ConSemblEX: A Consensus-Based Transcriptome Assembly Approach that Extends ConSemble and Improves Transcriptome Assembly

An accurate transcriptome is essential to understanding biological systems enabling omics analyses such as gene expression, gene discovery, and gene-regulatory network construction. However, assembling an accurate transcriptome is challenging, especially for organisms without adequate reference genomes or transcriptomes. While several methods for transcriptome assembly with different approaches exist, it is still difficult to establish the most accurate methods. This thesis explores the different transcriptome assembly methods and compares their performances using simulated benchmark transcriptomes with varying complexity. We also introduce ConSemblEX to improve a consensus-based ensemble transcriptome assembler, ConSemble, in three main areas: we provide the ability to use any number of assemblers, provide a variety of consensus assembly outputs, and provide information about the effect of each assembler in the final assembly. Using five assembly methods both in the de novo and genome-guided approaches, we showed how ConSemblEX can be used to explore various strategies for consensus assembly, such as ConSemblEX-4+, to find the optimum assembly. Compared to the original ConSemble, ConSemblEX improved the de novo assembly performance, increasing the precision by 14% and F1 by 5%, and significantly reducing the FP by 49%. In the genome-guided assembly, ConSemblEX had identical performance to the original ConSemble. We showed that ConSemblEX provides tools to explore how different methods perform and behave depending on the datasets. With the ConSemblEX-select assembly, we further demonstrated that we can improve consensus-based assembly more by choosing optimum overlap sets among different methods. Such information provides the foundation to develop machine learning algorithms in the future to further improve transcriptome assembly performance. Adviser: Jitender Deogu

Taking forward a 'One Health' approach for turning the tide against the Middle East respiratory syndrome coronavirus and other zoonotic pathogens with epidemic potential

The appearance of novel pathogens of humans with epidemic potential and high mortality rates have threatened global health security for centuries. Over the past few decades new zoonotic infectious diseases of humans caused by pathogens arising from animal reservoirs have included West Nile virus, Yellow fever virus, Ebola virus, Nipah virus, Lassa Fever virus, Hanta virus, Dengue fever virus, Rift Valley fever virus, Crimean-Congo haemorrhagic fever virus, severe acute respiratory syndrome coronavirus, highly pathogenic avian influenza viruses, Middle East Respiratory Syndrome Coronavirus, and Zika virus. The recent Ebola Virus Disease epidemic in West Africa and the ongoing Zika Virus outbreak in South America highlight the urgent need for local, regional and international public health systems to be be more coordinated and better prepared. The One Health concept focuses on the relationship and interconnectedness between Humans, Animals and the Environment, and recognizes that the health and wellbeing of humans is intimately connected to the health of animals and their environment (and vice versa). Critical to the establishment of a One Health platform is the creation of a multidisciplinary team with a range of expertise including public health officers, physicians, veterinarians, animal husbandry specialists, agriculturalists, ecologists, vector biologists, viral phylogeneticists, and researchers to co-operate, collaborate to learn more about zoonotic spread between animals, humans and the environment and to monitor, respond to and prevent major outbreaks. We discuss the unique opportunities for Middle Eastern and African stakeholders to take leadership in building equitable and effective partnerships with all stakeholders involved in human and health systems to take forward a 'One Health' approach to control such zoonotic pathogens with epidemic potential

Monkeypox - Enhancing Public Health Preparedness for an Emerging Lethal Human Zoonotic Epidemic Threat in the Wake of the Smallpox Post-Eradication Era

The identification of monkeypox in 3 separate patients in the United Kingdom in September raised media and political attention on an emerging public health threat. Nigeria, whose last confirmed case of monkeypox was in 1978, is currently experiencing an unusually large and outbreak of human monkeypox cases, a ‘One Human-Environmental-Animal Health’ approach is being effectively used to define and tackle the outbreak. As of 13th October 2018, there have been one hundred and sixteen confirmed cases the majority of whom are under 40 years. Over the past 20 years ten Central and West African countries have reported monkeypox cases which have risen exponentially. We review the history and evolution of monkeypox outbreaks in Africa and USA, the changing clinical presentations, and discuss possible factors underlying the increasing numbers being detected including the cessation of smallpox vaccination programs. Major knowledge gaps remain on the epidemiology, host reservoir, and emergence, transmission, pathogenesis and prevention of monkeypoz

HIV-1 Viral loas assays for resource-limited settings

Tremendous strides have been made in treating HIV-1 infection in industrialized countries. Combination therapy with antiretroviral (ARV) drugs suppresses virus replication, delays disease progression, and reduces mortality. In industrialized settings, plasma viral load assays are used in combination with CD4 cell counts to determine when to initiate therapy and when a regimen is failing. In addition, unlike serologic assays, these assays may be used to diagnose perinatal or acute HIV-1 infection. Unfortunately, the full benefits of antiretroviral drugs and monitoring tests have not yet reached the majority of HIV-1-infected patients who live in countries with limited resources. In this article we discuss existing data on the performance of alternative viral load assays that might be useful in resource-limited settings

Emergence of new SARS-CoV-2 Variant of Concern Omicron (B.1.1.529) - highlights Africa's research capabilities, but exposes major knowledge gaps, inequities of vaccine distribution, inadequacies in global COVID-19 response and control efforts

Nearly two years since the start of the SARS-CoV-2 pandemic, which has caused over 5 million deaths, the world continues to be on high COVID-19 alert. The World Health Organization (WHO), in collaboration with national authorities, public health institutions and scientists have been closely monitoring and assessing the evolution of SARS-CoV-2 since January 2020 (WHO 2021a; WHO 2021b). The emergence of specific SARS-CoV-2 variants were characterised as Variant of Interest (VOI) and Variant of Concern (VOC), to prioritise global monitoring and research, and to inform the ongoing global response to the COVID-19 pandemic. The WHO and its international sequencing networks continuously monitor SARS-CoV-2 mutations and inform countries about any changes that may be needed to respond to the variant, and prevent its spread where feasible. Multiple variants of the virus have emerged and become dominant in many countries since January 2021, with the Alpha, Beta, Gamma and Delta variants being the most prominent to date. (Table 1)

Is Africa prepared for tackling the COVID-19 (SARS-CoV-2) epidemic. Lessons from past outbreaks, ongoing pan-African public health efforts, and implications for the future

Soon after the novel coronavirus, SARS-CoV-2 (2019-nCoV), was first identified in a cluster of patients with pneumonia (Li et al., 2020), in the Chinese city of Wuhan on 31 December 2019, rapid human to human transmission was anticipated (Hui et al., 2020). The fast pace of transmission is wreaking havoc and stirring media hype and public health concern (Ippolito et al., 2020) globally. When the World Health Organization (WHO) declared the disease, (now officially named COVID-19) a Public Health Emergency of International Concern (PHEIC) on 31st January 2020 (WHO, 2020a), the Director General Dr Tedros Ghebreyesus justified the decision by stating that WHOs greatest concern was the potential for the virus to spread to countries with weaker health systems. Repeated outbreaks of other preventable emerging and re-emerging infectious diseases with epidemic potential have taken their toll on the health systems of many African countries. The devastating 2014–2016 Ebola Virus Epidemic (WHO, 2020b) in West Africa, demonstrated how ill-prepared the affected countries were to rapidly identify the infection and halt transmission (WHO, 2020d, Largent, 2016, Hoffman and Silverberg, 2018, Omoleke et al., 2016). Similarly, the smoldering remnants of the 2018–19 Ebola Virus outbreak in the Democratic Republic of Congo, have demonstrated even for health services with considerable experience of dealing with a certain emerging pathogen, geography and sociopolitical instability, can hamper the response (Aruna et al., 2019)

Drug-resistant tuberculosis: time for visionary political leadership.

Two decades ago, WHO declared tuberculosis a global emergency, and invested in the highly cost-effective directly observed treatment short-course programme to control the epidemic. At that time, most strains of Mycobacterium tuberculosis were susceptible to first-line tuberculosis drugs, and drug resistance was not a major issue. However, in 2013, tuberculosis remains a major public health concern worldwide, with prevalence of multidrug-resistant (MDR) tuberculosis rising. WHO estimates roughly 630 000 cases of MDR tuberculosis worldwide, with great variation in the frequency of MDR tuberculosis between countries. In the past 8 years, extensively drug-resistant (XDR) tuberculosis has emerged, and has been reported in 84 countries, heralding the possibility of virtually untreatable tuberculosis. Increased population movement, the continuing HIV pandemic, and the rise in MDR tuberculosis pose formidable challenges to the global control of tuberculosis. We provide an overview of the global burden of drug-resistant disease; discuss the social, health service, management, and control issues that fuel and sustain the epidemic; and suggest specific recommendations for important next steps. Visionary political leadership is needed to curb the rise of MDR and XDR tuberculosis worldwide, through sustained funding and the implementation of global and regional action plans

Factors influencing neonatal male circumcision uptake among expecting couples in Zambia: formative findings

Male circumcision is a protective HIV prevention strategy. However, uncircumcised Zambian men are reluctant to undergo voluntary medical male circumcision (VMMC). Tailored interventions are necessary to stimulate the uptake of early infant male circumcision (EIMC) and VMMC in Zambia. This feasibility study presents the formative process of utilising the PRECEDE framework in the development of a family-centred EIMC/VMMC intervention, Like Father Like Son, and its application in an existing VMMC intervention, Spear & Shield. We found that fear of the pain associated with EIMC procedures, foreskin disposal, beliefs in children's autonomy and rights, and men's dominance in health decision-making were factors affecting EIMC uptake. Perceived benefits for infants included improved hygiene, protection from HIV infection, and faster recovery. Reinforcing factors included female partners and fathers' MC status. The availability and access to EIMC services and information, skill and experience of health workers, and engagement and belief in traditional circumcision practices were factors enabling EIMC uptake. These individual, interpersonal, and structural factors positively and negatively influencing EIMC uptake in the Zambian clinic context were integrated into the intervention for expecting parents. Feedback from community advisory boards suggested the process was effective in developing a culturally tailored and acceptable EIMC/VMMC promotion intervention

Assessment of the Xpert MTB/RIF Assay for Diagnosis of Tuberculosis with Gastric Lavage Aspirates in Children in Sub-Saharan Africa: A Prospective Descriptive Study

Background: Rapid and accurate diagnosis of pulmonary tuberculosis in children remains challenging because of difficulties in obtaining sputum samples and the paucibacillary nature of the disease. The Xpert MTB/RIF assay is useful for rapid diagnosis of childhood tuberculosis with sputum and nasopharyngeal samples. We assessed this assay for the detection of tuberculosis and multidrug resistant (MDR) tuberculosis with gastric lavage aspirate (GLA) samples in children admitted to hospital. Methods: We did a prospective study to assess the sensitivity and specificity of the Xpert MTB/RIF assay with GLA samples for the detection of pulmonary tuberculosis and MDR tuberculosis in new paediatric inpatient admissions at the University Teaching Hospital, Lusaka, Zambia. Children aged 15 years or younger were recruited between June, 2011, and May, 2012. GLA and sputum were analysed by standard smear-microscopy, mycobacterial growth indicator tube (MGIT) culture, MGIT drug-susceptibility testing, and the Xpert MTB/RIF assay. Sensitivity of the Xpert MTB/RIF assay was assessed with the Pearson χ2 or Fishers exact test. Findings: Of 930 children, 142 produced sputum and GLA was obtained from 788 non-sputum producers. Culture-positive tuberculosis was identified in 58 (6·2%) of 930 children: ten from sputum producers and 48 from GLA of non-sputum producers. The sensitivity and specificity of the Xpert MTB/RIF assay were similar: sensitivity was 68·8% (95% CI 53·6-80·9) for GLA versus 90·0% (54·1-99·5; p=0·1649) for sputum samples; specificity was 99·3% (98·3-99·8) for GLA and 98·5% (94·1-99·7; p=0·2871) for sputum samples. The Xpert MTB/RIF assay detected an extra 28 tuberculosis cases compared with smear microscopy and was significantly more sensitive than smear microscopy for both sputum (90·0% [54·1-99·5] vs 30·0% [8·1-64·6], p=0·01) and GLA (68·8% [53·6-80·9] vs 25·0% [14·1-40·0], p<0·0001). The assay load did not differ significantly by sample type (p=0·791). 22 children were infected with HIV and tuberculosis and significant differences in assay performance could not be detected when stratifying by HIV status for either sample type. The Xpert MTB/RIF assay detected rifampicin resistance in three GLA samples: two confirmed as MDR tuberculosis and one false positive. Interpretation: Analyses of GLA samples with the Xpert MTB/RIF assay is a sensitive and specific method for rapid diagnosis of pulmonary tuberculosis in children who cannot produce sputum. The single site nature of our study invites caution. Funding: European Commission, European Developing Countries Clinical Trials Partnership, and UBS Optimus Foundation. © 2013 Elsevier Ltd