Eddie Mwenje

Phylogenetic relationships among Armillaria species inferred from partial elongation factor 1-alpha DNA sequence data

Armillaria species are important root rot pathogens with a wide host range and a worldwide distribution. The taxonomy of these fungi has been problematic for many years but the understanding of the relationships between them has been substantially improved through the application of DNA sequence comparisons. In this study, relationships between different Armillaria species were determined using elongation factor 1-alpha DNA sequence data for the first time. A total of 42 isolates, representing the majority of Armillaria species, with diverse geographic distributions and hosts, were included in this study. PCR amplification yielded products of 600 bp for all the isolates. Phylogenetic trees resulting from parsimony analysis showed that this gene region is useful for studying relationships between species. Generally, results were similar to those emerging from previous comparisons using ITS and IGS-1 sequence data. Phylogenetic trees generated from the dataset grouped the African taxa in a strongly supported clade, basal to the rest of the Armillaria species included in the study. The Armillaria species originating from the Northern Hemisphere formed a monophyletic group. Within this group, isolates of A. mellea constituted four subclades, representing their geographical origin. The phylogenetic relationships among species from the Southern Hemisphere were not entirely resolved. However, A. pallidula, A. fumosa and A. hinnulea grouped in a strongly supported clade and isolates of A. limonea formed a sister clade with those of A. luteobubalina. This is the first time a single-copy protein coding gene has been used to study phylogenetic relationships in Armillaria, and overall the data support previously held views regarding the relationships between species.

Molecular characterisation of Armillaria species from Zimbabwe

Armillaria species are amongst the most important pathogens of trees and have a world-wide distribution. In recent years, the taxonomy of Northern Hemisphere Armillaria spp. has been extensively treated, but those occurring in Africa are poorly known. Previously, isolates of Armillaria from Zimbabwe have been grouped based on morphology and biochemical tests. In this study, six isolates representing the three previously characterized groups of Armillaria spp. occurring in Zimbabwe were analysed using DNA-based techniques. Three distinct clusters emerged from both PCR-RFLP and analysis of sequence data for the IGS-1 rRNA operon. The three groups corresponded to those previously identified based on morphology and biochemical tests. Differences in IGS-1 sequences strongly suggest that the Zimbabwean groups represent three distinct taxa. Isolates belonging to Group I, previously assumed to be to A. heimii, were similar to those identified as A. fuscipes from South Africa and La Reunion. Group II isolates resided in a clade apart from all other isolates and appear to represent A. heimii. The remaining isolates residing in Group III clustered with isolates from Zambia and Cameroon. These are different from A. heimii and A. fuscipes and apparently represent an undescribed taxon.

MATHEMATICAL MODELING OF CHEMOTHERAPY OF HUMAN TB INFECTION

This work assesses the impact of the first line drug regimen on active disease control under the stipulated time of tuberculosis (TB) treatment. In an effort to understand why a robust immune response mechanism sometimes fails to completely control TB infection, we first developed a model that captures the human immune response mechanisms to Mycobacterium tuberculosis (Mtb) infection. We then extended the model to include drug therapy. The drug therapy model is used to assess the potency of the recommended six-month TB drug chemotherapy in infected individuals. The efficacy of each drug was explored and observations show that low drug efficacy values result in extension of treatment period. The numerical results confirm typical clinical disease progression patterns noticed in individuals under TB therapy. The drug model simulations and analysis show that administration of the recommended first line three-drug regimen normally cures the TB infection. Using the model, we established that only Isoniazid monotherapy drug treatment, and any combination therapy of two drugs including Isoniazid are potent enough to resolve the TB infection.

Effects of tree cover and season on soil nitrogen dynamics and microbial biomass in an African savanna woodland dominated by Colophospermum mopane

The objective of this study was to investigate the effects of tree cover and season on soil N dynamics and microbial biomass in a semi-arid southern African savanna in Zimbabwe. We used a randomized complete block design with five blocks of 100 × 100 m, demarcated in a 10-ha pocket of Colophospermum mopane-dominated woodland protected from grazing and fire. In each block, we randomly selected three mopane trees with large canopies (8.3 m crown diameter) and another three with small canopies (2.7 m crown diameter). We determined soil organic carbon and nutrient concentrations, litterfall N and C inputs, microbial biomass and N transformations beneath large and small mopane trees as well as in the intercanopy areas. Soil organic carbon, microbial biomass, N, P and K were more than twice those beneath large trees than in the intercanopy areas. Rainy-season net mineral N accumulation rate in the surface soil (0-10 cm) ranged from 3.71 μg g - 1 mo - 1 in the intercanopy areas to 8.80 μg g - 1 mo - 1 beneath large trees; correspondingly, net nitrate accumulation rate ranged from 1.33 to 3.60 μg g - 1 mo - 1. Dry-season net mineral N and net nitrate accumulation rates were similar across sampling sites and did not exceed 2 and 0.4 μg g - 1 mo - 1, respectively. Litterfall N inputs were positively and significantly correlated with soil N availability, microbial biomass N and N transformations. At all sampling sites, microbial biomass and mineral N pools in the dry season were maximum when soil moisture (∼5%) and N transformations were minimum. In contrast, when soil moisture (9-13%) and N transformations were maximum in the rainy season, microbial biomass and mineral N pools were minimum. It is concluded that the improved soil conditions beneath isolated trees in semi-arid savannas may enhance herbaceous biomass yield especially of canopy shade-tolerant species.

Optimal control for HIV-1 multi-drug therapy

Optimal control theory is applied to a mathematical model that describes the interaction of the immune system with the human immunodeficiency virus (HIV) and that permits the administration of triple HIV drug therapy. The optimal control represents a percentage effect the chemotherapy consisting of fusion inhibitors (FIs), reverse transcriptase inhibitors (RTIs), and protease inhibitors (PIs) has on the interaction of CD4+T-cells with the virus. First, we maximize the benefit based on the T-cell count and minimize the systemic cost based on the percentage of chemotherapies given and then build an objective functional to minimize the viral replication and treatment systemic costs. Our results indicate that highly toxic drugs and small dosage sizes have the potential for improving the quality of life and reducing economic costs of therapy. An optimal control strategy that seeks to maximize CD4+ T-cells has the potential to provide better treatment results over the optimal treatmet strategy that seeks to minimize the viral production. The addition of FIs to the current HIV treatment strategy of RTIs and PIs improves to relax both concentration and dose sizes of RTIs and PIs.

Modeling the TB/HIV-1 Co-Infection and the Effects of Its Treatment

Modeling the interaction of Tuberculosis (TB) and AIDS (HIV) drugs in the treatment of the TB/HIV co-infection shows that the treatment of Mtb (Mycobacterium tuberculosis) and AIDS improves. The administration of HIV drugs without TB drugs during co-infection favors the treatment of HIV, but the patient will eventually die of the Mtb opportunistic infection. Reducing the interaction of TB and HIV drugs and increasing the performance (efficiency of inhibition) of Reverse Transcriptase Inhibitors (RTIs) in CD4+ T cells improves the treatment of HIV and leads to the preferential replication of HIV particles in macrophages. The simultaneous administration of TB and HIV drugs is to be recommended for it prevents patients from dying of the Mtb opportunistic infection.

IN-VIVO MATHEMATICAL STUDY OF CO-INFECTION DYNAMICS OF HIV-1 AND MYCOBACTERIUM TUBERCULOSIS

Human Immunodeficiency Virus type-1 (HIV-1) fuels the pathogenesis of Mycobacterium tuberculosis (Mtb) in humans. We develop a mathematical model in an attempt to understand the immune mechanisms that are involved during the co-infection of Mtb and HIV-1. Our study reveals that infection of an Mtb infected individual with HIV-1 results in fast development of active TB. The mathematical model analysis and simulations show that Mtb infection is linked to HIV infection through macrophages and CD4+ T cells. The study shows that depletion of macrophages and CD4+ T cells by HIV-1 worsens the picture of Mtb infection and in-turn Mtb infection affects the progression of HIV-1 infection since it is also capable of inducing rapid replication of HIV. Our analytical and numerical simulations show that macrophages are a potential reservoir of HIV particles during HIV-1 infection. Co-infection simulations reveal that co-infection exacerbates more the pathogen that caused the first infection. Simulations also show that co-infection disease progression patterns converge to a similar trend after a considerable time interval irrespective of which pathogen first caused infection and the second pathogen that caused co-infection. This work suggests directions for further studies and potential treatment strategies.

THE ROLE OF DENDRITIC CELLS AND OTHER IMMUNE MECHANISMS DURING HUMAN INFECTION WITH MYCOBACTERIUM TUBERCULOSIS

Human immune response mechanisms are crucial in the control of Mycobacterium tuberculosis (Mtb) infection. Understanding the human immune mechanisms and Mtb dynamics will assist in understanding the occurrence of different clinical outcomes experienced by individuals infected with Mtb. This work elaborates the role of dendritic cells (DCs) and other immune mechanisms in Mtb infection. We develop a model to predict disease progression scenarios, that is latency or active disease. Model analysis shows that occurrence of active disease is much attributed to the Mtb pathogens ability to persist outside the intracellular environment and that strong immune response results in latent TB while relatively weak immune response result in active tuberculosis (TB). Our numerical results show that DCs recruitment, antigen (Ag) uptake and maturation affect the priming of the immune response and T cells levels at the site of infection. This study shows the crucial link between the innate immune mechanisms and the adaptive immune mechanisms. It also suggests directions for further basic studies and potential new treatment strategies.