C A Alford

University of Alabama at Birmingham, Birmingham, AL, United States

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Publications (133)1505.6 Total impact

  • Charles A. Alford, Sergio Stagno, Robert F. Pass
    Ciba Foundation Symposium 77 - Perinatal Infections, 05/2008: pages 125 - 147; , ISBN: 9780470720608
  • Annals of the New York Academy of Sciences 12/2006; 477(1):123 - 127. · 4.38 Impact Factor
  • C A Alford, S Stagno, R F Pass, W J Britt
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    ABSTRACT: Cytomegalovirus is the most common cause of congenital and perinatal viral infections throughout the world. Congenital infection occurs in 1% of all live births in developed countries and in an even higher percentage in developing nations. As a result of transmission during birth, by breast milk, and by blood transfusion, perinatal infections are much more prevalent than congenital infections. The vast majority of these infections are chronic, subclinical forms, but symptomatic infections are sufficiently prevalent and dangerous to represent a major unsolved public health problem throughout the world. In this review the epidemiologic, clinical, immunologic, and therapeutic facets of cytomegaloviral infections in pregnant women and their offspring will be discussed.
    Reviews of infectious diseases 01/2001; 12 Suppl 7:S745-53.
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    ABSTRACT: Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns in the United States. A phase II evaluation was done of ganciclovir for the treatment of symptomatic congenital CMV infection. Daily doses of 8 or 12 mg/kg were administered in divided doses at 12-h intervals for 6 weeks. Clinical and laboratory evaluations sought evidence of toxicity, quantitative virologic responses in urine, plasma drug concentrations, and clinical outcome. A total of 14 and 28 babies received 8 and 12 mg/kg/day, respectively. Five additional babies received ganciclovir on a compassionate plea basis. Significant laboratory abnormalities included thrombocytopenia (< or = 50,000/mm3) in 37 babies and absolute neutropenia (< or = 500 mm3) in 29 babies. Quantitative excretion of CMV in the urine decreased; however, after cessation of therapy, viruria returned to near pretreatment levels. Hearing improvement or stabilization occurred in 5 (16%) of 30 babies at 6 months or later, indicating efficacy.
    The Journal of Infectious Diseases 05/1997; 175(5):1080-6. · 5.85 Impact Factor
  • The Pediatric Infectious Disease Journal 01/1995; 13(12):1139-42. · 3.57 Impact Factor
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    ABSTRACT: The pharmacokinetic characteristics of ganciclovir were determined in neonates (age range, 2 to 49 days) after an 1-hour intravenous infusion of a single dose of either 4 mg/kg (n = 14) or 6 mg/kg (n = 13). Twenty-seven newborns with symptomatic cytomegalovirus inclusion disease were enrolled in this open phase I-II pharmacokinetics, safety, and tolerance trial of ganciclovir at one of two doses. Ganciclovir disposition was best described by a one-compartment open model with zero-order input and first-order elimination. The mean elimination half-life (t((1/2))) for both dose groups was 2.4 hours. The mean apparent volume of distribution (Vd) was 669 +/- 70 ml/kg for the 4 mg/kg group and 749 +/- 59 ml/kg for the 6 mg/kg group. The mean total body clearance (CL) for the 4 mg/kg and 6 mg/kg groups was 189 +/- 28 ml/hr/kg and 213 +/- 21 ml/hr/kg, respectively. No significant differences were observed in Vd or CL between the two groups. The Vd, expressed in milliliters, increased with increasing patient weight (r = 0.689; p = 0.0001). The CL, expressed in milliliters per hour per kilogram, increased with increasing age (r = 0.413; p = 0.032). No significant differences were observed between the two dose groups for the area under the curve normalized for dose (AUC/Dose) or the maximum plasma concentration normalized for dose (C(max)/Dose), indicating that ganciclovir exhibited linear pharmacokinetics in these neonates.Clinical Pharmacology and Therapeutics (1993) 53, 15-21; doi:10.1038/clpt.1993.4.
    Clinical Pharmacology &#38 Therapeutics 02/1993; 53(1):15-21. · 6.85 Impact Factor
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    ABSTRACT: Intrauterine transmission of cytomegalovirus (CMV) can occur whether a mother has prior immunity or acquires CMV for the first time during pregnancy. The degree of protection afforded an infected infant by the presence of antibody in the mother before conception is uncertain. We compared the outcomes of CMV-infected infants born to mothers who acquired primary CMV infection during pregnancy (primary-infection group) with those of CMV-infected infants born to mothers with immunity (recurrent-infection group). Screening for viruria identified 197 newborns with congenital CMV infection. Stored serum samples were used to categorize maternal infection as either primary or recurrent. We followed 125 infants from the primary-infection group and 64 from the recurrent-infection group. Serial medical, audiologic, psychometric, and eye examinations were used to identify sequelae of CMV infection. Only infants in the primary-infection group had symptomatic CMV infection at birth (18 percent). After a mean follow-up of 4.7 years, one or more sequelae were seen in 25 percent of the primary-infection group and in 8 percent of the recurrent-infection group. Thirteen percent of infants whose mothers had primary infection during pregnancy had mental impairment (IQ less than or equal to 70), as compared with none of those whose mothers had recurrent CMV infections. Sensorineural hearing loss was found in 15 percent of those in the primary-infection group and in only 5 percent of those in the recurrent-infection group. Bilateral hearing loss was identified only among children in the primary-infection group (8 percent). The presence of maternal antibody to CMV before conception provides substantial protection against damaging congenital CMV infection in the newborn. Primary maternal infection during pregnancy is associated with more severe sequelae of congenital CMV infection.
    New England Journal of Medicine 04/1992; 326(10):663-7. · 54.42 Impact Factor
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    ABSTRACT: Knowledge of the natural history of symptomatic congenital cytomegalovirus (CMV) infection in the newborn is essential in order to anticipate complications and assess the potential benefit from antiviral therapy. To define the disease course we reviewed data on 106 neonates with symptomatic congenital CMV infection diagnosed and managed by the investigators. Petechiae, jaundice and hepatosplenomegaly were each noted in 70% or more patients. Microcephaly was noted in 54 of 102 (53%) at birth. Elevated alanine aminotransferase, conjugated hyperbilirubinemia and thrombocytopenia were seen in 83, 81 and 77%, respectively. Eighty-six percent had at least two of the manifestations highly suggestive of congenital infection. Platelet count fell to its nadir during the second week of life whereas elevated alanine aminotransferase and direct bilirubin persisted past the first month. In spite of the difficulty in assessing central nervous system function in the newborn, evidence of damage was present in the majority. Seventy-two had microcephaly, poor suck, lethargy/hypotonia or seizures. Abnormal computerized tomographic scan was present in 16 of 20 (80%) and decreased hearing in 20 of 39 (56%). Cerebrospinal fluid protein was greater than 120 mg/dl in 24 of 52 (46%) and this elevation was associated with neurologic abnormalities as well as hearing loss. The mean length of hospital stay was 13 and 22.4 days for term and preterm infants, relatively. Thirteen infants (12%) died during the first 6 weeks of life. Disseminated CMV infection with multiorgan involvement was evident in 7 of 9 at postmortem examination. We conclude that neonates with symptomatic congenital CMV infection have a multi-system disease with significant morbidity and mortality.
    The Pediatric Infectious Disease Journal 03/1992; 11(2):93-9. · 3.57 Impact Factor
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    ABSTRACT: Knowledge of the natural history of symptomatic congenital cytomegalovirus (CMV) infection in the newborn is essential in order to anticipate complications and assess the potential benefit from antiviral therapy. To define the disease course we reviewed data on 106 neonates with symptomatic congenital CMV infection diagnosed and managed by the investigators. Petechiae, jaundice and hepatosplenomegaly were each noted in 70% or more patients. Microcephaly was noted in 54 of 102 (53%) at birth. (C) Williams & Wilkins 1992. All Rights Reserved.
    The Pediatric Infectious Disease Journal 01/1992; 11(2). · 3.57 Impact Factor
  • International Journal of Gynecology & Obstetrics - INT J GYNECOL OBSTET. 01/1992; 37(1):68-68.
  • W J Britt, R F Pass, S Stagno, C A Alford
    Transplantation Proceedings 07/1991; 23(3 Suppl 3):115-7. · 0.95 Impact Factor
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    ABSTRACT: Despite the use of vidarabine, herpes simplex virus (HSV) infection in neonates continues to be a disease of high morbidity and mortality. We undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal HSV infection. Babies less than one month of age with virologically confirmed HSV infection were randomly and blindly assigned to receive either intravenous vidarabine (30 mg per kilogram of body weight per day; n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated disease). After adjustment for differences between groups in the extent of disease, there was no difference between vidarabine and acyclovir in either morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease confined to the skin, eyes, or mouth died. Of the 31 babies in this group who were treated with vidarabine and followed for a year, 88 percent (22 of 25) were judged to be developing normally after one year, as compared with 98 percent (45 of 46) of the 54 treated with acyclovir (95 percent confidence interval for the difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14 percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors, 43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing normally after one year (95 percent confidence interval for the difference, -11 to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14 of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent confidence interval for the difference, -20 to 40); of the survivors, 58 percent (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing normally after one year (95 percent confidence interval for the difference, -40 to 50). Both medications were without serious toxic effects. In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease.
    New England Journal of Medicine 03/1991; 324(7):444-9. · 54.42 Impact Factor
  • C Alford
    Advances in experimental medicine and biology 02/1991; 310:293-9. · 1.83 Impact Factor
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    ABSTRACT: Using the decision analysis technique and multivariate regression methods, a statistical model was established to define the utility of brain biopsy for diagnostic evaluation of patients with suspected herpes simplex encephalitis (HSE). Two strategies were compared: strategy I, brain biopsy with acyclovir (ACV) treatment for 10 days in biopsy-positive patients, and strategy II, ACV therapy without brain biopsy. Strategy I resulted in a greater 6-month survival rate when the likelihood of patients having HSE was less than 70%. Based on the current estimated prevalence of HSE (for patients with suspected HSE) of 35%, strategy I showed a slight advantage of a 3.2% increase in 6-month survival rate. An individual patient's chance of a positive brain biopsy can be predicted using a mathematical equation based on several important clinical assessments. This equation in conjunction with the decision analysis is a useful guide for the clinical management of patients with regard to brain biopsy.
    The Journal of Infectious Diseases 02/1991; 163(1):17-22. · 5.85 Impact Factor
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    ABSTRACT: A total of 432 patients underwent brain biopsy for presumptive herpes simplex encephalitis. Three patient groups were identified. The first group, 195 patients (45%), had herpes simplex encephalitis confirmed by the isolation of herpes simplex virus from brain tissue at biopsy (193 patients) or autopsy (2 patients). The second group, 95 patients (22%), had diseases that were identified but that were not caused by herpes simplex virus. Three subgroups were recognized: (1) 38 patients (9%) with treatable disease, (2) 40 patients (9%) with nontreatable but diagnosed viral infection, and (3) 17 patients (4%) with identified diseases neither of viral etiology nor treatable. The third group, 142 patients (33%), remained without a diagnosis. Clinical presentation of patients in the second group was similar to that of those with herpes simplex encephalitis and those without a diagnosis. Patients in the subgroup with nontreatable but diagnosed viral infections had the greatest likelihood of returning to normal.
    JAMA The Journal of the American Medical Association 08/1989; 262(2):234-9. · 29.98 Impact Factor
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    ABSTRACT: A total of 432 patients underwent brain biopsy for presumptive herpes simplex encephalitis. Three patient groups were identified. The first group, 195 patients (45%), had herpes simplex encephalitis confirmed by the isolation of herpes simplex virus from brain tissue at biopsy (193 patients) or autopsy (2 patients). The second group, 95 patients (22%), had diseases that were identified but that were not caused by herpes simplex virus. Three subgroups were recognized: (1) 38 patients (9%) with treatable disease, (2) 40 patients (9%) with nontreatable but diagnosed viral infection, and (3) 17 patients (4%) with identified diseases neither of viral etiology nor treatable. The third group, 142 patients (33%), remained without a diagnosis. Clinical presentation of patients in the second group was similar to that of those with herpes simplex encephalitis and those without a diagnosis. Patients in the subgroup with nontreatable but diagnosed viral infections had the greatest likelihood of returning to normal.(JAMA. 1989;262:234-239)
    JAMA The Journal of the American Medical Association 07/1989; 262(2):234-239. · 29.98 Impact Factor
  • C A Alford, K Hayes, W Britt
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    ABSTRACT: Using radioimmunoassay followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we compared serial IgG precipitin antibody responses to cytomegalovirus (CMV) proteins in three groups of 29 pregnant women who had primary CMV infection. Five women had CMV mononucleosis, and four of them infected their fetuses. Twenty-four women had subclinical infection, and eight infected their fetuses. There were no qualitative differences in the precipitin responses against the virus-encoded proteins in three different infected cellular antigens (cytoplasmic, nuclear, and high-speed pellet) between these three groups of women. There was also no qualitative difference in responses whether the infection was clinically apparent or subclinical. Quantitation by densitometer, however, revealed that women with mononucleosis and those with subclinical infection who infected their fetuses had a more intense and prolonged antibody response than did women with subclinical infection who failed to transmit CMV in utero.
    The Journal of Infectious Diseases 12/1988; 158(5):917-24. · 5.85 Impact Factor
  • K Hayes, C Alford, W Britt
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    ABSTRACT: We determined serial IgG antibody responses to cytomegalovirus (CMV)-encoded proteins in sera collected over a one-year interval from 14 subjects with CMV mononucleosis. Antigens from infected human fibroblasts included three components: cytoplasmic, nuclear, and high-speed pellet. Antibody was detected by radioimmunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Twenty to 21 bands were observed with the cytoplasmic component, whereas 10 and 9, respectively, were seen with the nuclear and high-speed pellet antigens. The most intense reactions occurred with the higher-molecular-mass proteins (50-215 kDa) by using the cytoplasmic and high-speed antigens and with the more rapidly migrating proteins (less than 50 kDa) by using the nuclear antigen. The precipitin responses increased for three months or more after onset of symptoms with the nuclear and high-speed pellet antigens but peaked within one to two months with the cytoplasmic antigen.
    The Journal of Infectious Diseases 11/1987; 156(4):615-21. · 5.85 Impact Factor
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    ABSTRACT: The Developmental Profile was completed on 32 prospectively followed children with symptomatic congenital cytomegalovirus infection (mean age 6 7/12 years; 78% white, 59% male). The distribution of intelligence and general developmental scores was bimodal; one group had severe deficits (mean IQ 28.8), the other had relatively less severe intellectual sequelae (mean IQ 91.6). Correlation analysis (Pearson r) showed that three variables--microcephaly, neurologic abnormalities, and chorioretinitis--when apparent during the first year of life, were all significantly associated with low intelligence. No correlation was found between IQ and severity of neonatal reticuloendothelial disease or hearing loss. Multiple regression analysis showed that age at testing, chorioretinitis, and neurologic sequelae accounted for 63% of the IQ variance in our sample. We conclude that children with symptomatic congenital cytomegalovirus infection have a greater range of intellectual outcomes than has been previously reported, and that certain early clinical manifestations may be useful in anticipating special needs.
    Journal of Pediatrics 10/1987; 111(3):343-8. · 4.04 Impact Factor
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    ABSTRACT: To identify possible sources of cytomegalovirus infection in pregnant women, we studied seven families with a recent case of congenital or maternal cytomegalovirus infection and a history of maternal contact with a young child shedding the virus. We used restriction-endonuclease techniques to compare the DNA of viral isolates collected from family members. Five families contained an infant who had congenital or perinatal infection, a mother who had had evidence of primary infection during her most recent pregnancy, and a child less than three years of age who was excreting cytomegalovirus. All five of the young children attended day-care centers at least part-time. In each of these five families, strains from family members were identical, and it is most likely that the toddler-aged child was the source of the virus for both the mother and the fetus or infant. In two other families, acquisition of cytomegalovirus by children in a day-care center was followed by seroconversion in the mother along with excretion of a strain of the virus identical to that in her child, as demonstrated by restriction-endonuclease analysis. Five of the seven fathers were tested for antibody to cytomegalovirus; four were seronegative, ruling them out as a source of infection in the mothers. These results not only strengthen evidence for the transmission of cytomegalovirus from child to mother but also indicate that infections acquired by a mother from a child can be transmitted to her fetus.
    New England Journal of Medicine 06/1987; 316(22):1366-70. · 54.42 Impact Factor

Publication Stats

6k Citations
1,505.60 Total Impact Points

Institutions

  • 1970–2008
    • University of Alabama at Birmingham
      • • Department of Medicine
      • • Department of Pediatrics
      • • Department of Psychology
      Birmingham, AL, United States
  • 1991
    • University of Alabama
      Tuscaloosa, Alabama, United States