Laboratory Models of Infection and Transmission of Mycobacterium ulcerans; causative agent of Buruli ulcer disease

Identification of the environmental reservoir of Mycobacterium ulcerans, the etiological agent of Buruli ulcer, within the aquatic ecosystem has been a salient research area within the last five years. Based on extensive environmental sampling and elegant laboratory models, associations have been made between the bacterial DNA and aquatic invertebrates, biofilms, plants, fish and detritus material captured on 0.2μm pore filters. These studies have suggested that M. ulcerans is widely distributed within many functional feeding groups and may be concentrated through different trophic links; however, the specific route of transmission to humans remains a mystery. In this study we have used laboratory models of infection to ascertain the role of aquatic invertebrates and fish in M. ulcerans transmission. A biologically relevant infection model in which M. ulcerans-infected mosquito larvae were fed to a species of predaceous hemiptera (African Belostomatidae) was used to demonstrate the persistent colonization of M. ulcerans and subsequent transmission of bacteria to naïve prey. The association of M. ulcerans with specific anatomical compartments showed that M. ulcerans accumulates preferentially on the exoskeleton. No difference was found between the ability of wild-type M. ulcerans and an M. ulcerans isogenic mycolactone-negative mutant to colonize belostomatids. These data show that African belostomatids can successfully be colonized by M. ulcerans and support the trophic transfer of M. ulcerans within the environment. We have shown that M. ulcerans with or without the toxin is not lethal to fish (Medaka) even at high doses following direct inoculation. Over time (23wks), infected Medaka do not exhibit any visible signs of infection or toxicity and histopathological sections do not reveal significant gross pathogenesis. M. ulcerans also appears not to replicate in infected Medaka. We also show that fish monocytes are susceptible to nanogram amounts of purified mycolactone. This is the first study to demonstrate the possibility of fish as a reservoir for M. ulcerans within the aquatic environment

SARS-CoV-2 viral shedding and transmission dynamics : implications of WHO COVID-19 discharge guidelines

This work was supported through the Alliance for Accelerating Excellence in Science in Africa (AESA), a funding, agenda-setting, programme management initiative of the African Academy of Sciences (AAS), the African- Union Development Agency (AUDA-NEPAD), founding and funding global partners and through a resolution of the summit of African Union Heads of Governments.The evolving nature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated periodic revisions of COVID-19 patient treatment and discharge guidelines. Since the identification of the first COVID-19 cases in November 2019, the World Health Organization (WHO) has played a crucial role in tackling the country-level pandemic preparedness and patient management protocols. Among others, the WHO provided a guideline on the clinical management of COVID-19 patients according to which patients can be released from isolation centers on the 10th day following clinical symptom manifestation, with a minimum of 72 additional hours following the resolution of symptoms. However, emerging direct evidence indicating the possibility of viral shedding 14 days after the onset of symptoms called for evaluation of the current WHO discharge recommendations. In this review article, we carried out comprehensive literature analysis of viral shedding with specific focus on the duration of viral shedding and infectivity in asymptomatic and symptomatic (mild, moderate, and severe forms) COVID-19 patients. Our literature search indicates that even though, there are specific instances where the current protocols may not be applicable ( such as in immune-compromised patients there is no strong evidence to contradict the current WHO discharge criteria.Publisher PDFPeer reviewe

SARS-CoV-2 Viral Shedding and Transmission Dynamics: Implications of WHO COVID-19 Discharge Guidelines

The evolving nature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated periodic revisions of COVID-19 patient treatment and discharge guidelines. Since the identification of the first COVID-19 cases in November 2019, the World Health Organization (WHO) has played a crucial role in tackling the country-level pandemic preparedness and patient management protocols. Among others, the WHO provided a guideline on the clinical management of COVID-19 patients according to which patients can be released from isolation centers on the 10th day following clinical symptom manifestation, with a minimum of 72 additional hours following the resolution of symptoms. However, emerging direct evidence indicating the possibility of viral shedding 14 days after the onset of symptoms called for evaluation of the current WHO discharge recommendations. In this review article, we carried out comprehensive literature analysis of viral shedding with specific focus on the duration of viral shedding and infectivity in asymptomatic and symptomatic (mild, moderate, and severe forms) COVID-19 patients. Our literature search indicates that even though, there are specific instances where the current protocols may not be applicable ( such as in immune-compromised patients there is no strong evidence to contradict the current WHO discharge criteria

Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics

Urinary tract infections (UTIs) are frequent hospital-acquired infection, with Escherichia coli and Proteus mirabilis accounting for 90% of complicated UTIs. Emergence of multidrug-resistant (MDR) bacteria have complicated the treatment UTIs. P. mirabilis related UTIs has been associated with the production of urinary stones and long-term infections in patients with catheters. P. mirabilis and other uropathogens constitute a largely unexplored pathogen group. The pathogen is resistant to most antibiotics as a result of its impermeable outer membrane (OM). The β-barrel assemble machinery folds and inserts outer membrane proteins; however, there are no antibiotics targeting the OM assemble in clinical use currently. Therefore, this study seeks to identify drugs that will inhibit the activity of P. mirabilis B complex proteins and also determine their effects on P. mirabilis OM biogenesis. This would be achieved by screening approved drugs against the P. mirabilis Bam complex using computer-based in silico screening and cellular-based assays. First, the binding effects of drugs on P. mirabilis B complex proteins will be determined using docking algorithms. The antimicrobial and antivirulence activity of selected drugs from in silico analysis will be screened against MDR P. mirabilis. Finally, the effect of active drug(s) on the OM biogenesis of wild-type P. mirabilis and mutant P. mirabilis will be determined using peptide nucleic acids (PNA). Western lot analysis will be used to determine the abundance of proteins involved in OM biogenesis. Successful completion of this study will lead to the identification of novel antibiotics against MDR P. mirabilis and associated mechanisms while providing the foundation for future research endeavours on other uropathogens

Challenges and Adverse Effects of Wearing Face Masks in the COVID-19 Era

Background: The use of face masks was a significant part of the WHO COVID-19 preventive protocols. While their usage has been effective, lack of adherence by individuals has been associated with discomfort and adverse side effects. This might facilitate unnecessary exposure to the SARS-CoV-2 virus, thereby increasing the incidence of COVID-19. This study assessed the side effects of prolonged mask-wearing and offers recommendations for present and future pandemics. Methods: Adverse side effects of face masks were evaluated from November 2021 to February 2022 with a structured Google Forms online questionnaire. The survey targeted regular and occasional face mask users around the world. All responders anonymously completed the survey, which included ten structured questions with a sub-section on the effects of the continuous use of face masks. The information obtained was analyzed using descriptive statistics, and the data were presented in graphs. Results: Almost 60% (1243) of the 2136 participants indicated discomfort while using face masks. Breathing difficulties and pain around the ears were cited as major causes of discomfort, accounting for 32% and 22%, respectively, of responses. Headaches were reported by 26.8% (572) of the respondents, with 44.6% experiencing one within 1 h of wearing a mask. Nine hundred and eight (908) respondents experienced nasal discomfort, while 412 individuals reported various skin-related discomfort, including excessive sweating around the mouth and acne. Conclusions: This study provides baseline data as to why there was less adherence to face mask use which includes headaches, skin irritation, ear pains, breathing difficulties, sore throat, dry eyes, and increased sweating around the mouth. As a result, this may contribute to an increased risk of infection. While COVID-19 lingers and the management of its undesirable effects persists into the future, it is vital that a superior mask design, concentrating on safety, comfort, and tolerability, be developed

Development of a field diagnostic tool for Schistosoma mansoni Praziquantel resistant markers in selected endemic communities

Schistosomiasis is a neglected tropical disease that affects more than 200 million people and 45% of infections have been shown to occur in school-aged children. A large percentage of the disease burden lies in Africa. In 2012, the WHO outlined a roadmap for the elimination of schistosomiasis by 2020; however, this was not achieved. Treatment for schistosomiasis is by the use of Praziquantel, a drug in use for over 30 years and there is a concern for emerging drug resistance. There are several species of the genus Schistosoma causing infection in humans. For this study, Schistosoma mansoni which causes intestinal schistosomiasis will be investigated. There are reports of lowering cure rates and suboptimal response to praziquantel following several cycles of mass drug administration (MDA). Praziquantel resistance has also been reported in some countries and laboratory-bred schistosome experiments. To address the concerns of resistance, this study aims to employ a two-part approach to assess the prevalence of S. mansoni. praziquantel resistance amongst school-aged children in schistosomiasis endemic communities in Ghana and develop a diagnostic tool to aid in field assessment of infections. To achieve this, the study will attempt to answer the following research questions: 1. Is there developing S. mansoni praziquantel resistance in communities that have undergone several mass drug administrations? 2. Is there an interplay between intermediate host exposure to praziquantel and the development of praziquantel drug resistance in the definitive host

Development of a Field Diagnostic Tool for Schistosoma mansoni Praziquantel Resistant Markers in Selected Endemic Communities

Schistosomiasis is a neglected tropical disease that affects more than 200 million people and 45% of infections have been shown to occur in school-aged children. A large percentage of the disease burden lies in Africa. In 2012, the WHO outlined a roadmap for the elimination of schistosomiasis by 2020; however, this was not achieved. Treatment for schistosomiasis is by the use of Praziquantel, a drug in use for over 30 years and there is a concern for emerging drug resistance. There are several species of the genus Schistosoma causing infection in humans. For this study, Schistosoma mansoni which causes intestinal schistosomiasis will be investigated. There are reports of lowering cure rates and suboptimal response to praziquantel following several cycles of mass drug administration (MDA). Praziquantel resistance has also been reported in some countries and laboratory-bred schistosome experiments. To address the concerns of resistance, this study aims to employ a two-part approach to assess the prevalence of S. mansoni. praziquantel resistance among school-aged children in schistosomiasis endemic communities in Ghana and develop a diagnostic tool to aid in field assessment of infections. To achieve this, the study will attempt to answer the following research questions: 1. Is there developing S. mansoni praziquantel resistance in communities that have undergone several mass drug administrations? 2. Is there an interplay between intermediate host exposure to praziquantel and the development of praziquantel drug resistance in the definitive host

Challenges and Adverse Effects of Wearing Face Masks in the COVID-19 Era

Background: The use of face masks was a significant part of the WHO COVID-19 preventive protocols. While their usage has been effective, lack of adherence by individuals has been associated with discomfort and adverse side effects. This might facilitate unnecessary exposure to the SARS-CoV-2 virus, thereby increasing the incidence of COVID-19. This study assessed the side effects of prolonged mask-wearing and offers recommendations for present and future pandemics. Methods: Adverse side effects of face masks were evaluated from November 2021 to February 2022 with a structured Google Forms online questionnaire. The survey targeted regular and occasional face mask users around the world. All responders anonymously completed the survey, which included ten structured questions with a sub-section on the effects of the continuous use of face masks. The information obtained was analyzed using descriptive statistics, and the data were presented in graphs. Results: Almost 60% (1243) of the 2136 participants indicated discomfort while using face masks. Breathing difficulties and pain around the ears were cited as major causes of discomfort, accounting for 32% and 22%, respectively, of responses. Headaches were reported by 26.8% (572) of the respondents, with 44.6% experiencing one within 1 h of wearing a mask. Nine hundred and eight (908) respondents experienced nasal discomfort, while 412 individuals reported various skin-related discomfort, including excessive sweating around the mouth and acne. Conclusions: This study provides baseline data as to why there was less adherence to face mask use which includes headaches, skin irritation, ear pains, breathing difficulties, sore throat, dry eyes, and increased sweating around the mouth. As a result, this may contribute to an increased risk of infection. While COVID-19 lingers and the management of its undesirable effects persists into the future, it is vital that a superior mask design, concentrating on safety, comfort, and tolerability, be developed

Distribution and Risk of Mycolactone-Producing Mycobacteria Transmission within Buruli Ulcer Endemic Communities in Côte d’Ivoire

In Buruli ulcer (BU) endemic communities, most mycolactone-producing mycobacteria (MPM), including Mycobacterium ulcerans, the causative agent, are present in water bodies used by inhabitants; yet, their mode of transmission is still unclear. This study aimed to assess the distribution of MPM strains, both from human suspected cases and aquatic environments, for identifying possible transmission modes within two BU endemic districts, Daloa and Tiassalé (Taabo), in Côte d’Ivoire. Collected samples were processed using conventional polymerase chain reaction and screened for the presence of non-tuberculous mycobacteria (NTM) and MPMs using 16S rRNA, IS2404 and enoyl reductase (ER) primers. MPM-positive samples were further discriminated using variable number tandem repeat (VNTR) typing and sequencing. 16S rRNA and IS2404 sequences confirmed that 94% of the clinical samples contained MPMs. For environmental samples, 53% were contaminated with NTMs, of which 17% contained MPMs particularly M. ulcerans, suggesting that water-related activities could predispose inhabitants to BU transmission. MPM discrimination by VNTR at four M. ulcerans Agy99 loci identified genotype C, previously reported in Côte d’Ivoire as the most dominant profile. Phylogenetic clustering on the basis of genetic diversity in the MIRU 1 locus showed two main M. ulcerans lineages in Côte d’Ivoire