Matthew Bates | University College London (original) (raw)
Papers by Matthew Bates
Journal of Molecular Biology, 2002
Class II fructose 1,6-bisphosphate aldolases (FBP-aldolases) catalyse the zinc-dependent, reversi... more Class II fructose 1,6-bisphosphate aldolases (FBP-aldolases) catalyse the zinc-dependent, reversible aldol condensation of dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P) to form fructose 1,6-bisphosphate (FBP). Analysis of the structure of the enzyme from Escherichia coli in complex with a transition state analogue (phosphoglycolohydroxamate, PGH) suggested that substrate binding caused a conformational change in the b5-a7 loop of the enzyme and that this caused the relocation of two glutamate residues (Glu181 and Glu182) into the proximity of the active site. Site-directed mutagenesis of these two glutamate residues (E181A and E182A) along with another active site glutamate (Glu174) was carried out and the mutant enzymes characterised using steady-state kinetics. Mutation of Glu174 (E174A) resulted in an enzyme which was severely crippled in catalysis, in agreement with its position as a zinc ligand in the enzyme's structure. The E181A mutant showed the same properties as the wild-type enzyme indicating that the residue played no major role in substrate binding or enzyme catalysis. In contrast, mutation of Glu182 (E182A) demonstrated that Glu182 is important in the catalytic cycle of the enzyme. Furthermore, the measurement of deuterium kinetic isotope effects using [1(S)-2 H]DHAP showed that, for the wild-type enzyme, proton abstraction was not the rate determining step, whereas in the case of the E182A mutant this step had become rate limiting, providing evidence for the role of Glu182 in abstraction of the C1 proton from DHAP in the condensation direction of the reaction. Glu182 lies in a loop of polypeptide which contains four glycine residues (Gly176, Gly179, Gly180 and Gly184) and a quadruple mutant (where each glycine was converted to alanine) showed that¯exibility of this loop was important for the correct functioning of the enzyme, probably to change the microenvironment of Glu182 in order to perturb its pK a to a value suitable for its role in proton abstraction. These results highlight the need for further studies of the dynamics of the enzyme in order to fully understand the complexities of loop closure and catalysis in this enzyme.
The European respiratory journal, Jan 25, 2015
We evaluated the diagnostic performance of two tests based on the release of lipoarabinomannan (L... more We evaluated the diagnostic performance of two tests based on the release of lipoarabinomannan (LAM) into the urine, the MTB-LAM-ELISA assay and the Determine TB-LAM-strip assay, in children with suspected tuberculosis (TB) in a high TB/HIV-prevalence setting.In a prospective study, 132 children with suspected active TB were assigned to diagnostic subgroups. Urine samples were subjected to testing by both assays to ascertain sensitivity and specificity. Host factors associated with positive LAM results were investigated and LAM excretion monitored after antituberculous treatment initiation.18 (13.6%) children had culture-confirmed pulmonary TB. The assays' sensitivity was higher in HIV-positive versus HIV-negative children: 70% (95% confidence interval 35-93%) versus 13% (0-53%) for MTB-LAM-ELISA and 50% (19-81%) versus 0% (0-37%) for Determine TB-LAM. In 35 (27%) children with excluded active TB, both assays showed a specificity of 97.1% (85-100%). Proteinuria and low body mass...
International Journal of Infectious Diseases, 2017
The convergence between tuberculosis (TB) and diabetes mellitus (DM) will represent a major publi... more The convergence between tuberculosis (TB) and diabetes mellitus (DM) will represent a major public health challenge in the near future. DM increases the risk of developing TB by two to three times and also increases the risk of TB treatment failure, relapse, and death. The global prevalence of DM is predicted to rise significantly in the next two decades, particularly in some of the low- and middle-income countries with the highest TB burden. Migration may add further complexity to the effort to control the impact on TB of the growing DM pandemic. Migration may increase the risk of DM, although the magnitude of this association varies according to country of origin and ethnic group, due to genetic factors and lifestyle differences. Migrants with TB may have an increased prevalence of DM compared to the native population, and the risk of TB among persons with DM may be higher in migrants than in autochthonous populations. Screening for DM among migrants, screening migrants with DM for active and latent TB, and improving access to DM care, could contribute to mitigate the effects of DM on TB.
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, Jan 12, 2016
Mycobacterium africanum comprises two phylogenetic lineages within the Mycobacterium tuberculosis... more Mycobacterium africanum comprises two phylogenetic lineages within the Mycobacterium tuberculosis complex (MTBC). M. africanum was first described and isolated in 1968 from the sputum of a Senegalese patient with pulmonary tuberculosis (TB) and it has been identified increasingly as an important cause of human TB, particularly prevalent in West Africa. The restricted geographical distribution of M. africanum, in contrast to the widespread global distribution of other species of MTBC, requires explanation. Available data indicate that M. africanum may also have important differences in transmission, pathogenesis, and host-pathogen interactions, which could affect the evaluation of new TB intervention tools (diagnostics and vaccines)-those currently in use and those under development. The unequal geographical distribution and spread of MTBC species means that individual research findings from one country or region cannot be generalized across the continent. Thus, generalizing data fro...
International Journal of Mycobacteriology, 2016
Reviews in Medical Virology, 2016
Lujo virus is a novel Old World arenavirus identified in Southern Africa in 2008 as the cause of ... more Lujo virus is a novel Old World arenavirus identified in Southern Africa in 2008 as the cause of a viral hemorrhagic fever (VHF) characterized by nosocomial transmission with a high case fatality rate of 80% (4/5 cases). Whereas this outbreak was limited, the unprecedented Ebola virus disease outbreak in West Africa, and recent Zika virus disease epidemic in the Americas, has brought into acute focus the need for preparedness to respond to rare but potentially highly pathogenic outbreaks of zoonotic or arthropod-borne viral infections. A key determinant for effective control of a VHF outbreak is the time between primary infection and diagnosis of the index case. Here, we review the Lujo VHF outbreak of 2008 and discuss how preparatory measures with respect to developing diagnostic capacity might be effectively embedded into existing national disease control networks, such as those for human immunodeficiency virus, tuberculosis, and malaria.
BMC Medicine, 2016
Autopsy studies are the gold standard for determining cause-of-death and can inform on improved d... more Autopsy studies are the gold standard for determining cause-of-death and can inform on improved diagnostic strategies and algorithms to improve patient care. We conducted a cross-sectional observational autopsy study to describe the burden of respiratory tract infections in inpatient children who died at the University Teaching Hospital in Lusaka, Zambia. Gross pathology was recorded and lung tissue was analysed by histopathology and molecular diagnostics. Recruitment bias was estimated by comparing recruited and non-recruited cases. Of 121 children autopsied, 64 % were male, median age was 19 months (IQR, 12-45 months). HIV status was available for 97 children, of whom 34 % were HIV infected. Lung pathology was observed in 92 % of cases. Bacterial bronchopneumonia was the most common pathology (50 %) undiagnosed ante-mortem in 69 % of cases. Other pathologies included interstitial pneumonitis (17 %), tuberculosis (TB; 8 %), cytomegalovirus pneumonia (7 %) and pneumocystis Jirovecii pneumonia (5 %). Comorbidity between lung pathology and other communicable and non-communicable diseases was observed in 80 % of cases. Lung tissue from 70 % of TB cases was positive for Mycobacterium tuberculosis by molecular diagnostic tests. A total of 80 % of TB cases were comorbid with malnutrition and only 10 % of TB cases were on anti-TB therapy when they died. More proactive testing for bacterial pneumonia and TB in paediatric inpatient settings is needed.
Expert review of molecular diagnostics, 2016
The unique pathogenesis of tuberculosis (TB) poses several barriers to the development of accurat... more The unique pathogenesis of tuberculosis (TB) poses several barriers to the development of accurate diagnostics: a) the establishment of life-long latency by Mycobacterium tuberculosis (M.tb) after primary infection confounds the development of classical antibody or antigen based assays; b) our poor understanding of the molecular pathways that influence progression from latent to active disease; c) the intracellular nature of M.tb infection in tissues means that M.tb and/or its components, are not readily detectable in peripheral specimens; and d) the variable presence of M.tb bacilli in specimens from patients with extrapulmonary TB or children. The literature on the current portfolio of molecular diagnostics tests for TB is reviewed here and the developmental pipeline is summarized. Also reviewed are data from recently published operational research on the GeneXpert MTB/RIF assay and discussed are the lessons that can be taken forward for the design of studies to evaluate the impac...
International Journal of Infectious Diseases, 2016
The appearance of novel pathogens of humans with epidemic potential and high mortality rates have... more 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.
South African Medical Journal, 2011
The Lancet. Infectious diseases, 2016
International Journal of Infectious Diseases, 2016
Tuberculosis (TB) remains a &... more Tuberculosis (TB) remains a 'global emergency' with an estimated 9.6 million new TB cases worldwide reported in 2014. Of these 28% were in the WHO Africa Region where the annual case detection rate was 281 per 100,000 population -more than double the global average of 133 per 100,000. Of the 9.6 million people who developed TB, an estimated 1.2 million (12%) were HIV-positive and the African Region accounted for 74% of these cases. Three million people with TB remain undiagnosed and untreated. Globally, an estimated 480,000 had multi-drug-resistant TB (MDR-TB). Whilst from Africa, only South Africa has reported high prevalence of MDR-TB, it is likely that all of sub-Saharan Africa has unreported high load of drug resistant TB. Tragically, in 2014 only 48 percent of individuals diagnosed with MDR-TB had successful treatment and estimated 190,000 people died of MDR-TB. Of the global TB funding gap of US$ 0.8 billion, the largest funding gap was in the African Region, amounting to US$ 0.4 billion in 2015. The MDR-TB pandemic in particular now threatens to devastate entire regions and may fundamentally alter the life expectancy and demographic profile of many countries in sub-Saharan Africa. The Theme designated for this year's World Tuberculosis (TB) Day, March 24(th) 2016, is 'Unite to End TB. From the Africa Region, there is an urgent need to seriously address the political, economic and social factors, which influence host-Mycobacterium tuberculosis interactions and result in disease. We discuss recent political and funder initiatives which provide renewed hope for alleviating Africa's TB and TB/HIV problems.
International Journal of Infectious Diseases, 2016
Mass gatherings at major international sporting events put millions of international travelers an... more Mass gatherings at major international sporting events put millions of international travelers and local host-country residents at risk of acquiring infectious diseases, including locally endemic infectious diseases. The mosquito-borne Zika virus (ZIKV) has recently aroused global attention due to its rapid spread since its first detection in May 2015 in Brazil to 22 other countries and other territories in the Americas. The ZIKV outbreak in Brazil, has also been associated with a significant rise in the number of babies born with microcephaly and neurological disorders, and has been declared a 'Global Emergency by the World Health Organization. This explosive spread of ZIKV in Brazil poses challenges for public health preparedness and surveillance for the Olympics and Paralympics which are due to be held in Rio De Janeiro in August, 2016. We review the epidemiology and clinical features of the current ZIKV outbreak in Brazil, highlight knowledge gaps, and review the public health implications of the current ZIKV outbreak in the Americas. We highlight the urgent need for a coordinated collaborative response for prevention and spread of infectious diseases with epidemic potential at mass gatherings events.
International Journal of Infectious Diseases, 2016
Tuberculosis (TB) is now the most common infectious disease cause of death globally. In 2014, an ... more Tuberculosis (TB) is now the most common infectious disease cause of death globally. In 2014, an estimated 9.6 million people developed active TB and there were 3 million people with active TB, including 360,000 with multi-drug resistant TB (MDR-TB) who were not diagnosed and they continue to fuel TB transmission in the community. Accurate data on the actual burden of TB and transmission risk associated with mass gatherings are scanty and unreliable due to small numbers studied and methodological issues. Every year an estimated 10 million pilgrims from 184 countries travel to the Kingdom of Saudi Arabia to perform the Hajj and Umrah pilgrimages. A large majority of pilgrims come from high TB and MDR-TB endemic areas and thus many may have undiagnosed active TB, sub-clinical TB and latent TB infection. The Hajj pilgrimage provide unique opportunities for KSA and the 184 countries from which pilgrims originate, to conduct high quality priority research studies on TB under the remit of the Global Center for Mass Gatherings Medicine. We discuss research opportunities for defining the TB burden, transmission risk, and optimal surveillance, prevention and control measures at the annual Hajj pilgrimage-these data are for developing international recommendations and guidelines for TB management and control at mass gatherings events.
Current Opinion in Pulmonary Medicine, Mar 1, 2011
Annals of translational medicine, 2015
The "Smartphone" is an almost universal possession in high-income populations, and is r... more The "Smartphone" is an almost universal possession in high-income populations, and is rapidly becoming so in lower-income regions, particularly among urban populations, and serves social networking and a quest for information and knowledge. The field of infectious disease diagnostics is at a potential watershed moment, with the essential building blocks for the development of diagnostic assays being ever more available and affordable, which is leading to creative innovative approaches to developing much-needed accurate and simple point-of-care (POC) diagnostic tools for high disease burden, low-income settings. We review the importance and implications of a paper published in Science Translational Medicine on the development of a smartphone-powered and -controlled multiplex immunological assay that tests for HIV and syphilis simultaneously. This is reviewed in the context of other prototype smartphone-enabled/assisted diagnostic devices, and how such developments might sha...
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 2011
International Journal of Infectious Diseases, 2015
Tuberculosis (TB) has been recognized as an important cause of morbidity and mortality in pregnan... more Tuberculosis (TB) has been recognized as an important cause of morbidity and mortality in pregnancy for nearly a century, but research and efforts to roll out comprehensive TB screening and treatment in high-risk populations such as those with a high prevalence of HIV or other diseases of poverty, have lagged behind similar efforts to address HIV infection in pregnancy and the prevention of mother-to-child-transmission. Immunological changes during pregnancy make the activation of latent TB infection or de novo infection more likely than among non-pregnant women. TB treatment in pregnancy poses several problems that have been under-researched, such as contraindications to anti-TB and anti-HIV drugs and potential risks to the neonate, which are particularly important with respect to second-line TB treatment. Whilst congenital TB is thought to be rare, data from high HIV burden settings suggest this is not the case. There is a need for more studies screening for TB in neonates and observing outcomes, and testing preventative or curative actions. National tuberculosis control programmes (NTPs) should work with antenatal and national HIV programmes in high-burden populations to provide screening at antenatal clinics, or to establish functioning systems whereby pregnant women at high risk can drop in to routine NTP screening stations.
New England Journal of Medicine, 2014
Journal of Molecular Biology, 2002
Class II fructose 1,6-bisphosphate aldolases (FBP-aldolases) catalyse the zinc-dependent, reversi... more Class II fructose 1,6-bisphosphate aldolases (FBP-aldolases) catalyse the zinc-dependent, reversible aldol condensation of dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P) to form fructose 1,6-bisphosphate (FBP). Analysis of the structure of the enzyme from Escherichia coli in complex with a transition state analogue (phosphoglycolohydroxamate, PGH) suggested that substrate binding caused a conformational change in the b5-a7 loop of the enzyme and that this caused the relocation of two glutamate residues (Glu181 and Glu182) into the proximity of the active site. Site-directed mutagenesis of these two glutamate residues (E181A and E182A) along with another active site glutamate (Glu174) was carried out and the mutant enzymes characterised using steady-state kinetics. Mutation of Glu174 (E174A) resulted in an enzyme which was severely crippled in catalysis, in agreement with its position as a zinc ligand in the enzyme's structure. The E181A mutant showed the same properties as the wild-type enzyme indicating that the residue played no major role in substrate binding or enzyme catalysis. In contrast, mutation of Glu182 (E182A) demonstrated that Glu182 is important in the catalytic cycle of the enzyme. Furthermore, the measurement of deuterium kinetic isotope effects using [1(S)-2 H]DHAP showed that, for the wild-type enzyme, proton abstraction was not the rate determining step, whereas in the case of the E182A mutant this step had become rate limiting, providing evidence for the role of Glu182 in abstraction of the C1 proton from DHAP in the condensation direction of the reaction. Glu182 lies in a loop of polypeptide which contains four glycine residues (Gly176, Gly179, Gly180 and Gly184) and a quadruple mutant (where each glycine was converted to alanine) showed that¯exibility of this loop was important for the correct functioning of the enzyme, probably to change the microenvironment of Glu182 in order to perturb its pK a to a value suitable for its role in proton abstraction. These results highlight the need for further studies of the dynamics of the enzyme in order to fully understand the complexities of loop closure and catalysis in this enzyme.
The European respiratory journal, Jan 25, 2015
We evaluated the diagnostic performance of two tests based on the release of lipoarabinomannan (L... more We evaluated the diagnostic performance of two tests based on the release of lipoarabinomannan (LAM) into the urine, the MTB-LAM-ELISA assay and the Determine TB-LAM-strip assay, in children with suspected tuberculosis (TB) in a high TB/HIV-prevalence setting.In a prospective study, 132 children with suspected active TB were assigned to diagnostic subgroups. Urine samples were subjected to testing by both assays to ascertain sensitivity and specificity. Host factors associated with positive LAM results were investigated and LAM excretion monitored after antituberculous treatment initiation.18 (13.6%) children had culture-confirmed pulmonary TB. The assays' sensitivity was higher in HIV-positive versus HIV-negative children: 70% (95% confidence interval 35-93%) versus 13% (0-53%) for MTB-LAM-ELISA and 50% (19-81%) versus 0% (0-37%) for Determine TB-LAM. In 35 (27%) children with excluded active TB, both assays showed a specificity of 97.1% (85-100%). Proteinuria and low body mass...
International Journal of Infectious Diseases, 2017
The convergence between tuberculosis (TB) and diabetes mellitus (DM) will represent a major publi... more The convergence between tuberculosis (TB) and diabetes mellitus (DM) will represent a major public health challenge in the near future. DM increases the risk of developing TB by two to three times and also increases the risk of TB treatment failure, relapse, and death. The global prevalence of DM is predicted to rise significantly in the next two decades, particularly in some of the low- and middle-income countries with the highest TB burden. Migration may add further complexity to the effort to control the impact on TB of the growing DM pandemic. Migration may increase the risk of DM, although the magnitude of this association varies according to country of origin and ethnic group, due to genetic factors and lifestyle differences. Migrants with TB may have an increased prevalence of DM compared to the native population, and the risk of TB among persons with DM may be higher in migrants than in autochthonous populations. Screening for DM among migrants, screening migrants with DM for active and latent TB, and improving access to DM care, could contribute to mitigate the effects of DM on TB.
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, Jan 12, 2016
Mycobacterium africanum comprises two phylogenetic lineages within the Mycobacterium tuberculosis... more Mycobacterium africanum comprises two phylogenetic lineages within the Mycobacterium tuberculosis complex (MTBC). M. africanum was first described and isolated in 1968 from the sputum of a Senegalese patient with pulmonary tuberculosis (TB) and it has been identified increasingly as an important cause of human TB, particularly prevalent in West Africa. The restricted geographical distribution of M. africanum, in contrast to the widespread global distribution of other species of MTBC, requires explanation. Available data indicate that M. africanum may also have important differences in transmission, pathogenesis, and host-pathogen interactions, which could affect the evaluation of new TB intervention tools (diagnostics and vaccines)-those currently in use and those under development. The unequal geographical distribution and spread of MTBC species means that individual research findings from one country or region cannot be generalized across the continent. Thus, generalizing data fro...
International Journal of Mycobacteriology, 2016
Reviews in Medical Virology, 2016
Lujo virus is a novel Old World arenavirus identified in Southern Africa in 2008 as the cause of ... more Lujo virus is a novel Old World arenavirus identified in Southern Africa in 2008 as the cause of a viral hemorrhagic fever (VHF) characterized by nosocomial transmission with a high case fatality rate of 80% (4/5 cases). Whereas this outbreak was limited, the unprecedented Ebola virus disease outbreak in West Africa, and recent Zika virus disease epidemic in the Americas, has brought into acute focus the need for preparedness to respond to rare but potentially highly pathogenic outbreaks of zoonotic or arthropod-borne viral infections. A key determinant for effective control of a VHF outbreak is the time between primary infection and diagnosis of the index case. Here, we review the Lujo VHF outbreak of 2008 and discuss how preparatory measures with respect to developing diagnostic capacity might be effectively embedded into existing national disease control networks, such as those for human immunodeficiency virus, tuberculosis, and malaria.
BMC Medicine, 2016
Autopsy studies are the gold standard for determining cause-of-death and can inform on improved d... more Autopsy studies are the gold standard for determining cause-of-death and can inform on improved diagnostic strategies and algorithms to improve patient care. We conducted a cross-sectional observational autopsy study to describe the burden of respiratory tract infections in inpatient children who died at the University Teaching Hospital in Lusaka, Zambia. Gross pathology was recorded and lung tissue was analysed by histopathology and molecular diagnostics. Recruitment bias was estimated by comparing recruited and non-recruited cases. Of 121 children autopsied, 64 % were male, median age was 19 months (IQR, 12-45 months). HIV status was available for 97 children, of whom 34 % were HIV infected. Lung pathology was observed in 92 % of cases. Bacterial bronchopneumonia was the most common pathology (50 %) undiagnosed ante-mortem in 69 % of cases. Other pathologies included interstitial pneumonitis (17 %), tuberculosis (TB; 8 %), cytomegalovirus pneumonia (7 %) and pneumocystis Jirovecii pneumonia (5 %). Comorbidity between lung pathology and other communicable and non-communicable diseases was observed in 80 % of cases. Lung tissue from 70 % of TB cases was positive for Mycobacterium tuberculosis by molecular diagnostic tests. A total of 80 % of TB cases were comorbid with malnutrition and only 10 % of TB cases were on anti-TB therapy when they died. More proactive testing for bacterial pneumonia and TB in paediatric inpatient settings is needed.
Expert review of molecular diagnostics, 2016
The unique pathogenesis of tuberculosis (TB) poses several barriers to the development of accurat... more The unique pathogenesis of tuberculosis (TB) poses several barriers to the development of accurate diagnostics: a) the establishment of life-long latency by Mycobacterium tuberculosis (M.tb) after primary infection confounds the development of classical antibody or antigen based assays; b) our poor understanding of the molecular pathways that influence progression from latent to active disease; c) the intracellular nature of M.tb infection in tissues means that M.tb and/or its components, are not readily detectable in peripheral specimens; and d) the variable presence of M.tb bacilli in specimens from patients with extrapulmonary TB or children. The literature on the current portfolio of molecular diagnostics tests for TB is reviewed here and the developmental pipeline is summarized. Also reviewed are data from recently published operational research on the GeneXpert MTB/RIF assay and discussed are the lessons that can be taken forward for the design of studies to evaluate the impac...
International Journal of Infectious Diseases, 2016
The appearance of novel pathogens of humans with epidemic potential and high mortality rates have... more 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.
South African Medical Journal, 2011
The Lancet. Infectious diseases, 2016
International Journal of Infectious Diseases, 2016
Tuberculosis (TB) remains a &... more Tuberculosis (TB) remains a 'global emergency' with an estimated 9.6 million new TB cases worldwide reported in 2014. Of these 28% were in the WHO Africa Region where the annual case detection rate was 281 per 100,000 population -more than double the global average of 133 per 100,000. Of the 9.6 million people who developed TB, an estimated 1.2 million (12%) were HIV-positive and the African Region accounted for 74% of these cases. Three million people with TB remain undiagnosed and untreated. Globally, an estimated 480,000 had multi-drug-resistant TB (MDR-TB). Whilst from Africa, only South Africa has reported high prevalence of MDR-TB, it is likely that all of sub-Saharan Africa has unreported high load of drug resistant TB. Tragically, in 2014 only 48 percent of individuals diagnosed with MDR-TB had successful treatment and estimated 190,000 people died of MDR-TB. Of the global TB funding gap of US$ 0.8 billion, the largest funding gap was in the African Region, amounting to US$ 0.4 billion in 2015. The MDR-TB pandemic in particular now threatens to devastate entire regions and may fundamentally alter the life expectancy and demographic profile of many countries in sub-Saharan Africa. The Theme designated for this year's World Tuberculosis (TB) Day, March 24(th) 2016, is 'Unite to End TB. From the Africa Region, there is an urgent need to seriously address the political, economic and social factors, which influence host-Mycobacterium tuberculosis interactions and result in disease. We discuss recent political and funder initiatives which provide renewed hope for alleviating Africa's TB and TB/HIV problems.
International Journal of Infectious Diseases, 2016
Mass gatherings at major international sporting events put millions of international travelers an... more Mass gatherings at major international sporting events put millions of international travelers and local host-country residents at risk of acquiring infectious diseases, including locally endemic infectious diseases. The mosquito-borne Zika virus (ZIKV) has recently aroused global attention due to its rapid spread since its first detection in May 2015 in Brazil to 22 other countries and other territories in the Americas. The ZIKV outbreak in Brazil, has also been associated with a significant rise in the number of babies born with microcephaly and neurological disorders, and has been declared a 'Global Emergency by the World Health Organization. This explosive spread of ZIKV in Brazil poses challenges for public health preparedness and surveillance for the Olympics and Paralympics which are due to be held in Rio De Janeiro in August, 2016. We review the epidemiology and clinical features of the current ZIKV outbreak in Brazil, highlight knowledge gaps, and review the public health implications of the current ZIKV outbreak in the Americas. We highlight the urgent need for a coordinated collaborative response for prevention and spread of infectious diseases with epidemic potential at mass gatherings events.
International Journal of Infectious Diseases, 2016
Tuberculosis (TB) is now the most common infectious disease cause of death globally. In 2014, an ... more Tuberculosis (TB) is now the most common infectious disease cause of death globally. In 2014, an estimated 9.6 million people developed active TB and there were 3 million people with active TB, including 360,000 with multi-drug resistant TB (MDR-TB) who were not diagnosed and they continue to fuel TB transmission in the community. Accurate data on the actual burden of TB and transmission risk associated with mass gatherings are scanty and unreliable due to small numbers studied and methodological issues. Every year an estimated 10 million pilgrims from 184 countries travel to the Kingdom of Saudi Arabia to perform the Hajj and Umrah pilgrimages. A large majority of pilgrims come from high TB and MDR-TB endemic areas and thus many may have undiagnosed active TB, sub-clinical TB and latent TB infection. The Hajj pilgrimage provide unique opportunities for KSA and the 184 countries from which pilgrims originate, to conduct high quality priority research studies on TB under the remit of the Global Center for Mass Gatherings Medicine. We discuss research opportunities for defining the TB burden, transmission risk, and optimal surveillance, prevention and control measures at the annual Hajj pilgrimage-these data are for developing international recommendations and guidelines for TB management and control at mass gatherings events.
Current Opinion in Pulmonary Medicine, Mar 1, 2011
Annals of translational medicine, 2015
The "Smartphone" is an almost universal possession in high-income populations, and is r... more The "Smartphone" is an almost universal possession in high-income populations, and is rapidly becoming so in lower-income regions, particularly among urban populations, and serves social networking and a quest for information and knowledge. The field of infectious disease diagnostics is at a potential watershed moment, with the essential building blocks for the development of diagnostic assays being ever more available and affordable, which is leading to creative innovative approaches to developing much-needed accurate and simple point-of-care (POC) diagnostic tools for high disease burden, low-income settings. We review the importance and implications of a paper published in Science Translational Medicine on the development of a smartphone-powered and -controlled multiplex immunological assay that tests for HIV and syphilis simultaneously. This is reviewed in the context of other prototype smartphone-enabled/assisted diagnostic devices, and how such developments might sha...
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 2011
International Journal of Infectious Diseases, 2015
Tuberculosis (TB) has been recognized as an important cause of morbidity and mortality in pregnan... more Tuberculosis (TB) has been recognized as an important cause of morbidity and mortality in pregnancy for nearly a century, but research and efforts to roll out comprehensive TB screening and treatment in high-risk populations such as those with a high prevalence of HIV or other diseases of poverty, have lagged behind similar efforts to address HIV infection in pregnancy and the prevention of mother-to-child-transmission. Immunological changes during pregnancy make the activation of latent TB infection or de novo infection more likely than among non-pregnant women. TB treatment in pregnancy poses several problems that have been under-researched, such as contraindications to anti-TB and anti-HIV drugs and potential risks to the neonate, which are particularly important with respect to second-line TB treatment. Whilst congenital TB is thought to be rare, data from high HIV burden settings suggest this is not the case. There is a need for more studies screening for TB in neonates and observing outcomes, and testing preventative or curative actions. National tuberculosis control programmes (NTPs) should work with antenatal and national HIV programmes in high-burden populations to provide screening at antenatal clinics, or to establish functioning systems whereby pregnant women at high risk can drop in to routine NTP screening stations.
New England Journal of Medicine, 2014