The physiopathology of dengue hemorrhagic fever (DHF), a severe form of Dengue Fever, is poorly understood. We are unable to identify patients likely to progress to DHF for closer monitoring and early intervention during epidemics, so most cases are sent home. This study explored whether patients with selected co-morbidities are at higher risk of developing DHF. A matched case-control study was conducted in a dengue sero-positive population in two Brazilian cities. For each case of DHF, 7 sero-positive controls were selected. Cases and controls were interviewed and information collected on demographic and socio-economic status, reported co-morbidities (diabetes, hypertension, allergy) and use of medication. Conditional logistic regression was used to calculate the strength of the association between the co-morbidities and occurrence of DHF. 170 cases of DHF and 1,175 controls were included. Significant associations were found between DHF and white ethnicity (OR = 4.70; 2.17–10.20), high income (OR = 6.84; 4.09–11.43), high education (OR = 4.67; 2.35–9.27), reported diabetes (OR = 2.75; 1.12–6.73) and reported allergy treated with steroids (OR = 2.94; 1.01–8.54). Black individuals who reported being treated for hypertension had 13 times higher risk of DHF then black individuals reporting no hypertension. This is the first study to find an association between DHF and diabetes, allergy and hypertension. Given the high case fatality rate of DHF (1–5%), we believe that the evidence produced in this study, when confirmed in other studies, suggests that screening criteria might be used to identify adult patients at a greater risk of developing DHF with a recommendation that they remain under observation and monitoring in hospital. Dengue is an arboviral disease that affects large areas of countries in tropical and subtropical regions of the world. Around 500,000 cases and 22,000 deaths of dengue hemorrhagic fever (DHF)/Dengue Shock Syndrome (DSS), the most severe presentations of this disease, occur annually. It is unclear why some cases of dengue fever (0.5% to 4%) progress to DHF/DSS. There is weak evidence that some diseases could have a role in this process, such as diabetes, hypertension, and allergies. In epidemics most dengue fever cases are sent home as there are too many to be kept in observation, but if it were possible to identify those with a higher risk of progression to DHF, they could be kept for observation, for early detection of signs, symptoms and alterations in laboratory tests suggestive of DHF, to enable timely and effective clinical management and early intervention. We study this issue and we believe that the evidence produced in this study, when confirmed in other studies, suggests that screening criteria might be used to identify adult patients at a greater risk of developing DHF with a recommendation that they remain under observation and monitoring in a hospital.

Light or moderate intensity infection with Schistosoma mansoni may contribute to growth deficits. We report on the effects of treatment for S. mansoni on growth and development in Brazilian schoolchildren. Anthropometric measurements were taken from 539 S. mansoni-infected children and their age- and sex-matched egg-negative controls between the ages of 7 and 15 years. The children as a whole exhibited chronic malnutrition, with growth retardation in height evident in 21% of the population. Infected children, however, were significantly smaller in height, weight, mid upper arm circumference (UAC), tricep skinfold (TSF), and subscapular skinfold (SSF) measurements than control children (P < 0.05). These differences were due primarily to a greater disparity between infected and egg-negative girls in height (P < 0.01), weight (P = 0.01), UAC (P = 0.02), and TSF (P < 0.01). Nevertheless, girls demonstrated a better level of development and nutrition compared with boys. While infected boys were shorter and weighed less than controls, these differences were not significant. Growth and development in girls was negatively correlated with intensity of infection. Coinfection with S. mansoni and Trichuris appeared to act synergistically in the development of malnutrition.

Recently, we observed that repeated Schistosoma mansoni infection and treatment boost Th2-associated cytokines and TGF-β production in baboons. Other studies have shown that some chronically infected baboons develop hepatic fibrosis. Because TGF-β, IL-2, and IL-4 have been shown to participate in development of fibrosis in murine schistosomiasis, the present study examined whether repeated exposure stimulates hepatic fibrosis in olive baboons. To test this hypothesis, animals were exposed to similar numbers of S. mansoni cercariae given once or repeatedly. After 19 wk of infection, animals were cured with praziquantel and reinfected once or multiple times. Hepatic granulomatous inflammation and fibrosis were assessed from serial liver biopsies taken at weeks 6, 9, and 16 after reinfection and egg Ag (schistosome egg Ag)-specific cytokine production by PBMC were measured simultaneously. Periportal fibroblast infiltration and extracellular matrix deposition (fibrosis), angiogenesis, and biliary duct hyperplasia developed in some animals. The presence and amount of fibrosis directly correlated with the frequency of exposure. Fibrosis was not associated with adult worm or tissue egg burden. The amount of fibrosis correlated with increased schistosome egg Ag-driven TGF-β at 6, 9, and 16 wk postinfection (rs = 0.9, 0.8, and 0.54, respectively, all p < 0.01) and IL-4 production (p = 0.02) at 16 wk postinfection and not IFN-γ, IL-2, IL-5, or IL-10. These data suggest that repeated exposure is a risk factor for periportal fibrosis by a mechanism that primes lymphocytes to produce increased levels of profibrotic molecules that include TGF-β and IL-4.