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Remittent fever

Remittent fever is a pattern of fever in which body temperature rises and falls daily, typically by 0.3°C to 1.4°C, but never returns to normal levels (below 37.2°C or 99°F).^[1]^[2] This distinguishes it from intermittent fever, where temperature periodically returns to normal, and from continuous fever, which remains steadily elevated without significant daily variation.^[3] The pattern is not diagnostic on its own but often signals an underlying infectious or inflammatory process, with symptoms including chills, sweats, and general malaise alongside the fluctuating temperature.^[1]

Characteristics and Patterns

Remittent fever exhibits daily amplitude variations, commonly between 0.3°C and 1.4°C in milder forms, though "hectic" variants can fluctuate more widely (≥1.4°C).^[1] Clinically, it may evolve from an initial intermittent pattern into a more sustained elevation if untreated, and temperature charting over several days is essential for identification.^[3] Unlike sustained fevers, the diurnal rhythm persists, with peaks often in the late afternoon or evening, reflecting the body's hypothalamic response to pyrogens such as cytokines released during infection.^[2]

Causes and Associated Conditions

The most common causes of remittent fever are bacterial infections, including pneumonia, typhoid fever, pyelonephritis, brucellosis, rickettsial infections, and infective endocarditis.^[2]^[1] It is also frequently linked to abscesses, ascending cholangitis, and other pyogenic processes, as well as tuberculosis and certain malignancies like lymphomas or hypernephromas.^[1] Non-infectious etiologies, such as drug reactions or autoimmune conditions, can occasionally produce this pattern, though infections predominate in acute cases.^[3] In tropical regions, it may indicate other vector-borne diseases like certain rickettsial infections.^[2]

Diagnosis and Management

Diagnosis relies on a thorough history, physical examination, and laboratory tests to identify the underlying cause, as the fever pattern alone rarely specifies the etiology.^[3] Blood cultures, imaging, and serologic assays are often employed, particularly for suspected bacterial or parasitic origins.^[1] Treatment focuses on addressing the root condition—such as antibiotics for bacterial infections or antimalarials for parasitic causes—while antipyretics like acetaminophen or ibuprofen provide symptomatic relief by reducing temperature spikes.^[3] Early intervention is critical, as prolonged remittent fever can lead to complications like dehydration or sepsis if the primary disease progresses.^[2]

Definition and Classification

Definition

Remittent fever is a distinctive pattern of fever characterized by daily fluctuations in body temperature that do not return to normal baseline levels, typically remaining above 37.2°C (99°F) throughout the day.^[1] Unlike other fever types, the temperature rises and falls but stays persistently elevated, reflecting ongoing physiological response without complete resolution.^[3] The amplitude of these daily variations typically ranges from 0.3°C to 1.4°C, with more pronounced swings classified as hectic fever if exceeding 1.4°C; note that classifications vary, with some sources describing fluctuations exceeding 2°C.^[1]^[2] This pattern often accompanies systemic symptoms such as chills, sweats, and malaise, highlighting its role as a clinical indicator of underlying inflammatory or infectious processes.^[1] The term "remittent fever" originated in the 19th century, when physicians used it to describe fevers without return to normal temperature, shifting focus in modern medicine to the diurnal variation without normalization.^[4] It commonly manifests in diseases like typhoid fever.^[2]

Comparison with Other Fever Patterns

Remittent fever is characterized by daily temperature fluctuations exceeding 1°C while remaining persistently above the normal baseline (typically >37.2°C), distinguishing it from other fever patterns through its incomplete diurnal remission.^[5] Note that classifications of fever patterns, including fluctuation amplitudes, vary across medical literature and are not always diagnostic on their own.^[3] In contrast, intermittent fever features spikes of elevated temperature that return fully to normal levels (≤37.2°C) between episodes, often on a daily or periodic basis, as seen in the quotidian pattern of malaria where paroxysms occur every 24 hours followed by euthermia.^[6] This return to baseline allows for clear afebrile intervals, unlike the sustained elevation in remittent fever. Continuous or sustained fever maintains an elevated temperature with minimal variation (<1°C over 24 hours), lacking the noticeable diurnal swings of remittent patterns; examples include typhoid fever or typhus, where the temperature plateaus without significant drops.^[7] Relapsing fever, however, involves episodic high fevers recurring after prolonged afebrile periods of several days to weeks, driven by antigenic variation in pathogens like Borrelia species in borreliosis, creating a cyclic pattern absent in the more consistent daily undulations of remittent fever.^[8] Saddleback or biphasic fever presents as two distinct peaks of elevation separated by a partial remission that does not reach normal levels, often over several days, as observed in dengue infections; this contrasts with remittent fever's ongoing, non-biphasic fluctuations without such defined dual phases.^[9] These distinctions aid in pattern recognition, particularly when visualizing temperature curves: intermittent shows sharp peaks dropping to baseline daily, continuous remains flat and high, relapsing has long gaps between spikes, saddleback exhibits a "saddle" dip between two rises, and remittent displays wavy elevations always above normal over 24-48 hours.

Fever Pattern	Key Temperature Behavior	Typical Fluctuation	Example Condition
Intermittent	Returns to normal between daily spikes	>1°C, reaches baseline	Quotidian malaria^[6]
Continuous/Sustained	Persistently elevated with little change	<1°C	Typhoid fever^[7]
Relapsing	Recurrent spikes after days/weeks afebrile	Variable, episodic	Borreliosis^[8]
Saddleback/Biphasic	Two peaks with intervening partial drop	>1°C between peaks	Dengue^[9]
Remittent	Fluctuates but stays above normal daily	>1°C, no baseline	Various infections^[5]

Clinical Presentation

Symptoms

Remittent fever is typically accompanied by a range of systemic symptoms that arise due to the body's inflammatory response and the persistent elevation in core temperature. Common manifestations include chills, characterized by subjective shivering or rigors that often precede or coincide with temperature rises, and profuse sweating, particularly during diurnal fluctuations, which can lead to significant fluid loss.^[1] Fatigue and malaise are nearly universal, contributing to a profound sense of weakness that limits physical exertion, while headache and myalgia—muscle aches—frequently occur as nonspecific indicators of the underlying physiological stress.^[1] Anorexia, or loss of appetite, is also prevalent, further exacerbating nutritional deficits during prolonged episodes.^[10] Associated physiological signs include tachycardia, where heart rate increases by approximately 15 beats per minute for each degree Celsius rise above normal, reflecting the cardiovascular compensation to elevated metabolic demands. Dehydration often develops from insensible losses through sweating and reduced oral intake, manifesting as dry mucous membranes and diminished urine output. In severe cases, particularly when temperatures exceed 40°C, delirium may emerge, presenting as altered mental status, confusion, or agitation due to the direct effects of hyperthermia on cerebral function.^[1]^[10] These symptoms tend to intensify during periods of peak temperature and partially abate during relative troughs, though they persist overall because the baseline temperature never normalizes, creating a cyclical pattern of discomfort driven by the fever's thermal variations. This progression disrupts daily functioning, interfering with sleep through night sweats and restlessness, suppressing appetite to the point of weight loss, and curtailing activity levels, thereby promoting lethargy and social withdrawal.^[1]^[11]^[12]

Temperature Patterns

Remittent fever features daily temperature fluctuations exceeding 1.1°C (2°F), with the body temperature falling each day but never returning to normal levels, typically remaining above 37.3°C (99.1°F).^[13] This pattern distinguishes it through sustained elevation despite variations, often reflecting ongoing inflammatory or infectious processes.^[1] The fever adheres to a diurnal rhythm, with peaks commonly occurring in the late afternoon or evening, around 6 p.m., and troughs in the early morning, resulting in variations greater than 2°C between these points.^[1] This cycle mirrors normal circadian thermoregulation but at an elevated baseline, though rare exceptions like reversed patterns can occur in specific conditions.^[1] Untreated remittent fever typically persists for 1-2 weeks, though durations of 3-21 days are common depending on the underlying cause, and it may extend longer or evolve into other patterns if the etiology progresses.^[1] Most infectious causes resolve within 7-10 days with appropriate intervention, but chronicity beyond 2-3 weeks raises concern for fever of undetermined origin.^[13] Accurate assessment requires oral or rectal thermometry, with rectal measurements preferred for precision as they are approximately 0.5°C higher than oral readings; electronic thermometers ensure supervised consistency.^[13] Serial charting of temperature every 4-6 hours over at least 72 hours is essential to confirm the remittent pattern and distinguish it from other febrile courses.^[1] Variations in remittent fever include milder forms with fluctuations of 0.3-1.4°C daily, contrasted by severe or hectic subtypes exhibiting amplitudes of 1.4°C (2.5°F) or more between peak and trough, often accompanied by pronounced chills during rises and sweats during falls.^[1] These severe swings signal more intense systemic involvement, such as in pyogenic infections.

Etiology

Infectious Causes

Remittent fever, characterized by daily temperature fluctuations exceeding 1–2°C without returning to normal, is frequently associated with various infectious pathogens, particularly in tropical and subtropical regions where transmission is endemic. Bacterial infections such as pneumonia, pyelonephritis, and pyogenic processes including intra-abdominal abscesses or ascending cholangitis commonly present with this pattern due to ongoing inflammation and bacteremia.^[1] Tuberculosis often causes low-grade remittent fever, especially in pulmonary or disseminated forms. Rickettsial infections, such as typhus, also feature remittent fever alongside rash and systemic symptoms.^[1] Among bacterial infections, enteric fevers caused by Salmonella enterica serovar Typhi (typhoid fever) and serovars Paratyphi A, B, or C (paratyphoid fever) classically present with a remittent pattern, often starting as a gradual stepwise rise in the first week of illness due to bacterial invasion of the bloodstream and reticuloendothelial system. This pattern peaks early, with temperatures reaching 39–40°C accompanied by relative bradycardia, and is more pronounced in non-immune travelers or in areas with poor sanitation. The incubation period for enteric fevers typically ranges from 7 to 14 days following ingestion of contaminated food or water.^[14]^[15] Malaria, caused by Plasmodium species such as P. falciparum and P. vivax, is a leading infectious etiology of remittent fever, especially in non-immune hosts where the typical cyclic paroxysms may merge into a continuous fluctuating pattern tied to the parasite's 48-hour erythrocytic schizogony cycle. In severe forms like bilious remittent malaria, persistent high fevers occur alongside gastrointestinal symptoms, reflecting hepatic involvement and hemolysis. This presentation is common in endemic tropical areas of Africa, Asia, and Latin America, with incubation periods of 7–30 days post-mosquito bite (Anopheles species). Globally, malaria accounts for a significant proportion of febrile illnesses in these regions, underscoring its epidemiological importance.^[16]^[17] Other bacterial infections linked to remittent fever include brucellosis (Brucella species), acquired via unpasteurized dairy or contact with infected animals in pastoral communities of the Mediterranean, Middle East, and Latin America. The fever exhibits an undulant or remittent course with daily spikes, reflecting intermittent bacteremia, and incubation periods of 5–60 days (average 1–2 weeks). Leptospirosis, caused by Leptospira interrogans and transmitted through water contaminated by animal urine in tropical flood-prone areas, begins with an acute remittent phase of high fever (38–40°C) and rigors, often after a 5–14 day incubation, potentially progressing to severe Weil's disease if untreated. Subacute bacterial endocarditis, typically due to viridans streptococci or enterococci in patients with underlying valvular damage, features low-grade remittent fevers from fluctuating bacteremia, with insidious onset over weeks to months.^[18]^[19]^[20]^[2]^[21] Viral causes are less common but can occur in certain acute viral infections. Epidemiologically, these infectious etiologies predominate in tropical and endemic areas, with higher incidence during rainy seasons facilitating vector or waterborne transmission; for instance, typhoid incubation is 7–14 days, while malaria's 7–30 days highlights the need for prolonged surveillance in returned travelers.^[2]

Non-Infectious Causes

Remittent fever, characterized by persistent elevation above normal baseline with diurnal fluctuations but without returning to normal, can arise from various non-infectious etiologies, including autoimmune disorders, malignancies, drug reactions, and rare central mechanisms. These causes often involve sterile inflammatory processes or dysregulated thermoregulation, contrasting with the more prevalent infectious origins of this fever pattern.^[2] In autoimmune and rheumatic conditions, adult-onset Still's disease (AOSD) frequently presents with remittent or quotidian fever patterns driven by cytokine flares, where temperatures spike daily to 39–40°C without normalizing between episodes, accompanied by arthralgias and evanescent rash. Systemic lupus erythematosus (SLE) flares can similarly produce remittent fevers due to immune complex-mediated inflammation and cytokine release, with peak temperatures ranging from 38–40.6°C in active disease, often resolving with immunosuppression. These patterns reflect episodic activation of innate immunity in the absence of pathogens.^[22]^[23] Neoplastic processes, particularly hematologic malignancies like Hodgkin lymphoma, may induce remittent "tumor fever" through intermittent tumor necrosis and release of endogenous pyrogens, leading to sustained low-grade elevations with variations up to 1–2°C daily, especially in advanced stages. Solid tumors, such as renal cell carcinoma, can cause similar remittent patterns via paraneoplastic cytokine production, though this is less common than in lymphomas and often signals disseminated disease.^[24]^[25] Drug-induced fever represents another key non-infectious cause, typically manifesting as a remittent or hectic pattern after 7–10 days of exposure to agents like beta-lactam antibiotics or antiepileptics (e.g., phenytoin), with temperatures of 39–40°C and relative bradycardia, resolving rapidly upon discontinuation. This hypersensitivity reaction involves immune-mediated pyrogen release without eosinophilia in all cases.^[26]^[27] Less common differentials include factitious fever, where individuals self-induce remittent patterns through surreptitious manipulation (e.g., heated thermometers or covert infections), often in healthcare workers or those with psychiatric comorbidities, persisting beyond six months in prolonged cases. Central nervous system disorders, such as hypothalamic dysregulation from tumors or trauma, can rarely produce remittent fever via impaired thermoregulatory centers, mimicking infectious profiles but without inflammatory markers.^[28] The underlying pathophysiology across these non-infectious causes centers on endogenous pyrogens, primarily interleukin-1 (IL-1) and IL-6, which are released by activated macrophages or tumor cells, acting on the hypothalamus to elevate the temperature set point through prostaglandin E2 synthesis, resulting in persistent but fluctuating hyperthermia. IL-6, in particular, amplifies this response in autoimmune and neoplastic settings, sustaining the remittent pattern via cyclooxygenase pathways.^[29]^[30]

Diagnosis

History and Physical Examination

The evaluation of remittent fever begins with a detailed patient history to identify potential etiologies, particularly infectious causes prevalent in endemic areas. Clinicians should inquire about recent travel to regions where diseases like malaria or typhoid fever are common, as exposure to mosquito bites or contaminated food and water can precipitate remittent patterns.^[16]^[31] The onset and timeline of symptoms are critical, including the duration of fever fluctuations exceeding 2°C daily without returning to normal, alongside associated features such as chills, headache, myalgias, or gastrointestinal complaints.^[2] A thorough medication review is essential to rule out drug-induced fevers, while assessing for occupational exposures, such as contact with livestock in brucellosis-endemic settings, or family clustering suggesting shared environmental risks.^[32] Patients often report diurnal variations in their fever pattern, with peaks in the late afternoon or evening, which can provide clues to underlying infections like typhoid or brucellosis.^[33] Documentation of these self-reported fluctuations helps confirm the remittent nature, distinguishing it from continuous or intermittent fevers. On physical examination, patients with remittent fever may appear dehydrated, with dry mucous membranes and reduced skin turgor, reflecting fluid losses from sweating and poor intake.^[34] Splenomegaly is a key finding in cases linked to malaria or typhoid, often accompanied by mild hepatomegaly.^[16]^[31] In non-infectious etiologies such as systemic lupus erythematosus, a characteristic malar rash or discoid lesions may be evident, while infective endocarditis can present with new or changing heart murmurs and peripheral embolic phenomena like Janeway lesions.^[35] Red flags warranting urgent evaluation include unintentional weight loss greater than 5% over six months or drenching night sweats, which may signal chronic infections like tuberculosis or underlying neoplasms such as lymphoma. These findings, combined with persistent remittent fever, necessitate a systematic approach to exclude serious pathology.^[36]

Diagnostic Tests

The diagnosis of remittent fever relies on identifying the underlying cause through a stepwise approach beginning with non-invasive laboratory tests and progressing to imaging and advanced procedures as needed.^[36] Initial laboratory evaluations typically include a complete blood count (CBC) to detect abnormalities such as anemia, leukocytosis suggesting bacterial infection, or thrombocytopenia, which may point to sepsis or parasitic causes.^[3] Inflammatory markers like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are routinely measured, often showing elevation in infectious or inflammatory etiologies.^[36] Blood cultures, obtained from multiple sites before antibiotics, are essential for isolating bacteria in cases suspected of typhoid fever or endocarditis.^[37] Specific serological and microbiological tests are selected based on clinical suspicion of common causes. For malaria, a frequent etiology, thick and thin blood smears or rapid diagnostic tests (RDTs) detecting Plasmodium antigens are performed, with smears providing species identification and RDTs offering quick results in resource-limited settings.^[38] In suspected typhoid fever, stool or urine cultures complement blood cultures, while the Widal test for Salmonella Typhi antibodies may be used in endemic areas despite its limitations due to high false-positive rates.^[39] For autoimmune conditions like systemic lupus erythematosus (SLE), an antinuclear antibody (ANA) panel is indicated if non-infectious causes are considered.^[36] Imaging studies support the laboratory findings by identifying focal pathology. A chest X-ray is commonly obtained to evaluate for pneumonia or signs suggestive of endocarditis, such as cardiomegaly.^[3] Abdominal ultrasound is useful for detecting splenomegaly, hepatomegaly, or abscesses, particularly in brucellosis or amebic infections.^[2] If initial tests are inconclusive, advanced imaging like computed tomography (CT) of the chest and abdomen may be pursued.^[36] In cases of persistent remittent fever exceeding three weeks—qualifying as fever of unknown origin (FUO)—a bone marrow biopsy is considered for occult infections, malignancies, or hemophagocytic syndromes, especially if cytopenias are present.^[36] This algorithmic progression prioritizes cost-effective, low-risk tests before invasive ones, guided by epidemiological and historical clues to refine the differential.^[2]

Management

Treatment of Underlying Cause

The treatment of remittent fever focuses on targeting the underlying etiology, whether infectious, autoimmune, or neoplastic, to resolve the fever pattern and associated symptoms. Identification of the specific cause through diagnostic evaluation guides the selection of therapies, with antimicrobial agents commonly used for infectious origins prevalent in regions where remittent fever is endemic, such as malaria-endemic areas.^[40] For infectious causes, antimicrobial therapy is tailored to the pathogen. In malaria due to Plasmodium species, which classically presents with remittent fever, the World Health Organization recommends artemisinin-based combination therapies (ACTs), such as artemether-lumefantrine or artesunate-amodiaquine, as first-line treatment for uncomplicated cases, typically administered for 3 days to rapidly reduce parasitemia and fever.^[40] For typhoid fever caused by Salmonella enterica serovar Typhi, intravenous ceftriaxone at 2 g daily for adults is a standard regimen, particularly in severe or hospitalized patients, with a duration of 10-14 days to achieve clinical cure and prevent relapse.^[41] In brucellosis from Brucella species, a combination of oral doxycycline (100 mg twice daily) plus gentamicin (5 mg/kg daily intramuscularly for 7 days) or rifampin (600-900 mg daily) is recommended, extending for 6-8 weeks to eradicate intracellular bacteria and resolve persistent fever.^[42] Non-infectious etiologies require anti-inflammatory or immunosuppressive agents. For autoimmune conditions like adult-onset Still's disease, which can manifest with remittent fever, initial treatment involves corticosteroids such as prednisone (0.5-1 mg/kg daily) to control systemic inflammation, often followed by disease-modifying antirheumatic drugs (DMARDs) like methotrexate (15-25 mg weekly) for steroid-sparing effects in refractory cases.^[43] In neoplastic fevers associated with malignancies such as lymphomas or solid tumors, oncologic interventions like chemotherapy (e.g., regimens specific to the cancer type) or radiation therapy are employed once the diagnosis is confirmed, leading to fever resolution upon tumor control.^[44] The duration of treatment is pathogen- or condition-specific; acute bacterial infections like typhoid typically require 7-14 days of antibiotics, while chronic ones like brucellosis demand 6 weeks or more to prevent recurrence.^[34] Monitoring involves serial clinical assessments, follow-up blood cultures to confirm pathogen clearance, and serological titers (e.g., for brucellosis or autoimmune markers) to guide therapy adjustments and ensure sustained response.^[45] Recommendations from authoritative bodies, including the World Health Organization for malaria and the Infectious Diseases Society of America for enteric fevers like typhoid, emphasize prompt initiation of targeted therapy based on local resistance patterns and patient factors to optimize outcomes in remittent fever cases.^[46]^[41] Symptomatic relief may serve as an adjunct during the initial phase of etiology-specific treatment.

Symptomatic Management

Symptomatic management of remittent fever primarily aims to reduce discomfort from elevated temperatures and prevent complications, while the underlying cause is addressed separately. Antipyretics such as acetaminophen or ibuprofen are commonly used to lower fever peaks without eliminating the fluctuating pattern. For adults, acetaminophen is typically dosed at 650 to 1000 mg orally every 4 to 6 hours as needed, not exceeding 4000 mg per day to avoid hepatotoxicity. Ibuprofen, an NSAID with anti-inflammatory properties, can be administered at 200 to 400 mg orally every 4 to 6 hours, with a maximum of 1200 mg per day for over-the-counter use. These medications should be taken with food to minimize gastrointestinal irritation, and alternating them may be considered under medical supervision for persistent symptoms. Maintaining hydration and adequate nutrition is crucial to counteract insensible fluid losses from fever, which can lead to dehydration. Patients are advised to consume plenty of oral fluids, such as water, electrolyte solutions, or clear broths, aiming for at least 2 to 3 liters per day depending on severity and body weight. In cases of significant dehydration evidenced by dry mucous membranes, reduced urine output, or orthostatic hypotension, intravenous fluids like normal saline may be administered, with close monitoring of electrolytes such as sodium and potassium to prevent imbalances. Nutritional support, including balanced meals, helps sustain energy levels, though appetite may be reduced during febrile episodes. Environmental measures focus on passive cooling to enhance comfort without inducing shivering, which could paradoxically raise core temperature. Recommendations include wearing lightweight, breathable clothing, maintaining a room temperature of 20 to 22°C (68 to 72°F) with good ventilation, and using a light sheet for covering. Tepid sponging with lukewarm water (around 37°C or 98.6°F) on the forehead, axillae, and groin for 10 to 20 minutes can provide relief, but ice packs or cold baths should be avoided as they may cause vasoconstriction and discomfort. Fans may assist in evaporative cooling if the patient is not chilled. Close monitoring for complications is essential, particularly in vulnerable adults such as the elderly or those with comorbidities. Healthcare providers should watch for signs of heatstroke, including temperatures exceeding 40°C (104°F), confusion, or seizures, which necessitate immediate intervention. Secondary infections may manifest as worsening symptoms or new focal signs, prompting reevaluation. Hospitalization criteria include persistent fever above 40°C unresponsive to antipyretics, altered mental status, severe dehydration, or hemodynamic instability. For mild cases managed at home, patient education emphasizes self-care strategies to empower individuals. Instructions include tracking temperature every 4 to 6 hours, adhering to antipyretic schedules, and seeking prompt medical attention if symptoms escalate. Encouraging rest in a quiet environment, avoiding strenuous activity, and recognizing warning signs like persistent vomiting or rash can prevent progression to severe illness.

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### Diagnostic Tests for Typhoid Fever
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### Diagnostic Tests for Malaria (Laboratory Methods)
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Apr 24, 2024 · Serologic tests, such as the Widal test, are not recommended because of the high rate of false positives. CDC offers testing for Salmonella ...
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The best available treatment, particularly for Plasmodium falciparum malaria, is artemisinin-based combination therapy (ACT). The primary objective of treatment ...
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Oct 16, 2018 · as typhoid and paratyphoid fever, and collectively as enteric fever. ... If susceptible, treatment with ceftriaxone, ciprofloxacin, TMP-SMX ...
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