Epidemiological Surge and Control Challenges of Cutaneous Leishmaniasis in Pakistan: A Systematic Review

Cutaneous Leishmaniasis (CL) is a major public health concern in Pakistan, with an increasing incidence and new complexity in transmission dynamics, diagnosis, and treatment. This systematic review synthesizes findings from 100 papers (2015-2024) to examine the epidemiology, risk factors, molecular trends, and control measures for CL across different ecological zones of Pakistan. The study found a 133% increase in reported cases (from 12,000 in 2015 to 28,100 in 2024; χ² = 47.3, *p* < 0.001), with hyper endemic clustering in Khyber Pakhtunkhwa (42.3%), Baluchistan (31.1%), and Punjab's Thal Desert (19.2%) (Moran's I = 0.51, *p* = 0.008). Urban centers have a 2.24-fold greater prevalence than rural locations (15.2 vs. 6.8 per 10,000; OR = 2.9, 95% CI: 2.1-4.0), owing to overcrowding and inadequate sanitation. Molecular analysis of 1,200 isolates reveals that Leishmania tropica (67.8%) is the leading urban pathogen, while L. major (29.3%) predominates in dry locations. Two unique L. tropica genotypes (T3/T4) exhibit multidrug resistance, with treatment failure rates of 40.2% (RR = 1.8, *p* = 0.01). Sand-fly vector dynamics show temperature-dependent transmission, with Phlebotomus sergenti (urban, *r* = 0.78) and P. papatasi (rural, *r* = 0.82) abundances substantially associated with warming trends. Poverty (OR = 3.5, PAF = 41.2%), bad housing (OR = 2.8), and refugee status (OR = 2.6) are identified as significant socioeconomic variables. Control treatments have varying efficacy: indoor residual spraying lowers incidence by 40.8% (95% CI: 35.2-46.4%), exceeding insecticide-treated nets (33.7%) but at a higher cost. The emergence of antimonial-resistant strains and climate-induced vector expansion pose a danger to long-term control, demanding integrated solutions that include precision mapping, species-specific medicines, and community engagement. This analysis emphasizes the critical need for a national surveillance system, climate-adaptive solutions, and cross-sectoral coordination to reduce Pakistan's expanding CL burden in the face of ecological and demographic change.