Overview of TB prophylaxis in Zimbabwe

1. Overview of TB Preventive Treatment

3. Factors that influence the
transmission of Mycobacterium
tuberculosis
Factor Description
Susceptibility Immune status of the exposed
individual (explains how prone to
getting the infection)
Exposure Duration, proximity and frequency of
exposure to an infectious individual
Infectiousness Number of tubercle bacilli expelled
into the air by the infectious
individual
Environment Surroundings of a living organism
which include the concentration of
infectious droplet nuclei, space,
ventilation, air circulation, lighting, air
pressure and specimen handling in
laboratory and related settings

4. Can we break the chain?
4

5. HIV – Strongest Known Risk Factor for TB
HIV+ and M.
TB infection
3-13%
each year
Lifetime
risk >50%
HIV- and M.
TB infection
5% during
first 2 yrs
Lifetime
risk 5-10%
Risk of developing
active TB disease

6. Difference Between
TB Infection and TB Disease
Latent TB Infection (LTBI) TB Disease (in the lungs)
Inactive tubercle bacilli in the body Active tubercle bacilli in the body
Tuberculin skin test may be positive or negative Tuberculin skin test may be positive or negative
Chest x-ray usually normal Chest x-ray usually abnormal
Sputum smears and cultures negative Sputum smears and cultures may be positive
No symptoms Symptoms such as cough, fever, weight loss
Not infectious Often infectious before treatment
Not a case of TB A case of TB

7. TB PREVENTION
• BCG injection- given at birth or 1st contact with new
born
- Provides some protection against developing severe
forms of TB such as meningitis in children
• TB Preventative Therapy (TPT)
- Medication is given to people with Latent TB infection
(sleeping TB) to prevent them from getting sick
(progressing to disease)
– People living with HIV (PLHIV)
– Contacts of TB
• Identifying and treating all TB cases
- Intervention backed by tracing contacts of those with
TB

8. TB PREVENTION
• Infection Prevention and Control in homes and
facilities
• -Administrative
• Triage
• Education of patients and community awareness
• Minimize patient waiting time
• Package of care for health care workers
• Training of staff
• Environmental
• PPE
8

9. What is TPT?
• What is TPT?
– TPT is the administration of anti-TB Medicines to individuals with
latent infection by M.tuberculosis in order to prevent progression to
active TB disease
• What’s the rationale?
– Tuberculosis is the most common cause of mortality and morbidity
among HIV infected persons
– TB is the second cause of morbidity and mortality in children
– Multiple studies have shown that TPT reduces TB incidence in HIV
infected patients by 33% – 64%*
– Although ART reduces the likelihood of developing TB disease, studies
have shown that TB incidence among HIV infected receiving ART is still
greater than in the general population**
– Use of TPT in patients who have successfully completed a course of TB
therapy has been shown to markedly reduce the risk of subsequent
active TB
9

10. Introduction of New TPT regimens 3HP and 3RH

11. Outline
• Why 3HP for TPT?
• 3HP for TPT: Key considerations
– Safety & Tolerability
– Use Special Populations: Children
– Contraindications
– Drug-Drug Interactions
• Summary and Key messages

12. PLHIV and Children < 5 are two high risk populations
requiring TPT in high burden countries
• TB is very common, and the leading cause of death in
PLHIV.
– PLHIV are up to 37 times more likely to develop
active TB following infection
– WHO recommends that all PLHIV take some form
of preventive therapy, usually as soon as they are
diagnosed with HIV and beginning ART
• Children under 5 years:
– Active TB is in the top 10 killer diseases of children < 5 years
– 1.1 million children fell ill with TB globally in 2018
– There were 205,000 child deaths due to TB (including
CLHIV) in 2018
WHO Global TB Report, October 2019

13. Globally, AIDS-related mortality amongst PLHIV is driven by a
small number of OIs, notably TB
TB
35%
Cryptococcal
Meningitis
18%
Toxoplasmosis
15%
PCP
15%
Severe
bacterial
infections and
other
17%
Source: WHO AHD Guidelines, 2017.
The majority of AIDS-related deaths of hospitalized adults are caused by
opportunistic infections, including:

14. Among TB exposed children, IPT reduces the risk of TB
disease by > 60%
Marais et al. IJTLD 2004; Ayieko,et al. BMCID 2014; Hsu,et al. Jama 1984.
30
20
10
0
40
<1 1 to 2 2 to 5 5 to 10 10 to 15
Children under 5 are at HIGHrisk
of progression to TB disease
PTB Disseminated TB
Age in Years
Disease
Progression
(%)
IPT reduces the risk of TB disease
by >60% among TB-exposed
children
• Full implementation of household contact management including TPT for
exposed children <5 years, CHLIV and for TST+ exposed children age 5-14
years
– Prevents 159,500 cases of TB and 108,400 deaths in children younger
than 15 years per year

15. Evidence shows that TPT reduces AIDS related mortality in
PLHIV
Badje et al, the Lancet Global health 2017; 5:e1080-89
TEMPRANO Trial Long term follow up:
• Reduction in TB mortality in PLHIV with high CD4 counts, after 6
months of IPT, independent of ART
• Immediate ART + 6H reduced TB and deaths including where with CD4
count > 500 cells/mm3

16. WHO today recommends a package of interventions for
patients with Advanced HIV Disease (AHD) including TPT

17. TPT is listed as a key intervention to be pursued in the
WHO’s END TB Strategy

18. WHO End TB Strategy: New products, including for TPT, are
needed for a 17% annual reduction in TB prevalence by 2035
Raviglione M: WHO END TB Strategy, 2015

19. Addendum to TB and HIV Guidelines on management of
latent TB

20. TPT options for children-Addendum to TB and HIV
Guidelines on management of latent TB – Regimen
choice
Population Group Preferred Treatment Alternative
Adults
PLHIV on Efavirenz (EFV) and
Dolutegravir (DTG) based regimen
Three months of weekly Rifapentine plus
Isoniazid
[3HP]
Six months of daily Isoniazid
alone [6H]
PLHIV on Tenofovir Alafenamide
(TAF)-based regimen, PIs and NVP
Six months of daily Isoniazid alone [6H] -
HIV negative contacts (adults and
adolescents >15 years)
Three months of weekly Rifapentine plus
Isoniazid [3HP]
Six months of daily Isoniazid
alone [6H]
Children
CLHIV on EFV-based regimen
(Adolescents, children >2yrs)
Three months of weekly Rifapentine plus
Isoniazid [3HP]
Six months of daily Isoniazid
alone [6H]
CLHIV on DTG -based regimen,
PIs and NVP
Six months of daily Isoniazid alone [6H]
HIV negative contacts (children
under 15 years)
Three months of daily Rifampicin plus
Isoniazid
[3RH]
Six months of daily Isoniazid
alone
[6H]
Special Groups
*MDR-TB Contacts Six months of daily Levofloxacin [6LFX]
20

21. In summary
• Zimbabwe is implementing three TPT treatment regimens as follows:
– weekly doses of isoniazid and rifapentine for three months, thus 12 doses (3HP)
– daily doses of isoniazid and rifampicin for three months (3RH)
– daily doses of isoniazid for 6 months (6H)
• Summary recommendations on the use of above regimens:
– 3HP is the recommended regimen for PLHIV aged above the age of two years with no
contraindications to 3HP.
– 3HP remains the recommended option for adult contacts aged above 15 years
– 3RH is the recommended regimen for HIV negative child contacts below the age of 15
years
– 6H is the recommended alternative regimen where contraindications to 3HP and 3RH
exist
– 6H is the recommended regimen for PLHIV on TAF-based regimen, PIs and NVP.
– 6H is the recommended alternative option for CLHIV on DTG-based regimen and PIs.
– 6H is the recommended option for pregnant women

22. Treatment completion guidance for recommended regimens
WHO: Operational Handbook on tuberculosis. Module 1: Prevention. Tuberculosis Preventive Treatment , 2020
Regimen
Total
duration
(months)
Expected
number
of doses
80% of
recommended
doses (days)
Extended time for treatment
completion (days)
(treatment duration +33%
additional time)
6H (daily) 6 182 146 239
3HR (daily) 3 84 68 120
3HP (weekly) 3 12 11* 120
*90% of recommended number of doses

23. WHY 3HP AND 3RH

24. Zimbabwe PLHIV Newly Enrolled into Care started on IPT (2018
& 2019)
106,046
118,800
20,193 (19%) 19825 (17%)
0
20,000
40,000
60,000
80,000
100,000
120,000
140,000
2018 2019
#of
patients
PLHIV enrolled into Care PLHIV newly enrolled into care started on TPT

25. When introducing a new product / drug, including for TPT,
many factors have to be considered
Patient factors Clinician factors
National Program
factors
• Efficacy (add
notes)
• Toxicity
• Tolerability
• Convenience
• Efficacy
• Toxicity
• Availability
• Additional
requirements for
use
• Drug interactions
• Special Patient
Populations
• Availability
• Toxicity
• Special Patient
Populations
• Cost efficacy
• Approach to
introduction

26. e.g. Factor #1: INH for TPT -> Is INH Safe?
• Risk of fatal DILI (drug induced liver injury): 0.001% to 0.06%
— Risk of liver injury from amoxicillin-clavulanate: 0.06%
— Risk of liver injury from cotrimoxazole: 0.005%
• Goldmine worker study in South Africa:
— Of 24,221 participants who received IPT, 17 cases of DILI
(0.07%) with one fulfilling criteria for severe adverse
reaction
• Rates of hepatitis are the same in PHLIV and HIV negative
individuals on 6H
YES! INH is comparatively safe with a very low risk of severe adverse reactions.
This risk is usually overstated!
deLamos et al. 2016, DDS; Akolo et al. 2015, World J Virol.; Churchyard et al. 2014, NEJM; Jick et al. 1995, Pharmacotherapy

27. e.g. Factor #2: TPT and drug resistance -> Does TPT promote
resistant TB?
Not if active TB is excluded:
• TB infected persons have few organisms, dividing slowly, hence
low risk of selecting for drug-resistance.
• Most resistance arises from suboptimal treatment of active
disease, so preventing active disease may be beneficial for
resistance.
• Remember to screen for TB at every visit

28. Does TPT cause resistance in children?
Colijn, et al. PLOS One2011
No!
• Children have paucibacillary TB disease:
— On average pulmonary burden of disease is <104 mycobacteria
— This is why smear and culture are often negative in pediatric
TB disease
• Mutations occur in 1 out of 106-109 dividing mycobacteria.
• Children do not typically have enough M. tuberculosis organisms
to allow resistance to occur

29. TPT in pregnancy
• Pregnant women living with HIV are at higher risk for TB
during pregnancy and postpartum, which can have severe
consequences for both the mother and the infant (Gupta
et. al 2007; Salazar-Austin et. al. 2018)
• Rifampicin- there is no safety or efficacy data are
available specifically for pregnant and postpartum
women (Denti et. al. 2015). Do not give 3HR
• There are limited data on the efficacy and safety of
rifapentine in pregnancy and therefore 3HP should not be
used in pregnancy until more safety data are available
• NB: 6H is safe to administer in pregnancy

30. TPT in pregnancy
Study
Comparison /
Setting
Key Conclusions
Tshepiso
 Birth outcomes
in HIV infected
women on IPT
 Soweto, South
Africa
 155 pregnant women
living with HIV who
reported receiving IPT
vs not and followed
for one year
 Fewer events among
infants exposed to IPT.
 Multivariate analysis
showed lower risk of
adverse pregnancy
outcomes among
mother-infant pairs
exposed to IPT during
pregnancy than IPT
unexposed mothers.
Salazar-Austin, Tshepiso Study Team. CROI 2019

31. Shorter regimens such as 3HR and 3HP are a potential game
changer for TB prevention - Public Health Case for 3HP
• Implementation of WHO guidelines for IPT for PLHIV and child contacts remains
poor
• A short-course regimen of isoniazid and rifapentine weekly for three months
(3HP) is now available
• 3HP:
— Is associated with less toxicity, better adherence & similar efficacy to IPT
— May be logistically easier for programmes to scale up
— Less side effects
— Better adherence
— Similar efficacy to IPT
— Less burden to health programs to implement
— Longer half-life and greater potency against MTB than rifampicin
— Safe with DTG and EFV- based regimens
• Scaling up 3HP will avert TB cases & deaths

32. 3HP Product Profile
Product Isoniazid/Rifapentine (H/P)
Current
Manufacturers
Sanofi and Macleods
Formulations • Single:
—(INH (H), RPT (P) or
— Double FDC INH/RPT
(HP) available
—INH 300mg, RPT 150mg
• Pediatric FDC of 3HP for
trial purposes undergoing
evaluation
• Administered once-weekly
for 12 weeks
Cost/Course RPT: $15/ INH $1-2 1 pack RPT, 1 INH, 1 B6

33. 3HP Product Profile: Treatment Dosage for Adults
Medicine Formulation
Weight bands for patients >14 years
30–35kg 36–45kg 46–55kg 56–70kg >70kg
Isoniazid 300 mg 3 3 3 3 3
Rifapentine 150 mg 6 6 6 6 6
Isoniazid +
Rifapentine*
300/300 mg 3 3 3 3 3
• *Fixed dose combination in development
• Add Pyridoxine 25mg weekly in PLHIV (increase to 50mg weekly if
symptoms of peripheral neuropathy)

34. 3HP Consideration: Safety -> 3HP is as safe as INH only
regimens
23 RCTs and 55 non - randomised studies
•3HP (11.5%), 6H (36.1%), 3HR (4.2%)
Rate of any adverse event
•3HP (1.7%) vs 6H (3.8%)
Withdrawals due to AEs
•3HP (2.2%) vs 6H (0.05%)
Flu like reactions
•3HP (1%), 6H(6.3%), 3HR (0.5%)
Hepatotoxicity
Pease: Pharmacoepidemiol Drug Saf. 2018

35. TPT related side effects in children are less frequent and less
severe. 3HP is well tolerated as more effective than 6H
1Villarino ME, JAMA Pediatr 2015
• Side effects of all
TPT regimens
typically less
frequent and less
severe in children
• Poor outcomes
can be prevented
with anticipatory
guidance and
quick
intervention
6H 3HP*
* In study participants who were children
The results of a study of 3HP in children aged 2 to 17 years indicated
that it is well-tolerated and as effective as 9 months of daily
isoniazid, only with higher completion rates1.

36. Pyridoxine (Vitamin B6) Supplementation dosing
Age Pyridoxine Dose (50mg)
Infant (< 1 years) ¼ tablet* (12.5mg)
Toddler (<5 years) ¼ tablet* (12.5mg)
School-aged (≧ 5 years) ½ tablet (25mg)
• Pyridoxine is only necessary for:
—Children living with HIV (CLHIV)
—Severely malnourished children (most clinically
diagnosed with TB)
—Pregnant adolescents
—People living with HIV (PLHIV)
*Crush or fragment into liquid or soft foods

37. Case studies – MAJOR SIDE EFFECTS AND MANAGEMENT!!

38. Case #1
A 7 year old with very
advanced HIV, on ART
(ABC/3TC/DTG) and
IPT
Oct ‘19
• No evidence of
active TB and
no IRIS or drug
allergy after 2
months of ART
• He has gained 2
kg since starting
ART
• 3HP for TPT is
started with
INH(10mg/kg
daily
1st clinic review since
initiation of 3HP
12 Dec
‘19
2 months later he
begins to complain
about an abnormal
feeling in his feet
History: Feeling is a
tingling sensation in
both feet, worse at
night, started toes,
now bottom of both
feet
12 Dec
’19
Exam:
• Afebrile, no
rash, no LA.
• Liver/spleen are
normal size,
• Motor function
normal
• Sensation is
decreased in
both feet below
the ankle
• There is no sign
of trauma
Many risk factors for
PN here!
INH - Peripheral
Neuropathy!
Risk factors for PN:
• Lack of pyridoxine use,
Advanced HIV infection,
?Malnutrition (B12,
folate)
Management:
• Pyridoxine 50 mg daily
• Multivitamin supplement
• Nutritional support
• Stop 3HP
• Monitor weekly
• Symptoms resolve you
may consider re-starting
INH at a later time

39. Case #2
19 year old lady,
started 3HP at your
clinic three weeks ago
Jan ‘20
• Came to your clinic,
symptoms of
vomiting, low fever
and loss of
appetite.
• Symptoms started
3 weeks ago and
became worse
during the recent
week.
• Has been on TLD
for 3 months.
• What will you do
next?
Not other new drugs
or traditional
medicines
Hx #2
Exam:
• Normal
Labs:
• ALT: 98UI/L
• AST: 75UI/L,
• Bilirubin: 16
mol/L
• WBC: 8.0
• Hb - 10.1.
• Hep A/B/C neg
Continued ART and
3HP
Feb
’20
2 weeks since last
visit:
• Physical exam
at 2 week
follow up:
jaundice,
hepatomegaly
are noted
• ALT: 180UI/L
• AST: 101UI/L
Always assess for risk
factors & related
symptoms e.g. viral
Hepatitis, medications,
alcohol, OIs
INH - Hepatitis!
Management of INH Hepatitis:
• Baseline LFTs: not usually
required prior to start 3HP
unless with risk factors or
symptoms. LFTs normal: no
further tests.
• LFTs abnormal: monitor
monthly LFT during IPT.
• LFTs <5x ULN, no symptoms:
Continue IPT, increase the
monitoring frequency
• LFTs ≥3 ULN plus symptom or
LFTs ≥ 5 ULN with or without
symptoms: Stop 3HP

40. #3 Rifapentine Safety profile
• RPT is a very well tolerated
drug, with lower overall
incidence of AEs
• Most often mild and self-
limited.
• Discontinuation rates observed
in clinical trials and in
programme data are low.
Common AEs Rare but serious
AEs
• Nausea
• Vomiting
• Diarrhea
• Loss of appetite
• Flu symptoms
• Headache
• Joint pain
• Itching or rash
• Eye redness
• Abnormal liver function tests
• Hepatotoxicity
• Hypersensitivity

41. Case studies – Share experiences of AEs

42. #4 Patient Monitoring on 3HP – Is Directly Observed Therapy
(DOT) necessary?
“iAdhere” study
• Randomized controlled trial of self-administered 3HP(SAT) vs
DOT in Hong Kong, South Africa, Spain, and the USA (77% in
USA)
• In US ≥18 years showed noninferior treatment completion and
safety of 3HP-SAT 1
• Did not recruit PLHIV taking or about to commence ART
SAT has not been studied in RCT for persons aged 2-18 years but
expert consensus resulted in CDC recommending SAT for anyone >2
years 2
WHO recommends: “All TPT can be self-
administered”
1. Belknap Ann Intern Med 2017 2. Borisov MMWR Morb Mortal Wkly Rep 2018

43. Routine monitoring should be done at every contact with
healthcare provider, CARG leader or CHW
Sound clinical judgement is required to ensure
that the benefits of TPT outweigh the risks
Monitoring visit checklist
Screen for active TB
Screen for AEs and
assess tolerability
Assess adherence and
provide support as
appropriate
Assess for new
medications that can
interfere with 3HP
Repeat AST for patients who
had a raised baseline test
Advise on missed doses
Baseline
laboratory work
Directly
observed
therapy

44. Adherence supportive interventions should be tailored to
• Specific risk groups
• Local context
People living with HIV will also be on ART which may facilitate adherence to 3HP,
but additional reminders may need to be in place for the weekly dosing such as
routine events (scheduled DSD meetings, CHW support etc)
Household contacts may require additional support as they are typically
healthy
Children will need caregiver support
Concerns about adherence should not be a barrier to 3HP
What do you need to know about adherence support?

45. Ensure confidentiality and obtain their
commitment to complete treatment before
initiating 3HP
Ensure that the patient understands TPT and has
materials available in patient’s or care giver’s
primary language and at appropriate literacy
level
Include patient’s family and/ or caregivers in
health education whenever possible.
Reinforce educational messages at each visit
Give clear instructions regarding side effects and
when to report them to a health care provider
Allow opportunities for questions and answers
Develop an adherence plan with support of a
Healthcare worker that specifically focuses on
weekly vs daily adherence strategies
How to counsel a patient on 3HP about adherence

46. How to counsel clients on Adverse Events
If you have symptoms concerning for
liver damage or severe hypersensitivity:
Do not take any further doses of 3HP
Contact a healthcare provider for advice as
soon as possible
Only continue taking 3HP once you have
been advised to by your healthcare
provider
Situations in which you should also contact
your healthcare provider:
Any persistent or concerning symptoms
Any change in your health or medical
situation (new medicine, new diseases)
Any change in your social situation (moving
away, change in job, not enough food)

47. How to counsel a caregiver on 3HP and adherence in children
Explain and emphasize to caregiver and child why
they must take the full course of treatment
Anticipate risk factors for poor adherence including
multiple caregivers, ensure family engages all
caregivers
• Provide adolescents with education and adherence
support directly, especially if living with HIV
Dealing with Medication Refusal:
• Change food type to better mask taste. Crush and place
in an easy to swallow food rather than mixing in water
• Provide a post-dose reward
If a child vomits within 30 minutes of a dose  re-
dose
• Must provide families with an extra dose
• Ensure families use of extra doses will not be
viewed negatively

48. Adult or adolescent >15 years
living with HIV
(any CD4 or ART status)
Screen for Active TB
disease
No symptom
suggestive of TB
Investigate for TB and
other diseases
Other diagnosis
TB Treatment
Initiate alternative
regimen (6H)
Assess for contra-
indications to 3HP
Contraindications to
3HP
No contraindication
Initiate 3HP
Defer preventive
treatment until contra-
indication resolved
TB diagnosed
Treat as
appropriate
Eligible for other TPT
regimens
Any one
symptom
Follow up and
consider TPTonce
illness resolved
Symptoms:
Currentcough
Any fever
Unintentional weightLoss
Any night sweats
Algorithm for adults and adolescents ≥15 years
living with HIV
1
2

49. Notes for the adult algorithm
Contra-indications to 3HP
• Active Hepatitis (acute or
chronic)
• ALT/AST > 3x ULN
(regardless of symptoms) if
these are known
• Regular & heavy alcohol use
• Severe peripheral Neuropathy
• Pregnant or breastfeeding
mothers
• Unwilling / unable to use
non hormonal
contraception
• On Protease Inhibitor – based
ART
2
WHO recommends symptom
screen (cough, fever, weight
loss, night sweats) to rule out
TB.
-no chest X-ray
-No proof of infection
(TST/IGRA) These are
therefore not necessary for
TPT initiation except where
mandated by national
programs.
1

50. Eligibility - contraindications to 3HP
Pregnancy and breastfeeding
3HP should not be given to pregnant or
breastfeeding women
Women of child bearing age need to use non-
hormonal contraception (condoms, diaphragm,
IDU)
Any liver damage:
• Active hepatitis
• ALT/AST >3x ULN even if asymptomatic
• Regular and heavy alcohol use (could use self-
reported alcohol of units/ week >28 (men)/ >21
weeks women)
INH can cause PN. Caution
should be exercised in
persons who have severe
disease. Vitamin B6 helps
prevent PN
Peripheral neuropathy
Numbness, burning, sharp pain, tingling ofhands
or feet
Diabetes, vitamin deficiency and medicationscan
cause PN
INH should not be given to
persons with known pre-
existing liver damage to avoid
an additive effect on liver
function
There is currently insufficient
data to support the use of
RPT and INH in pregnancy.
Rifapentine can decrease
levels of hormonal
contraception

51. 3HP Consideration #3: What is NOT a contraindication to
3HP?
As all
things
TPT…
• Previous TB preventive
treatment
— Close contacts of index
patients should receive TPT
after every new exposure;
regardless of the contact’s
age, HIV status or TPT
history
• Successful completion of TB
treatment
— Any new exposure to TB
warrants a new course of
TPT

52. 3HP DDIs with anti-malarial treatment
KEY:
• DDI may reduce exposure to artemisinin-based
combination therapy (ACT)
• Rifamycin (e.g. RPT) and/or INH-induced liver
injury may be worsened by an amodiaquine-
containing ACTs with dire consequences
• Rifamycins have been shown to have anti-
plasmodial activity, enhancing the antimalarial
effect of Quinine for example
Badejo et al BMC Malaria Journal 2014
• Treatment of malaria in an individual on anti-TB drugs requires
dexterity in order to avoid adverse drug interactions
• PLHIV in areas where malaria or severe bacterial infections are
common should receive 3HP together with cotrimoxazole.

53. How to use 3HP in settings where malaria is prevalent
WHO. Guidelines for the treatment of malaria, 3rd edition. 2015
• Rifampicin, of the same
medication class as RPT, is
known to decrease
oArtemisin combination
therapy (ACTs)
oDoxycycline
oMefloquin
oQuinine
oPrimaquine
oTafenaquine
• Restart 3HP once the
episode of malaria is
resolved
Malaria present when screening for TPT
eligibility - Delay 3HP start
New malaria while on 3HP - treat for
malaria and monitor clinically
Malaria recrudescence while on 3HP –
retreat malaria following national
guidelines
Severe malaria (impaired consciousness,
low blood glucose, jaundice, kidney
failure, anemia and parasitemia >10%),
Treat malaria urgently – STOP 3HP

54. 54
Pharmacovigilance
 The science and activities relating to the detection,
assessment, understanding and prevention of
adverse effects or any other drug-related problem
(WHO).
 An arm of patient care and surveillance
 Aims at getting the best outcome from TB preventive
treatment with medicines

55. 55
Why pharmacovigilance for anti-TB medicines?
 Poor information on incidence of ADRs - Difficult
to assess the risk benefit ratio of treatment
interventions.
 To have locally generated data on ADRs.
 Some of the medicines used in the treatment of
DR-TB are new or repurposed molecules whose
ADR induction profile is not well understood
 More than one medicine for at least 6 months
(speaker notes)

56. 56
 Reporting of ADR by health care workers
in Zimbabwe, copies are downloadable
from : www.mcaz.co.zw
« It is critical for health care workers to document and report every incident that
signifies an ADR regardless of the presenting severity. This is particularly
important for TPT medicines since they are newer and experience of use is
limited”
Adverse drug reaction reporting

57. 57
All Adverse Drug Events are reported to the National Pharmacovigilance Centre (MCAZ)
through existing national pharmacovigilance tools
MCAZ National PV center (est. 1998)
• Key Focus: Regulation, Drug monitoring, Patient Care &
Safety, Advocacy
• Functions:
• Drug Testing, Capacity Building,
• Causality Assessments,
• PV knowledge base management
• Policy guidance
• WHO Reporting (Uppsala Centre)
• AE and SAE data collection (Paper, Electronic)

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Importance of Recording and Reporting
58
Patient level
 Assess patient progress
 Allow sharing of information with patient
 Aid staff in making treatment decisions
 Help staff provide adequate services to patient and make referrals
 Ensure continuum of care and transfer of information between health
facilities
Programmatic level:
Provide relevant information to NTP
Help improve service delivery
Establish baseline information and identify trends
Instil accountability at all levels

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Data Collection Tools – TPT Register

60. 60
THANK YOU