Post kala-azar dermal leishmaniasis in East Africa, with a focus on Sudan: Review of three decades of experience and research

Post kala-azar dermal leishmaniasis (PKDL) is a well-known complication of visceral leishmaniasis (VL, kala-azar) in East Africa, with most cases reported from Sudan; the first description of PKDL dates back to 1921. Some three decades ago, increased interest (in Africa as well in other endemic regions) in PKDL was sparked through a letter published in the Lancet (1991) by the Leishmania research group of the University of Khartoum, describing PKDL in the absence of active VL. Shortly thereafter, a huge outbreak of VL was reported from the Upper Nile state and Gedaref state, which continues to date. Epidemiological studies reported PKDL incidences after VL in up to 50%–60% of VL patients, with age, poor nutrition, and inadequate drug treatment as the most important risk factors. However, the high PKDL rates were not uniformly found in all villages, where determinants such as tribal (genetic) background, socioeconomic circumstances, and exposure may differ. PKDL cases without preceding VL or with concomitant VL (para kala-azar dermal leishmaniasis) were described. Over the years, PKDL cases have been increasingly recognized with detailed clinical description, clinical staging, and combination of other post kala-azar manifestations, such as in the eye (conjunctivitis, blepharitis, and uveitis) and nasal mucosa. Diagnosis was initially done by clinically or microscopic techniques; later, the value of polymerase chain reaction (PCR) was demonstrated. Insight was gained in differential diagnosis, and, importantly, the evolving immune responses from VL (predominantly Th2) to cure (predominantly Th1) with PKDL as an intermediate condition (mixed Th2/Th1). The different immune response was also found to underlie the different most common forms: macular and papulo-nodular. Biomarkers were examined (clinical including imaging, parasitological, and serological and immunological parameters). A study about the natural history indicated that 85% of PKDL cases would self-heal, while other, more severe and persisting cases required treatment. Several studies were carried out to improve treatment outcomes of VL and PKDL with groundbreaking work in combined chemo and immunotherapy. While anthroponotic transmission of VL was assumed in PKDL patients as the reservoir, data on previous and recent entomological studies also provide evidence for zoonotic transmission. Important observations were made on sand fly biting behavior, strategies on the use of insecticide spraying, and the role of animals as zooprophylaxis and/or zoopotentation.