Lecture 9 - TB and HIV/AIDS

Question 1

M. tuberculosis, bovis, africanum are together known as ‘….’ . TB is spread from person to person through air via …. (= infectious particles of respiratory secretions). When these nuclei reach the lungs, … are taken up by phagocytosis by macrophages and are not … .

5-10% of people will develop active TB after MTB infection. This is dependent on: state of … system and location of the …. multiplication.

Those with … infection (MTB multiplies in context of sensitized immune system) have cavitating … lesions, because of Delayed-Type-… responses. In those cavitating lesions, large number of multiplying bacilli are contained by … cells and granulomata (commonly in apices of lungs).

Risk factors for infection: prolonged contact with people with … TB and environmental features associated with … + comprised … system (HIV/corticosteroid therapy).

Answer 1

M. tuberculosis, bovis, africanum are together known as ‘complex MTB’. TB is spread from person to person through air via droplet nuclei (= infectious particles of respiratory secretions). When these nuclei reach the lungs, bacilli are taken up by phagocytosis by macrophages and are not killed.

5-10% of people will develop active TB after MTB infection. This is dependent on: state of immune system and location of the bulk of MTB multiplication.

Those with latent infection (MTB multiplies in context of sensitized immune system) have cavitating caseous lesions, because of Delayed-Type-Hypersensitivity responses. In those cavitating lesions, large number of multiplying bacilli are contained by giant cells and granulomata (commonly in apices of lungs).

Risk factors for infection: prolonged contact with people with pulmonary TB and environmental features associated with poverty + comprised immune system (HIV/corticosteroid therapy).

Question 2

People with HIV who are exposed to complex MTB are … times more likely to develop active TB.

Answer 2

20-30 times.

Question 3

Clinical features TB besides “persistent coughing with sputum and/or blood”.

Answer 3

• Fever
• Night sweats
• Weight loss
• Malaise

Question 4

Diagnosis of TB.

Answer 4

• Isolation of MTB by culture
• PPD
• Interferon Gamma Release Assays (IGRA) - in response to MTB antigens
• Xpert MTB/RIF

Question 5

What is the disadvantage about isolation of MTB and sputum smear microscopy?

Answer 5

MTB has slow growth.

Sputum smear microscopy is not sensitive (onle half of TB cases detected).

Question 6

Why is Xpert MTB/RIF widely used?

What are disadvantages?

Answer 6

• Has high sensitivity and specificity
• Detects rifampicin resistance
• Can be used on desk top without laboratory isolation facilities

Disadvantages: expensive, requirement of uninterrupted power supply.

Question 7

Management of TB:

• Antibiotic chemotherapy
• BCG vaccination for prevention
• DOTS strategy

Describe them.

Answer 7

Antibiotic chemotherapy by using at least 3 drugs concurrently for 6 months (rifampizin, isoniazid and pyrazinamide).

BCG vaccination for prevention - live attenuated vaccine, is most effective in protecting children, does not protect adults very well against lung TB.

DOTS strategy - direct observation therapy, standardized treatment regimen and recording of sputum.

Question 8

Failure of diagnosing TB in South Africa because of:

… and logistic system failure = resource … settings.

Diagnosis of TB is dependent on:

• Effective and … management of human resources
• … supply of clinical materials.

Answer 8

Failure of diagnosing TB in South Africa because of:

Clinical and logistic system failure = resource constrained settings.

Diagnosis of TB is dependent on:

• Effective and responsive management of human resources
• Uninterrupted supply of clinical materials.

Question 9

The emergence of drug-resistant tuberculosis (MDR-TB) is a major threat to … TB control. MDR-TB does not respond to … and rifampicin (first-line anti-TB drugs).

MDR-TB is treatable by using …-line drugs. However, these options are limited and require extensive … with medicines that are expensive and toxic.

A major concern is the potential widening disparity between access to diagnostics and …, because the capacity of well-supervisioned secondary … programmes is small.

Answer 9

The emergence of drug-resistant tuberculosis (MDR-TB) is a major threat to global TB control. MDR-TB does not respond to isoniazid and rifampicin (first-line anti-TB drugs).

MDR-TB is treatable by using second-line drugs. However, these options are limited and require extensive chemotherapy with medicines that are expensive and toxic.

A major concern is the potential widening disparity between access to diagnostics and treatment, because the capacity of well-supervisioned secondary treatment programmes is small.

Question 10

HIV/AIDS is a … problem, but disease burden on developing populations. … is major aetiological agent of AIDS. HIV1 and HIV2 are both spread by … contact and by the injection of virus in … or blood products.

Reduction in mortality with ART: highly effective in suppressing viral … , reducing the amount of the virus in the blood to … levels and slowing … of HIV disease.

…. has biggest and most high-profile HIV epidemic. It has largest antiretroviral therapy programme globally, largely financed by own domestic … .

Biggest group affected of HIV: sex …, men who have sex with …, transgender …, people who inject …, … and orphans, adolescent girls.

Answer 10

HIV/AIDS is a global problem, but disease burden on developing populations. HIV1 is major aetiological agent of AIDS. HIV1 and HIV2 are both spread by sexual contact and by the injection of virus in blood or blood products.

Reduction in mortality with ART: highly effective in suppressing viral replication, reducing the amount of the virus in the blood to undetectable levels and slowing progress of HIV disease.

South Africa has biggest and most high-profile HIV epidemic. It has largest antiretroviral therapy programme globally, largely financed by own domestic resources.

Biggest group affected of HIV: sex workers, men who have sex with men, transgender women, people who inject drugs, children and orphans, adolescent girls.

Question 11

Virus in some African communities transmitted more by heterosexual contact, … from infected mothers.

Answer 11

Virus in some African communities transmitted more by heterosexual contact, perinatally from infected mothers.

Question 12

Diagnosis options:

• Voluntary … and testing (VCT)
• Anti-HIV … (ELISA, DAT, DOT immunoassays)
• Monitoring … counts, viral load estimates

Treatment:

• ….

Answer 12

Diagnosis options:

• Voluntary counselling and testing (VCT)
• Anti-HIV antibodies (ELISA, DAT, DOT immunoassays)
• Monitoring CD4 counts, viral load estimates

Treatment:

• ART - anti-retroviral therapy

Question 13

Prevention/Control strategies (3):

Answer 13

• Use of condoms, clean needles, treatment of STIs, circumcision.
• Prevention of mother to child transmission - nevirapine single dose during labour.
• Voluntary councelling testing

Question 14

What did the introduction of ART change in the clinical course of HIV?

Answer 14

HIV became a chronic condition (in developed countries).

In developing countries it was expensive and remained fatal illness.

Question 15

Pre-ART-care consists of 3 stages:

1. Diagnosis and CD4 count
2. Not ART eligible: pre-ART-care until ART eligible
3. ART eligible: pre-treatment steps and then ART

What is an unfortunate consequense of not giving everybody ART straight away?

Answer 15

You can lose people between each step and stage: right after diagnosis, CD4 count, pre-ART-care, pre-treatment and after ART initiation.

Less than a third of HIV positive patients not eligible for ART remained in pre-ART-care.

Question 16

Where ART starts too late: ART is more succesful if it is started before the CD4 count falls far below 350 cells/mm3 of blood.

What is another unfortunate consequence of starting ART not straight away?

Answer 16

Many HIV-positive people in resource-limited countries who receive ART still do not have a normal life expectancy. They start ART when they have a very low CD4 count.

Question 17

Why was there reluctance to provide ART in developing countries?

Due to concerns that treatment was too …, too complex, and that drug … would be promoted by inadequate programmes.

It was argued that ART was not cost-effective and that … interventions should be prioritized.

What became clear when programmes began to enrol increasing numbers of patients?

Lack of … health personnel would prove to be a major bottleneck in increasing … to treatment. There is a critical … of basic essential health staff.

Answer 17

Why was there reluctance to provide ART in developing countries?

Due to concerns that treatment was too expensive, too complex, and that drug resistance would be promoted by inadequate programmes.

It was argued that ART was not cost-effective and that prevention interventions should be prioritized.

What became clear when programmes began to enrol increasing numbers of patients?

Lack of qualified health personnel would prove to be a major bottleneck in increasing access to treatment. There is a critical shortage of basic essential health staff.

Question 18

Simplifying drug regimens and monitoring: The delivery of ART at the primary care level required a regimen that is … to store, simple to take, and could be administered by …-trained health staff via standardized guidelines (fixed-dose combination ART).

Because distance to health services is associated with poorer adherence and higher rates of defaulting from care, the … of antiretroviral care to health centres in rural areas is critical for improving programme outcomes.

Answer 18

Simplifying drug regimens and monitoring: The delivery of ART at the primary care level required a regimen that is easy to store, simple to take, and could be administered by lesser-trained health staff via standardized guidelines (fixed-dose combination ART).

Because distance to health services is associated with poorer adherence and higher rates of defaulting from care, the decentralization of antiretroviral care to health centres in rural areas is critical for improving programme outcomes.

Question 19

HIV infection is most potent known risk factor for active TB. TB is leading cause of death in South Africa.

The potential effects of changing HIV treatment policy on TB outcomes in South Africa considered two dimensions of ART expansion:

Answer 19

• Improving coverage of pre-ART and ART services.
• Expanding CD4-based ART eligibility criteria.

Question 20

What is the consequence of ART expansion on TB?

Answer 20

ART expansion could substantially reduce TB incidence and mortality in South Africa and could provide a platform for collaborative HIV-TB programs to effectively halt HIV-associated TB.