1. Event DateEvent Title Event Description: http://www.timetoast.com/timelines/malaria-timeline 23rd Jun, 0323 Death of Alexander the Great On the route to India beyond Mesopotamia, it was believed Alexander died of Malaria. 23rd Jun, 0400 First Malariologist 400 BCE Hippocrates was the first malariologist, who described various malaria and described the difference between continuous fever and the intermittent malarial fever. 23rd Jun, 1227 Death of Genghis Khan The Mongol warlord, who had set up one of the largest land empire ever known have suffered from malaria in the spring of 1227. 1st Jan, 1570 1570 BCE On the banks of the Nile River residents recorded observations of diseases into the oldest surviving medical document from Ancient Egypt, the Ebers Papyrus. Ebers Papyrus consisted of 700 drugs and 800 creations

2. This day relenting God Hath placed within my hand A wondrous thing; and God Be praised. At his command, Seeking his secret deeds With tears and toiling breath, I find thy cunning seeds, O million-murdering Death. I know this little thing A myriad men will save, O Death, where is thy sting? Thy victory, O Grave?

3. February 10 -19, 2014 Lipa City, Philippines

4.  Review the interventions, which can be applied from the pre-elimination to the prevention of reintroduction stage, and decide which are most appropriate under specific conditions in each stage  List the four approaches (strategic elements) that define a malaria elimination programme, giving examples of relevant tools for each and explain why these approaches are critical to achieving malaria elimination  List the objectives of malaria treatment in elimination programmes

5.  Describe and justify antimalarial treatment policies for P. falciparum and P. vivax in malaria elimination programmes  Describe the indications and objectives of mass drug administration  List the different vector control methods and their value and limitations in the different stages of malaria elimination  Describe the technical and operational issues related to vector control measures

6. Control Strategy Application of menu interventions to gradually reduce the burden of the disease in a population Elimination Strategy Application of targeted and locally adapted measures to track down the last foci and cases of malaria – making sure parasites are killed

7. 2. TREAT 1. DETECT 3. Manage FOCI 4. Prevent IMPORTATION Take other measures to prevent infection of anophelines/ infection of other persons by anophelines already infected

8. Treat all infections in a community, symptomatic or asymptomatic, to interrupt transmission Rapidly Reducing the Parasite Reservoir Prevent Transmission as well as Cure Disease Avert Complications & Death

9. In an elimination setting all malaria cases should be detected and confirmed by parasitological tests that identify species, stage and load of infection. Microscopy - highly sensitive and specific in identifying parasite species, stages and quantification of malaria parasites. A system for quality assurance is essential. Rapid diagnostic tests (RDTs) may be useful for (i) the screening of travellers (ii) wherever there is lack skilled microscopy Polymerase chain reaction (PCR) may be used for population screening and for identifying morphologically similar species e.g.. P. malariae and P. knowlesi). It is presently not indicated for the case management of fever. Serologic methods detect antibodies that may be due to current or past infection. They may be useful in epidemiological studies to get an idea about the load of malaria in the community.

11.  Radical treatment of Pf  Radical treatment of Pv  Treatment of Severe Malaria (addition of single dose primaquine once patient can take oral meds)  Use of antimalarials for reducing parasite reservoir  Chemoprophylaxis

12. Artemisinins (ACTs)  destroy immature, developing gametocytes,  less effective on mature gametocytes Primaquine  selectively kills gametocytes.  A single oral dose of 0.75 mg base/kg body weight primaquine (45 mg base for adults) is recommended to reduce falciparum transmission provided risk of G6PD deficient patients are considered (given on the first day of ACT treatment, NOT in pregnancy and in young children),

13. Updated WHO Policy Recommendation (October 2012 ) A single 0.25 mg base/kg primaquine dose be given to all patients with parasitologically-confirmed P. falciparum malaria in: (1)areas threatened by artemisinin resistance where single dose primaquine as a gametocytocide for P. falciparum malaria is not being implemented, and (2) elimination areas which have not yet adopted primaquine http://www.who.int/malaria/pq_updated_policy_ recommendation_en_102012.pdf

14. P. vivax  for chloroquine-sensitive, oral chloroquine 25 mg/kg, given at an initial dose of 10 mg/kg followed by 10 mg/kg on the 2 nd day and 5 mg/kg on the third day  W/o G6PD - To be given with primaquine, anti-relapse medicine at a dose of 0.25 mg base/kg bw, once a day for 14 days  For Southeast Asia and Oceania – dose is 0.5 mg/kg bw  Alternatively 0.75 mg base/kg bw given once a week for 8 weeks P. ovale – same as P. vivax P. malariae - Chloroquine

15. Maintain Small Stocks of - Quality Assured Anti-malarial Medicines - Effective for rapid treatment -Within expiry date

16.  Full cooperation of the private health sector.  All patients, whether nationals, temporary or permanent immigrants, people in transit, or residents of neighbouring countries who live in border areas can easily access services - -- FOC diagnosis & treatment including consultation fees.  Monitoring of the national supply of antimalarial medicines;  STOP over-the-counter sale of antimalarial medicines;  maintenance of skills of health personnel and updating of their knowledge.

17.  Mass Screening and Treatment (MSAT)  Mass Drug Administration(MDA)  Seasonal Treatment to reduce P. vivax hypnozoite carriers

18. Mass screening for parasitaemia and treating all infected persons in a targeted area or population, regardless whether they are symptomatic or not = aim is to rapidly reduce the size of infectious reservoir in targeted area  screening tools : RDT vs. Microscopy vs. PCR  repeated at intervals once or twice  time-consuming and may miss low-density parasitaemia. Exclusions: contraindications to the medicines used, pregnant women, young infants and other population groups Not for relapsing malarias (no test for detecting hypnozoites) MSAT or FSAT

19. Campaign for treating every individual in a defined population or geographical area with antimalarial treatment on a given day, in a coordinated manner. A well conducted MDA can result in a major reduction in the parasite mass The treatment is usually the same as is used in case management for the species, which is targeted. usually considered in the end-stage, for management of last remaining small foci, with accessible population and very low risk of importation Full cooperation of the community is essential to reach 100% coverage MDA

20. Rebound  The area can return to its original prevalence levels, if vectorial capacity is not reduced and maintained at below the critical level.  time to return to the original levels of transmission depends on the prevailing vectorial capacity.  The rebound may be associated with higher morbidity and mortality if people lost herd-immunity against malaria.  A coordinated attack of vector control and use of drugs to reduce the parasite reservoir may solve the problem of rebound. Enhance resistance against the medicines if larger population of parasites targeted with MDA Mass drug administration difficult to explain to the population Side effects, especially of primaquine

21. Used to interrupt transmission in areas with seasonal transmission of P. vivax (about 3-5 months), where foci are small and high coverage can be achieved,  All individuals to be treated with primaquine for 14 days (Except pregnant women and children under one year)  Usually conducted in spring, about two months before the onset of transmission.  The pre-condition: primaquine is not associated with any significant risk of toxicity in the target population, population is fully informed of signs of primaquine toxicity, fully cooperative. Seasonal Treatment of P. vivax Hypnozoite Carriers

22. Which is the FOCUS?  Surveillance, malaria surveys, GR  vector control and entomological investigations;  involvement of local authorities, local communities and inter- sectoral action.

23.  inter-country coordination and collaboration;  prevention of malaria in residents who travel to endemic countries, including chemoprophylaxis, prevention of mosquito bites, standby treatment and case management;  screening, health education, easy access to free-of- charge diagnosis and treatment and other measures to cope with the importation of parasites by international travellers and migrants;

24. Risk typeMalaria riskType of prevention Type I Very limited risk of malaria transmission Mosquito bite prevention only Type II Risk of P. vivax malaria only; or fully chloroquine-sensitive P. falciparum Mosquito bite prevention plus chloroquine chemoprophylaxis Type III a Risk of P. vivax and P. falciparum malaria transmission, combined with emerging chloroquine resistant Mosquito bite prevention plus chloroquine+proguanil chemoprophylaxis Type IV(1) High risk of P. falciparum malaria, in combination with reported antimalarial drug resistance; or (2) Moderate/low risk of P. falciparum malaria, in combination with reported high level of drug resistance Mosquito bite prevention plus atovaquone-proguanil, doxycycline or mefloquine chemoprophylaxis (selected according to reported resistance pattern)

25.  Be Aware of the risk, the incubation period, the possibility of delayed onset, and the main symptoms.  Avoid being Bitten by mosquitoes, especially between dusk and dawn.  Take Chemoprophylaxis when appropriate, to prevent infection from developing into clinical disease.  Immediately seek Diagnosis and treatment if a fever develops 1 week or more after entering an area where there is a malaria risk and up to 3 months (or, rarely, later) after departure from a risk area.

26. Vector Control Know your enemy

27.  Combining IRS and LLIN  Space spraying  LSM and other larval control measures  Withdrawal of prevention measures with NO or LOW transmission

29. Parameters minmaxBaseline m valuea valuep valueDurationcombi m = mosquito densities per person 050078.5 40 78.5 15 a = antropophilic index 010.7 0.35 0.7 p = daily survival rate of the vector 0.050.950.71 0.35 0.71 0.61 0.71 n =number of days for full maturation of sporozoites 123015 b =effectiveness of a vector 010.01 duration of infection 140015 7.5 r =recovery rate 1 0.002 50.0667 0.066670.1333 Results ma^2 38.46519.69.616238.465 7.35 p^n 0.00587 1.4488E-070.005870.000600.00587 -LN(p) 0.3425 1.0498220.34250.49430.3425 C =vectorial capacity 0.659620.336110.164915.3085E-060.659620.04690.1260 R(0) =basic reproduction rate 9.894275.041672.473577.963E-054.947140.35160.9453 LSM, RepelZoophroAdult VCEDPTEDPT + LLIN, IRS Non-irritant Adult VC LSM, Repel

30. In all these approaches, malaria surveillance is a common denominator. It is the backbone of any elimination programme. Indicators of Effective Surveillance Continuing detection of imported malaria cases Absence of gametocyte positive P. falciparum case

31.  Case-based SS – each case can be easily classified by its probable geographic origin  Incidence of malaria is analyzed village-wise  Surveillance is complete: Nearly all fever cases are observed by the health services in accordance with the 3T principle (tested, treated and tracked) and all results of malaria testing reported. Whether or not this is the case can be assessed by population surveys for treatment seeking behaviour and health facility surveys for completeness of reporting.

32. 2. TREAT 1. DETECT 3. Manage FOCI 4. Prevent IMPORTATION Take other measures to prevent infection of anophelines/ infection of other persons by anophelines already infected 1. EARLY DETECTION OF ALL CASES 2. PREVENTION OF ONWARD TRANSMISSION FROM CASES 3. MANAGEMENT OF FOCI 4. MANAGEMENT OF IMPORTATION OF MALARIA PARASITES

33.  legislation making malaria a notifiable disease.  quality assured microscopy as the standard routine method;  epidemiological investigation of every confirmed case;  national malaria case register;  radical treatment;  active case detection as routine or reactively, as needed;  vector control as necessary;  if possible, parasite genotyping and parasite isolate banks.

34.  Vigilance Full integration to GHS ? ACD in high risk area? MSAT ? IEC ? – travellers, prescribers Medicine Stock  Chemoprophylaxis  Vector Control Pro-active Reactive

35. Discuss the technical and operational conditions for optimal implementation of IRS and LLINs interventions, respectively.

36. What factors determine whether and how quickly malaria returns if vector control is stopped?

37. In what ways can operational research guide and promote case management in malaria elimination, including diagnosis and the use of antimalarial drugs?

38. After two years with zero reported locally transmitted falciparum malaria cases in a country in the Arabian peninsula, three cases are detected in an oasis, where there are 3000 inhabitants. The oasis frequently hosts overland travellers, some of whom might come from areas where malaria is endemic. The spray-team has started a total coverage operation. The Minister of Health wants you to do mass drug administration (MDA), unless you have convincing arguments for a better strategy. The Minister has also told you that any severe side effects of MDA must be avoided. What are your options? Discuss pros and cons for each.

39. Prepare a matrix of rows representing all the interventions discussed here and 4 columns representing the 4 phases from control to prevention of reintroduction. Fill in the cells for a selected country or area contemplating elimination to identify the role of each intervention in each phase.

40. Discuss pros and cons of combining IRS and LLINs in the elimination phase.