T3 ONE HEALTH MALAWI Research Papers AMR


T3 ONE HEALTH MALAWI Research Papers AMR

AMR - AntiMicrobial Resistance

2021

  • TITLE - Whole genome sequence analysis of Shigella from Malawi identifies fluoroquinolone resistance
  • AUTHOR - George E. Stenhouse, Khuzwayo C. Jere, Chikondi Peno, Rebecca J. Bengtsson, End Chinyama, Jonathan Mandolo, Amy Cain, Miren Iturriza-Gmara, Naor Bar-Zeev, Nigel A. Cunliffe, Jennifer Cornick, Kate S. Baker
  • JOURNAL - Microbial Genomics
  • ABSTRACT - Increasing antimicrobial resistance and limited alternative treatments have led to fluoroquinolone-resistant Shigella strain inclusion on the WHO global priority pathogens list. In this study we characterized multiple Shigella isolates from Malawi with whole genome sequence analysis, identifying the acquirable fluoroquinolone resistance determinant qnrS1. 
  • ISSUE - 5
  • VOLUME - 7
  • DOI - 10.1099/mgen.0.000532

2022

  • TITLE - Understanding antimicrobial use in subsistence farmers in Chikwawa District Malawi, implications for public awareness campaigns
  • AUTHOR - Eleanor E MacPherson, Joanna Reynolds, Esnart Sanudi, Alexander Nkaombe, Chimwemwe Phiri, John Mankhomwa, Justin Dixon, Clare I R Chandler
  • JOURNAL - PLOS Global Public Health
  • ABSTRACT - Drug resistant infections are increasing across the world and urgent action is required to preserve current classes of antibiotics. Antibiotic use practices in low-and-middle-income countries have gained international attention, especially as antibiotics are often accessed beyond the formal health system. Public awareness campaigns have gained popularity, often conceptualising antimicrobial resistance (AMR) as a problem of excess, precipitated by irrational behaviour. Insufficient attention has been paid to people‚ lived experiences of accessing medicines in low-income contexts. In Chikwawa District, Malawi, a place of extreme scarcity, our study aimed to understand the care and medicine use practices of households dependent on subsistence farming. Adopting an anthropological approach, we undertook medicine interviews (100), ethnographic fieldwork (six-month period) and key informant interviews (33) with a range of participants in two villages in rural Chikwawa. The most frequently used drugs were cotrimoxazole and amoxicillin, not considered to be of critical importance to human health. Participants recognised that keeping, sharing, and buying medicines informally was not the right thing. However, they described using antibiotics and other medicines in these ways due to conditions of extreme precarity, the costs and limitations of seeking formal care in the public sector, and the inevitability of future illness. Our findings emphasise the need in contexts of extreme scarcity to equip policy actors with interventions to address AMR through strengthening health systems, rather than public awareness campaigns that foreground overuse and the dangers of using antibiotics beyond the formal sector. 
  • ISSUE - 6 
  • VOLUME - 2
  • DOI - 10.1371/journal.pgph.0000314

2021

  • TITLE - Understanding antimicrobial resistance through the lens of antibiotic vulnerabilities in primary health care in rural Malawi
  • AUTHOR - Eleanor E MacPherson, Joanna Reynolds, Esnart Sanudi, Alexander Nkaombe, Chimwemwe Phiri, John Mankhomwa, Justin Dixon, Clare I R Chandler
  • JOURNAL - Global Public Health
  • ABSTRACT - The diminishing effectiveness of antimicrobials raises serious concerns for human health. While policy makers grapple to reduce the overuse of antimicrobial medicines to stem the rise of antimicrobial resistance, insufficient attention has been paid to how this applies to low-resource contexts. We provide an in-depth portrayal of antimicrobial prescribing at primary health care level in rural Chikwawa District, Malawi. Ethnographic fieldwork took place over 18 months (2018-2020). We surveyed 22 health facilities in the district, observed 1348 health worker-patient consultations, and carried out 49 in-depth interviews with staff and patients. Care was centred around provision of an antimicrobial. Amid chronic lack of essential medicines and other resources, clinic interactions were tightly scripted, providing patients little time to question or negotiate their treatment. We develop the concept of 'antibiotic vulnerabilities' to reveal multiple ways in which provision of antimicrobials in rural Malawi impacts care in conditions of extreme scarcity. Antibiotics are central and essential to primary care. As targets for optimal antimicrobial prescribing take a more central role in global policy, close attention is required of the ramifications for the delivery of care to ensure that efforts to stem resistance do not undermine the goal of improved health for all.
  • DOI - 10.1080/17441692.2021.2015615

2021

  • TITLE- The metabolic, virulence and antimicrobial resistance profiles of colonizing Streptococcus pneumoniae shift after pneumococcal vaccine introduction in urban Malawi
  • AUTHOR - Andrea Gori, Uri Obolski, Todd D. Swarthout, Jos Louren, Caroline M. Weight, Jen Cornick, Arox Kamng‚ Thandie S. Mwalukomo, Jacquline Msefula, Comfort Brown, Martin C. Maiden, Neil French, Sunetra Gupta, Robert S. Heyderman
  • JOURNAL - medRxiv
  • ABSTRACT - Streptococcus pneumoniae accounts for at least 300,000 deaths from pneumonia, septicaemia and meningitis among children under 5-years-old worldwide. Protein‚Äìpolysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten to undermine this success. Here, we address the hypothesis that following vaccine introduction in high disease and carriage burden settings, adapted pneumococcal genotypes emerge with the potential to facilitate vaccine escape. We show that beyond serotype replacement, there are marked changes in S. pneumoniae carriage population genetics amongst 2804 isolates sampled 4-8 years after the 2011 introduction of PCV-13 in urban Malawi. These changes are characterised by metabolic genotypes with distinct virulence and antimicrobial resistance (AMR) profiles. This included exclusive genes responsible for metabolism and carbohydrate transport, and toxin-antitoxin systems located in an integrative-conjugative region suggestive of horizontal gene transfer. These emergent genotypes were found to have differential growth, haemolytic, or epithelial adhesion/invasion traits that may confer advantage in the nasopharyngeal niche. Together these data show that in the context of PCV13 introduction in a high burden population, there has been a shift in the pneumococcal population dynamics with the emergence of genotypes that have undergone multiple adaptations extending beyond simple serotype replacement, a process that could further undermine vaccine control and promote the spread of AMR.
  • DOI - 10.1101/2021.07.21.21260914

2017

  • TITLE- Pigs, zoonoses and antimicrobial resistance in Kenya and Malawi
  • AUTHOR - Catherine Wilson
  • JOURNAL -
  • ABSTRACT -

2019

  • TITLE- Knowledge, attitudes and practices related to self-medication with antimicrobials in Lilongwe, Malawi
  • AUTHOR - Cecilia S Sambakunsi, Lars Smbrekke, Christine A Varga, Vernon Solomon, John S Mponda
  • JOURNAL - Malawi Medical Journal
  • ABSTRACT - The use of antimicrobials is associated with the emergence of antimicrobial resistance (AMR), and self-medication increases the risk of the inappropriate use of antimicrobials. This study aims to describe the knowledge, attitudes, and practices (KAP) regarding self-medication with antimicrobials among residents in Lilongwe, Malawi. Methodology This study has a cross-sectional, mixed-methods design. We conducted two focus group discussions (n=15) to describe community attitudes towards self-medication with antimicrobials and used a structured questionnaire to collect data on individual KAP regarding self-medication from 105 respondents. Results Self-medication was common, and the sources of these medicines were market vendors, pharmacies, drugs shared with friends and family and those leftover from previous treatments. The lack of medical supplies, long distances to health facilities, poor attitudes of medical professionals towards patients, and past experience with the disease and treatment are the main factors that influence self-medication. KAP respondents had little knowledge of antimicrobials, their use, or any awareness of AMR. Seventy-four per cent (n=78) were unable to differentiate antimicrobials from other categories of medicines, and 92.4% wrongly responded that antimicrobials could be used to stop a fever. Concerning attitudes towards self-medication, over 54% wrongly believe that antimicrobials are effective in treating common colds. In regard to practice, 53% reported that they would use antimicrobials to treat upper respiratory infections, and 41% agreed that they must complete antibiotic therapy even if they are improving. Logistic regression analysis found that stocking antimicrobials at home for future use significantly promotes self-medication whereas an awareness of AMR would reduce self-medication. Conclusion Self-medication is a public health risk that needs to be addressed urgently. Findings from this study point to the need for multifaceted interventions. 
  • ISSUE - 4
  • VOLUME - 31
  • DOI - 10.4314/mmj.v31i4.2

2020

  • TITLE - Knowledge, attitude and perception on antimicrobial use and antimicrobial resistance among final year medical students in the College of Medicine, Malawi
  • AUTHOR - Alfred Kamoto, Gertrude Chapotera, Fatima Suleman
  • JOURNAL - Malawi Medical Journal
  • ABSTRACT - Medical curricula need to provide adequate knowledge on antimicrobial medicine use and antimicrobial resistance (AMR). Such knowledge is critical in shaping correct attitudes and perceptions among future prescribers. However, the extent of preparation provided by medical curricula remains unknown.AimThe current study sought to determine knowledge, attitude and perception on antimicrobial use and AMR among final year medical students in Malawi.MethodsA descriptive cross-sectional study was undertaken among all final year medical students at the College of Medicine, University of Malawi in 2016. Total population sampling and self-administered questionnaires were used. Data were entered using Microsoft Excel and analysed with Epi info. Descriptive analysis for categorical data was done using frequencies and proportions, and for continuous data using measures of central tendency.ResultsThe response rate in this study was 95%. The mean and median aggregated scores were 7.2 and 7, respectively, for the 11 knowledge questions. Over 88% of the respondents answered more than half of the knowledge questions correctly. Respondents agreed that antimicrobials are overused both at national (50; 69%) and at hospital (52; 72%) levels.ConclusionThis study reports high aggregated knowledge scores on antimicrobial use and resistance with wide variations on correct knowledge scores per question. The study further shows varying level in attitudes and perceptions among medical students. Overall, there were gaps on antimicrobial use and knowledge of AMR which the medical curriculum should addresses. 
  • ISSUE - 3
  • VOLUME - 32
  • DOI - 10.4314/mmj.v32i3.3

2022

  • TITLE - Investigating risks for human colonisation with extended spectrum beta-lactamase producing E. coli and K. pneumoniae in Malawian households: a one health longitudinal cohort study
  • AUTHOR - Derek Cocker, Kondwani Chidziwisano, Madalitso Mphasa, Taonga Mwapasa, Joseph M. Lewis, Barry Rowlingson, Melodie Sammarro, Winnie Bakali, Chifundo Salifu, Allan Zuza, Mary Charles, Tamandani Mandula, Victor Maiden, Stevie Amos, Shevin T Jacob, Henry Kajumbula, Lawrence Mugisha, David Musoke, Rachael Byrne, Thomas Edwards, Rebecca Lester, Nicola Elviss, Adam Roberts, Andrew C Singer, Christopher Jewell, Tracy Morse, Nicholas A Feasey
  • JOURNAL - medRxiv
  • ABSTRACT - Low- and middle-income countries (LMICs) have high morbidity and mortality from drug-resistant infections, especially from enteric bacteria such as Escherichia coli. LMICs have varying infrastructure and services in the community to separate people from human and animal waste, creating risks for ESBL-Enterobacterales (ESBL-E) transmission. Limited data exist from Southern Africa on the prevalence of ESBL-E the community. In this longitudinal cohort study we took a one-health approach to investigating prevalence and distribution of ESBL-E in urban, peri-urban and rural Malawian households between May 2018 and October 2020. We described human health, antibiotic usage (ABU), health seeking behaviour, structural and behavioural environmental health practices, and animal husbandry at these households. In parallel, human and animal stool and diverse environmental samples were collected and cultured to identify presence of ESBL E. coli and ESBL K. pneumoniae. Univariable and multivariable analysis was performed to determine associations with human ESBL-E colonisation. We recruited 300 households, totalling 841 visits, and a paucity of environmental health infrastructure and materials for safe sanitation was noted across all sites. In total, 11,975 samples were cultured and ESBL-E were isolated from 41.8% (n=1190) of human stool and 29.8% (n=290) of animal stool samples. Animal species with particularly high rates of ESBL-E colonisation included pigs (56.8%, n=21) poultry (32.5%, n=148) and dogs (58.8% n= 30). ESBL-E were isolated from 66.2% (n=339) of river water samples and 46.0% (n=138) of drain samples. Urban areas had greater ESBL-E contamination of food, household surfaces, floors and the external environment, alongside the highest rates of ESBL-E colonisation in humans (47.1%, n=384) and animals (55.1%, n=65). Multivariable models illustrated that human ESBL E. coli colonisation was associated with the wet season (aOR = 1.66, 95%CrI: 1.38-2.00), living in urban areas (aOR = 2.01, 95%CrI: 1.26-3.24), advanced age (aOR = 1.14, 95%CrI: 1.05-1.24) and in households where animals were observed interacting with food (aOR = 1.62, 95%CrI: 1.17-2.28) or kept inside (aOR = 1.58, 95%CrI: 1.00-2.43). Human ESBL K. pneumoniae colonisation was also associated with the wet season (aOR = 2.23, 95%CrI: 1.63-2.76. We identified extremely high levels of ESBL-E colonisation in humans and animals and contamination of the environment in Southern Malawi. Urbanisation and season are key risks for ESBL-E colonisation, perhaps reflecting environmental contamination as toilets overflow in high population density areas in heavy rains in the wet season. Without adequate efforts to improve environmental health, ESBL transmission is likely to persist in this setting.
  • DOI - 10.1101/2022.08.16.22278508

2021

  • TITLE - Impact of pneumococcal and malaria vaccines for children on antimicrobial resistance in Malawi
  • AUTHOR - Swarthout, Todd
  • JOURNAL - Kamuzu University of Health Sciences
  • ABSTRACT -

2019

  • TITLE - Hygiene practices of dairy farmers and milk bulking centres and their influence on development of biofilm; a case of Lilongwe, Malawi
  • AUTHOR - Banda, Richard Fredrick Dickson
  • JOURNAL -
  • ABSTRACT -

2019

  • TITLE - High Sepsis-Related Mortality and Antimicrobial Resistance at a Referral Hospital in Malawi
  • AUTHOR - Meghan Prin, Lauren Onofrey, Laura N. Purcell, Anthony G. Charles
  • JOURNAL - Journal of the American College of Surgeons
  • ISSUE - 4
  • VOLUME - 229
  • DOI - 10.1016/j.jamcollsurg.2019.08.294

2020

  • TITLE - Genomic epidemiology of Escherichia coli isolates from a tertiary referral center in Lilongwe, Malawi
  • AUTHOR - Gerald Tegha, Emily J. Ciccone, Robert Krysiak, James Kaphatika, Tarsizio Chikaonda, Isaac Ndhlovu, David van Duin, Irving Hoffman, Jonathan J. Juliano, Jeremy Wang
  • JOURNAL -
  • ABSTRACT - Antimicrobial resistance (AMR) is a global threat, including in sub-Saharan Africa. However, little is known about the genetics of resistant bacteria in the region. In Malawi, there is growing concern about increasing rates of antimicrobial resistance to most empirically used antimicrobials. The highly drug resistant Escherichia coli sequence type (ST) 131, which is associated with the extended spectrum Œ≤-lactamase blaCTX-M-15, has been increasing in prevalence globally. Previous data from isolates collected between 2006 and 2013 in southern Malawi have revealed the presence of ST131 and the blaCTX-M-15 gene in the country. We performed whole genome sequencing (WGS) of 58 clinical E. coli isolates at Kamuzu Central Hospital, a tertiary care centre in central Malawi, collected from 2012 to 2018. We used Oxford Nanopore Technologies (ONT) sequencing, which was performed in Malawi. We show that ST131 is observed more often (14.9% increasing to 32.8%) and that the blaCTX-M-15 gene is occurring at a higher frequency (21.3% increasing to 44.8%). Phylogenetics indicates that isolates are highly related between the central and southern geographic regions and confirms that ST131 isolates are contained in a single group. All AMR genes, including blaCTX-M-15, were widely distributed across sequence types. We also identified an increased number of ST410 isolates, which in this study tend to carry a plasmid-located copy of blaCTX-M-15 gene at a higher frequency than blaCTX-M-15 occurs in ST131. This study confirms the expanding nature of ST131 and the wide distribution of the blaCTX-M-15 gene in Malawi. We also highlight the feasibility of conducting longitudinal genomic epidemiology studies of important bacteria with the sequencing done on site using a nanopore platform that requires minimal infrastructure. 
  • DOI - 10.1099/mgen.0.000490

2022

  • TITLE - Genomic and antigenic diversity of colonizing Klebsiella pneumoniae isolates mirrors that of invasive isolates in Blantyre, Malawi
  • AUTHOR - Joseph M. Lewis, Madalitso Mphasa, Rachel Banda, Mathew A. Beale, Jane Mallewa, Eva Heinz, Nicholas R. Thomson, Nicholas A. Feasey
  • JOURNAL -
  • ABSTRACT - Members of the Klebsiella pneumoniae species complex, particularly K. pneumoniae subsp. pneumoniae are antimicrobial resistance (AMR) associated pathogens of global importance, and polyvalent vaccines targeting Klebsiella O-antigens are in development. Whole-genome sequencing has provided insight into O-antigen distribution in the K. pneumoniae species complex, as well as population structure and virulence determinants, but genomes from sub-Saharan Africa are underrepresented in global sequencing efforts. We therefore carried out a genomic analysis of extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae species complex isolates colonizing adults in Blantyre, Malawi. We placed these isolates in a global genomic context, and compared colonizing to invasive isolates from the main public hospital in Blantyre. In total, 203 isolates from stool and rectal swabs from adults were whole-genome sequenced and compared to a publicly available multicounty collection and previously sequenced Malawian and Kenyan isolates from blood or sterile sites. We inferred phylogenetic relationships and analysed the diversity of genetic loci linked to AMR, virulence, capsule and LPS O-antigen (O-types). We find that the diversity of Malawian K. pneumoniae subsp. pneumoniae isolates represents the species‚Äô population structure, but shows distinct local signatures concerning clonal expansions. Siderophore and hypermucoidy genes were more frequent in invasive versus colonizing isolates (present in 13 % vs 1 %) but still generally lacking in most invasive isolates. O-antigen population structure and distribution was similar in invasive and colonizing isolates, with O4 more common (14%) than in previously published studies (2‚Äì5 %). We conclude that host factors, pathogen opportunity or alternate virulence loci not linked to invasive disease elsewhere are likely to be the major determinants of invasive disease in Malawi. Distinct ST and O-type distributions in Malawi highlight the need to sample locations where the burden of invasive Klebsiella disease is greatest to robustly define secular trends in Klebsiella diversity to assist in the development of a useful vaccine. Colonizing and invasive isolates in Blantyre are similar, hence O-typing of colonizing Klebsiella isolates may be a rapid and cost-effective approach to describe global diversity and guide vaccine development. 
  • DOI - 10.1099/mgen.0.000778

2019

  • TITLE - Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages
  • AUTHOR - Patrick Musicha, Chisomo L Msefula, Alison E Mather, Chrispin Chaguza, Amy K Cain, Chikondi Peno, Teemu Kallonen, Margaret Khonga, Brigitte Denis, Katherine J Gray, Robert S Heyderman, Nicholas R Thomson, Dean B Everett, Nicholas A Feasey
  • JOURNAL - Journal of Antimicrobial Chemotherapy
  • ABSTRACT - ESBL-producing Klebsiella pneumoniae (KPN) pose a major threat to human health globally. We carried out a WGS study to understand the genetic background of ESBL-producing KPN in Malawi and place them in the context of other global isolates. We sequenced genomes of 72 invasive and carriage KPN isolates collected from patients admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. We performed phylogenetic and population structure analyses on these and previously published genomes from Kenya (n‚Åü=‚Åü66) and from outside sub-Saharan Africa (n‚Åü=‚Åü67). We screened for presence of antimicrobial resistance (AMR) genetic determinants and carried out association analyses by genomic sequence cluster, AMR phenotype and time. Malawian isolates fit within the global population structure of KPN, clustering into the major lineages of KpI, KpII and KpIII. KpI isolates from Malawi were more related to those from Kenya, with both collections exhibiting more clonality than isolates from the rest of the world. We identified multiple ESBL genes, including blaCTX-M-15, several blaSHV, blaTEM-63 and blaOXA-10, and other AMR genes, across diverse lineages of the KPN isolates from Malawi. No carbapenem resistance genes were detected; however, we detected IncFII and IncFIB plasmids that were similar to the carbapenem resistance-associated plasmid pNDM-mar. There are multiple ESBL genes across diverse KPN lineages in Malawi and plasmids in circulation that are capable of carrying carbapenem resistance. Unless appropriate interventions are rapidly put in place, these may lead to a high burden of locally untreatable infection in vulnerable populations. 
  • ISSUE - 5 
  • VOLUME - 74
  • DOI - 10.1093/jac/dkz032

2020

  • TITLE - Estimating the burden of antimicrobial resistance in Malawi: protocol for a prospective observational study of the morbidity, mortality and economic cost of third-generation cephalosporin resistant bloodstream infection
  • AUTHOR - Rebecca Lester, Hendran Maheswaran, Christopher P. Jewell, David G. Lalloo, Nicholas A. Feasey
  • JOURNAL - Wellcome Open Research
  • ABSTRACT - Antimicrobial resistance (AMR) is a global public health concern, but the problems are context specific, with each county or setting facing differing challenges. In sub-Saharan Africa, third-generation cephalosporin resistant Enterobacterales (3GCR-E) are of particular concern, given the widespread reliance on ceftriaxone for treatment of severe infection in this setting. In Malawi, despite rising prevalence of 3GCR-E, the health-impact of these infections has not been described. This study is designed to estimate attributable mortality, morbidity and economic cost of 3GCR-E bloodstream infection (BSI) in a large, urban hospital. Methods: This study will investigate the burden of AMR by recruiting a a prospective longitudinal cohort of patients who have bloodstream infection with 3GCR-E, at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients whose blood culture is positive for either third-generation cephalosporin susceptible (3GC-S) or third-generation resistant (3GC-R) Enterobacterales will be enrolled and provide clinical and healthcare economic data. Patients will be followed throughout their hospital stay and to 6-months post discharge. The primary outcomes for the study are mortality and morbidity from 3GCR-E. Healthcare economic outcomes will be assessed by comparing healthcare provider costs, indirect patient costs and health-related quality of life outcomes in patients with 3GC-S and 3GC-R BSI. Based on our observation that some patients with clinical suspicion of sepsis and 3GC-R BSI are surviving without an effective antibiotic, we review each patient prospectively and classify what role the isolated bacteria is playing in the patient‚Äôs clinical presentation. Each BSI episode will be classified into the following categories: definite Gram-negative sepsis, probable Gram-negative sepsis, transient or occult bacteraemia, or contaminated blood culture. These classifications will be incorporated into our analysis. Ethics and dissemination: The study protocol has been approved by the Malawi College of Medicine Research Ethics Committee and by the Liverpool School of Tropical Medicine Research Ethics committee. 
  • ISSUE - 5
  • DOI - 10.12688/wellcomeopenres.15719.2 

2018

  • TITLE - Emerging Resistance to Empiric Antimicrobial Regimens for Pediatric Bloodstream Infections in Malawi (1998‚Äì2017)
  • AUTHOR - Pui-Ying Iroh Tam, Patrick Musicha, Kondwani Kawaza, Jenifer Cornick, Brigitte Denis, Bridget Freyne, Dean Everett, Queen Dube, Neil French, Nicholas Feasey, Robert Heyderman
  • JOURNAL - Clinical Infectious Diseases
  • ABSTRACT - The adequacy of the World Health Organization‚Äôs Integrated Management of Childhood Illness (IMCI) antimicrobial guidelines for the treatment of suspected severe bacterial infections is dependent on a low prevalence of antimicrobial resistance (AMR). We describe trends in etiologies and susceptibility patterns of bloodstream infections (BSI) in hospitalized children in Malawi. We determined the change in the population-based incidence of BSI in children admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi (1998‚Äì2017). AMR profiles were assessed by the disc diffusion method, and trends over time were evaluated. A total 89643 pediatric blood cultures were performed, and 10621 pathogens were included in the analysis. Estimated minimum incidence rates of BSI for those ‚â§5 years of age fell from a peak of 11.4 per 1000 persons in 2002 to 3.4 per 1000 persons in 2017. Over 2 decades, the resistance of Gram-negative pathogens to all empiric, first-line antimicrobials (ampicillin/penicillin, gentamicin, ceftriaxone) among children ‚â§5 years increased from 3.4% to 30.2% (P < .001). Among those ‚â§60 days, AMR to all first-line antimicrobials increased from 7.0% to 67.7% (P < .001). Among children ‚â§5 years, Klebsiella spp. resistance to all first-line antimicrobial regimens increased from 5.9% to 93.7% (P < .001). The incidence of BSI among hospitalized children has decreased substantially over the last 20 years, although gains have been offset by increases in Gram-negative pathogens‚Äô resistance to all empiric first-line antimicrobials. There is an urgent need to address the broader challenge of adapting IMCI guidelines to the local setting in the face of rapidly-expanding AMR in childhood BSI. 
  • ISSUE - 1 
  • VOLUME - 69
  • DOI - 10.1093/cid/ciy834

2020

  • TITLE - Emergence of carbapenemase-producing Enterobacteriaceae in Malawi
  • AUTHOR - Joseph M. Lewis, Rebecca Lester, Madalitso Mphasa, Rachel Banda, Thomas Edwards, Nicholas R. Thomson, Nicholas Feasey
  • JOURNAL - Journal of Global Antimicrobial Resistance
  • ABSTRACT -
  • VOLUME - 20
  • DOI - 10.1016/j.jgar.2019.12.017

2020

  • TITLE - Cephalosporin resistance in Malawi
  • AUTHOR - Kathryn Haigh, Queen Dube, Watipaso Kasambara, Nicholas A Feasey, Rebecca Lester
  • JOURNAL - The Lancet Infectious Diseases
  • ABSTRACT -
  • ISSUE - 3
  • VOLUME - 20
  • DOI - 10.1016/s1473-3099(20)30047-5

2021

  • TITLE - Burden, Antibiotic Resistance, and Clonality of Shigella spp. Implicated in Community-Acquired Acute Diarrhoea in Lilongwe, Malawi
  • AUTHOR - Abel F.N.D. Phiri, Akebe Luther King Abia, Daniel Gyamfi Amoako, Rajab Mkakosya, Arnfinn Sundsfjord, Sabiha Y. Essack, Gunnar Skov Simonsen
  • JOURNAL - Tropical Medicine and Infectious Disease
  • ABSTRACT - Although numerous studies have investigated diarrhoea aetiology in many sub-Saharan African countries, recent data on Shigella species‚Äô involvement in community-acquired acute diarrhoea (CA-AD) in Malawi are scarce. This study investigated the incidence, antibiotic susceptibility profile, genotypic characteristics, and clonal relationships of Shigella flexneri among 243 patients presenting with acute diarrhoea at a District Hospital in Lilongwe, Malawi. Shigella spp. were isolated and identified using standard microbiological and serological methods and confirmed by identifying the ipaH gene using real-time polymerase chain reaction. The isolates‚Äô antibiotic susceptibility to 20 antibiotics was determined using the VITEK 2 system according to EUCAST guidelines. Genes conferring resistance to sulfamethoxazole (sul1, sul2 and sul3), trimethoprim (dfrA1, dfrA12 and dfrA17) and ampicillin (oxa-1 and oxa-2), and virulence genes (ipaBCD, sat, ial, virA, sen, set1A and set1B) were detected by real-time PCR. Clonal relatedness was assessed using ERIC-PCR. Thirty-four Shigella flexneri isolates were isolated (an overall incidence of 14.0%). All the isolates were fully resistant to sulfamethoxazole/trimethoprim (100%) and ampicillin (100%) but susceptible to the other antibiotics tested. The sul1 (79%), sul2 (79%), sul3 (47%), dfrA12 (71%) and dfrA17 (56%) sulfonamide and trimethoprim resistance genes were identified; Oxa-1, oxa-2 and dfrA1 were not detected. The virulence genes ipaBCD (85%), sat (85%), ial (82%), virA (76%), sen (71%), stx (71%), set1A (26%) and set1B (18%) were detected. ERIC-PCR profiling revealed that the Shigella isolates were genetically distinct and clonally unrelated, indicating the potential involvement of genetically distinct S. flexneri in CA-AD in Malawi. The high percentage resistance to ampicillin and sulfamethoxazole/trimethoprim and the presence of several virulence determinants in these isolates emphasises a need for continuous molecular surveillance studies to inform preventive measures and management of Shigella-associated diarrhoeal infections in Malawi. 
  • ISSUE - 2
  • VOLUME - 6
  • DOI - 10.3390/tropicalmed6020063

2019

  • TITLE - Antimicrobial Resistant Organisms in Sepsis at a Referral Hospital in Malawi
  • AUTHOR - Meghan Prin, Lauren Onofrey, Clement Kadyaudzu, Anthony Charles
  • JOURNAL - SSRN Electronic Journal
  • ABSTRACT - There are scarce data describing the etiology and clinical sequelae of sepsis in LMICs. In particular, the prevalence of antibiotic resistant organisms is not well characterized. This study describes the prevalence of sepsis amongst critically ill patients, antibiotic stewardship, and the prevalence of antimicrobial resistant pathogens at a referral hospital in Malawi.Methods: We conducted an observational prospective cohort study of adults admitted to the ICU or HDU of a referral hospital in Malawi from January 29 to March 15, 2018. We stratified the cohort based on the prevalence of sepsis, defined by a qSOFA score ‚â•2 plus suspected infection. We measured clinical characteristics, blood and urine cultures, and antimicrobial sensitivities from positive cultures.Findings: During the study period, 103 patients were admitted and 76 patients were analyzed. The cohort was 47% male, and the median age 30 years (IQR, 23-40). Most participants (74%) had initiated antibiotics prior to study recruitment, commensurate with a suspicion of infection in 68% of patients. Four blood cultures (5%) were positive, two from patients with sepsis. All blood bacterial isolates were multi-drug resistant. Of seven patients with urinary tract infection, three had sepsis secondary to multi-drug resistant bacteria. Hospital mortality for patients with sepsis was 73% versus 22% for non-septic patients (p=0¬∑001).Interpretation: Mortality associated with sepsis in the ICU and HDUs at this Malawi hospital is high. Bacteremia was infrequently detected, but isolated pathogens were multi-drug resistant. These data highlight the need for laboratory infrastructure to guide antibiotic stewardship in Malawi.Funding Statement: This study was supported in part by the NIH Fogarty International Center Postdoctoral Research Fellowship to Dr. Prin and by the Friedman Award from Columbia University College of Physicians and Surgeons to Dr. Onofrey.Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: The study protocol was approved by the National Health Sciences Research Council of Malawi and the Institutional Review Boards of both American universities with which the study was affiliated, and the requirement for written informed consent was waived by all ethics oversight bodies.
  • DOI - 10.2139/ssrn.3420428

2020

  • TITLE - Antimicrobial resistance in bacteria associated with childhood pneumonia in Malawi
  • AUTHOR - Mitchell Moody
  • JOURNAL - Access Microbiology
  • ABSTRACT -
  • ISSUE - 1
  • VOLUME - 2
  • DOI - 10.1099/acmi.mim2019.po0012

2020

  • TITLE - Antimicrobial Resistance in Bacteria Associated with Childhood Community Acquired Pneumonia in Malawi
  • AUTHOR - Mitchell Moody, Chris Watson, Emma Caraher and Gordon Cooke
  • JOURNAL - Microbiology Research
  • ABSTRACT -

2022

  • TITLE - A Qualitative Study of Antibiotic Use Practices in Intensive Small-Scale Farming in Urban and Peri-Urban Blantyre, Malawi: Implications for Antimicrobial Resistance
  • AUTHOR - John Mankhomwa, Rachel Tolhurst, Eunice M'biya, Ibrahim Chikowe, Pemphero Banda, Jimmy Mussa, Henry Mwasikakata, Victoria Simpson, Nicholas Feasey, Eleanor E. MacPherson
  • JOURNAL - Frontiers in Veterinary Science
  • ABSTRACT - The routine use of antimicrobials in meat production has been identified as a driver of antimicrobial resistance (AMR) in both animals and humans. Significant knowledge gaps exist on antibiotic use practices in farming, particularly in sub-Saharan Africa. This paper sought to generate in-depth understanding of household antibiotic use practices in food animals in urban- and peri-urban Blantyre. We used a qualitative research methodology focusing on households that kept scavenging animals and those engaged in small-scale intensive farming of food animals. Methods used were: medicine-use surveys with 130 conducted with a range of households; in-depth interviews (32) with a range of participants including farmers, community based veterinary health workers and veterinary shop workers; and stakeholder interviews (17) with policy makers, regulators, and academics. Six months of ethnographic fieldwork was also undertaken, with households engaged in farming, veterinary officers and veterinary stores. Our findings suggest antibiotic use in animals was more common in households that used small-scale intensive farming techniques, but rare in households that did not. For farmers engaged in small-scale intensive farming, antibiotics were often considered vital to remain solvent in a precarious economic and social environment, with limited access to veterinary services. A complex regulatory framework governed the import, prescription, and administration of antibiotics. Veterinary stores provided easy access to antibiotics, including colistin, an antibiotic on the WHO's critically important antibiotics for human health. Our work suggests that the high dependence on antibiotics for small-scale intensive farming may contribute to the growth of drug resistant infections in Malawi. The socio-economic drivers of antibiotic use mean that interventions need to take a holistic approach to address the high dependence on antibiotics. Key interventions could include improving farmers' access to affordable veterinary services, providing information about appropriate antibiotic use including withdrawal periods and feed supplementation, as well as improvements in regulation (nationally and internationally) and enforcement of current regulations. Taken together these approaches could lead to antibiotic use being optimised in feed animals. 
  • ISSUE - 9
  • DOI - 10.3389/fvets.2022.876513

2022

  • TITLE - A novel, magnetic bead‚Äêbased extraction method for the isolation of antimicrobial resistance genes with a case study in river water in Malawi
  • AUTHOR - Rachel L. Byrne, Derek Cocker, Ghaith Alyayyoussi, Madalitso Mphasa, Mary Charles, Tamandani Mandula, Christopher T. Williams, Jonathan Rigby, Jack Hearn, Nicholas Feasey, Emily R. Adams, Thomas Edwards
  • JOURNAL - Journal of Applied Microbiology
  • ABSTRACT - The environment is increasingly recognized as an important reservoir of antimicrobial resistance genes (ARGs), which can be identified using molecular platforms. Yet, environmental surveillance remains an underutilised tool as there is no agreement on the best strategy for sample processing. We aim to develop a low‚Äêcost extraction method independent to commercial kits or reagents. We present a novel, magnetic bead‚Äêbased method for the isolation of ARGs from river water named MagnaExtract. We present this with analytic limit of detection as well as a case study in Southern Malawi. Here we compare the DNA yield from MagnaExtract with commercially available QIAGEN kits and the crude boil and spin method, using a high‚ resolution melt analysis PCR panel designed for the detection of third‚Äêgeneration cephalosporin and carbapenem‚Äêresistant genes from 98 water samples. The MagnaExtract method is comparable, and in some instance's superior to commercially available kits for the isolation of ARGs from river water samples. The MagnaExtract approach offers a simple, affordable, high yielding extraction method that could be used for the detection of ARGs from river water samples in surveillance campaigns in East Africa.
  • DOI - 10.1111/jam.15755



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