ModelVivax

Vivax model

The vivax model contains components for primary infection and relapse, blood-stage clearance, clinical illness and infectiousness to mosquitoes. It dovetails with the vector model, and chemotherapy, including liver-stage drugs, and other interventions in OpenMalaria.

The Vivax within-host model components work as an alternative to the falciparum-specific within-host models. [As of version 36] parasite densities are not modelled.

Link to schema documentation

Vivax broods

In the model, a brood is the set of hypnozoites resulting from an innoculation together with the primary infection.

The number of hypnozoite releases is fixed at the time of infection (see sampleNHypnozoites()). The time of each release is determined to be infectionTime + latentPeriod +relapseLatentPeriod + delay where delay is sampled from a truncated log-normal distribution (see sampleReleaseDelay()).

The first release from each brood commences a blood-stage infection denoted the primary. Subsequent releases during a blood-stage infection from the same brood, or within a short time-period afterwards (the "blood stage protection latency"), do nothing; releases after this time will start a new blood-stage infection denoted a relapse. Note that blood stage infections from a different brood have no affect on this brood. The length of each blood-stage infection is sampled from a Weibull distribution.

Patency

All active blood stages are patent. The host is patent if any brood has a patent blood stage. Otherwise (even if dormant hypnozoites are present) the host is not patent. Since this would not be true for low-density infections, work is currently underway to parameterize the blood-stage component correctly. Currently the prevalence will be overestimated for all settings.

Transmission

If the host is patent, a fixed probability of transmission-to-mosquitoes applies (this is adjusted by transmission-blocking vaccines). Otherwise the chance of transmission is zero.

Treatment

Since parasite densities are not modelled, simulated PK/PD treatment is not possible. Instead, the simple treatment model can be used to clear liver- and blood-stages. Liver-stage treatment clears all hypnozoites from all broods, preventing relapses. Blood-stage treatment clears all blood-stage infections, but also nullifies the usual blood-stage protection latency, meaning that a relapse is possible the next step if liver-stage treatment is not also used.

Pathogenesis

Each blood stage which starts (modelling blood-stages from each brood independently) has a chance of causing a clinical event. The probability of this depends on whether the blood-stage was the primary infection or a relapse, whether the relapse occurred when a blood-stage infection by the same brood was present, and the cumulative number of primary blood-stage infections previously experienced by the host.

Given an event, there is a fixed chance that it is severe; otherwise it is an uncomplicated case. Since it is unlikely that there is a constant probability of severe disease, future work will parameterize this more realistically.