Plasmodium/Malaria

Overview

Definition

Malaria is a parasitic disease caused by unicellular Unicellular Cell Types: Eukaryotic versus Prokaryotic parasites of the Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs genus and transmitted by mosquitoes of the Anopheles genus.

Epidemiology

• Malaria occurs throughout most of the tropical regions of Africa, Central and South America, parts of the Caribbean, Asia ASIA Spinal Cord Injuries, Eastern Europe, and the South Pacific.
• In 2019, the WHO reported 229 million cases and 409,000 deaths from malaria, which is a decrease from 239 million cases in 2010.
• Children < 5 years old account for ⅔ of deaths from malaria.
• Malaria is not endemic to the United States, but there are approximately 2,000 cases diagnosed each year (mostly travelers and immigrants from sub-Saharan Africa and South Asia ASIA Spinal Cord Injuries).

Etiology

• Carried by Anopheles mosquitoes and transmitted to humans through bites
• Caused by species of the Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs genus:
  • P. falciparum: 
    • Most common (approximately 70% of cases)
    • Most lethal
    • Predominates in sub-Saharan Africa, New Guinea, Haiti, and the Dominican Republic
  • P. vivax: causes approximately 20% of cases and more common in North and South America
  • P. ovale: comprises < 1% of isolates and relatively unusual outside of Africa
  • P. malariae: uncommon, found in most endemic areas (especially in sub-Saharan Africa)

Pathophysiology

Transmission

• Transmitted by female mosquitoes of the Anopheles species through bites
• Transmission intensity is defined by the entomologic inoculation rate (EIR).
• Low transmission: EIR < 10/year
• High transmission: EIR ≥ 50/year
• Stable infection:
  • Defined as constant, year-round transmission with EIR ≥ 50/year
  • Usually asymptomatic in adults residing in stable areas due to immunity

Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs life cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation

Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs is a genus of unicellular Unicellular Cell Types: Eukaryotic versus Prokaryotic eukaryotes, which are obligate parasites of vertebrates and insects.

1. An infected female Anopheles mosquito (primary host) bites the human and injects sporozoites Sporozoites The product of meiotic division of zygotes in parasitic protozoa comprising haploid cells. These infective cells invade the host and undergo asexual reproduction producing merozoites (or other forms) and ultimately gametocytes. Antimalarial Drugs from its saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy into the blood of the human host.
2. Sporozoites Sporozoites The product of meiotic division of zygotes in parasitic protozoa comprising haploid cells. These infective cells invade the host and undergo asexual reproduction producing merozoites (or other forms) and ultimately gametocytes. Antimalarial Drugs travel through the circulatory system, reach the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy within 30 minutes, then asexually divide thousands of times until mature schizonts (multinucleated cell stage in the asexual cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation of Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs) undergo multiple fissions to form merozoites.
3. In the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, infected hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy rupture and release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology thousands of merozoites into the blood of the host.
4. In the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, P. ovale and P. vivax can transform into a dormant stage called hypnozoites that may cause late relapse Relapse Relapsing Fever by reactivating after many months.
5. Merozoites can infect new liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy cells to transform into schizonts and release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology trophozoites Trophozoites Cells or feeding stage in the life cycle of sporozoan protozoa. In the malarial parasite, the trophozoite develops from the merozoite and then splits into the schizont. Trophozoites that are left over from cell division can go on to form gametocytes. Amebicides, which infect red blood cells Red blood cells Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology ( RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology).
6. In RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology, they multiply and transform into mature schizonts.
7. Infected RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology eventually rupture, releasing more merozoites into the bloodstream and causing symptoms and cyclical fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever due to proinflammatory cytokines Proinflammatory Cytokines Metabolic Syndrome:
   • This process takes 48 hours for P. falciparum, P. vivax, and P. ovale.
   • 72 hours for P. malariae
   • 24 hours for P. knowlesi
8. Merozoites continue asexual replication in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology (although a few undergo sexual reproduction) and transform into gametocytes within the RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology.
9. Gametocytes are ingested by a new mosquito during a blood meal from an infected human (male gametocytes are microcytes, female gametocytes are macrocytes).
   • Within the mosquito’s stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy, Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs undergoes sexual reproduction ( fertilization Fertilization To undergo fertilization, the sperm enters the uterus, travels towards the ampulla of the fallopian tube, and encounters the oocyte. The zona pellucida (the outer layer of the oocyte) deteriorates along with the zygote, which travels towards the uterus and eventually forms a blastocyst, allowing for implantation to occur. Fertilization and First Week → zygote Zygote The fertilized ovum resulting from the fusion of a male and a female gamete. Fertilization and First Week → ookinete → oocyst Oocyst Zygote-containing cysts of sporozoan protozoa. Further development in an oocyst produces small individual infective organisms called sporozoites. Then, depending on the genus, the entire oocyst is called a sporocyst or the oocyst contains multiple sporocysts encapsulating the sporozoites. Toxoplasma/Toxoplasmosis → sporoblast).
   • The resulting sporozoites Sporozoites The product of meiotic division of zygotes in parasitic protozoa comprising haploid cells. These infective cells invade the host and undergo asexual reproduction producing merozoites (or other forms) and ultimately gametocytes. Antimalarial Drugs accumulate in the salivary glands Salivary glands The salivary glands are exocrine glands positioned in and around the oral cavity. These glands are responsible for secreting saliva into the mouth, which aids in digestion. There are 3 major paired salivary glands: the sublingual, submandibular, and parotid glands. Salivary Glands: Anatomy to start the cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation over when the mosquito bites the next human.

Pathophysiology

• Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs alters erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology in several ways:
  • Derives energy from anaerobic glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis → hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia, ↑ lactic acid
  • Reduces membrane deformability → hemolysis, anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly
  • Digests hemoglobin → forms the toxic product Product A molecule created by the enzymatic reaction. Basics of Enzymes hemozoin
• RBC lysis causes a release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of inflammatory cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response.
• Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly and endothelial damage lead to platelet consumption and thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia.
• Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs is cytoadherent to the endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology and other cells and can undergo sequestration in various human tissues:
  • Microvascular disease: occlusion of small vessels, capillary leakage, infarcts
  • Cerebral malaria: sequestration in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
  • Renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
• Host factors play a significant role in susceptibility and disease severity:
  • RBC antigens: Absence of the Duffy antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination provides protection against P. vivax malaria.
  • Some RBC diseases confer partial protection against malaria:
    • Sickle cell anemia Sickle cell anemia A disease characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs. It is the clinical expression of homozygosity for hemoglobin S. Sickle Cell Disease
    • Thalassemia Thalassemia Thalassemia is a hereditary cause of microcytic hypochromic anemia and results from a deficiency in either the α or β globin chains, resulting in hemoglobinopathy. The presentation of thalassemia depends on the number of defective chains present and can range from being asymptomatic to rendering the more severely affected patients to be transfusion dependent. Thalassemia (reduced parasite multiplication)
    • Ovalocytosis, hereditary elliptocytosis
    • Pyruvate kinase Pyruvate kinase Atp:pyruvate 2-o-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (l, r, m1, and m2). Glycolysis deficiency
  • Some polymorphisms of tumor Tumor Inflammation necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage factor-alpha (TNF-ɑ) may influence severity.
  • People living in endemic areas often develop partial immunity.

Clinical Presentation

Uncomplicated malaria

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period: 7–30 days
• Symptoms:
  • Initial presentation includes headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, malaise Malaise Tick-borne Encephalitis Virus, and myalgia Myalgia Painful sensation in the muscles. Ion Channel Myopathy.
  • Paroxysmal chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever, high fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever (> 40℃), tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, and diaphoresis coincide with cycles of RBC destruction:
    • Initially occurs daily at irregular intervals
    • Later occurs every 2nd day for P. vivax, P. ovale, and P. falciparum; every 3rd day for P. malariae
  • Hemolytic anemia Hemolytic Anemia Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia causes:
    • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
    • Weakness
    • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)
    • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
  • GI symptoms:
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
    • Abdominal pain Abdominal Pain Acute Abdomen
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics
    • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
    • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa

Severe malaria

• Can occur with P. falciparum and P. knowlesi parasitemia
• Multiple organ systems can be affected:
  • Decreased consciousness, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Profound weakness
  • Respiratory distress
  • Circulatory collapse
  • Coagulopathy
  • Renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome, hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions (“blackwater fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever”)
  • Hepatic failure Hepatic failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis
  • Metabolic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis
  • Severe anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
  • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia

Diagnosis

History and physical exam

• Residence or travel to an endemic region
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
• Pallor ( anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types)
• Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly (appears around day 4)

Laboratory tests

• CBC:
  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types (decreased hemoglobin and hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia), increased reticulocyte Reticulocyte Immature erythrocytes. In humans, these are erythroid cells that have just undergone extrusion of their cell nucleus. They still contain some organelles that gradually decrease in number as the cells mature. Ribosomes are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic ‘reticulum’ (not the same as the endoplasmic reticulum), hence the name reticulocytes. Erythrocytes: Histology counts
  • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
• Metabolic panel:
  • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia
  • Renal abnormalities 
  • Elevated indirect bilirubin Indirect Bilirubin Liver Function Tests and transaminases Transaminases A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Autoimmune Hepatitis 
• Blood smear Blood smear Myeloperoxidase Deficiency: 
  • Thick: Specificity may be difficult, but greater sensitivity.
  • Thin: Specificity is easier, but less sensitivity.
  • Findings:
    • Trophozoite ring within RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology
    • Schizont containing merozoites
    • Red granules (Schüffner granules) are seen throughout the RBC cytoplasm with P. vivax and P. ovale.
    • Gametocytes in peripheral blood are only seen with P. falciparum.
  • Rapid diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests: > 90% specificity and sensitivity
  • PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) assay: specific and sensitive, but rarely available in endemic settings

Management and Prophylaxis

Management

• All confirmed cases of malaria must be reported.
• Indications for hospitalization Hospitalization The confinement of a patient in a hospital. Delirium:
  • Young children
  • Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis individuals
  • Individuals without acquired immunity
  • Hyperparasitemia of 4%–10% (risk of progression to severe disease)
• Treat with antimalarial drugs Antimalarial drugs Malaria, a vector-borne parasitic disease caused by Plasmodium spp., is transmitted via injection of sporozoites or immature forms of the parasite into a person’s bloodstream. Sporozoites then infect the hepatocytes and differentiate into schizonts, which subsequently rupture, and merozoites invade red blood cells. Antimalarial Drugs: 
  • Avoid the same drug for treatment if it was already used for prophylaxis Prophylaxis Cephalosporins.
  • Chloroquine Chloroquine The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. Antimalarial Drugs or hydroxychloroquine Hydroxychloroquine A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. Immunosuppressants for sensitive species
  • Doxycycline or atovaquone Atovaquone A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols. Antimalarial Drugs/ proguanil Proguanil A biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent. Antimalarial Drugs (Malarone) for areas resistant to Chloroquine Chloroquine The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. Antimalarial Drugs
  • Mefloquine Mefloquine A phospholipid-interacting antimalarial drug (antimalarials). It is very effective against plasmodium falciparum with very few side effects. Antimalarial Drugs: Use in areas with chloroquine-resistant P. falciparum if above is not available.
  • Use primaquine Primaquine An aminoquinoline that is given by mouth to produce a radical cure and prevent relapse of vivax and ovale malarias following treatment with a blood schizontocide. It has also been used to prevent transmission of falciparum malaria by those returning to areas where there is a potential for re-introduction of malaria. Adverse effects include anemias and GI disturbances. Antimalarial Drugs for hypnozoites if P. vivax or P. ovale are identified.
  • If life-threatening, use IV quinidine Quinidine An optical isomer of quinine, extracted from the bark of the cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potentials, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission. Class 1 Antiarrhythmic Drugs (Sodium Channel Blockers) or artesunate (monotherapy is usually inefficient for severe malaria due to P. falciparum).

Prophylaxis Prophylaxis Cephalosporins

• Medications need to be initiated before traveling to endemic regions:
  • For areas with chloroquine-sensitive P. falciparum: Use chloroquine Chloroquine The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. Antimalarial Drugs.
  • For areas with chloroquine-resistant P. falciparum: Use doxycycline, mefloquine Mefloquine A phospholipid-interacting antimalarial drug (antimalarials). It is very effective against plasmodium falciparum with very few side effects. Antimalarial Drugs, or atovaquone-proguanil (Malarone).
  • For areas without P. falciparum: Use primaquine Primaquine An aminoquinoline that is given by mouth to produce a radical cure and prevent relapse of vivax and ovale malarias following treatment with a blood schizontocide. It has also been used to prevent transmission of falciparum malaria by those returning to areas where there is a potential for re-introduction of malaria. Adverse effects include anemias and GI disturbances. Antimalarial Drugs.
  • For pregnant patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship: Use chloroquine Chloroquine The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. Antimalarial Drugs or mefloquine Mefloquine A phospholipid-interacting antimalarial drug (antimalarials). It is very effective against plasmodium falciparum with very few side effects. Antimalarial Drugs.
• Mosquito nets
• Long-sleeved clothes
• Insect repellent Insect repellent Substances causing insects to turn away from them or reject them as food. St. Louis Encephalitis Virus
• Window screens in homes

Differential Diagnosis

• Dengue Dengue An acute febrile disease transmitted by the bite of aedes mosquitoes infected with dengue virus. It is self-limiting and characterized by fever, myalgia, headache, and rash. Severe dengue is a more virulent form of dengue. Dengue Virus fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever: a viral disease transmitted by mosquitoes. Presentation may include malaise Malaise Tick-borne Encephalitis Virus, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, abdominal discomfort, and muscle aches in association with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Myalgia Myalgia Painful sensation in the muscles. Ion Channel Myopathy and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways from dengue Dengue An acute febrile disease transmitted by the bite of aedes mosquitoes infected with dengue virus. It is self-limiting and characterized by fever, myalgia, headache, and rash. Severe dengue is a more virulent form of dengue. Dengue Virus fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever are usually more severe than myalgia Myalgia Painful sensation in the muscles. Ion Channel Myopathy due to malaria. Dengue Dengue An acute febrile disease transmitted by the bite of aedes mosquitoes infected with dengue virus. It is self-limiting and characterized by fever, myalgia, headache, and rash. Severe dengue is a more virulent form of dengue. Dengue Virus fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever can be complicated by severe thrombocytopenia Severe Thrombocytopenia Thrombocytopenia, bleeding, and shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock. Diagnosis is established with antigen detection Antigen detection Respiratory Syncytial Virus. Management is mostly supportive.
• Chikungunya Chikungunya Chikungunya virus belongs to the Alphavirus genus and causes a viral infection characterized by fever and joint pain. Symptoms usually appear within 1 week of infection. Additional manifestations of chikungunya virus may include muscle pain, headache, maculopapular rash, and lymphadenopathy. Chikungunya Virus: a viral illness transmitted by mosquitoes. Presentation includes abrupt onset of fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and joint pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. Chikungunya Chikungunya Chikungunya virus belongs to the Alphavirus genus and causes a viral infection characterized by fever and joint pain. Symptoms usually appear within 1 week of infection. Additional manifestations of chikungunya virus may include muscle pain, headache, maculopapular rash, and lymphadenopathy. Chikungunya Virus resembles dengue Dengue An acute febrile disease transmitted by the bite of aedes mosquitoes infected with dengue virus. It is self-limiting and characterized by fever, myalgia, headache, and rash. Severe dengue is a more virulent form of dengue. Dengue Virus fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, but is milder, self-limiting Self-Limiting Meningitis in Children, and often with a rash Rash Rocky Mountain Spotted Fever. Treatment includes supportive care.
• Zika Zika Zika virus belongs to the genus Flavivirus and is primarily transmitted by Aedes aegypti mosquitoes, but can also be transmitted sexually and transplacentally. Although most infected patients are asymptomatic, some may present with low-grade fever, pruritic rash, and conjunctivitis. Zika Virus Infection: a virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology causing conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis and headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess. Zika Zika Zika virus belongs to the genus Flavivirus and is primarily transmitted by Aedes aegypti mosquitoes, but can also be transmitted sexually and transplacentally. Although most infected patients are asymptomatic, some may present with low-grade fever, pruritic rash, and conjunctivitis. Zika Virus Infection is associated with Guillain-Barré syndrome Guillain-Barré syndrome Guillain-Barré syndrome (GBS), once thought to be a single disease process, is a family of immune-mediated polyneuropathies that occur after infections (e.g., with Campylobacter jejuni). Guillain-Barré Syndrome and can cause infant microcephaly Microcephaly A congenital abnormality in which the cerebrum is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (desk reference for neuroscience, 2nd ed. ). Fetal Alcohol Spectrum Disorder if infected during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care. Diagnosis is established with serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus and management is mostly supportive.
• Leptospirosis Leptospirosis Leptospira is a spiral or question mark-shaped, gram-negative spirochete with hook-shaped ends. The major clinical species is Leptospira interrogans, which causes a mild flu-like illness in a majority of cases. The manifestations are biphasic, with Leptospira found in the blood initially. Leptospira/Leptospirosis: a bacterial disease associated with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, rigors Rigors Fever, myalgia Myalgia Painful sensation in the muscles. Ion Channel Myopathy, and headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess. Myalgia Myalgia Painful sensation in the muscles. Ion Channel Myopathy is usually more severe than in malaria. Presentation may also include petechial hemorrhages Petechial Hemorrhages Brown-Séquard Syndrome in the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions or mucous membranes. Diagnosis is established with culture and treatment includes antibiotics.