding about common malaria symptoms but not about the complications associated with severe cases. More important, we found that less than 20% of the respondents recognized indoor residual sprays and insecticide-treated nets as effective preventive measures, which are the most efficient preventive methods. Our study highlights the perceptions the people of Trujillo have about malaria. From our observations, we put forward recommendations to implement a comprehensive campaign to educate the Trujillo population about malaria preventive methods and to recruit local and international efforts to distribute insecticide-treated nets.Item Clinical Impact of Malaria Rapid Diagnostic Testing at a US Children’s Hospital(Oxford, 2019-04-16) Enane, Leslie A; Sullivan, Kaede V; Spyridakis, Evangelos; Feemster, Kristen A; Pediatrics, School of MedicineBackground Children who develop malaria after returning to a setting in which the disease is not endemic are at high risk for critical delays in diagnosis and initiation of antimalarial therapy. We assessed the clinical impact of the implementation of malaria rapid diagnostic testing (RDT) on the management of children with malaria at an urban US children’s hospital that serves a large immigrant population. Methods This was a retrospective cohort study of all children diagnosed with laboratory-confirmed malaria at the Children’s Hospital of Philadelphia (CHOP) between 2000 and 2014. RDT using a US Food and Drug Administration–approved immunochromatographic assay was introduced at CHOP on August 1, 2007. We compared clinical management and outcomes of patients with malaria diagnosed before and after RDT introduction. Results We analyzed 82 pediatric malaria cases (32 before and 50 after RDT implementation). The majority of these patients had traveled to West Africa (91.5%) and were infected with Plasmodium falciparum (80.5%). The mean time to a positive result decreased from 10.4 to 0.9 hours (P < .001) after the introduction of RDT for patients with P falciparum. The mean time to antimalarial therapy decreased from 13.1 to 6.9 hours (P =; .023) in hospitalized patients. We found no significant reduction in the mean number of clinical signs of severe malaria between 0 and 48 hours of hospitalization and no difference in the need for exchange transfusion, time to resolution of parasitemia, or length of hospital stay. Conclusions Implementation of RDT for malaria was associated with shorter times to malaria diagnosis and initiation of antimalarial therapy. The results of this study support RDT in the optimal management of patients with malaria who present in settings in which the disease is not endemic.Item Delaying Iron Therapy until 28 Days after Antimalarial Treatment Is Associated with Greater Iron Incorporation and Equivalent Hematologic Recovery after 56 Days in Children: A Randomized Controlled Trial123(Oxford Academic, 2016-08) Cusick, Sarah E; Opoka, Robert O; Abrams, Steven A; John, Chandy C; Georgieff, Michael K; Mupere, Ezekiel; Pediatrics, School of MedicineBackground: Iron therapy begun concurrently with antimalarial treatment may not be well absorbed because of malaria-induced inflammation. Delaying the start of iron therapy may permit better iron absorption and distribution., Objective: We compared erythrocyte iron incorporation in children who started iron supplementation concurrently with antimalarial treatment or 28 d later. We hypothesized that delayed iron supplementation would be associated with greater incorporation and better hematologic recovery., Methods: We enrolled 100 children aged 6–59 mo with malaria and hemoglobin concentrations of 50.0–99.9 g/L who presented to Mulago Hospital, Kampala, into a randomized trial of iron therapy. All children were administered antimalarial treatment. Children with zinc protoporphyrin (ZPP) ≥80 μmol/mol heme were randomly assigned to start iron supplementation concurrently with the antimalarial treatment [immediate iron (I) group] or 28 d later [delayed iron (D) group]. All children were administered iron-stable isotope 57Fe on day 0 and 58Fe on day 28. We compared the percentage of iron incorporation at the start of supplementation (I group at day 0 compared with D group at day 28, aim 1) and hematologic recovery at day 56 (aim 2)., Results: The percentage of iron incorporation (mean ± SE) was greater at day 28 in the D group (16.5% ± 1.7%) than at day 0 in the I group (7.9% ± 0.5%; P < 0.001). On day 56, concentrations of hemoglobin and ZPP and plasma ferritin, soluble transferrin receptor (sTfR), hepcidin, and C-reactive protein did not differ between the groups. On day 28, the hemoglobin (mean ± SD) and plasma iron markers (geometric mean; 95% CI) reflected poorer iron status in the D group than in the I group at this intervening time as follows: hemoglobin (105 ± 15.9 compared with 112 ± 12.4 g/L; P = 0.04), ferritin (39.3 μg/L; 23.5, 65.7 μg/L compared with 79.9 μg/L; 58.3, 110 μg/L; P = 0.02), sTfR (8.9 mg/L; 7.4, 10.7 mg/L compared with 6.7 mg/L; 6.1, 7.5 mg/L; P = 0.01), and hepcidin (13.3 ng/mL; 8.3, 21.2 ng/mL compared with 38.8 ng/mL; 28.3, 53.3 ng/mL; P < 0.001)., Conclusions: Delaying the start of iron improves incorporation but leads to equivalent hematologic recovery at day 56 in Ugandan children with malaria and anemia. These results do not demonstrate a clear, short-term benefit of delaying iron. This trial was registered at clinicaltrials.gov as NCT01754701.Item Evidence for potential underestimation of clinical folate deficiency in resource-limited countries using blood tests(Oxford, 2017-08) Antony, Aśok C.; Medicine, School of MedicineAlthough a low serum folate concentration is a useful biomarker of pure folate deficiency, the presence of vitamin B12 deficiency or hemolysis or both in individuals with low folate status predictably raises serum folate levels. Therefore, in resource-limited settings where dietary folate deficiency can coexist with vitamin B12 deficiency or malaria or both, the serum folate concentration can range from normal to high, leading to serious underestimation of tissue folate status. This review traces the genesis of an inappropriate overreliance on the serum folate concentration to rule out folate deficiency in vulnerable populations of women and children. Of significance, without due consideration of a chronically inadequate dietary folate intake, authors of influential studies have likely wrongly judged these populations to have an adequate folate status. Through repetition, this error has led to a dangerous entry into the contemporary medical literature that folate deficiency is rare in women and children. As a consequence, many millions of under-resourced women and children with mild to moderate tissue folate deficiency may have been deprived of folate replacement. This review uses historical documents to challenge earlier conclusions and re-emphasizes the need for contextual integration of clinical information in resource-limited settings.Item Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphom between 2003 and 2011: a historical cohort study(Wiley, 2016-09-15) Buckle, Geoffrey; Maranda, Louise; Skiles, Jodi; Ong'echa, John Michael; Foley, Joslyn; Epstein, Mara; Vik, Terry A.; Schroeder, Andrew; Lemberger, Jennifer; Rosmarin, Alan; Remick, Scot C.; Bailey, Jeffrey A.; Vulule, John; Otieno, Juliana A.; Moormann, Ann M.; Pediatrics, School of MedicineDiscovering how to improve survival and establishing clinical reference points for children diagnosed with endemic Burkitt lymphoma (eBL) in resource-constrained settings has recaptured international attention. Using multivariate analyses, we evaluated 428 children with eBL in Kenya for age, gender, tumor stage, nutritional status, hemoglobin, lactate dehydrogenase (LDH), Epstein-Barr virus (EBV) and Plasmodium falciparum prior to induction of chemotherapy (cyclophosphamide, vincristine, methotrexate, and doxorubicin) to identify predictive and prognostic biomarkers of survival. During this ten year prospective study period, 22% died in-hospital and 78% completed six-courses of chemotherapy. Of those, 16% relapsed or died later; 31% achieved event-free-survival; and 31% were lost to follow-up; the overall one-year survival was 45%. After adjusting for co-variates, low hemoglobin (<8g/dL) and high LDH (>400 mU/ml) were associated with increased risk of death (adjusted Hazard Ratio (aHR)=1.57 [0.97 to 2.41]) and aHR=1.84, [0.91 to 3.69], respectively). Anemic children with malaria were 3.55 times more likely to die [1.10 to 11.44] compared to patients without anemia or malarial infection. EBV load did not differ by tumor stage nor was it associated with survival. System-level factors can also contribute to poor outcomes. Children were more likely to die when inadvertently overdosed by more than 115% of the correct dose of cyclophosphamide (aHR=1.43 [0.84 to 2.43]), or doxorubicin (aHR=1.25, [0.66 to 2.35]), compared to those receiving accurate doses of the respective agent in this setting. This study codifies risk factors associated with poor outcomes for eBL patients in Africa and provides a benchmark by which to assess improvements in survival for new chemotherapeutic approaches.Item Increased circulation time of Plasmodium falciparum underlies persistent asymptomatic infection in the dry season(Nature, 2020-12) Andrade, Carolina M.; Fleckenstein, Hannah; Thomson-Luque, Richard; Doumbo, Safiatou; Lima, Nathalia F.; Anderson, Carrie; Hibbert, Julia; Hopp, Christine S.; Tran, Tuan M.; Li, Shanping; Niangaly, Moussa; Cisse, Hamidou; Doumtabe, Didier; Skinner, Jeff; Sturdevant, Dan; Ricklefs, Stacy; Virtaneva, Kimmo; Asghar, Muhammad; Vafa Homann, Manijeh; Turner, Louise; Martins, Joana; Allman, Erik L.; N'Dri, Marie-Esther; Winkler, Volker; Llinás, Manuel; Lavazec, Catherine; Martens, Craig; Farnert, Anna; Kayentao, Kassoum; Ongoiba, Aissata; Lavstsen, Thomas; Osório, Nuno S.; Otto, Thomas D.; Recker, Mario; Traore, Boubacar; Crompton, Peter D.; Portugal, Silvia; Medicine, School of MedicineThe dry season is a major challenge for Plasmodium falciparum parasites in many malaria endemic regions, where water availability limits mosquito vectors to only part of the year. How P. falciparum bridges two transmission seasons months apart, without being cleared by the human host or compromising host survival, is poorly understood. Here we show that low levels of P. falciparum parasites persist in the blood of asymptomatic Malian individuals during the 5- to 6-month dry season, rarely causing symptoms and minimally affecting the host immune response. Parasites isolated during the dry season are transcriptionally distinct from those of individuals with febrile malaria in the transmission season, coinciding with longer circulation within each replicative cycle of parasitized erythrocytes without adhering to the vascular endothelium. Low parasite levels during the dry season are not due to impaired replication but rather to increased splenic clearance of longer-circulating infected erythrocytes, which likely maintain parasitemias below clinical and immunological radar. We propose that P. falciparum virulence in areas of seasonal malaria transmission is regulated so that the parasite decreases its endothelial binding capacity, allowing increased splenic clearance and enabling several months of subclinical parasite persistence.Item Intestinal Injury in Ugandan Children Hospitalized With Malaria(Oxford, 2022-12-11) Ngai, Michelle; Hawkes, Michael T.; Erice, Clara; Weckman, Andrea M.; Wright, Julie; Stefanova, Veselina; Opoka, Robert O.; Namasopo, Sophie; Conroy, Andrea L.; Kain, Kevin C.; Pediatrics, School of MedicineBackground Severe malaria is associated with multiple organ dysfunction syndrome (MODS), which may involve the gastrointestinal tract. Methods In a prospective cohort study in Uganda, we measured markers of intestinal injury (intestinal fatty-acid binding protein [I-FABP] and zonula occludens-1 [ZO-1]) and microbial translocation (lipopolysaccharide binding protein [LBP] and soluble complement of differentiation 14 [sCD14]) among children admitted with malaria. We examined their association with biomarkers of inflammation, endothelial activation, clinical signs of hypoperfusion, organ injury, and mortality. Results We enrolled 523 children (median age 1.5 years, 46% female, 7.5% mortality). Intestinal FABP was above the normal range (≥400 pg/mL) in 415 of 523 patients (79%). Intestinal FABP correlated with ZO-1 (ρ = 0.11, P = .014), sCD14 (ρ = 0.12, P = .0046) as well as markers of inflammation and endothelial activation. Higher I-FABP levels were associated with lower systolic blood pressure (ρ = −0.14, P = .0015), delayed capillary refill time (ρ = 0.17, P = .00011), higher lactate level (ρ = 0.40, P < .0001), increasing stage of acute kidney injury (ρ = 0.20, P = .0034), and coma (P < .0001). Admission I-FABP levels ≥5.6 ng/mL were associated with a 7.4-fold higher relative risk of in-hospital death (95% confidence interval, 1.4–11, P = .0016). Conclusions Intestinal injury occurs commonly in children hospitalized with malaria and is associated with microbial translocation, systemic inflammation, tissue hypoperfusion, MODS, and fatal outcome.Item Malaria(AMA, 2022-02-08) Walter, Kristin; John, Chandy C.; Pediatrics, School of MedicineItem Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia(ASH, 2017) Opoka, Robert O.; Ndugwa, Christopher M.; Latham, Teresa S.; Lane, Adam; Hume, Heather A.; Kasirye, Phillip; Hodges, James S.; Ware, Russell E.; John, Chandy C.; Pediatrics, School of MedicineHydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle-cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM (Novel use Of Hydroxyurea in an African Region with Malaria) was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2.5 mg/kg per day for 12 months. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events (AEs), clinical and laboratory effects, and hematological toxicities. Children received either hydroxyurea (N = 104) or placebo (N = 103). Malaria incidence did not differ between children on hydroxyurea (0.05 episodes per child per year; 95% confidence interval [0.02, 0.13]) vs placebo (0.07 episodes per child per year [0.03, 0.16]); the hydroxyurea/placebo malaria incidence rate ratio was 0.7 ([0.2, 2.7]; P = .61). Time to infection also did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%; P = .001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious AEs, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria). Hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or AEs. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined. This trial was registered at www.clinicaltrials.gov as #NCT01976416.Item An overview of malaria in pregnancy(Elsevier, 2019-08) Bauserman, Melissa; Conroy, Andrea L.; North, Krysten; Patterson, Jackie; Bose, Carl; Meshnick, Steve; Pediatrics, School of MedicineOne hundred twenty-five million pregnant women are at risk for contracting malaria, a preventable cause of maternal and infant morbidity and death. Malaria parasites contribute to adverse pregnancy and birth outcomes due to their preferential accumulation in placental intervillous spaces. Pregnant women are particularly vulnerable to malaria infections, and malaria infections during pregnancy put their fetuses at risk. Malaria in pregnancy is associated with anemia, stillbirth, low birth weight and maternal and fetal death. We review the challenges to diagnosing malaria in pregnancy, as well as strategies to prevent and treat malaria in pregnancy. Finally, we discuss the current gaps in knowledge and potential areas for continued research.