Objective In contrast to what is observed in the general population, a low body mass index (BMI) has been associated with accelerated mortality in patients with rheumatoid arthritis (RA). The aim of this study was to assess whether weight loss might explain these seemingly paradoxical observations. Methods Our study included patients identified from the Veterans Affairs (VA) RA Registry. Dates of death were abstracted from VA electronic medical records. The BMI at each study visit and the change from the previous visit were determined. The maximum BMI of each patient was also obtained from medical records. The annualized rate of BMI loss was determined from the slope of change (per year) in BMI over visits within the preceding 13 months. Cox multivariable proportional hazards models were used to assess associations between BMI measures and mortality. Results In a sample of 1,674 patients, 312 deaths occurred over 9,183 person-years. A loss in BMI of ≥1 kg/m2 was associated with a greater risk of death, after adjustment for demographics, comorbidities, BMI, smoking, and RA therapies (hazard ratio [HR] 1.99, 95% confidence interval [95% CI] 1.53–2.59, P < 0.001). This association remained significant in a subsample analysis adjusting for C-reactive protein and physical function (HR 1.81, 95% CI 1.36–2.41, P < 0.001). Weight loss at an annualized rate of ≥3 kg/m2 was associated with the greatest risk of death (HR 2.49, 95% CI 1.73–3.57, P < 0.001). Low BMI (<20 kg/m2) in patients with a history of obesity (>30 kg/m2) was associated with the greatest risk (HR 8.52, 95% CI 4.10–17.71, P < 0.001). Conclusion Weight loss is a strong predictor of death in patients with RA. These observations may explain the observed obesity paradox and do not support a biologically protective role of obesity.

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BackgroundVector-borne transmission of Trypanosoma cruzi is seen exclusively in the Americas where an estimated 8 million people are infected with the parasite. Significant research in southern Peru has been conducted to understand T. cruzi infection and vector control, however, much less is known about the burden of infection and epidemiology in northern Peru.MethodologyA cross-sectional study was conducted to estimate the seroprevalence of T. cruzi infection in humans (n=611) and domestic animals [dogs (n=106) and guinea pigs (n=206)] in communities of Cutervo Province, Peru. Sampling and diagnostic strategies differed according to species. An entomological household study (n=208) was conducted to identify the triatomine burden and species composition, as well as the prevalence of T. cruzi in vectors. Electrocardiograms (EKG) were performed on a subset of participants (n=90 T. cruzi infected participants and 170 age and sex-matched controls). The seroprevalence of T. cruzi among humans, dogs, and guinea pigs was 14.9% (95% CI: 12.2 – 18.0%), 19.8% (95% CI: 12.7- 28.7%) and 3.3% (95% CI: 1.4 – 6.9%) respectively. In one community, the prevalence of T. cruzi infection was 17.2% (95% CI: 9.6 - 24.7%) among participants < 15 years, suggesting recent transmission. Increasing age, positive triatomines in a participant's house, and ownership of a T. cruzi positive guinea pig were independent correlates of T. cruzi infection. Only one species of triatomine was found, Panstrongylus lignarius, formerly P. herreri. Approximately forty percent (39.9%, 95% CI: 33.2 - 46.9%) of surveyed households were infested with this vector and 14.9% (95% CI: 10.4 - 20.5%) had at least one triatomine positive for T. cruzi. The cardiac abnormality of right bundle branch block was rare, but only identified in seropositive individuals.ConclusionsOur research documents a substantial prevalence of T. cruzi infection in Cutervo and highlights a need for greater attention and vector control efforts in northern Peru.

BackgroundAlthough 80% of malaria occurs in children under five years of age, infants under six months of age are known to have low rates of infection and disease. It is not clear why this youngest age group is protected; possible factors include maternal antibodies, unique nutrition (breast milk), and the presence of foetal haemoglobin (HbF). This work aims to gain insight into possible mechanisms of protection, and suggest pathways for focused empirical work, by modelling a range of possible effects of foetal haemoglobin and other red blood cell (RBC) developmental changes on parasite dynamics in infants.MethodsA set of ordinary differential equations was created to investigate the leading hypotheses about the possible protective mechanisms of HbF-containing red blood cells, in particular whether HbF suppresses parasite population growth because parasite multiplication in individual RBCs is lower, slower or absent. The model also incorporated the intrinsic changes in blood volume and haematocrit that occur with age, and the possibility of parasite affinities for HbF-containing RBCs or reticulocytes.ResultsThe model identified several sets of conditions in which the infant remained protected, or displayed a much slower growth of parasitaemia in the first few months of life, without any intervening immune response. The most protective of the hypothesized mechanisms would be the inhibition of schizont division in foetal RBCs so that fewer merozoites are produced. The model showed that a parasite preference for HbF-containing RBCs increases protective effects for the host, while a preference for reticulocytes has little effect.ConclusionsThe results from this simple model of haematological changes in infants and their effects on Plasmodium falciparum infection dynamics emphasize the likely importance of HbF and RBC number as an explanatory factor in paediatric malaria, and suggest a framework for organizing related empirical research.