A bioassay method validation framework for laboratory and semi-field tests used to evaluate vector control tools
Agnes Matope, Rosemary S. Lees, Angus Spiers
et al.
Abstract Vector control interventions play a fundamental role in the control and elimination of vector-borne diseases. The evaluation of vector control products relies on bioassays, laboratory and semi-field tests using live insects to assess the product’s effectiveness. Bioassay method development requires a rigorous validation process to ensure that relevant methods are used to capture appropriate entomological endpoints which accurately and precisely describe likely efficacy against disease vectors as well as product characteristics within the manufacturing tolerance ranges for insecticide content specified by the World Health Organization. Currently, there are no standardized guidelines for bioassay method validation in vector control. This report presents a framework for bioassay validation that draws on accepted validation processes from the chemical and healthcare fields and which can be applied for evaluating bioassays and semi-field tests in vector control. The validation process has been categorized into four stages: preliminary development; feasibility experiments; internal validation, and external validation. A properly validated method combined with an appropriate experimental design and data analyses that account for both the variability of the method and the product is needed to generate reliable estimates of product efficacy to ensure that at-risk communities have timely access to safe and reliable vector control products.
Arctic medicine. Tropical medicine, Infectious and parasitic diseases
A systematic review of neglected tropical diseases (NTDs) in Myanmar.
Myo Maung Maung Swe, Aung Pyae Phyo, Ben S Cooper
et al.
<h4>Background</h4>Neglected tropical diseases (NTDs) affect most impoverished communities in developing countries, like Myanmar in Southeast Asia. NTDs have been understudied and underreported in Myanmar.<h4>Methods</h4>A systematic review of published and grey literature (1900-2023) on neglected tropical diseases (NTDs) in Myanmar was conducted. The literature search included five international databases: PubMed, EMBASE, Ovid Global Health, and Web of Science Core Collection and one national database: the Myanmar Central Biomedical Library (locally published papers and grey literature). The selection criteria included articles with all types of study designs of current or previous infections conducted in humans, that reported NTDs, recognised by WHO, US CDC, and listed in PLoS NTDs. We included melioidosis and rickettsioses which we consider also meet the definition of an NTD.<h4>Results</h4>A total of 5941 records were retrieved and screened, of which, 672 (11%) met the selection criteria and were included in this review. Of the included articles, 449 (65%) were published after 2000 and 369 (55%) were from two regions (Yangon and Mandalay) of Myanmar. Of the included articles, 238 (35%) reported bacterial NTDs, 212 (32%) viral NTDs, 153 (23%) helminth NTDs, 25 (4%) protozoal NTDs and 39 (6%) reported more than one aetiology. Based on reported frequency in descending order, the bacterial NTDs were leprosy, Escherichia coli enteritis, salmonellosis, cholera, shigellosis, melioidosis, leptospirosis and rickettsioses; the viral NTDs were dengue, chikungunya and Japanese encephalitis virus (JEV) infection; the protozoal NTDs were amoebiasis, giardiasis and leishmaniasis, and the helminth NTDs were ascariasis, trichuriasis, hookworm disease, filariasis and strongyloidiasis.<h4>Conclusion</h4>This review summarises NTDs reported in Myanmar over the past 100 years. The findings suggest that most NTDs are likely to be under reported, especially from the majority of the country which is far from academic centres. Research capacity building together with strengthening of laboratory systems would lead to better understanding of the true burden of NTDs in Myanmar.<h4>Trial registration</h4>PROSPERO registration ID: CRD42018092627.
Arctic medicine. Tropical medicine, Public aspects of medicine
The Importance of Exercising Caution When Comparing Results from Malaria Vaccines Administered on the EPI Schedule and on a Seasonal Schedule
A. Birkett, R. Miller, L. Soisson
We are writing in response to Phil Rosenthal’s article “Malaria in 2022: Challenges and Progress,” which was published recently in the American Journal of Tropical Medicine and Hygiene. In that article, Dr. Rosenthal states that “new data on the R21 vaccine, which is also based on CSP [circumsporozoite protein] antigens, with preventive efficacy 75% in African children, [was] considerably greater than that seen in RTS,S trials.” Although the data published by the University of Oxford and partners on the Phase 2 results of their trial in Burkina Faso did demonstrate high levels of efficacy, the data cannot be reliably compared with Phase 3 trial results for RTS,S/AS01 (RTS,S). The R21/Matrix-M (R21) Phase 2 trial was conducted at one center in one country only. The study reported vaccine efficacy of 77% (95% CI: 66–84) in Nanoro, Burkina Faso, over 12-months of follow-up. The study was performed in a highly seasonal transmission setting, with vaccination coordinated to ensure peak immunity at the time of peak risk (so-called seasonal vaccination); peak risk occurred during the first 6 months of follow-up, followed by the low transmission dry season, with only a single clinical case observed in the control arm between days 200 and 300 of follow-up. It is therefore most appropriate to express these data as efficacy over one season and/or 6 months to align with the period of risk. Additional data, in settings of perennial transmission or over multiple seasons in regions of highly seasonal transmission, are needed to determine appropriately the efficacy of this vaccine candidate over longer follow-up periods and to enable more meaningful comparison to the RTS,S Phase 3 data. The RTS,S Phase 3 trial was conducted at 11 centers across seven countries, including regions of both seasonal and perennial transmission. Aligned with the EPI schedule for dosing based on child age, the RTS,S vaccine delivery was not optimized to achieve peak immunity during the high transmission setting, nor do 6-month data occur during highest force of infection. The vaccine efficacy against clinical malaria, over 6 months of follow-up, across all 11 sites, was 68% (95% CI: 64–72); at the same Nanoro site, the vaccine efficacy was 72% (95% CI: 60–80). Direct comparisons of relatively short-acting vaccines or monoclonal antibodies employing different delivery strategies should be avoided, and hence the data available to date do not support the superiority of one vaccine over another. We look forward to learning more about the longer-term follow-up from the promising R21 Phase 2 trial and from the ongoing Phase 3 trial, which will provide more definitive information about the vaccine candidate’s efficacy, durability, and safety in a significantly larger population and across multiple malaria transmission settings. The availability of additional malaria vaccines, complementing RTS,S, could be highly beneficial to comprehensive malaria control efforts.
Diagnostic Performance of Three rK39 Rapid Diagnostic Tests and Two Direct Agglutination Tests for the Diagnosis of Visceral Leishmaniasis in Southern Iran
Z. Rezaei, B. Pourabbas, Vera Kühne
et al.
To evaluate the diagnostic performance of five alternative serodiagnostic tests, serum samples from 100 confirmed visceral leishmaniasis (VL) patients, 197 healthy endemic individuals, and 58 non-VL patients living in southern Iran were compared. The VL patients were defined as individuals with a positive result of the immunofluorescent antibody test (IFAT), having clinical signs and symptoms and appropriate response to treatment. The index tests were two direct agglutination tests, DAT-ITM (Institute of Tropical Medicine, Antwerp, Belgium) and DAT-KIT (Royal Tropical Institute, Amsterdam, The Netherlands), and three rapid diagnostic tests (RDTs), Kalazar Detect (InBios International Inc., USA), IT Leish (Bio-Rad, catalog 710124), and Leishmania test (Cypress Diagnostic Company, Belgium). Sensitivities of DAT-ITM and DAT-KIT were low, respectively, 56% and 59%, while specificities were acceptable, respectively, 98% and 93%. Observed sensitivities and specificities of RDTs were higher (71%, 81%, 70% and 99%, 99%, 98% for Kalazar Detect, IT Leish, and Leishmania test, respectively). Even with a maximum sensitivity of 81%, RDTs missed almost one-fifth of VL patients that were positive in IFAT. We conclude that RDTs in VL patients do not possess adequate performance in southern Iran and require some improvement, but they can still be helpful in the diagnosis and screening of the disease in this region due to their high specificity and speed.
World Dengue Day: A call for action
Nattachai Srisawat, Usa Thisyakorn, Zulkifli Ismail
et al.
Commemorating the 2021 ASEAN Dengue Day and advocacy for World Dengue Day, the International Society for Neglected Tropical Diseases (ISNTD) and Asian Dengue Voice and Action (ADVA) Group jointly hosted the ISNTD-ADVA World Dengue Day Forum–Cross Sector Synergies in June 2021. The forum aimed to achieve international and multisectoral coordination to consolidate global dengue control and prevention efforts, share best practices and resources, and improve global preparedness. The forum featured experts around the world who shared their insight, research experience, and strategies to tackle the growing threat of dengue. Over 2,000 healthcare care professionals, researchers, epidemiologists, and policy makers from 59 countries attended the forum, highlighting the urgency for integrated, multisectoral collaboration between health, environment, education, and policy to continue the march against dengue. Sustained vector control, environmental management, surveillance improved case management, continuous vaccine advocacy and research, capacity building, political commitment, and community engagement are crucial components of dengue control. A coordinated strategy based on science, transparency, timely and credible communication, and understanding of human behavior is needed to overcome vaccine hesitancy, a major health risk further magnified by the COVID-19 pandemic. The forum announced a strong call to action to establish World Dengue Day to improve global awareness, share best practices, and prioritize preparedness in the fight against dengue. Author summary The growing threat of dengue poses a significant public health burden endangering the well-being and socioeconomic development of many countries across the world. The International Society for Neglected Tropical Diseases (ISNTD) and Asian Dengue Voice and Action (ADVA) group brought together the collaborative efforts of healthcare care professionals, researchers, epidemiologists, environmentalists, and policy makers to coordinate international dengue control strategy. A strong call to action to establish a World Dengue Day was announced to improve global awareness, share best practices, and prioritize preparedness in the fight against dengue. The World Dengue Day highlighted the need for all governments, healthcare professionals, civil societies, public and private sectors, schools and universities, and citizens in dengue-endemic countries to form a strong coalition to encourage and accelerate a collective dengue control response.
Arctic medicine. Tropical medicine, Public aspects of medicine
Imported cases of 2019-novel coronavirus (2019-nCoV) infections in Thailand: Mathematical modelling of the outbreak
P. Sookaromdee, V. Wiwanitkit
Imported cases of 2019-novel coronavirus (2019-nCoV) infections in Thailand: Mathematical modelling of the outbreak Pathum Sookaromdee, Viroj Wiwanitkit TWS Medical Center, Bangkok, Thailand Department of Community Medicine, Dr DY Patil University, Pune, India Hainan Medical University, Haikou, China Chulalongkorn University, Bangkok, Thailand Outbreak of a new emerging disease is usually an important consideration in medicine and public health. In December 2019, a new emerging disease started in China and becomes the global concern in early January 2020[1,2]. The disease, 2019-novel coronavirus (2019-nCoV) infection, already existed outside China and the importation of disease is the cause of emerging 2019-nCoV infections in new settings. Thailand, a tropical country in Indochina, is the first country that reported the first 2019-nCoV infection outside China. Until the present (31 January 2020), the number of cases is 29 and still increasing. An interesting issue in dealing with the new disease outbreak is nature of disease spreading. The use of medical mathematical modelling technique can help clinical epidemiologist better understand the situation of outbreak[3]. Focusing on the situation of imported emerging disease, the specific knowledge on the disease epidemic is limited. Here, the authors use clinical mathematical modelling technique for explaining the disease outbreak of imported cases of 2019-nCoV infection in Thailand. The available data on imported cases of outbreak during the first month of outbreak (January 2020) of imported cases in Thailand are analyzed. The time function mathematical model was applied. First, the local data on number of imported cases of 2019-nCoV infections from Thai Center of Disease Control are collected for further study. The accelerate rate of disease spreading is calculated. The definition of accelerate rate is “accelerate rate = velocity/time”, which herby written as A = V/T (or V = AT). Then, the integration was applied for prediction of accumulate imported cases of 2019nCoV infections (I). The final equation based on the integration model can be written as I = 2AT + AT + C where C is a constant. Based on the available data (Figure 1), the acceleration rate of disease spreading is equal to 0.42 case/day[4]. From integration modelling, the final model is derived as “0.84T + 0.42T + C where C is constant.” This model can help better understand the nature of imported emerging disease and useful for planning for disease control and management.
Global Health in Medical Education: A Call for More Training and Opportunities
P. Drain, A. Primack, D. Hunt
et al.
Antineoplastic kinase inhibitors: A new class of potent anti-amoebic compounds.
Conall Sauvey, Gretchen Ehrenkaufer, Da Shi
et al.
Entamoeba histolytica is a protozoan parasite which infects approximately 50 million people worldwide, resulting in an estimated 70,000 deaths every year. Since the 1960s E. histolytica infection has been successfully treated with metronidazole. However, drawbacks to metronidazole therapy exist, including adverse effects, a long treatment course, and the need for an additional drug to prevent cyst-mediated transmission. E. histolytica possesses a kinome with approximately 300-400 members, some of which have been previously studied as potential targets for the development of amoebicidal drug candidates. However, while these efforts have uncovered novel potent inhibitors of E. histolytica kinases, none have resulted in approved drugs. In this study we took the alternative approach of testing a set of twelve previously FDA-approved antineoplastic kinase inhibitors against E. histolytica trophozoites in vitro. This resulted in the identification of dasatinib, bosutinib, and ibrutinib as amoebicidal agents at low-micromolar concentrations. Next, we utilized a recently developed computational tool to identify twelve additional drugs with human protein target profiles similar to the three initial hits. Testing of these additional twelve drugs led to the identification of ponatinib, neratinib, and olmutinib were identified as highly potent, with EC50 values in the sub-micromolar range. All of these six drugs were found to kill E. histolytica trophozoites as rapidly as metronidazole. Furthermore, ibrutinib was found to kill the transmissible cyst stage of the model organism E. invadens. Ibrutinib thus possesses both amoebicidal and cysticidal properties, in contrast to all drugs used in the current therapeutic strategy. These findings together reveal antineoplastic kinase inhibitors as a highly promising class of potent drugs against this widespread and devastating disease.
Arctic medicine. Tropical medicine, Public aspects of medicine
From informed consent to adherence: factors influencing involvement in mass drug administration with ivermectin for malaria elimination in The Gambia
Alexandra Fehr, Claudia Nieto-Sanchez, Joan Muela
et al.
Abstract Background The World Health Organization (WHO) recommends consideration of mass drug administration (MDA) for malaria control in low-endemic settings approaching elimination. However, MDA remains a controversial strategy, as multiple individual, social, and operational factors have shown to affect its acceptability at local levels. This is further complicated by inconsistent definitions of key indicators derived from individual and community involvement—coverage, adherence, and compliance—that cast doubts about the actual and potential epidemiological impact of MDA on disease control and elimination. This study aimed to identify limitations and enabling factors impacting involvement at different stages of a large cluster-randomized trial assessing the effect of combining dihydroartemisinin-piperaquine (DP) and ivermectin (IVM) in malaria transmission in The Gambia. Methods This social science study used a mixed-methods approach. Qualitative data were collected in intervention and control villages through ethnographic methods, including in-depth interviews (IDIs), focus group discussions (FGDs), and participant observation conducted with trial participants and decliners, community leaders, and field staff. A cross-sectional survey was conducted in the intervention villages after the first year of MDA. Both strands of the study explored malaria knowledge and opinions, social dynamics influencing decision-making, as well as perceived risks, burdens, and benefits associated with this MDA. Results 157 IDIs and 11 FGDs were conducted, and 864 respondents were included in the survey. Barriers and enabling factors to involvement were differentially influential at the various stages of the MDA. Issues of social influence, concerns regarding secondary effects of the medication, costs associated with malaria, and acceptability of the implementing organization, among other factors, differently affected the decision-making processes throughout the trial. Rather than a linear trajectory, involvement in this MDA trial was subjected to multiple revaluations from enrolment and consent to medicine intake and adherence to treatment. Conclusions This study went beyond the individual factors often associated with coverage and adherence, and found that nuanced social dynamics greatly influence the decision-making process at all phases of the trial. These issues need to be consider for MDA implementation strategies and inform discussions about more accurate ways of reporting on critical effectiveness indicators.
Arctic medicine. Tropical medicine, Infectious and parasitic diseases
Factors associated with soil-transmitted helminths infection in Benin: Findings from the DeWorm3 study.
Euripide F G A Avokpaho, Parfait Houngbégnon, Manfred Accrombessi
et al.
<h4>Background</h4>Despite several years of school-based MDA implementation, STH infections remain an important public health problem in Benin, with a country-wide prevalence of 20% in 2015. The DeWorm3 study is designed to assess the feasibility of using community-based MDA with albendazole to interrupt the transmission of STH, through a series of cluster-randomized trials in Benin, India and Malawi. We used the pre-treatment baseline survey data to describe and analyze the factors associated with STH infection in Comé, the study site of the DeWorm3 project in Benin. These data will improve understanding of the challenges that need to be addressed in order to eliminate STH as a public health problem in Benin.<h4>Methods</h4>Between March and April 2018, the prevalence of STH (hookworm spp., Ascaris and Trichuris trichiura) was assessed by Kato-Katz in stool samples collected from 6,153 residents in the community of Comé, Benin using a stratified random sampling procedure. A standardized survey questionnaire was used to collect information from individual households concerning factors potentially associated with the presence and intensity of STH infections in pre-school (PSAC, aged 1-4), school-aged children (SAC, aged 5-14) and adults (aged 15 and above). Multilevel mixed-effects models were used to assess associations between these factors and STH infection.<h4>Results</h4>The overall prevalence of STH infection was 5.3%; 3.2% hookworm spp., 2.1% Ascaris lumbricoides and 0.1% Trichuris. Hookworm spp. were more prevalent in adults than in SAC (4.4% versus 2.0%, respectively; p = 0.0001) and PSAC (4.4% versus 1.0%, respectively; p<0.0001), whilst Ascaris lumbricoides was more prevalent in SAC than in adults (3.0% versus 1.7%, respectively; p = 0.004). Being PSAC (adjusted Odds Ratio (aOR) = 0.2, p< 0.001; adjusted Infection Intensity Ratio (aIIR) = 0.1, p<0.001) or SAC (aOR = 0.5, p = 0.008; aIIR = 0.3, p = 0.01), being a female (aOR = 0.6, p = 0.004; aIIR = 0.3, p = 0.001), and having received deworming treatment the previous year (aOR = 0.4, p< 0.002; aIIR = 0.2, p<0.001) were associated with a lower prevalence and intensity of hookworm infection. Lower income (lowest quintile: aOR = 5.0, p<0.001, 2nd quintile aOR = 3.6, p = 0.001 and 3rd quintile aOR = 2.5, p = 0.02), being a farmer (aOR = 1.8, p = 0.02), medium population density (aOR = 2.6, p = 0.01), and open defecation (aOR = 0.5, p = 0.04) were associated with a higher prevalence of hookworm infection. Lower education-no education, primary or secondary school- (aIIR = 40.1, p = 0.01; aIIR = 30.9, p = 0.02; aIIR = 19.3, p = 0.04, respectively), farming (aIIR = 3.9, p = 0.002), natural flooring (aIIR = 0.2, p = 0.06), peri-urban settings (aIIR = 6.2, 95%CI 1.82-20.90, p = 0.003), and unimproved water source more than 30 minutes from the household (aIIR = 13.5, p = 0.02) were associated with a higher intensity of hookworm infection. Improved and unshared toilet was associated with lower intensity of hookworm infections (aIIR = 0.2, p = 0.01). SAC had a higher odds of Ascaris lumbricoides infection than adults (aOR = 2.0, p = 0.01) and females had a lower odds of infection (aOR = 0.5, p = 0.02).<h4>Conclusion</h4>Hookworm spp. are the most prevalent STH in Comé, with a persistent reservoir in adults that is not addressed by current control measures based on school MDA. Expanding MDA to target adults and PSAC is necessary to substantially impact population prevalence, particularly for hookworm.<h4>Trial registration</h4>ClinicalTrials.gov NCT03014167.
Arctic medicine. Tropical medicine, Public aspects of medicine
NTDs in the age of urbanization, climate change, and conflict: Karachi, Pakistan as a case study
O. Fazal, P. Hotez
1 Rice University, Houston, Texas, United States of America, 2 Departments of Pediatrics and Molecular Virology and Microbiology, Texas Children’s Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America, 3 Hagler Institute for Advanced Study at Texas A&M University, College Station, Texas, United States of America, 4 Department of Biology, Baylor University, Waco, Texas, United States of America, 5 James A Baker III Institute of Public Policy, Rice University, Houston, Texas, United States of America, 6 Scowcroft Institute of International Affairs, Bush School of Government and Public Service, Texas A&M University, College Station, Texas, United States of America
28 sitasi
en
Medicine, Geography
Bidens pilosa L. (Asteraceae): Botanical Properties, Traditional Uses, Phytochemistry, and Pharmacology
Arlene P. Bartolome, I. Villaseñor, Wen‐Chin Yang
There are 230 to 240 known Bidens species. Among them, Bidens pilosa is a representative perennial herb, globally distributed across temperate and tropical regions. B. pilosa has been traditionally used in foods and medicines without obvious adverse effects. Despite significant progress in phytochemical and biological analyses of B. pilosa over the past few years, comprehensive and critical reviews of this plant are anachronistic or relatively limited in scope. The present review aims to summarize up-to-date information on the phytochemistry, pharmacology, and toxicology of B. pilosa from the literature. In addition to botanical studies and records of the traditional use of B. pilosa in over 40 diseases, scientific studies investigating the potential medicinal uses of this species and its constituent phytochemicals for a variety of disorders are presented and discussed. The structure, bioactivity, and likely mechanisms of action of B. pilosa and its phytochemicals are emphasized. Although some progress has been made, further rigorous efforts are required to investigate the individual compounds isolated from B. pilosa to understand and validate its traditional uses and develop clinical applications. The present review provides preliminary information and gives guidance for further basic and clinical research into this plant.
250 sitasi
en
Biology, Medicine
Genus Spondias: A Phytochemical and Pharmacological Review
Salma Sameh, Eman Al‐Sayed, R. M. Labib
et al.
It is believed that many degenerative diseases are due to oxidative stress. In view of the limited drugs available for treating degenerative diseases, natural products represent a promising therapeutic strategy in the search for new and effective candidates for treating degenerative diseases. This review focuses on the genus Spondias which is widely used in traditional medicine for the treatment of many diseases. Spondias is a genus of flowering plants belonging to the cashew family (Anacardiaceae). This genus comprises 18 species distributed across tropical regions in the world. A variety of bioactive phytochemical constituents were isolated from different plants belonging to the genus Spondias. Diverse pharmacological activities were reported for the genus Spondias including cytotoxic, antioxidant, ulcer protective, hepatoprotective, anti-inflammatory, antiarthritic, and antidementia effects. These attributes indicate their potential to treat various degenerative diseases. The aim of this review is to draw attention to the unexplored potential of phytochemicals obtained from Spondias species, thereby contributing to the development of new therapeutic alternatives that may improve the health of people suffering from degenerative diseases and other health problems.
69 sitasi
en
Biology, Medicine
Utility of the Rose Bengal Test as a Point-of-Care Test for Human Brucellosis in Endemic African Settings: A Systematic Review
Abel B. Ekiri, Christopher Kilonzo, Brian H. Bird
et al.
In endemic African areas, such as Tanzania, Brucella spp. cause human febrile illnesses, which often go unrecognized and misdiagnosed, resulting in delayed diagnosis, underdiagnosis, and underreporting. Although rapid and affordable point-of-care tests, such as the Rose Bengal test (RBT), are available, acceptance and adoption of these tests at the national level are hindered by a lack of local diagnostic performance data. To address this need, evidence on the diagnostic performance of RBT as a human brucellosis point-of-care test was reviewed. The review was initially focused on studies conducted in Tanzania but was later extended to worldwide because few relevant studies from Tanzania were identified. Databases including Web of Science, Embase, MEDLINE, and World Health Organization Global Index Medicus were searched for studies assessing the diagnostic performance of RBT (sensitivity and specificity) for detection of human brucellosis, in comparison to the reference standard culture. Sixteen eligible studies were identified and reviewed following screening. The diagnostic sensitivity (DSe) and specificity (DSp) of RBT compared to culture as the gold standard were 87.5% and 100%, respectively, in studies that used suitable “true positive” and “true negative” patient comparison groups and were considered to be of high scientific quality. Diagnostic DSe and DSp of RBT compared to culture in studies that also used suitable “true positive” and “true negative” patient comparison groups but were considered to be of moderate scientific quality varied from 92.5% to 100% and 94.3 to 99.9%, respectively. The good diagnostic performance of RBT combined with its simplicity, quickness, and affordability makes RBT an ideal (or close to) stand-alone point-of-care test for early clinical diagnosis and management of human brucellosis and nonmalarial fevers in small and understaffed health facilities and laboratories in endemic areas in Africa and elsewhere.
Arctic medicine. Tropical medicine
Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections
M. Bakowski, C. McNamara
The intracellular bacteria now known as Wolbachia were first described in filarial worms in the 1970s, but the idea of Wolbachia being used as a macrofilaricidal target did not gain wide attention until the early 2000s, with research in filariae suggesting the requirement of worms for the endosymbiont. This new-found interest prompted the eventual organization of the Anti-Wolbachia Consortium (A-WOL) at the Liverpool School of Tropical Medicine, who, among others have been active in the field of antiwolbachial drug discovery to treat filarial infections. Clinical proof of concept studies using doxycycline demonstrated the utility of the antiwolbachial therapy, but efficacious treatments were of long duration and not safe for all infected. With the advance of robotics, automation, and high-speed computing, the search for superior antiwolbachials shifted away from smaller studies with a select number of antibiotics to high-throughput screening approaches, centered largely around cell-based phenotypic screens due to the rather limited knowledge about, and tools available to manipulate, this bacterium. A concomitant effort was put towards developing validation approaches and in vivo models supporting drug discovery efforts. In this review, we summarize the strategies behind and outcomes of recent large phenotypic screens published within the last 5 years, hit compound validation approaches and promising candidates with profiles superior to doxycycline, including ones positioned to advance into clinical trials for treatment of filarial worm infections.
30 sitasi
en
Medicine, Biology
Chromolaena odorata: A neglected weed with a wide spectrum of pharmacological activities (Review).
K. Vijayaraghavan, J. Rajkumar, S. N. Bukhari
et al.
75 sitasi
en
Medicine, Biology
A Review on Annona squamosa L.: Phytochemicals and Biological Activities.
Chengyao Ma, Ya-yun Chen, Jian-wei Chen
et al.
71 sitasi
en
Biology, Medicine
Scorpionism in Brazil: exponential growth of accidents and deaths from scorpion stings
Pasesa Pascuala Quispe Torrez, Flávio Santos Dourado, Rogério Bertani
et al.
Arctic medicine. Tropical medicine
Dynamics and monitoring of insecticide resistance in malaria vectors across mainland Tanzania from 1997 to 2017: a systematic review
Deokary Joseph Matiya, Anitha B. Philbert, Winifrida Kidima
et al.
Abstract Background Malaria still claims substantial lives of individuals in Tanzania. Insecticide-treated nets (ITNs) and indoor residual spray (IRS) are used as major malaria vector control tools. These tools are facing great challenges from the rapid escalating insecticide resistance in malaria vector populations. This review presents the information on the dynamics and monitoring of insecticide resistance in malaria vectors in mainland Tanzania since 1997. The information is important to policy-makers and other vector control stakeholders to reflect and formulate new resistance management plans in the country. Methods Reviewed articles on susceptibility and mechanisms of resistance in malaria vectors to insecticides across mainland Tanzania were systematically searched from the following databases: PubMed, Google scholar, HINARI and AGORA. The inclusion criteria were articles published between 2000 and 2017, reporting susceptibility of malaria vectors to insecticides, mechanisms of resistance in the mainland Tanzania, involving field collected adult mosquitoes, and mosquitoes raised from the field collected larvae. Exclusion criteria were articles reporting insecticide resistance in larval bio-assays, laboratory strains, and unpublished data. Reviewed information include year of study, malaria vectors, insecticides, and study sites. This information was entered in the excel sheet and analysed. Results A total of 30 articles met the selection criteria. The rapid increase of insecticide resistance in the malaria vectors across the country was reported since year 2006 onwards. Insecticide resistance in Anopheles gambiae sensu lato (s.l.) was detected in at least one compound in each class of all recommended insecticide classes. However, the Anopheles funestus s.l. is highly resistant to pyrethroids and DDT. Knockdown resistance (kdr) mechanism in An. gambiae s.l. is widely studied in the country. Biochemical resistance by detoxification enzymes (P450s, NSE and GSTs) in An. gambiae s.l. was also recorded. Numerous P450s genes associated with metabolic resistance were over transcribed in An. gambiae s.l. collected from agricultural areas. However, no study has reported mechanisms of insecticide resistance in the An. funestus s.l. in the country. Conclusion This review has shown the dynamics and monitoring of insecticide resistance in malaria vector populations across mainland Tanzanian. This highlights the need for devising improved control approaches of the malaria vectors in the country.
Arctic medicine. Tropical medicine, Infectious and parasitic diseases
Lippia javanica (Burm.f.) Spreng.: Traditional and Commercial Uses and Phytochemical and Pharmacological Significance in the African and Indian Subcontinent
A. Maroyi
Lippia javanica occurs naturally in central, eastern, and southern Africa and has also been recorded in the tropical Indian subcontinent. The potential of L. javanica as herbal or recreational tea and herbal medicine and its associated phytochemistry and biological properties are reviewed. The extensive literature survey revealed that L. javanica is used as herbal tea and has ethnomedicinal applications such as in colds, cough, fever, malaria, wounds, diarrhoea, chest pains, bronchitis, and asthma. Multiple classes of phytochemicals including volatile and nonvolatile secondary metabolites such as alkaloids, amino acids, flavonoids, iridoids, and triterpenes as well as several minerals have been identified from L. javanica. Scientific studies on L. javanica indicate that it has a wide range of pharmacological activities which include anticancer, antiamoebic, antidiabetic, antimalarial, antimicrobial, antioxidant, antiplasmodial, and pesticidal effects. Although many of the traditional uses of L. javanica have been validated by phytochemical and pharmacological studies, there are still some gaps where current knowledge could be improved. Lippia javanica is popular as both herbal and recreational tea, but there is need for more precise studies to evaluate the safety and clinical value of its main active crude and pure compounds and to clarify their mechanisms of action.