Malaria vaccine

Abstract

Malaria has long been recognized as a public health problem. At the community level, vector control, and antimalarial medicines are the main means for reducing incidence, morbidity, and mortality of malaria. A vaccine not only would bring streamlining in the prevention of morbidity and mortality from malaria but also would be more accessible if integrated with Expanded Programme of Immunization (EPI). Globally, an estimated 3.4 billion people are at risk of malaria. Most cases (80%) and deaths (90%) occurred in Africa, and most deaths (77%) are in children under 5 years of age. An effective vaccine has long been envisaged as a valuable addition to the available tools for malaria control. Although research toward the development of malaria vaccines has been pursued since the 1960s, there are no licensed malaria vaccines. The RTS,S/AS01 vaccine, which targets P. falciparum, has reached phase 3 clinical trials and results are promising. Malaria Vaccine Technology Road Map 2013 has envisaged the world aiming for a licensed vaccine by 2030 that would reduce malaria cases by 75% and be capable of eliminating malaria. It will not only fill the gaps of today’s interventions but also be a cost-effective method of decreasing morbidity and mortality from malaria.

Keywords: :

• malaria
• vaccine
• elimination
• need

Introduction

Malaria is a potentially lethal infectious disease that has been co-evolving with humanity. It is an arthropod-borne disease and has long been recognized as a public health problem. There are five types of Plasmodium parasites causing malaria, namely P. vivax, P. falciparum, P. ovale, P. malariae, and P. knowlesi, with the most common being P. vivax and P. falciparum. Only the female Anopheles mosquito can transmit malaria. About 20 different Anopheles species are locally important around the world.¹ Malaria also can be transmitted between people through used needles/syringes, organ transplants, and blood transfusions. In rare instances, an infected mother may pass malaria to her baby during delivery (birth), known as congenital malaria.²

Approximately half of the world's population is at risk of malaria, with the hub being the sub-Saharan Africa. However, Asia, Latin America, and to a lesser extent the Middle East and parts of Europe are also affected. Vulnerable population for malaria being the young children, pregnant women, international travelers from non-endemic areas, and immigrants from endemic areas and their children.¹

At the community level, vector control and antimalarial medicines are the main means for reducing malaria. Vector control is the only intervention that can reduce malaria transmission from very high levels to close to zero. For individuals, personal protection against mosquito bites represents the first line of defense for malaria prevention. Two forms of vector control are effective in a wide range of circumstances: Insecticide-treated mosquito nets (ITNs) and Indoor residual spraying.¹

There has been evidence that humans can be vaccinated against malaria. Individuals born in endemic areas who survive the first years of exposure continue to develop parasitemia on natural exposure, but become resistant first to severe, life-threatening malaria and then to clinical disease. Frequent re-exposure is required to maintain this condition of immunity with infection (concomitant immunity).³ A vaccine will not only bring streamlining in prevention of morbidity and mortality from malaria but also be better accessible if integrated with the Expanded Programme of Immunization (EPI).

Global Burden of Disease

The World Malaria Report 2013 documents that there are 97 countries and territories with ongoing malaria transmission and 7 countries in the prevention of reintroduction phase, making a total of 104 countries and territories in which malaria is considered endemic. An estimated 3.4 billion people are at risk of malaria. WHO estimates that 207 million cases of malaria occurred globally in 2012 and 627 000 deaths. Most cases (80%) and deaths (90%) occurred in Africa, and most deaths (77%) were in children under 5 y of age. In South East Asia, the number of confirmed malaria cases were 2 million in 2012. Three countries accounted for 96% of reported cases in 2012: India (52%), Myanmar (24%), and Indonesia (22%).⁴ India accounts for 700 000 cases; nearly half of the cases were caused by P. falciparum.⁵ In recent years, United Arab Emirates (2007), Morocco (2010), Turkmenistan (2010), and Armenia (2011) have been certified by the WHO Director-General as having eliminated malaria.¹

Need for Malaria Vaccine

Substantial changes in malaria epidemiology are being observed in many but not all settings following reduction in malaria transmission in association with scaling-up of malaria control measures.⁶ Reduced transmission is associated with a shift in the peak age of clinical malaria to older children, and therefore the median age of hospitalization due to malaria has increased in some settings.^7-9

In recent years, resistance against insecticides and antimalarial drugs has been observed as a major hurdle in combatting malaria. Mosquito resistance to pyrethroids (insecticides) has emerged in many countries. In some areas, resistance to all four classes of insecticides has been detected. Countries in sub-Saharan Africa and India are of significant concern in that these countries are characterized by high levels of malaria transmission and widespread reports of insecticide resistance¹

To date, drug resistance has been documented in P. falciparum, P. vivax, and P. malariae. In Africa there is evidence that the spread of resistance coincided with increases in child mortality and morbidity.¹⁰ Expanding access to artemisinin-based combination therapies (ACTs) in malaria-endemic countries has been integral to the remarkable recent success in reducing the global malaria burden. No alternative antimalarial medicine is available that offers the same level of efficacy and tolerability as ACTs.¹¹

A vaccine will be an essential tool in stopping malaria because the current fight against the disease is being waged on a variety of fronts, including the distribution of bed-nets, the promotion of indoor spraying, and the development of new medicines and insecticides. A vaccine would fill the gap left by these interventions. Even a modestly efficacious malaria vaccine would protect hundreds of thousands of people from disease and death each year. Moreover it will be a more cost-effective intervention in combatting the disease.

Current Status of Vaccine

An effective vaccine against malaria has long been envisaged as a valuable addition to the available tools for malaria control. Although research toward the development of malaria vaccines has been pursued since the 1960s, there are no licensed malaria vaccines.

WHO lists 27 malaria vaccine candidates in clinical trials, with most in early stages of testing; RTSS/AS01 is the only vaccine with promising results. The RTS,S/AS01 vaccine, targeting P. falciparum, is in phase 3 clinical trials. This vaccine is being developed in a partnership between GlaxoSmithKline (GSK) and PATH Malaria Vaccine Initiative (MVI), with MVI receiving funds from the Bill and Melinda Gates Foundation. The vaccine is comprised of a fusion protein of a malaria antigen—the C-terminus of the P. falciparum circumsporozoite (CS) antigen—with hepatitis B surface antigen, and includes a new and potent adjuvant.⁴ In October 2013, a third set of results on the efficacy of this vaccine was reported for 6- to 14-wk-old and 5- to 17-mo-old age groups.¹² In the 5- to 17-mo age group, efficacy estimates pooled across all trial sites remained statistically significant against clinical malaria (46%) and severe malaria (36%). Reductions in both malaria hospitalizations (42%) and all-cause hospitalizations (19%) were noted over 18 mo of age. By contrast, at 27% in the 6- to 14-wk age group, the efficacy estimate for severe malaria was not statistically significant (although efficacy against clinical malaria remained statistically significant). The reasons for this difference between the age groups were unclear, but co-administration with DTP-containing vaccines and the presence of maternally acquired antibodies to malaria may contribute to a lower immune response in infants aged 6–14 wk.⁴

The full Phase 3 trial results will become available to WHO in late 2014 and will include 30 mo of follow-up safety and efficacy data from groups of children aged 6–14 wk and 5–17 mo, together with data on efficacy and safety of a booster dose and site-specific efficacy. The timelines of the Phase 3 trial may allow a WHO review and recommendation in late 2015, as a potential addition to the current WHO-recommended malaria preventive measure. The WHO process for review also will depend on the timings and outcome of the regulatory review that will be performed by the European Medicines Agency in 2014–2015.⁴

A recent probabilistic sensitivity and uncertainty analysis of one model provided useful insights into some of the uncertainties involved in establishing parameters for malaria transmission models. According to this report, the use of RTS,S/AS01 could be highly cost–effective in many settings with low to moderate transmission, depending on the price of the vaccine and the duration of the vaccine’s protection.¹³

Malaria Vaccine Technology Road Map 2013 has envisaged the world as aiming for a licensed vaccine by 2030 that would reduce malaria cases by 75% and be capable of eliminating malaria.¹⁴

Conclusion

Malaria vaccine will be an asset to the preventive strategies prevailing against this menacing disease. It will not only fill the gaps of today’s interventions but also be a cost-effective method of decreasing morbidity and mortality from malaria. It will be better accessed and accepted by the community. If integrated with EPI schedule, it will be a boon to the society. Malaria has long been dreaded by humanity, and now is the time to step ahead with a vision to eliminate the disease.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

10.4161/hv.28482