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1.
Vet Med Sci ; 10(3): e1441, 2024 May.
Article in English | MEDLINE | ID: mdl-38613179

ABSTRACT

BACKGROUND: Coxiellosis is a neglected zoonosis for occupationally exposed people in many parts of the world. Sheep and goats are two important small ruminants that act as reservoirs for human contamination; however, there is a lack of comprehensive data on the epidemiological aspects of coxiellosis in sheep and goats at regional and global levels. The aim of this study was to systematically review the available articles on seroprevalence of coxiellosis in sheep and goats and estimate the overall seroprevalence in different regions. METHODS: A systematic search strategy was performed in five electronic repositories for articles published until December 2021. Relevant data were extracted from the selected articles based on the inclusion criteria. A random effect meta-analysis model was used to analyse the data. Results are presented as the prevalence of seropositivity as a percentage and 95% confidence intervals. RESULTS: The global pooled seroprevalence of coxiellosis in sheep was 17.38% (95% confidence interval [CI]: 15.59%-19.17%). Overall, the regional level pooled prevalence estimates in sheep ranged from 15.04% (95% CI: 7.68%-22.40%) to 19.14% (95% CI: 15.51%-22.77%), depending on region. The global pooled seroprevalence of coxiellosis in goats was 22.60% (95% CI: 19.54%-25.66%). Overall, the regional level pooled prevalence estimates in goats ranged from 6.33% (95% CI: 2.96%-9.71%) to 55.13% (95% CI: 49.61%-60.65%), depending on the region. The prevalence estimates also varied significantly in both sheep and goats depending on age, sex, and rearing systems of the animals (p < 0.001). CONCLUSION: Seroprevalence of coxiellosis in both sheep and goats is considerable. Routine monitoring of the sheep and goat populations is needed to prevent spillover infection in other livestock and humans.


Subject(s)
Goat Diseases , Sheep Diseases , Sheep , Humans , Animals , Seroepidemiologic Studies , Ruminants , Goats , Zoonoses/epidemiology , Livestock , Goat Diseases/epidemiology , Sheep Diseases/epidemiology
2.
BMJ Open ; 14(4): e079776, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38582533

ABSTRACT

BACKGROUND: The last 3 years have witnessed global health challenges, ranging from the pandemics of COVID-19 and mpox (monkeypox) to the Ebola epidemic in Uganda. Public health surveillance is critical for preventing these outbreaks, yet surveillance systems in resource-constrained contexts struggle to provide timely disease reporting. Although community health workers (CHWs) support health systems in low-income and middle-income countries (LMICs), very little has been written about their role in supporting public health surveillance. This review identified the roles, impacts and challenges CHWs face in public health surveillance in 25 LMICs. METHODS: We conducted a scoping review guided by Arksey and O'Malley's framework. We exported 1,156 peer-reviewed records from Embase, Global Health and PubMed databases. After multiple screenings, 29 articles were included in the final review. RESULTS: CHWs significantly contribute to public health surveillance in LMICs including through contact tracing and patient visitation to control major infectious diseases such as HIV/AIDS, malaria, tuberculosis, Ebola, neglected tropical diseases and COVID-19. Their public health surveillance roles typically fall into four main categories including community engagement; data gathering; screening, testing and treating; and health education and promotion. The use of CHWs in public health surveillance in LMICs has been impactful and often involves incorporation of various technologies leading to improved epidemic control and disease reporting. Nonetheless, use of CHWs can come with four main challenges including lack of education and training, lack of financial and other resources, logistical and infrastructural challenges as well as community engagement challenges. CONCLUSION: CHWs are important stakeholders in surveillance because they are closer to communities than other healthcare workers. Further integration and training of CHWs in public health surveillance would improve public health surveillance because CHWs can provide health data on 'hard-to-reach' populations. CHWs' work in public health surveillance would also be greatly enhanced by infrastructural investments.


Subject(s)
COVID-19 , Hemorrhagic Fever, Ebola , Humans , Developing Countries , Community Health Workers/education , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Public Health Surveillance , COVID-19/epidemiology , COVID-19/prevention & control
3.
Article in English | MEDLINE | ID: mdl-38597520

ABSTRACT

The worldwide monkeypox (mpox) outbreak in 2022 showed a high frequency of sexually transmitted infections (STI). A cross-sectional study was carried out using secondary data from the Brazilian official mpox surveillance systems. A total of 10,169 mpox cases were identified, with a median age of 32 years. Among them, 92.3% were male at birth and 57.5% were men who have sex with other men (MSM). Approximately 11% were diagnosed with STI, including 5.8% with syphilis and 2.5% with genital herpes. Individuals aged from 25 to 34 years, MSM, individuals with HIV-positive status, and those manifesting skin eruptions or penile edema were associated with STI. Laboratory investigation for mpox must be implemented as a priority in STI clinics (especially for MSM) to mitigate neglected cases, ensure appropriate treatments, and prevent misdiagnoses.


Subject(s)
Gonorrhea , HIV Infections , Monkeypox , Sexual and Gender Minorities , Sexually Transmitted Diseases , Adult , Humans , Male , Brazil/epidemiology , Cross-Sectional Studies , Demography , Disease Outbreaks , Gonorrhea/diagnosis , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/complications , Homosexuality, Male , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/epidemiology
4.
mBio ; : e0085924, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38639536

ABSTRACT

Visceral leishmaniasis is a deadly infectious disease and is one of the world's major neglected health problems. Because the symptoms of infection are similar to other endemic diseases, accurate diagnosis is crucial for appropriate treatment. Definitive diagnosis using splenic or bone marrow aspirates is highly invasive, and so, serological assays are preferred, including the direct agglutination test (DAT) or rK39 strip test. These tests, however, are either difficult to perform in the field (DAT) or lack specificity in some endemic regions (rK39), making the development of new tests a research priority. The availability of Leishmania spp. genomes presents an opportunity to identify new diagnostic targets. Here, we use genome data and a mammalian protein expression system to create a panel of 93 proteins consisting of the extracellular ectodomains of the Leishmania donovani cell surface and secreted proteins. We use these panel and sera from murine experimental infection models and natural human and canine infections to identify new candidates for serological diagnosis. We observed a concordance between the most immunoreactive antigens in different host species and transmission settings. The antigen encoded by the LdBPK_323600.1 gene can diagnose Leishmania infections with high sensitivity and specificity in patient cohorts from different endemic regions including Bangladesh and Ethiopia. In longitudinal sampling of treated patients, we observed reductions in immunoreactivity to LdBPK_323600.1 suggesting it could be used to diagnose treatment success. In summary, we have identified new antigens that could contribute to improved serological diagnostic tests to help control the impact of this deadly tropical infectious disease. IMPORTANCE: Visceral leishmaniasis is fatal if left untreated with patients often displaying mild and non-specific symptoms during the early stages of infection making accurate diagnosis important. Current methods for diagnosis require highly trained medical staff to perform highly invasive biopsies of the liver or bone marrow which pose risks to the patient. Less invasive molecular tests are available but can suffer from regional variations in their ability to accurately diagnose an infection. To identify new diagnostic markers of visceral leishmaniasis, we produced and tested a panel of 93 proteins identified from the genome of the parasite responsible for this disease. We found that the pattern of host antibody reactivity to these proteins was broadly consistent across naturally acquired infections in both human patients and dogs, as well as experimental rodent infections. We identified a new protein called LdBPK_323600.1 that could accurately diagnose visceral leishmaniasis infections in humans.

5.
Washington, D.C.; OPS; 2024-04-01. (PAHO/CDE/HT/23-0014).
in Spanish | PAHO-IRIS | ID: phr-59464

ABSTRACT

En los últimos años, la OPS ha estado colaborando con diferentes interesados directos —como especialistas en VLTH‑1, gerentes de programas de salud y personas con infección por el VLTH‑1— a fin de definir prioridades y delinear estrategias eficaces para hacer frente a esta infección desatendida. Una de las prioridades definidas por los interesados directos es la prevención de la transmisión maternoinfantil del VLTH‑1. Sin embargo, para que sea posible prevenir la transmisión vertical, las embarazadas con infección por el VLTH‑1 deben conocer su estado serológico respecto a esta infección. En la Región de las Américas, la cobertura del tamizaje del VLTH‑1 en donantes de sangre es alta, aunque el tamizaje prenatal sigue siendo limitado. Los países siguen encontrando obstáculos para implantar el uso de las pruebas de diagnóstico de la infección por el VLTH. No hay directrices internacionales para el diagnóstico de la infección por el VLTH‑1 y la orientación nacional puede variar de un país a otro. En este contexto, la OPS organizó un taller para debatir sobre el diagnóstico de la infección por el VLTH‑1, en particular en el contexto de la salud maternoinfantil. En la Región de las Américas se observa un interés cada vez mayor por el tamizaje prenatal de la infección por el VLTH‑1 y algunos países como Chile, Brasil, Santa Lucía y Colombia transmitieron su experiencia durante el taller. Entre las buenas prácticas figuran el programa para prevenir la transmisión maternoinfantil del VLTH‑1, integrado en la iniciativa ETMI Plus, en Santa Lucía; la estrecha colaboración entre la sociedad civil, expertos en la infección por el VLTH‑1 y responsables de las políticas en Brasil; iniciativas para aumentar la concientización sobre la infección por el VLTH‑1 en la Región; y la elaboración de directrices clínicas sobre la infección por el VLTH por distintos países de la Región. Se determinaron diversas prioridades, como aumentar la concientización acerca de la infección por el VLTH, elaborar directrices y capacitación de apoyo para los profesionales de la salud, fortalecer la colaboración entre países y promover la inclusión de la infección por el VLTH en los programas de eliminación.


Subject(s)
Human T-lymphotropic virus 1 , Maternal and Child Health , Infectious Disease Transmission, Vertical , Neglected Diseases
6.
Washington, D.C.; PAHO; 2024-04-01. (PAHO/CDE/HT/23-0014).
in English | PAHO-IRIS | ID: phr-59463

ABSTRACT

In recent years, PAHO has been engaging with different stakeholders, including HTLV‑1 specialists, health managers and people living with HTLV-1 to define priorities and to delineate effective strategies to tackle this neglected infection. One of the priorities identified by stakeholders is the prevention of HTLV-1 mother-to-child transmission. However, to be able to prevent vertical transmission, pregnant women living with HTLV-1 must be aware of their status. The coverage of HTLV-1 screening of blood donors is high in the region, but antenatal screening is still limited. Countries still face barriers to implement diagnostic tests for HTLV. There are no international guidelines for HTLV-1 diagnostics and national guidance may vary between countries. In this context, PAHO promoted a workshop to discuss the diagnosis of HTLV-1 infection, particularly in the context of maternal and child health. Increased interest on HTLV-1 antenatal screening has been observed in the region and countries such as Chile, Brazil, Saint Lucia and Colombia shared their experience during the workshop. Good practices included the program to prevent HTLV-1 mother-to-child transmission, that is integrated with the EMTCT Plus initiative in Saint Lucia, strong collaboration between civil society, HTLV-1 experts and policy-makers in Brazil, initiatives to increase awareness about HTLV-1, and the construction of HTLV clinical guidelines by different countries in the Region. Priorities identified include increasing awareness about HTLV, developing guidelines and support training of health-care workers, strengthening the collaboration between countries, and promoting the inclusion of HTLV into elimination programs.


Subject(s)
Human T-lymphotropic virus 1 , Maternal and Child Health , Infectious Disease Transmission, Vertical , Neglected Diseases
7.
Article in Chinese | MEDLINE | ID: mdl-38604680

ABSTRACT

Tropical diseases, notably neglected tropical diseases and infectious diseases of poverty, remain major health problems endangering the poorest and most-marginalized people in the world. The Special Programme for Research and Training in Tropical Diseases (TDR), which is co-sponsored by the World Health Organization, the United Nations Children's Fund (UNICEF), the United Nations Development Programme (UNDP) and the World Bank, is an important programme that helps facilitate, support, guide and coordinate global efforts to combat tropical diseases. On July 2023, TDR formally issued its 2024-2029 strategy, which proposed the direction and proprieties of global tropical disease prevention and control in the next six years. Based on its original focus on supporting researchers and research institutions from low and middle-income countries to conduct research on tropical diseases and building their research capabilities, this strategy proposed some new developments, which mainly included incorporating tropical disease prevention and control into the overall framework of addressing major global health challenges and achieving the health goals set by the United Nations Sustainable Development Goals (SDGs) to combat tropical diseases and contribute to achieving health goals of SDGs in a collaborative and integrated manner; supporting implementation research and encouraging practitioners and social innovators to participate in research to enable generation of solutions that may be used to solve local health problems; promoting and encouraging the One Health concept and interdisciplinary and cross-departmental collaboration; shifting gradually its focus from disease prevention and control to addressing the health needs of the poorest and most-marginalized populations. These new developments deserve the attention of personnel and institutions in China dedicated to the prevention and control of tropical diseases in order to help their future researches and activities.


Subject(s)
Communicable Diseases , One Health , Child , Humans , Global Health , World Health Organization , Poverty
8.
Eur J Med Chem ; 271: 116396, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38643671

ABSTRACT

Neglected tropical diseases (NTDs) comprise diverse infections with more incidence in tropical/sub-tropical areas. In spite of preventive and therapeutic achievements, NTDs are yet serious threats to the public health. Epidemiological reports of world health organization (WHO) indicate that more than 1.5 billion people are afflicted with at least one NTD type. Among NTDs, leishmaniasis, chagas disease (CD) and human African trypanosomiasis (HAT) result in substantial morbidity and death, particularly within impoverished countries. The statistical facts call for robust efforts to manage the NTDs. Currently, most of the anti-NTD drugs are engaged with drug resistance, lack of efficient vaccines, limited spectrum of pharmacological effect and adverse reactions. To circumvent the issue, numerous scientific efforts have been directed to the synthesis and pharmacological development of chemical compounds as anti-infectious agents. A survey of the anti-NTD agents reveals that the majority of them possess privileged nitrogen, sulfur and oxygen-based heterocyclic structures. In this review, recent achievements in anti-infective small molecules against parasitic NTDs are described, particularly from the SAR (Structure activity relationship) perspective. We also explore current advocating strategies to extend the scope of anti-NTD agents.

9.
PLoS One ; 19(4): e0301414, 2024.
Article in English | MEDLINE | ID: mdl-38578773

ABSTRACT

The prioritization of research topics in the health domain is a critical step toward channelling efforts and resources into areas that have received less attention. The objective of this study is to evaluate the implementation of research priorities determined at the national level within Iran for the period spanning five years between 2009 and 2013. We extracted the required data from the Iranian Registry of Clinical Trials (IRCT) website. Then we conducted a matching process between the titles of trials registered in the IRCT until December 3rd, 2013, and the list of national health research priorities in the domains of communicable and non-communicable diseases. The latter was compiled and regulated by the Research and Technology Deputy of the Ministry of Health since 2008. Out of the total 5,049 clinical trials registered in IRCT, 92.3% were carried out within the domain of non-communicable diseases, while 6.1% pertained to the field of communicable diseases and the remaining 1.3% in other fields. 56.4% of the clinical trials conducted in the field of communicable diseases and 32.8% of those conducted in the field of non-communicable diseases were consistent with the research priorities determined in these two fields. During the five-year period of the prioritization goal, there was no significant improvement in adherence to the list of priorities compared to the previous five-year period. Furthermore, certain priorities were neglected within both areas during these periods. It is possible to evaluate the effectiveness of research prioritization using the data obtained from the registration centers of clinical trials. Our study has revealed that the list of priorities has not garnered adequate attention from the research community within the country. Hence, remedial measures are imperative to ensure the priorities are given more attention after publication.


Subject(s)
Communicable Diseases , Noncommunicable Diseases , Humans , Iran , Goals , Routinely Collected Health Data , Registries
10.
Indian J Ophthalmol ; 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38454868

ABSTRACT

Neglected tropical diseases (NTDs) encompass a group of approximately 20 diseases prevalent in tropical and subtropical regions, closely associated with poverty, affecting over a billion people in low-income countries. This manuscript aims to explore the ocular manifestations and burden of two significant NTDs, namely Hansen's disease and trachoma while addressing gaps in understanding and management. Hansen's disease, caused by Mycobacterium leprae, has a long history and presents with diverse neurological and ocular manifestations. Despite the availability of treatment, ocular complications persist, leading to significant visual impairment in some cases. The manuscript emphasizes the importance of early diagnosis, regular ophthalmic examinations, and follow-ups to prevent and control ocular complications, reducing the burden of visual impairment and blindness. Trachoma, caused by Chlamydia trachomatis, remains the leading infectious cause of blindness in underdeveloped and remote areas. The manuscript highlights the clinical diagnosis and implementation of the World Health Organization's (WHO's) SAFE (surgery, antibiotics, facial hygiene, and environmental sanitation) strategy to prevent transmission and associated blindness. However, challenges in health surveillance tools and underreporting of trachoma cases are addressed, emphasizing the need for improved strategies to combat the disease effectively. Through a comprehensive review of the ocular manifestations and management of Hansen's disease and trachoma, this manuscript contributes to the existing knowledge base and enhances a deeper understanding of these NTDs. Addressing gaps in understanding and management emphasizes the importance of implementing WHO's strategies and collaborative efforts to achieve the global goal of reducing the burden of NTDs and improving community health and well-being. The manuscript underscores the significance of early intervention, preventive measures, and technological advancements, providing valuable insights for policymakers, healthcare professionals, and researchers working in the field of NTDs.

11.
Br J Biomed Sci ; 81: 12366, 2024.
Article in English | MEDLINE | ID: mdl-38434675

ABSTRACT

The concept of One Health has been developed as the appreciation that human health is intricately connected to those of other animals and the environment that they inhabit. In recent years, the COVID-19 pandemic and noticeable effects of climate change have encouraged national and international cooperation to apply One Health strategies to address key issues of health and welfare. The United Nations (UN) Sustainable Development Goals have established targets for health and wellbeing, clean water and sanitation, climate action, as well as sustainability in marine and terrestrial ecosystems. The One Health Quadripartite comprises the World Health Organization (WHO), the World Organization for Animal Health (WOAH-formerly OIE), the United Nations Food and Agriculture Organization (FAO) and the United Nations Environment Programme (UNEP). There are six areas of focus which are Laboratory services, Control of zoonotic diseases, Neglected tropical diseases, Antimicrobial resistance, Food safety and Environmental health. This article discusses the concept of One Health by considering examples of infectious diseases and environmental issues under each of those six headings. Biomedical Scientists, Clinical Scientists and their colleagues working in diagnostic and research laboratories have a key role to play in applying the One Health approach to key areas of healthcare in the 21st Century.


Subject(s)
COVID-19 , One Health , Animals , Humans , Ecosystem , Pandemics/prevention & control , COVID-19/epidemiology
12.
Exp Parasitol ; 260: 108747, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38518969

ABSTRACT

Leishmaniasis are neglected infectious diseases caused by kinetoplastid protozoan parasites from the genus Leishmania. These sicknesses are present mainly in tropical regions and almost 1 million new cases are reported each year. The absence of vaccines, as well as the high cost, toxicity or resistance to the current drugs determines the necessity of new treatments against these pathologies. In this review, several compounds with potentialities as new antileishmanial drugs are presented. The discussion is restricted to the preclinical level and molecules are organized according to their chemical nature, source and molecular targets. In this manner, we present antimicrobial peptides, flavonoids, withanolides, 8-aminoquinolines, compounds from Leish-Box, pyrazolopyrimidines, and inhibitors of tubulin polymerization/depolymerization, topoisomerase IB, proteases, pteridine reductase, N-myristoyltransferase, as well as enzymes involved in polyamine metabolism, response against oxidative stress, signaling pathways, and sterol biosynthesis. This work is a contribution to the general knowledge of these compounds as antileishmanial agents.

13.
J Clin Virol ; 171: 105662, 2024 04.
Article in English | MEDLINE | ID: mdl-38432097

ABSTRACT

Monkeypox virus (MPXV) is responsible for causing a zoonotic disease called monkeypox (mpox), which sporadically infects humans in West and Central Africa. It first infected humans in 1970 and, along with the variola virus, belongs to the genus Orthopoxvirus in the poxvirus family. Since the World Health Organization declared the MPXV outbreak a "Public Health Emergency of International Concern" on July 23, 2022, the number of infected patients has increased dramatically. To control this epidemic and address this previously neglected disease, MPXV needs to be better understood and reevaluated. In this review, we cover recent research on MPXV, including its genomic and pathogenic characteristics, transmission, mutations and mechanisms, clinical characteristics, epidemiology, laboratory diagnosis, and treatment measures, as well as prevention of MPXV infection in light of the 2022 and 2023 global outbreaks. The 2022 MPXV outbreak has been primarily associated with close intimate contact, including sexual activity, with most cases diagnosed among men who have sex with men. The incubation period of MPXV infection usually lasts from 6 to 13 days, and symptoms include fever, muscle pains, headache, swollen lymph nodes, and a characteristic painful rash, including several stages, such as macules, papules, blisters, pustules, scabs, and scab shedding involving the genitals and anus. Polymerase chain reaction (PCR) is usually used to detect MPXV in skin lesion material. Treatment includes supportive care, antivirals, and intravenous vaccinia immune globulin. Smallpox vaccines have been designed with four givens emergency approval for use against MPXV infection.


Subject(s)
Monkeypox , Sexual and Gender Minorities , Male , Animals , Humans , Monkeypox/diagnosis , Monkeypox/drug therapy , Monkeypox/epidemiology , Monkeypox virus/genetics , Homosexuality, Male , Zoonoses
14.
Adv Parasitol ; 123: 51-123, 2024.
Article in English | MEDLINE | ID: mdl-38448148

ABSTRACT

The ascarids are a large group of parasitic nematodes that infect a wide range of animal species. In humans, they cause neglected diseases of poverty; many animal parasites also cause zoonotic infections in people. Control measures include hygiene and anthelmintic treatments, but they are not always appropriate or effective and this creates a continuing need to search for better ways to reduce the human, welfare and economic costs of these infections. To this end, Le Studium Institute of Advanced Studies organized a two-day conference to identify major gaps in our understanding of ascarid parasites with a view to setting research priorities that would allow for improved control. The participants identified several key areas for future focus, comprising of advances in genomic analysis and the use of model organisms, especially Caenorhabditis elegans, a more thorough appreciation of the complexity of host-parasite (and parasite-parasite) communications, a search for novel anthelmintic drugs and the development of effective vaccines. The participants agreed to try and maintain informal links in the future that could form the basis for collaborative projects, and to co-operate to organize future meetings and workshops to promote ascarid research.


Subject(s)
Anthelmintics , Zoonoses , Animals , Humans , Zoonoses/prevention & control , Caenorhabditis elegans , Academies and Institutes , Research , Anthelmintics/therapeutic use
15.
Am J Trop Med Hyg ; 110(4): 633-638, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38471147

ABSTRACT

Leishmaniases are a group of diseases under the category of neglected tropical diseases targeted for global elimination. However, they continue to pose major clinical and public health problems, especially among those living in poor socioeconomic conditions. Here, we summarize leishmaniasis elimination efforts in Bhutan. Between 1994 and 2022, Bhutan recorded 54 cases of leishmaniasis across 14 of its 20 districts. There are seven species of Phlebotomus and three species of Sergentomyia sand flies documented in the country. At a subnational level, all endemic districts recorded a visceral leishmaniasis annual incidence <1 per 10,000 population, meeting the regional elimination targets. Serological testing with ELISA and molecular testing with polymerase chain reaction were established at the Royal Center for Disease Control in 2022. A leishmaniasis prevention and management guideline was adopted in 2023 to aid clinicians in diagnosis and management. Active and passive case surveillance was integrated with the national infectious disease early warning and response system. Risk-based entomological surveillance and control have also been prioritized. Climate change may play a major role in rendering districts in the temperate zone favorable for vector proliferation. The country's medical university introduced a diploma course in medical entomology in 2023 to augment the human resources needed for vector surveillance efforts. However, leishmaniasis elimination lacks dedicated programmatic management amid competing priorities for resources against other infectious diseases. Leishmaniasis elimination requires a targeted and programmatic approach in Bhutan, including cross-border collaborative efforts with neighboring Indian states. Bhutan remains highly committed to achieving leishmaniasis elimination targets.


Subject(s)
Leishmaniasis, Visceral , Leishmaniasis , Phlebotomus , Psychodidae , Animals , Humans , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/prevention & control , Bhutan/epidemiology , Leishmaniasis/epidemiology , Leishmaniasis/prevention & control , Asia, Southern
16.
Bioorg Chem ; 146: 107302, 2024 May.
Article in English | MEDLINE | ID: mdl-38521010

ABSTRACT

Leishmaniasis, a group of neglected infectious diseases, encompasses a serious health concern, particularly with visceral leishmaniasis exhibiting potentially fatal outcomes. Nucleoside hydrolase (NH) has a fundamental role in the purine salvage pathway, crucial for Leishmania donovani survival, and presents a promising target for developing new drugs for visceral leishmaniasis treatment. In this study, LdNH was immobilized into fused silica capillaries, resulting in immobilized enzyme reactors (IMERs). The LdNH-IMER activity was monitored on-flow in a multidimensional liquid chromatography system, with the IMER in the first dimension. A C18 analytical column in the second dimension furnished the rapid separation of the substrate (inosine) and product (hypoxanthine), enabling direct enzyme activity monitoring through product quantification. LdNH-IMER exhibited high stability and was characterized by determining the Michaelis-Menten constant. A known inhibitor (1-(ß-d-Ribofuranosyl)-4-quinolone derivative) was used as a model to validate the established method in inhibitor recognition. Screening of three additional derivatives of 1-(ß-d-Ribofuranosyl)-4-quinolone led to the discovery of novel inhibitors, with compound 2a exhibiting superior inhibitory activity (Ki = 23.37 ± 3.64 µmol/L) compared to the employed model inhibitor. Docking and Molecular Dynamics studies provided crucial insights into inhibitor interactions at the enzyme active site, offering valuable information for developing new LdNH inhibitors. Therefore, this study presents a novel screening assay and contributes to the development of potent LdNH inhibitors.


Subject(s)
Leishmania donovani , Leishmaniasis, Visceral , Humans , N-Glycosyl Hydrolases/metabolism , Chromatography, Affinity , 4-Quinolones
17.
PLoS Pathog ; 20(3): e1012012, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38457443

ABSTRACT

Small molecules (less than 1,500 Da) include major biological signals that mediate host-pathogen-microbiome communication. They also include key intermediates of metabolism and critical cellular building blocks. Pathogens present with unique nutritional needs that restrict pathogen colonization or promote tissue damage. In parallel, parts of host metabolism are responsive to immune signaling and regulated by immune cascades. These interactions can trigger both adaptive and maladaptive metabolic changes in the host, with microbiome-derived signals also contributing to disease progression. In turn, targeting pathogen metabolic needs or maladaptive host metabolic changes is an important strategy to develop new treatments for infectious diseases. Trypanosoma cruzi is a single-celled eukaryotic pathogen and the causative agent of Chagas disease, a neglected tropical disease associated with cardiac and intestinal dysfunction. Here, we discuss the role of small molecules during T. cruzi infection in its vector and in the mammalian host. We integrate these findings to build a theoretical interpretation of how maladaptive metabolic changes drive Chagas disease and extrapolate on how these findings can guide drug development.


Subject(s)
Chagas Disease , Microbiota , Trypanosoma cruzi , Animals , Humans , Gene-Environment Interaction , Chagas Disease/metabolism , Trypanosoma cruzi/metabolism , Disease Progression , Mammals
18.
BMJ Case Rep ; 17(3)2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38458767

ABSTRACT

Eumycetoma, a subcutaneous infection caused by various fungi with pathognomonic discharging grain, is rarely reported in Malaysia. This case concerns a eumycetoma infection in an immunocompetent man who presented with progressive left foot swelling complicated with pustules, sinuses and pale grain discharge for the past year after recurrent thorn pricks. Histological findings of the grain and tissue showed foci of septate fungal hyphae. Tissue culture yielded no growth. Amplification and sequencing of the rDNA internal transcribed spacer 1 (ITS1), ITS4 and large subunit regions of the tissue identified the causative agent as Fusarium falciforme, highlighting the role of molecular diagnostic method in identifying fungal species in eumycetoma. The patient was treated with surgical excision and oral itraconazole with excellent improvement. However, he presented again with recurrence after defaulting therapy. F. falciforme has been implicated in causing diseases in crops and sea turtles. Therefore, the One Health approach should be adopted to manage this emerging species.


Subject(s)
Fusarium , Mycetoma , Male , Humans , Mycetoma/diagnosis , Mycetoma/drug therapy , Neglected Diseases , Itraconazole/therapeutic use
19.
Int Microbiol ; 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38502456

ABSTRACT

Antibiotics are commonly used to treat infectious diseases; however, persistence is often expressed by the pathogenic bacteria and their long-term relative effect on the host have been neglected. The present study investigated the impact of antibiotics in gut microbiota (GM) and metabolism of host. The effect of ampicillin antibiotics on GM of Drosophila melanogaster was analyzed through deep sequencing of 16S rRNA amplicon gene. The dominant phyla consisted of Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, Planctomycetes, Chloroflexi, Euryarchaeota, Acedobacteria, Verrucomicrobia, and Cyanobacteria. It was found that the composition of GM was significantly altered on administration of antibiotics. On antibiotic treatments, there were decline in relative abundance of Proteobacteria and Firmicutes, while there were increase in relative abundance of Chlorophyta and Bacteroidota. High abundance of 14 genera, viz., Wolbachia, Lactobacillus, Bacillus, Pseudomonas, Thiolamprovum, Pseudoalteromonas, Vibrio, Romboutsia, Staphylococcus, Alteromonas, Clostridium, Lysinibacillus, Litoricola, and Cellulophaga were significant (p ≤ 0.05) upon antibiotic treatment. Particularly, the abundance of Acetobacter was significantly (p ≤ 0.05) declined but increased for Wolbachia. Further, a significant (p ≤ 0.05) increase in Wolbachia endosymbiont of D. melanogaster, Wolbachia endosymbiont of Curculio okumai, and Wolbachia pipientis and a decrease in the Acinetobacter sp. were observed. We observed an increase in functional capacity for biosynthesis of certain nucleotides and the enzyme activities. Further, the decrease in antimicrobial peptide production in the treated group and potential effects on the host's defense mechanisms were observed. This study helps shed light on an often-overlooked dimension, namely the persistence of antibiotics' effects on the host.

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