By Jeremy R. Hammond, Guest Contributor
The World Health Organization (WHO), a pair of articles recently published in The BMJ have revealed, is sponsoring an experimental study of a controversial malaria vaccine among African children without obtaining informed consent from parents.
Data from prior clinical trials of the vaccine, manufactured by the British multinational pharmaceutical corporation GlaxoSmithKline (GSK), have shown it to be associated with an increased risk of clinical malaria after four years, a tenfold increased risk of meningitis, an increased risk of cerebral malaria (in which the parasitic organisms block the flow of blood to the brain, causing swelling and potential brain damage), and an increased risk of death that was disproportionately higher for female children.
Concerningly, apart from failing to properly inform parents about the risks or even letting parents know that their children are being experimented upon, the WHO intends to make a decision based on this trial about whether to recommend the vaccine for routine use throughout sub-Saharan Africa after just twenty-four months of study, which is not enough time to determine the vaccine’s effect on mortality.
This is especially concerning in light of scientific research showing that other non-live vaccines—such as the diphtheria, tetanus, and whole-cell pertussis (DTP) vaccine—are associated with an increased rate of childhood mortality. The WHO, however, has dismissed this evidence and continues to recommend the DTP vaccine for routine use in children in developing countries.
The behavior of policymakers at the WHO, while highly alarming, is not at all surprising given the organization’s conflicts of interest, including industry funding and members of its vaccine advisory group having financial ties to pharmaceutical companies.
- Waning of Vaccine-Conferred Immunity After Four Years
- The Importance of Natural Immunity and Scientific Uncertainty about How It’s Achieved
- Increased Risk of Clinical Malaria Among Vaccinated Children After Four Years
- Increased Risk of Death Among Children Receiving the Malaria Vaccine
- How the WHO Is Threatening Both Children’s Health and the Right to Informed Consent
- The WHO’s Conflicts of Interest
- The UN, Too, Is Threatening the Right to Informed Consent
Waning of Vaccine-Conferred Immunity After Four Years
GSK’s malaria vaccine has long been under development, but while the company and the WHO appear intent on rolling it out across Africa, concerning data from clinical trials has been publicly known for years. In 2013, the results of four years of trial follow-up in Kilifi, Kenya, were published in the New England Journal of Medicine (NEJM). The data showed that, while apparently effective at preventing clinical malaria initially, after four years, the vaccine had negative effectiveness, meaning that children who received the vaccine had an increased risk of symptomatic parasitic infection.
That study involved randomly vaccinating Kenyan children aged five to seventeen months with either the experimental malaria vaccine or a rabies vaccine. Importantly, the clinical endpoint of the trial was malaria incidence, not mortality. Even so, the data showed a vaccine efficacy of only 43.6 percent in the first year, which fell to –0.4 percent in the fourth year. While the negative efficacy was not statistically significant, the study authors acknowledged that the results show that the immunity conferred by the vaccine wanes after just a few years.
While the vaccine was judged to be initially effective in stimulating the production of antibodies against the sporozoite stage of the parasite, which is the form typically introduced into the blood of human hosts by mosquitos, the researchers acknowledged that a high level of anti-sporozoite antibodies doesn’t necessarily equate to immunity and that the immunity conferred by the vaccine differs from that acquired naturally through infection.
While anti-sporozoite antibodies “may mediate protection and were associated with a reduced risk of clinical malaria”, a waning of antibody titers was observed over time in children who received the malaria vaccine.
Additionally, they suggested that because children receiving the malaria vaccine had reduced exposure to later blood-stage parasites, they would have had “delayed acquisition of natural immunity”, which could also help explain the negative efficacy by the fourth year. In other words, the rapidly waning vaccine-conferred immunity was achieved at an opportunity cost of a delayed and superior natural immunity.… scientific reviews highlight the complexity of immunity to malaria and that even after 100 years we still have much to learn.
The Importance of Natural Immunity and Scientific Uncertainty about How It’s Achieved
The uncertainties about how immunity to malarial parasites is achieved were elucidated in an editorial in the journal Parasitology in 2016. Noting that “individuals living in endemic areas naturally acquire immunity to symptomatic malaria”, its authors pointed out that “immune correlates of protection” were not yet understood by scientists. While certain “antigen-specific immune responses associated with protection against malaria infection and disease” have been identified, scientific reviews “highlight the complexity of immunity to malaria and that even after 100 years we still have much to learn.”
“A lack of understanding of the mechanisms by which natural immunity to malaria is achieved and how it is maintained”, they noted, “has long been proclaimed as a major hurdle to the development of a malaria vaccine.”
Highly important to this question is the “variable nature of malaria epidemiology in different endemic areas”, which “underlines the importance of natural exposure in development of immunity”. In areas with lower transmission, population immunity is not achieved, and clinical infections occur frequently “in all age groups”. By contrast, “immunity is acquired through constant exposure to the parasite”, which is especially important for infants, who are at highest risk of dying from malaria.
This is because, in endemic areas, infants are protected from birth to around six months of age through the transfer of antibodies from naturally immune mothers to their babies. (This is known as passive maternal immunity and can occur both prenatally through the placenta and postnatally through breastmilk, though the authors don’t specify the relative importance of each of these mechanisms in the specific case of malaria.)
The authors pointed out that in the absence of mass vaccination campaigns, the number of malaria cases worldwide had halved over the past decade. Somewhat paradoxically, “because immunity is acquired through constant exposure to the parasite, with the decrease in transmission, there are increasing concerns about declining immunity in communities and a shift towards greater susceptibility to symptomatic disease.”
Whereas in endemic areas, natural immunity is generally acquired in childhood, in areas where transmission has been successfully reduced, “rebounds of malaria infections and shifts in cases to older individuals are occurring”.
As this shift continues, the risk could increase to infants born to mothers who have not yet had enough exposure to acquire natural immunity and therefore aren’t able to confer passive immunity to their babies.… it is undoubtedly a reflection of the myopic focus within the scientific community on developing vaccines as a one-size-fits all solution for disease prevention, as opposed to first dedicating the resources necessary to understand the risk factors for severe disease and differing individual immune responses and then developing targeted interventions.
While the vaccine is designed to stimulate the production of anti-malaria antibodies, as the authors of the Parasitology paper point out, another branch of the immune system known as cell-mediated immunity also plays an important role.
They observed a dearth of science in this area, with most studies having focused on antibody responses and “relatively few” that have “investigated cellular responses to malaria infection.” While they did not comment upon the reasons for this, it is undoubtedly a reflection of the myopic focus within the scientific community on developing vaccines as a one-size-fits all solution for disease prevention, as opposed to first dedicating the resources necessary to understand the risk factors for severe disease and differing individual immune responses and then developing targeted interventions.
Although “there remains much to be learnt about naturally acquired immunity to malaria”, the authors noted that the science is clear that cell-mediated immunity “plays a critical role in determining the outcome of disease and development and maintenance of immunity.”
A broad array of cellular responses not involving the production of antibodies are important for the development of immunity, and how these responses might affect the immune responses to a malaria vaccine—or vice versa—remains “unknown.”
This is concerning because non-live vaccines such as GSK’s malaria vaccine generally tend to skew the immune response toward humoral, or antibody, immunity and away from cell-mediated immunity, which is another means by which mass vaccination could potentially cause long-term detriment to population immunity in African communities.
Nevertheless, the journal editors incongruously pointed to the ability of humans to acquire natural immunity as “a strong rationale for the development of a malaria vaccine”—and despite the remaining uncertainties about how the vaccine will affect the immune system and data showing serious potential harms, GSK and the WHO are pushing for implementation of the vaccine in the routine childhood schedules of African countries.
Increased Risk of Clinical Malaria Among Vaccinated Children After Four Years
The four-year follow-up study itself provided evidence that the malaria vaccine achieves humoral immunity at the opportunity cost of lost cell-mediated immunity. Despite the waning of antibody levels over time among children who received the malaria vaccine, even in the fourth year, during which negative efficacy was observed, these children still had significantly higher anti-sporozoite antibody titers than children in the control group. This indicates that mechanisms other than the production of anti-sporozoite antibodies are important for immunity and in the long-term protected children in the control group from malaria.
As the authors reiterated, the observed waning immunity of the vaccine might have been due to a delayed “acquisition of natural immunity to blood-stage parasites” in children who received the malaria vaccine in comparison with those who didn’t.That is, the data showed a negative efficacy, meaning that children who received the malaria vaccine were at a higher risk of clinical malaria than those who didn’t.