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Vivax After Falciparum Study Group

The aim of this study group is to explore the link between P. vivax recurrence and prior P. falciparum treatment, including increased risk of vivax parasitaemia due to acute malaria infection.

Overview

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. A publication is under final review and should be released December 2018.

Rationale

Recurrent P. vivaxparasitaemia 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 orP. falciparum.

Objectives

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.

Essential inclusion criteria

- 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

Desirable criteria:

- 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

Data standardisation and statistical analysis

Once all the data sets have been uploaded in the WWARN Data Repository, according to the WWARN Clinical Data Management and Statistical Plan, all the data sets 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 will be developed prior to commencing the analysis and will be shared with all contributors.

Study group governance and ownership

The Study Group comprises participating investigators who contribute relevant data sets to pooled analysis and technical experts. Data sets remain the property of the investigator. More details about sharing data with WWARN and how WWARN will use data are available on the WWARN website. Prof Ric Price (ric [dot] price [at] wwarn [dot] org) is Study Group leader, with Robert Commons (rob [dot] commons [at] wwarn [dot] org) as study coordinator.