HIV This Week

Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS. 2009;23:525-30.

Cryptococcal meningitis is one of the most important HIV-related opportunistic infections, especially in the developing world. In order to help develop global strategies and priorities for prevention and treatment, it is important to estimate the burden of cryptococcal meningitis. Par and colleagues undertook a global burden of disease estimation using published studies. They used the median incidence rate of available studies in a geographic region to estimate the region-specific cryptococcal meningitis incidence; this was multiplied by the 2007 Joint United Nations Programme on HIV/AIDS (UNAIDS) HIV population estimate for each region to estimate cryptococcal meningitis cases. To estimate deaths, the authors assumed a 9% 3-month case-fatality rate among high-income regions, a 55% rate among low-income and middle-income regions, and a 70% rate in sub-Saharan Africa, based on studies published in these areas and expert opinion. Published incidence ranged from 0.04 to 12% per year among persons with HIV. Sub-Saharan Africa had the highest yearly burden estimate (median incidence 3.2%, 720 000 cases; range, 144 000-1.3 million). Median incidence was lowest in Western and Central Europe and Oceania (</=0.1% each). Globally, approximately 957 900 cases (range, 371 700-1 544 000) of cryptococcal meningitis occur each year, resulting in 624 700 deaths (range, 125 000-1 124 900) by 3 months after infection. This study, the first attempt to estimate the global burden of cryptococcal meningitis, finds the number of cases and deaths to be very high, with most occurring in sub-Saharan Africa. Further work is needed to better define the scope of the problem and track the epidemiology of this infection, in order to prioritize prevention, diagnosis, and treatment strategies.

Editors’ note: This study estimated that deaths due to cryptococcal meningitis in sub-Saharan Africa may be exceeding those due to tuberculosis. This highlights the substantial disease burden of cryptococcal meningitis and the urgent need to improve diagnostic capacity, expand treatment options, and identify preventive measures. One strategy would promote early detection using the serum cryptococcal antigen test and treatment of asymptomatic or latent cryptococcal infection with fluconazole. Expanding access to antiretroviral treatment is likely helping now to reduce the risk of cryptococcal disease, but disease burden remains very high and serious attention needs to be directed to better public health and clinical management of this disease.

Beadsworth MB, Cohen D, Ratcliffe L, Jenkins N, Taylor W, Campbell F, Beeching NJ, Azadeh B. Autopsies in HIV: still identifying missed diagnoses. Int J STD AIDS. 2009;20:84-6.

This study reviews the deaths and autopsies carried out over 23 years, 1983- 2005 , in a British Infection Unit in HIV patients. Of 115 HIV patients known to have died, Beadsworth and colleagues obtained data on 93%. Of this 80% were male, median age 38 (25-68) years; 83% were Caucasian; 12% Black African. Major risk factors were men who have sex with men, 52%; heterosexual in Africa, 17%; and injecting drug use, 8%. The commonest diagnosis pre- and post-autopsy diagnosis was pneumonia. Changes in diagnoses in the 38% who underwent autopsy were high (the authors requested autopsy in 50%). Primary diagnosis changed in 70%, and 36% of all opportunistic infections were missed. This included six of nine cytomegalovirus, all tuberculosis, and 75% of Kaposi’s sarcoma. Lymphoma was overdiagnosed. Thus, despite excellent resources, the majority of primary diagnoses were wrong, suggesting inadequacy of current diagnostics. To improve these and improve both epidemiological data and future management autopsy should be considered for all deaths.

Editors’ note: Although HIV-related mortality has fallen dramatically due to antiretroviral therapy and chemoprophylaxis for opportunistic infections, deaths still occur and we need to better understand what causes them. Autopsy is an important tool for auditing clinical diagnoses, improving diagnostics and management, and enhancing clinical governance in HIV medical practice. This study found errors in the reported primary cause of death in 70% of the deaths occurring in this HIV practice over a 23-year period. Three cases of tuberculosis among the 41 autopsies performed had been completely missed before death. Wherever possible, both physicians and families should request an autopsy in every death of an HIV-positive person in the interests of improved care for those who are living.