HUMAN TUBERCULOSIS
Globally, tuberculosis (TB) causes more human deaths than any other single infectious disease, with approximately 95% of cases and 98% of deaths occurring in the developing world. It is estimated that over 2 billion people are infected with the M. tuberculosis bacterium, which is equal to one-third of the world’s population. TB is a chronic bacterial infection that is spread in humans through the air and usually infects the lungs, although other organs are sometimes involved. Most persons who are infected with TB are asymptomatic (i.e., latent TB), with a relatively small percentage subsequently developing symptoms of the disease – i.e., active TB. The World Health Organization (WHO) estimates that each year another 8 million people worldwide will develop active TB. Mortality is estimated at 3 million annually.
M. tuberculosis is the primary etiologic agent of TB in humans. In addition to humans, a broad range of animal species are susceptible to TB, usually resultant from infection with M. bovis. Though more rarely isolated in humans, the bacterium M. bovis is responsible for tuberculosis in domestic ungulates (e.g., cattle, goats, sheep, etc.) as well as wild animals (e.g., deer, elk, badgers, possums) and captive exotic animals (e.g., elephants, giraffes, and camels, among others). Humans infected with M. bovis who subsequently go on to develop TB exhibit clinical symptoms indistinguishable from M. tuberculosis-infected TB, the pathogeneses of which are identical. While animal-to-human M. bovis infection is well documented, evidence of human-to-human transmission of M. bovis is limited and largely anecdotal. In infected populations, M. bovis shows a high degree of virulence for both humans and animals.
The WHO estimates that human TB morbidity and mortality for the 1990’s was 88 million and 30 million, respectively, with similar predictions for the current decade unless policies and practices in detection and treatment are dramatically altered. Most cases of TB occur in developing countries, 22 of which (mostly in Southeast Asia and Africa) have been designated “high prevalence endemic countries”.
The economic effects of TB are devastating, both for individuals and communities. The disease tends to strike individuals in their most productive years of 15-50. The adverse financial impact due to the potential loss of family income coupled with the expense of transportation to get to often distant health facilities for treatment and the cost of administering and monitoring TB for 6-9 months of daily therapy (i.e., DOTS) all conspire against both the macro-economy (i.e., society as a whole) as well as the micro-economy (i.e., family or individual) of those developing countries least able to afford it. Yet with the right treatment TB can be cured for less than US$20 per patient. The worldwide annual cost of TB control is estimated to be $4 Billion.
As a highly contagious, air-borne disease, transmission of TB usually results from close or casual contact with infected persons. When an infected person sneezes, coughs, spits, or talks they disseminate TB microorganisms that can be inhaled. Once introduced into the lungs, TB is able to avoid being destroyed by the body’s macrophages or granulomas – specialized cells of the immune system that destroy many bacteria, viruses, and other foreign bodies. As a result, the bacteria are able to spread throughout the newly infected person’s body, multiply, survive, and remain dormant for years. This stage of TB is called Latent TB. Active TB occurs when the bacteria infiltrate organ systems, the most common being the lungs (pulmonary TB). Clinical symptoms of TB include severe coughing, chest pain, blood in the sputum, acute weight loss, fever, and chronic fatigue.
TB and HIV interact perniciously, especially in sub-Saharan Africa where in some countries it is estimated that more than 50% of the population is infected with HIV. Because HIV weakens the body’s immune system, persons with latent TB who are also HIV reactive are at significantly greater risk of converting to active TB than their HIV nonreactive counterparts. In these areas of the world, TB has become the leading cause of death among people with HIV/AIDS.
Despite the importance of TB as a global public health problem, diagnosis and treatment of the disease, while effective, still relies on highly inaccurate diagnostic procedures that are more than 100 years old. Currently, a diagnosis of TB most often relies on Acid Fast Bacillus (AFB) smear technology from multiple sputum samples, developed by Robert Koch in 1882. However, this test may not detect as many as 50% of TB cases. Use of culture technology is slow (taking 3-4 weeks or longer) and not readily available in large areas of the developing world. Additionally, its cost is generally prohibitive in most cases. Reliance on X-Ray technology is highly insensitive as the technology can’t differentiate TB from Cancer or other pneumonias. Newer technologies are on the horizon, but they are both technologically demanding and expensive.
Alternative technologies that may supplement smear screening and increase the overall detection rate of TB include serological tests. CHEMBIO Diagnostic Systems, Inc. is developing such an assay that is rapid, easy to use, doesn’t require sophisticated equipment (can be used by most technicians in remote rural clinic settings), and augments the accuracy of more traditional test strategies.
HUMAN TB Resources:
International Union Against Tuberculosis and Lung Disease (IUATLD) - www.worldlunghealth.org
Foundation for Innovative New Diagnostics (FIND) - www.finddiagnostics.org
Global Health Strategies - www.ghstrat.com
Stop TB Partnership - www.stoptb.org
TB Education & Training Resources a service of the Center for Disease Control (CDC) and Prevention, Division of TB Elimination (DTBE) - www.findtbresources.org
World Health Organization’s TB Specimen Bank - www.who.int/tdr/disease/tb
Free Encyclopedia on Tuberculosis - www.en.wikipedia.org/wiki/Tuberculosis
VETERINARY TUBERCULOSIS
Humans can and do get infected with TB from animals, a type of trans-species communication known as zoonosis. In the case of TB, this zoonotic disease process is caused by the bacterium M. bovis, a member of the M. tuberculosis complex group. The incidence of TB zoonosis shows considerable regional variation depending on the presence and extent of the disease in the animal population, social and economic variables, standards of food hygiene, and the effective implementation of farm management preventative measures. In general, the infection of M. bovis in humans is higher in rural areas where there are higher rates of infected herd animals. The transmission of bovine TB from cattle to humans was substantially reduced in the 1930’s after the introduction of pasteurization of milk. Today, it is believed that the relatively low report rate of M. bovis associated with human TB is due in part to the failure of laboratories to distinguish between M. tuberculosis and M. bovis, and to social reluctance to report positive cases.TB in animal species is generally referred to as “Bovine TB” secondary to the prevalence of the disease in cattle. Bovine TB has affected animal and human health since ancient times, manifesting in lesions of the lung, bone, and other body parts. Although visible symptoms are highly species specific, the disease frequently presents as weight loss and general debilitation, and can be fatal. In highly developed areas of the world (i.e., North America, Australia, New Zealand, Japan, and Western Europe) TB elimination programs have been vigorously instituted into herd populations based on the test and slaughter method, with substantial success. Elsewhere in the world, the disease is widespread and its prevalence and associated risks to public health are closely linked to relative levels of economic development and the practicalities of implementing control measures for infected herd populations.
M. bovis bacteria are frequently excreted by infected animals via exhaled air, sputa discharge, feces, milk, urine, and vaginal and uterine discharges, as well as from peripheral lymph nodes. Housing (in contrast to free-range) and zero-grazing may predispose animals to the disease. For example, the highest incidence of bovine TB is routinely observed where intensive dairy production is most common, notably in the milk sheds. Transmission of bovine TB can also occur through animal contact with infected environmental sources such as soil and water.
Many TB-infected free-range wildlife populations may be visibly asymptomatic, showing no obvious clinical symptoms even when lesions are well developed, thus making timely detection problematic. In addition, even though seemingly asymptomatic, these animals are highly contagious. No practical treatment or preventive measures exist for free-ranging wildlife other than relatively ineffective cull practices, while sylvatic reservoir hosts often complicate domestic herd eradication efforts – for example, the ongoing challenges within the United Kingdom concerning TB management in cattle and badger populations.
Numerous methods are available for the detection of animals infected with TB. To date, skin testing remains the only “reliable” test to detect bovine TB. Among these, the CFT (Caudal-Fold Tuberculin Test) is often used as a frontline skin screening TB test. An accredited veterinarian is generally required to perform and read such skin tests. A positive response to the CFT test indicates that the animal has mounted an immune response capable of recognizing M. bovis. The test hasn’t shown to be as specific or sensitive when used on other animal species aside from Bovids, whether free-range or exotic. Skin testing often produces high rates of both false positive and negative results, particularly when the species tested is not bovid. Exposure to other closely related mycobacteria – such as M. avium (avian tuberculosis) and M. paratuberculosis (Johne’s disease) – represent two examples of other mycobacterium species that can yield a false positive CFT test. A false negative CFT response can occur in an animal that is infected with bovine TB but is also co-morbidly infected with another disease that prevents a proper immune response, is in the very early stages of the disease, or in the event of problematic test administration. It is estimated that the false negative rate of the CFT test may be as high as 15%. In other species, the tuberculin skin test is so unreliable that alternative tests are required in order to confirm TB infection
TB due to either M. tuberculosis or M. bovis has gained increasing recognition as a serious emerging disease of multiple zoo and other exotic wildlife species, as well as in captive wildlife herds (e.g., Cervid species). Tuberculin skin testing has proven to be unreliable or ineffective for most of these species, necessitating reliance on other diagnostic procedures such as the culturing of trunk washings in elephants, which in turn are proving to be similarly insensitive and nonspecific.
Serological assays have shown promise as a diagnostic alternative to skin testing or culture testing for many of these species. Serological blood based TB assays are appealing not only due to better sensitivity and specificity for captive wildlife, exotic zoo species, and other non-traditional livestock, but also because they require only a single handling event, thereby minimizing capture-associated injuries. The serological test concept is simple, rapid, easy to interpret, inexpensive, and is very useful as a slaughter surveillance test or an effective and efficient trap and cull assay.
Chembio Diagnostic Systems, Inc. has developed a family of novel lateral-flow serological tests for TB for non-human primates (PrimaTB STAT-PAK®), white tail deer, reindeer, and elk (CervidTB STAT-PAK®), cattle (BovidTB STAT-PAK®), badgers (BrockTB STAT-PAK®), camels, llamas, and alpacas (CamelidTB STAT-PAK®) and exotic species such as elephants (ElephantTB STAT-PAK®). These tests are all antibody detection assays that employ unique cocktails of carefully selected recombinant antigens of M. bovis and M. tuberculosis. The tests can use serum, plasma, or whole blood samples and yield a result positive or negative result within 20 minutes.
Veterinary TB Resources:
Elephant Care International (www.elephantcare.org)
Elephant News (www.elephant-news.com)
Michigan Department of Natural Resources (www.michigan.gov/dnr)
Ontario Ministry of Agriculture, Food and Rural Affairs (www.omafra.gov.on.ca)
United States Animal Health Association (www.usaha.org)
United States Department of Agriculture Animal and Plant Health Inspection Service (www.aphis.usda.gov)
Veterinary Association (www.worldvet.org)
World Organization for Animal Health (www.oie.int)
World Animal Health & Nutrition News (www.animalpharmnews.com)
|
|
