Drug Resistant Tuberculosis

Drug Resistant Tuberculosis

What is Tuberculosis?
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB). Tuberculosis generally affects the lungs, but can also affect other parts of the body. Most infections do not have symptoms, in which case it is known as latent tuberculosis. About 10% of latent infections progress to active disease which, if left untreated, kills about half of those infected.

Tuberculosis is one of the top ten disease that leading cause death worldwide. 

There are nearly two millions people died every year.

        1. TB discoveries

24^th March 1882 (Robert Koch) is the person who is discovery TB by using staining technique that identified Tuberculosis bacillus and he could make definite diagnosis made possible 1890. 

Robert Koch was also discovered Tuberculin skin Test that is the popular diagnostic which is used when injected into skin. 

In 1895 Roentgen was discovery of X-rays and he could make early diagnosis of pulmonary disease. 

                                                      Robert Koch (1843-1910)

2. Pharmacological discoveries

a.       In 1956-1960 they could find the combination therapy of Isoianzid and Pyrazinamid cures TB

b.      In 1955 Cycloserine

c.       In 1962 Ethambutol

d.      In 1963 Rifampicin

e.      In 1970-1977 Combination of Rifampicin and Isoniazid adopted as International regime for treatment of TB

     3.   Introduction

Tuberculosis is a common infectious disease of human beings, mainly caused by Mycobacterium tuberculosis MTB.

Drug resistant tuberculosis (DR-TB) is a major public health problem in developing countries such as Asia, China.

    4.  Epidemiology

Globally, 3.7% of the newly diagnosed and 20% of the previously treated cases for TB were estimated to have MDR-TB in 2012.

The highest level of MDR-TB are found in Central Asia and Eastern

Europe where in certain countries more than 50% of previously treated and more than 20% of new TB cases have MDR-TB.

Almost 60% of MDR-TB in newly diagnosed cases have been reported from China, Russian Federation and India.

5.    Signs and symptoms

      Tuberculosis may infect any part of the body, but most commonly occurs in the lungs (known as pulmonary tuberculosis)

General signs and symptoms include fever, chill, night sweat, loss appetite, weight loss and fatigue.

6.  Global status 2015

7.       Multi drug resistant

What is Multi drug Resistant (MDR-TB)?

MDR-TB caused by strains of Mycobacterium Tuberculosis resistant both Rifampicin and Isoniazid with or without resistance to other drugs.

Single Isoniazid or Rifampicin resistance is not MDR - TB

8.       Classification of Drugs

3 Groups depending upon the degree of effectiveness and potential side effects

1. First Line: (Primary agents)

                                                               i.      are the most effective and have lowest toxicity.  Isoniazid Rifampin

2. Second Line:

                                                               i.      Less effective and more toxic effects

                                                             ii.      include (in no particular order):  p-amino salicylic acid, Streptomycin, Ethambutol

3. Third Line

                                                               i.      are least effective and most toxic.  Amikacin, Kanamycin, Capreomycin, Viomycin, Kanamycin, Cycloserine

        9. Extensive Multi Drug Resistance (XDR)

What is extensively drug resistant tuberculosis (XDR TB)?

Extensively drug resistant TB (XDR TB) is a relatively rare type of MDR TB. XDR TB is defined as TB which is resistant to isoniazid and rifampin, plus resistant to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).

10.Factors Contributing to Development  and Spread of MDR and XDR TB

Weak TB programs (DOTS)  

§  Low completion/cure rates

§  Lack of treatment follow up and patient support

§  Unreliable drug supply

§  Diagnostic delay

           Absent or inadequate infection control measures

          Uncontrolled use of 2^nd line drugs 

          Or Fluroquinolones resistance

         11. Transmission of X –MDR

Like other forms of TB, XDR-TB is spread through the air. When a person with infectious TB coughs, sneezes, talks or spits, they propel Mycobacterium  into the air. 

12. Best options to diagnose X-MDR tuberculosis

To evaluate drug susceptibility, the bacteria need to be cultivated and tested in a suitable laboratory. Final diagnosis in this way for TB, and especially for XDR-TB, may take from 6 to 16 weeks To reduce the time needed for diagnosis, new tools for rapid TB diagnosis are urgently needed. 

13. When to suspect MDR TB ?

Patients not showing any reduction in bacillary population after 3-months of regular treatment with Cat II regimen

Sputum positive patients who are contacts of a known MDR TB patient.

14. How to evaluate MDR TB ?

MDR TB is only a laboratory proved HR resistance. Clinical suspicion should be followed by lab. Confirmation. Laboratories should be quality controlled.

15. Extreme Drug resistant Tuberculosis (XDR-TB) and AIDS

It can also be contracted without a patient receiving any previous treatment for TB

Mostly associated with HIV positive patients

HIV has the potential to fast tracking XDR-TB into an uncontrollable epidemic

Average survival period for patients infected with XDR-TB is 16 days.

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Leptospirosis

Leptospirosis
DEFINITION
• Leptospirosis is a bacterial disease that affects humans and animals. It is caused by bacteria of the genus Leptospira. In humans, it can cause a wide range of symptoms, some of which may be mistaken for other diseases. Some infected persons, however, may have no symptoms at all.

• Leptospirosis is caused by infection with pathogenic spirochetes of the genus Leptospira.

EPIDEMIOLOGY
• Leptospirosis is a zoonosis of global distribution. It happened in mostly in raining seasons.
• It causes approximately 1.03 million cases per year. In 2015, South-East Asia is the highest incidence of leptospirosis about  55.54 cases per 100,00 population. In Thailand, the incidence rate is 39.04 % and 37.48 in the South and the Northeast, respectively.

• Leptospirosis is maintained in nature by chronic renal infection of carrier animals, especially rodents.
• Infections typically occur following occupational or recreational exposure to water or soil contaminated with rodent urine.
• In developing countries with poor housing standards, leptospirosis outbreaks occur regularly in urban settings a er heavy rainfall and flooding.
 
MICROBIOLOGY

• Twenty-one named leptospiral species have been described, of which 11 are known to be pathogenic.
• Genus Leptospira, order Spirochetales, family leptospiraceae
• There are about 250 servars from 20 species causes diseases and animals.

 
Leptospirosis that looked in the Dark field Microscopic

Leptospirosis Transmission Cycle and Risk factors

DIAGNOSIS
• Clinical diagnosis requires a high index of suspicion based on epidemiological exposure.
• Serologic tests are helpful when positive but may have poor sensitivity during the first week of illness.
• The signs and symptoms of early leptospirosis are nonspecific such as muscle pain, fever, headache....etc.

THERAPY
• Antibiotic therapy should be initiated as early in the course of the disease as suspicion allows.
For mild disease, doxycycline, amoxicillin, or oral ampicillin is recommended. For more severe disease, intravenous cetriaxone, ampicillin, or penicillin is used.
• Patients with early renal disease with high-output renal dysfunction and hypokalemia should receive aggressive volume repletion and potassium supplementation.
• Patients who progress to oliguric renal failure should undergo rapid initiation of hemodialy- sis or peritoneal dialysis, which is typically required on only a short-term basis.


PREVENTION
• most effective preventive strategy is to reduce direct contact with potentially infected animals and indirect contact with urine-contaminated soil and water.
• Chemoprophylaxis with doxycycline 200 mg once a week is recommended for individuals who will be unavoidably exposed to endemic environments.

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