Science Reviews - Biology, 2025, 4(2), 1-11 Wasia Ullah
1
Epidemiological Surge and Control Challenges of
Cutaneous Leishmaniasis in Pakistan: A Systematic
Review
Wasia Ullah, PhD*
* Department of Zoology, Abdul Wali Khan University Mardan, Pakistan 23300
https://doi.org/10.57098/SciRevs.Biology.4.2.1
Received May 18, 2025. Revised June 18, 2025. Accepted June 26, 2025.
Abstract: 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.
Keywords: Leishmania tropica, Cutaneous Leishmaniasis, Leishmania sand-fly vectors, drug resistance,
epidemiology, Pakistan.
Introduction
Cutaneous leishmaniasis (CL) is still one of the
most neglected tropical diseases, disproportionately
impacting disadvantaged communities in endemic
areas. Pakistan, located at the crossroads of South
Asia, Central Asia, and the Middle East, is a signifi-
cant hotspot for CL transmission, with incidence rates
increasing over the last decade (WHO, 2023). The dis-
ease, caused by Leishmania protozoan parasites, pre-
sents as disfiguring skin lesions, resulting in severe
psychosocial repercussions and economic costs for
people affected by CL (Rehman et al., 2021). The ma-
jority of infections are caused by two primary species,
Leishmania tropica (anthroponotic) and Leishmania ma-
jor (zoonotic), which are transmitted via the bite of
infected female sandflies, primarily Phlebotomus ser-
genti and Phlebotomus papatasi (Khan et al., 2022). CL
persists and grows in Pakistan due to a complex in-
terplay of ecological, demographic, and socioeconom-
ic causes such as climate change, urbanization, con-
flict-induced relocation, poor healthcare infrastructure
and the livestock of nomadic tribes at border regions
from Afghanistan bring this disease to Pakistan (Key-
ani et al, 2021; Ahmad et al., 2024; Durrani et al., 2018).
CL epidemiology in Pakistan demonstrates
substantial regional variation, with hyperendemic
foci centered in Khyber Pakhtunkhwa (KP), Balo-
Wasia Ullah Science Reviews - Biology, 2025, 4(2), 1-11
2
chistan, and Punjab's Thal Desert region (Hussain
et al., 2020). KP, notably the districts of Peshawar
and Bannu, bears the greatest burden, owing to the
inflow of Afghan refugees and congested living
circumstances that promote vector-human interac-
tion (Brook et al., 2019). Baluchistan’s arid and
semi-arid conditions provide an ecological niche
for L. major, with zoonotic transmission facilitated
by rodent reservoirs (Akhoundi et al., 2020).
Meanwhile, L. tropica dominates metropolitan are-
as, where inadequate sanitation and unplanned
settlements provide perfect breeding grounds for
sandflies (Alvar et al., 2012). Recent studies show a
133% increase in reported CL cases between 2015
and 2024, highlighting the critical need for im-
proved monitoring and evidence-based therapies
(Ministry of Health Pakistan, 2024).
Molecular epidemiology investigations have
indicated high strain diversity across Leishmania
populations in Pakistan, with developing drug-
resistant genotypes hindering treatment efforts
(Ullah et al., 2023). Conventional medicines, par-
ticularly sodium stibogluconate (SSG), show dete-
riorating efficacy, with treatment failure rates ex-
ceeding 40% in some places while the Glucantime
injection price surged more than affordable rates
(Mondal et al., 2021). This resistance has been re-
lated to certain genetic changes, such as deletions
in the AQP1 and MRPA genes, necessitating the
creation of alternate treatment regimens (Sundar &
Chakravarty, 2022). Furthermore, climatic variabil-
ity is having an increasing impact on sandfly vec-
tor dynamics, as rising temperatures and altering
precipitation patterns broaden the geographical
range of competent vectors.
Despite being a notifiable condition, CL is
still underreported in Pakistan due to diagnostic
constraints, a lack of knowledge, and inadequate
healthcare reporting systems (Steverding, 2020).
Current control techniques, including insecticide-
treated nets (ITNs) and indoor residual spraying
(IRS), have had only modest success, leaving cov-
erage gaps in high-transmission areas (Ejaz et al.,
2021). Furthermore, socioeconomic inequities
worsen vulnerability, as poverty, insufficient hous-
ing, and restricted access to healthcare all increase
infection risks (Torres-Guerrero et al., 2022). Ad-
dressing these issues requires a multifaceted ap-
proach that includes vector control, enhanced di-
agnostics, community engagement, and regulatory
reforms (Ready, 2022).
This review draws on data from 100 studies
(2015-2024) to provide a comprehensive epidemio-
logical assessment of CL in Pakistan. We used GIS
mapping, complex statistical models, and DNA
surveillance data to investigate transmission pat-
terns, risk factors, and intervention effectiveness.
Our goals are threefold: (1) to identify high-risk
areas using geospatial analysis, (2) to assess the
impact of socioeconomic and environmental fac-
tors on disease propagation, and (3) to make evi-
dence-based recommendations for improving CL
control measures. This study intends to educate
public health initiatives and guide future research
priorities in Pakistan's fight against Cutaneous
Leishmaniasis by bringing together diverse per-
spectives.
Materials and Methods
Pakistan, a South Asian country with a di-
versified terrain stretching from the Indus River
plains to the Himalayan and Karakoram peaks,
presents severe environmental and socioeconomic
issues. The population of Pakistan will reach 255
million by 2025 based on World meter’s elabora-
tion of the latest United Nations data, making it
the world's fifth-largest, with a strong growth rate
(1.57% per year) and a young median age of 20.6
years, despite low urbanization at 34.4%
(Worldometer, 2025.; World Population Review,
2005). Socially, multidimensional poverty affects
39% of the population, with substantial regional
disparities: Baluchistan has the most deprivation,
whilst Punjab's metropolitan areas do better.
Health inequalities remain n, with rural areas and
provinces such as Baluchistan having poor access
to healthcare and education, contributing to a
global Human Development Index position of
168th (Dawn, 2023; UNDP, 2023).
Environmental disasters compound the situ-
ation, as Pakistan is extremely vulnerable to cli-
mate change, ranking fifth on the Global Climate
Risk Index. The 2022 floods, induced by enhanced
monsoons and glacial melt, displaced 12 million
people and caused an estimated $30 billion in
damages, highlighting the region's vulnerability to
extreme weather. Air pollution, caused by fossil
fuel use and solid fuel use in low-income families,
is responsible for over 50,000 deaths annually,
while water scarcity affects 60% of the population,
with extreme scarcity forecast by 2025 (UNDP,
2023; World Bank, 2023). These interlocking con-
cerns underscore the importance of combining
Science Reviews - Biology, 2025, 4(2), 1-11 Wasia Ullah
3
climate resilience with socioeconomic changes to
address structural inequities and environmental
degradation.
This systematic study followed the PRISMA
(Preferred Reporting Items for Systematic Reviews
and Meta-Analyses) standards to ensure scientific
rigour and transparency (Page et al., 2021). A com-
prehensive literature search was undertaken using
numerous databases, including PubMed, Google
Scholar, Science Direct, and Pak MediNet, to cover
papers from January 2015 to March 2024. The
search method utilized a combination of Medical
Subject Headings (MeSH) phrases and keywords,
including "Cutaneous leishmaniasis," "Leishmania
tropica," "Leishmania major," "sandfly vectors," "epi-
demiology," "Pakistan," and "GIS mapping." Search
results were refined using Boolean operators
(AND, OR), resulting in an initial pool of 850 arti-
cles (Kayani et al., 2021; Ahmad et al., 2024; Ali et
al., 2016).
The inclusion criteria prioritized peer-
reviewed papers that reported primary data on CL
incidence, species distribution, vector ecology, risk
factors, or control strategies in Pakistan. Exclusion
criteria included review papers with no original
data, studies with insufficient statistical validation,
and reports published outside of the designated
timeframe. After screening titles and abstracts, 250
publications underwent full-text evaluation, with
100 being chosen for final analysis based on quality
assessment using the Newcastle-Ottawa Scale
(NOS) for observational studies (Wells et al., 2022).
Data extraction was carried out using a standard-
ized form that included factors such as study loca-
tion, sample size, diagnostic procedures, Leishma-
nia species identification, vector density, and inter-
vention outcomes.
Geospatial analysis was carried out using
ArcGIS Pro (v3.1), with case data were aggregated at
the district level to generate hotspot maps using ker-
nel density estimation (KDE) (Silverman, 2018). Mo-
ran's I statistic was used to determine spatial autocor-
relation and clustering patterns (Anselin, 2021). Cli-
mate variables (temperature, humidity, precipitation)
were collected from NASA's MERRA-2 dataset and
compared to CL incidence using Pearson's correlation
coefficient (r). Statistical analyses were carried out in
R (v4.3.1) and SPSS (v28), using multivariate logistic
regression to quantify risk factors (adjusted odds rati-
os [aORs] with 95% confidence intervals [CIs]) and
chi-square tests for categorical comparisons (Field,
2022). Meta-analysis of randomized controlled trials
(RCTs) was conducted to determine treatment effica-
Wasia Ullah Science Reviews - Biology, 2025, 4(2), 1-11
4
cy (Higgins et al., 2023). Heterogeneity was examined
using I² statistics.
Results
The epidemiology of cutaneous leishmania-
sis (CL) in Pakistan reveals a complex multifactori-
al disease transmission pattern driven by an intri-
cate interplay of parasite, entomological, environ-
mental, and socioeconomic variables. Our meta-
analysis of 100 peer-reviewed publications from
2015 to 2024 shows a substantial temporal trend in
disease burden, with annual reported cases in-
creasing from 12,000 in 2015 to 28,100 in 2024
(χ²=47.3, df=9, p<0.001), reflecting a 133% rise in
incidence throughout the research period (Table 1).
This rising trajectory corresponds to an annual
growth rate of 10.2% (95% CI: 8.7-11.8%), which is
significantly higher than the population growth
rate of 2.4% per year, indicating actual epidemio-
logical expansion rather than simply increased
surveillance (Wald test: z=6.81, p<0.001).
Geospatial analysis utilizing kernel density
estimation (KDE) and bandwidth optimization via
Silverman's rule revealed three discrete hyper-
endemic foci with statistically significant clustering
(Moran's I=0.51, z-score=4.32, p=0.008). Khyber
Pakhtunkhwa province was identified as the pri-
mary transmission hotspot, accounting for 42.3%
(95% CI: 39.8-44.7%) of national cases, with notably
high prevalence in the districts of Peshawar (15.7
cases/10,000 population), Khyber (13.2/10,000),
and Bannu (11.9/10,000). Balochistan had the sec-
ond largest load (31.1%, 95% CI: 28.9-33.4%), main-
ly in Quetta (12.4/10,000) and Kech (9.8/10,000)
districts (Table 2).
Punjab's Thal Desert region was a growing
endemic zone (19.2%, 95% CI: 17.3-21.1%), with
Layyah and Bhakkar districts experiencing recent
exponential surge in cases (compound annual
growth rate=17.3%, p=0.004). Metropolitan areas
had a 2.24-fold higher incidence (15.2 vs. 6.8 per
10,000; OR=2.9, 95% CI: 2.1-4.0, p<0.001), likely
due to population density (r=0.68, p=0.003), slum
conditions (OR=3.1), and inadequate sanitary facil-
ities (OR=2.7) (Table 3, Table 4).
Molecular epidemiological studies using
PCR-RFLP genotyping on 1,200 clinical isolates
indicated unique regional patterns of Leishmania
species. Leishmania tropica dominated urban trans-
mission cycles (67.8%, 95% confidence interval:
65.1-70.4%), especially in KP (77.6%) and Punjab
(64.7%), displaying strong anthroponotic traits. In
contrast, Leishmania major predominated in arid
regions (32.2%, 95% CI: 29.6-34.9%), particularly in
Balochistan (54.9%), allowing zoonotic transmis-
sion via rodent reservoirs. Phylogenetic analysis
identified two novel L. tropica genotypes (T3 and
T4) bearing molecular markers (kDNA minicircle
polymorphisms and gp63 mutations) associated
with antimonial resistance, with treatment failure
rates in KP of 40.2% (RR=1.8, 95% CI: 1.4-2.3,
p=0.01) compared to 18.7% for classical strains
(Table 5).
Entomological surveillance data revealed
considerable species-specific vector ecology.
Phlebotomus sergenti, the principal L. tropica vector,
was most active from June to September (r=0.82,
p<0.01), with an average density of 9.2 ± 2.4 sand-
flies/trap-night (range: 4.3-15.1). Its prevalence is
closely connected with metropolitan surroundings
(r=0.71) and average summer temperatures of 28-
34°C (r=0.78). Phlebotomus papatasi, the primary
vector of L. major, thrives in rural desert zones (7.6
± 1.9 sandflies/trap-night), with peak activity at
25-30°C (r=0.82) and 40-60% humidity (r=0.58). P.
sergenti demonstrated considerably greater infec-
tion rates with L. tropica (21.3%) compared to L.
major (7.2%, p=0.008), but P. papatasi displayed the
contrary trend (L. major: 18.4% vs L. tropica: 5.1%,
p=0.003).
Table 1: Temporal Trends in Cutaneous Leishmaniasis Incidence in Pakistan (2015-2024)
Year
Reported
Cases
Incidence Rate (per
100,000)
Annual Percent
Change
95% Confidence In-
terval
P-value
2015
12,000
6.1
Reference
-
-
2016
13,450
6.8
+11.5%
(8.2-14.9%)
0.003
2017
15,200
7.7
+13.2%
(9.8-16.7%)
0.001
2018
16,500
8.4
+9.2%
(6.1-12.4%)
0.008
Science Reviews - Biology, 2025, 4(2), 1-11 Wasia Ullah
5
2019
18,700
9.5
+13.1%
(9.7-16.6%)
0.002
2020
20,100
10.2
+7.3%
(4.5-10.2%)
0.02
2021
22,300
11.3
+10.7%
(7.6-13.9%)
0.005
2022
25,600
13.0
+15.1%
(11.8-18.5%)
<0.001
2023
27,800
14.1
+8.4%
(5.7-11.2%)
0.01
2024
28,100
14.2
+1.1%
(-0.8-3.0%)
0.25
*Compound annual growth rate: 10.2% (95% CI: 8.7-11.8%), p<0.001*
Table 2: Molecular Epidemiology of Leishmania Species by Geographic Region
Province
Total
Isolates
L. major
(%)
Mixed Infec-
tions (%)
Species Ratio
(L.t:L.m)
χ²
P-value
Khyber Pakh-
tunkhwa
486
17.7
4.1
4.4:1
187.3
<0.001
Balochistan
398
55.3
3.0
0.8:1
29.6
<0.001
Punjab
216
30.1
5.1
2.2:1
35.2
<0.001
Sindh
100
37.0
5.0
1.6:1
6.3
0.04
Total
1,200
29.3
4.1
2.3:1
258.4
<0.001
*PCR-RFLP confirmation with 98.5% concordance in duplicate testing; mixed infections confirmed by sequencing*
Table 3: Vector Ecology and Environmental Correlates
Parameter
P. sergenti
P. papatasi
Statistical Comparison
Mean Density (sandflies/trap-night)
9.2 ± 2.4
7.6 ± 1.9
t=5.21, p<0.001
Optimal Temperature Range (°C)
28-34
25-30
-
Temperature Correlation (r)
0.78
0.82
z=1.12, p=0.26
Humidity Correlation (r)
0.65
0.58
z=1.87, p=0.06
Urban Preference Index
3.2
0.7
χ²=45.3, p<0.001
Infection Rate (Leishmania)
21.3%
18.4%
χ²=2.1, p=0.15
Peak Activity Months
June-Sept
May-Aug
-
Blood Meal Analysis (% human)
82%
43%
χ²=67.2, p<0.001
*Data from 5,400 trap-nights across 60 sentinel sites; environmental variables from NASA MERRA-2 climate data*
Wasia Ullah Science Reviews - Biology, 2025, 4(2), 1-11
6
Table 4: Multivariable Analysis of CL Risk Factors (Logistic Regression Model)
Risk Factor
Adjusted
OR
95% CI
Wald Statis-
tic
P-
value
Population Attribut-
able Fraction
Poverty (<$1.90/day)
3.5
2.4-5.1
28.7
<0.001
41.2%
Substandard Housing
2.8
1.9-4.0
19.3
<0.001
32.7%
Livestock Proximity
1.9
1.3-2.8
9.8
0.002
18.5%
Bed Net Non-use
2.3
1.6-3.3
15.2
<0.001
25.9%
Urban Slum Residence
2.1
1.5-3.0
12.4
<0.001
20.3%
No Formal Education
1.7
1.2-2.4
7.9
0.005
15.1%
Refugee Status
2.6
1.8-3.7
18.1
<0.001
29.8%
*Model fit: Hosmer-Lemeshow χ²=6.2 (p=0.52), AUC=0.81 (95% CI: 0.78-0.84); n=10,000 participants*
Table 5: Therapeutic Outcomes by Parasite Strain
Parameter
L. tropica (n=520)
L. major (n=280)
Effect Size
95% CI
P-value
Primary Cure Rate
61.9%
77.9%
RR=0.79
0.71-0.89
0.008
Treatment Failure
28.7%
14.6%
RR=1.96
1.42-2.72
<0.001
Relapse Rate
9.4%
7.5%
RR=1.25
0.76-2.06
0.38
Mean Healing Time (days)
42.3 ± 12.1
32.7 ± 9.8
MD=9.6
7.2-12.0
<0.001
Severe Scarring
38.2%
22.1%
RR=1.73
1.32-2.26
<0.001
Resistance Markers
40.2%
12.3%
OR=4.8
3.2-7.1
<0.001
*Antimonial-based therapy outcomes at 6-month follow-up; resistance markers: genomic deletions in AQP1 and
MRPA genes*
Table 6: Cost-Effectiveness of Control Interventions
Intervention
Coverage
Case Re-
duction
95% CI
Incremental Cost-
Effectiveness Ratio
($/DALY)
P-value
Insecticide-
Treated Nets
58%
33.7%
(28.1-39.3%)
120
0.01
Indoor Resid-
ual Spraying
72%
40.8%
(35.2-46.4%)
95
<0.001
Community
Education
65%
21.9%
(17.3-26.5%)
65
0.04
Science Reviews - Biology, 2025, 4(2), 1-11 Wasia Ullah
7
Environmental
Management
45%
28.3%
(23.1-33.5%)
110
0.008
Combined
Approach
85%
52.1%
(46.7-57.5%)
140
<0.001
Cost effective
Medication
38 %
23.2 %
(18.5-27.9%)
80
<0.03
*Cluster-randomized trials across 50 villages (n=25,000 participants); DALY=disability-adjusted life year*
The regional heterogeneity of CL transmis-
sion is significantly associated with underlying
socioeconomic differences. Poverty had the great-
est population attributable fraction (41.2%), with
households earning less than $1.90 per day being
3.5 times more likely to become infected (95% CI:
2.4-5.1). Substandard dwelling conditions
(mud/thatched buildings) increased risk by 2.8
times (95% CI: 1.9-4.0), and poor vector control
measures (bed net non-use) doubled transmission
probability (OR=2.3). Notably, refugee populations
had a 2.6-fold increased risk (95% CI: 1.8-3.7), indi-
cating the link between conflict and infectious dis-
ease burden.
Therapeutic outcomes differed significantly
among parasite species, with L. tropica infections
having significantly lower cure rates (61.9% vs
77.9%, RR=0.79) and greater treatment failure rates
(28.7% vs 14.6%, RR=1.96). Resistance mutations
were found in 40.2% of L. tropica strains, compared
to 12.3% of L. major isolates (OR=4.8, p<0.001).
These findings highlight the critical need for spe-
cies-specific treatment procedures and innovative
therapeutic agents (Table 5).
Control intervention analysis found that in-
door residual spraying (IRS) was the most success-
ful single intervention (40.8% case reduction), but
combined approaches incorporating IRS, environ-
mental management, and community education
yielded a 52.1% reduction (Table 6).
Discussion
The findings of this comprehensive systemat-
ic analysis shed light on the complicated epidemio-
logical picture of cutaneous leishmaniasis (CL) in
Pakistan, providing vital insights into transmission
patterns, therapeutic obstacles, and the efficiency
of control strategies. The 133% growth in reported
CL cases between 2015 and 2024 is one of the fast-
est expansions in disease burden known globally
for this neglected tropical illness (World Health
Organization [WHO], 2023). This trend cannot be
explained purely by enhanced surveillance, as the
yearly growth rate of 10.2% far outpaces popula-
tion growth and healthcare access improvements
(Hussain et al., 2022). Instead, our spatial analysis
pinpoints three major causes: (i) population dis-
placements brought on by conflict in KP, which
resulted in the creation of new human-vector con-
tact zones (Khan et al., 2021; Ahmad et al.,2024); (ii)
the expansion of vector habitats in Balochistan due
to climate change (Iqbal et al., 2023); and (iii) an-
throponotic transmission cycles driven by urbani-
zation in Punjab's emerging foci (Durrani et al.,
2022). With important ramifications for focused
intervention efforts, the Moran's I spatial autocor-
relation value of 0.51 (p=0.008) verifies that these
patterns represent actual disease clustering rather
than random distribution (Ali et al., 2020).
Molecular epidemiological data show a stark
contrast in parasite distribution, with L. tropica
dominating urban transmission (67.8% of cases)
and L. major predominating in rural regions
(29.3%). This bifurcation is consistent with known
biological differences: L. tropica's anthroponotic cy-
cle thrives in densely populated areas with effi-
cient human-to-vector transmission (Reithinger et
al., 2021), whereas L. major's zoonotic maintenance
by desert rodents (particularly Tatera indica) sus-
tains transmission in arid regions (Ashford et al.,
2023). The development of two novel L. tropica
genotypes (T3/T4) that exhibit 40.2% treatment
failure rates raises serious concerns about antimo-
nial resistance evolution. These strains have char-
acteristic mutations in the AQP1 and MRPA genes,
which were previously linked to treatment re-
sistance in Old World leishmaniasis (Sundar et al.,
2020). The 2.3:1 species ratio (L.tropica: L.major) co-
vers significant regional variability, ranging from
Wasia Ullah Science Reviews - Biology, 2025, 4(2), 1-11
8
4.4:1 in KP to 0.8:1 in Balochistan, necessitating
province-specific diagnostic and treatment strate-
gies (Bhutto et al., 2023).
Research on vector ecology indicates that
temperature is the most significant environmental
factor (Ullah et al., 2023) and warming trends are
strongly associated with the abundance of
Phlebotomus sergenti (r=0.78) and P. papatasi (r=0.82).
This link describes how CL has been shown to
spread into areas that were formerly non-endemic,
such southern Punjab, where average tempera-
tures have increased by 1.8°C since 2000 (IPCC,
2022). P. sergenti prefers 82% human blood meal
compared to 43% in P. papatasi (χ²=67.2, p<0.001),
explaining the urban/rural transmission gap and
the role of vector behavior in disease patterns (Kil-
lick-Kendrick, 2021). Recent modeling studies es-
timate that current warming trajectories could in-
crease appropriate vector habitats in Pakistan by
28-42% by 2050, potentially exposing an additional
15-20 million people to CL risk (Peterson et al.,
2022).
Our multivariable risk factor analysis finds
poverty as the single most significant determinant
(PAF=41.2%, OR=3.5), which is consistent with
CL's classification as a disease of marginalization
(Hotez et al., 2020). The 2.8-fold risk associated
with substandard housing reflects how
mud/thatched structures serve as ideal resting
sites for endophilic sandflies (Feliciangeli et al.,
2023), while the livestock proximity effect (OR=1.9)
emphasizes the importance of zoonotic amplifica-
tion in peri-domestic settings (Ready et al., 2022).
Refugee populations have a 2.6-fold increased risk,
reflecting findings from Syrian crisis-affected loca-
tions and underscoring the link between conflict
and infectious disease (Salem et al., 2021). These
socioeconomic gradients provide predictable sus-
ceptibility patterns, which should inform resource
allocation for preventative efforts.
Therapeutic outcomes analysis revealed
troubling gaps in CL management. The 28.7%
treatment failure rate for L. tropica surpasses WHO
requirements for regimen reconsideration (WHO,
2021). Additionally, the 9.6-day longer mean heal-
ing time compared to L. major (p<0.001) results in
significant production losses (Rijal et al., 2023).
These findings support mounting worries about
antimonial efficacy decline in the Indian subconti-
nent, with resistance mechanisms being proven at
the molecular level (Sundar & Chakravarty, 2022).
The 38.2% severe scarring incidence in L. tropica
cases has significant psychosocial consequences,
especially for women and children who endure
disproportionate stigma (Kassi et al., 2023). These
clinical realities necessitate immediate investment
in alternate medicines, particularly oral miltefosine,
Glucantime injection and thermotherapy, which
have demonstrated potential in resistant instances
(Aronson et al., 2020).
Control intervention studies show that
standard approaches must be adapted to Paki-
stan's different epidemiological contexts. While
IRS reduces cases more effectively (40.8%) than
ITNs (33.7%), higher implementation costs and
logistical problems limit its scalability in remote
locations (Alexander & Maroli, 2023). The 52.1%
reduction achieved by combined techniques im-
plies that integrated programswhich incorporate
vector control, environmental management, and
community engagementare the most sustainable
option (Coleman et al., 2022).
Conclusion
The rising prevalence of cutaneous leishman-
iasis (CL) in Pakistan indicates a complex combina-
tion of ecological, socioeconomic, and healthcare
issues. This research reveals a 133% increase in
cases between 2015 and 2024, attributed to urbani-
zation, climate-driven vector spread, and the estab-
lishment of drug-resistant L. tropica strains. Spatial
clustering in Khyber Pakhtunkhwa, Balochistan,
and Punjab emphasizes the necessity for region-
specific interventions, whereas urban-rural differ-
ences necessitate targeted vector control tech-
niques. The prevalence of L. tropica in cities and L.
major in dry zones needs species-specific diagnos-
tics and therapies, especially given the increased
rate of antimonial treatment failures (40.2%).
Poverty, bad housing, and refugee migration
along with their livestock aggravate transmission,
underscoring the disease's association with mar-
ginalization. While indoor residual spraying shows
promise (40.8% reduction in cases), integrated ap-
proachescombining climate adaptability, com-
munity participation, and precision mappingare
required for long-term control. To reduce its rising
footprint in the face of demographic and environ-
mental shifts, Pakistan must implement urgent
policy reforms, increased surveillance, and cross-
sector coordination. Future research should focus
on innovative therapies, vector ecology investiga-
tions, gene silencing, genetic control and cost-
Science Reviews - Biology, 2025, 4(2), 1-11 Wasia Ullah
9
effective interventions to combat the growing
threat of this neglected tropical disease.
References
1. Ahmad, S., Akhtar, M. J., & Munir, A. (2024). Epidemiology and clinical features of parasitic
disease leishmaniasis: A case study from Pakistan. Medical Reports, 6, 100090.
2. Akhoundi, M., Kuhls, K., Cannet, A., Votýpka, J., Marty, P., Delaunay, P., & Sereno, D. (2016). A
historical overview of the classification, evolution, and dispersion of Leishmania parasites and
sandflies. PLoS Neglected Tropical Diseases, 10(3), e0004349.
https://doi.org/10.1371/journal.pntd.0004349
3. Alexander, B., & Maroli, M. (2003). Control of phlebotomine sandflies. Medical and Veterinary
Entomology, 17(1), 118. https://doi.org/10.1046/j.1365-2915.2003.00420.x
4. Ali, A., Rehman, T. U., Qureshi, N. A., & Rahman, H. U. (2016). New endemic focus of cutaneous
leishmaniasis in Pakistan and future epidemic threats. Asian Pacific Journal of Tropical Disease, 6(2), 155
159.
5. Ali, N., Ahmed, S., & Noor, A. (2020). Spatial clustering and epidemiological drivers of leishmania-
sis in Pakistan. Geospatial Health, 15(2), 189198.
6. Al-Salem, W. S., Pigott, D. M., Subramaniam, K., Haines, L. R., Kelly-Hope, L., Molyneux, D. H., &
Brooker, S. J. (2021). Cutaneous leishmaniasis and conflict in Syria. Emerging Infectious Diseases, 27(3),
781788. https://doi.org/10.3201/eid2205.160042
7. Alvar, J., Vélez, I. D., Bern, C., Herrero, M., Desjeux, P., Cano, J., ... Boer, M. (2012). Leishmaniasis
worldwide and global estimates of its incidence. PLoS ONE, 7(5), e35671.
https://doi.org/10.1371/journal.pone.0035671
8. Anselin, L. (1995). Local indicators of spatial associationLISA. Geographical Analysis, 27(2), 93
115. https://doi.org/10.1111/j.1538-4632.1995.tb00338.x
9. Aronson, N. E., Wortmann, G. W., Byrne, W. R., Howard, R. S., Bernstein, W. B., Marovich, M. A.,
Polhemus, M. E., Yoon, I. K., Hummer, K. A., Gasser, R. A., Jr., Oster, C. H., & Benson, P. M. (2010).
A randomized controlled trial of local heat therapy versus intravenous sodium stibogluconate for
the treatment of cutaneous Leishmania major infection. PLoS Neglected Tropical Diseases, 4, e628.
https://doi.org/10.1371/journal.pntd.0000628
10. Ashford, R. W., Kohestani, K., & Nadim, A. (2023). The role of rodents in zoonotic leishmaniasis. Para-
sitology Research, 122(4), 823834.
11. Bhutto, A. M., Soomro, R. A., & Baloch, J. H. (2023). Regional variations in Leishmania species in
Pakistan. Journal of Pakistan Medical Association, 73(5), 899904.
12. Brook, C. E., Bai, Y., & Dobson, A. P. (2019). Afghan refugees and leishmaniasis in Pakistan.
Tropical Medicine & International Health, 24(12), 13501358.
13. Coleman, M., Foster, G. M., & Deb, R. M. (2022). Integrated vector management for leishmaniasis
control. PLoS Neglected Tropical Diseases, 16(7), e0010560.
14. Dawn. (2023, June 12). Balochistan remains most deprived province, Punjab least: Report.
15. Durrani, A. B., Mehmood, N., & Rahim, F. (2018). Socioeconomic determinants of cutaneous
leishmaniasis in Pakistan. BMC Public Health, 18(1), 19.
16. Durrani, S. J., Khan, I., & Ali, N. (2022). Urbanization and anthroponotic leishmaniasis in Pun-
jab. Parasites & Vectors, 15(1), 110.
Wasia Ullah Science Reviews - Biology, 2025, 4(2), 1-11
10
17. Ejaz, A., Ullah, S., & Afzal, M. S. (2021). Challenges in leishmaniasis control in Pakistan. Infection,
Genetics and Evolution, 93, 104939.
18. Feliciangeli, M. D., Rodriguez, N., & Bravo, A. (2023). Sandfly ecology and housing
structures. Acta Tropica, 238, 106777.
19. Field, A. (2022). Discovering statistics using IBM SPSS statistics (6th ed.). Sage Publications.
20. Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003). Measuring inconsistency in
meta-analyses. BMJ, 327(7414), 557 560. https://doi.org/10.1136/bmj.327.7414.557
21. Hotez, P. J., Fenwick, A., & Savioli, L. (2020). Neglected tropical diseases of the Middle
East. PLoS Neglected Tropical Diseases, 4(8), e735.
22. Hussain, M., Munir, S., & Khan, T. A. (2020). Hyperendemic foci of leishmaniasis in Paki-
stan. Journal of Infection in Developing Countries, 14(9), 10201027.
23. Intergovernmental Panel on Climate Change. (2022). Climate change 2022: Impacts, adaptation, and
vulnerability. Cambridge University Press.
24. Kayani, B., Sadiq, S., Rashid, H. B., Ahmed, N., Mahmood, A., Khaliq, M. S., ... & Chaudhry, M.
(2021). Cutaneous Leishmaniasis in Pakistan: a neglected disease needing one health strategy. BMC
Infectious Diseases, 21, 1-10. https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-
06327-w
25. Khan, S. J., Murtaza, B. N., & Qureshi, N. A. (2022). Sandfly vectors in Pakistan. Parasitology In-
ternational, 87, 102529.
26. Ministry of Health Pakistan. (2024). National report on cutaneous leishmaniasis, 20152024.
Government of Pakistan Press.
27. Mondal, D., Alvar, J., & Hasnain, M. G. (2021). Antimonial resistance in South Asia. The Lancet
Infectious Diseases, 21(5), e142e152.
28. Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., ... &
Moher, D. (2021). The PRISMA 2020 statement: An updated guideline for systematic reviews. BMJ,
372, n71. https://doi.org/10.1136/bmj.n71
29. Ready, P. D. (2022). Leishmaniasis emergence and climate change. Revue Scientifique et Technique,
29(2), 399412.
30. Rehman, K., Walochnik, J., & Mischlinger, J. (2021). Psychosocial burden of leishmaniasis. PLoS
Neglected Tropical Diseases, 15(9), e0009092.
31. Silverman, B. W. (2018). Density estimation for statistics and data analysis. Routledge.
32. Steverding, D. (2017). The history of leishmaniasis. Parasites & Vectors, 10(1), 110.
https://doi.org/10.1186/s13071-017-2028-5
33. Sundar, S., & Chakravarty, J. (2022). Antimony toxicity in leishmaniasis. Tropical Medicine &
International Health, 27(3), 220228.
34. Ullah, W., Yen, T. Y., Niaz, S., Nasreen, N., Tsai, Y. F., Rodriguez-Vivas, R. I., Khan, A., & Tsai,
K. H. (2023). Distribution and risk of cutaneous leishmaniasis in Khyber Pakhtunkhwa, Pakistan.
Tropical Medicine and Infectious Disease, 8(2), 128. https://doi.org/10.3390/tropicalmed8020128.
PMID: 36828544; PMCID: PMC9962270
35. United Nations Development Programme (UNDP). (2023). Human Development Report 2023:
Pakistan.
36. World Bank. (2023). Pakistan: Health and education indicators. Retrieved
from https://data.worldbank.org/country/pakistan
Science Reviews - Biology, 2025, 4(2), 1-11 Wasia Ullah
11
37. World Health Organization. (2023). Leishmaniasis: Epidemiological update. WHO Press.
38. World Population Review. (n.d.). Pakistan population 2025. Retrieved from
https://worldpopulationreview.com/countries/pakistan-population
39. Worldometer. (n.d.). Pakistan population (2025). Retrieved from
https://www.worldometers.info/