The potential role of interleukin-37 in infectious diseases.

Interleukin-37 (IL-37) is a newly introduced cytokine to interleukin-1 family. Many studies have demonstrated that IL-37 owns immunosuppressive effects against both innate and acquired immune responses via inhibition of several inflammatory mediators. Thence, IL-37 has anti-inflammatory action in some diseases including cancer, autoimmune diseases, cardiovascular diseases and infectious diseases. Recent investigations have reported the important role of IL-37 in immunity against viral, bacterial and fungal infections as they prevent inappropriate immune activation and suppress the inflammation induced by these infectious agents. Thus, IL-37 could play a crucial role in protecting host tissues from injury during infections by damping excessive inflammatory reactions. However, the precise roles of IL-37 in infectious diseases remain largely unknown. The current review shed light on the pivotal role of IL-37 in infectious diseases such as the human immunodeficiency virus-1 (HIV-1), viral myocarditis, hepatitis C virus (HCV), hepatitis B virus (HBV), tuberculosis, leprosy, pneumococcal pneumonia, listeria infection, aspergillosis, candidiasis and eumycetoma. In conclusion, this review reported that IL-37 has a crucial role in reducing infection-associated inflammation and has a good impact on inflammation-induced pathology. However, tight regulation that achieved balance between effector immune responses that required for pathogen elimination and limited tissue damage that resulted from excessive inflammation should be existed in the potential IL-37 therapy to prevent clinical complications of a disease.

Emerging/re-emerging viral diseases & new viruses on the Indian horizon.

Infectious diseases remain as the major causes of human and animal morbidity and mortality leading to significant healthcare expenditure in India. The country has experienced the outbreaks and epidemics of many infectious diseases. However, enormous successes have been obtained against the control of major epidemic diseases, such as malaria, plague, leprosy and cholera, in the past. The country's vast terrains of extreme geo-climatic differences and uneven population distribution present unique patterns of distribution of viral diseases. Dynamic interplays of biological, socio-cultural and ecological factors, together with novel aspects of human-animal interphase, pose additional challenges with respect to the emergence of infectious diseases. The important challenges faced in the control and prevention of emerging and re-emerging infectious diseases range from understanding the impact of factors that are necessary for the emergence, to development of strengthened surveillance systems that can mitigate human suffering and death. In this article, the major emerging and re-emerging viral infections of public health importance have been reviewed that have already been included in the Integrated Disease Surveillance Programme.

Updates on the use of vaccines in dermatological conditions.

Numerous vaccines are being actively developed for use in dermatologic diseases. Advances in the fields of immunotherapy, genetics and molecular medicine have allowed for the design of prophylactic and therapeutic vaccines with immense potential in managing infections and malignancies of the skin. This review addresses the different vaccines available for use in dermatological diseases and those under development for future potential use. The major limitation of our review is its complete reliance on published data. Our review is strictly limited to the availability of published research online through available databases. We do not cite any of the authors' previous publications nor have we conducted previous original research studies regarding vaccines in dermatology. Strength would have been added to our paper had we conducted original studies by our research team regarding the candidate vaccines delineated in the paper.

Vasculitis and infectious diseases.

Vasculitis usually presents without a well-known underline cause (idiopathic vasculitis), nevertheless, it is sometimes possible to find out one or more causative agents (secondary vasculitis). Nowadays, thanks to the increasing amount of precise diagnostic tools, a piece of idiopathic vasculitis is reclassified as associated with probable etiology, which can be set off by several factors, such as infections. Infections are considered to be the most common cause of secondary vasculitis. Virtually, every infectious agent can trigger a vasculitis by different mechanisms which can be divided in two main categories: direct and indirect. In the former, infectious agents destroy directly the vascular wall leading, eventually, to a subsequent inflammatory response. In the latter, indirect form, they stimulate an immune response against blood vessels. Different infectious agents are able to directly damage the vascular wall. Among these, it is possible to recognize Staphylococcus spp, Streptococcus spp, Salmonella spp, Treponema spp, Rickettsia spp, Cytomegalovirus, Herpes Simplex Virus 1 and 2, and many others which have a peculiar tropism for endothelial cells. Conversely, another group of microbial agents, such as Mycobacterium tuberculosis, Mycobacterium leprae, Hepatits B Virus, Human Immunodeficiency Virus and others, trigger vasculitis in the indirect way. This is due to the fact that they can share epitopes with the host or modify self-antigens, thus leading to a cross-self reaction of the immune system. These mechanism, in turn, leads to immunological responses classified as type I-IV by Gell-Coombs. Nevertheless, it is difficult to strictly separate the direct and indirect forms, because most infectious agents can cause vasculitis in both ways (mixed forms). This paper will analyze the link between infectious agents and vasculitis, focusing on direct and indirect secondary vasculitis, and on a group of probable infection-related idiopathic vasculitis, and finally on a group of idiopathic vasculitis with microbiological triggers. Furthermore, a diagnostic and therapeutic approach to vasculitis when an underline infection has been suspected is suggested.

Palaeopathology and genes: investigating the genetics of infectious diseases in excavated human skeletal remains and mummies from past populations.

The aim of this paper is to review the use of genetics in palaeomicrobiology, and to highlight the importance of understanding past diseases. Palaeomicrobiology is the study of disease pathogens in skeletal and mummified remains from archaeological contexts. It has revolutionarised our understanding of health in the past by enabling a deeper knowledge of the origins and evolution of many diseases that have shaped us as a species. Bacterial diseases explored include tuberculosis, leprosy, bubonic plague, typhoid, syphilis, endemic and epidemic typhus, trench fever, and Helicobacter pylori. Viral diseases discussed include influenza, hepatitis B, human papilloma virus (HPV), human T-cell lymphotrophic virus (HTLV-1) and human immunodeficiency virus (HIV). Parasitic diseases investigated include malaria, leishmaniasis, Chagas' disease, roundworm, whipworm, pinworm, Chinese liver fluke, fleas and lice. Through a better understanding of disease origins and their evolution, we can place into context how many infectious diseases are changing over time, and so help us estimate how they may change in the future.

[History of human epidemic and endemic diseases in the southwest Indian Ocean]. / Histoire des épidémies et des endémoépidémies humaines dans le sud-ouest de l'océan Indien.

Smallpox has been known in the Mascarene Islands since 1729, and in 1898, the vaccinogenic and anti-rabies Institute of Tananarive, the future Pasteur Institute of Madagascar, was created to combat it. Cholera first arrived in the Mascarenes in 1819, but did not affect the Comoros Islands and Madagascar until the current pandemic. Bubonic plague has beset the ports of Madagascar and the Mascarenes since 1898. Girard and Robic developed the anti-plague vaccine in 1931 at the Pasteur Institute of Madagascar. The Mascarenes lost their reputation as Eden when malaria arrived in 1841, and this disease remains prominent in Madagascar and Comoros. Leprosy has been known in La Réunion since 1726 and is still very present in Mayotte, Anjouan, and Madagascar. Leptospirosis is a public health problem, except in Madagascar and the Comoros. Dengue, chikungunya, and Rift Valley fever are also present. HIV/AIDS is not a major concern, except in Mauritius, where it was spread by injection drug use, in the Seychelles and in Madagascar's largest cities. Madagascar is the principal site worldwide of chromoblastomycosis, first described there in 1914.

Neglected tropical diseases of Oceania: review of their prevalence, distribution, and opportunities for control.

Among Oceania's population of 35 million people, the greatest number living in poverty currently live in Papua New Guinea (PNG), Fiji, Vanuatu, and the Solomon Islands. These impoverished populations are at high risk for selected NTDs, including Necator americanus hookworm infection, strongyloidiasis, lymphatic filariasis (LF), balantidiasis, yaws, trachoma, leprosy, and scabies, in addition to outbreaks of dengue and other arboviral infections including Japanese encephalitis virus infection. PNG stands out for having the largest number of cases and highest prevalence for most of these NTDs. However, Australia's Aboriginal population also suffers from a range of significant NTDs. Through the Pacific Programme to Eliminate Lymphatic Filariasis, enormous strides have been made in eliminating LF in Oceania through programs of mass drug administration (MDA), although LF remains widespread in PNG. There are opportunities to scale up MDA for PNG's major NTDs, which could be accomplished through an integrated package that combines albendazole, ivermectin, diethylcarbamazine, and azithromycin, in a program of national control. Australia's Aboriginal population may benefit from appropriately integrated MDA into primary health care systems. Several emerging viral NTDs remain important threats to the region.

Polymerase chain reaction-based molecular diagnosis of cutaneous infections in dermatopathology.

Conventional methods, including microscopy, culture, and serologic studies, are a mainstay in the diagnosis of cutaneous infection. However, owing to limitations associated with these techniques, such as low sensitivity for standard microscopy and in the case of culture delay in diagnosis, polymerase chain-reaction based molecular techniques have taken on an expanding role in the diagnosis of infectious processes in dermatopathology. In particular, these assays are a useful adjunct in the diagnosis of cutaneous tuberculosis, atypical mycobacterial infection, leprosy, Lyme disease, syphilis, rickettsioses, leishmaniasis, and some fungal and viral infections. Already in the case of tuberculosis and atypical mycobacterial infection, standardized polymerase chain-reaction assays are commonly used for diagnostic purposes. With time, additional molecular-based techniques will decrease in cost and gain increased standardization, thus delivering rapid diagnostic confirmation for many difficult-to-diagnose cutaneous infections from standard formalin-fixed paraffin-embedded tissue specimens.

Human genetic susceptibility to intracellular pathogens.

Intracellular pathogens contribute to a significant proportion of infectious disease morbidity and mortality worldwide. Increasing evidence points to a major role for host genetics in explaining inter-individual variation in susceptibility to infectious diseases. A number of monogenic disorders predisposing to infectious disease have been reported, including susceptibility to intracellular pathogens in association with mutations in genes of the interleukin-12/interleukin-23/interferon-γ axis. Common genetic variants have also been demonstrated to regulate susceptibility to intracellular infection, for example the CCR5Δ32 polymorphism that modulates human immunodeficiency virus-1 (HIV-1) disease progression. Genome-wide association study approaches are being increasingly utilized to define genetic variants underlying susceptibility to major infectious diseases. This review focuses on the current state-of-the-art in genetics and genomics as pertains to understanding the genetic contribution to human susceptibility to infectious diseases caused by intracellular pathogens such as tuberculosis, leprosy, HIV-1, hepatitis, and malaria, with a particular emphasis on insights from recent genome-wide approaches. The results from these studies implicate common genetic variants in novel molecular pathways involved in human immunity to specific pathogens.

Health assessment of free-ranging three-banded (Tolypeutes matacus) and nine-banded (Dasypus novemcinctus) armadillos in the Gran Chaco, Bolivia.

The Gran Chaco, Bolivia, has a total of seven species of armadillos with the three-banded (Tolypeutes matacus) and nine-banded (Dasypus novemcinctus) the most commonly hunted by the local Isoseño-Guarani people. Armadillos are known carriers of zoonotic pathogens, including Mycobacterium leprae, Toxoplasma gondii, and Trypanosoma cruzi; thus human handling and consumption of these species may have a significant public health impact. A health assessment that included physical examinations, hematology, plasma biochemical analyses, levels of exposure to selected infectious agents, and endoparasite and ectoparasite identification was performed on nine-banded and three-banded armadillos in the Gran Chaco, Bolivia. Based on clinical findings, the general health of these armadillos was rated as good. However, many of the nine-banded armadillos (64%) had abrasions and wounds, probably related to the capture method. The blood value results from a subset of these armadillos are presented as baseline values for free-ranging populations of both these species in Bolivia. Serologic antibody tests for M. leprae were negative in three-banded (n = 8) and nine-banded (n = 2) armadillos. Three-banded armadillos were antibody positive for Eastern equine encephalitis virus (8/8; 100%) and Saint Louis encephalitis virus (5/8; 62.5%). Two of 12 (16.7%) three-banded armadillos tested were antigen positive for Dirofilaria immitis. Nine-banded armadillos were antibody positive for T. gondii (3/9; 33.3%), Eastern equine encephalitis virus (5/8; 62.5%), and T. cruzi (2/9; 22.2%). Two of eight (25%) nine-banded armadillos were antigen positive for D. immitis. A number of endo- and ectoparasites were identified in/on both species of armadillos. Results from this study support the possibility that the handling and consumption of these species by the local Isoseño-Guarani people may have a public health impact.

The impact of treatment with tumour necrosis factor-alpha antagonists on the course of chronic viral infections: a review of the literature.

Biologics that antagonize the biological activity of tumour necrosis factor (TNF)-alpha, namely infliximab, etanercept and adalimumab, are increasingly used for treatment of immune-mediated inflammatory diseases, including psoriasis, worldwide. TNF-alpha antagonists are known to increase the risk of reactivation and infection, particularly of infections with intracellular bacteria such as Mycobacterium tuberculosis. More frequently these agents are given to patients with viral infections. Viral hepatitis and human immunodeficiency virus infections are often present in these patients, with a considerable geographical variation. Other concomitant viral infections such as herpes, cytomegalovirus and varicella zoster virus may occur much more frequently than tuberculosis or leprosy. General recommendations about the management related to possible problems associated with anti-TNF-alpha treatment and these viral infections are lacking. This short review will give an overview of the most recent data available on the effects of anti-TNF-alpha therapy on viral infections with a particular focus on patient management and screening recommendations.

Antiphospholipid antibodies, antiphospholipid syndrome and infections.

Since the association between antiphospholipid antibodies (aPL) and syphilis was first described, many other viral, bacterial and parasitic infections have been shown to induce antiphospholipid antibodies, notably anticardiolipin antibodies (aCL). A review of the literature shows that while aCL occur frequently in viral infections, particularly in HIV (49.75%), HBV (24%) and HCV (20%), it is very rarely associated with anti-beta2 glycoprotein I antibodies (anti-beta2GPI) and is not correlated with thrombosis risk or hematological manifestations of the antiphospholipid syndrome (APS). Concerning bacterial infections, aCL is often present in leprosy (42.7%), where it is frequently associated with the presence of anti-beta2GPI (44.8%), and in syphilis infections (8 to 67%), though without correlation with thrombotic events. Though few individual patients with unequivocal infection-induced aPL satisfy criteria for APS, the lack of statistical association with thrombotic events strongly argues against the identification of a true APS subset in this context. However, physicians should keep in mind the fact that an infection, generally bacterial, in patients with confirmed APS, may lead to catastrophic antiphospholipid syndrome with a possible fatal outcome.

Brevipalpus-transmitted plant virus and virus-like diseases: cytopathology and some recent cases.

An increasing number of diseases transmitted by Brevipalpus mite species (Acari: Tenuipalpidae) is being identified that affect economically important plants such as citrus, coffee, passion fruit, orchids, and several ornamentals. All of these diseases are characterized by localized lesions (chlorotic, green spots, or ringspots) on leaves, stems, and fruits. Virus or virus-like agents are considered to be the causal agents, possibly transmitted in a circulative-propagative manner by Brevipalpus mites. The virus or virus-like particles are short, rod-like, or bacilliform, that induce two characteristic types of cell alteration: (1) 'Nuclear type'--nuclei of parenchyma and epidermal cells in the lesions often contain a large electron lucent inclusion. Short, naked, rod-like (40-50 nm x 100-110 nm) particles may be seen in the viroplasm or nucleoplasm and in the cytoplasm. These particles are commonly arranged perpendicularly on the membranes of the nuclear envelope or endoplasmic reticulum (ER). In a very few instances, they were found to be membrane-bound, within the ER cavities. (2) 'Cytoplasmic type'--short bacilliform particles (60-70 nm x 110-120 nm) are present within the cisternae of the ER and often have electron dense viroplasm of varied shapes present in the cytoplasm. Bacilliform particles may be seen budding into the ER lumen near the viroplasm. These particles resemble those of members of the Rhabdoviridae, but are shorter. The only sequenced virus of this group, orchid fleck virus (OFV), has a negative sense (bipartite) type ssRNA genome, but its organization is similar to known rhabdoviruses, which are monopartite. Both types of cytopathological effects have been found associated with citrus leprosis. In orchids, OFV has a 'nuclear type' of cytopathology, but in some species the 'cytoplasmic type' has been found associated with ringspot symptoms. In Hibiscus and Clerodendron, green spot symptoms have been associated with the cytoplasmic type of cell alteration, while chlorotic spots, in the same species, are associated with the nuclear type. In a few cases, both types of cytopathological effects have been found in the same tissue and cell.

Interleukin-18 (IL-18) and infectious diseases, with special emphasis on diseases induced by intracellular pathogens.

Interleukin-18 (IL-18) is a novel cytokine mainly produced by activated macrophages. IL-18 was originally called interferon-gamma inducing factor, due to its action in inducing IFN-gamma secretion from Th1 cells, NK cells and NKT cells. It has been reported that IL-18 may play important roles in various diseases including cancer and infectious diseases. This review deals with the roles of IL-18 in infectious diseases, with special emphasis on IL-18 in infectious diseases caused by intracellular pathogens including Mycobacterium tuberculosis, Mycobacterium leprae, Listeria monocytogenes and Salmonella typhimurium.

Lichenoid and granulomatous dermatitis.

BACKGROUND: The prototypic lichenoid eruptions, lichen planus (LP), lichenoid drug eruptions, secondary syphilis, and collagen vascular disease, are defined histologically by a band-like lymphocytic infiltrate in close apposition to the epidermis. We describe a novel form of lichenoid dermatitis with a granulomatous component. DESIGN: Skin biopsies from 40 patients demonstrating a band-like lymphocytic infiltrate with concomitant granulomatous inflammation were encountered over 4 years. Clinicians were contacted to elucidate underlying triggers and medical illnesses. RESULTS: A lichenoid dermatitis, a linear eruption, vasculitis, annular erythema, and erythroderma were among the clinical presentations. A drug-based etiology was implicated in 14 cases: the drugs included antibiotics, lipid-lowering agents, anti-inflammatory drugs, antihistamines, hydroxychloroquine sulfate, and angiotensin-converting enzyme inhibitors. Over one-third of patients with drug-related eruptions had other medical illnesses associated with cutaneous granulomatous inflammation, namely rheumatoid arthritis (RA), Crohn's disease, hepatitis C, diabetes mellitus, and thyroiditis. A microbial trigger was implicated in 12 patients in the context of infective id reactions to herpes zoster, Epstein-Barr virus (EBV), or streptococci, or active infections by Mycobacterium tuberculosis, M. leprae, fungi, and spirochetes. The remainder had hepatobiliary disease and RA without obvious exogenous triggers, cutaneous T-cell lymphoma (CTCL), and idiopathic lichenoid eruptions (i.e. LP, lichen nitidus, and lichen striatus). One patient with LP had underlying multicentric reticulohistiocytosis. The histiocytic infiltrate assumed one or more of five light microscopic patterns: (i) superficially disposed loose histiocytic aggregates; (ii) cohesive granulomata within zones of band-like lymphocytic infiltration with or without deeper dermal extension; (iii) a diffuse interstitial pattern; (iv) scattered singly disposed giant cells; and (v) granulomatous vasculitis. Additional features included lymphocytic eccrine hidradenitis in those patients with drug reactions, hepatobiliary disease, and antecedent viral illnesses, tissue eosinophilia and erythrocyte extravasation in drug hypersensitivity, granulomatous vasculitis in patients with microbial triggers, drug hypersensitivity or RA, and lymphoid atypia in lesions of CTCL or drug hypersensitivity. CONCLUSIONS: The cutaneous lichenoid and granulomatous reaction may reflect hepatobiliary disease, endocrinopathy, RA, Crohn's disease, infection, or a drug reaction. One-fifth of cases represent idiopathic lichenoid disorders. Lymphoproliferative disease or pseudolymphomatous drug reactions must be considered in those cases showing lymphoid atypia.

Health in Bihar -- an overview.

PIP: This article presents an overview of the health situation in Bihar for the last 50 years. Although demographic improvements have been noted in the past years, the incidence of various diseases remains high and socioeconomic status low in Bihar. Protein-energy malnutrition, nutritional anemia and blindness are common. Safe drinking water and sanitary facilities are still not available to a large number of people. Furthermore, a number of communicable diseases are prevalent in the country. This is exemplified in the Kala-azar or visceral leishmaniasis epidemic in 1992, which reported 75,523 cases and 1417 deaths. Kala-azar cases have started rising again since 1996, and it is estimated that there might be another epidemic in the first decade of the 21st century if the situation is allowed to continue. Other infectious diseases, which threaten the health situation in Bihar, are malaria, tuberculosis, leprosy, and HIV/AIDS. Moreover, population and decadal growth rate have more than doubled over the last 40 years. Maternal mortality remains very high, but survival chances of children have increased due to immunization and other programs. In general, it was demonstrated that the present health situation in Bihar is a matter of grave concern, and requires an urgent solution.^ieng

Overcoming prejudice.

PIP: People of African descent comprise a large proportion of Brazil's population. While racism exists in the country, it is commonly denied. Most Afro-Brazilians live in poor areas, with poor health care services, sanitation, schools, and transport. Since HIV is linked to poverty, Afro-Brazilians are more affected by HIV than is the overall population. Although Afro-Brazilians contribute to Brazil's culture, they do not benefit from that contribution. Recognizing this considerable social problem, Project Araye was created in 1996 to address issues of race and HIV. Building upon religious and cultural traditions, the project is staffed by Afro-Brazilians who are knowledgeable in both health issues and Afro-Brazilian culture. Project Araye supports a wide range of diverse community leaders in linking sexual health and HIV with other health concerns which affect Afro-Brazilians such as sickle-cell anemia, diabetes, and leprosy. One important challenge has been overcoming the target population's denial of HIV and encouraging Afro-Brazilians to accept that HIV also affects them. Community leaders include religious leaders, rap musicians, artists, and other people respected by various communities. Activities include visits to samba dance schools, Umbanda and Candomble temples, and street youth groups to provide HIV-related information.^ieng