Session 2

Key area in the revised guidelines

Clinical and Programmatic Management

of TB, TB-HIV, and Leprosy in Malawi

9th Edition, 2024

Background
• There has been an evolution of
TB treatment guidelines over
the years.

• This has been guided by the

normative guidance from WHO.

• The 2018 TB guideline has

passed the five year mark
hence a need for revision.

• The 9th Edition has combined

TB and leprosy guidelines.
Guideline revision process
• Stakeholders engagement and working sessions
• stakeholders divided into several working groups, for
example
• Case finding
• Diagnosis
• Treatment
• Childhood TB
• TB/HIV
• Latent TB infection
• Validation meeting
WHO updated
documents
Case definitions

Bacteriologically Biological specimen is positive by smear microscopy, culture or WRD (e.g., Xpert MTB/RIF). All such
confirmed TB: cases should be notified, regardless of whether TB treatment has started or not.

Clinically Does not fulfil the criteria for bacteriological confirmation. Includes diagnoses based on X-ray
diagnosed TB abnormalities or suggestive histology and EPTB cases without laboratory confirmation.
case Clinically diagnosed cases subsequently found to be bacteriologically positive (before or after
starting treatment) should be reclassified as bacteriologically confirmed.

Pulmonary TB involving the lung parenchyma or the tracheobronchial tree.

Tuberculosis Miliary TB, TB intra-thoracic lymphadenopathy (mediastinal and/or hilar) or Tuberculous pleural
(PTB) effusion, with radiographic abnormalities in the lungs,
EPTB+PTB= PTB for registration purpose

EPTB Any bacteriologically confirmed or clinically diagnosed case of TB involving organs other than the
lungs, e.g., pleura, lymph nodes, abdomen, genitourinary tract, skin, joints and bones, meninges.
 Classifications based on history of previous TB
treatment
New Patients have never been treated for TB or have taken anti-TB drugs for < 1
month.
Previously Previously treated patients have received 1 month or more of anti-TB drugs
treated in the past
o Relapse: Patients have previously been treated for TB, were declared cured or
treatment completed at the end of their most recent course of treatment and are now
diagnosed with a recurrent episode of TB.

o Treatment after failure: Patients is those who have previously been treated for TB
and whose treatment failed at the end of their most recent course of treatment.

o Treatment after loss to follow-up: patients have previously been treated for TB
and were declared lost to follow-up at the end of their most recent course of treatment.

o Other previously treated: Patients have previously been treated for TB but the
outcome after their most recent course of treatment is unknown or undocumented.

o Patients with unknown previous TB treatment history do not fit into any of the
Treatment outcomes-new definition
(2021)
Cured A pulmonary TB patient with bacteriologically confirmed TB at the beginning of treatment
who completed treatment as recommended by the national policy , with evidence of
bacteriological response and no evidence of failure.

Treatment A person who completed treatment as recommended by the national policy , whose outcome
completed doesn’t meet the definition of cure or treatment failure

Treatment A patient whose treatment regimen need to be terminated or permanently changed to a new
failed treatment strategy.

Lost to follow- A patient who didn’t start treatment or whose treatment was interrupted for 2 months and
up above

Died A patient who died before starting treatment or during the course of treatment
TB case Finding
Adopted the WHO recommendations for targeted systematic TB screening
among the following Population sub-groups
Strong • Household contacts and other close contacts of individuals with TB disease including
recommendations MDR-TB
• People living with HIV (PLHIV)
• Workers in silica exposed workplaces e.g., miners.
• Prison staff, prison inmates, and people in penitentiary institutions

Conditional • People with untreated fibrotic lesions on chest X-ray

recommendations • People in high TB burden settings (estimated TB prevalence >100/100,000) who are
seeking care or who are in care and belong to selected risk groups, and HCWs

• Subpopulations which have risk factors for TB including urban poor communities, the
homeless, rural communities, migrants, refugees, internally displaced persons, and
other vulnerable groups with limited access to health care services
 Operational Definition of Terms for systematic TB screening
• Presumptive TB case: This refers to a patient who presents with symptoms and /or signs suggestive of
TB
• Systematic screening for active TB: This is the systematic identification of people at risk of TB disease in a
predetermined target group, by assessing using tests, examinations or other procedures that can be applied rapidly.
• Active TB case-finding (ACF): Is the systematic identification of presumptive TB cases from a
predetermined target population/ community initiated by HCWs or volunteers
• Passive Case Finding: Requires that affected individuals are aware of their symptoms, have access to
HFs where they present themselves spontaneously, and are evaluated by HCWs or volunteers who
recognize the symptoms of TB and who have access to a reliable laboratory.
• Intensified case finding (ICF): Healthcare provider-initiated TB screening among high-risk population
such as PLHIV.
• Enhanced TB case finding (ECF): The creation of population awareness of TB symptoms through
advocacy and community mobilization to encourage self-presentation for TB screening.
• Initial screening: The first screening test, examination or other procedure applied in the population
eligible for screening.
• Computer-aided detection (CAD): The use of specialized software to interpret abnormalities on chest
radiographs that are suggestive of TB. CAD may be used for screening or triage presumptive TB cases
Overall organization of the Case finding strategy

• Health facilities
• Community level
• institution and
other with
overcrowding
setting:
Facility based systematic TB Case Finding
• TB screening should be done at Priority target groups
all outpatient departments
(OPDs), under five clinics, • OPD attendees • Prisoners and miners presenting to the
inpatients departments, HIV • Household contact of index TB health facilities
cases • Undernourished people or people
clinics, non-communicable • People previously treated or with a body mass index ≤ 18
disease clinics and other exposed to TB • People in the in-patient department
service outlets. • People with an untreated fibrotic • People with chronic renal failure
lesion shown on CXR • People on treatments that
• Priority target group while it is • People with chronic respiratory compromise their immune system
recommended to administer TB disease • Older people (60 years and older)
screening to all individuals • People presenting with pneumonia • People in mental health clinics or
presenting to the HFs at each • People with diabetes mellitus institutions
service delivery point, priority • People who smoke • Health care workers
should be given to individuals
with high risk for TB infection
or risk of developing active TB
disease.
TB Screening tool
1. WHO 4 symptom screening 2. CXR as screening tool
High risk population groups: Other population Groups not Chest X-ray together with computer aided detection for TB
PLHIV / included in High Risk for TB. can be used as screening tool for the following high-risk
Prisoners/Miner/mining group presenting to health facilities where applicable:
community/HCWs
• PLHIV with advanced HIV disease and/or high viral load
1. Cough (any duration) 1. Cough lasting >2 • Prison Inmates
2. Fever (any duration) weeks • Miners
3. Night sweats (any 2. Fever lasting >2 weeks • Household contact of index bacteriologically confirmed
duration), 3. Weight loss and PTB cases
4. Weight loss 4. Profuse night sweats • Undernourished people or people with a body mass
lasting >2 weeks index ≤ 18,
• People with chronic renal failure,
• Older people (60 years and older)
• Anyone fulfilling ANY of • Anyone fulfilling ANY
the above criteria will of the above criteria
be labelled as a will be labelled as a
presumptive TB case presumptive TB case
 Facility based TB screening
• Who
• HCWs: all HCWs attending to the patient visiting the HFs includes: Nurses, clinicians, Health
Surveillance Assistants, Patients/ward attendants and lab personnel Screening can also be done
using trained volunteers or non-clinical staff for example FAST promoters.
• Documentation: Presumptive TB register.
•Where:
• Adult OPD, Under five OPDs, HIV clinic, Inpatient departments, Diabetes clinics clinic, TB clinic and
all other facility entry points

•Diagnostic tool
• GeneXpert and other WRD tests for all priority group
• Microscopy for non-priority group
 FAST strategies (Finding TB patients, Actively Separate safely and Treat effectively)
Target group • All individuals presenting to health facility for any reason should be asked for TB symptoms
• Individual with high risk for TB infection or developing active TB disease who present to health
facilities with any form of respiratory symptoms

Screening tool • WHO recommended 4 symptom screening

• SM and CXR for eligible groups– in selected sites (CXR)

By Whom FAST can be done by nurses, clinical officers, health surveillance assistants, lab personnel, volunteers
based in the facility,

where Health facilities designated to implement the FAST approach.

• Adult OPD, under five OPDs, HIV clinic, in-patient departments, Diabetic clinic, TB clinic and all
other entry points

Diagnostic tool • Gene Xpert and other WRD test for priority groups
• Microscopy for non-GeneXpert site
TB Screening algorithm- at Health facility
 Algorithm: community based active TB screening

• TB screening
algorithm among
High-risk group using
symptom, CXR and AI
(active case finding)
• Combined
symptom and
chest X-ray
screening has
been shown to
increase the yield
of TB cases.
Contact investigation
• Contact investigation: CI is a systematic process intended to identify undiagnosed cases of TB among
the contacts of an index case.
• Index Case/Index patients: the index case is the initially identified and diagnosed case of new or
recurrent PTB of any age in specific household or other comparable setting in which others may have
been exposed.
• Household Contact: A person who shared the same enclosed living space for one or more nights or for
frequent or extended periods during the day with the index case during the 3 months before the
commencement of the current treatment episode.
• Close TB Contact: A person who is not in the household but shares an enclosed space (such as a social
gathering, workplace, or facility) for extended periods with the index case (definition above) during the
3 months before the commencement of the current treatment episode.

Priority should be given when the index TB patients have any of the following characteristics
● Bacteriologically confirmed PTB
● Presumptive or confirmed or clinically diagnosed Drug-Resistant TB
● Children under 5 years of age with TB (to find the source of infection)

• Reverse Contact Investigation

• Recommended when children less than 5 years old are diagnosed with PTB
Contact investigation flow chart
 TB CF among children
OPD including IMNCI • Screen all patients using screening criteria for TB
clinics • All presumptive TB patients should be tested using WRD
• A diagnostic criterion for children needs to be used for these groups

Paediatric wards • All paediatric presumptive TB cases need to be screened for TB

• Screening criteria and tests need to be review
• A screening register to monitor coverage of screening, yield will be made
available

HIV clinics • TB screening regularly using symptomatic TB screening at each visit

• All identified presumptive TB cases need to be tested using WRD
• Patients with positive
Treatment decision algorithm for diagnosis of childhood TB

Child <10 years with symptoms suggestive of Pulmonary TB

• The algorithm is
aimed at assisting
Presence of danger sign requiring urgent medical care ?
Stabilize and
transfer as needed
Yes
clinicians in
No
screening and
Collect respiratory/stool/other non respiratory specimens for mWRD testing (e.g., Xpert MTB/
RIF or Ultra), including in children living with HIV, urine LF-LAM, if available having a high index
of suspicion for
Did Mwrd-detect TB
childhood TB.
No

Yes Child <2 years /HIV pos / SAM

Yes
• The guideline has
Score sign and symptom
also incorporated a 4
No months regimen for
the management of
non severe
Sign & symptoms
Cough >= 2 wks +2
Fever >=2wks +5 Chest Xray

childhood TB.
Lethargy +3 Cavity +6
Enlarged LN +17 After 2 weeks ,if symptoms persist ---use the scoring
Weight loss +3
Haemoptysis +4 Opacities +5
YES Is sum >10? Night sweats +2
Swollen lymph +4
Tachycardia +2
Miliary pattern +15
Effusion +8 (2RHZE/2HR) present
Tachypnea -1
on pages 82 and 83.

No
Treat most likely non TB conditions
Do not treat with TB treatment -follow • The introduction of
up in 1-2 weeks

Initiate appropriate TB treatment

stool as a sample for
Presumptive TB with contact to TB in
previous 12 month-are eligible for TB

pediatric pulmonary
treatment
Treatment of TB in children
Age Intensive Phase Treatment of Drug-Susceptible non-severe
/Continuation Phase Pulmonary TB
All children with severity of 2 HRZE/4 HR • Eligibility Criteria for 4-month regimens in
TB
children/adolescents 3 months-16 years

Children with peripheral 2 HRZE/2 HR • Non-severe TB determination will be done where

Lymph Node TB( non- there is a capacity for Xray and ability to
severely ill) differentiate severe / non severe TB
Children with non-severe
form of TB

Children 3 month to 15 years 2 HRZE/4 HR

TB Meningitis and 2 HRZE/10 HR

osteoarticular diseases
6HRZEto(Alternative)
Screening in children who has contacts with
people with PTB
HIV negative contcat HIV Postive contcats
Screening criteria Screening criteria
• Cough >2 wks. • Cough , Fever , Night sweats
• Fever more than 2 weeks • Poor weight gain/ Unexplained weight loss Failure to thrive and/or
• Poor weight gain or weight loss malnutrition
in the past 3 months • Chest radiography
• Young children , reduced • History of close contact with a TB case within the past year
playfulness or lethargy should • Drowsiness/lethargy and convulsions, especially focal seizures.
be included

Diagnostic specimen Respiratory specimen: expectorated sputum, Induced sputum, gastric

aspirate , Nasopharyngeal aspirate (NPA), Stool ,
Non-respiratory specimen: CSF, lymph node tissue

Diagnoistic • Xpert MTB/RIF Ultra – Primary diagnostic test

• CXR, clinical decision
• LF-LAM, Truenat
TB Diagnsotic Method
TB diagnosis Method Sample types
 Smear microscopy  Sputum
 Molecular method  Induced samples (bronchoalveolar
 Line Probe assay (LPA), lavage)
 MTB  Stool
GeneXpert/RIF/Ultra/XDR  Urine
 Truenat MTB plus assay  Cerebral spinal fluid (CSF)
 Culture and drug susceptibility  Other body fluids (pleural, ascitic,
testing (DST) synovial, pericardial)
 Urine LF-LAM  Tissues (biopsy)
 Histology  Fine needle aspirate (FNA)
 Clinical suspicion
 Imaging - CT/MRI/FASH/CXR
 Smear Microscopy (ZN/FM)

• Direct smear microscopy is the cornerstone test for the

diagnosis of drug-susceptible PTB.
• Can not distinguish between viable from non-viable MTB
• Can not differentiate between different species of mycobacteria.
• Limited to monitoring of treatment response, and to assess
infectiousness of patients.

24
Genotypic testing-GeneXpert MTB/RIF (Ultra)
• GeneXpert MTB/RIF (Ultra) is a stand alone and fully
automated molecular test
• Uses real time PCR to detect the presence of TB, as well as
testing for resistance to Rifampicin.
• It’s a Point of care test, takes almost 2 hours to deliver results.

Limitations for GeneXpert MTB/Rif (Ultra)

• It cannot be used for monitoring of TB treatment (follow-up)

• It requires a continuous electricity supply.
• It does not inform susceptibility to isoniazid (INH) or SLDs
• Requires temperature controlled environment (air conditioner)
 GeneXpert MTB/XDR
• The Xpert MTB/XDR test is intended for use as a reflex test for a
specimen (unprocessed sputum, concentrated sputum sediments, or
MGIT culture) that is determined to be MTB positive.
Intended Use
• The Xpert MTB/XDR test is intended for use as a reflex test for a
specimen (unprocessed sputum, concentrated sputum sediments,
or MGIT culture) that is determined to be MTB positive.

• This test is intended as an aid in the diagnosis of XDR tuberculosis

(TB) when used in conjunction with clinical and other laboratory
findings.
 Lateral Flow Urine Lipoarabinomannan Assay (LF-LAM)
• LF-LAM is being used for the diagnosis tb in PLHIV
• It is common in disseminated TB with renal involvement resulting in the presence of LF-
LAM in the urine
• A urine-TB LF-LAM is a rapid antigen test.

Eligibility criteria for urine LF-LAM test in Malawi (FOR USE IN HIV POSITIVE INDIVIDUALS
ONLY)

• CD4 count <200 cells/mm3,

• Stage 3 or 4 WHO HIV clinical stage

• Viral load of 1000+ in ART experienced clients (on ART for >1 year)

• Seriously ill (1)

• All children with HIV aged under 5 years with unsuppressed VL on ART should be
considered as having advanced disease.

• Only one criteria has to be met to qualify for Urine LAM

27
 Advantage Limitation
•Bedside- rapid antigen • Other samples than urine (e.g. sputum, serum,
test –takes 25 minutes to plasma, CSF or other body fluids) or pooled
get results. urine specimens should not be used.
•Performed by non –Lab • Does not differentiate between the various
Staff species of Mycobacterium, such as M.
•No electricity required tuberculosis, M. leprae, and M. avium.
•Urine is easy to collect • Not used for monitoring treatment
• Does not detect resistance
• Low sensitivity and specificity

N.B. For all LF-LAM eligible client, Additional Suputum specimen

should be collecetd for Xpert test
28
STOOL METHOD
• Simple one step (SOS) stool processing method using the Xpert ultra to
diagnose pulmonary TB in children and adolescents
• Stool should be the primary sample if a child is unable to produce
sputum and generally stool is accepted by caregivers than induced
sputum
• It provides timely results with good sensitivity and specificity in children
for bacteriological confirmation of TB
• Indicated for all presumptive children and adolescents ages from 0-14
years
• After doing a pilot study, the method is now being rolled out to the rest
of the facilities.
29
TRUENAT
• A chip-based real time PCR test for the semi-quantitative
detection and diagnosis of MTBC in human sputum
samples.
• A sputum specimen is liquefied and lysed and the DNA from
the sample is then extracted and analyzed.
• Used for detection of MTB and Rifampicin resistance
• Minimal power requirements hence uses battery
• It is a point of care test, takes almost 35 minutes to deliver
results
• In Malawi is scaling up the services in peripheral health
facilities
• Results for the Truenat TB tests and the Xpert MTB/RIF tests
generate the same type of information (e.g., MTB detected
 Line Probe Assay (LPA)
• LPA is a rapid and accurate test to identify both FL and SL DST.

• It can be performed either directly from smear-positive sputum samples or from culture isolates.

• Results can be confirmed within two days.

• Used for specification of NTMs

Advantages of LPA Disadvantages of LPA

• Can be performed directly on positive sputum • Requires well-trained staff;

samples. •Requires at least three rooms for the different
• Highly sensitive (98%) and specific (99%) steps

• Rapid test (results within two days) • Infection control precautions require

• Capacity to perform large numbers of tests per sophisticated biosafety level (BSL-3).

day.
31
TB Culture diagnostic method
• Provides a definitive diagnosis of TB ▪ Solid culture media
• Primarily for monitoring MDR-TB - Results may take up to 8 weeks for a negative

patient’s response to therapy culture and from third week to eighth week for a
positive culture.
• Helps to perform DST

•
▪Liquid culture media
May take several weeks for results
outcome -Specially enriched broth-based culture method
(BACTEC MGIT 320/960)
• Requires a special lab structure, culture
-Makes MTB growth from 4th day to 21 days for
media and trained personnel
positive samples or 42 days for negative ones.
 Drug Susceptibility Testing (DST)
• Conventional DST (also known as phenotypic DST)
– Culture based
• Solid media (Lowenstein-Jensen:) – results in 4-6 weeks
• Liquid media (MGIT) – results within 2 weeks
– Expensive, requires high functioning laboratory
• Molecular DST (also known as genotypic DST)
– DNA assay based
– Examples: Xpert MTB/RIF/Ultra/XDR/LPA
– Designed for use at local laboratories (GeneXpert)

33
Conventional DST: technical considerations

First-line drugs
• Well standardized and reliable for Isoniazid, Rifampicin and
Ethambutol
Second-line drugs
• Linezolid, Delamanid, Bedaquiline, Clofazimine, FLQs-(Mox and Levo)

34
Tuberculosis Preventive Treatment (TPT)
• The guideline has now incorporated the shorter TB preventive
treatment options

• It has also expanded the scope of TPT provision to all contact of

bacteriologically confirmed pulmonary tuberculosis regardless
of age.

• It has also outlined the eligibility criteria for each of the

proposed regimens

• The new additions are 3HP made of rifapentine and isoniazid

and 3 RH consisting of Rifampicin and Isoniazid.
TPT Eligibility criteria
• All Under 5 years Contacts of bacteriologically confirmed pulmonary TB regardless of HIV
status.
• All Over 5 year contacts of Bacteriologically confirmed pulmonary TB regardless of HIV
status

• Other
• People who are initiating anti-TNF treatment, or receiving dialysis, or preparing for an organ or
hematological transplant, or who have silicosis
• Newly diagnosed PLHIV up to 3 months on ART

In Summary: All contacts of bacteriologically confirmed pulmonary TB regardless of Age or

HIV status are eligible for TPT
Contacts of Clinically diagnosed pulmonary TB are not.
 TPT regimen
Regimen Recommendation
3HP: 3-month course of once weekly Preferred regimen for all age groups 2 years and above, regardless of HIV
isoniazid and rifapentine status unless contraindicated

Child friendly dispersible rifapentine now available to be used with

100INH to make 3HP

3RH: 3 months of daily Rifampicin and Suitable for all age groups 0-15 who are HIV negative due to Rifamycin
Isoniazid and INSTI interactions (DTG etc)

6H: 6-months course of daily dose of Suitable for all age groups regardless of HIV status ie. Children less than 2
isoniazid. years
 Management of Treatment interruption for
TPT
Target Preferred regimen
group

3HR , 6H Less Resume TPT immediately upon return and add the number of days of missed dose to the total
than 2 treatment duration
wks.

More  If treatment interruption occurred after 80% of the doses expected in the regimen were taken:
than 2 • No action is required.
wks. • Continue and complete the remaining treatment
 If less than 80% of the does expected in the regimen were taken, and treatment course can be
completed within the expected time, for completion( treatment duration +33% additional time)
• No action is required.
• Continue and complete the remaining treatment as per original plan
 If less than 80% of doses expected in the regimen were taken, and treatment course can’t be
completed
• Continue the remaining treatment
• Complete the remaining doses to make it full doses as per the guideline
Integrated TB diagnostic algorithm
GeneXpert MTB/Rif Ultra: RR detected
result interpretation
In the case of presumptive TB patients who undergo Xpert MTB/Rif testing and receive
a test result indicating the detection of Mycobacterium tuberculosis (MTB) and
Rifampicin resistance (RR), the interpretation should be as follows:

1. Before conducting a repeat test, it is essential to assess whether the

presumptive TB patient is at a high or low risk of having drug-resistant TB.

2. If the patient is determined to be at a high risk of DR-TB and the test results
confirm resistance to rifampicin, commence the patient on a treatment regimen
for MDR/RR-TB following the established guidelines.

3. In cases where the patient is deemed to be at low risk of DR-TB, perform a

second molecular WRD test using a different sample. The outcome of the
second test should be considered for clinical decisions
The following group are considered as Key
population group
• PLHIV
• Prison Inmates
• Miners, and mining communities
• Household contact or close contacts of people with TB of index bacteriologically
confirmed PTB cases
• Undernourished people or people with a body mass index ≤ 18,
• People with chronic renal failure, hospitalized patient
• Older people (60 years and older)
• Refugees/ immigrants
• Urban dwellers should be prioritized
• Workplaces with high occupational exposure
 High risk for DR-TB
 Previously treated patients, including those who were lost to follow-up, relapsed or failed a treatment
regimen;
 Non-converters (smear-positive at end of intensive phase); DR-TB patients’ household or close contacts;
 Symptomatic contacts of a patient who died while on directly observed TB treatment; health care
workers;
 High density urban settlements; prisoners; people in refugee camps; immigrants from settings with a
high prevalence of DR-TB;
 Internally displaced population and patients with danger signs.
 Another group of people to be considered as high-risk DR-TB because of the paucibacillary nature of
their samples or high risk of unfavorable treatment outcomes if the repeat test is false negative include:
 People living with HIV; EPTB samples; children; people with comorbidities like diabetics and older people (55 years
and above)
Algorithm using 10-colour Xpert
machine 50 GeneXpert
platforms in
country
installed

Pre XDR/XDR
platforms

DST for the

following;
• INH
• Floroquinolo
ne
• Ethionamide
• 2nd line
injectables
Treatment of MDR/RR-TB
The introduction of all oral shorter treatment
regimens for DR-TB.
• These are bedaquiline based regimens.
• There is an eligibility criteria for these proposed regimens
which is now reflected in the guideline.
• All oral 6 months BPaLM regimen.
• All oral 9 months
(2Bdq-Lfx-Lzd-Cfz-Cs/4Bdq-Lfx-Cfz-Cs/3Lfx-Cfz-Cs)
• All oral 9 months for paediatric on ART with protease
inhibitors 2Dlm-Lfx-Lzd-Cfz-Cs/4Dlm-Lfx-Cfz-Cs/3Lfx-Cfz-Cs.
• Longer all oral treatment regimens
 BPaLM treatment regimen
• The initial preference for eligible MDR/RR TB patients
should be;
• 6-month Bedaquiline, Pretomanid, linezolid, and moxifloxacin
(BPaLM)

• In instances of documented fluoroquinolone resistance (in

patients with pre-XDR-TB),
• 6-month bedaquiline, pretomanid, linezolid (BPaL) may be used
without moxifloxacin.
 Eligibility for BPaL/M
The BPaLM/BPaL regimen can be considered for patients with MDR/RR-TB under
the following circumstances
 Patient is aged 14 years or older
 No known allergy to any of the BPaLM component drugs;
 No evidence of resistance to Bedaquiline, Linezolid, Delamanid or Pretomanid,
 All people regardless of HIV status;
 No XDR-TB according to the up-to-date WHO definitions
 The patient is not pregnant or breastfeeding or, if the patient is a premenopausal woman, is
willing to use effective contraception.
Exclusion criteria for BPaL/M
 Patients with a high risk of treatment failure, such as extensive TB disease
 Patients with EPTB , however, patients with TB pleural effusion and children with TB
lymphadenitis may be considered for this treatment regimen
 Although bedaquiline, linezolid and fluoroquinolones have been used to treat MDR/RR-TB
in children, there are no data about the use of pretomanid in children, and further study is
required to expand the use of BPaLM/BPaL to children.
 Pregnant and breastfeeding women. For patients who become pregnant during treatment, it
will be necessary to discontinue the BPaLM/ BPaL regimen and prescribe another regimen
 Exposure to any of the drugs composing the regimen for ≥30 days. When exposure is
greater than 1 month, resistance to the specific drugs with such exposure must be ruled out
before considering the regimen
 Other considerations
There is limited or no evidence of BpaLM/BpaL use in some patient groups;
thus, a longer or other regimen should be considered as an option:

 Patients with low BMI (<17 kg/m2),

 Altered hepatic enzymes (3 times greater than the upper limit of normal),
 Baseline anaemia (haemoglobin <8 g/ dL),
 Thrombocytopenia (platelet count <150 000/mm3) or
 Pre-existing peripheral neuropathy of Grade 3–4.

 History of cardiac disease or concomitant drugs that prolong QTc.

 Regimen options and factors to be considered for selection of treatment
regimens for patients with MDR/RR-TB

Regimen MDR/RR-TB Pre-XDR- XDR-TB Extensive Extrapulmonary TB Age <14 years

fluoroquinolone TB pulmonary
susceptible TB disease

6-month Yes (BPaLM) Yes (BPaL) No No No No

BPaLM/BPaL

9-month modified Yes No No No No Yes

all-oral

Longer Yes*/No Yes*/No Yes Yes Yes Yes

standardized or
individualized 18-
month
 Introduction of the leprosy treatment guidelines

• Chronic infection caused by a bacteria Mycobacterium leprae (M. leprae)

• Primarily affects the peripheral nerves, skin, mucosa and few other
organs
• If left untreated, can cause permanent and progressive physical
deformities of the hands, feet, and eyes.
• Multi drug therapy (Dapsone, Rifampicin and Clofazimine) for the
management of various forms of leprosy and the role of steroid in the
management of leprosy reactions which are medical emergencies.
The discoverer
Dr. Gerhard Henrick Armuer Hansen, a Norwegian who discovered the
causal organism in 1873.
Therefore it is also known as Hansen’s disease (HD)
 Leprosy Epidemiology
Transmission of leprosy from source of infection to susceptible host is determined by the factors related to
agent, host and environment
Agent
• Leprosy is caused by bacteria - Mycobacterium leprae
• slow growing bacillus and replicates in 12-14 days.
• An acid-fast bacillus and non-cultivable in artificial media
Incubation Period
• Incubation period for leprosy is variable even 20 years or more.
• Average incubation period for the disease is considered as 5 years.
Source of infection
• untreated person affected by leprosy (Human being) is the main source of infection.
• the person affected becomes non-infectious with a few doses
of treatment, multidrug therapy(MDT)
Transmission of infection
• Transmitted from untreated person affected by leprosy to a susceptible person through droplets, mainly via the
respiratory tract.
• Prolonged contact with an un-treated person is a factor in transmission of infection
• healthy household contacts, social contacts are at higher risk of developing leprosy
Leprosy prevalence, prevalence rate and
annual trends in Malawi since 2010
Cases Rate
800 0.50

700 0.45
0.40
600
0.35
671
500 0.30
677
400 632 573 0.25
518
300 556 0.20
584 531 516 0.15
200 459 554 411 0.10
439
100 0.05
0 0.00
2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
 Diagnosis of Leprosy

• Mostly done clinically. 95% clinical diagnosis

• Presence of one or more of the cardinal signs is diagnostic of leprosy
Cardinal Signs to Diagnose Leprosy
1. One or more hypopigmented skin patches with loss of sensation
2. One or more thickened peripheral nerve and with loss of
sensation in the areas supplied by the nerve, and/or weakness of
the muscle supplied by that nerve
3. A Positive Slit Skin Smear for Mycobacterium leprae
Note: There are many skin diseases that mimick leprosy
 Classification and treatment of Leprosy
Classification Treatment of Leprosy
Leprosy can be classified into:
• Paucibacillary leprosy (PB leprosy) Leprosy is curable
• Treated with Multi-drug
• A case of leprosy, with one to 5 skin patches
therapy (MDT)
with loss of sensation and without
demonstrated presence of bacilli in a slit skin
-Rifampicin, Dapsone and
Clofazimine
smear
• Duration depends on
• Multibacillary leprosy (MB classification.
leprosy) -6 months for PB Leprosy
• 6 or more skin patches with
-12 months for MB Leprosy
loss/impairment of sensation; or
with nerve involvement • Drugs available in blister packs
• Demonstrated presence of bacilli in - available for adults and children
a slit skin smear irrespective of the (10- 14 years).
number of skin lesions
Multi-drug therapy (MDT)
MDT child (10-14 years) MDT adult blister
blister pack
pack

Back view of
Front view of MDT Front view of MDT MDT adult
Back view of MDT adult blister pack blister pack
child blister pack child blister pack
Leprosy Reaction
• This is sudden onset of inflamed lesions in leprosy
• may occur before, during treatment and after treatment.
• These are not drug adverse effects, but rather
immunological reaction of the body to M. leprae.
• Don’t stop MDT
• They are the main cause of deformities and disabilities in
leprosy
• Treatable with non-steroidal anti-inflammatories in mild
cases and Prednisolone in severe cases

Clinical manifestations for Leprosy reactions

• Inflammation of the already existing skin patches and nerves- Type 1
Leprosy reactions
• Appearance of red subcutaneous painful nodules- Type 2
• Involvement of other systems such as the eyes, nose, joints, testes, lymph
nodes, kidney and the liver
Disabilities, Stigma and Prevention

Disabilities, Stigma Prevention

• Disabilities can occur before, during and
• There is no prevention of
after treatment
Leprosy in the form of a vaccine
• Disabilities are the main cause of stigma • The causative agent, M.leprae is
and discrimination non-cultivable hence it is
difficult to produce a vaccine for
• Stigma causes challenges in early case
leprosy prevention
detection and successful completion of
treatment. • Early diagnosis and prompt
treatment is very important
• Many persons affected by the disease • Single dose rifampicin to
especially those with disabilities continue to contacts without active leprosy
experience social exclusion, depression and
loss of lively hood. Their families also suffer
stigma.
POST TB ASSOCIATED DISABILITIES AND MANAGEMENT
Definition of Post TB associated disability General post TB associated
TB associated disability refers to the range of health
disabilities
conditions which, such as illness, the disease and/or its
• Pulmonary impairments
treatment, in interaction with personal and
environmental factors, limit the day to day physical,
• Mental health disorders
social and economic functioning of people with TB and
especially in this case, TB survivors.
• Musculo-skeletal impairments
Definition of Post TB Lung Disease
• Neurological impairments
Post-TB Lung Disease refers to the residual pulmonary
manifestations and structural changes that persist in • Hearing impairments
individuals after successful completion of treatment for
tuberculosis (TB). Even after the eradication of active
TB infection, the lungs may sustain damage due to the • Visual impairments
inflammatory response triggered by the Mycobacterium
tuberculosis bacterium. • Renal impairments
POST TB ASSOCIATED DISABILITIES AND
MANAGEMENT
• Post TB lung disease: signs and symptoms
• Diagnostic criteria for PTLD
• Persistent respiratory symptoms
• Spirometry
• Abnormalities in lung function tests (spirometry)
• Abnormalities on chest X-ray
• Reduced exercise tolerance
• Management of PTLD
• Pulmonary rehabilitation
• Symptomatic management
• Pulmonary rehabilitation components
• Components: Assessment: Exclusion and Inclusion
• Components of PR in Malawi
• End line assessment: At 6 weeks , At 12 weeks and As seen appropriate up to one year
• M&E: The Facility tb register to be updated to capture the Post TB screening
 M& E
Changes have been made on the following registers
• Facility TB register( inclussion of Post TB diseases)
• TPT regsiter( all option for TPT included)
• Lab register: Additions done on Examination requested, Indications for Urine
Lam, Reflex test (XDR) Result
• Reporting templates updated to reflect changes made
• Presumptive TB Register
UPDATED FACILITY TB REGISTER – INCLUSION OF PTLD AND PRP DATA ELEMENTS

Facility TB register Updates: Inclusion of PTLD and PRP data elements to help in recording and reporting of PTLD data.
Reporting tools updated to reflect changes made
TPT Register ----- Updates

TPT Register: Inclusion of TPT options. Reporting tools updated to reflect the changes in the data recording tool.
 Laboratory Register --- Updates

Reporting Laboratory Results

ZN iLED LF LAM Stool

Number of presumptive
TB cases Examined

Number positive TB cases

Patients linked to TB
registration sites

Additions done on Examination requested, Indications for Urine Lam, Reflex test (XDR) Result
Reporting templates updated to reflect changes made
Key Updates On TB
Recording and
Reporting Tools
TB and Leprosy RR tools updates
Key registers updated
• Facility TB register( inclussion of Post TB diseases)
• TPT regsiter( all option for TPT included)
• Contact tracing register (Inclusion of 12 month follow screening outcome)
• Lab register: Additions done on Examination requested, Indications for Urine Lam, Reflex test (XDR)
Result
• Presumptive TB Register (Inclusion of Xray Screening result)
• Reporting templates updated to reflect changes made
• Leprosy Register
• Leprosy case reporting tool
Registers and reporting tools introduced
• Leprosy Contact tracing register
• Leprosy patient treatment card
• Leprosy CI reporting form
• Leprosy treatment outcome reporting form
1. TB LABORATORY SAMPLE REQUST FORM KEY UPDATES

Reason for change:-

• Ensures alignment to the changes made to TB diagnosis methods.
• Ensures inclusion of key data elements important for decision making
2. Laboratory Register --- Updates

Reason for change:-

• Ensures alignment to the changes made to TB diagnosis methods.
• Ensures inclusion of key data elements important for decision making

Laboratory Results reporting:-

• Reporting to be done by diagnostic method
• Centralize LF-LAM testing to allow complete reporting??. Observed discrepancy DHA vs NTLEP LF LAM data.
3. Presumptive TB Register--- Updates

Reason for change:-

• Ensures alignment to the changes made to TB screening in high-risk populations at facility level.
• Ensures inclusion of key data elements important for decision making

Case Detection Effort reporting:-

• The changes does not affect the current reporting of case detection effort data.
• Changes to the reporting structure will be made if need be.
 4. FACILITY TB REGISTER – Key Updates
Reason for change:-
• Ensures continuity of care for PTB patients.
• Ensures inclusion of key data elements important for decision making

Reporting of case finding data:

• The change does not have any effect on reporting of TB cases
• PTLD reporting form developed. To be treated as a different module.
 5. Contact Investigation Register
Reason for change:-
• Ensures documentation of HH contacts follow up @ 12 months
• Ensures inclusion of key data elements important for decision making

Reporting of CI data:
• Introduction of new reporting data elements to demonstrate contact follow up screening outcome @ 6 and 12
months.
• Guidance on frequency of reporting to be provided as soon as possible.
Possible Implementation challenges:
• Missing 12 month follow up screening result --- Need to define better implementation modalities.
 TPT Register ----- Key Updates
Reason for change:-
• Ensures documentation of different TPT options and treatment monitoring.
• Ensures inclusion of key data elements important for decision making

Reporting TPT data:

• Reporting will be done by TPT regimen for both enrollment and outcome data.
• The current frequency of reporting to be maintained.
THANK YOU