2.1 Malaria Flashcards
Malaria is the most important parasitic disease of humans as almost half of the world’s population lives in areas endemic to malaria:
• Mostly, Asia, South America and Africa
• Estimated 200 million cases of malaria worldwide every year, resulting in approximately 500000 deaths (mostly among African children < 5 years old)
• Once prevalent throughout much of the inhabited world, but has now been eliminated from the USA, Canada, Europe, and Russia
• Protozoan disease transmitted by Anopheles mosquitoes → falciparum and vivax malaria causes indirect mortality in pregnancy from abortion and _____________________
The endemicity of malaria is defined as parasitaemia rates in children 2 – 9 years old:
- Hypoendemic: _______
- Mesoendemic: _______
- Hyperendemic: _______
- Holoendemic: _______
Singapore was certified malaria-free by the WHO in 1982 and malaria remains legally notifiable under the Infectious Diseases Act:
• Imported malaria constituted 96.7% of all cases from 2008 – 2015 (mostly from Asia (India: 62%; Indonesia: 17.7%))
• Mostly caused by __________ (75%) and __________ (20%)
intrauterine growth retardation (increases infant mortality)
≤ 10%;
11 – 50%;
51 – 74%;
≥ 75%;
P. vivax; P. falciparum
5 types of malaria: • Plasmodium falciparum • Plasmodium vivax • Plasmodium ovale • Plasmodium malariae • Plasmodium knowlesi (Southeast Asia, zoonotic malaria from \_\_\_\_\_\_\_\_\_\_\_\_\_)
- Most common: ________________
- Most severe: P. falciparum (_____________ can also cause severe disease)
- Mixed infections: around 5%
monkey reservoir;
P. vivax and P. falciparum;
P. knowlesi and P. vivax
Characteristics of Different Malaria Species (Geography)
- P. falciparum predominates in Africa, New Guinea, and Hispaniola (Haiti and the Dominican Republic) –> common, dominant malaria species in ____________
- P. vivax is more common in the Americas and the western Pacific. The prevalence of these two species is approximately equal in the Indian subcontinent, eastern Asia, and Oceania. –> common, dominant malaria species _____________
- P. malariae is uncommon and is found in most endemic areas, especially in _____________.
- P. ovale, even less common, is relatively unusual outside of Africa and, where it is found, comprises <1 percent of isolates.
- P. knowlesi, similar morphologically to P. malariae, has been identified by molecular methods in patients in Malaysia, the Philippines, Thailand, and Myanmar. This species has not yet been proven to be transmitted from humans to mosquitoes (a monkey reservoir may be required).
Africa;
outside Africa ;
sub-Saharan Africa;
Incubation for P. faciparum
7-14 days
Up to 1 year in semi immune
Incubation for P. vivax?
12-17 days
Hypnozoites in liver may cause relapse
Incubation for P. ovale?
15-18 days
Hypnozoites in liver may cause relapse
May lie dormant in blood for up to 1 year
Incubation for P. malariae?
18-40 days
which malaria species relapse from liver?
p.vivax and p. ovale
Transmission
• Primarily through bite of an _________________
• Mostly ______________ biting
• Mosquito longevity important - to transmit malaria, the mosquito must survive for _________
• Climactic factors e.g. temperature, humidity, rainfall
- Warmer regions closer to equator, transmission more intense and ____________
- Cooler regions, transmission less intense, more seasonal. P. vivax more prevalent due to ___________________
- Even within malaria-endemic countries, malaria transmission does not occur in all parts
• The most effective mosquito vectors are those such as ____________ in Africa
The _________________ (EIR; the number of infectious female anopheline bites per person per year) is a term used to indicate transmission intensity. While there are seasonal and geographic differences, an EIR of is low transmission, 10 to is intermediate, and is a high transmission area. In general, the higher the EIR, the greater the burden of malaria, particularly on young children.
infected female Anopheles mosquito;
dawn and dusk;
> 10 days;
year round;
tolerance of lower ambient temperatures;
Anopheles gambiae;
entomologic inoculation rate
The Life Cycle of the Malaria Parasite
1) Transmission of malaria occurs through a vector, the mosquito, that ingests gametocytes—the sexual form of the parasite—when feeding on an infected human.
2) Gametocytes, which are both male and female, mate within the gut of the mosquito and undergo __________ and then migrate through the midgut wall of the mosquito and form an _________, within which thousands of ________ develop.
3) These are then injected into a human during the next blood meal(s), where they rapidly make their way to the liver and infect hepatocytes and begin asexually (mitotically) replicating. After a period of ca. 6–15 days, the liver schizonts rupture, releasing thousands of __________ into the blood where they invade red blood cells.
4) Over the next ca. 48 h, the parasite begins replicating mitotically, progressing through a set of stages (ring, trophozoite and schizont), and produces an average of 16 new daughter merozoites per schizont. The schizonts then burst in near synchrony with other parasites, producing the characteristic fever cycle that embodies the clinical manifestations of the disease. With each replication, some of the merozoites, instead of producing new merozoites, develop into ____________, which can then infect susceptible mosquitoes, bringing the transmission cycle full circle.
meiosis;
oocyst;
sporozoites;
merozoites;
gametocytes;
The Life Cycle of the Malaria Parasite
- Mosquitoes inject sporozoites when they bite human host
- Sporozoites travel to the liver, invade a hepatocyte and multiply into schizonts. After about a week, each infected shizont ruptures releasing thousands of merozoites into the bloodstream
- _______________ (P. vivax and P. ovale) may remain quiescent. Reactivation and release into the circulation cause late onset diseases many months after initial infection
- Erythrocytic stage
- ___________ invade the RBCs and begin the asexual cycle
- Asexual replication occurs through a set of stages (ring, trophozoite and schizont) within each RBC to give the characteristic appearance seen in blood film
- Schizonts burst in near synchrony producing characteristic fever cycle (tertian vs. quartan) and clinical manifestation of the disease - Some merozoites form gametocytes (sexual forms) which are taken up by a feeding mosquito
- Gametocytes mate within the gut of the mosquito and undergo meiosis
- Migrate through midgut wall of the mosquito and form an __________, within which thousands of sporozoites develop
Hypnozoites;
Merozoites;
oocyst
[Pathogenesis of severe malaria: sequestration]
- Red Blood Cells infected with the malaria parasites stick to the side of the small blood vessels and cause ______________
- If the microvascular obstruction is critical, this can affect oxygen delivery and result in organ damage and severe malaria
microvascular obstruction
[Clinical Presentation]
- ________________ post exposure
- Assess for symptoms and signs of severe malaria
Symptoms:
- Fevers, rigors, myalgia, headache
- Nausea, vomiting, diarrhoea, abdominal cramps
Signs:
- Anaemia, jaundice
- Splenomegaly, hepatomegaly
- ______________ “black water fever”
Note DDx: influenza, typhoid, bacteraemia, dengue, leptospirosis, yellow fever etc.
7 days – 12 months;
Haemoglobinuria
[Severe malaria]
Diagnostic Features (any one)
Clinical:
- Cerebral malaria – any neurological abnormalities, GCS <11, seizures
- Prostration
- Jaundice
- Acute respiratory distress
- Abnormal bleeding
- Shock
Laboratory:
- Hyperparasitaemia (% RBC infected with Plasmodium) >10% (>____________)
- Hypoglycaemia
- Acidosis
- Severe ____________
- Acute ______ failure
- Occurs in 2% of patients with malaria (mainly P. falciparum, also reported in P. knowlesi and P. vivax) with 10-30% mortality
- The patient only needs to meet one of the above criteria to be diagnosed with severe malaria
- Medical emergency and management in the intensive care unit
500,000/mcL;
anaemia;
renal
[Microscopy – Gold Standard Diagnostic Test]
Thick and thin blood smears, stained with _________ are examined under microscope
- Thick blood smears look for ____________
- Thin blood smears to determine ___________
- Thin blood smears to determine the percent parasitemia
Repeat malaria smears for detection and monitoring of response to treatment
Variable technique and experience of laboratory personnel affect diagnostic accuracy
Giemsa;
presence of infection;
species of malaria;
[Rapid Diagnostic Tests]
OptiMAL-IT
- Detects _____________
- Accuracy reduced at __________
- May be positive following a recent treatment
BinaxNOW Malaria
- Detects ______________
- Results in 15 mins
- High sensitivity and specificity
- Not reliable for _________
parasite LDH;
low parasitaemias;
Plasmodium antigens (immunochromatographic assay);
P.ovale
Advantages and Limitations of RDT
• Advantages: ___________________
• Disadvantages: must confirm with microscopy, not widely available, limited species information, no information about % of parasitaemia, unreliable in pts with _______________ (may remain positive up to 1 month after therapy), some strains of P. falciparum have lost _____________ (false negatives)
not operator-dependent, faster diagnosis ;
history of malaria;
HRP2 antigen
[PCR for Plasmodium DNA]
Pros
• Very sensitive
• Most useful for _______________
Cons
• Not readily available at most hospital and clinic labs
• Time to results is lengthy
• Expensive
determining species of malaria
[IFA for Antibodies to Malaria]
Pros
• Sensitive
• Able to get some information on species, but cross-reactivity can occur
• Most useful for _____________________
Cons
• Should NEVER be used for _____________
• Not readily available at most hospital and clinic labs
• Antibodies can be present for a few years after exposure to malaria
• Expensive
retrospectively diagnosing past infections;
diagnosing acute infections
[Treatment of Severe Malaria]
Medical emergency requiring ICU care
________ or __________ plus ________ or _____________
Artemisinin based combination therapy (ACT) - Artesunate
- Preferred therapy for ______________ with lower mortality rates in adults and children
Quinine or quinidine
- SE: ______, _________, ______, ________
Monitor CNS (__________), respiratory, renal function (_______), fluids and glucose, anaemia (_______), concomitant bacterial infection and empiric antibiotics
Artesunate; Quinine/ quinidine; Doxycycline; Clindamycin
severe malaria ;
QT prolongation, cardiotoxicity, hypoglycaemia, tinnitus;
seizures; dialysis; transfusion
[Treatment of Uncomplicated Falciparum Malaria]
Admit for supportive care if clinically appropriate
Artemisinin Based Combination Therapy (ACTs)
If ACTs unavailable:
- _____________
- Quinine-based regimen (in combination with doxycycline or clindamycin)
- Mefloquine (Lariam) (in combination with doxycycline)
Atovaquone-proquanil (Malarone)
[Treatment of Uncomplicated Plasmodium Vivax]
_________ still effective for most countries (Except Indonesia and East Malaysia-Use ACTs)
If chloroquine unavailable:
- ACTs
- Atovaquone-proquanil (Malarone)
Liver Stage or Hypnozoites
- Requires use of ____________ to kill hypnozoites (to prevent relapses
Chloroquine;
primaquine
Test for G6PD
- Test for G6PD deficiency in patients requiring ____________
- Daily primaquine causes potentially dangerous haemolysis in G6PD-deficient patients.
- In patients with mild variants of G6PD deficiency, weekly primaquine for 8 weeks is safer than, and probably as effective as, daily treatment.
primaquine
Resistance
- Consult urgently with ID/micro if pt not responding, may need 2nd line therapy
- ______________ P falciparum present in Western Cambodia and the Thailand–Myanmar border
- Resistance to __________________ emerged previously in this area, and in both cases the resistance genes spread to Africa and caused millions of deaths
- Artemisinin-resistant parasites are cleared slowly from the blood after artemisinin combination treatment.
Artemisinin-resistant;
both chloroquine and sulfadoxine–pyrimethamine
[Chemoprophylaxis]
Recommended for travellers during potential exposure to malaria
Type of chemoprophylaxis dependent on local patterns of susceptibility to antimalarials and the likelihood of acquisition of malaria
No antimalarials gives 100% protection
P. vivax and P. ovale can present many months after return despite compliance with chemoprophylaxis
Combine with bite avoidance measures (insect repellents e.g. DEET, protective clothing, bed nets and screens, restriction of outdoor activities at night)
Atovaquone-proguanil – combination medication for _____________________. Daily dosing, discontinue 7 days after return
SE: GI side effects, expensive
Doxycycline – low cost. Daily dosing for _______________
SE: GI, esophagitis, ______________, __________
Mefloquine – highly effective, mefloquine resistant areas along Thai-Cambodian border. Weekly dosing for 4 weeks after return
- SE: mild headache, CNS, rare seizures and psychosis. - Screen for psychiatric, neurologic or cardiac conduction disorder
short term travelers and to drug resistant areas;
28 days after return;
photosensitivity, vaginal candidiasis;
