Efeitos do Foscarnet sobre a infecção pelos herpesvírus bovino tipos 1 e 5 em coelhos / Effects of Foscarnet on the infection by bovine herpesviruses 1 and 5 in rabbits

O efeito antiviral do Foscarnet (PFA) foi demonstrado anteriormente em células de cultivo infectadas com três herpesvírus bovino (BoHV). No presente estudo, investigaram-se os seus efeitos sobre a infecção e doença causadas pelo BoHV-1 e BoHV-5 em coelhos infectados experimentalmente. Coelhos inoculados com o BoHV-5 pela via intraconjuntival (IC) e tratados com o PFA (100mg/kg/dia) a partir do dia 1 pós-inoculação (pi) apresentaram uma redução nos títulos de vírus excretados entre os dias 2 e 6 pi em comparação com o grupo não-tratado; essa diferença foi significativa no dia 3 pi [F(9,108) = 2,23; P<0,03)]. Os coelhos inoculados com o BoHV-5 e tratados com o PFA apresentaram uma redução significativa nos índices de morbidade e mortalidade (95,4 por cento [21/22] nos controles; 50 por cento [11/22] nos tratados; [P<0,0008]). Em coelhos inoculados com o BoHV-1 pela via IC, o tratamento com o PFA resultou em redução nos títulos de vírus excretados, entre os dias 1 e 4, e 6 e 7 pi. Esses animais apresentaram um período de incubação mais curto e um curso clínico mais longo comparando-se com o grupo controle não tratado (P<0,005 e P<0,04, respectivamente). O PFA também reduziu a freqüência e severidade da doença ocular nos coelhos inoculados com o BoHV-1. Esses resultados demonstram que o PFA possui atividade frente ao BoHV-1 e BoHV-5 in vivo e são promissores para o uso desse fármaco em terapias experimentais das infecções herpéticas dos animais domésticos.

The activity of Foscarnet (PFA) against three bovine herpesviruses (BoHVs) was previously demonstrated in cell culture. Herein we evaluated the effects of PFA on the infection and disease by BoHV-1 and BoHV-5 in a rabbit model. Rabbits inoculated with BoHV-5 in the conjunctival sac (IC) and treated with PFA (100 mg/kg/day) from day 1 to 17 post-inoculation (pi) shed less virus between days 2 and 6 pi comparing to untreated controls; this difference was significant at day 3 pi [F(9,108) = 2,23; P<0.03]. The morbidity and mortality rates of rabbits inoculated with BoHV-5 IC or intranasally (IN) were also significantly reduced in PFA-treated rabbits (50 percent; 11/22) comparing to untreated controls (95.4 percent; 21/22) (P<0.0008). In rabbits inoculated IC with BoHV-1, a reduction in virus shedding was observed in PFA-treated animals between days 1 and 4 pi; 6 and 7 pi. In addition, PFA-treated rabbits presented a longer incubation period and a shorter clinical course comparing to untreated controls (P<0.005 and P<0.04, respectively). The frequency and severity of ocular signs were also reduced in the PFA-treated group. These results demonstrate that PFA is effective against BoHV-1 and BoHV-5 in vivo and open the way towards its use in experimental therapy of herpetic infections in domestic animals.

Intravitreal foscarnet for cytomegalovirus retinitis in patients with AIDS.

To determine the visual outcome, progression, and complications of patients with acquired immuno-deficiency syndrome-related cytomegalovirus (CMV) retinitis treated with intravitrealfoscarnet (2.4 mg in 0.1 ml per injection), a retrospective study was carried out in 193 patients. Induction therapy consisted of two injections a week until the lesions were inactive. Maintenance therapy consisted of one injection a week until relapse, then re-induction was instituted. In 301 treated eyes, visual acuity remained stable in 184 (61%), improved in 16 (5%), and decreased in 101 (34%). Of these, 15 retinal detachments, 13 intravitreal hemorrhages, 3 endophthalmitis, and 2 cataract occurred. Median time of first progression was 15 weeks. Involvement of the fellow eye occurred in 35% of the patients during treatment of the first eye. Intravitreal foscarnet appeared to be a useful alternative treatment for patients intolerant or unaffordable to intravenous anti-CMV drugs, but the complications of this treatment should also be considered.

Cytomegalovirus retinitis in AIDS patients: a clinical review

Cytomegalovirus (CMV) retinitis is an ocular condition previously seen in organ transplant recipients, patient on chemotherapy for malignancy, and in infants with congenital infections. As it present in immunocompromised, the AIDS patient has integrated this group of patients that can present with CMV retinitis. Moreover, it is the leading cause of opportunistic ocular infection in the AIDS patient, and the second most common ocular manifestation. As new drugs and modes of administration are studied that can effectively halt this progressively blinding condition, the awareness and recognition of CMV retinitis on AIDS patients has become increasingly important. This author will review the epidemiology, clinical presentation, and differential diagnosis of this condition. The current treatments being used and complications will also be discussed