1 Malaria Co-Author

Malaria Author: Thomas E Herchline, MD Professor of Medicine, Wright State University, Boonshoft School of Medicine; Medical Consultant, Public Health, Dayton and Montgomery County (Ohio) Tuberculosis Clinic Thomas E Herchline, MD is a member of the following medical societies: Alpha Omega Alpha, Infectious Diseases Society of America, Infectious Diseases Society of Ohio. Co-author: Ryan Q Simon, MD Infectious Disease Specialist, Wright State Physicians, Wright State University of Medicine Chief Editor Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Centre; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation Additional Contributors Emilio V Perez-Jorge, MD, FACP Staff Physician, Division of Infectious Diseases, Lexington Medical Centre Emilio V Perez-Jorge, MD, FACP is a member of the following medical societies: American College 1 of Physicians-American Society of Internal Medicine, Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, South Carolina Infectious Diseases Society Acknowledgements Michael Stuart Bronze, MD Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Centre Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation Joseph Richard Masci, MD Professor of Medicine, Professor of Preventive Medicine, Mount Sinai School of Medicine; Director of Medicine, Elmhurst Hospital Centre Joseph Richard Masci, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, Association of Professors of Medicine, and Royal Society of Medicine Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Centre College of Pharmacy; Editor-in-Chief, Medscape Drug Reference 2 Course Content Malaria Practice Essentials Signs and Symptoms History Diagnosis Approach Considerations Imaging Studies Microhematocrit centrifugation Fluorescent dyes/ultraviolet indicator tests Polymerase chain reaction assay Lumber puncture Blood smears Thick smears Thin smears Alternative to Blood Smear testing Rapid diagnostic tests (RDT) Other tests Management Approach Considerations Pregnancy Pediatrics Diet and Activity Monitoring Pharmacologic Therapy Pharmacologic treatment in pregnancy Inpatient Care Deterrence and prevention Investigational malaria vaccines Consultation Medication Summary 3 Malaria Practice Essentials Malaria is a potentially life-threatening disease caused by infection with Plasmodium protozoa transmitted by an infective female Anopheles mosquito. Plasmodium falciparum infection carries a poor prognosis with a high mortality if untreated, but it has an excellent prognosis if diagnosed early and treated appropriately. See the image below. Malarial merozoites in the peripheral blood. Note that several of the merozoites have penetrated the erythrocyte membrane and entered the cell. Signs and symptoms Patients with malaria typically become symptomatic a few weeks after infection, though the symptomatology and incubation period may vary, depending on host factors and the causative species. Clinical symptoms include the following: 4 • Headache (noted in virtually all patients with malaria) • Cough • Fatigue • Malaise • Shaking chills • Arthralgia • Myalgia • Paroxysm of fever, shaking chills, and sweats (every 48 or 72 hours, depending on species) Less common symptoms include the following: • Anorexia and lethargy • Nausea and vomiting • Diarrhea • Jaundice Most patients with malaria have no specific physical findings, but splenomegaly may be present. Severe malaria manifests as the following: • Cerebral malaria (sometimes with coma) • Severe anemia • Respiratory abnormalities: Include metabolic acidosis, associated respiratory distress, and pulmonary edema; signs of malarial hyperpneic syndrome include alar flaring, chest retraction, use of accessory muscles for respiration, and abnormally deep breathing • Renal failure (typically reversible) History In patients with suspected malaria, obtaining a history of recent or remote travel to an endemic area is critical. Asking explicitly if they travelled to a tropical area at any time in their life may enhance recall. Maintain a high index of suspicion for malaria in any patient exhibiting any malarial symptoms and having a history of travel to endemic areas. Also determine the patient's immune status, age, and pregnancy status; allergies or other medical conditions that he or she may have; and medications that he or she may be using. 5 Patients with malaria typically become symptomatic a few weeks after infection, although the host's previous exposure or immunity to malaria affects the symptomatology and incubation period. In addition, each Plasmodium species has a typical incubation period. Importantly, virtually all patients with malaria present with headache. Clinical symptoms also include the following: • Cough • Fatigue • Malaise • Shaking chills • Arthralgia • Myalgia Paroxysm of fever, shaking chills, and sweats (every 48 or 72 h, depending on species) The classic paroxysm begins with a period of shivering and chills, which lasts for approximately 1-2 hours and is followed by a high fever. Finally, the patient experiences excessive diaphoresis, and the body temperature of the patient drops to normal or below normal. Many patients, particularly early in infection, do not present the classic paroxysm but may have several small fevers spikes a day. Indeed, the periodicity of fever associated with each species (i.e. 48 h for P falciparum, P vivax, and P ovale [or tertian fever] ; 72 h for P malariae [or quartan fever]) is not apparent during initial infection because of multiple broods emerging in the bloodstream. In addition, the periodicity is often not observed in P falciparum infections. Patients with long-standing, synchronous infections are more likely to present with classic fever patterns. In general, however, the occurrence of periodicity of fever is not a reliable clue to the diagnosis of malaria. Less common malarial symptoms include the following: • Anorexia and lethargy • Nausea and vomiting • Diarrhea • Jaundice Notably, infection with P vivax, particularly in temperate areas of India, may cause symptoms up to 6- 12 months after the host leaves the endemic area. In addition, patients infected with P vivax or P ovale may relapse after longer periods, because of the hypnozoite stage in the liver. P malariae does not have a hypnozoite stage, but patients infected with P malariae may have a prolonged, asymptomatic erythrocytic infection that becomes symptomatic years after leaving the endemic area. Tertian and quartan fevers are due to the cyclic lysis of red blood cells that occurs as trophozoites complete their cycle in erythrocytes every 2 or 3 days, respectively. P malariae causes quartan fever; P vivax and P ovale cause the benign form of tertian fever, and P falciparum causes the malignant form. The cyclic pattern of fever is very rare. Travelers to forested areas of Southeast Asia and South America have become infected by Plasmodium knowlesi, a dangerous species normally found only in long tailed and pigtail macaque monkeys (Macaca fascicularis and M nemestrina, respectively). This species can cause severe illness and death in humans, but, under the microscope, the parasite looks similar to the more benign P malariae and has sometimes been misdiagnosed. 6 Plasmodium falciparum is the most common of the four human malaria parasites across much of Sub- Saharan Africa. Because P malariae infection is typically relatively mild, Plasmodium knowlesi infection should be suspected in persons residing or traveling in the above geographical areas who are severely ill and have microscopic evidence of P malariae infection. Diagnosis may be confirmed via polymerase chain reaction (PCR) assay test methods. Diagnosis The patient history should include inquiries into the following: • Recent or remote travel to an endemic area • Immune status, age, and pregnancy status • Allergies or other medical conditions • Medications currently being taken The following blood studies should be ordered: • Blood culture • Hemoglobin concentration • Platelet count • Liver function • Renal function • Electrolyte concentrations (especially sodium) • Monitoring of parameters suggestive of hemolysis (haptoglobin, lactic dehydrogenase [LDH], reticulocyte count) • In select cases, rapid HIV testing • White blood cell count: Fewer than 5% of malaria patients have leukocytosis; thus, if leukocytosis is present, the differential diagnosis should be broadened • If the patient is to be treated with primaquine, glucose-6-phosphate dehydrogenase (G6PD) level • If the patient has cerebral malaria, glucose level to rule out hypoglycemia

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