Malaria

Question 1

How is Malaria transmitted and why is it so specific?

Hint; specific for four major reasons

Answer 1

Through blood transfusions which can include vertical transmission, but it’s so specific as it requires a vector from a

1. FEMALE anopheline mosquito as they require blood to make eggs (male mosquitos just eat nectar)
2. only 30-40 species of all female anopheles mosquitos can transmit malaria
3. Mostly biting at night (many sleep under mosquito nets)
4. They have different behaviours
   - Anthropophilic/zoophilic; can prefer to bite humans or animals (or both)
   - Endophagy/esophagy: prefer indoors/outdoors
   - diverse breeding sites

Question 2

What organisms/hosts can malaria exist inside of, how many species of it can exist inside humans? Name them

Answer 2

Mammals, reptiles, birds but only 5 species affect humans

1. P. Falciparum
2. P. Vivax
3. P malariae; long lived infections
4. P. Ovale
5. P knowlesi (monkey malaria but can be fatal to humans)

Question 3

How transmissible are vector-borne diseases?

Answer 3

Highly transmissible, as there are many carriers that can bite someone and spread the infection

Question 4

What vector borne disease has the highest morbidity and mortality? Which continent has it not infected?

Answer 4

Malaria! Hasn’t infected Antarctica

Question 5

What was malariotherapy?

Answer 5

People discovered that when they had neurosyphilis they could be cured by experiencing fevers so scientists intentionally infected people with malaria to cause fevers and kill the temperature sensitive syphilis bacteria (Many died, but since neurosyphilis was terminal this was considered better)

Question 6

What’s DDT and who originally started to use it? What happened because of it?

Answer 6

The Rockefeller foundation started to use DDT is an insecticide to spray households, had a long residual effect to prevent malaria. However, it also soon after caused a resistant strain of mosquitos - this pushed the WHO to initiate a global malaria education campaign to eliminate the disease

Question 7

Name four reasons that the WHO’s initiative to eliminate malaria initially work?

Answer 7

• only provided funding to countries saying elimination was their main goal (excluding high prevalence areas like sub Saharan Africa)
• difficult to spray all households with DDT, and resistance and vector behaviour changed
• main drug used for treatment was chloroquine and a resistant strain emerged soon after
• governmental funding was not maintained

Question 8

What is the commonest strain of malaria and where geographically is it greatest?

Answer 8

P falciparum, Sub Saharan Africa

Question 9

What is the second commonest strain of malaria and where geographically is it greatest? Why does it not most prevalent in the same geographical area as the most common strain and where is generally found?

Answer 9

P. Vivax, not fatal but quite dehabilitating. Generally found in temperate zones but it isn’t as common in sub Saharan Africa as many have the ‘Duffy negativity phenotype’ providing resistance to this strain

Question 10

Why is P falciparum the most fatal malaria and what is different about the pathology between P. Falciparum and P. Vivax species of malaria?

Answer 10

Can develop into cerebral malaria (parasites sequester in the brain causing coma and death). P. Vivax can incubate in the liver and reactivate even after treatment

Question 11

Who is resistant to malaria?

Answer 11

Those that carry the sickle cell gene are resistant to malaria

Question 12

Which species of malaria is similar to P. Vivax?

Answer 12

P. Ovale

Question 13

Describe the life cycle of malaria (including the two stages)

Answer 13

Primary stage:
1. Infected mosquito bites, sucks blood and injects some anaesthetic (so you don’t feel it) and the sporozoite (developmental stage of plasmodium parasite)

2. Sporozoite heads to the liver and stays there for 9-14 days

Secondary stage: merozoite, 1 sporozoite = ~10,000 merozoites
3. Burst out of liver cells and induce an immune reaction, symptoms begin

4. Cyclical symptoms begin: Merozoites invade blood cells and continually replicate inside, bursting out every 1-3 days and infecting more RBCs

At this point, merozoites can continue infecting blood cels or differentiate into their sexual stage = gametocytes and the next mosquito that bites you may take up the gametocytes

5. Once inside the mosquito the parasite takes 9-12 days to develop: Gametocytes become oocytes and go into the mosquito midgut and develop further into sporozoites which stay in the salivary glands = mosquito becomes a malaria carrier

Question 14

How long after exposure to symptoms tend to occur? What does the presence of symptoms depend on?

Answer 14

8-25 days following infection (when merozoites burst out of blood cells).

Symptoms depend on the age and an area’s intensity of transmissibility: after repeated exposure an individual may develop immunity to symptoms (but not immunity to the disease) - therefore, children tend to present with clinical symptoms in areas where malaria is prevalent. Some individuals are also naturally asymptomatic

Question 15

What influences the speed of the parasite’s development inside a mosquito

Answer 15

The temperature (faster when warm) and efficiency/behaviour of the mosquito (does it prefer humans>animals, indoors or outdoors, etc)

Question 16

Name two other characteristics female anopheline mosquitos should require (other than being female) to effectively transmit malaria

Answer 16

1. Need to be older; as many mosquitos are thought to have a half life of >1 week in the wild, but the parasite requires 9-12 days to develop
2. Longer flight range to spread the disease further

Question 17

Other than sub-Saharan Africa where else is there an abundance of anophaline species?

Answer 17

Southeast Asia (due to all the islands, many have developed separately which make them harder to target)

Question 18

Name four symptoms of uncomplicated malaria and specify which is more related to chronic malaria

Answer 18

Fever, headache, sweats, vomiting and splenomegaly (Chronic)

Question 19

Name the symptoms associated with severe malaria (including the three specific to P.falciparum)

Answer 19

1. P. Falciparum causes cerebral malaria: seizures, coma and death
2. Other symptoms: severe anemia, hypoglycaemia, acute kidney failure and RDS

Question 20

Name three things that can occur due to malaria in pregnancy

Answer 20

Stillbirth, low birth weight and infant mortality

Question 21

Which age groups are most commonly affected by severe AND clinical malaria in low and high transmission areas? Does the parasite prevalence change amongst different age groups?

Answer 21

Low transmission areas:
Severe: >5
Clinical: all ages

High transmission areas:
Severe: >5 years
Clinical: >2 years

Parasite prevalence doesn’t really change amongst age groups (only its more prevalent in high transmission areas)

Question 22

Name the five ways malaria is diagnosed and the pros and/or cons of each

Answer 22

1. Clinical using symptoms; often results in overdiagnosis when a child presents with malaria-like symptoms, this wastes anti malarial drugs and doesn’t treat the real cause of the fever

Following two aren’t very specific; detect 100 parasites/microL of blood

2. Microscopy; depends on skill and can be subjective
3. Rapid diagnostic test (RDT); detects parasite antigen in the blood, much easier to use than microscope

Molecular diagnostics: expensive, used more for research>diagnostic

• PCR; detects even low levels, but need established lab and sterile conditions so they developed…
• Loop-mediated isothermal amplification (LAMP): quicker and easier

Question 23

How is malaria treated and how effective is treatment?

When can you receive treatment?

Answer 23

Drugs work but many don’t get them in time (undiagnosed or treatment unavailability)

Can receive treatment..

1. after diagnosis
2. chemoprophylaxis for those who have travelled to malaria endemic areas
3. IPT/intermittent preventative treatment for young children and pregnant women in high-risk populations who live in endemic areas (every 4 weeks)

Question 24

Name three drugs that are or were used commonly to treat malaria, given the potential for resistance to occur how are drugs recommended to be taken?

Answer 24

1. Chloroquine until widespread resistance (cheap, quick and safe)
2. Quinine for severe malaria
3. Artemisinin-based combination therapy (ACT)
   Given high potential for resistance it’s recommended to use two drugs with different modes of action

Question 25

Other than the potential for resistance, what are the disadvantages of the three ACT drugs and how was this overcome?

Answer 25

They have a short half-life so were combined with longer acting drugs from a different class (and many have been coformulated/2 in 1!)

Question 26

What are two aspects of malaria treatment that may reduce adherence?

Answer 26

There are multiple doses needed to be taken over a certain time period and some may have bad reactions to them

Question 27

What is one explanation for the growing prevalence of resistance against malaria treatment?

Answer 27

Counterfeit drugs: sub standard versions of malarial tablets (sometimes not coformulated and lower doses than they should be) which encourages resistance

Question 28

Briefly describe the three ways we can measure malaria transmission intensity, which is the gold standard?

Answer 28

1. Vector monitoring: Gold standard Entomological inoculation rate (EIR) 2. Clinical monitoring; determines incidence/those who present with symptoms passively or actively 3. Community monitoring: gives a parasite prevalence: proportion of the population currently infected (i.e parasites in the blood) and can be determined through diagnostic techniques

Question 29

What does EIR mean? Name the three steps used in the to measure it and the disadvantages of the process

Answer 29

Entomological inoculation rate means the average number of infectious bites a person receives over a specified time (also has to do with how many mosquito bites you receive generally) Measuring process: Disadvantages: Labour intensive and difficult to standardize, can be hard to find infectious mosquitos in areas of low transmissibility 1. Collect anopheline mosquitos with traps 2. Human biting rate: How many of those collected are biting humans 3. Sporozoite rate: How many that bite humans are infected with ‘sporozoites’

Question 30

Briefly describe the two ways clinical monitoring can be done, what are the cons of each?

Answer 30

Passive case detection: waiting for people to come to health facilities with symptoms, important for long term monitoring and elimination BUT many cases are asymptomatic and not all communities are able to use health facilities, data and diagnostic quality can also be low Active case detection: going into the community and actively screening people

Question 31

How can malaria be controlled?

Answer 31

1. Targeting vectors: insecticide treated nets (ITN), indoor residual spraying (IRS) 2. Target the parasite in humans: mass screening, IPT, seasonal malaria chemoprevention (SMC) in children, mass drug administration (MDA)

Question 32

What are some benefits of controlling malaria with an insecticide treated net (ITN), what are two disadvantages?

Answer 32

1. Most cost effective 2. Physical barrier 3. Treatment repels insects 4. If it doesn’t kill the insect it shortens it’s lifespan (and older mosquitos are better at transmitting the infection) However, this also changes the behaviours of the vector and more may start biting during the day, and many people use the net for alternative uses (especially when they don’t understand the need to have one)

Question 33

What are five disadvantages to using IRS (indoor residual spraying) to control malaria?

Answer 33

1. Vectors need to be endophilic (bite inside) 2. Community coverage; >80% need to be sprayed 3. Community resistance/ don’t want the spray 4. Logistically difficult to reach all the houses 5. Spraying needs to be repeated

Question 34

How many classes are there of insecticide, which class is the best and used for nets? When can resistance develop and what is the overarching consequence of this? re disadvantages to using insecticides?

Answer 34

4 classes, pyrethroids are the most toxic to mosquitos but not mammals Development of resistance occurs with widespread use and when vectors are exposed to ineffectual doses (i/e old nets, insufficient spraying), and there aren’t many new insecticides available

Question 35

What are three resistance management strategies for insecticides?

Answer 35

1. Insecticide combinations 2. Rotate spraying (1 insecticide for 6 months) 3. Monitoring

Question 36

What is the first malaria vaccine to get through to a phase 3 trial? What is its general mechanism of action? How many doses does it have and which age group it is most effective with?

Answer 36

``` RTS S vaccine, makes the immune system respond to sporozoites before they can invade the liver cells. 4 doses (need the fourth dose for effect!!), more effective in older children>infants ```

Question 37

What is WHO’s recommendation for use of the RTS S vaccine?

Answer 37

Use in combination with other control measures (not one size fits all)

Question 38

What foundation has been the most recent founder behind eradicating malaria?

Answer 38

The Bill and Melinda Gates foundation

Question 39

Describe the further developments made in malaria surveillance in the country Zanzibar

Answer 39

Once an individual has come in with symptoms (passive surveillance) they aggregate the data with every health facility and follow up with the individual’s household

Question 40

What is a vector? Which animals are commonly vectors?

Answer 40

A living organism that transmits an infectious agent from an infected animal to human or another animal, vectors are commonly arthropods (i.e mosquitos, ticks, flies, etc)

Question 41

Briefly describe the two ways vectors can transmit infectious diseases

Answer 41

1. Actively: biological vectors may carry pathogens that can multiple within their bodies and be delivered to new hosts (usually by biting) 2. Passively: mechanical vectors (i.e flies) can pick up an infectious agent on the outside of their body and transmit them through physical contact

Question 42

What is a zoonotic disease?

Answer 42

Diseases that can be transmitted directly or indirectly between animals and humans

Question 43

List 4 major challenges currently faced while trying to eliminate malaria

Answer 43

1. Lack of new tools 2. Insecticide resistance threatens the tow most effective tools 3. Resistance to ACTs 4. Funding