scispace - formally typeset
Search or ask a question
Author

Sadia Shakoor

Bio: Sadia Shakoor is an academic researcher from Aga Khan University. The author has contributed to research in topics: Medicine & Tuberculosis. The author has an hindex of 19, co-authored 97 publications receiving 2326 citations. Previous affiliations of Sadia Shakoor include The Aga Khan University Hospital & Aga Khan University Hospital.
Topics: Medicine, Tuberculosis, Serotype, Population, Biology


Papers
More filters
Journal ArticleDOI
TL;DR: The findings suggest that although single-pathogen strategies have an important role in the reduction of the burden of severe diarrhoea disease, the effect of such interventions on total diarrhoeal incidence at the community level might be limited.

668 citations

Journal ArticleDOI
07 Mar 2018-Mbio
TL;DR: The first large-scale emergence and spread of a novel extensively drug-resistant S. Typhi clone in Sindh, Pakistan is reported, highlighting the evolving threat of antibiotic resistance in S. typhi and the value of antibiotic susceptibility testing and whole-genome sequencing in understanding emerging infectious diseases.
Abstract: Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom. Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable genetic clonality and sequence conservation, identified a large number of resistance determinants, and showed that these isolates were of haplotype H58. The XDR S Typhi clone encodes a chromosomally located resistance region and harbors a plasmid encoding additional resistance elements, including the blaCTX-M-15 extended-spectrum β-lactamase, and carrying the qnrS fluoroquinolone resistance gene. This antibiotic resistance-associated IncY plasmid exhibited high sequence identity to plasmids found in other enteric bacteria isolated from widely distributed geographic locations. This study highlights three concerning problems: the receding antibiotic arsenal for typhoid treatment, the ability of S Typhi to transform from MDR to XDR in a single step by acquisition of a plasmid, and the ability of XDR clones to spread globally.IMPORTANCE Typhoid fever is a severe disease caused by the Gram-negative bacterium Salmonella enterica serovar Typhi. Antibiotic-resistant S Typhi strains have become increasingly common. Here, we report the first large-scale emergence and spread of a novel extensively drug-resistant (XDR) S Typhi clone in Sindh, Pakistan. The XDR S Typhi is resistant to the majority of drugs available for the treatment of typhoid fever. This study highlights the evolving threat of antibiotic resistance in S Typhi and the value of antibiotic susceptibility testing and whole-genome sequencing in understanding emerging infectious diseases. We genetically characterized the XDR S Typhi to investigate the phylogenetic relationship between these isolates and a global collection of S Typhi isolates and to identify multiple genes linked to antibiotic resistance. This S Typhi clone harbored a promiscuous antibiotic resistance plasmid previously identified in other enteric bacteria. The increasing antibiotic resistance in S Typhi observed here adds urgency to the need for typhoid prevention measures.

478 citations

Journal ArticleDOI
Angel Mendez Acosta, Cesar Banda Chavez, Julian Torres Flores, Maribel Paredes Olotegui, Silvia Rengifo Pinedo, Dixner Rengifo Trigoso, Angel Orbe Vasquez, Imran Ahmed, Didar Alam, Asad Ali, Zulfiqar A Bhutta, Shahida Qureshi, Sadia Shakoor, Sajid Bashir Soofi, Ali Turab, Aisha K. Yousafzai, Anita K. M. Zaidi, Ladaporn Bodhidatta, Carl J. Mason, Sudhir Babji, Anuradha Bose, Sushil John, Gagandeep Kang, Beena Kurien, Jayaprakash Muliyil, Mohan Venkata Raghava, Anup Ramachandran, Anuradha Rose, William Pan, Ramya Ambikapathi, Danny Carreon, Vivek Charu, Leyfou Dabo, Viyada Doan, Jhanelle Graham, Christel Hoest, Stacey Knobler, Dennis Lang, Benjamin J.J. McCormick, Monica McGrath, Mark A. Miller, Archana Mohale, Gaurvika M. L. Nayyar, Stephanie Psaki, Zeba A Rasmussen, Stephanie A. Richard, Jessica C. Seidman, Vivian Ota Wang, Rebecca Blank, Michael Gottlieb, Karen H. Tountas, Caroline Amour, Estomih Mduma, Tahmeed Ahmed, AM Shamsir Ahmed, Mondol Dinesh, Fahmida Tofail, Rashidul Haque, Iqbal Hossain, M Munirul Islam, Mustafa Mahfuz, Ram Krishna Chandyo, Prakash Shrestha, Rita Shrestha, Manjeswori Ulak, Robert E. Black, Laura E. Caulfield, William Checkley, Ping Chen, Margaret Kosek, Gwenyth O. Lee, Pablo Peñataro Yori, Laura E. Murray-Kolb, Barbara A. Schaefer, Laura L. Pendergast, Cláudia B. Abreu, Alexandre Havt Bindá, H. Costa, Alessandra Di Moura, José Q. Filho, Álvaro M. Leite, Aldo A. M. Lima, Noélia L. Lima, Ila F. N. Lima, Bruna Leal Lima Maciel, Milena Lima de Moraes, Francisco Suetônio Bastos Mota, Reinaldo B. Oriá, Josiane da Silva Quetz, Alberto M. Soares, Erling Svensen, Strand Tor, Crystal L. Patil, Pascal O. Bessong, Cloupas Mahopo, Angelina Mapula, Cebisa Nesamvuni, Emanuel Nyathi, Amidou Samie, Leah J. Barrett, Jean Gratz, Richard Guerrant, Eric R. Houpt, Liz Olmsted, William A. Petri, James A Platts-Mills, Rebecca J. Scharf, Binob Shrestha, Sanjaya K. Shrestha 
TL;DR: The hypothesis is that enteropathogen infection contributes to undernutrition by causing intestinal inflammation and/or by altering intestinal barrier and absorptive function, and it is further postulated that this leads to growth faltering and deficits in cognitive development.
Abstract: MILLER, Mark ; GOTTLIEB, Michael ; BHUTTA, Zulfiqar ; KANG, Gagandeep ; JOHN, Sushil ; KOSEK, Margaret ; LIMA, Aldo A. M. ; ORIA, Reinaldo ; SHRESTHA, Sanjaya Kumar ; SHRESTHA, Prakash Sunder ; BESSONG, Pascal ; AHMED, Tahmeed ; HAQUE, Rashidul ; SVENSE, Erling ; CAULFIELD, Laura ; MURRAY-KOL, Laura ; BLACK, Robert ; GUERRANT, Richard ; PETRIF, William ; HOUPTH, Eric ; CONCANNON, Patrick ; RICH, Stephen ; DILLINGHAM, Rebecca ; MASON, Carl J. ; BODHIDATTA, Ladaporn ; GORDON, Jeffrey I. ; KNIGH, Rob ; WUK, Felicia. The MAL-ED study : a multinational and multidisciplinary approach to understand the relationship between enteric pathogens, malnutrition, gut physiology, physical growth, cognitive development, and immune responses in infants and children up to 2 years of age in resource-poor environments. Clinical Infectious Diseases, v. 59, p. S193-S206, 2014.

306 citations

Journal ArticleDOI
TL;DR: A association between Campylobacter and linear growth shortfalls and both increased intestinal permeability and intestinal and systemic inflammation is demonstrated and potential interventions are identified.
Abstract: Background. Enteropathogen infections have been associated with enteric dysfunction and impaired growth in children in low-resource settings. In a multisite birth cohort study (MAL-ED), we describe the epidemiology and impact of Campylobacter infection in the first 2 years of life. Methods. Children were actively followed up until 24 months of age. Diarrheal and nondiarrheal stool samples were collected and tested by enzyme immunoassay for Campylobacter. Stool and blood samples were assayed for markers of intestinal permeability and inflammation. Results. A total of 1892 children had 7601 diarrheal and 26 267 nondiarrheal stool samples tested for Campylobacter. We describe a high prevalence of infection, with most children (n = 1606; 84.9%) having a Campylobacter-positive stool sample by 1 year of age. Factors associated with a reduced risk of Campylobacter detection included exclusive breastfeeding (risk ratio, 0.57; 95% confidence interval, .47–.67), treatment of drinking water (0.76; 0.70–0.83), access to an improved latrine (0.89; 0.82–0.97), and recent macrolide antibiotic use (0.68; 0.63–0.74). A high Campylobacter burden was associated with a lower length-for-age Z score at 24 months (−1.82; 95% confidence interval, −1.94 to −1.70) compared with a low burden (−1.49; −1.60 to −1.38). This association was robust to confounders and consistent across sites. Campylobacter infection was also associated with increased intestinal permeability and intestinal and systemic inflammation. Conclusions. Campylobacter was prevalent across diverse settings and associated with growth shortfalls. Promotion of exclusive breastfeeding, drinking water treatment, improved latrines, and targeted antibiotic treatment may reduce the burden of Campylobacter infection and improve growth in children in these settings.

142 citations

Journal ArticleDOI
Stephanie W. Lo1, Rebecca A. Gladstone1, Andries J. van Tonder1, John A. Lees2, Mignon du Plessis, Rachel Benisty3, Noga Givon-Lavi3, Paulina A. Hawkins4, Jennifer E. Cornick5, Brenda Kwambana-Adams6, Brenda Kwambana-Adams7, Pierra Y. Law8, Pak-Leung Ho8, Martin Antonio6, Dean Everett9, Ron Dagan3, Anne von Gottberg, Keith P. Klugman4, Lesley McGee10, Robert F. Breiman4, Stephen D. Bentley1, Abdullah Brooks, Alejandra Corso, Alexander Davydov, Alison J. Maguire, Andrew J. Pollard, Anmol M. Kiran, Anna Skoczynska, Benild Moiane, Bernard Beall, Betuel Sigaúque, David M. Aanensen, Deborah Lehmann, Diego Faccone, Ebenezer Foster-Nyarko, Ebrima Bojang, Ekaterina Egorova, Elena Voropaeva, Eric Sampane-Donkor, Ewa Sadowy, Godfrey Bigogo, Helio Mucavele, Houria Belabbès, Idrissa Diawara, Jennifer C. Moïsi, Jennifer R. Verani, Jeremy D. Keenan, Jyothish N Nair Thulasee Bhai, Kedibone M. Ndlangisa, Khalid Zerouali, K L Ravikumar, Leonid Titov, Linda de Gouveia, Maaike Alaerts, Margaret Ip, Maria Cristina de Cunto Brandileone, Hasanuzzaman, Metka Paragi, Michele Nurse-Lucas, Mushal Ali, Naima Elmdaghri, Nicholas J. Croucher, Nicole Wolter, Nurit Porat, Ozgen Koseoglu Eser, Patrick Eberechi Akpaka, Paul Turner, Paula Gagetti, Peggy-Estelle Tientcheu, Philip E. Carter, Rafal Mostowy, Rama Kandasamy, Rebecca Ford, Rebecca Henderson, Roly Malaker, Sadia Shakoor, Samanta Cristine Grassi Almeida, Samir K. Saha, Sanjay Doiphode, Shabir A. Madhi, Shamala Devi Sekaran, Somporn Srifuengfung, Stephen K. Obaro, Stuart C. Clarke, Susan A. Nzenze, Tamara Kastrin, Theresa J. Ochoa, Veeraraghavan Balaji, Waleria Hryniewicz, Yulia Urban 
TL;DR: In this paper, a whole-genome sequenced 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programs in Hong Kong (n=78), Israel, South Africa, Malawi, Nigeria, The Gambia, and USA were collected from children younger than 3 years.
Abstract: Summary Background Invasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global Pneumococcal Sequence Clusters (GPSCs) by analysing 20 027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanism of serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits. Methods We whole-genome sequenced 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programmes in Hong Kong (n=78), Israel (n=701), Malawi (n=226), South Africa (n=1351), The Gambia (n=203), and the USA (n=674). The genomes represented pneumococci from before and after pneumococcal conjugate vaccine (PCV) introductions and were from children younger than 3 years. We identified predominant serotypes by prevalence and their major contributing lineages in each country, and assessed any serotype replacement by comparing the incidence rate between the pre-PCV and PCV periods for Israel, South Africa, and the USA. We defined the status of a lineage as vaccine-type GPSC (≥50% 13-valent PCV [PCV13] serotypes) or non-vaccine-type GPSC (>50% non-PCV13 serotypes) on the basis of its initial serotype composition detected in the earliest vaccine period to measure their individual contribution toward serotype replacement in each country. Major pneumococcal lineages in the PCV period were identified by pooled incidence rate using a random effects model. Findings The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. These serotypes were associated with more than one lineage, except for serotype 5 (GPSC8). Serotype replacement was mainly mediated by expansion of non-vaccine serotypes within vaccine-type GPSCs and, to a lesser extent, by increases in non-vaccine-type GPSCs. A globally spreading lineage, GPSC3, expressing invasive serotypes 8 in South Africa and 33F in the USA and Israel, was the most common lineage causing non-vaccine serotype invasive pneumococcal disease in the PCV13 period. We observed that same prevalent non-vaccine serotypes could be associated with distinctive lineages in different countries, which exhibited dissimilar antibiotic resistance profiles. In non-vaccine serotype isolates, we detected significant increases in the prevalence of resistance to penicillin (52 [21%] of 249 vs 169 [29%] of 575, p=0·0016) and erythromycin (three [1%] of 249 vs 65 [11%] of 575, p=0·0031) in the PCV13 period compared with the pre-PCV period. Interpretation Globally spreading lineages expressing invasive serotypes have an important role in serotype replacement, and emerging non-vaccine serotypes associated with different pneumococcal lineages in different countries might be explained by local antibiotic-selective pressures. Continued genomic surveillance of the dynamics of the pneumococcal population with increased geographical representation in the post-vaccine period will generate further knowledge for optimising future vaccine design. Funding Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control.

133 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.

10,401 citations

Journal ArticleDOI
TL;DR: All-cause age-standardised YLD rates decreased by 3·9% from 1990 to 2017; however, the all-age YLD rate increased by 7·2% while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100).

7,419 citations

Journal ArticleDOI
TL;DR: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors.
Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

6,968 citations

Journal ArticleDOI
TL;DR: The global situation of antibiotic resistance, its major causes and consequences, and key areas in which action is urgently needed are described and identified.
Abstract: The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.

3,181 citations