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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.

Splenomegaly
  • Abstract 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]
  • Mild splenomegaly was present on abdominal examination but rest of the physical examinations were normal. On investigating he was found to have anaemia, thrombocytopaenia with gametocytes of Plasmodium falciparum on peripheral blood smear.[ncbi.nlm.nih.gov]
  • Fever (100%), splenomegaly (86.7%), hepatomegaly (26.7%), leukopenia (13.3%), thrombocytopenia (80%), elevated liver function tests (40%), and increased serum creatinine levels (13.3%) were found in the patients.[ncbi.nlm.nih.gov]
  • The triad of malaria, fever, pallor and splenomegaly were noted in the study group.[alliedacademies.org]
  • Splenic rupture may be associated with P vivax infection secondary to splenomegaly resulting from RBC sequestration. P vivax infects only immature RBCs, leading to limited parasitemia.[emedicine.medscape.com]
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]
  • Abstract Although Plasmodium falciparum malaria and Q fever are both prevalent in Africa, there have been no reports of co-infection to date.[ncbi.nlm.nih.gov]
  • The present case report is meant to educate about the presentation, hospital course, and differential diagnoses of a patient traveling from Western Africa with fever and chills.[ncbi.nlm.nih.gov]
  • About 3 weeks after the onset of symptoms, the patient was hospitalized because of a high fever. Blood and urine cultures and malaria smears were all negative, and a subsequent bone marrow study was performed to evaluate fever of unknown origin.[ncbi.nlm.nih.gov]
  • Matched urine and finger-prick blood samples from participants 2 years of age with fever (axillary temperature of 37.5 C) or with a history of fever in the preceding 48 h were tested with UMT and microscopy (as the gold standard).[ncbi.nlm.nih.gov]
Anemia
  • Hypotension, convulsions, severe anemia were the main presentations.[ncbi.nlm.nih.gov]
  • These findings indicate a need for increased vigilance for hemolytic events in malaria patients, particularly those with predisposing factors for anemia.[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]
  • The disease was revealed only by anemia. The diagnosis relied on blood smear which showed a parasitemia 2012 International Society of Travel Medicine. [Indexed for MEDLINE] Free full text[ncbi.nlm.nih.gov]
  • 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 present case report is meant to educate about the presentation, hospital course, and differential diagnoses of a patient traveling from Western Africa with fever and chills.[ncbi.nlm.nih.gov]
  • A 37-year-old woman had a 24-hour history of generalized weakness and chills 2 days after returning from Nigeria. She had received mefloquine as prophylaxis, but the patient did not take the medication.[ncbi.nlm.nih.gov]
  • 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]
  • ., 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]
  • Why Malaria Is Harmful Malaria can cause high fever , chills, and flu-like symptoms that can be life-threatening when not treated quickly. The disease is caused by Plasmodium parasites, which are carried by Anopheles mosquitoes .[webmd.com]
Pain
  • Abstract 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]
  • This explains why PFM is associated with symptoms as different as fever, headaches, myalgia, abdominal pain, vomiting and diarrhea.[symptoma.com]
  • 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]
  • The initial symptoms of malaria are flu-like and include: a high temperature of 38C or above feeling hot and shivery headaches vomiting muscle pains diarrhoea generally feeling unwell These symptoms are often mild and can sometimes be difficult to identify[nhs.uk]
  • 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]
High Fever
  • We report the case of a patient who developed high fever, then respiratory distress during a trip to Haiti who was admitted to our hospital and diagnosed with malaria. During recovery the patient developed ARDS in the hospital.[ncbi.nlm.nih.gov]
  • About 3 weeks after the onset of symptoms, the patient was hospitalized because of a high fever. Blood and urine cultures and malaria smears were all negative, and a subsequent bone marrow study was performed to evaluate fever of unknown origin.[ncbi.nlm.nih.gov]
  • Why Malaria Is Harmful Malaria can cause high fever , chills, and flu-like symptoms that can be life-threatening when not treated quickly. The disease is caused by Plasmodium parasites, which are carried by Anopheles mosquitoes .[webmd.com]
  • The most common symptoms of malaria are high fever, headache, diarrhoea, chills and vomiting, which manifest themselves some 1-4 weeks after infection, whilst relapses due to Plasmodium vivax may occur months and in some cases, to 8 years later.[gacetasanitaria.org]
  • Initially, malaria feels like the flu with high fever, fatigue , and body aches, with hot and cold stages. Signs and symptoms in children may be nonspecific, leading to delays in diagnosis.[emedicinehealth.com]
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]
  • 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]
  • Also symptoms like headache, myalgia, cough, breathlessness, nausea, bleeding tendencies, dark colored / decreased urine output and altered sensorium / convulsions were enquired.[alliedacademies.org]
  • However, headaches, muscle pains, backache, abdominal pains, cough, feeling more tired than usual and feeling generally unwell are all symptoms of malaria.[viceprovost.tufts.edu]
  • Dizziness , malaise , muscle pain , abdominal pain , nausea , vomiting , mild diarrhea , and dry cough are also generally associated.[en.wikipedia.org]
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]
  • The most frequently observed events were asthenia (682 cases), vomiting (482 cases) and somnolence (174 cases). Most reported AEs were of mild or moderate intensity and resolved without corrective treatment.[ncbi.nlm.nih.gov]
  • The initial symptoms of malaria are flu-like and include: a high temperature of 38C or above feeling hot and shivery headaches vomiting muscle pains diarrhoea generally feeling unwell These symptoms are often mild and can sometimes be difficult to identify[nhs.uk]
  • This explains why PFM is associated with symptoms as different as fever, headaches, myalgia, abdominal pain, vomiting and diarrhea.[symptoma.com]
  • This attack could be signified by a fever higher than 38% that can fluctuate over the course of a couple of hours, headaches, influenza, diarrhoea, nausea and vomiting.[euroclinix.net]
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]
  • This attack could be signified by a fever higher than 38% that can fluctuate over the course of a couple of hours, headaches, influenza, diarrhoea, nausea and vomiting.[euroclinix.net]
  • 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]
  • 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]
  • Also symptoms like headache, myalgia, cough, breathlessness, nausea, bleeding tendencies, dark colored / decreased urine output and altered sensorium / convulsions were enquired.[alliedacademies.org]
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]
  • 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]
  • This explains why PFM is associated with symptoms as different as fever, headaches, myalgia, abdominal pain, vomiting and diarrhea.[symptoma.com]
  • Fever was the commonest symptom followed by headache, nausea with vomiting, myalgia, cough, altered sensorium, abdominal pain, jaundice. The triad of malaria, fever, pallor and splenomegaly were noted in the study group.[alliedacademies.org]
  • However, headaches, muscle pains, backache, abdominal pains, cough, feeling more tired than usual and feeling generally unwell are all symptoms of malaria.[viceprovost.tufts.edu]
Hypotension
  • Hypotension, convulsions, severe anemia were the main presentations.[ncbi.nlm.nih.gov]
  • 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]
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]
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]
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]
  • Abstract A 13-year-old adolescent daughter of a missionary presented with fever and jaundice 1 week after returning from Africa. Examination of peripheral blood film revealed the diagnosis of Plasmodium falciparum infection.[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]
  • Bleeding and Jaundice Bleeding was present as melena in a small number (2%) of P. falciparum malaria.[alliedacademies.org]
  • The complications according to WHO criteria were: cerebral malaria (n 2, 4.9%), cerebral malaria Jaundice (n 8, 19.5%), cerebral anaemia (n 4, 9.7%), cerebral malaria Jaundice renal failure (n 10, 24.4%), cerebral malaria Jaundice renal failure anaemia[omicsonline.org]
Scleral Icterus
  • Her physical examination was remarkable for scleral icterus, dry mucous membranes, and tachycardia.[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]
  • This case report illustrates an example of how a patient with recent travel history to West Africa presenting with typical fevers, myalgias, and fatigue could be considered to have either or both diseases. REFERENCES 1.[journals.lww.com]
Kidney Failure
  • 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]
  • 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]
  • In addition to fever, patients may experience complications such as severe hemolytic anemia caused by the destruction of the red cells, yellow skin discoloration, kidney failure , pulmonary edema ( fluid in the lungs ), cerebral malaria, convulsions ,[emedicinehealth.com]
  • Severe symptoms also present anemia due to destruction of red blood cells, hemoglobinuria, acute respiratory distress, low blood pressure, acute kidney failure, metabolic acidosis, and hypoglycemia.[microbewiki.kenyon.edu]
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]
  • The initial symptoms of malaria are flu-like and include: a high temperature of 38C or above feeling hot and shivery headaches vomiting muscle pains diarrhoea generally feeling unwell These symptoms are often mild and can sometimes be difficult to identify[nhs.uk]
  • This explains why PFM is associated with symptoms as different as fever, headaches, myalgia, abdominal pain, vomiting and diarrhea.[symptoma.com]
  • Probably the worst headache, body aches, and chills you could possibly imagine. It felt like I was being stung repeatedly by an electric shock gun and could barely control my movements.[gatesnotes.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
  • 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]
  • MANAGEMENT OF SEIZURES Generalized seizures are more common in children with P. falciparum malaria than in those with malaria due to other species.[ncbi.nlm.nih.gov]
  • PFM treatment consists in antiparasitic therapy and possibly additional measures that remedy complications like anemia, acidosis, hypoglycemia and seizures.[symptoma.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[webmd.com]
  • Symptoms of severe malaria might include: breathing difficulties coma confusion death focal neurologic signs seizures severe anemia.[parasitesinhumans.org]
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]
  • Symptoms of severe malaria might include: breathing difficulties coma confusion death focal neurologic signs seizures severe anemia.[parasitesinhumans.org]
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]

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.
Microcytosis
  • The prevalence of haematological manifestations such as moderate (48.0%) and severe (8.0%) anaemia, leucopenia (26.9%) and microcytosis (30.8%) was significantly higher among Plasmodium-STH co-infected participants.[ncbi.nlm.nih.gov]
Plasmodium Falciparum
  • KEYWORDS: Glomerulonephritis; IgA nephropathy; Malaria; Plasmodium falciparum[ncbi.nlm.nih.gov]
  • Abstract We describe the case of a 14-year-old Caucasian male, a resident in the Democratic Republic of the Congo, who was observed in Portugal with severe Plasmodium falciparum malaria with high-level parasitemia and severe thrombocytopenia.[ncbi.nlm.nih.gov]
  • Abstract We conducted a study in Binh Phuoc, Vietnam, in 2015 on the therapeutic efficacy of dihydroartemisinin/piperaquine for Plasmodium falciparum malaria.[ncbi.nlm.nih.gov]
  • Abstract During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus.[ncbi.nlm.nih.gov]
  • CONCLUSION: Plasmodium falciparum GPI-induced apoptosis might participate in the lethality of malaria.[ncbi.nlm.nih.gov]
Coxiella Burnetii
  • We report a case who returned from the Comoros archipelago diagnosed by serologic analysis as well as detection of Coxiella burnetii DNA in acute-phase serum.[ncbi.nlm.nih.gov]

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:

  • artemether and lumefantrine
  • artesunate and amodiaquine
  • artesunate and mefloquine
  • artesunate and sulfadoxine–pyrimethamine
  • dihydroartemisinin and piperaquine

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.
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Last updated: 2018-06-21 19:41