Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa.

BACKGROUND: Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)-related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy. METHODS: We randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day). Each patient assigned to receive amphotericin B was also randomly assigned to receive fluconazole or flucytosine as a partner drug. After induction treatment, all the patients received fluconazole consolidation therapy and were followed to 10 weeks. RESULTS: A total of 721 patients underwent randomization. Mortality in the oral-regimen, 1-week amphotericin B, and 2-week amphotericin B groups was 18.2% (41 of 225), 21.9% (49 of 224), and 21.4% (49 of 229), respectively, at 2 weeks and was 35.1% (79 of 225), 36.2% (81 of 224), and 39.7% (91 of 229), respectively, at 10 weeks. The upper limit of the one-sided 97.5% confidence interval for the difference in 2-week mortality was 4.2 percentage points for the oral-regimen group versus the 2-week amphotericin B groups and 8.1 percentage points for the 1-week amphotericin B groups versus the 2-week amphotericin B groups, both of which were below the predefined 10-percentage-point noninferiority margin. As a partner drug with amphotericin B, flucytosine was superior to fluconazole (71 deaths [31.1%] vs. 101 deaths [45.0%]; hazard ratio for death at 10 weeks, 0.62; 95% confidence interval [CI], 0.45 to 0.84; P=0.002). One week of amphotericin B plus flucytosine was associated with the lowest 10-week mortality (24.2%; 95% CI, 16.2 to 32.1). Side effects, such as severe anemia, were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen. CONCLUSIONS: One week of amphotericin B plus flucytosine and 2 weeks of fluconazole plus flucytosine were effective as induction therapy for cryptococcal meningitis in resource-limited settings. (ACTA Current Controlled Trials number, ISRCTN45035509 .).

The spectrum of skin diseases in a rural setting in Cameroon (sub-Saharan Africa).

BACKGROUND: Skin disorders are generally considered to be more prevalent in the rural areas of Cameroon. This study was carried out to verify this assumption by describing the spectrum of skin disorders in a rural setting of Cameroon. METHODS: We carried out a community-based clinical skin examination of 400 consenting subjects from 4 villages of Cameroon: Nyamanga (27%), Yebekolo (24%), Mbangassina (23%) and Bilomo (26%). RESULTS: The overall prevalence of skin diseases in our sample was 62% {95% CI: 57.2%, 66.8%} (248/400). The commonest skin disorders were: fungal infections (25.4%), parasitic infestations (21.4%), atrophic skin disorders (11.7%), hypertrophic skin disorders (9.7%), disorders of skin appendages {acne} (8.9%), benign neoplasm (6.5%), bacterial skin infections (5.2%), pigmentation disorders (4.8%), and dermatitis/eczema (4.0%). Skin infections and infestations constituted 52.82% of all skin disorders. The overall prevalence of infectious and parasitic infestation was 32.75% {95%CI: 28.17%, 37.59%} (131/400) as against 29.25% {95%CI: 24.83%, 33.98%} (117/400) for non-infectious disorders.Among people with skin infections/parasitic infestations, those with fungal infections and onchocercal skin lesions were the most prevalent, accounting for 48.1% (63/131) and 35.1% (46/131); and an overall prevalence of 15.75% {95%CI: 12.3%, 19.7%} (63/400) and 11.5% {95%CI: 8.5%, 15.0%} (46/400) respectively.There was secondary bacterial infection in 12.1% {95%CI: 8.31%, 16.82%} (30/248) of subjects with skin diseases. Hypertrophic and atrophic disorders of the skin were mainly keloids (9.68%), scarification marks (6.05%) and burn scars (5.65%). Skin diseases like dermatitis and eczema (4.03%), malignant tumours and pigmentation disorders were rare in our sample.The proportion of subjects diagnosed with skin disorders after examination (62.8%) was significantly higher than the proportion of 40.8% that declared having skin diseases (p < 0.0001). CONCLUSION: The prevalence of skin diseases in the rural Mbam valley is alarming, dominated by easily treatable or preventable skin infections and their magnitude is highly neglected by the community, contrasting with findings in the urban setting. Similar studies are needed in other ecological/demographic settings of the country in order to construct a better understanding of the epidemiology of skin disorders. This would lead to the development of national policies to improve skin care.

Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries.

In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.

Multiple myeloma revealed by spinal cord compression and herpes zoster in a 36-year-old Cameroonian.

Multiple myeloma is a malignant plasma cell disorder occurring mostly in people above 60 years old. The authors describe a case of multiple myeloma in a 36-year-old patient revealed by spinal cord compression and Herpes zoster with a rapidly unfavourable outcome.