Papyrus Ebers “world’s oldest medical textbook” includes the first written record of malaria. Written about 1500 BC, but believed to be copied from earlier texts, perhaps dating as far back as 3400 BC. Found in Luxor around 1862.

UNIT 4: APPROACHES AND TOOLS SPECIFIC TO ELIMINATION PROGRAMMES Allan Schapira Elimination course, Luxor, 18/11/12

Learning objectives List the 4 approaches (strategic elements) that define a malaria elimination programme, giving examples of relevant tools for each and explain why these 4 approaches are critical to achieving malaria elimination Outline a plan for a quality assurance system for laboratory diagnosis in malaria elimination programmes List the objectives of malaria treatment in elimination programmes 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 measures of vector control methods and their value and limitations in different settings. Describe the technical and operational issues related to vector control measures. Describe the role of vector control measures in the different stages of malaria elimination

4 approaches/strategic elements Case 2. Treat, take other measures to prevent infection of anophelines/infection of other persons by anophelines already infected 1. Detect Case 3. Manage foci 4. Prevent importation "Like chess, (malaria) is played with a few pieces, but is capable of an infinite variety of situations“malaria L.W. Hackett

Early detection of cases and prevention of transmission from them 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.

Management of malaria foci WHAT IS A FOCUS? surveillance malaria surveys geographical reconnaissance vector control and entomological investigations; involvement of local authorities, local communities and inter-sectoral action.

Management of importation of malaria parasites 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; ABCD.

Surveillance: key intervention for elimination In all these approaches, malaria surveillance is a common denominator. It is the backbone of any elimination programme. Surveillance for elimination is examined in depth in Unit 5.

Malaria microscopy quality assurance -minimum requirements Central coordinator. A reference group of microscopists at the head of a hierarchical structure, supported by an external QA programme. Good logistical management, including maintenance of microscopes. Clear standard operating procedures (SOPs) at all levels of the system. Good initial training with competency standards. Regular retraining and assessment/grading of competency, supported by a reference slide set (slide bank). A sustainable cross-checking (validation) system that detects gross inadequacies, with good feed-back and system to address inadequate performance. Good supervision at all levels. Adequate budget. STEER MANAGE TRAIN CHECK PAY

Get started on QA Describe and diagnose existing system/situation – Resources – Structure – Workload, performance – Rapid Quality Evaluation – Know about: Other disease programmes General laboratory services Academic institutions

Identify the most serious problems Which may be – local, – systemic, – technical, – financial Prioritize addressing them

Maybe more important to augment the system progressively and solidly than to follow this scheme in all details. Festina lente

On techniques, SOPs, check-lists The devil is in the details Buy the best Giemsa or - usually better – prepare your own Get the pH right Use the SOPs and check-lists Love your microscope!

Recap: Diagnosis in a malaria elimination programme In an elimination setting all malaria cases should be detected and confirmed by parasitologic tests that identify species, stage and load of infection. Microscopy is highly sensitive and specific in identifying parasite species and stages and quantification of malaria parasites. A system for quality assurance is essential. Malaria rapid diagnostic tests (RDTs) may be useful for (i) the screening of travellers and (ii) wherever there is lack skilled microscopy The polymerase chain reaction (PCR) may be used for population screening and for identifying morphologically similar species (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.

Some food for thought “The presence of asymptomatic infections, the inability to accurately diagnose microparasitaemic infections and gametocytemia, and the difficulty in achieving adequately powered studies in the context of low malaria prevalence all have serious implications for malaria elimination campaigns. The World Health Organization (WHO) defines malaria as eliminated in an area if there is zero incidence of locally acquired clinical cases in a defined geographical area during three consecutive years [29]. In settings with large numbers of asymptomatically infected people, how can this be assessed without testing populations for serological evidence of recent exposure? Until sufficient measures for elimination are developed for use in areas with persistent pockets of asymptomatic or minimally symptomatically infected individuals, or a successful mass drug administration campaign or vaccine is implemented, how is it possible to claim that these malaria reservoirs are truly eliminated? What is the implication for continued transmission if even just one person is misclassified as negative who is actually carrying parasites? “ Stresman et al. (2012). Malaria research challenges in low prevalence settings Malaria Journal, 11:353 doi: /

Use of antimalarial medicines Radical treatment of Pf Radical treatment of Pv Mass screening and treatment Mass drug administration Seasonal mass treatment to eliminate P.vivax hypnozoite carriers Chemoprophylaxis

Gametocytocidal treatment (Radical treatment of PF) 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 ( on the first day of ACT treatmen, NOT in pregnancy and in young children). Updated WHO Policy Recommendation (October 2012 )) ● A single 0.25 mg base/kg primaquine dose be given to all patiens 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 n_ pdf n_ pdf

Use of antimalarial drugs for rapidly reducing the parasite reservoir Treat all infections in a community, symptomatic or asymptomatic, to interrupt transmission 1) Mass screening and treatment ( MSAT) – Mass screening for parasitaemia and treating all infected persons in a targeted area or population, irrespective of whether they are symptomatic or not – screening tools : RDT will miss large proportion of infections, its value is questionable for elimination-- microscopy is better, some cases will also be missed ; PCR more sensitive – Not for relapsing malarias (no test for detecting hypnozoites) – repeated at intervals once or twice – time-consuming and may miss low-density parasitaemias. – Exclusions: contraindications to the medicines used, pregnant women, young infants and other population groups

2) Mass Drug Administration (MDA) 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 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 to reach 100%. coverage The treatment is usually the same as is used in case management for the species, which is targeted. Mass treatment is currently under consideration for foci of artemisinin resistance in Southeast Asia

MDA- concerns ● 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

3) Seasonal treatment of vivax hypnozoite carriers 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.

Full cooperation of the private health sector and other sectors providing services services to diagnose and treat malaria that are free of charge to patients, whether nationals, temporary or permanent immigrants, people in transit, or residents of neighbouring countries who live in border areas; "free" includes consultation fees. monitoring of the national supply of antimalarial medicines; a stop to the over-the-counter sale of antimalarial medicines; maintenance of skills of health personnel and updating of their knowledge.

Vector Control 1. Adult mosquito control Insecticide-treated mosquito nets (ITNs) Indoor residual spraying (IRS) Space spraying 2. Reducing human-vector contact Insecticide-treated mosquito nets (ITNs) Improved housing including screens Repellents and mosquito coils 3. Larval control Chemical and biological larviciding Source reduction

Group A: Group B: Group C: All groups: (operational research)

Exercise Discuss the technical and operational conditions for optimal implementation of IRS and LLINs interventions.

Exercise What factors determine how quickly malaria returns if vector control is stopped?

Exercise Prepare a plan of action for establishing quality assurance for malaria microscopy in a selected country represented in the group.

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

Exercise After two years with 0 reported locally transmitted falciparum malaria cases in a country in the Arabian peninsula, 3 autochtonous 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 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.