Functional diversity and bilobe targeting by the MORN Domain Proteins of Leishmania major

Leishmania is a protozoan parasite responsible for a spectrum of diseases known as leishmaniasis. The cell body of Leishmania consists of single copies of several organelles whose faithful duplication are crucial for survival. Previously, a novel cytoskeletal organelle called the bilobe was discovered while studying Golgi biogenesis in T. brucei. TbMORN1 became the first identified structural component of the bilobe with exclusive localization. TbMORN1 is composed of 15 MORN-repeats which may imply that the MORN-repeats are responsible for its bilobe targeting. Given that MORN proteins have only been characterized in T. brucei among the kinetoplastids, I chose to study the MORN proteins of L. major an important experimental model. 22 uncharacterized proteins were annotated to contain MORN-repeats in L. major, 14 of which share the feature of exclusively containing MORN-repeats ranging from 3-15 repeats, while the remaining 7 carry additional functional domains. The strategy was to express two apparently varied LmaMORNs (LmaMORN5 and LmaMORN6) from each other and from MORN1 in L. major promastigotes, screen them for bilobe localization and investigate their possible function. I showed that both LmaMORN5 and LmaMORN6 target the bilobe and the basal bodies while LmaMORN6 additionally stained the flagellum indicating flagellar function. These localizations were true even after detergent extraction, implying intimate associations with the bilobe and other cytoskeletal structures, hinting at a structural role. LmaMORN5 contained two compartmentalized regions along its sequence under selective pressure, shown to be secreted into the cytoplasm of infected macrophages and seemed to increased parasites infectivity six-fold, suggesting a possible role as a virulence factor. Thus, I reported for the first time two other MORN proteins (LmaMORN5 and LmaMORN6) in L. major that targets the bilobe in a manner similar to TbMORN1 in T. brucei, while each appear to display a differential functional role in the parasite’s biology

Efficacy of common laboratory disinfectants and heat on killing trypanosomatid parasites

The disinfectants TriGene, bleach, ethanol and liquid hand soap, and water and temperature were tested for their ability to kill bloodstream forms of Trypanosoma brucei, epimastigotes of Trypanosoma rangeli and promastigotes of Leishmania major. A 5-min exposure to 0.2% TriGene, 0.1% liquid hand soap and 0.05% bleach (0.05% NaOCl) killed all three trypanosomatids. Ethanol and water destroyed the parasites within 5 min at concentrations of 15-17.5% and 80-90%, respectively. All three organisms were also killed when treated for 5 min at 50 degrees C. The results indicate that the disinfectants, water and temperature treatment (i.e. autoclaving) are suitable laboratory hygiene measures against trypanosomatid parasites

Impact of educational intervention on knowledge and awareness of TB among secondary school students in The Gambia

Objectives: Health education and awareness campaigns about tuberculosis (TB) can empower adolescents on different aspects of the disease and its management, resulting in early and appropriate care seeking behavior through their advocacy in the community. We assessed the impact of educational intervention on knowledge and awareness about TB among adolescents in the greater Banjul area of The Gambia where approximately 70% of national TB cases are notified.Materials and Methods: A school-based, interventional analytical study, and interactive educational workshop was conducted among grade 12 students of the Methodist Academy Secondary School in Bakau, Banjul The Gambia. The workshop activities included illustrative demonstrations using posters, flipcharts, infographics, and games to convey TB messages in six domains: (1) Basic knowledge; (2) symptoms; (3) risk factors (4) modes of transmission; (5) treatment; and (6) care and support. Structured questionnaires were used to assess changes in the student’s knowledge and awareness about TB in the six domains before and after the workshop. Data were analyzed using proportional percentages, mean (95% CI) and differences standard error (SE) and student paired t-test.Results: Ninety-six students participated in the workshop out of which 92 (96%) students completed both pre- and post-test questionnaires. Sixty-eight percent of the students were females and 58% were from the science stream of the grade 12 students who participated in our workshop. The mean difference and SE between the pre- and post-workshop test scores in the six domains were: basic knowledge: +1.4 (0.2; P < 0.0001); symptoms: +1.5 (0.2; P < 0.0001); risk factors: +3.1 (0.3; P < 0.0001); modes of transmission: +1.2 (0.2; P < 0.0001); treatment: +0.8 (0.1; P < 0.0001); and care and support of TB: +0.5 (0.1; P = 0.0001).Conclusion: This school-based educational interactive workshop significantly improved the knowledge and awareness of the students especially in understanding the causative agent and risk factors of TB disease. We recommend exposure of students to TB educational activities as part of the school curriculum. The knowledge acquired in this workshop is likely to have impact on the wider community and should be assessed in future follow-up studies to determine if it impacts positively on views held within the wider community

Establishing and operating a 'virtual ward' system to provide care for patients with COVID-19 at home: experience from The Gambia.

Health systems in sub-Saharan Africa have remained overstretched from dealing with endemic diseases, which limit their capacity to absorb additional stress from new and emerging infectious diseases. Against this backdrop, the rapidly evolving COVID-19 pandemic presented an additional challenge of insufficient hospital beds and human resource for health needed to deliver hospital-based COVID-19 care. Emerging evidence from high-income countries suggests that a 'virtual ward' (VW) system can provide adequate home-based care for selected patients with COVID-19, thereby reducing the need for admissions and mitigate additional stress on hospital beds. We established a VW at the Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, a biomedical research institution located in The Gambia, a low-income west African country, to care for members of staff and their families infected with COVID-19. In this practice paper, we share our experience focusing on the key components of the system, how it was set up and successfully operated to support patients with COVID-19 in non-hospital settings. We describe the composition of the multidisciplinary team operating the VW, how we developed clinical standard operating procedures, how clinical oversight is provided and the use of teleconsultation and data capture systems to successfully drive the process. We demonstrate that using a VW to provide an additional level of support for patients with COVID-19 at home is feasible in a low-income country in sub-Saharan Africa. We believe that other low-income or resource-constrained settings can adopt and contextualise the processes described in this practice paper to provide additional support for patients with COVID-19 in non-hospital settings

Age-Dependent Maturation of Toll-Like Receptor-Mediated Cytokine Responses in Gambian Infants

The global burden of neonatal and infant mortality due to infection is staggering, particularly in resource-poor settings. Early childhood vaccination is one of the major interventions that can reduce this burden, but there are specific limitations to inducing effective immunity in early life, including impaired neonatal leukocyte production of Th1-polarizing cytokines to many stimuli. Characterizing the ontogeny of Toll-like receptor (TLR)-mediated innate immune responses in infants may shed light on susceptibility to infection in this vulnerable age group, and provide insights into TLR agonists as candidate adjuvants for improved neonatal vaccines. As little is known about the leukocyte responses of infants in resource-poor settings, we characterized production of Th1-, Th2-, and anti-inflammatory- cytokines in response to agonists of TLRs 1-9 in whole blood from 120 Gambian infants ranging from newborns (cord blood) to 12 months of age. Most of the TLR agonists induced TNFα, IL-1β, IL-6, and IL-10 in cord blood. The greatest TNFα responses were observed for TLR4, -5, and -8 agonists, the highest being the thiazoloquinoline CLO75 (TLR7/8) that also uniquely induced cord blood IFNγ production. For most agonists, TLR-mediated TNFα and IFNγ responses increased from birth to 1 month of age. TLR8 agonists also induced the greatest production of the Th1-polarizing cytokines TNFα and IFNγ throughout the first year of life, although the relative responses to the single TLR8 agonist and the combined TLR7/8 agonist changed with age. In contrast, IL-1β, IL-6, and IL-10 responses to most agonists were robust at birth and remained stable through 12 months of age. These observations provide fresh insights into the ontogeny of innate immunity in African children, and may inform development of age-specific adjuvanted vaccine formulations important for global health

Grain yield response of fonio (Digitaria exilis) varieties to fertilizer and cost- effectiveness under two different production systems in The Gambia

Fonio is an easy crop to grow because it grows well even on poor sandy soils, as well as in areas with low rainfall. The crop can withstand long dry spells during the production season which are becoming a common occurrence in the West African sub-region. In The Gambia, the common name for the crop is “Findi”. It is commonly grown in fields that were previously cultivated with groundnut. Fonio is one of the oldest cereal crops grown in the country; however, its cultivation has drastically declined to the extent that it is currently considered a minor crop in the country. Fonio is a very fast-growing crop and matures earlier than most cereals. Its ability to withstand dry spells and its high nutritive value makes it an ideal climate-smart crop. For this reason, there is renewed momentum in promoting the crop in the country. Despite these renewed efforts in its promotion, there still exists a huge gap in terms of information on improved production practices that could help uplift the existing low yields. Appropriate agronomic practices that can boost fonio productivity are not well documented at national level. To gather information on the input requirements and utilizations, adaptability and productivity of fonio in The Gambia, experiments were conducted in 2018 and 2019 with the aim of generating important production information that could guide efficient production and enhance productivity. Results obtained showed that fonio responded positively to application of fertilizer. Application of 100 kg ha -1 comprising half NPK (15-15-15) and half urea was sufficient to produce financially beneficial yields. Results also indicated that “Findiba”, which is a landrace may not be suitable for cultivation anymore due to its long growth period amidst the short and erratic nature of the rainfall. The Momo and the Momosato varieties which are of shorter durations and high-yielding are more suitable in the existing climatic conditions of the country

Differential in vitro activity of the DNA topoisomerase inhibitor idarubicin against Trypanosoma rangeli and Trypanosoma cruzi

In this study the effect of eight DNA topoisomerase inhibitors on the growth Trypanosoma rangeli epimastigotes in cell culture was investigated. Among the eight compounds tested, idarubicin was the only compound that displayed promising trypanocidal activity with a half-maximal growth inhibition (GI(50)) value in the sub-micromolar range. Fluorescence-activated cell sorting analysis showed a reduction in DNA content in T. rangeli epimastigotes when treated with idarubicin. In contrast to T. rangeli, against Trypanosoma cruzi epimastigotes idarubicin was much less effective exhibiting a GI(50) value in the mid-micromolar range. This result indicates that idarubicin displays differential toxic effects in T. rangeli and T. cruzi. Compared with African trypanosomes, it seems that American trypanosomes are generally less susceptible to DNA topoisomerase inhibitors