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.
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 One:e8305).
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 cephalosporinresistant 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 One:e1001104).
• 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; 99:7687–7692; Deurenberg & Stobberingh,
2008;Infect Genet Evol 2008; 8:747–763).
•
MRSA host species adaptation: ST398
Introduction
Facts on Africa:
World’s second largest continent and
second most populous after Asia
Account for one seventh of the
world’s 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/map-africa-3/
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, 72:325-328).
•
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, 74:223-224) and Ethiopia (Geyid and Lemeneh, 1991, Ethiop Med J:
29:149-161).
Global Prevalence and Epidemiology of MRSA
Africa?
Stefani et al., (2012): IJAA; 39:273– 282.
?
Otto M (2012): Cell Microbiol pages n/a-n/a, DOI: 10.1111/j.14625822.2012.01832.x
De Lencastre and Tomasz A (2011): IJMM; 301:623-629.
?
Otter JA, French GL (2010): Lancet Infect Dis; 10:227-239.
Prevalence, antibiotic resistance and epidemiology of MRSA in Africa
Methicillin resistance detected by oxacillin (E-test)
Prevalence of MRSA in Africa: Nigeria (West Africa),
South Africa (South Africa) and East Africa (Eritrea)
Prevalence of MRSA (Nigeria): 12.5-16.2%
Six tertiary institutions in North-East Nigeria;
(January-December, 2007) 12/96
Four health care institutions in South-West
Nigeria; (January-April 2009) 11/68
Prevalence of MRSA (South Africa): 27%
14 health care institutions in KwaZulu-Natal –
South Africa:
March 2001-August 2003) 61/227
278 S. aureus isolates (National Reference
Laboratory, Eritrea) 26/278
Prevalence of MRSA (Eritrea): 9.4%
Prevalence of MRSA in North Africa
Borg et al., (2007) JAC, 60:1310-1315.
Antibiotic resistance and epidemiology of MRSA in South Africa
South Africa
Pulsotype F: resistant to ciprofloxacin,
susceptible to rifampicin (t037-ST239-III –
Brazilian/Hungarian clone)
Pulsotype A: resistant to rifampicin; ( t064ST1173-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: 58:1219-1226.
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
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 ( t064ST1173-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. 2010;48:4608-4611
Moodley et al., JCM; 2010, 48:4608-4611
Antibiotic resistance and epidemiology of MRSA in Nigeria
West Africa
ST8: South-West Nigeria
ST241: single locus variant of ST239 – Maiduguri: North-East Nigeria
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
Fluoroquinolone-resistant PVL-positive multiresistant MRSA in the hospital setting
Tunisia; PVL+ve ST80-IV
Morocco
ST239/241
Algeria
PVL +ve;
ST80-IV
Epidemiology of MRSA in North Africa
Predominant MRSA clones in Africa
PVL+ve-ST80-IV
PVL +ve ST5-IV/V ?
ST239/241-III
ST88-IV ?
ST88-IV/V ?
ST612-IV,
ST239-III
http://www.enchantedlearning.com/geography/africa/outlinemap/map.GIF
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.
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
http://www.admerproject.org/
Antibiotic Drug Use, Monitoring and Evaluation of Resistance
Collaboration 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
-
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Price of cotrimoxazole:
Nigeria: $2 (20 tablets)
Liberia: $1.20 (20 tablets)
Tanzania: $2 (20 tablets)
Prophylaxis 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.
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