Cutaneous leishmaniasis (CL) is a zoonotic infection caused by obligate intracellular protozoa of the genus Leishmania. This study aimed to investigate CL in Khyber Pakhtunkhwa, Pakistan and to estimate the risk of epidemics. Clinico-epidemiological data of 3188 CL patients were collected from health facilities in 2021. Risk factors were analyzed using the chi-square test. ArcGIS V.10.7.1 was applied for spatial analysis. The association between CL occurrence and climatic variables was examined by Bayesian geostatistical analysis. The clinical data revealed males or individuals younger than 20 years old were more affected. Most patients presented with a single lesion, and the face was the most attacked body part. CL was prevalent in the southern region in winter. A proportional symbol map, a choropleth map, and a digital elevation model map were built to show the distribution of CL. Focal transmission was predicted by inverse distance weighting interpolation. Cluster and outlier analysis identified clusters in Bannu, Dir Lower, and Mardan, and hotspot analysis suggested Bannu as a high-risk foci. Bayesian geostatistical analysis indicated that increasing precipitation and temperature as well as low altitudes were associated with CL infection. The study has provided important information for public health sectors to develop intervention strategies for future CL epidemics.

Cutaneous leishmaniasis (CL), an emerging vector-borne ailment in Khyber Pakhtunkhwa (KPK), Pakistan, exhibits diverse spread patterns and outbreaks. To comprehend its epidemiology and identify parasite species, we conducted an active survey on suspected CL cases (n=8845) in KPK. Microscopy and internal transcribed spacer-1 PCR–restriction fragment length polymorphism (RFLP) molecular techniques detected Leishmania spp. in blood samples. Phylogenetic analysis gauged genetic affinities with other areas. District Bannu displayed the highest CL impact (14.58%), while Swat had the lowest impact (4.33%) among cases. Annual blood examination rate, parasite incidence and slide positivity rate were 4.96 per 1000 people, 0.0233 and 0.047%, respectively. CL infections were prevalent in 1- to 20-y-olds, with males (57.17%) more vulnerable than females (42.82%). Single lesions occurred in 43.73% of patients, while 31.2% people had two lesions, 17.31% had three lesions and 7.74% had more than three lesions. Most had sand-fly exposure but lacked preventive measures like repellents and bed nets. Leishmania tropica was confirmed via RFLP analysis in amplified samples. Phylogenetic analysis unveiled genetic parallels between L. tropica of KPK and isolates from China, Iran, Afghanistan, India, Syria and Morocco. Urgent comprehensive control measures are imperative. Early detection, targeted interventions and raising awareness of CL and sand-fly vectors are vital for reducing the disease's impact. International collaboration and monitoring are crucial to tackle Leishmania spp.’s genetic diversity and curtail its cross-border spread.

In this study, we used in silico techniques to identify available parasite treatments, representing a promising therapeutic avenue. Building upon our computational initiatives aimed at discovering natural inhibitors for various target enzymes from parasites causing neglected tropical diseases (NTDs), we present novel findings on three turmeric-derived phytochemicals as inhibitors of Leishmania pteridine reductase I (PTR1) through in silico methodologies. PTR1, a crucial enzyme in the unique folate metabolism of trypanosomatid parasites, holds established therapeutic significance. Employing MOE software, a molecular docking analysis assesses the efficacy of turmeric phytochemicals against Leishmania PTR1. Validation of the docking protocol is confirmed with an RMSD value of 2. Post-docking, compounds displaying notable interactions with critical residues and binding affinities ranging between −6 and −8 kcal/mol are selected for interaction pattern exploration. Testing twelve turmeric phytochemicals, including curcumin, zingiberene, curcumol, curcumenol, eugenol, bisdemethoxycurcumin, tetrahydrocurcumin, tryethylcurcumin, turmerones, turmerin, demethoxycurcumin, and turmeronols, revealed binding affinities ranging from −5.5 to −8 kcal/mol. Notably, curcumin, demethoxycurcumin, and bisdemethoxycurcumin exhibit binding affinities within −6.5 to −8 kcal/mol and establish substantial interactions with catalytic residues. These phytochemicals hold promise as lead structures for rational drug design targeting Leishmania spp. PTR in future applications. This work underscores the potential of these identified phytochemicals in the development of more effective inhibitors, demonstrating their relevance in addressing neglected tropical diseases caused by parasites.

Dengue fever remains a major public health concern in tropical areas, with recurrent outbreaks in Pakistan's cities. This study investigates the epidemiology and risk factors associated with the 2022 dengue outbreak in Peshawar District, Khyber Pakhtunkhwa. A total of 9,490 laboratory-confirmed cases were analyzed from four major hospitals from June 2022 to December 2022, making this one of the region's largest documented outbreaks. The outbreak followed distinct temporal patterns, with peak transmission occurring during the 40th epidemiological week (8-14 October; n=1,288 cases), which coincided with post-monsoon conditions. Town 3 was identified as the epicenter (37.2% of cases), with significant clustering in slum areas (OR = 2.1, 95% CI: 1.8-2.4, p < 0.001). Demographic study found a greater occurrence among males (68.2%) and young individuals aged 20-29 years (27.1%), indicating occupational and behavioral exposure risks. The case fatality rate remained low (0.031%), indicating better clinical treatment than in earlier epidemics. Environmental factors such as uncovered water storage (76.0%; OR=3.4, p24 hours (92.0%; OR=5.2, p<0.001), as well as behavioral factors such as non-use of mosquito nets (93.0%; OR=6.3, p<0.001) and sleeping outdoors (44.0%; OR=2.8, p<0.001), were identified as critical risk factors. Travel history was documented in 61.5% of cases, emphasizing human mobility as an important transmission factor. The findings highlight the intricate interaction of meteorological, infrastructural, and social behavioral variables influencing dengue spread in urban Pakistan. This study provides evidence for targeted treatments, highlighting the need for integrated vector control techniques, better water infrastructure, and community-based awareness campaigns to reduce future epidemics in high-risk urban settings.

Background: Malaria is a serious public health issue in Pakistan. This study investigated the spatiotemporal patterns, seasonal dynamics, and molecular confirmation of malaria in District Malakand, Khyber Pakhtunkhwa, from 2011 to 2017. Methods: Clinical data were collected from the District Headquarters Hospital over 7 y. A random sample of 120 patients from 2017 was used for microscopic and molecular identification. Spatial-temporal patterns were analysed using ArcGIS (Environmental Systems Research Institute (Esri), Redlands, California, United States). Statistical analyses were performed using SPSS (IBM Corporation, Armonk, New York, United States) and R software (R Foundation for Statistical Computing, Vienna, Austria). Results: Of 41 863 tests, 6246 were positive, yielding an overall test positivity rate of 14.92%. Males (58.89%) were more affected than females. The highest proportion of cases was in the 1–20-y age group. The annual test positive rate declined from 32.97% in 2011 to 10.77% in 2017. Seasonally, autumn had the highest case proportion (46.73%); winter the lowest (7.09%). Spatial analysis identified Gharhi, Dargai and Haryankot as high-burden areas. Inverse distance weighting highlighted these as hotspots for potential transmission. PCR confirmed microscopy-based species identification. Conclusions: Malaria in Malakand peaks in autumn, affecting males and individuals aged <20 y most. Neighbouring villages are at risk from hyper-endemic areas. Microscopy remains a dependable diagnostic tool here.

Background: Malaria and typhoid fever are significant infectious diseases in tropical and subtropical regions, particularly in areas with poor sanitation and widespread vector breeding grounds. Malaria is caused by protozoan parasites of the Plasmodium genus, while typhoid fever is a bacterial infection resulting from Salmonella enterica serovar Typhi. Despite their distinct etiologies, co-infection with both pathogens is frequently reported in malaria-endemic regions, complicating diagnosis and treatment. Reliable diagnostic tools are crucial to distinguish these infections, as overlapping symptoms often lead to misdiagnosis and inappropriate treatment. Objective: This study aimed to determine the prevalence of malaria, typhoid fever, and their co-infection in the Swat, Dir Lower, and Mardan districts of Khyber Pakhtunkhwa, Pakistan, while evaluating diagnostic challenges and public health implications. Methods: A cross-sectional study was conducted from November 2018 to April 2019 in hospitals across the selected districts. A total of 400 febrile patients, aged 1 to 40 years, were randomly recruited. Blood samples were collected and tested using the malaria parasite (MP) test for Plasmodium species and the Widal agglutination test for Salmonella Typhi detection. Data were analyzed using SPSS, and chi-square tests were applied to assess statistical significance between demographic variables and infection rates. Results: Malaria was detected in 168 patients (42.00%), while 126 (31.50%) tested positive for typhoid fever. Co-infection with both pathogens was found in 34 patients (8.50%). The highest prevalence of malaria was recorded in Mardan (44.11%), followed by Swat (41.79%) and Dir Lower (38.80%). Typhoid fever was most prevalent in Mardan (33.82%), with slightly lower rates in Swat (31.34%) and Dir Lower (28.35%). Co-infection rates were highest in Swat (9.70%), followed by Mardan (8.20%) and Dir Lower (7.50%). The incidence was higher in children (12.00% in ages 1–10) and females (9.50%) compared to males (7.50%). Seasonal variation showed co-infection peaking in November (10.28%) and April (10.44%), with the lowest rates in January and February (5.97%). Statistical analysis showed no significant gender (p = 0.5907) or age-group (p = 0.4402) differences in co-infection prevalence. Conclusion: The findings indicate a substantial burden of malaria and typhoid fever in the study regions, with notable co-infection rates and diagnostic challenges. The high rate of false positives in Widal testing suggests the need for more reliable diagnostic tools, such as molecular and blood culture techniques, to improve disease identification and management. Public health interventions focusing on improved sanitation, vaccination, and enhanced diagnostic accuracy are essential to reduce the disease burden in endemic areas.