BackgroundControversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.Methodology/Principal FindingsWe performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms ‘schistosomiasis’, ‘dosing’ and ‘praziquantel’ and hand searches of personal collections and bibliographies of recovered articles. In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection. Observed cure rates (positive to negative conversion in egg detection assays) were, for S. mansoni, 69–91% cure after two doses vs. 42–79% after one dose and, for S. haematobium, 46–99% cure after two doses vs. 37–93% after a single dose. Treatment benefits in terms of reduction in intensity (mean egg count) were also different for the two species—for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose. Cost-effectiveness analysis was performed based on Markov life path modeling.Conclusions/SignificanceAlthough schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni)–$211 (S. haematobium) per additional lifetime QALY gained by double treatment in school-based programs. More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be reduced through more effective coverage, significant additional benefits are expected to accrue in the targeted communities.
Introduction Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation (CVM) associated with fetal growth abnormalities. Genetic and environmental factors have been identified that contribute to pathogenesis, but the role of the placenta is unknown. The purpose of this study was to systematically examine the placenta in HLHS with and without growth abnormalities. Methods HLHS term singleton births were identified from a larger cohort when placenta tissue was available. Clinical data were collected from maternal and neonatal medical records, including anthropometrics and placental pathology reports. Placental tissues from cases and controls were analyzed to assess parenchymal morphology, vascular architecture and leptin signaling. Results HLHS cases (n = 16) and gestational age-matched controls (n = 18) were analyzed. Among cases, the average birth weight was 2993 grams, including 31% that were small for gestational age. When compared with controls, gross pathology of HLHS cases demonstrated significantly reduced placental weight and increased fibrin deposition, while micropathology showed increased syncytial nuclear aggregates, decreased terminal villi, reduced vasculature and increased leptin expression in syncytiotrophoblast and endothelial cells. Discussion Placentas from pregnancies complicated by fetal HLHS are characterized by abnormal parenchymal morphology, suggesting immature structure may be due to vascular abnormalities. Increased leptin expression may indicate an attempt to compensate for these vascular abnormalities. Further investigation into the regulation of angiogenesis in the fetus and placenta may elucidate the causes of HLHS and associated growth abnormalities in some cases.
Introduction: Recent evidence suggests that preterm birth is a possible risk factor for high blood pressure (BP) in later life. The most widely quoted blood pressure centiles for very low birth weight (VLBW, ≤1500 g birth weight) infants at corrected term gestation is based on a cohort with mostly late preterm or term infants (Zubrow curves). Objectives: The objective of this study was to determine the clinical utility of the Zubrow curves in diagnosis of hypertension in VLBW infants at their term corrected gestational age (CGA). Patients and Methods: In a case-control study, we compared BP in 75 VLBW infants at 40 weeks CGA (cases) to 69 full term infants admitted to neonatal intensive care unit (NICU) (controls). Results: In spite of having lower weights, VLBW infants compared to term infants (2612.8 ± 546 vs. 3308.2 ± 373 g, P ≤ 0.001) had higher average systolic (88.8 ± 7.6 vs. 82.33 ± 8.5 mm Hg; P ≤ 0.001) and mean BP (61.2 ± 6.6 vs. 57.61 ± 6.9, P = 0.01). Although 41% (31/75) VLBW infants would have met the criteria for hypertension according to Zubrow curves only 4% (3/75) were diagnosed with hypertension. Conclusion: Since Zubrow BP centiles were based on a heterogeneous population of infants including preterm and term infants, new BP centiles based on chronological data from VLBW infants would allow a better definition of hypertension in these infants and identify the threshold BP for initiating treatment.
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