COVID-19: Salient Aspects of Coronavirus Infection, Vaccines and Vaccination Testing and their Implications

In the present study, three basic aspects related to COVID-19 are presented. (a) The occurrence of coronavirus infection is analyzed statistically as number of coronaviruses infected alveolar cells compared to normal alveolar cells in human lungs. The mole concept is used to estimate the number of normal alveolar cells per human lung. The number of coronavirus infections in infected alveolar cells is estimated from the published Lower Respiratory Tract (LRT) load data. The Poisson probability distribution is aptly applied to imply the incubation period of the coronavirus infection to be within day-3 to day-7, with the cumulative probability of 75%. The incubation period within day-0 to day-10 has a cumulative probability of 98%. It implies a 10-day quarantine to isolate an uninfected individual as a precautionary measure. (b) Three vaccines to combat COVID-19, which adopt distinct paradigms while preparing them, are analyzed. These are Moderna's mRNA-1273, Oxford-AstraZeneca's ChAdOx1 nCoV-19 and Bharat BioTech's COVAXIN. The mole concept is used to estimate the antigen mass density per dose of each of these vaccines as 10, 0.1 and 1 (g per cubic-cm), respectively. The vaccines are deemed to be compatible to neutralize the infection. (c) A statistical analysis is performed of the Moderna's mRNA-1273 vaccine efficacy of 94.1% and Oxford's ChAdOx1 nCoV-19 vaccine efficacy of 62.1% in terms of groups of volunteers testing negative to vaccine by chance. In the Moderna vaccination testing scenario, since the probability of negative response of vaccine is small, the Poisson probability distribution for 95% cumulative probability is used to describe the vaccination testing in 300 samples of 47 volunteers each. Thus, 87% of samples have average group of 3 volunteers testing negative to vaccine. About 6% of samples have all volunteers testing positive to vaccine. In the Oxford vaccination testing scenario, since the probability of negative response of vaccine is finite, the Gaussian probability distribution for 95% probability is used to describe the vaccination testing in 75 samples of 120 volunteers each. Thus, 68% of samples have average group of 45 volunteers testing negative to vaccine. No sample has all volunteers testing positive to vaccine. A vaccine, irrespective of its efficacy being high or low, is necessary for mass immunization.

Genetic and environmental influences on the evolution of virulence in the HIV-associated opportunistic human fungal pathogen Cryptococcus neoformans

The fungus Cryptococcus neoformans is considered the leading cause of death in immunocompromised patients. Despite numerous investigations concerning its molecular epidemiology, there are only a few studies addressing the impacts of varying factors on genotype-phenotype correlations. It remains largely unknown whether genetic and environmental variabilities among isolates from different sources may have dramatic consequences on virulence. In this study, we analyzed 105 Chinese C. neoformans isolates, including 54 from HIV-infected patients, 44 from HIV-uninfected individuals and 7 from a natural environment, to investigate factors influencing the outcome of C. neoformans infection. MLST analysis clearly identified sequence type (ST) 5 as the prevalent sequence type in all clinical isolates and interestingly, genotypic diversities were observed in isolates from both HIV-uninfected individual and natural environment but not those from HIV-infected patients. Moreover, we found that compared to those from HIV-infected patients, the isolates from HIV-uninfected individuals exhibited enhanced virulence-associated traits including significantly elevated capsule production and melanin formation, increases in survival in human cerebrospinal fluid (CSF), less effective uptake by host phagocytes, and higher mortality in a mouse model of cryptococcosis. Consistently, pathogenic phenotypes were associated with CD4 counts of patients, implying environmental impact on within-host C. neoformans virulence. Importantly, a large-scale whole-genome sequencing analysis revealed that genomic variations within genes related to specific functions may act as a vital driving force of host intrinsic virulence evolution. Taken together, our results support a strong genotype-phenotype correlation suggesting that the pathogenic evolution of C. neoformans could be heavily affected by both genetic and environmental factors.

The definition of tuberculosis infection based on the spectrum of tuberculosis disease

Latent tuberculosis infection was the term traditionally used to indicate tuberculosis (TB) infection. This term was used to define “a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens through tests such as the tuberculin skin test (TST) or an interferon-γ release assay (IGRA) without clinically active TB”. Recent evidence indicates that the spectrum from TB infection to TB disease is much more complex, including a “continuum” of situations didactically reported as uninfected individual, TB infection, incipient TB, subclinical TB without signs/symptoms, subclinical TB with unrecognised signs/symptoms, and TB disease with signs/symptoms. Recent evidence suggests that subclinical TB is responsible for important M. tuberculosis transmission. This review describes the different stages described above and their relationships. It also summarises the new developments in prevention, diagnosis and treatment of TB infection as well as their public health and policy implications.Educational aimsTo describe the evolution of the definition of “tuberculosis infection” and didactically describe the continuum of stages existing between TB infection and disease.To discuss the recommended approaches to prevent, diagnose and treat TB infection.

Bioaccumulation of Pyrethroid in Parasite Wenyonia acuminata (Cestoda: Caryophyllaeidae) and Host fish Synodontis clarias (Linnaeus, 1758) from Lekki Lagoon, Lagos Nigeria

This study was aimed at determining the concentration of pyrethroid in the surface water, sediment, Weyonia acuminata and Synodontis clarias fish in Lekki lagoon, Lagos, Nigeria. In-situ physicochemical analysis of the surface water was conducted using a calibrated handheld multi-parameter probe (Horiba Checker Model U-10). Intestinal samples from infected and uninfected fish were analyzed for pyrethroid concentrations, microbial colonization, proteins (PRO), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), malonaldehyde (MDA) and glutathione peroxidase (GPx). The histopathology of infected and uninfected intestinal tissues were analyzed using Haematoxylin and Eosin (H&E) stains and examined under a binocular light microscope (Model 230485). A total of 39 out of 98 S. clarias fish were infected with cestode parasite, Wenyonia acuminate, amounting to 39% parasite prevalence. Among the tested pyrethroids, Cyfluthrin and Alpha –cypermethrin had significant sorption of 1.62 and 3.27 respectively from the aqueous phase to the bottom sediment of the lagoon. Pyrethroid concentration was in the order of sediment > parasite> water > intestine> liver. The cholesterol, triglycerides, and LDL (low density lipids) in the parasite were higher than in the host fish (p<0.05). On the other hand, the fish hepatic protein, high density lipids (HDL) and glucose were higher than the levels in the parasites (p<0.05). There was a high prevalence of gut microbes (30 - 40%), which include Salmonella sp, Escherichia coli, Pseudomonas sp and Bacillus sp among individuals infected with gut Cestodes, Wenyonia sp compared with uninfected individual which had higher gut Staphylococcus sp., Klebsiella sp., and Proteus sp. (10- 40%). among the congeners of pyrethroids analyzed, Cyfluthrin > Alpha-Cyermethrin had significant sorption on the sediment, however unlike a benthopelagic fish, no pyrethroid was accumulated in the S. clarias from the sediment. The fish however accumulated Alpha-Cypermethrin from the aqueous phase. The parasite on the other hand accumulated Bathroid significantly from the surface water and bottom sediment which may be linked to the higher stress levels observed in the parasite than the host fish. The parasite in turn inflicted histological alterations on the host intestine, marked by moderate inflammation of mucosa, alteration of the villi microstructure, moderate stunting of the villous structure and moderate fibrosis of villous structure. The study demonstrated the efficiency of histopathological and microbial analysis in biomonitoring studies enteric parasites and early detection of pyrethroid toxicity respectively compared to bioaccumulation analysis.