Recent developments in human African trypanosomiasis

PURPOSE OF REVIEW: Sleeping sickness has re-emerged as a serious problem in sub-Saharan Africa, with an estimated 100000 deaths each year. South Sudan, the Democratic Republic of Congo and Angola have experienced serious epidemics of the Gambian form of the disease. The control of Gambian sleeping sickness, which relies primarily on active case finding followed by chemotherapy, is being threatened by problems of drug resistance. Recently, Rhodesian sleeping sickness has also posed a health risk to travellers visiting game parks in East Africa. RECENT FINDINGS: Because of war-related constraints, which have prevented case detection, the prevalence of Gambian sleeping sickness commonly exceeds 5% and reached 29% in one focus in south Sudan. The incidence of Gambian infections refractory to melarsoprol treatment has also risen sharply in northern Uganda, northern Angola and southern Sudan, with failure rates as high as 26.9%. Molecular techniques based on the gene for human serum resistance (SRA) have enabled the identification of human infective parasites in the domestic animal reservoir. This molecular tool has shown that the Rhodesian form of the disease is being carried in cattle northwards in Uganda towards areas endemic for the Gambian form. The coalescence of distributions of the chronic and acute forms of the disease will present problems for both control and treatment. SUMMARY: This review surveys the molecular tools that are improving our understanding of the epidemiology of sleeping sickness, and highlights the search for new diagnostics and drugs to deal with the disease.     

Endothelial cell dysfunction in systemic vasculitis: new developments and therapeutic prospects

PURPOSE OF REVIEW: The role of the endothelium as an active player rather than a passive victim of inflammation has received considerable interest in atherosclerosis, but less so in systemic vasculitis (SV). However, the accumulating multi-organ damage seen in SV probably includes the endothelium. Assessment of endothelial function is now a standard clinical research tool in cardio-vascular departments. The exciting insights provided by their application to SV, in both primary disease and connective tissue diseases (CTD), is reviewed here. RECENT FINDINGS: Diffuse endothelial cell dysfunction (ECD) documented by several techniques occurs commonly in adult and childhood SV. Similar ECD is also seen in CTD. The mechanisms probably relate to inflammatory cytokines such as TNF. The particular role of vasculitic, as opposed to synovial or internal organ inflammation, may be release of secondary mediators directly into the blood stream- whence they can reach distant endothelial beds to induce this diffuse ECD. SUMMARY: Endothelial injury is the first step in atherosclerosis, where peripheral abnormalities correlate with coronary artery responses. The diffuse ECD in CTD suggests that vascular inflammation may initiate the accelerated CVS disease there. The new findings of similar ECD in primary SV predicts enhanced atherosclerosis here too. In Kawasaki syndrome, persistent late ECD correlates with abnormal coronary responses. In adult SV, initial data also suggests increased subclinical atherosclerosis. The role of endothelial function in the clinical outcome of SV deserves more attention. Research to pinpoint the mechanisms of ECD should lead to more specific therapies that may ameliorate the continuing late morbidity and mortality of SV.     

Recent developments in Helicobacter pylori vaccination.

This reviews discusses the recent progress in the development of a vaccine against Helicobacter pylori. To date, this gram-negative, spiral-shaped bacterium is one of the most common infections of mankind. Infection usually occurs during childhood, and when left untreated results in lifelong colonization of the stomach. Helicobacter pylori infection is a chronic gastritis that can lead to peptic ulcer disease, gastric adenocarcinoma and gastric B-cell lymphoma. Antimicrobial therapy is currently the method of choice for curing H. pylori infection, but complex dosing, inconsistent efficiency, development of antibiotic resistance, costs and various side effects compromise widespread use. As a consequence, new strategies for the prevention and eradication of H. pylori infections are being explored. Vaccines are an attractive option, because they are both effective and economic in use. Natural infection with H. pylori usually results in a strong inflammatory Th1-type CD4(+)T-cell response that does not seem to have any protective effects. Successful vaccination studies indicate that a Th2-type response is required for protection, but the exact mechanisms involved in protective immunization are still poorly understood. Although commercial development of products for clinical trial is underway, many important issues, such as lack of a suitable mucosal adjuvant, and prevention of potential side effects, such as postimmunization gastritis, need to be resolved.     

Recent developments in idiotypic network theory.

A recent class of mathematical models of the immune network is reviewed. The models in this class are based upon the bell-shaped activation function that is known to be characteristic for receptor cross-linking. These network models have a large number of self-regulatory properties. This review discusses of number of these properties, i.e. immunological memory, suppression, and repertoire selection.     

Angiogenesis. Possibilities for therapeutic intervention in rheumatic diseases

In contrast to vasculogenesis, angiogenesis is defined as the formation of new vessels from preexisting ones. Physiologically, this multistep process occurs in adults during the reproductive cycle and during pregnancy, pathophysiologically it can be found in wound healing, inflammation and carcinogenesis. The underlying mechanisms are vasodilatation and increasing permeability, destabilization of vessel walls and degradation of extracellular matrix, followed by the proliferation and migration of endothelial cells. Migrated endothelial cells form vascular tubes at sites of ischemia and these tubes are finally stabilized by pericytes and smooth muscle cells. This process is controlled by a complex interaction of angiogenic and angiostatic factors. In contrast to carcinogenesis, the role of angiogenesis for the pathogenesis and therapy of rheumatic diseases is less understood. Two examples for pathologically disturbed angiogenesis, rheumatoid arthritis and systemic sclerosis, are discussed in this review with respect to therapeutic options.     

Recent developments in leishmaniasis

PURPOSE OF REVIEW: The leishmaniases, caused by protozoan parasites of the genus Leishmania, are a significant health problem in many regions of the world. This review highlights the recent advances in the study of leishmaniasis related to parasite biology, disease pathogenesis, clinical evaluation and treatment, and prevention. RECENT FINDINGS: Genetic heterogeneity and clonal diversity is common among Leishmania strains. Gene knockout, overexpression, and re-introduction studies have identified a number of genes that play a role in parasite virulence. Surprisingly, the importance of the surface lipophosphoglycan in parasite virulence appears to differ among Leishmania spp. Studies in experimental animal models have further defined the roles of CD4 and CD8 T cells, IL-4, IL-10, and IL-12 in the control, maintenance, or progression of disease. The effect of Leishmania on dendritic cells and macrophage effector function has also been an important area of investigation. A number of new vaccine candidates have been identified through experimental animal studies. Clinical studies of leishmaniasis have focused on the host determinants of disease (most notably HIV co-infection), serological and DNA-based diagnostic assays, and treatment. Antimony-resistant cases of cutaneous and visceral leishmaniasis have become more common; liposomal amphotericin and oral miltefosine are promising alternative therapies. SUMMARY: Significant advances have been made in the areas of pathogenesis, host defence, and treatment of leishmaniasis. A number of new vaccine candidates and potential targets of drug therapy have been identified, but progress from preclinical studies to clinical trials has been slow. Translational research, built upon the solid foundation of existing and ongoing basic investigation, is a high priority.     

Recent developments in pertussis

Pertussis causes nearly 300,000 deaths in children every year. Most deaths take place in developing countries, but the infection remains a priority everywhere. Pertussis vaccination protects infants and children against death and admission to hospital, but breakthrough disease in vaccinated people can happen. In high-mortality countries, the challenge is to improve timeliness and coverage of childhood vaccination and surveillance. In regions with low mortality and highest coverage, pertussis is frequently the least well-controlled disease in childhood vaccination programmes. Some countries have reported a rise in pertussis in adolescents, adults, and pre-vaccination infants, but how much these changes are real or a result of improved recognition and surveillance remains uncertain. In response, several countries have introduced adolescent and adult acellular pertussis vaccine boosters. The effect so far is unknown; assessment is impeded by poor data. Uncertainties still persist about key variables needed to model and design vaccination programmes, such as risk of transmission from adults and adolescents to infants. New vaccination strategies under investigation include vaccination of neonates, family members, and pregnant women.     

Angiogenesis and rheumatoid arthritis: pathogenic and therapeutic implications.

Rheumatoid arthritis can be considered as one of the family of 'angiogenesis dependent diseases'. Angiogenesis in rheumatoid arthritis is controlled by a variety of factors found in the synovial fluid and pannus tissue. Modulation of the angiogenic component of the disease may alter the pathogenesis of the condition, and subsequent cartilage and joint destruction, by reducing the area of the endothelium in the pannus and restricting pannus growth. Current therapeutic strategies exert, to varying extents, an inhibitory effect on the angiogenic process. In particular, the mode of action of the slow acting antirheumatic drugs may be due to their effect on the angiogenic response. The development of novel angiostatic treatments for chronic inflammatory joint disease may lead to a new therapeutic approach in controlling disease progression.     

Recent developments in understanding the pathogenesis of aplastic anemia.

Bone marrow failure in aplastic anemia (AA) could result from abnormalities of hematopoietic stem cells, abnormal control of hematopoiesis, or abnormalities of the hematopoietic environment. Bone marrow transplantation, in vitro marrow culture techniques, and studies in animal models of marrow failure have provided insights on the possible pathogenetic mechanisms underlying AA. Studies in man and in murine models suggest that most often AA results from injuries to hematopoietic stem cells. Despite the intriguing report of abnormal regulatory cells in congenitally anemic mice, instances of marrow failure due to defective humoral or cellular control of hematopoiesis have not been identified in man. In vitro studies employing allogeneic marrow targets have suggested that immune suppression of hematopoiesis may occasionally mediate AA in man. Marrow failure due to abnormalities of the hematopoietic microenvironment has been suggested by experience with bone marrow transplantation, but no direct study of this possibility has been reported. Based on available evidence, it seems likely that AA will prove to be many diseases that share common clinical and morphologic features.     

Recent developments in diet and gout

PURPOSE OF REVIEW: Gout is the most common inflammatory arthritis in men, affecting approximately 1-2% of adult men in Western countries. United States gout prevalence has approximately doubled over the past two decades. In recent years, key prospective epidemiological and open-labeled dietary studies, coupled with recent advances in molecular biology elucidating proximal tubular urate transport, have provided novel insights into roles of diet and alcohol in hyperuricemia and gout. This review focuses on recent developments and their implications for clinical practice, including how we advise patients on appropriate diets and alcoholic beverage consumption. RECENT FINDINGS: Studies have observed an increased risk of gout among those who consumed the highest quintile of meat, seafood and alcohol. Although limited by confounding variables, low-fat dairy products, ascorbic acid and wine consumption appeared to be protective for the development of gout. SUMMARY: The most effective forms of dietary regimen for both hyperuricemia and gout flares remains to be unidentified. Until confirmed by a large, controlled study, it is prudent to advise patients to consume meat, seafood and alcoholic beverages in moderation, with special attention to food portion size and content of non-complex carbohydrates which are essential for weight loss and improved insulin sensitivity.