1.1 Parasites and vectors - Introduction

Question 1

Overview

Answer 1

In order to understand malaria as a disease, it is necessary to know about the biology of the parasites that cause the disease and the vectors that transmit it. In this section, you will revise what you already know about these parasites and then reflect on the history of the discovery of the malaria parasites and their life-cycles. You will learn about the nature of the parasites belonging to the genus Plasmodium, especially those that infect hosts other than humans, and about how some of these have been used as models for human malaria. Next, you will consider in some detail the life-cycles of the malaria parasites of humans and the nature and life-cycle of the Anopheles mosquitoes that transmit malaria. This section is intended to provide you with the basic information you require in order to follow the rest of the module, so you may have to return to it again later.

Question 2

Aims and objectives Aims

Answer 2

This session introduces thesubjectof malaria and guides you to where particular topics are considered in more depth in later sessions.

Question 3

Aims and objectives Objectives

Answer 3

After working through this session, you should be able to: Describe the life-cycle of malaria parasites. Compare the species of malaria parasites that infect humans. Explain why malaria is a major health problem. Suggest ways in which it might be possible tocontrolmalaria.

Question 4

Introduction

Answer 4

Malaria is highlyendemicin most of sub-Saharan Africa, the Indian subcontinent, South-East Asia and in parts of Central and South America. The World Health Organization estimated that about 214 million persons became infected and 438,000 died worldwide from malaria in 2015. About 88% of the deaths occurred in sub-Saharan Africa, mostly in children and mainly from infection withPlasmodium falciparum. In Africa, Plasmodium falciparum is by far the most important species. While P. falciparum infections are also widespread in Asia and South America, P. vivax is more common, and is a major cause of malaria morbidity, and can be fatal though much less commonly. Other species of Plasmodium that infect humans are P. knowlesi, which is mainly a species that infects macaque monkeys in South-East Asia, P.ovale and P.malariae.

Question 5

Introduction

Answer 5

Malaria eradication campaigns were launched in the 1950s and 1960s but failed due to a lack of sufficient resources and commitment as well as the spread of drug-resistant parasites and development of resistance to common insecticides inanophelinemosquitoes. This failure was followed by a resurgence of malaria in a number of endemic tropical countries. However, greater commitment and support, notably since the year 2000, leading to better and more widely applied preventive, diagnostic and treatment measures have decreased the global malaria burden over the last decade. Because P. falciparum is the species of malaria parasite that causes most mortality in humans, research has been focused on this species though recently there has been greater recognition of the impact of P. vivax infections.

Question 6

The life-cycle of malaria parasites (based onPlasmodium falciparum)

Answer 6

A knowledge of the complex life-cycle of the parasite is essential for an understanding of the disease. Infection begins when a female Anopheles mosquito injects the infective sporozoite stages directly into the bloodstream. Within 30-60 minutes, sporozoites invade liver hepatocytes and initiate a phase of multiplication resulting in the formation of an exoerythrocytic (in mammals ideally termed a pre-erythrocytic) schizont. This phase, which is not pathogenic, lasts a minimum of 6-7 days, each sporozoite invading a hepatocyte giving rise to about 30,000 uninucleate forms called merozoites.

Question 7

The life-cycle of malaria parasites (based onPlasmodium falciparum) Life cycle

Answer 7

A mosquito bites the human host, releasing parasites into the bloodstream. The parasites need to get inside a cell quickly to avoid the patrolling immune cells so head straight to the liver to hide there The body is still unaware the parasite is present so there are no symptoms yet Inside the liver cells, the parasites replicate until they are full and burst out. They now target the red blood cells to gain access to the entire body and to further shelter from the immune system. When inside the red cells they drastically alter the cell make up The immune system becomes aware something is happening in the body and tries to target the red blood cells. To attack infected cells, the white blood cells usually recognise parasite proteins on the outside and destroy it But the parasite evades this by constantly changing the proteins it expresses on the outside of the cell. The immune system cannot keep up. Each time red cells burst and deplete, they release toxins into the body, causing fever, chills, sweating, headaches, fatigue, vomiting and seizure. While this is going on, parasites can continue to replicate and differentiate into transmission stages. A process only possible in the human host. Transmission stages then need to be picked up by the mosquito host again to spread further. Once back inside the mosquito, the parasite will undergo reproduction, taking two to three weeks. Until reproduction is complete, the mosquito cannot pass the infectious parasites on. And the cycle continues. An infected mosquito bites another human host and parasites release into their bloodstream.

Question 8

The life-cycle of malaria parasites (based onPlasmodium falciparum) Erythrocytic schizogony

Answer 8

The merozoites released from the liver stages enter the bloodstream and within 1-2 minutes are able to attach to and enter a red blood cell. Inside the red blood cell (erythrocyte), the merozoite becomes a feeding stage, theerythrocytictrophozoite(ring stage). The trophozoite ingests and digests haemoglobin and multiplies asexually to produce an erythrocyticschizontthat matures to produce a new generation of merozoites (as shown in the figure below) that, on rupture of their host red blood cell, immediately initiate a new asexual multiplication cycle by invading new erythrocytes.

Question 9

The life-cycle of malaria parasites (based onPlasmodium falciparum) Erythrocytic schizogony

Answer 9

Image description. The stages of erythrocytic schizogony shown in the flow diagram are presented below as a numbered list. Merozoites enter a red blood cell, then forward to Ring stage, then forward to Trophozoite, then forward to Immature schizont, then forward to Mature schizont, then forward to Ruptured cell, then forward to Merozoites enter a red blood cell.

Question 10

The life-cycle of malaria parasites (based onPlasmodium falciparum) Erythrocytic schizogony

Answer 10

InP. falciparum,P. vivaxandP. ovale, 12-24 new merozoites are produced about 48 hours after entry into a red blood cell. This erythrocytic cycle takes 72 hours inP. malariaeand 24 hours inP. knowlesi. This asexual reproductive cycle is repeated many times. In severeP. falciparummalaria up to 40% of red blood cells may become infected.

Question 11

The life-cycle of malaria parasites (based onPlasmodium falciparum) Gamete formation

Answer 11

While most merozoites initiate a new asexual cycle, some develop differently to produce uninucleate male (micro) and female (macro) sexual forms, the gametocytes.

Question 12

The life-cycle of malaria parasites (based onPlasmodium falciparum) Gamete formation

Answer 12

Merozoites differentiating into macrogametocytes and microgrametocytes. Image description. Merozoites infect the human host’s red blood cells and either differentiate into first, immature, then mature macrogametocytes which are female, or into first, immature, then mature microgametocytes which are male.

Question 13

The life-cycle of malaria parasites (based onPlasmodium falciparum) Zygote formation

Answer 13

These gametocytes develop to release extracellular male and female gametes in the midgut of another mosquito when taken up in the blood meal. Fertilisation follows, resulting in the formation of azygote(the ookinete), which burrows through the midgut wall, encysts on the outer surface and becomes anoocyst. The fertilisation of the female gamete (macrogametocyte) by the male gamete (microgametocyte) results in an ookinete which becomes an oocyst in the midgut wall of the mosquito.

Question 14

The life-cycle of malaria parasites (based onPlasmodium falciparum) Oocyst growth stages

Answer 14

Within the oocyst there is a third phase of multiplication resulting in the formation of large numbers of sporozoites. These enter the haemocoel, reachingthe salivary glands from where they are able to initiate a new infection when the mosquito feeds. Sporozoites leave the bursting oocyst (attached to the mosquito’s stomach wall), enter the haemocoel then enter the mosquito’s salivary glands and initiate a new infection the next time it feeds. The malaria life-cycle is complex but don’t worry, we’ll come back to it again in Session 5 (Life-cycle of the Plasmodium species) of this section.

Question 15

Question 1 How much of the life-cycle of malarial parasites can you remember so far?

Answer 15

Sporozoitesare injected into the bloodstream by a mosquito. Within 30-60 minutes, sporozoites invade liver hepatocytes and initiate a phase of multiplication resulting in the formation of a pre-erythrocytic schizont. This phase, which is not pathogenic, gives rise to 10,000 uninucleate cells called merozoites .

Question 16

Question 2 Complete the following sentences by entering the missing word into the text boxes.

Answer 16

In the human host, some merozoites differentiate into sexual forms calledgametocytes. Fertilisation follows, resulting in the formation of a zygote called an ookinete which burrows through the midgut wall, encysts on the outer surface and becomes an oocyst. In the next topic, we’ll consider the clinical aspects of malaria…

Question 17

Clinical aspects of malaria

Answer 17

The cycles of multiplication in the blood described in the previous topic are responsible for the symptoms of malaria including the periodic fevers that are caused by the release of various toxic substances when the schizonts mature and the merozoites are released. All species ofPlasmodiumcause anaemia, as you would expect with a parasite that destroys erythrocytes, plus hypoglycaemia. The regular fevers seen with malaria occur when the schizonts in a single infection mature and rupture at the same time. In P. falciparum this synchrony is often not seen in the early stages of infection so there may be daily (quotidian) fevers initially, though the tertian pattern does become established later. The diseases caused by the different parasites are known as:

Question 18

Clinical aspects of malaria P. falciparumtertian malaria

Answer 18

Plasmodium falciparumis the most important of the human species of malaria as it is highly pathogenic. Although present also in Asia and South America, it is particularly concentrated in Africa and is responsible for almost all recorded malaria in sub-Saharan Africa. Along with measles, malnutrition, diarrhoea and pneumonia it is responsible for most of the deaths in children. In addition pregnant women living in highly malarious areas may develop severe anaemia; malaria is an important cause of foetal death. In areas of low transmission all age groups are atrisk and, sometimes,epidemicsoccur.P. falciparumhas a blood stage asexual cycle of 48 hours.

Question 19

Clinical aspects of malaria P. vivaxtertian malaria

Answer 19

Plasmodium vivaxoccurs throughout the tropics and subtropics and is the predominant species in temperate climates. It is very rare in West Africa. Relapses of infection occur because some liver stages (hypnozoites) remain dormant for weeks, months or years, then become activated.The pattern of the relapses varies depending on thestrain of parasiteP. vivax.P. vivaxhas a blood stage asexual cycle of 48 hours.

Question 20

Clinical aspects of malaria P. ovaletertian malaria

Answer 20

P. ovaleis mainly found in tropical Africa whereP. vivaxis rare although it is also present in New Guinea, the Philippines and occasionally reported in other parts of South-East Asia.P. ovale’s global distribution is more limited than the otherPlasmodiumspecies. It produces a type of fever similar to vivax malaria and also relapse but generally milder clinical symptoms.P. ovalehas a blood stage asexual cycle of 48 hours.

Question 21

Clinical aspects of malaria P. malariaequartan malaria

Answer 21

Plasmodium malariaehas a very broad distribution in tropical and subtropical parts of the world, including tropical Africa, south-east Asia and, less commonly, the Americas. It is considerably less prevalent thanP. vivaxandP. falciparum. This parasite affects humans differently from the other species because of its morphological characters and by its slow development in both the human and insect host. The course of the disease is not unduly severe it can cause nephropathy and although the parasite can persist at low levels in the bloodstream for many years.P. malariaehas a blood stage asexual cycle of 72 hours.

Question 22

Clinical aspects of malaria P. knowlesiquotidian malaria

Answer 22

Plasmodium knowlesiinfections occur mainly in South-East Asia where it is frequently misdiagnosed asP. malariaeby microscopy. Normally a parasite of macaque monkeys, transmission to humans by anopheline mosquitoes is from monkeys rather than from other humans. It can cause severe, sometimes fatal malaria in humans and the typical fever is quotidian (daily).P. knowlesitherefore has a blood stage asexual cycle of about 24 hours (Vythilingamet al.2006, Millar & Cox-Singh 2015) .

Question 23

Clinical aspects of malaria Incubation period

Answer 23

Theincubation period, the interval between sporozoite infection and the onset of clinical symptoms, differs for each of the species of malaria, as shown in the table below. We’ll look at that in more detail now. P falciparum 7-27 days, P vivax 13-17 days, P ovale 16-18 days, P malariae 28-30 days, P knowlesi probably 12 days.

Question 24

Clinical aspects of malaria P. falciparumincubation period

Answer 24

When a patient is infected withP. falciparumit takes7-27 days(an average of 12) for the first clinical signs to appear. If the patient lacksimmunity, infection may quickly become an acute form caused by severe anaemia or by sequestration in the brain and other organs. During the last third of the asexual cycle ofP. falciparum, the infected red blood cells stop circulating and stick to endothelial cells of the capillaries. Sequestration of infected erythrocytes in capillaries of the brain plays a role in causing cerebral malaria. Cerebral malaria is often associated with coma, a severe manifestation of the disease, which can have a 20% mortality rate (we will cover this in more detail in Section 2 (The disease) Session 1 (Immunology)). Patients who recover from cerebralmalaria may still suffer lifelong neurological sequelae.P. falciparuminfections do not relapse because there are no hypnozoites) butrecrudescence may occur up to one year later. Infection can persist in the blood for three years in some instances.

Question 25

Clinical aspects of malaria P. vivaxincubation period

Answer 25

The incubation period forP. vivaxis typically about13-17 daysalthough some strains can have long incubation periods of up to 12 months. As already described, an important characteristic ofP. vivaxis the presence and persistence of hypnozoites in the liver, which may produce relapses repeatedly over a period of years. ThereforeP. vivaxis better adapted to survive cooler or dry seasons and transmit itself during summers in temperate zone countries where it was once widespread.

Question 26

Clinical aspects of malaria P. ovaleincubation period

Answer 26

LikeP. vivax,P. ovalehas an incubation period of approximately16-18 daysand persistent hypnozoites in the liver which can produce relapses of infection.

Question 27

Clinical aspects of malaria P. malariaeincubation period

Answer 27

P.malariaehas the longest incubation period of the species, typically28-30 (range 23-69) days. LikeP. falciparumthere is only one cycle ofpre-erythrocyticschizogony. Persistent parasitaemia at low or undetectable levels can lead torecrudescence of symptoms and mixed infections often occur, particularly withP. falciparum.

Question 28

Clinical aspects of malaria P. knowlesiincubation period

Answer 28

P. knowlesihas an incubation period probably of about 12 days and one cycle of pre-erythrocyticschizogony. It can cause severe and often fatal disease in humans.

Question 29

Clinical aspects of malaria

Answer 29

Note: it is better not to use terms like ‘malignant tertian malaria’ forP.falciparumand ‘benign tertian malaria’ forP.vivax. To callP. falciparummalaria malignant implies that the others are non-malignant which is untrue, andP.vivaxis certainly not benign.

Question 30

Immune responses

Answer 30

Most people acquire some degree ofimmunityfollowing infection, and less than 0.5% of those infected with malaria in endemic areas actually die. However, theimmune responseis not very effective. You will study this in detail later in Session 2.1 The disease: Immunology, but you can start thinking about: Why immunity takes a long time to build up, and so requires repeated infections. Why infections in the blood tend to persist for a long time, often at a low level. Why many people can be infected without showing clinical symptoms. The life-cycle of the malaria parasite therefore presents a number of immunological problems for the host, and challenges for the development of effective and safe vaccines. The immune response involves all stages of the life cycle and both antibody and cell-mediated responses are induced. Immunity and pathology are closely linked in malaria. Antibodies, free radicals such as nitric oxide and inflammatory cytokines such as tumour necrosis factor (TNF) are involved in both protection and pathology (we will cover this in more detail in Session 2.2 The disease: Pathology and pathogenesis). Progress that has been made towards development of vaccines is described in Session 3.6 Epidemiology and prevention: Vaccination.

Question 31

Diagnosis

Answer 31

Diagnosis of malaria has advanced considerably in recent years and we shall consider in particular how this has improved treatment,control and epidemiology. To begin, you should answer the following question:

Question 32

Question 3 Which of the following do you think are commonly used routinely to diagnose malaria in a clinical setting in endemic countries?

Answer 32

Microscopy and antigen detection are commonly used routinely to diagnose malaria in a clinical setting in endemic countries. As with all parasitic infections, microscopy is the gold standard for diagnosing malaria with use of thick and thin blood films. There are also a number of rapid diagnostic tests (RDT) available that are based on immunochromatographic (dipstick) detection of Plasmodium-specific molecules. Antibody detection (serology) is incorrect because, although DNA probes and PCR are much more sensitive than blood film and RDT tests, and are being used for detection of low-grade infections, this is not yet being done routinely (we will look at these procedures in more detail in Section 4 (Treatment and prevention) Session 2 (Treatment)). There is currently no diagnostic urine test for malaria

Question 33

Entomology, epidemiology and control Entomology

Answer 33

Malaria is transmitted by female mosquitoes of the genusAnopheles. Eggs are laid in water and hatch into larvae that moult to give rise to pupae and, subsequently, adults. Only the females suck blood, which they require for egg production (we will cover this and the role of the mosquitoes as vectors of malaria in more detail in Session 1.6Parasites and vectors: Mosquitoes and their life-cycles). Image description: Its body bent so far forward towards the skin surface, makes this feeding female Anopheles merus mosquito appear to almost topple over. Viewed from the lateral perspective, the specimen had landed on a human hand, and was in the process of obtaining its blood meal through its sharp, needle-like labrum, which it had inserted into its human host. Note the reddish color of the labrum, as it was filled with blood. Also note the red-colored abdomen that had become enlarged due to its blood meal contents. A. merus is a member of the A. gambiae species complex. This image depicts a lateral view of a feeding female Anopheles albimanus mosquito. This specimen had landed on a human skin surface, and was in the process of obtaining its blood meal through its sharp, needle-like labrum, which it had inserted into its human host. Note the red colour of the labrum, as it was filled with blood, and the bright-red abdomen that had become enlarged due to its blood meal contents.

Question 34

Entomology, epidemiology and control Epidemiology

Answer 34

Malaria is one of the most ancient diseases of humans and at one time affected almost every country of the tropical and temperate world between the latitudes of 64°N and 30°S but is now almost entirely confined to the tropics. The actual distribution depends on a number of factors affecting the survival of the mosquito, including altitude and humidity as well as on the duration of sporogony which is affected by temperature. In colder climates the length of sporogony can be longer than a mosquito’s life expectancy and therefore transmission is restricted. Within any locality, the prevalence of the disease depends on the numbers of infected individuals and their level of immunity and access to treatment, as well as the characteristics and numbers of the mosquito vector species. Among several classifications used in malaria epidemiology, the most useful are endemic or epidemic, and stable malaria or unstable malaria, terms which are self-explanatory but will be described later in more detail.

Question 35

Entomology, epidemiology and control Control

Answer 35

There are two maincontrolstrategies: anti-mosquito or anti-parasite. Measures to control malaria transmission are directed against both the adults and larvae of the Anopheles vectors.

Question 36

Question 4 From the outline you have been given of theAnophelesmosquito life cycle, can you think of any anti-mosquito measures that might be effective in controlling transmission?

Answer 36

Controlmeasures might include: elimination or minimisation of water collections where mosquito vectors lay eggs and undergo larval development, applying larvicides to water habitats, breeding of fish that feed on larvae, use of bed-nets, especially insecticide-impregnated nets (ITN), applying insecticides to walls of houses, so-called indoor residual spraying (IRS), personal protection such as clothing and insect repellents, and reducing vector populations through release of appropriate genetically-engineered mosquitoes. Unfortunately, the spread of insecticide resistance has seriously affected mosquitocontrolprogrammes (we will look at this in more detail in Session 4.1Treatment and prevention: Biochemistryand Session 5.1Some practical aspects: Laboratory and field diagnosis).

Question 37

Entomology, epidemiology and control Chemotherapy

Answer 37

Anti-parasite measures are currently restricted to the use of antimalarial drugs for chemoprevention or cure. WHO has recommended widescale use of the first malaria vaccine, RTS,S/AS01, in 2021. However roll out is only expected to start in late 2023. As a result of widespread resistance developing to once common and relatively inexpensive drugs, such as chloroquine and sulphadoxine in P. falciparum, artemisinin-based combination therapies (ACTs) have now become the standard first-line treatment, particularly for falciparum malaria. Combining drugs is believed to slow the development of drug resistance and we shall consider which drugs and drug combinations are used. There are also a number of promising new drugs at various stages of development (we will look at this issue in more detail in Session 4.2 Treatment and prevention: Treatment.

Question 38

Entomology, epidemiology and control International initiatives for malaria control

Answer 38

The World Health Organization developed aGlobal Technical Strategy (GTS) for Malaria 2016–2030which sets out targets for elimination and control of malaria over this period. The GTS was updated in 2021 following review of progress against the 2020 targets and can be accessed from the WHO website, using the link above. The Global Fund to Fight AIDS, Tuberculosis and Malaria is a financing partnership providing support to countries most in need and aimed at eliminating the three diseases. Details may be accessed through the website, linked above.

Question 39

Question 5 From your reading, can you identify five examples of strategies that are contributing to recent successes in malariacontrol in some countries?

Answer 39

Widespread indoor residual spraying (IRS), Use of inexpensive, quality-assured rapid diagnostic tests (RDTs), Increasing insecticide-treated mosquito nets (ITN) ownership, Provision of sufficient courses of artemisinin-based combination therapies (ACTs), and Intermittent or seasonal preventive treatment (IPT) of vulnerable populations in high transmission areas with anti-malaria drugs. We will look at the WHO and other international efforts to control malaria in more detail in Section 4.1Treatment and prevention: Biochemistry.

Question 40

Entomology, epidemiology and control Impact of climate change on malaria

Answer 40

The spatial limits of malaria distribution and seasonal activity are sensitive to climate factors (Caminadeet al.2014). Global environmental change is expected to affect profoundly the transmission of the parasites that cause human malaria, with evidence suggesting a strong correlation between malaria incidence and changes in temperature, rainfall and humidity. Amongst the anthropogenic drivers of change, the loss of natural forest cover (‘deforestation’) is arguably the most conspicuous, and its rate is projected to increase in the coming decades (Guerra et al. 2006). An estimated 8.4 billion people could be at risk from malaria and dengue by the end of the century if emissions keep rising at current levels (Colon-Gonzalez et al. 2021).

Question 41

Entomology, epidemiology and control Impact of climate change on malaria

Answer 41

Malaria suitability is estimated to gradually increase as a consequence of a warming climate in most tropical regions, especially highland areas in the African region (e.g. Ethiopia, Kenya and South Africa), the Eastern Mediterranean region (e.g. Somalia, Saudi Arabia and Yemen), and the Americas (e.g. Peru, Mexico and Venezuela).The predicted expansion towards higher altitudes and temperate regions suggests that outbreaks can occur in areas where people might be immunologically naïve and public health systems unprepared. In regions already affected by the disease, the impact of climate on malaria is mainly related to changing rainfall patterns, or increased flooding risk. Areas of standing water created by heavy rainfall provide breeding grounds for malaria-carrying mosquitoes. Now, rainy seasons are getting more erratic, and increased flooding due to rising sea levels adds to the danger.

Question 42

Entomology, epidemiology and control Malaria and landscape factors

Answer 42

Land use and land cover changes, such as deforestation, agricultural expansion and urbanisation, are one of the largest anthropogenic environmental changes globally. Recent initiatives to evaluate the feasibility of malaria eradication have highlighted impacts of landscape changes on malaria transmission and the potential of these changes to undermine malaria control and elimination efforts (Fornace et al. 2021). Deforestation has been found to heighten malaria risk factors in some settings, suggesting that in some circumstances forest conservation could belong in a portfolio of anti-malaria interventions. Image description: Mapping changes to land cover in Sabah, Malaysia. (A) Study site in February 2014. (B) Same study site in May 2014 after the start of clearing to create a rubber plantation. Deforestation can increase malaria risk factors such as mosquito growth rates and biting rates in some settings. But deforestation affects more than mosquitoes – it is associated with socio-economic changes that affect malaria rates in humans (Bauhoff & Busch 2020). The complexity of land-use changes driving deforestation such as urbanisation, agriculture, irrigation or resource mining can alter the environment in different ways. For example, deforestation in the Amazon has been shown to increase mosquitoes’ larval habitat through the creation of areas with abundant sunlight and pooling water, resulting in increased human biting activity (Vittor et al. 2006). Alternatively, immigration and rapid population movements, stirring human-vector interactions, are other mechanisms affecting malaria transmission in frontier areas.

Question 43

Question 6 All malarial diseases are characterised by what? Select your answer(s) from the options below. You can select more than one option. Anaemia and hypoglycaemia, Periodic fevers interspersed with periods of intense chill, Coma, Skin rashes

Answer 43

All malarial diseases are characterised anaemia and hypoglycaemia and periodic fevers interspersed with periods of intense chill. A coma is the result of sequestration of infected red blood cells causing cerebral malaria and this is only characteristic of P. falciparum and not all five diseases. Skin rashes are not characteristic of malaria patients.

Question 44

Question 7 Diagrammatic representation of the life-cycle

Answer 44

Need to go to the word document

Question 45

Question 8 Now, select the correct host location below for each label (A-M).

Answer 45

Need to go to the word document

Question 46

Question 9 On average, which of the species of malaria has the longest incubation period?

Answer 46

P. malariaehas the longest incubation period of the five species, typically 28-30 (range 23-69) days. The incubation period for P. falciparum is typically about 7-27 days. The incubation period for P. vivax is typically about 13-17 days. The incubation period for P. vivax is typically about 16-18 days. The incubation period for P. knowlesi is thought to be about 12 days.

Question 47

Summary

Answer 47

About 50% of the world’spopulation presently live in countries where malaria transmission occurs; 241 (range 218-269) million people were infected and 627 (range 583-765) thousand deaths occurred in 2020, mostly children in sub-Saharan Africa.

Question 48

Summary

Answer 48

Human malaria is caused by infection with five species of protozoan parasites belonging to the genusPlasmodium:P. falciparum,P. vivax,P. malariae, andP. ovaleand transmitted between infected persons by female mosquitoes belonging to the genusAnopheles.P. knowlesiis a monkey malaria parasite that can be naturally transmitted byAnophelesvectors to humans in South East Asia.

Question 49

Summary

Answer 49

The life-cycle ofPlasmodiumis complex and involvessporozoitesinjected by a mosquito, anexoerythrocyticphase in the liver, repeated cycles ofschizogonyin the blood, the formation of sexual stages andsporogonyin another mosquito

Question 50

Summary

Answer 50

Malaria infections are characterised by periodic fever, anaemia andhypoglycaemiaand, inP. falciparum,sequestrationof infected red blood cells which can cause cerebral malaria

Question 51

Summary

Answer 51

Someimmunityto malaria is usual but immunity takes a long time to build up and requires repeated exposure to infection.

Question 52

Summary

Answer 52

Control measures are directed toward: a) Prevention, reducing vector populations and human-vector contact, and the use of drugs as chemoprevention in vulnerable groups. In 2021 WHO recommended widescale use of the first, partially effective, malaria vaccine, RTS,S/AS01. b) Case management, through early diagnosis and effective drug treatment of patients.

Question 53

Glossary Endemic

Answer 53

Epidemiological term describing an infection in a community where it is maintained with constantincidenceofcasesfor many years without external inputs.

Question 54

Glossary Morbidity

Answer 54

Any departure, subjective or objective, from a state of physiological or psychological well-being. In practice, morbidity encompasses disease, injury, and disability

Question 55

Glossary Anopheline

Answer 55

A common adjective applied to mosquitoes belonging to the genusAnopheles.

Question 56

Glossary Sporozoite

Answer 56

The final product ofsporogony. Sporozoites migrate to the salivary gland of the mosquito.

Question 57

Glossary Hepatocyte

Answer 57

A liver cell responsible for synthesis, degradation and storage. Hepatocytes make up 70% of the liver.

Question 58

Glossary Exoerythrocytic

Answer 58

Exoerythrocytic (or pre-erythrocytic) defines the malaria parasite (sporozoite) at the liver stage of infection. Replication within thehepatocytesis often described as exoerythrocytic (or pre-erythrocytic)schizogony. However it is important to note that the termpre-erythrocyticis also used to describe the stages of the malaria parasites (merozoitesreleased from mature hepaticschizonts) that appeared before parasites invade the blood cells.

Question 59

Glossary Schizont

Answer 59

Last stage of plasmodial replication withinhepatocyteanderythrocytesby which nuclear division of the malaria parasite has finished and discretemerozoiteshave started to form within the infected cell.

Question 60

Glossary Merozoites

Answer 60

Part of the asexual reproductive cycle ofplasmodia: in malaria, the parasite stage released by mature liver and bloodschizonts, and responsible for invadingerythrocytes.

Question 61

Glossary Erythrocyte

Answer 61

Red blood cell.

Question 62

Glossary Trophozoite

Answer 62

The earlyerythrocyticfeeding stage of the malaria parasite that later becomes aschizont.

Question 63

Glossary Normal distribution

Answer 63

A bell-shaped distribution which is symetrical (probably the most important distribution instatistics). Also called z-distribution.

Question 64

Glossary Oocyst

Answer 64

In the malaria parasite, a structure formed around thezygotewithin which the development ofsporozoitesoccurs.

Question 65

Glossary Epidemic

Answer 65

A diseaseoutbreakin which the number ofcasesincreases significantly over the normal,endemic, background level, in a specified, geographically definedpopulationgroup.

Question 66

Glossary Incubation period

Answer 66

The interval from receipt of infection to the time of onset of clinical symptoms.

Question 67

Glossary Immunity

Answer 67

The ability to resist infection.

Question 68

Glossary Immune response

Answer 68

The cellular and molecular events that result inimmunity.

Question 69

Glossary Antibody

Answer 69

Immunoglobulinmoleculesecreted byB cells.

Question 70

Glossary Pathology

Answer 70

The anatomical changes produced as a result of a disease process.

Question 71

Glossary Cytokine

Answer 71

A smallproteinmessenger which mediates communication between cells of theimmune system.

Question 72

Glossary Tumour necrosis factor

Answer 72

A pro-inflammatorycytokine. Also called tumour necrosing factor. Abbreviated to TNF.

Question 73

Glossary Prevalence

Answer 73

Theproportionof individuals with the infection or disease of interest in a definedpopulationat a specific point in time. Prevalence is determined by dividing the number of people estimated to be infected by the total population size. Prevalence is most commonly measured at a single point in time (the ‘point prevalence’). Compare with the definition ofincidence.

Question 74

Glossary Schizogony

Answer 74

The phase of asexual multiplication of the malaria parasite inhepatocytesorerythrocytes. The final product is aschizontwhich on maturation ruptures to releasemerozoites.

Question 75

Glossary Sporogony

Answer 75

The sexual development of the malaria parasite in a mosquito.

Question 76

Glossary Hypoglycaemia

Answer 76

Physiological state of low level of glucose (sugar) in blood.

Question 77

Glossary Sequestration

Answer 77

In malaria, a process in whichschizonts, infectederythrocytesandleukocytesstop circulating and attach to vascularendothelium. This process can lead tocerebral malaria. Also called cytoadherence.