1. Unit 5 Surveillance from Control to Elimination tools and procedures to get information about malaria Training course on Elimination Chiangmai, Thailand 10-21 August 2015

2. Unit 5 - Objectives 1.Surveillance activities in different phases 2.Role of diagnosis in elimination, esp microscopy 3.Interpreting laboratory reports 4.Quality Assurance for Microscopy (and RDTs) 5.Use of geographical information system 6.Case detection 7.Investigation of case and foci 8.Classification of cases and foci 9.Data recording and reporting 10.Epidemiological Indicators used in surveillance 11.Establish a surveillance system

3. “ Surveillance” in different phases of malaria control to elimination involves transitions/changes. “Malaria surveillance” has different meanings in different situations (pages 1-5, WHO Surveillance Manual, Box 1.1/1.2/1.3) – High transmission (e.g. >10% prevalence) – Low transmission (<10% prevalence) – Very low transmission – No transmission In GMS countries, some areas are in Control Phase and other areas in Pre-elimination/Elimination Phase.

4. Table 1 Differences btw Control and Elimination (p.2) Phase:Control Phase Elimination phase Transmission:High/ModerateLowVery low Incidence: Cases/deaths common Little variation (time/geography) Cases/deaths less common, according to mosquito exposure Variable(time/geography) Marginal populations Cases irregular Imported cases may be high % Focal distribution Fevers: Health Facility attendance: High % due to malaria Small % due to malaria Low % due to malaria Very small % due to malaria Aim of program Reduce deaths & casesCase reductionStop transmission Resources: Data recording: Low quality/poor access to services Aggregate numbers (prevalence/surveys) Wide availability of diagnosis/treatment List of inpatients & deaths->list all cases Resources to investigate every case Case details Investigation: Inpatient cases??Inpatient case->outbreaksEvery individual case

5. Moving from phase to phase to zero In simple terms, the difference between: 10,000 vs 1000 vs 100 vs 10 vs 0 10,000 cases per year – impossible to look at every case 100 cases per year – Very possible to look at every case The transition from control to elimination depends on resourcing and staffing vs number of cases.

6. 1-Surveillance for Elimination Surveillance becomes a core intervention Staff have to go out of the office Field investigations of cases and clusters (foci) Case by case and focus by focus Simple framework of systematic activities Full documentation for eventual certification

7. 1-Surveillance for Elimination Not complicated, but a new method Set of strategies is available, but to be adapted to: – Receptivity – vulnerability of country – strata – focus

8. 1-Surveillance for Elimination WHEN and WHERE DO WE START? OPERATIONAL STRATIFICATION STEP BY STEP ELIMINATION (at sub-national)

9. 1-Surveillance for Elimination Stratification: ADMINSTRATIVE UNITS FOCUS API (10/1000) ONE CASE

10. 1-Surveillance for Elimination Find every case and finally the last parasite When we find parasite, we prevent all transmission by mosquito. Clean the foci and keep them all malaria-free for 3 years Not only sick people, but also reservoir Prevent re-infection from outside

11. Exercise 5.1 Using Box 1.1 to 1.3 (WHO Elimination Surveillance manual), make a table of the differences in each phase. Each box starts with how case registration is handled, so start there.

12. Example FeatureControl (high)Control (low)Elimination Register of individual cases Cases, sometimes without parasitological confirmation, at health facility only (maybe a log book) Cases, all parasitologically confirmed at health facility level, with aggregate data at district level Cases, with all case details for every case. Etc…..

13. 2.Laboratory diagnosis for malaria elimination Malaria diagnosis MicroscopyRDTsMolecular PCR LAMP Immuno- diagnosis

14. ??

15. Role of microscopy Advantages Good sensitivity (if microscopist well trained) Can quantify & differentiate parasite species and stages, including gametocytes Provides results quickly (if staff in place!) to guide treatment decisions Preserved slides serve as good documentation material for later certification Disadvantages Good training and regular refresher training (every 2-3 years) is required Labor intensive Requires strong QA and supervision to maintain quality Impractical or costly at peripheral health facilities? Microscopy skills are gradually disappearing in many countries, partly due to declining slides to be examined

16. Quality assurance for malaria microscopy

17. Microscopy QA systems: Critical for countries to maintain reliable diagnosis! Needs well-organized institutional set-up with dedicated staff and reference laboratories at national and subnational level (laboratory network) Involves a system for cross-checking of slides and on-site supervision by senior microscopist/Validator Training and regular re-fresher training of microscopists (every 2-3 years minimum) is essential External Competency Assessment (ECA) with rating of microscopists (Level 1-4), known also as Accreditation Establishing of malaria slide bank Proficiency testing – distribution of prepared stained blood slides in a blinded manner to laboratories in the Network

18. Support for microscopy QA implemented through WHO and ACTMalaria External competency assessment in Viet Nam, June 2012, Photo from Ken Lilley Regional malaria slide bank at the Research Institute for Tropical Medicine, Manila, Philippines

20. Role of RDTs Advantages Easy to use for everyone, minimal training required Provides quick results Practical for large-scale field deployment Reasonably good sensitivity for symptomatic cases, but low sensitivity for asymptomatic cases (or in non-immune patient) Disadvantages Cannot detect low density infections Cannot detect gametocytes Cannot quantify parasitaemias Pf/PAN tests cannot distinguish Pf from mixed infection (but other RDTs are available) In elimination programs, probably need confirmation by microscopy (at least for a minimum sample of tests) Heat stability is problem?

21. Instruction and supervision in RDT use has changed malaria diagnosis at peripheral health facilities RDTs were introduced Vanuatu during 2009-2010, which increased diagnostic services for malaria at health facility level throughout the country from 10% to 90%.

22. Many RDTs in the market - independent guidance on selection and procurement of malaria RDTs

23. QA Batch testing of malaria RDTs

25. Role of PCR Advantages Very high sensitivity and specificity! Easy to collect finger-prick blood samples, dried on filter paper and sent to lab – large scale epidemiological surveys Provides the possibility for other parasite gene studies, e.g. genotyping in drug efficacy studies Disadvantages Very demanding technique to implement and sustain Requires lots of training Requires high-standard technical service and maintenance Impractical outside major hospitals and laboratories Takes longer time to get results back – thus no role in routine case management Expensive

26. PCR lab setup requirements

27. An exception to previous statements (Cambodia)

31. Role of LAMP Advantages Very high sensitivity and specificity! Easy to collect finger-prick blood, dried on filter paper and sent to lab – large scale epidemiological surveys Provides (relatively) quick results Inexpensive? Disadvantages Demanding to implement and sustain Requires good training Requires some technical service and maintenance Impractical outside laboratories??

32. Role of immuno-diagnosis/serology Advantages Very sensitive malaria screening tool, e.g. screening of blood donations Can rule out infection in a returning traveler with persistent intermittent symptoms, but negative microscopy Can be used as part of epidemiological surveillance to identify areas of continued transmission in the pre- elimination phase Disadvantages Requires good laboratory support and lots of training Expensive Plays a limited (if any) role in the elimination phase

33. So, which method to use for elimination?? 1)Quality-assured microscopy continues to be number 1 method for routine case detection and verification 2)If microscopy not possible to sustain, RDTs offer a reasonable alternative; however, blood slides should be kept and sent for confirmation and QA in a minimum sample of cases and non-cases. 3)Microscopy and RDTs can also be used for active case detection, although cases will likely be missed 4)RDTs can be used for quick screening (eg, at airport) 5)Molecular methods will find additional cases – likely to increase effectiveness of active case finding – but is not feasible in many (most) settings

34. WHO recommendations on malaria diagnosis in low- transmission settings (Sept 2014) WHO recommendations (Sept 2014) clearly say that whatever is recommended today, there are likely to be changes as time goes on. They state that microscope or RDT is best compromise for elimination, but then they go on to describe situations where Nucleic Acid Amplification (eg PCR) can or should be used. In other words, despite the attempt to give clear guidelines, there is some slipping and sliding…

35. 2-Laboratory diagnosis - Exercises Exercise 5.2a  Evaluate the strengths and weaknesses of RDT diagnosis for elimination – is the RDT suitable for use in elimination phase?  E.g., consider the RDT your program uses now, the different types of RDTs now available, sensitivity/specificity, and how this may change in future. Exercise 5.2b  Evaluate the strengths and weaknesses of microscopic diagnosis for elimination – is the microscope suitable for use in elimination phase?  E.g., consider the deterioration of microscope skills vs the rising use of RDTs.

36. Interpretation of lab results These are all important: – Species – Stages of P.falciparum (esp gametocytes) – Parasite densities (parasites per ul or 1+/2+/3+) What If report only says “Positive”…. What If report has full details, but clinical staff does not understand the meaning….

37. P.falciparum gametocytes and asexual stages are present in first blood exam, Meaning the case has been detected late – Pf gametocytes appear about 10-12 days after asexual stages Meaning an investigation should ask: – Why was a blood exam not ordered earlier? – Was the diagnosis missed at earlier time? – Did the patient not understand the seriousness of his disease? – Etc. Interpretation of lab results (example)

38. P.falciparum asexual stages are reported in number of 100,000 per ul, or 5+ Meaning: – High risk of deterioration and death, emergency care needed immediately Interpretation of lab results (example)

39. Exercise 5.3 What kind of information should be reported in a lab report (elimination phase)? What is the value or purpose of each kind of information?