9-Malaria.ppt according to infectious disease

Infectious disease

2. MALARIAMALARIA
Alfiya I. FazulzyanovaAlfiya I. Fazulzyanova, ,
Candidate of Medical SciencesCandidate of Medical Sciences,,
Associate ProfessorAssociate Professor
20212021
Kazan State MedicalKazan State Medical UniversityUniversity
Department of Infectious DiseasesDepartment of Infectious Diseases

3. Course Objectives
Basic understanding of malaria
–Topicality of the problem
–Geographical distribution
–Types of plasmodium
–Life Cycle of Malarial parasite
–Epidemiology
–Clinical feature
–Diagnosis
–Treatment
–Prevention

4. DEFINITION
Malaria is
•A mosquito-borne infectious disease
•Caused by Protozoan parasites of the genus
Plasmodium
•Transmitted only by
Anopheles Mosquitoes
•Characterized by classical
malarial paroxysm, anemia
and hepatospleenomegaly

5. Background
•First recorded mention are from 1500 BC in
China and Egypt;
•Malaria derived from the Italian expression
“mala area” i.e “bad air” associated with
mashes where mosquitos breed;
•First real milestone in the understanding of
malaria was in 1880 by a French Army
Surgeon – Alphonse Laveran – disease
caused by a single cell organism.

6. Background
•He therefore proposed that malaria was caused by
this protozoan, the first time protozoa were identified
as causing disease. For this and later discoveries,
he was awarded the 1907 Nobel Prize for
Physiology or Medicine;

•Shortly after Ronald Ross – Scottish Doctor showed
that mosquito transmitted disease while feeding in
the blood;
•In 1820 Pierre Joseph Pelletier and Joseph
Bienaime Caventou separated the alkaloides
Cinchonine and Kinine (quinine) from powdered
fever tree bark, allowing for the creation of
standardized doses of the active ingredients.

7. Topicality of the problem:
from the epidemiologic point of view:
•Most prevalent disease in the world
–41% of world’s population live in areas where
malaria is transmitted (≈ 2.1 billion);
–200-300 million new cases annually;
(with an estimated 216 million cases of malaria occurred
worldwide in 2016 and 445000 people died, mostly
children in the African Region)

9. Malaria-endemic countries in the Eastern Hemisphere

10. Topicality of the problem
from the clinical point of view:
•Malaria remains a major public health problem, even
though it is both preventable and treatable;

•Up to 30% of outpatient cosultations, up to 20% of
hospital admissions, up to 10-30% of malaria fatality
rate amongst hospitalized malaria patients;
It contributes to poverty; In Africa alone, costs of
illness, treatment, and premature death from malaria
are at least $ 12 billion per year;
•Disability from severe form of disease. Malaria is the
fouth leading cause of death.

11. Topicality of the problem:
from the clinical point of view:
•Most children in malaria endemic areas have first malaria
infection during first two years of life before they acquire clinical
immunity;
•In young children malaria can progress rapidly to severe
malaria and death; 90% of malaria deaths occur in children
under five;
•WHO recommends that all under fives be presumptively
treated with anti-malarial medication within 24 hrs of onset
of fever to prevent severe malaria and death.

12. Plasmodium Species
•P. falciparum
–Most severe and prevalent (40-60% of cases);
It found worldwide in tropical and subtropical areas, and
especially in Africa where this species predominates;
- Infects RBCs of all ages – multiples rapidly in the blood,
and can thus cause severe blood loss (anemia),
- Cаn clog small blood vessels (when this occurs in the brain,
cerebral malaria results, a complication that can be fatal)
–Widespread CHLOROQUINE resistance
ETIOLOGY/1

13. •P. vivax
–It is found mostly in Asia, Latin America, and in some
parts of Africa; 30-40% of cases;
–Liver phase (ability to form “hypnozoites” in the liver, that
can activate and invade the blood (“relapse”) several
months or years after the infecting mosquito bite);
–INFECTS YOUNG RBCs: LESS SEVERE THAN
FALCIPARUM
•P. ovale
–It is found mostly in Africa (especially West Africa) and
the islands of the western Pacific. It is biologically and
morphologically very similar to P. vivax;
–Liver phase (ability to form “hypnozoites” in the liver)
–INFECTS YOUNG RBCs
ETIOLOGY/2

14. ETIOLOGY/3
•P. malariae
–found worldwide;
–is the only human malaria parasite species that has a quartan
cycle (three-day cycle);
–If untreated, P. malariae causes a long-lasting, chronic
infection (can persist SUBCLINICALLY) that in some cases
can last a lifetime. In some chronically infected patients P.
malariae can cause serious complications such as the
nephrotic syndrome.
–INFECTS OLD RBCs
•P. knowlesi
- is found throughout Southeast Asia as a natural pathogen of
long-tailed and pig-tailed macaques. It has recently been
shown to be a significant cause of zoonotic malaria in that
region, particularly in Malaysia.
- has a 24-hour replication cycle and so can rapidly progress
from an uncomplicated to a severe infection; fatal cases have
been reported.

16. Transmission
•Man is the only important
reservoir;
•Vector is female Anopheles mosquito;
–Temperature: below 30º C, above 20º C
–Rainfall: thrive in tropical areas
–Altitude: rarely exist above 2000 meters
–Terrain: coastal areas and lowlands with
lots of freshwater breeding sites

18. Transmission
Transmission is also possible through:

1.1.Blood transfusionBlood transfusion
2.2.Contaminated needleContaminated needle
3.3.Organ transplantOrgan transplant
4.4.CongenitalCongenital

19. Susceptibility

•Universal susceptibility;
- high risk groups:
»Pregnant women
»Children
»Living in non endemic area
»Splenectomy
»AIDS
•No absolute immunity;
–Partial immunity in areas of high endemicity.

20. Plasmodium Life Cycle
The life cycle involves two phases and two
hosts:
•Schizogony (asexual phase)
–occurs in human, intermediate host;
–exo-erythrocytic stage (in liver);
–erythrocytic stage (in blood);
•Sporogony (sexual phase)
–occurs in mosquito gut.

21. Plasmodium Life Cycle
•Exo-erythrocytic (liver) stage:
–is asymptomatic and involves sporozoites, tissue
merozoites and schizonts,
–and in the case of vivax and ovale, hypnozoites;
•Duration:
P. Falciparum 6 days
P. Vivax 8-9 days*
P. Ovale 8-9 days*
P. Malariae 14-16 days
•* hypnozoites after 7-11 months

22. Plasmodium Life Cycle
•Erythrocytic stage (in blood);
–is symptomatic,
–results from the cascade effect of
rupturing RBCs,
–involves the trophozoites, erythrocytic merozoites and
schizonts, and gametocytes;
•Duration:
P. Falciparum 48 hrs
P. Vivax 48 hrs
P. Ovale 48 hrs
P. Malariae 72 hrs

24. •Relapses:
–early (the nearest) – after 2-2.5 months;
–late (remote) – after 7-11 months;

–erythrocytic – P. malaria;
–exo-erythrocytic – P. vivax, P. ovale;
•Duration of invasion:
P. Falciparum 5-7 months (up to 1.5 yr)
P. Vivax 3 yrs (4-6 yrs)
P. Ovale 3 yrs (4-6 yrs)
P. Malariae decades

26. Incubation Period
•P. Falciparum 6-7-8-9-14 days
•P. Vivax 7-14-21 days*
•P. Ovale 14-20 days*
•P. Malariae 18-30-40 days
* May be 8 - 10 months or longer for some strains
(hypnozoites).

27. Clinical features
•Classical cyclic paroxysm:
–Cold stage: lasts 15 minutes to several hours,
symptoms include feeling cold, shivering, and teeth chattering;
skin is pale and cold,
may see cyanosis of the lips and nail beds.

–Hot stage: lasts 2 to 6 hours, fever is up to 40-41º C,
symptoms include severe headache, malaise, myalgia, anorexia,
nausea and vomiting, diarrhea, dry cough, and shortness of breath;
may have delirium, seizures in young children,
–Sweating stage: lasts 2 to 4 hours,
the fever falls rapidly; there is profuse sweating, weakness.
–Afterward, the patient may be exhausted and sleep for hours, but is
much improved. Feel well for period of time, then cycle repeats itself.

28. Presentation
•Fever 96%
•Chills 96%
•Headache 79%
•Muscle Pain 60%
•Palpable liver 33%
•Palpable Spleen 28%
•Nausea or vomiting 23%
•Abdominal pain/diarrhea 6%

29. Complicated Malaria
•Hyperparisitemia: (>3%)
•Hypoglycemia (<60 mg/dl): esp. in pregnant females
•Severe anemia (hct < 21% or rapidly falling hct)
•Renal failure
•Hyponatremia
•Cerebral malaria
•Prolonged hypothermia
•High output vomiting or diarrhea
•Hemoglobinuria
•Pulmonary Edema/ARDS
•Coagulation Abnormalities and Thrombocytopenia
•Cardiovascular collapse and shock

30. •Tropical
splenomegaly in
a patient with
evidence of
hypersplenism
living in a P.
falciparum
endemic area.

31. Diagnosis
•History and Physical exam
- a diagnosis of malaria cannot be confirmed or
excluded clinically;
•Light Microscopy, thick and thin smear
Remains the gold standard for diagnosis
Giemsa stain
distinguishes between species and life cycle stages
parasitemia is quantifiable
Threshold of detection: thin film - 100 parasites/
thick film: 5 -20 parasites/
•Malaria antigen rapid diagnostic test (RDT,
antigen capture techniques, OptiMal test)
- detects plasmodium lactate dehydrogenase
(pLDH) which is species specific;

32. Diagnosis
•PCR tests are also available for detecting
malaria parasites:
- Although these tests are more sensitive than
routine microscopy, results are not usually available
as quickly as microscopy results should be, thus
limiting the utility of this test for acute diagnosis;
- PCR testing is most useful for definitively identifying
the species of malaria parasite and detecting mixed
infections (pecies confirmation by PCR is available at the
CDC malaria laboratory);
•CBC
Anemia
Leukopenia, or leukocytosis
No eosinophilia

38. Plasmodium falciparum

40. Plasmodium vivax

42. Plasmodium ovale

44. Plasmodium malariae

45. Optimal Treatment Approach
•Rapid case identification;
•Rapid PARASITOLOGICAL classification;
•Rapid initiation of therapy:
treatment should be guided by three main
factors:
- the infecting
 
Plasmodium
 species
;
- the clinical status of the patient (+ supportive
care);
- the drug susceptibility of the infecting parasites
as determined by the geographic area where the
infection was acquired and the previous use of
antimalarial medicines;

46. Treatment
Antimalarial Medications
can be classified in many ways:
•Biological activity
–Tissue Stage Schizonticides
•Liver schizonts and hypnozoites
–Blood Stage Schizontocides
•Interrupt RBC schizogony
–Gametocytocides
–Sporontocides
•Their use
–prophylaxis
–acute treatment
–Standby
•Chemical structure

47. Treatment
CHLOROQUINE sensitive infections:
•Description Inhibits parasite growth by concentrating within acid
vesicles of the parasite and increasing its internal pH. In addition,
inhibits hemoglobin utilization and metabolism by the parasite.
•Adult Dose 600 mg base (=1,000 mg salt) PO immediately,
followed by 300 mg base (=500 mg salt)
PO at 6, 24, and 48 h
Total dose: 1,500 mg base (=2,500 mg salt).
•Precautions Sodium channel blocking activity may increase
toxicity of type Ia antidysrhythmic drugs or others with quinidinelike effects;
ECG should be checked to monitor increased QRS interval effect

49. Treatment
For P. falciparum (or Species Not Identified) acquired
in areas without chloroquine-resistant strains, which
include Central America west of the Panama Canal,
Haiti, the Dominican Republic, and most of the Middle
East, patients can be treated with oral chloroquine;
-A chloroquine dose of 600 mg base (= 1,000 mg salt) should be given
initially, followed by 300 mg base (= 500 mg salt) at 6, 24, and 48 hours
after the initial dose for a total chloroquine dose of 1,500 mg base (=2,500
mg salt);
- Alternatively, hydroxychloroquine may be used at a dose of 620 mg
base (=800 mg salt) po given initially, followed by 310 mg base (=400 mg
salt) po at 6, 24, and 48 hours after the initial dose for a total
hydroxychloroquine dose of 1,550 mg base (=2,000 mg salt).

50. Treatment
For P. falciparum infections acquired in areas with chloroquine
resistance, four treatment options are available:
artemisinin-based combination therapies (ACTs), artemether-
lumefantrine (Coatrem);
atovaquone-proguanil (Malarone); or artemether-lumefantrine
(Coartem);
quinine sulfate plus doxycycline, tetracycline, or clindamycin
(Quinine treatment should continue for 7 days for infections acquired in
Southeast Asia and for 3 days for infections acquired in Africa or South
America);
mefloquine (is associated with rare but potentially severe neuropsychiatric
reactions when used at treatment doses, recommended only when the
other options cannot be used)

51. Treatment
•VIVAX and OVALE therapy should include PRIMAQUINE
15mg PO QD x 14 days
•CDC now recommends:
PRIMAQUINE 30mg PO QD x 14 days
- Because primaquine can cause hemolytic anemia in persons with
glucose-6-phosphate-dehydrogenase (G6PD) deficiency, persons
must be screened for G6PD deficiency prior to starting primaquine
treatment. For persons with borderline G6PD deficiency or as an
alternate to the above regimen, primaquine may be given at the dose
of 45 mg (base) orally one time per week for 8 weeks;
•the WHO recommends adding a single, low primaquine dose of
0.25 mg/kg to full artemether-lumefantrine treatment to
patients with P. falciparum malaria to further reduce malaria
transmission (also effective against mature gametocytes)

52. CHEMOPROPHYLAXIS
•Chemoprophylaxis is recommended for
travellers, migrant labourers and military
personnel exposed to malaria in highly
endemic areas.

53. RECOMMENDED READINGS
Malaria in India. Guidelines for its control. National Vector Borne
Disease Control Programme.
http://www.nvbdcp.gov.in/malaria-new.html
National drug policy on malaria (2013). Ministry of Health and Family
Welfare/Directorate of National Vector Borne Disease
Control Programme, Govt. of India.
http://www.nvbdcp.gov.in
WHO Guidelines for the treatment of malaria, second edition.
Geneva: World Health Organization (2010).
http://www.who.int/ malaria/publications/atoz/
9789241547925/enindex.html

54. Thank youThank you