Yuankai Wu
Department of infectious diseases The Third Affiliated Hospital
Malaria
a vector-borne disease caused by single celled parasites, the Plasmodium protozoa, and transmitted by female Anopheles mosquitoes. Characterized by malarial paroxysm of chills, fever and sweats.
Still an enormous pubic health problem and one of the most common infectious diseases.
History of malaria
Malaria has infected humans for over 50,000 years. first recorded in 2700 BC in China. originates from Medieval Italian: mala aria "bad air"; was formerly called ague or marsh fever due to its association with swamps and marshland
History of malaria
1880, a French army doctor first observed parasites in patients RBC. the 1907 Nobel Prize for Physiology or Medicine.
1898, Britain's Sir Ronald Ross finally proved that malaria is transmitted by mosquito.(1902 Nobel Prize)
Charles Louis Alphonse Laveran MullerSwiss chemist, discovered DDT to kill mosquito in 1930 (1984 Noble) WagnerAustrian psychiatristused the high fever of malaria to treat dementia in stage-III syphilis(1927 Nobel)
Malaria
1. Etiology (life cycle) 2. Epidemiology 3. Pathogenesis and pathology 4. Clinical manifestation 5. Diagnosis 6. Differential diagnosis 7. Therapy 8. Prevention 9. Summary
Etiology
Plasmodium protozoa
P. falciparum (the deadliest); P. malariae ; P. ovale ; P. vivax (the most common);
Life cycle
Sexual cycle in mosquito
Gametocyte, gamete, zygote, ookinete, oocyst, sporoblast,
sporozoite
Erythrocytic stage:
ring form, trophozoite, schizont, gametocyte
Ring form
Trophozoite
Schizonte
Gametocyte
Sporozoite
Tachysporozoite Bradysporozoite
Merozoite
Release merozoites
Release merozoites
Fertilization
Epidemiology
Source of infection
Patients Asymptomatic carriers
Epidemiology
Route of transmission
Bite by female anopheles mosquitoes.
Vertical transmission (placenta) Blood transfusion
Epidemiology
Susceptibility
All susceptible Travelers and foreigner
Epidemiology
Epidemiological feature
Seasons: Summer and Autumn (temperature)
In china, P. vivax is predominant, P. falciparum second, P. malariae and P. ovale seldem. Endemic areas: tropic or sub-tropic area.
Death (/10,000)
Year
Pathogenesis
Toxic mediators Inflammatory responses
metabolic disturbances Chill, fever, sweat
hypoglycaemia
Anemia Hemolysis
Cerebral malaria
Pulmonary edema Impaired microcirculation DIC
Clinical manifestation
Incubation period: 7~30d (7~12, 13~15, 24~30) Malaria paroxysm: chills, fever and sweating. Periodicity: every 48h (P. vivax, P. ovale) every 72h (P. malariae) every 36-48h (P. falciparum) Between attacks: feel fine (P. vivax, ovale or malariae) or miserable (P. falciparum)
40 39
38 37 1 2 3 4 5 6 7 8 9 10 11 12 13
synchronization
Days
Intermittent fever
Cerebral malaria:
Neurologic sign: hyper-reflexion and bilateral Babinskis sign. Focal neurologic finding occurs rarely.
Infected RBC
P. falciparum: RBCs of any age. P. vivax and P. ovale: younger RBCs. P. malariae: older RBCs.
Multiply speed
P. falciparum: 36-48h P. vivax and P. ovale: 48h P. malariae: 72h
Relapse:
hypnozoites in the hepatocytes. only found in P. vivax and P. ovale. usually 3~6mon after cured.
Complications
Hemolytic urinemic syndrome (black water fever) Pulmonary edema. Hyperreactive malarial splenomegaly. Shock, hypotension. Diarrhoea, jaundice, splenic rupture. Anemia, hemorrhage, DIC. Hypoglycaemia, metabolic acidosis.
Complications
Hemolytic urinemic syndrome
More common in adults, rare in children. More frequent in patients without immunity and with high parasitemia and G6PD deficiency after quinine or primaquine. Intravascular hemolysis, hemoglobinuria. Lumbago, dark urine(black water), jaundice, oliguria, renal failure.
Complications
Hemolytic urinemia syndrome(black water fever). Pulmonary edema. Hyperreactive malarial splenomegaly. Shock, hypotension. Diarrhoea, jaundice, splenic rupture. Anemia, hemorrhage, DIC. Hypoglycaemia, metabolic acidosis.
Complications
Pulmonary edema
Uncommon, even in severe infection. Patients with hyperparasitemia. Results from capillary leak rather than heart failure. A fatal complication. Treated with positive-pressure artificial ventilation.
Complications
Hemolytic urinemia syndrome(black water fever). Pulmonary edema. Hyperreactive malarial splenomegaly. Shock, hypotension. Diarrhoea, jaundice, splenic rupture. Anemia, hemorrhage, DIC. Hypoglycaemia, metabolic acidosis.
Complications
Hyperreactive malarial splenomegaly
Tropical splenomegaly syndrome (TSS). Seen in older children and adults. Associated with repeated infection In hyperendemic area. Anemia, massive splenomegaly, elevated IgM levels and malarial antibody. Usually responds to prolonged treatment with prophylactic antimalarial drugs.
Complications
Hemolytic urinemia syndrome(black water fever). Pulmonary edema. Hyperreactive malarial splenomegaly. Shock, hypotension. Diarrhoea, splenic rupture. Hemorrhage, DIC. Hypoglycaemia, metabolic acidosis.
Diagnosis
Epidemiological history
Traveled in endemic areas (bitten by a mosquito)
Blood transfusion or organ transplantion
Clinical manifestation
Typical malaria paroxysm Intermittent fever, Several small fever spikes
Pathogenic detection
Thick and thin film
Diagnosis
Pathogenic Investigations
Microscopic diagnosis
Diagnosis
Microscopic diagnosis
Diagnosis
Pathogenic Investigations
Microscopic diagnosis
Quantitative buffy coat(QBC)
Differential diagnosis
Infectious diseases Influenza Sepsis Typoid, paratypoid fever Leptosirosis Dengue fever Japanese B encephalitis toxic dysentery Hemorrhagic fever with renal failure Acute intravascular hemolysis
Non-infectious diseases Lymphoma, leukaemia Malignant histocytosis Connective tissue diseases
Prognosis
Curable if treated in early stage. Chronic malaria in hyperendemic areas. Kill up to 15%~20% children<5y in Africa.
Treatment
Symptomatic and supportive measures
Relief of high fever Intravenous injection to sustain fluid balance Treatment hypoglycemia Dehydration in cerebral malaria Blood transfusion for severe anemia Hemodialysis when renal failure
Antimalarial treatments.
Antimalarial Treatment
Tissue schizonticides (causal prophylaxis)
Pyrimethamine and Primaquine
Antimalarial strategy
Chloroquine Blood schizonticides
Artimesinine, Artesunate
Primaquine Tafenoquine
Available drugs
Quinine
0.65g tid7d Seldom used now
The first effective treatment for malaria came from the bark of cinchona tree, which contains quinine.
Available drugs
Chloroquine (phosphate)
Most common used
1.0 po., 0.5 po.6~8h later on the first day 0.5 po. Qd on the second and third day
Available drugs
Artemisinine and Artesunate
Powerful and less resistant Artemisinine
1.0 po., 0.5 po.6~8h later on the first day 0.5 po. Qd on the second and third day
Artesunate
100mg bid1d50mg bid4d
Available drugs
Primaquine (phosphate)
Most commonly used Gametocide Prevent relapse and block transmission
7.5mg tid 8d
Cerebral malaria
Artesunate
60mg iv. drip, at 0, 4, 24, 48hr 50mg bid 2~3d
Chloroquine
16mg/kg8mg/kg conscious po.
Quinine
500mg q12h conscious po.
Caution
Repeat the thick and thin blood smear Do not use Doxycycline, Primaquine, Mefloquine, Atovaquone-proguanil in Pregnant women. Routine G6PD test?
Prevention
Control the source of transmission Cut off the route of transmission
Prevention
Source of transmission
Cases management
Cure the patients and carriers use gametocides and blood schizonticides simultaneously. Chloroquine / artemisinine / artesunate and primaquine / tafenoquine
Prevention
Route of transmission
Vector control
Kill anopheles mosquitoes: insecticide spraying
Avoid multiply of mosquitoes:
Personal protection
Mosquito nets Repellents
Long clothes
Prevention
Protection of susceptible population
Active prophylaxis
Vaccine
Under development
Passive prophylaxis
Chemoprophylxis
Chloroquine (sensitive, pregnant women or children) Mefloquine, Doxycycline, Pyrimethamine.
summary
Malaria is a vector-borne parasitic disease caused by plasmodium protozoa All the four species plasmodium need anopheles mosquitoes and human to complete its life cycle. Transmitted by a bite of anopheles mosquito. Characterized by the malaria paroxysm (chill, high fever,and sweats) The thick film and thin film can diagnose a malaria. Use the blood schizonticides and gametocides simultaneously to kill the parasite. Prevention refers to the cases management, vector control, personal protection, vaccine and chemoprophylaxis. Malaria is still a enomous public health problem world wide.
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Species Periodicity
P.malariae Quartan
Typical
Yes
P. falciparum Irregular/tertian
Intermittent irregular
Yes
Tertian
Typical
Yes
Attacks
Recrudesce nce Relapse Complicati ons
Yes Rare
Yes Rare
Useful Links
Centers for Disease Control and Preventionhttp://www.cdc.gov/ Global Fund to Fight AIDS, TB and Malariahttp://www.who.int/malaria/ Global Health Advocates Innovative Vector Control Consortium Lubombo Spatial Development Initiative Malaria Foundation International Malaria Journal Malaria Vaccine Initiative Medical Research Council Medicines for Malaria Venture Multilateral Initiative on Malaria Nature Medicine (Malaria) President's Malaria Initiative Roll Back Malaria Partnership South Africa Department of Health (Malaria) East and Southern African Malaria Control UNICEF World Health Organisation World Bank