Immune Mediators of Protective and Pathogenic Immune Responses in Patients with Mild and Fatal Human Monocytotropic Ehrlichiosis

ABSTRACT: BACKGROUND: Ehrlichia chaffeensis is a bacterial pathogen that causes fatal human monocytic ehrlichiosis (HME) that mimic toxic shock-like syndrome. Murine studies indicate that over activation of cellular immunity followed by immune suppression plays a central role in mediating tissue injury and organ failure during fatal HME. However, there are no human studies that examine the correlates of resistance or susceptibility to severe and fatal HME. RESULTS: In this study, we compared the immune responses in two patients with mild/non fatal and severe/fatal HME who had marked lymphopenia, thrombocytopenia and elevated liver enzymes. The levels of different immunological factors in the blood of those patients were examined and compared to healthy controls. Our data showed that fatal HME is associated with defective production of Th1 cytokines such as ( IFNgamma and IL-2), increased anti-inflammatory (IL-10 and IL-13) and pro-inflammatory (TNF-alpha, IL-1alpha, IL-1beta, and IL-6) cytokines, increased levels of macrophages, T cells, and NK cells chemokines such as MCP-1, MIP-1alpha, MIP-1beta but not RANTES and IP-10, increased levels of neutrophils chemokine and growth factor (IL-8 and G-CSF), and elevated expression of tumor necrosis factor receptor (TNFR), and toll like receptors 2 and 4 compared to patients with non fatal HME and healthy controls. CONCLUSIONS: Fatal Ehrlichia-induced toxic shock is associated with defective Th1 responses, possible immune suppression mediated by IL-10. In addition, marked leukopenia observed in patients with fatal disease could be attributed to enhanced apoptosis of leukocytes and/or elevated chemokine production that could promote migration of immune cells to sites of infection causing tissue injury.     

Systolic time intervals in the differential diagnosis of constrictive pericarditis and cardiomyopathy.

Systolic time intervals (STI) were measured from simultaneously recorded phonocardiograms, carotid pulse tracings, and electrocardiograms in 11 patients with constrictive pericarditis and in 10 patients with cardiomyopathy to assess the value of STI in the differential diagnosis of the two conditions. The predicted ejection fraction was calculated from the STI. The results were compared and found significantly different in the two groups of patients. The ratio PEP/LVET and the ejection fraction were found to have greater discriminatory values and separated the two groups clearly. Measurement of STI, a simple, noninvasive bedside technique, appears to be useful in distinguishing between constrictive pericarditis and cardiomyopathy.     

Mode of action and adverse effects of lipid lowering drugs

Serum lipids, cholesterol and triglycerides are incorporated into hydrophilic lipoproteins, which include chylomicrons, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL) and high density lipoproteins (HDL). An elevated level of these lipoproteins, except for HDL, is the basis of all hyperlipidemias. However, only some of the lipoprotein fractions, particularly LDL and remnant particles, are potential risk factors for atherogenesis and subsequent cardiovascular disease. Several classes of pharmacological agents are currently available to increase the breakdown and reduce the synthesis of LDL and remnant factors. These include nicotinic acid and its analogs, fibric acid derivatives (e.g., clofibrate, gemfibrozil, bezafibrate), bile acid resins (e.g., cholestyramine), HMG-CoA reductase inhibitors (e.g., lovastatin, simvastatin, pravastatin) and probucol. Lipid lowering drugs of different classes have a synergistic effect on lipid metabolism and combination therapy is often used. Lipid lowering drugs are prescribed as long-term preventive therapy in apparently asymptomatic people. Several studies indicate that secondary prevention with lipid lowering drugs is cost-effective, particularly in patients with symptomatic coronary artery disease.     

Microbial contamination of drinking water from risky tubewells situated in different hydrological regions of Bangladesh

This study, conducted in 40 selected upazilas covering four hydrological regions of Bangladesh, aimed at determining the risk of selected shallow tubewells (depth <30m) used for drinking purpose (n = 26,229). This was based on WHO’s sanitary inspection guidelines and identifying the association of sanitary inspection indicators and risk scores with microbiological contamination of shallow tubewells. The main objective of the study was to observe the seasonal and regional differences of microbial contamination and finally reaching a conclusion about safe distance between tubewells and latrines by comparing the contamination of two tubewell categories (category-1: distance ≤10 m from nearest latrine; n = 80 and category 2: distances 11–20 m from nearest latrine; n = 80) in different geographical contexts. About 62% of sampled tubewells were at medium to high risk according to WHO’s sanitary inspection guidelines, while the situation was worst in south-west region. Microbiological contamination was significantly higher in sampled category-1 tubewells compared to category-2 tubewells, while the number of contaminated tubewells and level of contamination was higher during wet season. About 21% (CI₉₅ = 12%–30%), 54% (CI₉₅ = 43%–65%) and 58% (CI₉₅ = 46%–69%) of water samples collected from category-1 tubewells were contaminated by E. coli, FC, and TC respectively during the wet season. The number of category-1 tubewells having E.coli was highest in the north-west (n = 8) and north-central (n = 4) region during wet season and dry season respectively, while the level of E.coli contamination in tubewell water (number of CFU/100 ml of sample) was significantly higher in north-central region. However, the south-west region had the highest number of FC contaminated category-1 tubewells (n = 16 & n = 17; respectively during wet and dry season) and significantly a higher level of TC and FC in sampled Category-1 tubewells than north-west, north-central and south-east region, mainly during wet season. Multivariate regression analysis could identified some sanitary inspection indicators, such as tubewell within <10 m of latrine, platform absent/broken, pollution source (i.e. household’s waste dumping point/poultry/dairy farm) within 10 m of tubewell and unimproved sanitation facility which were significantly associated with presence of microbial contaminants in tubewell water (p < 0.01). A tubewell with high risk level was associated with a higher chance of having FC and TC in tubewell water than a tubewell with a medium risk during wet season, but no such conclusion could be drawn in case of E.coli contamination. Construction of pit latrine in areas with high water table should be highly discouraged. Raised sealed pits or flush/pour flash to septic tank could be installed considering sanitary inspection criteria. Water should be treated before drinking.