Effects of MVA85A vaccine on tuberculosis challenge in animals: systematic review

Background The existing Bacillus Calmette–Guérin (BCG) vaccination provides partial protection against tuberculosis (TB). The modified vaccinia ankara virus-expressing antigen 85A (MVA85A) aims to boost BCG immunity. We evaluated the animal evidence supporting the testing of MVA85A in humans. Methods Our protocol included in vivo preclinical studies of the MVA85A booster with BCG compared with BCG alone, followed by a TB challenge. We used standard methods for systematic review of animal studies, and summarized mortality, measures of pathology and lung bacterial load. The comprehensive literature search was to September 2014. Two independent investigators assessed eligibility and performed data extraction. We assessed study quality and pooled bacteria load using random effect meta-analysis. Findings We included eight studies in 192 animals. Three experiments were in mice, two in guinea pigs, two in macaques and one in calves. Overall, study quality was low with no randomization, baseline comparability not described and blinding not reported. For animal death (including euthanasia due to severe morbidity), studies were underpowered, and overall no benefit demonstrated. No difference was shown for lung pathology measured on an ordinal scale or bacterial load. The largest mortality trial carried out in macaques had more deaths in the MVA85A vaccine group, and was published after a trial in South Africa had started recruiting children. Conclusions This independent assessment of the animal data does not provide evidence to support efficacy of MVA85A as a BCG booster. More rigorous conduct and reporting of preclinical research are warranted, and we believe the results of studies should be publicly available before embarking on trials in humans, irrespective of the findings

Effects of MVA85A vaccine on tuberculosis challenge in animals: systematic review

Abstract Background: The existing Bacillus Calmette-Gué rin (BCG) vaccination provides partial protection against tuberculosis (TB). The modified vaccinia ankara virus-expressing antigen 85A (MVA85A) aims to boost BCG immunity. We evaluated the animal evidence supporting the testing of MVA85A in humans. Methods: Our protocol included in vivo preclinical studies of the MVA85A booster with BCG compared with BCG alone, followed by a TB challenge. We used standard methods for systematic review of animal studies, and summarized mortality, measures of pathology and lung bacterial load. The comprehensive literature search was to September 2014. Two independent investigators assessed eligibility and performed data extraction. We assessed study quality and pooled bacteria load using random effect meta-analysis. Findings: We included eight studies in 192 animals. Three experiments were in mice, two in guinea pigs, two in macaques and one in calves. Overall, study quality was low with no randomization, baseline comparability not described and blinding not reported. For animal death (including euthanasia due to severe morbidity), studies were underpowered, and overall no benefit demonstrated. No difference was shown for lung pathology measured on an ordinal scale or bacterial load. The largest mortality trial carried out in macaques had more deaths in the MVA85A vaccine group, and was published after a trial in South Africa had started recruiting children. Conclusions: This independent assessment of the animal data does not provide evidence to support efficacy of MVA85A as a BCG booster. More rigorous conduct and reportin

Multiplication of microbes below 0.690 water activity: implications for terrestrial and extraterrestrial life

Since a key requirement of known life-forms is available water (water-activity; aw), searches for signatures of past life in terrestrial and extraterrestrial environments have recently targeted places known to have contained significant quantities of biologically available water. The lower limit of water activity that enables cell division is ~0.605 which, until now, was only known to be exhibited by a single eukaryote; the sugar-tolerant, fungal xerophile Xeromyces bisporus. The first forms of life on Earth were, however, prokaryotic. Furthermore, early life on Earth inhabited high-salt environments, suggesting an ability to withstand low water activity. Recent evidence indicates that some halophilic Archaea and Bacteria have water activity limits more or less equal to those of X. bisporus. Regardless of species, cellular systems are sensitive to minute differences in water activity (of w-units) so there is a need to determine water-activity values to three decimal places. We discuss water activity in relation to the limits of Earth’s present-day biosphere; the possibility of microbial multiplication by utilizing water from thin, aqueous films or non-liquid sources; whether prokaryotes were the first organisms able to multiply at the 0.605-aw limit; and whether extraterrestrial aqueous milieu of ≥0.605 aw can resemble fertile microbial habitats found on Earth

Is there a common water-activity limit for the three domains of life?

Archaea and Bacteria constitute a majority of life systems on Earth but have long been considered inferior to Eukarya in terms of solute tolerance. Whereas the most halophilic prokaryotes are known for an ability to multiply at saturated NaCl (water activity (a w) 0.755) some xerophilic fungi can germinate, usually at high-sugar concentrations, at values as low as 0.650-0.605 a w. Here, we present evidence that halophilic prokayotes can grow down to water activities of <0.755 for Halanaerobium lacusrosei (0.748), Halobacterium strain 004.1 (0.728), Halobacterium sp. NRC-1 and Halococcus morrhuae (0.717), Haloquadratum walsbyi (0.709), Halococcus salifodinae (0.693), Halobacterium noricense (0.687), Natrinema pallidum (0.681) and haloarchaeal strains GN-2 and GN-5 (0.635 a w). Furthermore, extrapolation of growth curves (prone to giving conservative estimates) indicated theoretical minima down to 0.611 a w for extreme, obligately halophilic Archaea and Bacteria. These were compared with minima for the most solute-tolerant Bacteria in high-sugar (or other non-saline) media (Mycobacterium spp., Tetragenococcus halophilus, Saccharibacter floricola, Staphylococcus aureus and so on) and eukaryotic microbes in saline (Wallemia spp., Basipetospora halophila, Dunaliella spp. and so on) and high-sugar substrates (for example, Xeromyces bisporus, Zygosaccharomyces rouxii, Aspergillus and Eurotium spp.). We also manipulated the balance of chaotropic and kosmotropic stressors for the extreme, xerophilic fungi Aspergillus penicilloides and X. bisporus and, via this approach, their established water-activity limits for mycelial growth (∼0.65) were reduced to 0.640. Furthermore, extrapolations indicated theoretical limits of 0.632 and 0.636 a w for A. penicilloides and X. bisporus, respectively. Collectively, these findings suggest that there is a common water-activity limit that is determined by physicochemical constraints for the three domains of life

POLICY ISSUES FOR POSSIBLE TEMPORAL AND SPATIAL RAINFALL DISTRIBUTION CHANGES DUE TO CLIMATE CHANGE

Global climate change is generally founded on increase in global temperatures whilst regionally the effects of the increase in temperatures are modelled in either increase or decrease in the form of precipitation which in Africa is in the form of rainfall. In Southern Africa it is generally predicted that there will be a 20 % decrease in precipitation by 2050. Rainfall studies are of utmost utility for understanding nature and hence the behavior of climate changes. Precipitation and temperature trend analyses and possible futuristic climatic changes have been done for Zimbabwe. The climate change effects on temporal and spatial distribution of rainfall may play a critical role in determining the policy issues direction related to water security and water related disaster challenges. This paper discusses policy issues related to possible temporal and spatial changes in rainfall distribution related to climate change with a main reliance on the graphical method of trend analysis and a main emphasis on development of policies related to harvesting of rain water and re-modelling weather early warning systems and shows the need for policy revision related to water resources and management

DOES AFRICA NEED ROBOT WIVES: A Genetic Opinion

The first introduction of robot wives on African soil can come soon as a solution to lack of companionship. This Opinion looks at the potential effect the introduction of artificial intelligence powered humanoid robot wives will have on the genetic population and gene pool across the African continent. The effect of the introduction of robot wives will depend on the level of prevalence of exclusive biological male and robot wife mating’s. High prevalence of exclusive biological male and robot wife mating’s can result in genetic drift and genetic erosion. Low prevalence of exclusive biological male and robot wife mating’s will have a minuscule effect on the genetic population gene pool and structure. Ubiquitous presence of robot wives across the continent can result in a negative eugenics effect that can lead to loss of genetic variation and low human population growth rates, affecting the African demographic structure. This opinion is meant to ignite discussion and debate on the concept of robot wives on the African Continent in the event that the humanoids eventually are introduced

LOW – COST MEDIA FORMULATIONS FOR CULTURE MAINTENANCE AND PROLIFIC FRUITING OF OYSTER MUSHROOMS (PLEUROTUS SPP.)

Modified media for Pleurotus sajor-caju and Pleurotus ostreatus was formulated and investigated in terms of its suitability and effect on the mycelial growth rate of the Pleurotus spp. strains. The modified media was of various whole-wheat grain: media (Malt extract agar[MEA] or Potato dextrose agar [PDA]) ratios of 1:1 to 1:5. Polyethylene (PEG) 6000 was also added as its effects on growth rate at minute concentrations were noted in earlier work. The 1:1 ratio mixture resulted in the drying of the wheat grain by the 8th day. The water content of the media formulations were all significantly different from the water content of conventional Malt Extract Agar (MEA, 3 %) (97.9 % water) and Potato dextrose Agar (PDA, 3 %) (97.9 % water). The water contents generally ranged from 14.3 % (1:2 MEA) to 57.4 % (1:4 PDA). There was no clear-cut trend for the water contents of the media formulations. The growth rate generally initially decreased below that obtained for normal media (MEA and PDA). However the growth rate increased above that for normal media for the 1:2 to 1:5 for MEA and 1:3 to 1:5 for PDA. The water content of the mixtures cannot be used to predict the growth rates. Generally mushrooms are taken to require adequate water however surprisingly growth higher than that for normal media was obtained for media with low water content. The increase in growth rate is attributed to the richness in terms of nutrients. PEG amended MEA media generally resulted in higher growth rates than non-amended media. This has been the case in earlier work done. The crushed wheat grain : media formulations ranging from 1:2 to 1:15 with PDA and no PDA treatments (the media formulation comprised only of distilled water and crushed grain) induced luxuriant mycelial growth and prolific fruiting of the Pleurotus spp. The water content of the crushed wheat grain: media formulations ranged from 75 % to 97 %. Water content generally increased from 1: 2 media to 1:15 media. Growth rate was highest for 1: 5 + PDA media. 1:2 – PDA had the lowest growth rate. The low –cost media formulations 1:3 to 1:5 (whole wheat grain) and 1:3 to 1:15 (crushed wheat grain) have potential use as low-cost alternatives to culture Pleurotus spp. for culture maintenance, spawn production, mushroom cultivation and bioremediation

OYSTER MUSHROOM SPAWN PRODUCTION: TYNDALLISATION AS AN ALTERNATIVE METHOD FOR STERILISATION OF GROWTH MEDIUM.

Tyndallisation involves boiling and cooling the medium for 2 to 3 successive days. The first and second heating is to kill the vegetative microbes and the germinated spores respectively. Thus a level of sterility is achieved. This basic concept was applied to the wheat grain used in the production of oyster mushroom spawn in a bid to facilitate an increased adoption of oyster mushroom production in Zimbabwe and possibly in other developing countries. The use of Tyndallisation as an alternative to autoclaving grain for oyster mushroom spawn production was investigated in a two-phased experiment. The first phase was for determining the period required to boil the water prior to boiling the wheat (Triticum aestivum) grain. This was investigated by boiling water for 5, 20 or 30 minutes prior to the normal Tyndallisation boiling (10 mins) for three days with overnight incubation. The second phase investigated the use of short boiling times for a longer duration. The wheat grain was boiled for 5 and 10 mins for 6 days with a 2 min prior boiling of the water. The spawn produced was tested for fruiting ability in banana substrate. Good quality spawn was obtained for the 30 mins boiling for the 2 and 3 days (first phase experiment) and the 5 mins boiling for 4 days (second phase experiment). Treatments varied significantly (ANOVA) in the number of days until presence of contamination. The duration of incubation for production of good quality spawn was determined to be one week. The spawn colonized well the banana substrate and oyster mushrooms fruited in the fifth week of incubation at ambient temperatures ranging from 200C – 250C. The Tyndallisation technology can be used by farmers in Zimbabwe and other developing countries to multiply oyster mushroom spawn to facilitate an increased adoption of oyster mushroom cultivation