, Kyle John Wilby2 and Mary H. H. Ensom1
(1)
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada
(2)
College of Pharmacy, Qatar University, Doha, Qatar
Malaria is a major tropical health burden worldwide and currently the most important parasitic disease in humans (White et al. 2014). It is prevalent in 108 countries that are inhabited by approximately 3 billion people. The most recent estimates from the World Health Organization (WHO) (WHO 2014a) suggest there were approximately 207 million cases of malaria in 2012 and 627,000 deaths related to the disease. Most deaths occurred among children living in Africa. However, since 2000, deaths due to malaria have decreased by 42 % worldwide and rates of malaria-related deaths among children in Africa have decreased by 54 % (WHO 2014a).
The four most common causes of malaria in humans are Plasmodium falciparum, P. vivax, P. malaria, and P. ovale. P. falciparum is the most fatal and represents the most common infection in Africa (Baird 2005). P. falciparum and P. vivax have approximately equal prevalence in Asia, and South and Central America (White et al. 2014). Transmission in these regions is typically much lower than in Africa and follows seasonal trends. In areas where transmission is high and persistent year around, acquired immunity can develop especially in adults. Unfortunately, children rarely acquire immunity and this is a contributor to the morbidity and mortality seen in this population.
The female Anopheles mosquito is responsible for the transmission of the Plasmodium parasites that cause clinical disease. The intensity of transmission is determined by the mosquito density, longevity, biting habits, and efficiency (White et al. 2014). Considering these factors, approximately 25 of over 400 anopheline species are good vectors for spread of infection. The Anopheles gambiae complex, which is present in Africa, not only satisfies these factors but is also robust to environmental change, breeds readily, and preferentially bites humans. These vector considerations highlight some of the current challenges relating to malaria spread and control.
The P. falciparum lifecycle (Fig. 1.1) consists of two stages: asymptomatic hepatic (pre-erythrocytic) followed by symptomatic blood (erythrocytic) stage (Casares et al. 2010). During the erythrocytic phase, patients commonly present with fever, chills, weakness, headache, nausea, vomiting, and diarrhea. While erythrocyte stages are most responsible for these observable clinical symptoms, damage to hepatocytes and hepatomegaly may occur due to hepatic invasion during pre-erythrocyte phases (Sowunmi 1996).
Fig. 1.1
Plasmodium falciparum Lifecycle (Wilby et al. 2012). The lifecycle of Plasmodium falciparum in the human host. (1) Sporozoites are introduced from an infected Anopheles mosquito, while taking a blood meal; (2) Sporozoites migrate to the hepatic circulation and infiltrate neighboring hepatocytes; (3) Sporozoites undergo development and differentiation in the hepatocytes, producing thousand of merozoites; (4) Merozoites are liberated from the hepatocyte in small cellular vesicles called merosomes, which disintegrate in the systemic circulation releasing the merozoites; (5) Merozoites invade erythrocytes and continue maturation and division to become schizonts; the red blood cell ruptures resulting in the systemic release of more merozoites, that infect more erythrocytes; (6) Some merozoites differentiate into male and female gametocytes; (7) Gametocytes are then consumed by uninfected female Anopheles mosquito during a blood meal; cycle is then repeated (Reproduced with permission from: Ann Pharmacother 2012; 46(3):384–93)
1.1 Clinical Presentation
Initial malaria symptoms are typically nonspecific in nature, which makes it challenging to differentiate from a systemic viral illness or vice versa. Symptoms typically consist of headache, fatigue, abdominal discomfort, and muscle and joint aches. These symptoms are commonly followed by fever, chills, perspiration, and anorexia (WHO 2010). If malaria is not recognized and treated promptly (especially for P. falciparum), severe malaria can develop which usually presents with at least one of the following: coma, metabolic acidosis, severe anemia, hypoglycemia, acute renal failure, or pulmonary edema (WHO 2010). The severity of symptoms depends on both the time before receiving effective treatment and degree of protective immunity acquired in the host. For example, adults and adolescents living in endemic areas will not always suffer from clinical disease, due to their acquired immunity and harboring of low-level parasite burdens.
1.2 Diagnosis
Accurate diagnosis is required for effective treatment and control of malaria. It is very important that diagnostic tests of high quality are available throughout endemic regions, due to the significant morbidity and mortality associated with the disease as well as considerable over-diagnosis resulting from the non-specific nature of presentation (WHO 2010). Furthermore, accurate diagnosis should be completed in a timely manner (rapidly, where applicable), in order to ensure proper care is given (WHO 2010).
The clinical decision-making process first begins when the patient presents with signs and/or symptoms. As discussed, typical malarial signs include elevated temperature and symptoms and are generally non-specific but include weakness, fatigue, headache, nausea, vomiting, diarrhea, or general malaise (WHO 2010). Severity of symptoms may vary greatly between individuals. Due to the non-specific nature of presenting complaints, it is not advised to base treatment decisions on clinical presentation alone without identification of malaria parasites in the blood (WHO 2014b).
Two forms of diagnostic testing are generally recommended (WHO 2010). Both require parasitological confirmation by either microscopy or a rapid diagnostic test (RDT) (WHO 2014b). Thick and thin blood film microscopy is typically considered the gold standard test for diagnosis. Identification of malaria parasites and determination of parasite burden help clinicians make treatment decisions. RDTs are available that work by detecting PfHRP2, pan-malaria or species-specific lactate dehydrogenase, or aldolase antigens in capillary blood. While RDTs offer a quick and efficient alternative to microscopy testing, some concerns still exist regarding species identification and overall sensitivity. Other limitations include price and the inability to quantify parasitemia (White et al. 2014). The WHO has published guidelines for evaluation of these tests, including considerations for field-based studies and testing (Bell and Peeling 2006).
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
