The Vivax After Falciparum Study Group was formed in March 2018, with an invitation to interested researchers with relevant data sets. Research groups with relevant data sets were contacted in early 2018, followed by data collation and analysis. The publication 'Risk of Plasmodium vivax parasitaemia after Plasmodium falciparum infection: a systematic review and meta-analysis' was released in Lancet Infectious Diseases in December 2018. IPD data curation is currently ongoing. 

Recurrent P. vivax parasitaemia increases morbidity and the risk of ongoing transmission of malaria. In Thailand there is an increased risk of Plasmodium vivax parasitaemia after treatment of P. falciparum infection. This is hypothesized to be due to patients with falciparum malaria who have occult  P. vivax infection with the dormant liver stages (hypnozoites) being reactivated by acute malaria.

The risk of P. vivax after P. falciparum is likely to vary between regions. Dormant liver stages of P. vivax lead to relapse and the pattern of relapse varies with geographical region. The timing and frequency of relapse varies from weeks to months.

Chloroquine (CQ) is currently the first-line treatment for P. vivax infection, but in areas where CQ resistance is prevalent the World Health Organization recommends artemisinin-based combination therapy. In order to reduce the risk of P. vivax following P. falciparum in some co-endemic areas, there may be a significant benefit in providing universal radical cure with an ACT and primaquine to patients infected with either P. vivax or P. falciparum.

1. To assess the risk of P. vivax parasitaemia up to day 63 following P. falciparum infection and compare to the risk of P. falciparum recurrence.

2. To quantify and compare the temporal distribution of P. vivax and P. falciparum recurrent parasitaemia.

3. To identify risk factors associated with P. vivax parasitaemia following the treatment of P. falciparum infection.

4. To compare the risk of P. vivax parasitaemia following P. falciparum infection with the expected background risk of P. vivax infection by location.

- Prospective therapeutic efficacy trials of uncomplicated P. falciparum infection (including monoinfection and mixed P. falciparum and P. vivax infection)

- Study undertaken in a location co-endemic for P. vivax and P. falciparum

- Study observation period ≥28 days

- Available data on the patients age and gender

- Documented day of recurrence of all species of malaria

- Study meta-data as described in the Data Management and Statistical Analysis Plan

- Baseline parasitaemia

- Baseline gametocytemia

- Haemoglobin or hematocrit measured on day 0

- Genotyping to potentially distinguish recrudescence and reinfection

- Mg/Kg dosing

- Malnutrition as gauged by weight and age +/- height or MUAC

Once all the data sets will be uploaded in the WWARN Data Repository, according to the WWARN Clinical Data Management and Statistical Plan, they will be standardised and pooled into a single database of quality-assured individual patient data. Baseline characteristics like parasitaemia, gametocytemia and haemoglobin will be presented in a table. Risk of P. vivax parasitaemia and P. falciparum recurrence will be investigated by Kaplan-Meier survival analysis. Risk factors for parasitaemia will be investigated by multivariate Cox regression analysis with random effects for study site.

A detailed statistical analysis plan has been developed and shared with all contributors.

The Study Group will comprise participating investigators who contribute relevant data sets to pooled analysis and technical experts. Data sets remain the property of the investigator. Prof Ric Price (ric.price@wwarn.org) is Study Group leader, with Robert Commons (rob.commons@wwarn.org) as Study Coordinator.

Read the results systematic review results published: Risk of Plasmodium vivax parasitaemia after Plasmodium falciparum infection: a systematic review and meta-analysis. Lancet Infectious Diseases. 2019; 19: 91-101