Publications by authors named "Aisha Khan"

132 Publications

ABO blood group association and COVID-19. COVID-19 susceptibility and severity: A review.

Hematol Transfus Cell Ther 2021 Sep 14. Epub 2021 Sep 14.

QU Health, Qatar University, Doha, Qatar.

Introduction: The SARS-CoV-2 pandemic has been affecting the health and economic, as well as social, life of the entire globe since the end of 2019. The virus causes COVID-19, with a wide range of symptoms among the infected individuals, from asymptomatic infection to mortality. This, along with a high infection rate, prompted efforts to investigate the potential mechanisms of the different clinical manifestations caused by SARS-CoV-2 among the infected populations.

Hypothesis: One of the possible mechanisms that has been reported is the ABO blood system polymorphism. Indeed, one of the major proposed mechanisms is the presence of naturally occurring anti-A antibodies in individuals of groups O and B, which could be partially protective against SARS-CoV-2 virions.

Objective And Method: This article aimed to review the published data on the potential effect of the ABO blood group system on the susceptibility to COVID-19 and the disease progression and outcomes.

Results: The reviewed data suggest that individuals of blood group A are at a higher risk of infection with SARS-CoV-2 and may develop severe COVID-19 outcomes, whereas blood group O is considered protective against the infection, to some extent. However, some of the available studies seem to have been influenced by unaccounted confounders and biases.

Conclusion: Therefore, further appropriately controlled studies are warranted to fully investigate the possible association between the ABO blood groups and COVID-19 susceptibility and severity.
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http://dx.doi.org/10.1016/j.htct.2021.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437766PMC
September 2021

Amniotic fluid-derived extracellular vesicles: characterization and therapeutic efficacy in an experimental model of bronchopulmonary dysplasia.

Cytotherapy 2021 Sep 17. Epub 2021 Sep 17.

Organicell Regenerative Medicine, Inc, Miami, Florida, USA.

Background Aims: Extracellular vesicles (EVs) are being tested for their use as novel therapeutics. However, the optimal source of EVs is currently under investigation. Amniotic fluid (AF) is a natural source of EVs that can be easily obtained for use in regenerative medicine, yet AF-EV characterization has not been fully explored.

Methods: Here the authors demonstrate AF as a rich source of EVs and identify the microRNA and proteomic cargo. Bioinformatics analysis of this cargo revealed multiple pathway targets, including immunomodulatory, anti-inflammatory and free radical scavenging networks. The authors further demonstrated the therapeutic potential of this EV product as a novel preventative agent for bronchopulmonary dysplasia (BPD).

Results: Intra-tracheal administration of AF-EVs preserved alveolar development, attenuated vascular remodeling and pulmonary hypertension, decreased lung pro-inflammatory cytokine expression and reduced macrophage infiltration in an experimental BPD model.

Conclusions: The authors' results suggest that AF is a viable biological fluid for EV harvest and that AF-EVs have strong therapeutic potential for pulmonary diseases, such as BPD, warranting further development to transition this novel EV product into the clinic.
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http://dx.doi.org/10.1016/j.jcyt.2021.07.011DOI Listing
September 2021

Treatment of a COVID-19 long hauler with an amniotic fluid-derived extracellular vesicle biologic.

Respir Med Case Rep 2021 30;34:101502. Epub 2021 Aug 30.

Organicell Regenerative Medicine, Inc., Miami, FL, USA.

Post-COVID-19 infection symptoms such as mental fog, tachycardia, and extreme fatigue are just a few of the symptoms wreaking havoc on patients' lives. Patients with long-term symptoms following COVID-19 are being called long haulers. To date, long haulers are receiving little to no guidance from physicians on their lingering COVID-19 symptoms with limited treatment options available. Zofin is an acellular biologic that contains the extracellular vesicle (EV) fraction of human amniotic fluid and is under investigation for use as a COVID-19 therapeutic. We obtained FDA and IRB approval to investigate the therapeutic use of Zofin in a single long hauler patient case experiencing prolonged shortness of breath and respiratory impairment. Administration of the EV product was shown to be safe. Furthermore, demonstrated respiratory improvements through chest X ray images and oxygen saturation measurement. The single patient IND studies were completed without any reported adverse events or safety concerns. Furthermore, these completed studies demonstrate the feasibility and a therapeutic potential of amniotic fluid-derived EVs for COVID-19 long hauler intervention.
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http://dx.doi.org/10.1016/j.rmcr.2021.101502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405236PMC
August 2021

Scalable culture techniques to generate large numbers of purified human Schwann cells for clinical trials in human spinal cord and peripheral nerve injuries.

J Neurosurg Spine 2021 Sep 3:1-10. Epub 2021 Sep 3.

1The Miami Project to Cure Paralysis.

Objective: Schwann cells (SCs) have been shown to play an essential role in axon regeneration in both peripheral nerve injuries (PNIs) and spinal cord injuries (SCIs). The transplantation of SCs as an adjunctive therapy is currently under investigation in human clinical trials due to their regenerative capacity. Therefore, a reliable method for procuring large quantities of SCs from peripheral nerves is necessary. This paper presents a well-developed, validated, and optimized manufacturing protocol for clinical-grade SCs that are compliant with Current Good Manufacturing Practices (CGMPs).

Methods: The authors evaluated the SC culture manufacturing data from 18 clinical trial participants who were recruited for autologous SC transplantation due to subacute SCI (n = 7), chronic SCI (n = 8), or PNIs (n = 3). To initiate autologous SC cultures, a mean nerve length of 11.8 ± 3.7 cm was harvested either from the sural nerve alone (n = 17) or with the sciatic nerve (n = 1). The nerves were digested with enzymes and SCs were isolated and further expanded in multiple passages to meet the dose requirements for transplantation.

Results: An average yield of 87.2 ± 89.2 million cells at P2 and 150.9 ± 129.9 million cells at P3 with high viability and purity was produced. Cell counts and rates of expansion increased with each subsequent passage from P0 to P3, with the largest rate of expansion between P2 and P3. Larger harvest nerve lengths correlated significantly with greater yields at P0 and P1 (p < 0.05). In addition, a viability and purity above 90% was sustained throughout all passages in nearly all cell products.

Conclusions: This study presents reliable CGMP-compliant manufacturing methods for autologous SC products that are suitable for regenerative treatment of patients with SCI, PNI, or other conditions.
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http://dx.doi.org/10.3171/2020.11.SPINE201433DOI Listing
September 2021

Characterization of extracellular vesicle miRNA identified in peripheral blood of chronic pancreatitis patients.

Mol Cell Biochem 2021 Dec 27;476(12):4331-4341. Epub 2021 Aug 27.

Division of Burn, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Plasma-derived extracellular vesicles (EV) can serve as markers of cell damage/disease but can also have therapeutic utility depending on the nature of their cargo, such as miRNA. Currently, there are challenges and lack of innovations regarding early diagnosis and therapeutic options within different aspects of management of patients suffering from chronic pancreatitis (CP). Use of EV as biomarkers for pancreatic health and/or as adjuvant therapy would make a difference in management of these patients. The aim of this study was to characterize the miRNA cargo of EV purified from the plasma of CP patients and compared to those of healthy participants. EVs were isolated from plasma of 15 CP patients and 10 healthy controls. Nanoparticle tracking analysis was used to determine frequency and size, while NanoString technology was used to characterize the miRNA cargo. Relevant clinical parameters were correlated with EV miRNA cargo. ~ 30 miRNA species were identified to have significantly (p < 0.05) different expression in EV from individuals with CP compared to healthy individuals; ~ 40 miRNA were differentially expressed in EV from pre-diabetic versus non-diabetic CP patients. miR-579-3p, while exhibiting significantly lower (~ 16-fold) expression in CP compared to healthy and lower (~ 24-fold) in CP narcotic users compared to the non-users, is actually enriched (~ 32-fold) within EV in pre-diabetic CP patients compared to non-diabetic CP patients. A unique pattern was identified in female CP patients. These data support the prospect of using a plasma-derived EV cargo to assess pancreatic health and its therapeutic potential in CP patients.
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http://dx.doi.org/10.1007/s11010-021-04248-5DOI Listing
December 2021

Transcatheter Artery Embolization for Postoperative Haemorrhage after Arterio-Venous Malformation - Safer Option.

Acta Med Litu 2021 9;28(1):159-164. Epub 2021 Mar 9.

Department of Imaging and Interventional Radiology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences Shillong, Meghalaya, India.

Summary Introduction: Hemorrhage is one of the commonest and dreaded complications especially with pelvic surgeries. Gestational trophoblastic neoplasias (GTN) are notorious for their propensity to bleed torrentially and metastasis to vital organs. GTN is associated with an arterio-venous malformation (AVM) about 10-15% of the time, which can lead to bleeding after surgery or after complete remission. After the failure of conventional management with chemotherapy or surgery one is compelled to take another modality of management. One of such methods is the use of transcatheter artery embolization in cases of GTN or post-hysterectomy cases of GTN. Transcatheter arteryembolization (TAE) was effective in controlling bleeding due to arterio-venous malformation in 96% of cases.

Case: 46 years P2L2A5 (para 2, living issue 2, abortion 5) post-hysterectomy patient presented with bleeding from the vagina after surgery. Twice she underwent vaginal vault repair after hysterectomy but failed. Ultrasonography (USG) showed arterio-venous malformation (AVM); angiography revealed massive extravasation from (left internal iliac artery and abnormal vascularity from the right internal iliac. She was taken up for bilateral internal iliac arteries embolization but again had a heavy bout of bleeding after one week. CT scan confirmed a residual lesion and she underwent a repeat embolization after which the bleeding stopped. Serum BHCG was advised during workup and it was 1997 IU/ml. A diagnosis of GTN was confirmed. The patient was discharged after two cycles of chemotherapy with advice to review for the third one on an outpatient department basis.

Conclusion: We concluded that TAE is an effective and safer alternative to surgery in postoperative bleeding from AV malformation in the case of GTN. It can be repeated and should be made to more liberal use in emergency settings.
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http://dx.doi.org/10.15388/Amed.2021.28.1.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311843PMC
March 2021

Pluripotent stem cell-derived corneal endothelial cells as an alternative to donor corneal endothelium in keratoplasty.

Stem Cell Reports 2021 Sep 5;16(9):2320-2335. Epub 2021 Aug 5.

The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address:

Here, we evaluate the efficacy of cryopreserved human embryonic stem cell (hESC)-derived corneal endothelial cells (CECs) to form a functional monolayer of corneal endothelium (CE) in rabbits and monkeys. We injected cryopreserved hESC-derived CECs into the anterior chamber of rabbits and monkeys either immediately after mechanical scraping of the central CE or a few days later when corneal edema developed. All preclinical models developed deturgesced and clear corneas following the injection of cryopreserved hESC-derived CECs and remained comparable to the corneas of the untreated eye. Confocal scanning microscopy confirmed an intact structure of hexagonal/polygonal cells and immunohistochemical analysis illustrated a monolayer expressing barrier and pump function proteins in the regenerated CE. The necropsy examination confirmed no remarkable change in multiple tissues assessed for teratoma formation. In conclusion, our data demonstrate the efficacy of cryopreserved hESC-derived CECs to form a functional CE on the denuded Descemet's membrane.
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http://dx.doi.org/10.1016/j.stemcr.2021.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452521PMC
September 2021

The National Heart, Lung, and Blood Institute-funded Production Assistance for Cellular Therapies (PACT) program: Eighteen years of cell therapy.

Clin Transl Sci 2021 Jul 19. Epub 2021 Jul 19.

The Emmes Company, LLC, Rockville, Maryland, USA.

The Production Assistance for Cellular Therapies (PACT) Program, is funded and supported by the US Department of Health and Human Services' National Institutes of Health (NIH) National Heart Lung and Blood Institute (NHLBI) to advance development of somatic cell and genetically modified cell therapeutics in the areas of heart, lung, and blood diseases. The program began in 2003, continued under two competitive renewals, and ended June 2021. PACT has supported cell therapy product manufacturing, investigational new drug enabling preclinical studies, and translational services, and has provided regulatory assistance for candidate cell therapy products that may aid in the repair and regeneration of damaged/diseased cells, tissues, and organs. PACT currently supports the development of novel cell therapies through five cell processing facilities. These facilities offer manufacturing processes, analytical development, technology transfer, process scale-up, and preclinical development expertise necessary to produce cell therapy products that are compliant with Good Laboratory Practices, current Good Manufacturing Practices, and current Good Tissue Practices regulations. The Emmes Company, LLC, serves as the Coordinating Center and assists with the management and coordination of PACT and its application submission and review process. This paper discusses the impact and accomplishments of the PACT program on the cell therapy field and its evolution over the duration of the program. It highlights the work that has been accomplished and provides a foundation to build future programs with similar goals to advance cellular therapeutics in a coordinated and centralized programmatic manner to support unmet medical needs within NHLBI purview.
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http://dx.doi.org/10.1111/cts.13102DOI Listing
July 2021

Impact of mother-baby friendly initiative plus approach on improving human milk feeding for neonates in hospital: a quality improvement before-and-after uncontrolled study.

Eur J Pediatr 2021 Jul 3. Epub 2021 Jul 3.

Maternal, Newborn and Child Health and Nutrition Program, PATH, Seattle, WA, 98121, USA.

Breastfeeding, use of pasteurised donor human milk when mother's own milk is unavailable and kangaroo mother care have independently proven benefits in improving survival of vulnerable sick babies. A triangulated approach called the Mother Baby Friendly Initiative Plus (MBFI+) model, bringing together the combined benefits of these proven interventions, was used to improve exclusive human milk feeding at health facilities through quality improvement and system strengthening approach. This quality improvement before-and-after uncontrolled study enrolled 5343 term and 278 very low birth weight (VLBW) mother-infant dyads. Pre- and post-intervention data were compared to evaluate effect on feeding-related healthcare processes and outcomes. Primary outcome which was incidence of exclusive human milk feeding during hospital stay, improved from 44 to 64.8% (RR 1.47, 95% CI: 1.40-1.55) among term and from 60.5 to 80.7% (RR: 1.33; 95% CI: 1.12-1.59) among VLBW neonates. Neonates receiving extended KMC improved from 43 to 71.1% (RR: 1.65; 95% CI: 1.30-2.10).Conclusion: MBFI+ approach improved exclusive human milk feeding among term and preterm VLBW neonates. What is Known: • Breastfeeding has immense health benefits to sick preterm neonates admitted in NICU. What is New: • Quality improvement approach can lead to system strengthening and can help overcome hindrances to achieve increased breastfeeding rates.
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http://dx.doi.org/10.1007/s00431-021-04141-9DOI Listing
July 2021

Estimation of the monetary burden of treated human cystic echinococcosis in Pakistan.

Acta Trop 2021 Oct 27;222:106026. Epub 2021 Jun 27.

Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States. Electronic address:

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato tapeworms, continues to be a public health problem in many endemic countries, including Pakistan. Patient level data, including age, sex, and cyst(s) location for surgically managed CE patients for the years 2013-2016 from hospitals located in Punjab and Khyber Pakhtunkhwa provinces were obtained from medical charts. Direct and indirect costs associated with surgically managed CE patients treated in private and public hospitals were then estimated and applied to country-level case numbers estimated through the Global Burden of Disease Study. A total cost of US$4,068,666 (95% CI: US$3,097,684 - US$5,295,702) was estimated for the year 2017, with US$3,951,853 (95% CI: US$2,981,400 - US$5,177,610) attributable to direct diagnosis and treatment-related costs and US$117,137 (95% CI: US$91,841 - US$146, 979) attributable to wage losses during the treatment period. Mean direct cost per patient (US$1,056) was approximately 72% of the country's per capita gross domestic product (GDP). Surgical management continues to be the treatment of choice for CE patients in Pakistan. If physicians were to adhere to World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) cyst stage-specific treatment guidelines, it is likely that the number of surgical interventions would decrease as would treatment costs.
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http://dx.doi.org/10.1016/j.actatropica.2021.106026DOI Listing
October 2021

The Interdisciplinary Stem Cell Institute's Use of Food and Drug Administration-Expanded Access Guidelines to Provide Experimental Cell Therapy to Patients With Rare Serious Diseases.

Front Cell Dev Biol 2021 8;9:675738. Epub 2021 Jun 8.

Leonard M. Miller School of Medicine, The Interdisciplinary Stem Cell Institute, University of Miami, Miami, FL, United States.

The U.S. Food and Drug Administration (FDA) provides guidance for expanded access to experimental therapies, which in turn plays an important role in the Twenty-first Century Cures Act mandate to advance cell-based therapy. In cases of incurable diseases where there is a lack of alternative treatment options, many patients seek access to cell-based therapies for the possibility of treatment responses demonstrated in clinical trials. Here, we describe the use of the FDA's expanded access to investigational new drug (IND) to address rare and emergency conditions that include stiff-person syndrome, spinal cord injury, traumatic brain stem injury, complex congenital heart disease, ischemic stroke, and peripheral nerve injury. We have administered both allogeneic bone marrow-derived mesenchymal stem cell (MSC) and autologous Schwann cell (SC) therapy to patients upon emergency request using Single Patient Expanded Access (SPEA) INDs approved by the FDA. In this report, we present our experience with 10 completed SPEA protocols.
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http://dx.doi.org/10.3389/fcell.2021.675738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217825PMC
June 2021

Community Based Assessment of Behavior and Awareness of Risk Factors of Cystic Echinococcosis in Major Cities of Pakistan: A One Health Perspective.

Front Public Health 2021 4;9:648900. Epub 2021 Jun 4.

Key Laboratory of Parasite and Vector Biology, National Health Commission of the People's Republic of China, Shanghai, China.

The parasitic disease, cystic echinococcosis (CE), is a serious health problem in Pakistan. Risk of disease transmission is increased by economic and political instability, poor living conditions, and limited awareness of hygienic practices. The current study aimed to investigate the community perception and awareness regarding the risk factors of CE in Pakistan, from a One Health perspective. We conducted a community-based survey involving 454 participants in the major cities of Pakistan. Quantitative data based on knowledge, attitude, and practices (KAP), the One Health concept, risk factors, and community perception of CE among the general population of the major cities of Pakistan were collected. The questions included those related to knowledge, attitude, practices, One Health concept, risk factors, and community perception. The Chi-squared test was applied to determine the associations regarding KAPs across socio-demographic parameters. KAPs had no significant associations with sociodemographic aspects such as age, sex, religion, ethnicity, education, marital status, occupation, or financial status of the participants. The findings indicated a lack of awareness about CE among the participants. Respondents were unaware of the risk factors and the One Health concept of CE. However, the community attitude and perception were positive toward the control of CE. Illiteracy, deficient sanitation systems and lack of awareness are the contributing factors to CE in Pakistan. It is necessary to make the community aware regarding CE and its importance. Increasing this awareness represents an important step toward the eradication and control of CE.
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http://dx.doi.org/10.3389/fpubh.2021.648900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213035PMC
July 2021

Proteomic analysis of bone marrow-derived mesenchymal stem cell extracellular vesicles from healthy donors: implications for proliferation, angiogenesis, Wnt signaling, and the basement membrane.

Stem Cell Res Ther 2021 06 5;12(1):328. Epub 2021 Jun 5.

Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, 1600 NW 10th Ave, RBSB 2023A, Miami, FL, 33136, USA.

Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown therapeutic potential in various in vitro and in vivo studies in cutaneous wound healing. Furthermore, there are ubiquitous studies highlighting the pro-regenerative effects of BM-MSC extracellular vesicles (BM-MSC EVs). The similarities and differences in BM-MSC EV cargo among potential healthy donors are not well understood. Variation in EV protein cargo is important to understand, as it may be useful in identifying potential therapeutic applications in clinical trials. We hypothesized that the donors would share both important similarities and differences in cargo relating to cell proliferation, angiogenesis, Wnt signaling, and basement membrane formation-processes shown to be critical for effective cutaneous wound healing.

Methods: We harvested BM-MSC EVs from four healthy human donors who underwent strict screening for whole bone marrow donation and further Good Manufacturing Practices-grade cell culture expansion for candidate usage in clinical trials. BM-MSC EV protein cargo was determined via mass spectrometry and Proteome Discoverer software. Corresponding proteomic networks were analyzed via the UniProt Consortium and STRING consortium databases.

Results: More than 3000 proteins were identified in each of the donors, sharing > 600 proteins among all donors. Despite inter-donor variation in protein identities, there were striking similarities in numbers of proteins per biological functional category. In terms of biologic function, the proteins were most associated with transport of ions and proteins, transcription, and the cell cycle, relating to cell proliferation. The donors shared essential cargo relating to angiogenesis, Wnt signaling, and basement membrane formation-essential processes in modulating cutaneous wound repair.

Conclusions: Healthy donors of BM-MSC EVs contain important similarities and differences among protein cargo that may play important roles in their pro-regenerative functions. Further studies are needed to correlate proteomic signatures to functional outcomes in cutaneous repair.
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http://dx.doi.org/10.1186/s13287-021-02405-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180068PMC
June 2021

Tick-borne Diseases in Sheep and Goats in Pakistan: A Systematic Review and Meta-analysis.

Acta Parasitol 2021 May 15. Epub 2021 May 15.

Infectious Diseases Division, Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan.

Background: Ticks are blood-sucking ectoparasites and transmit various types of protozoal, bacterial, and viral diseases in a wild as well as domestic animals and humans globally. Only a few  published reports are avaliable on the prevalence of tick-borne diseases in sheep and goats in Pakistan.

Aim And Objective: The aim of this systematic review and meta-analysis was to evaluate the prevalence (2000-2020) of tick-borne disease (theileriosis, babesiosis, Crimean-Congo hemorrhagic fever infection, and anaplasmosis) in sheep and goats in Pakistan.

Methods: A systematic review of articles published in English language (since 2000-2020) was conducted using PubMed and Google Scholar. Diagnostic methods used in the original reference articles were PCR, PCR-RLB, microscopy, and ELISA.

Results: The overall prevalence of theileriosis, babesiosis, anaplasmosis, and Crimean-Congo hemorrhagic fever (CCHF) infections was 15.40%, 21.18%, 26.78%, and 11.62%, respectively. The prevalence of anaplasmosis was 22.06% (90/408) in sheep, 21.11% (76/360) in goats, and 40% (120/300) in both sheep and goats with substantial differences (P < 0.001). The prevalence of babesiosis among sheep was 29.88% (104/348) with highly significant differences (P < 0.001), in goats was 29.88% (25/60) with slightly significant differences (P < 0.031%), and in both sheep and goats were 7% (21/300) with highly significant differences (P < 0.001) according to subgroup analysis. The percentage of prevalence of theileriosis was 17.70% (207/1169) in sheep with highly substantial differences (P < 0.001), 4.51% (31/687) in goats with significant differences (P < 0.133), and 25% (125/500) in both sheep and goats with a significant difference among them (P < 0.001). The prevalence of CCHF among sheep was 18.63% (149/800) and 4.63% (37/800) in goats, respectively. The widely used detection method was microscopy (45.56%) followed by ELISA (38.38%), PCR (12.56%), and PCR-RLB (3.48%) test, respectively. This is a comprehensive report on the status of tick-borne disease in sheep and goats in Pakistan.

Conclusion: Based on our results, among tick-borne diseases anaplasmosis had the highest prevalence rate in sheep and goats. Due to its high prevalence, control measures should be taken to diagnose and prevent it.
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http://dx.doi.org/10.1007/s11686-021-00396-2DOI Listing
May 2021

Haplotype comparisons of mitochondrial gene sequences (1, , 1) among Pakistan and its neighbouring countries.

Parasitology 2021 08 26;148(9):1019-1029. Epub 2021 Apr 26.

National Institute of Parasitic Diseases, Chinese Centre for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); Key Laboratory of Parasite and Vector Biology; National Health Commission of the People's Republic of China; WHO Collaborating Centre for Tropical Diseases; National Center for International Research on Tropical Diseases; Shanghai; China.

Echinococcus granulosus sensu lato (s.l.) is a zoonotic parasite that causes cystic echinococcosis (CE) in humans. However, E. granulosus sensu stricto (s.s.) is considered the predominant species in CE infections worldwide. According to the population genetic diversity and structure of E. granulosus s.l., gene flow can explain the parasite drift among the neighbouring countries of Pakistan. The mitochondrial (mt) co1 (n = 47), nadh1 (n = 37) and cytb (n = 35) nucleotide sequences of E. granulosus s.l. isolates from Pakistan, Iran, China and India were retrieved from the National Centre for Biotechnology Information database to determine the genealogical relationships. The sequences were grouped as the mt-co1 (genotypes G1 and G3, G6-G7), mt-cytb (genotypes G1 and G3), and mt-nadh1(genotypes G1 and G3). The data were analysed using bioinformatic tools. A total of 19 polymorphic sites for the mt-co1 sequence (374 bp) were observed of which 31.6% (6/19) were parsimony-informative sites. Unique singleton haplotypes within the E. granulosus s.s. haplotype network based on the mt-co1 gene were highly prevalent (68.4%; 13/19) in Pakistani isolates followed by Chinese, Indian and Iranian isolates; four polymorphic sites were detected in the E. canadensis (G6/G7). In E. canadensis mt-co1 haplotype network, 75% (3/4) unique singleton haplotypes were from the Iranian isolates. Twelve polymorphic sites were found using the mt-cytb sequence (547 bp); 25% (3/12) were parsimony-informative and there were 66.7% (8/12) unique singleton haplotypes within the mt-cytb haplotype network in E. granulosus s.s. with the most reported from Pakistan followed by Iran and China. 20 polymorphic sites were detected in E. granulosus s.s. mt-nadh1 sequences (743 bp); 20% (4/20) were parsimony-informative. There were 66.7% (8/12) main single haplotypes within the mt-nadh1 haplotype network, with the most reported from Pakistan followed by that from India, Iran and China. The sequence analyses show low nucleotide diversity and high haplotype diversity in general.
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http://dx.doi.org/10.1017/S0031182021000688DOI Listing
August 2021

Neglected Tropical Diseases in Pakistan: A Story of Neglect.

Iran J Parasitol 2020 Oct-Dec;15(4):618-620

Department of Biosciences, COMSATS University Islamabad (CUI), Park Road, Chakh Shahzad, Islamabad, Pakistan.

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http://dx.doi.org/10.18502/ijpa.v15i4.4882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039485PMC
April 2021

A Phase II study of autologous mesenchymal stromal cells and c-kit positive cardiac cells, alone or in combination, in patients with ischaemic heart failure: the CCTRN CONCERT-HF trial.

Eur J Heart Fail 2021 04 13;23(4):661-674. Epub 2021 Apr 13.

UTHealth University of Texas Health Science Center at Houston School of Public Health, Houston, TX, USA.

Aims: CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy.

Methods And Results: Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (-22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6-min walking distance, and peak oxygen consumption did not differ significantly among groups.

Conclusions: This is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline-directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients.
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http://dx.doi.org/10.1002/ejhf.2178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357352PMC
April 2021

Phase 1 Safety Trial of Autologous Human Schwann Cell Transplantation in Chronic Spinal Cord Injury.

J Neurotrauma 2021 May 3. Epub 2021 May 3.

The Miami Project to Cure Paralysis, Departments of University of Miami, Miami, Florida, USA.

A phase 1 open-label, non-randomized clinical trial was conducted to determine feasibility and safety of autologous human Schwann cell (ahSC) transplantation accompanied by rehabilitation in participants with chronic spinal cord injury (SCI). Magnetic resonance imaging (MRI) was used to screen eligible participants to estimate an individualized volume of cell suspension to be implanted. The trial incorporated standardized multi-modal rehabilitation before and after cell delivery. Participants underwent sural nerve harvest, and ahSCs were isolated and propagated in culture. The dose of culture-expanded ahSCs injected into the chronic spinal cord lesion of each individual followed a cavity-filling volume approach. Primary outcome measures for safety and trend-toward efficacy were assessed. Two participants with American Spinal Injury Association Impairment Scale (AIS) A and two participants with incomplete chronic SCI (AIS B, C) were each enrolled in cervical and thoracic SCI cohorts ( = 8 total). All participants completed the study per protocol, and no serious adverse events related to sural nerve harvest or ahSC transplantation were reported. Urinary tract infections and skin abrasions were the most common adverse events reported. One participant experienced a 4-point improvement in motor function, a 6-point improvement in sensory function, and a 1-level improvement in neurological level of injury. Follow-up MRI in the cervical (6 months) and thoracic (24 months) cohorts revealed a reduction in cyst volume after transplantation with reduced effect over time. This phase 1 trial demonstrated the feasibility and safety of ahSC transplantation combined with a multi-modal rehabilitation protocol for participants with chronic SCI.
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http://dx.doi.org/10.1089/neu.2020.7590DOI Listing
May 2021

Impact of COVID-19 pandemic on surveillance of Crimean-Congo haemorrhagic fever (CCHF) in Pakistan.

Travel Med Infect Dis 2021 May-Jun;41:102011. Epub 2021 Mar 10.

Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan. Electronic address:

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http://dx.doi.org/10.1016/j.tmaid.2021.102011DOI Listing
May 2021

Neurophysiological Changes in the First Year After Cell Transplantation in Sub-acute Complete Paraplegia.

Front Neurol 2020 18;11:514181. Epub 2021 Jan 18.

The Miami Project to Cure Paralysis, Miller School of Medicine, The University of Miami, Miami, FL, United States.

Neurophysiological testing can provide quantitative information about motor, sensory, and autonomic system connectivity following spinal cord injury (SCI). The clinical examination may be insufficiently sensitive and specific to reveal evolving changes in neural circuits after severe injury. Neurophysiologic data may provide otherwise imperceptible circuit information that has rarely been acquired in biologics clinical trials in SCI. We reported a Phase 1 study of autologous purified Schwann cell suspension transplantation into the injury epicenter of participants with complete subacute thoracic SCI, observing no clinical improvements. Here, we report longitudinal electrophysiological assessments conducted during the trial. Six participants underwent neurophysiology screening pre-transplantation with three post-transplantation neurophysiological assessments, focused on the thoracoabdominal region and lower limbs, including MEPs, SSEPs, voluntarily triggered EMG, and changes in GSR. We found several notable signals not detectable by clinical exam. In all six participants, thoracoabdominal motor connectivity was detected below the clinically assigned neurological level defined by sensory preservation. Additionally, small voluntary activations of leg and foot muscles or positive lower extremity MEPs were detected in all participants. Voluntary EMG was most sensitive to detect leg motor function. The recorded MEP amplitudes and latencies indicated a more caudal thoracic level above which amplitude recovery over time was observed. In contrast, further below, amplitudes showed less improvement, and latencies were increased. Intercostal spasms observed with EMG may also indicate this thoracic "motor level." Galvanic skin testing revealed autonomic dysfunction in the hands above the injury levels. As an open-label study, we can establish no clear link between these observations and cell transplantation. This neurophysiological characterization may be of value to detect therapeutic effects in future controlled studies.
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http://dx.doi.org/10.3389/fneur.2020.514181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848788PMC
January 2021

Demographic representation in clinical trials for cell-based therapy.

Contemp Clin Trials Commun 2021 Mar 7;21:100702. Epub 2021 Jan 7.

Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.

Inclusion of women and minorities in clinical research is critical to fully assess the safety and efficacy of innovative therapies. With inadequate representation of demography, generalizability is impaired since pharmacokinetics and pharmacodynamics differ in these patient populations. This study was designed to analyze the voluntary participation rates of different demographic groups in cell-based therapy clinical trials conducted by the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami, Miller School of Medicine. ISCI conducted eight clinical trials between 2007 and 2017. The trials enrolled patients with ischemic and non-ischemic cardiomyopathy, idiopathic pulmonary fibrosis (IPF), aging-frailty, and Type-2 Diabetes. Participants received cell-based therapy (n = 218) or placebo (n = 33). Among the 251 participants, 29.5% were Hispanic and 20% were women. The proportion of individuals participating in each trial was compared to that of the respective disease populations attending University of Miami Health System clinics to calculate the participation to prevalence ratio (PPR). Distribution of women accurately reflected the population attending the University of Miami Health System in trials for dilated cardiomyopathy (DCM) and aging-frailty but was under-represented in others. Similarly, Hispanics and whites were accurately represented in three of the five disease fields, with Hispanics under-represented in frailty and diabetes, and whites over-represented in DCM and IPF. Black patients were accurately represented in the diabetes trial but were under-represented in all others. This study provides insight into challenges of achieving representative inclusion in research. Novel community engagement strategies are necessary to improve inclusion of women and under-represented minorities in clinical research of cell-based therapy.
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http://dx.doi.org/10.1016/j.conctc.2021.100702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817424PMC
March 2021

A new risk stratification system of prostate cancer to identify high-risk biochemical recurrence patients.

Transl Androl Urol 2020 Dec;9(6):2572-2586

Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Biochemical recurrence (BCR) is considered a decisive risk factor for clinical recurrence and the metastasis of prostate cancer (PCa). Therefore, we developed and validated a signature which could be used to accurately predict BCR risk and aid in the selection of PCa treatments.

Methods: A comprehensive genome-wide analysis of data concerning PCa from previous datasets of the Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO) was performed. Lasso and Cox regression analyses were performed to develop and validate a novel signature to help predict BCR risk. Moreover, a nomogram was constructed by combining the signature and clinical variables.

Results: A total of 977 patients were involved in the study. This consisted of patients from the TCGA (n=405), GSE21034 (n=131), GSE70770 (n=193) and GSE116918 (n=248) datasets. A 9-mRNA signature was identified in the TCGA dataset (composed of C9orf152, EPHX2, ASPM, MMP11, CENPF, KIF4A, COL1A1, ASPN, and FANCI) which was significantly associated with BCR (HR =3.72, 95% CI: 2.30-6.00, P<0.0001). This signature was validated in the GSE21034 (HR =7.54, 95% CI: 3.15-18.06, P=0.019), GSE70770 (HR =2.52, 95% CI: 1.50-4.22, P=0.0025) and GSE116918 datasets (HR =4.75, 95% CI: 2.51-9.02, P=0.0035). Multivariate Cox regression and stratified analysis showed that the 9-mRNA signature was a clinical factor independent of prostate-specific antigen (PSA), Gleason score (GS), or AJCC T staging. The mean AUC for 5-year BCR-free survival predictions of the 9-mRNA signature (0.81) was higher than the AUC for PSA, GS, or AJCC T staging (0.52-0.73). Furthermore, we combined the 9-mRNA signature with PSA, GS, or AJCC T staging and demonstrated that this could enhance prognostic accuracy.

Conclusions: The proposed 9-mRNA signature is a promising biomarker for predicting BCR-free survival in PCa. However, further controlled trials are needed to validate our results and explore a role in individualized management of PCa.
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http://dx.doi.org/10.21037/tau-20-1019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807327PMC
December 2020

Investigation of Echinococcus multilocularis in foxes and dogs in Pakistan by detection of copro-DNA.

Parasitol Res 2021 Feb 14;120(2):731-737. Epub 2021 Jan 14.

Department of Biosciences, COMSATS University Islamabad (CUI), Park Road, Chakh Shahzad, Islamabad, Pakistan.

Alveolar echinococcosis (AE) is a zoonosis caused by Echinococcus multilocularis, a heteroxenous parasite belonging to Cestoda class. AE is currently considered an important public health issue, but epidemiological and notably molecular data from several endemic countries, including Pakistan, are sparse. Here we report the first detection of Echinococcus multilocularis in wildlife from Pakistan after real-time PCR and sequencing confirmation in the faecal samples of three foxes from northern Kaghan and Siran regions. The occurrence is estimated at 4.4% (95% CI 0.9-12.4). In order to go further in the epidemiological investigations on E. multilocularis and due to the potential presence of other Echinococcus species, we suggest the need for further epidemiological surveys targeting E. multilocularis and E. granulosus sensu lato isolates from humans and intermediate hosts as well as definitive hosts from wildlife in Pakistan.
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http://dx.doi.org/10.1007/s00436-020-07001-xDOI Listing
February 2021

Epidemiological and pathological characteristics of Cutaneous Leishmaniasis from Baluchistan Province of Pakistan.

Parasitology 2021 04 23;148(5):591-597. Epub 2020 Dec 23.

Department of Biosciences, COMSATS University Islamabad, Park Road, Chak Shahzad, Islamabad, Pakistan.

Cutaneous Leishmaniasis (CL) is considered a neglected tropical disease which in Pakistan can now be considered as a growing public health problem. The exact figures on the magnitude of the disease are lacking both at the national and regional level and only a few health centres are available for diagnosis of CL. The present study was designed to identify the epidemiology of CL infection from August 2018 to December 2019 and to assess clinical aspects of CL in Baluchistan Province of Pakistan. A total of 4072 clinically suspected CL cases were analysed statistically. The highest number of CL cases were reported in May, followed by April, January and then July, February and June and the lowest number of cases were observed in March and November. The highest prevalence rate was found in males where 38% of reported cases were aged 0-9 years. The majority (24.4%) of lesions were found on the hands followed by the face in which cheeks, ears and nose were the effected organs. About 50% of the participants have single lesion while 14% of the participants had two and nearly 3% of the participants have six lesions. The atypical clinical presentations were observed in Baluchistan and common unusual presentations were lupus erythematosus. The study findings suggest that more epidemiological studies and health education campaigns are needed for the population awareness regarding CL in Baluchistan. It is recommended that risk factors should be evaluated to establish control and management strategies to prevent disease at the individual and community level.
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http://dx.doi.org/10.1017/S0031182020002413DOI Listing
April 2021

The spectrum of beta-thalassemia mutations in the 22 Arab countries: a systematic review.

Expert Rev Hematol 2021 01 29;14(1):109-122. Epub 2020 Dec 29.

Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University , Doha, Qatar.

Objectives: To investigate the mutational spectrum in the  gene in Arab patients with β-thal.

Methods: Authors searched five databases (PubMed, Science Direct, Scopus, Web of Science, and Google Scholar) from the time of inception until March 2020.

Results: The authors search strategy yielded 3,229 citations, of which 48 eligible studies captured. 105 mutations were captured, of these, 99 were shared between Arabs and other ethnic groups, six mutations were unique to Arabs (c.92 + 2 T > G, c.-240 G > A, c.150delC, c.420dupT, deletion of 192 bp spanning exon 1, intron 1, and the first two bases of exon 2 of  gene, and deletion of 9.6 kb, including exon 1 and intron 2 of  gene). The most common  gene mutations among Arabs were c.93-21 G > A, c.118 C > T, c.92 + 1 G > A, c.92 + 6 T > C, c.92 + 5 G > C, c.315 + 1 G > A, and c.27dupG. Consanguinity is high among Arab patients with β-thal. Migration into Arab countries led to allelic heterogeneity among Arab patients with β-thal.

Conclusion: Our findings present a platform for further genetic epidemiological studies for Arab patients with β-thal.
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http://dx.doi.org/10.1080/17474086.2021.1860003DOI Listing
January 2021

Rejuvenation of Senescent Endothelial Progenitor Cells by Extracellular Vesicles Derived From Mesenchymal Stromal Cells.

JACC Basic Transl Sci 2020 Nov 28;5(11):1127-1141. Epub 2020 Oct 28.

Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.

Mesenchymal stromal cell (MSC) transplantation is a form of the stem-cell therapy that has shown beneficial effects for many diseases. The use of stem-cell therapy, including MSC transplantation, however, has limitations such as the tumorigenic potential of stem cells and the lack of efficacy of aged autologous cells. An ideal therapeutic approach would keep the beneficial effects of MSC transplantation while circumventing the limitations associated with the use of intact stem cells. This study provides proof-of-concept evidence that MSC-derived extracellular vesicles represent a promising platform to develop an acellular therapeutic approach that would just do that. Extracellular vesicles are membranous vesicles secreted by MSCs and contain bioactive molecules to mediate communication between different cells. Extracellular vesicles can be taken up by recipient cells, and once inside the recipient cells, the bioactive molecules are released to exert the beneficial effects on the recipient cells. This study, for the first time to our knowledge, shows that extracellular vesicles secreted by MSCs recapitulate the beneficial effects of MSCs on vascular repair and promote blood vessel regeneration after ischemic events. Furthermore, MSCs from aged donors can be engineered to produce extracellular vesicles with improved regenerative potential, comparable to MSCs from young donors, thus eliminating the need for allogenic young donors for elderly patients.
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http://dx.doi.org/10.1016/j.jacbts.2020.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691285PMC
November 2020

Retraction "".

Ann Transl Med 2020 Sep;8(18):1206

Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

[This retracts the article DOI: 10.21037/atm.2019.10.113.].
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http://dx.doi.org/10.21037/atm-2020-28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576034PMC
September 2020

Sex-based differences and aging in tactile function loss in persons with type 2 diabetes.

PLoS One 2020 12;15(11):e0242199. Epub 2020 Nov 12.

Department of Pain Medicine Research, University of Texas M.D. Anderson Cancer Center, Houston, TX, United States of America.

Background: Recent evidence of significant sex-based differences in the presentation of Type 2 Diabetes Mellitus (DM) and its complications has been found in humans, which may contribute to sex-based differences in reduced functionality and quality of life. Some functionality, such as tactile function of the hands, has significant direct impact on quality of life. The purpose of the current study was to explore the impact of DM and sex on tactile function, with consideration of variability in health state measures.

Research Design And Methods: A case-control single time point observational study from 2012-2020 in an ethnically diverse population-based community setting. The sample consists of 132 adult individuals: 70 independent community dwelling persons with DM (PwDM) and 62 age- and sex-matched controls (42 males and 90 females in total). The Semmes-Weinstein monofilament test was used to evaluate tactile sensation of the hands.

Results: Tactile sensation thresholds were adversely impacted by sex, age, degree of handedness, high A1c, diagnosis of DM, and neuropathy. Overall, strongly right-handed older adult males with poorly controlled DM and neuropathy possessed the poorest tactile discrimination thresholds. When self-identified minority status was included in a secondary analysis, DM diagnosis was no longer significant; negative impacts of age, neuropathy, degree of handedness, and high A1c remained significant.

Conclusions: The data indicate significant impacts of male sex, age, degree of handedness, self-identified minority status, and metabolic health on the development of poor tactile sensation. This combination of modifiable and non-modifiable factors are important considerations in the monitoring and treatment of DM complications.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242199PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660517PMC
January 2021

Cutaneous Leishmaniasis (CL): A Cross-Sectional Community Based Survey on Knowledge, Attitude and Practices in a Highly Endemic Area of Waziristan (KPK Province), Pakistan.

Acta Trop 2021 Jan 6;213:105746. Epub 2020 Nov 6.

Department of Biosciences, COMSATS University Islamabad (CUI), Park Road, Chak Shahzad, Islamabad, Pakistan. Electronic address:

Recent outbreaks of Cutaneous Leishmaniasis (CL) in Waziristan make the disease a public health concern in Khyber Pakhtunkhwa (KPK) province, Pakistan. The awareness and behavior of local community towards the disease is an important factor towards effective control and management of CL in endemic areas of Pakistan. A cross-sectional community based survey was piloted in new emerging district of North Waziristan Agency (KPK province), Pakistan from August 2019- February 2020. The study aimed to examine the Knowledge, Attitude and Practices (KAP) of the local community members regarding CL. The results revealed that majority of the participants were male. Only 48.2% participants have knowledge about CL and the respondents had a moderate knowledge of CL vector and the disease. Few of the respondents were aware that CL is caused by sand flies, their breeding place, biting time, transmission of CL and control measures. Skin infection and sand-flies were the main disease symptoms and disease vector were known to some of the respondents. Most of the respondents showed positive attitude towards disease seriousness and believed that the disease could be cured and can be treated through modern medicines. Admission to hospitals, cleanliness and use of bed nets were the treatment measures for the disease in suspected patients, whereas some believed that the use of bed nets could be helpful in preventing the leishmaniasis. Moderate knowledge of the CL and its transmission in the study area emphasize the need to initiate health education and awareness campaigns to reduce the disease risk and burden in this highly endemic area in near future.
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http://dx.doi.org/10.1016/j.actatropica.2020.105746DOI Listing
January 2021
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