Malaria Diagnostics: Introduction to operational issues Mark Perkins, MD Chief Scientific Officer Foundation for Innovative New Diagnostics

Conventional microscopy for malaria detection

Scale up of RDTs and ACTs in India Millions of kits/doses

Impact of RDT training intervention on antimalarial prescribing *Generalized estimating equations controlling for history of fever and age, adjustment for repeated measures on the same day. Site Relative change in proportion of patients prescribed antimalarial Antimalarial doses saved per 1000 patients RR (95% CI)*p-value Mubende0.32 (0.29 – 0.36)< Jinja0.44 (0.39 – 0.50)< Tororo0.73 (0.70 – 0.77)< Hopkins H, et al.

Satisfactory outcome at Day 5: - Improved on treatment prescribed at Day 0 and - Did not seek care elsewhere Site Proportion with satisfactory outcome at Day 5 p-value No RDTs (n = 682) RDTs (n = 653) Mubende 95%96% Jinja 93%94% 0.845

Safety of non-treatment of RDT- negative fever in <5s Recruited febrile children aged 6 months to 10 years Excluded gravely ill RDT testing: no antimalarial if negative result. Home visit at day 7 If ill before day 7, retest with RDT, reassess at day febrile children (median age 2.5 years) 41 (14%) RDT+259 (86%) RDT - 3% loss to follow-up (moved/wrong address) 281/290 (97%) cured at day (99%) cured at day 14 31/259 (12%) returned with fever (med 3.5d) No new positive RDTs D'Acremont 2009 ASTMH

High mortality among patients admitted to hospital and treated for malaria Admissions for malaria n=17,313 Severe disease n=4670 (27%) Readable slide results n=4474 (95%) No criteria for severe disease n=12,643 (73%) 120 deaths (1%) No criteria for severe disease n=12,643 (73%) 120 deaths (1%) Expert microscopy negative n=2412 (54%) Expert microscopy negative n=2412 (54%) Dead n=142 (7%) Dead n=142 (7%) Alive n=1920 (93%) Alive n=1920 (93%) Dead n=292 (12%) Dead n=292 (12%) Alive n=2120 (88%) Alive n=2120 (88%) Expert microscopy positive n=2062 (46%) Expert microscopy positive n=2062 (46%) Reyburn H

ITN, IRS introduction Phased introduction of RDTs

Impact of malaria RDTs on case reporting and ACT use RDT introduction

Map of malaria incidence

Polio case numbers 1988: 350, : 7, : 2, : 483

Rapidly increasing range of malaria RDT products

CNM, MoH, Cambodia 30 °C Central Med Store Ankor Ban HC Sampour Lon HC Temperature monitoring of RDT storage by MoH & WHO, Cambodia

Operational issues RDT roll-out Procurement and distribution: –Test selection –Timely procurement distribution –Waste management – Return? Burn? Bury? Training and supervision: –Training in in case management, not just RDT testing –Retraining and monitoring QA/QC: –After purchase –After distribution –Integrate QA/QC systems for diagnostics not restricted to malaria Monitoring & evaluation: –Result reporting for surveillance and for product vigilance –Integrate M&E across diseases –Electronic systems Private sector use

Aim : To identify solutions to logistic and financial obstacles in the performance and availability of RDTs. Activities : –Jobs-aids bank and manuals for the transport and storage of RDTs. –Temperature monitoring with “LogTag” devices started in April 2009 in Senegal, Burkina Faso, Ethiopia, Philippines. –Visit to Uganda of the School of Mines, University of Colorado for the design of a coolbox for RDT storage. –Survey on RDT distribution and prices in the private sector started in April 2009 in Senegal, Peru, Philippines, Tanzania, Nigeria, CAR. –Project to assess the impact of RDTs use on rate of malaria cases and use of ACTs. Obstacles to RDT implementation: Supply chain / Transport

Field evaluation of existing RDTs: Blood transfer devices / Pregnancy Aim: To contribute in the field performance of RDTs (training material, blood safety, and test use accuracy). Activities: –Assessment of the impact of long-term practices of health workers using RDT training material on RDT performance. Zambia. –National Implementation Strategy and RDT regulatory guidelines in Uganda. –Improvement of blood transfer devices (accuracy, safety, and ease-of-use). –Utility of RDTs and LAMP as replacement of preventive treatment in pregnancy. Uganda Nigeria Senegal Burkina Faso Philippines Uganda Nigeria Philippines

Product testing is part of a larger FIND strategy for QA of malaria RDTs Manufacturer Supply chain managementTransport and storage End users -Appropriate training and instructions -Management of positive and negative results Stage 1: Product testing Evaluate product performance Stage 2: Lot testing Confirm product quality on arrival in country before dissemination to the field Stage 3: PCWs Ensure health workers and patients that RDTs has maintained accuracy through transport and storage Before purchase Before distribution Before use

Aim: To establish a global specimen bank and regional capacity to support the development and evaluation of malaria diagnostics. Activities: Publication of the first FIND/WHO report on product testing of malaria RDTs in April Second round of product testing is ongoing and results expected before end of Product testing with reference materials

Activities: Lot testing of RDTs in Cambodia, Philippines, and Ethiopia and capacity building in other countries. Characterization of recombinant proteins for future lot testing panel. Lot Testing Protein concentration RECOMBINANT PANEL HRP2 variants, Pf, Pv pLDH and aldolase

Positive Control Wells (PCWs): Quality control by health workers Aim: To provide capacity to test quality of RDTs in remote places and increase user’s confidence. Activities: PCWs stable at 60°C have been produced. Evaluation of thermostability at HTD and job-aids in Uganda in July 2009.