| Title:
|
Combining malaria vaccination with chemoprevention: a promising new approach to malaria control |
| Abstract:
|
Malaria control has stalled in a number of African countries and novel approaches to malaria control are needed for these areas. The encouraging results of a recent trial conducted in young children in Burkina Faso and Mali in which a combination of the RTSS/AS01(E) malaria vaccine and seasonal malaria chemoprevention led to a substantial reduction in clinical cases of malaria severe malaria and malaria deaths compared with the administration of either intervention given alone suggests that there may be other epidemiological/clinical situations in which a combination of malaria vaccination and chemoprevention could be beneficial. Some of these potential opportunities are considered in this paper. These include combining vaccination with intermittent preventive treatment of malaria in infants with intermittent preventive treatment of malaria in pregnancy (through vaccination of women of child-bearing age before or during pregnancy) or with post-discharge malaria chemoprevention in the management of children recently admitted to hospital with severe anaemia. Other potential uses of the combination are prevention of malaria in children at particular risk from the adverse effects of clinical malaria such as those with sickle cell disease and during the final stages of a malaria elimination programme when vaccination could be combined with repeated rounds of mass drug administration. The combination of a pre-erythrocytic stage malaria vaccine with an effective chemopreventive regimen could make a valuable contribution to malaria control and elimination in a variety of clinical or epidemiological situations and the potential of this approach to malaria control needs to be explored. |
| Published:
|
2021-09-06 |
| Journal:
|
Malar J |
| DOI:
|
10.1186/s12936-021-03888-8 |
| DOI_URL:
|
http://doi.org/10.1186/s12936-021-03888-8 |
| Author Name:
|
Greenwood Brian |
| Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/greenwood_brian |
| Author Name:
|
Cairns Matthew |
| Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/cairns_matthew |
| Author Name:
|
Chaponda Mike |
| Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/chaponda_mike |
| Author Name:
|
Chico R Matthew |
| Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/chico_r_matthew |
| Author Name:
|
Dicko Alassane |
| Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/dicko_alassane |
| Author Name:
|
Ouedraogo Jean Bosco |
| Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/ouedraogo_jean_bosco |
| Author Name:
|
Phiri Kamija S |
| Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/phiri_kamija_s |
| Author Name:
|
ter Kuile Feiko O |
| Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/ter_kuile_feiko_o |
| Author Name:
|
Chandramohan Daniel |
| Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/chandramohan_daniel |
| sha:
|
66a50906570ac497d844c3397777ae8c7dee67c2 |
| license:
|
cc-by |
| license_url:
|
https://creativecommons.org/licenses/by/4.0/ |
| source_x:
|
PMC |
| source_x_url:
|
https://www.ncbi.nlm.nih.gov/pubmed/ |
| pubmed_id:
|
34488784 |
| pubmed_id_url:
|
https://www.ncbi.nlm.nih.gov/pubmed/34488784 |
| pmcid:
|
PMC8419817 |
| pmcid_url:
|
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419817 |
| url:
|
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419817/ |
| has_full_text:
|
TRUE |
| Keywords Extracted from Text Content:
|
Burkina Faso
RTS
infants
women
sickle cell
S/AS01 E
vaccine
Mali
children
IPTi-SP
sub-Sahel
amodiaquine
Burkina Faso
HPV vaccines
UK
IPTp
human papiloma virus vaccine
DHA-PQ
Plasmodium falciparum
EPI
SMC
PMC
[1]
liver
liver schizonts
artemether-lumefantrine
children
Mali.
MDA
rabies
cellular
IPTi
dihydroartemisinin-piperaquine
EPI vaccines
mother
piperaquine
Children
sickle cell
S/AS01 E + SMC
burden-High
IPTp-SP
malariaendemic
anti-malarials
Mali
dapsone
Senegal
sporozoites PfSPZ
Clinicaltrial.gov NCT03178643
HPV
primaquine
PfSPZ
Ghana,
London
RTS
sulfadoxine-pyrimethamine
SP + AQ
blood
Sierra Leone
haemoglobin
S/ AS01 E
cell
NCT04844099
women
Maloprim ®
placenta
AMA1
long-acting
chloroquine
infants
S/AS01 E
Rh5 antigen
PfSPZ-CVac
vaccine
hepatitis A
pyrimethamine
brian.greenwood@lshtm.ac.uk 1 London School
[7] [8] [9]
travellers |
| Extracted Text Content in Record:
|
First 5000 Characters:Malaria control has stalled in a number of African countries and novel approaches to malaria control are needed for these areas. The encouraging results of a recent trial conducted in young children in Burkina Faso and Mali in which a combination of the RTS,S/AS01 E malaria vaccine and seasonal malaria chemoprevention led to a substantial reduction in clinical cases of malaria, severe malaria, and malaria deaths compared with the administration of either intervention given alone suggests that there may be other epidemiological/clinical situations in which a combination of malaria vaccination and chemoprevention could be beneficial. Some of these potential opportunities are considered in this paper. These include combining vaccination with intermittent preventive treatment of malaria in infants, with intermittent preventive treatment of malaria in pregnancy (through vaccination of women of child-bearing age before or during pregnancy), or with post-discharge malaria chemoprevention in the management of children recently admitted to hospital with severe anaemia. Other potential uses of the combination are prevention of malaria in children at particular risk from the adverse effects of clinical malaria, such as those with sickle cell disease, and during the final stages of a malaria elimination programme when vaccination could be combined with repeated rounds of mass drug administration. The combination of a pre-erythrocytic stage malaria vaccine with an effective chemopreventive regimen could make a valuable contribution to malaria control and elimination in a variety of clinical or epidemiological situations, and the potential of this approach to malaria control needs to be explored.
Substantial progress has been made in the control of malaria in the past 2 decades, with the incidence of malaria deaths reduced by over a half and malaria cases by nearly a third. In the same period, ten countries have been certified by The World Health Organization (WHO) as having eliminated malaria [1] . However, progress has stalled in recent years in many countries in sub-Saharan Africa, where malaria remains a major cause of death and serious illness in young children. This levelling off in progress has led the WHO to establish a 'High burden-High Impact' programme [2] targeted at India and the ten African countries with the highest burden of malaria. Novel approaches to malaria control are required in these countries. The encouraging results of a recent trial conducted in young children in Burkina Faso and Mali, where malaria transmission is highly seasonal, suggest
Malaria Journal *Correspondence: brian.greenwood@lshtm.ac.uk 1 London School of Hygiene and Tropical Medicine, London, UK Full list of author information is available at the end of the article that a potential new approach to malaria control in countries where this is proving challenging is combining vaccination with a pre-erythrocytic malaria vaccine with chemoprevention [3] . This paper reviews some of the situations in which this might be a useful new approach to malaria control.
Three of the most advanced Plasmodium falciparum malaria vaccines (RTS,S/AS01 E , PfSPZ and R21) are pre-erythrocytic vaccines, which induce an immune response directed at the sporozoite or liver stage of the parasite's life-cycle. The humoral and cellular immune responses induced by these vaccines are highly effective at preventing in the short term the establishment or full development of liver schizonts, but the persistence and rupture of a single schizont are sufficient to establish a blood-stage infection that could result in a severe episode of malaria or even death. An approach that is currently being explored to overcome this challenge is combining a pre-erythrocytic stage vaccine with one that induces an immune response against blood stages of the parasite, thus aborting the infection [4] . However, the development of an effective blood-stage vaccine has proved challenging because of polymorphism in the key blood-stage antigens, such as AMA1, that have been the initial targets for blood-stage vaccine development [5] . A vaccine based on the conserved Rh5 antigen may overcome this problem [6] , but this candidate vaccine is still only at an early stage of clinical development. In contrast to the immune response induced by the first generation of blood-stage vaccine candidates, antimalarial drugs to which the parasite is sensitive can rapidly kill any blood-stage parasites regardless of the parasite strain and provide protection for several weeks dependent upon the anti-malarial used. Therefore, combining vaccination and chemoprevention in an appropriately targeted way could play an important role in the control of malaria where this is currently proving difficult.
Chemoprevention at a population level is used for malaria control in highly endemic areas in various ways, including intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-S |
| Keywords Extracted from PMC Text:
|
MDA
long-acting
AMA1
dapsone
Ghana,
IPTp
IPTi-SP
PfSPZ
cellular
DHA-PQ
liver schizonts
Plasmodium falciparum
PfSPZ-CVac
blood
Mali.
NCT04844099
sickle cell
haemoglobin
Clinicaltrial.gov NCT03178643
Burkina Faso
burden-High
anti-malarials
women
vaccine
travellers
IPTi
S/AS01E
Maloprim®
Mali
cell
primaquine
Ghana
PMC
placenta
pyrimethamine
Children
S/AS01E
infants
SMC
HPV vaccines
dihydroartemisinin-piperaquine
piperaquine
RTS
rabies
Sierra Leone
EPI vaccines
amodiaquine
hepatitis A
artemether-lumefantrine
's
Rh5 antigen
EPI
sub-Sahel
[1]
chloroquine
children
IPTp-SP
Senegal
HPV
sulfadoxine-pyrimethamine
mother
sporozoites PfSPZ
human papiloma virus vaccine
liver |
| Extracted PMC Text Content in Record:
|
First 5000 Characters:Substantial progress has been made in the control of malaria in the past 2 decades, with the incidence of malaria deaths reduced by over a half and malaria cases by nearly a third. In the same period, ten countries have been certified by The World Health Organization (WHO) as having eliminated malaria [1]. However, progress has stalled in recent years in many countries in sub-Saharan Africa, where malaria remains a major cause of death and serious illness in young children. This levelling off in progress has led the WHO to establish a 'High burden-High Impact' programme [2] targeted at India and the ten African countries with the highest burden of malaria. Novel approaches to malaria control are required in these countries. The encouraging results of a recent trial conducted in young children in Burkina Faso and Mali, where malaria transmission is highly seasonal, suggest that a potential new approach to malaria control in countries where this is proving challenging is combining vaccination with a pre-erythrocytic malaria vaccine with chemoprevention [3]. This paper reviews some of the situations in which this might be a useful new approach to malaria control.
Three of the most advanced Plasmodium falciparum malaria vaccines (RTS,S/AS01E, PfSPZ and R21) are pre-erythrocytic vaccines, which induce an immune response directed at the sporozoite or liver stage of the parasite's life-cycle. The humoral and cellular immune responses induced by these vaccines are highly effective at preventing in the short term the establishment or full development of liver schizonts, but the persistence and rupture of a single schizont are sufficient to establish a blood-stage infection that could result in a severe episode of malaria or even death. An approach that is currently being explored to overcome this challenge is combining a pre-erythrocytic stage vaccine with one that induces an immune response against blood stages of the parasite, thus aborting the infection [4]. However, the development of an effective blood-stage vaccine has proved challenging because of polymorphism in the key blood-stage antigens, such as AMA1, that have been the initial targets for blood-stage vaccine development [5]. A vaccine based on the conserved Rh5 antigen may overcome this problem [6], but this candidate vaccine is still only at an early stage of clinical development. In contrast to the immune response induced by the first generation of blood-stage vaccine candidates, antimalarial drugs to which the parasite is sensitive can rapidly kill any blood-stage parasites regardless of the parasite strain and provide protection for several weeks dependent upon the anti-malarial used. Therefore, combining vaccination and chemoprevention in an appropriately targeted way could play an important role in the control of malaria where this is currently proving difficult.
Chemoprevention at a population level is used for malaria control in highly endemic areas in various ways, including intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP), intermittent preventive treatment of malaria in infants with SP (IPTi-SP), seasonal malaria chemoprevention (SMC) and mass drug administration (MDA). However, the potential benefit of combining vaccination and malaria chemoprevention with an effective schizonticidal drug or drug combination has only recently been explored [7–9].
The first phase of a trial undertaken in young children in Burkina Faso and Mali to investigate the impact of combining vaccination with the RTS,S/AS01E malaria vaccine with SMC has recently been completed [7, 8]. In this study, conducted in areas of highly seasonal malaria transmission, 5920 children were enrolled at the age of 5–17 months and allocated to one of three groups. Children in one group received four, monthly courses of SMC with sulfadoxine-pyrimethamine plus amodiaquine (SP + AQ) each year during the malaria transmission season (the standard of care in both countries) plus control non-malarial vaccines (rabies and hepatitis A), those in a second group received RTS,S/AS01E plus an SMC placebo, and those in a third group received both RTS,S/AS01E and SMC. RTS,S/AS01E was administered in three, monthly priming doses prior to the 2017 malaria transmission season, and then a single booster dose was given shortly before the start of the malaria transmission season during each of the following two years (2018 and 2019). All children were provided with an insecticide-treated bednet at the start of the trial. The primary trial endpoint was the incidence of clinical attacks of malaria; predefined secondary endpoints included hospital admissions with malaria and death from malaria [7]. During three years of follow-up, RTS,S/AS01E alone was non-inferior to SMC in preventing malaria and the combination of the two interventions led to a substantial reduction in the incidence of uncomplicated cases of malaria, hospital admissions with malaria and dea |
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