Smallpox complications

In the variola major type of smallpox, complications in children include blindness, scarring, and bony deformities (Kortepeter, Rowe, Eitzen, 2002). 

Methisa2one [1910-68-5] C qH qN OS (l-methyl-3-thiosemicarba2one of 2-oxoindole, (7), one of the more active in the isatin-3-thiosernicarba2one [487-16-1] series, has been used in the treatment and prevention of smallpox and vaccinia infections that develop as complications of smallpox vaccination... 

In the field of immunization, for example, an exceptionally low probability of a serious or lethal reaction seems to have become the latest national requirement. Smallpox vaccination was routine for almost all children several decades ago and considered extremely safe. Now many regard it as a dangerous procedure because of the possibility of disastrous results - severe complications or even death - in as few as one case in a million. 

The antibody response to yellow fever vaccine was impaired in protein-deficient children with kwashiorkor compared to the well-nourished controls. Polio antibody production was normal in the malnourished children, all of whom also responded in the normal fashion to smallpox vaccination. They had no evidence of disseminated vaccinia (B8). In Guatemala, on the other hand, smallpox vaccination of children who had fully recovered from severe protein-calorie malnutrition led to a drop in their nitrogen retention with the added complication of disseminated vaccinia (V3). 

Immunosuppression During therapy, do not use live virus vaccines (eg, smallpox). Do not immunize patients who are receiving corticosteroids, especially high doses, because of possible hazards of neurological complications and a lack of antibody response. This does not apply to patients receiving corticosteroids as replacement therapy. 

Eckart RE, Love SS, Atwood JE, et al. Incidence and follow-up of inflammatory cardiac complications after smallpox vaccination. J Am Coll Cardiol 2004 44(1) 201-5. 

Smallpox vaccine is not recommended for use in certain groups who may be at risk for complications of the vaccine, in up to 0.2% or more of immunized populations, immunosuppressed individuals, pregnant women, and patients with atopic dermatitis may develop complications related to vaccinia, the orthopox virus used in smallpox vaccine. Vaccinia immunoglobulin can be given to those at risk for these complications. Smallpox vaccine can also be given up to 4 days postexposure as postexposure prophylaxis with significant reduction in mortality. 

Table 1 Frequencies of some complications per 1000000 smallpox vaccinations...

Adverse reactions to smallpox vaccination vary from what may be called a normal reaction via anomalous reactions to real complications. These can be divided into two categories (6) ... 

The frequencies of some complications in 1968 in the USA per 1000000 smallpox vaccinations in primarily vaccinated and revaccinated subjects are shown in Table 1 (7). 

Neurological complications of smallpox vaccination can cause paralysis of 26 patients with such symptoms, most were children under 2 years (29). 

The most dreaded complication of smallpox vaccination is postvaccinial encephalitis or encephalomyelitis, which is said to occur even without a cutaneous vaccination reaction (30), although this occurs rarely, if at all (2,31). It is mainly a complication of primary vaccination. There is increased morbidity with increasing age, especially around puberty. It is rare after revaccination. 

Skin reactions after smallpox vaccination can cause the following complications (2,3) ... 

Nephritis is a very rare complication of smallpox vaccination (49). 

Although routine smallpox vaccination of infants was discontinued in the UK in 1971, some 20-28 cases of complications of vaccination continue to be reported yearly to the Committee on Safety of Medicines (64), including both cross-infection and fetal infection (64). 

Dixon CW, editor. Treatment and Nursing. Sequelae Complications. Smallpox. 1st ed. London J and A Churchill Ltd, 1962 143. 

Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968 results of ten statewide surveys. J Infect Dis 1970 122(4) 303-9. 

Eggers C. Die postvakzinale Polyneuritis als Komplikation nach Pockenschtitzimpfung. [The post-vaccinal polyneuritis as complication following smallpox-vaccination.] Monatsschr Kinderheilkd 1974 122(4) 169-71. 

Paufique L, Durand L, Magnard G, Dome PA. Complications oculopalpebrales de la vaccination antivar-iolique vaccine palpebrale. [Oculo-palpebral complications of smallpox vaccination palpebral vaccinia.] Bull Soc Ophtalmol Fr 1968 68(7) 673-7. 

Gordon HH. Complications of smallpox vaccination Basal cell carcinoma, keloids, acute buhons reaction. Cutis 1974 13 444. 

Singhal RK. Osteo-articular complications of smallpox vaccination. J Indian Med Assoc 1970 55(l) 20-2. 

With the global eradication of smallpox, smallpox immunization was stopped in all countries of the world, and complications of smallpox vaccination became largely of historical interest. However, recently, the threat of... 

Flat-type refers to the characteristic lesions, which are flush with the skin rather than raised vesicles. In outbreaks in India, flat-type smallpox was responsible for between 5 and 10% of cases, with most of the flat-type cases (72%) occurring in children (25). Constitutional symptoms associated with the 3 day prodrome are more severe than in ordinary smallpox and continue after the rash develops. Patients have a high fever and appear toxic throughout the course of the illness. Oral lesions tend to be extensive, and the skin lesions evolve slowly. By the 7 or 8 day, the flat skin lesions appear buried in the skin. In comparison to ordinary smallpox, the vesicles contain little fluid and do not develop the characteristic umbilication. Unlike ordinary smallpox, flat-type smallpox lesions are soft and velvety in texture. The lesions may contain hemorrhages. Respiratory complications are common, and the prognosis for flat-type smallpox is grave. Most cases are fatal (25). 

Patients having a febrile prodrome and either one other major criterion or at least four minor criteria are at moderate risk for smallpox. For patients at moderate risk, physicians should alert infection control and immediately institute contact precautions and respiratory isolation. If possible, they should obtain dermatology and/or infectious disease consultation and obtain digital photographs of the lesions. Given a moderate risk situation, the appropriate clinical diagnosis is essential, and physicians must rule out varicella or complication of vaccinia (smallpox vaccine). Therefore, for moderate risk patients, the history is essential, specifically the history of clinical varicella infection, history of vaccination for varicella and history of possible exposure to vaccinia (smallpox) vaccine. 

Inadvertent inoculation, the most frequent complication of smallpox vaccination, refers to the transmission of the vaccinia virus from the inoculation site to another part of the recipient s body (autoinoculation) or to the bodies of close contacts (Fig. 2.8 see color plate 2.8). It can occur because live vaccinia virus is present at the inoculation site from about 4 days after inoculation until the crust separates from the skin. Maximum viral shedding occurs 4-14 days after inoculation. Inadvertent inoculation is responsible for approximately half of all complications for primary vaccination and revaccination. Because inadvertent inoculation frequently results from touching the vaccination site and transmitting the virus manually, the most common affected sites are the face, eyelid, nose, mouth, genitalia, and rectum. Most cases heal without any specific treatment. Inadvertent inoculation of the eye can lead to comeal scarring and subsequent vision loss. Occasionally, vaccinia immune globulin (VIG) is necessary to treat periocular lesions (26). 

For people with high-risk exposure to smallpox, there are no contraindications to the vaccine, because persons at greatest risk from vaccine complications are also at greatest risk for mortality from the disease (32). However, for preevent vaccination purposes, in the absence of circulating smallpox disease, the following groups of people should not receive smallpox vaccine (32) ... 

The risks of vaccine complications outweigh the likelihood of a smallpox attack. Significant populations are at greater risk of complications, including people with eczema, immune deficiency, and pregnant women. 

Although Section 304 satisfied some of the liability concerns, it failed to address health care worker worries about compensation for lost wages due to side effects of the vaccine (27). In addition. Section 304 did not address hospital and health care worker concerns about whether compensation would be adequate for victims of vaccine complications, including victims, such as household contacts, who were not vaccine recipients. Consequently, on April 30, 2003, the President signed a law to compensate health care workers or first responders injured by the preevent smallpox vaccination program. The law established a no-fault fund that had the following provisions (35) ... 

K3. Kempe, C. H., Studies on smallpox and complications of small-pox vaccination. Pediatrics 26, 176-189 (1960). 

In addition to the viruses mentioned above, some other viral pathogens are noticeable, of which several are profiled herewith as varitype representatives Rift Valley fever, yellow fever, Norwalk, and hepatitis A. The smallpox virus is presented later. Notably, the handling of viruses is much more complicated then that of bacteria hence, it is less likely to be mastered by terrorist organizations, individuals, or perpetrators, with reference being made to the viruses mentioned below as well as others. 

Vidarabine is used mainly in human HSV-1 and HSV-2 encephalitis, decreasing the mortality rate from 70 to 30%. Whitley et al. (57) reported that early vidarabine therapy is helpful in controlling complications of localized or disseminated herpes zoster in immunocompromised patients. Vidarabine also is useful in neonatal herpes labialis or genitalis, vaccinia virus, adenovirus, RNA viruses, papovavirus, CMV, and smallpox virus infections. Given the efficacy of vidarabine in certain viral infections, the U.S. FDA approved a 3% ointment for the treatment of herpes simplex keratoconjunctivitis and recurrent epithelial keratitis, and a 2% IV injection for the treatment of herpes simplex encephalitis and herpes zoster infections (Table 43.3). A topical ophthalmic preparation of vidarabine is useful in herpes simplex keratitis but shows little promise in herpes simplex labialis or genitalis. The monophosphate esters of vidarabine are more water-soluble and can be used in smaller volumes and even intramuscularly. These esters are under clinical investigation for the treatment of hepatitis B, systemic and cutaneous herpes simplex, and herpes zoster virus infections in immunocompromised patients. 

Bacterial superinfection of pox lesions was relatively uncommon except in the absence of proper hygiene and medical care. Arthritis and osteomyelitis developed late in the course of disease in about 1% to 2% of patients, more frequently occurred in children, and was often manifested as bilateral joint involvement, particularly of the elbows.70 Viral inclusion bodies could be demonstrated in the joint effusion and bone marrow of the involved extremity. This complication reflected infection and inflammation of a joint followed by spread to contiguous bone metaphyses, and sometimes resulted in permanent joint deformity.71 Cough and bronchitis were occasionally reported as prominent manifestations of smallpox, with attendant implications for spread of contagion however, pneumonia was unusual.72 Pulmonary edema occurred frequently in hemorrhagic- and flat-type smallpox. Orchitis was noted in approximately 0.1% of patients. Encepha-... 

Fig. 27-6. Ocular vaccinia following inadvertent autoinoculation with vaccine. This complication can cause corneal scarring and hence visual impairment. Ocular vaccinia should be treated aggressively with a topical antiviral drug under close ophthalmological supervision. Reprinted with permission from Fenner F, Henderson DA, Arlta I, Jezek Z, Ladnyi ID. Smallpox and Its Eradication. Geneva, Switzerland World Health Organization 1988 298. Photograph by C. H. Kempe.

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