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AN UPDATE ON MALARIA
Dr A P Naveen Kumar
DNB FICP
Chief Specialist – General
Medicine
Visakha Steel General Hospital
EPIDEMIOLOGY
 Malaria continues to cause unacceptably high levels of disease and death
 There were an estimated 247 million cases and 619 000 deaths globally in 2021
 Malaria is preventable and treatable
 Global priority is to reduce the burden of disease and death while retaining the long-term
vision of malaria eradication
World Malaria Day 2023 will be marked under the theme
“Time to deliver zero malaria
invest, innovate, implement”
Within this theme, WHO will focus on the third “i” –
implement – and notably the critical importance of reaching
marginalized populations with the tools and strategies that are
available today
DIAGNOSIS
Parasitological diagnosis
 All cases of suspected malaria should have a parasitological test (microscopy or RDT) to
confirm the diagnosis
 Both microscopy and RDTs should be supported by a quality assurance programme.
Light microscopy
 Microscopy not only provides a highly sensitive, specific diagnosis of malaria when performed well
but also allows quantification of malaria parasites and identification of the infecting species
 Light microscopy involves relatively high costs for training and supervision, and the accuracy of
diagnosis is strongly dependent on the competence of the microscopist
 Microscopy technicians may also contribute to the diagnosis of non-malarial diseases
Rapid Diagnosis Tests -RDT
 Current tests are based on the detection of histidine-rich protein 2 (HRP2), which is specific for P. falciparum,
pan-specific or species-specific Plasmodium lactate dehydrogenase (pLDH) or pan-specific aldolase
 The tests have many potential advantages, including:
• rapid provision of results and extension of diagnostic services to the lowest-level health facilities
• fewer requirements for training and skilled personnel
• reinforcement of patient confidence in the diagnosis and in the health service in general.
At present, molecular diagnostic tools based on nucleic-acid amplification techniques
(e.g. loop-mediated isothermal amplification or polymerase chain reaction [PCR]) do
not have a role in the clinical management of malaria
PCR can be used to diagnose placental infection in asymptomatic women
TREATMENT
RECOMMENDATIONS ,BENEFIT AND HARM
 Recommendation: Treat adults and children with uncomplicated P. falciparum malaria (including
infants, pregnant women in their second and third trimesters and breastfeeding women) with an
ACT
Desirable effects
 • Studies have consistently demonstrated that the six WHO-recommended ACTs result in < 5% PCR-
adjusted treatment failures in settings with no resistance to the partner drug (high- quality
evidence)
Undesirable effects
 • Increased cost.
Artemisinin-based combination therapy -ACT
Children and adults with uncomplicated P. falciparum malaria
should be treated with one of the following ACTs*
• artemether-lumefantrine (AL)
• artesunate-amodiaquine (AS+AQ)
• artesunate-mefloquine (ASMQ)
• dihydroartemisinin-piperaquine (DHAP)
• artesunate + sulfadoxine-pyrimethamine (AS+SP)
• artesunate-pyronaridine (ASPY) (2022)
NEWER COMBINATIONS
 Arterolane + piperaquine is a combination of a synthetic ozonide and piperaquine phosphate that is
registered in India
 Artemisinin + piperaquine base combines two well-established, well-tolerated compounds. It differs
from previous treatments in that the piperaquine is in the base form, the artemisinin dose is
relatively low, and the current recommendation is for only a 2-day regimen
 Artemisinin + naphthoquine is also a combination of two relatively old compounds that is currently
being promoted as a single-dose regimen
DURATION OF TREATMENT
 A 3-day course of the artemisinin component of ACTs covers two asexual cycles, ensuring that
only a small fraction of parasites remain for clearance by the partner drug, thus reducing the
potential development of resistance to the partner drug
 Shorter courses (1–2 days) are therefore not recommended, as they are less effective, have less
effect on gametocytes and provide less protection for the slowly eliminated partner drug.
Reducing the transmissibility of treated
infection
In low-transmission areas, a single dose of 0.25 mg/kg bw primaquine should
be given with an ACT to patients with P. falciparum malaria (except pregnant
women, infants aged < 6 months and women breastfeeding infants aged < 6
months) to reduce transmission
G6PD testing is not required
Recurrent falciparum malaria
 Recurrence of P. falciparum malaria can result from reinfection or recrudescence
(treatment failure )
 Failure within 28 days - The recommended second-line treatment is an alternative
ACT known to be effective in the region
 Failure after 28 days Recurrence of fever and parasitaemia > 4 weeks after
treatment may be due to either recrudescence or a new infection
CO INFECTED WITH HIV
 Patients co-infected with HIV and uncomplicated P. falciparum malaria,
artesunate + SP is not recommended if they are being treated with co-
trimoxazole
 Artesunate + amodiaquine is not recommended if they are being treated with
efavirenz or zidovudine.
Seasonal malaria chemoprevention
 In areas of seasonal malaria transmission, children belonging to age groups at high risk of severe malaria
should be given antimalarial medicines during peak malaria transmission seasons to reduce disease burden
 The added value of a seasonally targeted intervention is likely to be greatest where transmission is intensely
seasonal
 Monthly cycles of sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) have been widely used for SMC in
African children under 5 years old and have been shown to be efficacious, safe, well tolerated, available and
inexpensive
 3-5 cycles
MALARIA IN PREGNANCY
Malaria in pregnant women is associated with high risks of both maternal and perinatal morbidity and
mortality
 reduced immune response
 less effectively clear malaria infections
 malaria parasites sequester and replicate in the placenta
Intermittent preventive treatment of malaria
in pregnancy (IPTp)
In malaria-endemic areas, pregnant women of all gravidities should be given antimalarial medicine at
predetermined intervals to reduce disease burden in pregnancy and adverse pregnancy and birth
outcomes.
Remark:
• Sulfadoxine-pyrimethamine (SP) has been widely used for malaria chemoprevention during pregnancy
and remains effective in improving key pregnancy outcomes.
• IPTp-SP should start as early as possible in the second trimester and not before week 13 of pregnancy.
• Doses should be given at least one month apart, with the objective of ensuring that at least three doses
are received.
• IPTp is generally highly cost-effective, widely accepted, feasible for delivery and justified by a large body
of evidence generated over several decades.
UNCOMPLICATED MALARIA TREATMENT IN
PREGNANCY
Pregnant women of all gestational ages diagnosed with uncomplicated malaria acquired in areas with
chloroquine-resistant P. falciparum can be treated
 artemether-lumefantrine
 mefloquine
 combination of quinine sulfate and clindamycin
Quinine treatment should continue for seven days for P. falciparum infections acquired in Southeast
Asia and for three days for infections acquired elsewhere; clindamycin treatment should continue for
seven days regardless of where the infection was acquired
Malaria.pptx
RADICAL TREATMENT
 For P. vivax or P. ovale infections, primaquine phosphate and tafenoquine for
radical treatment of hypnozoites should not be given during pregnancy
 Pregnant patients with P. vivax or P. ovale infections should be maintained on
chloroquine chemoprophylaxis for the duration of their pregnancy. The
chemoprophylactic dose of chloroquine phosphate is 300 mg base (500 mg salt)
orally once per week.
 After delivery, for pregnant patients with normal G6PD activity infected with P. vivax or P. ovale
subsequent treatment with primaquine phosphate or tafenoquine
 Tafenoquine is not recommended during breastfeeding.
Malaria.pptx
CONTRAINDICATED
 Doxycycline and tetracycline are generally not indicated for use in pregnant women
 However, in rare instances, doxycycline or tetracycline can be used in combination with quinine if other
treatment options are not available
 Atovaquone-proguanil is not indicated for use in pregnant women
Chemoprophylaxis in pregnant travellers
 Avoid travel to endemic areas
 Travellers to chloroquine sensitive areas –Chloroquine phosphate 500 mgs salt
once a week started 2 weeks before travel and continued for 4 weeks after the
last exposure
 Travellers to chloroquine resistant areas –Mefloquine phosphate 250 mgs salt
once a week started 2 weeks before travel and continued for 4 weeks after the
last exposure
VACCINE IN PREGNANCY
A membrane protein, PfEMP1-P falciparum erythrocyte membrane protein also
called VAR2CSA -antigen has been identified and under evalaution
MALARIA VACCINE
 WHO recommends the RTS,S/AS01 (RTS,S) MOSQUIRIX by GSK malaria
vaccine to prevent malaria in children at risk
 The recommendation for the first malaria vaccine was informed by results
from the ongoing pilot programme in Ghana, Kenya and Malawi
 Four years on for the pilots, nearly 1.5 million children have been
reached with their first dose of malaria vaccine since 2019.
Strong recommendation for , High certainty evidence
The RTS,S/AS01 malaria vaccine should be used for the prevention of P. falciparum malaria in children living in
regions with moderate to high transmission as defined by WHO
• The RTS,S/AS01 malaria vaccine should be provided in a 4-dose schedule in children from 5 months age
• Countries may consider providing the RTS,S/AS01 vaccine seasonally, with a five-dose strategy, in areas with highly
seasonal malaria or with perennial malaria transmission with seasonal peaks
• Countries that choose to introduce the vaccine in a five-dose seasonal strategy are encouraged to document their
experiences, including adverse events following immunization
• RTS,S/AS01 malaria vaccine should be provided as part of a comprehensive malaria control strategy.
Vaccine characteristics, content, dosage, administration and
storage
 RTS,S/AS01 is a pre-erythrocytic recombinant protein vaccine, based on the RTS,S recombinant antigen. It comprises
the hybrid polypeptide RTS, in which regions of the P. falciparum circumsporozoite protein known to induce humoral
(R region) and cellular (T region) immune responses are covalently bound to the hepatitis B virus surface antigen (S)
 After reconstitution, the total volume is 1ml (two doses of 0.5 ml)
 Vial should be discarded within six hours after reconstitution
 The reconstituted 0.5ml vaccine should be administered by injection into the deltoid muscle in children aged 5 months
or older
 The shelf life of the RTS,S/AS01 vaccine is three years
SCHEDULE
 WHO recommends that the first dose of vaccine be administered from 5 months of age
 There should be a minimum interval of four weeks between doses
 The vaccine should be administered in a three-dose primary schedule, with a fourth dose provided
12–18 months after the third dose to prolong the duration of protection
 However, there can be flexibility in the schedule to optimize delivery, for example, to align the
fourth dose with other vaccines given in the second year of life
CO ADMINISTRATION
 RTS,S/AS01 given in conjunction with routine childhood vaccines has been evaluated in several trials
 RTS,S/AS01 can be given concomitantly with any of the following monovalent or combination
vaccines: diphtheria, tetanus, whole cell pertussis, acellular pertussis, hepatitis B, Haemophilus
influenzae type b, oral poliovirus, measles, rubella, yellow fever, rotavirus and pneumococcal
conjugate vaccines
 No co-administration studies have been conducted with RTS,S/AS01 and meningococcus A, typhoid
conjugate, cholera, Japanese encephalitis, Tick-borne encephalitis, rabies, mumps, influenza or
varicella vaccines
Benefits and harms
 There were significant reductions in clinical malaria (51%); and severe malaria (45%), demonstrated
after 12 months' follow-up of the first three doses in the Phase 3 trial
 There were 1774 clinical malaria cases averted per 1000 children vaccinated with four RTS,S/AS01
doses over 46 months' follow-up in the Phase 3 trial
 There were significant reductions in clinical malaria (24%) demonstrated after 7 years’ follow-up
after vaccination among a subset of children in the Phase 3 trial living in areas of moderate to high
transmission; they did not have an excess risk of clinical or severe malaria
 The RTS,S/AS01 vaccine is safe and well tolerated
 There is a small risk of febrile seizures within seven days (mainly within 2–3 days) of vaccination
 As with any vaccine introduction, proper planning and training of staff to conduct appropriate
pharmacovigilance should take place beforehand
NEWER VACCINES
 Two vaccine candidates are approaching late-stage clinical evaluation: the R21/MatrixM vaccine candidate
targeting PfCSP protein and the attenuated whole sporozoite vaccine PfSPZ
 Additional candidates targeting other malaria lifecycle stages include the Rh5 blood-stage vaccine candidate
[148] and Pfs25 and Pfs230 vaccine candidates targeting sexual-stage antigens to prevent human-to-mosquito
transmission (NCT02942277)
 New technologies, such as DNAand mRNA-based vaccines , the ongoing development of adjuvants [150], and
delivery platforms such as virus-like particles (VLPs; the delivery platform used for RTS,S/AS01) and vesicle-
based technologies are being explored for use in malaria vaccines
Thank you
Malaria.pptx

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Malaria.pptx

  • 1. AN UPDATE ON MALARIA Dr A P Naveen Kumar DNB FICP Chief Specialist – General Medicine Visakha Steel General Hospital
  • 2. EPIDEMIOLOGY  Malaria continues to cause unacceptably high levels of disease and death  There were an estimated 247 million cases and 619 000 deaths globally in 2021  Malaria is preventable and treatable  Global priority is to reduce the burden of disease and death while retaining the long-term vision of malaria eradication
  • 3. World Malaria Day 2023 will be marked under the theme “Time to deliver zero malaria invest, innovate, implement” Within this theme, WHO will focus on the third “i” – implement – and notably the critical importance of reaching marginalized populations with the tools and strategies that are available today
  • 5. Parasitological diagnosis  All cases of suspected malaria should have a parasitological test (microscopy or RDT) to confirm the diagnosis  Both microscopy and RDTs should be supported by a quality assurance programme.
  • 6. Light microscopy  Microscopy not only provides a highly sensitive, specific diagnosis of malaria when performed well but also allows quantification of malaria parasites and identification of the infecting species  Light microscopy involves relatively high costs for training and supervision, and the accuracy of diagnosis is strongly dependent on the competence of the microscopist  Microscopy technicians may also contribute to the diagnosis of non-malarial diseases
  • 7. Rapid Diagnosis Tests -RDT  Current tests are based on the detection of histidine-rich protein 2 (HRP2), which is specific for P. falciparum, pan-specific or species-specific Plasmodium lactate dehydrogenase (pLDH) or pan-specific aldolase  The tests have many potential advantages, including: • rapid provision of results and extension of diagnostic services to the lowest-level health facilities • fewer requirements for training and skilled personnel • reinforcement of patient confidence in the diagnosis and in the health service in general.
  • 8. At present, molecular diagnostic tools based on nucleic-acid amplification techniques (e.g. loop-mediated isothermal amplification or polymerase chain reaction [PCR]) do not have a role in the clinical management of malaria PCR can be used to diagnose placental infection in asymptomatic women
  • 10. RECOMMENDATIONS ,BENEFIT AND HARM  Recommendation: Treat adults and children with uncomplicated P. falciparum malaria (including infants, pregnant women in their second and third trimesters and breastfeeding women) with an ACT Desirable effects  • Studies have consistently demonstrated that the six WHO-recommended ACTs result in < 5% PCR- adjusted treatment failures in settings with no resistance to the partner drug (high- quality evidence) Undesirable effects  • Increased cost.
  • 11. Artemisinin-based combination therapy -ACT Children and adults with uncomplicated P. falciparum malaria should be treated with one of the following ACTs* • artemether-lumefantrine (AL) • artesunate-amodiaquine (AS+AQ) • artesunate-mefloquine (ASMQ) • dihydroartemisinin-piperaquine (DHAP) • artesunate + sulfadoxine-pyrimethamine (AS+SP) • artesunate-pyronaridine (ASPY) (2022)
  • 12. NEWER COMBINATIONS  Arterolane + piperaquine is a combination of a synthetic ozonide and piperaquine phosphate that is registered in India  Artemisinin + piperaquine base combines two well-established, well-tolerated compounds. It differs from previous treatments in that the piperaquine is in the base form, the artemisinin dose is relatively low, and the current recommendation is for only a 2-day regimen  Artemisinin + naphthoquine is also a combination of two relatively old compounds that is currently being promoted as a single-dose regimen
  • 13. DURATION OF TREATMENT  A 3-day course of the artemisinin component of ACTs covers two asexual cycles, ensuring that only a small fraction of parasites remain for clearance by the partner drug, thus reducing the potential development of resistance to the partner drug  Shorter courses (1–2 days) are therefore not recommended, as they are less effective, have less effect on gametocytes and provide less protection for the slowly eliminated partner drug.
  • 14. Reducing the transmissibility of treated infection In low-transmission areas, a single dose of 0.25 mg/kg bw primaquine should be given with an ACT to patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months) to reduce transmission G6PD testing is not required
  • 15. Recurrent falciparum malaria  Recurrence of P. falciparum malaria can result from reinfection or recrudescence (treatment failure )  Failure within 28 days - The recommended second-line treatment is an alternative ACT known to be effective in the region  Failure after 28 days Recurrence of fever and parasitaemia > 4 weeks after treatment may be due to either recrudescence or a new infection
  • 16. CO INFECTED WITH HIV  Patients co-infected with HIV and uncomplicated P. falciparum malaria, artesunate + SP is not recommended if they are being treated with co- trimoxazole  Artesunate + amodiaquine is not recommended if they are being treated with efavirenz or zidovudine.
  • 17. Seasonal malaria chemoprevention  In areas of seasonal malaria transmission, children belonging to age groups at high risk of severe malaria should be given antimalarial medicines during peak malaria transmission seasons to reduce disease burden  The added value of a seasonally targeted intervention is likely to be greatest where transmission is intensely seasonal  Monthly cycles of sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) have been widely used for SMC in African children under 5 years old and have been shown to be efficacious, safe, well tolerated, available and inexpensive  3-5 cycles
  • 19. Malaria in pregnant women is associated with high risks of both maternal and perinatal morbidity and mortality  reduced immune response  less effectively clear malaria infections  malaria parasites sequester and replicate in the placenta
  • 20. Intermittent preventive treatment of malaria in pregnancy (IPTp) In malaria-endemic areas, pregnant women of all gravidities should be given antimalarial medicine at predetermined intervals to reduce disease burden in pregnancy and adverse pregnancy and birth outcomes. Remark: • Sulfadoxine-pyrimethamine (SP) has been widely used for malaria chemoprevention during pregnancy and remains effective in improving key pregnancy outcomes. • IPTp-SP should start as early as possible in the second trimester and not before week 13 of pregnancy. • Doses should be given at least one month apart, with the objective of ensuring that at least three doses are received. • IPTp is generally highly cost-effective, widely accepted, feasible for delivery and justified by a large body of evidence generated over several decades.
  • 21. UNCOMPLICATED MALARIA TREATMENT IN PREGNANCY Pregnant women of all gestational ages diagnosed with uncomplicated malaria acquired in areas with chloroquine-resistant P. falciparum can be treated  artemether-lumefantrine  mefloquine  combination of quinine sulfate and clindamycin Quinine treatment should continue for seven days for P. falciparum infections acquired in Southeast Asia and for three days for infections acquired elsewhere; clindamycin treatment should continue for seven days regardless of where the infection was acquired
  • 23. RADICAL TREATMENT  For P. vivax or P. ovale infections, primaquine phosphate and tafenoquine for radical treatment of hypnozoites should not be given during pregnancy  Pregnant patients with P. vivax or P. ovale infections should be maintained on chloroquine chemoprophylaxis for the duration of their pregnancy. The chemoprophylactic dose of chloroquine phosphate is 300 mg base (500 mg salt) orally once per week.
  • 24.  After delivery, for pregnant patients with normal G6PD activity infected with P. vivax or P. ovale subsequent treatment with primaquine phosphate or tafenoquine  Tafenoquine is not recommended during breastfeeding.
  • 26. CONTRAINDICATED  Doxycycline and tetracycline are generally not indicated for use in pregnant women  However, in rare instances, doxycycline or tetracycline can be used in combination with quinine if other treatment options are not available  Atovaquone-proguanil is not indicated for use in pregnant women
  • 27. Chemoprophylaxis in pregnant travellers  Avoid travel to endemic areas  Travellers to chloroquine sensitive areas –Chloroquine phosphate 500 mgs salt once a week started 2 weeks before travel and continued for 4 weeks after the last exposure  Travellers to chloroquine resistant areas –Mefloquine phosphate 250 mgs salt once a week started 2 weeks before travel and continued for 4 weeks after the last exposure
  • 28. VACCINE IN PREGNANCY A membrane protein, PfEMP1-P falciparum erythrocyte membrane protein also called VAR2CSA -antigen has been identified and under evalaution
  • 29. MALARIA VACCINE  WHO recommends the RTS,S/AS01 (RTS,S) MOSQUIRIX by GSK malaria vaccine to prevent malaria in children at risk  The recommendation for the first malaria vaccine was informed by results from the ongoing pilot programme in Ghana, Kenya and Malawi  Four years on for the pilots, nearly 1.5 million children have been reached with their first dose of malaria vaccine since 2019.
  • 30. Strong recommendation for , High certainty evidence The RTS,S/AS01 malaria vaccine should be used for the prevention of P. falciparum malaria in children living in regions with moderate to high transmission as defined by WHO • The RTS,S/AS01 malaria vaccine should be provided in a 4-dose schedule in children from 5 months age • Countries may consider providing the RTS,S/AS01 vaccine seasonally, with a five-dose strategy, in areas with highly seasonal malaria or with perennial malaria transmission with seasonal peaks • Countries that choose to introduce the vaccine in a five-dose seasonal strategy are encouraged to document their experiences, including adverse events following immunization • RTS,S/AS01 malaria vaccine should be provided as part of a comprehensive malaria control strategy.
  • 31. Vaccine characteristics, content, dosage, administration and storage  RTS,S/AS01 is a pre-erythrocytic recombinant protein vaccine, based on the RTS,S recombinant antigen. It comprises the hybrid polypeptide RTS, in which regions of the P. falciparum circumsporozoite protein known to induce humoral (R region) and cellular (T region) immune responses are covalently bound to the hepatitis B virus surface antigen (S)  After reconstitution, the total volume is 1ml (two doses of 0.5 ml)  Vial should be discarded within six hours after reconstitution  The reconstituted 0.5ml vaccine should be administered by injection into the deltoid muscle in children aged 5 months or older  The shelf life of the RTS,S/AS01 vaccine is three years
  • 32. SCHEDULE  WHO recommends that the first dose of vaccine be administered from 5 months of age  There should be a minimum interval of four weeks between doses  The vaccine should be administered in a three-dose primary schedule, with a fourth dose provided 12–18 months after the third dose to prolong the duration of protection  However, there can be flexibility in the schedule to optimize delivery, for example, to align the fourth dose with other vaccines given in the second year of life
  • 33. CO ADMINISTRATION  RTS,S/AS01 given in conjunction with routine childhood vaccines has been evaluated in several trials  RTS,S/AS01 can be given concomitantly with any of the following monovalent or combination vaccines: diphtheria, tetanus, whole cell pertussis, acellular pertussis, hepatitis B, Haemophilus influenzae type b, oral poliovirus, measles, rubella, yellow fever, rotavirus and pneumococcal conjugate vaccines  No co-administration studies have been conducted with RTS,S/AS01 and meningococcus A, typhoid conjugate, cholera, Japanese encephalitis, Tick-borne encephalitis, rabies, mumps, influenza or varicella vaccines
  • 34. Benefits and harms  There were significant reductions in clinical malaria (51%); and severe malaria (45%), demonstrated after 12 months' follow-up of the first three doses in the Phase 3 trial  There were 1774 clinical malaria cases averted per 1000 children vaccinated with four RTS,S/AS01 doses over 46 months' follow-up in the Phase 3 trial  There were significant reductions in clinical malaria (24%) demonstrated after 7 years’ follow-up after vaccination among a subset of children in the Phase 3 trial living in areas of moderate to high transmission; they did not have an excess risk of clinical or severe malaria
  • 35.  The RTS,S/AS01 vaccine is safe and well tolerated  There is a small risk of febrile seizures within seven days (mainly within 2–3 days) of vaccination  As with any vaccine introduction, proper planning and training of staff to conduct appropriate pharmacovigilance should take place beforehand
  • 36. NEWER VACCINES  Two vaccine candidates are approaching late-stage clinical evaluation: the R21/MatrixM vaccine candidate targeting PfCSP protein and the attenuated whole sporozoite vaccine PfSPZ  Additional candidates targeting other malaria lifecycle stages include the Rh5 blood-stage vaccine candidate [148] and Pfs25 and Pfs230 vaccine candidates targeting sexual-stage antigens to prevent human-to-mosquito transmission (NCT02942277)  New technologies, such as DNAand mRNA-based vaccines , the ongoing development of adjuvants [150], and delivery platforms such as virus-like particles (VLPs; the delivery platform used for RTS,S/AS01) and vesicle- based technologies are being explored for use in malaria vaccines