Case 2: Dave ILOs

For this first case only, we will provide some ILOs to ensure that you all cover the essential areas of
the case.
Please remember you should construct detailed answers, including specific quantifiable information
wherever possible, this needs to be evidence based and fully referenced.
You should also critically evaluate the information you investigate to link to the patient pathway and
care provision.

Pathophysiology
What can cause pyrexia in humans? What is the mechanism behind this? (Maggie)
Pyrexia, also known as fever, is when an individual’s core body temperature exceeds a ‘set point’ regulated by
the body’s thermoregulatory centre in the hypothalamus. The normal temperature of the human body is
approximately 37oc, but can vary by up to 1oc throughout the day in healthy individuals. The most common
cause of pyrexia is,
• Viral infections
• Bacterial infections
• Heat exhaustion
• Certain inflammatory conditions such as rheumatoid arthritis
• A malignant tumour
• Some medications, such as antibiotics and drugs used to treat high blood pressure or seizures
• Some immunizations, such as the diphtheria, tetanus, pneumococcal or COVID vaccine
Pyrogens are substances that cause fever. Exogenous pyrogens are usually microbes or their products. Fever is
the result of exogenous pyrogens that induce release of endogenous pyrogens, such as interleukin-1 (IL-1),
tumour necrosis factor-alpha (TNF-alpha), and IL-6 and other cytokines, which then trigger cytokine receptors,
or of exogenous pyrogens that directly trigger Toll-like receptors.
(Balli S, Shumway KR, Sharan S. Physiology, Fever. [Updated 2023 Sep 4]. In: StatPearls [Internet]. Treasure
Island (FL): StatPearls Publishing; 2024 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK562334/)
(10.1186/s13054-016-1375-5)

What other symptoms are seen and what is the mechanism behind these? (Maggie)
Other symptoms observed
Myalgia - Myalgia describes muscle aches and pain. Malaria infection induces a combination of
inflammation and oxidative damage in skeletal and cardiac muscles leading to the enhanced
degradation of key contractile proteins, which in turn is responsible for the compromised muscle
function. (Marrelli, M.T. and Brotto, M. (2016) ‘The effect of malaria and anti-malarial drugs on
skeletal and cardiac muscles’, Malaria Journal, 15(1). doi:10.1186/s12936-016-1577-y.)
Headache – headaches from malaria are believed to be caused by pro-inflammatory cytokines, such
as tumour necrosis factor and interleukin 1, produced in response to a malarial infection.
(Wiwanitkit V. Headache and malaria: a brief review. Acta Neurol Taiwan. 2009 Mar;18(1):56-9.
PMID: 19537576.) This symptom could also be caused by the doxycycline which has been prescribed.
Diarrhoea - Tumor necrosis factor has been implicated in malaria and free oxygen radicals which can
cause tissue injury in the liver, pancreas and intestine are enhanced during malaria infection. This
can result in various disorders of the digestive system including diarrhoea and intestinal bleeding.
(Prasad RN, Virk KJ. Malaria as a cause of diarrhoea--a review. P N G Med J. 1993 Dec;36(4):337-41.
PMID: 7941765.) Diarrhoea is also a side effect of doxycycline.
Visible dehydration – this is most likely caused by the diarrhoea.
Lower abdominal cramping – most likely caused by the same mechanism causing the diarrhoea.
Tinnitus – is a rare side-effect of doxycycline

Patient history/Risk factors

Why was travel history important? (Maggie)
Travel history is important because malaria is endemic in certain areas of the world. Establishing if a patient
has travelled to one of these countries, narrows down the possible diagnosis, speeding up treatment time. It
also helps to differentiate between which strain of malaria a patient has, by identifying which parasite are
most common in that area. Once the strain is identified, information on the life cycle is available. This allows
treatment to be specific and targeted. (Ahmed, S. et al. (2020) ‘Travel is a key risk factor for malaria
transmission in pre-elimination settings in Sub-Saharan africa: A review of the literature and meta-analysis’,
The American Journal of Tropical Medicine and Hygiene, 103(4), pp. 1380–1387. doi:10.4269/ajtmh.18-0456.)

What other risk factors are associated with this clinical presentation? - (Elsa) -
Risk factors associated with malaria including age (young adults and infants, elderly are at greater
risk of serious complications), immunocompromised/immunosuppressed patients, travellers
(especially those who have recently travelled to areas where malaria is endemic), pregnant women
and neonates, geographical location, distance to mosquito breeding sites, household construction,
the level of household crowding, poor housing conditions, personal protection measures against
mosquitoes, lack of knowledge and education about prevention of malaria, (Essendi et al, 2019).

Diagnostics
What is the differential diagnosis for this patient and why? - (Elsa) -
Differential diagnosis for malaria includes meningitis or encephalitis, lower respiratory tract
infections, influenza or other viral infection such as Epstein-Barr virus or cytomegalovirus,
gastroenteritis, UTI, lymphoma, sepsis, viral hepatitis, HIV seroconversion, Legionella, Leptospirosis.
In terms of other travel related infections;
Lassa fever, Crimean-Congo haemorrhagic fever, Marburg and Ebola.
Typhoid – symptoms of typhoid are similar to malaria, weakness, stomach pain, diarrhoea,
headache.
Dengue, West Nile virus and Japanese encephalitis.
Trypanosomiasis.
Rabies.
Chikungunya
Often these other diagnoses have similar or the same symptoms, as well as this a lot of these
diseases (especially the later half) are endemic in Thailand, this includes malaria, chikungunya, HIV,
Hepatitis A and B, Zika, typhoid, Japanese encephalitis, leptospirosis, respiratory infections.
(NICE, 2024).

What is typhoid and how is it diagnosed? - (Elsa)

A prospectively, multisystemic illness caused by Salmonella typhi and Salmonella paratyphoid. It is
an enteric fever which is characterised by systemic illness along with abdominal pain and fever.
Paratyphoid fever is clinically indistinct from typhoid fever. Major cause of mortality and morbidity
in overcrowded unhygienic areas. Transmitted by faecal-oral route through contaminated water,
undercooked foods, fomites of infected patients. Humans are the only host. Malnutrition as well as
the use of streptomycin destroy and disrupt the normal flora which heightens the invasion and
increases susceptibility to this infection (Bhandari et al, 2022).
Diagnosing.
Blood culture (only positive in 40-60% of cases, therefore low sensitivity (40-80%).
Stool and urine cultures usually positive after the first week of infections, sensitivity is even lower
(stool culture sensitivity 31.3% and specificity 91.5%).
Thrombocytopenia may be a marker of severe illness and accompany disseminated intravascular
coagulation (Bhutta et al, 2006).
Typhidot and Typhidot-M serological testing to detect IgM and IgG antibodies (sensitivity 90.3%,
specificity 93.1%)
For resistant subtypes - screening for presumptive isolates of S.typhi and S.paratyphi for resistance
to third generation cephalosporins with discs or gradient strips using EUCAST methodology.
(GOV.UK, 2017)

What are the lifecycles of Plasmodium spp.?- (Jasmine)

(CDC, 2019)
What are the different stages seen on the blood?- (Jasmine)

How does the lab perform each of the tests?- (Jasmine)

How does the lab test for malaria? (detailed explanations of all relevant tests)- (Angena)

Sample required for diagnosis: an EDTA-anti-coagulated venous blood sample.

Depending on local protocols, your department of microbiology or haematology will diagnose

malaria by microscopic analysis of thick and thin blood films.

Blood test:

Within an hour of the blood sample being drawn, the laboratory should receive it. It is not
necessary to wait on giving blood until after fever spikes.
Blood films and a portion of the blood sample used to make the diagnosis should be sent by
all laboratories diagnosing malaria to the Malaria Reference Laboratory for validation.

Blood film negative malaria

When blood films are negative, a diagnosis of malaria cannot be ruled out; thus, blood films
should be checked every day for three days while alternative diagnoses are taken into
account.

What is the significance of parasitaemia?- (Angena)

Parasitaemia a condition in which parasites are present in the blood. It is used especially to
indicate the presence of parasites without clinical symptoms. Higher parasitemias are
associated with an increased risk of death, anemia and recrudescence of the infection
following treatment.

What is the testing protocol for malaria diagnosis and monitoring? - (Angena)

What are the technical and clinical significance of each of the results? (sahand)
Malaria tests can be blood smear, rapid diagnostic test, and PCR. There are different types of malaria
parasites that infect humans. The tests can tell which type you have. This information is important for
choosing the right treatment to cure the disease.
Malaria testing is also used to help control the spread of the disease. That's because mosquitos
become infected with malaria parasites when they bite a person who has malaria. Then they spread
the disease by biting others. Testing helps you get treatment to get rid of the parasites before more
mosquitos get the parasite by biting you. (MedlinePlus,2020)

Treatment/prognosis
What is prophylaxis? (sahand)
The term prophylaxis means preventive. It comes from the Greek word “phylax,” meaning “to
guard” and “watching.” Prophylactic treatment is used in healthcare to preserve health and prevent
the spread of disease, The term prophylactic antibiotics refers to antibiotics that are given to prevent
infection rather than treat it. (verywellhealth,2022)

What prophylaxis is available for malaria? When would this be used and how effective is it? (sahand)
Malarial chemoprophylaxis functions by targeting the liver schizont, blood schizont, or hypnozoite
stages of the plasmodium life cycle. The three most commonly prescribed medications for
chemoprophylaxis are atovaquone-proguanil, doxycycline, and mefloquine, Studies examining the
efficacy of the medications have found them all to be equally effective in the prevention of malaria in
short-term travellers, but atovaquone-proguanil and doxycycline appear to have the fewest side
effects. For long term travellers, studies suggest that adherence is lower in young travellers and those
on mefloquine. (NIH, 2023)
• Some tablets need to start a few days before you travel, whilst others may need to be started a week or
more before travel. This means there will be enough antimalarial medication in your system to start
preventing infection as soon you arrive in the country.

• 1) What is the mode of action of each therapy? (Suraj)

• There are two antimalarial drug (medication) is given to the patient.
• 1)Doxycycline (primarily developed as an antibiotic, doxycycline works as an antimalarial drug
by preventing the growth and multiplication of Plasmodium parasites, which are responsible
for malaria. It does this via several methods, including:
• Inhibition of Protein Synthesis: Doxycycline attaches itself to the parasite's 30S
ribosomal subunit, causing disruptions in the process and impeding the synthesis of
vital proteins required for the parasite's survival. (PubMed)

• Interference with Parasite Metabolism: Doxycycline inhibits parasites from effectively

metabolizing food items and producing energy, which hinders their capacity to grow
and survive. This is achieved by upsetting metabolic pathways.
•
• Decrease in Parasite Load: Doxycycline contributes to the body's general decrease in
parasite load, which helps to relieve malaria symptoms and eradicate the infection.
•

2) Quinine (Inhibition of Parasite Growth: Quinine inhibits Plasmodium parasites from

developing and growing in number, especially Plasmodium falciparum, which is the species
that causes the most severe type of malaria. It achieves this by focusing on the parasites at
various phases of their life cycle, such as the erythrocytic stage, during which they multiply
inside red blood cells.

Quinine Disrupts Parasite Metabolism: Quinine interferes with the Plasmodium parasites'
capacity to digest foods and produce energy by interfering with their metabolic processes. The
disruption impairs the parasites' strength and prevents them from multiplying inside the host's
body.i1

Interference with Haemoglobin Digestion: During their intraerythrocytic stage, Plasmodium

parasites break down haemoglobin as a source of nutrition. Quinine obstructs this process by
preventing the parasites from degrading haemoglobin.) (CDC)

2) What treatments are available for malaria infection? (Suraj)

1) Antimalarial Drugs: These are prescriptions created especially to combat malaria. The type of
malaria parasite causing the infection and the area from which it originated determine which
medication is best. Typical antimalarial medications include:
• Chloroquine

1
• Artemisinin-based combination therapies (ACTs) like artemether-lumefantrine, artesunate-
amodiaquine, and dihydroartemisinin-piperaquine.
• Quinine
• Mefloquine
• Atovaquone-proguanil
• Doxycycline
• Primaquine
2)Vector Control: Since infected mosquitoes bite people carrying the malaria virus, vector control
strategies include environmental management and mosquito control programs may help stop the
disease's spread.
3)Preventive methods: To lower the risk of infection in places where malaria is endemic, preventive
measures such indoor residual spraying, bed nets coated with insecticide, and prophylactic
antimalarial drugs may be advised.
4) Others
Patients may need supportive care in addition to antimalarial medication in cases of severe malaria,
particularly those brought on by Plasmodium falciparum. Among the things that supportive care
might include:
intravenous hydration to avoid being dehydrated
Transfusions of blood in patients with severe anaemia
When a patient has respiratory distress, oxygen therapy
treatment for side effects include renal failure or brain malaria. (WHO)

3) How is transmission to others prevented? (Suraj)

Chemoprophylaxis: People at risk of infection, such as visitors to endemic regions, may take
antimalarial drugs to prevent infection in areas where malaria is endemic. We refer to this as
chemoprophylaxis.
Screening and Surveillance: Screening and surveillance programs help monitoring the
prevalence and geographic distribution of malaria as well as the identification and monitoring
of cases. Active case detection can be useful in finding and treating asymptomatic carriers
who may be responsible to continued transmission, especially in high-risk populations like
refugees or migrant workers.

Community Education and Engagement: Programs for community-based health education

may enhance knowledge about safeguarding and control approaches to malaria, improve
early detection and treatment-seeking behavior, and foster community engagement in vector
control efforts. (CDC 2019)

Your work should include but not be limited to the above. You should answer all ILOs in
detail and add your own where appropriate. Think about infection in general and the
significance of travel., with a focus on the details of malaria infection.

References for our information.

Essendi et al (2019) - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591804/
NICE (2024) - https://cks.nice.org.uk/topics/malaria/diagnosis/differential-diagnosis/
Bhandari (2022). - https://www.ncbi.nlm.nih.gov/books/NBK557513/
GOV.UK (2017) -
https://assets.publishing.service.gov.uk/media/5a82024640f0b62305b91fdd/hpr4517_S-
TYPHI_ARA.pdf
Bhutta et al (2006) - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1489205/
https://www.severemalaria.org/severe-malaria/severe-malaria-criteria-features-definition
CDC, (2019) -
https://www.cdc.gov/malaria/about/biology/index.html#:~:text=The%20malaria%20parasite
%20life%20cycle,which%20rupture%20and%20release%20merozoites%20.