The study of antibiotic resistance and epidemiology of MRSA in Africa:
patterns, problems and prospects
Adebayo SHITTUDepartment of Microbiology
Faculty of ScienceObafemi 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 cephalosporin-resistant 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 clonesCC5: 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
Map of Africahttp://www.vbmap.org/africa-maps-4/map-africa-3/
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
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).
Otto M (2012): Cell Microbiol pages n/a-n/a, DOI: 10.1111/j.1462-5822.2012.01832.x
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Stefani et al., (2012): IJAA; 39:273– 282. De Lencastre and Tomasz A (2011): IJMM; 301:623-629.
Otter JA, French GL (2010): Lancet Infect Dis; 10:227-239.
Global Prevalence and Epidemiology of MRSA
Africa?
Methicillin resistance detected by oxacillin (E-test)
Prevalence, antibiotic resistance and epidemiology of MRSA in Africa
Six tertiary institutions in North-East Nigeria; (January-December, 2007) 12/96
Prevalence of MRSA (Nigeria): 12.5-16.2%
Four health care institutions in South-West Nigeria; (January-April 2009) 11/68
Prevalence of MRSA in Africa: Nigeria (West Africa), South Africa (South Africa) and East Africa (Eritrea)
14 health care institutions in KwaZulu-Natal – South Africa:
March 2001-August 2003) 61/227
Prevalence of MRSA (South Africa): 27%
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
Pulsotype F: resistant to ciprofloxacin, susceptible to rifampicin (t037-ST239-III – Brazilian/Hungarian clone)
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: 58:1219-1226.
South Africa
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
Moodley A et al. J. Clin. Microbiol. 2010;48:4608-4611
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)
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.
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
Moodley et al., JCM; 2010, 48:4608-4611
ST8: South-West Nigeria
ST241: single locus variant of ST239 – Maiduguri: North-East Nigeria
Antibiotic resistance and epidemiology of MRSA in Nigeria
West Africa
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
Central Africa: ST88, ST5
86 MRSA isolates from seven major tertiary health care centres in Cameroon, Madagascar, Morocco, Niger and Senegal
Epidemiology of MRSA in North Africa
Algeria PVL +ve; ST80-IV
Tunisia; PVL+ve ST80-IVMorocco
ST239/241
Fluoroquinolone-resistant PVL-positive multi-resistant MRSA in the hospital setting
ST612-IV, ST239-III
PVL+ve-ST80-IV
ST239/241-III
ST88-IV ?
http://www.enchantedlearning.com/geography/africa/outlinemap/map.GIFP
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T5
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Predominant MRSA clones in Africa
ST88-IV/V ?
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.
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
Research on MRSA in Africa: Prospects for the Future
http://www.admerproject.org/Antibiotic Drug Use, Monitoring and Evaluation of ResistanceCollaboration 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)
- 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