Cough alone a poor predictor of TB: look for fever and weight loss too

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Attempts to improve TB diagnosis rates among HIV-positive people may be hampered by an over-simplistic search for one symptom at the expense of a wider range of symptoms, according to studies of intensified TB case finding presented last week at the 38th World Lung Health Conference in Cape Town, South Africa.

Intensified case finding is intended to increase TB diagnosis rates among people who are already in HIV care. At present the degree of focus on TB diagnosis varies from one treatment programme to another, and some use only passive case-finding, diagnosing TB only when patients present to their doctor with serious TB-related symptoms.

Other programmes actively attempt to find cases of TB, often using home-based carers or a regular screening questionnaire during hospital visits to identify new cases.

Glossary

culture

In a bacteria culture test, a sample of urine, blood, sputum or another substance is taken from the patient. The cells are put in a specific environment in a laboratory to encourage cell growth and to allow the specific type of bacteria to be identified. Culture can be used to identify the TB bacteria, but is a more complex, slow and expensive method than others.

active TB

Active disease caused by Mycobacterium tuberculosis, as evidenced by a confirmatory culture, or, in the absence of culture, suggestive clinical symptoms.

latent TB

A form of TB that is not active. Persons with latent TB are infected with M. tuberculosis but do not have any symptoms and they cannot spread TB infection to others. Only specific tests will tell if anyone has latent TB. Treatment for latent TB is recommended in people living with HIV. 

isoniazid

An antibiotic that works by stopping the growth of bacteria. It is used with other medications to treat active tuberculosis (TB) infections, and on its own to prevent active TB in people who may be infected with the bacteria without showing any symptoms (latent TB). 

smear

A specimen of tissue or other material taken from part of the body and smeared onto a microscope slide for examination. A Pap smear is a specimen of material scraped from the cervix (neck of the uterus) examined for precancerous changes.

Accurate symptom-based screening is important in settings where there is a high burden of active TB in the population, and where task-shifting has devolved much initial or routine care of people with HIV to clinical officers, nurses and other non-physician grades.

Intensified case-finding is especially important in settings where there is a high level of latent TB infection that might progress to active tuberculosis.

In Cambodia two-thirds of the population are estimated to have latent TB, according to Dr Michael Kimmerling of the University of Alabama, Birmingham, reporting on an intensified case finding study in Cambodia.

The study was conducted among 2,000 people receiving home care in rural Cambodia, of whom 785 were HIV-positive. The overall pulmonary TB rate in the home care population was 5.8%, but among HIV-positive people it was 16%, compared to 2.4% in HIV-negative people.

The study was designed to determine whether persistent cough alone was a sensitive enough symptom of TB to be used as a routine screening symptom for TB case finding by home-based carers, or whether other symptoms might predict TB better.

The researchers looked at a panel of symptoms, elicited through open-ended questioning, and looked at how the presence or absence of these symptoms predicted the presence of TB, as measured by the gold standard of TB culture.

The researchers found that a cough lasting three weeks or more was the least sensitive symptom predicting TB. In contrast, a combination of persistent fever, rapid weight loss noticeable to the patient within the previous month and haemoptysis (coughing up blood) detected every case of TB in both HIV-positive and HIV-negative patients.

A second study in Cambodia, presented by Dr Kevin Cain of the US Centers for Disease Control found that a cough lasting more than two to three weeks did not in itself predict the presence of TB. His study, which is still ongoing, plans to enrol 2050 HIV-positive patients with no history of TB treatment or isoniazid preventive treatment in the past year in Vietnam, Cambodia and Thailand.

Preliminary results suggest that the presence of cough, fever and weight loss picked up 93% of TB cases, leading Dr Cain to suggest that a cough lasting two to three weeks should not in itself be an entry point for further TB investigation in patients who are TB smear-negative, as WHO guidelines currently recommend.

A third study, carried out in Ethiopia among 438 HIV-positive patients, looked at the best way of excluding active TB before offering isoniazid preventive therapy in a setting where only one laboratory in the region can do TB culture and up to 60% of TB cases are smear-negative.

Dr Meaza Demissie of CDC’s Global AIDS Program reported on cross-sectional data from newly diagnosed HIV-positive patients in the Ethiopian capital Addis Ababa. In this study symptom screening was compared with the gold standard, a TB culture-positive lab result, to assess the patterns of symptoms that best identified TB.

Once again, her study found that cough alone was not very sensitive at discriminating between TB and other common or garden chest infections. Screening for cough alone would miss 56% of cases, she reported.

If fever and weight loss are not present, but the patient suffers a cough, their illness is less likely to be a cough, Dr Demissie found. Screening for four symptoms – cough, weight loss, fever and night sweats – identified the highest number of TB cases correctly.

The findings of the three studies are also important for improving patient education, said Dr Michael Kimmerling. “Patients are coming to these clinics because they are sick, they think they’ve got HIV, when in fact they’ve got TB.”

Improving the recognition of potential symptoms of TB in the community, which is treatable, may improve rates of TB diagnosis and treatment as well as rates of HIV diagnosis.

References

Cain K et al. Developing a clinical algorithm to diagnose TB in HIV-infected persons in SE Asia. 38th World Lung Health Conference, Cape Town, symposium on intensifide case finding, 2007.

Demissie MD et al. Testing different TB screening strategies: intensified TB case finding among HIV-infected personnel at a voluntary counselling and testing centre, Addis Ababa, Ethiopia. 38th World Lung Health Conference, Cape Town, symposium on intensifide case finding, 2007.

Kimmerling ME et al. Active TB case finding within a continuum of care package: linking TB and HIV services through voluntary counselling and testing centres in Battambang province, Cambodia. 38th World Lung Health Conference, Cape Town, symposium on intensifide case finding, 2007.