4.2 Adult and adolescent algorithms

Diagnostic algorithm 1

PTB in HIV-negative patients with low risk of MDR-TB

a. When the patient’s serological status is unknown, this algorithm should be used in settings with HIV prevalence < 5%.

b. Patients are considered to be at low risk of multidrug-resistant TB (MDR-TB) if they do not meet one of the following criteria: 1) resident in areas with high MDR-TB prevalence; 2) all retreatment categories; 3) exposure to a known MDR-TB case; 4) patient remaining smear + at 2 months; 5) exposure to institutions with high risk of MDR-TB (e.g. prisons).

c. Danger signs: respiratory rate > 30/min and/or fever > 39°C and/or pulse rate > 120/min and/or unable to walk.

d. Smear microscopy: two sputum examinations performed on the same day.

e. Broad spectrum ATB:
If no danger signs: amoxicillin for 7 days (NO fluoroquinolones);
If danger signs: parenteral ATB (e.g. ceftriaxone).

f. Clinical response to a broad spectrum antibiotic does not rule out TB. Patient should be informed to return for reassessment if symptoms recur.

g. According to setting:
Xpert MTB/RIF available: two sputum smear microscopy on the same day and one Xpert MTB/RIF from one of the samples collected for smear microscopy;
Xpert MTB/RIF not available: two sputum smear microscopy on the same day.

h. In groups of patients with high level of resistance to isoniazid (> 10%) it is recommended to perform a conventional DST at baseline (and/or a line probe assay) in order to provide adequate treatment.

i. According to setting:
In groups of patients with prevalence of MDR-TB < 10%, patients seriously ill should immediately be initiated under empiric MDR-TB treatment. H and R will be included in the regimen until confirmation of MDR-TB by conventional methods. If the patient is stable, the clinician may choose to wait for confirmation before initiating a MDR treatment.
In groups of patients with prevalence of MDR-TB ≥ 10%, patients should be initiated under empiric MDR-TB treatment. Consider adding H in settings where mono-resistance to R is not uncommon.

j. Clinical signs and chest X-ray (CXR) findings tend to be more typical in those who are HIV-negative having active TB:


TB

Bacterial pneumonia

Clinical signs

Weight loss, productive cough, purulent sputum, haemoptysis, pleuritic chest pain

Acute onset
Fever

CXR

• Infiltrates, nodules with or without cavitation in the upper lobes and in the superior segments of the lower lobes.
Pleural effusions
Adenopathy in the mediastinum or hila (rare in TB in adults and adolescents)
Miliary disease

Lobar consolidation

When clinical signs AND CXR are strongly suggestive of active TB, treatment should be initiated without waiting for diagnosis confirmation.

Diagnostic algorithm 2

PTB in HIV-positive patients

a. When the patient’s serological status is unknown, this algorithm should be used in settings with HIV prevalence > 5%.

b. TB suspect is defined as: cough for more than 2 weeks or any cough with at least one of the following signs: loss of weight, night sweats, fever, and suspicion based on clinical judgment.

c. Danger signs: respiratory rate > 30/min and/or fever > 39°C and/or pulse rate > 120/min and/or unable to walk.

d. According to setting:
Xpert MTB/RIF available: two sputum smear microscopy on the same day AND one Xpert MTB/RIF from one of the samples collected for smear microscopy;
Xpert MTB/RIF not available: two sputum smear microscopy on the same day.

e. In patients groups with high level of resistance to isoniazid (> 10%) it is recommended to perform a conventional DST at baseline (and/or a line probe assay) in order to provide adequate treatment.

f. When possible a culture should be performed. A positive culture result at any point in time in the algorithm should lead to a full TB treatment.

g. TB treatment should be started when clinical signs AND chest X-ray (CXR) are suggestive of TB (Note k).

h. Broad spectrum ATB/PCP:
If no danger signs: amoxicillin for 7 days (or recommended oral agent for community-acquired pneumonia in the area). Do NOT use fluoroquinolones;
If danger signs: parenteral ATB (e.g. ceftriaxone) AND high dose cotrimoxazole.

i. If no danger signs: patient should be re-assessed after 7 days.
If danger signs: patient should be assessed daily and if no response, TB treatment should be considered after 3 to 5 days.
Clinical response to broad-spectrum ATB does not rule out TB. Patient should be informed to return for reassessment if symptoms recur.

j. Differential diagnosis of a coughing HIV-infected adult/adolescent: bacterial (including atypical) pneumonia, PCP, fungal infection, non-tuberculous mycobacteria, nocardiosis, Kaposi sarcoma and lymphoma.

k. The diagnosis should be based on clinical assessment, CXR and CD4 results, whether cotrimoxazole preventive therapy (CPT) was used, and other treatment already used in the patient. If the index of suspicion for active TB is high, empiric TB treatment should be initiated without waiting for diagnosis confirmation. Other treatments such as broad-spectrum ATB or therapy for PCP may be needed in addition to TB treatment.


TB

PCP (HIV+)

Bacterial pneumonia

Clinical signs

• Current cough
Weight loss
Purulent sputum and haemoptysis less likely if HIV-positive with low CD4 count
Fever
Night sweats
Pleuritic chest pain

Dry cough
Dyspnoea ++
Hypoxemia
Not on CPT
More likely if low CD4 count

Acute onset
High fever

CXR

• Upper lobe infiltrates and cavitation only likely in HIV-positive adults with higher CD4 counts. Any lobe of the lung may be affected
• In HIV-positive adults with lower CD4 counts, the following 4 patterns are suggestive of TB:
1. miliary pattern
2. pleural effusion without airspace (with straw-coloured liquid aspirate)
3. hilar and mediastinal adenopathy
4. large heart (especially if symmetrical and rounded)

Bilateral interstitial infiltrate with reticulonodular markings that are more pronounced in the lower lobes
Findings lag behind symptoms and may be normal early in the disease

Lobar consolidation


l. In the absence of any improvement of clinical signs (no weight gain, persistent cough, pain, etc.) AND no improvement on CXR after 2 months of a well conducted TB treatment, diagnosis and treatment should be reconsidered. MDR-TB should also be considered.

m. In addition to the differential diagnosis in Note k above, DR-TB should be considered.

n. Immediately start empiric MDR treatment, even if positive predictive value of Xpert MTB/RIF for R resistance is low (this is done to avoid the rapid and high mortality due to untreated MDR-TB in HIV patients). H and R should be included in the regimen until confirmation of MDR-TB by conventional methods if the patient comes from a group with less than a prevalence of MDR-TB < 10%. In groups of patients with prevalence of MDR-TB ≥ 10%, patients should be initiated under an empiric MDR treatment without H or R, although one can consider adding H in settings where mono-resistance to R is not uncommon.

Diagnostic algorithm 3 with Xpert MTB/RIF

PTB in patients with high risk of MDR-TB

a. The following patients are considered to be at high risk of MDR-TB: 1) resident in areas with high MDR-TB prevalence; 2) all retreatment categories; 3) exposure to a known MDR-TB case; 4) patient remaining smear-positive at 2 months; 5) exposure to institutions with high risk of MDR-TB (e.g. prisons).

b. Groups of patients at risk of MDR-TB are also at risk of other types of DR-TB as well. DST to the first-line should be performed in order to provide adequate treatment for possible mono- or poly-drug resistance.

c. In populations with a prevalence < 10% of MDR-TB, the resistance to R diagnosed by Xpert MTB/RIF must be confirmed by conventional methods. Drug sensitivity testing (DST) to both first-line drugs and secondline TB drugs should be performed if possible.

d. • In groups of patients with prevalence of MDR-TB < 10%, the decision to start the MDR-TB treatment will be made on clinical presentation of the patient and immunological status. Patients seriously ill and/or HIV+ should be initiated immediately under empiric MDR-TB treatment. H and R will be included in the regimen until confirmation by conventional methods.
• In groups of patients with prevalence of MDR-TB ≥ 10%, the patient should be initiated using an empiric MDR-TB treatment. Consider adding H in settings where mono-resistance to R is not uncommon.

e. Baseline sputum smear microscopy result on 1 specimen in order to: 1) allow patient follow-up with microscopy; 2) take immediate decisions related to TB infection control.