Why Africa needs to be involved in the development of ÍøÒ×ÌåÓý vaccines

9 September 2020 - Shabir A Madhi

Understanding the epidemiology of ÍøÒ×ÌåÓý and moving forward would be critical to determining policy on the need to adopt interventions.

The ÍøÒ×ÌåÓý pandemic continues to exact a toll on the health front, with about 25.5 million cases and 851,000 deaths documented as of 1 September 2020. Soberingly, this count represents only a conservative estimate of the number of people who have been infected by SARS-CoV-2 and who have died of ÍøÒ×ÌåÓý. 

Central to this undercount has been the limited capabilities and capacity even in high-income countries to undertake adequate testing of suspected cases with symptoms suggestive of ÍøÒ×ÌåÓý, which is further exacerbated by the majority of adults (40%-60%) and children under 18 years (80%) likely to be asymptomatic. Consequently, even in the US, the country with the highest number of reported cases (6.03 million) and deaths (183,500), and where the testing rate is about 253 per 1,000 population, modelling suggests that the actual number of infections may be threefold to twelvefold higher in different states than has been documented.

In Africa, the capabilities to test for SARS-CoV-2 infection is severely constrained because of limited laboratory capacity. Despite the Africa Centres for Disease Control and Prevention indicating that about 43 sub-Saharan African countries have the ability to test for ÍøÒ×ÌåÓý, these are generally only available at a single central laboratory. Consequently, such testing facilities would be of limited value in quantifying the burden of ÍøÒ×ÌåÓý in many of these sub-Saharan African countries. Furthermore, the limited test capabilities is compounded by the high costs of such tests, and the global shortage of SARS-CoV-2 testing materials ¨C which is even more challenging to overcome in Africa, which is almost completely dependent on the import of the required reagents for ÍøÒ×ÌåÓý testing. 

South Africa, despite having the highest testing rate for ÍøÒ×ÌåÓý in sub-Saharan Africa (62 per 1,000 population), nevertheless, lags behind the testing rate of many high-income countries (>150 per 1,000). Also, the positivity rate for tests conducted in South Africa was ~27% at the peak of the pandemic, and although declining to 13% in the past week, it still remains higher than the 5% threshold suggestive of adequacy in testing rates and control of virus transmission. Consequently, despite ~54% (680,000) of the 1.253-million ÍøÒ×ÌåÓý cases reported in Africa being documented in South Africa, this itself probably represents a gross underestimate (possibly sevenfold to tenfold) of SARS-CoV-2 infections that have occurred in South Africa. 

Characterising the burden of ÍøÒ×ÌåÓý, and any other disease, is more than an academic exercise. Understanding the epidemiology of ÍøÒ×ÌåÓý currently and moving forward, would be critical to determining policy on the need to adopt interventions, including the ÍøÒ×ÌåÓý vaccines that are being developed.

This underestimate in ÍøÒ×ÌåÓý cases (and, by extrapolation, reported deaths) due to limited testing capacity is further highlighted by the disconnect between Nigeria and South Africa, both of which were ranked to be among the highest risk of ÍøÒ×ÌåÓý outbreaks in Africa due to their global interconnectivity. In contrast to South Africa (population 59 million), Nigeria has a population size that is 3.3-fold greater (195 million), but has reported less than one-tenth (n=54,250) the number of ÍøÒ×ÌåÓý cases compared to South Africa, and only 1,023 ÍøÒ×ÌåÓý deaths. The testing rate for ÍøÒ×ÌåÓý in Nigeria (1.95 per 1,000 population) is, however, 32-fold lower than in South Africa. Consequently, the burden of ÍøÒ×ÌåÓý in Nigeria is likely to be even more grossly underestimated than in South Africa, and unfortunately the same would apply for most other sub-Saharan African countries where testing rates have generally been under 10 per 1,000 population.   

Sero-epidemiological surveillance (testing for antibodies to SARS-CoV-2 to determine if infections may have taken place at least three weeks before) are about to be launched in South Africa, and would better quantify the proportion of the population likely to have been infected. Similarly, such sero-epidemiological studies could assist in characterising the extent of SARS-CoV-2 infection that has occurred in other African countries, in the absence of being able to test in any meaningful manner for quantification of active ÍøÒ×ÌåÓý case detection. Such surveillance, coupled with epidemiological characterisation of excess mortality due to ¡°natural causes¡± (assuming adequacy of vital registration data systems) over and above that anticipated for the period when the pandemic occurred, could assist in quantifying the burden of ÍøÒ×ÌåÓý suffered in Africa. However, this is often only measurable after the pandemic has passed, as occurred for the swine flu pandemic in 2009.   

Characterising the burden of ÍøÒ×ÌåÓý, and any other disease, is more than an academic exercise. Understanding the epidemiology of ÍøÒ×ÌåÓý currently and moving forward, would be critical to determining policy on the need to adopt interventions, including the ÍøÒ×ÌåÓý vaccines that are being developed. Mischaracterisation of the burden of ÍøÒ×ÌåÓý in sub-Saharan Africa, particularly underestimating it due to lack of testing capacity, could paradoxically lead to African countries being compromised in advocating for and obtaining early and timeous access to safe and effective ÍøÒ×ÌåÓý vaccines. 

The lack of robust epidemiological data, largely due to inadequate health care and laboratory testing capacity in low-middle income countries (LMIC), has often contributed to a 10 to 20-year lag in the introduction of life-saving childhood vaccines into their public immunisation programmes relative to its availability in high-income countries. Examples of this include vaccines such as Haemophilus influenzae type b conjugate vaccine and pneumococcal conjugate vaccine, which protect against the leading causes of meningitis (brain infection) and pneumonia (lung infection) in children under five years of age. In the absence of immunisation, the bacteria targeted by these two vaccines caused more than one million childhood deaths annually, >95% of which occurred in LMIC (including approximately 50% in Africa which constitutes less than one-fifth of the global under-five childhood population). 

The costs of these vaccines, and supply chain constraints contribute to the lag in introduction of these life-saving vaccines into LMIC public immunisation programs. However, often the lack of local epidemiological data to quantify the burden of disease and absence of local vaccine effectiveness studies from the region, has served as an excuse by governments not to mobilise resources for the introduction of these life-saving vaccines into their public immunisation programmes. Unfortunately, gathering local epidemiological data and undertaking vaccine effectiveness studies only after the vaccines have been licensed in high-income countries, inadvertently leads to millions of preventable deaths occurring while such evidence is generated.  

Similarly, largely driven by paucity of laboratory testing capacity during the 2009 swine flu pandemic caused by the H1N1pdm2009 virus, there was a complete mischaracterisation of the burden of swine flu suffered in LMIC until after the pandemic. Notably, LMIC in the WHO African and south Asian countries reported the least number of swine flu cases during the pandemic, yet subsequently modelling estimated that 51% of all deaths due to the swine flu occurred in south Asia and Africa. 

The global death toll from the swine flu pandemic included an estimated 201,200 respiratory deaths (range 105,700-395,600), and 83,300 cardiovascular deaths (46,000-179,900). Notably, there was also a flurry of activity to develop a vaccine against the swine flu virus during the pandemic, albeit using more tried and tested approaches leveraging on experiences with manufacture of seasonal influenza viruses. All the research on swine flu vaccine, including clinical phase I-IV studies, were undertaken exclusively in high-income countries, with no studies in Africa or south Asia. Consequently, despite a swine flu vaccine being developed during the course of the pandemic, following which it was deployed in many high-income countries, its availability in South Africa (which was the first in sub-Saharan Africa to gain access to the vaccine) only transpired after the pandemic had ended. 

Of the 26 ÍøÒ×ÌåÓý vaccines currently in human trials (many of which have multiple studies in different countries), only two are being conducted in Africa. This is consistent with the legacy of clinical trials more generally, where less than 5% of all clinical trials are done in Africa, despite it constituting 18% (1.3 billion people) of the global population. 

Although not the only factor, the lack of involvement by African scientists in the development of the swine flu vaccine either by design (not their own, other than perhaps lack of initiative) or due to capability constraints, together with limited epidemiological studies quantifying the burden of swine flu in sub-Saharan Africa, diminished their ability to advocate for early access to the vaccine. This was compounded by vaccine manufacturers prioritising supply of the limited available doses of vaccine to high-income countries, where the licensure of the vaccine would have occurred immediately post-development. 

Unfortunately, Africa remains almost totally dependent on vaccine developers and manufacturers in other continents for access to vaccines. Other than limited ability to produce yellow fever vaccine in Senegal, and limited manufacturing capacity of basic childhood vaccines in two north African countries, no vaccine manufacturing capacity exists on the continent. Furthermore, there has not been any discovery of a new vaccine that has been led by African scientists, largely a consequence of the systematic under-investment on the part of governments and the private sector in the field of research and development. 

This, unfortunately places Africa at an immediate disadvantage in accessing vaccines, and perpetuates its dependency on non-African countries. This, despite political talk about Africa needing to prioritise vaccine-manufacturing capabilities, with very little progress having occurred since the adoption by the Ministerial Conference on Immunization in Africa in February 2016 of a resolution to promote and invest in regional capacity for the development and production of vaccines. In the absence of a strategic private-academia-public partnership, coupled with the ongoing brain drain of African scientists to higher-income countries where they are able to form part of teams geared toward vaccine discovery at its different stages of development, this situation is unlikely to change. Also, aspiring for a sudden break from the past and expecting manufacturing facilities to be set up in Africa within a 6-12 months framework to have an impact on the ÍøÒ×ÌåÓý pandemic, is unlikely to yield any measurable success. 

Fortunately, African scientists have been more involved in collaborating with international institutions in the clinical evaluation of vaccines, albeit in many sub-Saharan African countries, often under the leadership of investigators from high-income country institutions. Nevertheless, the infrastructure and local expertise does exist in at least a few sub-Saharan African countries for local scientists to assume a leading role in the clinical development and evaluation of ÍøÒ×ÌåÓý vaccines. There has been some muted protest about vaccine trials being conducted in Africa under the notion that Africans are being used as ¡°guinea pigs¡±. However, the reality is there is no rush on the part of vaccine developers (either from the private sector or academia) to conduct studies in Africa. 

Of the 26 ÍøÒ×ÌåÓý vaccines currently in human trials (many of which have multiple studies in different countries), only two are being conducted in Africa. This is consistent with the legacy of clinical trials more generally, where less than 5% of all clinical trials are done in Africa, despite it constituting 18% (1.3 billion people) of the global population. 

The emergent vaccine-nationalism in many high-income countries, pre-ordering at premium prices vaccines that are yet to be licensed and suggesting regulations to restrict the export of ÍøÒ×ÌåÓý vaccines manufactured in those countries, is a further challenge to ensuring an equitable and timeous distribution of ÍøÒ×ÌåÓý vaccines especially to LMIC. 

Notably, both of the ÍøÒ×ÌåÓý vaccine studies in Africa are occurring in South Africa, following the initiative of local investigators to advocate and convince the vaccine developers to, at the least, provide the vaccine for such studies to be undertaken here, while in parallel being responsible for mobilising the resources to do so. The reasons for the paucity of ÍøÒ×ÌåÓý vaccine studies in Africa are multifactorial, including cumbersome regulatory pathways that need to be navigated to get approvals to conduct such studies. 

Furthermore, the harsh reality is that there is little interest on the part of manufacturers to undertake such studies on the continent which is unlikely to be a major market for the vaccine. Consequently, unless African scientists are proactive in engaging with the vaccine manufacturers,  together with other stakeholders such as the WHO, the continent risks once again lagging behind by a number of years before it will be able to successfully advocate for timeous access to ÍøÒ×ÌåÓý vaccines once these are licensed. 

Although being involved in the clinical development of the ÍøÒ×ÌåÓý vaccine pipeline does not necessarily guarantee immediate access to the vaccine for South Africa (or other African countries) should it be shown to be effective; it nevertheless generates evidence of the likely public health impact of these vaccines in our own context sooner than later. This could assist in disrupting the legacy of delaying the introduction of life-saving vaccines into Africa due to the lack of local evidence. Furthermore, it does place moral and ethical pressure on the vaccine manufacturers to prioritise the country for vaccine supply, should the studies contribute to the eventual licensure of the vaccine. Notably, for both of the ÍøÒ×ÌåÓý vaccines currently being evaluated in South Africa, the Bill & Melinda Gates Foundation is funding Serum Institute of India, to develop manufacturing facilities to produce these vaccines, to accelerate timeous access to these ÍøÒ×ÌåÓý vaccines to LMIC should the clinical trials confirm their safety and efficacy. 

The emergent vaccine-nationalism in many high-income countries, pre-ordering at premium prices vaccines that are yet to be licensed and suggesting regulations to restrict the export of ÍøÒ×ÌåÓý vaccines manufactured in those countries, is a further challenge to ensuring an equitable and timeous distribution of ÍøÒ×ÌåÓý vaccines especially to LMIC. 

To mitigate this, the ÍøÒ×ÌåÓý Vaccines Global Access (Covax) Facility, which is co-led by the WHO, the Coalition for Epidemic Preparedness Innovations and Gavi, provides a possible pathway in assisting especially LMIC to gaining timeous access to ÍøÒ×ÌåÓý vaccines. This will at least aim at providing access to sufficient numbers of ÍøÒ×ÌåÓý vaccine doses to target populations at high risk of ÍøÒ×ÌåÓý and frontline healthcare workers. 

However, for countries such as South Africa to benefit from this initiative requires clear planning and commitment on the part of the government to provide the funds upfront to procure ÍøÒ×ÌåÓý vaccines through the advanced market commitment model that is envisioned by COVAX. Delaying in doing so, unfortunately diminishes the country¡¯s prospects of gaining early and timeous access to safe and effective ÍøÒ×ÌåÓý vaccines. Also, not gearing up plans to access ÍøÒ×ÌåÓý vaccines now is something that the country can ill afford, considering the health, economic and societal repercussions that the pandemic has already inflicted on South Africans and probably similarly elsewhere in sub-Saharan Africa.

Shabir Madhi is Professor of Vaccinology at Wits University. Daily Maverick is a media partner for the ¡°Meeting the Challenge of ÍøÒ×ÌåÓý in Africa¡± conference held virtually from 1-4 September and co-hosted by the Universities of Columbia and the Witwatersrand. This article is based on a keynote address made at the symposium.