Differing causes of lung infections in HIV-positive patients: implications for diagnosis and treatment

The underlying cause of respiratory infections that cannot be detected using standard sputum tests differs between Asia and Africa, according to French research published in the July 11^th edition of AIDS. But after bronchoscopy examinations, pneumocystis pneumonia was identified as the main cause in Asia, with tuberculosis and variety of bacterial infections being the underlying causes in Asia. The investigators hope that their findings will help healthcare workers in resource-limited settings select the most appropriate diagnostic tests for patients with difficult to diagnose respiratory complaints.

It is well known that patients with HIV have an increased risk of respiratory tract infections. Even modest immune damage can leave individuals vulnerable to bacterial infections, and more advanced HIV disease can involve a risk of infections such as pneumocystis jiroveci pneumonia (commonly called PCP).

Tuberculosis is an important cause of respiratory tract infections amongst patients with HIV in both Africa and Asia. Another important cause of such infections in Africa is pneumococcal pneumonia, with PCP being common in Asia.

But it can be difficult to establish the precise cause of respiratory disease in patients whose sputum samples are negative for infections because fibreoptic bronchoscopy investigations are not available in many resource-limited settings.

Because of this the World Health Organization (WHO) has developed treatment algorithms for patients with HIV depending on the likelihood of such an infection being tuberculosis, pneumonia or PCP. But the use of such algorithms needs to take into account the local prevalence of these infections and such information is rare and conflicting.

Therefore French investigators performed a prospective study involving 462 patients. These patients were recruited in four countries, two of which were in Africa (Central African Republic and Senegal), the other two in Asia (Cambodia and Vietnam). All the patients were hospitalised because of respiratory disease and were confirmed to be HIV-positive. The study had the aim of establishing three things:

• The characteristics of hospitalised HIV-positive patients with respiratory disease that could not be diagnosed using sputum tests.
• The main causes of respiratory disease in each setting.
• If there were any patient or microbacterial characteristics that would enable the most appropriate use of WHO guidelines for the treatment of respiratory infections.

Most of the patients (63%) were recruited in Asia, 59% were men and the median age was 34 years. The patients had advanced-stage HIV disease, with 85% having a WHO stage III or IV diagnosis. The median CD4 cell count was just 25 cells/mm³, and median body mass index was 17.

Many patients were unaware of their HIV infection at the time of their admission to hospital (44% Cambodia, 66% Senegal, 80% Central African Republic; 84% Vietman).

Few of the patients who were aware of their HIV infection were taking anti-HIV drugs (13%) or prophylaxis for PCP (33%). But the investigators found that patients in Africa (25%) were more likely than those in Asia (9%) to be taking antiretroviral therapy.

Chest X-rays showed that 42% of individuals had diffuse lung abnormalities with a further 45% having localised abnormalities.

There was significant variation between countries in the proportion of patients who had a second sputum sample examined after their first sputum sample was negative (3% Cambodia – 94% Central African Republic).

A fibreoptic bronchoscopy was performed on 354 patients (77%), with approximately equal proportions of patients in each of the four countries having this investigation.

It was possible to provide a definitive or probable diagnosis on the basis of microbiology or pathology for 317 individuals. The most frequent cause of lung disease in these patients was PCP (43%), followed by bacterial pneumonia (40%), and tuberculosis (26%).

There were significant differences between Africa and Asia in the percentage of patients diagnosed with particular infections. More patients were diagnosed with PCP in Asia (56%) than Africa (6%, p < 0.001). By contrast, both bacterial pneumonia and tuberculosis were more common in Africa (45% and 56%) than Asia (20% and 34%). A particularly high rate of tuberculosis was observed in the Central African Republic (60%), and almost two-thirds of patients were diagnosed with bacterial pneumonia in Senegal.

The most common bacterial causes of pneumonia differed between the four countries in the study, with Staphylococcus aureas and Pseudomonas being common in Cambodia; Haemophilus influenzae and Acinetobacter in Vietnam; Pseudomonas and Klebsiella pneumoniae in Senegal; and Streptococcus pneumoniae in the Central African Republic.

These results led investigators to recommend different strategies for diagnosing sputum negative respiratory infection in Asia and Africa. Because respiratory infections in Asia are caused by a wide range of infections they suggest, “when possible, fiberoptic bronchoscopy must be performed rapidly if clinical data are not highly suggestive of bacterial pneumonia, [PCP] or tuberculosis.”

In Africa, however, because bacterial pneumonia and tuberculosis are responsible for the majority of cases “fibreoptic bronchoscopy should be restricted to patients with clinical and/or radiological findings not suggestive of bacterial pneumonia, tuberculosis, antibiotic failure” or who have three consecutive negative sputum tests.