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General information on G6PD deficiency
Plasmodium vivax malaria & Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency
Partnership for Vivax Elimination
P.vivax Life cycle in Humans
No test for liver
stage of vivax
NB: Some infections may not lead to
hypnozoites; some hypnozoites may not
relapses
S1.1
P. vivax malaria can relapse without a bite from an infected
mosquitoes a bite from an infected mosquito ted mosquito
Many relapses
weeks / months
after first infection
Illness, anemia,
possible
complications
including death
First
infection
Acute malaria
Obstacle to
malaria
elimination
Onward transmission
S1.1
`
`
`
P. vivax has a dormant liver stage which causes relapses
No test for liver
stage of vivax
NB: Some infections may not lead to
hypnozoites; some hypnozoites may not
relapses
Primaquine
(14-days)
[Chloroquine]
(3-days)
S1.1
Any questions?
• P. vivax malaria causes relapse of the malaria disease
• Relapse can lead to anemia, other illnesses and even death
• P. vivax malaria causes most malaria cases in countries / areas close to malaria
elimination
• P. vivax malaria is treated with chloroquine or an ACT to treat the acute malaria
infection and primaquine to prevent relapses
Key points to remember:
S1.1
What is G6PD deficiency?
By the end of this session you should be able to:
- Explain G6PD deficiency and how it affects P. vivax malaria care
S1.2
7
Why is G6PD deficiency important for vivax patients?
 WHO guidelines state that “the G6PD status of patients should be used to guide administration of
primaquine for preventing relapse” of vivax malaria.
 To prevent drug-induced hemolytic anemia it is important to identify a patient’s G6PD status
before prescribing primaquine or tafenoquine for vivax malaria.
 In Myanmar, the treatment for patients infected by P. vivax malaria is Chloroquine (CQ) (3 days)
and Primaquine (PQ) (14 days)
 The dosage for PQ is usually a total dose of 0.25 mg/kg day over 14 days in G6PD normal patients or
eight weeks treatment with a weekly dose in G6PD deficient patients.
Partnership for Vivax Elimination
8
What is G6PD Enzyme and its deficiency
 Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency: An X-linked recessive disorder which
results in the decreased activity of the G6PD enzyme.
 G6PD enzyme protects red blood cells from oxidative stress:
 Leads to decreased synthesis of NADPH (reduced form of nicotinamide adenine dinucleotide
phosphate)& glutathione (antioxidants)
 NADPH helps restore glutathione stores so that glutathione can then reduce reactive oxygen
species (H2O2) to less harmful compounds (H2O).
 The G6PD enzyme plays a critical role in protecting red blood cells (RBCs) from damage
and premature destruction from by-products of normal cell processes as well as external
challenges.
 Many mutations have been identified that cause G6PD deficiency. Some of these mutations disrupt
the normal structure and stability of the enzyme – leading to low levels of G6PD activity inside the
red blood cells – or G6PD deficiency.
Partnership for Vivax Elimination
9
• G6PD Status can be categorized as deficient, intermediate, or normal.
• People can have a mix of red blood cells – some with low G6PD activity and some with high G6PD activity.
If someone has mostly red blood cells with low G6PD activity, they are considered G6PD deficient.
If someone who has mostly blood cells with high G6PD activity, they are considered G6PD normal.
If someone has mixed blood cells, with high and low activity, they are considered G6PD intermediate. Only
females can be considered G6PD intermediate.
G6PD status
10
G6PD
Gender Male Female
Low (deficient) <= 3.9 U/g Hb <= 3.9 U/g Hb
Gender Male Female
Medium (Intermediate) - 4-6 U/g Hb
G6PD status category by gender
Gender Male Female
Normal >= 4 U/g Hb >6 U/g Hb
Any questions?
• The G6PD enzyme helps protect red blood cells from damage
• If people have low or medium G6PD enzyme activity, they are at risk of hemolysis with anti-relapse
treatment
• About 0.5-8.6% of the Myanmar population is estimated having G6PD deficiency – it is important
to identify them before treating with primaquine
Key points to remember:
S1.2
12
G6PD and RBC lifespan
Partnership for Vivax Elimination
What does it mean to have medium or low levels of G6PD?
 G6PD activity level is inherited and affects 400 million people globally
 More than 180 G6PD deficiency genetic variants ranging from mild to severe
 G6PD deficiency is more common in males
 People with low levels of G6PD activity can lead a totally normal life; they only need to
avoid certain medicines and food
G6PD enzyme activity
Normal
Deficient /
low
Normal
Deficient / low
Intermediate /
medium
G6PD enzyme activity
S1.2
14
PQ effect on RBC
 Due to PQ’s oxidant nature, Primaquine metabolites oxidize hemoglobin and generate
reactive oxygen compounds
 leading to depletion of protective Glutathione (Bloom et al., 1983, Summerfield and
Tudhope, 1978) --- lead to a dose related hemolytic anemia.
The severity of hemolysis is determined by
 dose of primaquine
 extent of G6PD-deficiency
 patient's physiological condition (Clyde, 1981, Youngster et al., 2010).
Partnership for Vivax Elimination
15
How G6PD enzyme protect RBC
Partnership for Vivax Elimination
16
PQ treatment effect on RBC among G6PD vivax/mix malaria
cases
Partnership for Vivax Elimination
Risks to patients with medium or low levels of G6PD
 Most people with G6PD deficiency never experience any symptoms unless
exposed to certain foods or medicines
 One serious potential side effect of some drugs taken by patients with low
or medium levels of G6PD activity is Acute Haemolytic Anaemia.
 Haemolysis or Acute Haemolytic Anemia is when red blood cells to rupture
/ burst (haemolysis)
 Red blood cells can be destroyed faster than the body can replace them
(acute hemolytic anemia - AHA)
S1.2
18
G6PD enzyme activity within RBC and risk factors
Partnership for Vivax Elimination
DARK URINE
Hemolysis
Dark urine caused by acute hemolytic anemia
NORMAL URINE
S1.2
20
THANK YOU
Partnership for Vivax Elimination

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2.P.vivax and G6PD_PAVE_25112022_PSI.pptx

  • 1. 1 General information on G6PD deficiency Plasmodium vivax malaria & Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency Partnership for Vivax Elimination
  • 2. P.vivax Life cycle in Humans No test for liver stage of vivax NB: Some infections may not lead to hypnozoites; some hypnozoites may not relapses S1.1
  • 3. P. vivax malaria can relapse without a bite from an infected mosquitoes a bite from an infected mosquito ted mosquito Many relapses weeks / months after first infection Illness, anemia, possible complications including death First infection Acute malaria Obstacle to malaria elimination Onward transmission S1.1 ` ` `
  • 4. P. vivax has a dormant liver stage which causes relapses No test for liver stage of vivax NB: Some infections may not lead to hypnozoites; some hypnozoites may not relapses Primaquine (14-days) [Chloroquine] (3-days) S1.1
  • 5. Any questions? • P. vivax malaria causes relapse of the malaria disease • Relapse can lead to anemia, other illnesses and even death • P. vivax malaria causes most malaria cases in countries / areas close to malaria elimination • P. vivax malaria is treated with chloroquine or an ACT to treat the acute malaria infection and primaquine to prevent relapses Key points to remember: S1.1
  • 6. What is G6PD deficiency? By the end of this session you should be able to: - Explain G6PD deficiency and how it affects P. vivax malaria care S1.2
  • 7. 7 Why is G6PD deficiency important for vivax patients?  WHO guidelines state that “the G6PD status of patients should be used to guide administration of primaquine for preventing relapse” of vivax malaria.  To prevent drug-induced hemolytic anemia it is important to identify a patient’s G6PD status before prescribing primaquine or tafenoquine for vivax malaria.  In Myanmar, the treatment for patients infected by P. vivax malaria is Chloroquine (CQ) (3 days) and Primaquine (PQ) (14 days)  The dosage for PQ is usually a total dose of 0.25 mg/kg day over 14 days in G6PD normal patients or eight weeks treatment with a weekly dose in G6PD deficient patients. Partnership for Vivax Elimination
  • 8. 8 What is G6PD Enzyme and its deficiency  Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency: An X-linked recessive disorder which results in the decreased activity of the G6PD enzyme.  G6PD enzyme protects red blood cells from oxidative stress:  Leads to decreased synthesis of NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)& glutathione (antioxidants)  NADPH helps restore glutathione stores so that glutathione can then reduce reactive oxygen species (H2O2) to less harmful compounds (H2O).  The G6PD enzyme plays a critical role in protecting red blood cells (RBCs) from damage and premature destruction from by-products of normal cell processes as well as external challenges.  Many mutations have been identified that cause G6PD deficiency. Some of these mutations disrupt the normal structure and stability of the enzyme – leading to low levels of G6PD activity inside the red blood cells – or G6PD deficiency. Partnership for Vivax Elimination
  • 9. 9 • G6PD Status can be categorized as deficient, intermediate, or normal. • People can have a mix of red blood cells – some with low G6PD activity and some with high G6PD activity. If someone has mostly red blood cells with low G6PD activity, they are considered G6PD deficient. If someone who has mostly blood cells with high G6PD activity, they are considered G6PD normal. If someone has mixed blood cells, with high and low activity, they are considered G6PD intermediate. Only females can be considered G6PD intermediate. G6PD status
  • 10. 10 G6PD Gender Male Female Low (deficient) <= 3.9 U/g Hb <= 3.9 U/g Hb Gender Male Female Medium (Intermediate) - 4-6 U/g Hb G6PD status category by gender Gender Male Female Normal >= 4 U/g Hb >6 U/g Hb
  • 11. Any questions? • The G6PD enzyme helps protect red blood cells from damage • If people have low or medium G6PD enzyme activity, they are at risk of hemolysis with anti-relapse treatment • About 0.5-8.6% of the Myanmar population is estimated having G6PD deficiency – it is important to identify them before treating with primaquine Key points to remember: S1.2
  • 12. 12 G6PD and RBC lifespan Partnership for Vivax Elimination
  • 13. What does it mean to have medium or low levels of G6PD?  G6PD activity level is inherited and affects 400 million people globally  More than 180 G6PD deficiency genetic variants ranging from mild to severe  G6PD deficiency is more common in males  People with low levels of G6PD activity can lead a totally normal life; they only need to avoid certain medicines and food G6PD enzyme activity Normal Deficient / low Normal Deficient / low Intermediate / medium G6PD enzyme activity S1.2
  • 14. 14 PQ effect on RBC  Due to PQ’s oxidant nature, Primaquine metabolites oxidize hemoglobin and generate reactive oxygen compounds  leading to depletion of protective Glutathione (Bloom et al., 1983, Summerfield and Tudhope, 1978) --- lead to a dose related hemolytic anemia. The severity of hemolysis is determined by  dose of primaquine  extent of G6PD-deficiency  patient's physiological condition (Clyde, 1981, Youngster et al., 2010). Partnership for Vivax Elimination
  • 15. 15 How G6PD enzyme protect RBC Partnership for Vivax Elimination
  • 16. 16 PQ treatment effect on RBC among G6PD vivax/mix malaria cases Partnership for Vivax Elimination
  • 17. Risks to patients with medium or low levels of G6PD  Most people with G6PD deficiency never experience any symptoms unless exposed to certain foods or medicines  One serious potential side effect of some drugs taken by patients with low or medium levels of G6PD activity is Acute Haemolytic Anaemia.  Haemolysis or Acute Haemolytic Anemia is when red blood cells to rupture / burst (haemolysis)  Red blood cells can be destroyed faster than the body can replace them (acute hemolytic anemia - AHA) S1.2
  • 18. 18 G6PD enzyme activity within RBC and risk factors Partnership for Vivax Elimination
  • 19. DARK URINE Hemolysis Dark urine caused by acute hemolytic anemia NORMAL URINE S1.2
  • 20. 20 THANK YOU Partnership for Vivax Elimination

Editor's Notes

  1. Trainers notes: Background - P. vivax is a species of Plasmodium parasite, and one of the dominant species in this region/country. Like all malaria species, P. vivax has a complex life cycle. It infects a mosquito host, where sexual reproduction occurs, and then through, the mosquito infects its human host, where asexual amplification occurs. Slide instructions: Ensure that the graphic is working prior to the training session. Explain each step of the life-cycle clicking through each stage. Plasmodium vivax malaria is a parasitic disease, transmitted by mosquitoes in the genus Anopheles. [CLICK] Once a patient has been infected, an incubation period of approximately 2 weeks occurs as active liver stages develop without symptoms. In humans, the infection consists of both a liver and a blood stage.   [CLICK] It is the subsequent infection of red blood cells that provoke the symptoms of an acute attack of malaria. [CLICK] Some of the liver stage parasites do not immediately develop like that. Instead they become dormant hypnozoites. These parasites are wholly silent and cannot be detected by any diagnostic means. [CLICK] Days, months or even years later, hypnozoites in the liver can awaken and cause a renewed attack of acute malaria called a relapse. If a patient does not receive specific therapy against hypnozoites, they often suffer six or more relapses within the first year. Each one comes with acute illness and opportunity for transmission to the people around them.
  2. Trainers notes: Explain how the life-cycle of p vivax changes the number of p vivax malaria cases participants see in the clinic: Patients can get sick from P vivax by being bitten by an infected mosquito Once they have been bitten, they may get sick and transmit malaria onwards via mosquitoes biting them They might also ‘relapse’ with p vivax again a few weeks or months after their first infection. If a patient relapses it means that the hynozoites ‘sleeping’ in their liver woke up and re-infected the patient. This infection was not spread from a mosquito. Take 5-10 minutes to discuss the potential consequences of vivax malaria for patients and communities. Prompts: What do you think the consequences of relapses are on the patient? How do you think relapses affect malaria in our communities?
  3. Trainers notes Remind participants about the life-cycle of P. vivax that you previously presented. Highlight to participants the stage of the life-cycle that is affected by blood- and liver-stage treatment. Note to participants that the blood-stage treatment (chloroquine/ACT) kills the blood-stage ring that we normally see in the blood slide Primaquine treats the liver-stage of p. vivax. Tell participants that if a patient is cleared of blood-stage parasites but has hynozoites, that we will not be able to detect them as there is no test that can currently do that Note that some infections may not lead to hynozoites being formed, and some hynozoites may not lead to relapse
  4. Trainers note Ensure you highlight the key points of the session. Take time to encourage participants to ask any questions about the session. Let participants know that they can always ask questions of you during breaks or lunch as well.
  5. Trainers notes: Time: 30 minutes Materials: Slide deck Preparation: Ensure that you have located and inserted maps of the distribution of vivax malaria and G6PDd prevalence in your country on the slide ‘Malaria and G6PDd Distribution’
  6. Trainers notes: Ensure you highlight the key points of the session. Take time to encourage participants to ask any questions about the session. Let participants know that they can always ask questions of you during breaks or lunch as well.
  7. Trainers notes: Note to participants that Hemolysis is the destruction of red blood cells.  Hemolysis can occur due to different causes and leads to the release of hemoglobin into the bloodstream. Take 2 minutes to ask participants if they have ever dealt with patients with hemolysis and specifically dark urine caused by hemolysis.