Summary
This article shows from hard records that the newly touted malaria vaccines were indeed
developed for short-term visitors from the outside world to malaria-endemic
zones (specifically military personnel and tourists). A strong market in sub-sahara Africa is
however required to make their production economically viable! Notwithstanding that they very poorly meet the
requirements to protect children in malaria-endemic regions such as Nigeria, we
are reluctant to castigate them entirely.
On the conditions that people (particularly the press!) are properly
educated that these are no silver bullets; and government does not attempt to
incorporate them into the list of essential vaccines to be vigorously recommended
for the masses – as the manufacturers are already subtly demanding!
Joshua Ojo
Ile-Ife. 1st
May, 2023
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First of all, we note
that there are actually two vaccines on the table. The first, RTS,S, is recommended and approved
by the WHO while the other, R21, is still undergoing trials. However, while the Federal Ministry of Health
has announced that the country has now placed
orders for RTS,S, expected to be delivered by April 2024; the NAFDAC has
given approval,
not to the RTS,S, but to the R21.
The approval given to
the R21 will allow it to be used in clinical trial settings in the
country. NAFDAC said it had shunned
participation in the clinical trials for RTS,S because its touted efficacy of
about 30% was simply not attractive enough
ab initio.
Speaking extensively on
Channels TV, the DG, Prof Moji Adeyeye, emphasised that unlike the case for
COVID vaccines, when NAFDAC gave approvals without actually testing the
products, the situation will be different this time. During COVID, the WHO had
foisted on NAFDAC some novel Protocols,
such as “Reliance”, which authorizes it to simply rubber-stamp whatever
decision has been announced by the WHO; and “Recognition” (which encourages it to regurgitate statements made
by so-called “more matured” Agencies from other countries – where the WHO
itself is circumspect of making any statements). This time around there would
be clinical trials in Nigeria, and that for R21would be commencing within 6 weeks.
That is some cheering
news, for a change!
But before we become
too engrossed in the subtle battle for supremacy among the malaria vaccines,
(and possibly between government Agencies also), we need to examine what
exactly is the place of vaccines in managing a disease that reportedly kills
about 200,000 Nigerians every year. This
figure represents 31.3% of total global mortality attributed to malaria.
Without any doubt, any
solution that could dent that horrible figure is to be celebrated and embraced.
The search for a useful vaccine for malaria had been on for more than 50 years,
and we must congratulate the brilliant researchers for their hard work, doggedness,
and at last, a visible result. It is tough enough trying to develop vaccines
against viruses and bacteria, a vaccine for malaria is another story
entirely. The disease is carried by a
parasite involving two hosts – the female anopheles mosquito and humans. The parasite itself has some 5 species that
infect humans, each existing in different forms at different stages of their
life-cycles. The life cycle begins as sporozoites deposited into human liver, and
later moves to the blood (erythrocytic phase) before finally ending up back in
the salivary gland of the anopheline mosquitoes, thus perpetuating the cycle. The daunting scientific difficulties involved
in trying to get a safe and effective vaccine against this challenge are well enunciated
in the literature, for example here
and here.
However, a vaccine
solution must be justified not only on its own merit, but also on how well it
fits in within the framework of holistic malaria management in a country. In particular, it should complement other
tools rather than jeopardize them.
Factors
determining the merit or otherwise of a vaccine solution include 1) Efficacy - that
is the whole point of the tool, anyway – how well does it work? 2) Duration of the efficacy - how long after
full dosage before the efficacy wanes and “boosters” become necessary? 3) Target
biological endpoint and its relevance - What exactly does it “prevent” – new infections?
hospitalizations? (Perhaps we should focus more on identifying and dealing with
the risk factors for severe malaria, and stop counting “cases”!). 4) Safety - are
the health risks introduced by the intervention justifiable relative to the
benefits? 5) the Logistics involved in its procurement, storage, and delivery
(for instance the number of doses required for full dosage: the higher this
number, the higher the chances of non-full compliance and consequent failure). 6) the Costs of the whole enterprise, and 7) possible
Spin-off benefits for other sectors.
As pointed out by DG
NAFDAC, the RTS,S vaccine would score very low based on these considerations. Not
only is the touted efficacy rather low at 30-40%, it needs to be administered
in four at least doses posing considerable programmatic challenges. The
duration of this efficacy has been determined to be about
only 7 months. Even with possible
financial supports (specific for the malaria vaccine, and for a limited period)
the (non-negotiable) cost of
$3-$4 per dose is not exactly pocket-friendly, especially for an expense
that might as well become an annual ritual of 4-5 doses per child.
However, the big issue
with the RTS,S is safety. It remains an
indelible ugly
stain on the WHO, that in the clinical trials for the RTS,S, conducted
directly under her auspices, the WHO withheld critical safety signals
raised during Phase III trials from African participants in the Phase IV
clinical trials. These were: “a ten times higher rate of meningitis, a
higher chance of cerebral malaria, and a doubling of deaths from all causes in
girls who had received the vaccine and not the placebo.”
Obviously, these are
very serious issues indeed. Though the WHO subsequently suggested that the safety
issues had been somewhat cleared,
many authorities flatly disagreed.
In any case, it is rather difficult mending trust so flagrantly breached.
We raise our first
pertinent question at this juncture: are the clinical trials to be conducted
under the auspices of NAFDAC for the R21 vaccine going to check out for these safety
issues also? And how long will it take
before the answers will become available?
In short, will the NAFDAC be open and transparent in making available to
the general public the protocols to be used for these clinical trials? Sadly, up to the present time, access to the
Vaccines and Biologics section on NAFDAC’s website remains passworded and
unavailable to the general public, unlike those for other categories, viz:
Food, Drugs & Medical Devices, Herbals & Cosmetics, Chemicals,
Narcotics, and Veterinary.
Clearly, there is need
for caution before one exuberantly concludes that the R21 will eventually outperform
the RTS,S. This more so, when it is realized that the two vaccines are actually
essentially based on the same principle and materials. Both target the pre-erythrocytic phase of
malaria, with the key antigen provoking an immune response being the
Circumsporozoite Protein (CSP) (secreted by the
sporozoites of Plasmodium falciparum), bundled with hepatitis B
virus epitopes. The major difference in
the two is that the concentration of the CSP is higher in R2,1 than in RTS,S;
and both have different adjuvants -
materials required to amplify the immune response. RTS,S uses GSK’s AS01 as
adjuvant, while R2,1 employs NOVAVAX’s MATRIX-M (same used for their COVID-19
vaccine).
There are other issues with
the two vaccines that raise serious concerns.
For instance, while it is indeed reasonable that these vaccines should
target Plasmodium falciparum which is responsible for as much as 98% of malaria
mortality in sub-sahara Africa, it is well known that other species,
particularly the Plasmodium vivax
could persist in the blood for years, thereby promoting the recurrence of
malaria in the absence of any new infection. Even more concerning are results from Kenya
suggesting that the RTS,S vaccine could delay the acquisition of the far more
robust natural immunity in recipients.
That leadsus to the second
broad consideration that could justify the incorporation of the vaccine tool
into the general holistic management of malaria: How well does it fit in with
existing tools?
The available
non-immunization approach to malaria management include General environmental sanitation
to eliminate stagnant pools of water where mosquitoes could breed - the principal assignment for Environmental
Health Officers a few decades ago; use of insecticide treated nets, use of
various manners of insecticides or repellants, use of chemical prophylaxis
(e.g. “Sunday-Sunday”, Daraprim), and appropriate therapeutics - both herbal
and synthetics. It is instructive to note, from NAFDAC’s
data, that malaria prevalence in
rural settings could be as high as 2.4 times that in urban setting, while the
ratio between prevalence in children from the lowest social economic stratum to
those from the highest could be as high as 7!
Other key determinants
affecting the spread of malaria include the well- known
fact that the use of the pesticide
glyphosate (also implicated in cancer) weakens the immune systems of mosquitoes
and render them more susceptible to infection by
Plasmodium falciparum, thereby promoting spread of malaria. Similarly, the
role of natural immunity in humans is also well-recognized. This is known to build up over the years for
people living in malaria-endemic regions, and it effectively pushes the mortality
burden squarely on children and pregnant women.
There is also some measure of protection offered by the sickle cell
trait (HbAS) as the premature breaking of erythrocytes truncates the lifecycle
of the parasite.
Apart
from the possibility of making ill-informed people to become complacent in their
attitudes to traditional control methods, introduction of vaccines, if not
carefully implemented, could drastically cut the level of funding and other
resources available for these other more potent measures.
One major general
outcry against vaccine-based
solutions is the “Disconcerting over-dependence on foreign expertise and
recommendations”. This robs Nigeria of what could have been at least some
positive spin-offs in terms of development of human capacity which could have
been useful in other sectors. Introducing
the RTS,S in October 2021, WHO DG, Tedros Ghebreyesus had exulted:
“This long-awaited malaria vaccine is a breakthrough for science. This is a
vaccine developed in Africa by African scientists and we’re very proud,” It is not clear at all what he means by this, seeing
that the vaccine was developed by the Walter Reed Army Institute of Research
in the US and is marketed by British drugmaker, GlaxoSmithKline.
It
is quite surprising that with our unenviable status as the malaria capital of
the world, we cannot negotiate special prices for vaccines, not to talk of
compelling the manufacturers to open factories here. It doesn’t require much imagination to perceive
some positive correlation between Ghana’s being the 1st country to
approve R21 and the decision of Serum Institute to
open its sub-Sahara facility in Accra.
And by the way, it is still a puzzle, the WHO’s Classification which
deems Nigeria as NOT
qualified to produce vaccines even for her own local use! Nigeria had actively
produced vaccines for over 6 decades, until 1991 when a supposed upgrade
grounded everything.
The peculiarity of
vaccines is that, unlike drugs, they are to be administered to people who are
not sick. Their justification is
entirely premised on subjective risk:benefit analyses. The subject is conjectured as liable to be
exposed to infection, is perceived to lack sufficient natural immunity to cope
when so-infected, and envisaged to also lack adequate access to effective
therapy to deal with the adverse outcome.
Obviously, this framework cannot be easily generalized; and risk
assessment for vaccine use must be personal to the individual.
It is a matter of historic fact that the currently
available malaria vaccines were developed largely for military (US military to
be specific) personnel who may need to be posted to malaria endemic
regions. Hence they were not designed to
prevent transmission; and their short-term efficacy of only a few months is generally
adequate for this military need. To be
frank, it would seem that the principal reason for presenting these vaccines
for the use of babies in malaria endemic regions is largely to provide a market
that would sustain the economics of mass production for the subjects they were
actually designed to serve. [see Institute of Medicine. 2006. Battling Malaria:
Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The
National Academies Press. https://doi.org/10.17226/11656].
In conclusion, while we
may not castigate the malaria vaccines for whatever they are worth, it is
important that we don’t confer them with silver-bullet status, which might
jeopardize the effectiveness of other more potent tools for malaria management.
As previously noted, people who wrongly assume their malaria worries are over
with the receipt of the vaccine might get complacent in their compliance with other
more fundamental measures bothering on environmental and lifestyle factors.
Even much more
importantly, government must do nothing to coerce people into taking the
product. There are good reasons to have
fears this could be attempted. The PATH Technical
Brief document lists a number of pre-conditions before a country will be
“eligible” to buy their products. One of
these is that such countries “will need to include the vaccine in both their
national malaria strategic plan and their national immunization plan”. Other specific
conditions call for the establishment of “joint
immunization-malaria coordination mechanism” and also “Strong community
engagement to ENSURE vaccine acceptance and resilient demand….” (page 7 - emphasis
added).
All these look like subtle
attempts to conflate malaria vaccines and other already accepted vaccines. In a
previous
article on the pentavalent vaccine, we cited WHO
documents which confirm that significant
health complications are introduced when multiple vaccines are
co-administered together (simply for logistic reasons) rather than in the
individual formats where they were originally developed.
All these may well explain
the tardiness of the Federal Ministry of Health (FMoH) to submit an application
for the RTS,S. For it looked evident that the announcement by the Ministry that
it was sending in an application at the third window, was largely in response
to growing vilification of the Ministry by the press who wondered why the
Ministry was not joining in the excitement over the vaccine and had let two
application windows fritter away.
It is worrisome to note
that Nigerian reporters seem to find it easier contacting GAVI to inquire about
Nigeria’s subscription to their product rather than asking the FMoH directly. Those who have read John Perkin’s Confession
of an Economic Hitman might read this as GAVI actually reaching out to these
local journalists to put pressure on the Honourable Minister! One may therefore better understand the reported
response of the Minister when the press eventually reverted to him: “The Minister of Health
could not be reached for comment. He did
not take his calls and had yet to respond to a text message sent to him on the
matter as of the time of filing this report.”
https://punchng.com/nigeria-misses-malaria-vaccine-application-window/?amp
