Post on 22-Oct-2020
MALARIA350-500 million cazuri in lume
Protozoarul din genul Plasmodium
MALARIA:
Vector – țânțarul Anopheles
http://en.wikipedia.org/wiki/Plasmodium
lay 50–200 eggs
larvae pupae
Falciparum (malaria tropică, malignă):
- predomină in Africa.
- 50% din toate cazurile de malarie,
- 90% din cazurile de deces
Vivax (malaria benignă terța):
- tropice / sub-tropice (America Latină, Asia, rar in Africa
- 43% din toate cazurile de malarie din lume
Ovale (malaria beningă terța):
- Africa Vest, sub-sahariană
- poate afecta persoanele gr. sangvin Duffy neg
Malariae (malaria benignă quarta):
- în sub-tropice, toată lume
- 7% din toate cazurile de malarie
- poate cauza malaria cronică (portaj la nivel subpirogenic)
Plasmodium knowlesi
• Malaria primatelor (rar afectează
oamenii)
• Asia Sud-Est (Borneo,
Cambodia,Malaysia, Myanmar,
Philippines, Singapore, Thailand)
• absentă in Africa
• Ciclul asexual erytrocitar 24 ore
• Febră zilnică
• Netratată – letalitate înaltă (similar
cu malaria falciparum)
• Microscopic similar cu Pl.malariae,
dar trophozoiții tineri – similar cu
Plasmodium falciparum
• Incubația 10-12 zile
• treatment: chloroquine și
primaquine
http://en.wikipedia.org/wiki/Borneohttp://en.wikipedia.org/wiki/Cambodiahttp://en.wikipedia.org/wiki/Malaysiahttp://en.wikipedia.org/wiki/Myanmarhttp://en.wikipedia.org/wiki/Philippineshttp://en.wikipedia.org/wiki/Singaporehttp://en.wikipedia.org/wiki/Thailandhttp://en.wikipedia.org/wiki/Africahttp://en.wikipedia.org/wiki/Chloroquinehttp://en.wikipedia.org/wiki/Primaquine
Dezvoltarea în țânțar:
Gametocit sporozoit
= 7-10 ≈21 zile
depende de:
1. specia parazitului
2. T0 >160C, optimal 25-300C
3. umeditate
4. altitudine (sub 2000 m)
Dezvoltare în hepatocit (etapa pre-eritrocitară)
Etapa eritrocitară
1. Modificarea structurii, proprietăților biochimice și mecanice ale
eritrocitelor
2. Eliberarea pigmentului malaric (heozoin), toxic p-u organismul uman,
la distrugerea eritrocitelor
3. Eliberarea în exces a citokinelor proinflamatorii TNF-a, IL-1b, IF-g
4. Creșterea permiabilității capilarelor
5. Activează moleculele de adeziune (CD36, ICAM1..) din celulele
endoteliale trigger p-u coagulare și formarea de rozete în malaria
Falciparum
6. Micșorează gluconeogeneza hipoglicemie
7. Afectare multiorganică: ficat, splina, SNC, rinichi, plămâni, cord, GI
(congestie venoasă, edem, depunere de hemozoin, regiuni de
microinfarct, ect)
Etapele patogenetice
The outcome of malaria is determined by
the balance between the pro- and anti-inflammatory cytokines
Confer degrees of protection from severe falciparum:
•α-thalassemia
risk reduced 70% homozygous HbC
risc reduced 90% by heterozygous HbS (sickle-cell trait)
In Duffy blood group neg. (No FyFy antigen) resistance to
vivax = explains the rarity of P. vivax in Africa
Prepatent period = time between sporozoite inoculation & appearance of parasites in blood
~ incubation periods can be prolonged for several months in vivax, ovale, malariae
Stages falcipar vivax ovale malaria
Șizogonie
tisulară6-9 d 8-12 d 10-14 d 15-18 d
Perioada de
incubație7-14 d 12-17 d 16-18 d 18-40 d
nr. merozoiți la
apariția
manifestărilor
clinice
40,000 10,000 15,000 2000
STAGES of the diseases
Perioada prodromală:
manifestări nespecifice
Febră, frison, cefalee,
lombalgii, manifestări GI
Paroxismul malaric clasic
Hepatosplenomegaliesfârșitul 1 săptămâni
Anemie hemolitică
A. FRISON
durata 15 min – 1 oră
Cefalee, mialgii, ↑ Ps, tusea, dispnee, dureri toracale, dureri abdominale,
manifestări GI, ~convulsii
Cauza: distrugerea în masă a eritrocitelor
B. CĂLDURĂ
durata 2-6 ore,
Febra 40C, fatigabilitate, astenie, cefalee
Merozoiții invadează noi eritrocite
C. TRANSPIRAȚII
Durata 2-4 ore,
transpirații profuze, scăderea litică a t0C
Durata totală a paroxismului malaric: 4-8 ore, foarte rar 12 ore
Paroxismul malaric clasic
Periodicitatea paroxismului malaric
= chea spre diagnostic
Plasmodiul î-si sincronizează
șizogonia eritrocitară
eșirea simultană a merozoiților din
eritrocite
șizogonia eritrocitară :
Vivax/ovale = 48h (“tertian” malaria)
Malariar = 72h (“quartan” malaria)
Falciparum = 48h (“sub-tertian” ), dar
nu are loc sincronizarea șizogoniei
Knowlesi = 24h
Malaria cerebrală:
• Glasgow
Indicators of severe malaria and poor prognosis
Manifestation Features
1. Cerebral malaria: Glasgow 30 min
can be after generalized convulsion
2. Severe anemia Ht 10000/µl
3. Renal failure Urine output 3.0 mg/dl) •Sequestration in glomerular capillaries
•Mesangial endothelial cell proliferation
•Immunoglobulin deposits
4. Metabolic / Lactic
acidosis
Metabolic acidosis arterial blood pH
Manifestation Features
5. Pulmonary edema
or ARDS
Breathlessness, bilateral crackles, etc.
pulmonary oedema. Basis: Rx, hypoxemia,
positive end-expiratory pressure
6. Hypoglycemia Blood glucose
11. Impaired
consciousness
not falling into the definition of cerebral malaria. These
patients are generally arousable
12. Prostration Extreme weakness, needs support
13. Hyperparasitemia 5% parasitized RBC or >250 000 parasites/µl (in
nonimmune)
14. Hyperpyrexia Core body temperature above 400C
15. Jaundice Serum bilirubin >43 mmol/l (>2.5 mg/dl).
16. Fluid / electrolyte
disturbances
Dehydration, postural hypotension, clinical hypovolemia
17. Vomiting Pts with persistent vomiting parenteral therapy.
18. Complicating or
associated infections
Aspiration bronchopneumonia, septicemia, urinary tract
infection etc.
19. Other indicators of
poor prognosis
WBC >12,000/cumm; high CSF lactate (>6 mmol/l); low CSF
glucose; AlAt >3xN; low antithrombin III levels; peripheral
schizontemia; papilloedema/retinal oedema
20. Malarial
Retinopathy
Frequent in children, less adults
Indicators of severe malaria and poor prognosis
http://www.malariasite.com/malaria/Hyperparasitemia.htmhttp://www.malariasite.com/malaria/Hyperparasitemia.htmhttp://www.malariasite.com/malaria/Complications8.htmhttp://www.malariasite.com/malaria/Fluid.htmhttp://www.malariasite.com/malaria/secondary_infections.htmhttp://www.malariasite.com/malaria/Complications3.htm
Signs Adults Children
Oncet Part of multi-
organ disease
Suddenly
Cough Uncommon In early stage
Respiratory distress (acidosis) Frequent
Convulsions Rare Frequent
Cerebral malaria Rare Frequent
Anemia Rare Frequent
Hypoglycemia Pregnant, quinine Common
Development of unconsciousness Insidious Rapid
Bleeding/clotting disturbances Up to 10% Rare
Jaundice Frequent Rare
Acute renal failure, hemoglobinuria Frequent Rare
Pulmonary edema, ARDS Frequent Rare
Metabolic acidosis + +
Coma recovery time Slow, 2-4 days Rapid, 1-2 d
Persistent neurological deficits
Tropical splenomegaly syndrome (HIMSS)
Large spleen>1000g
Moderate anaemia
High IgM level
Liver sinusoidal lymphocytosis
Chronic low-grade malarial infection
WHO is recommend:
• parasitological confirmation before treatment is started
• Giemsa stain
rapid diagnostic test (RDT) Antigen Detection Tests for Malaria
Vivax
enlarged RBC
Schüffner's dots
'ameboid' trophozoite
prefer reticulocytes
Ovale
similar to vivax
compact trophozoite
fewer merozoites in schizont
elongated RBC
prefer reticulocytes
Malariae
compact parasite
merozoites in rosette
prefers senescent RBC
Under the microscope, mature P.knowlesi are indistinguishable from
those of P. malariae
Falciparum
numerous rings
smaller rings
no trophozoites or schizonts
cresent-shaped gametocytes
all RBC
Monitoring of parasitaemia every 12h during the first 2–3 days of treatment
response to the antimalarials
RDTs can remain positive for up to 4 weeks after clearance of parasitaemia.
Haematological and biochemical findings in severe malaria
•Normocytic anaemia (⇢Hb
Aims of antimalaria treatment
Aims Causation Drugs class Drugs
Alleviate
sympt.
Blood forms Fast-acting
blood
schizontocide
Slow-acting
blood
schizontocide
choloroquine (+other 4-aminoquinolines)
quinine, quinidine, mefloquine, halofantrine,
antifolates (pyrimethamine, proquanil,
sulfadoxine, dapsone),
artemisinin & its derivatives (artesunate,
artemether, dihydroartemisinin)
doxycycline (+ other tetracycline antibiotics)
Blood + tissue Blood + mild
tissue
schizontocide
proquanil, pyrimethamine, tetracyclines
Prevent
relapses
Hypnozoites Tissue
schizontocide
primaquine
Prevent
spread
Gametocytes Gametocidal primaquine, artemisinin derivatives, 4-
aminoquinolines (limited?)
Sporozoytes Sporontocidal proquanil, pyrimethamine, atovaquone
Never use mefloquine after quinine (may increase myocardial toxicity)
• La administrarea tratamentului antimalaric vor fi
luați în considerație factorii:
– Specia plasmodiumului
– Statutul clinic al pacientului
– Susceptibilitatea la antimalatice:
• regiunea geografică
• Administrarea de antimalarice în scop profilactic
Drug Class Examples
Fast-acting blood
schizontocide
choloroquine (+ other 4-aminoquinolines),
quinine, quinidine, mefloquine, halofantrine,
antifolates (pyrimethamine, proquanil, sulfadoxine, dapsone),
artemisinin derivatives (quinhaosu)
Slow-acting blood
schizontocide
doxycycline (+ other tetracycline antibiotics)
Blood + mild tissue
schizontocide
proquanil, pyrimethamine, tetracyclines
Tissue schizontocide primaquine
Gametocidal primaquine, artemisinin derivatives, 4-aminoquinolines
Combinations Fansidar (pyrimethamine + sulfadoxine), Maloprim (pyrimethamine +
dapsone), Malarone (atovaquone + proquanil)
Tratamentul cazurilor non-complicate de P.Falciparum
Combinarea a ≥2 antimalarice cu diferit mecanism de acțiune
Includerea în tratament a artemisin-ului (ACT) :
Durata 3 zile:
• artemether + lumefantrine (Coartem) ,
• artesunate + amodiaquine,
• artesunate + mefloquine,
• artesunate + sulfadoxine-pyrimethamine,
• dihydrortemisinin + piperaquine.
or
• Atovaquone-proguanil (Malarone)
Antimalarice de linia II:
• artesunate + tetracycline /doxycycline /clindamycin 7 zile;
• quinine + tetracycline /doxycycline /clindamycin
• Mefloquine (Lariam)
1 doză de primaquine la sfârșitul tratamentului = scop: gametocid
Teatment Falciparum malaria severe
Antimalarice timp de ≥24 h:
• Artesunate 2.4 mg/kg IV/IM; la 0ore 12ore 24ore 1/d/zi.
Alternativa:
• Quinine 20mg salt/kg IV (I doză 10mg/kg x la 8 ore lent
rata de infuzie = 5mg/kg/oră); risc de hipoglicemie la gravide
Artemether IM 3.2mg/kg 1.6mg/kg/day
Apoi 3 zile:
– artemether plus lumefantrine,
– artesunate plus amodiaquine,
– dihydroartemisinin plus piperaquine,
– artesunate plus sulfadoxine-pyrimethamine,
– artesunate plus clindamycin or doxycycline,
– quinine plus clindamycin or doxycycline
https://www.malariasite.com/antimalarial-
combinations/
vivax & ovlae
Treatment of malaria in pregnancy
Chloroquine can be used safely in all trimesters of pregnancy.
Artemisinin can be considered if the situation demands.
Quinine can be used in pregnancy, but watchful about hypoglycemia.
Mefloquine contraindicated in the first trimester of pregnancy
Pyrimethamine/ sulphadoxine contraindicated in the first and last trimesters.
Halofantrine, tetracycline, doxycycline absolutely contraindicated
Primaquine contraindicated in pregnancy
Therefore pregnant with P. vivax chloroquine 500 mg weekly as
suppressive chemoprophylaxis against relapse of malaria.
In the I with uncomplicated falciparum quinine + clindamycin for 7 days
and quinine monotherapy if clindamycin is not available.
Artesunate + clindamycin for 7 days if this treatment fails.
Chemoprophylaxishttps://www.cdc.gov/malaria/travelers/country_table/a.html
Primary chemoprophylaxis regimens involve:
a) taking a medicine before travel
b) during travel
c) a period of time after leaving the malaria endemic area
Presumptive antirelapse therapy (terminal prophylaxis). before travel
during
travel
after
leaving
+
Primaquin
Contraindi
cation
Atovaquone/Proguanil
(Malarone)
1-2d 1/day 7d last 1we 1 semester
pregnacy
Mefloquine (> 6 we) 2we 1/we 4we last 2we depression
Doxycycline (up to 6 we) 1-2d 1/day 4we last 2we pregnacy
Chloroquine 1-2we 1/we 4we last 2we
Primaquine 1-2d 1/day 7d - G6PD-
deficiency
Pregnant + P. vivax: chloroquine 500mg weekly = suppressive chemoprophyl.