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15 pages, 7202 KiB  
Review
Community-Directed Vector Control to Accelerate Onchocerciasis Elimination
by Benjamin Jacob, Edwin Michael and Thomas R. Unnasch
Pathogens 2024, 13(3), 268; https://doi.org/10.3390/pathogens13030268 - 21 Mar 2024
Viewed by 1029
Abstract
Onchocerciasis, or river blindness, has historically been one of the most important causes of blindness worldwide, and a major cause of socio-economic disruption, particularly in sub-Saharan Africa. Its importance as a cause of morbidity and an impediment to economic development in some of [...] Read more.
Onchocerciasis, or river blindness, has historically been one of the most important causes of blindness worldwide, and a major cause of socio-economic disruption, particularly in sub-Saharan Africa. Its importance as a cause of morbidity and an impediment to economic development in some of the poorest countries in the world motivated the international community to implement several programs to control or eliminate this scourge. Initially, these involved reducing transmission of the causative agent Onchocerca volvulus through controlling the vector population. When ivermectin was found to be a very effective drug for treating onchocerciasis, the strategy shifted to mass drug administration (MDA) of endemic communities. In some countries, both vector control and ivermectin MDA have been used together. However, traditional vector control methods involve treating rivers in which the black fly vectors breed with insecticides, a process which is expensive, requires trained personnel to administer, and can be ecologically harmful. In this review, we discuss recent research into alternatives to riverine insecticide treatment, which are inexpensive, ecologically less harmful, and can be implemented by the affected communities themselves. These can dramatically reduce vector densities and, when combined with ivermectin MDA, can accelerate the time to elimination when compared to MDA alone. Full article
(This article belongs to the Special Issue Research on the Epidemiology and Transmission of Filarial Diseases)
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21 pages, 12047 KiB  
Article
Repurposed Drugs That Activate Autophagy in Filarial Worms Act as Effective Macrofilaricides
by Denis Voronin, Nancy Tricoche, Ricardo Peguero, Anna Maria Kaminska, Elodie Ghedin, Judy A. Sakanari and Sara Lustigman
Pharmaceutics 2024, 16(2), 256; https://doi.org/10.3390/pharmaceutics16020256 - 09 Feb 2024
Viewed by 918
Abstract
Onchocerciasis and lymphatic filariasis are two neglected tropical diseases caused by filarial nematodes that utilize insect vectors for transmission to their human hosts. Current control strategies are based on annual or biannual mass drug administration (MDA) of the drugs Ivermectin or Ivermectin plus [...] Read more.
Onchocerciasis and lymphatic filariasis are two neglected tropical diseases caused by filarial nematodes that utilize insect vectors for transmission to their human hosts. Current control strategies are based on annual or biannual mass drug administration (MDA) of the drugs Ivermectin or Ivermectin plus Albendazole, respectively. These drug regimens kill the first-stage larvae of filarial worms (i.e., microfilariae) and interrupt the transmission of infections. MDA programs for these microfilaricidal drugs must be given over the lifetime of the filarial adult worms, which can reach 15 years in the case of Onchocerca volvulus. This is problematic because of suboptimal responses to ivermectin in various endemic regions and inefficient reduction of transmission even after decades of MDA. There is an urgent need for the development of novel alternative treatments to support the 2030 elimination goals of onchocerciasis and lymphatic filariasis. One successful approach has been to target Wolbachia, obligatory endosymbiotic bacteria on which filarial worms are dependent for their survival and reproduction within the human host. A 4–6-week antibiotic therapy with doxycycline, for example, resulted in the loss of Wolbachia that subsequently led to extensive apoptosis of somatic cells, germline, embryos, and microfilariae, as well as inhibition of fourth-stage larval development. However, this long-course regimen has limited use in MDA programs. As an alternative approach to the use of bacteriostatic antibiotics, in this study, we focused on autophagy-inducing compounds, which we hypothesized could disturb various pathways involved in the interdependency between Wolbachia and filarial worms. We demonstrated that several such compounds, including Niclosamide, an FDA-approved drug, Niclosamide ethanolamine (NEN), and Rottlerin, a natural product derived from Kamala trees, significantly reduced the levels of Wolbachia in vitro. Moreover, when these compounds were used in vivo to treat Brugia pahangi-infected gerbils, Niclosamide and NEN significantly decreased adult worm survival, reduced the release of microfilariae, and decreased embryonic development depending on the regimen and dose used. All three drugs given orally significantly reduced Wolbachia loads and induced an increase in levels of lysosome-associated membrane protein in worms from treated animals, suggesting that Niclosamide, NEN, and Rottlerin were effective in causing drug-induced autophagy in these filarial worms. These repurposed drugs provide a new avenue for the clearance of adult worms in filarial infections. Full article
(This article belongs to the Special Issue Emerging Pharmaceutical Therapeutics for Neglected Tropical Diseases)
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11 pages, 263 KiB  
Review
Zambia: A Narrative Review of Success and Challenges in Lymphatic Filariasis Elimination
by Kingford Chimfwembe, Hugh Shirley, Natalie Baker and Richard Wamai
Trop. Med. Infect. Dis. 2024, 9(1), 21; https://doi.org/10.3390/tropicalmed9010021 - 15 Jan 2024
Viewed by 1791
Abstract
The establishment of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to stop the transmission of infection has significantly reduced the incidence of lymphatic filariasis, a debilitating mosquito-borne neglected tropical disease. The primary strategies that have been employed include mass drug administration (MDA) [...] Read more.
The establishment of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to stop the transmission of infection has significantly reduced the incidence of lymphatic filariasis, a debilitating mosquito-borne neglected tropical disease. The primary strategies that have been employed include mass drug administration (MDA) of anthelminthics and morbidity management and disability prevention (MMDP). While some countries have been able to reach elimination status in Africa, there is still active transmission of LF in Zambia. The nematode responsible for the disease is Wuchereria bancrofti, which is transmitted by Anopheles mosquitoes. To alleviate the suffering of those infected by the disease, the Zambian Ministry of Health launched a program to eliminate LF as a public health problem in 2003. This project reviewed the efforts to achieve the elimination of LF in Zambia, past and present government policies, and the anticipated challenges. MDAs have been conducted since 2014 and coverage has been between 87% and 92%. Zambia has now moved towards pre-transmission assessment surveys (PRETAS) and transmission assessment surveys (TAS). MMDP is a major priority and planned to be conducted between 2022 and 2026. COVID-19 presented a new challenge in the control of LF, while climate change, immigration, co-infections, and funding limitations will complicate further progress. Full article
(This article belongs to the Section Neglected and Emerging Tropical Diseases)
27 pages, 13910 KiB  
Article
Optimization of the Flavonoid Extraction Process from the Stem and Leaves of Epimedium Brevicornum and Its Effects on Cyclophosphamide-Induced Renal Injury
by Meiling Shi, Hongyan Pei, Li Sun, Weijia Chen, Ying Zong, Yan Zhao, Rui Du and Zhongmei He
Molecules 2024, 29(1), 207; https://doi.org/10.3390/molecules29010207 - 29 Dec 2023
Cited by 1 | Viewed by 988
Abstract
Cyclophosphamide (CTX) is a broad-spectrum alkylated antitumor drug. It is clinically used in the treatment of a variety of cancers, and renal toxicity is one of the adverse reactions after long-term or repeated use, which not only limits the therapeutic effect of CTX, [...] Read more.
Cyclophosphamide (CTX) is a broad-spectrum alkylated antitumor drug. It is clinically used in the treatment of a variety of cancers, and renal toxicity is one of the adverse reactions after long-term or repeated use, which not only limits the therapeutic effect of CTX, but also increases the probability of kidney lesions. The total flavonoids of Epimedium stem and leaf (EBF) and Icariin (ICA) are the main medicinal components of Epimedium, and ICA is one of the main active substances in EBF. Modern pharmacological studies have shown that EBF has a variety of biological activities such as improving osteoporosis, promoting cell proliferation, antioxidant and anti-inflammatory properties, etc. However, few studies have been conducted on the nephrotoxicity caused by optimized CTX extraction, and protein-ligand binding has not been involved. This research, through the response surface optimization extraction of EBF, obtained the best extraction conditions: ethanol concentration was 60%, solid-liquid ratio of 25:1, ultrasonic time was about 25 min. Combined with mass spectrometry (MS) analysis, EBF contained ICA, ichopidin A, ichopidin B, ichopidin C, and other components. In this study, we adopted a computational chemistry method called molecular docking, and the results show that Icariin was well bound to the antioxidant target proteins KEAP1 and NRF2, and the anti-inflammatory target proteins COX-2 and NF-κB, with free binding energies of −9.8 kcal/mol, −11.0 kcal/mol, −10.0 kcal/mol, and −8.1 kcal/mol, respectively. To study the protective effect of EBF on the nephrotoxicity of CTX, 40 male Kunming mice (weight 18 ± 22) were injected with CTX (80 mg/kg) for 7 days to establish the nephrotoxicity model and were treated with EBF (50 mg/kg, 100 mg/kg) for 8 days by gavage. After CTX administration, MDA, BUN, Cre, and IL-6 levels in serum increased, MDA increased in kidney, GPT/ALT and IL-6 increased in liver, and IL-6 increased in spleen and was significant ((p < 0.05 or (p < 0.01)). Histopathological observation showed that renal cortex glomerular atrophy necrosis, medullary inflammatory cell infiltration, and other lesions. After administration of EBF, CTX-induced increase in serum level of related indexes was reduced, and MDA in kidney, GPT/ALT and IL-6 in liver, and IL-6 in spleen were increased. At the same time, histopathological findings showed that the necrosis of medullary and corticorenal tubular epithelium was relieved at EBF (50 mg/kg) dose compared with the CTX group, and the glomerular tubular necrosis gradually became normal at EBF (100 mg/kg) dose. Western blot analysis of Keap1 and Nrf2 protein expression in kidney tissue showed that compared with model CTX group, the drug administration group could alleviate the high expression of Keap1 protein and low expression of Nrf2 protein in kidney tissue. Conclusion: After the optimal extraction of total flavonoids from the stems and leaves of Epimedium, the molecular docking technique combined with animal experiments suggested that the effective component of the total flavonoids of Epimedium might activate the Keap1-Nrf2 signaling pathway after treatment to reduce the inflammation and oxidative stress of kidney tissue, so as to reduce kidney damage and improve kidney function. Therefore, EBF may become a new natural protective agent for CTX chemotherapy in the future. Full article
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11 pages, 1444 KiB  
Article
High Specificity but Low Sensitivity of Lab-on-a-Disk Technique in Detecting Soil-Transmitted Helminth Eggs among Pre- and School-Aged Children in North-Western Tanzania
by Humphrey D. Mazigo, Nyanda C. Justine, Jeffer Bhuko, Sarah Rubagumya, Namanya Basinda, Maria M. Zinga, Deodatus Ruganuza, Vyacheslav R. Misko, Matthieu Briet, Filip Legein and Wim De Malsche
Trop. Med. Infect. Dis. 2024, 9(1), 5; https://doi.org/10.3390/tropicalmed9010005 - 21 Dec 2023
Viewed by 1655
Abstract
An estimated 1.5 billion people are infected with soil-transmitted helminths (hookworms, Ascaris lumbricoides and Trichuris trichiura). These infections are targeted for elimination by the World Health Organization (WHO) by 2030, with the main interventions being mass drug administration using albendazole or mebendazole. [...] Read more.
An estimated 1.5 billion people are infected with soil-transmitted helminths (hookworms, Ascaris lumbricoides and Trichuris trichiura). These infections are targeted for elimination by the World Health Organization (WHO) by 2030, with the main interventions being mass drug administration using albendazole or mebendazole. Tanzania is one of the endemic countries; it has been implementing MDA to school-aged children for more than a decade and the infection prevalence and intensity of infection have declined. Thus, at this point, the monitoring and evaluation of infection prevalence and intensity of infections, and assessing drug efficacy is crucial and requires accurate diagnostic tests. The currently used standard diagnostic test, the Kato–Katz (KK) technique, has several limitations and the WHO is calling for the development and evaluation of new diagnostic tests. The Lab-on-a-disk (LOD) was developed and tested in the endemic areas of north-western Tanzania to evaluate its sensitivity and specificity using KK and the formol-ether concentration technique. The results showed that when using a duplicate KK slide, the LOD had a sensitivity and specificity of 37.2% (95% CI: 30.7–43.9) and 67.3% (95% CI: 63.1–71.3%). Using four KK slides as a standard technique, the overall sensitivity and specificity were 37.7% (95% CI: 33.1–42.6) and 70.7% (95% CI: 65.5–75.6). The LOD attained high specificity but low sensitivity especially in detecting eggs of Trichuris trichiura. The LOD technique has potential as a promising diagnostic test, but its sensitivity still requires improvement. Full article
(This article belongs to the Section Neglected and Emerging Tropical Diseases)
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10 pages, 444 KiB  
Article
Efficacy of Single-Dose Praziquantel for the Treatment of Schistosoma mansoni Infections among School Children in Rwanda
by Joseph Kabatende, Lazare Ntirenganya, Michael Mugisha, Abbie Barry, Eugene Ruberanziza, Emile Bienvenu, Ulf Bergman and Eleni Aklillu
Pathogens 2023, 12(9), 1170; https://doi.org/10.3390/pathogens12091170 - 17 Sep 2023
Viewed by 1117
Abstract
Preventive chemotherapy with single-dose praziquantel is the WHO-recommended intervention strategy to eliminate schistosomiasis as a public health problem in endemic countries. Surveillance of drugs used in mass drug administration (MDA) programs is recommended to evaluate its effectiveness in reducing transmissions. After a decade-long [...] Read more.
Preventive chemotherapy with single-dose praziquantel is the WHO-recommended intervention strategy to eliminate schistosomiasis as a public health problem in endemic countries. Surveillance of drugs used in mass drug administration (MDA) programs is recommended to evaluate its effectiveness in reducing transmissions. After a decade-long implementation of a school-based MDA program in Rwanda, we conducted efficacy surveillance of single-dose praziquantel MDA against S. mansoni infection. Two weeks before MDA, stool examinations were performed to screen MDA-eligible school children (n = 4998) for S. mansoni infection using the Kato–Katz technique, and 265 (6.5%) children tested positive for the infection. All children received praziquantel and albendazole as preventive chemotherapy through the MDA campaign. Infected children were enrolled and followed for efficacy monitoring, and stool examination was repeated after three weeks post-MDA (n = 188). Before treatment, 173 (92%) had a light infection, and 15 (8%) had a moderate infection intensity. The primary and secondary outcomes were parasitological cure and egg reduction rates at three weeks post-treatment. The overall cure and egg reduction rates for S. mansoni infection were 97.9% (95% CI = 94.6–99.4) and 97.02%, respectively. Among the 173 children with light infection intensity, 170 (98.3%, 95% CI = 95.0–99.6) were cured, and among the 15 children who had moderate infection intensity, 14 (93.3%) were cured. No significant association between cure rate and pre-treatment infection intensity was observed. We conclude that single-dose praziquantel is efficacious against light-to-moderate S. mansoni infection. Preventive chemotherapy with praziquantel effectively reduces schistosome reservoirs and transmission among school-age children. Full article
(This article belongs to the Special Issue Parasites: Epidemiology, Treatment and Control)
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22 pages, 1249 KiB  
Review
Review of Recent Prevalence of Urogenital Schistosomiasis in Sub-Saharan Africa and Diagnostic Challenges in the Field Setting
by Sung-Tae Hong
Life 2023, 13(8), 1670; https://doi.org/10.3390/life13081670 - 31 Jul 2023
Cited by 1 | Viewed by 1441
Abstract
Human schistosomiasis is one of neglected tropical diseases that remain highly prevalent in sub-Saharan Africa (SSA). Human schistosomiasis is mainly caused by two species, Schistosoma haematobium and S. mansoni, leading to urogenital and intestinal schistosomiasis, respectively. The World Health Organization (WHO) recommends [...] Read more.
Human schistosomiasis is one of neglected tropical diseases that remain highly prevalent in sub-Saharan Africa (SSA). Human schistosomiasis is mainly caused by two species, Schistosoma haematobium and S. mansoni, leading to urogenital and intestinal schistosomiasis, respectively. The World Health Organization (WHO) recommends mass drug administration (MDA) with praziquantel as the primary method of global intervention. Currently, MDA with praziquantel covers over half of the target population in endemic SSA countries. However, an accurate diagnosis is crucial for monitoring and evaluating the effectiveness of MDA. The standard diagnosis of both urogenital and intestinal schistosomiasis relies on the microscopic identification of eggs. However, the diagnostic sensitivity of this approach is low, especially for light or ultra-light infections. This is because Schistosoma eggs are laid inside of the venous plexus of the urinary bladder or mesenteric vein, where the adult flukes live. Approximately half of the eggs circulate in the blood vessels or are packed in neighboring tissues, while the remaining half are expelled into the lumen of the urinary bladder or intestine intermittently when the blood vessels are ruptured. In the field setting, the accuracy of any diagnostic method is critical for proper management of the intervention. The present article reviews the recent prevalence of urogenital schistosomiasis in SSA and highlights the practical limitations of diagnostic methods such as urine microscopy, urine reagent strips, molecular diagnosis, and ultrasound scanning in the field setting. Despite continuous global efforts to eliminate schistosomiasis over the past 20 years, many areas still remain endemic in SSA. No single diagnostic approach achieves acceptable sensitivity and specificity in the field setting. Therefore, any field survey should employ a combination of these methods based on the purpose of the study to accurately monitor and evaluate urogenital schistosomiasis. Based on diagnostic values and a cost–benefit analysis, a urine reagent strip test can replace urine microscopy in the field setting. The WHO criteria by ultrasound diagnosis should be updated including the echogenic snow sign and contour distortion. Full article
(This article belongs to the Section Epidemiology)
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9 pages, 510 KiB  
Article
Lymphatic Filariasis Elimination Status: Wuchereria bancrofti Infections in Human Populations after Five Effective Rounds of Mass Drug Administration in Zambia
by Belem Blamwell Matapo, Evans Mwila Mpabalwani, Patrick Kaonga, Martin Chitolongo Simuunza, Nathan Bakyaita, Freddie Masaninga, Namasiku Siyumbwa, Seter Siziya, Frank Shamilimo, Chilweza Muzongwe, Enala T. Mwase and Chummy Sikalizyo Sikasunge
Trop. Med. Infect. Dis. 2023, 8(7), 333; https://doi.org/10.3390/tropicalmed8070333 - 22 Jun 2023
Cited by 2 | Viewed by 1741
Abstract
Lymphatic filariasis (LF), also commonly known as elephantiasis, is a neglected tropical disease (NTD) caused by filarial parasites. The disease is transmitted via a bite from infected mosquitoes. The bites of these infected mosquitoes deposit filarial parasites, Wuchereria or Brugia, whose predilection [...] Read more.
Lymphatic filariasis (LF), also commonly known as elephantiasis, is a neglected tropical disease (NTD) caused by filarial parasites. The disease is transmitted via a bite from infected mosquitoes. The bites of these infected mosquitoes deposit filarial parasites, Wuchereria or Brugia, whose predilection site is the lymphatic system. The damage to the lymph system causes swelling in the legs, arms, and genitalia. A mapping survey conducted between 2003 and 2011 determined LF as being endemic in Zambia in 96 out of 116 districts. Elimination of LF is known to be possible by stopping the spread of the infection through large-scale preventive chemotherapy. Therefore, mass drug administration (MDA) with diethylcarbamazine citrate (DEC) (6 mg/kg) and Albendazole (400 mg) for Zambia has been conducted and implemented in all endemic districts with five effective rounds. In order to determine whether LF prevalence has been sufficiently reduced to levels less than 2% antigenemia and less than 1% microfilaremia, a pre-transmission assessment survey (pre-TAS) was conducted. Therefore, post-MDA pre-TAS was conducted between 2021 and 2022 in 80 districts to determine the LF prevalence. We conducted a cross-sectional seroprevalence study involving 600 participants in each evaluation unit (EU) or each district. The study sites (sentinel and spot-check sites) were from districts that were the implementation units (IUs) of the LF MDA. These included 80 districts from the 9 provinces. A total of 47,235 people from sentinel and spot-check locations were tested. Of these, valid tests were 47,052, of which 27,762 (59%) were females and 19,290 (41%) were males. The survey revealed in the 79/80 endemic districts a prevalence of Wb antigens of 0.14% and 0.0% prevalence of microfilariae. All the surveyed districts had an optimum prevalence of less than 2% for antigenaemia, except for Chibombo district. The majority of participants that tested positive for Wuchereria bancrofti (Wb) Antigens (Ag) were those that had 2, 3, and 4 rounds of MDA. Surprisingly, individuals that had 1 round of MDA were not found to have circulating antigens of Wb. The study showed that all the surveyed districts, except for Chibombo, passed pre-TAS. This further implies that there is a need to conduct transmission assessment surveys (TASs) in these districts. Full article
(This article belongs to the Section Vector-Borne Diseases)
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21 pages, 2776 KiB  
Article
Antioxidant and Hepatoprotective Potential of Echinops ritro L. Extracts on Induced Oxidative Stress In Vitro/In Vivo
by Dimitrina Zheleva-Dimitrova, Rumyana Simeonova, Magdalena Kondeva-Burdina, Yonko Savov, Vessela Balabanova, Gokhan Zengin, Alexandra Petrova and Reneta Gevrenova
Int. J. Mol. Sci. 2023, 24(12), 9999; https://doi.org/10.3390/ijms24129999 - 10 Jun 2023
Cited by 2 | Viewed by 1571
Abstract
Echinops ritro L. (Asteraceae) is traditionally used in the treatment of bacterial/fungal infections and respiratory and heart ailments. The aim of this study was to evaluate the potential of extracts from E. ritro leaves (ERLE) and flowering heads (ERFE) as antioxidant and hepatoprotective [...] Read more.
Echinops ritro L. (Asteraceae) is traditionally used in the treatment of bacterial/fungal infections and respiratory and heart ailments. The aim of this study was to evaluate the potential of extracts from E. ritro leaves (ERLE) and flowering heads (ERFE) as antioxidant and hepatoprotective agents on diclofenac-induced lipid peroxidation and oxidative stress under in vitro and in vivo conditions. In isolated rat microsomes and hepatocytes, the extracts significantly alleviated oxidative stress by increasing cell viability and GSH levels and reducing LDH efflux and MDA production. During in vivo experiments, the administration of the ERFE alone or in combination with diclofenac resulted in a significant increase in cellular antioxidant protection and a decrease in lipid peroxidation witnessed by key markers and enzymes. A beneficial influence on the activity of the drug-metabolizing enzymes ethylmorphine-N-demetylase and aniline hydroxylase in liver tissue was found. In the acute toxicity test evaluation, the ERFE showed no toxicity. In the ultrahigh-performance liquid chromatography–high-resolution mass spectrometry analysis, 95 secondary metabolites were reported for the first time, including acylquinic acids, flavonoids, and coumarins. Protocatechuic acid O-hexoside, quinic, chlorogenic and 3, 5-dicaffeoylquinic acid, apigenin; apigenin 7-O-glucoside, hyperoside, jaceosidene, and cirsiliol dominated the profiles. The results suggest that both extracts should be designed for functional applications with antioxidant and hepatoprotective capacity. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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12 pages, 1391 KiB  
Article
Reduced Type 2 Innate Lymphocyte Cell Frequencies in Patent Wuchereria bancrofti-Infected Individuals
by Ruth S. E. Tamadaho, Jubin Osei-Mensah, Kathrin Arndts, Linda Batsa Debrah, Alexander Y. Debrah, Laura E. Layland, Achim Hoerauf, Kenneth Pfarr and Manuel Ritter
Pathogens 2023, 12(5), 665; https://doi.org/10.3390/pathogens12050665 - 30 Apr 2023
Cited by 1 | Viewed by 1100
Abstract
Approximately 51 million individuals suffer from lymphatic filariasis (LF) caused mainly by the filarial worm Wuchereria bancrofti. Mass drug administration (MDA) programs led to a significant reduction in the number of infected individuals, but the consequences of the treatment and clearance of [...] Read more.
Approximately 51 million individuals suffer from lymphatic filariasis (LF) caused mainly by the filarial worm Wuchereria bancrofti. Mass drug administration (MDA) programs led to a significant reduction in the number of infected individuals, but the consequences of the treatment and clearance of infection in regard to host immunity remain uncertain. Thus, this study investigates the composition of myeloid-derived suppressor cells (MDSCs), macrophage subsets and innate lymphoid cells (ILCs), in patent (circulating filarial antigen (CFA)+ microfilariae (MF)+) and latent (CFA+MF−) W. bancrofti-infected individuals, previously W. bancrofti-infected (PI) individuals cured of the infection due to MDA, uninfected controls (endemic normal (EN)) and individuals who suffer from lymphoedema (LE) from the Western Region of Ghana. Frequencies of ILC2 were significantly reduced in W. bancrofti-infected individuals, while the frequencies of MDSCs, M2 macrophages, ILC1 and ILC3 were comparable between the cohorts. Importantly, clearance of infection due to MDA restored the ILC2 frequencies, suggesting that ILC2 subsets might migrate to the site of infection within the lymphatic tissue. In general, the immune cell composition in individuals who cured the infection were comparable to the uninfected individuals, showing that filarial-driven changes of the immune responses require an active infection and are not maintained upon the clearance of the infection. Full article
(This article belongs to the Section Parasitic Pathogens)
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15 pages, 295 KiB  
Article
Efficacy of Single-Dose Albendazole for the Treatment of Soil-Transmitted Helminthic Infections among School Children in Rwanda—A Prospective Cohort Study
by Joseph Kabatende, Abbie Barry, Michael Mugisha, Lazare Ntirenganya, Ulf Bergman, Emile Bienvenu and Eleni Aklillu
Pharmaceuticals 2023, 16(2), 139; https://doi.org/10.3390/ph16020139 - 17 Jan 2023
Cited by 3 | Viewed by 2350
Abstract
Mass drug administration (MDA) of single-dose albendazole to all at-risk populations as preventive chemotherapy (deworming) is recommended by WHO to halt transmission of soil-transmitted helminth (STH) in endemic countries. We assessed the effectiveness of single-dose albendazole against STH infection in the western province [...] Read more.
Mass drug administration (MDA) of single-dose albendazole to all at-risk populations as preventive chemotherapy (deworming) is recommended by WHO to halt transmission of soil-transmitted helminth (STH) in endemic countries. We assessed the effectiveness of single-dose albendazole against STH infection in the western province of Rwanda, where STH prevalence remains high despite the implementation of preventive chemotherapy for over a decade. Two weeks before the scheduled MDA, 4998 school children (5–15 years old) were screened for STH infections (Ascaris lumbricoides, Trichuris trichiura, and hookworm), and 1526 children who tested positive for at least one type of STH parasite were enrolled and received single-dose albendazole (400 mg) through MDA. A follow-up stool exam was performed at three weeks post-treatment using Kato–Katz. Efficacy was assessed by cure rate (CR), defined as the proportion of children who became egg-free, and egg reduction rates (ERRs) at three weeks post-treatment. The CR and ERR for hookworms (CR = 96.7%, ERR = 97.4%) was above, and for Ascaris lumbricoides (CR = 95.1%, ERR = 94.6%) was borderline compared with the WHO efficacy threshold (CR and ERR ≥ 95%). However, the CR and ERR for T. trichiura (CR = 17.6% ERR = 40.3%) were below the WHO threshold for efficacy (CR and ERR ≥ 50%). Having moderate-to-heavy infection intensity and coinfection with another type of STH parasites were independent risk factors for lower CR and ERR against Trichirus trichiura (p < 0.001). Single-dose albendazole used in the MDA program is efficacious for the treatment and control for hookworms and Ascaris lumbricoides infections but not effective for Trichirus trichiura. An alternative treatment regimen is urgently needed to prevent, control, and eliminate STH as a public health problem. Full article
(This article belongs to the Section Pharmacology)
16 pages, 2265 KiB  
Article
Low Sulfur Amino Acid, High Polyunsaturated Fatty Acid Diet Inhibits Breast Cancer Growth
by Riccardo Turchi, Flavia Tortolici, Monica Benvenuto, Carolina Punziano, Anastasia De Luca, Stefano Rufini, Raffaella Faraonio, Roberto Bei, Daniele Lettieri-Barbato and Katia Aquilano
Int. J. Mol. Sci. 2023, 24(1), 249; https://doi.org/10.3390/ijms24010249 - 23 Dec 2022
Cited by 2 | Viewed by 2500
Abstract
Cancer cells may acquire resistance to stress signals and reprogram metabolism to meet the energetic demands to support their high proliferation rate and avoid death. Hence, targeting nutrient dependencies of cancer cells has been suggested as a promising anti-cancer strategy. We explored the [...] Read more.
Cancer cells may acquire resistance to stress signals and reprogram metabolism to meet the energetic demands to support their high proliferation rate and avoid death. Hence, targeting nutrient dependencies of cancer cells has been suggested as a promising anti-cancer strategy. We explored the possibility of killing breast cancer (BC) cells by modifying nutrient availability. We used in vitro models of BC (MCF7 and MDA-MB-231) that were maintained with a low amount of sulfur amino acids (SAAs) and a high amount of oxidizable polyunsatured fatty acids (PUFAs). Treatment with anti-apoptotic, anti-ferroptotic and antioxidant drugs were used to determine the modality of cell death. We reproduced these conditions in vivo by feeding BC-bearing mice with a diet poor in proteins and SAAs and rich in PUFAs (LSAA/HPUFA). Western blot analysis, qPCR and histological analyses were used to assess the anti-cancer effects and the molecular pathways involved. We found that BC cells underwent oxidative damage to DNA and proteins and both apoptosis and ferroptosis were induced. Along with caspases-mediated PARP1 cleavage, we found a lowering of the GSH-GPX4 system and an increase of lipid peroxides. A LSAA/HPUFA diet reduced tumor mass and its vascularization and immune cell infiltration, and induced apoptosis and ferroptotic hallmarks. Furthermore, mitochondrial mass was found to be increased, and the buffering of mitochondrial reactive oxygen species limited GPX4 reduction and DNA damage. Our results suggest that administration of custom diets, targeting the dependency of cancer cells on certain nutrients, can represent a promising complementary option for anti-cancer therapy. Full article
(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)
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12 pages, 1516 KiB  
Article
The Indispensability of Snail Control for Accelerating Schistosomiasis Elimination: Evidence from Zanzibar
by Mtumweni Ali Muhsin, Xinyao Wang, Fatma Mohammed Kabole, January Zilabumba and Kun Yang
Trop. Med. Infect. Dis. 2022, 7(11), 347; https://doi.org/10.3390/tropicalmed7110347 - 03 Nov 2022
Cited by 3 | Viewed by 3070
Abstract
Schistosomiasis is a serious and neglected global tropical disease, affecting upwards of 230 million people, with more than 95% of infections concentrated in Africa. For many years, the main schistosomiasis control strategy in Africa focused on mass drug administration (MDA). The aim of [...] Read more.
Schistosomiasis is a serious and neglected global tropical disease, affecting upwards of 230 million people, with more than 95% of infections concentrated in Africa. For many years, the main schistosomiasis control strategy in Africa focused on mass drug administration (MDA). The aim of this study was to compare the difference between MDA alone and alongside another intervention, namely snail control, by exploring effective measures for eliminating schistosomiasis. Retrospective data of human prevalence on Schistosoma haematobium and major control measures were collected from the China-Zanzibar-WHO Cooperation Project for Schistosomiasis Elimination (CZW) and the Zanzibar Elimination of Schistosomiasis Transmission (ZEST) project since 2012. The optimal order polynomial regression fitting model and joinpoint regression model (JRM) were used to analyze trends in schistosomiasis prevalence and the consistency of change points with strengthening of the control measures. In Unguja Island, the main control measure was MDA, and prevalence decreased to a nadir in 2019, and then rebounded. The R2 value of the optimal fitting model was 0.6641. There was a single JRM changepoint in 2019, the annual percent change (APC) was −19.3% (p < 0.05) from 2012 to 2019, and the APC was 59.7% (p > 0.05) from 2019 to 2021. In Pemba Island, the main control measures until 2016 was MDA, while integrated measures of MDA and snail control were implemented from 2017, the prevalence continuously decreased, and the R2 value was 0.8673. There was also a single JRM changepoint in 2017, the APC was −22.2% (p < 0.05) from 2012 to 2017, and was maintained at −8.6% (p > 0.05) from 2017 to 2021. Our data indicate that, while it is challenging to eliminate schistosomiasis by MDA alone, integrated measures, including both MDA and snail control, can prevent reinfection and help to eliminate the diseases in Africa. Full article
(This article belongs to the Special Issue Control of Schistosome Intermediate Hosts)
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14 pages, 1305 KiB  
Article
Safety Surveillance of Mass Praziquantel and Albendazole Co-Administration in School Children from Southern Ethiopia: An Active Cohort Event Monitoring
by Tigist Dires Gebreyesus, Eyasu Makonnen, Tafesse Tadele, Habtamu Gashaw, Workagegnew Degefe, Heran Gerba, Birkneh Tilahun Tadesse, Parthasarathi Gurumurthy and Eleni Aklillu
J. Clin. Med. 2022, 11(21), 6300; https://doi.org/10.3390/jcm11216300 - 26 Oct 2022
Cited by 4 | Viewed by 1143
Abstract
Preventive chemotherapy (PC) with praziquantel and albendazole co-administration to all at-risk populations is the global intervention strategy to eliminate schistosomiasis and soil-transmitted helminth (STH) from being public health problems. Due to weak pharmacovigilance systems, safety monitoring during a mass drug administration (MDA) is [...] Read more.
Preventive chemotherapy (PC) with praziquantel and albendazole co-administration to all at-risk populations is the global intervention strategy to eliminate schistosomiasis and soil-transmitted helminth (STH) from being public health problems. Due to weak pharmacovigilance systems, safety monitoring during a mass drug administration (MDA) is lacking, especially in sub-Saharan Africa. We conducted large-scale active safety surveillance to identify the incidence, types, severity, and associated risk factors of adverse events (AEs) following praziquantel and albendazole MDA in 5848 school children (5–15 years old). Before MDA, 1484 (25.4%) children were prescreened for S. mansoni and STH infections, of whom 71.8% were infected with at least one parasite; 34.5% (512/1484) had S. mansoni and 853 (57.5%) had an STH infection. After collecting the baseline socio-demographic, clinical, and medical data, including any pre-existing clinical symptoms, participants received single dose praziquantel and albendazole MDA. Treatment-associated AEs were actively monitored on days 1 and 7 of the MDA. The events reported before and after the MDA were cross-checked and verified to identify MDA-associated AEs. The cumulative incidence of experiencing at least one type of MDA-associated AE was 13.3% (95% CI = 12.5–14.2%); 85.5%, 12.4%, and 1.8% of reported AEs were mild, moderate, and severe, respectively. The proportion of experiencing one, two, or ≥ three types of AEs was 57.7%, 34.1%, and 8.2%, respectively. The cumulative incidence of AEs in S. mansoni- and (17.0%) and STH (14.1%)-infected children was significantly higher (p < 0.001, χ2 = 15.0) than in non-infected children (8.4%). Headache, abdominal pain, vomiting, dizziness, and nausea were the most common AEs. Being female, older age, having S. mansoni or STH infection were significant predictors of MDA-associated AEs. In summary, praziquantel and albendazole co-administration is generally safe and tolerable. MDA-associated AEs are mostly mild-to-moderately severe and transient. The finding of few severe AEs and significantly high rates of AEs in helminth-infected children underscores the need to integrate pharmacovigilance in MDA programs, especially in high schistosomiasis and STH endemic areas. Full article
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18 pages, 2386 KiB  
Article
Impact of a 5-Year Mass Drug Administration Programme for Soil-Transmitted Helminthiases on the Spatial Distribution of Childhood Anaemia in Burundi from 2007 to 2011
by Mohamad Assoum, Giuseppina Ortu, Maria-Gloria Basáñez, Colleen Lau, Archie C. A. Clements, Kate Halton, Alan Fenwick and Ricardo J. Soares Magalhães
Trop. Med. Infect. Dis. 2022, 7(10), 307; https://doi.org/10.3390/tropicalmed7100307 - 17 Oct 2022
Cited by 1 | Viewed by 1493
Abstract
Background: Childhood anaemia affects 1.8 billion people globally. Little is known about the long-term impact of mass drug administration (MDA) for the control of soil-transmitted helminthiases (STH) on the spatiotemporal variation of anaemia prevalence and severity. We describe the long-term spatiotemporal impact of [...] Read more.
Background: Childhood anaemia affects 1.8 billion people globally. Little is known about the long-term impact of mass drug administration (MDA) for the control of soil-transmitted helminthiases (STH) on the spatiotemporal variation of anaemia prevalence and severity. We describe the long-term spatiotemporal impact of a 5-year STH MDA programme (2007–2011) on the prevalence of anaemia and anaemia severity in school-aged children (SAC) in Burundi. Methodology/Principal Findings: We used annual haemoglobin concentration and STH data collected during 2007–2011 in 31 schools in Burundi. Spatial dependence in prevalence and severity of anaemia was assessed using semivariograms. Bayesian geostatistical models were developed to (a) quantify the role of STH (adjusted for other anaemia determinants) in the spatiotemporal distribution of anaemia prevalence/severity, and (b) predict the geographical variation of both outcomes across Burundi. Adjusted population data were used to estimate the geographical distribution of the number of SAC at risk of anaemia and with low and moderate/severe anaemia. Infections with Ascaris lumbricoides and Trichuris trichiura were positively and significantly associated with childhood anaemia; hookworm infections were not. A significant decrease in anaemia prevalence, from 40–50% (2008) to 10–20% (2011) was predicted in western areas. The predicted prevalence of low-severity anaemia decreased from 40–50% (2008) to <20% (2011) in southern and eastern areas. Moderate/high-severity anaemia was concentrated in western regions of Burundi, with pockets of moderate/high-severity anaemia in central and northern regions in 2008. The overall number of predicted anaemic children decreased from 443,657 (2008) to 232,304 (2011), with a resurgence after MDA disruption in 2010 (to 480,605). Prevalence of low- and moderate-severity anaemia was higher in boys than in girls. Conclusions/Significance: Despite ongoing MDA, the prevalence of anaemia in SAC remained high and increased in certain parts of the country. It is recommended that MDA programmes targeting STH are complemented with specific anaemia interventions. Full article
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