Cryptococcal meningitis screening is worth the money in Uganda

13 February 2019

Cost should not be a barrier for the full implementation of cryptococcal meningitis screening programmes for people living with HIV as per World Health Organization recommendations.

A busy antenatal clinic in Uganda

Screening for cryptococcal meningitis – an infection responsible for 15% of all global AIDS-related deaths – is both cost-effective and life-saving, according to an analysis of several different implementation scenarios in Uganda.

From the view of the Ugandan Ministry of Health, researchers analysed the potential total cost and lives saved of a fully implemented cryptococcal meningitis screening and pre-emptive treatment programme, against the cost of meningitis treatment and hospitalisation which are costly and burdensome for already stretched health systems.

Cryptococcal meningitis arises from a fungal infection that has spread to the brain and spinal cord causing meningitis. Its onset is common among those living with HIV with an extremely compromised immune system – access to effective and early antiretroviral treatment can ensure they fight-off opportunistic infections such as cryptococcal meningitis in the first place.

You can screen for the cryptococcal antigen (CrAg) which will show up on a test weeks before the onset of meningitis. Testing positive for the antigen means people can be pre-emptively treated using fluconazole. CrAg screening and pre-emptive treatment for patients with advanced HIV has been shown to reduce deaths by 28% in Tanzania and Zambia.

While screening for cryptococcal meningitis in people living with HIV with a CD4 count ≤100 cells per copy is recommended by the World Health Organization and many national programmes, it is poorly implemented in lower resourced contexts. In Uganda, where this study takes place, just 19% of those eligible for CrAg screening were actually screened, and of those who had a CrAg-positive diagnosis, only 65% received pre-emptive therapy.

This study had three objectives. The first was to look at the total cost of CrAg screening and treatment using a model that assumed 80% of all people with CD4 count ≤100 cells per copy were screened (this was used as the base model).  Treatment calculations included pre-emptive treatment for asymptomatic CrAg-positive individuals, and hospitalisation and treatment for those with symptomatic CrAg-positive results and for those missed by screening programmes. They then conducted sensitivity analysis looking at different proportions of CrAg screening and treatment.

The cost of a CrAg test was estimated to be US$ 3.41 per test. The full course of pre-emptive treatment with fluconazole was $39.06. The total year cost of hospitalization and therapy using the drugs for a person with cryptococcal meningitis in Uganda was estimated at $630 using drugs fluconazole and amphotericin for the base model.

In the base model, CrAg screening cost $436,314, pre-emptive treatment cost $295,431, and hospitalisation for those with meningitis cost $2,624,979. This totalled $3,356,724, but saved 7,320 lives, for a cost of $459 per life saved compared to not doing anything at all.

Even in a scenario where 50% of patients were hospitalised with CrAg screening, it had essentially the same total costs as the same amount of hospitalisation without CrAg screening, but an additional 2,910 lives are saved annually. In a scenario with 100% CrAg screening, 1,900 lives are saved in addition to saving $86,000 for the health system compared to not doing anything at all.

A second objective then considered changes in mortality and costs against different meningitis treatment regimens using different drug combinations, which included fluconazole, amphotericin and flucytosine – the last not currently available in Uganda. Health outcomes, hospitalisation costs and survival rates varied across eight screening and treatment strategies.

The researchers found that CrAg screening is cost-saving and results in less deaths when meningitis is treated with amphotericin + flucytosine, or fluconazole + flucytosine. When compared to no screening, it resulted in lower costs and fewer deaths.  In the absence of flucytosine, CrAg screening and treatment of meningitis with amphotericin and fluconazole averts the most deaths.

The third objective reviewed the cost of CrAg screening in the era of test-and-treat, where CD4 testing was not available and assuming 16% of those screened were CrAg-postive. In this scenario it is important to test people for CrAg and start pre-emptive treatment before antiretroviral therapy initiation.

These results were equally as positive, despite the very low CrAg prevalence in the HIV test-and-treat model, because of the availability of antiretroviral treatment. CrAg screening averts 43% of deaths, at a cost of $662 per death averted.

The authors commented, “Ministries of health could invest in national CrAg screening programs, knowing that the cost of screening is offset by the averted deaths and associated costs from cryptococcal meningitis, regardless of meningitis treatment strategy. Investment in such a screening program requires a steady supply of CrAg tests and fluconazole for pre-emptive treatment.”

They note that even fluconazole stock-outs are common, especially in rural areas in Uganda. But if no action in procurement is taken by the government, Ministries of Health will end up spending more on hospitalisation to treat cryptococcal meningitis, with increased mortality.

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Photo credit:
©Gemma Taylor

Written by Caitlin Mahon

Content Specialist - HIV & Sexual Health