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Neglected Tropical Diseases (NTDs): Early Detection and Treatment towards Rational Control

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A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Neglected and Emerging Tropical Diseases".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 17580

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Dr. Oyetunde T. Oyeyemi

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Guest Editor

Department of Biological Sciences, University of Medical Sciences, Odoshida Campus, Ondo P.M.B. 536, Ondo State, Nigeria
Interests: NTDs; epidemiology; immunodiagnostics; drug development

Dr. Mirjam Schunk

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Guest Editor

Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, Leopoldstrasse 5, 80802 Munich, Germany
Interests: neglected tropical diseases; novel diagnostics and treatment strategies in parasitic diseases; travel medicine; vaccinology

Special Issue Information

Dear Colleagues,

Neglected tropical diseases (NTDs) contribute significantly to the global health burden. Diagnosis and treatment are crucial to the control of NTD transmission. The increase in morbidity in late diagnosis and the frequent occurrence of the development of resistance to mainstay drugs for the management of many NTDs make diagnosis and treatment interventions among the core strategies highlighted to achieve the 2030 NTDs elimination target. These two interventions have evolved from classical or traditional methods to more advanced approaches such as proteomics, nanotechnology, DNA technology, microRNAs, and other small non-coding RNAs. Recently, there has been renewed advocacy on operational approaches for the deployment of NTDs diagnostics and treatment. The latter aims to provide a paradigm shift towards achieving equity in the mapping of NTD cases and mass drug administration in endemic countries.

This Special Issue welcomes submissions from one or more of the following NTDs: Chagas disease, dengue, dracunculiasis, endemic treponematoses, cysticercosis, human African trypanosomiasis, leishmaniasis, echinococcosis, leprosy, foodborne trematode infections, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis, soil-transmitted helminthiases, Buruli ulcer, and trachoma.

The focus of the submissions will address diagnosis and treatment approaches toward the control of the listed NTDs. Importantly, this Special Issue shall also welcome submissions that apply the One Health and operational research framework to the diagnosis and treatment of one or more NTDs.

Dr. Oyetunde T. Oyeyemi
Dr. Mirjam Schunk
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Tropical Medicine and Infectious Disease is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

NTDs
diagnosis
treatment
One Health
operational research

Published Papers (10 papers)

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12 pages, 1881 KiB

Open AccessArticle

Combination Vaccines of Fasciola gigantica Saposin-like Protein-2 and Leucine Aminopeptidase

by Narin Changklungmoa, Werachon Cheukamud, Wipaphorn Jaikua, Krai Meemon, Prasert Sobhon and Pornanan Kueakhai

Trop. Med. Infect. Dis. 2023, 8(7), 334; https://doi.org/10.3390/tropicalmed8070334 - 22 Jun 2023

Viewed by 1311

Abstract

Saposin-like protein-2 (SAP-2) and leucine aminopeptidase (LAP) are major proteins involved in the digestive process of Fasciola gigantica (Fg). Both SAP-2 and LAP are highly expressed in F. gigantica; therefore, they could be vaccine candidates for fasciolosis. The aims of this study are (1) to observe the tissue expression of F. gigantica SAP-2 (FgSAP-2) and F. gigantica LAP (FgLAP) in F. gigantica by indirect immunofluorescence technique under confocal microscopy and (2) to test the vaccine potentials of individual and combined recombinant (r) FgSAP-2 and rFgLAP against F. gigantica in Imprinting Control Region (ICR) mice (n = 10 per group). By indirect immunofluorescence-confocal microscopy, FgSAP-2 and FgLAP were localized in the caecal epithelium but at different sites: FgSAP-2 appeared in small granules that are distributed in the middle and lower parts of the cytoplasm of epithelial cells, while FgLAP appeared as a line or zone in the apical cytoplasm of caecal epithelial cells. For vaccine testing, the percent protection of combined rFgSAP-2 and rFgLAP vaccines against F. gigantica was at 80.7 to 81.4% when compared with aluminum hydroxide (alum) adjuvant and unimmunized controls, respectively. The levels of IgG1 and IgG2a in the sera were significantly increased in single and combine vaccinated groups compared with the control groups. Vaccinated mice showed reduced liver damage when compared with control groups. This study indicates that the combined rFgSAP-2 and rFgLAP vaccine had a higher vaccine potential than a single vaccine. These results support the further testing and application of this combined vaccine against F. gigantica infection in farmed livestock animals. Full article

(This article belongs to the Special Issue Neglected Tropical Diseases (NTDs): Early Detection and Treatment towards Rational Control)

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12 pages, 4349 KiB

Open AccessArticle

Malacological Survey and Spatial Distribution of Intermediate Host Snails in Schistosomiasis Endemic Districts of Rwanda

by Joseph Kagabo, Chester Kalinda, Project Nshimiyimana, Jean Bosco Mbonigaba, Eugene Ruberanziza, Elias Nyandwi and Nadine Rujeni

Trop. Med. Infect. Dis. 2023, 8(6), 295; https://doi.org/10.3390/tropicalmed8060295 - 28 May 2023

Cited by 1 | Viewed by 2364

Abstract

Background: Schistosomiasis, due to S. mansoni, is prevalent in Rwanda. However, there is a paucity of information related to the abundance, species, distribution, and infectivity of Schistosoma intermediate host snails. Methods: Snails were collected from 71 sites, including lakeshores and wetlands. Snails obtained were morphologically identified, and cercariae were shed using standard procedures. Cercariae were molecularly characterized using PCR. GPS coordinates were used to generate geospatial maps of snail distribution that were overlaid with geospatial distribution of schistosomiasis among pre-school children in the same areas. Results: Overall, 3653 snails were morphologically classified as Bulinus spp. and 1449 as Biomphalaria spp. A total of 306 snails shed cercariae, 130 of which were confirmed as S. mansoni cercaria by PCR. There was no significant difference in the proportion of S. mansoni cercariae in wetlands compared to lakeshores. Conclusion: Rwandan water bodies harbor an important number of snails that shed S. mansoni cercariae. Furthermore, a strong spatial correlation was observed between the distribution of schistosomiasis in children and the spatial distribution of snail infectivity with S. mansoni. The presence of Bulinus spp. Suggests a potential risk of S. haematobium, although molecular analysis did not show any current transmission of this parasite. Full article

(This article belongs to the Special Issue Neglected Tropical Diseases (NTDs): Early Detection and Treatment towards Rational Control)

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18 pages, 2306 KiB

Open AccessEditor’s ChoiceArticle

Lupeol Acetate and α-Amyrin Terpenes Activity against Trypanosoma cruzi: Insights into Toxicity and Potential Mechanisms of Action

by Daniel Pardo-Rodriguez, Andres Cifuentes-López, Juan Bravo-Espejo, Ibeth Romero, Jorge Robles, Claudia Cuervo, Sol M. Mejía and Jair Tellez

Trop. Med. Infect. Dis. 2023, 8(5), 263; https://doi.org/10.3390/tropicalmed8050263 - 03 May 2023

Viewed by 2443

Abstract

Background: Chagas disease is a potentially fatal disease caused by the parasite Trypanosoma cruzi. There is growing scientific interest in finding new and better therapeutic alternatives for this disease’s treatment. Methods: A total of 81 terpene compounds with potential trypanocidal activity were screened and found to have potential T. cruzi cysteine synthase (TcCS) inhibition using molecular docking, molecular dynamics, ADME and PAIN property analyses and in vitro susceptibility assays. Results: Molecular docking analyses revealed energy ranges from −10.5 to −4.9 kcal/mol in the 81 tested compounds, where pentacyclic triterpenes were the best. Six compounds were selected to assess the stability of the TcCS–ligand complexes, of which lupeol acetate (ACLUPE) and α-amyrin (AMIR) exhibited the highest stability during 200 ns of molecular dynamics analysis. Such stability was primarily due to their hydrophobic interactions with the amino acids located in the enzyme’s active site. In addition, ACLUPE and AMIR exhibited lipophilic characteristics, low intestinal absorption and no structural interferences or toxicity. Finally, selective index for ACLUPE was >5.94, with moderate potency in the trypomastigote stage (EC₅₀ = 15.82 ± 3.7 μg/mL). AMIR’s selective index was >9.36 and it was moderately potent in the amastigote stage (IC₅₀ = 9.08 ± 23.85 μg/mL). Conclusions: The present study proposes a rational approach for exploring lupeol acetate and α-amyrin terpene compounds to design new drugs candidates for Chagas disease. Full article

(This article belongs to the Special Issue Neglected Tropical Diseases (NTDs): Early Detection and Treatment towards Rational Control)

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7 pages, 247 KiB

Open AccessCommunication

Low Seroprevalence of WNV in Namibian Dogs Suggests a Limited Effectiveness as Sentinels for Infection Monitoring

by Umberto Molini, Giovanni Franzo, Barbara Bonfini, Lourens de Villiers, Mari de Villiers, Siegfried Khaiseb, Federica Monaco, Giovanni Savini and Nicola D’Alterio

Trop. Med. Infect. Dis. 2023, 8(4), 203; https://doi.org/10.3390/tropicalmed8040203 - 29 Mar 2023

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Abstract

West Nile virus (WNV) is an important zoonotic Flavivirus responsible for mild fever to severe neurological disease in humans and horses. Despite the occurrence of major previous outbreaks in Namibia and the likelihood of the current endemicity of the virus, only limited investigations and monitoring activities of WNV have been performed in the country. The use of animal sentinels is a valuable approach toward investigating the infection presence in an area and to predict the potential occurrence of human outbreaks. Serological investigations in dogs hold several advantages, considering their infection susceptibility, the ease of sample handling, and the evaluation of risk factors of pet owners that share the same habit with their pets. To evaluate the usefulness of such a sero-epidemiological investigation in Namibia, a broad serosurvey was performed in 2022 that included 426 archived domestic dog samples from eight Namibian regions. Although the ELISA prevalence, indicative of Flavivirus infection, was relatively high (16.43%; 95 CI: 13.10–20.39%), the virus neutralization test confirmed only a minority of cases, highlighting a prevalence of 2.82% (95 CI: 1.47–4.90%), significantly lower than in Namibian donkeys and reports from other countries. Variables that could explain the recorded differences remain to be explored, including animal exposure, variable vector presence, distribution, and feeding preferences. The study results suggest the limited usefulness of dogs as sentinels for WNV monitoring in Namibia. Full article

(This article belongs to the Special Issue Neglected Tropical Diseases (NTDs): Early Detection and Treatment towards Rational Control)

13 pages, 2658 KiB

Open AccessArticle

Fasciola gigantica Cathepsin L1H: High Sensitivity and Specificity of Immunochromatographic Strip Test for Antibody Detection

by Phawiya Suksomboon, Pornanan Kueakhai and Narin Changklungmoa

Trop. Med. Infect. Dis. 2023, 8(3), 164; https://doi.org/10.3390/tropicalmed8030164 - 11 Mar 2023

Cited by 1 | Viewed by 1723

Abstract

Fasciolosis is a zoonotic disease caused by Fasciola gigantica or F. hepatica infections, which are frequently occurring parasites in animals and humans. The present gold-standard diagnostic technique involves finding parasite eggs through microscopy. However, this method is also restricted due to low specificity and low sensitivity. An alternative to coprological diagnosis is the immunochromatographic strip (ICS) test, which is rapid, simple, convenient, and cost-effective, with high sensitivity and high specificity. Cathepsin L1H (CathL1H) is a cysteine protease secreted by F. gigantica, which is found in high amounts in newly excysted juvenile (NEJ) and juvenile stages. Cathepsin L1H plays an important role in both the immune response to invading pathogens and in the ability of some pathogens to evade the host immune system. The present study aims to develop an ICS test and detect antibodies against CathL1H in mice and cattle serum using the recombinant F. gigantica Cathepsin L1H (rFgCathL1H) and rabbit anti-rFgCathL1H antibody. The F. gigantica-infected serum and non-infected serum of mice and cattle were tested using the ICS test. Moreover, the strip results were confirmed with an indirect enzyme-linked immunosorbent assay (indirect ELISA). The relative sensitivity, specificity, and accuracy of the ICS strip were 97.5, 99.99, and 99.00%, respectively. Therefore, these data suggest that the ICS method could be used to detect F. gigantica antibodies to highly enhance throughput, reduce costs, and determine the best alternative on-site method. Full article

(This article belongs to the Special Issue Neglected Tropical Diseases (NTDs): Early Detection and Treatment towards Rational Control)

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17 pages, 3183 KiB

Open AccessArticle

Antileishmanial Activity and In Silico Molecular Docking Studies of Malachra alceifolia Jacq. Fractions against Leishmania mexicana Amastigotes

by Leonor Cervantes-Ceballos, Jairo Mercado-Camargo, Esther del Olmo-Fernández, María Luisa Serrano-García, Sara M. Robledo and Harold Gómez-Estrada

Trop. Med. Infect. Dis. 2023, 8(2), 115; https://doi.org/10.3390/tropicalmed8020115 - 14 Feb 2023

Cited by 1 | Viewed by 2000

Abstract

Malachra alceifolia Jacq. (family Malvaceae), known as “malva,” is a medicinal plant used as a traditional therapy in many regions of America, Africa and Asia. Traditionally, this plant is used in the form of extracts, powder and paste by populations for treating fever, stomachache, inflammation, and parasites. However, the ethnopharmacological validation of M. alceifolia has been scarcely researched. This study showed that the chloroform fraction (MA-IC) and subfraction (MA-24F) of the leaves of M. alceifolia exhibited a potential antileishmanial activity against axenic amastigotes of Leishmania mexicana pifanoi (MHOM/VE/60/Ltrod) and had high and moderate cytotoxic effects on the viability and morphology of macrophages RAW 264.7. This study reports, for the first time, possible terpenoid metabolites and derivatives present in M. alceifolia with activity against some biosynthetic pathways in L. mexicana amastigotes. The compounds from the subfractions MA-24F were highly active and were analyzed by gas chromatography-mass spectrometry (GC-MS) and by a molecular docking study in L. mexicana target protein. This study demonstrates the potential modes of interaction and the theoretical affinity energy of the metabolites episwertenol, α-amyrin and methyl commate A, which are present in the active fraction MA-24F, at allosteric sites of the pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, triose phosphate isomerase, aldolase, phosphoglucose isomerase, transketolase, arginase and cysteine peptidases A, target proteins in some vital biosynthetic pathways were responsible for the survival of L. mexicana. Some phytoconstituents of M. alceifolia can be used for the search for potential new drugs and molecular targets for treating leishmaniases and infectious diseases. Furthermore, contributions to research and the validation and conservation of traditional knowledge of medicinal plants are needed globally. Full article

(This article belongs to the Special Issue Neglected Tropical Diseases (NTDs): Early Detection and Treatment towards Rational Control)

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10 pages, 1509 KiB

Open AccessBrief Report

Influence of Testosterone in Neglected Tropical Diseases: Clinical Aspects in Leprosy and In Vitro Experiments in Leishmaniasis

by Laís Lima de Oliveira Rekowsky, Daniela Teles de Oliveira, Rodrigo Anselmo Cazzaniga, Lucas Sousa Magalhães, Lenise Franco Albuquerque, Jonnia Maria Sherlock Araujo, Martha Débora Lira Tenório, Tiziane Cotta Machado, Michael W. Lipscomb, Priscila Lima dos Santos, Amelia Ribeiro de Jesus, Márcio Bezerra-Santos and Ricardo Luís Louzada da Silva

Trop. Med. Infect. Dis. 2023, 8(7), 357; https://doi.org/10.3390/tropicalmed8070357 - 10 Jul 2023

Viewed by 1266

Abstract

Neglected tropical diseases encompass a group of chronic and debilitating infectious diseases that primarily affect marginalized populations. Among these diseases, leprosy and leishmaniasis are endemic in numerous countries and can result in severe and disfiguring manifestations. Although there have been reports indicating a higher incidence of leprosy and leishmaniasis in males, the underlying factors contributing to this observation remain unclear. Therefore, the objective of this study was to examine both clinical and experimental evidence regarding the role of testosterone in leprosy and leishmaniasis. A prospective clinical study was conducted to compare the clinical forms of leprosy and assess circulating testosterone levels. Additionally, the impact of testosterone on Leishmania amazonensis-infected macrophages was evaluated in vitro. The findings demonstrated that serum testosterone levels were higher in women with leprosy than in the control group, irrespective of the multi- or pauci-bacillary form of the disease. However, no differences in testosterone levels were observed in men when comparing leprosy patients and controls. Interestingly, increasing doses of testosterone in macrophages infected with L. amazonensis resulted in a higher proportion of infected cells, decreased CD40 expression on the cell surface, elevated expression of SOCS1, and decreased expression of IRF5. These findings provide biological evidence to support the influence of testosterone on intracellular infections, though the interpretation of clinical evidence remains limited. Full article

(This article belongs to the Special Issue Neglected Tropical Diseases (NTDs): Early Detection and Treatment towards Rational Control)

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8 pages, 945 KiB

Open AccessCase Report

A Rare Case of Imported Cutaneous Leishmaniasis Caused by Leishmania infantum in the Republic of Korea, 2021

by Hyun Jung Kim, Eun Jin Kim, Jee Woong Choi, You Chan Kim, Hee-Il Lee and Hyun-Il Shin

Trop. Med. Infect. Dis. 2023, 8(4), 223; https://doi.org/10.3390/tropicalmed8040223 - 12 Apr 2023

Viewed by 1421

Abstract

Leishmaniasis is a neglected tropical disease and an infectious disease transmitted by sandflies that occurs worldwide. In the absence of physicians seeking to identify the causes of disease in non-endemic areas, appropriate diagnoses cannot be made, thereby hampering effective treatment. In this report, we examined a nodular lesion on a patient’s chin by performing a biopsy and molecular analysis. The biopsy finding led to the identification of a Leishmania amastigote. On the basis of PCR analysis of the internal transcribed spacer 1 gene and 5.8 S ribosomal RNA with a subsequent BLAST search, we identified the causal organism as Leishmania infantum. The patient, who had visited Spain from 1 July to 31 August 2018, was accordingly diagnosed with cutaneous leishmaniasis and was administered liposomal amphotericin B, which successfully treated the skin lesion. Travel history plays an important role in the diagnosis of leishmaniasis, and physicians should bear in mind that travelers can also introduce diseases and pathogens to non-endemic areas. Identification of Leishmania at the species level will increase the efficacy of treatment. Full article

(This article belongs to the Special Issue Neglected Tropical Diseases (NTDs): Early Detection and Treatment towards Rational Control)

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12 pages, 898 KiB

Open AccessProject Report

Towards Inclusive Diagnostics for Neglected Tropical Diseases: User Experience of a New Digital Diagnostic Device in Low-Income Settings

by Adeola Onasanya, Michel Bengtson, Temitope Agbana, Opeyemi Oladunni, Jo van Engelen, Oladimeji Oladepo and Jan Carel Diehl

Trop. Med. Infect. Dis. 2023, 8(3), 176; https://doi.org/10.3390/tropicalmed8030176 - 16 Mar 2023

Cited by 2 | Viewed by 1482

Abstract

Designing new and inclusive diagnostic tools to detect Neglected Tropical Diseases (NTDs) to achieve rational disease control requires a co-design process where end-users’ input is important. Failure to involve all potential end-users in new diagnostics for NTDs can result in low use and adoption failure, leading to persistent infection hot spots and ineffective disease control. There are different categories of potential end-users of new diagnostic tools for NTD control, and it is unclear if there are differences between the user efficiency, effectiveness, perception, and acceptability across these end-user categories. This study evaluated the usability, user perception, contextual factors affecting the user’s experience, and acceptability of a new digital optical diagnostic device for NTDs across three types of potential end users. A total of 21 participants were tested. Laboratory scientists, technicians, and Community Health Extension Workers (CHEWs) in training achieved similar scores on the usability and user perception questionnaires with no statistically significant difference between end-user categories. All participants also have high scores for the user perception domains which strongly correlate with the acceptability of the AiDx NTDx Assist device. This study indicates that, by providing digital diagnostic tools in combination with minimal training and support, CHEWs undergoing training and, by extension, CHEWs post-training, can be involved in the diagnoses of NTDs, potentially enhancing a community’s capabilities to diagnose, treat, and control NTDs. Full article

(This article belongs to the Special Issue Neglected Tropical Diseases (NTDs): Early Detection and Treatment towards Rational Control)

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8 pages, 1653 KiB

Open AccessCase Report

Clinical Implications for the Comprehensive Interpretation of Radiologic and Immunodiagnostic Tests in Patients Suspected of Parasitic Hepatic Cyst, a Rare Case in Korea

by Jae-Sung Yoo, Min-Kyu Kang, Jung-Gil Park, Hyung-Joo Kim and Joon-Hyuk Choi

Trop. Med. Infect. Dis. 2023, 8(3), 155; https://doi.org/10.3390/tropicalmed8030155 - 02 Mar 2023

Cited by 1 | Viewed by 1483

Abstract

Cystic echinococcosis (CE) is a representative neglected tropical disease (NTD) with increased morbidity and mortality but is ignored and overlooked in developed countries. Serological and radiographic findings are helpful in distinguishing these parasites; however, conflicting results of these can make it difficult to diagnose if medical knowledge of hepatic parasitic disease, including the etiology, features of imaging, and immunodiagnostic test, is not acquired. We report the case of a male patient with dyspepsia and right epigastric pain who had positive results for cysticercosis antibodies on immunodiagnostic examination. Abdominal ultrasonography revealed two huge communicating cystic lesions measuring 8–11 cm. Further evaluations for cysticercosis of the brain (neurocysticercosis) and eyes (intraocular cysticercosis) were unremarkable throughout the brain imaging test and fundus examination. A laparoscopic right hemi-hepatectomy was performed for diagnosis and treatment. On histopathological examination, diverse stages of Echinococcus granulosus were identified. Albendazole was administered postoperatively, and the patient was also followed up. We should be aware of the etiologies that have been prevalent in parasite infection thought to be the cause of hepatic cysts. Moreover, we make an effort to ascertain the patient’s nationality, past travel experiences, and immediate environment, including any animals and pets. We present the case of a patient who was worried about the possibility of liver invasion of cysticercus due to the positivity of the cysticercosis antibody and was ultimately diagnosed with CE. Full article

(This article belongs to the Special Issue Neglected Tropical Diseases (NTDs): Early Detection and Treatment towards Rational Control)

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