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  • 1
    Publication Date: 2014-08-13
    Description: The World Health Organization recommends administration of measles vaccine (MV) at age 9 months in low-income countries. We tested the measles virus antibody response at 4.5, 9, 18, and 24 months of age for children randomly assigned to receive standard-titer Edmonston-Zagreb MV at 4.5 and 9 months, at 9 months, or at 9 and 18 months of age. At 4.5 months of age, 75% had nonprotective measles virus antibody levels. Following receipt of MV at 4.5 months of age, 77% (316/408) had protective antibody levels at 9 months of age; after a second dose at 9 months of age, 97% (326/337) had protective levels at 24 months of age. In addition, the response at both 9 and 24 months of age was inversely correlated with the antibody level at receipt of the first dose of MV, and the second dose of MV, received at 9 months of age, provided a significant boost in antibody level to children who had low antibody levels. In the group of 318 children who received MV at 9 months of age, with or without a second dose at 18 months of age, 99% (314) had protective levels at 24 months of age. The geometric mean titer at 24 months of age was significantly lower in the group that received MV at 4.5 and 9 months of age than in the group that received MV at 9 months of age ( P = .0001). In conclusion, an early 2-dose MV schedule was associated with protective measles virus antibody levels at 24 months of age in nearly all children. Clinical Trials Registration.  NCT00168558.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
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  • 2
    Publication Date: 2013-01-05
    Description: Background.  Phosphatidylserine (PS) and surface carbohydrates (SC) are known as virulence factors that may contribute to the different clinical symptoms ranging from self-healing cutaneous leishmaniasis lesions to fatal visceral disease. Leishmania (Viannia) braziliensis causes localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). Methods.  We analyzed PS exposure and SC expression associated with 2 primary L. braziliensis isolates from patients with LCL or MCL. The role of PS exposure was also addressed during promastigotes phagocytosis by macrophages. Results.  We observed higher PS exposure on the surface of late stationary growth phase promastigotes from patients with LCL, compared with those from patients with MCL, and both strains were alive during PS display. Reduction in the infectivity index was observed during macrophage interaction with late stationary growth phase promastigotes in which PS was blocked by annexin V. The major surface carbohydrates detected on LCL and MCL promastigotes were α-Man, α-Glc, and α-Gal. However, α-β-GalNAc, although observed on the surface of the LCL strain during the late stationary growth phase was highly expressed on the surface of early stationary growth phase promastigotes. Conclusions.  Our results suggest that PS and SC can modulate interactions between Leishmania organisms and host cells and may be important for the outcome of the clinical course of diseases caused by L. braziliensis .
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
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  • 3
    Publication Date: 2016-03-20
    Description: Background.  Due to development of multidrug-resistant Plasmodium falciparum new antimalarial therapies are needed. In Guinea-Bissau, routinely used triple standard-dose chloroquine remained effective for decades despite the existence of "chloroquine-resistant" P. falciparum . This study aimed to determine the in vivo efficacy of higher chloroquine concentrations against P. falciparum with resistance-conferring genotypes. Methods.  Standard or double-dose chloroquine was given to 892 children aged 〈15 years with uncomplicated malaria during 3 clinical trials (2001–2008) with ≥35 days follow-up. The P. falciparum resistance–conferring genotype ( pfcrt 76T) and day 7 chloroquine concentrations were determined. Data were divided into age groups (〈5, 5–9, and 10–14 years) because concentrations increase with age when chloroquine is prescribed according to body weight. Results.  Adequate clinical and parasitological responses were 14%, 38%, and 39% after standard-dose and 66%, 84%, and 91% after double-dose chloroquine in children aged 〈5, 5–9, and 10–14 years, respectively, and infected with P. falciparum genotypes conferring chloroquine resistance (n = 195, P 〈 .001). In parallel, median chloroquine concentrations were 471, 688, and 809 nmol/L for standard-dose and 1040, 1494, and 1585 nmol/L for double-dose chloroquine. Conclusions.  Chloroquine resistance is dose dependent and can be overcome by higher, still well-tolerated doses.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
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  • 4
    Publication Date: 2014-05-10
    Description: Observational studies and trials from low-income countries indicate that measles vaccine has beneficial nonspecific effects, protecting against non–measles-related mortality. It is not known whether measles vaccine protects against hospital admissions. Between 2003 and 2007, 6417 children who had received the third dose of diphtheria, tetanus, and pertussis vaccine were randomly assigned to receive measles vaccine at 4.5 months or no measles vaccine; all children were offered measles vaccine at 9 months of age. Using hospital admission data from the national pediatric ward in Bissau, Guinea-Bissau, we compared admission rates between enrollment and the 9-month vaccination in Cox models, providing admission hazard rate ratios (HRRs) for measles vaccine versus no measles vaccine. All analyses were conducted stratified by sex and reception of neonatal vitamin A supplementation (NVAS). Before enrollment the 2 groups had similar admission rates. Following enrollment, the measles vaccine group had an admission HRR of 0.70 (95% confidence interval [CI], .52–.95), with a ratio of 0.53 (95% CI, .32–.86) for girls and 0.86 (95% CI, .58–1.26) for boys. For children who had not received NVAS, the admission HRR was 0.53 (95% CI, .34–.84), with an effect of 0.30 (95% CI, .13–.70) for girls and 0.73 (95% CI, .42–1.28) for boys ( P = .08, interaction test). The reduction in admissions was separately significant for measles infection (admission HRR, 0 [95% CI, 0–.24]) and respiratory infections (admission HRR, 0.37 [95% CI, .16–.89]). Early measles vaccine may have major benefits for infant morbidity patterns and healthcare costs. Clinical trials registration NCT00168558.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
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  • 5
    Publication Date: 2014-08-19
    Description: Background.  We studied features that predict the presence of human papillomavirus (HPV) in a new sexual partnership. Methods.  We analyzed data from the "HPV Infection and Transmission Among Couples Through Heterosexual Activity" (HITCH) Cohort Study of recently formed partnerships ("dyads"). Women aged 18–24 and their male partners were recruited during 2005–2010 in Montreal, Canada. We tested genital swabs for detection of 36 HPV types. We defined HPV in a partnership as the presence of 1 or more HPV types in either or both partners. Using baseline data from 482 dyads, we calculated prevalence ratios to evaluate candidate risk factors. Results.  Most women (88%) were unvaccinated. Sixty-seven percent of dyads harbored HPV. For 49% of dyads, both partners were HPV+. HPV was least prevalent in dyads who were in their first vaginal sex relationship (17%) and was virtually ubiquitous in dyads for which both partners had concurrent partners (96%). Dyads that always used condoms with previous partner(s) were 27% (95% confidence interval, 9%–42%) less likely to have HPV. Conclusions.  The finding that condom use limited onward spread to future partners is in support of condom promotion to prevent sexually transmitted infections. Ongoing monitoring of HPV in sexual networks is needed, particularly in populations with suboptimal vaccine coverage.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
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  • 6
    Publication Date: 2014-11-21
    Description: Williams–Beuren syndrome is a developmental multisystemic disorder caused by a recurrent 1.55–1.83 Mb heterozygous deletion on human chromosome band 7q11.23. Through chromosomal engineering with the cre-loxP system, we have generated mice with an almost complete deletion (CD) of the conserved syntenic region on chromosome 5G2. Heterozygous CD mice were viable, fertile and had a normal lifespan, while homozygotes were early embryonic lethal. Transcript levels of most deleted genes were reduced 50% in several tissues, consistent with gene dosage. Heterozygous mutant mice showed postnatal growth delay with reduced body weight and craniofacial abnormalities such as small mandible. The cardiovascular phenotype was only manifested with borderline hypertension, mildly increased arterial wall thickness and cardiac hypertrophy. The neurobehavioral phenotype revealed impairments in motor coordination, increased startle response to acoustic stimuli and hypersociability. Mutant mice showed a general reduction in brain weight. Cellular and histological abnormalities were present in the amygdala, cortex and hippocampus, including increased proportion of immature neurons. In summary, these mice recapitulate most crucial phenotypes of the human disorder, provide novel insights into the pathophysiological mechanisms of the disease such as the neural substrates of the behavioral manifestations, and will be valuable to evaluate novel therapeutic approaches.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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