Mycobacterium kansasii infection

 

Mycobacterium kansasii infection

PKGhatak,MD

Mycobacterium kansasii is a harmless mycobacterium for healthy people. It is a different picture for people with long standing chronic lung diseases like cystic fibrosis, alpha1 antitrypsin deficiency and immune depressed people because of HIV infection, autoimmune diseases, or under medical treatment for cancer, etc.

Mycobacterium kasasii (M.kansasii) belongs to a group of mycobacteria known as NMB (non-mycobacteria tuberculosis) which is distinct from MTB responsible for Pulmonary tuberculosis.

Mycobacterium kansasii.

M.kanasasii are acid fast, slow growing NMB. The colony produces an orange colored smooth colony when grown on solid media and exposed to light. In the dark, the colony is colorless and rough. It tests negative for niacin and positive for catalase and has other similar biochemical features of NTBs. M.kansasii unlike other NTM is not universally present in soil and water, and colonization of the respiratory tract in healthy adults is a rare event. In addition to infection of the lungs, M.kansasii also infects vertebrae, bone marrow, spleen, liver, muscles and skin.

In the USA the incidences of new cases of M.kansasii are increasing as the mycobacteria tuberculosis infections are declining.

Texas recorded the most new cases of M.kansaii followed by Louisiana and Florida. As the name implies M.kansasii is prevalent in Kansas and also seen in the adjoining mid central states. White populations are more susceptible to M.kanasasii infection.

Globally - the miners in South Africa have high rates of new infections, and also in Wales, UK.

Two groups are commonly infected -adults with underlying conditions and children between 4 and 6 yr old along with young adults.

Pulmonary diseases due to M.kansasii.

Three distinct clinical presentations are recognized.1. Cavitary pulmonary tuberculosis, 2. Nodular bronchiectasis, 3. Disseminated infection.

The incidence of hemoptysis is 30%, weight loss is about 50%, and chest pain is seen in 25% of cases. Other symptoms like cough, production of sputum, fever, etc. have no specificity to this infection. Children and young adults present with cervical adenopathy in addition to pulmonary infections.

X-ray features. A single or multiple thin walled cavities in the apical portion of the lungs and hilar lymph node enlargement in association with bilateral pulmonary infiltrates are seen. In patients with severely depressed CD4 cell count then localization of the infection or cavity formation does not happen and dissemination of disease is usual. These findings along with a positive acid-fast organism in the sputum nearly clinch a clinical diagnosis of NMB infection.

Nodular bronchiectasis.

Inflammatory reactions and tissue destruction produce a weakened wall of smaller size bronchial tubes result in the development of multiple nodule shaped bronchiectasis in the central lung field. Frequent bouts of productive cough with streaks of blood along with other symptoms of infection are usually present. Secondary fungal and bacterial infections are frequent occurrences.

Disseminated infection.

Disseminated infection is mostly present in severely immunosuppressed patients. Bides lungs, bones, spleen, subcutaneous tissues, and kidneys are infected.

The sputum and bronchial washings should not be treated with KOH in the laboratory (a normal practice), because KOH kills M. kansasii and no growth will result in culture. Rapid liquid culture media should be used in growing M.kasasii, a growth in 2 weeks is expected. Newer techniques of species identification should be done. These tests are the Molecular hybridization test, PCR restriction analysis, Nucleic acid amplification test, Restriction fragment length polymorphism, Polymorphic tandem repeats, DNA genomics probe, etc.

Species identification not only speeds up identification but is also used as a guide in the selection of anti-tubercular drugs.

Non-pulmonary M.kasasii infection.

Cervical lymphadenitis in children is primarily due to M. tuberculosis followed by M.bovis. Of the NTM the M.avis complex infection predominates. M.kansasii cervical adenitis is the next common cause of childhood cervical adenopathy. The submandibular, submaxillary nodes are primarily involved but submantal, preauricular and periauricular glands are also infected. The skin over the enlarged glands appears glossy, glands feel rubbery to touch. Often the swollen glands rupture and produce chronic discharging sinus tracts. Many children have low grade fever, anorexia and fail to gain weight.

Osteomyelitis of the spine and sacroiliac.

The flat bones are susceptible to infection due to a rich blood supply. Often pain and fever are followed by abscess formation. In lower thoracic and lumbar vertebra osteomyelitis the abscess drains down the psoas fascia to the groin and can rupture producing a pus draining sinus tract.

When the spleen is infected generally an abscess forms and patients can present as fever of unknown origin. Liver, bone marrow granulomas and skin lesions are seen. Rarely, a meningoencephalitis develops.

Non-pulmonary infections are more common following a hematogenous spread and HIV infected people with CD4 cell counts below 50 are susceptible to these complications.

Diagnosis.

Biopsy tissues. All biopsied tissues should be stained for acid fast and cultured. Identification should be augmented by the newer methods listed above. Fungal and bacterial cultures are done at the same time.

Lymph nodes and bone marrow typically show several noncaseating granulomas with variable numbers of aid fast organisms.

In disseminated M.kasasii infection blood culture, urine and bone marrow cultures usually show growth in 2 weeks. All positive cultures are tested for drug resistance.

Treatment.

M.kansasii are resistant to pyrazinamide and resistance to INH & Rifampin is increasing. The initial anti-tubercular medications include INH, Rifampin, and Ethambutol. If M.kansasii is resistant to any 1^st line drugs then Azithromycin, Fluoroquinolones, Sulfamethoxazole and Streptomycin are added in various combinations.

Complications. Pleural effusion is a rarity, pneumothorax is occasionally seen.

Treatment of cervical adenitis.

Early surgery should be done and is a very effective way to cure. In advanced cases with draining sinus tracts treated with anti-tubercular medications for 3 to 6 months followed by surgery.

Mortality and morbidity vary according to the extent of the disease at the time of presentation and the immunological status of patients.

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Clinical Presentation of Pulmonary Tuberculosis

 Clinical Presentation of Pulmonary Tuberculosis

PKGhatak,MD

Pulmonary Tuberculosis presents in multiple ways.

Pulmonary tuberculosis is a very old disease. Evidence of tuberculosis was detected in 4,000 old Egyptian mummies. Description of TB like disease was recorded in 3,500 old Sanskrit literature, and still, older evidence was uncovered in Israel in a skeleton found in an old grave. Currently, pulmonary tuberculosis is still very much prevalent globally and is a curse for people of Southeast Asian and Northern African countries. 10,000 new cases were detected worldwide and 1.5 million people died of tuberculosis in 2018.

Pulmonary tuberculosis has several modes of presentation. The clinical presentations of clinical illness due to TB vary according to the prevailing standard of sanitation and public health of countries.

Latent Tuberculosis in Western countries.

Immigrants coming to western countries require to have a negative chest x-ray as a prerequisite for a visa. Tuberculosis (TB) tests are mandatory in many countries for employment in schools, universities, hospitals, healthcare, nursing homes and would be new nursing home residents and workers in the retail business. Some of the applicants react positive to Interferon gamma release blood test or the old fashioned TB skin test.

This positive TB tested people are completely symptom free, have no indication of prior TB infection, and are unable to recall coming in contact with an infectious TB patient.

A careful review of a recent chest x-ray or CT chest will identify a small nodule in the upper part of the lungs, and also occasionally a small regional calcified lymph node. Induced sputum smears and cultures are done routinely and are negative.

The Public Health Department (PHD) must be notified and state mandated treatment protocol and follow up are taken up by the PHD.

Reactivation of Latent TB.

Two ways the reactivation of latent TB present - Local spread and Pleural effusion.

Local spread.

Many immigrants from countries where TB is prevalent may not be subjected to TB surveillance upon arrival in the new country. They remain symptoms fee for a very long time until the cellular immunity is reduced by an infection like HIV, and immunosuppressed conditions due to Diabetes mellitus, prolonged use of corticosteroids, immunosuppressed drug therapy in organ transplants and cancer chemotherapy. The dormant TB bacteria residing within the macrophage cells wake up and become metabolically active and begin to multiply. Eventually, TB bacteria break up the cellular barrier and invade adjoining tissues.

As TB becomes an active disease the patient may experience profuse night sweats, unproductive cough, evening chills and a low grade fever and loss of weight.

The clinical examination followed by laboratory tests reveals a positive Interferon gamma release assay (IGRA) and a single pulmonary nodule in the upper zone of the lung in the CT chest. These abnormal shadows often show two distinct densities - a denser central core and a lighter peripheral cellular infiltrate zone 

The major concern at this stage is – it is cancer or granuloma. TB bacteria is one of the few other microscopic organisms that produce granuloma.

The most direct way to distinguish between the two is to obtain tissue by skinny needle biopsy with ultrasound/ fluoroscopic guidance.

But if the granuloma is due to TB infection that might contaminate the path of the needle and might help to spread TB to pleura and subcutaneous tissues.

The alternative is to wait 3 to 6 months and obtain a repeat CT scan and then evaluate the activity of the lesion and then decide when to biopsy.

This decision must depend on the best judgment of the attending physician and the patient. There are risks both ways.

Induced sputum for cytology for cancer and fungal and TB are also performed as a part of the initial evaluation. Depending on the culture media used for TB culture, positive growth may or may be available in 4 to 6 weeks. Bronchoscopic brushing and washings are examined for cancer and infective agents. The success rate of identification of cancer/ infection is better by examining the bronchoscopy materials, but the success rate is not 100 %. The IGRS test of bronchial brushing and wash fluid containing mononuclear cells has a much higher rate of positivity of IGRS compared to peripheral blood lymphocytes.

Pleurisy and Pleural Effusion.

Clinical presentation.

The onset of chest pain, fever, and mild non-productive cough suddenly occurs in young apparently young healthy individuals. Pleural space TB inflammation takes place in one of the two ways - hypersensitive reaction and direct infection.

Hypersensitive reaction.

It is the usual mode. The initial symptom is a sudden onset of chest pain aggravated by breathing. The two layers of pleura, rubbing against each other during inhalation and produce chest pain. A few days or weeks later the pain suddenly diminishes once the pleural fluid begins to accumulate. Then the patient feels heaviness in one side of the chest and may develop a low grade persistent fever.

In the pleuritic state, audible friction rubs on auscultation is diagnostic of pleurisy but not diagnostic of TB pleurisy only. The right sided pleural effusion is usually seen and less than 10 % of cases of TB pleural effusion may be bilateral. The pleural fluid is easily obtained by bedside thoracentesis, at the same time pleural biopsy is performed by a special needle (Abram's needle). A pleural biopsy is safe because the lung is separated from the pleura by a layer of fluid and the chance of pneumothorax is minimal.

The TB pleural fluid is light yellow in color, the protein contains over 3 gm/dL, cell count 100 to 1000 /ml and predominantly lymphocytic, glucose content is less than 40 mg/dL, ADL (adenosine deaminase) test on T-lymphocytes is typically over 45U/L but below 200U/L. The ADL is the most sensitive (93%) and specific test (94%) for TB pleural effusion. IGRA assays are specific, but sensitivity is 70% in the peripheral blood and 97% in pleural fluid lymphocytes. TB culture grown in liquid media is in the 50 % range. TB bacteria in smears are rarely seen in hypersensitive TB pleurisy/pleural effusion. In hypersensitive pleural effusion, a pleural biopsy may or may not show caseating granuloma. If granuloma is present then a few TB bacteria can be identified in pleural TB infection.

TB infection of Pleura.

A subpleural TB nodule ruptures in the pleural space. The escaped TB bacteria infects the pleura. Occasionally the TB bacteria are carried into the pleural space by the lymphatics. The contamination of the pleura in one way or another result in pleurisy and pleural effusion. The clinical presentation, however, is a bit different. Here, any age group of people may be infected, except children. The patients are ill if they have progressive primary pulmonary TB infection. In latent TB patients, most patients are symptoms free prior to pleural effusion. A short period of pleuritic chest pain followed by pleural effusion occurs like the hypersensitive pleural effusion.

Chest X-ray reveals, in addition to plural effusion, the site of latent TB infection.  The character of pleural fluid is no different from the hypersensitive pleural effusion and additionally, RBCs in variable numbers are present. The pleural biopsy reveals caseating granulomas and TB bacteria are generally identified in the granuloma. The smear of the fluid may not show TB bacteria but cultures in liquid media are always positive. If the TB bacteria are scanty, they can be identified by Nucleic Acid Amplification Test (NAAT)

Primary Pulmonary Tuberculosis.

Primary pulmonary tuberculosis is a global health problem. People in every country of the globe are contracting pulmonary tuberculosis every year.

Two factors have made tuberculosis eradication a daunting task. 1. TB bacterial survival resiliency. 2. Handicapped immune system to fight TB infection. Human TB bacteria that produce primary pulmonary tuberculosis are called Mycobacteria Tuberculosis, in short MTB.

MTB survival resiliency.

MTB are rod shaped, nonmotile, slow growing bacteria and need oxygen to grow. It lives inside Macrophages and multiplies under favorable conditions. MTB has a three-layered cell wall. The multilayered cell wall blocks TB drugs to enter the bacterial body in sufficient concentration to kill the MTB.

Handicapped Immunity.

In any infection, both the Cellular and Humoral immune systems are activated. But in MTB infection the Humoral immunity remains largely inactive. The CD4 cells, macrophages and other immune T-cells collectively fight against MTB invasion.

Mode of MTB primary pulmonary infection.

 MTB is a respiratory pathogen, human to human transmission occurs via infected droplets. Causal contact with an open MTB case (TB bacteria in sputum) does not cause infection; prolonged contact and repeated exposures over months are necessary. Overcrowded prisons, sailors in submarines, residents in dormitories, hostels and nursing homes are ideal places for MTB transmission.

A majority of inhaled droplets are caught by the mucociliary escalator and are eliminated. A few MTB reaches the alveoli. MTB penetrates the alveolar wall and enters the interstitial tissues and is promptly caught and swallowed by the tissue macrophages. Macrophages are unable to digest the MTB due to the presence of enzymes in bacteria that neutralize the digestive enzymes of macrophages, and the bacterial wall is indigestible. Additional macrophages and lymphocytes accumulate around the infected macrophage and a nodule is formed. 85 % of the initial infections are contained and confined locally. But MTB remains dormant inside the infected macrophages. This infected nodule becomes Latent TB.

Progressive Pulmonary TB.

People with suppressed cellular immunity are unable to limit the initial infection. The MTB multiplies and break out of macrophages and infect the adjoining areas, some of the infected macrophages carry the bacteria to the regional lymph follicles/nodes and these two infected areas are collectively called the primary complex. Further growth and progression of infection continue. 6 to 9 months after the initial infection the patient starts to experience symptoms.

In advanced countries, only 1/3 of newly diagnosed cases are due to fresh infections and the rest 2/3 are due to the reactivation of latent TB.

Symptoms are - lack of energy, easy fatigue, anorexia, loss of weight, short but successive unproductive coughs and profuse night sweats are common.

Further progression of the disease produces: 1. Wide areas of Pulmonary infection and is known as primary progressive Tuberculosis. 2. Hemoptysis. 3. Miliary TB.

Primary Progressive Pulmonary Tuberculosis.

These patients are sick and weak. Persistent low grade fever, wasting of muscles, anemia, cough productive mucopurulent sputum and occasional streaks of blood in sputum is present. Confirmation of pneumonia is not difficult but there are no special clinical features of MTB pneumonia.

Chest x-ray shows infiltration in the upper zone of the lung, usually on the right side and spread of the disease in the adjoining lobes. In some cases, thick walled cavity is seen in the upper lobe or apical portion of the middle lobe. In nursing home patients, middle lobe and lower lobe infiltrations are common.

Sputum smears and cultures are the cornerstones of MTB diagnosis. IGRA assay of peripheral blood is both sensitive and specific. In occasional cases, NAAT (Nucleic acid amplification) test may be necessary.

Hemoptysis. Blood-streaked sputum is an indication of the progression of disease and destruction of the lungs. That leads to bringing up frank red blood.

Almost all patients present with hemoptysis undergo bronchoscopic examination. It not only helps to diagnose MTB but also eliminates the possibility of lung cancer and fungal infection.

Miliary Tuberculosis.

MTB not only destroys the lung parenchymal tissues but also penetrates blood vessels and spreads far and wide. MTB can also spread via lymphatics. The tissues rich in oxygen support further MTB growth. Lungs, meninges, bone marrow, and kidneys are common sites of extrapulmonary TB infection.

The patients are very malnourished, very weak and unable to cough properly. Sputum production is generally absent or minimal. Patients are febrile and may show abnormal liver, renal functions and electrolyte imbalance. Both acute and chronic phase reactants are positive. In severely immunosuppressed patients with low CD4 cell count, the TB skin tests and IGRS test may be negative.

The chest x-ray is virtually diagnostic, and a bone marrow biopsy showing granulomas and MTB are easily demonstrated. Bone marrow cultures are necessary for the final diagnosis and also for the detection of drug resistance. Concurrent HIV infection must be eliminated by proper tests.

All Pulmonary MTB cases must be reported to the local Public Health Department (PHD). PHD use approved treatment protocol, makes sure of TB drug delivery and compliance of patient in taking TB drugs, and performs contact tracing and chemoprophylaxis of appropriate people.

In addition to these modes of presentation of MTB pulmonary infections, some unusual presentations are also identified in unsuspected patients on bronchoscopy. The use of more advanced tests helps to identify MTB infections. That part is not discussed here.

Non-MTB mycobacterial pulmonary infections are less common but the number of new cases is growing. This subject is discussed in a separate place.

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