NurseRatchet
12-11-02, 21:29
Selected exerpts on smallpox from the Agency for Healthcare Research and Quality with AUB School of Medicine Bioterrorism site. Site Link. (http://www.bioterrorism.uab.edu/EIPBA/Smallpox/moreExtInfo.html) Provided under fair use for education and discussion doctrine. All rights reserved to copyright holder.
Epidemiology and Epizootology
Humans are the only natural reservoirs of variola virus. Person-to-person transmission of smallpox occurs by aerosol droplets expelled from the oropharynx of infected persons, or by direct contact with an infected person. The virus can also be spread through contaminated bedding and clothing.
Despite the fact that smallpox is less contagious than influenza or measles, it is still considered a highly contagious disease. The lesion dose index CTW50,the amount of agent inhaled in aerosol form that is required to cause manifest illness in 50% of susceptible humans, is less than 10 viral particles. The patient can be already infectious in the last day of incubation period, and remains contagious until the scabs drop off. The virus can remain viable for months on objects from the victim's surroundings. Though smallpox is spread most readily during dry, cool winter months, the disease can be transmitted in any climate and in all parts of the world.
Vaccination and isolation of infected patients are the only effective protection against the disease. If a patient is vaccinated within 2 or 3 days of exposure, they will most likely not develop the disease. Vaccination 4 or 5 days after exposure may significantly reduce mortality.
Classification and Etiology
Smallpox is a double-stranded DNA virus, and is a member of the genus orthopoxvirus, family Poxviridae. The poxvirus genome is the largest known viral genome. The virus has a characteristically brick-shaped structure and is about 200 mm in diameter. Poxviruses are unique because they replicate in the cytoplasm, rather than the nucleus, of host cells. Other members of the orthopox genus (monkeypox, vaccinia) can infect and cause cutaneous lesions in humans, but only smallpox is readily transmitted from person to person.
Pathologic Anatomy
The endothelial cells lining the sinusoids of the liver are often swollen and occasionally proliferating or necrotic. Reticular cell hyperplasia occurs in the bone marrow and spleen. The spleen is usually engorged and contains many large lymphoid cells. The liver is generally considerably heavier than normal, but this does not appear to be due to engorgement or fatty infiltration. Encephalitis is an occasional complication.
Clinical Manifestations and Diagnosis
Three types of smallpox have been described:
1. Typical smallpox: the characteristic variola major infection that occurs in 95%-98% of infections.
2. Hemorrhagic smallpox: seen in fewer than 3% of patients and characterized by intense toxemia and mucosal hemorrhage.
3. Flat-type smallpox: observed in 2-5% of patients and characterized by severe, systemic toxicity and the evolution of flat, focal skin lesions.
Duration
Subjective and objective clinical symptoms characteristic of the following four periods in the progression of smallpox infection are discussed:
1) Incubation period: virus actively replicating and spreading to lymph nodes and target tissues; patient is generally asymptomatic. The onset of high fever marks the end of the incubation period.
2) Prodromal period: marked by the beginning of subjective, nonspecific clinical symptoms. Patients are most infectious during the first week of this period. Once the fever subsides, the rash usually appears.
3) Manifestation period: development of smallpox lesions and characteristic objective symptoms.
4) Outcome period: associated either with recovery or severe toxemia and death.
Types of smallpox, their details are given below:
1) Typical (variola major)
Incubation Period : 7-14 days for natural infection
1-5 for infection due to deliberate release of aerosolized virus*
Prodromal Period : 2-3 days
Manifestation Period : 8-9 days
Period of Outcome : 2nd week of illness
2) Hemorrhagic
Incubation Period : 7-14 days
Prodromal Period : 1-2 days
Manifestation Period : 5-6 days
Period of Outcome - N/A
3) Flat
Incubation Period : 7-14 days
Prodromal Period : 1-2 days
Manifestation Period : 2-3 days
Period of Outcome - N/A
Suggestive Symptoms
The symptoms, their description and period are given below:
1) Fever : Sudden onset, 38.5o C and 40.5o C. High fever has been associated with delirium in some smallpox cases. Subsides after 2-3 days, at whichpoint the characteristic smallpox rash usually appears. Occurs during prodromal period (rash marks the end of prodromal and start of manifestation).
2) Pain: Headache - may be severe - during early prodromal
3) Pain: Other: - severe backaches, occasional abdominal pain - during prodromal period
4) Fatigue/Malaise - common - during prodromal period
5) Nausea - occasional - during prodromal period
6) Cardiovascular - None
Objective Symptoms
Although the pathogenesis of smallpox involves (lymph nodes, etc.), objective clinical manifestations of the disease are usually limited to the characteristic lesions of the skin and mucous membranes.
The organ/system symptoms, their description and period are given below:
1) Skin Rash
Erythematous ("rose") rash associated with early viremia during late prodormal period
Centripetally distributed purpuric or petechial eruption developing on an erythematous background near the groin or other flexures, also associated with early viremia. Extensive petechial rash is associated with hemorrhagic smallpox - late prodromal, early manifestation.
Maculopapular rash develops on the mucosa of the mouth, pharynx, face, and forearms. The rash then spreads to the trunk and legs - during manifestation
Within 1-2 days after appearance, the maculopapular rash becomes vesicular, then pustular. Pustules are characteristically round and deeply embedded in the dermis - during manifestation
After 8-9 days, crusts begin to form on pustules. As the patient recovers, the scabs separate and characteristic pitted scarring gradually develops. The scars are most evident on the face and result from the destruction of sebaceous glands, shrinking of granulated tissue, and fibrosis.
2) Mucous Membranes : Mucosal hemorrhage occurs as a result of extensive, confluent maculopapular rash in hemorrhagic smallpox infection - during manifestation
3) Immune Lymph Nodes Systemic reactions : Toxemia associated with circulating immune complexes and soluble variola antigens is the usual cause of death in smallpox patients. This toxemia appears especially severe in cases of hemorrhagic and flat (malignant) smallpox - during outcome period. Secondary bacterial infections are rare.
Differential Diagnosis
Smallpox is most frequently misdiagnosed as varicella, or chickenpox, infection. The most effective criteria for distinguishing the two infections is an examination of the following characteristics of the lesions:
Time and pattern of appearance: The most obvious distinction between the two infections involves the time period over which the skin lesions appear. In chickenpox infection, the lesions occur in successive "crops". It is possible, when examining a patient, to observe several different stages of lesion maturation and development at the same time. In smallpox infection, the lesions appear more or less simultaneously.
Density and location: Chickenpox lesions tend to be denser over the trunk (centrifugal distribution), while smallpox lesions are denser on the face and extremities (centripetal distribution). Chickenpox lesions are almost never seen on the palms or soles of the feet. Smallpox lesions, especially in severe cases, can often be found in these areas.
Physiology: Chickenpox lesions tend to be superficial, while smallpox lesions are much deeper, affecting the sebaceous glands and leaving pitted, fibromatous scars.
Monkeypox is another infection to be considered in the differential diagnosis of smallpox infection. Patients with monkeypox develop fever, respiratory symptoms, and synchronized lesions like patients with smallpox. Patients with monkeypox, however, seem more prone to develop inguinal and cervical lymphadenopathy and appear to have a lower mortality rate (3%-10%). Pneumonia secondary to monkeypox has a 50% mortality rate.
Mortality and Survivability
Note that for typical smallpox, there is a low mortality rate in vaccinated persons.
Type of smallpox ...................Unvaccinated ....Vaccinated
Ordinary (typical) smallpox ......30% ..................3%
Hemorrhagic smallpox .............99% .................94%
Flat (malignant) smallpox ........95% .................66%
Protection/Isolation/Notification
The discovery of a single suspected case of smallpox must be treated as an international health emergency and be brought immediately to the attention of national officials through local and state health authorities.
As soon as the diagnosis of smallpox is made, all individuals in whom smallpox is suspected should be isolated immediately and all household and other face-to-face contacts should be vaccinated and placed under surveillance. Because the widespread dissemination of smallpox virus by aerosol poses a serious threat in hospitals, patients should be isolated in the home or other non-hospital facilities whenever possible. Home care for most patients is a reasonable approach, given the fact that little can be done for a patient other than to offer supportive therapy.
The rationale for vaccinating all patients suspected to have smallpox in case of an aerosol release of smallpox and a subsequent outbreak is to ensure that misdiagnosed patients are not placed at risk of acquiring smallpox. Vaccination administered within the first few days after exposure and perhaps as late as 4 days may prevent or significantly ameliorate subsequent illness. An emergency vaccination program is also indicated that would include all health care workers at clinics or hospitals that might receive patients; all other essential disaster response personnel, such as police, firefighters, transit workers, public health staff, and emergency management staff; and mortuary staff who might have to handle bodies. It is recommended that all such personnel for whom vaccination is not contraindicated should be vaccinated immediately irrespective of prior vaccination status.
Post-Exposure Prophylaxis and Treatment
Vaccination administered within 4 days of first exposure has been shown to offer some protection against acquiring infection and significant protection against a fatal outcome.
During the 1960s, methisazone received extensive attention as an antiviral chemotherapy for variola virus infection. Although some clinical studies found only a trend toward decreased attack rates, most evidence suggested that methisazone decreased both morbidity and mortality when administered prophylactically to susceptible contacts of patients with smallpox.
Other antiviral compounds such as rifampin and S-adenosylhomocysteine hydrolase inhibitors have activity against vaccinia, and hence may be useful in the prophylaxis or treatment of smallpox. Cytosine arabinoside (Ara-C) and adenine arabinoside (Ara-A), despite their in vitro efficacy against vaccinia infection, did not demonstrate any benefit in treatment of smallpox in small clinical studies.
Supportive therapy with antibiotics is indicated for treatment of secondary bacterial infections associated with smallpox.
-------------------------
Additional information at the site includes an excellent collection of graphics, CME credits courses for physicians, nurses, etc.
NR
Epidemiology and Epizootology
Humans are the only natural reservoirs of variola virus. Person-to-person transmission of smallpox occurs by aerosol droplets expelled from the oropharynx of infected persons, or by direct contact with an infected person. The virus can also be spread through contaminated bedding and clothing.
Despite the fact that smallpox is less contagious than influenza or measles, it is still considered a highly contagious disease. The lesion dose index CTW50,the amount of agent inhaled in aerosol form that is required to cause manifest illness in 50% of susceptible humans, is less than 10 viral particles. The patient can be already infectious in the last day of incubation period, and remains contagious until the scabs drop off. The virus can remain viable for months on objects from the victim's surroundings. Though smallpox is spread most readily during dry, cool winter months, the disease can be transmitted in any climate and in all parts of the world.
Vaccination and isolation of infected patients are the only effective protection against the disease. If a patient is vaccinated within 2 or 3 days of exposure, they will most likely not develop the disease. Vaccination 4 or 5 days after exposure may significantly reduce mortality.
Classification and Etiology
Smallpox is a double-stranded DNA virus, and is a member of the genus orthopoxvirus, family Poxviridae. The poxvirus genome is the largest known viral genome. The virus has a characteristically brick-shaped structure and is about 200 mm in diameter. Poxviruses are unique because they replicate in the cytoplasm, rather than the nucleus, of host cells. Other members of the orthopox genus (monkeypox, vaccinia) can infect and cause cutaneous lesions in humans, but only smallpox is readily transmitted from person to person.
Pathologic Anatomy
The endothelial cells lining the sinusoids of the liver are often swollen and occasionally proliferating or necrotic. Reticular cell hyperplasia occurs in the bone marrow and spleen. The spleen is usually engorged and contains many large lymphoid cells. The liver is generally considerably heavier than normal, but this does not appear to be due to engorgement or fatty infiltration. Encephalitis is an occasional complication.
Clinical Manifestations and Diagnosis
Three types of smallpox have been described:
1. Typical smallpox: the characteristic variola major infection that occurs in 95%-98% of infections.
2. Hemorrhagic smallpox: seen in fewer than 3% of patients and characterized by intense toxemia and mucosal hemorrhage.
3. Flat-type smallpox: observed in 2-5% of patients and characterized by severe, systemic toxicity and the evolution of flat, focal skin lesions.
Duration
Subjective and objective clinical symptoms characteristic of the following four periods in the progression of smallpox infection are discussed:
1) Incubation period: virus actively replicating and spreading to lymph nodes and target tissues; patient is generally asymptomatic. The onset of high fever marks the end of the incubation period.
2) Prodromal period: marked by the beginning of subjective, nonspecific clinical symptoms. Patients are most infectious during the first week of this period. Once the fever subsides, the rash usually appears.
3) Manifestation period: development of smallpox lesions and characteristic objective symptoms.
4) Outcome period: associated either with recovery or severe toxemia and death.
Types of smallpox, their details are given below:
1) Typical (variola major)
Incubation Period : 7-14 days for natural infection
1-5 for infection due to deliberate release of aerosolized virus*
Prodromal Period : 2-3 days
Manifestation Period : 8-9 days
Period of Outcome : 2nd week of illness
2) Hemorrhagic
Incubation Period : 7-14 days
Prodromal Period : 1-2 days
Manifestation Period : 5-6 days
Period of Outcome - N/A
3) Flat
Incubation Period : 7-14 days
Prodromal Period : 1-2 days
Manifestation Period : 2-3 days
Period of Outcome - N/A
Suggestive Symptoms
The symptoms, their description and period are given below:
1) Fever : Sudden onset, 38.5o C and 40.5o C. High fever has been associated with delirium in some smallpox cases. Subsides after 2-3 days, at whichpoint the characteristic smallpox rash usually appears. Occurs during prodromal period (rash marks the end of prodromal and start of manifestation).
2) Pain: Headache - may be severe - during early prodromal
3) Pain: Other: - severe backaches, occasional abdominal pain - during prodromal period
4) Fatigue/Malaise - common - during prodromal period
5) Nausea - occasional - during prodromal period
6) Cardiovascular - None
Objective Symptoms
Although the pathogenesis of smallpox involves (lymph nodes, etc.), objective clinical manifestations of the disease are usually limited to the characteristic lesions of the skin and mucous membranes.
The organ/system symptoms, their description and period are given below:
1) Skin Rash
Erythematous ("rose") rash associated with early viremia during late prodormal period
Centripetally distributed purpuric or petechial eruption developing on an erythematous background near the groin or other flexures, also associated with early viremia. Extensive petechial rash is associated with hemorrhagic smallpox - late prodromal, early manifestation.
Maculopapular rash develops on the mucosa of the mouth, pharynx, face, and forearms. The rash then spreads to the trunk and legs - during manifestation
Within 1-2 days after appearance, the maculopapular rash becomes vesicular, then pustular. Pustules are characteristically round and deeply embedded in the dermis - during manifestation
After 8-9 days, crusts begin to form on pustules. As the patient recovers, the scabs separate and characteristic pitted scarring gradually develops. The scars are most evident on the face and result from the destruction of sebaceous glands, shrinking of granulated tissue, and fibrosis.
2) Mucous Membranes : Mucosal hemorrhage occurs as a result of extensive, confluent maculopapular rash in hemorrhagic smallpox infection - during manifestation
3) Immune Lymph Nodes Systemic reactions : Toxemia associated with circulating immune complexes and soluble variola antigens is the usual cause of death in smallpox patients. This toxemia appears especially severe in cases of hemorrhagic and flat (malignant) smallpox - during outcome period. Secondary bacterial infections are rare.
Differential Diagnosis
Smallpox is most frequently misdiagnosed as varicella, or chickenpox, infection. The most effective criteria for distinguishing the two infections is an examination of the following characteristics of the lesions:
Time and pattern of appearance: The most obvious distinction between the two infections involves the time period over which the skin lesions appear. In chickenpox infection, the lesions occur in successive "crops". It is possible, when examining a patient, to observe several different stages of lesion maturation and development at the same time. In smallpox infection, the lesions appear more or less simultaneously.
Density and location: Chickenpox lesions tend to be denser over the trunk (centrifugal distribution), while smallpox lesions are denser on the face and extremities (centripetal distribution). Chickenpox lesions are almost never seen on the palms or soles of the feet. Smallpox lesions, especially in severe cases, can often be found in these areas.
Physiology: Chickenpox lesions tend to be superficial, while smallpox lesions are much deeper, affecting the sebaceous glands and leaving pitted, fibromatous scars.
Monkeypox is another infection to be considered in the differential diagnosis of smallpox infection. Patients with monkeypox develop fever, respiratory symptoms, and synchronized lesions like patients with smallpox. Patients with monkeypox, however, seem more prone to develop inguinal and cervical lymphadenopathy and appear to have a lower mortality rate (3%-10%). Pneumonia secondary to monkeypox has a 50% mortality rate.
Mortality and Survivability
Note that for typical smallpox, there is a low mortality rate in vaccinated persons.
Type of smallpox ...................Unvaccinated ....Vaccinated
Ordinary (typical) smallpox ......30% ..................3%
Hemorrhagic smallpox .............99% .................94%
Flat (malignant) smallpox ........95% .................66%
Protection/Isolation/Notification
The discovery of a single suspected case of smallpox must be treated as an international health emergency and be brought immediately to the attention of national officials through local and state health authorities.
As soon as the diagnosis of smallpox is made, all individuals in whom smallpox is suspected should be isolated immediately and all household and other face-to-face contacts should be vaccinated and placed under surveillance. Because the widespread dissemination of smallpox virus by aerosol poses a serious threat in hospitals, patients should be isolated in the home or other non-hospital facilities whenever possible. Home care for most patients is a reasonable approach, given the fact that little can be done for a patient other than to offer supportive therapy.
The rationale for vaccinating all patients suspected to have smallpox in case of an aerosol release of smallpox and a subsequent outbreak is to ensure that misdiagnosed patients are not placed at risk of acquiring smallpox. Vaccination administered within the first few days after exposure and perhaps as late as 4 days may prevent or significantly ameliorate subsequent illness. An emergency vaccination program is also indicated that would include all health care workers at clinics or hospitals that might receive patients; all other essential disaster response personnel, such as police, firefighters, transit workers, public health staff, and emergency management staff; and mortuary staff who might have to handle bodies. It is recommended that all such personnel for whom vaccination is not contraindicated should be vaccinated immediately irrespective of prior vaccination status.
Post-Exposure Prophylaxis and Treatment
Vaccination administered within 4 days of first exposure has been shown to offer some protection against acquiring infection and significant protection against a fatal outcome.
During the 1960s, methisazone received extensive attention as an antiviral chemotherapy for variola virus infection. Although some clinical studies found only a trend toward decreased attack rates, most evidence suggested that methisazone decreased both morbidity and mortality when administered prophylactically to susceptible contacts of patients with smallpox.
Other antiviral compounds such as rifampin and S-adenosylhomocysteine hydrolase inhibitors have activity against vaccinia, and hence may be useful in the prophylaxis or treatment of smallpox. Cytosine arabinoside (Ara-C) and adenine arabinoside (Ara-A), despite their in vitro efficacy against vaccinia infection, did not demonstrate any benefit in treatment of smallpox in small clinical studies.
Supportive therapy with antibiotics is indicated for treatment of secondary bacterial infections associated with smallpox.
-------------------------
Additional information at the site includes an excellent collection of graphics, CME credits courses for physicians, nurses, etc.
NR