Infectious disease immunodeficiency

Viruses are small infectious agents composed of a nucleic acid genome (DNA or RNA) encased by structural proteins and in some cases a lipid envelope. They are the causative agents of a number of human infectious diseases, the most important for public health today being acquired immunodeficiency syndrome (AIDS), hepatitis, influenza, measles, and vituses causing diarrhoea (e.g., rotavirus). In addition, certain viruses contribute to the development of cancer. Antiviral drugs inhibit viral replication by specifically targeting viral enzymes or functions and are used to treat specific virus-associated diseases. 

A variety of other clinically important infections, such as brucellosis, listeriosis, salmonellosis, and various Mycobacterium infections, are of interest as these are often localized in organs rich in MPS cells. Liposome encapsulation has been demonstrated to improve therapeutic indices of several drugs in a number of infectious models. The natural avidity of macrophages for liposomes can also be exploited in the application of the vesicles as carriers of immunomodulators to activate these cells to an microbicidal, antiviral, or tumoricidal state. These studies were recently reviewed by Emmen and Storm (1987), Popescu et al. (1987), and Alving (1988). In addition to the treatment of "old" infectious diseases, the concept of MPS-directed drug delivery is of considerable interest for the therapy AIDS, possibly enabling control of human immunodeficiency virus replication in human macrophages. 

Considerable data is available suggesting thatmild-to-moderate immunosuppression can lead to an increase in infectious disease. The types of infections that occur tend to result from either common pathogens (e.g., causing upper respiratory tract infections) or latent viruses (e.g., herpes cold sores), rather than opportunistic organisms such as Pnuemocyctis carinii. These are usually not life-threatening, except in certain susceptible populations, such as the elderly. Opportunistic infections, in contrast, are more prevalent in individuals where severe forms of immunosuppression are present, such as primary immunodeficiency diseases or HIV/AIDS. 

The major gap in clarifying the shape of the dose-response curve (i.e., between immune response and disease) is a lack of large scale epidemiological studies in populations with mild-to moderate immunodeficiency that have been monitored simultaneously for immune system parameters and clinical disease. Attempts in conducting such studies will be complicated by many non-immune factors which can affect infectious disease incidences. 

Similarly, under certain disease conditions, altered NA innervation and/or AR signaling capacity impairs sympathetic communication with cells of the immune system, influencing disease progression. Altered catecholamine communication with the immune system is evident in autoimmune diseases such as arthritis and multiple sclerosis [5-7] and in infectious diseases, such as leprosy and a mouse model of acquired immunodeficiency syndrome [15, 43, 44], The impact of altered NA innervation of... 

Immune Globulin (IG) IG is a sterile solution containing antibodies from human blood. It is obtained by cold ethanol fractionation of large pools of blood plasma and contains 15-18 percent protein. Intended for intramuscular administration, IG is primarily indicated for routine maintenance of immunity of certain immunodeficient persons and for passive immunity against measles and hepatitis. IG does not transmit hepatitis B virus, human immunodeficiency virus (HIV), or other infectious diseases. 

SCIDGeneTherapy Trial Infantswithsevere combined immunodeficiency disease (SCID, bubble boy syndrome) have a gene defect that leads to a complete lack of white blood cells. Without treatment, these infants die from comphcations of infectious diseases during the first few years of life. The only treatment currently approved for this condition is a bone marrow transplant. 

Kaplan, J.E., Hanson, D., Dworkin, M.S., Frederick, T., Bertolli, J., Lindegren, M.L., Holmberg, S. and Jones, J.L. (2000) Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clinical Infectious Diseases, 30, S5—S14. 

Immunostimulants are potentially of benefit in immunodeficiency disorders such as acquired immunodeficiency syndrome (AIDS), in chronic infectious diseases, and in some selected malignancies, especially those that involve the lymphatic system. 

Of course the corollary of preventing infectious disease is the treatment of chronic infection, and this may be where CpG ODN holds the most promise, with respect to infectious disease. There are populations throughout the world that are chronically infected with, and act as biological reservoirs for, intracellular pathogens, such as the hepatitis B and C viruses, the human immunodeficiency virus, Mycobacterium... 

The infectious killer disease, tuberculosis (TB), is the leading cause of death worldwide from a single human pathogen, claiming more adult lives than diseases such as acquired immunodeficiency syndrome (AIDS), malaria, diarrhea, leprosy, and all other tropical diseases combined. The organism usually responsible, the tubercle bacillus, Mycobacterium tuberculosis (MT), was discovered by Robert Koch in 1882. However, M. bovis, which infects cattle, may also infect humans, and M. africanum is a cause of TB in West Africa. Furthermore, a number of normally nonpathogenic mycobacteria, especially M. avium, M. intracellulare, and M. scrofulaceum, cause opportunistic infectious disease in patients with AIDS. Pulmonary TB, the most common type of the disease, is usually acquired by inhalation of the bacillus from an infectious patient and causes irreversible lung destruction (Newton et al., 2000). 

Babu, P. G., Saraswathi, N. K., Vaidyanathan, H., and John, T. J. (1993). Reduction of the cost of testing for antibody to human immunodeficiency virus, without losing sensitivity, by pooling sera. Indian Journal of Medical Research Section A-Infectious Diseases, 97, 1-3. 

The value of spotting the unusual has been demonstrated by a number of infectious disease outbreaks in the United States. A classic example is the initial reports of the human immunodeficiency virus epidemic. Alert clinicians in California and New York City noted clusters of rare illnesses, Kaposi s sarcoma and Pneumocystis carinii pneumonia, among homosexual male clients in their practices (CDC, 1981a, 1981b). In May 1993, a New Mexico medical examiner reported two deaths from acute respiratory failure 5 days apart (CDC, 1993). 

SCID severe combined immunodeficiency, a genetic disorder in which both arms (B cells and T cells) of the adaptive immune system are crippled. This disease is fatal if untreated due to extreme susceptibility to infectious diseases. 

Originally, the Committee on Infectious Diseases of the American Academy of Pediatrics and the Advisory Committee on Immunization Practices (ACIP) recommended that severely immunocompromised patients with HIV infection should not receive measles vaccine (139). However, in 1988, recognizing the severity of measles in immunodeficient individuals, it revised its measles immunization guidelines and recommended that... 

WofsyCB. Use oftrimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonitis in patients with acquired immunodeficiency syndrome. Reviews of infectious diseases. 1987 Mar-Apr 9 SuppI 2 S184-94. 

A growing application of the strip type of technology for immunoassay is for infectious disease testing and the rapid detection of various infectious antigens and antibodies including Chlamydia,group A streptococci, " Helicobacter pylori, ° infectious mononucleosis, and human immunodeficiency virus. These tests commonly use a lateral-flow format for urine, serum, plasma, or whole blood samples in conjunction with analytical techniques, such as enzyme immunoassay and immunochromatography. An alternative... 

---