Papers by Alimuddin Zumla
Journal of the Royal Society of Medicine
Viruses
The Republic of Congo (RoC) declared a chikungunya (CHIK) outbreak on 9 February 2019. We conduct... more The Republic of Congo (RoC) declared a chikungunya (CHIK) outbreak on 9 February 2019. We conducted a ONE-Human-Animal HEALTH epidemiological, virological and entomological investigation. Methods: We collected national surveillance and epidemiological data. CHIK diagnosis was based on RT-PCR and CHIKV-specific antibodies. Full CHIKV genome sequences were obtained by Sanger and MinION approaches and Bayesian tree phylogenetic analysis was performed. Mosquito larvae and 215 adult mosquitoes were collected in different villages of Kouilou and Pointe-Noire districts and estimates of Aedes (Ae.) mosquitos’ CHIKV-infectious bites obtained. We found two new CHIKV sequences of the East/Central/South African (ECSA) lineage, clustering with the recent enzootic sub-clade 2, showing the A226V mutation. The RoC 2019 CHIKV strain has two novel mutations, E2-T126M and E2-H351N. Phylogenetic suggests a common origin from 2016 Angola strain, from which it diverged around 1989 (95% HPD 1985–1994). Th...
International Journal of Infectious Diseases
Following greater attention and follow-up of patients with treated pulmonary tuberculosis (TB), i... more Following greater attention and follow-up of patients with treated pulmonary tuberculosis (TB), it has emerged that infections are more likely to occur in this cohort of patients. This comes as no surprise, as pulmonary TB is a destructive process that leads to cicatrization, alteration of parenchyma, bronchiectasis, and scarring of the lung, with reduction of lung volumes and an impact on pulmonary function. In addition to relapse and re-infection with TB, other pathogens are increasingly recognized in post-TB patients. This paper serves as a summary and guide on how to approach the post-TB patient with new signs and symptoms of pulmonary infection in order to ensure optimal management and rehabilitation.
The Lancet Planetary Health
Outbreaks of deadly zoonotic diseases with epidemic potential have plagued humans for centuries. ... more Outbreaks of deadly zoonotic diseases with epidemic potential have plagued humans for centuries. While global attention is currently focused on the WHO Blueprint list of priority diseases, which include Crimean-Congo haemorrhagic fever, Ebola, Marburg, Lassa fever, Middle East respiratory syndrome, Rift Valley fever, Nipah and henipaviral diseases, there are other, neglected, zoonoses, 1 which also need attention. A good example of this neglect is anthrax, 2 caused by the bacterium Bacillus anthracis. Anthrax is frequently fatal in domestic and wild animals and large outbreaks can occur in both groups. 2 Anthrax can also be lethal in humans, causing overwhelming gastrointestinal or pulmonary disease. 2 B anthracis is ubiquitous and can survive as a viable spore under extreme weather conditions in the soil for a 100 years, 3 and thus cannot be eradicated. Anthrax remains a severely under-reported disease in Africa, Asia, and South America, where humans frequently butcher and eat animals infected with B anthracis. 4,5 It is unlikely that this situation will change in the mediumterm because public health services in these regions are inadequately prepared and resourced to address the recurrent, widespread, sporadic anthrax outbreaks according to best public health practice. 6 In livestockdependent communities, survival is closely linked to the health of their animals. When sickness prevails, decisions on disposing of animals are sometimes in conflict with the need to use or consume this precious resource, putting the community at risk of anthrax exposure. Anthrax in wildlife is neglected because of the absence of legal or economic incentives to promote wildlife health. WHO recommendations 6 for disposal of carcasses do not fully appreciate practical context and resource barriers to employ these measures in anthrax-endemic communities. Destroying carcasses by burying or incineration is costly, and frozen, flooded, treeless, or rocky ground can make this virtually impossible. Consequently, carcasses are often left to rot or are discarded into flooding rivers. 5 Billions of B anthracis spores are released into soil and the environment as a result. Furthermore, domestic animals now dominate the global mammal biomass 7 on a shrinking rangeland. This dominance is leading to high densities of livestock in some regions, and persistent anthrax hotspots.
International Journal of Infectious Diseases
Tuberculin skin test (TST) is over a century old but it continues to be used widely. When IGRAs... more Tuberculin skin test (TST) is over a century old but it continues to be used widely. When IGRAs were introduced it was anticipated that they would rapidly replace TST. Neither TST nor IGRAs have a high accuracy for predicting active TB. Latest WHO recommendation are that either TST or IGRA can be used to test for LTBI. TST will be clinically useful until more accurate tests become available.
Latent TB Infection (LTBI) – Mycobacterium tuberculosis pathogenesis and the dynamics of the granuloma battleground
International Journal of Infectious Diseases
International Journal of Infectious Diseases
Tuberculosis endemic countries. Tuberculosis is an important infectious disease cause of morbid... more Tuberculosis endemic countries. Tuberculosis is an important infectious disease cause of morbidity and death in transplant recipients. Tuberculosis can also cause loss of kidney allograft Screening of both donor and recipient for latent TB infection (LTBI) pretransplant is required A high degree of clinical awareness of the possibility of active TB disease or LTBI is required for early diagnosis and treatment.
International Journal of Infectious Diseases
International Journal of Infectious Diseases
The changing treatment landscape for MDR/XDR-TB-can current clinical trials revolutionise and inf... more The changing treatment landscape for MDR/XDR-TB-can current clinical trials revolutionise and inform a brave new world?.
International Journal of Infectious Diseases
Multidrug-resistant TB (MDR-TB) is a major threat to global health. In 2017, only 50% of patients... more Multidrug-resistant TB (MDR-TB) is a major threat to global health. In 2017, only 50% of patients with MDR-TB who received WHO-recommended treatment were cured. Most MDR-TB patients who recover continue to suffer from functional disability due to lung damage. Whilst new MDR-TB treatment regimens are becoming available, conventional drug therapies need to be complemented with hostdirected therapies (HDTs) to reduce tissue damage and improve functional treatment outcomes. This viewpoint highlights recent data on biomarkers, immune cells, circulating effector molecules and genetics which could be utilised for developing personalised HDTs. Novel technologies currently used for cancer therapy which could facilitate in-depth understanding of host genetics and the microbiome in patients with MDR-TB are discussed. Against this background, personalised cell-based HDTs for adjunct MDR-TB treatment to improve clinical outcomes are proposed as a possibility for complementing standard therapy and other HDT agents. Insights into the molecular biology of the mechanisms of action of cellular HDTs may also aid to devise non-cell-based therapies targeting defined inflammatory pathway (s) in Mtb-driven immunopathology.
The Lancet. Respiratory medicine, Apr 1, 2018
International Journal of Infectious Diseases
On September 26, 2018, history will be made. For the first time ever, the United Nations General ... more On September 26, 2018, history will be made. For the first time ever, the United Nations General Assembly will meet in New York (WHO, 2018a,b) with a specific focus on tuberculosis (TB), which is the leading cause of death from an infectious disease worldwide (WHO, 2017). The theme of the meeting is 'United to End TB: An Urgent Global Response to a Global Epidemic' (United Nations, 2018a). Heads of state will gather in New York at the first-ever United Nations General Assembly High-Level Meeting on Tuberculosis (UNGA-HLM-TB) to accelerate efforts in ending TB and reach all affected people with prevention and care. This unprecedented meeting has focused global attention and generated high expectations of a major 'step-up' change for advancing political will to bring the devastating global TB epidemic under control. The UNGA-HLM-TB will be attended by heads of state, government ministers, the UN Secretary General, other UN leaders, parliamentarians, scientists, healthcare workers, civil society, community representatives, private sector individuals, and UN ambassadors, among other advocates (United Nations, 2018b). The UNGA-HLM-TB will be only the fifth time in the history of the United Nations that the General Assembly has called for a highlevel meeting devoted to a specific health issue.
International Journal of Infectious Diseases
The identification of monkeypox in 3 separate patients in the United Kingdom in September raised ... more 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.
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, Mar 1, 2018
World TB Day, March 24th commemorates the day in March 1882 when Professor Robert Koch made the g... more World TB Day, March 24th commemorates the day in March 1882 when Professor Robert Koch made the groundbreaking announcement in Berlin of his discovery of Mycobacterium tuberculosis as the cause of Tuberculosis (TB) (Koch, 1882). At the time of his announcement, there was a deadly TB epidemic, rampaging throughout Europe and the Americas, causing the death of one out of every seven people. Since Koch's announcement, Mycobacterium tuberculosis has defied worldwide efforts by public health systems, researchers, governments and the World Health Organization (WHO) to eradicate it. The data presented in the WHO Global TB Report 2017 (World Health Organization, 2017a) makes very gruesome reading. In 2016 there were an estimated 10.4 million people who developed TB disease worldwide, of which 90% were adults, 35% female and 10% were HIV-co-infected people. An estimated 40% of active TB cases go undiagnosed each year. One hundred and thirty-six years since Koch's announcement, TB remains a major global public health issue and TB has surpassed HIV/AIDS and malaria as the world's top cause of death from an infectious disease! On World TB Day, March 24th, 2018, we need to reflect on the current status quo of the continuing devastating global TB epidemic. For a disease which has had effective treatment available for the past 50 years, TB exerts a huge and unacceptable global impact on morbidity and mortality rates. In 2016, TB caused the unnecessary deaths of an estimated 1.7 million people of which 0.4 million were among people living with HIV (World Health Organization, 2017a). Thirty high TB burden countries accounted for 87% of the 10.4 million incident TB cases globally. Five countries, India, Indonesia, China, the Philippines and Pakistan accounted for 56% of the 10.4 million cases. Of these, China, India and Indonesia accounted for 45% of total global cases in 2016 and Nigeria and South Africa each accounted for 4% (Koch, 1882). Drug-resistant TB (DR-TB) has been reported from every corner of the globe and has become an ominous threat to global health security. In 2016, there were 600,000 new cases with resistance to rifampicin (RR-TB), of which 490,000 had multidrug-resistant TB (MDR-TB) defined as resistance to rifampicin and isoniazid. Worryingly, three high TB endemic countries with strong and growing economies, India, China and the Russian Federation, had almost half (47%) of the 490,000 MDR-TB cases. Extensively drug resistant TB (XDR-TB, defined as MDR-TB plus resistance to any fluoroquinolone and at least one of three injectable second-line drugs, amikacin,
Concrete action now: UN High-Level Meeting on Tuberculosis
The Lancet. Infectious diseases, Jan 23, 2018
Clinical Infectious Diseases
Background. Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant de... more Background. Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant determination of routine laboratory biomarkers and Ebola viremia to explore the potential role of viral replication in specific organ damage. Methods. We recruited patients with detectable Ebola viremia admitted to the EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilità Sociale (ONG ONLUS) Ebola Treatment Center in Sierra Leone. Repeated measure of Ebola viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), activated prothrombin time (aPTT), international normalized ratio (INR), creatinine, and blood urea nitrogen (BUN) were recorded. Patients were followed up from admission until death or discharge. Results. One hundred patients (49 survivors and 51 nonsurvivors) were included in the analysis. Unadjusted analysis to compare survivors and nonsurvivors provided evidence that all biomarkers were significantly above the normal range and that the extent of these abnormalities was generally higher in nonsurvivors than in survivors. Multivariable mixed-effects models provided strong evidence for a biological gradient (suggestive of a direct role in organ damage) between the viremia levels and either ALT, AST, CPK LDH, aPTT, and INR. In contrast, no direct linear association was found between viremia and either creatinine, BUN, or bilirubin. Conclusions. This study provides evidence to support that Ebola virus may have a direct role in muscular damage and imbalance of the coagulation system. We did not find strong evidence suggestive of a direct role of Ebola virus in kidney damage. The role of the virus in liver damage remains unclear, but our evidence suggests that acute severe liver injury is not a typical feature of Ebola virus disease.
Scientific reports, Jan 24, 2017
The definition of the immunological response to Zika (ZIKV) infection in humans represents a key ... more The definition of the immunological response to Zika (ZIKV) infection in humans represents a key issue to identify protective profile useful for vaccine development and for pathogenesis studies. No data are available on the cellular immune response in the acute phase of human ZIKV infection, and its role in the protection and/or pathogenesis needs to be clarified. We studied and compared the phenotype and functionality of T-cells in patients with acute ZIKV and Dengue viral (DENV) infections. A significant activation of T-cells was observed during both ZIKV and DENV infections. ZIKV infection was characterized by a CD4 T cell differentiation toward effector cells and by a lower frequency of IFN-γ producing CD4 T cells. Moreover, a substantial expansion of CD3(+)CD4(-)CD8(-) T-cell subset expressing Vδ2 TCR was specifically observed in ZIKV patients. Vδ2 T cells presented a terminally differentiated profile, expressed granzyme B and maintained their ability to produce IFN-γ. These fi...
The European respiratory journal, May 1, 2017
Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resist... more Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) t...
International journal of mycobacteriology, 2016
Tuberculosis (TB) causes 1.3 million deaths annually. There are 0.5 million cases of multidrug re... more Tuberculosis (TB) causes 1.3 million deaths annually. There are 0.5 million cases of multidrug resistant TB (MDR-TB) and the number of cases is rising globally. The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/extensively drug-resistant TB, and those with comorbidity of TB with human immunodeficiency virus and noncommunicable diseases in sub-Saharan Africa is unacceptable. The TB drug pipeline remains sparse. New innovations for shortening the duration of therapy and improving treatment outcomes (cure and long-term functional disability due to lung damage) are urgently required. A wide range of host-directed therapies (HDT) are now available which require evaluation as adjuncts to current TB drug treatment. Examples are: The Host-directed Therapies Network consortium of 64 partners was launched in Cape Town after a meeting hosted by the South African Medical Research Council in April 2015. This network (which is open to anyone ...
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Papers by Alimuddin Zumla