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Maternal colonization or infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae in Africa: A systematic review and meta-analysis

  • Andre N.H. Bulabula
    Correspondence
    Corresponding author at: Division of Health Systems and Public Health, Department of Global Health, Academic Unit for Infection Prevention and Control, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
    Affiliations
    Division of Health Systems and Public Health, Department of Global Health, Academic Unit for Infection Prevention and Control, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

    Infection Control Africa Network – ICAN, Cape Town, South Africa
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  • Angela Dramowski
    Affiliations
    Division of Health Systems and Public Health, Department of Global Health, Academic Unit for Infection Prevention and Control, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

    Infection Control Africa Network – ICAN, Cape Town, South Africa
    Search for articles by this author
  • Shaheen Mehtar
    Affiliations
    Division of Health Systems and Public Health, Department of Global Health, Academic Unit for Infection Prevention and Control, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

    Infection Control Africa Network – ICAN, Cape Town, South Africa
    Search for articles by this author
Open AccessPublished:September 07, 2017DOI:https://doi.org/10.1016/j.ijid.2017.08.015

      Highlights

      • The prevalence of colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in pregnant and/or post-partum women in Africa is 17% (95% confidence interval 10–23%).
      • The pooled proportions from reviewed studies suggest a greater proportion of ESBL-E colonization in pregnant women compared to post-partum women.
      • The rate of maternal colonization with ESBL-E is greater in community settings than in hospital settings.
      • The most frequently reported ESBL-encoding gene in Africa is CTX-M.

      Abstract

      Objective

      To summarize published studies on the prevalence of and risk factors for maternal bacterial colonization and/or infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in pregnant and/or post-partum women in Africa.

      Methods

      A systematic review was conducted using the PubMed, Scopus, and Google Scholar databases. Bibliographies of included eligible studies were manually searched to identify additional relevant articles. No language restriction was applied. The timeframe of the search included all records from electronic database inception to July 15, 2017. A random-effects meta-analysis was performed to summarize the prevalence and the 95% confidence intervals (CI) of ESBL-E colonization or infection in pregnant or post-partum women in Africa. The meta-analysis was conducted using STATA IC 13.1 software and the metaprop function/plugin.

      Results

      Ten studies (seven on pregnant women and three on post-partum women) were included, documenting a 17% prevalence of maternal colonization with ESBL-E in Africa (95% CI 10–23%). The prevalence of ESBL-E in community isolates exceeded that in isolates from the hospital setting (22% vs. 14%). The most frequently reported ESBL-encoding gene was CTX-M (cefotaxime hydrolyzing capabilities). Data on risk factors for maternal ESBL-E colonization and infection are very limited.

      Conclusions

      The prevalence of colonization and/or infection with ESBL-E in pregnant and post-partum women in Africa exceeds that reported from high- and middle-income settings, representing a risk for subsequent neonatal colonization and/or infection with ESBL-E.

      Keywords

      Introduction

      Antimicrobial resistance (AMR) is a growing threat to human health globally (
      • WHO
      Antimicrobial resistance.
      ,
      • Frieden Tom
      Antibiotic resistance threats.
      ). A major mechanism of AMR is the production of extended-spectrum beta-lactamase (ESBL) enzymes, which confer resistance to penicillins, cephalosporins, and monobactams, but not to cephamycins and carbapenems (
      • Paterson David L.
      • Bonomo Robert A.
      Extended-spectrum beta-lactamases: a clinical update.
      ,
      • Pitout Johann D.D.
      • Nordmann Patrice
      • Laupland Kevin B.
      • Poirel Laurent
      Emergence of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in the community.
      ), leaving limited therapeutic options for AMR infections. In 2013, the US Centers for Disease Control and Prevention (CDC) identified ESBL-producing Enterobacteriaceae (ESBL-E) as a serious threat (
      • Frieden Tom
      Antibiotic resistance threats.
      ). In addition, the World Health Organization (WHO) has published a priority pathogens list, and resistant ESBL-E are classified as ‘critical’, priority number 1 (
      • WHO
      Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics.
      ).
      ESBL- E occur worldwide in both community and hospital settings (
      • Paterson David L.
      • Bonomo Robert A.
      Extended-spectrum beta-lactamases: a clinical update.
      ,
      • Pitout Johann D.D.
      • Nordmann Patrice
      • Laupland Kevin B.
      • Poirel Laurent
      Emergence of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in the community.
      ,
      • Sonda Tolbert
      • Kumburu Happiness
      • van Zwetselaar Marco
      • Alifrangis Michael
      • Lund Ole
      • Kibiki Gibson
      • et al.
      Meta-analysis of proportion estimates of extended-spectrum-beta-lactamase-producing Enterobacteriaceae in East Africa hospitals.
      ,
      • Storberg Viktor
      ESBL-producing Enterobacteriaceae in Africa a non-systematic literature review of research published 2008–2012.
      ,
      • Luvsansharav Ulzii-Orshikh
      • Hirai Itaru
      • Niki Marie
      • Sasaki Tadahiro
      • Makimoto Kiyoko
      • Komalamisra Chalit
      • et al.
      Analysis of risk factors for a high prevalence of extended-spectrum {beta}-lactamase-producing Enterobacteriaceae in asymptomatic individuals in rural Thailand.
      ), and the reported incidence of infections in paediatric and neonatal populations is increasing (
      • Paterson David L.
      • Bonomo Robert A.
      Extended-spectrum beta-lactamases: a clinical update.
      ,
      • Sonda Tolbert
      • Kumburu Happiness
      • van Zwetselaar Marco
      • Alifrangis Michael
      • Lund Ole
      • Kibiki Gibson
      • et al.
      Meta-analysis of proportion estimates of extended-spectrum-beta-lactamase-producing Enterobacteriaceae in East Africa hospitals.
      ,
      • Storberg Viktor
      ESBL-producing Enterobacteriaceae in Africa a non-systematic literature review of research published 2008–2012.
      ,
      • Flokas Myrto Eleni
      • Karanika Styliani
      • Alevizakos Michail
      • Mylonakis Eleftherios
      Prevalence of ESBL-producing Enterobacteriaceae in pediatric bloodstream infections: a systematic review and meta- analysis.
      ,
      • Peirano Gisele
      • Pitout Johann D.D.
      Molecular epidemiology of Escherichia coli producing CTX-M beta-lactamases: the worldwide emergence of clone ST131 O25:H4.
      ,
      • Tansarli Giannoula S.
      • Poulikakos Panagiotis
      • Kapaskelis Anastasios
      • Falagas Matthew E.
      Proportion of extended-spectrum β-lactamase (ESBL)-producing isolates among Enterobacteriaceae in Africa: evaluation of the evidence-systematic review.
      ,
      • Dramowski Angela
      • Cotton Mark F.
      • Rabie Helena
      • Whitelaw Andrew
      Trends in paediatric bloodstream infections at a South African referral hospital.
      ,
      • Logan Latania K.
      • Braykov Nikolay P.
      • Weinstein Robert A.
      • Laxminarayan Ramanan
      Extended-spectrum β-lactamase-producing and third-generation cephalosporin-resistant Enterobacteriaceae in children: trends in the United States, 1999-2011.
      ). Clinical infections with ESBL-E are associated with increased morbidity (including prolonged hospital stay), increased healthcare costs, and higher mortality rates compared to infections with non-ESBL-E (
      • Blomberg Bjørn
      • Jureen Roland
      • Manji Karim P.
      • Bushir S.
      • Mwakagile Davis S.M.
      • Urassa Willy K.
      • et al.
      High rate of fatal cases of pediatric septicemia caused by gram-negative bacteria with extended-spectrum beta-lactamases in Dar es Salaam, Tanzania high rate of fatal cases of pediatric septicemia caused by gram-negative bacteria with extended-spectrum B.
      ,
      • Zaoutis Theoklis E.
      • Goyal Monika
      • Chu Jaclyn H.
      • Coffin Susan E.
      • Bell Louis M.
      • Nachamkin Irving
      • et al.
      Risk factors for and outcomes of bloodstream infection caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species in children.
      ,
      • Kim Yun-kyung
      • Pai Hyunjoo
      • Lee Hoan-jong
      • Park Su-eun
      • Choi Eun-hwa
      • Kim Jungmin
      • et al.
      Bloodstream infections by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in children: epidemiology and clinical outcome.
      ,
      • Ndir Awa
      • Diop Amadou
      • Faye Pape Makhtar
      • Cissé Moussa Fafa
      • Ndoye Babacar
      • Astagneau Pascal
      Epidemiology and burden of bloodstream infections caused by extended-spectrum beta-lactamase producing Enterobacteriaceae in a Pediatric Hospital in Senegal.
      ). Among neonates, children, and pregnant/post-partum women, ESBL-E are frequently implicated in urinary tract infections (UTI) (
      • Pitout Johann D.D.
      • Nordmann Patrice
      • Laupland Kevin B.
      • Poirel Laurent
      Emergence of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in the community.
      ,
      • Peirano Gisele
      • Pitout Johann D.D.
      Molecular epidemiology of Escherichia coli producing CTX-M beta-lactamases: the worldwide emergence of clone ST131 O25:H4.
      ) and bloodstream infections (BSI) (
      • Luvsansharav Ulzii-Orshikh
      • Hirai Itaru
      • Niki Marie
      • Sasaki Tadahiro
      • Makimoto Kiyoko
      • Komalamisra Chalit
      • et al.
      Analysis of risk factors for a high prevalence of extended-spectrum {beta}-lactamase-producing Enterobacteriaceae in asymptomatic individuals in rural Thailand.
      ,
      • Flokas Myrto Eleni
      • Karanika Styliani
      • Alevizakos Michail
      • Mylonakis Eleftherios
      Prevalence of ESBL-producing Enterobacteriaceae in pediatric bloodstream infections: a systematic review and meta- analysis.
      ,
      • Dramowski Angela
      • Cotton Mark F.
      • Rabie Helena
      • Whitelaw Andrew
      Trends in paediatric bloodstream infections at a South African referral hospital.
      ,
      • Zaoutis Theoklis E.
      • Goyal Monika
      • Chu Jaclyn H.
      • Coffin Susan E.
      • Bell Louis M.
      • Nachamkin Irving
      • et al.
      Risk factors for and outcomes of bloodstream infection caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species in children.
      ,
      • Loh K.Y.
      • Sivalingam N.
      Urinary tract infections in pregnancy.
      ). Among neonatal ESBL-E infections, Klebsiella pneumoniae and Escherichia coli are the most frequently isolated species (
      • Flokas Myrto Eleni
      • Karanika Styliani
      • Alevizakos Michail
      • Mylonakis Eleftherios
      Prevalence of ESBL-producing Enterobacteriaceae in pediatric bloodstream infections: a systematic review and meta- analysis.
      ,
      • Dramowski Angela
      • Cotton Mark F.
      • Rabie Helena
      • Whitelaw Andrew
      Trends in paediatric bloodstream infections at a South African referral hospital.
      ,
      • Zaidi Anita K.M.
      • Huskins W. Charles
      • Thaver Durrane
      • Bhutta Zulfiqar A.
      • Abbas Zohair
      • Goldmann Donald A.
      Hospital-acquired neonatal infections in developing countries.
      ).
      Well-established risk factors for early-onset neonatal sepsis include maternal infections (e.g. UTIs and chorioamnionitis) and prolonged rupture of the membranes (
      • Chan Grace J.
      • Lee Anne C.C.
      • Baqui Abdullah H.
      • Tan Jingwen
      • Black Robert E.
      Risk of early-onset neonatal infection with maternal infection or colonization: a global systematic review and meta-analysis.
      ,
      • Chan Grace J.
      • Lee Anne C.C.
      • Baqui Abdullah H.
      • Tan Jingwen
      • Black Robert E.
      Prevalence of early-onset neonatal infection among newborns of mothers with bacterial infection or colonization: a systematic review and meta-analysis.
      ). In a well-powered systematic review, additional risk factors identified were maternal bacterial colonization of the vaginal tract (
      • Chan Grace J.
      • Lee Anne C.C.
      • Baqui Abdullah H.
      • Tan Jingwen
      • Black Robert E.
      Risk of early-onset neonatal infection with maternal infection or colonization: a global systematic review and meta-analysis.
      ,
      • Chan Grace J.
      • Lee Anne C.C.
      • Baqui Abdullah H.
      • Tan Jingwen
      • Black Robert E.
      Prevalence of early-onset neonatal infection among newborns of mothers with bacterial infection or colonization: a systematic review and meta-analysis.
      ) and poor antenatal care (defined as less than four antenatal visits per pregnancy) (
      • Mizumoto B.R.
      • Moreira B.M.
      • Santoro-Lopes G.
      • Cunha A.J.
      • Dos Santos R.M.R.
      • Pessoa-Silva C.L.
      • et al.
      Quality of antenatal care as a risk factor for early onset neonatal infections in Rio de Janeiro, Brazil.
      ,
      • Lincetto Ornella
      • Mothebesoane-anoh Seipati
      • Gomez Patricia
      • Munjanja Stephen
      Antenatal care.
      ).
      Although ESBL-E are well-documented as important bloodstream pathogens in several African settings (
      • Flokas Myrto Eleni
      • Karanika Styliani
      • Alevizakos Michail
      • Mylonakis Eleftherios
      Prevalence of ESBL-producing Enterobacteriaceae in pediatric bloodstream infections: a systematic review and meta- analysis.
      ,
      • Kim Yun-kyung
      • Pai Hyunjoo
      • Lee Hoan-jong
      • Park Su-eun
      • Choi Eun-hwa
      • Kim Jungmin
      • et al.
      Bloodstream infections by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in children: epidemiology and clinical outcome.
      ,
      • Kang Cheol-in
      • Kim Sung-han
      • Park Wan Beom
      • Kim Hong-bin
      • Kim Eui-chong
      • Oh Myoung-don
      • et al.
      Bloodstream infections due to beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for mortality and treatment outcome, with special emphasis on antimicrobial therapy.
      ,
      • Schiappa D.A.
      • Hayden M.K.
      • Matushek M.G.
      • Hashemi F.N.
      • Sullivan J.
      • Smith K.Y.
      • et al.
      Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation.
      ), little is known about the determinants and magnitude of maternal colonization with ESBL-E. Factors contributing to the development of AMR (including ESBL-E) in Africa include socio-economic challenges and health-associated factors (
      • Kariuki Samuel
      • Dougan Gordon
      Antibacterial resistance in sub-Saharan Africa: an underestimated emergency.
      ) (suboptimal hygiene and sanitation (
      • Toole M.J.
      • Basikila P.
      • Male S.
      • Lindgren J.
      • Roberts L.
      • Robinson D.
      • et al.
      Public-health impact of Rwandan refugee crisis — what happened in Goma, Zaire, in July-1994.
      ), weak health systems (
      • Essack S.Y.
      • Desta A.T.
      • Abotsi R.E.
      • Agoba E.E.
      Antimicrobial resistance in the WHO African region: current status and roadmap for action.
      ), lack of laboratory capacity (
      • Okeke I.N.
      • Lamikanra A.
      • Edelman R.
      Socioeconomic and behavioral factors leading to acquired bacterial resistance to antibiotics in developing countries.
      ), and misuse of and easy access to antibiotics (
      • Okeke I.N.
      • Lamikanra A.
      • Edelman R.
      Socioeconomic and behavioral factors leading to acquired bacterial resistance to antibiotics in developing countries.
      )). A high burden of immunocompromised patients (HIV infection (
      • Emacar J.
      • Okemo P.
      • Gatheri G.
      • Kariuki S.
      Antibiotic resistance patterns of Escherichia coli isolated from HIV-sero positive adults at Mbagathi district hospital, Nairobi, Kenya.
      ) and diabetes (
      • Ntirenganya Cyprien
      • Manzi Olivier
      • Muvunyi Claude Mambo
      • Ogbuagu Onyema
      High prevalence of antimicrobial resistance among common bacterial isolates in a tertiary healthcare facility in Rwanda.
      )), environmental contamination (
      • Dusé A.G.
      Infection control in developing countries with particular emphasis on South Africa.
      ), and inadequate decontamination of medical devices (
      • Dusé A.G.
      Infection control in developing countries with particular emphasis on South Africa.
      ), are other important factors exacerbating AMR pathogen transmission in Africa. The relationship between these factors and maternal colonization or infection with ESBL-E is unclear and requires investigation.
      This systematic review and meta-analysis summarizes the magnitude of colonization or infection with ESBL-E among pregnant and post-partum women in Africa and the associated risk factors. Knowledge of the burden and risk factors of maternal colonization or infection with ESBL-E will assist with clinical care, infection prevention, and antibiotic stewardship, and inform the future development of targeted interventions to reduce both maternal and neonatal ESBL-E-associated morbidity and mortality.

      Methods

      Literature search

      A systematic review was conducted in PubMed, Scopus, and Google Scholar. The search strategy included the following words, medical subject heading (MeSH) terms, and Boolean operators: “(enterobacteriaceae OR bacteria OR resistant OR resistance OR ‘non-susceptible’ OR “non susceptible” OR “not susceptible”) AND (coloni* OR infect* OR carri*) AND ((Africa OR Algeria OR Angola OR Benin OR Botswana OR Burkina Faso OR Burundi OR Cabo Verde OR Cameroon OR Central African Republic OR Chad OR Comoros OR Democratic Republic of the Congo OR Republic of the Congo OR Cote d’Ivoire OR Djibouti OR Egypt OR Equatorial Guinea OR Eritrea OR Ethiopia OR Gabon OR Gambia OR Ghana OR Guinea OR Guinea-Bissau OR Kenya OR Lesotho OR Liberia OR Libya OR Madagascar OR Malawi OR Mali OR Mauritania OR Mauritius OR Morocco OR Mozambique OR Namibia OR Niger OR Nigeria OR Rwanda OR “Sao Tome and Principe” OR Senegal OR Seychelles OR Sierra Leone OR Somalia OR South Africa OR South Sudan OR Sudan OR Swaziland OR Tanzania OR Togo OR Tunisia OR Uganda OR Zambia OR Zimbabwe)) AND (ESBL OR extended-spectrum-beta-lactamase OR extended-spectrum-β-lactamase OR extended spectrum beta lactamase) AND ((pregnant OR pregnancy OR gestation OR post-delivery OR postdelivery OR “post delivery” OR post-part* OR postpartum OR “post partum” OR perinatal OR antenatal OR prenatal OR women))”. Bibliographies of eligible studies were manually searched to identify additional relevant articles. It was attempted to contact the authors of relevant studies to obtain specific details. Following the screening of publications, a total of 10 articles were included (Table 1).
      Table 1Characteristics of studies included in the review.
      NumberAuthor and year of publicationCountryStudy designClinical samplesPopulationNumber of participants colonized with ESBL-E/Total participants (% colonized)ESBL-E species included (isolate) and proportionSetting
      1
      • Olufunke Oluduro Anthonia
      • Abiodun Aregbesola Oladipupo
      • Dunah Fashina Christina
      Extended spectrum beta- lactamase- producing uropathogenic Escherichia coli in pregnant women diagnosed with urinary tract infections in South-Western Nigeria.
      NigeriaCross-sectionalUrinePregnant women69/264 (26.1%)Escherichia coli 69/264Hospital
      2
      • Onwuezobe A.
      Extended spectrum beta-lactamase producing uropathogens in asymptomatic pregnant women attending antenatal care in an urban community secondary health facility.
      NigeriaCross-sectionalUrinePregnant women16/80 (20%)Klebsiella pneumoniae 8/16

      Escherichia coli 6/16

      Klebsiella oxytoca 1/16

      Enterobacter cloacae 1/16
      Community
      3
      • Chereau Fanny
      • Herindrainy Perlinot
      • Garin Benoit
      • Huynh Bich Tram
      • Randrianirina Frederique
      • Padget Michael
      • et al.
      Colonization of extended-spectrum-beta-lactamase- and NDM-1-producing Enterobacteriaceae among pregnant women in the community in a low-income country: a potential reservoir for transmission of multiresistant Enterobacteriaceae to neonates.
      MadagascarCross-sectionalStoolPregnant women66/356 (18.6%)Escherichia coli 46/66

      Klebsiella pneumoniae 11/66

      Enterobacter cloacae 5/66

      Citrobacter freundii 3/66

      Morganella morganii 1/66
      Community
      4
      • Nelson E.
      • Kayega J.
      • Seni J.
      • Mushi M.F.
      • Kidenya B.R.
      • Hokororo A.
      • et al.
      Evaluation of existence and transmission of extended spectrum beta lactamase producing bacteria from post-delivery women to neonates at Bugando Medical Center, Mwanza-Tanzania.
      TanzaniaCross-sectionalStoolPost-partum women16/113 (15%)Escherichia coli 6/20

      Enterobacter spp 3/20

      Klebsiella pneumoniae 1/20

      Citrobacter spp 2/20

      Pantoea spp 3/20

      Proteus spp 1/20
      Hospital
      5
      • Kaba M.
      • Manenzhe R.I.
      • Moodley C.
      • Zar H.J.
      • Nicol M.P.
      Epidemiology of extended-spectrum beta-lactamase- and carbapenemase-producing bacteria in stool from apparently healthy children, South Africa. (Poster presentation).
      South AfricaCross-sectionalStoolPost-partum women4/90 (4.4%)Klebsiella pneumoniae 2/90

      Escherichia coli 1/90

      Enterobacter cloacae 1/90
      Community
      6
      • Sáez-lópez Emma
      • Guiral Elisabet
      • Fernández-orth Dietmar
      • Villanueva Sonia
      Vaginal versus obstetric infection Escherichia coli Isolates among pregnant women: antimicrobial resistance and genetic virulence profile.
      MozambiqueCross-sectionalVaginal swabsPregnant women1/51 (1.9%)Escherichia coli 1/51Hospital
      7Djuikoue (2016)CameroonCross-sectionalStoolPregnant women15/26 (57.7%)Escherichia coli 15/26Community
      8
      • Fortini Daniela
      • Fashae Kayode
      • Villa Laura
      • Feudi Claudia
      • Carattoli Alessandra
      • Garcı Aurora
      A novel plasmid carrying bla CTX-M-15 identified in commensal Escherichia coli from healthy pregnant women in Ibadan, Nigeria.
      NigeriaCross-sectionalStoolPregnant women32/101 (31.7%)Escherichia coli 32/101Hospital
      9
      • Bebell Lisa M.
      • Ngonzi Joseph
      • Bazira Joel
      • Fajardo Yarine
      • Boatin Adeline A.
      • Siedner Mark J.
      • et al.
      Antimicrobial-resistant infections among postpartum women at a Ugandan referral hospital.
      UgandaProspective cohortUrine

      Blood
      Post-partum women8/174 (4.6%)Escherichia coli 5/174

      Klebsiella pneumoniae 3/174
      Hospital
      10
      • Tito Chaula
      • Seni Jeremiah
      • Ng’walida Nhandi
      • Kajura Alphaxaid
      • Mirambo Mariam M.
      • Devinney Rebekah
      • et al.
      Urinary tract infections among HIV-positive pregnant women in Mwanza city, Tanzania, are high and predicted by low CD4+ count.
      TanzaniaCross-sectionalUrinePregnant women4/49 (8.2%)Escherichia coli 4/49Hospital
      ESBL-E, extended-spectrum beta-lactamase-producing Enterobacteriaceae.

      Study selection and eligibility criteria

      All publications describing colonization and/or infection with ESBL-E in pregnant or post-partum African women in both community and hospital settings were selected, irrespective of the study design. Primary study designs reporting the proportion or prevalence of ESBL-E in pregnant or post-partum women, as well as risk factors, were eligible. No language restriction was applied. The timeframe of the search included all records from electronic database inception to July 15, 2017. The article selection and exclusion process is shown in Figure 1.

      Data extraction

      A data extraction form was designed to capture the following information: first author and year of publication; country; study design (any type); study setting (community or hospital); study population; number and percentage of women colonized or infected with ESBL-E; total number of women recruited into the study; ESBL-E isolates and their proportions; molecular identification of ESBL-E isolates (if performed); factors associated with ESBL-E colonization or infection in women.

      Data synthesis

      A random-effects meta-analysis was performed to summarize the proportions and the 95% confidence intervals (CI) of ESBL-E in pregnant or post-partum women in Africa. To ensure proportionate weight distribution to studies presenting extreme prevalence (near 0 or 1), the Freeman–Tukey arcsine methodology was applied (
      • Nyaga Victoria N.
      • Arbyn Marc
      • Aerts Marc
      Metaprop: a Stata command to perform meta-analysis of binomial data.
      ). The between-study heterogeneity was assessed using the I2 statistic (which quantifies the percentage of variation across studies due to heterogeneity rather than to chance): I2 <75% was considered as moderate heterogeneity (
      • Higgins Julian P.T.
      • Thompson Simon G.
      Quantifying heterogeneity in a meta-analysis.
      ) and >75% reflected high heterogeneity, in which case subset analyses were performed. The random-effects model was chosen based on the anticipated assumption that studies reporting on the magnitude of ESBL-E in pregnant and post-partum women used different laboratory methods, were conducted in different settings (hospital and community), or had other unknown factors influencing the magnitude of ESBL-E in pregnant and post-partum women in Africa. The meta-analysis was performed using STATA IC version 13.1 software and the metaprop function/plugin, which is a specific STATA program designed for the meta-analysis of binomial data, allowing pooling of proportions (
      • Nyaga Victoria N.
      • Arbyn Marc
      • Aerts Marc
      Metaprop: a Stata command to perform meta-analysis of binomial data.
      ). A total of 1304 participants were pooled from the studies included (927 pregnant women and 377 post-partum women).

      Reporting of the meta-analysis of observational studies

      This meta-analysis of observational studies is reported in compliance with the MOOSE statement and checklist (
      • Stroup D.F.
      • Berlin J.A.
      • Morton S.C.
      • et al.
      Meta-analysis of observational studies in epidemiology: a proposal for reporting.
      ) (Meta-analysis of Observational Studies in Epidemiology).

      Assessment of bias

      The Newcastle–Ottawa Scale (
      • Herzog R.
      • Alvarez-Pasquin M.J.
      • Diaz C.
      • Del Barrio J.L.
      • Estrada J.M.
      • Gil A.
      Newcastle-Ottawa Scale adapted for cross-sectional studies.
      ) adapted for cross-sectional studies (see below) was used to assess the risk of bias for each selected study. This scale includes an evaluation of participant selection, comparability, and outcome; each section has a maximum number of ‘stars’ that can be awarded as a score (5, 2, and 3, respectively). For the overall quality assessment, the maximum score is 10 stars. Studies with a minimum score of 3 were considered of acceptable methodological quality for inclusion in the meta-analysis (Table 2).
      Table 2Risk of bias assessment for studies included in the quantitative synthesis (all observational studies).
      Stars (*) represent the number of points awarded for the category; *=1, **=2.
      Author and year of publicationSelectionComparabilityExposureOverall quality assessment score (out of a maximum of 10)
      Representativeness of the sampleAscertainment of exposureComparability of the groups on the basis of design or analysisAssessment of outcome
      • Olufunke Oluduro Anthonia
      • Abiodun Aregbesola Oladipupo
      • Dunah Fashina Christina
      Extended spectrum beta- lactamase- producing uropathogenic Escherichia coli in pregnant women diagnosed with urinary tract infections in South-Western Nigeria.
      *Truly representative of average pregnant women with ESBL Enterobacteriaceae*Pregnant women diagnosed with clinical isolates producing ESBL − DDSTStudy did not control for other factors*Independent blind assessment4
      • Onwuezobe A.
      Extended spectrum beta-lactamase producing uropathogens in asymptomatic pregnant women attending antenatal care in an urban community secondary health facility.
      *Truly representative of average pregnant women with ESBL Enterobacteriaceae**Pregnant women diagnosed with clinical isolates producing ESBL − DDSTStudy did not control for other factors*Independent blind assessment4
      • Kaba M.
      • Manenzhe R.I.
      • Moodley C.
      • Zar H.J.
      • Nicol M.P.
      Epidemiology of extended-spectrum beta-lactamase- and carbapenemase-producing bacteria in stool from apparently healthy children, South Africa. (Poster presentation).
      *Truly representative of post-partum women with ESBL Enterobacteriaceae in the community**ESBL production was confirmed using the combination disc testStudy did not control for other factors*Independent blind assessment4
      • Chereau Fanny
      • Herindrainy Perlinot
      • Garin Benoit
      • Huynh Bich Tram
      • Randrianirina Frederique
      • Padget Michael
      • et al.
      Colonization of extended-spectrum-beta-lactamase- and NDM-1-producing Enterobacteriaceae among pregnant women in the community in a low-income country: a potential reservoir for transmission of multiresistant Enterobacteriaceae to neonates.
      *Truly representative of pregnant women with ESBL Enterobacteriaceae in the community**Production of ESBL in ESC-resistant Enterobacteriaceae was confirmed by DDST (CASFM)*Study controlled for other factors, multivariate analysis*Independent blind assessment5
      • Nelson E.
      • Kayega J.
      • Seni J.
      • Mushi M.F.
      • Kidenya B.R.
      • Hokororo A.
      • et al.
      Evaluation of existence and transmission of extended spectrum beta lactamase producing bacteria from post-delivery women to neonates at Bugando Medical Center, Mwanza-Tanzania.
      *Truly representative of post-partum women with ESBL Enterobacteriaceae in the hospital*Rectal swabs plated onto MacConkey agar (OXOID, Basingstoke, UK) supplemented with cefotaxime 2 mg/l for preliminary screening of ESBL bacterial isolatesStudy did not control for other factors*Independent blind assessment3
      • Sáez-lópez Emma
      • Guiral Elisabet
      • Fernández-orth Dietmar
      • Villanueva Sonia
      Vaginal versus obstetric infection Escherichia coli Isolates among pregnant women: antimicrobial resistance and genetic virulence profile.
      No description of participant selection**ESBL producers were identified by DDST using CTX, AMC and CAZStudy did not control for other factors*Independent blind assessment3
      • Djuikoue Ingrid Cécile
      • Woerther Paul-louis
      • Toukam Michel
      • Burdet Charles
      • Ruppé Etienne
      • Gonsu Kamga Hortense
      • et al.
      Intestinal carriage of extended spectrum beta-lactamase producing E. Coli in women with urinary tract infections, Cameroon.
      ,
      • Djuikoue Ingrid Cècile
      • Woerther Paul Louis
      • Toukam Michel
      • Burdet Charles
      • Ruppè Etienne
      • Gonsu Kamga Hortense
      • et al.
      Intestinal carriage of extended spectrum beta-lactamase producing E. Coli in women with urinary tract infections, Cameroon.
      *Truly representative of outpatient women consulting for a suspicion of UTI, during the study period**The presence of ESBL was determined using the double disc diffusion phenotypic method*Study controlled for other factors, multivariate analysis*Independent blind assessment5
      • Fortini Daniela
      • Fashae Kayode
      • Villa Laura
      • Feudi Claudia
      • Carattoli Alessandra
      • Garcı Aurora
      A novel plasmid carrying bla CTX-M-15 identified in commensal Escherichia coli from healthy pregnant women in Ibadan, Nigeria.
      *Truly representative of healthy pregnant women on the day of admission to hospital in Ibadan (Nigeria)**Phenotypic and genotypic characterization of ESBL productionStudy did not control for other factors*Independent blind assessment4
      • Tito Chaula
      • Seni Jeremiah
      • Ng’walida Nhandi
      • Kajura Alphaxaid
      • Mirambo Mariam M.
      • Devinney Rebekah
      • et al.
      Urinary tract infections among HIV-positive pregnant women in Mwanza city, Tanzania, are high and predicted by low CD4+ count.
      *Truly representative of HIV-positive pregnant women attending the PMTCT clinics; all consenting HIV-positive pregnant women were included during the study period**ESBL production was

      concomitantly tested on the same Mueller–Hinton agar plate, using the DDST method
      *Study controlled for other factors, multivariate analysis*Independent blind assessment5
      • Bebell Lisa M.
      • Ngonzi Joseph
      • Bazira Joel
      • Fajardo Yarine
      • Boatin Adeline A.
      • Siedner Mark J.
      • et al.
      Antimicrobial-resistant infections among postpartum women at a Ugandan referral hospital.
      *Truly representative of febrile, hypothermic, or normothermic post-partum women in the hospital**ESBL phenotype if synergy was observed between AMC and CAZ or CTXThe study design allowed a 4:1 ratio of normothermic to febrile/hypothermic post-partum women, but did not control for other factors**Record linkage and the statistical test used clearly described and appropriate; p-value presented5
      AMC, amoxicillin–clavulanic acid; CASFM, Committé Antibiogramme − Société Française de Microbiologie; CAZ, ceftazidime; CTX, cefotaxime; DDST, double disc synergy test; ESBL, extended-spectrum beta-lactamase-producing; ESC, extended-spectrum cephalosporin; PMTCT, prevention of mother to child transmission; UTI, urinary tract infection.
      a Stars (*) represent the number of points awarded for the category; * = 1, ** = 2.

      Results

      Geographic distribution of articles describing ESBL-E in women in Africa

      Ten observational studies were included for quantitative analysis. These were from Nigeria (n = 3), Tanzania (n = 2), Madagascar (n = 1), South Africa (n = 1), Mozambique (n = 1), Uganda (n = 1), and Cameroon (n = 1). Six studies reported on pregnant women and four on post-partum women. Three studies reported ESBL-E isolates from urine, five others from stool, one from vaginal swabs, and one from both urine and blood.

      Proportion estimates of ESBL-E in pregnant and post-partum women in Africa

      Through meta-analysis of the eligible studies, the overall pooled estimate of the ESBL-E proportion in pregnant and post-partum women in Africa was determined to be 0.17 (95% CI 0.10–0.23) or 17% (95% CI 10–23%) (Figure 2). The heterogeneity was high (I2 = 93.6%, p< 0.001).
      Figure 2
      Figure 2Pooled proportion of ESBL-E in pregnant and post-partum women in Africa.
      The pooled proportion of ESBL-E in pregnant women was 0.22 (95% CI 0.12–0.31) (Figure 2) and that of ESBL-E in post-partum women was 0.07 (95% CI 0.02–0.12). The pooled proportion of ESBL-E in hospital settings was 0.14 (95% CI 0.05–0.23) compared to 0.22 (95% CI 0.09–0.34) in community settings (Figure 3).
      Figure 3
      Figure 3Pooled proportion of ESBL-E in women, Hospital vs Community settings.
      The pooled proportion of ESBL-E infections was 0.13 (95% CI 0.01–0.27) compared to 0.19 (95% CI 0.01–0.27) for ESBL-E colonized pregnant and post-partum women (Figure 4).
      Figure 4
      Figure 4Pooled proportion of ESBL-E in women by “infection or colonization” status.

      Molecular epidemiology of ESBL-E colonization/infection

      • Chereau Fanny
      • Herindrainy Perlinot
      • Garin Benoit
      • Huynh Bich Tram
      • Randrianirina Frederique
      • Padget Michael
      • et al.
      Colonization of extended-spectrum-beta-lactamase- and NDM-1-producing Enterobacteriaceae among pregnant women in the community in a low-income country: a potential reservoir for transmission of multiresistant Enterobacteriaceae to neonates.
      (Madagascar) identified 66 ESBL-producing isolates in pregnant women, including E. coli (n = 46), Klebsiella spp (n = 11), Enterobacter cloacae (n = 5), Citrobacter freundii (n = 3), and Morganella morganii (n = 1). Forty-five isolates carried a blaCTX-M gene, 15 carried blaSHV and blaCTX-M genes, and two carried a blaSHV gene alone. No blaESBL gene and no cefoxitin resistance was detected in four ESBL-producing E. coli isolates.
      • Sáez-lópez Emma
      • Guiral Elisabet
      • Fernández-orth Dietmar
      • Villanueva Sonia
      Vaginal versus obstetric infection Escherichia coli Isolates among pregnant women: antimicrobial resistance and genetic virulence profile.
      identified one ESBL-E isolate and it carried the CTX-M-15 gene.
      • Kaba M.
      • Manenzhe R.I.
      • Moodley C.
      • Zar H.J.
      • Nicol M.P.
      Epidemiology of extended-spectrum beta-lactamase- and carbapenemase-producing bacteria in stool from apparently healthy children, South Africa. (Poster presentation).
      reported that one mother–infant pair was ESBL-positive at birth with SHV-5-producing E. cloacae.
      • Djuikoue Ingrid Cécile
      • Woerther Paul-louis
      • Toukam Michel
      • Burdet Charles
      • Ruppé Etienne
      • Gonsu Kamga Hortense
      • et al.
      Intestinal carriage of extended spectrum beta-lactamase producing E. Coli in women with urinary tract infections, Cameroon.
      reported that among 15 E. coli ESBL, all were CTX-M group 1 (n = 15).
      • Fortini Daniela
      • Fashae Kayode
      • Villa Laura
      • Feudi Claudia
      • Carattoli Alessandra
      • Garcı Aurora
      A novel plasmid carrying bla CTX-M-15 identified in commensal Escherichia coli from healthy pregnant women in Ibadan, Nigeria.
      found E. coli (n = 32) producing CTX-M-15.

      Detection and confirmation of ESBL in the laboratory: what methods were used?

      Five studies (
      • Nelson E.
      • Kayega J.
      • Seni J.
      • Mushi M.F.
      • Kidenya B.R.
      • Hokororo A.
      • et al.
      Evaluation of existence and transmission of extended spectrum beta lactamase producing bacteria from post-delivery women to neonates at Bugando Medical Center, Mwanza-Tanzania.
      ,
      • Olufunke Oluduro Anthonia
      • Abiodun Aregbesola Oladipupo
      • Dunah Fashina Christina
      Extended spectrum beta- lactamase- producing uropathogenic Escherichia coli in pregnant women diagnosed with urinary tract infections in South-Western Nigeria.
      ,
      • Aljabri Khalid S.
      • Bokhari Somoa A.
      • Khan Murtadha J.
      Original article.
      ,
      • Bebell Lisa M.
      • Ngonzi Joseph
      • Bazira Joel
      • Fajardo Yarine
      • Boatin Adeline A.
      • Siedner Mark J.
      • et al.
      Antimicrobial-resistant infections among postpartum women at a Ugandan referral hospital.
      ,
      • Tito Chaula
      • Seni Jeremiah
      • Ng’walida Nhandi
      • Kajura Alphaxaid
      • Mirambo Mariam M.
      • Devinney Rebekah
      • et al.
      Urinary tract infections among HIV-positive pregnant women in Mwanza city, Tanzania, are high and predicted by low CD4+ count.
      ), detected ESBL production using the double disc synergy test (DDST).
      • Chereau Fanny
      • Herindrainy Perlinot
      • Garin Benoit
      • Huynh Bich Tram
      • Randrianirina Frederique
      • Padget Michael
      • et al.
      Colonization of extended-spectrum-beta-lactamase- and NDM-1-producing Enterobacteriaceae among pregnant women in the community in a low-income country: a potential reservoir for transmission of multiresistant Enterobacteriaceae to neonates.
      ,
      • Djuikoue Ingrid Cècile
      • Woerther Paul Louis
      • Toukam Michel
      • Burdet Charles
      • Ruppè Etienne
      • Gonsu Kamga Hortense
      • et al.
      Intestinal carriage of extended spectrum beta-lactamase producing E. Coli in women with urinary tract infections, Cameroon.
      , and
      • Kaba M.
      • Manenzhe R.I.
      • Moodley C.
      • Zar H.J.
      • Nicol M.P.
      Epidemiology of extended-spectrum beta-lactamase- and carbapenemase-producing bacteria in stool from apparently healthy children, South Africa. (Poster presentation).
      utilized both synergy testing and molecular identification of ESBL (PCR sequencing).
      • Sáez-lópez Emma
      • Guiral Elisabet
      • Fernández-orth Dietmar
      • Villanueva Sonia
      Vaginal versus obstetric infection Escherichia coli Isolates among pregnant women: antimicrobial resistance and genetic virulence profile.
      and
      • Fortini Daniela
      • Fashae Kayode
      • Villa Laura
      • Feudi Claudia
      • Carattoli Alessandra
      • Garcı Aurora
      A novel plasmid carrying bla CTX-M-15 identified in commensal Escherichia coli from healthy pregnant women in Ibadan, Nigeria.
      used molecular identification of ESBL.

      Factors associated with ESBL-E in pregnant women in Africa

      Three studies included a multivariate analysis of risk factors for ESBL-E colonization/infection among pregnant women.
      • Chereau Fanny
      • Herindrainy Perlinot
      • Garin Benoit
      • Huynh Bich Tram
      • Randrianirina Frederique
      • Padget Michael
      • et al.
      Colonization of extended-spectrum-beta-lactamase- and NDM-1-producing Enterobacteriaceae among pregnant women in the community in a low-income country: a potential reservoir for transmission of multiresistant Enterobacteriaceae to neonates.
      identified private indoor access to drinking water (odds ratio (OR) 3.8, 95% CI 1.2–11.6) and living in an individual house (OR 2.2, 95% CI 1.0–4.8) as independent risk factors for ESBL-E colonization among Malagasy women (after adjusting for delivery period and study area).
      • Djuikoue Ingrid Cècile
      • Woerther Paul Louis
      • Toukam Michel
      • Burdet Charles
      • Ruppè Etienne
      • Gonsu Kamga Hortense
      • et al.
      Intestinal carriage of extended spectrum beta-lactamase producing E. Coli in women with urinary tract infections, Cameroon.
      ) found that the detection of antimicrobial activity in the stool sample was the only independent risk factor associated with ESBL E. coli carriage in Cameroonian women (OR 5.4, 95% CI 2.0–14.7).
      • Bebell Lisa M.
      • Ngonzi Joseph
      • Bazira Joel
      • Fajardo Yarine
      • Boatin Adeline A.
      • Siedner Mark J.
      • et al.
      Antimicrobial-resistant infections among postpartum women at a Ugandan referral hospital.
      ) identified single marital status (OR 2.6, 95% CI 1.1–6.1, p = 0.026), low CD4+ count of <200/μl (OR 2.9, 95% CI 1.1–7.7, p = 0.031), and current UTI symptoms (OR 2.5, 95% CI 1.1–6.0, p = 0.03) as independent predictors of ESBL-E infection.
      The following elements were not found to be significantly associated with ESBL-E colonization/infection in these three studies: being employed or being a housewife (
      • Tito Chaula
      • Seni Jeremiah
      • Ng’walida Nhandi
      • Kajura Alphaxaid
      • Mirambo Mariam M.
      • Devinney Rebekah
      • et al.
      Urinary tract infections among HIV-positive pregnant women in Mwanza city, Tanzania, are high and predicted by low CD4+ count.
      ), drinking water supply from a spring or a well (
      • Chereau Fanny
      • Herindrainy Perlinot
      • Garin Benoit
      • Huynh Bich Tram
      • Randrianirina Frederique
      • Padget Michael
      • et al.
      Colonization of extended-spectrum-beta-lactamase- and NDM-1-producing Enterobacteriaceae among pregnant women in the community in a low-income country: a potential reservoir for transmission of multiresistant Enterobacteriaceae to neonates.
      ), and hospitalization in the last 3 months (
      • Djuikoue Ingrid Cécile
      • Woerther Paul-louis
      • Toukam Michel
      • Burdet Charles
      • Ruppé Etienne
      • Gonsu Kamga Hortense
      • et al.
      Intestinal carriage of extended spectrum beta-lactamase producing E. Coli in women with urinary tract infections, Cameroon.
      ,
      • Djuikoue Ingrid Cècile
      • Woerther Paul Louis
      • Toukam Michel
      • Burdet Charles
      • Ruppè Etienne
      • Gonsu Kamga Hortense
      • et al.
      Intestinal carriage of extended spectrum beta-lactamase producing E. Coli in women with urinary tract infections, Cameroon.
      ).

      Discussion

      The close relationship of the mother–infant pair represents a potential risk for cross-transmission of maternal pathogens leading to neonatal colonization or infection. Several studies have confirmed the role of maternal colonization in the subsequent development of neonatal sepsis (particularly for group B Streptococcus, but also for ESBL-E) (
      • Chan Grace J.
      • Lee Anne C.C.
      • Baqui Abdullah H.
      • Tan Jingwen
      • Black Robert E.
      Risk of early-onset neonatal infection with maternal infection or colonization: a global systematic review and meta-analysis.
      ,
      • Kaba M.
      • Manenzhe R.I.
      • Moodley C.
      • Zar H.J.
      • Nicol M.P.
      Epidemiology of extended-spectrum beta-lactamase- and carbapenemase-producing bacteria in stool from apparently healthy children, South Africa. (Poster presentation).
      ,
      • Denkel Luisa A.
      • Schwab Frank
      • Kola Axel
      • Leistner Rasmus
      • Garten Lars
      • von Weizsacker Katharina
      • et al.
      The mother as most important risk factor for colonization of very low birth weight (VLBW) infants with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E).
      ,
      • Rettedal S.
      • Löhr I.H.
      • Bernhoff E.
      • Natås O.B.
      • Sundsfjord A.
      • Øymar K.
      Extended-spectrum β-lactamase-producing Enterobacteriaceae among pregnant women in Norway: prevalence and maternal-neonatal transmission.
      ).
      However, the scarcity of research on determinants of maternal colonization in Africa is worrisome. This meta-analysis of eligible published studies determined an overall pooled prevalence of colonization or infection with ESBL-E in pregnant and post-partum women in Africa of 17% (95% CI 10–23%). This rate of colonization or infection with ESBL-E is in line with a well-powered systematic review conducted in Africa by
      • Tansarli Giannoula S.
      • Poulikakos Panagiotis
      • Kapaskelis Anastasios
      • Falagas Matthew E.
      Proportion of extended-spectrum β-lactamase (ESBL)-producing isolates among Enterobacteriaceae in Africa: evaluation of the evidence-systematic review.
      , who reported proportions varying from 1.5% to 22.8% (pooled from 13 studies with isolates from clinical urine samples) among patients either infected or colonized with Enterobacteriaceae. However, these proportions were not for pregnant and post-partum women as specific groups. The pooled ESBL-E rate documented herein is substantially higher than the rates found in high- and middle-income countries, e.g., Norway (2.9%) (
      • Rettedal S.
      • Löhr I.H.
      • Bernhoff E.
      • Natås O.B.
      • Sundsfjord A.
      • Øymar K.
      Extended-spectrum β-lactamase-producing Enterobacteriaceae among pregnant women in Norway: prevalence and maternal-neonatal transmission.
      ) and Argentina (5.4%) (
      • Villar Hugo Edgardo
      • Aubert Victoria
      • Baserni Marisa Noemí
      • Jugo Monica Beatriz
      Maternal carriage of extended-spectrum beta-lactamase-producing Escherichia coli isolates in Argentina.
      ). Possible explanations for increased ESBL-E carriage among African populations (both in community (
      • Pitout Johann D.D.
      • Nordmann Patrice
      • Laupland Kevin B.
      • Poirel Laurent
      Emergence of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in the community.
      ,
      • Pallecchi Lucia
      • Malossi Monica
      • Mantella Antonia
      • Gotuzzo Eduardo
      • Trigoso Christian
      • Bartoloni Alessandro
      • et al.
      Detection of CTX-M-type β-lactamase genes in fecal Escherichia coli isolates from healthy children in Bolivia and Peru.
      ) and hospital settings) include poverty, suboptimal hygiene, contamination of drinking water (faeces (
      • Bain Robert
      • Cronk Ryan
      • Wright Jim
      • Yang Hong
      • Slaymaker Tom
      • Bartram Jamie
      Fecal contamination of drinking-water in low- and middle-income countries: a systematic review and meta-analysis.
      ), antibiotics), water sewage, communal toilets, easy access to antibiotics among pregnant and post-partum women in Africa, and possibly also increased use of antibiotics in livestock in Africa (
      • Kariuki Samuel
      • Dougan Gordon
      Antibacterial resistance in sub-Saharan Africa: an underestimated emergency.
      ). Another possible explanation is that the lack of trained healthcare workers (
      • Kimang’a A.N.
      A situational analysis of antimicrobial drug resistance in Africa: are we losing the battle?.
      ) and weak laboratory and infection control capacity (
      • Petti C.A.
      • Polage C.R.
      • Quinn T.C.
      • Ronald A.R.
      • Sande M.A.
      Laboratory medicine in Africa: a barrier to effective health care.
      ) may contribute to healthcare-associated transmission of ESBL-E to pregnant and post-partum women.
      Another important finding is that the pooled proportion of ESBL-E in community settings exceeded that in hospital settings (22% vs. 14%) (Figure 3). This finding may have been influenced by the high prevalence of ESBL-E in community isolates (58%) in the Cameroonian study. However, another explanation may be the effect of high-level ESBL-E contamination of community water and food sources, lack of sanitation, and possibly overuse of antibiotics. The apparent difference in ESBL-E proportions between community and hospital settings could also be explained by the fact that all included studies from the community only studied ESBL-E colonization. In this meta-analysis, the proportion of ESBL-E colonization was found to be greater than ESBL-E infection.
      The detection of ESBL-E in samples from hospitalized pregnant women with short lengths of stay may represent community-acquired colonization and/or infection with ESBL-E. Because ESBL-E stool carriage persists for a variable length of time (
      • Ahmed Salwa Fouad
      • Ali Mostafa Mohamed M.
      • Mohamed Zienat Kamel
      • Moussa Tarek A.
      • Klena John D.
      Fecal carriage of extended-spectrum β-lactamases and AmpC-producing Escherichia coli in a Libyan community.
      ), the study population may have acquired ESBL-E during pregnancy that then persisted up to delivery and the post-partum period, reflecting community-acquired antimicrobial resistance genes rather than healthcare-associated acquisition.
      The pooled proportion of ESBL-E was higher among pregnant women than post-partum women (22% vs. 7%) (Figure 2). This difference may be explained by a greater probability of UTIs with ESBL-E during pregnancy than in the post-partum period (
      • Sáez-lópez Emma
      • Guiral Elisabet
      • Fernández-orth Dietmar
      • Villanueva Sonia
      Vaginal versus obstetric infection Escherichia coli Isolates among pregnant women: antimicrobial resistance and genetic virulence profile.
      ). It may also possibly represent differences in asymptomatic bacteriuria during pregnancy, differences in antibiotic prescribing practices, and different decision-making when choosing to send samples from pregnant vs. post-partum women for culture.
      The clinical significance of increased ESBL-E-associated UTI during pregnancy is the potential for adverse pregnancy and neonatal outcomes, including intrauterine growth restriction, low birth weight, premature rupture of the membranes, foetal death, and neonatal infections (
      • Loh K.Y.
      • Sivalingam N.
      Urinary tract infections in pregnancy.
      ,
      • Romero R.
      • Oyarzun E.
      • Mazor M.
      • Sirtori M.
      • Hobbins J.C.
      • Bracken M.
      Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth weight.
      ,
      • Ovalle A.
      • Levancini M.
      Urinary tract infections in pregnancy.
      ,
      • Matuszkiewicz-Rowińska Joanna
      • Małyszko Jolanta
      • Wieliczko Monika
      Urinary tract infections in pregnancy: old and new unresolved diagnostic and therapeutic problems.
      ).
      In this systematic review and meta-analysis, a few studies attempted to report on factors associated with ESBL-E colonization in women in Africa; however, the risk factors analysed varied from one study to another and their pooled estimates could not be produced. The molecular epidemiology of the ESBL-E enzymes identified in the Madagascar (
      • Chereau Fanny
      • Herindrainy Perlinot
      • Garin Benoit
      • Huynh Bich Tram
      • Randrianirina Frederique
      • Padget Michael
      • et al.
      Colonization of extended-spectrum-beta-lactamase- and NDM-1-producing Enterobacteriaceae among pregnant women in the community in a low-income country: a potential reservoir for transmission of multiresistant Enterobacteriaceae to neonates.
      ), Nigeria (
      • Fortini Daniela
      • Fashae Kayode
      • Villa Laura
      • Feudi Claudia
      • Carattoli Alessandra
      • Garcı Aurora
      A novel plasmid carrying bla CTX-M-15 identified in commensal Escherichia coli from healthy pregnant women in Ibadan, Nigeria.
      ), Cameroon (
      • Djuikoue Ingrid Cècile
      • Woerther Paul Louis
      • Toukam Michel
      • Burdet Charles
      • Ruppè Etienne
      • Gonsu Kamga Hortense
      • et al.
      Intestinal carriage of extended spectrum beta-lactamase producing E. Coli in women with urinary tract infections, Cameroon.
      ), and Mozambique (
      • Sáez-lópez Emma
      • Guiral Elisabet
      • Fernández-orth Dietmar
      • Villanueva Sonia
      Vaginal versus obstetric infection Escherichia coli Isolates among pregnant women: antimicrobial resistance and genetic virulence profile.
      ) studies was in keeping with the global predominance of the CTX-M clone, which is also widely reported in community-acquired UTI (
      • Pitout Johann D.D.
      • Nordmann Patrice
      • Laupland Kevin B.
      • Poirel Laurent
      Emergence of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in the community.
      ,
      • Peirano Gisele
      • Pitout Johann D.D.
      Molecular epidemiology of Escherichia coli producing CTX-M beta-lactamases: the worldwide emergence of clone ST131 O25:H4.
      ,
      • Pallecchi Lucia
      • Malossi Monica
      • Mantella Antonia
      • Gotuzzo Eduardo
      • Trigoso Christian
      • Bartoloni Alessandro
      • et al.
      Detection of CTX-M-type β-lactamase genes in fecal Escherichia coli isolates from healthy children in Bolivia and Peru.
      ,
      • Livermore David M.
      • Canton Rafael
      • Gniadkowski Marek
      • Nordmann Patrice
      • Rossolini Gian Maria
      • Arlet Guillaume
      • et al.
      CTX-M: Changing the face of ESBLs in Europe.
      ).
      This systematic review has several strengths. A comprehensive search of several electronic databases was performed, in addition to manual searches and attempts to contact authors of relevant studies to obtain specific details. The authors made an effort to search the ‘grey literature’ by using Google Scholar, as many African publications are not listed in PubMed or Scopus. This appears to be the first systematic review and meta-analysis on ESBL-E colonization and/or infection focusing on pregnant and post-partum women in Africa. This group is of particular importance for vertical transmission and subsequent neonatal colonization and/or infection. Each study was thoroughly assessed for risk of bias.
      While informative, this systematic review and meta-analysis has a number of limitations. The number of eligible studies was small, demonstrating the apparent lack of studies on ESBL-E colonization and infection in this population group: pregnant and post-partum women in Africa. Given the limited sample size, the findings of this systematic review and meta-analysis may not be generalizable to all pregnant and/or post-partum women in Africa. The publications retrieved and included in the meta-analysis were all observational studies, a study type that is prone to many biases, including selection and information biases (
      • Archer Sujata L.
      • Horn Linda VAN
      Perspectives in practice publishing nutrition research: a review of 2006.
      ).
      More robust studies are needed to understand how frequently pregnant and/or post-partum women become colonized or infected with ESBL-E in Africa, as well as the related risk factors in both community and hospital settings, to inform future interventions to reduce their rates. Interventions could include improved sanitation and water supplies, education of mothers on personal hygiene, restriction of antibiotic use during pregnancy, and strengthening of infection prevention in healthcare facilities.

      Plain language summary

      The level of colonization and/or infection with ESBL-E in pregnant and post-partum women in Africa is higher than that reported from high- and middle -income settings. In African pregnant and post-partum women, the prevalence of ESBL-E in community isolates exceeds that in hospital isolates. Maternal ESBL-E colonization/infection represents a risk for mother to child pathogen transmission with the potential for subsequent neonatal colonization and/or infection.

      Key recommendation

      Further studies are needed to establish ESBL-E colonization and infection rates amongst pregnant and post-partum women and their determinants in all African regions. Interventions to reduce ESBL-E colonization and carriage in Africa should focus on preventing both community- and healthcare-associated ESBL-E acquisition. Potential interventions could include the provision of safe sanitation and clean water supplies, education of mothers on personal hygiene, restricted use of antibiotics in pregnancy, and strengthening of infection prevention efforts in healthcare facilities (hand hygiene and appropriate disinfection of obstetric equipment and the environment).

      Research gaps

      It is not well understood how frequently pregnant and post-partum women become colonized and infected with ESBL-E, which risk factors promote ESBL-E colonization/infection, and how this could be prevented or managed, both in community and hospital settings in Africa. In addition, health systems research is needed to increase the understanding of the problem of antimicrobial resistance in maternal and neonatal infections at the macro (leadership or governance), meso (healthcare facilities and programmes), and micro (pregnant women or service consumers) levels.

      Funding sources

      None.

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