Background: Dapsone is an antibiotic used in the management of leprosy. Following the worldwide adoption of the dapsone-containing multidrug therapy for treating leprosy, an upsurge in the reported frequency of dapsone hypersensitivity syndrome (DHS) has been observed. DHS is associated with a high fatality rate among patients from low-resourced settings and patients with syndrome-associated hepatitis.
Case presentation: This is a case of a Ghanaian male who, while being treated for leprosy with the multidrug therapy, developed exfoliative dermatitis and signs of liver damage, 6 weeks after treatment initiation. He was managed for dapsone-related exfoliative dermatitis and infectious causes of liver damage were investigated. However, the patient's condition rapidly deteriorated with a fatal outcome despite discontinuation of dapsone. DHS was only considered as a differential diagnosis postmortem.
Conclusion: This case highlights the importance of having a high index of suspicion for DHS in all patients on dapsone and the need for a thorough workup for all leprosy patients who present with exfoliative dermatitis and signs of liver involvement within the latency period of the syndrome, especially in low resource settings. Furthermore, it stresses the need for prompt and appropriate treatment as DHS can quickly become fatal in such settings.
{"title":"Lack of Suspicion of Dapsone Hypersensitivity Syndrome in a Leprosy Patient: Case Report with Fatal Outcome.","authors":"Ruth Ansah, Ebenezer Ameyaw Arkoh, Benedict Okoe Quao, Mirjam Groger","doi":"10.2147/RRTM.S434947","DOIUrl":"10.2147/RRTM.S434947","url":null,"abstract":"<p><strong>Background: </strong>Dapsone is an antibiotic used in the management of leprosy. Following the worldwide adoption of the dapsone-containing multidrug therapy for treating leprosy, an upsurge in the reported frequency of dapsone hypersensitivity syndrome (DHS) has been observed. DHS is associated with a high fatality rate among patients from low-resourced settings and patients with syndrome-associated hepatitis.</p><p><strong>Case presentation: </strong>This is a case of a Ghanaian male who, while being treated for leprosy with the multidrug therapy, developed exfoliative dermatitis and signs of liver damage, 6 weeks after treatment initiation. He was managed for dapsone-related exfoliative dermatitis and infectious causes of liver damage were investigated. However, the patient's condition rapidly deteriorated with a fatal outcome despite discontinuation of dapsone. DHS was only considered as a differential diagnosis postmortem.</p><p><strong>Conclusion: </strong>This case highlights the importance of having a high index of suspicion for DHS in all patients on dapsone and the need for a thorough workup for all leprosy patients who present with exfoliative dermatitis and signs of liver involvement within the latency period of the syndrome, especially in low resource settings. Furthermore, it stresses the need for prompt and appropriate treatment as DHS can quickly become fatal in such settings.</p>","PeriodicalId":21138,"journal":{"name":"Research and Reports in Tropical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-14eCollection Date: 2023-01-01DOI: 10.2147/RRTM.S410785
Sarah Sturrock, Samantha Sadoo, Carol Nanyunja, Kirsty Le Doare
Neonatal sepsis causes significant global morbidity and mortality, with the highest burden in resource-limited settings where 99% of neonatal deaths occur. There are multiple challenges to achieving successful treatment of neonates in this setting. Firstly, reliable and low-cost strategies for risk identification are urgently needed to facilitate treatment as early as possible. Improved laboratory capacity to allow identification of causative organisms would support antimicrobial stewardship. Antibiotic treatment is still hampered by availability, but also increasingly by antimicrobial resistance - making surveillance of organisms and judicious antibiotic use a priority. Finally, supportive care is key in the management of the neonate with sepsis and has been underrecognized as a priority in resource-limited settings. This includes fluid balance and nutritional support in the acute phase, and follow-up care in order to mitigate complications and optimise long-term outcomes. There is much more work to be done in identifying the holistic needs of neonates and their families to provide effective family-integrated interventions and complete the package of neonatal sepsis management in resource-limited settings.
{"title":"Improving the Treatment of Neonatal Sepsis in Resource-Limited Settings: Gaps and Recommendations.","authors":"Sarah Sturrock, Samantha Sadoo, Carol Nanyunja, Kirsty Le Doare","doi":"10.2147/RRTM.S410785","DOIUrl":"10.2147/RRTM.S410785","url":null,"abstract":"<p><p>Neonatal sepsis causes significant global morbidity and mortality, with the highest burden in resource-limited settings where 99% of neonatal deaths occur. There are multiple challenges to achieving successful treatment of neonates in this setting. Firstly, reliable and low-cost strategies for risk identification are urgently needed to facilitate treatment as early as possible. Improved laboratory capacity to allow identification of causative organisms would support antimicrobial stewardship. Antibiotic treatment is still hampered by availability, but also increasingly by antimicrobial resistance - making surveillance of organisms and judicious antibiotic use a priority. Finally, supportive care is key in the management of the neonate with sepsis and has been underrecognized as a priority in resource-limited settings. This includes fluid balance and nutritional support in the acute phase, and follow-up care in order to mitigate complications and optimise long-term outcomes. There is much more work to be done in identifying the holistic needs of neonates and their families to provide effective family-integrated interventions and complete the package of neonatal sepsis management in resource-limited settings.</p>","PeriodicalId":21138,"journal":{"name":"Research and Reports in Tropical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10728307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138808470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Enora Le Bec, Madibele Kam, Sigiriya Aebischer Perone, Philippa Boulle, Justin Cikomola, Maria Eugenia Gandur, Mario Gehri, Sylvia Kehlenbrink, David Beran
Abstract: Lack of awareness, access to insulin and diabetes care can result in high levels of morbidity and mortality for children with type 1 diabetes (T1DM) in sub-Saharan Africa (SSA). Improvements in access to insulin and diabetes management have improved outcomes in some settings. However, many people still present in diabetic ketoacidosis (DKA) in parallel to misdiagnosis of children with T1DM in contexts with high rates of communicable diseases. The aim of this study was to highlight the complexity of diagnosing pediatric T1DM in a healthcare environment dominated by infectious diseases and lack of adequate health system resources. This was done by developing clinical vignettes and recreating the hypothetico-deductive process of a clinician confronted with DKA in the absence of identification of pathognomonic elements of diabetes and with limited diagnostic tools. A non-systematic literature search for T1DM and DKA in SSA was conducted and used to construct clinical vignettes for children presenting in DKA. A broad differential diagnosis of the main conditions present in SSA was made, then used to construct a clinician’s medical reasoning, and anticipate the results of different actions on the diagnostic process. An examination of the use of the digital based Integrated Management of Childhood Illness diagnostic algorithm was done, and an analysis of the software’s efficiency in adequately diagnosing DKA was assessed. The main obstacles to diagnosis were low specificity of non-pathognomonic DKA symptoms and lack of tools to measure blood or urine glucose. Avenues for improvement include awareness of T1DM symptomatology in communities and health systems, and greater availability of diagnostic tests. Through this work clinical vignettes are shown to be a useful tool in analyzing the obstacles to underdiagnosis of diabetes, a technique that could be used for other pathologies in limited settings, for clinical teaching, research, and advocacy. Keywords: type 1 diabetes, underdiagnosis, sub-Saharan Africa, clinical vignette
{"title":"Using Clinical Vignettes to Understand the Complexity of Diagnosing Type 1 Diabetes in Sub-Saharan Africa","authors":"Enora Le Bec, Madibele Kam, Sigiriya Aebischer Perone, Philippa Boulle, Justin Cikomola, Maria Eugenia Gandur, Mario Gehri, Sylvia Kehlenbrink, David Beran","doi":"10.2147/rrtm.s397127","DOIUrl":"https://doi.org/10.2147/rrtm.s397127","url":null,"abstract":"Abstract: Lack of awareness, access to insulin and diabetes care can result in high levels of morbidity and mortality for children with type 1 diabetes (T1DM) in sub-Saharan Africa (SSA). Improvements in access to insulin and diabetes management have improved outcomes in some settings. However, many people still present in diabetic ketoacidosis (DKA) in parallel to misdiagnosis of children with T1DM in contexts with high rates of communicable diseases. The aim of this study was to highlight the complexity of diagnosing pediatric T1DM in a healthcare environment dominated by infectious diseases and lack of adequate health system resources. This was done by developing clinical vignettes and recreating the hypothetico-deductive process of a clinician confronted with DKA in the absence of identification of pathognomonic elements of diabetes and with limited diagnostic tools. A non-systematic literature search for T1DM and DKA in SSA was conducted and used to construct clinical vignettes for children presenting in DKA. A broad differential diagnosis of the main conditions present in SSA was made, then used to construct a clinician’s medical reasoning, and anticipate the results of different actions on the diagnostic process. An examination of the use of the digital based Integrated Management of Childhood Illness diagnostic algorithm was done, and an analysis of the software’s efficiency in adequately diagnosing DKA was assessed. The main obstacles to diagnosis were low specificity of non-pathognomonic DKA symptoms and lack of tools to measure blood or urine glucose. Avenues for improvement include awareness of T1DM symptomatology in communities and health systems, and greater availability of diagnostic tests. Through this work clinical vignettes are shown to be a useful tool in analyzing the obstacles to underdiagnosis of diabetes, a technique that could be used for other pathologies in limited settings, for clinical teaching, research, and advocacy. Keywords: type 1 diabetes, underdiagnosis, sub-Saharan Africa, clinical vignette","PeriodicalId":21138,"journal":{"name":"Research and Reports in Tropical Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135714718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: In 2019, the East African Community (EAC) lost 12,048,918 disability-adjusted life-years (DALY) across all ages from neglected tropical diseases (NTDs). The specific objectives of the study reported in the paper were to estimate for EAC the monetary value of DALYs sustained by all ages from NTDs, and the potential productivity losses within the working age bracket of 15 years and above.
Methods: The EAC total monetary value of DALYs lost from all 20 NTDs is the sum of each partner state's monetary value of DALYs lost from all 20 NTDs. The ith partner state's monetary value of DALY from jth disease equals ith state's GDP per capita net of current health expenditure multiplied by DALYs lost from jth disease in 2019. The EAC total productivity losses attributable to DALYs lost from all 20 NTDs is the sum of lost productivity across the seven partner states. The ith partner state's productivity loss associated with jth disease equals ith state's GDP per capita net of current health expenditure multiplied by DALYs lost from jth disease and the ith state's labour force participation rate adjusted for underutilization (unemployment and time-related underemployment) in 2019.
Results: The total 12,048,918 DALYs lost in EAC from NTDs had a of International Dollars (Int$) 21,824,211,076 and an average of Int$ 1811 per DALY. The 2,614,464 DALYs lost from NTD among 15-year-olds and above caused an estimated of Int$ 2,588,601,097 (0.392% of the EAC gross domestic product in 2019), and an average of Int$ 990.1 per DALY.
Conclusion: The study succeeded in estimating the monetary value of DALYs sustained by all ages from 20 NTDs, and the potential productivity losses within the working age bracket of 15 years and above in the seven EAC partner states. The DALYs lost from NTD among 15-year-olds and above caused a sizeable loss in the economic productivity of EAC.
{"title":"Monetary Value of Disability-Adjusted Life Years and Potential Productivity Losses Associated With Neglected Tropical Diseases in the East African Community.","authors":"Joses Muthuri Kirigia, Patrick Kinyua Kubai","doi":"10.2147/RRTM.S382288","DOIUrl":"https://doi.org/10.2147/RRTM.S382288","url":null,"abstract":"<p><strong>Introduction: </strong>In 2019, the East African Community (EAC) lost 12,048,918 disability-adjusted life-years (DALY) across all ages from neglected tropical diseases (NTDs). The specific objectives of the study reported in the paper were to estimate for EAC the monetary value of DALYs sustained by all ages from NTDs, and the potential productivity losses within the working age bracket of 15 years and above.</p><p><strong>Methods: </strong>The EAC total monetary value of DALYs lost from all 20 NTDs is the sum of each partner state's monetary value of DALYs lost from all 20 NTDs. The ith partner state's monetary value of DALY from jth disease equals ith state's GDP per capita net of current health expenditure multiplied by DALYs lost from jth disease in 2019. The EAC total productivity losses attributable to DALYs lost from all 20 NTDs is the sum of lost productivity across the seven partner states. The ith partner state's productivity loss associated with jth disease equals ith state's GDP per capita net of current health expenditure multiplied by DALYs lost from jth disease and the ith state's labour force participation rate adjusted for underutilization (unemployment and time-related underemployment) in 2019.</p><p><strong>Results: </strong>The total 12,048,918 DALYs lost in EAC from NTDs had a of International Dollars (Int$) 21,824,211,076 and an average of Int$ 1811 per DALY. The 2,614,464 DALYs lost from NTD among 15-year-olds and above caused an estimated of Int$ 2,588,601,097 (0.392% of the EAC gross domestic product in 2019), and an average of Int$ 990.1 per DALY.</p><p><strong>Conclusion: </strong>The study succeeded in estimating the monetary value of DALYs sustained by all ages from 20 NTDs, and the potential productivity losses within the working age bracket of 15 years and above in the seven EAC partner states. The DALYs lost from NTD among 15-year-olds and above caused a sizeable loss in the economic productivity of EAC.</p>","PeriodicalId":21138,"journal":{"name":"Research and Reports in Tropical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b9/3d/rrtm-14-35.PMC10317842.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10180428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Malawi is a small landlocked country in Southern Africa, which faces a number of development challenges. It is one of the world's poorest nations and over 70% of the population live below the International Poverty Line of $2.15 per day. Health inequalities are a well-documented problem and those most affected are women and children. Non-governmental organizations (NGOs) play a vital role in supplementing government efforts to provide health services to vulnerable people in areas that are difficult to reach. The World Medical Fund (WMF) is a small medical charity that operates in the central, rural, Nkhotakota region of Malawi where many children lack access to even basic health services. To date, WMF has successfully provided free care and treatment for over 400,000 sick children, but its initiatives, such as mobile clinics, rely entirely on external donations. Since 2000, the funding resources available to small NGOs have declined and efforts to attract funding have become increasingly competitive. Frequently, the criteria used for funding decisions are too rigid, and do not reflect the difficult operating conditions on the ground in rural Africa. As one of the world's most highly resource constrained healthcare environments, Malawi illustrates the need for more flexible funding criteria from donors so that NGOs can carry out their work to save children's lives.
{"title":"Exploring the Funding Challenges Faced by Small NGOs: Perspectives from an Organization with Practical Experience of Working in Rural Malawi.","authors":"Faiz Kermani, Sbita Tia Anna Reandi","doi":"10.2147/RRTM.S424075","DOIUrl":"https://doi.org/10.2147/RRTM.S424075","url":null,"abstract":"<p><p>Malawi is a small landlocked country in Southern Africa, which faces a number of development challenges. It is one of the world's poorest nations and over 70% of the population live below the International Poverty Line of $2.15 per day. Health inequalities are a well-documented problem and those most affected are women and children. Non-governmental organizations (NGOs) play a vital role in supplementing government efforts to provide health services to vulnerable people in areas that are difficult to reach. The World Medical Fund (WMF) is a small medical charity that operates in the central, rural, Nkhotakota region of Malawi where many children lack access to even basic health services. To date, WMF has successfully provided free care and treatment for over 400,000 sick children, but its initiatives, such as mobile clinics, rely entirely on external donations. Since 2000, the funding resources available to small NGOs have declined and efforts to attract funding have become increasingly competitive. Frequently, the criteria used for funding decisions are too rigid, and do not reflect the difficult operating conditions on the ground in rural Africa. As one of the world's most highly resource constrained healthcare environments, Malawi illustrates the need for more flexible funding criteria from donors so that NGOs can carry out their work to save children's lives.</p>","PeriodicalId":21138,"journal":{"name":"Research and Reports in Tropical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0c/0b/rrtm-14-99.PMC10479561.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rangel de Sousa Costa, Luiz Celso Hygino da Cruz, Simone Rachid de Souza, Nina Ventura, Diogo Goulart Corrêa
Paracoccidioidomycosis (PCM) is a infection caused by the thermodimorphic fungus Paracoccidioides spp. (P. lutzii and, mainly, P. brasiliensis). This infection predominantly affects rural male workers aged between 30 and 50 years old who deal with soil on daily activities. Clinically, the disease is classified as acute/subacute phase, which evolves rapidly, secondary to dissemination of the fungus through to the phagocytic-mononuclear system, leading to fever, weight loss, and anorexia, associated with hepatosplenomegaly and lymphadenopathy, which can be complicated with suppuration and fistulization; and chronic phase, which corresponds to 74% to 95% of symptomatic cases, with a common pulmonary involvement. Central nervous system involvement is almost always a characteristic of the chronic form. Inhalation is the most common route of primary infection, usually affecting the lungs, forming the primary complex. From the primary complex, hematogenic dissemination can occur to any organ, including the brain and spinal cord. Although PCM of the central nervous system diagnosis is usually based on histopathological analysis and the imaging features are not specific for PCM, computed tomography and magnetic resonance imaging can demonstrate evidences of granuloma, abscess, meningitis, or a combination of these lesions, contributing to a preoperative diagnosis, especially when considered in conjunction with epidemiology. In this article, we review the pathophysiology, clinical manifestations and imaging aspects of neuro-PCM.
{"title":"Insights into Magnetic Resonance Imaging Findings in Central Nervous System Paracoccidioidomycosis: A Comprehensive Review.","authors":"Rangel de Sousa Costa, Luiz Celso Hygino da Cruz, Simone Rachid de Souza, Nina Ventura, Diogo Goulart Corrêa","doi":"10.2147/RRTM.S391633","DOIUrl":"https://doi.org/10.2147/RRTM.S391633","url":null,"abstract":"<p><p>Paracoccidioidomycosis (PCM) is a infection caused by the thermodimorphic fungus <i>Paracoccidioides</i> spp. (P. <i>lutzii</i> and, mainly, <i>P. brasiliensis</i>). This infection predominantly affects rural male workers aged between 30 and 50 years old who deal with soil on daily activities. Clinically, the disease is classified as acute/subacute phase, which evolves rapidly, secondary to dissemination of the fungus through to the phagocytic-mononuclear system, leading to fever, weight loss, and anorexia, associated with hepatosplenomegaly and lymphadenopathy, which can be complicated with suppuration and fistulization; and chronic phase, which corresponds to 74% to 95% of symptomatic cases, with a common pulmonary involvement. Central nervous system involvement is almost always a characteristic of the chronic form. Inhalation is the most common route of primary infection, usually affecting the lungs, forming the primary complex. From the primary complex, hematogenic dissemination can occur to any organ, including the brain and spinal cord. Although PCM of the central nervous system diagnosis is usually based on histopathological analysis and the imaging features are not specific for PCM, computed tomography and magnetic resonance imaging can demonstrate evidences of granuloma, abscess, meningitis, or a combination of these lesions, contributing to a preoperative diagnosis, especially when considered in conjunction with epidemiology. In this article, we review the pathophysiology, clinical manifestations and imaging aspects of neuro-PCM.</p>","PeriodicalId":21138,"journal":{"name":"Research and Reports in Tropical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ad/d1/rrtm-14-87.PMC10406117.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10319558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juan Carlos Gabaldón-Figueira, Nieves Martinez-Peinado, Elisa Escabia, Albert Ros-Lucas, Eric Chatelain, Ivan Scandale, Joaquim Gascon, María-Jesús Pinazo, Julio Alonso-Padilla
Chagas disease is the most important protozoan infection in the Americas, and constitutes a significant public health concern throughout the world. Development of new medications against its etiologic agent, Trypanosoma cruzi, has been traditionally slow and difficult, lagging in comparison with diseases caused by other kinetoplastid parasites. Among the factors that explain this are the incompletely understood mechanisms of pathogenesis of T. cruzi infection and its complex set of interactions with the host in the chronic stage of the disease. These demand the performance of a variety of in vitro and in vivo assays as part of any drug development effort. In this review, we discuss recent breakthroughs in the understanding of the parasite's life cycle and their implications in the search for new chemotherapeutics. For this, we present a framework to guide drug discovery efforts against Chagas disease, considering state-of-the-art preclinical models and recently developed tools for the identification and validation of molecular targets.
{"title":"State-of-the-Art in the Drug Discovery Pathway for Chagas Disease: A Framework for Drug Development and Target Validation.","authors":"Juan Carlos Gabaldón-Figueira, Nieves Martinez-Peinado, Elisa Escabia, Albert Ros-Lucas, Eric Chatelain, Ivan Scandale, Joaquim Gascon, María-Jesús Pinazo, Julio Alonso-Padilla","doi":"10.2147/RRTM.S415273","DOIUrl":"https://doi.org/10.2147/RRTM.S415273","url":null,"abstract":"<p><p>Chagas disease is the most important protozoan infection in the Americas, and constitutes a significant public health concern throughout the world. Development of new medications against its etiologic agent, <i>Trypanosoma cruzi</i>, has been traditionally slow and difficult, lagging in comparison with diseases caused by other kinetoplastid parasites. Among the factors that explain this are the incompletely understood mechanisms of pathogenesis of <i>T. cruzi</i> infection and its complex set of interactions with the host in the chronic stage of the disease. These demand the performance of a variety of in vitro and in vivo assays as part of any drug development effort. In this review, we discuss recent breakthroughs in the understanding of the parasite's life cycle and their implications in the search for new chemotherapeutics. For this, we present a framework to guide drug discovery efforts against Chagas disease, considering state-of-the-art preclinical models and recently developed tools for the identification and validation of molecular targets.</p>","PeriodicalId":21138,"journal":{"name":"Research and Reports in Tropical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/db/5e/rrtm-14-1.PMC10277022.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9722561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Leishmaniasis is a vector-borne protozoan infection that has a wide clinical spectrum in the tropics and subtropics. Kidney damage is frequently associated with increased morbidity and mortality in visceral leishmaniasis (VL) patients. However, up to date, there is a very limited report on the effect of visceral leishmaniasis on kidney function profiling in Ethiopia.
Objective: To evaluate the renal function profile in human visceral leishmaniasis (kala-azar) patients.
Materials and methods: Human blood was taken from VL patients (n = 100) and healthy controls (n = 100) attending Kahsay Abera and Mearg Hospitals, Western Tigray of Ethiopia. Serum was separated according to the conventional protocol and kidney function profiling (creatinine, urea, and uric acid) was analyzed by Mindray 200E automated chemistry analyzer. The estimated glomerular filtration rate (eGFR) was also assessed in this study. The obtained data were processed using SPSS Version 23.0. Descriptive statistics, independent-test, and bivariate correlations were used for data analysis. P values <0.05 were considered statistically significant at a 95% confidence level.
Results: The mean serum creatinine level was found significantly higher, while respective serum urea and eGFR were significantly lower in VL patients compared to healthy controls. Specifically, from 100 VL cases, an increased level of serum creatinine, urea, and uric acid was found in 10%, 9% and 15% VL cases, respectively; meanwhile, a decreased serum urea and eGFR have been reported from 33% to 44% VL cases, respectively.
Conclusion: The finding of this study asserted that visceral leishmaniasis causes derangement in kidney activities characterized by alteration of renal function profile. This may indicate that VL is the determinant factor for developing kidney dysfunction. This study encourages researchers to engage in visceral leishmaniasis and its effect on other organ function profiles in humans and identify potential markers for both prevention and intervention.
背景:利什曼病是一种病媒传播的原虫感染,在热带和亚热带地区具有广泛的临床谱。肾脏损害通常与内脏利什曼病(VL)患者的发病率和死亡率增加有关。然而,到目前为止,关于内脏利什曼病对埃塞俄比亚肾功能分析的影响的报道非常有限。目的:探讨人内脏利什曼病(黑热病)患者的肾功能特点。材料和方法:人血取自埃塞俄比亚西提格雷Kahsay Abera和Mearg医院的VL患者(n = 100)和健康对照(n = 100)。按常规方案分离血清,用迈瑞200E全自动化学分析仪分析肾功能(肌酐、尿素、尿酸)。本研究还评估了估计的肾小球滤过率(eGFR)。所得数据采用SPSS Version 23.0进行处理。采用描述性统计、独立检验和双变量相关性进行数据分析。结果:与健康对照组相比,VL患者的平均血清肌酐水平显著升高,而血清尿素和eGFR均显著降低。具体来说,在100例VL病例中,血清肌酐、尿素和尿酸水平分别在10%、9%和15%的VL病例中升高;同时,血清尿素和eGFR下降分别从33%到44%的VL病例报告。结论:本研究结果表明,内脏利什曼病引起以肾功能改变为特征的肾脏活动紊乱。这可能表明VL是发生肾功能障碍的决定因素。这项研究鼓励研究人员参与内脏利什曼病及其对人类其他器官功能的影响,并确定预防和干预的潜在标志。
{"title":"Evaluation of Renal Function Profile in Human Visceral Leishmaniasis (Kala-Azar) Patients: A Case of Western Tigray, Ethiopia.","authors":"Kibrom Gerezgiher Asfaw, Solomon Tebeje Gizaw, Natesan Gnanasekaran","doi":"10.2147/RRTM.S410137","DOIUrl":"https://doi.org/10.2147/RRTM.S410137","url":null,"abstract":"<p><strong>Background: </strong>Leishmaniasis is a vector-borne protozoan infection that has a wide clinical spectrum in the tropics and subtropics. Kidney damage is frequently associated with increased morbidity and mortality in <i>visceral leishmaniasis</i> (<i>VL</i>) patients. However, up to date, there is a very limited report on the effect of visceral leishmaniasis on kidney function profiling in Ethiopia.</p><p><strong>Objective: </strong>To evaluate the renal function profile in human <i>visceral leishmaniasis</i> (kala-azar) patients.</p><p><strong>Materials and methods: </strong>Human blood was taken from <i>VL</i> patients (n = 100) and healthy controls (n = 100) attending Kahsay Abera and Mearg Hospitals, Western Tigray of Ethiopia. Serum was separated according to the conventional protocol and kidney function profiling (creatinine, urea, and uric acid) was analyzed by Mindray 200E automated chemistry analyzer. The estimated glomerular filtration rate (eGFR) was also assessed in this study. The obtained data were processed using SPSS Version 23.0. Descriptive statistics, independent-test, and bivariate correlations were used for data analysis. P values <0.05 were considered statistically significant at a 95% confidence level.</p><p><strong>Results: </strong>The mean serum creatinine level was found significantly higher, while respective serum urea and eGFR were significantly lower in <i>VL</i> patients compared to healthy controls. Specifically, from 100 <i>VL</i> cases, an increased level of serum creatinine, urea, and uric acid was found in 10%, 9% and 15% <i>VL</i> cases, respectively; meanwhile, a decreased serum urea and eGFR have been reported from 33% to 44% <i>VL</i> cases, respectively.</p><p><strong>Conclusion: </strong>The finding of this study asserted that <i>visceral leishmaniasis</i> causes derangement in kidney activities characterized by alteration of renal function profile. This may indicate that <i>VL</i> is the determinant factor for developing kidney dysfunction. This study encourages researchers to engage in <i>visceral leishmaniasis</i> and its effect on other organ function profiles in humans and identify potential markers for both prevention and intervention.</p>","PeriodicalId":21138,"journal":{"name":"Research and Reports in Tropical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/81/23/rrtm-14-21.PMC10315324.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10178183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Even though podoconiosis can cause physical, financial, and social impairments, it is commonly overlooked by organizations, and one-fourth of the predicted worldwide burden will fall on Ethiopia. In spite of this, there are only a few attempts for prevention and control in certain areas in Ethiopia. Updated statistics on prevalence and contributing factors could make local efforts at prevention, control, and rehabilitation more effective. Thus, this study was aimed to assess the prevalence of podoconiosis and its associated factors among Ilu Aba Bor zone residents, South West Ethiopia.
Methods: A community-based cross-sectional study was conducted on 491 participants from March 25 to April 25, 2022. Data were entered into Epi-Data version 4.6.0, then exported to SPSS version 25 for final analysis. In the bi-variable regression, variables with P-values less than 0.25 were included in the multivariable model. Finally, multivariable logistic regression was performed to identify factors associated with podoconiosis at a 5% level of significance.
Results: In this study area, podoconiosis prevalence was found to be 5.7% [3.6-7.2]. In multivariable regression model, lower tertile wealth status [AOR=2.09; (95% CI (1.384, 5.343)], no formal education [AOR=2.23; (95% CI; 1.179-3.820)] and average distance to reach water source to home [AOR=2.061; (95% CI: 1.78-7.35)] were significantly associated podoconiosis.
Conclusion and recommendation: According to this study, one in every seventeen individuals had podoconiosis, which is a significant prevalence when compared to earlier studies. Podoconiosis was observed to be associated with factors like wealth status, educational attainment, and distance from water source. To address this public health issue, strong preventive and therapeutic treatments should be used.
背景:尽管足癣病会导致身体、经济和社会障碍,但它通常被组织所忽视,预计全球四分之一的负担将落在埃塞俄比亚。尽管如此,在埃塞俄比亚的某些地区只有很少的预防和控制的尝试。关于流行情况和影响因素的最新统计数据可使当地在预防、控制和康复方面的努力更加有效。因此,本研究旨在评估足癣病在埃塞俄比亚西南部Ilu Aba Bor地区居民中的患病率及其相关因素。方法:以社区为基础,于2022年3月25日至4月25日对491名参与者进行横断面研究。数据输入Epi-Data 4.6.0版本,导出到SPSS 25版本进行最终分析。在双变量回归中,p值小于0.25的变量被纳入多变量模型。最后,进行多变量逻辑回归,以5%的显著性水平确定与足癣病相关的因素。结果:本研究区足癣患病率为5.7%[3.6-7.2]。在多变量回归模型中,低收入群体的财富状况[AOR=2.09;(95% CI(1.384, 5.343)),未接受过正规教育[AOR=2.23;(95%可信区间;(1.179-3.820)]、到达水源到家的平均距离[AOR=2.061;(95% CI: 1.78-7.35)]与足癣病显著相关。结论和建议:根据这项研究,每17个人中就有1人患有足癣病,与早期研究相比,这是一个显著的患病率。据观察,足锥病与财富状况、受教育程度和距离水源的距离等因素有关。为解决这一公共卫生问题,应采取强有力的预防和治疗措施。
{"title":"From Neglected to Public Health Burden: Factors Associated with Podoconiosis in Resource Limited Setting in Case of Southwest Ethiopia: A Community Based Cross Sectional Study.","authors":"Gebiso Roba Debele, Eyasu Shifera, Yohannes Lulu Dessie, Debela Dereje Jaleta, Megersso Urgessa Borena, Shuma Gosha Kanfe, Kabtamu Nigussie, Galana Mamo Ayana, Temam Beshir Raru","doi":"10.2147/RRTM.S412624","DOIUrl":"https://doi.org/10.2147/RRTM.S412624","url":null,"abstract":"<p><strong>Background: </strong>Even though podoconiosis can cause physical, financial, and social impairments, it is commonly overlooked by organizations, and one-fourth of the predicted worldwide burden will fall on Ethiopia. In spite of this, there are only a few attempts for prevention and control in certain areas in Ethiopia. Updated statistics on prevalence and contributing factors could make local efforts at prevention, control, and rehabilitation more effective. Thus, this study was aimed to assess the prevalence of podoconiosis and its associated factors among Ilu Aba Bor zone residents, South West Ethiopia.</p><p><strong>Methods: </strong>A community-based cross-sectional study was conducted on 491 participants from March 25 to April 25, 2022. Data were entered into Epi-Data version 4.6.0, then exported to SPSS version 25 for final analysis. In the bi-variable regression, variables with P-values less than 0.25 were included in the multivariable model. Finally, multivariable logistic regression was performed to identify factors associated with podoconiosis at a 5% level of significance.</p><p><strong>Results: </strong>In this study area, podoconiosis prevalence was found to be 5.7% [3.6-7.2]. In multivariable regression model, lower tertile wealth status [AOR=2.09; (95% CI (1.384, 5.343)], no formal education [AOR=2.23; (95% CI; 1.179-3.820)] and average distance to reach water source to home [AOR=2.061; (95% CI: 1.78-7.35)] were significantly associated podoconiosis.</p><p><strong>Conclusion and recommendation: </strong>According to this study, one in every seventeen individuals had podoconiosis, which is a significant prevalence when compared to earlier studies. Podoconiosis was observed to be associated with factors like wealth status, educational attainment, and distance from water source. To address this public health issue, strong preventive and therapeutic treatments should be used.</p>","PeriodicalId":21138,"journal":{"name":"Research and Reports in Tropical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0e/b2/rrtm-14-49.PMC10350399.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9837654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thalia Pacheco-Fernandez, Hannah Markle, Chaitenya Verma, Ryan Huston, Sreenivas Gannavaram, Hira L Nakhasi, Abhay R Satoskar
Leishmaniasis is a neglected tropical disease endemic primarily to low- and middle-income countries, for which there has been inadequate development of affordable, safe, and efficacious therapies. Clinical manifestations of leishmaniasis range from self-healing skin lesions to lethal visceral infection with chances of relapse. Although treatments are available, secondary effects limit their use outside the clinic and negatively impact the quality of life of patients in endemic areas. Other non-medicinal treatments, such as thermotherapies, are limited to use in patients with cutaneous leishmaniasis but not with visceral infection. Recent studies shed light to mechanisms through which Leishmania can persist by hiding in cellular safe havens, even after chemotherapies. This review focuses on exploring the cellular niches that Leishmania parasites may be leveraging to persist within the host. Also, the cellular, metabolic, and molecular implications of Leishmania infection and how those could be targeted for therapeutic purposes are discussed. Other therapies, such as those developed against cancer or for manipulation of the ferroptosis pathway, are proposed as possible treatments against leishmaniasis due to their mechanisms of action. In particular, treatments that target hematopoietic stem cells and monocytes, which have recently been found to be necessary components to sustain the infection and provide a safe niche for the parasites are discussed in this review as potential field-deployable treatments against leishmaniasis.
{"title":"Field-Deployable Treatments For Leishmaniasis: Intrinsic Challenges, Recent Developments and Next Steps.","authors":"Thalia Pacheco-Fernandez, Hannah Markle, Chaitenya Verma, Ryan Huston, Sreenivas Gannavaram, Hira L Nakhasi, Abhay R Satoskar","doi":"10.2147/RRTM.S392606","DOIUrl":"https://doi.org/10.2147/RRTM.S392606","url":null,"abstract":"<p><p>Leishmaniasis is a neglected tropical disease endemic primarily to low- and middle-income countries, for which there has been inadequate development of affordable, safe, and efficacious therapies. Clinical manifestations of leishmaniasis range from self-healing skin lesions to lethal visceral infection with chances of relapse. Although treatments are available, secondary effects limit their use outside the clinic and negatively impact the quality of life of patients in endemic areas. Other non-medicinal treatments, such as thermotherapies, are limited to use in patients with cutaneous leishmaniasis but not with visceral infection. Recent studies shed light to mechanisms through which <i>Leishmania</i> can persist by hiding in cellular safe havens, even after chemotherapies. This review focuses on exploring the cellular niches that <i>Leishmania</i> parasites may be leveraging to persist within the host. Also, the cellular, metabolic, and molecular implications of <i>Leishmania</i> infection and how those could be targeted for therapeutic purposes are discussed. Other therapies, such as those developed against cancer or for manipulation of the ferroptosis pathway, are proposed as possible treatments against leishmaniasis due to their mechanisms of action. In particular, treatments that target hematopoietic stem cells and monocytes, which have recently been found to be necessary components to sustain the infection and provide a safe niche for the parasites are discussed in this review as potential field-deployable treatments against leishmaniasis.</p>","PeriodicalId":21138,"journal":{"name":"Research and Reports in Tropical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/64/6f/rrtm-14-61.PMC10364832.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9875181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}