The clinical signs and symptoms of malaria

Learn how to recognize the clinical signs and symptoms of malaria from our expert in this Clinical Guide article.
Last update29th Apr 2021

The process from initial infection to the clinical manifestations of malaria is known as the incubation period and takes approximately six weeks. But what clinical signs help us to identify malaria?

Malaria infection and the hypothalamus

Remember, in the life cycle of malaria, that after infection, the Plasmodium sporozoites travel to the liver where they divide. Once inside the liver merozoites, or small parasitic cells, are released into the bloodstream. From there, red blood cells (RBCs) are invaded, and the merozoites continue to divide, filling the RBCs until they burst. This releases parasites, along with malaria pigment and deoxyribonucleic acid (DNA). These components are picked up by the immune system, activating inflammatory processes that target the hypothalamus. The hypothalamus responds by resetting the patient’s central thermostat to a higher than normal temperature, say 39°C.

Figure 1. When infected red blood cells (RBCs) burst, releasing malarial parasites, pigment and deoxyribonucleic acid (DNA), an immune response is triggered causing the hypothalamus to reset the patient’s central thermostat to a higher temperature.

The cold stage of malaria

In response to a change in its central thermostat temperature, the body shivers to generate heat. Shivering raises body temperature to reach the temperature that was set in the hypothalamus. This is the cold stage of malaria, where the patient will exhibit bed shaking, bone-rattling chills, and fever, which typically last from 15 minutes to 1 hour.

Figure 2. During the cold stage, the body aggressively shivers to elevate body temperature in response to hypothalamic elevation of the central thermostat after malaria infection. This may last 15 minutes to 1 hour.

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The hot stage of malaria

Eventually, shivering will help the body reach that 39°C threshold of high fever, and we move into the hot stage. So, the chills and shaking are gone, but like any other fever, it’s often accompanied by other symptoms such as muscle aches that generally make the patient feel horrible. Unfortunately, this stage may last from 6 to 10 hours.

Figure 3. During the hot stage of malaria infection, the patient will feel generally unwell with persistent fever and muscle aches. This stage lasts from 6 to 10 hours.

The defervescence stage of malaria

After a while, as the central thermostat begins to reset, the body will look to cool itself. This is known as the defervescence stage, during which patients will generally experience drenching sweats, which rapidly reduce the body temperature.

And after defervescence, the patient may have no symptoms at all.

Figure 4. The defervescence phase of malaria infection is characterized by a normalization of the central thermostat setting. The body begins to cool itself by sweating to rapidly reduce body temperature.

Manifestations of malaria infection cycles

Let's talk more about these cycles. They are based on the time it typically takes from red blood cell invasion to bursting and merozoite release. And it’s different for different types of malaria.

The most common types—P. falciparum, P. vivax, and P. ovale—cycle approximately every 48 hours. So, we would see fever on day one, no fever on day two, fever again on day three, and so on. This is known as tertian malaria.

P. malariae cycles at 72 hours before the red cells burst. So that cycle would be fever on day one, no fever on days two and three, then fever again on day four. This is quartan malaria.

In contrast, P. knowlesi cycles daily, so we would see all of these stages in a 24-hour period. This is known as quotidian malaria.

Table 1. A comparison of the clinical patterns of fever and associated classifications for five main strains of Plasmodium.

Now if a patient only got bitten by one mosquito, we might see cycles like this. But the patient may be bitten by different mosquitoes on different days, or even mosquitos carrying a different type of malaria. So, if we’re looking for pure cycles, look again! The stages may end up overlapping.

Figure 5. The cyclic pattern of clinical signs of malaria is often masked by overlapping cycles.

That’s it for now. If you want to improve your understanding of key concepts in medicine, and improve your clinical skills, make sure to register for a free trial account, which will give you access to free videos and downloads. We’ll help you make the right decisions for yourself and your patients.

Recommended reading

  • Ashley, EA, Phyo, AP, and Woodrow, CJ. 2018. Malaria. Lancet391: 1608­–1621. PMID: 29631781
  • Fairhurst, RM and Wellems, TE. 2014. “Malaria (Plasmodium Species)”. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, edited by Bennett, JE, Dolin, R, Blaser, MJ. 8th edition. Philadelphia: Elsevier Saunders. (Fairhurst and Wellems 2014, 3070–3090)
  • Phillips, MA, Burrows, JN, Manyando, C, et al. 2017. Malaria. Nat Rev Dis Primers3: 17050. PMID: 28770814
  • World Health Organization. 2019. World malaria report 2019. World Health Organizationhttps://www.who.int/publications/i/item/world-malaria-report-2019

About the author

John F. Fisher, MD MACP FIDSA
Professor of Medicine (Infectious Diseases) at the Medical College of Georgia, Augusta University, USA.
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