Interview with Dr. Karen Smith

-What needs to be done in the fight against TB to move from a policy of control to one of eradication?

A move to eradication would require a significant increase in resources. Current funding is barely adequate to control TB in many areas. Moving to a policy of eradication would require outreach into communities with the largest numbers of individuals with latent TB infection – particularly communities with recent immigrants from areas of the world with high rates of TB. These communities would need effective education on the reasons for diagnosing and treating LTBI. In addition, medical services for diagnosis and treatment would need to be made available at little to no cost and in very convenient ways, e.g. home delivery of medication.

A second key area which would need to be addressed for a effective eradication policy is global TB. Only by substantially decreasing TB rates around the world are we likely to achieve eradication in the US.

At this point, I don’t think a policy of eradication is even feasible outside of the most developed countries.

-What further resources would be the greatest asset to current TB control efforts? (Money, equipment, personnel, etc?)

The greatest need is political will. Only with persistent political will will it be possible to achieve the sustained commitment to control activities necessary for TB control. This commitment is essential even as rates of TB decline to avoid resurgences such as that seen in the late 1980s and early 1990s in the US.

-Where should monetary resources be coming from? UN and WHO, or from individual governments?

Neither the UN nor WHO have much direct funding available for this kind of activity. Each country’s government must be committed to TB control or all the money in the world will not be effective. The amount of money needed can realistically only come from international aid from the richest countries, such as the US, and organizations like the International Monetary Fund.

-What are drug companies doing to facilitate the global control of TB?

I’m not aware of any significant activities on the part of drug companies in the fight against global TB.

-What is the situation with Hmong refugees in California? Correspondingly, what is the status of tuberculosis in Northern California?

I’m going to refer you to Dr. Jennifer Flood, Chief of the Surveillance and Epidemiology Course, at the state TB Control Branch to answer this question. Dr. Flood will have the latest on this as I’m a bit out of touch. You can reach her at jflood@dhs.ca.gov. Tell her I directed you to her.

2004 TB Fact Sheet

A fact sheet of TB statistics from 2004.

DOTS Success Graphs



Political and NGO Support

Significant sources of monetary funding come from UN and WHO.

The Global Fund to fight AIDS, Tuberculosis, and Malaria
Funding from this organization goes toward global detection programs, treatment of individuals through DOTS, and development of new treatments for MDR-TB.

To see a list of TB control groups The Global Fund donates to, follow the link below:
http://www.theglobalfund.org/search/default.aspx?lang=en&component=Tuberculosis

In total, the Global Fund has dedicated a maximum of $488,232,345.10 to nations across the globe.
However, this money has been spread, for the most part between 10 nations: Bolivia, Dominican Republic, Ecuador, El Salvador, Guyana, Haiti, Honduras, Nicaragua, Panama, and Peru, which receives the most at 20,000,000.

The Stop TB Partnership
The Stop TB Initiative produced the Amsterdam Declaration to Stop TB in March 2000 which demanded action to fight TB from delegations from the 20 countries with the highest burden of TB.
On May 19, 2005, the Stop TB Partnership signed an agreement to increase inter-agency activity and cooperation with the Global Fund to Fight AIDS, Tuberculosis, and Malaria.

Future TB Control Campaigns

Future TB Control Campaigns:

In 1991 the World Health Assembly published targets for global tuberculosis control. At this conference, tuberculosis was recognized as a notable global health problem. In 2002, North and South America saw 370,000 new cases of TB; of these, 53,000 resulted in deaths.

The following table displays the World Health Organization’s goals for world wide TB control in 2005.

WHO Targets for TB in 2005
- 70% Case Detection Rate Both for Infectious Cases & Sputum Smear+
- 85% Success Rate

In 2004, the World Health Organization also released their objectives for TB and various other diseases by the year 2015.

Millenium Development Goals (MDG) 2015
Goal 6:
Combat HIV/AIDS, malaria and other diseases.
Target 8:
Have halted by 2015 and begun to reverse the incidence of malaria and TB.
Indicators
1. Prevalence and death rate associated with TB.
2. Proportion of TB cases detected and cured under DOTS.

Although all countries in Southeast Asia have adopted DOTS and expansion has accelerated over the past 1-2 years, as yet, only 25% (up from only 10% last year) of the population in the region has access to DOTS. This is in spite of the demonstration in all countries that DOTS has more than tripled the treatment success rate from 23% to 77%.

In response to these and similar findings, WHO and other proponents of the DOTS method have prioritized expansion of treatment to rural regions as crucial to effective control campaigns.

25 May 2005 World Health Assembly 58 (LVIII):

The 58th World Health Assembly noted with concern the increasing number of MDR-TB cases worldwide, and the increasing morbidity and mortality in HIV-positive patients, especially in the African Region.
The assembly also expressed anxiety that the Millennium Development Goals mentioned above would not be met due to inconsistent international funding.

In response, the Assembly encouraged each member-state:
To estimate the amount of resources that would be required for TB control and prevention (including MDR-TB), and to subsequently estimate the available domestic and international funding, in order to identify whatever funding gaps might exist.
To establish “STOP TB Partnerships,” committees that would facilitate the expansion of DOTS treatment through agencies already present in the nation.
To ascertain that all citizens were aware of and had access to DOTS.
To strengthen collaboration between TB services and AIDS programs, recognizing their commonalities.
To make tuberculosis control one of their primary health care concerns.

The Assembly also expressed a desire to rewrite the “Millennium Development Goals” to specifically include tuberculosis, rather than listing it with “other diseases.”

Barriers to Tuberculosis Control

There are a plethora of barriers to controlling tuberculosis today. Here are just a few:

Lack of understanding and education about the disease in the areas most impacted by it. (This is in part due to poor literacy and means of educating in under-developed countries.)

Lack of money/income. (Infected patients are unable to afford medication.)

Stigma of tuberculosis. (The disease has stereotypical ties to lower-income populations and HIV.)

Physicians are uneducated generally about TB diagnosis, treatment, or about DOTS (Directly Observed Treatment, Short Course), one of the most effective ways of successfully treating.



TB is not a priority for many health care officials/physicians, or those who wish to work in this area are unable to.

Decentralized information about the disease and its spread does not make it into the right hands.

Also, decentralization means that the process of diagnosis and treatment is not standardized.

Faulty equipment and supplies in developing countries.

Poor infrastructure leading to mishaps and time delays of transportation.

Current health care systems can not support the rapidly rising number of patients with TB that are co-infected with HIV (one of the major causes of this rise).

Lack of partnerships between NGOs, physicians, and governments to treat patients.

Bureaucratic delays in treatment and diagnosis.

Risk of terrorism, coups, civil war, etc. in some developing countries makes treatment difficult and attracting competent doctors even more challenging.

Multi-drug resistant TB expensive and time-consuming to treat.

Lack of sufficient political will and financial backing in certain counties.

Lack of media coverage and public education to alert citizens of potential health threats.

Sub-standard drugs available.

Image courtesy the International Federation of Red Cross @ http://www.ifrc.org/what/health/diseases/tb/images/p6285.jpg.

Epidemiology

How is TB transmitted?

Only those with pulmonary tuberculosis can transmit the disease as it is transmitted with aerosol droplets. The infected person expels these droplets via sneezes, spitting, or coughing. The average untreated patient will transmit TB to twenty others each year. Populations that are particularly at risk include those from areas with infected individuals, especially areas of epidemic or outbreak, those in close contact with patients with active TB (including health care workers and officials), low-income groups, high-risk groups of ethnicities or races, children, people with immuno-suppression, and drug users who inject.

Only those with active cases of TB can pass on the infection and the likelihood of their transmitting the disease is affected by the number of droplets they release, the location in which they were released, the length of time individuals were exposed, and the virulence of their infection.

Pathogenesis

Only about 5% of those infected will immediately develop an active case of tuberculosis; over their lifetimes, another 5% will develop active disease cases. However, if active disease is left untreated, the mortality rate rises to 50%.

How does TB infect the body?

TB bacilli enters to the lungs’ alveoli and infect the macrophages within them. Inside the macrophages, TB mycobacteria divide and move on to the lymph nodes, through the bloodstream, and finally to other tissues and organ structures. In response the body utilizes the T-cells, B-cells, and macrophages to form granulomatous inflammations, which contain the bacteria but do not destroy them.

A TB infection typical fluctuates with periods of cell death and tissue damage followed by period of healing and rebuilding. During the former periods, the disease infiltrates the bronchi with necrotic substances, which are coughed up and continue the infection.

Latent vs. Active

To diagnosis latent infection, the PPD tuberculin skin test is used. This test reveals a response to purified protein derivatives of the Mycobacterium tuberculosis.

Active infection will also appear positive on this test, but must also exhibit other symptoms such as in a chest x-ray.

Tuberculosis Disease

If the TB bacilli overcome the infected person’s immune system, this person will contract TB disease. 5% of the infected population has this occur immediately after infection; 5% more contract the disease later in life. Diabetes, HIV, and other co-infections increase the odds of active disease. HIV-infected individuals have a risk rate of 10% per YEAR as compared to 10% per lifetime of a HIV-free patient. Other factors, such as drug use by injection, recent infection or improper historical treatment of TB, any immuno-suppressing therapy, head/neck cancer, certain types of gastro-intestinal surgery, low body weight, and so forth, increase the risks for individuals. Those with who are Asian and African or descendents of Asians or Africans often are more likely to have lymph node tuberculosis than Caucasians.

Some graphs tracking populations of TB infection









Images courtesy Aeras Global TB Vaccine Foundation @ http://www.aeras.org/tb/epidemiology/ and Population Services International @ http://www.psi.org/our_programs/images/tb2.gif.

Current Treatment of TB

There are treatments for patients with both latent and active TB infections.

LATENT TB INFECTION (LTBI) TREATMENT

This sort of treatment aids public health campaigns in suppressing and eradicating TB by controlling the infection's progression to active disease.

Not all those with possible latent infections are treated. Often those with 5mm of positive tuberculin or with skin tests of 10mm of tuberculin or more are targetted for treatment since they are at high-risk. As well, those in close contact with TB patients, especially children under four and those with weak immune systems should be treated with a course of medication and given another TB skin test ten to twelve weeks after exposure.

Many treatments are available:

INH, or Isoniazid, taken for nine months is 93% effective in treating the disease, reducing the risk of active TB from 10% to approximately 1%. A treatment period of six months, while not as effective, offered a 69% chance of treatment and may be more cost-effective.

Rifamin taken for four months, or pyrazinamide, is no longer considered as effective for latent TB. However, they may be taken if INH is unavailable.


ACTIVE TB TREATMENT

The best treatment in the status quo is a "cocktail" of INH, pyrazinamide, rifampicin, and ethambutol. For a non-drug resistant case, four months of INH and rifampicin after two months of the four-drug combination is typical. Meds are given daily or two-three times a week.

Each of the drugs in the combination has a different function, which is why they are used together. Rifampicin and INH kill the TB bacteria, ethambutol slows bacterial growth, pyrazinamide fights off the bacteria which hide in macrophages, and so forth. If the patient receives one drug, it will act efficiently against the particular bacteria it is good at killing or inhibiting, but in the next months the patient will relapse with bacteria that were not impacted by this drug.

If the cocktail fails to work, streptomycin, capreomycin, cycloserine, new macrolides, quinolones, and protionamide are commonly used.




DOTS AND MONITORING

Patients must be observed on a monthly basis (or more frequently) for symptoms and to see if they are following their course of treatment strictly. This observation should continue until cultures test negatively.

DOTS, or Directly Observed Treatment Short-Course is endorsed by the World Health Organization and means that health officials or workers must directly observe patients injecting their treatment for the first two+ months of their course. This strategy has been approximately 95% effective in treating the disease.

SIDE EFFECTS OF TREATMENT

20-25% of patients should experience some side effects, although only 5% should change drugs because of the severity of these effects. Hepatic injury is the biggest concern as far as side effects go. Effects on the central and peripheral nervous systems have also been observed in treatments using INH (due to lack of vitamin B6). Vitamin B6 supplements are given to counterbalance this depletion.

Image courtesy Centers for Disease Control and Prevention @ http://www.cdc.gov/mmwr/preview/mmwrhtml/figures/r211a1f1.gif.

Biology of TB

Mycobacterium tuberculosis, which causes TB, is a aerobic type of bacteria. Mycobacterium TB divides over a period of 16 to 20 hours, which is considered slow growth; other bacteria usually take minutes to divide. The bacteria morphology is small and shaped like a rod. Mycobacterium TB can exist outside a host for weeks and can thwart mild disinfectants and will grow in its host.



To diagnose the mycobacterium tuberculosis, a slide of it is stained. Known as an "acid-fast bacillis (AFB)," Mycobacterium TB holds a few stains after being exposed to an acidic solution. One of the more common staining techniques employed is the Ziehl-Neelsen treatment in which the AFB mycobacterium TB is stained a bold red color (as seen in the photograph above). The auramine-rhodamine stain technique and fluorescent microscopy are also effective in detecting the mycobacterium.

Biologically speaking, three other kinds of mycobacteria can also lead to TB, including Mycobacterium bovis, africanum, and microti. M. microti does not effect TB in humans, and the other two forms of TB bacteria rarely cause TB. Mycobacterium avium anad kansasii often appear to be tuberculosis but are not.

Image courtesy Wikipedia @ http://upload.wikimedia.org/wikipedia/en/5/56/TB_AFB_smear.jpg.

TB History

Tuberculosis has been around for many, many years. TB in humans appeared with the first domesticated cattle.

4000 BC -- Skeletons this early and on show signs of TB. Mummies found on excavations also have evidence of TB.

460 BC -- Hippocrates identified TB as a deadly and common disease of ancient society.

1820s -- TB finally declared a disease, but is not named TB. (Until then, its symptoms had been interpretted as multiple diseases/infections.)

1839 -- J. L. Schoenlein declared this disease tuberculosis.

1859 -- first sanatorium for TB opens in Poland.

3/24/1882 -- Robert Koch discovers Mycobacterium tuberculosis.

1885 -- first sanatorium opens in US.

1905 -- Koch wins Nobel Prize for his work.

1906- Albert Calmette and Camille Guerin develop BCG, which provided the first sucessful immunization drug for TB.

7/18/1921 -- France uses BCG to immunize country. (Other countries do not until after WW II).

1850 -- Death toll in Europe was 5 per 1,000 cases.

1880s -- TB declared contagious.

19th and early 20th centuries -- Impoverished citizens in large cities are striken with TB. By 1918, France experienced 1/6 of its deaths from TB. Campaigns to reduce the spread of the disease began in Europe/US, with a focus reducing public spitting.


1908 -- 3/4 of those in sanatoria die in five years or less.

1913 -- Medical Research Council formed in Britain, focusing first on TB.

1946 -- The first treatment is developed: streptomycin (antibiotic).

1950 -- Death tool in Europe was 5 per 10,000 cases.

1993 -- WHO declares TB a "global health emergency."

2003 -- Scientists create a more virulent strain of TB by accident (they disabled some genes that gave the strain unique properties).

Status Quo -- A resurgence of the disease has occurred due to multi-drug resistant strains of TB.

Image courtesy the University of Virginia @ http://www.faculty.virginia.edu/blueridgesanatorium/poster_health.jpg.

What is tuberculosis (TB)?

Tuberculosis is an infection caused by Mycobacterium tuberculosis, a form of bacteria. Most frequently, it infects the lungs (pulmonary) but also can impact the circulatory system (miliary), lymphatic system, central nervous system (meningitis), bones, and other organ systems.



Tuberculosis is also known as TB, consumption, white plague, wasting disease, phthisis, scrofula, king's evil, Pott's disease of the spine, etc.

TB infects two billion people (1/3 the world's population) and nine million new cases appear each year. Two million deaths result annually.

Most infected cases are asymptomatic -- about 5% will immediately result in active TB and another 5% will develop TB within their lifetimes. 90% never develop the actual disease. 50% of active cases, if left untreated, will result in death. TB has the 2nd highest mortality rate of all infectious diseases worldwide, after HIV/AIDS and before malaria.

Drug-resistant strains of TB are growing. In 1993, the World Health Organization (WHO) declared TB a global health emergency. A resurgence of TB has been caused mainly by HIV/AIDS (which increases suspectibility), immigration, and the lack of TB control porgrams.

Image courtesy Wikipedia @ http://upload.wikimedia.org/wikipedia/en/4/43/13_TBC.jpg.