PKDL remains a major post-treatment complication across Eastern Africa
Post-kala-azar dermal leishmaniasis PKDL continues to complicate the control of visceral leishmaniasis across Eastern Africa, where persistent skin disease can keep transmission alive long after the visceral infection has been treated. In this systematic review and meta-analysis, investigators assembled the regional evidence base to quantify incidence, identify risk factors, and examine treatment outcomes in a setting where elimination efforts depend on detecting a condition that often appears after patients have already left formal care. The analysis drew on 11 studies and 4,699 patients from Sudan, Ethiopia, Kenya, and Uganda, bringing together a scattered literature that had not previously been synthesized for this region.
The pooled cumulative PKDL incidence was 18.2% with a 95% confidence interval of 4.7% to 49.7%, and heterogeneity was extreme at I2 = 98.1%. That level of spread is not a statistical footnote; it reflects a disease whose expression shifts with geography, treatment era, surveillance intensity, and follow-up duration. Follow-up windows ranged from 6 to 24 months, which alone can alter how often late dermal disease is captured. In a condition that may emerge well after visceral symptoms improve, shorter follow-up can miss meaningful burden while longer observation reveals the true post-treatment load.
Treatment era, geography, and follow-up shaped the burden
The most striking pattern was regional and temporal divergence. Sudan carried the highest pooled incidence at 56.7% in studies from the sodium stibogluconate monotherapy era between 1994 and 2000, while Ethiopia reported 4.6% in 2021 and multi-country cohorts reported 8.2% in 2022. More recent supervised treatment data from Sudan and Kenya in 2024 showed substantially lower incidence. Across the full evidence base, incidence fell from 56.7% before 2010 to 6.4% after 2010, tracking with the move away from sodium stibogluconate monotherapy.
A one-sentence clinical reality stands out here: the drug used to treat visceral leishmaniasis can shape whether patients later return with dermal disease. The post-2010 decline is biologically plausible because more effective and better supervised regimens likely reduce residual parasitic persistence, the substrate for later skin involvement. PKDL is not simply a cosmetic sequel to prior infection; it can preserve the human reservoir that feeds renewed transmission between epidemics. In that sense, regimen choice has consequences well beyond the index hospitalization.
Risk factors point to modifiable and nonmodifiable drivers
Several risk factors repeatedly emerged across the included studies. Treatment regimen was the most important modifiable factor, reinforcing that post-visceral outcomes are partly determined by the antimicrobial strategy used during VL care. Younger age also appeared as a risk factor, suggesting either age-linked host immune responses or differences in exposure and follow-up detection. Geographic location mattered as well, which likely captures a blend of parasite ecology, health-system access, and local treatment protocols.
HIV co-infection added another layer of vulnerability. Immunosuppression can impair durable parasite clearance and may permit low-level persistence that later manifests in the skin. In regions where HIV and leishmaniasis overlap, the post-treatment course becomes harder to predict and more difficult to surveil. The review does not convert those associations into a single causal pathway, but the pattern is clinically coherent: impaired cellular immunity, incomplete parasite eradication, and inconsistent access to follow-up all make PKDL more likely to surface after visceral disease is treated.
Miltefosine plus paromomycin delivered the strongest treatment signal
Treatment data were summarized narratively rather than pooled, but one result stood out sharply. The miltefosine plus paromomycin combination achieved a clinical cure rate of 98.2% in a Phase II trial and outperformed liposomal amphotericin B combinations. That degree of response is notable in a disease where treatment programs often struggle with prolonged courses, toxicity concerns, and the practical difficulty of maintaining adherence after patients have already completed therapy for visceral leishmaniasis.
The mechanism behind that clinical performance is easy to understand even without overstatement. Pairing two antileishmanial agents may improve parasite clearance in dermal tissue, reducing the chance that residual organisms remain available to sustain chronic skin lesions or transmission. For Eastern African programs, a high cure rate with an oral-plus-parenteral strategy could matter as much operationally as it does biologically, particularly if it simplifies delivery in remote areas. Still, the evidence base remains limited enough that a single strong Phase II result cannot settle regional treatment policy on its own.
Surveillance gaps remain a barrier to elimination goals
The review makes a clear point about surveillance. PKDL cannot be controlled well if countries do not look for it long enough, in enough places, and with enough consistency after VL treatment. The broad confidence interval around the pooled incidence estimate reflects both true epidemiologic variation and an uneven evidence base. Differences in how studies defined follow-up, how intensively they searched for cases, and how treatment regimens were implemented all shaped the final numbers.
Standardized surveillance is therefore not a bureaucratic add-on; it is the core clinical infrastructure needed to understand whether transmission is truly declining. Multicountry prospective studies would help separate drug effects from program effects and would allow clearer comparisons across age groups, HIV status, and local transmission patterns. Without that structure, regional control efforts will continue to rely on incomplete estimates and fragmented cohorts.
What the Eastern Africa data support now
PKDL remains a significant post-treatment complication in Eastern Africa, but the burden is not fixed. The shift away from sodium stibogluconate monotherapy appears to align with lower incidence, and treatment regimen now stands out as the most actionable risk factor in the analysis. The strongest therapeutic signal favors miltefosine plus paromomycin, yet the evidence still comes from a limited number of studies with wide heterogeneity and uneven follow-up.
The central unresolved issue is not whether PKDL matters; it clearly does. The harder question is how quickly regional programs can standardize case detection, align treatment protocols, and generate multicountry prospective data robust enough to guide elimination strategies across Eastern Africa.