Tuberculosis

Signs and Symptoms

• Cough of more than two weeks which is usually productive (In HIV-positive adolescents and adults, a
cough of any duration.)
• Hemoptysis (Sputum with blood stain)
• Fever
• Chest pain
• Excessive night sweats and
• Loss of weight

Extra- pulmonary tuberculosis may involve many sites of the body such as the pleura, pericardium, lymph
nodes, meninges, bones, gastrointestinal tract, genitourinary system, epididymis, eyes and skin.

• Pleural tuberculosis:
o Cough which may be non-productive
o Pleuritic chest pain (Pain when breathing in)
o Fever
o Night sweats.
• Pericardial tuberculosis:
o Chest pain
o Low pulse volume
o Cardiac tamponade (difficulties in breathing, tachycardia, hypotension, blood pressure decreasing with inhalation, and sudden collapse of the patient)
• Lymph node tuberculosis:
o Lymph node tuberculosis may affect any site though it is more common in the cervical region.
o Lymph nodes are usually painless.
o Where caseation with liquefaction and sinus formation occurs, they may be painful.
• Meningeal tuberculosis:
o Headache (insidious)
o Neck stiffness,
o Vomiting
o Change in mentation (Confusion, drowsiness)
o Convulsions
o Paralysis
• Bone tuberculosis:
o Bone deformity (Most common ones - gibbus formation due to vertebral collapse and may result in
paraplegias)
o Osteomyelitis
o Arthritis (Swelling, Pain)
o Cold abscess formation may also occur.
• Gastrointestinal tuberculosis:
o Chronic diarrhea,
o Malabsorption,
o Intestinal obstruction.
o Abdominal distention (Ascites, lymph adenopathy)
o Pelvic abscesses.
• Genito-urinary tuberculosis:
o Renal tuberculosis may be asymptomatic, causing symptoms such as:
o Hematuria (blood in urine)
o Sterile pyuria with extensive renal involvement.
o Genital – Tuberculosis may cause symptoms such as:
o Infertility
o Salpingitis
o Tubal abscess are presentations of infection of the fallopian tubes while epididymal tuberculosis may
present as painless swellings.
o Ocular tuberculosis
o Hylectenular conjunctivitis,
o Iritis
o Choroiditis.
• Dermal tuberculosis:
o Dermal tuberculosis may include lupus vulgaris
o Erythema nodusum (painful nodules under the skin).
• Adrenal tuberculosis:
o Adrenal tuberculosis may cause adrenal insufficiency (Low BP, Weight loss, dizziness and palm
sweating and fainting).

Investigations

A diagnosis of TB can be made based on bacteriological confirmation and/or clinical evaluation (signs, symptoms and radiology). All presumptive TB patients should be subjected to laboratory investigations for TB and appropriate baseline investigations. If a negative result is obtained but a clinician suspects TB, radiological and clinical evaluation can be used to guide diagnosis.
• Laboratory Tuberculosis investigations
o GeneXpert® MTB/RIF or Ultra (Cepheid)
o Truenat™ (Molbio Diagnostics)
o TB loop-mediated isothermal amplification (LAMP)
o Smear microscopy
o Lateral flow urine lipoarabinomannan assay (LF-LAM)
o Line probe assay (LPA)
o Solid and liquid culture
• Baseline Investigations
o Full blood count
o CRP/ESR
o Urea and Creatinine
o Liver Enzymes (AST and ALT)
o Albumin
• Radiological Investigations
o X – ray
o CT Scan
o MRI
o Ultra Sound
• Other Investigations
o Biopsy
o Electrolytes
o CSF analysis
o Radiological changes that occur in Pulmonary Tuberculosis include:
o Milliary
o Cavitation
o Lobar consolidation
o Pleural effusion
o Parenchymal infiltrates
o Hilar lymphadenopathy
o Sometimes Chest X-rays may not show any abnormality
o Radiological findings in HIV-infected individuals depend on the degree of immunosuppression

Treatment

• Treatment of tuberculosis is divided into two phases:
o Initial/Intensive Phase
o Continuation Phase
• Treatment involves the use of combination of tuberculosis drugs.

NB: There is no place for the use of monotherapy in the treatment of tuberculosis nor for a trial of treatment

Table 83 Adult Standard TB Regimens

The total duration of treatment is 12 months for TB meningitis and tuberculomas because of serious risk of disability and mortality; and for osteoarticular/spinal TB and ocular TB because of difficulties of assessing response to treatment.

Indications for steroids in the treatment of tuberculosis in adults:
• TB meningitis
• TB pericarditis
• TB Immune Reconstitution Inflammatory Syndrome
• Severe hypersensitivity reactions to anti-TB drugs
• Hypoadrenalism
• Renal tract TB (to prevent ureteric scarring)
• TB laryngitis with life-threatening airway obstruction
Note: Steroids doses must be tapered, and not be stopped abruptly.

Recommended doses of adjuvant steroid therapy

Table 84: Recommended doses of adjuvant steroid therapy (drug of choice is prednisolone)

Table 85: Weight bands for dosing of anti-tuberculous drugs (adults)

Children Standard TB medicines and recommended regimens

TB treatment in children and adolescents includes a 2-month intensive phase followed by a continuation phase of 2–4 months.

Children and adolescents aged between 3 months and 16 years with non-severe TB are treated with a 4-month treatment course.

Table 86:Children Standard TB Regimens

Abbreviations: EPTB (Extrapulmonary Tuberculosis) PTB (Pulmonary Tuberculosis) TB (Tuberculosis) RH (Rifampicin/isoniazid)

Table 87: Classification of non-severe and severe TB

Table 88:Weight bands for dosing of anti-tuberculous drugs in children

Table 89:Weight bands for dosing of anti-tuberculous drugs in children

Indications for steroids in the treatment of tuberculosis in children:

• TB meningitis
• TB pericarditis
• TB Immune Reconstitution Inflammatory Syndrome
• Massive pleural effusion
• Massive lymphadenopathy with pressure effects
• Severe hypersensitivity reactions to anti-TB drugs
• Hypoadrenalism
• Renal tract TB (to prevent ureteric scarring)
• TB laryngitis with life-threatening airway obstruction

Steroids doses must be tapered, and not be stopped abruptly
The doses for Prednisolone, the steroid of choice in TB treatment, are as follows:
• TB meningitis 1–2 mg/kg (max 60 mg) for 2 weeks, then taper off over 6 weeks
• TB pericarditis 1–2 mg (max 60 mg) for 4 weeks, then half for 4 weeks (max 30 mg/day), then taper off
over several weeks
• TB pleural effusion (severe)/or IRIS and others 0.5 to 1 mg (max 30 mg) for 1–2 weeks, then taper off over several weeks

Description

Table 90 DR definitions

Signs and Symptoms

The clinical features of a patient with DR-TB are not different from those of DS-TB patients (both PTB and
EPTB)

Investigations

• Microbiological diagnosis of Drug-Resistant TB
• GeneXpert MTB/RIF and Ultra
• Trunat MTB/RIF
• LPA
• Culture (solid and liquid) and DST
• WGS

Treatment

DR-TB treatment regimens
There are two main treatment regimens currently recommended for use in Zambia; both are oral-based
regimens.
• All oral shorter regimen
• All oral longer regimen
Use of the second-line injectable regimen is no longer recommended.

Grouping of second-line drugs

Second line drugs are grouped as shown in Table below

Table 91: Second line drugs

 Pretomanid is a new drug that has not yet been assigned to a group

Shorter regimen for MDR/RR-TB and Pre-XDR-TB The Preferred oral shorter regimen has a duration of 6 months, consisting of Bedaquiline (Bdq), Pretomanid (Pa), Linezolid (Lzd) and Moxifloxacin (Mfx) (BPaLM) for patients with MDR/RR TB and BPaL for patients with Pre-XDR

Table 92: Eligibility criteria for Pretomanid

Patient eligibility
Patients with moxifloxacin resistance should be prescribed BPaL instead of BPaLM

The alternative shorter regimen is a 9-month regimen preferred in adults, children and pregnant women

Table 93: Intensive and continuation phases for shorter regimen

 NB: Initial phase: 4-6 Bdq [6]-Lfx [Mfx]-Lzd [2]-E-Z-Hh-Cfz then Continuation phase 5 Lfx [Mfx]-Cfz-Z-E

Refer to dosing chart below in Table 95

All oral longer treatment regimen
Patients who do not qualify for all oral shorter regimen receive 18-20 months all oral longer regimen based on
WHO drug grouping as follows:

Initial phase: 6Bdq-Lzd-Cfz-Lfx (Mfx) then
Continuation phase: 12Lzd-Cfz-Lfz (Mfx)

Table 94:Intensive and continuation phases for longer regimen

DR-TB treatment in special populations

All these patient categories MUST be discussed at provincial and/or national DR-TB CEC meetings

Table 95: DR TB treatment in special populations

For abbreviations refer to Table 90 second line drug grouping; Pretomanid is abbreviated Pa, Hh indicates
high-dose isoniazid

Note:
• All treatments for these patients should be guided by DR CEC (district, provincial or national)
• An individualized regimen can be designed for a patient when pDST results are available. The regimen
should compose of at least 5 effective drugs This must be done in conjunction with the national CEC
• There is more than one possible combination for the longer regimen
• All patients on DRTB treatment must be followed up monthly with sputum culture/DST
• All patients on DRTB drugs must be monitored closely for adverse drug reactions and Grade 3-4 adverse reaction reported to the CEC and ZAMRA
• Ambulatory model of care is preferred over the inpatient model of care unless there are compelling
indications for patient admission

Tuberculosis and Immunocompromised Patients
• Immunocompromised patients may develop tuberculosis owing to reactivation of previously latent disease or due to new infection. All TB diagnosed patients should be counselled and tested for HIV. The infection may be caused by other mycobacteria e.g. M. avium complex in which case specialist advice is needed.

Management of TB/HIV co-infected patients
• TB treatment should be initiated first, followed by ART as soon as the patient can tolerate ART, preferably
within the first 2 weeks of TB treatment, except for TB meningitis (start after 8 weeks).
• All TB patients with HIV should start ART regardless of CD4 count.
• Modifications to the ARV regimen should be made to avoid overlapping toxicities and drug-drug
interactions between ART and TB medications (ART guidelines).
• Co-infected patients have an increased risk of drug toxicity and TB Immune Reconstitution Inflammatory
Syndrome (IRIS).
• Prednisolone 40 mg twice daily for 2 weeks then 20 mg once daily for 2 weeks for TB IRIS Prevention.

Extensively Drug-Resistant Tuberculosis (XDR-TB)
• Recognized earlier in 2006 in South Africa, extensively drug-resistant TB (XDR-TB) is MDR-TB that is also resistant to three or more of the six classes of second-line drugs.

Monitoring
• Required monitoring and frequency

Table 96: Monitoring Chart

Since Isoniazid and Rifampicin are associated with liver toxicity, the hepatic function should be checked before
and during treatment with these drugs. Patients on dual treatment of HIV and TB are likely to have liver/renal toxicity and should therefore be monitored closely.

Supportive
• The following supportive strategies should be part of package of care
• Adherence,
• Nutritional support
• Tracing
• Home based care

Complications

• Pneumothorax
• Empyema or pyopneumothorax and laryngitis with advanced disease.
• Respiratory failure and right ventricular failure may develop as a late complication due to extensive
pulmonary destruction and fibrosis.
• Colonization of cavities with Aspergillus fumigatus may occur resulting in haemoptysis.
• Post TB lung disease is common.
• Disability manifesting was exertional dyspnea is now becoming common.
• Constrictive pericarditis is a complication of TB pericarditis.
• Meningeal tuberculosis can result in hydrocephalus and focal deficits.
• TB of the spine may result in permanent neurological deficits.
• Gastrointestinal tuberculosis may lead to the development of ascites and malabsorption.

Referral Criteria

• The patients with following features should be referred:
• Poor vitals such low oxygenation and Hypotension (Low blood pressure)
• Cardiac tamponade
• Drug induced liver injury (worsening liver enzymes)
• Difficulties in breathing
• Stroke and Paralysis
• Hydrocephalus

TB Preventive Therapy (TPT)
• The most effective method of preventing the spread of tuberculosis is the detection and effective treatment
of infectious cases, i.e. the bacteriologically confirmed cases. Poor hygiene, malnutrition and overcrowding
in places such as prisons, orphanages, facilitate the spread of tuberculosis.
• TPT is recommended for the following at risk groups:

• Adults and adolescents living with HIV
• Adults and adolescents (10 years and older) living with HIV (PLHIV) regardless of immune status, previous TB treatment or ART status
• Infants and Children who are living with HIV
  • Infants (aged < 12 months) living with HIV who are in contact with a case of TB
  • Children (aged ≥ 12 months to 10yrs) living with HIV unlikely to have TB disease on symptomatic screening with or without history of TB contact

• HIV negative Infants and children who are contacts of bacteriologically confirmed pulmonary TB

• Other HIV-negative at-risk individuals
  • Miners and ex-miners with silicosis
  • Close and household contacts of bacteriologically confirmed pulmonary TB patients
  • Patients receiving immunosuppressive treatment
  • Patients with Chronic Kidney
  • Undernourished Individuals
  • Incarcerated populations (Inmates) who are in close contact with bacteriologically confirmed pulmonary TB

• Health Care workers who meet the criteria of having additional risks for TB s.a HIV, diabetes

NB: Before giving TPT always rule out the possibility of active TB in the individual

TB Preventive Therapy Options
There are three regimens that are recommended for treatment of TBI in Zambia. The treatment regimen
depends on the patient category. These include 6 months, 3 months and 1 month regimens.

Table 97: TB preventive regimens, dosing, and cautions