When the World Health Organization’s Strategic Advisory Group of Experts on Immunisation (SAGE) considers, on October 6, evidence to decide on the roll out of the first malarial vaccine (RTS,S), the latest body of research – testing a vaccine combination with antimalarial drugs which demonstrated efficacy in preventing hospitalisations from severe malaria and deaths – is likely to bolster the case for voting aye.
Without drugs
According to a paper recently published in the New England Journal of Medicine, the study measured the efficacy of vaccination with or without chemoprevention (drugs). The authors noted: “The combination of these interventions resulted in a substantially lower incidence of uncomplicated malaria, severe malaria, and death from malaria than either intervention alone.”
One of the authors of the paper, Daniel Chandramohan, of the London School of Hygiene and Tropical Medicine, says: “In the phase III trial, vaccine RTS,S was 50% efficacious in children more than one year old and 25% in infants, compared to a control vaccine during an 18 months follow up period.”
When the vaccine was used along with chemoprevention, efficacy went up to 70%, or over. The protective efficacy of the combination as compared with chemoprevention alone was 62.8% against clinical malaria, 70.5% against hospital admission with severe malaria and 72.9% against death from malaria. The protective efficacy of the combination as compared with the vaccine alone against these outcomes was 59.6% , 70.6%, and 75.3% respectively, the study notes. “We were surprised by this incredible effect of the combination of vaccine plus chemo. That is the reason these results are likely to shift the WHO’s position on using this combination,” he says.
Dr. Chandramohan who is from Nagercoil in Tamil Nadu, qualified in medicine at the Madurai Medical College, is a professor of public health with special interest in malaria, pneumonia and meningitis. He goes on to explain that the Malaria vaccine was first authorised in 2015 by the European Medicines Agency for use in Africa in infants and children. However, WHO requested for more safety data and a large pilot study was done in Kenya, Malawi and Ghana involving 7,50,000 children. The results of this study will be presented to WHO expert committee on October 6, he explains.
The instant study involving a combination of the vaccine and drugs was done among 6,861 children (five to 17 months of age) in the Sahel and sub-Sahel regions of Africa, seasonally, with three groups randomly receiving just the drugs, the vaccine alone, and the vaccine and drugs together. They were followed up for three years. “We have now shown that indeed in seasonal transmission areas in Africa this vaccine is safe and is more efficacious when given along with chemoprophylaxis during the transmission season,” he adds.
The malaria vaccine prevents the parasite developing in humans. However, some break through infections could happen. When there is a vaccine break through infection, the antimalarial drug kills those parasites. In addition, each course of the drug has chemoprophylactic effect for at least 3 weeks and during that period the vaccine and drugs together prevent any new infections, Dr. Chandramohan explains further. “The results of this trial are applicable to Africa only,” he says, “We don’t know how effective it will be in India, as we have not yet tested this vaccine outside Africa.”
Logistical issues
Are there logistical issues delivering a five-dose vaccine and additional antimalarial drugs in resource-poor countries? For the five-dose vaccine, the first three doses can be given to infants through Expanded Programme of Immunisation (EPI) and the annual booster doses can be given either through EPI or in campaign mode. “In Africa, the seasonal malaria chemoprevention that involves the administration of antimalarial drugs four times a year, has been successfully given to around 25 million children in West Africa. So I think it is feasible to deliver the combination at scale, though there may be logical challenges,” says Dr. Chandramohan.
