AIDS action Issue 31 Page 1 2
Issue 31 December 1995 - February 1996
Tackling TB and HIV
A third of the world's population is infected with tuberculosis (TB). Every year three million people die from TB, mostly in developing countries where it kills one in five adults. Despite the development of effective anti-tuberculosis drugs, TB causes more deaths than any other infectious disease. It is now one of the main causes of death in people with HIV infection and, since the mid-1980s, has increased dramatically in developing and industrialised countries. Like HIV, having TB is associated with poverty and often results in discrimination and stigma, and abuse of human rights.
But TB can be cured. With correct treatment, people with TB - including those who also have HIV infection - are no longer infectious after two to three weeks and almost all are cured after taking appropriate drugs for at least six months. Without treatment more than half of those with TB disease are likely to die. Proper treatment also prevents the spread of TB because it makes people non-infectious.
What is TB?
Tuberculosis is usually caused by infection with the bacillus Mycobacterium tuberculosis. TB normally affects the lungs - this is called pulmonary TB. Sometimes the TB germs enter the bloodstream and spread to other organs in the body - this is called extra-pulmonary TB.
Pulmonary TB is much more common than extra-pulmonary TB. When a person is exposed to TB germs and becomes infected, they have TB infection (or latent TB). Sometimes the infection progresses to TB disease (tuberculosis, active tuberculosis or active disease). Once infected with TB a person remains infected for the rest of their life. But most people do not become ill with TB disease and infectious to others.
A healthy immune system can stop the germs from multiplying enough to cause this one illness. But the TB germs may continue to multiply and destroy the lung tissues, leading to active TB disease, particularly if a person is in poor health, or has HIV infection. The symptoms of pulmonary TB disease are cough for more than three weeks (sometimes with bloody sputum) and chest pain. Exhaustion, night sweats, fever and weight loss are symptoms of both pulmonary and extra-pulmonary TB.
Active pulmonary TB is the only form of the disease which is infectious, spreading from person to person via the air. The lungs of a person with active disease develop cavities (spaces) which are full of TB germs. When the person coughs or sneezes large numbers of TB germs from the lungs are sprayed into the air in tiny droplets. Family, friends and health workers who have close contact with a person who has infectious TB are at greatest risk. TB spreads most easily in over-crowded and badly ventilated places. Sputum smear tests are used to find out if a person has active TB and is infectious. A positive sputum smear test means that a person is coughing up TB germs and should be treated.
Special issue TB and HIV
TB prevention and treatment
HIV and TB links
Education and training
preventive TB therapy
TB and HIV
A growing crisis
WHO has predicted a global TB epidemic, causing 30 million deaths during the 1990s. The number of new TB cases worldwide each year is expected to increase from around seven million in 1990 to over ten million by 2000. There are two main reasons why TB is a growing problem: neglect of TB programmes and the spread of HIV. Effective TB control requires a properly functioning health service with good management, diagnostic facilities, trained staff and regular drug supplies including reserve stocks. But financing TB programmes has not been a priority.
There has also been little community education to tell people about TB symptoms, reduce discrimination and to encourage them to seek treatment.
In some places there has always been a stigma attached to TB. People risk losing their jobs and housing if it becomes known that they have TB. The stigma and stress may be worse for women. In some cultures, having TB may make it difficult to find a husband or result in divorce. links between HIV and TB are worsening the stigma.
Worldwide the number of people infected with both HIV and TB is rising and will reach four million by the year 2000. About half of TB patients in sub-Saharan Africa are also infected with HIV. In Tanzania, TB cases doubled between 1983 and 1991, a third of them related to HIV. In Asia, TB is already one of the most important life threatening opportunistic infections associated with HIV. In Europe and North America the rise in TB cases since the mid-1980s is due partly to HIV, but also to other factors such as increasing homelessness and poverty, and worsening public health systems.
How do TB and HIV interact?
HIV and TB interact in several ways in individuals:
Reactivation of latent infection People who are infected with both TB and HIV are 25-30 times more likely to develop TB disease than people infected only with TB. This is because HIV stops the immune system working effectively and TB germs are able to multiply rapidly. In developing countries where many people are infected with TB and HIV, HIV-associated TB disease is very common.
Primary infection New TB infection in people with HIV can progress to active disease very quickly. In the USA active TB disease in two-thirds of people with both infections is due to recent infection rather than reactivation of latent infection. People with HIV are at risk of being newly infected if they are exposed to TB germs because their weakened immune system makes them more vulnerable.
Recurring infection People with HIV who have been cured of TB may be more at risk of developing TB again. However it is not clear whether this is because of re-infection or relapse.
In the community there are more new cases of active TB because more people infected with TB develop active disease, and those newly infected become ill faster. This means that there are more people in the community who are infectious to others. Larger numbers of people with active disease means that more people will die from TB unless they are treated. Tuberculosis is now one of the leading causes of death in people infected with HIV. In Abidjan, Côte d'Ivoire, for example, a third of people with AIDS are thought to have died from TB. But TB mortality is only higher in people with HIV if it is untreated. HIV-associated TB can be treated effectively if people are diagnosed early and given proper treatment.
The association of TB with HIV means that people suffer additional discrimination. If a young adult develops TB other people may assume that they also have HIV. Health workers need to respect the confidentiality of TB patients in the same way as that of people with HIV, while also ensuring that communities and families know how to prevent its spread. TB in people with HIV is no more infectious than TB in people who do not have HIV.
Community education is needed to increase awareness that TB is curable and, most important, that people are no longer infectious after the first few weeks of treatment. It is essential to tackle the stigma and fear associated with both TB and HIV.
TB and HIV
Principles of TB control
Proper detection and treatment
People can only spread TB to others when they have active TB disease. The key to TB care and prevention is to identify people who are infectious and to provide prompt and effective treatment to make them non-infectious and cure them.
Case finding should prioritise identifying people with smear positive active TB because they are the most important source of infection in the community. Passive case finding means diagnosing infectious smear positive people who come to health facilities with symptoms of TB.
Active case finding means trying to reach all those in a community who may have infectious TB disease. It is important to check children under five in a patient's family. However, in general active case finding is more expensive than passive case finding and studies have shown that fewer people may complete treatment.
Treatment and supervision
Anti-tuberculosis drug treatment is 95 per cent effective only when it is used correctly, so it is most important that TB patients complete their treatment. The treatment is based on a combination of drugs taken for at least six months, in two phases: an initial phase and a continuation phase. The combination of drugs varies as does the length of treatment (see pages 8-9). People may find it difficult to take anti-tuberculosis drugs for a long period of time. But they can be helped by a well supervised programme and use of DOT (directly observed therapy) which means watching the person take their drugs (see page 11). It is especially important that patients take their treatment during the initial phase to make them non-infectious.
BCG vaccine protects children against the most severe and life-threatening forms of TB disease in childhood, such as tuberculous meningitis. BCG does not reduce the risk of being infected with TB, and its impact on preventing pulmonary disease is limited. So BCG has a very restricted role in TB control because it does not prevent transmission of infection in the community.
BCG vaccination should be given to young children as early in life as possible, preferably immediately after birth. The only exception is if the mother is sputum smear positive when the baby is born. In this situation the infant should be given preventive therapy for six months. At six months a tuberculin test should be done. If it is negative BCG vaccination should be given.
Giving BCG vaccine to HIV-positive infants may increase complications or disseminated BCG disease (illness caused by the vaccine itself) in infants with severe immunodeficiency. However, the benefits of BCG vaccination outweigh the possible risks to HIV positive infants. Therefore BCG vaccine should be given to all infants, including those who may be HIV positive, and only withheld from infants with symptomatic HIV disease.
Preventive therapy (or chemoprophy-laxis) means giving anti-tuberculosis drugs to an individual with TB infection (or at very high risk of being infected) to prevent progression to active disease. In developing countries preventive therapy is only usually recommended for young infants whose mothers have active pulmonary TB, and children under five who are living with a person with infectious TB. Chemoprophy-laxis is also beneficial for individuals with HIV and TB infections, to preventing them from developing active TB disease. However, there are still many unanswered questions, and providing preventive therapy is not a feasible option for most national TB programmes (see page 15).
Women and TB
TB is often more likely to be detected and treated in men than in women Women and men may be equally affected but often fewer women seek treatment for reasons including:
lack of time because of work and family demands
lack of money and transport
the need to get permission or be accompanied by a male member of the family to a health centre
stigma (some forms of TB can cause infertility)
poor education which limits access to information about symptoms and treatment of active disease
lack of female health workers in cultures where female modesty is important
TB programmes need to be more responsive to the needs of women If they are to successfully increase case finding and treatment.
Source Smith I, and Hodelson P, personal communication
Ways to work together: HIV and TB programmes
TB control requires a well organised national programme. A poor programme is worse than none at all, because of the risk of large numbers of people being given inadequate treatment. This means they will continue to be infectious to others and this can lead to the development of TB strains resistant to available drugs. WHO and IUATLD (the International Union Against TB and Lung Disease) have developed standard guidelines for national TB programmes, which are responsible for planning, policy, budgets, supervision and training. An effective programme needs:
a recording and reporting system that provides information about case categories and treatment results
to train staff to screen, diagnose and treat patients
a reliable sputum smear microscopy service, with adequate equipment and trained laboratory personnel
treatment services which provide directly supervised short course chemotherapy and health education
a reliable supply of drugs and diagnostic materials.
A TB programme should facilitate links between primary, district, regional and national levels and with HIV/STD programmes too. Health workers should always follow national TB programme guidelines. If there is no functioning TB programme in your area, use WHO TB treatment guidelines.
Collaboration between TB and HIV/AIDS programmes
People with HIV and TB face similar problems of stigma and fear, and have needs for care and support, and for counselling and confidentiality. Closer collaboration between TB control and AIDS programmes in these areas could be useful. For example, more integrated approaches to community education could help to change attitudes to both infections and reduce stigma. Collaboration in home care and follow up of patients with TB and with HIV/AIDS could help to increase adherence to TB treatment and identification of people with active TB.
Nurses in Kenya, trained in HIV counselling and who plan care for people with AIDS after discharge from hospital, are extending their services to patients on TB wards.
In Ghana a peer support group for people with HIV, working with health staff, discusses TB prevention, early TB recognition, and treatment adherence during home visits.
Hospital community outreach teams in South Africa visit people with HIV and TB at home. Many patients have both infections and the integrated approach helps to share limited resources such as transport, to reduce stigma and to increase community acceptance.
TB programme activities (showing possible links with HIV services)
Central TB unit, MOH
plan, monitor and supervise national activities
liaise with HIV/AIDS/STD and essential drugs programmes
co-ordinate training, drugs and diagnostic supplies
Regional TB co-coordinators
liaise with central TB unit
ensure effective co-ordination of above activities in region, and liaise with HIV services
regular technical supervision of district TB officers
review case finding and treatment reports
District TB officer (with DMO)
supervise and visit primary facilities
collect data for and maintain district TB register, with quarterly reports on new cases, relapses and treatment results
support case finding activities
supervise effective microscopy service and records
arrange training and supervisory activities, including HIV-related issues
ensure referral possible if necessary
maintain drugs and equipment
make appropriate links with district AIDS committee and AIDS team at hospital.
encourage community education and links with AIDS NGOs providing home care and education
identify people with possible TB symptoms and trace contacts
take sputum samples and liaise with laboratory
provide efficient referral and treatment services: appropriate regimens and sputum testing, counselling health education, local organisation of DOT ( clinic visits, community workers, AIDS home care services)
keep TB treatment cards and records up to date
follow up defaulting patients and discharge patients who are cured or have completed treatment
carry out community education ( with HIV services if appropriate)
report regularly to district level
ensure staff understand HIV and TB links, and are aware of needs for counselling etc.
What can NGOs do?
NGOs should make sure that their activities complement the national TB programme and discuss what role they can play to support the national programme with the district TB officer. Local AIDS organisations are playing a vital role in community education and care including:
Ensuring that community members recognise TB symptoms, and understand that it can be cured
Encouraging people with symptoms including those who may have HIV to be screened for TB and to seek treatment
Encouraging people to take their treatment using DOTS systems
Countering misbeliefs and stigma about AIDS and TB
Educating people about the ways in which TB is spread and encouraging them to cover the mouth when coughing and to spit into a container and dispose of sputum carefully
Providing home care and support to people with TB and HIV.
What can health workers do?
Health workers need to be friendly and aware of the person's needs for confidentiality, and to:
Ask about symptoms - if a person has had a cough for more than three weeks and chest pain, get a sputum test done
Make sure that the person understands that the full course of treatment is needed even if the symptoms soon go, and discuss the person's fears and worries about TB (and HIV)
Be aware of the possibility that the person may have HIV, and offer HIV counselling and testing if it is appropriate and available
Help them to take their full course of treatment
Make sure they understand that they are no longer infectious after 2-3 weeks
Examine family and household contacts for TB, especially if they are ill
Keep proper records and visit the person at home if they don't come for their appointment or drugs
Ensure that supplies of anti-TB drugs are available and do not run out
Refer difficult cases to a centre with a physician or TB specialist
Check HIV patients for TB and make sure that people with both infections do not receive thiacetazone.
Detection and diagnosis
Health workers should suspect TB if patients present with the following symptoms and history:
cough for more than three weeks
blood in the sputum
chest pain for more than one month
increasing weakness and loss of weight
had TB in the past or previously treated for cough
close contact with a smear positive case
positive tuberculin test
wasting - decrease in weight with no obvious reason
two or more episodes of fever with no obvious cause such as malaria
TB treatment should not be started on the basis of clinical symptoms alone (unless non-pulmonary disease is suspected when immediate referral and treatment are very important). The main diagnostic tools are:
sputum smear microscopy
culture of bacteria
tuberculin skin testing
chest radiography (x-ray)
Sputum smear microscopy
Sputum smear microscopy is the most useful diagnostic tool in low income countries. Sputum examination is cheaper, easier and more reliable than taking x-rays, more reliable than tuberculin testing, and cheaper and easier than culturing. It is possible to detect most smear positive cases of pulmonary TB using sputum smear microscopic examination.
The method of collection of the sputum is important. It should be produced away from other people, placed in a tightly covered labelled container and delivered to the laboratory as soon as possible. If TB is suspected, ideally three sputum . specimens should be collected within 24 hours: during the first consultation; by the person at home the next morning; and at the second consultation.
Two positive sputum smears are enough to confirm the diagnosis of TB.
If the first smear is positive and the second is negative (or vice versa), a third smear needs to be examined.
If the first smear is positive and the person does not return for the second consultation they need to be followed up and encouraged to return. Without treatment they will infect others and their own condition will get worse.
Health workers in areas without smear facilities need to look for clinical symptoms and history suggesting TB and refer the person to a health facility for screening.
One negative smear result is not enough to exclude a diagnosis of TB.
Smear microscopy requires well-trained laboratory workers and well-maintained equipment. Poorly trained staff or inadequate equipment can lead to over-diagnosis of smear negative and under-diagnosis of smear positive cases. Sputum smear microscopy is also used to check cure, which is based on smear conversion from positive to negative.
Sputum smear examination laboratory technique to screen sputum for TB, where acid fast bacilli (AFB) are stained red by the Ziehl Neelsen method, and then identified and counted using microscopy
Smear positive TB at least two initial sputum smears positive for AFB or one AFB positive smear and one positive culture
Smear negative at least three negative smears, but TS suggestive symptoms and x-ray abnormalities or positive culture
Adherence person takes appropriate drug regimen for required time (also known as compliance)
New case a patient with sputum positive pulmonary TB who has never had treated for TB or has taken anti-TB drugs for less than 4 weeks
Relapse a patient who returns smear positive having previously been treated for TB and declared cured after the completion of their treatment
Failure case a patient who was initially smear positive who began treatment and who remained or became again smear positive at five months or later during the course of treatment
Return after default a patient who returns, sputum smear positive, after having left treatment for at least two months
Transfer in a patient recorded in another administrative area register and transferred into another area to continue treatment (treatment results should be reported to the district where the patient was initially registered)
Transfer out a patient who has been transferred to another area register
Cured initially smear positive patient who completed treatment and had negative smear result on at least two occasions (one a t treatment completion)
Treatment completed initially smear negative patient who received full course of treatment or smear positive who completed treatment, with negative smear at end of initial phase, but no or only negative smear during continuation, and none at treatment end.
A specimen of sputum is sent to a specialised laboratory where TB bacilli, if they are present, can be 'grown' or cultured. Culturing is more sensitive than sputum smear microscopy but in many countries facilities and personnel are not available. It is also expensive and the results can take several weeks to come back. This delays confirmation of the diagnosis and starting treatment. Culturing is therefore often inappropriate as a diagnostic tool but is used to test TB bacilli for drug resistance and sensitivity where a patient is not responding to treatment. Culturing is also used for sputum smear negative cases where active TB is suspected.
Tuberculin skin testing
Tuberculin skin testing, which measures the body's response to TB, is also less useful in clinical diagnosis, except in children. An individual can produce a positive tuberculin test result if they are infected with TB or have been vaccinated with BCG. The tuberculin test cannot reliably differentiate between TB infection and TB disease. The test may also give a 'false negative' result if someone is infected with TB and HIV (see below).
Chest radiography or x-ray is expensive and usually available only in hospitals. It is not the most reliable way of diagnosing TB, although it can be a useful supportive tool to help medical officers to diagnose smear negative TB. Chest abnormalities which show up on x-ray may be due to other conditions or previous TB disease. Relying on x-ray results can lead to over-diagnosis of TB and unnecessary drug treatment. But chest radiography may not detect the early stages of TB disease, and the signs of pulmonary TB (such as cavitations) usually seen on x-ray are less common in people with HIV.
Detection and diagnosis of TB in people with HIV
In most people in the early stages of HIV infection, symptoms of TB disease are the same as in people without HIV infection. In areas where many people have HIV infection, TB programmes should continue to focus on identifying infectious sputum smear positive cases through microscopy. However, diagnosis of TB in individual patients using the standard diagnostic tools can be more difficult if they have advanced HIV infection.
HIV positive people with pulmonary TB may have a higher frequency of
negative sputum smears. Confirming the diagnosis may require sputum culture.
The tuberculin skin test often fails to work in people who are HIV positive because it relies on measuring the response of a person's immune system. If the immune system has been damaged by HIV, it may not respond even though the person is infected with TB. HIV positive people with TB therefore have a higher frequency of false negative tuberculin skin test results.
Chest radiography may be less useful in people with HIV because they have less cavitation. Cavities (spaces in the lungs) usually develop because the immune response to the TB bacilli leads to some destruction of lung tissue. In people with HIV, who do not have a fully functioning immune system, there is less tissue destruction and hence less lung cavitation.
Cases of extra-pulmonary TB seem to be more common in people who are co-infected.
The health worker may suspect HIV
infection because TB is difficult to diagnose,
and the person is sick with other
HIV-related infections. Offer confidential
counselling and testing if available
and appropriate. However, it is not necessary to know the person's HIV
For people thought, or known to have, HIV with TB symptoms:
Screen for TB using sputum smear microscopy.
If the result is positive start treatment.
If the smear result is negative but it is suspected that the patient has TB, sputum culture should be carried where feasible to confirm the diagnosis.
Give TB treatment to those with positive culture results.
Alternatively, where culture cannot be done, treatment can be given to those judged by a doctor to have active TB on the basis of x-ray and clinical symptoms.
Many HIV-infected smear negative patients thought to have TB in fact have other diseases. It is important to exclude the possibility of other infections before starting TB treatment. Usually this is done by treating first with a regular antibiotic for two weeks, and repeating the smear tests at the end of the two weeks if the person still has symptoms. If smear positive, start anti-TB treatment, but refer if still smear negative.
Treatment for TB
The principles of treatment are:
an appropriate combination of drugs to prevent development of resistance;
prescribed in the right dosage;
taken regularly by the patient under supervision;
for a sufficient period of time.
Drugs The most commonly used first line anti-tuberculosis drugs are: isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z), streptomycin (S), and thiacetazone (T). Some of these drugs are available in combined preparations, for example isoniazid with rifampicin (RH) and isoniazid with ethambutol (EH). Treatment regimens which contain both isoniazid and rifampicin are the most effective. Because rifampicin is such a useful anti-TB drug, its use in treating diseases other than TB should be carefully limited. It is important to supervise treatment regimens containing rifampicin.
Length of treatment Until recently the standard treatment regimen was 12-18 months. However, people are likely not to complete such a long course of treatment, which means they are not cured and continue to infect others in the community. Regimens can be shortened to 6-8 months if they include rifampicin. These regimens are called Short Course Chemotherapy (SCC).
Since the late 1980s WHO has encouraged national TB programmes to introduce SCC regimens which include rifampicin. Because of financial constraints many developing countries are still using the old standard 12 month course. However, the drugs for the short treatment course are only a little more expensive. Successful completion of treatment is also higher and better cure rates are achieved. This means that SCC regimens are a better use of resources. Whatever regimen is used, making sure that the person takes the full course is essential (see page 12).
Treatment of people with smear positive TB should always include:
an initial intensive phase - in this phase a combination of four drugs is given daily, to eliminate as many TB bacilli as possible and prevent the development of drug resistance. The initial phase of therapy should be given for a minimum of two months and continues until the patient becomes smear negative. Most people will have become smear negative after two months of treatment.
a continuation phase - in this phase fewer drugs are given but the treatment needs to be continued for long enough (depending on the SCC regimen the continuation phase can be four or six months) to ensure that the patient is permanently cured and does not relapse after completion of treatment. Some TB programmes are limiting the use of streptomycin because it has to be given by injection. This is more expensive and risks spreading HIV where it is difficult to guarantee proper sterilisation of needles and syringes. Thiacetazone is no longer recommended in areas where HIV infection is common because of side effects (see page 10). Intermittent therapy means taking anti-tuberculosis drugs three times a week instead of daily. There is no difference between intermittent and daily regimens in terms of the length of time before sputum conversion from positive to negative, or the final outcome.
Pregnant women and young infants
Pregnant or breastfeeding women who have TB should be treated with short course chemotherapy, regardless of HIV status.
Rifampicin, isoniazid, pyrazinamide, ethambutol are safe for use in pregnant women.
Streptomycin should not be given to pregnant women as it may cause deafness in the baby.
If the mother has smear negative pulmonary TB at the time of birth the infant should be vaccinated as normal with BCG (unless she or he has HIV-related illness)
If the mother is sputum smear positive at the time of birth and the infant is well, he or she should be given preventive therapy (isoniazid 5mg/kg in a single daily dose for 6 months) but not BCG. Give a tuberculin test to the infant after the six month preventive therapy If the result is negative vaccinate with BCG.
If the infant is unwell with TB symptoms give full anti-tuberculosis treatment.
How to assess cure? To be sure that TB is cured, a patient who is initially smear positive must produce a smear negative result after treatment. The change from sputum smear positive to sputum smear negative is called smear conversion. Patients need to be followed up to ensure that information on sputum conversion and outcome of treatment is obtained. The patient's sputum should be examined after the initial two months of treatment. If it is smear negative, they can start the continuation phase. The sputum should be examined again at the end of the fourth or fifth month to identify people who have failed treatment. During the last month of treatment a final smear is taken to identify cure, or treatment failure. Patients cannot be classified as cured if there is no sputum conversion from positive to negative. This applies to initially sputum negative patients, or to sputum smear positive cases who completed treatment with negative smears at the end of the initial phase, but with no or only one negative sputum examination in the continuation phase and none at the end of treatment. Sputum conversion is the only way to be sure that a person is cured, even if they complete treatment and have no clinical symptoms. If it is impossible to examine the sputum, then the patient is classified as 'treatment completed'.
Failure to respond
People fail to respond to treatment either because:
they are not taking their drugs OR
they have drug resistant TB.
Not taking the drugs is the most common reason for treatment failure. If a person continues to be sick, with persistent cough, fails to gain weight and has persistent positive sputum after treatment for some time, use the WHO recommended retreatment regimen for both HIV positive and HIV negative patients who:
remain sputum positive after five months of treatment (failure case)
interrupt treatment for more than 2 months and return smear positive (return after default case)
return smear positive after completing treatment and being declared cured (relapse case).
The therapy for retreatment should be fully supervised for at least three months, and longer if the patient is still sputum smear positive after three months. If the patient still fails to respond they may have resistant TB bacilli and need to be referred.
if a patient fails to respond to the treatment regimen, refer for assessment
treatment should be supervised as poor adherence is even more likely with more toxic and longer regimens
good record keeping is essential to distinguish between people with new active TB, or who have failed treatment, because the treatment regimens are different.
Source: Treatment of TB, Guidelines for National Programmes, WHO.
Side effects of drug treatment
Serious side effects to TB drugs are rare. Minor side effects do not mean that treatment should be stopped, but people need reassurance and to be warned about possible side effects in advance. Side effects which are associated with certain drugs include:
Skin rashes and itching - reaction to thiacetazone and other drugs.
Shock and fever - can be caused by rifampicin, pyrazinamide and/or streptomycin.
Problems with sight - can be caused by ethambutol. Patients should be warned to report any problems with their vision. Ethambutol is not usually given to children who are too young to be able to report visual problems.
Hepatitis - liver disease where the patient develops jaundice. Commonly due to isoniazid but may also be caused by rifampicin and pyrazinamide.
Dizziness - caused by streptomycin, most frequently in older individuals or children. Streptomycin should never be given to pregnant women because it can cause deafness in the unborn child.
Reaction in the joints such as pain, swelling, heat - caused by pyrazinamide.
Flu-like illness and/or abdominal pain - caused by rifampicin.
Red/orange colour of body fluids such as tears or urine - caused by rifampicin.
If patients develop any of the following serious side effects stop the treatment and refer them to a doctor immediately:
serious skin conditions (more common in people with HIV - see page 10)
problems with urinating and possible renal failure
Treatment issues for people with HIV
Caring for people with HIV and TB
The treatment of HIV infected people with TB is the same as for other TB patients with a few exceptions. HIV positive people with active TB can be effectively treated using SCC. There are two main issues to consider:
Uncertainty about HIV status
You may suspect that a person who has TB symptoms also has HIV infection, but their HIV status is not confirmed. It may be helpful to offer an HIV test, but only where voluntary testing with pre-and post-test counselling is available and confidential. However, it is not necessary for the person to have an HIV test before they begin TB treatment. Avoid prescribing thiacetazone to anyone with HIV or who may be at risk.
Adverse reactions and side effects
The most important issue in treating HIV positive patients for TB is adverse drug reactions, especially to thiacetazone. Thiacetazone, a sulphonamide, has been one of the main drugs used for TB treatment, in part because of its low cost. However, it causes severe and sometimes fatal reactions in up to 20 per cent of HIV positive TB patients, including severe skin rashes where the skin peels off.
There is a danger that people will not seek treatment because they are concerned about side effects. In Zambia, for example, it has been reported that even people without HIV, who are not at risk of severe side effects, do not want the 'drug that causes the rash'.
What does this mean in places where many people who need TB treatment are infected with HIV?
Educating staff and patients about side effects and continuing to prescribe thiacetazone is not acceptable given the seriousness of the adverse reactions and the proportion of patients with both infections who suffer from them.
Testing all TB patients for HIV to exclude them from thiacetazone regimens is not practical, as most countries do not have enough facilities, test kits and trained counsellors for voluntary testing. Some people would prefer not to know their HIV status. The cost of testing all patients would also be very high.
Using an SCC regimen that does not include thiacetazone is now recommended in places where HIV is common. In a district hospital in Zambia a study found that HIV testing and treating only those with HIV with more expensive ethambutol instead of thiacetazone cost the same as treating all patients with the non-thiacetazone regimen. These regimens are now rapidly becoming less expensive.
Skin reactions and care
Unless the reaction is very mild, stop all drugs until the person's condition settles down. Then restart the drugs one at a time, starting with those least likely to have caused the reaction. Add a new drug every few days if there is no reaction, until the person is on the full regimen again, but without thiacetazone.
If there is a fever and rash, give an antihistamine drug if available
If there is a very severe reaction, treat with steroids: 40-60mg prednisolone daily in a single oral dose, reducing the dose gradually every 2 days or 200mg hydrocortisone 3-4 times daily given intravenously, and intravenous fluids as required.
Severe reactions to thiacetazone and other drugs can cause most of the skin to blister and peel off. Hospital care is needed, using similar principles as for the management of burns. This means:
Protecting the exposed surface from further damage
Cleaning the wound with normal saline. After cleaning, the wound can be left exposed, or covered with 0.5 per cent chlorhexidine swabs moistened and changed, or bathed with potassium permanganate
Silver sulphadiazine cream, an anti-septic widely used in the treatment of burns, should not be used
Control of infection is vital to avoid sepsis.
Nutritional support is important. Feeding via a gastric tube is sometimes needed.
Sources: Dr Ricardo Barradas and Dr Paula Perdigoo, Maputo Central Hospital, Mozambique, and WHO.
TB programmes need to make sure that people with active TB take all their drugs and complete their treatment (treatment adherence) whether they are being treated in hospital or at home.
Patients should only be hospitalised if there is no alternative. Transmission of TB may be greater in over-crowded hospitals than in a community setting. Some programmes hospitalise patients for the initial phase of therapy, if there is no other way to guarantee supervision.
What is DOTS?
Ambulatory treatment (when the person is well enough to be at home and takes their medication on a daily or intermittent basis) is the recommended approach, but it only works when the person is supervised taking their treatment by a health worker when they visit a clinic or during home visits by an outreach or community health worker.
This system, called Directly Observed Therapy, Short course (DOTS) is a method to ensure high levels of adherence and completion of TB treatment. It means setting up a system to ensure that each person swallows every dose of their drugs. DOTS aims to help patients complete their treatment - the 'supervisor' can be a source of encouragement and support for the patient.
The DOTS system works:
In Botswana TB patients attend the nearest primary health care facility to their home for daily supervised treatment. People who fail to attend are followed up and traced by community health workers, usually family welfare educators, during home visits. High adherence, of over 90 per cent, has been achieved through intensive repeated health education of patients and their relatives, constant supervision and follow-up and integration into PHC at the community level.
A DOTS programme in New York City uses outreach workers to reach people at home, in work places or living on the streets, and has achieved an increase of 40 per cent in treatment completion from 1989 to 1994.
WHO recommends that every country should adopt the DOTS approach, but only where there is a properly functioning TB programme, with trained staff, good record keeping and guaranteed supplies of drugs. Of the 8 million people who develop TB disease each year, only about 500,000 have DOTS because of poor health services. Many people are still sent away with six months prescription for drugs, and often fail to take the complete course. This unsupervised treatment also contributes to drug resistance.
These are ways to help people complete treatment
Enabling incentives such as travel expenses or a meal
Written or verbal agreements between the person and health provider about treatment
Setting up support groups, led by people cured of TB
Making sure all members of the person's family understand the treatment and make sure the person takes their medicine
Explaining about TB and common side effects of treatment, so that the patient will not be worried and stop taking the drugs if minor side effects occur
Education and training
Working with communities
Encouraging people to seek and complete TB treatment is essential for successful TB care and control. Understanding local beliefs, community education and health worker training all play important roles. Beliefs about TB and its causes are important influences on people's behaviour. For example, studies have found that people may:
believe that TB cannot be cured and do not know that with proper treatment people are no longer infectious
think TB is a disease sent from god, or caused by magic or witchcraft
be unaware of TB and its symptoms, how it is spread, and its seriousness
think that TB only affects 'cursed' or 'bad' people
consider TB patients to be unclean
link TB with AIDS leading to additional stigma
People may self treat or use traditional healers instead of modern health services and drugs, if illness is believed to be caused by magic or witchcraft. Stigma means people may deny their illness or try to hide it from their community or family. Fear of rejection can be an important reason for not seeking help from health care services and for not completing a course of treatment. Understanding these attitudes and beliefs can help health workers to give more appropriate advice and to provide more relevant community health education.
Health worker attitudes and resources can cause people to delay seeking treatment and fail to complete their therapy. In Nepal, games have been used during training to help health workers reconsider their attitudes.
TB Treatment game
This game aims to help health workers explore why people might stop taking their TB drugs. It can be played by individuals or small groups, playing against each other.
Players have to try to cross the TB treatment river, using the stepping stones. If they reach the other side they have completed their treatment and are cured. However, there are many reasons why they might slip off the stones, and fail to take their drugs.
Ask participants to describe a health worker's typical reaction to someone who stops treatment - often anger and frustration. Then ask them to think of all the reasons why people with TB might not complete treatment, and to pick out the 10 most important ones,
Hand out copies of the game with the stepping stones left blank, and ask participants to write in the 10 reasons
Draw a circle about 50cm in diameter on the floor, and divide into 6 equal wedges. Write the numbers 1 to 6 in the wedges. Draw a boundary line 2-3m away from the centre of the circle.
The player stands behind the boundary line, and throws a coin into the circle. If the coin lands inside a wedge, then the player moves across that number of stepping stones. If the coin lands outside the circle, or on a line, then the player has fallen off the stone, and is out. If the first throw is out, allow the person to throw again until they land in a wedge and reach a stone. Each person continues throwing until they reach the other side or fall off a stone.
Discuss the game with participants:
How many people fell off? Is this figure similar to the proportion who don't complete their treatment?
Which stones did people fall off most - are these common reasons in real life?
Of the reasons given, for which can the person be blamed? And the health workers? Is it fair for health workers to be angry with people who default?
How can health workers encourage people to complete their treatment?
Usually only one or two reasons are the person's fault, and the rest are the health service's responsibility. Finish by asking whether in fact it is the patient who should be angry with the health worker, rather than the other way around! Another useful exercise is to ask the health workers, in small groups, to draw a TB patient. Pin the pictures up and use them as a discussion starting point. Ask questions such as: What signs and symptoms do the pictures show? What kinds of people have they drawn? Health workers often draw a picture of an adult man. Ask Does this mean that health workers are less likely to consider TB in women?
Source: Smith I, Tuberculosis control learning games, Tropical Doctor, July I993 and personal communication
Education and training
In South Africa a TB project found that poor communication between patients and health workers and lack of educational material were important reasons why people failed to complete their treatment. Health education material in TB clinics was mostly not relevant to people's lives, covering clinical signs and symptoms and with pictures of lungs and bacteria. Health workers were unaware of the concerns of people with TB.
The project started by training nurses to run group discussions with patients. The discussions revealed that people with TB had low self esteem, experienced stigma, were afraid of infecting others, and stopped taking treatment if they felt better after a couple of months to save time and money.
They needed clear information and more support from health workers, so a booklet was developed using a story and photographs based on the experience of a woman with TB, showing true-to-life success, failures and difficulties. The draft was pre-tested among TB patients and received a very positive response - many felt it could have been their story. At the back of each booklet is a treatment calendar which enables people to keep track of their treatment and encourages completion.
Evaluation has shown that patients who are given a copy of the booklet are more likely to complete their treatment than those who are not, and that the participatory research process helped to improve nurses' understanding and communication skills.
Source: Judy Dick and Hester van de Walt, Medical Research Council, South Africa.
Preventing TB in health facilities
Preventing TB spread
Identify and treat people with infectious TB
If possible, keep potentially infectious patients separate and advise them to cover their mouth and nose when coughing if possible with a clean cloth. Surgical masks are not very effective, are expensive and increase stigmatisation of TB patients.
All patients with TB symptoms, especially those with a cough, should be screened for TB by sputum smear microscopy.
Remember that the most infectious TB patients are those with pulmonary disease who are sputum smear positive, and that people are no longer infectious after 2-3 weeks of treatment.
Treatment should be in immediate a diagnosis of TB is confirmed.
Handle sputum safely
Sputum specimens should be collected away from general waiting rooms or hospital wards in a special receptacle or spittoon with a lid.
Laboratories processing sputum specimens should follow guidelines to prevent transmission to laboratory workers. Preparing a smear is a potentially risky procedure and laboratory personnel should always wear mask and gloves.
Care for people with infectious TB separately
Patients should only be hospitalised for TB treatment if absolutely necessary.
Patients with smear positive pulmonary TB who are hospitalised should be accommodated in separate wards, away from patients without TB, during the initial phase of treatment until they are no longer infectious (smear negative). It is most important that infectious TB patients are separated from infants and people with HIV, who may be more susceptible.
HIV/AIDS patients suspected of having TB should not be admitted wards until the diagnosis is confirmed and treatment bun.
Ventilate wards and waiting areas
Proper ventilation is one of the most effective measures to reduce TB.
Waiting areas should be large, well ventilated or aired several times a day, with the windows open and uncurtained to allow sunlight in. Alternatively patients can wait outside where there is more air circulating.
Outpatient clinics where screening for TB takes place should also be well ventilated.
TB wards with closed doors and windows open to the outside are ideal.
Fans are useful for moving air from the wards to the outside.
In colder climates where the windows need to be closed, it is important that air flow from TB wards is not directed to other arts of the hospital.
Use natural UV light
Ultra Violet (UV) light kills TB germs. Sunlight is a good source of UV light.
Special UV lights are not recommended because they have not been shown to be effective. They are also expensive, require careful maintenance, and can be harmful if not installed properly.
Protect health care workers and others
If possible, health workers who know they are infected with HIV should avoid working with TB patients. Those who are not sure of their HIV status need counselling to help them decide whether or not they want to have an HIV test. In some places HIV positive health workers are offered prevention therapy if they are working with infectious TB patients. The same principles apply as to other HIV positive individuals (see page 15).
People with TB need to understand that they can transmit TB germs to staff, other patients and visitors, and be encouraged to take the steps described above, to reduce the risk
Small children and infants who have to remain in hospital when their mothers are being treated for TB should be given preventive treatment with isoniazid see page 8 .
Source: Control of tuberculosis transmission in health care settings. Joint statement of the IUATLD and WHO TB Programme.
TB chemoprophylaxis means treating people with symptomless TB infection to prevent the development of active disease. Preventive therapy has been shown to be beneficial for people with both TB and HIV infections who are at risk of rapid progression to active TB disease. Daily isoniazid (isoniazid preventive therapy or IPT) can reduce the incidence of active TB in HIV positive people. Before IPT can be considered, voluntary HIV counselling and testing facilities need to be available for people who may have HIV.
There are still many questions about IPT. It is not clear at what stage of HIV disease chemoprophylaxis should be given, or which drug regimens might be most effective. It is also not clear for how long people should continue to take preventive therapy and whether the benefits continue after completing the recommended period of therapy.
Who should get IPT?
IPT should only be given to HIV positive people who have TB infection but who do not have active TB. Those with active TB need full treatment. Giving only one drug to a person with active TB can help resistant strains of TB to develop. Proper TB screening is essential to ensure that preventive therapy is not given to patients with active TB. But it is not always easy to confirm whether HIV positive individuals have active TB disease or TB infection (see page 7).
The WHO guidelines for tuberculosis preventive therapy in HIV positive individuals should be followed (see below). The guidelines emphasise that IPT should only be considered for HIV infected people with a positive tuberculin skin test who do not have active TB.
Limitations of IPT
Resources In most developing countries, voluntary counselling and testing for HIV, screening all HIV positive patients for TB infection, and providing drugs for preventive therapy are not possible. Although IPT can prolong healthy life in individuals with HIV and TB infections, resources should be prioritised for identifying and treating smear positive patients.
Side effects Hepatoxicity (the risk of hepatitis) is one of the most common side effects of IPT and can be fatal. The risk is higher in adults aged over 35 years. However in HIV positive people the benefits of IPT generally outweigh the risk of toxicity, except in people with chronic active hepatitis or possibly those with more advanced HIV disease.
Drug resistance Preventive therapy could potentially increase drug resistance if it is wrongly given to those who have active TB. The effects on the development of drug resistance of large scale preventive therapy with one drug are not known.
Adherence Without good support and supervision, there may be problems in ensuring people take preventive therapy for long periods of time, especially if they do not have symptoms of TB disease.
Isoniazid preventive therapy can be of value to individuals with both HIV and tuberculosis infection.
Education about TB and its link to HIV infection should be part of HIV pre-and post-test counselling.
People who are HIV positive:
should be screened for TB by clinical examination.
should receive a tuberculin skin test.
if the tuberculin test is positive they should receive a chest x-ray.
People with symptoms consistent with tuberculosis and/or an abnormal chest x-ray should have sputum collected for bacteriological examination culture.
People with a positive skin test in whom active TB has been excluded (by x-ray and culture) should be given isoniazid at the daily dose of 5mg/kg up to a maximum of 300 mg for 6-12 months.
Persons receiving preventive therapy should be monitored monthly for adherence, toxicity and the development of active TB.
Source: Preventive therapy for TB in HIV-infected persons, Lancet vol 345, 1995.
Drug resistance means that certain
strains or types of TB bacilli are not
killed by the anti-tuberculosis drugs
given during treatment. Some strains
can be resistant to one or more drug.
WHO defines a multi-drug resistant (MDR) strain as one that is at least
resistant to isoniazid and rifampicin. A
person infected with MDR TB will
therefore not be cured by short
course chemotherapy which relies on
these two drugs.
Why does drug resistance develop? Drug resistance is caused by inadequate TB treatment and poor TB control programmes. The most common reasons for the development of resistance are:
irregular supply of drugs
lack of supervision and follow up
There are two types of drug resistance:
Acquired resistance is where resistance develops as a result of inadequate treatment. Use of a single drug is the most important cause of acquired resistance. This is because some TB bacilli are naturally resistant to anti-TB drugs. If a single drug is used to treat a patient who is infected with a large number of TB bacilli only those which are sensitive to that drug are killed, allowing the resistant bacilli to multiply. This is the reason for using several drugs during the initial intensive phase of treatment, until the number of bacilli has been greatly reduced.
Primary resistance is when an individual is infected by someone who already has drug resistant TB bacilli. The newly infected person will have TB that is drug resistant from the outset. The number of people with primary resistance - who have drug resistant TB but who have not been treated for TB before - is increasing.
AIDS action Issue 31 15 Page 16
Current issue / Resources
Is MDR TB a major problem?
In all countries and especially those where the number of cases of TB is rising rapidly because of the association with HIV, the development of resistant strains of TB is a serious concern. Between 50 and 100 million people worldwide are thought to be infected with strains of resistant TB. An accurate picture of drug resistance is not available because few countries have a reliable drug resistance surveillance system. Resistance varies, for example in Africa resistance to isoniazid is estimated at between 5 per cent and 10 per cent. Resistance to rifampicin, one of the most effective TB drugs, is thought to be low in Africa because the drug has not been widely available. But there are signs that resistance to rifampicin is developing: for example. it has been reported in Thailand. Drug resistance is potentially a serious problem in countries where prescription of anti-TB drugs by private physicians is not well controlled. WHO and IUATLD have developed guidelines to help countries detect strains resistant to the main TB drugs through national surveillance programmes. Better information will help countries to decide which is the most appropriate SCC drug regimen and the best strategies for retreatment.
What are the dangers of MDR TB?
The most serious danger is that MDR TB is much more difficult to treat, even where second line drugs are available. Treatment of MDR TB can take at least two years and the results are poor. Second line drugs cost 30-35 times as much as drugs used in SCC treatment of non-resistant TB. Patients with MDR TB may need to be hospitalised and isolated, which adds to the cost of treatment, to prevent transmission of primary resistant strains to others. In the USA it is estimated that treating one case of MDR TB costs ten times as much as treating a case of TB sensitive to the usual drugs. Careful precautions are necessary to prevent transmission, especially to health workers caring for MDR TB patients.
Clinical tuberculosis provides practical information on all aspects of TB control and clinical care.
Available for £3.00 in English, French, 'Spanish and Portuguese from TALC, PO Box 49, St Albans, AL1 4AX, Herts, UK.
Tuberculosis guide for low-income countries is a handbook providing information for staff involved in primary level prevention and care.
Single copies in English, French or Spanish free from IUATLD, 68 Boulevard Saint-Michel, 75006 Paris, France.
TB and HIV: SidAlerte Supplement is a quarterly magazine in French and English covering good policy and practice in TB and HIV care and prevention.
For subscription details write to SidAlerte International, 7 rue du Lac, 69003 Lyon, France.
Childhood TB is a new briefing paper from AHRTAG.
Available free to readers in developing countries.
'Preventing infections in health-care settings' provides practical guidelines on reducing the risk of blood and air-borne infections.
Available free to readers in developing countries and for £5.00 elsewhere, from AHRTAG.
Please write to AHRTAG if you would like a full list of the reference materials used for this special TB and HIV issue.
Articles were written by Kathy Attawell. with contributions from Dr ET Maganu, Dr Rumisha, Dr Ian Smith, Dr Paul Janssen, Sally Smith, Dr David Wilkinson, Patricia Hudelson, S Chondoka, P Bwalya, Esther Sumatojo and others credited in text. AA takes full responsibility for any inaccuracies in the text.
Executive editor Nel Druce
Assistant editor Sian Long
Design and production Ingrid Emsden
Editorial advisory group Calle Almedal, Kathy Attawell, Nina Castillo, Professor E M Essien, Dr Sam Kalibala, Ashok Row Kavi, Dr Ute Küpper, Professor Keith MacAdam, Dr Tuti Parwati Merati, Dr Claudia Garcia Moreno, Dr Chandra Mouli, Dr Anthony Pinching, Dr Peter Poore, Barbara Wallace, Dr Michael Wolff
Special issue reviewers Dr Sergio Spinaci, Dr Petra Graf and Dr. Paul Nunn (WHO TB Programme), Dr Eric van Praag and colleagues (WHO AIDS/STD), Programme Dr Don Enarson (IUATLD), and Dr Peter Poor, Dr Kevin De Cook, Dr John Porter, Dr Alison Elliott Dr Alwyn Mwinga
Publishing partners ABIA (Brazil) Colectivo Sol (Mexico) ENDA (Senegal) HAIN (the Philippines) Consultants based at University Eduardo Mondlane (Mozambique)
AHRTAG's AIDS programme is supported by CAFOD, Charity Projects, Christian Aid, FINNIDA, HIVOS, ICCO, Memisa Medicus Mundi, Misereor, Norwegian Red Cross, ODA, Oxfam, Save the Children Fund, SIDA, UNICEF and WHO/GPA.
Misereor and Norwegian Health Association NORAD provided additional support for this issue.
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