1. Unit 4 Approaches and Interventions in Pre- Elimination, Elimination and Prevention of Reintroduction Case Management, G6PD, etc and selections of interventions Dr Gao Qi, Dr Krongthong Thimasarn Training course in Malaria Elimination for the Greater Mekong Sub-region Chiangmai Thailand 10-21 August 2015

2. Interventions based on Antimalarial medicines Methods of case detection and details of diagnosis will be discussed in the next learning unit. Objectives of case management in Elimination – To cure disease and prevent complications and deaths – To reduce parasite reservoir & prevent transmission ‘to find parasite’ Both symptomatic & symptomatic, Complete parasitological cure >> all forms (sexual and asexual)

3. First line treatment Uncomplicated P. f One of the 5 ACTs (as of 2015 3 rd edition WHO guidelines) – ATM/LUM – ATS/AMQ – ATS/MEF – DHA/PIP – ATS/SP (ACT is not recommended for 1 st trimester pregnant women) – Primaquine (PQ) a single dose of 0.25mg/kg against mature gametocytes; preferably on Day 0- – PQ contraindicated in Pregnant, breed feeding women and infants Uncomplicated Non-Pf – Pv Po CQ + 14d PQ or weekly PQ for 8 weeks – Pm CQ alone – Pk CQ or ACT CQ resistant Pv –any ACT (except ATS/SP) + PQ 14d ------ Mixed infections (Pf + another species) – ACT + PQ 14d -------- Directly Observed Treatment (DOT) for all cases

4. Diagnosis and Treatment with Effective Medicines (Malaria Case Management) 3 rd edition – March 2015

5. Other issues related to drugs Quality assurance of drugs (in all phases) STOP artemisinin monotherapy (in all phases) STOP over the counter sale of antimals Logistics –drug stockpile in low malarious areas Treatment by private sector & its desired role – In pre- elimination phase- quality Dx and Rx – In elimination phase – case notification and investigation

6. Use of antimalarial drugs for reducing parasite reservoir Mass drug administration (MDA) -obsolete control methods from the Global Malaria Eradication Programme -No. blood exam -‘mopping up operation’ – treat everyone (except pregnant women, infants, etc.) simultaneously. Some high risk groups might be left out -may result in major reduction in parasite mass but situation may return back to its original levels -drug pressure – selective resistance -will not be successful if high level importation (migration) – ideal in small islands without much pop movement -Usually combined with Vector Control

7. Use of antimalarial drugs for reducing parasite reservoir (cont) Mass drug administration (MDA) -may be reconsidered in GMS, in combination with mass screening. -Drugs: ACT but should be a different ACT - + PQ -Mass treatment is now under consideration for foci of ART resistance in GMS – no final conclusion

8. Use of antimalarial drugs for reducing parasite reservoir Mass screening and treatment (MSAT) by microscopy, RDT or PCR - low parasitaemia will be missed by microscopy and RDT - sensitivity of PCR is highest, but PCR is more costly, results must be rapidly available (for treatment) Focal screening and treatment (FSAT) - same as MSAT but smaller scale

9. G6PD test Elimination of P.v is more difficult than P.f due to relapse of P. v. Radical treatment is needed for P.v in elimination High G6PD rate & G6PD test before using PQ is need in GMR New RDT for G6PD test is one of technical challenge at present.

10. Seasonal Pv treatment with PQ There are transmission & non-transmission season in some countries. Relapse case of P. v is the major resource for malaria transmission in next year. So, anti-relapse treatment with PQ for P. v cases before transmission season is one of major interventions both in malaria control & elimination stages. Seasonal P.v PQ treatment (not applicable for GMS ）

11. Chemoprophylaxis for traveller In control stage, chemoprophylaxis for traveller mostly rely on anti-malaria drug (CQ, SP, PPQ or MQ) In elimination stage, A,B,C,D for traveller A: Aware of risk for traveller B: Avoid Bitten by mosquito C: Chemoprophylaxis when appropriate D: Diagnosis & treatment if fever

12. IPTp and IPTi Intermittent preventive treatment in pregnancy (IPTp) & Intermittent preventive treatment in infancy ( IPTi) have be recommended in high endemic areas by WHO mostly in Africa IPTp and IPTi are not applicable for GMS from control to elimination

13. Box 4.1 The four approaches of malaria elimination 1. Early detection of all cases 2. Prevention of onward transmission from cases 3. Management of malaria foci 4. Management of importation of malaria parasites

14. Selection of interventions

15. Experiences from PR China

16. Differences in control, elimination and post elimination phases ControlEliminationPost-e GoalReduce morbidity & mortality No local infected case Prevention Reintroduction TargetHigh endemic areas/population case & fociImported case InterventionPopulation based MDA, ITN & IRS Case & Foci based intervention Surveillance & response IndicatorCoverageTimelineHealth ability

17. controlpre-elimination elimination prevention of reintroduction SPR < 5% in fever cases < 1 case/1000 population/year no local infected cases WHO no local infected cases 0.01% for 3 year < 1 case/10000 for 3 year China Type IType II Type III IncidenceNo. of case

18. Case Detection & Notification ① Case Investigation & Classification ③ Focus Investigation & response ⑦ Hospital County CDC Diagnosis Treatment Report Diagnosis Treatment Report Lab Confirmed Case Classification Lab Confirmed Case Classification Focus investigation RADC Entomological Focus investigation RADC Entomological Focus Response Vector Control Target MDA Health education Focus Response Vector Control Target MDA Health education The new “1,3,7” strategy 1 Day (24 hrs) 3 Days 7 Days

19. Case detection & reporting within 1 day  All of suspected case received laboratory test before treatment  All of clinical & confirmed cases reported by hospital ( where case found) within 1day  Clinical cases: With history in endemic & typically symptom, but negative by microscopy & RDT  Confirmed cases: With symptoms & positive by microscopy, RDT or PCR

21. Case definition & investigation within 3 days Case lab confirm Double Microscopy PCR Case classify Case investigation Local case Imported case 1. All of reported cases re-confirmed 2. All of confirmed cases classified

22. Foci investigate & response with 7d Foci investigate & action RADC Health education vector control IRS Vector survey Target MDA

23. WHOChina Endemic: Transmission is occurring and is not effectively controlled Foci with transmission: Village with indigenous or introduced case Residual active: Transmission occurring with transmission within the past 2 years New active: Transmission occurring with no local transmission New potential: imported, induced or relapsing cases occurring during transmission season with no transmission in past 2 years or more Foci with potential transmission Village with imported/relapse case & vector in transmission season Residual non-active: No local transmission but with a history of local transmission within the past 2 years Foci without transmission Village without vector or not in transmission season Cleared-up: No local transmission during the past 2 years with a history of malaria and suitable for transmission.

24. Foci investigation & action within 7days Foci response  Foci with transmission ( Blocking transmission) Vector control, Target MDA & health education  Foci with potential transmission ( Prevention) Vector control & health educations  Foci without transmission Health educations

25. About 20,000 cases in 20 provinces,762 counties in 2008 Before malaria elimination 2008 More than 30 millions malaria in 1970’s ＜ 50 local cases in 2 provinces ， 9 counties in 2014

26. Thanks ！