African animal trypanocide resistance: A systematic review and meta-analysis.

Background: African animal trypanocide resistance (AATr) continues to undermine global efforts to eliminate the transmission of African trypanosomiasis in endemic communities. The continued lack of new trypanocides has precipitated drug misuse and overuse, thus contributing to the development of the AATr phenotype. In this study, we investigated the threat associated with AATr by using the major globally available chemotherapeutical agents. Methods: A total of seven electronic databases were screened for an article on trypanocide resistance in AATr by using keywords on preclinical and clinical trials with the number of animals with treatment relapse, days taken to relapse, and resistant gene markers using the PRISMA checklist. Data were cleaned using the SR deduplicator and covidence and analyzed using Cochrane RevMan®. Dichotomous outputs were presented using risk ratio (RR), while continuous data were presented using the standardized mean difference (SMD) at a 95% confidence interval. Results: A total of eight publications in which diminazene aceturate (DA), isometamidium chloride (ISM), and homidium chloride/bromide (HB) were identified as the major trypanocides were used. In all preclinical studies, the development of resistance was in the order of HB > ISM > DA. DA vs. ISM (SMD = 0.15, 95% CI: -0.54, 0.83; I 2 = 46%, P = 0.05), DA vs. HB (SMD = 0.96, 95% CI: 0.47, 1.45; I 2 = 0%, P = 0.86), and HB vs. ISM (SMD = -0.41, 95% CI: -0.96, 0.14; I 2 = 5%, P = 0.38) showed multiple cross-resistance. Clinical studies also showed evidence of multi-drug resistance on DA and ISM (RR = 1.01, 95% CI: 0.71-1.43; I 2 = 46%, P = 0.16). To address resistance, most preclinical studies increased the dosage and the treatment time, and this failed to improve the patient's prognosis. Major markers of resistance explored include TbAT1, P1/P2 transporters, folate transporters, such as F-I, F-II, F-III, and polyamine biosynthesis inhibitors. In addition, immunosuppressed hosts favor the development of AATr. Conclusion: AATr is a threat that requires a shift in the current disease control strategies in most developing nations due to inter-species transmission. Multi-drug cross-resistance against the only accessible trypanocides is a major public health risk, justifying the need to revise the policy in developing countries to promote control of African trypanosomiasis.

Anxiety, Anger and Depression Amongst Low-Income Earners in Southwestern Uganda During the COVID-19 Total Lockdown.

Background: Low-income earners are particularly vulnerable to mental health, consequence of the coronavirus disease 2019 (COVID-19) lockdown restrictions, due to a temporary or permanent loss of income and livelihood, coupled with government-enforced measures of social distancing. This study evaluates the mental health status among low-income earners in southwestern Uganda during the first total COVID-19 lockdown in Uganda. Methods: A cross-sectional descriptive study was undertaken amongst earners whose income falls below the poverty threshold. Two hundred and fifty-three (n = 253) male and female low-income earners between the ages of 18 and 60 years of age were recruited to the study. Modified generalized anxiety disorder (GAD-7), Spielberger's State-Trait Anger Expression Inventory-2 (STAXI-2), and Beck Depression Inventory (BDI) tools as appropriate were used to assess anxiety, anger, and depression respectively among our respondents. Results: Severe anxiety (68.8%) followed by moderate depression (60.5%) and moderate anger (56.9%) were the most common mental health challenges experienced by low-income earners in Bushenyi district. Awareness of mental healthcare increased with the age of respondents in both males and females. A linear relationship was observed with age and depression (r = 0.154, P = 0.014) while positive correlations were observed between anxiety and anger (r = 0.254, P < 0.001); anxiety and depression (r = 0.153, P = 0.015) and anger and depression (r = 0.153, P = 0.015). Conclusion: The study shows the importance of mental health awareness in low resource settings during the current COVID-19 pandemic. Females were identified as persons at risk to mental depression, while anger was highest amongst young males.

COVID-19-Related Mental Health Burdens: Impact of Educational Level and Relationship Status Among Low-Income Earners of Western Uganda.

Objective: The study aimed to investigate the relationship between mental health with the level of education, relationship status, and awareness on mental health among low-income earners in Western Uganda. Methods: This was a cross-sectional descriptive study carried out among 253 participants. Anxiety, anger, and depression were assessed using a modified generalized anxiety disorder (GAD-7), Spielberger's State-Trait Anger Expression Inventory-2, and Beck Depression Inventory item tools, respectively. Results: The majority of our respondents were male (n = 150/253, 59.3), had a secondary level of education (104/253, 41.1), and were single (137/253, 54.2). No formal education and primary education (r2 = 47.4% and 6.4%, respectively) had a negative correlation with awareness of mental health care. In addition, no formal education had a positive correlation with anger and depression (r2 = 1.9% and 0.3%, respectively). Singleness in this study had a negative correlation with awareness of mental health care, anger, and depression (r2 = 1.9, 0.8, and 0.3%, respectively), and a positive correlation with anxiety (r2 = 3.9%). Conclusion: It is evident that education and relationship status influenced awareness on mental health care and mental health state among low-income earners in Western Uganda during the first COVID-19 lockdown. Therefore, policymakers should strengthen social transformation through the proper engagement of low-income earners in this COVID-19 era.

Effects of ß-Blockers on the Sympathetic and Cytokines Storms in Covid-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative virus in the development of coronavirus disease 2019 (Covid-19) pandemic. Respiratory manifestations of SARS-CoV-2 infection such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) leads to hypoxia, oxidative stress, and sympatho-activation and in severe cases leads to sympathetic storm (SS). On the other hand, an exaggerated immune response to the SARS-CoV-2 invasion may lead to uncontrolled release of pro-inflammatory cytokine development of cytokine storm (CS). In Covid-19, there are interactive interactions between CS and SS in the development of multi-organ failure (MOF). Interestingly, cutting the bridge between CS and SS by anti-inflammatory and anti-adrenergic agents may mitigate complications that are induced by SARS-CoV-2 infection in severely affected Covid-19 patients. The potential mechanisms of SS in Covid-19 are through different pathways such as hypoxia, which activate the central sympathetic center through carotid bodies chemosensory input and induced pro-inflammatory cytokines, which cross the blood-brain barrier and activation of the sympathetic center. ß2-receptors signaling pathway play a crucial role in the production of pro-inflammatory cytokines, macrophage activation, and B-cells for the production of antibodies with inflammation exacerbation. ß-blockers have anti-inflammatory effects through reduction release of pro-inflammatory cytokines with inhibition of NF-κB. In conclusion, ß-blockers interrupt this interaction through inhibition of several mediators of CS and SS with prevention development of neural-cytokine loop in SARS-CoV-2 infection. Evidence from this study triggers an idea for future prospective studies to confirm the potential role of ß-blockers in the management of Covid-19.

The Rise of SARS-CoV-2 Variants and the Role of Convalescent Plasma Therapy for Management of Infections.

Novel therapies for the treatment of COVID-19 are continuing to emerge as the SARS-Cov-2 pandemic progresses. PCR remains the standard benchmark for initial diagnosis of COVID-19 infection, while advances in immunological profiling are guiding clinical treatment. The SARS-Cov-2 virus has undergone multiple mutations since its emergence in 2019, resulting in changes in virulence that have impacted on disease severity globally. The emergence of more virulent variants of SARS-Cov-2 remains challenging for effective disease control during this pandemic. Major variants identified to date include B.1.1.7, B.1.351; P.1; B.1.617.2; B.1.427; P.2; P.3; B.1.525; and C.37. Globally, large unvaccinated populations increase the risk of more and more variants arising. With successive waves of COVID-19 emerging, strategies that mitigate against community transmission need to be implemented, including increased vaccination coverage. For treatment, convalescent plasma therapy, successfully deployed during recent Ebola outbreaks and for H1N1 influenza, can increase survival rates and improve host responses to viral challenge. Convalescent plasma is rich with cytokines (IL-1ß, IL-2, IL-6, IL-17, and IL-8), CCL2, and TNFα, neutralizing antibodies, and clotting factors essential for the management of SARS-CoV-2 infection. Clinical trials can inform and guide treatment policy, leading to mainstream adoption of convalescent therapy. This review examines the limited number of clinical trials published, to date that have deployed this therapy and explores clinical trials in progress for the treatment of COVID-19.

A Descriptive-Multivariate Analysis of Community Knowledge, Confidence, and Trust in COVID-19 Clinical Trials among Healthcare Workers in Uganda.

Background-misinformation and mistrust often undermines community vaccine uptake, yet information in rural communities, especially of developing countries, is scarce. This study aimed to identify major challenges associated with coronavirus disease 2019 (COVID-19) vaccine clinical trials among healthcare workers and staff in Uganda. Methods-a rapid exploratory survey was conducted over 5 weeks among 260 respondents (66% male) from healthcare centers across the country using an online questionnaire. Twenty-seven questions assessed knowledge, confidence, and trust scores on COVID-19 vaccine clinical trials from participants in 46 districts in Uganda. Results-we found low levels of knowledge (i.e., confusing COVID-19 with Ebola) with males being more informed than females (OR = 1.5, 95% CI: 0.7-3.0), and mistrust associated with policy decisions to promote herbal treatments in Uganda and the rushed international clinical trials, highlighting challenges for the upcoming Oxford-AstraZeneca vaccinations. Knowledge, confidence and trust scores were higher among the least educated (certificate vs. bachelor degree holders). We also found a high level of skepticism and possible community resistance to DNA recombinant vaccines, such as the Oxford-AstraZeneca vaccine. Preference for herbal treatments (38/260; 14.6%, 95% CI: 10.7-19.3) currently being promoted by the Ugandan government raises major policy concerns. High fear and mistrust for COVID-19 vaccine clinical trials was more common among wealthier participants and more affluent regions of the country. Conclusion-our study found that knowledge, confidence, and trust in COVID-19 vaccines was low among healthcare workers in Uganda, especially those with higher wealth and educational status. There is a need to increase transparency and inclusive participation to address these issues before new trials of COVID-19 vaccines are initiated.

Bee Venom-A Potential Complementary Medicine Candidate for SARS-CoV-2 Infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by severe cytokine storm syndrome following inflammation. SARS-CoV-2 directly interacts with angiotensin-converting enzyme 2 (ACE-2) receptors in the human body. Complementary therapies that impact on expression of IgE and IgG antibodies, including administration of bee venom (BV), have efficacy in the management of arthritis, and Parkinson's disease. A recent epidemiological study in China showed that local beekeepers have a level of immunity against SARS-CoV-2 with and without previous exposure to virus. BV anti-inflammatory properties are associated with melittin and phospholipase A2 (PLA2), both of which show activity against enveloped and non-enveloped viruses, including H1N1 and HIV, with activity mediated through antagonist activity against interleukin-6 (IL-6), IL-8, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). Melittin is associated with the underexpression of proinflammatory cytokines, including nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinases (ERK1/2), and protein kinase Akt. BV therapy also involves group III secretory phospholipase A2 in the management of respiratory and neurological diseases. BV activation of the cellular and humoral immune systems should be explored for the application of complementary medicine for the management of SARS-CoV-2 infections. BV "vaccination" is used to immunize against cytomegalovirus and can suppress metastases through the PLA2 and phosphatidylinositol-(3,4)-bisphosphate pathways. That BV shows efficacy for HIV and H1NI offers opportunity as a candidate for complementary therapy for protection against SARS-CoV-2.

Misconceptions on COVID-19 Risk Among Ugandan Men: Results From a Rapid Exploratory Survey, April 2020.

Background: Transmission of COVID-19 in developing countries is expected to surpass that in developed countries; however, information on community perceptions of this new disease is scarce. The aim of the study was to identify possible misconceptions among males and females toward COVID-19 in Uganda using a rapid online survey distributed via social media. Methods: A cross-sectional survey carried out in early April 2020 was conducted with 161 Ugandans, who purposively participated in the online questionnaire that assessed understandings of COVID-19 risk and infection. Sixty-four percent of respondents were male and 36% were female. Results: We found significant divergences of opinion on gendered susceptibility to COVID-19. Most female respondents considered infection risk, symptoms, severe signs, and death to be equally distributed between genders. In contrast, male respondents believed they were more at risk of infection, severe symptoms, severe signs, and death (52.7 vs. 30.6%, RR = 1.79, 95% CI: 1.14-2.8). Most women did not share this perception and disagreed that males were at higher risk of infection (by a factor of three), symptoms (79% disagree), severe signs (71%, disagree), and death (70.2% disagree). Overall, most respondents considered children less vulnerable (OR = 1.12, 95% CI: 0.55-2.2) to COVID-19 than adults, that children present with less symptoms (OR = 1.57, 95% CI: 0.77-3.19), and that there would be less mortality in children (OR = 0.92, 95% CI: 0.41-1.88). Of female respondents, 76.4% considered mortality from COVID-19 to be different between the young and the elderly (RR = 1.7, 95% CI: 1.01-2.92) and 92.7% believed young adults would show fewer signs than the elderly, and 71.4% agreed that elderly COVID-19 patients would show more severe signs than the young (OR = 2.2, 95% CI: 1.4, 4.8). While respondents considered that all races were susceptible to the signs and symptoms of infection as well as death from COVID-19, they considered mortality would be highest among white people from Europe and the USA. Some respondents (mostly male 33/102, 32.4%) considered COVID-19 to be a "disease of whites" (30.2%). Conclusion: The WHO has identified women and children in rural communities as vulnerable persons who should be given more attention in the COVID-19 national response programs across Africa; however, our study has found that men in Uganda perceive themselves to be at greater risk and that these contradictory perceptions (including the association of COVID-19 with "the white" race) suggest an important discrepancy in the communication of who is most vulnerable and why. Further research is urgently needed to validate and expand the results of this small exploratory study.

University Lecturers and Students Could Help in Community Education About SARS-CoV-2 Infection in Uganda.

BACKGROUND: The World Health Organization has placed a lot of attention on vulnerable communities of Africa due to their chronically weak health care systems. Recent findings from Uganda show that medical staff members have sufficient knowledge but poor attitudes toward coronavirus disease 2019 (COVID-19) pandemic. AIM: The aim of this study was to determine the knowledge, attitudes, and preparedness/practices of lecturers and students in the fight against COVID-19. METHOD: This was a descriptive cross-sectional study of 103 lecturers and students both men and women of age group 18 to 69 years in western Uganda. Data were obtained through a pretested questionnaire availed online. RESULTS: Knowledge on COVID-19 symptoms was highest in this order: fever > dry cough > difficulty breathing > fatigue > headache with no significant differences between lecturers and students. Knowledge of participants on transmission of COVID-19 was highest in the order of cough drops > contaminated surfaces > person-to-person contact > asymptomatic persons > airborne > zoonotic with no significant differences among lecturers and students. Lecturers and students were all willing to continue using personal protective equipment like masks, and personal practices such as covering the mouth while sneezing and coughing, no handshaking, and washing of hands with no significant differences in the responses. The positive attitudes that COVID-19 could kill, anyone can get COVID-19, and willing to abide by the set regulations against the pandemic showed personal concerns and desired efforts against COVID-19. CONCLUSION: The study identifies lecturers and students as potential stakeholders in the fight against community transmission of COVID-19.