Microbiology
Pathogens
Which of the following is the gold standard for diagnosis of malaria:
Answer:
Thick and thin blood films are gold standard for diagnosis of malaria. Three negative blood films are required to exclude a diagnosis. Thick blood film is used for malaria diagnosis and thin blood film to diagnose the species of Plasmodium. Newer, more rapid antigen detection tests may also be used.Malaria
Microbiology / Pathogens / Malaria
Last Updated: 25th May 2023
Malaria is an infection of red blood cells caused by a protozoan parasite. Endemic malaria is predominantly found in the tropics and subtropics.
Species
There are four different Plasmodium species relevant in humans:
- Plasmodium falciparum
- Plasmodium vivax
- Plasmodium ovale
- Plasmodium malariae
Some red blood cell defects (e.g. sickle cell disease, thalassaemia and glucose 6-phosphate dehydrogenase deficiency) confer some protection against P. falciparum malaria.
Life Cycle
- Transmission
- The Plasmodium spp. is transmitted to the human host by the bite of the female Anopheles mosquito, which injects sporozoites present in its salivary glands into the bloodstream.
- Hepatic stage
- The sporozoites travel to the liver where they invade, replicate and mature in liver parenchymal cells over 1 - 2 weeks (asymptomatic period) to form hepatic schizonts.
- The hepatic schizonts subsequently rupture releasing merozoites into the bloodstream.
- Some sporozoites from latent hepatic schizonts (hypnozoites) that can reactivate months to years later (P. ovale and P vivax only).
- Erythrocytic stage
- The released merozoites invade erythrocytes and multiply rapidly forming erythrocytic schizonts.
- The erythrocytic schizont subsequently ruptures releasing more merozoites into the bloodstream and resulting in destruction of the RBC, provoking an acute inflammatory response with release of cytokines responsible for most of the clinical features of malaria.
- Reproductive stage
- Some merozoites develop into gametocytes which can reenter the Anopheles mosquito when an infected individual is rebitten, and develop in the mosquito gut into sporozoites, which migrate to the insect's salivary glands.
![By CDC/Alexander J. da Silva, PhD/Melanie Moser [Public domain], via Wikimedia Commons](https://primary-cdn.frcemsuccess.com/wp-content/uploads/2017/02/Plasmodium-lifecyle.jpg)
Life Cycle of Plasmodium Falciparum. (Image by CDC/Alexander J. da Silva, PhD/Melanie Moser [Public domain], via Wikimedia Commons)
Clinical Features
Malaria may be “uncomplicated” or “severe.”
- Uncomplicated malaria: Symptoms may include fever, chills, sweats, headaches, muscle pains, nausea and vomiting.
- Severe malaria: Symptoms may include confusion, coma, focal neurologic signs, severe anaemia, and respiratory difficulties. A patient with symptoms of severe malaria should be assessed quickly and treated immediately. Severe malaria is most often caused by the most dangerous parasite, Plasmodium falciparum.
Complications of malaria include:
- Cerebral involvement
- Anaemia
- Metabolic and lactic acidosis
- Renal failure
- Pulmonary oedema
- Hypoglycaemia
- Hypovolaemia/shock
- Bleeding/DIC
- Jaundice
Diagnosis
Malaria should be considered in all acutely unwell or pyrexic travellers returning from endemic areas.
A thick and thin blood film examined by an experienced microscopist and correlated with a clinical history is the gold standard for diagnosis. Diagnosis is made with serial blood film examination - three negative malaria smears 12 - 24 hours apart blood films are required to exclude a diagnosis. Thick blood film is used for malaria diagnosis and thin blood film to diagnose the species of Plasmodium.
Newer, more rapid antigen detection tests may also be used. Antigen dipstick tests are simple but have three main problems:
- they are less sensitive than microscopy
- they rely on detecting parasite antigen rather than live parasite and may therefore be positive in patients who have been recently treated (up to 2 weeks) or come from a malaria endemic area and have a low level of asymptomatic parasitaemia,
- it is not possible to determine the parasitaemia or stage of parasite
Classification:
- Uncomplicated:
- Parasitaemia ≤2% and no schizonts (on blood film) and no clinical complications
- Severe:
- Severe Parasitaemia >2%
- or Parasitaemia ≤2% with schizonts reported on blood film
- or Parasitaemia ≤2% with complications (see list above)
Treatment
Please note:
- Malaria is a notifiable disease in England, Northern Ireland, and Wales.
- Expert advice must be sought in all patients suspected to have malaria.
- The recommendations on treatment reflect UK malaria treatment guidelines 2016, agreed by UK malaria specialists. They are aimed for residents of the UK and for use in a non-endemic setting.
- If the infective species is not known, or if the infection is mixed and includes falciparum parasites, initial treatment should be as for falciparum malaria.
FALCIPARUM MALARIA:
Patients with falciparum malaria should usually be admitted to hospital initially due to the risk of rapid deterioration even after starting treatment.
Artemisinin combination therapy is recommended for the treatment of uncomplicated P. falciparum malaria. Artemether with lumefantrine is the drug of choice; artenimol with piperaquine phosphate is a suitable alternative. Oral quinine or atovaquone with proguanil hydrochloride can be used if an artemisinin combination therapy is not available. Quinine is highly effective but poorly-tolerated in prolonged treatment and should be used in combination with an additional drug, usually oral doxycycline.
Severe or complicated falciparum malaria should be managed in a high dependency unit or intensive care setting. Intravenous artesunate (available for ‘named-patient’ use from infectious disease units or specialist tropical disease centres) is indicated in all patients with severe or complicated falciparum malaria, or those at high-risk of developing severe disease (such as if more than 2% of red blood cells are parasitized), or if the patient is unable to take oral treatment. Following a minimum of 24 hours of intravenous artesunate treatment, and when the patient has improved and is able take oral treatment, a full course of artemisinin combination therapy should be given. A full course of oral quinine with doxycycline, or atovaquone with proguanil hydrochloride are suitable alternatives.
Treatment of severe or complicated falciparum malaria should not be delayed whilst obtaining artesunate. Quinine by intravenous infusion should be given if artesunate is not immediately available; it should be continued until the patient can take oral quinine to complete a full course. Oral doxycycline should also be given when the patient can swallow.
In most parts of the world, P. falciparum is now resistant to chloroquine which should not therefore be used for treatment. Mefloquine is also no longer recommended for treatment because of concerns about adverse effects and non-completion of courses.
FALCIPARUM MALARIA IN PREGNANCY:
Falciparum malaria in pregnancy carries a higher risk of severe disease; it requires prompt treatment by specialists in hospital and close observation. Uncomplicated falciparum malaria in the second and third trimesters of pregnancy should be treated with artemether with lumefantrine. Quinine with clindamycin can be used in all trimesters. Quinine can increase the risk of uterine contractions and hypoglycemia.
Severe or complicated falciparum malaria is associated with a high risk of fatality, pregnancy loss, and complications. Due to efficacy, treatment with intravenous artesunate in any trimester of pregnancy is preferred; intravenous quinine (with clindamycin) can be used as an alternative if artesunate is not available.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
