Parasitology - Blood and Tissue Protozoa (Malaria)

Question 1

Name some species in the Sporozoa group.

Answer 1

• Plasmodium falciparum
• P.vivax
• P.malariae
• Toxoplasma gondii
• Isospora belli
• Cryptosporidium parvum
• Cyclospora cayetanensis

Question 2

Briefly describe Protozoa.

Answer 2

• Single-celled eukaryotic organisms that range in size from 2-100 μm and can have various organs to aid motility, such as pseudopods, flagella, and cilia.
• They can reproduce sexually via fusion of gametocytes, or asexually by binary fission.

Some are pathogenic to humans and multiplication in the host can be controlled by either the immune system or drugs. The disease can be severe in the immunocompromised.

Protozoa are most prevalent in the tropical and sub-tropical areas.

Question 3

What are the two main stages in the lifecycle of most protozoa?

Answer 3

• Trophozoite: actively feeding and multiplying stage.
• Cyst: infectious, protective, quiescent stage.

Question 4

What main species are medically important blood and tissue Protozoa?

Answer 4

• Plasmodium spp.
• Babesia spp.
• Toxoplasma spp.
• Sarcocystis spp.
• Acanthoamoeba spp.
• Balamuthia spp.
• Naegleria spp.
• Leishmania spp.
• Trypanosoma spp.

Question 5

What are the five species that can cause malaria?

Answer 5

1. Plasmodium vivax
2. P.ovale
3. P.malariae
4. P.falciparum
5. P.knowlesi

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Question 6

Charles Louis Alphonse Laveran (18 June 1845 – 18 May 1922) was a French physician. What did he discover?

Answer 6

The cause of malaria is a protozoan.

Question 7

Sir Ronald Ross (13 May 1857 – 16 September 1932) was an Indian-born British doctor who received the Nobel Prize for Physiology or Medicine in 1902. What did he discover?

Answer 7

He found the malarial parasite in the gastrointestinal tract of the Anopheles mosquito, which lead to the realisation that malaria is transmitted by the Anopheles fly, specifically female.

Question 8

In 2015, approximately __ ______ people – nearly half of the world’s population – were at risk of malaria. Most malaria cases and deaths occur in ___-_______ ________. However, Asia, Latin America, and, to a lesser extent, the Middle East, are also at risk. In 2015, __ countries and territories had ongoing malaria transmission.

Some population groups are at considerably higher risk of contracting malaria, and developing severe disease, than others. These include infants, children under _ _____ of age, _______ women and patients with ___/____, as well as non-immune migrants, mobile populations and travellers. National malaria control programmes need to take special measures to protect these population groups from malaria infection, taking into consideration their specific circumstances.

Answer 8

In 2015, approximately 3.2 billion people – nearly half of the world’s population – were at risk of malaria. Most malaria cases and deaths occur in sub-Saharan Africa. However, Asia, Latin America, and, to a lesser extent, the Middle East, are also at risk. In 2015, 97 countries and territories had ongoing malaria transmission.

Some population groups are at considerably higher risk of contracting malaria, and developing severe disease, than others. These include infants, children under 5 years of age, pregnant women and patients with HIV/AIDS, as well as non-immune migrants, mobile populations and travellers. National malaria control programmes need to take special measures to protect these population groups from malaria infection, taking into consideration their specific circumstances.

Question 9

According to the latest WHO estimates, released in December 2015, there were ___ _______ cases of malaria in 2015 and ___,____ deaths.

___-________ _______ continues to carry a disproportionately high share of the global malaria burden. In 2015, the region was home to __% of malaria cases and __% of malaria deaths.

In areas with high transmission of malaria, children under _ are particularly susceptible to infection, illness and death; more than two thirds (70%) of all malaria deaths occur in this age group.

Answer 9

According to the latest WHO estimates, released in December 2015, there were 214 million cases of malaria in 2015 and 438 000 deaths.

Sub-Saharan Africa continues to carry a disproportionately high share of the global malaria burden. In 2015, the region was home to 88% of malaria cases and 90% of malaria deaths.

In areas with high transmission of malaria, children under 5 are particularly susceptible to infection, illness and death; more than two thirds (70%) of all malaria deaths occur in this age group.

Question 10

What are the symptoms of malaria?

Answer 10

• Infections can be either asymptomatic or result in clinical symptoms. The incubation period is usually 10-15 days, but can appear years later in latent infections.
• Influenza-like symptoms: fever, sweats, headache, muscle pain, diarrhoea, vomiting.
• Untreated can become life-threatening: breathing problems, seizures, organ failure, severe anaemia, falciparum most severely can block blood vessels.

Question 11

Outline the stages of reproduction of Plasmodium spp. (including both sexual and asexual stages)

Answer 11

1. Sporozoites are injected into the bloodstream of a human through an infected female Anopheles fly (salivary glands).
2. The sporozoites first infect hepatocytes.
3. Over the next 5-10 days the parasite differentiates and multiplies inside the hepatocytes. 20,000 - 40,000 merozoites are released into the blood.
4. These invade the red blood cells.
5. During the intraerythrocytic stage the merozoites develop and multiply over the next 48 h. When the RBCs burst 15-32 merozoites are released.
6. A small proportion of infected RBCs have parasites undergoing differentiation into either male or female gametes (which can be taken up by blood meal).
7. In the insect mid-gut the male and female gametes fuse to form a zygote, which differentiates and grows into sporozoites in the salivary gland of the mosquitoes.

Question 12

What are the stages of development of malaria in erythrocytes? [5]

Answer 12

1. Ring stage
2. Early trophozoite
3. Trophozoite
4. Schizont
5. Merozoites

Question 13

What disease does Plasmodium vivax cause?

Answer 13

Benign tertian malaria

Question 14

Outline the main features of P. vivax.

Answer 14

Plasmodium vivax only invades young immature erythrocytes which enlarge and contain pink granules (Shuffner’s dots).

Has an incubation period of 10-17 days, which is followed by influenza-like symptoms with headache, muscle pains, photophobia, anorexia, nausea and vomiting.

• Have ring-shaped mature trophozoites
• Amoeboid mature trophozoites

Question 15

Outline the pathogenesis of Plasmodium vivax.

Answer 15

Plasmodium vivax causes benign tertian malaria.

After infection and invasion of erythrocytes, increasingly more erythrocytes are ruptured in order to liberate merozoites and toxic cellulr debris (haemoglobin), which leads to typical patterns of chills, fever and malarial rigours (paroxysms (sudden recurrence)) appearing periodically (48 hourly).

This can progress to severe attacks concominant with the period of infection, replication, and cell lysis. if left untreated then chronic P.vivax infections last for years and can lead to brain, kidney, and liver damage.

Question 16

How are P.vivax (benign tertian malaria) infections treated?

Answer 16

The World Health Organisation recommends a 14-day course of primaquine (0.25mg/kg/day) to eradicate the liver stage of the parasite and prevent relapse of the disease.

Question 17

Outline the lifecycle of P.vivax.

Answer 17

1. P.vivax is injected into the host when the mosquito takes a blood meal, injecting sporozoites.
2. The sporozoites travel in the blood to the liver where they infect hepatocytes (hypnozoite) and develop into schizonts.
3. The schizonts develop into merozoites, rupture the cells and enter the blood.
4. The merozoites infect immature erythrocytes, and develop into immature trophozoites (ring stage).
5. Some go on to form merozoites, and some form gametocytes.
6. The gametocytes are taken up when a mosquito takes a blood meal.
7. Macrogamete → Ookinete → Oocyst → Trophozoites

Question 18

What are the three main stages of the P.vivax lifecycle?

Answer 18

1. Mosquito stage: sporogonic cycle
2. Human liver stage: exo-erythrocytic cycle
3. Human blood stage: erythrocytic cycle

Question 19

Outline Plasmodium ovale.

Answer 19

P.ovale is similar to P.vivax in physiology and structure, the Schuffner’s dots are pale pink granules and the mature schizont contains half the number of merzoites.

Found in tropical Africa, Asia and South America.

Has clinical symptoms similar to P.vivax (influenza-like symptoms with headache, muscle pains, photophobiam anorexia, nausea and vomiting).

Untreated P.ovale infection lasts for one year, as opposed to several years for P.vivax.

Question 20

How is P.ovale treated?

Answer 20

Primaquine to prevent from latent liver infections.

Question 21

What disease does Plasmodium malariae cause?

Answer 21

Quartan malaria (malarial malaria)

Question 22

Outline P.malariae infection.

Answer 22

P.malariae infects only mature erythrocytes with a rigid cell membrane, thus the parasites’s cell growth is dictated by the size and shape of the RBC. The cell infection can be seen by typical band and bar formation.

Epidemiologically, P.malariae is less prevalent than other plasmodia.

The clinical symptoms include an 18-40 days to years incubation period (longest), influenza-like symptoms with 72 hour periodic fever (febrile paroxysms), with untreated infections lasting around 20 years.

Question 23

How is P.malariae treated?

Answer 23

Primaquine

Question 24

What disease does Plasmodium falciparum cause?

Answer 24

Malignant tertian malaria (falciparum malaria)

Question 25

Outline ***Plasmodium falciparum* infection**.

Answer 25

Epidemiologically, *P.falciparum* is found **almost exclusively** in **tropical** and **subtropical regions**. *P.falciparum* invades **any type** of **erythrocyte**, and is stuck on the **margins** of the infected cells (**accolé position**), and **multiple sporozoites** can infect single erythrocyte. Growing trophozoite stages and schizonts are rarely seen in blood films; peripheral blood smears contain only ring forms. The clinical symptoms include an incubation period of **7-10 days** (shortest), early **influenza-like** daily symptoms (**chills, fever, nausea, vomiting, diarrhoea**), periodicity becomes **tertian** (**36-48 hours**). *P.falciparum* infection is **fatal** if left untreated; it can lead to **cerebral malaria** (common in Africa), **black water fever** (due to kidney damage), haemoglobinuria leads to **acute renal failure** and tubular necrosis, liver involvement leads to bile vomiting and serious dehydration.

Question 26

Label: * 1 * 2-18 * 2-10 * 19-26 * 26 * 27, 28 * 29, 30

Answer 26

* 1: normal erythrocyte * 2-18: trophozoites * 2-10: ring-stage trophozoites * 19-26: schizonts * 26: ruptured schizont * 27, 28: mature macrogametocytes (female) * 29, 30: mature microgametocytes (male)

Question 27

Outline ***P.knowelsi* infection**.

Answer 27

*P.knowelsi* is an emerging fifth human malarial parasite. It infects macaque mokeys, although there have been hundreds of human cases reported from Malaysia. It hasa short lifecycle (24 hours), and can infect all types of erythrocytes. It can be asymptomatic, but is marked by thrombocytopenia (platelet deficiency)

Question 28

How is ***P.knowelsi*** **prevented**, **diagnosed**, and **treated**?

Answer 28

* **Prevented**: avoid bites of mosquitos, preventative medicine * **Dignosis**: PCR * **Treatment**: good response to **chloroquine** and **primaquine**

Question 29

Outline the main **differences** between **malarial parasites** (distribution, danger, RBC cycle, RBC infection, liver hypnozoites)

Answer 29

Question 30

How does **malaria evade** the host's **immune system**?

Answer 30

* **Through polymorphism of dominant surface antigens** * **​**Recent work suggests that the mechanisms controlling gene activation and silencing might contribute to preferential recombination between antigen encoding genes * **By living within the host erythrocytes** * **​**There is no antigen presenting pathway to detect the parasites.

Question 31

How are ***Plasmodium*** species **diagnosed**?

Answer 31

Diagnosis can be made through understnding of the **travel history** of the patient, prompt clinical review and differential diagnosis. **Microscopic examination** of **thick films** (concentration method) of **blood** to identify the parasite. **Microscopic examination** of **thin films** of **blood** (Giesma staining). Identification of the **specific species** through **PCR** and **serology**.

Question 32

What **features** (microscopy) can help **identify** a **malaria parasite**? [7]

Answer 32

* **Size** of the **erythrocyte** → enlarged suggestive of *P.vivax* or *P.ovale*. * Presence of **Schuffner** (*P.vivax, P.ovale*) or **Maurer's** (*P.falciparum*) **dots**. * Different **stages present** → late trophozoites and schizonts of *P.falciparum* not normally present in peripheral blood, but are in other species. * **Morphology** of **trophozoites** and **schizonts**. * **Morphology** of **gametocytes** → round/crescent. * The **quality** of **malarial pigment** → coarse pigment suggestive of *P.malariae*. * The **level of parasitaemia** and presence of multiple infections of erythrocytes → sugggestive of *P.falciparum*.

Question 33

**Identify** these **malaria species**. What are their **identifying features**?

Answer 33

1. **P.malariae** → typical band and bar forms 2. **P.vivax** → Schuffner's dots 3. **P.falciparum** → crescent form (sausage) gametocytes

Question 34

Outline how **malaria** is **prevented** and **controlled**.

Answer 34

**Key interventions for control include:** * prompt and effective treatment with **artemisinin-based *combination*** therapies.(*flaciparum*) * Understanding the chloroquine resistant regions. * **New drugs** give excellent results in multi-drug resistant strains (phenathrene methanols, halofantrine, lumafantrine). * Use of **insecticidal nets** by people at risk. * Indoor **residual spraying** with **insecticide** to control mosquito vectors.

Question 35

How can **malaria** currntly be **prevented** and **treated**?

Answer 35

* **Chloroquine** or **quinine** * Treatment with other drugs in chloroquine-resistant regions (chloroquine+proguanil, atovaquone+proguanil, mefloquine, doxycycline) * **Prompt** and effective treatment with **artemisinin-based *combination* therapies**. * **Primaquine** to **prevent relapse** of the latent forms of *P.vivax* and *P.ovale*.