Phased implementation of screening for cryptococcal disease in South Africa.

Cryptococcus neoformans is the most common cause of laboratory-confirmed meningitis in South Africa. 1 Despite the increased coverage of antiretroviral treatment (ART), the country' s incidence of cryptococcal meningitis remains high, and in routine care settings, the disease has a case-fatality ratio of >50% at 12 weeks post-diagnosis. 2-4 Screening and pre-emptive antifungal treatment is desirable to prevent the development of cryptococcal meningitis and associated deaths. 5-7 Implementing a high-throughput screening programme has been simplified by the development of a sensitive and specific lateral flow assay (LFA) (Immuno-Mycologics, Norman, OK, USA) designed to rapidly detect cryptococcal antigen (CrAg) in several body fluids. In its Rapid Advice guidelines, the World Health Organization (WHO) indicates that, before initiating ART in populations with a high prevalence of cryptococcal antigenaemia, routine screening for cryptococcal disease may be considered among ART-naïve adults who have a CD4+ T-lymphocyte count <100 cells/µl. 10 In two South African ART cohorts, the prevalence of incident antigenaemia among patients with a CD4+ T-lymphocyte count <100 cells/µl was 4% and 7% respectively. This is greater than the breakpoint above which screening was found to be potentially cost-saving in a Ugandan study. To reduce disability and deaths associated with HIV infection, it has been suggested that laboratory-based screening and pre-emptive antifungal treatment of cryptococcal disease be routinely implemented as part of the South African National Strategic Plan for HIV, STIs and TB, 2012-2016. 15 This initiative also complements government's efforts to prioritise primary health care (PHC), with a shift towards early detection of cryptococcal disease at PHC clinics rather than delayed diagnosis of cryptococcal meningitis at hospital level. The National Department of Health has recommended phasing in cryptococcal screening to the provincial departments (Dr Yogan Pillay, personal communication). In the first phase of the programme, lab-based screening will begin at almost 500 health facilities in Gauteng and the Free State, served by three National Health Laboratory Service (NHLS) laboratories performing CD4+ T-lymphocyte testing. In a lab-based strategy, NHLS laboratories will reflexively test the remnant specimen of any blood sample with CD4+ T-lymphocyte count <100 cells/µl for CrAg using the LFA. Results will be reported to the clinician, together with CD4+ T-lymphocyte count results, using existing paper and electronic methods. A phased approach will establish the feasibility and appropriate workflow in these labs. This strategy was selected over point-of-care (POC) testing for several reasons. • First, over 400 000 specimens submitted for CD4+ …