Malaria Flashcards
To learn about malaria!
Malaria is an ___ disease and is still one of the leading causes of ___ in the world.
ancient, mortality
Where does the name malaria come from?
Italian for “bad air”
Who is Charles Laveran and why is he important?
In 1880, Laveran proposed that malaria was caused by the protozoan organism, Plasmodium. He was awarded a Nobel Prize in 1907 for this discovery.
Who is Ronald Ross and why is he important?
In the late 1890s, Ross discovered that malaria is transmitted in a cycle from human to human by mosquitoes. He was awarded a Nobel Prize in 1902 for this discovery.
In 2016, WHO estimated how many malaria cases and deaths? What percentage of these estimates were in Sub-Saharan Africa?
216 million cases worldwide; 445,000 deaths worldwide; 89% of malaria cases; 91% of malaria deaths
How many countries and territories had ongoing transmission in 2016?
97
Approximately how many people are currently at risk of malaria?
3.2 billion (40% of the world’s population)
A 2012 study (Murray et al.) suggest a greater number of deaths in Africa in 2010 than the WHO estimated. What is that number, and who comprise these extra deaths?
1,133,000 deaths (more than double the WHO estimate); people over 5 years old
Malaria is one of the leading causes of death from ___ disease, especially in children under __ years of age.
infectious; 5
Why is it that 90% of deaths occur in Sub-Sharan Africa?
- Socioeconomic conditions
- Treating malaria accounts for up to 40% of public health expenditures
- The vector: the African mosquito vector species has a long lifespan and tendency to bite humans
What is the only mosquito genus and gender that is capable of spreading malaria?
Anopheles, female
Malaria transmission is generally seasonal. When does it peak and why?
During or just after the rainy season due to increased mosquito replication in standing water
How many species of Anopheles worldwide can transmit?
20
Certain species of Anopheles can transmit malaria better. What kind of Anopheles transmit better, and what was the specific species mentioned in class?
Night biters; Anopheles gambiae
Now, malaria is primarily a disease of the tropics. But in the late 1800s, where was malaria endemic? What war did it play a role in?
New England; malaria was a major cause in morbidity in the Civil War
How many cases of malaria were there in the United States in 1914? What states were these cases in primarily?
600,000; Louisiana and Florida
How many cases of and deaths from imported malaria did the CDC report in the United States in 2011?
1,920 cases; 5 deaths
In 2003, local transmission of malaria was reported in what state?
Florida
What are the two mosquito species capable of transmitting malaria in the Southern United States?
A. albimanus and A. freeborni
When and where was A. gambiae found?
Brazil in 1930
Before Fred Soper DDT, what was used as a mosquito vector control?
Diesel oil and Paris green
What happened right before Soper was brought in to eliminate A. gambiae?
Epidemic in 1938
DDT was the first insecticide that when applied to houses could…
kill mosquitoes for up to a month.
What was the timespan for eradication of malaria in the United States?
1947-1951
In order to eradicate malaria, CDC worked with state and local health agencies in how many Southeastern states?
13
How many house spray applications were performed by the end of 1949?
4,650,000
In the US in 1947, ___ malaria cases were reported, but by 1950, only ___ were reported.
15,000; 2,000
By what year was malaria considered eradicated from the United States?
1951
What years did the global campaign for malaria eradication take place?
1955-1963
What comprised the global campaign to eradicate malaria?
Combined systematic spraying of Fred Soper DDT to kill mosquitoes and treatment of infected patients with chloroquine
Was the eradication campaign effective in Sri Lanka? What is the evidence to prove this?
Very effective; Sri Lanka went from 1 million cases in 1955 to just 18 cases in 1963.
How much did the campaign cost?
~$430 million
Eradication of malaria in sub-Saharan Africa was never fully implemented. Why not? (3 reasons)
- Financial issues: the cost was high and the US Congress withdrew funding in 1963.
- Drug resistance: Chloroquine resistance of the Plasmodium species began to occur and spread.
- Problems with DDT: Widespread use of DDT in agriculture led to widespread DDT resistance. Also, DDT was found to be a devastating environmental pollutant causing severe damage to wildlife and non-harmful insects.
What were the problems with DDT?
Widespread use of DDT in agriculture led to widespread DDT resistance. Also, DDT was found to be a devastating environmental pollutant causing severe damage to wildlife and non-harmful insects.
When did the recent global campaign to prevent malaria occur?
1990s to 2009
What are the three facets of the recent global campaign to treat malaria?
- Prompt treatment for all episodes of disease (within 24 hours of the onset of symptoms if possible)
- Bednet use combined with insecticides
- Indoor residual spraying to kill mosquitoes that rest on the walls and roofs of houses
Malaria is what kind of parasite?
An intracellular protozoan parasite
What four species cause malaria in humans? Which two of these are the main cause agents?
Plasmodium vivax, P. falciparum, P. ovale, P. malariae
What species causes malaria in rodents?
P. berghei
Malaria infects ___ ___ ___, which makes parasites relatively easy to find in blood.
Red blood cells
How does the Plasmodium parasite evade key adaptive immune mechanisms, like cytotoxic T-cells?
By living in RBCs
Walk me through the cycle of malaria disease cycle.
First, a female Anopheles mosquito bites a human. In the mosquito’s gut are Plasmodium sporozoites, which are then released into the bloodstream. → Sporozoites travel through the bloodstream to the liver, where the sporozoites reproduce asexually to form merozoites. → Liver cells then burst and release merozoites into the bloodstream (7-10 days after mosquito bite). → The merozoites invade red blood cells and multiply, causing cells to burst. The cycle continues. Each time a cell bursts, systemic inflammation, chills, fever, and sweating occur. Malaria disease is from merozoite formation.
Malaria disease is from what?
Merozoite formation
What share of RBCs can P. falciparum parasites infect?
60%
Malaria can cause severe ___ because of its lysis of RBCs.
anemia
How can P. falciparum be distinguished from other species of Plasmodium?
Blood smears
In endemic areas, almost 100% of children of yearly ___ malaria, but only 1-2% have severe complications related to ___ malaria.
symptomatic; cerebral
What species of Plasmodium causes most deaths? Why?
P. falciparum; malaria brain infections
Cerebral malaria has a mortality of __%.
20
Describe innate immunity response to malaria.
Parasites eliminated by phagocytosis and C’ activation outside cells.
Describe adaptive immunity response to malaria.
Complicated immune response to malaria with different antigens expressed by different morphological forms: Abs and CTL against liver infected cells. T helper cells and B cells provide antibody triggered lysis to kill infected RBCs.
What are the four reasons why malaria is a successful pathogen?
- Very well-adapted for humans and no animal reservoir
- Also evolved for transmission only in Anopheles mosquito
- Gametocytes represent sexual stage where they can infect mosquitoes: after being taken up into the gut, the sporozoites replicate throughout the mosquito and after 2 weeks, the sporozoites enter the salivary glands of the mosquito.
- Plasmodium parasites are very good at evading immune response.
Can individuals develop partial immunity? What does this mean?
Yes, individuals living in regions with endemic malaria usually develop partial immunity probably after multiple infections. This does not necessarily protect against infection, but can reduce symptoms or prevent disease.
How does the parasite evade immunity?
The Plasmodium parasite can alter RBC surface antigen expression.
How do knobs on infected RBCs make it harder to the body to destroy?
While the liver and spleen can filter out infected RBCs, knobs allow infected RBCs to attach to walls before entering the liver or spleen.
What is rosetting?
Infected RBCs can get “sticky.” They surround themselves with uninfected RBCs as a protective mechanism.
What kinds of blood cells are unlikely to rosette?
Uninfected O-type blood cells
What encodes the key variant surface antigens (VSA) on the surface of P. falciparum?
50-60 var genes
What family of proteins do the key variant surface antigens (VSA) comprise?
The P. falciparum erythrocyte membrane protein 1 (PfEMP1) family of proteins
What does the Var gene do?
The Var gene products help RBCs bind to vascular endothelium and stop RBCs from circulating to spleen for degradation.
What are the five anti-malarial drugs?
1) Chloroquine: Thought to inhibit heme-polymerization. Great resistance since the 1970s.
2) Antifolates: Block one-carbon transfer reactions required or nucleotide biosynthesis
3) Malarone: Interferes with mitochondrial electron transport
4) Artemisinin: Extracted from Chinese herb
5) Common antibiotics: Inhibit parasite growth
Is there a good malaria vaccine?
No!
What is a non-medical solution to protect against malaria that is affordable and effective? What is the evidence of this?
Pyrethroid-insecticide (permethrin) treated nets. In one large trial, deaths of children under 1 year old from malaria were reduced by 22%.
What are two natural resistances to malaria?
- Heterozygous for sickle cell hemoglobin; unclear why, but it may be that infected cells sickle under low oxygen tension conditions which allows for increased removal of sickle infected cells
- Blood type: uninfected O type RBCs are less likely to rosette
What is the functional significance of rosetting? (3)
Rosettes formed by Plasmodium falciparum infected cells might lead to obstruction of blow flow, facilitate merozoite reinvasion, and shield infected RBCs from antibodies.
What are two issues for malaria vaccine design?
- Short window before malaria gets to the liver and renders IgG antibodies useless
- The Plasmodium parasite can change antigen expression: which antigens at what stage in the life cycle do you vaccinate with?
What is the most promising malaria vaccine?
RTS,S - a recombinant vaccine against pre-liver stage
What is the current spending on malaria control?
$100 million per year
What is the estimated cost of effective malaria control?
$2.5-4 billion per year
What is the trend of malaria burden in the last 10 years?
Increasing
What are five possible reasons for recent increase in malaria?
- Increased drug resistance
- Insecticide resistance
- Environmental changes (dams and agriculture can increase mosquito breeding grounds)
- Civil unrest (reduced action in prevention and public health)
- Travel
