VIRAL EXANTHEMS OTHER SYSTEMIC INFECTIONS LEARNING OBJECTIVES 1. Recognize common viral exanthems based on clinical manifestations. 2. Characterize common systemic infections based on etiologic agent, , signs, clinical manifestations, diagnosis, treatment and prevention. 3. Compare and contrast mosquito-borne viral diseases such as dengue, chikungunya, and zika virus disease according to etiologic agent, signs and symptoms, diagnosis, and prevention. OVERVIEW OF VIRAL EXANTHEMS An exanthem is a skin rash accompanied by systemic symptoms such as fever, headache, and malaise. Etiologies include infectious pathogens, medication reactions, and sometimes, a combination of both. In children, exanthems are most often related to infection, the most common of which are of viral etiology. MACULAR & MACULOPAPULAR EXANTHEMS MEASLES (RUBEOLA) Measles is a highly contagious acute viral infection primarily affecting the respiratory system. Incubation period: 11-12 days Typically presents with: An initial phase (prodrome: 2-4 days) marked by high fever (up to 105°F), general discomfort, and the classic triad of cough, coryza (runny nose), and conjunctivitis (3C’s) Koplik spots, a distinctive enanthema inside the mouth may also appear 2–3 days after symptoms first appear. MACULAR & MACULOPAPULAR EXANTHEMS MEASLES (RUBEOLA) ▪ A subsequent maculopapular rash ❖The rash usually emerges around 14 days after exposure, beginning on the face and gradually spreading to the trunk and lower limbs. Individuals are contagious from 4 days before to 4 days after the onset of the rash. In some cases, especially among immunocompromised patients, the rash may not develop. MACULAR & MACULOPAPULAR EXANTHEMS MEASLES (RUBEOLA) Measles rash: Coalescing erythematous macules and papules that appear on the face at the hairline and spread downward to the neck, trunk, arms, legs, and feet; When the rash appears, a person’s fever may spike to more than 40°C Eruption typically resolves in the same order as its appearance, and will often desquamate. MACULAR & MACULOPAPULAR EXANTHEMS MEASLES (RUBEOLA) https://www.cdc.gov/measles/symptoms/photos.html MACULAR & MACULOPAPULAR EXANTHEMS MEASLES (RUBEOLA) Complications: Individuals that are more likely to suffer from measles complications: Children younger than 5 years of age Adults older than 20 years of age Pregnant women People with compromised immune systems, such as from leukemia or HIV infection Common complications Ear infections occur in about one out of every 10 children with measles. Diarrhea is reported in less than one out of 10 people with measles. https://www.cdc.gov/measles/symptoms/complications.html MACULAR & MACULOPAPULAR EXANTHEMS MEASLES (RUBEOLA) Severe complications https://www.cdc.gov/measles/symptoms/complications.html MACULAR & MACULOPAPULAR EXANTHEMS MEASLES (RUBEOLA) Transmission: by direct contact with infectious droplets or by airborne spread when an infected person breathes, coughs, or sneezes. infectious 4 days before and 4 days after rash onset Measles virus can remain infectious in the air for up to two hours after an infected person leaves an area. up to 9 out of 10 susceptible persons with close contact to a measles patient will develop measles. MACULAR & MACULOPAPULAR EXANTHEMS MEASLES (RUBEOLA) Treatment and prevention • no specific antiviral therapy for measles • supportive management to help relieve symptoms and address complications • isolation for four days after development of rash • airborne precautions should be followed in healthcare settings. • Vaccination: measles-mumps-rubella (MMR) vaccine; measles-mumps-rubella-varicella (MMRV) vaccine; MACULAR & MACULOPAPULAR EXANTHEMS RUBELLA (GERMAN MEASLES) Caused by Rubella virus: an enveloped, positive-stranded RNA virus classified as a Rubivirus in the Matonaviridae family The average incubation period of rubella virus is 17 days, with a range of 12 to 23 days. characterized by a mild, maculopapular rash along with lymphadenopathy, and a slight fever. Rash occurs in 50-80% of infected people, which usually starts on the face, becomes generalized within 24 hours, and lasts a median of 3 days; Lymphadenopathy: often involves posterior auricular or suboccipital lymph nodes, lasting between 5 and 8 days. About 25% to 50% of infections are asymptomatic. MACULAR & MACULOPAPULAR EXANTHEMS RUBELLA (GERMAN MEASLES) Complications Arthralgia or arthritis may occur in up to 70% of adult women with rubella. Rare complications include thrombocytopenic purpura and encephalitis. When rubella infection occurs during pregnancy, especially during the first trimester, serious consequences can result. miscarriages, fetal deaths/stillbirths severe birth defects known as congenital rubella syndrome (CRS) o cataracts o heart defects o hearing impairment MACULAR & MACULOPAPULAR EXANTHEMS RUBELLA (GERMAN MEASLES) Transmission • By direct or droplet contact from nasopharyngeal secretions. • Humans are the only natural hosts. • People infected with rubella are most contagious when the rash is erupting, but they can be contagious from 7 days before to 7 days after the rash appears. Treatment and Prevention • supportive • prompt isolation of people suspected to have rubella, should be isolated for 7 days after they develop rash. • Vaccination: MMR, MMRV MACULAR & MACULOPAPULAR EXANTHEMS ROSEOLA INFANTUM caused by human herpesvirus (HHV) types 6 and 7 or the Roseolovirus genus in the subfamily of Betaherpesvirinae. highly prevalent in the healthy population By the end of the second year of life, approximately 75% of all children are seropositive for HHV-6 approximately 24% of all children with HHV-6 infection will manifest clinical symptoms of Roseola. frequently shed in saliva of healthy donors the pathogenic potential of reactivated virus ranges from asymptomatic infection to severe diseases in transplant recipients. Incubation period of 5–15 days MACULAR & MACULOPAPULAR EXANTHEMS ROSEOLA INFANTUM • Infected children develop high fevers that last 3–5 days, followed by the acute onset of a rosey pink, nonpruritic macular rash, predominantly on the neck and trunk. • Roseola infection can cause leukopenia, and rarely, thrombocytopenia and hepatitis. • Patients generally recover without sequelae. • However, approximately 22% of patients with roseola may develop febrile seizures. • Management is supportive. • No vaccine is available MACULAR & MACULOPAPULAR EXANTHEMS ERYTHEMA INFECTIOSUM – 5TH DISEASE caused by parvovirus B19 – a nonenveloped, ssDNA virus belonging to the Parvoviridae family. the only parvovirus that has been linked directly to disease in humans. spreads through respiratory secretions, such as saliva, sputum, or nasal mucus, when an infected person coughs or sneezes. most contagious during period of “just a fever and/or cold” and before the appearance of the rash or joint pain and swelling No longer contagious when the rash appears Incubation period: 1 – 2 weeks MACULAR & MACULOPAPULAR EXANTHEMS ERYTHEMA INFECTIOSUM manifests in three overlapping stages. First stage: fiery-red facial erythema described as having a 'slapped cheeks' appearance Second stage: a reticulate macular or urticarial exanthem 1– 4 days after the slapped cheek eruption third stage: intermittent exanthem recurring in response to stimuli, such as local irritation, high temperatures and emotional stress. Arthropathy may occur in up to 60% of adults and in approximately 10% of children MACULAR & MACULOPAPULAR EXANTHEMS ERYTHEMA INFECTIOSUM classic 'slapped cheek' appearance of erythema infectiosum. MACULAR & MACULOPAPULAR EXANTHEMS ERYTHEMA INFECTIOSUM Parvovirus B19 infection can suppress red blood cell production, causing transient aplastic crisis, chronic red cell aplasia, hydrops fetalis or congenital anemia. Treatment and prevention Supportive/ symptomatic relief Although treatment is supportive, at-risk patients may require transfusions or intravenous immunoglobulin therapy No antiviral medication available No vaccine available strict infection control practices NUMBERED DISEASES OF CHILDHOOD: RASHES “ in 1905 when pediatricians tried to describe the six then known diseases which cause rashes by giving them numbers.” http://pediatric-house-calls.djmed.net/numbered-skin-rashdiseases-childhood/ CHICKENPOX caused by varicella-zoster virus (VZV), a DNA virus, of the herpesvirus group. Primary infection with VZV causes varicella. After the primary infection, VZV stays in the body (in the sensory nerve ganglia) as a latent infection. Reactivation of latent infection causes herpes zoster (shingles) incubation period for varicella is 10 to 21 days (average: 14-16 days) after exposure to a varicella or a herpes zoster rash A mild prodrome of fever and malaise may occur 1 to 2 days before rash onset, particularly in adults. In children, the rash is often the first sign of disease. CHICKENPOX Varicella in Unvaccinated Persons The rash is generalized and pruritic. It progresses rapidly from macular to papular to vesicular lesions before crusting. The rash usually appears first on the chest, back, and face, then spreads over the entire body Symptoms typically last 4 to 7 days. • Varicella in vaccinated Persons (Breakthrough Varicella) – Infection occurring in a vaccinated person more than 42 days after varicella vaccination. – is usually mild; typically with low grade or no fever, and fewer than 50 skin lesions. – 25% to 30% of people will have clinical features similar to unvaccinated people with varicella. CHICKENPOX Transmission spread from person to person by direct contact, inhalation of aerosols from vesicular fluid of skin lesions of acute varicella or zoster, and possibly through aerosolized infected respiratory secretions A person with varicella is considered contagious beginning one to two days before rash onset until all the chickenpox lesions have crusted. Vaccinated people may develop lesions that do not crust. These people are considered contagious until no new lesions have appeared for 24 hours. CHICKENPOX • Complications o Most common complications - In children: Bacterial infections of the skin and soft tissues - In adults: Pneumonia o Severe complications - caused by the virus: cerebellar ataxia, encephalitis, viral pneumonia, and hemorrhagic conditions. - Due to bacterial infections: Septicemia, Toxic shock syndrome, Necrotizing fasciitis Osteomyelitis, Bacterial pneumonia, Septic arthritis CHICKENPOX • Treatment and Prevention o varicella-zoster immune globulin can prevent varicella from developing or lessen the severity of the disease. o Antiviral drug: oral acyclovir or valacyclovir treatment, recommended for: - Healthy people older than 12 years of age - People with chronic cutaneous or pulmonary disorders - People receiving long-term salicylate therapy - People receiving short, intermittent, or aerosolized courses of corticosteroids o standard precautions plus airborne precautions (negative air-flow rooms) and contact precautions until lesions are dry and crusted. SHINGLES People with herpes zoster most commonly have a rash in one or two adjacent dermatomes (localized zoster); does not usually cross the body’s midline. Disseminated zoster can be difficult to distinguish from varicella. The rash is usually painful, itchy, or tingly. The rash develops into clusters of vesicles. New vesicles continue to form over three to five days and progressively dry and crust over. They usually heal in two to four weeks. SHINGLES Complications: Postherpetic neuralgia (PHN) ➢ is the most common complication of herpes zoster. ➢ persists in the area where the rash once was for more than 90 days after rash onset. ➢ can last for weeks or months, and occasionally, for years. - Other complications ➢ ophthalmic involvement (herpes zoster ophthalmicus) ➢ bacterial superinfection of the lesions, ➢ cranial and peripheral nerve palsies ➢ visceral involvement, such as meningoencephalitis, pneumonitis, hepatitis, and acute retinal necrosis. SHINGLES SHINGLES SHINGLES Management • Recombinant zoster vaccine (RZV, Shingrix) is the recommended vaccine to prevent shingles and its complications for adults 50 years and older. • Several antiviral medicines—acyclovir, valacyclovir, and famciclovi • most effective when started as soon as possible after the rash appears. • Pain medicine may help relieve the pain caused by shingles. • Wet compresses, calamine lotion, and colloidal oatmeal baths (a lukewarm bath mixed with ground up oatmeal) may help relieve itching. OTHER SYSTEMIC INFECTIONS DENGUE Dengue is common in more than 100 countries around the world. Each year, up to 400 million people get infected with dengue. Approximately 100 million people get sick from infection 22,000 die from severe dengue. DENGUE CASES IN THE PHILIPPINES 2023 2022 2021 2020 2019 2018 0 50000 100000 150000 DEATHS 2018 2019 2020 2021 2022 2023 200000 250000 CASES CASES 216190 237563 90135 79872 252700 195603 DEATHS 1083 1869 324 285 894 657 300000 DENGUE Dengue is caused by one of any of four related viruses: Dengue virus 1, 2, 3, and 4. For this reason, a person can be infected with a dengue virus as many as four times in his or her lifetime Dengue virus (DENV), a single-stranded positive sense RNA virus DENGUE TRANSMISSION Dengue viruses are spread to humans through the bite of an infected Aedes species (Ae. aegypti or Ae. albopictus) mosquito. typically lay eggs near standing water in containers that hold water usually bite during the day, peaking during early morning and late afternoon/evening become infected when they bite a person infected with the virus. DENGUE TRANSMISSION From mother to child A pregnant woman already infected with dengue can pass the virus to her fetus during pregnancy or around the time of birth. To date, there has been one documented report of dengue spread through breast milk. Through infected blood, laboratory, or healthcare setting exposures Rarely, dengue can be spread through blood transfusion, organ transplant, or through a needle stick injury. DENGUE CLINICAL MANIFESTATIONS 1 in 4: About one in four people infected with dengue virus will get sick. For people who get sick with dengue, symptoms can be mild or severe. Severe dengue can be life-threatening within a few hours and often requires care at a hospital. DENGUE CLINICAL MANIFESTATIONS Severe Dengue About 1 in 20 people who get sick with dengue will develop severe dengue. Severe dengue can result in shock, internal bleeding, and even death. When there is history of dengue in the past, the person is more likely to develop severe dengue. Dengue begins abruptly after a typical incubation period of 5–7 days, and the course follows 3 phases: febrile, critical, and convalescent. Symptoms of dengue typically last 2–7 days. Most people will recover after about a week. DENGUE CLINICAL MANIFESTATIONS From 1975 through 2009, symptomatic dengue virus infections were classified according to the WHO guidelines as: • dengue fever • dengue hemorrhagic fever (DHF) • dengue shock syndrome DENGUE CLINICAL MANIFESTATIONS Guideline on classification of symptomatic cases as dengue or severe dengue (WHO, 2009) • Dengue is defined by a combination of ≥2 clinical findings in a febrile person who traveled to or lives in a dengue-endemic area. ➢ Clinical findings include nausea, vomiting, rash, aches and pains, a positive tourniquet test, leukopenia, and the following warning signs: abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy, restlessness, and liver enlargement. DENGUE CLINICAL MANIFESTATIONS Guideline on classification of symptomatic cases as dengue or severe dengue (WHO, 2009) • Severe dengue is defined as dengue with any of the following symptoms: severe plasma leakage leading to shock or fluid accumulation with respiratory distress; severe bleeding; or severe organ impairment such as elevated transaminases ≥1,000 IU/L, impaired consciousness, or heart impairment. DENGUE PHASES OF DENGUE Febrile Phase • Fever typically lasts 2–7 days, may be biphasic. • Other signs and symptoms: o severe headache; retro-orbital eye pain o muscle, joint, and bone pain; o macular or maculopapular rash; o minor hemorrhagic manifestations o Warning signs of progression to severe dengue may occur in the late febrile phase to resolution of fever (defervescence) • persistent vomiting, severe abdominal pain, • fluid accumulation, liver enlargement, difficulty breathing • lethargy/restlessness, • postural hypotension, • progressive increase in hematocrit • mucosal bleeding DENGUE CLINICAL MANIFESTATIONS Critical Phase • Begins at defervescence and typically lasts 24–48 hours. • Most patients clinically improve during this phase • Patients with significant extravasation of fluid, within a few hours, can develop severe dengue due to increased capillary permeability • pleural effusions, ascites, hypoproteinemia, or hemoconcentration; compensatory narrowing of pulse pressure • Hypotension and irreversible shock and death • Patients can also develop severe hemorrhagic manifestations • Rarely, patients may develop hepatitis, myocarditis, pancreatitis, and encephalitis. • Laboratory findings: leukopenia, thrombocytopenia, hyponatremia, elevated hepatic transaminases, and a normal erythrocyte sedimentation rate. DENGUE CLINICAL MANIFESTATIONS Convalescent Phase • • As plasma leakage subsides, reabsorption of extravasated fluids begins, stabilizing hemodynamic status. • diuresis ensues • Hematocrit decreases • WBC and platelet counts start to rise normal. The convalescent-phase rash may desquamate and be pruritic. DENGUE DIAGNOSIS • “Clinicians should consider dengue in a patient with a clinically compatible illness, and who lives in or recently traveled to a disease-endemic area in the 2 weeks before symptom onset. • Patients typically present with acute onset of fever, headache, body aches, and sometimes rash spreading from the trunk. • All patients with clinically suspected dengue should receive appropriate management to monitor for shock and reduce the risk of complications resulting from increased vascular permeability and plasma leakage and organ damage without waiting for diagnostic test results to be received.” https://www.cdc.gov/dengue/healthcare-providers/diagnosis.html https://www.cdc.gov/dengue/healthcare-providers/diagnosis.html DENGUE DIAGNOSIS: TESTING Molecular test: Nucleic Acid Amplification Test (NAAT) - A NAAT is a generic term referring to molecular tests used to detect viral genomic material (example: RT-PCR) - NAAT assays provide confirmed evidence of infection Dengue Virus Antigen Detection: NS1 - NS1 tests detect the non-structural protein NS1 of dengue virus, a protein secreted during dengue infection. DENGUE TREATMENT No specific antiviral agent is available. Supportive care is advised: Adequate hydration No aspirin containing drugs, no NSAID (like ibuprofen) because of their anticoagulant properties Control of fever by paracetamol and tepid sponge baths Avoid mosquito bites (to reduce risk of further transmission) For severe dengue: close observation and frequent monitoring Prophylactic platelet transfusions in dengue patients are not beneficial and may contribute to fluid overload. Administration of corticosteroids has no demonstrated benefit, except in the case of autoimmune-related complication DENGUE PREVENTION AND CONTROL Vaccine: (Dengvaxia®) for people ages 9-45 years old. 3 shots, 6 months apart WHO: recommends that the vaccine only be given to persons with confirmed prior dengue virus infection. people who receive the vaccine and have not been previously infected with a dengue virus may be at risk of developing severe dengue if they get dengue after being vaccinated. No prophylaxis is available to prevent dengue. Travelers going to areas with risk of dengue should take steps to avoid mosquito bites. CHIKUNGUNYA Mosquito-borne viral disease that often occurs as large outbreaks Seen in countries in Africa, Asia, Europe, Indian and Pacific Oceans, and in Caribbean islands Characterized by acute onset of fever and severe polyarthralgia Caused by: Chikungunya virus Single-stranded RNA virus of Genus Alphavirus; Family Togaviridae Insect vector: Aedes aegypti and Aedes albopictus CHIKUNGUNYA CLINICAL MANIFESTATIONS Most are symptomatic Incubation period: usually 3–7 days (range 1–12 days) Primary clinical findings: acute onset of fever and polyarthralgia Joint symptoms usually symmetric, often involving the hands and feet; can be severe and debilitating Other symptoms: Headache, myalgia, arthritis, conjunctivitis, nausea/vomiting, maculopapular rash Laboratory findings: Lymphopenia, thrombocytopenia, elevated creatinine, elevated hepatic transaminases are CHIKUNGUNYA VIRUS VERSUS DENGUE VIRUS Difficult to clinically distinguish chikungunya and dengue based Both are transmitted by the same mosquitoes Both can circulate in the same area and cause occasional co-infections in the same patient Chikungunya virus more likely to cause high fever, severe polyarthralgia, arthritis, rash, and lymphopenia Dengue virus more likely to cause neutropenia, thrombocytopenia, hemorrhage, shock, and deaths Patients with suspected chikungunya should be managed as dengue until dengue has been ruled out CHIKUNGUNYA MANAGEMENT No specific antiviral therapy is available Supportive, symptomatic treatment Adequate Hydration; fever and pain management Evaluate for other serious conditions (e.g., dengue, malaria, and bacterial infections Fever and pain control Initially managed with paracetamol If the patient may have dengue, do not use aspirin or other NSAIDs until they have been afebrile ≥48 hours have no warning signs for severe dengue* For persistent joint pain; may benefit from use of NSAIDs, corticosteroids, or physiotherapy CHIKUNGUNYA PREVENTION AND CONTROL No vaccine or medication is available to prevent infection Avoid mosquito bites Empty standing water from outdoor containers Support local vector control programs People suspected to have chikungunya or dengue should be protected from further mosquito exposure during the first week of illness to reduce the risk of further transmission People at increased risk for severe disease should consider not traveling to areas with ongoing chikungunya outbreaks ZIKA Caused by a mosquito-borne flavivirus Transmitted primarily by Aedes mosquitoes Incubation perod: 3–14 days. Most infected persons are asymptomatic Generally with mild presentations: fever, rash, conjunctivitis, muscle and joint pain, malaise or headache. Zika virus infection during pregnancy can cause infants to be born with microcephaly and other congenital malformations, known as congenital Zika syndrome. Infection with Zika virus is also associated with other complications of pregnancy including preterm birth and miscarriage. Associated with An increased risk of neurologic complications in adults and children, including Guillain-Barré syndrome, neuropathy and myelitis. https://www.who.int/news-room/fact-sheets/detail/zika-virus ZIKA Transmission: from a pregnant woman to her fetus. Infection during pregnancy can cause certain birth defects. through sex from a person who has Zika to his or her sex partners. There is no treatment available for Zika virus infection Supportive management: Hydration and Control of fever and pain No vaccine is currently available. Prevention: Avoid mosquito bites, specially among pregnant women, women of reproductive age, and young children. Vector control programs https://www.who.int/news-room/fact-sheets/detail/zika-virus TYPHOID AND PARATYPHOID FEVER Typhoid fever: a life-threatening illness caused by Salmonella typhi Paratyphoid fever is a life-threatening illness caused by Salmonella paratyphi bacteria. Globally, each year, typhoid fever affects about 11 to 21 million people and paratyphoid fever affects about 5 million people usually TYPHOID AND PARATYPHOID FEVER Incubation period: for typhoid fever: ≈ 6 to 30 days for paratyphoid fever: 1 to 10 days for Transmission: commonly through the consumption of drinking water or food contaminated with the feces of people who have typhoid fever or paratyphoid fever or of people who are chronic carriers of the responsible bacteria. TYPHOID AND PARATYPHOID FEVER Clinical Presentation: Typhoid fever and paratyphoid fever have similar symptoms̵. a sustained fever that can be as high as 103–104°F (39–40°C). Weakness; headache Stomach pain; diarrhea or constipation Loss of appetite; cough Some develop a rash of flat, rose-colored spots. Without treatment, the illness lasts for 3 to 4 weeks, with mortality rate ranging from 12% to 30%. Up to 10% of untreated patients may have relapse about 1 to 3 weeks after recovering from the initial illness; which is often milder than the initial illness. Stool or urine cultures for Salmonella typhi may remain positive for more than one year, a chronic carrier state occurring in up to 5% of infected people TYPHOID AND PARATYPHOID FEVER Diagnosis Multiple cultures are usually needed to identify the pathogen Blood culture is the mainstay of diagnosis. Bone marrow cultures can remain positive despite antibiotic therapy. Stool and urine cultures are positive less frequently. Serologic tests, such as the Widal test, are not recommended because of the high rate of false positives. Treatment Typhoid fever and paratyphoid fever are treated with antibiotics. Antimicrobial resistance in typhoid fever has been increasing. Prevention: Vaccines are available for Salmonella typhi, none for Salmonella paratyphi Safe eating and drinking habits
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