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The study of antibiotic resistance and epidemiology of MRSA in Africa: patterns, problems and prospects

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Title: The study of antibiotic resistance and epidemiology of MRSA in Africa: patterns, problems and prospects


1
The study of antibiotic resistance and
epidemiology of MRSA in Africa patterns,
problems and prospects
  • Adebayo SHITTU
  • Department of Microbiology
  • Faculty of Science
  • Obafemi Awolowo University
  • Ile-Ife, NIGERIA

ISSSI, 2012 Lyon, France, 28 August, 2012.
2
Introduction
  • Methicillin-resistant Staphylococcus aureus
    (MRSA) continues to be a major challenge to human
    health (hospital and community infections).
  • It has been established as a pathogen for a wide
    variety of domestic animals and linked with
    livestock associated infections.
  • The mecA gene (carried by the staphylococcal
    chromosome cassette SCC element)
  • - encodes an altered penicillin-binding protein
    (PBP) 2a
  • MRSA multi-resistance to antibiotics, spread of
    epidemic clones
  • Multicentre matched outcome study of 659 surgical
    patients (Duke Infection Control Hospital Network
    DICON).
  • Skin and soft tissue infections (SSIs) due to
    MRSA led to
  • - 7-fold increased risk of death,
  • - 35-fold increased risk of hospital
    readmission,
  • - more than 3 weeks of additional
    hospitalization, and
  • - more than 60,000 of additional charges.
  • compared with uninfected controls (Anderson et
    al., 2009 PloS Onee8305).

3
Introduction
  • 31 countries that participated in the European
    Antimicrobial Resistance Surveillance System
    (EARSS) in 2007.
  • - blood stream infections (BSIs) caused by
    methicillin-resistant Staphylococcus aureus
    (MRSA) and third-generation cephalosporin- resis
    tant Escherichia coli
  • - 27,711 episodes of MRSA bloodstream infections
    (BSIs) were associated with
  • - 5,503 excess deaths
  • - 255,683 excess hospital days in the
    participating EU countries
  • - Total costs attributed to excess hospital
    stays for MRSA was 44 million Euros.
  • (de Kraker et al., 2011 PloS Onee1001104).
  • Worldwide MRSA clones
  • CC5 ST5 SCCmec type II (New York/Japan)
    ST5-IV (paediatric) ST228-I (southern
    German)
  • CC8 ST250-I (Archaic clone) ST8-IV (EMRSA
    -2,-6) ST8-II (Irish-1) ST239-III
    (Brazilian/Portuguese) ST247-I (Iberian)
  • CC22 ST22-IV (EMRSA-15)
  • CC30 ST36-II (EMRSA-16)
  • CC45 ST45-IV (Berlin)
  • (Enright et al., 2002 Proc Natl Acad Sci USA
    9976877692 Deurenberg Stobberingh,
    2008Infect Genet Evol 2008 8747763).
  • MRSA host species adaptation ST398

4
Introduction
Facts on Africa Worlds second largest
continent and second most populous after Asia
Account for one seventh of the worlds
population Made up of 57 countries Over 1,000
languages Malaria is Africa's leading cause of
under-five mortality Diarrheal diseases remain
the biggest cause of sickness-linked death
Map of Africa http//www.vbmap.org/africa-maps-4/m
ap-africa-3/
5
Introduction
  • HIV, tuberculosis, malaria and various enteric
    and pneumococcal infections considered more
    important cause of morbidity and mortality than
    infections due to S. aureus/MRSA in
    resource-rich but mismanaged countries in
    Africa.
  • A number of reports on the three waves on the
    epidemiology of MRSA have been described
    extensively in developed countries but the
    disease burden is not well understood and
    appreciated in Africa.
  • Data on antibiotic resistance, distribution of
    MRSA clones in Africa
  • - Reduce ineffective antibiotic prescribing,
    poor clinical outcome assist and guide
    therapy.
  • - Provide insights to mechanism of
    dissemination guide infection control measures.
  • One of the earliest reports of MRSA in Africa was
    in a Durban hospital in South Africa (Scragg et
    al., 1978, Trans R Soc Trop Med Hyg, 72325-328).
  • This was followed by studies in Nigeria (Rotimi
    et al., 1987, Cent Afr J Med, 32 155-158), South
    Africa (Peddie et al., 1988, S Afr Med J,
    74223-224) and Ethiopia (Geyid and Lemeneh,
    1991, Ethiop Med J 29149-161).

6
Global Prevalence and Epidemiology of MRSA
Africa?
Stefani et al., (2012) IJAA 39273 282.
De Lencastre and Tomasz A (2011) IJMM
301623-629.
?
?
Otto M (2012) Cell Microbiol pages n/a-n/a, DOI
10.1111/j.1462-5822.2012.01832.x
Otter JA, French GL (2010) Lancet Infect Dis
10227-239.
7
Prevalence, antibiotic resistance and
epidemiology of MRSA in Africa
Methicillin resistance detected by oxacillin
(E-test)
8
Prevalence of MRSA in Africa Nigeria (West
Africa), South Africa (South Africa) and East
Africa (Eritrea)
Prevalence of MRSA (Nigeria) 12.5-16.2
Prevalence of MRSA (South Africa) 27
Six tertiary institutions in North-East Nigeria
(January-December, 2007) 12/96
14 health care institutions in KwaZulu-Natal
South Africa March 2001-August 2003) 61/227
Four health care institutions in South-West
Nigeria (January-April 2009) 11/68
278 S. aureus isolates (National Reference
Laboratory, Eritrea) 26/278
Prevalence of MRSA (Eritrea) 9.4
9
Prevalence of MRSA in North Africa
Borg et al., (2007) JAC, 601310-1315.
10
Antibiotic resistance and epidemiology of MRSA in
South Africa
Pulsotype F resistant to ciprofloxacin,
susceptible to rifampicin (t037-ST239-III
Brazilian/Hungarian clone)
South Africa
Pulsotype A resistant to rifampicin (
t064-ST1173-IV t064-ST1338-IV PVL-negative DLV
and SLV of ST612 respectively).
Pulsotype G susceptible to tetracycline and
minocycline (t045-ST5-III similar to New
York/Japan clone)
61 MRSA isolates 14 health care institutions in
KZN South Africa (227 consecutive non-duplicate
S. aureus isolates March 2001-August
2003) Shittu et al., 2009 JMM 581219-1226.
11
MRSA-ST612-IV resistant to rifampicin,
gentamicin and cotrimoxazole MRSA-ST239-III
susceptible to rifampicin
100MRSA 10CAMRSA 90HAMRSA Five hospitals in
Cape Town January 2007 to December, 2008
12
61 MRSA isolates 14 health care institutions in
KZN South Africa (227 consecutive non-duplicate
S. aureus isolates March 2001-August 2003) Seven
Pulsotypes Pulsotype A Predominant in KZN
hospitals ( t064-ST1173-IV t064-ST1338-IV
PVL-negative DLV and SLV of ST612
respectively). Pulsotype F Predominant in
hospitals in Durban (t037-ST239-SCCmec III
Brazilian/Hungarian clone) Pulsotype G Observed
in Durban, Pietermaritzburg (t045-ST5-SCCmec III
similar to New York/Japan clone)
Predominant clones in South Africa MRSA-ST612-IV
and ST239-III MRSA-ST239-III and ST612-IV
Multiresistance Resistance to gentamicin and
cotrimoxazole a common feature Resistance to
mupirocin (MRSA-ST239-III) emerging trend in
South Africa
320 MRSA isolates August 2005-November 2006
nine provinces of South Africa Type
D-spaCC12-ST239-III identified in all the
provinces with the exception of the Eastern and
Western Cape. Type K-spaCC64-SCCmecIV-ST612 most
widespread clone not detected in Limpopo,
Gauteng, and North West Provinces.
Moodley A et al. J. Clin. Microbiol.
2010484608-4611
Moodley et al., JCM 2010, 484608-4611
13
Antibiotic resistance and epidemiology of MRSA in
Nigeria
West Africa
ST8 South-West Nigeria ST241 single locus
variant of ST239 Maiduguri North-East Nigeria
14
86 MRSA isolates from seven major tertiary health
care centres in Cameroon, Madagascar, Morocco,
Niger and Senegal
Central Africa ST88, ST5
Predominant clones in West Africa multiresistant
MRSA-ST239/241-III Niger and Northern
Nigeria PVL-positive MRSA-ST5-IV/V
Senegal Resistance to tetracycline and
cotrimoxazole common feature to ST239/241, ST5
and ST88
15
Fluoroquinolone-resistant PVL-positive
multi-resistant MRSA in the hospital setting
Tunisia PVLve ST80-IV
Morocco ST239/241
Algeria PVL ve ST80-IV
Epidemiology of MRSA in North Africa
16
Predominant MRSA clones in Africa
PVLve-ST80-IV
ST239/241-III
PVL ve ST5-IV/V ?

ST88-IV ?
ST88-IV/V ?
ST612-IV, ST239-III
http//www.enchantedlearning.com/geography/africa/
outlinemap/map.GIF
17
Problems associated with basic research on MRSA
in Africa
  • Lack of funding preference for priority
    diseases malaria, HIV/AIDS, tuberculosis.
  • Laboratory Service
  • - Lack of basic infrastructure especially at
    the level of Primary Health Care.
  • - Inability to incorporate antibiotic
    susceptibility testing as an integral part of
    laboratory practice at the level of Primary
    Health Care.
  • - Lack of knowledge and expertise on molecular
    tools in understanding the evolution of
    infectious diseases/brain drain.
  • - Lack of cooperation, support and network
    between countries on a regional and
    continental level.

18
Research on MRSA in Africa Prospects for the
Future
  • http//www.african-german-staph.net/ - funded by
    the DFG (Germany)
  • Three African locations
  • Albert Schweitzer Hospital Lambarene Gabon
  • Ifakara Health Research and Development Center,
    Bagamoyo, Tanzania
  • Center for Investigations on Health, Manhica,
    Mozambique
  • Three German locations
  • University of Münster (Institute of Medical
    Microbiology, Institute of Hygiene)
  • University of Freiburg (Division of Infectious
    Diseases)
  • University of Saarland (Institute of Medical
    Microbiology and Hygiene, Center of
    Bioinformatics, and Institute of Biomedical
    Engineering)
  • Collection of 100 clinical and 100 commensal S.
    aureus isolates/location (altogether 1200
    isolates).
  • spa typing The technique for this analysis has
    been distributed to all participating labs
    (African and German).
  • Microarray Analysis

19
http//www.admerproject.org/ Antibiotic Drug Use,
Monitoring and Evaluation of Resistance Collaborat
ion between Denmark and Ghana Emergence of a
critical mass of medical personnel/scientists in
a number of African countries. Resistance to
trimethoprim/sulphamethoxazole (cotrimoxazole) is
a common feature in the following MRSA clones in
Africa ST8-IV/V, ST239-III, ST88-IV, ST612-IV
and the Egyptian ST80-IV - available
over-the-counter (OTC) in many African countries
self medication - Price of cotrimoxazole
Nigeria 2 (20 tablets) Liberia 1.20 (20
tablets) Tanzania 2 (20 tablets) - Prophylaxi
s or treatment of Pnemocystis infections in
HIV-positive patients - need to understand the
mechanism for resistance Need for various
initiatives - Improve laboratory service in the
surveillance of antimicrobial resistance (S.
aureus/MRSA) at the national, regional and
continental level in Africa. - Develop
strategies (e.g. early detection of PVL ve S.
aureus/MRSA) which impact on quality of
patient care. - Encourage cheap and effective
infection control strategies based on hand
hygiene. - Surveillance of imported S.
aureus/MRSA in Africa. - Cooperation, support
and network between countries on a regional and
continental level.
20
ACKNOWLEDGEMENTS
  • Professor D.O. Kolawole Kwara State University,
    Nigeria
  • Dr Edet Udo University of Kuwait, Kuwait City
  • Professor Johnson Lin University of
    KwaZulu-Natal, South Africa
  • Dr Donald Morrison Scottish MRSA Reference
    Centre, Glasgow
  • Dr Ulrich Nübel Robert Koch Institute,
    Wernigerode, Germany
  • Dr Birgit Strommenger Robert Koch Institute,
    Wernigerode, Germany
  • Dr Franziska Layer Robert Koch Institute,
    Wernigerode, Germany
  • Dr Srdjan Stepanovic deceased
  • Professor Iruka Okeke Haverford College, USA
  • Members of the German-African Network on the
    Staphylococci
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