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Trop. Med. Infect. Dis., Volume 9, Issue 2 (February 2024) – 23 articles

Cover Story (view full-size image): Current treatments for leishmaniasis are unsafe and susceptible to resistance. Combination therapy could solve these problems due to the involvement of several mechanisms of action and the potential synergistic effect of both compounds. A repurposing drug screen identified the leishmanicidal effect of pyrvinium pamoate. Combinations of this drug were tested separately with miltefosine and paromomycin on axenic amastigotes and intramacrophagic amastigotes from mice experimentally infected with Leishmania infantum. The combinations showed synergistic behaviour, especially in the case of the combination of pyrvinium pamoate with paromomycin, exhibiting low cytotoxicity and good tolerability in murine intestinal organoids, thus revealing the potential of these combinations for the treatment of leishmaniasis. View this paper
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10 pages, 1618 KiB  
Brief Report
Spike S2 Subunit: Possible Target for Detecting Novel SARS-CoV-2 Variants with Multiple Mutations
by Teerada Ponpinit, Yutthana Joyjinda, Weenassarin Ampoot, Siriporn Yomrat, Phatthamon Virojanapirom, Chanida Ruchisrisarod, Abhinbhen W. Saraya, Pasin Hemachudha and Thiravat Hemachudha
Trop. Med. Infect. Dis. 2024, 9(2), 50; https://doi.org/10.3390/tropicalmed9020050 - 15 Feb 2024
Viewed by 1130
Abstract
Novel SARS-CoV-2 variants have multiple mutations that may impact molecular diagnostics. The markedly conserved S2 subunit may be utilized to detect new variants. A comparison of 694 specimens (2019–2022) in Thailand using a commercial RT-PCR kit and the kit in combination with S2 [...] Read more.
Novel SARS-CoV-2 variants have multiple mutations that may impact molecular diagnostics. The markedly conserved S2 subunit may be utilized to detect new variants. A comparison of 694 specimens (2019–2022) in Thailand using a commercial RT-PCR kit and the kit in combination with S2 primers and a probe was performed. Delayed amplification in ORF1ab was detected in one BA.4 omicron, whereas no amplification problem was encountered in the S2 target. There were no statistically significant differences in mean Ct value between the target genes (E, N, ORF1ab, and S2) and no significant differences in mean Ct value between the reagents. Furthermore, 230,821 nucleotide sequences submitted by 20 representative counties in each region (Jan–Oct 2022) have been checked for mutations in S2 primers and probe using PrimerChecker; there is a very low chance of encountering performance problems. The S2 primers and probe are still bound to the top five currently circulating variants in all countries and Thailand without mismatch recognition (Jun–Nov 2023). This study shows the possible benefits of detecting S2 in combination with simultaneously detecting three genes in a kit without affecting the Ct value of each target. The S2 subunit may be a promising target for the detection of SARS-CoV-2 variants with multiple mutations. Full article
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17 pages, 313 KiB  
Review
Human Cytomegalovirus (HCMV) Genetic Diversity, Drug Resistance Testing and Prevalence of the Resistance Mutations: A Literature Review
by Ivana Grgic and Lana Gorenec
Trop. Med. Infect. Dis. 2024, 9(2), 49; https://doi.org/10.3390/tropicalmed9020049 - 15 Feb 2024
Viewed by 1454
Abstract
Human cytomegalovirus (HCMV) is a pathogen with high prevalence in the general population that is responsible for high morbidity and mortality in immunocompromised individuals and newborns, while remaining mainly asymptomatic in healthy individuals. The HCMV genome is 236,000 nucleotides long and encodes approximately [...] Read more.
Human cytomegalovirus (HCMV) is a pathogen with high prevalence in the general population that is responsible for high morbidity and mortality in immunocompromised individuals and newborns, while remaining mainly asymptomatic in healthy individuals. The HCMV genome is 236,000 nucleotides long and encodes approximately 200 genes in more than 170 open reading frames, with the highest rate of genetic polymorphisms occurring in the envelope glycoproteins. HCMV infection is treated with antiviral drugs such as ganciclovir, valganciclovir, cidofovir, foscarnet, letermovir and maribavir targeting viral enzymes, DNA polymerase, kinase and the terminase complex. One of the obstacles to successful therapy is the emergence of drug resistance, which can be tested phenotypically or by genotyping using Sanger sequencing, which is a widely available but less sensitive method, or next-generation sequencing performed in samples with a lower viral load to detect minority variants, those representing approximately 1% of the population. The prevalence of drug resistance depends on the population tested, as well as the drug, and ranges from no mutations detected to up to almost 50%. A high prevalence of resistance emphasizes the importance of testing the patient whenever resistance is suspected, which requires the development of more sensitive and rapid tests while also highlighting the need for alternative therapeutic targets, strategies and the development of an effective vaccine. Full article
11 pages, 268 KiB  
Article
Determinants of Immunovirological Response among Children and Adolescents Living with HIV-1 in the Central Region of Cameroon
by Rodolphe Steven Dobseu Soudebto, Joseph Fokam, Nelly Kamgaing, Nadine Fainguem, Ezechiel Ngoufack Jagni Semengue, Michel Carlos Tommo Tchouaket, Rachel Kamgaing, Aubin Nanfack, Yagai Bouba, Junie Yimga, Collins Chenwi Ambe, Hyacinthe Gouissi, Jeremiah Efakika Gabisa, Krystel Nnomo Zam, Alex Durand Nka, Samuel Martin Sosso, Gregory-Edie Halle-Ekane, Marie-Claire Okomo and Alexis Ndjolo
Trop. Med. Infect. Dis. 2024, 9(2), 48; https://doi.org/10.3390/tropicalmed9020048 - 14 Feb 2024
Viewed by 1153
Abstract
About 90% of new HIV-1 infections in children occur in sub-Saharan Africa, where treatment monitoring remains suboptimal. We sought to ascertain factors associated with immunovirological responses among an ART-experienced paediatric population in Cameroon. A laboratory-based and analytical study was conducted from January 2017 [...] Read more.
About 90% of new HIV-1 infections in children occur in sub-Saharan Africa, where treatment monitoring remains suboptimal. We sought to ascertain factors associated with immunovirological responses among an ART-experienced paediatric population in Cameroon. A laboratory-based and analytical study was conducted from January 2017 throughout December 2020 wherein plasma viral load (PVL) analyses and CD4 cell counts were performed. Viral suppression (VS) was defined as PVL < 1000 copies/mL and immunological failure (IF) as CD4 < 500 cells/µL for participants ≤5 years and CD4 < 250 cells/µL for those >5 years; p < 0.05 was considered statistically significant. Overall, 272 participants were enrolled (median age: 13 [9–15.5] years; 54% males); median ART duration 7 [3–10] years. Globally, VS was achieved in 54.41%. VS was 56.96% in urban versus 40.48% in rural areas (p = 0.04). IF was 22.43%, with 15.79% among participants ≤5 years and 22.92% among those >5 years (p = 0.66). IF was 20.43% in urban versus 33.33% in rural areas (p = 0.10). Following ART, IF was 25.82% on first-line (non-nucleoside reverse transcriptase inhibitors; NNRTI-based) versus 10.17% on second-line (protease inhibitor-based) regimens (p = 0.01). Interestingly, IF was 7.43% among virally suppressed versus 40.32% among virally unsuppressed participants (p < 0.0001). A low VS indicates major challenges in achieving AIDS’ elimination in this paediatric population, especially in rural settings and poor immune statuses. Scaling up NNRTI-sparing regimens alongside close monitoring would ensure optimal therapeutic outcomes. Full article
12 pages, 2816 KiB  
Case Report
Unusual Localization of AIDS-Related Kaposi’s Sarcoma in a Heterosexual Male during the COVID-19 Pandemic: A Case Report
by Manuela Arbune, Monica-Daniela Padurariu-Covit, Carmen Tiutiuca, Raul Mihailov, Elena Niculet, Anca-Adriana Arbune and Alin-Laurentiu Tatu
Trop. Med. Infect. Dis. 2024, 9(2), 47; https://doi.org/10.3390/tropicalmed9020047 - 13 Feb 2024
Viewed by 1337
Abstract
Kaposi’s sarcoma is an AIDS-defining illness and remains the most frequent tumor arising in HIV-infected patients with multifactorial etiology. We present a case of a 30-year-old Caucasian male with an 18-year history of HIV infection. The patient was presented with a one-week history [...] Read more.
Kaposi’s sarcoma is an AIDS-defining illness and remains the most frequent tumor arising in HIV-infected patients with multifactorial etiology. We present a case of a 30-year-old Caucasian male with an 18-year history of HIV infection. The patient was presented with a one-week history of fever, non-productive cough, and skin lesions. There was an associated weakness and weight loss in a duration of 6 months. Clinical examination showed fever, generalized lymphadenopathy, lower limb edema, ascites, and violaceous cutaneous eruption comprising patches, plaques, and nodules. He also had a red nodule on the left conjunctiva, as well as on his oral mucosa. His CD4+ count was below 10/mm3 and ARN-HIV viral load was above 100,000 c/mL, in relation to the antiretroviral failure after five drug regimens. The role of co-infections in oncogenesis and the course of Kaposi’s sarcoma were considered in recent studies. Delayed diagnosis of Kaposi’s sarcoma in the present case resulted in a negative impact for this patient during the COVID-19 pandemic. Full article
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17 pages, 3021 KiB  
Article
Genomic and Phylogenetic Characterisation of SARS-CoV-2 Genomes Isolated in Patients from Lambayeque Region, Peru
by Sergio Luis Aguilar-Martinez, Gustavo Adolfo Sandoval-Peña, José Arturo Molina-Mora, Pablo Tsukayama-Cisneros, Cristian Díaz-Vélez, Franklin Rómulo Aguilar-Gamboa, D. Katterine Bonilla-Aldana and Alfonso J. Rodriguez-Morales
Trop. Med. Infect. Dis. 2024, 9(2), 46; https://doi.org/10.3390/tropicalmed9020046 - 11 Feb 2024
Viewed by 1568
Abstract
Objective: this study aims to identify and characterise genomic and phylogenetically isolated SARS-CoV-2 viral isolates in patients from Lambayeque, Peru. Methods: Nasopharyngeal swabs were taken from patients from the Almanzor Aguinaga Asenjo Hospital, Chiclayo, Lambayeque, Peru, which had been considered mild, moderate, and [...] Read more.
Objective: this study aims to identify and characterise genomic and phylogenetically isolated SARS-CoV-2 viral isolates in patients from Lambayeque, Peru. Methods: Nasopharyngeal swabs were taken from patients from the Almanzor Aguinaga Asenjo Hospital, Chiclayo, Lambayeque, Peru, which had been considered mild, moderate, and severe cases of COVID-19. Patients had to have tested positive for COVID-19, using a positive RT-PCR for SARS-CoV-2. Subsequently, the SARS-CoV-2 complete viral genome sequencing was carried out using Illumina MiSeq®. The sequences obtained from the sequence were analysed in Nextclade V1.10.0 to assign the corresponding clades, identify mutations in the SARS-CoV-2 genes and perform quality control of the sequences obtained. All sequences were aligned using MAFFT v7.471. The SARS-CoV-2 isolate Wuhan NC 045512.2 was used as a reference sequence to analyse mutations at the amino acid level. The construction of the phylogenetic tree model was achieved with IQ-TREE v1.6.12. Results: It was determined that during the period from December 2020 to January 2021, the lineages s C.14, C.33, B.1.1.485, B.1.1, B.1.1.1, and B.1.111 circulated, with lineage C.14 being the most predominant at 76.7% (n = 23/30). These lineages were classified in clade 20D mainly and also within clades 20B and 20A. On the contrary, the variants found in the second batch of samples of the period from September to October 2021 were Delta (72.7%), Gamma (13.6%), Mu (4.6%), and Lambda (9.1%), distributed between clades 20J, 21G, 21H, 21J, and 21I. Conclusions: This study reveals updated information on the viral genomics of SARS-CoV-2 in the Lambayeque region, Peru, which is crucial to understanding the origins and dispersion of the virus and provides information on viral pathogenicity, transmission and epidemiology. Full article
(This article belongs to the Special Issue COVID-19 Variants, Vaccines and New Waves)
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14 pages, 1789 KiB  
Article
Epidemiology of Dengue in Argentina during the 2010/11 to 2019/20 Seasons: A Contribution to the Burden of Disease
by Solana Rapaport, Mariana Mauriño, María Alejandra Morales, Cintia Fabbri, Victoria Luppo, María Pía Buyayisqui, Teresa Varela, Carlos Giovacchini and Analía Urueña
Trop. Med. Infect. Dis. 2024, 9(2), 45; https://doi.org/10.3390/tropicalmed9020045 - 10 Feb 2024
Viewed by 1297
Abstract
Background: Dengue is an important public health problem in Argentina, as in many other countries. We reviewed and updated information on the dengue disease burden in Argentina over a 10-year period. Methods: We conducted a retrospective descriptive study from 2010 to 2020 based [...] Read more.
Background: Dengue is an important public health problem in Argentina, as in many other countries. We reviewed and updated information on the dengue disease burden in Argentina over a 10-year period. Methods: We conducted a retrospective descriptive study from 2010 to 2020 based on data from the National Health Surveillance System. The main outcomes included dengue cases, incidence rates, deaths, and serotype distribution by season, age group, and region. Results: A total of 109,998 confirmed cases of dengue were reported. Seasonality stands out, prevailing during summer and autumn. Two main outbreaks (seasons 2015/16 and 2019/20), with increasing magnitude, were observed. The 2019/20 season showed the highest number of cases (58,731) and incidence rate (135/100,000). The Northeast region had the highest number of cases and incidence rate. In 2020, for the first time, autochthonous cases were registered in the Cuyo region. The only region with no autochthonous cases was the South. Adolescents and young adults showed the highest incidence rate. The case fatality rate for the period was 0.05%. Four serotypes circulated, but the predominant one was DEN-1 (78%). Conclusions: Dengue has been expanding temporally and spatially. Although the DEN-1 serotype widely predominated, the increasing circulation of other serotypes raises concerns regarding re-exposure and the severity of future cases. Understanding epidemiological trends is key to defining public prevention and control policies. Full article
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11 pages, 768 KiB  
Article
Serological Comparison of Native Antigen ELISAs with Rapid ICT Test Kits for the Diagnosis of Human Alveolar and Cystic Echinococcosis in China
by Shu-Kun Yang, Wei Zhang, Na Zhu, Donald P. McManus, Darren J. Gray, Archie C. A. Clements, Angela M. Cadavid Restrepo, Gail M. Williams, Ting Zhang, Guo-Rong Ma, Yan-Hui Yang and Yu-Rong Yang
Trop. Med. Infect. Dis. 2024, 9(2), 44; https://doi.org/10.3390/tropicalmed9020044 - 07 Feb 2024
Viewed by 1184
Abstract
Background: The aim of this study was to compare the diagnostic performance of native antigen ELISAs and ADAMU-AE/CE commercial ICT test kits in subjects either exposed to Echinococcus infection or with clinically diagnosed alveolar (AE) or cystic (CE) echinococcosis. Methods: A total of [...] Read more.
Background: The aim of this study was to compare the diagnostic performance of native antigen ELISAs and ADAMU-AE/CE commercial ICT test kits in subjects either exposed to Echinococcus infection or with clinically diagnosed alveolar (AE) or cystic (CE) echinococcosis. Methods: A total of 370 subjects with a previous clinical confirmation of CE or AE from northwestern China were recruited. Serum samples were also obtained from 3923 children/teenagers during a community survey. All sera were tested using native antigen ELISAs. The ADAMU-AE/CE test kits were subsequently used for the serology of the 370 clinically confirmed individuals and of 251 children/teenagers that were ELISA antibody-positive for both Echinococcus species but ultrasound-negative during baseline survey. An analysis of the association between the serological tests and ultrasound classification was carried out amongst 89 AE and 164 CE cases. A Kappa consistency analysis was undertaken to compare the diagnostic performance of the native antigen ELISAs and the ADAMU kits and the ultrasound imaging results. The χ² test was also used for a comparison of the different seropositivity rates between the groups. Findings: There was poor consistency (Kappa = 0.26 and 0.28 for AE and CE respectively) between the native antigen ELISAs and the ADAMU kits for the diagnosis of AE and CE among the cases and the surveyed children/teenagers, but a relatively good consistency (Kappa = 0.63) between the ADAMU-AE kit and ultrasound observations for the AE cases. Additionally, of the 251 teenagers co-positive for both AE and CE antibodies by the native antigen ELISAs, only one was found positive by the ADAMU-AE kit, verified as a new AE case on subsequent ultrasound follow-up. The remainder (N = 250) were negative by serology using the ADAMU-AE/CE kits and by ultrasound examination. The two native antigen ELISAs did not discriminate well between cases of clinically diagnosed AE and CE. In contrast, ADAMU-AE and ADAMU-CE commercial ICT test kits readily differentiated cases of AE from CE with specificities of 99% for AE and 100% for CE. Conclusions: The ADAMU-AE/CE kits proved reliable, accurate, and amenable diagnostic tools in the clinical setting for confirmation of suspected AE/CE cases. The native antigen ELISAs tests can provide useful information on the level of human exposure to Echinococcus infection. Full article
(This article belongs to the Special Issue Echinococcosis: From Parasite–Host Interaction to Rapid Detection)
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18 pages, 1062 KiB  
Article
A Qualitative Analysis of the Perceptions of Stakeholders Involved in Vector Control and Vector-Borne Disease Research and Surveillance in Orinoquia, Colombia
by Gloria Isabel Jaramillo-Ramirez, Maria Claudelle Tacugue, Grace M. Power, Rimsha Qureshi, Frederik Seelig, Juliana Quintero, James G. Logan and Robert T. Jones
Trop. Med. Infect. Dis. 2024, 9(2), 43; https://doi.org/10.3390/tropicalmed9020043 - 06 Feb 2024
Viewed by 1445
Abstract
Colombia has a tropical climate and environmental conditions that favour the circulation of most of the known vector-borne diseases (VBDs). Protocols have been established and implemented to address the threats of these diseases, but they are for country-wide use and do not take [...] Read more.
Colombia has a tropical climate and environmental conditions that favour the circulation of most of the known vector-borne diseases (VBDs). Protocols have been established and implemented to address the threats of these diseases, but they are for country-wide use and do not take into consideration the nuances of the different environments of the country. Almost the entire population is vulnerable to infection with one or more VBD. This study aims to characterise the perceptions and experiences of stakeholders involved in vector control and VBDs in the Orinoquia region in Colombia. Two panel discussions, and 12 semi-structured interviews, were conducted. Experts from the Colombian National Health Institute (INS), health secretaries from Meta, Guaviare and Vichada Departments, academic researchers, and individuals from private vector control companies participated. All sessions were recorded, transcribed, and translated, and then subject to thematic analysis. Three major themes emerged: involvement, limitations, and recommendations. Results showed that participants are engaged in vector surveillance activities, education, and vector control research. Participants focused on problems of disjointed efforts towards VBD control between health secretaries and the health ministry, as well as societal issues, such as socioeconomic, cultural, and political issues, which became the rationale for the lack of vector control resources. Responses in the panel discussions and interviews overlapped in opinions, and suggested that vector control could be improved through better communication between vector control bodies, strengthened engagement with vulnerable communities, more collaborative actions, and a more balanced distribution of resources. Full article
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0 pages, 3054 KiB  
Article
Inhibiting Liver Autophagy and Promoting Hepatocyte Apoptosis by Schistosoma japonicum Infection
by Zhihao Yu, Tingting Jiang, Fangfang Xu, Jing Zhang, Yuan Hu and Jianping Cao
Trop. Med. Infect. Dis. 2024, 9(2), 42; https://doi.org/10.3390/tropicalmed9020042 - 04 Feb 2024
Cited by 1 | Viewed by 1246 | Correction
Abstract
We established a mouse model of Schistosoma japonicum infection in order to study the effects of the infection on hepatocyte autophagy and apoptosis. We also stimulated HepG2 cells with soluble egg antigens (SEA) in vitro. At two, four, and six weeks post-infection, quantitative [...] Read more.
We established a mouse model of Schistosoma japonicum infection in order to study the effects of the infection on hepatocyte autophagy and apoptosis. We also stimulated HepG2 cells with soluble egg antigens (SEA) in vitro. At two, four, and six weeks post-infection, quantitative real-time PCR and Western blot (WB) were used to detect liver expression levels of autophagy and apoptosis-related proteins. HepG2 cells were treated with different concentrations of SEA. The changes in the levels of autophagy-related proteins and HepG2 cell apoptosis were detected. The Lc3b, Beclin1, Atg7, and Atg12 mRNA levels were significantly lower at four and six weeks after infection than those in the uninfected group. At four and six weeks following infection, the levels of Beclin1, LC3BII/I, Atg7, and p62 proteins were considerably lower than those in the uninfected group. The protein levels of pro-apoptotic Bax and cleaved caspase 3 and fibrosis-related proteins α-SMA and collagen 3 in the liver post-infection were significantly higher than those in uninfected mice. HepG2 cells stimulated with SEA showed decreased levels of Beclin1, p62, and Atg7 proteins and significantly increased apoptosis rates. The findings demonstrated that following infection with S. japonicum, mice’s liver fibrosis worsened, hepatic autophagy was suppressed, and hepatocyte apoptosis was encouraged. Full article
(This article belongs to the Section Neglected and Emerging Tropical Diseases)
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17 pages, 8931 KiB  
Article
Targeting with Structural Analogs of Natural Products the Purine Salvage Pathway in Leishmania (Leishmania) infantum by Computer-Aided Drug-Design Approaches
by Haruna Luz Barazorda-Ccahuana, Eymi Gladys Cárcamo-Rodriguez, Angela Emperatriz Centeno-Lopez, Alexsandro Sobreira Galdino, Ricardo Andrez Machado-de-Ávila, Rodolfo Cordeiro Giunchetti, Eduardo Antonio Ferraz Coelho and Miguel Angel Chávez-Fumagalli
Trop. Med. Infect. Dis. 2024, 9(2), 41; https://doi.org/10.3390/tropicalmed9020041 - 03 Feb 2024
Viewed by 1611
Abstract
Visceral Leishmaniasis (VL) has a high death rate, with 500,000 new cases and 50,000 deaths occurring annually. Despite the development of novel strategies and technologies, there is no adequate treatment for the disease. Therefore, the purpose of this study is to find structural [...] Read more.
Visceral Leishmaniasis (VL) has a high death rate, with 500,000 new cases and 50,000 deaths occurring annually. Despite the development of novel strategies and technologies, there is no adequate treatment for the disease. Therefore, the purpose of this study is to find structural analogs of natural products as potential novel drugs to treat VL. We selected structural analogs from natural products that have shown antileishmanial activities, and that may impede the purine salvage pathway using computer-aided drug-design (CADD) approaches. For these, we started with the vastly studied target in the pathway, the adenine phosphoribosyl transferase (APRT) protein, which alone is non-essential for the survival of the parasite. Keeping this in mind, we search for a substance that can bind to multiple targets throughout the pathway. Computational techniques were used to study the purine salvage pathway from Leishmania infantum, and molecular dynamic simulations were used to gather information on the interactions between ligands and proteins. Because of its low homology to human proteins and its essential role in the purine salvage pathway proteins network interaction, the findings further highlight the significance of adenylosuccinate lyase protein (ADL) as a therapeutic target. An analog of the alkaloid Skimmianine, N,N-diethyl-4-methoxy-1-benzofuran-6-carboxamide, demonstrated a good binding affinity to APRT and ADL targets, no expected toxicity, and potential for oral route administration. This study indicates that the compound may have antileishmanial activity, which was granted in vitro and in vivo experiments to settle this finding in the future. Full article
(This article belongs to the Special Issue Bioinformatics On the Quest for New Antileishmanial Drugs)
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13 pages, 1337 KiB  
Article
Infection of Leishmania donovani in Phlebotomus orientalis Sand Flies at Different Microhabitats of a Kala-Azar Endemic Village in Eastern Sudan
by Altayeb Khogali, Dia-Eldin A. Elnaiem, Ramón Díaz-Regañón, Tayseer Jibreel, Bakri Y. M. Nour, Samira Hamid Abdelrahman, Ricardo Molina and Maribel Jiménez
Trop. Med. Infect. Dis. 2024, 9(2), 40; https://doi.org/10.3390/tropicalmed9020040 - 02 Feb 2024
Viewed by 1483
Abstract
A study was carried out to compare the infection rates of Leishmania donovani in Phlebotomus orientalis sandflies at different microhabitats of a VL endemic village in Gedarif state, Sudan. DNA extracts of 1078 P. orientalis sand fly females sampled by CDC light traps [...] Read more.
A study was carried out to compare the infection rates of Leishmania donovani in Phlebotomus orientalis sandflies at different microhabitats of a VL endemic village in Gedarif state, Sudan. DNA extracts of 1078 P. orientalis sand fly females sampled by CDC light traps from indoor, outdoor, peri-domestic, and sylvatic sites, in three transmission seasons, March–June 2016–18, in Helat-Belo village, were subjected to independent PCR amplifications targeting Leishmania kDNA and the cpb gene followed by ITS1 region sequencing. Leishmania kDNA was detected in 1.4% of the 1078 P. orientalis females captured in the area. Two of these specimens showed a characteristic 741 bp band of L. donovani after cpb gene amplification. The DNA sequence of the ITS1 region of the parasites matched the ITS1 L. donovani genotype F. There were no signficant differences between rates of infection of L. donovani in P. orientalis captured at different sites. Blood meals found in infected flies origninated from human (5 specimens), cattle (4 specimens) and donkey (2 specimens). The finding of fresh cow and donkey blood in the infected flies suggests the possible role of these animals in the zoopotentiation and/or zooprophylaxis against VL. The study provides important information for VL transmission models and control programs in East Africa. Full article
(This article belongs to the Special Issue Emerging Topics in Leishmaniasis Research)
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20 pages, 6773 KiB  
Review
Mitochondrial Cytochrome bc1 Complex as Validated Drug Target: A Structural Perspective
by Lothar Esser and Di Xia
Trop. Med. Infect. Dis. 2024, 9(2), 39; https://doi.org/10.3390/tropicalmed9020039 - 01 Feb 2024
Viewed by 1460
Abstract
Mitochondrial respiratory chain Complex III, also known as cytochrome bc1 complex or cyt bc1, is a validated target not only for antibiotics but also for pesticides and anti-parasitic drugs. Although significant progress has been made in understanding the mechanisms of [...] Read more.
Mitochondrial respiratory chain Complex III, also known as cytochrome bc1 complex or cyt bc1, is a validated target not only for antibiotics but also for pesticides and anti-parasitic drugs. Although significant progress has been made in understanding the mechanisms of cyt bc1 function and inhibition by using various natural and synthetic compounds, important issues remain in overcoming drug resistance in agriculture and in evading cytotoxicity in medicine. In this review, we look at these issues from a structural perspective. After a brief description of the essential and common structural features, we point out the differences among various cyt bc1 complexes of different organisms, whose structures have been determined to atomic resolution. We use a few examples of cyt bc1 structures determined via bound inhibitors to illustrate both conformational changes observed and implications to the Q-cycle mechanism of cyt bc1 function. These structures not only offer views of atomic interactions between cyt bc1 complexes and inhibitors, but they also provide explanations for drug resistance when structural details are coupled to sequence changes. Examples are provided for exploiting structural differences in evolutionarily conserved enzymes to develop antifungal drugs for selectivity enhancement, which offer a unique perspective on differential interactions that can be exploited to overcome cytotoxicity in treating human infections. Full article
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22 pages, 2300 KiB  
Systematic Review
Molecular Prevalence and Subtypes Distribution of Blastocystis spp. in Humans of Latin America: A Systematic Review
by Carmine Fusaro, Jaime E. Bernal, Rosa Baldiris-Ávila, Rafael González-Cuello, Julio Cisneros-Lorduy, Arley Reales-Ruiz, Raimundo Castro-Orozco and Yohanna Sarria-Guzmán
Trop. Med. Infect. Dis. 2024, 9(2), 38; https://doi.org/10.3390/tropicalmed9020038 - 01 Feb 2024
Viewed by 1437
Abstract
Blastocystis spp. are among the few enteric parasites with a prevalence that can reach up to approximately 80% in communities of developing countries. This systematic review updates and summarizes available literature on the molecular prevalence and subtype distribution of Blastocystis spp. in Latin [...] Read more.
Blastocystis spp. are among the few enteric parasites with a prevalence that can reach up to approximately 80% in communities of developing countries. This systematic review updates and summarizes available literature on the molecular prevalence and subtype distribution of Blastocystis spp. in Latin American people. This work follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The literature revised covers from 1 January 2015 to 6 October 2023 in seven different scientific databases, and the material was selected through inclusion and exclusion criteria. According to data found in the 36 selected articles, the prevalence of Blastocystis spp. in Latin America ranged between 5.8% (Bolivian rural communities) and 94.0% (Colombian general public). Generally, genomic DNA was extracted from approximately 200 mg fecal sediments using commercial kits, such as the QIAamp Stool Mini Kit (QIAGEN, Hilden, Germany) or the Norgen Stool DNA Isolation Kit (Norgen Biotek Corporation, Thorold, ON, Canada). Subtype-specific primers (such as the couple of primers BhRDr–RD5) developed from unique sequences of the SSU rRNA gene were applied to Blastocystis subtyping. Ten specific subtypes (STs) were found as well as various mixed infections, and the most circulating Blastocystis STs were in the order ST3, ST1, ST2, and ST4. The most recent data about Blastocystis spp. molecular epidemiology and the STs in communities of Latin America are limited to studies from specific countries. Novel scientific data from the other countries are required to obtain a complete picture and truly understand the distribution and prevalence of Blastocystis spp. and the STs. Full article
(This article belongs to the Section Neglected and Emerging Tropical Diseases)
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12 pages, 394 KiB  
Article
Risk Screening Tools Could Potentially Miss HIV-Positive Individuals Who Seek Testing Services: A Secondary Program Data Analysis on the Performance Characteristics of an Adolescent and Adult HIV Risk Screening Tool in Uganda
by Marvin Lubega, Katherine Guerra, Megan Ginivan, Yewande Kamuntu, George Senyama, Andrew Musoke, Fiona Gambanga, Shaukat Khan, Geoffrey Taasi, Sylivia Nalubega and John Bosco Junior Matovu
Trop. Med. Infect. Dis. 2024, 9(2), 37; https://doi.org/10.3390/tropicalmed9020037 - 01 Feb 2024
Viewed by 1224
Abstract
Improving HIV testing efficiency saves financial and material resources for health. We conducted a secondary data analysis of routinely collected HIV risk-screening program data in Uganda, from October to November 2019, to determine the performance characteristics of the adolescent and adult HIV risk [...] Read more.
Improving HIV testing efficiency saves financial and material resources for health. We conducted a secondary data analysis of routinely collected HIV risk-screening program data in Uganda, from October to November 2019, to determine the performance characteristics of the adolescent and adult HIV risk screening tools in public health facilities. A total of 19,854 clients had been screened for HIV testing eligibility and tested for HIV. The overall positivity rate (cluster-weighted prevalence of HIV) among those screened was 4.5% (95% CI: 4.1–4.8) versus 3.71% (95% CI: 3.06–4.50) among those not screened. The sensitivity and specificity of the risk screening tool were 91% (95% CI: 89–93) and 25% (24.2–26), respectively. With screening, the number needed to test to identify one PLHIV was reduced from 27 to 22. Although risk screening would have led to a 24.5% (4825/19,704) reduction in testing volume, 9.3% (68/732) of PLHIV would have been missed and be misclassified as not eligible for testing. The cost saving per PLHIV identified was minimally reduced by 3% from USD 69 without screening to USD 66.9 with screening. Since the treatment-adjusted prevalence of HIV is dropping globally, overzealous use of risk screening tools to determine who to test or not carries the potential of missing PLHIV due to their limited specificity. We recommend the use of scientifically validated HIV risk screening tools, and a need to explore the use of HIV self-testing as a test for tirage to minimize misclassification of people who seek HIV testing services. Full article
(This article belongs to the Special Issue HIV Testing, Prevention and Care Interventions)
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19 pages, 854 KiB  
Review
Cystic Echinococcosis in the Early 2020s: A Review
by Mihai-Octav Hogea, Bogdan-Florin Ciomaga, Mădălina-Maria Muntean, Andrei-Alexandru Muntean, Mircea Ioan Popa and Gabriela Loredana Popa
Trop. Med. Infect. Dis. 2024, 9(2), 36; https://doi.org/10.3390/tropicalmed9020036 - 31 Jan 2024
Cited by 1 | Viewed by 1536
Abstract
Cystic echinococcosis (CE) is a zoonosis caused by metacestodes, the larval stage of Echinococcus granulosus. Although the World Health Organization (WHO) has defined CE as a neglected disease, it is the second most important foodborne parasitic disease, and it remains an important public [...] Read more.
Cystic echinococcosis (CE) is a zoonosis caused by metacestodes, the larval stage of Echinococcus granulosus. Although the World Health Organization (WHO) has defined CE as a neglected disease, it is the second most important foodborne parasitic disease, and it remains an important public health issue, considering its zonal endemicity and potential morbidity. The control and prevention of CE is a relevant WHO target, especially from a One Health perspective, as the disease affects not only animals and humans but also the food chain. Since not all countries have a CE surveillance strategy or reporting system and specific management guidelines, recent epidemiological data are relatively scarce, and research concerning the specific geographical distribution of the disease is ongoing. To add new information to the subject, we have analyzed and collected data from national guidelines and several medical databases. Out of the 751 research articles that were originally identified, only 52 were included in the investigation after applying specific inclusion and exclusion criteria. Notable international projects that have provided significant contributions and had a positive impact are presented. The available data were correlated with WHO recommendations on the subject, thus showcasing the measures taken and those that are still needed to properly control the disease’s spread. Full article
(This article belongs to the Section Neglected and Emerging Tropical Diseases)
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13 pages, 4724 KiB  
Article
Anthelmintic Effect of Cannabidiol against Echinococcus granulosus sensu stricto
by Clara María Albani, Giselle Fuentes, Cristina Lujan Ramírez, Patricia Eugenia Pensel, Florencia Gatti, Adriana Albanese, Diego Nutter, Matías Ezequiel Aguirre, Yésica Dolores Di Iorio and María Celina Elissondo
Trop. Med. Infect. Dis. 2024, 9(2), 35; https://doi.org/10.3390/tropicalmed9020035 - 31 Jan 2024
Viewed by 1362
Abstract
Cystic echinococcosis is a global parasitic zoonosis caused by infection with the larval stage of Echinococcus granulosus sensu lato. Cystic echinococcosis affects more than 1 million people worldwide, causing important economic costs in terms of management and livestock associated losses. Albendazole is the [...] Read more.
Cystic echinococcosis is a global parasitic zoonosis caused by infection with the larval stage of Echinococcus granulosus sensu lato. Cystic echinococcosis affects more than 1 million people worldwide, causing important economic costs in terms of management and livestock associated losses. Albendazole is the main drug used in treating human cystic echinococcosis. In spite of this, its low aqueous solubility, poor absorption, and consequently erratic bioavailability are the cause of its chemotherapeutic failures. Based on the described problem, new treatment alternatives urgently need to be developed. The aim of the present research was to study the in vitro and in vivo efficacy of cannabidiol (CBD), the second most abundant component of the Cannabis sativa plant, was demonstrated against E. granulosus sensu stricto. CBD (50 µg/mL) caused a decrease in protoscoleces viability of 80 % after 24 h of treatment which was consistent with the observed tegumental alterations. Detachment of the germinal layer was observed in 50 ± 10% of cysts treated with 50 µg/mL of CBD during 24 h. In the clinical efficacy study, all treatments reduced the weight of cysts recovered from mice compared with the control group. However, this reduction was only significant with ABZ suspension and the CBD + ABZ combination. As we could observe by the SEM study, the co-administration of CBD with ABZ suspension caused greater ultrastructural alteration of the germinal layer in comparison with that provoked with the monotherapy. Further in vivo research will be conducted by changing the dose and frequency of CBD and CBD + ABZ treatments and new available CBD delivery systems will also be assayed to improve bioavailability in vivo. Full article
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10 pages, 551 KiB  
Article
The Yield of Active Tuberculosis Disease and Latent Tuberculosis Infection in Tuberculosis Household Contacts Investigated Using Chest X-ray in Yogyakarta Province, Indonesia
by Betty Nababan, Rina Triasih, Geoffrey Chan, Bintari Dwihardiani, Arif Hidayat, Setyogati C. Dewi, Lana Unwanah, Arif Mustofa and Philipp du Cros
Trop. Med. Infect. Dis. 2024, 9(2), 34; https://doi.org/10.3390/tropicalmed9020034 - 31 Jan 2024
Viewed by 1401
Abstract
In Indonesia, the implementation of tuberculosis (TB) contact investigation is limited, with low detection rates. We report the yield of and risk factors for TB disease and infection for household contacts (HHCs) investigated using chest X-ray (CXR) screening. We identified HHCs aged five [...] Read more.
In Indonesia, the implementation of tuberculosis (TB) contact investigation is limited, with low detection rates. We report the yield of and risk factors for TB disease and infection for household contacts (HHCs) investigated using chest X-ray (CXR) screening. We identified HHCs aged five years and above of bacteriologically confirmed index cases from 2018 to 2022 in Yogyakarta City and Kulon Progo. All HHCs were offered screening for TB symptoms; TB infection testing with either tuberculin skin testing or interferon gamma release assay; and referral for CXR. Sputum from those with symptoms or CXR suggestive of TB was tested with Xpert MTB/RIF. Risk factors for active TB disease and latent TB infection (LTBI) were identified by logistic regression models. We screened 2857 HHCs for TB between June 2020 and December 2022, with 68 (2.4%) diagnosed with active TB. Of 2621 HHCs eligible for LTBI investigation, 1083 (45.7%) were diagnosed with LTBI. The factors associated with active TB were age, being underweight, diabetes mellitus, urban living, and sleeping in the same house as an index case. Factors associated with LTBI were increasing age and male gender. Conclusions: Screening for HHC including CXR and TST/IGRA yielded a moderate prevalence of TB disease and infection. Full article
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13 pages, 777 KiB  
Article
Surveillance of Soil-Transmitted Helminth Infection in Preschool Child Population: Do Changes in Behavior and Immunological Responses Affect Prevalence?
by Riyadi Adrizain, Monika Verena Nagari, Hadyana Sukandar, Afiat Berbudi, Djatnika Setiabudi and Budi Setiabudiawan
Trop. Med. Infect. Dis. 2024, 9(2), 33; https://doi.org/10.3390/tropicalmed9020033 - 30 Jan 2024
Viewed by 1474
Abstract
Soil-transmitted helminths (STHs) persist as a significant global public health issue among neglected tropical diseases (NTDs), particularly in children. STH infection can induce immune responses that affect the course of the disease; if treatment fails, chronic infection can lead to stunting, especially among [...] Read more.
Soil-transmitted helminths (STHs) persist as a significant global public health issue among neglected tropical diseases (NTDs), particularly in children. STH infection can induce immune responses that affect the course of the disease; if treatment fails, chronic infection can lead to stunting, especially among children aged 24–59 months, which is a vulnerable period for growth and development. We conducted a correlational, cross-sectional data collection study to evaluate the characteristics and association of 25(OH)D, interleukin-5 (IL-5), and interleukin-13 (IL-13) with the prevalence of STH infection in children aged 24–59 months in Bandung District, Indonesia, in October 2019–January 2023. We recruited 694 subjects (401 stunted and 293 normal-height children). The prevalence of STH infection among the stunted and normal-height groups was 5.7% (95% CI: 3.85–8.46%) and 3.4% (95% CI; 1.86–6.17%) (p = 0.156), respectively. The probability of the prevalence of STH infection in children with levels of 25(OH)D, IL-5, and IL-13 below the cut-off point was 6,93 to 16.71 times higher. We found a relationship between IL-5, IL-13, and environmental factors and the prevalence of STH infection in stunted children. Full article
(This article belongs to the Special Issue Community Engagement and Neglected Tropical Diseases (NTDs))
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18 pages, 5139 KiB  
Article
The Spatiotemporal Distribution and Molecular Characterization of Circulating Dengue Virus Serotypes/Genotypes in Senegal from 2019 to 2023
by Idrissa Dieng, Cheikh Talla, Mamadou Aliou Barry, Aboubacry Gaye, Diamilatou Balde, Mignane Ndiaye, Mouhamed Kane, Samba Niang Sagne, Moussa Moise Diagne, Boly Diop, Boubacar Diallo, Amadou Alpha Sall, Ousmane Faye, Abdourahmane Sow, Gamou Fall, Cheikh Loucoubar and Oumar Faye
Trop. Med. Infect. Dis. 2024, 9(2), 32; https://doi.org/10.3390/tropicalmed9020032 - 27 Jan 2024
Viewed by 1339
Abstract
Dengue virus is becoming a major public health threat worldwide, principally in Africa. From 2016 to 2020, 23 outbreaks were reported in Africa, principally in West Africa. In Senegal, dengue outbreaks have been reported yearly since 2017. Data about the circulating serotypes and [...] Read more.
Dengue virus is becoming a major public health threat worldwide, principally in Africa. From 2016 to 2020, 23 outbreaks were reported in Africa, principally in West Africa. In Senegal, dengue outbreaks have been reported yearly since 2017. Data about the circulating serotypes and their spatial and temporal distribution were limited to outbreaks that occurred between 2017 and 2018. Herein, we describe up-to-date molecular surveillance of circulating DENV serotypes in Senegal between 2019 to 2023 and their temporal and spatial distribution around the country. For this purpose, suspected DENV-positive samples were collected and subjected to dengue detection and serotyping using RT-qPCR methods. Positive samples were used for temporal and spatial mapping. A subset of DENV+ samples were then sequenced and subjected to phylogenetic analysis. Results show a co-circulation of three DENV serotypes with an overall predominance of DENV-3. In terms of abundance, DENV-3 is followed by DENV-1, with scarce cases of DENV-2 from February 2019 to February 2022. Interestingly, data show the extinction of both serotype 1 and serotype 2 and the only circulation of DENV-3 from March 2022 to February 2023. At the genotype level, the analysis shows that sequenced strains belong to same genotype as previously described: Senegalese DENV-1 strains belong to genotype V, DENV-2 strains to the cosmopolitan genotype, and DENV-3 strains to Genotype III. Interestingly, newly obtained DENV 1–3 sequences clustered in different clades within genotypes. This co-circulation of strains belonging to different clades could have an effect on virus epidemiology and transmission dynamics. Overall, our results highlight DENV serotype replacement by DENV-3, accompanied by a wider geographic distribution, in Senegal. These results highlight the importance of virus genomic surveillance and call for further viral fitness studies using both in vitro and in vivo models, as well as in-depth phylogeographic studies to uncover the virus dispersal patterns across the country. Full article
(This article belongs to the Section Vector-Borne Diseases)
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20 pages, 1360 KiB  
Review
Antibiotic Prescribing in Dental Medicine—Best Practices for Successful Implementation
by Oana Săndulescu, Liliana Lucia Preoțescu, Adrian Streinu-Cercel, Gülşen Özkaya Şahin and Mihai Săndulescu
Trop. Med. Infect. Dis. 2024, 9(2), 31; https://doi.org/10.3390/tropicalmed9020031 - 26 Jan 2024
Viewed by 1685
Abstract
With rising rates of antimicrobial resistance throughout the world, it is time to revisit antibiotic prescribing policies and practices, and dentistry is an important area for focused intervention, as it accounts for up to 15% of all antimicrobial prescriptions. In this narrative review, [...] Read more.
With rising rates of antimicrobial resistance throughout the world, it is time to revisit antibiotic prescribing policies and practices, and dentistry is an important area for focused intervention, as it accounts for up to 15% of all antimicrobial prescriptions. In this narrative review, we have analyzed the current state of the knowledge, attitudes, and practice regarding antimicrobial use among dental professionals, and we have identified a set of seven recurring themes that drive inappropriate antibiotic prescribing in dental medicine. These include: 1. Prescribing antibiotics to delay or avoid dental treatment. 2. Overlooking the 5Ds—dental treatment (source control), dental condition (indication), drug (antibiotic choice), dose, and duration. 3. Relying on education from the distant past and on previous experience. 4. The heterogeneity of (too many) guideline recommendations leads to confusion and over-prescribing. 5. Decreased access to guideline information in private practice. 6. Psychological factors such as pressure to prescribe, comfort prescribing and the weekend effect, and 7. Feeling removed from antimicrobial resistance and externalizing responsibility. Based on the existing knowledge, we propose a framework based on four key pillars for focused intervention: 1. Education. 2. Internalizing responsibility. 3. Recognizing recurring counter-productive practices, and 4. Addressing recurring counter-productive practices. This framework can be applied in different dental settings to ensure best practices for the successful implementation of rational antimicrobial prescribing. Full article
(This article belongs to the Special Issue Unravelling Antimicrobial Resistance in Our Environment)
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17 pages, 3579 KiB  
Article
In Vitro and Ex Vivo Synergistic Effect of Pyrvinium Pamoate Combined with Miltefosine and Paromomycin against Leishmania
by Estela Melcón-Fernández, Giulio Galli, Rafael Balaña-Fouce, Nerea García-Fernández, María Martínez-Valladares, Rosa M. Reguera, Carlos García-Estrada and Yolanda Pérez-Pertejo
Trop. Med. Infect. Dis. 2024, 9(2), 30; https://doi.org/10.3390/tropicalmed9020030 - 25 Jan 2024
Viewed by 1671
Abstract
One of the major drawbacks of current treatments for neglected tropical diseases is the low safety of the drugs used and the emergence of resistance. Leishmaniasis is a group of neglected diseases caused by protozoa of the trypanosomatidae family that lacks preventive vaccines [...] Read more.
One of the major drawbacks of current treatments for neglected tropical diseases is the low safety of the drugs used and the emergence of resistance. Leishmaniasis is a group of neglected diseases caused by protozoa of the trypanosomatidae family that lacks preventive vaccines and whose pharmacological treatments are scarce and unsafe. Combination therapy is a strategy that could solve the above-mentioned problems, due to the participation of several mechanisms of action and the reduction in the amount of drug necessary to obtain the therapeutic effect. In addition, this approach also increases the odds of finding an effective drug following the repurposing strategy. From the previous screening of two collections of repositioning drugs, we found that pyrvinium pamoate had a potent leishmanicidal effect. For this reason, we decided to combine it separately with two clinically used leishmanicidal drugs, miltefosine and paromomycin. These combinations were tested in axenic amastigotes of Leishmania infantum obtained from bone marrow cells and in intramacrophagic amastigotes obtained from primary cultures of splenic cells, both cell types coming from experimentally infected mice. Some of the combinations showed synergistic behavior, especially in the case of the combination of pyrvinium pamoate with paromomycin, and exhibited low cytotoxicity and good tolerability on intestinal murine organoids, which reveal the potential of these combinations for the treatment of leishmaniasis. Full article
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10 pages, 221 KiB  
Article
The Challenges of Tuberculosis Management beyond Professional Competence: Insights from Tuberculosis Outbreaks among Ethiopian Immigrants in Israel
by Hashem Bishara, Daniel Weiler-Ravell, Amer Saffouri and Manfred Green
Trop. Med. Infect. Dis. 2024, 9(2), 29; https://doi.org/10.3390/tropicalmed9020029 - 24 Jan 2024
Viewed by 1372
Abstract
Controlling tuberculosis (TB) among immigrants from high-incidence countries presents a public health concern as well as a medical challenge. In this article, we investigate a TB outbreak in a community of people of Jewish descent who emigrated from Ethiopia to Israel (Israeli Ethiopians) [...] Read more.
Controlling tuberculosis (TB) among immigrants from high-incidence countries presents a public health concern as well as a medical challenge. In this article, we investigate a TB outbreak in a community of people of Jewish descent who emigrated from Ethiopia to Israel (Israeli Ethiopians) that started in June 2022. The index case was a 20-year-old female who had recently immigrated to Israel with her family. Her pre-immigration tuberculin skin test was positive. After excluding active TB, treatment with daily isoniazid for latent TB (LTB) was started shortly after her arrival. A year later, she was diagnosed with smear-positive, culture-positive, pulmonary TB. Investigation of 83 contacts revealed five additional patients with active TB, and three of whom were members were of her household. In this article, we report the current TB outbreak, review previously published TB outbreaks involving Israeli Ethiopians, analyze the factors that triggered each of these outbreaks, and discuss the challenges that face the Israeli TB control program in an era of declining TB incidence and diminishing resources available for TB control. Full article
(This article belongs to the Special Issue Ending Tuberculosis Epidemic: Current Status and Future Prospects)
2 pages, 133 KiB  
Obituary
Remembering Professor Peter A. Leggat, AM, ADC (1961–2023)
by Colleen Lau and John Frean
Trop. Med. Infect. Dis. 2024, 9(2), 28; https://doi.org/10.3390/tropicalmed9020028 - 24 Jan 2024
Viewed by 1155
Abstract
Professor Peter Leggat, the Immediate Past President of the Australasian College of Tropical Medicine (ACTM), passed away peacefully in Brisbane on 20 September 2023 [...] Full article
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