Malaria( introduction, treatment an complications of malaria)

A Detailed PPT on Malaria

1. Malaria Theresa Obiananma- Chukwuma .

2. OUTLINE . Introduction Definition Risk factors Mode of transmission Pathophysiology Clinical features Acute uncomplicated malaria Severe malaria -Definition -case management -treatment

3. Treatment Practical concept . Real case management Take home . Ctd . . .

4. Introduction Malaria is an acute febrile illness caused by Plasmodium parasites which are spread through the bite of infected female Anopheles mosquito. It is a life-threatening disease, is preventable and curable.

5. Ctd … In 2020, the WHO African region was home to 95% of malaria cases and 96% of malaria deaths. Children under 5 accounted for an estimated 80% 0f all malaria deaths in the region. In Nigeria, Malaria is endemic i.e. the diseases is widespread in the country (native to Nigeria); and under-five mortality from Malaria in the country is high.

6. Introduction ctd … Human malaria is caused by one or more of four parasites: Plasmodium falciparum, P vivax, P ovale and P malariae . Distribution of these parasites vary geographically and not all species of malaria are transmitted in all malarious areas. P falciparum is the species most commonly associated with life-threatening malaria, and it is transmitted at some level in nearly all areas where malaria occurs.

7. Ctd … P falciparum accounts for over 90% of all malaria infections in sub-Saharan Africa while Vivax malaria is the most predominant species in the Indian subcontinent, central America and South America. A unique feature of P vivax and ovale is the presence of hypnozoites during their life cycle, that can persist in the liver for months to years, causing periodic relapses of peripheral parasitemia and illness

8. Risk factors for severe disease Some population groups are at considerably higher risk of contracting malaria and developing severe disease. This would include: Infants and under-fives Pregnant women Patients with HIV/AIDS People with low immunity from nonendemic malaria zones During pregnancy, malaria can be a cause of significant maternal morbidity, as well as fetal/ infant morbidity and mortality.

9. Mode of infection & transmission Malaria is typically transmitted by: The bite of an infective female Anopheles mosquito Transplacental transmission (congenital malaria) Blood transfusion Needle sharing Organ donation

10. Malaria immunity In general, immunity to malaria is acquired after repeated exposure to the malaria parasite; individuals who survive their initial infections develop some degree of immunity. In highly endemic regions the greatest prevalence of uncomplicated as well as severe malaria occurs in children less than 5 years, whose immunity is not fully developed

11. Ctd … Immunity in malaria involves: decreasing prevalence with increasing age (in endemic areas) development of tolerance for the presence of malaria parasites in the blood with minimum symptoms relative protection from severe illness The overall level of immunity to malaria is highest in areas where transmission is the most intense

12. Ctd … In endemic areas, children younger than 5 years of age have repeated and often serious attacks of malaria. Survivors develop partial immunity Thus, older children and adults often have asymptomatic parasitemia Most deaths from malaria occur in children younger that 5 years

13. Malaria illness The average incubation period from infective mosquito bite to onset of symptoms is 9 - 30 days or longer, depending on: The species of the parasite Immune status Infecting dose And the use of antimalarial drugs

14. Pathophysiology Asexual forms of the parasites called sporozoites are introduced into the bloodstream by the bite of an infected mosquito Sporozoites enter into the hepatocytes and undergo maturation and multiplication This phase, called pre-erythrocytic schizogony, lasts for about 6 – 16 days, and gives rise to thousands of merozoites that are released into the bloodstream During this time, there are no symptoms

15. Ctd … The merozoites enter into the erythrocytes, undergo further asexual maturation called erythrocytic schizogony, and some differentiate into sexual forms. After maturation, rupture of the erythrocytes occur releasing merozoites into the bloodstream, and invasion of more erythrocytes Rupture of red blood cells also results in the release of malaria toxins into the circulation

16. Ctd …. These toxins activate peripheral mononuclear cells which stimulate the release of cytokines. It is believed that the balance between pro-inflammatory and anti-inflammatory cytokines, chemokines, growth factors, and effector molecules determines disease severity. Cytokines implicated include IL-1B, IL-6, IL-8, TNF, and IL-10, but their role remains unclear. Alterations in retinoids also occur in malaria

17. Clinical features Two main patterns of clinical presentation: 1- uncomplicated malaria 2- severe malaria

18. Acute uncomplicated malaria Fever (mostly high grade) Headache Vomiting Anorexia Chills Myalgia Diarrhea Jaundice / cough

19. Severe malaria Severe malaria typically results from delayed treatment of uncomplicated malaria. It is characterized by clinical or laboratory evidence of vital organ dysfunction.

20. Definition Severe malaria is a life threatening disease, characterized by the presence of one or more of the following, occurring in the absence of an identified alternative cause, and in the presence of P. falciparum asexual parasitemia. Impaired consciousness : GCS <11 or BCS < 3 in children (common) Acidosis : base deficit of >8mEq/L (common) plasma bicarbonate of <15mM/L venous plasma lactate of >5mM/L severe acidosis manifesting as respiratory distress- rapid, deep and laboured breathing

21. Ctd … Hypoglycemia : blood plasma glucose <2.2mM (<40mg/dl) Hyperparasitemia : > 20% in any epidemiological context > 100,000/ uL (2.5% parasitemia) Severe malarial anemia : Hb conc < 5g/dl or Hct <15% in children < 12 yrs OR Hb conc < 7g/dl or Hct <20% in adults PLUS Parasite >10,000/ uL

22. Ctd … Renal impairment (acute kidney injury): Plasma or serum creatinine >265uM (3mg/dl) or blood urea >20mM (common in adults esp non-immune) Jaundice : plasma or serum bilirubin >50µM (3mg/dl) together with a parasite count >100,000/µL Pulmonary edema : radiologically confirmed OR Oxygen sat <92% on room air with RR >30/min; often with chest in-drawing and crepitations on auscultation (uncommon)

23. Ctd …. Significant bleeding : including recurrent or prolonged bleeding from nose gums or vein puncture sites; hematemesis or melaena (up to 10% in adults) Shock : Compensated: impaired perfusion (temp gradient on leg or CR ≥ 3 secs) but NO hypotension Decompensated: Syst BP < 70mmHg in children or 80mmHg in adults with evidence of impaired perfusion

24. Ctd … Seizures : multiple convulsions in a day (common) i.e. more than 2 episodes within 24h Prostration / obtundation (common) generalized weakness so that the patient is able to sit, stand or walk unsupported

25. Case management “The most important element in the clinical diagnosis of malaria is a high index of suspicion ” –WHO WHO recommends that all suspected cases of malaria should be confirmed using parasite-based diagnostic testing through either: Microscopy Rapid diagnostic test The gold standard is microscopy

26. Treatment: severe malaria Parenteral antimalarial agents should be given for a minimum of 24h, even if the patient can tolerate oral medications earlier. Parenteral artesunate is the recommended treatment for severe malaria;

27. Dosing Artesunate 2.4mg/kg body weight; IV or IM at time of admission (time = 0), then 12h and 24 h Then once a day until the patient is able to take oral medications Children weighing <20kg should receive a higher dose of Artesunate 3mg /kg/dose

28. Alternative treatment If parenteral Artesunate is unavailable, use Artemether in preference to Quinine for severe malaria Artemether : 3.2mg/kg IM at admission Then 1.6mg/kg /day Quinine : Quinine hydrochloride 20mg /kg (loading dose) at admission Then 10mg/kg 8 hrly

29. Follow-on treatment Treatment should be completed by giving a full course of effective WHO recommended, artemisinin-based combination therapy (ACT) as soon as the patient is able to take oral medications) but not before the minimum 24h of parenteral treatment) Add a single dose of Primaquine in areas of low transmission. Artemether-Lumefantrine Artesunate / Amodiaquine Artesunate-Mefloquine Artesunate + Sulfadoxine -Pyrimethamine Dihydroartemisinin -Piperaquine

30. Antibiotics ANTIBIOTICS ARE NOT USED TO TREAT MALARIA It is however important to note the considerable clinical overlap between sepsis, pneumonia and severe malaria, and these conditions may overlap. It is also often impossible to rule out sepsis in a severely ill child who is in shock or obtunded So whenever possible, blood cultures should be taken on admission

31. Ctd … Thus, children with suspected severe malaria and associated alterations in level of consciousness, or other features of sepsis should be started on broad spectrum antibiotics immediately, together with antimalarial treatment. And treatment should be completed unless a bacterial infection is excluded

32. Practical concepts Overtreatment: RDT false positive tests Microscopy and timing Substandard treatment in peripheral centers

33. Real life example A 52 year old Australian woman, Stephenie Rodriguez, had both feet amputated after contracting malaria in Nigeria. She was attending some programs in Nigeria, including the Hive Africa Global Leadership Program conference in Lagos in September 2019, where she was the key note speaker.

34. Ctd …. During the trip in Nigeria, a gathering of travel executives had invited her for a photo shoot next to a pool of stagnant water She subsequently contracted cerebral malaria, diagnosed in Boston where she fell into coma. It so happened that Artesunate sent her into septic shock and organ failure. The doctors gave her a 2% chance of survival

35. Ctd … She battled for her life for 18 months As a last attempt to save her life, vasopressors were administered to redirect blood flow form the limbs (extremities) to her vital organs The drugs caused her feet and hands to darken from necrosis, and at one point, she witnessed her own toe fall into her hand Stephenie had 36 surgeries to amputate and replace her feet

36. Take home message

37. Thank you