Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

HCV synergizes with body weight in the promotion of insulin resistance.

Hepatitis C virus (HCV) infection appears to contribute to the development of insulin resistance (IR). Among the multiple determinants of IR, body mass index (BMI) is the most important. We investigated the contribution of HCV to BMI-associated IR using a transgenic mouse model expressing HCV core protein. Eight transgenic and five nontransgenic littermate controls were evaluated. Glucose and insulin tolerance tests (ITT) were performed on two separate occasions. Multivariate linear mixed modelling was used to evaluate and compare the effect of weight on IR between HCV core transgenic and nontransgenic controls. There were no statistically significant differences in glucose or ITT (P = 0.58 and P = 0.59, respectively) between the two groups, and no difference in median weights between transgenic and control mice (P = 0.11). However, there was greater variance in the distributions of Tg when compared to nontransgenic mice for both glucose and insulin tolerance. When evaluating this closely, a differential contribution of weight to IR curves between these groups was noted (P = 0.05). Among nontransgenic mice, IR curves for mice of different weights were comparable, however, for transgenic mice, higher weights resulted in larger levels of IR curves with slower decay. In all animals, steatosis was absent or minimal. We conclude that weight has a greater effect on IR in HCV core expressing transgenic mice than littermate controls. HCV therefore synergizes with weight in the promotion of IR. Steatosis was not a prerequisite for the development of IR, implying that HCV's effects on IR may be independent of steatosis.

Necrotising pneumonia is an increasingly detected complication of pneumonia in children.

Necrotising pneumonia (NP) is a severe complication of community-acquired pneumonia characterised by liquefaction and cavitation of lung tissue. The present study describes the epidemiology, aetiology, management and outcomes of children hospitalised with NP over a 15-yr period. A retrospective observational study of NP cases was conducted from January 1990 to February 2005 analysing clinical presentation, laboratory data, hospital course and long-term follow-up. A total of 80 NP cases were identified, with the number of detected cases increasing from 12, in the period 1993-1996, to 40 in the period 2001-2004. In total, 69 (86%) cases had pleural effusion with a low pH (mean 7.08) and 38 (48%) patients had positive cultures, with Streptococcus pneumoniae as the predominant organism. Recently, other organisms, most notably methicillin-resistant Staphylococcus aureus, emerged. Patients had prolonged hospitalisations (median 12 days). A total of 69 patients required pleural interventions and those receiving chest drainage alone had similar outcomes to those managed surgically. All patients had full clinical resolution within 2 months of presentation. Necrotising pneumonia has increasingly been identified as a complication of paediatric pneumonia. Streptococcus pneumoniae remains the predominant organism, but since 2002, different bacteria have been isolated and the age range of cases has broadened. Despite the serious morbidity, massive parenchymal damage and prolonged hospitalisations, long-term outcome following necrotising pneumonia is excellent.

The identity of Leishmania isolated from sand flies and vertebrate hosts in a major focus of cutaneous leishmaniasis in Baturite, northeastern Brazil.

During a field investigation carried out in Baturite, Brazil from 1989 to 1991, sand flies, sympatric rodents, domestic dogs and humans were surveyed for leishmaniasis. Twenty strains of Leishmania were isolated by in vitro culture from Lutzomyia whitmani, three strains were obtained from Rattus rattus, two strains from dogs, and five strains from humans. The isolates were characterized by isoenzyme electrophoresis by hybridization with kinetoplast DNA-specific probes. All the samples were identified as L. (Viannia) braziliensis. The importance of these results in the dynamics of the Leishmania infection in this focus is discussed.

Short-term toxicity study of erythrosine on wistar rats hepatic mitochrondrial respiration

El colorante alimentario xanteno eritrosina presentó, en investigación anterior realizada in vitro, un fuerte efecto inhibitorio en mitocondrias aisladas de hígado y de riñones de ratas. Por ese motivo, fue seleccionado para una investigación del mismo efecto después de su administración por vía oral en ratas wistar. La eritrosina fue administrada en el agua de bebida, durante 90 días, a ratas machos y hembras recién destetadas, en las dosis de 0,100,500 y 1000 mg del colorante/kg depeso corporal por día. Al final del experimento, la función respiratoria de las mitocondrias aisladas del hígado de los animales que consumieron eritrosina, no fue distinta (p>0,05) del grupo control. Durante el período de estudio no hubo diferencia significativa (p>0,05) en la ganacia de peso de los animales. La observación al microscopio de los sistemas digestivo, respiratorio, urinario y linfoide no mostró anomalías. Preparaciones histológicas indicaron dilatación del cecum y una moddrada adherencia del colorante de la mucosa intestinal

Short-term toxicity study of erythrosine on wistar rats hepatic mitochrondrial respiration

El colorante alimentario xanteno eritrosina presentó, en investigación anterior realizada in vitro, un fuerte efecto inhibitorio en mitocondrias aisladas de hígado y de riñones de ratas. Por ese motivo, fue seleccionado para una investigación del mismo efecto después de su administración por vía oral en ratas wistar. La eritrosina fue administrada en el agua de bebida, durante 90 días, a ratas machos y hembras recién destetadas, en las dosis de 0,100,500 y 1000 mg del colorante/kg depeso corporal por día. Al final del experimento, la función respiratoria de las mitocondrias aisladas del hígado de los animales que consumieron eritrosina, no fue distinta (p>0,05) del grupo control. Durante el período de estudio no hubo diferencia significativa (p>0,05) en la ganacia de peso de los animales. La observación al microscopio de los sistemas digestivo, respiratorio, urinario y linfoide no mostró anomalías. Preparaciones histológicas indicaron dilatación del cecum y una moddrada adherencia del colorante de la mucosa intestinal(AU)