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Malaria (Definition (parasitic infection caused by protozoa of genus…
Malaria
Definition
parasitic infection caused by protozoa of genus Plasmodium
5 species - plasmodium falciparum - most life threatening
- naturally transmitted to humans through bite by infected Anopheles mosquito
- potentially transmitted by blood transfusion or organ transplantation
- widely distributed throughout tropical and subtropical regions -
Epidemiology: 96 countries - endemic
- 3.4 billion people at risk - estimated 214 million malaria cases in 2015 --> 438, 000 deaths
- pregnant women and children under 5 years remain most susceptible to disease in endemic areas
- most common tropical disease in UK
- 1 mill deaths
- preg - 25% severe maternal anaemia (10-20% low birth weight, 5-10% neonatal and infant death)
- affected of countries- near equator (high humidity)
Risk factors:
- poor - 60% of deaths from malaria occur in poorest 20% of population - lack of access to effective Tx
- young children and infants
- pregnant women
- elderly people
- non-immune people (travellers, foreign workers)
- travel to areas of high humidity and ambient temperature b/w 20-30degrees celcius
- travel at times of high seasonal rainfall
- visits to rural locations - African villages
- staying in cheap backpacker accommodation
- being outdoors b/w dusk and dawn
- longer durations of travel
Genetic factors protecting against Malaria:
- SCA - removed by spleen before development of schizonts
- ovalocytosis - RBCs - rigid - resist parasitic infection
- duffy blood group -ve - duffy blood group Ag - receptor for attachment of merozoites of Vivax
- newborn infants - natural protection for 1st few monts of life - high conc of HbF
- beta thalassaemia - protects against severe falciparum infection
Signs and Symptoms:
Fever, often recurring
Chills
Rigors
Headache
Cough
Myalgia
Gastrointestinal upset
anemia (destruction of red blood cells by malarial parasite + decerased production of RBCs in bone marrow)
Signs
Fever
Splenomegaly
Hepatomegaly
Jaundice
+/- abdominal tendernessSigns of severe disease (usually P. falciparum)
Impaired consciousness.
Shortness of breath.
Bleeding.
Fits.
Hypovolaemia.
Hypoglycaemia.
Acute kidney injury.
Nephrotic syndrome.
Acute respiratory distress syndrome (during treatment).
- red blood cells containing harmful protozoa adhere to cerebral blood vessels --> cuts of supply of o2 and nutrients to these blood vessels
Clincal Course:
- asymptomatic parasitaemia - older children and adults (natural immunity living in endemic areas)
- acute uncomplicated malaria
- any age - some degree of immunity
- ill, no life threatening symptoms
- fever - constant symptom
- characteristic paroxysms - coincide with release of merozoites from lysed RBCS --> fever, chills and rigors (release of cytokines)
-- cold stage (rigors)
-- hot stage (high temp, body and joint pains, vomiting and diarrhea)
-- perspiration stage (fall in temp)
- vomiting
- diarrhea
- convulsions
- jaundice --> hemolysis
- anorexia, cough, malaise, splenomegaly, tender hepatomegaly
- severe malaria
- Cerebral malaria - life-threatening form of encephalopathy - common characteristic of type of malaria caused by Plasmodium Falciparum - 20-50% of people with malaria
- ataxia, monoparesis, cortical blindness, aphasia/dysarthria, hearing impairment, cortical defects
- hypoglycaemia
- metabolic acidosis
- acute RF
- Pul edema
- circulatory shock
- blackwater fever -reduced perfusion, acute tubular necrosis, early dialysis (peritoneal), continue quinine
- previously infected, non immune adults with severe falciparum malaria and complication of quinine therapy
- massive hemoyisis --> haemoglobinuria (black urine)
Pernicious Malaria:
- refers to series of phenomena - occurring in falciparum (1-3 days)
- children and non immune adults --> coma and death (cerebral malaria) - capillary blockage
Pathophysiology
Life Cycle: mosquitoes feed on human blood, sporozoites - introduced from saliva and within few minutes infect liver cells --> parasites multiply rapidly --> schizont containing thousands of merozoites
- period of days - several weeks - varies with Plasmodium species - infected hepatocytes release the merozoites - quickly infect red red cells
- intraerythrocytic parasites - continue asexual reproduction to produce more merozoites --> gametocytes capable of infecting the next hungry mosquito
- during asexual reproduction in red cells, each of 4 forms of malaria develops into trophozoites with somewhat distinctive appearance
- species of malaria --> identified with appropriaretely stained thick smears of peripheral blood
- Saliva - enzyme --> sporozoite
- sporozoite --> hepatocyte (multiplies) --> schizont
- schizont --> merozoites --> infects RBCs
- erythrocytic cycle --> release of more merozoites (cyclic infection of RBCs --> spikes in temperature)
- sexual forms -- micro (male) gametocytes/macro (ovum)
- fuse together (fertilisation) in mosquito
- ookinete (gut of mosquito)
- oocyst
Hypnozoite - dormant Phases of development in Man:
2 phases
Inside Liver
- pre erythrocytic schizogony - no clinical symptoms, no pathological damage
- exo-erythrocytic schizogony - cause of relapse
Inside RBCs (erythrocytic phase)
- erythrocytic schizogony - cause of malarial paroxysms
- gametogony - infects mosquito
Modes of Transmission:
- sporozoite - induced malaria - injetion of emulsion of salivary glands of mosquito containing sporozoites
- trophozoitce induced malaria - injeciton of blood from a malarial patient - asexual forms of erythrocytic schizogony
- Elevated cytokines - TNF alpha, IL-1, plasma TNF alpha --> higher in fatal cases
- TNF alpha - promoter polymorphism - disease severity
- role for NO
- lactic acidosis and hypogylcaemia
- thiamine deficiency
- volume depletion
Treatment
Prophylaxis: :effective chemoprophylaxis and insecticide-treated nets (ITNs) - prevents 90% of malaria
- travellers should be encouraged - use prophylatic regime
- encouraging migrant travellers visiting family and friends to take prophylactic medication
Non-falciparum malaria: usually managed on out-patient basis - unless patient has other comorbities
G6PD activity - measured in P. vivax or P ovale infections (as primaquine - necessary to eliminate dormant hypozoites and prevent recurrence) can cause hemolysis in those with G6PD deficiency Tx
- Chloroquine - drug of choice for treatment of all non-falciparum malaria - highly effective against P. malariae and P. ovale and most strains of P. vivax
- where chloroquine fails - resistant P. vivax malaria - can be treated with quinine , artemether and lumefantrine or atovaquone-proguanil as for uncomplicated falciparum malaria
- prevention of relapse - primaquine is used to destroy liver stage parasites (unlicenced use)
- for Tx of P. ovale 15mg primaquine for 14 days
- some strains of P. vivax require higher doses to prevent relapse - 30mg primaquine/day for 14 days
- expert help - enlisted in treating those with G6PD deficiency
Falciparam malaria:
- admitted to hospital
- oral quinine sulfate 600mg/8 hours for 5-7 days + doxycycline 200mg daily (or clindamycine 450mg/8h preg) - 7 days
- atovaquone-proguanil (Malarone) - four standard tablets daily for 3 days
- artemether with lumefantrine (riamet) >35kg, 4 tablets stat and then further 4 talets 8, 24, 36, 48, 60 hours
- IV quinine dihydrochloride is the first-line antimalarial drug. A loading dose of 20 mg/kg (to a maximum of 1.4 g) over four hours, followed by 10 mg/kg (to a maximum of 700 mg) every eight hours for the first 48 hours or until the patient can swallow is usual to reach high therapeutic blood levels quickly, although alternative regimens exist. ECG monitoring is required.
- Oral quinine sulfate 600 mg tds should be substituted once the patient is well enough to complete a 5- to 7-day course in total.
- Artesunate regimen - for named adult patient use only, on expert advice. This is usually given as an IV injection, repeated at 12 and 24 hours and daily thereafter. Rectal formulations also exist but tend to be used in resource-poor settings where IV therapy is not possible. NB: IV artesunate has not been licensed in the UK but there is accumulating evidence that it offers a significant benefit over quinine where patients have very severe malaria or high parasite counts. A Cochrane review suggests that parenteral artesunate is the drug of choice for adults with severe malaria, in various parts of the world.[22]
- A second drug should always accompany these regimes. Current recommendations are for doxycycline 200 mg od (or clindamycin 450 mg tds for pregnant women) for a total of seven days from when the patient can swallow.
Types
-
4 species of genus Plasmodium: P. falciparum, P vivax, P. ovale, P. malariae
- orginated from animal malarias in central Africa but spread around globe by human migration
P. Vivax or P. ovale infection:
- illness is relatively mild
- anemia develops slowly and may be tender hepatosplenomegaly
- spontaneous recovery usually occurs within 2-6 weeks
- hypnozoites in liver cause relapses for many years after infection
- Causes benign tertian malaria - fever every third day.
- Incubation period of 12-17 days.
- Relapse due to dormant parasites in the liver.
Vivax:
- widest geographical distribution
- tropical/subtropical areas but rare in Africa
- 43%
Ovale:
- Relapsing course as with P. vivax.
- Incubation period of 15-18 days.
P. malaraie: 7%
- mild illness
- chronic course
- parasitaemia - persist for years with or without symptosm
- children - glomerulonephritis and nephrotic syndrome
- Causes benign quartan malaria - fever every fourth day - but this is frequently not observed, particularly in early infection.
- Long incubation period (18-40 days).
- Parasites can remain dormant in the blood. 5-10% present over a year after infection. With chronic infection, can cause nephrotic syndrome.
P. falciparum infection: 50% of all malaria cases
- found in tropics and sub tropics
- chills, headache, muscular aching, weakness, vomiting, cough, diarrhoea, abdominal pain
- acute renal failure, pulmonary edema, generalised convulsions, circulatory collapse, coma and death
- causes self limiting illness similar to other types of malaria
- paroxysms of fever less marked
- cause serious complications and vast majority of malaria deaths due to P. falciparum
- can deteriorate rapidly and children in particular progress from reasonable health to coma and death within hours
1% red cells infected --> severe disease - patients with apparently low parasite levels may develop complications
- cerebral malaria - diminished consciousness, confusion, convulsions, progressing to coma and death
- Responsible for severe disease and malaria-related deaths.
- Incubation 7-14 days (up to one year if semi-immune); most travellers present within eight weeks.
- Classical tertian and subtertian periodicity (paroxysms at 48- and 36-hour intervals) are rare; daily (quotidian) or irregular are more common.
Periodicity of Fever: erythrocyte schizogony - time taken for trophozoites to mature into merozoites before release
- falciparum - shortest
- intermediate - vivax
- longest - malariae
Recurrences in Malaria:
- reinfection
- certain events related to parasite's life cycle
Recrudescence
- falciparum and malariae
- perisistence of blood infection - even after clinical illness has subsided
- numbers may increase later --> reappearance of clinical symptoms
- most upto ~ 1 year - malariae - occur even after decades
Relapse:
- special form of parasites - hypnozoites
- hyponozoites - sporozoites that remain dormant after infecting liver
- activated --> pre erythrocytic schizogony - exoerythrocytic schizogony
Absence of treatment:
- falsiparum - terminate in 1 year
- specific immunity
- stain specific - reinfection possible by other strains
Ovale and Vivax
- hypnozoites after disappearance of parasites from blood
- periodic relapses upto 5 years
Malariae
Investigations
thick and thin blood smears - stained with Giemsa stain - gold standard (low cost, high sensitivity and specificity) - suspicion of malaria - venous blood specimen in EDTA tube - sent to lab in under 1 hour (2 further films over 48 hours - if blood film negative - before excluding diagnosis)
- blood film may be negative in malaria - esp if pregnancy where parasite biomass can be sequestered in placenta
- rapid diagnostic tests - detect parasite antigens and availale and dipstick based investigations are easier to use without microscopy training
- nucleic acid based tests including polymeraise chain reaction
- thick - detecting malarai - larger volume of blood examined --> detection of even low levels of parasitaemia + densitiy for monitoring and Tx
- thin - parasite morphology + identify strain
- All cases of malaria should be notified to public health authorities and blood specimen sent to Malaria Reference Lab
- FBC - typically reveals thrombocytopenia and anaemia - leukocytosis - rarely seen but indicator of poor prognosis when present
- G6PD activity - prior to giving primaquine
- LFTs - often abnormal
- U/E - show lowered Na+ and increased creatinine
- low blood glucose may be present in severe disease
Complications
- Black water Fever
- impaired consciousness or seizures (cerebral malaria)
- renal impairment
- Metabolic acidosis
- hypogylcaemia - RBCs utilise glucose
- lactic acidosis
- thiamine deficiecy
- pulmonary edema or acute respiratory distress syndrome
- anaemia
- splenic rupture
- disseminated intravascular coagulopathy
- shock
- haemoglobinuria
- multiple organ failure
- death
