Genetic diversities of Mycobacterium tuberculosis complex species in Western Kenya.

Background: Tuberculosis (TB) remains a high-burden infectious disease worldwide. Mycobacterium tuberculosis complex (MTBC) is the aetiological agent of TB. Research Gap: The TB burden is significantly linked to the development of drug-resistant strains. Thus, there is an urgent need for close surveillance of MTBC circulating in a given region, such as Western Kenya, for treatment of TB. Aim: To determine the proportion of MTBC species, strains and genetic diversities in circulation in HIV/AIDS-prevalent regions, and Western Kenya in particular. The clinical MTBC isolates were collected from Moi Teaching and Referral Hospital (MTRH) at Eldoret-Kenya during 2013-14. All clinical MTBC isolates were confirmed by the gold standard method (Löwenstein-Jensen medium culture) before inclusion in the investigation. Methodology: Twelve-loci mycobacterium interspersed repetitive unit - variable-number tandem repeats (MIRU-VNTR) genotyping was performed to determine the circulating species/strains of MTBC using the www.miru-vntrplus.org web platform. Allelic diversity was calculated using the Hunter-Gaston diversity index (HGDI). Results: The species M. tuberculosis, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium pinnipedii, Mycobacterium microti, Mycobacterium caprae and Mycobacterium canetti were identified in the MTBC population. These strains were found in the Beijing, Latin American Mediterranean, Uganda 1/2, East African Indian, Ilama, West African 1/2, Harlem, URAL, Ghana, Seal, Cameroon and Vole etc. regions of Western Kenya. Notably, some isolates had unknown (new/unassigned) species. The strains were grouped into nine clusters with a clustering rate of 31.18 % and a high allelic diversity index of 0.53 was observed. Conclusion: The present findings suggest that there is an urgent need for more awareness among healthcare professionals and stakeholders concerning the existence of foreign MTBC species/strains in Kenya. Furthermore, 12-loci MIRU-VNTR may not be suitable for the surveillance of MTBC strains in circulation in Kenya. Thus, high-resolution techniques such as whole-genome sequencing need to be adopted to resolve the genetic diversity and establish evolutionary trends for future and archived samples. This knowledge will be crucial in restraining TB, providing insights into new drug development, and developing prevention, control and treatment strategies for TB.

Knowledge, attitude and perception towards COVID-19 among representative educated sub-Saharan Africans: A cross-sectional study during the exponential phase of the pandemic.

Coronavirus disease 2019 (COVID-19) pandemic, caused by the Severe Acute Coronavirus 2 (SARS-CoV-2), is a global health threat with extensive misinformation and conspiracy theories. Therefore, this study investigated the knowledge, attitude and perception of sub-Saharan Africans (SSA) on COVID-19 during the exponential phase of the pandemic. In this cross-sectional survey, self-administered web-based questionnaires were distributed through several online platforms. A total of 1046 respondents from 35 SSA countries completed the survey. The median age was 33 years (18-76 years) and about half (50.5%) of them were males. More than 40% across all socio-demographic categories except the Central African region (21.2%), vocational/secondary education (28.6%), student/unemployed (35.5%), had high COVID-19 knowledge score. Socio-demographic factors and access to information were associated with COVID-19 knowledge. Bivariate analysis revealed that independent variables, including the region of origin, age, gender, education and occupation, were significantly (p < 0.05) associated with COVID-19 knowledge. Multivariate analysis showed that residing in East (odds ratio [OR]: 7.9, 95% confidence interval (CI): 4.7-14, p<0.001), Southern (OR: 3.7, 95% CI: 2.1-6.5, p<0.001) and West (OR: 3.9, 95% CI: 2.9-5.2, p<0.001) Africa was associated with high COVID-19 knowledge level. Apart from East Africa (54.7%), willingness for vaccine acceptance across the other SSA regions was <40%. About 52%, across all socio-demographic categories, were undecided. Knowledge level, region of origin, age, gender, marital status and religion were significantly (p < 0.05) associated with COVID-19 vaccine acceptance. About 67.4% were worried about contracting SARS-CoV-2, while 65.9% indicated they would consult a health professional if exposed. More than one-third of the respondents reported that their governments had taken prompt measures to tackle the pandemic. Despite high COVID-19 knowledge in our study population, most participants were still undecided regarding vaccination, which is critical in eliminating the pandemic. Therefore, extensive, accurate, dynamic and timely education in this aspect is of ultimate priority.

SARS-CoV-2 variants evolve convergent strategies to remodel the host response.

SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA.1 did not. ISG suppression correlated with the expression of viral innate immune antagonist proteins, including Orf6, N, and Orf9b, which we mapped to specific mutations. Later Omicron subvariants BA.4 and BA.5 more potently suppressed innate immunity than early subvariant BA.1, which correlated with Orf6 levels, although muted in BA.4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest that SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics.

Network modeling suggests HIV infection phenocopies PI3K-AKT pathway mutations to enhance HPV-associated cervical cancer.

Women coinfected with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV) are six times as likely to develop invasive cervical carcinoma compared to those without HIV. Unlike other HIV-associated cancers, the risk of cervical cancer development does not change when HPV/HIV coinfected women begin antiretroviral therapy, suggesting HIV-associated immune suppression is not a key driver of cervical cancer development in coinfected women. Here, we investigated whether the persistent secretion of inflammatory factors in HIV-positive patients on antiretroviral therapy could enhance cancer signaling in HPV-infected cervical cells via endocrine mechanisms. We integrated previously reported HIV-induced secreted inflammatory factors (Hi-SIFs), HIV and HPV virus-human protein interactions, and cervical cancer patient genomic data using network propagation to understand the pathways underlying disease development in HPV/HIV coinfection. Our results pinpointed the PI3K-AKT signaling pathway to be enriched at the interface between Hi-SIFs and HPV-host molecular networks, in alignment with PI3K pathway mutations being prominent drivers of HPV-associated, but HIV independent, cervical cancer development. Furthermore, we experimentally stimulated cervical cells with 14 Hi-SIFs to assess their ability to activate PI3K-AKT signaling. Strikingly, we found 8 factors (CD14, CXCL11, CXCL9, CXCL13, CXCL17, AHSG, CCL18, and MMP-1) to significantly upregulate AKT phosphorylation (pAKT-S473) relative to a phosphate buffered saline control. Our findings suggest that Hi-SIFs cooperate with HPV infection in cervical cells to over-activate PI3K-AKT signaling, effectively phenocopying PI3K-AKT pathway mutations, resulting in enhanced cervical cancer development in coinfected women. Our insights could support the design of therapeutic interventions targeting the PI3K-AKT pathway or neutralizing Hi-SIFs in HPV/HIV coinfected cervical cancer patients.

Probing SARS-CoV-2-positive plasma to identify potential factors correlating with mild COVID-19 in Ghana, West Africa.

BACKGROUND: West Africa has recorded a relatively higher proportion of asymptomatic coronavirus disease 2019 (COVID-19) cases than the rest of the world, and West Africa-specific host factors could play a role in this discrepancy. Here, we assessed the association between COVID-19 severity among Ghanaians with their immune profiles and ABO blood groups. METHODS: Plasma samples were obtained from Ghanaians PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive individuals. The participants were categorized into symptomatic and asymptomatic cases. Cytokine profiling and antibody quantification were performed using Luminex™ multiplex assay whereas antigen-driven agglutination assay was used to assess the ABO blood groups. Immune profile levels between symptomatic and asymptomatic groups were compared using the two-tailed Mann-Whitney U test. Multiple comparisons of cytokine levels among and between days were tested using Kruskal-Wallis with Dunn's post hoc test. Correlations within ABO blood grouping (O's and non-O's) and between cytokines were determined using Spearman correlations. Logistic regression analysis was performed to assess the association of various cytokines with asymptomatic phenotype. RESULTS: There was a trend linking blood group O to reduced disease severity, but this association was not statistically significant. Generally, symptomatic patients displayed significantly (p < 0.05) higher cytokine levels compared to asymptomatic cases with exception of Eotaxin, which was positively associated with asymptomatic cases. There were also significant (p < 0.05) associations between other immune markers (IL-6, IL-8 and IL-1Ra) and disease severity. Cytokines' clustering patterns differ between symptomatic and asymptomatic cases. We observed a steady decrease in the concentration of most cytokines over time, while anti-SARS-CoV-2 antibody levels were stable for at least a month, regardless of the COVID-19 status. CONCLUSIONS: The findings suggest that genetic background and pre-existing immune response patterns may in part shape the nature of the symptomatic response against COVID-19 in a West African population. This study offers clear directions to be explored further in larger studies.

Loop-mediated isothermal amplification for Candida species surveillance in under-resourced setting: a review of evidence.

INTRODUCTION: Non-albicans Candida species (NACS) have emerged as a major public health burden, although they are still underappreciated. Some NACS have intrinsic antifungal resistance, requiring constant surveillance to improve patient care and thwart outbreaks of recalcitrant candida infections. However, effective Candida species surveillance has relied on PCR-based or other high-end techniques that are largely unaffordable in under-resourced countries. Loop-mediated isothermal amplification (LAMP) has emerged as a potentially effective and affordable technique for infectious disease surveillance, especially in under-resourced settings. AREAS COVERED: We critically reviewed current literature on the application of LAMP for Candida species identification in pure fungal isolates, and in clinical and non-clinical samples. EXPERT OPINION: LAMP has been studied for Candida species identification, including the NACS. Besides a short turnaround time, LAMP has analytical sensitivity and specificity that are not only higher than culture method but also comparable with conventional and quantitative PCR techniques. However, extensive evaluation of LAMP for Candida species detection using various types of clinical and environmental samples is required before deploying the technique for Candida species surveillance.

Pathogen-Induced Epigenetic Modifications in Cancers: Implications for Prevention, Detection and Treatment of Cancers in Africa.

Cancer is a major public health burden worldwide. Tumor formation is caused by multiple intrinsic and extrinsic factors. Many reports have demonstrated a positive correlation between the burden of infectious pathogens and the occurrence of cancers. However, the mechanistic link between pathogens and cancer development remains largely unclear and is subject to active investigations. Apart from somatic mutations that have been widely linked with various cancers, an appreciable body of knowledge points to alterations of host epigenetic patterns as key triggers for cancer development. Several studies have associated various infectious pathogens with epigenetic modifications. It is therefore plausible to assume that pathogens induce carcinogenesis via alteration of normal host epigenetic patterns. Thus, Africa with its disproportionate burden of infectious pathogens is threatened by a dramatic increase in pathogen-mediated cancers. To curb the potential upsurge of such cancers, a better understanding of the role of tropical pathogens in cancer epigenetics could substantially provide resources to improve cancer management among Africans. Therefore, this review discusses cancer epigenetic studies in Africa and the link between tropical pathogens and cancer burden. In addition, we discuss the potential mechanisms by which pathogens induce cancers and the opportunities and challenges of tropical pathogen-induced epigenetic changes for cancer prevention, detection and management.

Parallels in Sepsis and COVID-19 Conditions: Implications for Managing Severe COVID-19.

Sepsis is a life-threatening systemic illness attributed to a dysregulated host response to infection. Sepsis is a global burden killing ~11 million persons annually. In December 2019, a novel pneumonia condition termed coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged and has resulted in more than 1,535,982 deaths globally as of 8th December 2020. These two conditions share many pathophysiological and clinical features. Notably, both sepsis and COVID-19 patients experience consumptive thrombocytopenia, haemolytic anaemia, vascular microthrombosis, multi-organ dysfunction syndrome, coagulopathy, septic shock, respiratory failure, fever, leukopenia, hypotension, leukocytosis, high cytokine production and high predisposition to opportunistic infections. Considering the parallels in the immunopathogenesis and pathophysiological manifestations of sepsis and COVID-19, it is highly likely that sepsis care, which has a well-established history in most health systems, could inform on COVID-19 management. In view of this, the present perspective compares the immunopathogenesis and pathophysiology of COVID-19 and non-SARS-CoV-2 induced sepsis, and lessons from sepsis that can be applicable to COVID-19 management.

Potential of laser-induced fluorescence-light detection and ranging for future stand-off virus surveillance.

Viruses remain a significant public health concern worldwide. Recently, humanity has faced deadly viral infections, including Zika, Ebola and the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The threat is associated with the ability of the viruses to mutate frequently and adapt to different hosts. Thus, there is the need for robust detection and classification of emerging virus strains to ensure that humanity is prepared in terms of vaccine and drug developments. A point or stand-off biosensor that can detect and classify viruses from indoor and outdoor environments would be suited for viral surveillance. Light detection and ranging (LiDAR) is a facile and versatile tool that has been explored for stand-off detection in different environments including atmospheric, oceans and forest sensing. Notably, laser-induced fluorescence-light detection and ranging (LIF-LiDAR) has been used to identify MS2 bacteriophage on artificially contaminated surgical equipment or released amidst other primary biological aerosol particles in laboratory-like close chamber. It has also been shown to distinguish between different picornaviruses. Currently, the potentials of the LIF-LiDAR technology for real-time stand-off surveillance of pathogenic viruses in indoor and outdoor environments have not been assessed. Considering the increasing applications of LIF-LiDAR for potential microbial pathogens detection and classification, and the need for more robust tools for viral surveillance at safe distance, we critically evaluate the prospects and challenges of LIF-LiDAR technology for real-time stand-off detection and classification of potentially pathogenic viruses in various environments.

Pausing the Fight Against Malaria to Combat the COVID-19 Pandemic in Africa: Is the Future of Malaria Bleak?

Malaria remains a major global health burden, killing hundreds of thousands annually, especially in sub-Saharan Africa. In 2019, a Phase IV Expanded Programme on Immunization (EPI)-linked malaria vaccine implementation was underway. However, in December 2019, a novel pneumonia condition termed coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with many clinical, epidemiological, and biological parallels to malaria, was reported in Wuhan, China. COVID-19 is spreading rapidly, and, as of the 3rd of June, 2020, more than 382,507 persons had died from COVID-19. Children under 5 years who suffer high malaria-attributable mortalities are largely asymptomatic for COVID-19. Considering that the malaria burden is highest in low-income tropical countries with little capacity to fund malaria control and eradication programs, the fight against malaria in these regions is likely to be hampered. Access to healthcare has generally been limited, while malaria interventions, such as seasonal malaria chemotherapy and distribution of insecticide-treated bed nets, have been suspended due to lockdowns. Likewise, the repurposing of antimalarials for treatment of COVID-19 shared symptoms and the shift in focus from the production of malaria rapid diagnostic tests (RDTs) to COVID-19 RDTs is a cause for concern in malaria-endemic regions. Children are less affected by the COVID-19 pandemic compared to the elderly. However, due to the fears of contracting SARS-CoV-2, the elderly who are worst affected by COVID-19 may not take children for malaria medication, resulting in high malaria-related mortalities among children. COVID-19 has disproportionately affected developed countries, threatening their donation capacity. These are likely to thwart malaria control efforts in low-income regions. Here, we present perspectives on the collateral impact of COVID-19 on malaria, especially in Africa.

Alternative sigma factor B (σB) and catalase enzyme contribute to Staphylococcus epidermidis biofilm's tolerance against physico-chemical disinfection.

Staphylococcus epidermidis is the predominant cause of recalcitrant biofilm-associated infections, which are often highly resistant to antibiotics. Thus, the use of physico-chemical agents for disinfection offers a more effective approach to the control of S. epidermidis biofilm infections. However, the underlying tolerance mechanisms employed by S. epidermidis biofilm against these physico-chemical disinfectants remain largely unknown. The expression of a σB-dependent gene, alkaline shock protein 23 (asp23) and catalase activity by S. epidermidis biofilm and planktonic cells exposed to heat (50 °C), 0.8 M sodium chloride (NaCl), 5 mM sodium hypochlorite (NaOCl) or 50 µM hydrogen peroxide (H2O2) for 60 minutes were compared. Significantly higher asp23 expression levels were observed in biofilms exposed to 50 °C, 5 mM NaOCl or 50 µM H2O2 compared to the corresponding planktonic cells (p < 0.05). Conversely, asp23 expression levels in biofilm and planktonic cells exposed to 0.8 M NaCl were not significantly different (p > 0.05). Further, biofilms exposed to 50 °C, 0.8 M NaCl, 5 mM NaOCl or 50 µM H2O2 exhibited significantly higher catalase activity than the planktonic cells (p < 0.05). These results suggest that activities of σB and catalase may be involved in the tolerance of S. epidermidis biofilm against physico-chemical disinfection.

Susceptibility patterns and the role of extracellular DNA in Staphylococcus epidermidis biofilm resistance to physico-chemical stress exposure.

BACKGROUND: Over 65% of human infections are ascribed to bacterial biofilms that are often highly resistant to antibiotics and host immunity. Staphylococcus epidermidis is the predominant cause of recurrent nosocomial and biofilm-related infections. However, the susceptibility patterns of S. epidermidis biofilms to physico-chemical stress induced by commonly recommended disinfectants [(heat, sodium chloride (NaCl), sodium hypochlorite (NaOCl) and hydrogen peroxide (H2O2)] in domestic and human healthcare settings remains largely unknown. Further, the molecular mechanisms of bacterial biofilms resistance to the physico-chemical stresses remain unclear. Growing evidence demonstrates that extracellular DNA (eDNA) protects bacterial biofilms against antibiotics. However, the role of eDNA as a potential mechanism underlying S. epidermidis biofilms resistance to physico-chemical stress exposure is yet to be understood. Therefore, this study aimed to evaluate the susceptibility patterns of and eDNA release by S. epidermidis biofilm and planktonic cells to physico-chemical stress exposure. RESULTS: S. epidermidis biofilms exposed to physico-chemical stress conditions commonly recommended for disinfection [heat (60 °C), 1.72 M NaCl, solution containing 150 µL of waterguard (0.178 M NaOCl) in 1 L of water or 1.77 M H2O2] for 30 and 60 min exhibited lower log reductions of CFU/mL than the corresponding planktonic cells (p < 0.0001). The eDNA released by sub-lethal heat (50 °C)-treated S. epidermidis biofilm and planktonic cells was not statistically different (p = 0.8501). However, 50 °C-treated S. epidermidis biofilm cells released significantly increased eDNA than the untreated controls (p = 0.0098). The eDNA released by 0.8 M NaCl-treated S. epidermidis biofilm and planktonic cells was not significantly different (p = 0.9697). Conversely, 5 mM NaOCl-treated S. epidermidis biofilms exhibited significantly increased eDNA release than the corresponding planktonic cells (p = 0.0015). Further, the 50 µM H2O2-treated S. epidermidis biofilms released significantly more eDNA than the corresponding planktonic cells (p = 0.021). CONCLUSIONS: S. epidermidis biofilms were less susceptible to physico-chemical stress induced by the four commonly recommended disinfectants than the analogous planktonic cells. Further, S. epidermidis biofilms enhanced eDNA release in response to the sub-lethal heat and oxidative stress exposure than the corresponding planktonic cells suggesting a role of eDNA in biofilms resistance to the physico-chemical stresses.