Malaria Flashcards
What is malaria?
Malaria is a mosquito borne-disease Caused by a parasite called plasmodium, which is transmitted via the bites of infected mosquitoes
Malaria parasites infect what organs in the body?
In the human body ,the parasites multiply in the liver, and then infect red blood cells
What is malaria transmitted by?
Transmitted by bite of infected female anopheline mosquito
Where is malaria most common?
Malaria is restricted to areas where these mosquitos can breed
- tropics between 60N and 40S (except areas > 2000m high)
e.g. Africa, India, Far East, S America
Describe the plasmodium phase?
- timespan of plasmodium phase that occurs within mosquito depends on ambient temperature
- lasts 8-30 days
- at temps < 16-18C mosquito does not live long enough for this phase to be completed
Other modes of malaria transmission?
- blood transfusion
- needle accidents
- rarely mother to foetus
Life cycle of malaria infection?
Pathology of malaria?
- Events start with bite of infected anopheles mosquitoes, Sporozoites enter liver in 1 hour infect the parenchymal cell.
- The most pronounced changes related to malaria involve the blood and the blood-forming system, the spleen and the liver.
Importance of red blood cells in malaria pathology?
- Red blood cells are the principal sites of infection in malaria
- All the clinical manifestations are primarily due to the involvement of red blood cells
What are the pathophysiological factors that are involved in the development of severe malaria?
- parasite biomass, malaria toxin(s) and inflammatory response
- cytoadherence, rosetting and sequestration
- altered deformability and fragility of parasitized erythrocytes
Describe the parasite biomass in the pathogenesis of malaria?
P. falciparum has the ability to invade RBCs of all ages, and with repeated cycles of development within the red cells
Describe cytoadherence in the pathogenesis of malaria?
- Structural changes in the infected red cells and the resulting increase in their rigidity and adhesiveness are major contributors
- These RBCs adhere to the capillary and postcapillary venular endothelium in the deep microvasculature
Describe rosetting in the pathogenesis of malaria?
The infected red cells also adhere to the uninfected red cells, resulting in the formation of red cell rosettes
Describe sequestration in the pathogenesis of malaria?
Cytoadherence leads to sequestration of the parasites in various organs
e.g. the heart, lung, brain, liver, kidney, intestines, adipose tissue, subcutaneous tissues, and placenta.
What are the 5 malaria species?
- falciparum
- vivax
- ovale
- malariae
- knowlesi
What types of RBC are infected by falciparum?
Younger cells, but can infect cells of all ages
- Most virulent and predominates in Africa
What types of RBC are infected by vivax and ovale?
Reticulocytes
- Common in central America and Indian subcontinent
- Causes relapsing malaria
What types of RBC are infected by malariae and knowlesi?
older cells
Symptoms of uncomplicated malaria?
First symptoms are non specific:
1. Headache, Lassitude, Fatigue, Abdominal discomfort, muscle and joint aches, diarrhea, nausea, vomiting
2. Followed by fever (irregular at first), chills, rigors, perspiration, anorexia
3. In some cases mild anemia, palpable spleen and slight enlargement of liver are also present
Complications of falciparum malaria?
CHAPLIN
Cerebral malaria/coma
Hypoglycemia
Anemia
Pulmonary edema
Lactic acidosis
Infections
Necrosis of renal tubules (ATN)
Acute complications of malaria?
renal impairment: creatinine > 3mg/dl
jaundice: bilirubin > 43
transaminases: > 3x normal
acidosis: plasma bicarbonate < 15mmo/l
venous lactate: > 5mmo/l
hypoglycaemia: < 2.2 mmol
Severe anaemia
Decreased platelet count
Prolonged INR
Haemoglobinuria
Elevated muscle enzymes( CPK) myoglobin
Risk factors for severe malaria?
- Malawians returning from non-malarious country (>1 year outside)
- Expatriates
- Pregnant women
- Advanced HIV/AIDS individuals not on treatment (take note that acute Malaria increases HIV viral load)
- Splenectomised individuals
Chronic complications of malaria?
- tropical splenomegaly
- quartan malarial nephropathy
What is tropical splenomegaly?
abnormal immunological response to repeated infections – with massive splenomegaly, hepatomegaly
Pathophysiology of tropical splenomegaly?
- uninhibited B cell production of IgM and formation of cryoglobulins (IgM aggregates and immune complexes)
- immunological process stimulates RES hyperplasia and clearance activity and eventually splenomegaly
Clinical features of tropical splenomegaly?
- pts present with abdominal mass or abd pain
- usually some degree of pancytopenia
- often malarial parasites not found in peripheral blood
- pts vulnerable to skin and respiratory sepsis – many die from overwhelming sepsis
Treatment of tropical splenomegaly?
antimalarial chemoprophylaxis, usually good outcome
What is Quartan malarial nephropathy?
Chronic or repeated infections with P malariae, maybe other malarial species
Pathophysiology of quartan malarial nephropathy?
Soluble immune complex deposition and injury to glomeruli
> nephrotic syndrome
Treatment of quartan malarial nephropathy?
Usually responds poorly to Tx
1. antimalarial agents
2. steroids
3. cytotoxics
Malaria in pregnancy in endemic areas?
Infected mothers remain asymptomatic despite intense parasitation of placenta due to sequestration of parasitised erythrocytes in microcirculation
Link between maternal HIV and malaria in pregnancy in endemic areas?
Maternal HIV infection predisposes pregnant women to higher prevalence of malaria and parasite density, and predisposes infants to congenital malaria infection and LBW
Complications of malaria in pregnancy in non-endemic areas?
- Pregnant women predisposed to severe infection
- fetal distress, premature labour, still birth, LBW - common
- Congenital malaria in <5%, directly related to parasite density in maternal blood and placenta
Chemoprophylaxis in malaria?
- Preferably , it should be started 1-2 weeks prior to travel to a malarious area.
- Chemoprophylaxis should continue during the stay in malarious area and for 1-4 weeks after departure from the area.
- Prophylaxis during pregnancy.
Examples of chemoprophylaxis?
- Atovaquone/Proguanil (Malarone) – 1 tablet daily
- Mefloquine 250mg weekly
- Primaquine 200mg daily
- Doxycycline 100mg daily
- Chloroquine 2 tablets weekly
Malaria vaccine?
Commissioned by Glaxosmithkline
Now approved by WHO
In children up to the age of 2 years
Dosage of malaria vaccine?
4 doses – starting from 5 months of age
1. First 3 doses given monthly
2. 4th dose close to the 2nd birthday
3. 5th dose optional in high burden countries
Note: Now trials being conducted for older children
Microscopic examination in the diagnosis of malaria?
- thick smear (quantitative)
- thin smear (qualitative)
Describe the thick smear test?
Thick (quantitative) film detects parasites and parasitemia
- More sensitive
- Can be repeated every 12 hrs for 48 hrs if still suspect malaria
Describe thin smear test?
to determine the malaria species
Malaria detection with rapid diagnostic tests?
- Various test kits are available to detect antigens derived from malaria parasites
- Such immunologic (“immunochromatographic”) tests most often use a dipstick or cassette format, and provide results in 2-15 minutes.
- Good specificity (96.7%) and Sensitivity(91.7%)
Other tests for diagnosis of malaria?
- PCR assay testing
- nucleic acid sequence-based amplification (NASBA)
- They are more sensitive than thick smears but are expensive and unavailable in most developing countries - The quantitative buffy coat (QBC)
- a technique that is as sensitive as thick smears
- Because results cannot be used to speciate Plasmodium, a thin smear must be examined
Tests to do in malaria patients?
- Haematological parameters
- haemoglobin and haematocrit, platelets, WBC, reticulocyte count - LDH
- Liver function test
- Blood glucose
- Coagulation studies
- Screening for G6PD Deficiency
- Renal function tests
- Urinalysis
- Blood culture
- HIV test
Why do we do coagulation studies?
malaria affects the coagulation status
Why do we screen for G6PD in malaria?
to avoid the antimalarials like primaquine that precipitates haemolysis
Why do we do renal function tests?
malaria affects the kidneys either directly or by hypovolaemia caused by vomiting, diarrhoea and fever
Why do we do urinalysis?
to detect haemolysis
Drug classes in malaria treatment?
- quinoline-related compounds
- antifolates
- artemisinin derivatives
- antimicrobials
Why are malaria drugs given in combination?
- No single drug that can eradicate all forms of the parasite’s life cycle has been discovered or manufactured yet
- Therefore, 1 or more classes of drugs often are given at the same time to combat malarial infection synergistically
What are treatment regimens dependent on?
Treatment regimens are dependent on the:
1. geographic location of infection
2. the likely Plasmodium species
3. the severity of disease presentation
Drugs that act on the hepatic stage in malarial infection?
- Atovaquone-proguanil
- Primaquine
- hepatic schizonticides
Drugs that act on the blood stage in malarial infection?
- Atovaquone-proguanil
- Doxycycline
- Mefloquine
- Chloroquine
- Artesunate
- Lumefantrine/Artemether
- Quinine
- Amodiaquine
Treatment of uncomplicated malaria?
Artemesin combination therapy ACT aka LA
1. Artemisin – rapid parasite clearance, 2. Lumefantrine – slow clearance from the system
- Given for uncomplicated malaria BD for 3 days
What to give for treatment failure?
Rx failure within 14 days
- Artemisin Amodiaquine (ASAQ) given OD for 3 days
Treatment for severe malaria?
Artesunate IM or IV – doses time 0, 12 hrs then 24 hours
- If better – switch to LA 8 hrs after last dose of Artesunate and give LA BD for 3 days
- If not eligible for LA – continue Artesunate OD for no more than 6 days
Note: Use Quinine if artesunate is contraindicated or not tolerated
Prophylaxis for malaria in pregnancy?
Intermittent Preventive Therapy (IPT)
– 3 doses of Sulfadoxime Pyrimethamine (SP) given each trimester
Note: If HIV positive and on CPT, no need for SP prophylaxis
Advantages of intermittent preventative therapy for malaria in pregnancy?
- increased birth weight by about 56g
- reduction in Low birth weight infants by about 20%
- reduction in placental parasitemia by 50%
- reduction in maternal parasitemia by 35%
Presentation of malaria in pregnancy?
Presentation is similar to non-pregnant women but Higher risk of:
1. hypoglycemia (especially if on Quinine)
2. anemia
3. pulmonary edema
Treatment for uncomplicated malaria in pregnancy?
LA - Lumefantrine/Artemether
Treatment failure of malaria in pregnancy?
- in 1st trimester - Quinine + Clindamycin for 7 days
- in 2nd and 3rd trimester - ASAQ
Treatment of severe malaria in pregnancy?
Artesunate
