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Plasmodium Falciparum Malaria

Plasmodium falciparum malaria is the most severe form of the parasitic disease, malaria. Its causative agent, the protozoan Plasmodium falciparum, is transmitted by mosquitoes pertaining to the genus Anopheles.

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Presentation

Clinical presentation of malaria does not only depend on its causative agent, but also on the innate immunity of the host [4]. In this context, locals often support higher parasitic loads than travelers, and inhabitants of high-transmission areas are less susceptible than those of low-transmission regions. The incubation period is usually a one to two weeks, but may also be considerably longer. This fact should be considered before excluding malaria as a differential diagnosis in patients who report to have traveled to endemic regions.

In general, patients experience flu-like symptoms like malaise, headaches, loss of appetite, myalgia and limb pain as well as nausea and vomiting during the prodromal phase of the disease, which lasts only few days. The sudden onset of high fever, chills, sweats and moderate to severe generalized pain are the hallmarks of PFM, and follow the prodromal phase. Initially, the patient's body temperature rises and decreases in irregular intervals, but after about a week, the temperature curve becomes regular and represents episodes of schizogony and erythrolysis. Most commonly, bouts of fever can be registered in intervals of 24, 36 or 72 hours. In some cases, patients suffer from continuous fever.

Complications may occur at any time. Depending on the compromised organ, patients may develop signs of cardiac, hepatic or renal failure, or central nervous system involvement. With regards to the latter, decreased levels of awareness up to coma, paresis, paralysis or seizures may be observed.

Fever
  • We estimate that 35.7% of all self-reported fevers were accompanied by a malaria infection in 2014, but that only 28.0% of those (10.0% of all fevers) were causally attributable to malaria.[ncbi.nlm.nih.gov]
  • Most commonly, bouts of fever can be registered in intervals of 24, 36 or 72 hours. In some cases, patients suffer from continuous fever. Complications may occur at any time.[symptoma.com]
Anemia
  • Hypotension, convulsions, severe anemia were the main presentations.[ncbi.nlm.nih.gov]
  • Abstract More than half of all young children and pregnant women are affected by anemia. Although its etiology is multi-factorial, malaria is likely to be a major contributor to chronic anemia in endemic areas.[gov.uk]
  • Key words Introduction In sub-Saharan Africa, malaria, hookworm, hemoglobinopathies and nutritional deficiencies may contribute to anemia. 1, 2 Frequently the etiology of anemia is uncertain and many cases are treated as iron deficiency anemia.[haematologica.org]
Chills
  • The major clinical findings of the patient were chills and fever. After examination of thin and thick blood smears prepared from the peripheral blood of the patient, P. falciparum parasites were observed.[ncbi.nlm.nih.gov]
  • ., and Joan Uehlinger, M.D. 1 Citing Article Figure 1 A 23-year-old man with sickle cell disease was admitted after reporting fever and chills. He had emigrated from West Africa three months earlier.[nejm.org]
Pain
  • This explains why PFM is associated with symptoms as different as fever, headaches, myalgia, abdominal pain, vomiting and diarrhea.[symptoma.com]
  • A 45-year-old man presented with a 4-day history of high-grade fever with rigours and a 2-day history of painful bluish black discolouration of extremities (acrocyanosis).[ncbi.nlm.nih.gov]
  • The pain was so intense; I actually believed I was dying, literally crying out in pain so bad that I was taken to a 24 hour clinic that night at 3am. Imagine feeling like that and trying to go to school, work, or take care of your family.[gatesnotes.com]
  • Signs and symptoms Symptoms of malaria may include: fever, which may come and go, or may be constant chills profuse sweating malaise (feeling of unwellness) muscle and joint pain headache confusion nausea loss of appetite diarrhoea abdominal pain cough[sahealth.sa.gov.au]
Malaise
  • A 32-year-old male patient presented with fever, shivering, malaise, and loss of appetite. He had travelled to West Africa. Laboratory findings were as follows: hemoglobin: 8.8 g/dL and anti-HIV: positive.[ncbi.nlm.nih.gov]
  • After a prodromal phase marked by flu-like symptoms such as malaise, headaches, loss of appetite, muscle and limb pain as well as nausea and vomiting, PFM patients develop fever.[symptoma.com]
  • Clinical Manifestation The early symptoms of malaria are nonspecific: malaise, fatigue, headache, abdominal discomfort, and muscle aches.[path.upmc.edu]
  • Signs and symptoms Symptoms of malaria may include: fever, which may come and go, or may be constant chills profuse sweating malaise (feeling of unwellness) muscle and joint pain headache confusion nausea loss of appetite diarrhoea abdominal pain cough[sahealth.sa.gov.au]
Splenomegaly
  • Two black African immigrants, with no history of recent travel outside France, received a diagnosis of a malignant lymphoproliferative disorder and splenomegaly, and they subsequently underwent splenectomy.[ncbi.nlm.nih.gov]
  • They present with headache, fever, anemia, splenomegaly, and cyclical fever.[osmosis.org]
  • The triad of malaria, fever, pallor and splenomegaly were noted in the study group.[alliedacademies.org]
Cough
  • Signs and symptoms Symptoms of malaria may include: fever, which may come and go, or may be constant chills profuse sweating malaise (feeling of unwellness) muscle and joint pain headache confusion nausea loss of appetite diarrhoea abdominal pain cough[sahealth.sa.gov.au]
  • Can also have vomiting, headache, chills, abdominal pain, cough, and diarrhea Severe malaria has a mortality of 5% to 30%, even with therapy Diagnostic criteria for severe malaria: Ashley 2018 Most common manifestations of severe malaria affect the brain[coreem.net]
  • The most severe form is caused by P. falciparum; variable clinical features include fever, chills, headache, muscular aching and weakness, vomiting, cough, diarrhoea and abdominal pain.[who.int]
Vomiting
  • Typical malaria symptoms include fever, chills, fatigue, headache, nausea, and vomiting. In severe cases, it can cause jaundice, seizures, coma, or death.[ncbi.nlm.nih.gov]
  • Patients that vomit everything, including anti-malarials, should be managed as severe malaria.[southsudanmedicaljournal.com]
  • This explains why PFM is associated with symptoms as different as fever, headaches, myalgia, abdominal pain, vomiting and diarrhea.[symptoma.com]
Nausea
  • Typical malaria symptoms include fever, chills, fatigue, headache, nausea, and vomiting. In severe cases, it can cause jaundice, seizures, coma, or death.[ncbi.nlm.nih.gov]
  • After a prodromal phase marked by flu-like symptoms such as malaise, headaches, loss of appetite, muscle and limb pain as well as nausea and vomiting, PFM patients develop fever.[symptoma.com]
  • Also symptoms like headache, myalgia, cough, breathlessness, nausea, bleeding tendencies, dark colored / decreased urine output and altered sensorium / convulsions were enquired.[alliedacademies.org]
  • Signs and symptoms Symptoms of malaria may include: fever, which may come and go, or may be constant chills profuse sweating malaise (feeling of unwellness) muscle and joint pain headache confusion nausea loss of appetite diarrhoea abdominal pain cough[sahealth.sa.gov.au]
Abdominal Pain
  • Signs and symptoms Symptoms of malaria may include: fever, which may come and go, or may be constant chills profuse sweating malaise (feeling of unwellness) muscle and joint pain headache confusion nausea loss of appetite diarrhoea abdominal pain cough[sahealth.sa.gov.au]
  • What is uncomplicated malaria and how might artemisinin-naphthoquine work Uncomplicated malaria is the mild form of malaria which usually causes a fever, with or without headache, tiredness, muscle pains, abdominal pains, nausea, and vomiting.[cochrane.org]
  • Can also have vomiting, headache, chills, abdominal pain, cough, and diarrhea Severe malaria has a mortality of 5% to 30%, even with therapy Diagnostic criteria for severe malaria: Ashley 2018 Most common manifestations of severe malaria affect the brain[coreem.net]
  • The most severe form is caused by P. falciparum; variable clinical features include fever, chills, headache, muscular aching and weakness, vomiting, cough, diarrhoea and abdominal pain.[who.int]
Jaundice
  • In severe cases, it can cause jaundice, seizures, coma, or death. Jaundice, caused by intravascular hemolysis is a usual complication of malaria, especially in patients with P. falciparum infection.[ncbi.nlm.nih.gov]
  • […] particularly to west-Africa should raise suspicion for malaria Clinical Manifestations Average incubation period for Falciparum is 12 days 95% will develop symptoms within 1 month Clinical findings with high likelihood ratios include periodic fevers, jaundice[coreem.net]
  • Severe malarial anaemia A haemoglobin concentration Renal impairment (acute kidney injury) Plasma or serum creatinine 265 μM (3 mg/dl) or blood urea 20 mM Jaundice Plasma or serum bilirubin 50 μM (3 mg/dl) together with a parasite count 100 000/μl Pulmonary[severemalaria.org]
  • Bleeding and Jaundice Bleeding was present as melena in a small number (2%) of P. falciparum malaria. Jaundice associated with vomiting was a significant symptom in many (16%) patients with fever of 10 days as reported in earlier studies [ 15, 18 ].[alliedacademies.org]
Scleral Icterus
  • Her physical examination was remarkable for scleral icterus, dry mucous membranes, and tachycardia.[ncbi.nlm.nih.gov]
Scleral Icterus
  • Her physical examination was remarkable for scleral icterus, dry mucous membranes, and tachycardia.[ncbi.nlm.nih.gov]
Hypotension
  • Hypotension, convulsions, severe anemia were the main presentations.[ncbi.nlm.nih.gov]
  • […] auscultation Significant bleeding Including recurrent or prolonged bleeding from nose gums or vein puncture sites; haematemesis or melaena Shock Compensated shock is defined as capillary refill 3 s or temperature gradient on leg (mid to proximal limb), but no hypotension[severemalaria.org]
  • Vasodilation and hypotension occur in response to the high fever. Anemia results following erythrocyte destruction and indirectly from increased phagocytosis of red cells, capillary hemorrhage, thrombosis, and decreased marrow function.[atsu.edu]
  • Tissue anoxia: this complication may be caused by sequestration of parasitized erythrocytes, resulting in impaired tissue perfusion; anemia; hypovolemia; or hypotension.[infectiousdiseaseadvisor.com]
  • Administration of this drug should be accompanied by cardiac and blood pressure monitoring for widening of the QRS complex and/or lengthening of the QTc interval and hypotension respectively 6.[infectiologyjournal.com]
Orthostatic Hypotension
  • High heartrate, jaundice, pallor, orthostatic hypotension, enlarged liver, and enlarged spleen are also diagnosed.[43] P. falciparum works via sequestration, a distinctive property not shared by few other Plasmodiae.[en.wikipedia.org]
Tachycardia
  • Her physical examination was remarkable for scleral icterus, dry mucous membranes, and tachycardia.[ncbi.nlm.nih.gov]
  • The temperature of nonimmune individuals and children often rises above 400C with tachycardia and sometime delirium. In patients with uncomplicated malaria, physical findings include fever, malaise, mild anemia, and (in some cases) palpable spleen.[path.upmc.edu]
  • At hospital admission, the patient had a temperature of 39 C, a slight tachycardia, paraesthesia of the lower lip, and splenomegaly. The rest of the findings of the examination were normal, without focal signs of infection.[academic.oup.com]
  • Its clinical features are similar to other changes observed in severe malaria, such as anxiety, dyspnea, tachycardia, diaphoresis, coma and generalized seizures.(34) In some patients, a deterioration in consciousness may be the only sign.(1) Metabolic[scielo.br]
Chest Pain
  • Patient complained that her fevers were associated with headaches, but not chills, rigors, or chest pain. Index of suspicion for malaria was high as patient had recently traveled from an endemic region.[journals.lww.com]
Acrocyanosis
  • A 45-year-old man presented with a 4-day history of high-grade fever with rigours and a 2-day history of painful bluish black discolouration of extremities (acrocyanosis).[ncbi.nlm.nih.gov]
Myalgia
  • This explains why PFM is associated with symptoms as different as fever, headaches, myalgia, abdominal pain, vomiting and diarrhea.[symptoma.com]
  • These symptoms include chills, headache, myalgias, and malaise, and they occur in a cyclic pattern. The parasite may also cause jaundice and anemia due to the lysis of the RBCs.[emedicine.medscape.com]
  • Also symptoms like headache, myalgia, cough, breathlessness, nausea, bleeding tendencies, dark colored / decreased urine output and altered sensorium / convulsions were enquired.[alliedacademies.org]
  • There is a brief prodromal period with symptoms of fever, headache, and myalgia. Symptoms begin with a cold stage (a shaking chill), following by a fever stage (40–41 C) that lasts about 24 hours, and finally a wet stage.[atsu.edu]
Back Pain
  • History: talked about having minor injury, hurt lower back, pain there bothering him. Some anemia (normochromic), basic hem/chem/urine/liver nothing remarkable. Physical exam, nothing remarkable. HIV negative.[microbe.tv]
  • The patient was an 18-year-old man who was admitted to Örebro Hospital (Örebro, Sweden) with a 3-day history of chest, stomach, and back pain and recurrent episodes of sweating and fever.[academic.oup.com]
Kidney Failure
  • Patients with severe falciparum malaria may develop liver and kidney failure, convulsions, and coma.[stanfordhealthcare.org]
  • Along with high fever, shaking chills and sweating, symptoms can include: Throwing up or feeling like you're going to Headache Diarrhea Being very tired ( fatigue ) Body aches Yellow skin ( jaundice ) from losing red blood cells Kidney failure Seizure[webmd.com]
  • If left untreated, uncomplicated malaria can develop into severe malaria with kidney failure, breathing difficulties, fitting, unconsciousness, and eventually death. The WHO recommends ACT for treating people with P. falciparum malaria.[cochrane.org]
  • failure Liver failure Pulmonary oedema Cerebral malaria, producing coma Death.[betterhealth.vic.gov.au]
  • Some less noticeable manifestations: abnormalities in blood coagulation hemoglobin in the urine high acidity of the blood hypoglycemia (low blood glucose) low blood pressure kidney failure.[parasitesinhumans.org]
Headache
  • Typical malaria symptoms include fever, chills, fatigue, headache, nausea, and vomiting. In severe cases, it can cause jaundice, seizures, coma, or death.[ncbi.nlm.nih.gov]
  • They present with headache, fever, anemia, splenomegaly, and cyclical fever.[osmosis.org]
  • This explains why PFM is associated with symptoms as different as fever, headaches, myalgia, abdominal pain, vomiting and diarrhea.[symptoma.com]
  • Malaria is an infection characterised by fever, shivering, chills, generally feeling unwell, headache and sweats, but it can present as a respiratory or gastrointestinal illness.[betterhealth.vic.gov.au]
Seizure
  • […] may precipitate some seizures, most seizures occur when the rectal temperatures are less than 38.0 o C. 61 By comparison with simple febrile seizures, the seizures in malaria are often recurrent, and 84% of the seizures are complex, most often with a[jnnp.bmj.com]
  • In severe cases, it can cause jaundice, seizures, coma, or death. Jaundice, caused by intravascular hemolysis is a usual complication of malaria, especially in patients with P. falciparum infection.[ncbi.nlm.nih.gov]
  • Diagnostic criteria for severe malaria: Ashley 2018 Most common manifestations of severe malaria affect the brain, lungs, and kidneys Patients with cerebral malaria can present encephalopathic or comatose, some severe enough to exhibit extensor posturing, or seizures[coreem.net]
  • It consists of A cold stage (sensation of cold, shivering) A hot stage (fever, headaches, vomiting; seizures in young children); and Finally a sweating stage (sweats, return to normal temperature, tiredness).[cdc.gov]
Confusion
  • The detection of IgG and IgM antibodies in serum and cerebrospinal fluid (CSF) against multiple viruses and bacteria reflected a non-specific polyclonal B cell activation and was more confusing than helpful for diagnostic decisions.[ncbi.nlm.nih.gov]
  • The condition is characterized by extremely grave systemic symptoms, mild jaundice, mental confusion, enlarged spleen and liver, increased respiratory rate, edema, GI symptoms, and anemia.[medical-dictionary.thefreedictionary.com]
  • Along with high fever, shaking chills and sweating, symptoms can include: Throwing up or feeling like you're going to Headache Diarrhea Being very tired ( fatigue ) Body aches Yellow skin ( jaundice ) from losing red blood cells Kidney failure Seizure Confusion[webmd.com]
  • Signs and symptoms Symptoms of malaria may include: fever, which may come and go, or may be constant chills profuse sweating malaise (feeling of unwellness) muscle and joint pain headache confusion nausea loss of appetite diarrhoea abdominal pain cough[sahealth.sa.gov.au]
Paresis
  • With regards to the latter, decreased levels of awareness up to coma, paresis, paralysis or seizures may be observed. Paroxysmal fever in a patient who reports to have lived in or traveled to endemic regions is highly suspicious of malaria.[symptoma.com]
Vertigo
  • […] migration and survival to the limbs Hypoplasia of the limb musculature of the upper extremities due to premature apoptosis Expressed in dark cell precursors that migrate to the vestibule and function in fluid homeostasis189 Vestibular symptoms132 (eg, vertigo[onlinelibrary.wiley.com]

Workup

Paroxysmal fever in a patient who reports to have lived in or traveled to endemic regions is highly suspicious of malaria. In contrast, PFM may not be on the list of differential diagnoses during the prodromal phase of the disease or during the first days after onset of fever. In any case, it is of utmost importance to diagnose P. falciparum infections as early as possible in order to avoid life-threatening complications [8].

Several rapid and sensitive diagnostic tests are available today [9]:

  • Microscopic examination of blood smears is still considered the gold standard. This diagnostic measure is readily available in every part of the world, is sensitive and cheap. Erythrolysis precedes this analysis and allows for quantifying parasitic loads. Of note, this technique is also applied to assess parasite clearance and response to therapy.
  • Rapid diagnostic tests rely on the presence of antigens in the blood of infected individuals. They are of low cost and are even more easily applicable than microscopic tests. However, they do not allow for a quantification of parasitemia. Test results may remain positive for several days even if effective treatment is provided.
  • Molecular biological tests may be applied to detect parasitic nucleic acids. In detail, polymerase chain reaction (PCR), real-time PCR and reverse transcriptase PCR protocols have been established as very sensitive diagnostic measures. Despite their high sensitivity, their applicability is limited by relatively high costs and the need for sophisticated equipment.
Hemoglobin Decreased
  • In other studies, the roles of microcytosis have been associated with the protection from P. falciparum -related hemoglobin decrease; in patients, a reduction of infection for part of parasite and most notary in homozygous α-thalassemic individuals have[intechopen.com]
Liver Enzymes Abnormal
  • Nevertheless, these liver enzyme abnormalities seem to be harmless, asymptomatic and self-limited.[ncbi.nlm.nih.gov]
Plasmodium Falciparum
  • Glomerulonephritis occurs as a rare form of renal manifestation in Plasmodium falciparum malaria. Herein, we report a case of falciparum malaria-associated IgA nephropathy for the first time.[ncbi.nlm.nih.gov]
  • Look at other dictionaries: Plasmodium falciparum — Verschiedene Formen von Plasmodium falciparum im gefärbten Blutausstrich Systematik ohne Rang: Alveolata ohne Rang … Deutsch Wikipedia Plasmodium falciparum — Blood smear of Plasmodium falciparum (gametocytes[medicine.academic.ru]

Treatment

PFM treatment consists in antiparasitic therapy and possibly additional measures that remedy complications like anemia, acidosis, hypoglycemia and seizures.

According to the most recent guidelines published by the World Health Organization [10]. , the following regimens are indicated in case of uncomplicated malaria:

Such treatment should be administered for three days.

In case the disease cannot be cured this way, artesunate may instead be combined with tetracycline antibiotics or doxycycline or clindamycin. Alternatively, quinine may be applied in combination with either of those antibiotics. These second-line treatments are to be administered for seven days.

Patients suffering from severe malaria are essentially treated the same way, but they should receive their drugs intravenously until they are able to tolerate oral medication.

Monotherapies are generally not recommended to avoid the development of resistances.

Their may be regional differences regarding the effectivity of determined treatment options. For instance, dihydroartemisinin plus piperaquine has been proven superior to artemether plus lumefantrine in Africa, while both treatments seem to be equally effective in Asia [11].

Prognosis

PFM is a life-threatening disease and accounts for the vast majority of malaria-related deaths. The single most important risk factor for a poor outcome is the delay of treatment [8]. Unfortunately, areas of high prevalence of P. falciparum often coincide with regions of low levels of economic development. Access to medical attention in general and effective therapeutics in particular is often restricted. This fact further underlines the importance of prevention and indeed, it has been estimated that mortality rates have been diminished by more than 50% during the last decades thanks to the implementation of corresponding measures.

Signs of organ failure as well as involvement of the central nervous system, severe anemia and high parasitemia (hemoglobin levels below 5 g/dl and more than 250,000 parasites/µl), acidosis, hypoglycemia and shock are unfavorable prognostic factors. With regards to parasitemia, the value given applies to regions of high prevalence of malaria. In contrast, much lower burdens may result lethal in geographic areas of lower prevalence.

Etiology

The protozoan parasite P. falciparum is the etiologic agent of PFM; it is transmitted by female mosquitoes of the genus Anopheles. An infection occurs upon injection of P. falciparum sporozoites into the patient's circulation during an insect bite.

A mosquito may ingest gametocytes, i.e., sexual-stage parasites, while feeding on an infected human [5]. Inside the insect's gut, gametocytes pass distinct developmental stages, form zygotes which turn into oocysts, and the latter eventually release sporozoites that migrate into the mosquito's salivary glands. As has been mentioned above, these sporozoites are infectious and give rise to PFM upon transmission.

Additionally, malaria may be acquired by receiving transfusions of blood products obtained from infected donors. In fact, malaria is still one of the most common transfusion-transmitted diseases [6].

Epidemiology

Although numbers regarding the annual incidence of PFM range from 200 to more than 450 million cases, they coincide in PFM being a very common infectious disease [1] [5]. Malaria-related mortality is almost exclusively associated with infections with P. falciparum, and it has been estimated that up to a million PFM patients die each year.

With regards to the geographical distribution of the disease, malaria may only be acquired within the distribution range of Anopheles spp. PFM is currently considered to be endemic to 87 countries in tropical and subtropical Africa, the Indian Subcontinent, Southeast Asia, Central America and norther South America. Corresponding maps are available elsewhere [1], but it should be noted that distribution ranges of carriers and pathogens may change over time and that, for clinical purposes, updated information should be consulted whenever possible. Today, highest burdens are encountered in the Democratic Republic of the Congo, Nigeria, India and Myanmar. Here, almost 1.5 billion people are at risk of contracting the disease.

Sex distribution
Age distribution

Pathophysiology

Upon transmission of haploid sporozoites during an insect bite, the latter reach the patient's liver and invade hepatocytes. Here, they grow and divide, thereby forming several thousands of haploid merozoites. Subsequently, merozoites exit hepatocytes, return to circulation and infect erythrocytes. In red blood cells, merozoites multiply by formation of mature schizonts and schizogony. This process involves the destruction of infected erythrocytes and gives rise to many new merozoites able to invade further red blood cells. In PFM patients, erythrolysis occurs repeatedly after reproduction cycles lasting one to three days, and is accompanied by bouts of fever. This rise in body temperature is provoked by the release of toxins during cell lysis and the ensuing activation of pro-inflammatory cascades. During such a bout of fever, pro-inflammatory cytokines and other mediators such as interleukin-1β, tumor necrosis factor-α and reactive oxygen species are released in great amounts by activated macrophages, leukocytes and endothelial cells [7].

Since virtually all tissues of the human body directly depend on blood supply, erythrolysis and pro-inflammatory events may occur in multiple organs. Excess release of the aforementioned mediators interferes with the function of the central nervous system, the cardiovascular system and several internal organs. This explains why PFM is associated with symptoms as different as fever, headaches, myalgia, abdominal pain, vomiting and diarrhea.

Of note, in some infected erythrocytes, merozoites develop into sexual forms of the parasite, namely into gametocytes. These gametocytes are ingested by mosquitoes biting the patients and give rise to the above described part of the parasite's life cycle that takes place in the insect.

Prevention

In general, any measure aiming at the prevention of insect bites contributes to reducing the individual risk of contracting malaria. However, neither travelers nor locals are able to completely prevent exposure to Anopheles spp. and thus, additional measures are required to prevent PFM. People who are traveling to endemic regions are recommended to prophylactically take antimalarials like chloroquine or mefloquine, or to carry stand-by medication in order to immediately initiate treatment in case an infection is suspected. Distinct compounds are available for chemoprophylaxis and the decision for or against a certain drug should be based on the current knowledge regarding resistances. Moreover, contraindications may exist for children, pregnant or lactating women. For instance, only chloroquine is approved for use in pregnant women, but there are endemic regions with high rates of resistance to this drug. Consequently, pregnant patients are recommended to avoid visiting such areas.

In endemic regions, programs aiming at larval source management have been implemented to hinder mosquito reproduction. These programs comprise measures to reduce the availability of water bodies for larval development, to introduce predators of Anopheles spp., and to kill larvae by use of larvicides [12].

Summary

Malaria is a parasitic disease that continues to be a major public health concern, particularly in tropical and subtropical regions. In total, more than 300 million malaria cases are registered annually and about one million people die each year from this disease [1]. There are distinct forms of malaria that differ with regards to their respective etiologic agents and disease severity. In detail, the following forms of malaria are distinguished:

PFM is triggered by infection with Plasmodium falciparum (P. falciparum). Because PFM is the most severe form of the disease, it is also referred to as malignant malaria. In contrast, all other forms of malaria are generally termed benign malaria. PFM accounts for the vast majority of malaria cases worldwide, but there are considerable geographical differences regarding the ratio of malignant and benign cases [2] [3]. Mortality is almost exclusively seen in PFM patients.

Patients infected with P. falciparum may develop uncomplicated or complicated malaria. The latter is diagnosed when the affected individual shows signs of organ failure, e.g., severe functional impairment of the central nervous system, heart, liver or kidneys. Such symptoms are often associated with high parasitemia. It is currently assumed that host-pathogen interactions are affected by numerous environmental factors, and that disease severity is the result of the entirety of these influences. For instance, thalassemia and other forms of hemoglobinopathy confer partial resistance against PFM and are thus highly prevalent in areas of malaria transmission [4]. People living in geographical regions of lower prevalence of malaria as well as those traveling to endemic areas are therefore more susceptible to the disease.

Treatment of PFM primarily consists in the administration of antimalarials, but patients suffering from complicated malaria often require additional therapies aiming at an improvement of organ function.

Patient Information

Malaria is a parasitic disease caused by infection with protozoans of the genus Plasmodium. There are distinct species, e.g., Plasmodium falciparum and Plasmodium vivax, which are all transmitted by mosquitoes of the genus Anopheles, but that provoke disorders of varying severity. The most severe form of malaria is triggered by infection with Plasmodium falciparum and is consequently called Plasmodium falciparum malaria (PFM).

It has been estimated that about 2.5 billion people are at risk of contracting PFM, and these people are mainly living in subtropical and tropical regions of Africa, America and Asia. Particularly high prevalence rates have been reported in the Democratic Republic of the Congo, Nigeria, India and Myanmar. While locals may dispose of a partial immunity against PFM, this does not apply to travelers who are generally considered to be highly susceptible to the disease.

Symptom onset typically occurs within two weeks after exposure to the parasite. After a prodromal phase marked by flu-like symptoms such as malaise, headaches, loss of appetite, muscle and limb pain as well as nausea and vomiting, PFM patients develop fever. Initially, their body temperature may rise in irregular intervals, but within a week of illness, regular patterns become recognizable: Bouts of fever are experienced in intervals of one to three days and thus correspond to the reproductive cycle of parasites. Fever is usually accompanied by chills, sweats and generalized pain. PFM patients may develop complications involving brain, heart, liver and kidney function at any time, and this is why PFM is considered a life-threatening disease.

Fortunately, patients generally respond well to therapy. Primarily, antimalarial drugs are administered to kill the parasites. Additional treatment may be required in case of organ compromise. Lethal outcomes are often related to delayed medical attention.

References

Article

  1. Hay SI, Okiro EA, Gething PW, et al. Estimating the global clinical burden of Plasmodium falciparum malaria in 2007. PLoS Med. 2010; 7(6):e1000290.
  2. Lemma H, San Sebastian M, Lofgren C, et al. Cost-effectiveness of three malaria treatment strategies in rural Tigray, Ethiopia where both Plasmodium falciparum and Plasmodium vivax co-dominate. Cost Eff Resour Alloc. 2011; 9:2.
  3. Atroosh WM, Al-Mekhlafi HM, Snounou G, et al. Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes. Malar J. 2016; 15(1):295.
  4. Taylor SM, Cerami C, Fairhurst RM. Hemoglobinopathies: slicing the Gordian knot of Plasmodium falciparum malaria pathogenesis. PLoS Pathog. 2013; 9(5):e1003327.
  5. Bousema T, Drakeley C. Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clin Microbiol Rev. 2011; 24(2):377-410.
  6. Kitchen AD, Chiodini PL. Malaria and blood transfusion. Vox Sang. 2006; 90(2):77-84.
  7. Lyke KE, Burges R, Cissoko Y, et al. Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls. Infect Immun. 2004; 72(10):5630-5637.
  8. Bartoloni A, Zammarchi L. Clinical aspects of uncomplicated and severe malaria. Mediterr J Hematol Infect Dis. 2012; 4(1):e2012026.
  9. Murphy SC, Shott JP, Parikh S, et al. Malaria diagnostics in clinical trials. Am J Trop Med Hyg. 2013; 89(5):824-839.
  10. World Health Organization. Guidelines for the Treatment of Malaria. Geneva: World Health Organization; 2015.
  11. Zani B, Gathu M, Donegan S, et al. Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum malaria. Cochrane Database Syst Rev. 2014; (1):Cd010927.
  12. Tusting LS, Thwing J, Sinclair D, et al. Mosquito larval source management for controlling malaria. Cochrane Database Syst Rev. 2013; (8):Cd008923.

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Last updated: 2019-07-11 20:16