1. Drivers of antibiotic resistance in Uganda and Zambia Presentation to the Global Health Council, Washington, DC, June 14, 2011 Alliance for the Prudent Use of Antibiotics Susan D. Foster, PhD MA Anibal Sosa, MD C.F. Najjuka, MD D. Mwenya, MSc

2. Objectives Objective 1: Improve knowledge of antibiotic use and resistance to provide baseline information for design of interventions. Objective 2: Analyze prescription and dispensing of antibiotics to identify processes and behaviors as targets for interventions. Objective 3: Assess laboratory capacity to conduct antibiotic surveillance and impact policy and clinical practice.

3. Project approach Review of published and unpublished data on resistance Hospital laboratory assessments: 29 laboratories and in Uganda, and 17 laboratories in Zambia Team of 92 Ugandan medical students examined 10,172 outpatient records from 11 sites in Uganda Team of 16 Zambian pharmacy interns examined 4,218 outpatient records from 8 sites in Zambia Interviews with formal health staff and attendants at drugshops and pharmacies Nearly 1,000 drug samples collected for quality testing 3

4. 4 92 Medical and pharmacy students trying out data entry program Medical and pharmacy students picking up equipment and getting per diems Uganda

5. Meeting with medical student data collectors after data collection had ended Visit to Mulago Hospital pediatric ward (project pharmacist Annette Naggayi on right, Matron in center, and Gates foundation staff on left) Copies of questionnaires being handed over to students going to field 5

6. ARSANA Project Site Source: Hopkins et al, JID 2008; 197:510-18 6

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9. Antibiotic resistance by drug 9

10. S. pneumoniae and H.influenzae resistance rates 10 Source: Zambia, Ndola Hospital records; Uganda, Netspear data

11. Rapid rise in resistance to cotrimoxazole in Uganda, 2001-2007 11

12. Cotrimoxazole – actual vs. recommended dosage 12

13. Amoxicillin – actual vs recommended dosage in Uganda 13

14. Antibiotic use in Zambia, by age 14 Liquid formulations

15. Antibiotic use in Uganda by age 15

16. Antibiotics at a Ugandan drugshop 16

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18. Diagnoses of pneumonia: Uganda 288 of 2347 (12.3%) children under 6 had a diagnosis of pneumonia 95 (33%) were judged to be “severe” and 193 (66%) “not severe.” 18

19. Availability of drugs needed to treat pneumonia in Uganda 19

20. Ineffective treatment of pneumonia in Uganda Why do so many die despite treatment? Cotrimoxazole is the most often used antibiotic (38.7%) S.pneumoniae ABR to cotrimoxazole exceeds 80-90% in Uganda (and Zambia) 88 children (30.5%) received cotrimoxazole alone no antibiotic was recorded for 19 children (7%) So about 37% of children with pneumonia received potentially ineffective antibiotic therapy for pneumonia. 20

21. Rates of failure of TLC by drug: Uganda N=270 samples (tablets and capsules only) collected at sites around Uganda; overall failure rate was 6.3%

22. Malaria / pneumonia overlap Uganda research: It is difficult for many clinicians to distinguish between malaria and pneumonia in young children – Källander K, Nsungwa-Sabiiti J & Peterson S (2004) Symptom overlap for malaria and pneumonia. Acta Tropica 90, 211–214. For 186 (64.6%) of the Ugandan children diagnosed with pneumonia, a clinical diagnosis of malaria was also recorded – 177 (61.5%) received at least one antimalarial Conversely, 65% of malaria cases also received one or more antibiotic, of which 55% was cotrimoxazole. 22

23. Malaria / pneumonia overlap Uganda research: It is difficult for many clinicians to distinguish between malaria and pneumonia in young children – Källander K, Nsungwa-Sabiiti J & Peterson S (2004) Symptom overlap for malaria and pneumonia. Acta Tropica 90, 211–214. For 186 (64.6%) of the Ugandan children diagnosed with pneumonia, a clinical diagnosis of malaria was also recorded – 177 (61.5%) received at least one antimalarial Conversely, 65% of malaria cases also received one or more antibiotic, of which 55% was cotrimoxazole. 23

24. Overdiagnosis of malaria by age and malaria transmission zone in Uganda 24 Over ¾ of overdiagnosed cases were in older children and adults, not in the under 5s

25. Summary of findings Resistance to the most common drug for respiratory infections – cotrimoxazole – is nearly 100% (S.pneumoniae) Antibiotic use is much higher in Uganda than Zambia – the malaria effect? Antibiotic susceptibility data are scarce and mostly urban 25

26. Summary of findings cont’d. Laboratory capacity is generally poor and patchy – but some centers doing AST could be upgraded to monitor treatment effectiveness and guide therapy choices – Data could be collected and used to ensure effective treatment and guidelines – A cost-effective way to collect essential data Malaria is driving antibiotic use, especially in Uganda – nearly 20% of antibiotics are prescribed for malaria in adults – Major savings to be made in both antibiotics and Coartem 26

27. Summary of findings, cont’d. Amoxicillin is used, but not for those who need it most – Used for older children and adults – Cost is higher (at least twice or more) than cotrim. Dosing of amoxicillin was too low for children above 1 – guidelines are known, but not followed Amoxicillin is fragile and needs careful handling Few syrups and suspensions “child friendly” formulations are in use Issues with under-dosing and administration 27

28. Summary of findings, cont’d Quality of drugs was generally good – few expired, none counterfeit – all contained active ingredient (some mislabeled) – Most failures were amoxicillin – stability issues Health providers in both formal and informal sector are eager to improve their antibiotic prescription practices – keen for information and training 28