Tuberculosis

PROBLEM

The magnitude of the global tuberculosis problem is enormous and TB has become the leading cause of adult death due to an infectious disease. The global impact of TB also affects the United States as >40% of all US TB cases occur among foreign-born individuals. Tuberculosis is now widespread in Eastern Europe and the former Soviet Union republics. Tuberculosis has emerged as a major public health problem in the Republic of Georgia, which appears to have among the highest rates of tuberculosis among former Soviet republics and on par with rates seen in some developing countries in Asia and Africa. Preliminary results from ongoing collaborative projects between Emory University (Henry M. Blumberg, M.D.) and the Georgia National TB Program (George Khechinashvili, MD, PhD) suggest that high rates of drug resistant tuberculosis including multidrug TB appear to be emerging in Georgia as has been reported for Russia and other former Soviet Union countries. Transmission of TB including multidrug resistant TB is also a major problem in Georgian prisons. There is a great need to improve the public health infrastructure, which would lead to a more effective TB control program in Georgia.

The U.S. (NIH)-Georgia Conference on HIV/AIDS, emerging infectious diseases and immunodeficiencies held in Tbilisi in May 1998 concluded tuberculosis is the highest priority health threat to Georgia today and should be the first priority for public health and research efforts. The rate of TB in Georgia is very high and similar to that found in some developing countries in Asia and Africa. The period prevalence (total
combined rate) of TB in Georgia in 1997 was approximately 200 cases per 100,000 population; 24.3% of cases identified are extrapulmonary. TB cases are also quite high among children including infants. With the breakup of the Soviet Union and the social/economic upheavals in Georgia, the infrastructure for TB control collapsed. The Georgian National TB Program (NTP) was established in 1995. An effective surveillance system has been established and cases are now reported to the NTP from throughout the country. In 1997, there were a total of 8,019 active TB cases in Georgia (including 5,138 newly diagnosed cases). These figures do not include TB cases in the prison system where it is estimated there are as many as 2000 active cases for a total of more than 10,000 active cases in Georgia in 1997.

Previously, the rate of drug resistant tuberculosis in Georgia has not been well defined due to the lack of capability of performing TB cultures in the past. Preliminary data from an ongoing project supported by a small grant from the CRDF suggests that there are high rates of drug resistant TB among newly diagnosed patients in Georgia. Data from susceptibility testing of 70 Mycobacterium tuberculosis isolates recovered from newly diagnosed patients in Tblisi indicates an overall rate of drug resistance of 45% including a 13% rate of multidrug resistant TB (MDR-TB) [from presentation at IUATLD Meeting referenced above].

Rates of MDR-TB among civilians appear to be as high as that reported by the ICRC for those with TB in Georgian prisons. This high rate of MDR-TB in Georgia is similar to the rate of MDR-TB reported by CDC for the Ivanovo Oblast in Russia in 1998. MDR-TB is associated with a high mortality and morbidity and indicates the need for the implementation of effective TB control efforts to prevent further development of drug resistance. High rates of MDR-TB will also greatly affect TB control strategies and the outcome of treatment.

In general, laboratory support has been limited and smear microscopy is often of poor or low quality in many locations; frequently patients have been diagnosed on clinical grounds only without laboratory confirmation of disease. In 1995 only about 5% of patients with pulmonary TB were smear positive; this increased to 20% in 1998 but still remains relatively low. This is due to a number of factors including lack of resources, outdated equipment, staff training and excessive number of laboratories and need for further training of physicians about diagnosis of disease. TB cultures and susceptibility testing have only generally not been available. Quality control measures in laboratories have been limited and at nearly all the laboratories (with the exception of the National Tuberculosis Program laboratory) safety equipment is not available (e.g., biological safety hood). At most laboratories, specimens are processed in an open room.

The Georgian National TB Program is collaborating with WHO and other international agencies but additional resources are needed in Georgia to establish an effective TB control program there. Currently, directly observed therapy, short course (DOTS program) is generally not available in Georgia. Laboratory support with the exception of the National Tuberculosis Laboratory/National Center for Tuberculosis and Lung Disease laboratory is often poor and there is a great need for additional training and education of laboratory, physician and nursing staff on the WHO recommended strategy (including DOTs). Given the apparent high rates of MDR-TB, it is essential that DOTS become establish. Once a DOTS program is well established, consideration of DOTS-Plus will be needed given the high rates of drug resistant TB.


(This information is taken from material prepared by Dr. Henry Blumberg, Associate Professor of Medicine [Infectious Diseases], Emory University School of Medicine.)


ACCOMPLISHMENTS

Partnership achievements and milestones:

Technical Consultation: Henry M. Blumberg, M.D., [Associate Professor of Medicine (Division of Infectious Diseases, Emory University School of Medicine and Hospital Epidemiologist, Grady Memorial Hospital)] was invited by the U.S. Agency for International Development (USAID) and CDC to provide technical consultation about ongoing TB activities in the Republic of Georgia and by the Emory-Atlanta-Tbilisi Health Partnership to identify areas of possible collaboration and cooperation. The visit was from August 7 through August 16, 1996. A report was provided to USAID and CDC upon return that outlined my findings and recommendations.

Presented a talk in Tbilisi entitled, The New Tuberculosis: Clinical and Molecular Epidemiology on August 8th, 1996 at the "Public Health Today: Vision of Tomorrow, A Conference on Public Health Surveillance Information Systems" which was sponsored by the Ministry of Health Republic of Georgia, USAID, and the U.S. Centers for Disease Control and Prevention (CDC).

Participation in the U.S./NIH--Georgian Joint Symposium: Research Opportunities in HIV/AIDS, Emerging Infectious Diseases and Immunodeficiencies. This conference was held in Tbilisi during the week of May 11th, 1998. Carlos del Rio, MD and Henry M. Blumberg, MD from Emory University attended the conference. There was a symposium session on TB; both Drs. Khechinashvili and Blumberg were invited to make presentations at this session. There was a second break out session on TB
that was moderated by Dr. Blumberg and presentations on tuberculosis were given by Georgian physicians and scientists.

Conclusions of the conference included a statement that tuberculosis is the highest priority health threat to Georgia today and should be the first priority for public health and research efforts. [See conference report].


GRANTS

Collaborative effort between the National Tuberculosis Program/National Center for Tuberculosis and Lung Disease in the Republic of Georgia and the Division of Infectious Diseases, Emory University School of Medicine

U.S. Civilian Research and Development Foundation (CRDF) for the Independent States of the Former Soviet Union. The project was entitled 'Clinical and Molecular Epidemiology of Tuberculosis in the
Republic of Georgia' 10/97-9/99 ($35,000).

U.S. Civilian Research and Development Foundation (CRDF) for the Independent States of the Former Soviet Union. Clinical and Molecular Epidemiology of Drug Resistant Tuberculosis in the Republic of Georgia. 7/00-12/01 ($57,000)

U.S. Department of Health and Human Services (DHHS) BTEP-ISTC Program. Clinical and Molecular Epidemiology of Multidrug Resistant Tuberculosis in the Republic of Georgia. 2001- 2004 ($308,000). [Collaboration between the Georgian National Center for Disease Control, the Georgian National TB Program/National Center for Tuberculosis and Lung Disease and Emory University and the US Centers for Disease Control and Prevention (CDC)]


Goals of the ongoing research projects include:

1. To conduct a drug susceptibility survey to determine the rates of drug resistance among patients with active tuberculosis in Tbilisi, Republic of Georgia. Drug susceptibility information will be of great use to TB control programs and in implementing effective control programs.

2. To study the clinical and molecular epidemiology of drug susceptible and drug resistant tuberculosis in the Republic of Georgia. Assess transmission dynamics of M. tuberculosis in the Republic of Georgia.

3. To evaluate the proportion of patients with tuberculosis disease who are co-infected with the human immunodeficiency virus (HIV) and Hepatitis C Virus (HCV) infection. This objective is being carried out in collaboration with the Georgian AIDS Clinical Center and Dr. Carlos del Rio of Emory University.

The above collaborations are helping efforts to improve the public health infrastructure and TB laboratory capabilities of Georgia.


MEDICAL STUDENT RESEARCH PROJECTS

Over the past 4 years, a number of Emory University School of Medicine medical students have traveled to the Republic of Georgia to carry out research projects as part of ongoing collaborations between Emory University and the Georgian National Tuberculosis Program/National Center for Tuberculosis and Lung Disease

April 1997. Andrew Trickey, a 4th year medical student at Emory conducted a project in collaboration with Drs. Khechinahsvili and Khulordava of the Georgian National TB Institute. A. Trickey spent one month in Tbilisi working at the TB Institute in April 1997. He assessed the amount of HIV co-infection among TB patients hospitalized at the TB Institute using a rapid and effective HIV test (Capillus). None of the 100 patients evaluated by HIV serological testing were HIV seropositive.

July 1998. Ana Markovic and Brent Kinder, rising 3rd year medical students
at Emory spent about one month in Tbilisi in July 1998. In collaboration with the National TB Program and with local Georgian medical students they carried out a tuberculin skin test screening survey among different types of health care workers (workers at TB institute, at the infectious disease institute, medical students and individuals from the community). PPDs were placed on more than 300 individuals at 5 different sites in Tbilisi. [See abstract above]

July-September 1999. Olwen Hahn and Michael Wittkamp, rising 3rd year medical students at Emory, and David Weinstock, M.D., a 3rd year resident in the Department of Medicine carried out a project to assess rates of tuberculosis infection and disease among internally displaced persons in Georgia. This work has recently been published in the International Journal of Tuberculosis and Lung Disease [see reference above, Weinstock et al].

July 2000. Jason Baker, a rising 3rd year medical student worked on a project to assess rates of HIV and hepatitis C virus (HCV) co-infection among patients with tuberculosis in the Republic of Georgia. [See abstract above, to be presented in March 2001 at the American Federation for Medical Research-Southern Section Meeting]

The greatest needs of the TB program include:

Implementation of DOTs in Georgia

Continuing to improve the TB laboratory infrastructure, especially at sites other than the National Tuberculosis Program Laboratory

Training and education to support the first two initiatives.

FUNDING


American International Health Alliance

Grants totaling $385,000, for tuberculosis and AIDS from the NIH and Civilian Research and Development Foundation (CRDF).

A three year partnership grant ($306,000) to study the clinical and molecular epidemiology of drug resistant tuberculosis in the Republic of Georgia and the Caucuses has been awarded recently from the U.S. State Department Biotechnology Engagement Program (BTEP)-International Science and Technology Center (ISTC) partner project program.

MORE INFORMATION

Henry M. Blumberg <hblumbe@emoryu1.cc.emory.edu>

Gia Khechinashvili <tbinst@access.sanet.ge>

Report of Technical Consultation Regarding Tuberculosis Prevention and Control Activities in the Republic of Georgia; 1996 trip. By Henry M. Blumberg MD, Assistant Professor of Medicine, Division of Infectious Diseases, Emory University School of Medicine. [PDF format]

LINKS

National Center of TB and Lung Diseases
[http://nt1.nilc.org.ge/nilc/web-pages/tb.htm]

Division of Infectious Diseases, Emory University School of Medicine
[http://www.emory.edu/ID/]

United States Civilian Research and Development Foundation
[ http://www.crdf.aa.psiweb.com/Welcome.html]

 

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