Serious gaps in the capacity to diagnose life-threatening fungal infections in Africa mean that people with advanced HIV may not receive treatment for AIDS-related illnesses such as cryptococcal meningitis and pneumocystis pneumonia, a 48-country survey reports in The Lancet Infectious Diseases.
The survey found that only 25% of people in Africa had routine access to cryptococcal antigen testing and 78% had access to diagnostic testing for pneumocystis jirovecii pneumonia (previously known as pneumocystis carinii, or PCP), one of the most common AIDS-defining illnesses. Symptoms of both infections are often mistaken for other illnesses, delaying treatment that could prevent the progression of either condition.
People outside eastern and southern Africa were least likely to have access to these tests. Even in countries that have made greater investments in laboratory capacity using HIV-related donor funding, some essential tests were rarely available, the survey found.
Fungal infections in people with HIV
In some African countries, half of all deaths from fungal infections have been estimated to occur in people with HIV. Fungal infections most commonly occur in people with HIV with CD4 counts below 200, defined as advanced HIV by the World Health Organization.
The three most common fungal infections in people with HIV in Africa are cryptococcal disease, pneumocystis pneumonia and histoplasmosis. Each infection requires specialised diagnostic testing.
In people with HIV, infection with Cryptococcus neoformans causes a slow-developing meningitis with fever and headache. Symptoms of cryptococcal disease can be difficult to distinguish from other illnesses until the condition is severe.
Cryptococcus can usually be detected in the blood or cerebrospinal fluid. The most sensitive and specific form of test is a lateral flow antigen test. Antigen can also be cultured but this is time-consuming. The World Health Organization recommends cryptococcal antigen testing should be carried out in people with HIV with CD4 counts below 200.
India ink staining of cerebrospinal fluid is a quick but less sensitive test that can be used to visualise cryptococcus under a microscope. Lumbar puncture – inserting a fine needle into the spine to sample cerebrospinal fluid – is also used as a diagnostic tool or to relieve pressure in the brain in cryptococcal meningitis.
Histoplasmosis causes non-specific symptoms such as fever, fatigue, weight loss, cough and chest pain. Histoplasmosis is best diagnosed by a urinary antigen test.
Pneumocystis pneumonia most often causes shortness of breath, fever, dry cough and fever. Chest X-ray and blood oxygen tests are insufficient to distinguish between fungal, bacterial and other causes of pneumonia.
Pneumocystis jirovecii is hard to culture, so it is usually diagnosed by staining samples of fluid from the lungs under a microscope. Obtaining sputum samples from the lung can be difficult in seriously ill people. PCR testing for Pneumocystis jirovecii is far more sensitive and must be used for testing babies and small children.
Global Action for Fungal Infections carried out a survey of diagnostic capacity for AIDS-related fungal infections in Africa between October 2020 and October 2022. The investigators identified 72 respondents in 48 countries who could provide either national or regional data, and insights on diagnostic testing. These findings were validated by webinars involving 191 participants from 43 countries.
Access to tests for cryptococcal disease
The capacity to carry out frequent cryptococcal antigen testing was largely restricted to 14 countries with a higher burden of HIV in eastern and southern Africa. Cryptococcal antigen testing was rarely carried out in west Africa despite the high prevalence of HIV in Nigeria and Cote d’Ivoire. In total, an estimated 43% of people in 22 African countries had no access to cryptococcal antigen testing.
Although India ink stain microscopy for cryptococcal diagnosis was available in most countries, an estimated 19% of people in Africa had limited or no access to this test.
Access to testing for histoplasmosis
Access to urinary antigen testing for histoplasmosis is very limited in the public sector in Africa. Seventy-four percent of Africans have no access to the test and regular private sector access was reported only for Eswatini, Kenya, Mozambique and South Africa.
Access to testing for pneumocystis jirovecii
Frequent use of PCR testing for pneumocystis jirovecii takes place in South Africa but elsewhere, PCR testing was either unavailable or used rarely to diagnose pneumocystis jirovecii. Seventy-eight percent of Africans are estimated to lack access to this test.
CD4 counts, used to identify people at higher risk of opportunistic infections, were available for 64% of people in Africa, the study estimated. CD4 counts were only carried out for new patients or those who are ill or admitted to hospital in 14 countries.
Fungal culture was frequently carried out in the public health sector in 22 countries but was available only in the private sector in 13 countries, notably Kenya. Fungal culture was unavailable in eight countries, including Zambia.
An MRI scan, which can be used to differentiate between numerous opportunistic infections affecting the brain, was available to 32% of people in Africa in 15 countries. An MRI scan was unavailable in the public health sector in 12 countries including Zimbabwe, Namibia and Eswatini.
Funding and implications
The study also looked at AIDS death rates and donor expenditure on HIV- and TB-related care from the Global Fund and PEPFAR. It found no correlation between funding and AIDS death rates. Although higher levels of spending lead to more people on antiretroviral treatment, extra cash for HIV programmes in some countries does not automatically translate into lower rates of late HIV diagnosis or improvements in the diagnosis and treatment of opportunistic infections in those countries.
“International agencies and governments need to be much more proactive in delivering diagnostic tests if AIDS mortality is to substantially fall,” the study authors conclude. They highlight the greatest gaps in countries suffering civil war and unrest and emphasise the importance of continuing to strengthen health systems in the countries with the least capacity.
They also stress that current efforts to improve access to cryptococcal antigen tests need to look beyond southern and eastern Africa and consider how to address major gaps in western and central Africa.
The Global Initiative to end Cryptococcal Meningitis deaths by 2030, launched in 2021, aims to improve access to diagnostics and medicines for treating cryptococcal meningitis. A strategic framework for ending cryptococcal meningitis deaths by 2030, developed by eight organisations, emphasises the importance of routine availability of cryptococcal antigen testing and investment by donors in improved diagnostic capacity, together with treatment with flucytosine and amphotericin B.
Lakoh S et al. Diagnostic capacity for invasive fungal infections in advanced HIV disease in Africa: a continent-wide survey. The Lancet Infectious Diseases, published online 21 December 2022.