1. Introduction to OpenMalaria
Drug-based interventions

2. Resources
Pathogenesis model description (when and how someone gets sick)
Smith T, Ross A, Maire N, Rogier C, Trape JF, Molineaux L An epidemiologic model of the incidence of acute illness in Plasmodium falciparum malaria. Am J Trop Med Hyg 75:56-62.
Case management model description (when and how someone is treated)
Tediosi F, Maire N, Smith T, Hutton G, Utzinger J, Ross A, Tanner M (2006) An approach to model the costs and effects of case management of Plasmodium falciparum malaria in sub-saharan Africa. Am J Trop Med Hyg 75: m

3. Model assumptions
Probability of clinical episode based on pyrogenic threshold
The health system acts on events as driven by the clinical illness model
Immunity acts by suppressing parasite densities
Infectivity of humans to mosquitoes a function of asexual parasite densities 10, 15 and 20 days previously, allowing for a delay resulting from the time course of gametocytaemia
All events occur within a five-day timeframe
Case management
Access to treatment
Diagnosis
Effectiveness of treatment

4. Method 1: drugs deployed through the health system
Describes drug effectiveness, compliance, and access to treatment for uncomplicated and severe illness
Linked to clinical illness model, on a five day timestep, starting from model initialization
Model will be calibrated, and immunity in the population acquired, with the described health system in place
Can also be an “intervention” to change health system to a new description (i.e. introduction of new first line treatment)

5. Method 1: drugs deployed through the health system
Two methods for parameterization:
Method A: Based on sector (public, private, etc)
Method B: Based on drugs
Why use Method A?
You want to use the original OpenMalaria Tanzania parameterization
Public sector is the main entry point for case management
You plan to conduct a cost-effectiveness analysis
Why use method B?
There are multiple drugs in the market you would like to describe
Treatment through many different channels
There exists data on access to and effectiveness of each drug (i.e. an ACTwatch country)
Detailed documentation:

6. Health system – parameter descriptions
Detailed documentation:

7. Method 2: drugs deployed through a stand-alone intervention
Deploy at specified time points to specific age groups or cohorts
and/or
Continuously when someone reaches a certain age
Stand-alone or “bundled” with a group of interventions
With or without a diagnostic (deterministic or stochastic)

8. Drug administration glossary (operational definitions)
Intervention
Definition
Test?
Primary goal
MSAT
Mass screen and treat
Test community for malaria parasites. If positive, give drug. Y
Clear parasites
MTAT
Mass test and treat
Same as MSAT
MDA
Mass drug administration
Drug distribution at the community level N
Clear parasites & prevention
IST
Intermittent screen and treat
Test specific groups for malaria parasites. If positive, give drug.
FSAT*
Focal screen and treat
Test a radius around an identified case (hotspots). If positive, give drug.
SMC
Seasonal malaria chemoprophylaxis
Drug distribution to community to prevent malaria during main transmission season.
Prevention
IPTi
Intermittent Preventive therapy of infants
Drug distribution to infants to prevent malaria. Given in 3 rounds.
IPTp
Intermittent preventive therapy of pregnant women
Drug distribution to pregnant women to prevent malaria. Given in 3 rounds.
*Not possible to simulate with OpenMalaria – no explicit spatial component

9. Method 2: drugs deployed through a stand-alone intervention
Specify separate drug action per timestep on blood and liver stages (or both) or
Specify an initial effectiveness of drug action and a decay function (like a vaccine)
Transmission-blocking
Prevents infection from human to mosquito (gametocytes)
Blood stage
Decreases number of parasites in the blood (trophozoites)
Pre-erythrocytic
Kills liver stage parasites (merozoites)
*Exception: Ivermectin (deployed like a vector control intervention)

10. Stand-alone drug interventions – parameter descriptions
Initial efficacy (proportion of infections cured) – either total, or for separate blood and liver stages
Duration of efficacy (either time to half or full decay)
Decay function
Diagnostic:
Cutoff for parasites per
Microlitre or
Specificity and 50%
density
Detailed documentation:

11. Example Research question
To predict the incremental cost-effectiveness of mass screen and treat (MSAT) campaigns as a strategy for malaria disease-burden reduction in sub-Saharan African settings with varying receptivity and access to case management, compared to the absence of MSAT

12. OpenMalaria parameterization
Health system parameterization
First-line treatment with Artemether-lumefantrine (Coartem)
Drug effectiveness (% of infections cleared): 85%
Compliance to drug regimen: 90%
For patients who did not comply, treatment 20% effective
MSAT parameterization
One round of treatment per year at different timing
Peak, month before peak, trough, month before trough, month after trough
Coverage: 85%

13. OpenMalaria experiment design
Assuming Namawala, Tanzania transmission setting
Starting annual average EIR: 2, 20, 50
LLIN coverage: 40%, 60%, 80%
Fevers accessing treatment using: 20%, 35%, 55%
Outcome measure
Incremental cost effectiveness ratio (ICER) per uncomplicated case averted from the comparator

14. Results
MSAT averted the most episodes where the number of episodes in the comparator was intermediate (different combinations of EIR and LLIN coverage)
MSAT has comparable cost-effectiveness to scaling up case management or LLINs at intermediate coverage levels of those interventions