Search

To investigate the possible occurrence of human immunodeficiency virus (HIV) or human T-cell lymphotropic virus, type I (HTLV-I) infections in the United States prior to 1979-1981, when acquired immune deficiency syndrome (AIDS) was first recognized, we tested sera from 310 pregnant women who participated in the Collaborative Perinatal Project during the period 1959-1964 for HIV and HTLV-I antibody. These samples included sera from 53 pregnant women who were intravenous drug users. The remainder were from women who had cervical epithelial abnormalities, who developed cervical carcinomas, who had had children with erythroblastosis fetalis, who had had children that developed malignant neoplasms early in life, or normal pregnant women. None of the 310 women had confirmed HIV or HTLV-I antibody. The rate of false-positive reactions with the HIV enzyme-linked immunosorbent assay (ELISA) antibody test in these long-frozen samples was similar to that observed in fresh sera. HIV antibody was detected in homosexual patients with AIDS; HTLV-I antibody was not detected in any of these sera. HTLV-I antibody was detected in 17 of 20 patients with tropical spastic paraparesis (TSP) and in two of seven patients with other neurological diseases diagnosed as transverse myelopathy and multiple sclerosis, and in none of nine normal controls; HIV antibody was not detected in any of these sera patients. Thus, we conclude that there was no serological evidence of infection with HIV or HTLV-I in the pregnant women studied; however, HIV antibody was present in all AIDS patients tested, and HTLV-I antibody was found in the majority of patients with TSP.

The Immunization Systems Management Group (IMG) was established to coordinate and oversee objective 2 of the Polio Eradication and Endgame Strategic Plan 2013-2018, namely, (1) introduction of ≥1 dose of inactivated poliovirus vaccine in all 126 countries using oral poliovirus vaccine (OPV) only as of 2012, (2) full withdrawal of OPV, starting with the withdrawal of its type 2 component, and (3) using polio assets to strengthen immunization systems in 10 priority countries. The IMG's inclusive, transparent, and partnership-focused approach proved an effective means of leveraging the comparative and complementary strengths of each IMG member agency. This article outlines 10 key factors behind the IMG's success, providing a potential set of guiding principles for the establishment and implementation of other interagency collaborations and initiatives beyond the polio sphere., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Hundreds of thousands of Rotary volunteers have provided support for polio eradication activities and continue to this day by making financial contributions to the Rotary PolioPlus program, participating in national immunization days, assisting with surveillance, working on local, national, and international advocacy programs for polio eradication, assisting at immunization posts and clinics, and mobilizing their communities for immunization activities (including poliovirus and other vaccines) and other health benefits. Rotary has contributed more than $1.61 billion for the global eradication of polio and has committed to provide an additional $35 million each year until 2018 (all dollar amounts represent US dollars). Its unwavering commitment to eradicate polio has been vital to the success of the program. Rotary is providing additional support for routine immunization and healthcare. When polio is finally gone, we will have the knowledge from the lessons learned with PolioPlus, such as the value of direct involvement by local Rotarians, the program for emergency funding, innovative tactics, and additional approaches for tackling other global issues, even those beyond public health. Rotary has already transitioned its grants program to include 6 areas of focus: disease prevention and treatment, water and sanitation, maternal and child health, basic education and literacy, economic and community development, and peace and conflict prevention/resolution. Funding for these grants in 2015-2016 was $71 million. The legacy of the polio program will be the complete eradication of poliovirus and the elimination of polio for all time., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

In the 1960s, early onset neonatal sepsis caused by group B Streptococcus (GBS) had an attack rate of 2 per 1000 live births and a 50% fatality rate. Early treatment and then antibiotic prophylaxis were shown to reduce morbidity and mortality rates; however, GBS remains a leading cause of perinatal infection. This article will review our investigations and related studies, including our studies in monkeys, that have contributed to current diagnosis, treatment, and prevention of disease caused by GBS. Although it has not been possible to eradicate GBS colonization, intravenous antibiotic prophylaxis given during parturition has been effective in the prevention of vertical transmission in animals and humans. Recently, diagnostic tests with polymerase chain reaction have offered promise for rapid accurate detection. This could lead to a major shift in the timing of diagnosis from the office setting to delivery suite. The potential for immunization remains a challenge.

Background: The monitoring of nevirapine (NVP) concentrations in pediatric patients has gained interest since the introduction of NVP as part of the preferred first-line antiretroviral regimen for human immunodeficiency virus (HIV)-infected children in resource-limited settings. Adequate trough concentrations of NVP predict successful therapy, whereas subtherapeutic levels are correlated with virologic failure and development of resistance. The aim of this study was to determine the extent of agreement between total and free plasma NVP concentrations and nonstimulated saliva NVP concentrations and to evaluate the feasibility of saliva sampling as an alternative tool for therapeutic drug monitoring of NVP in children., Design and Methods: The study was designed as an observational cohort analysis. NVP concentrations were obtained in paired plasma and saliva samples of pediatric patients receiving antiretroviral therapy, including NVP. NVP plasma and saliva concentrations were determined by a tandem-mass spectrometric method. The intraclass correlation coefficient and Bland-Altman analysis were used to evaluate agreement and to assess pattern in any discrepancies between measurements., Results: For the random paired plasma and saliva NVP sampling, 19 African-American children (8 boys, 11 girls) with a median age of 8.0 years were enrolled. Two male subjects were recruited for the 12 hour NVP plasma and saliva pharmacokinetics study. The intraclass correlations between saliva and serum measurements of NVP concentrations indicated >90% agreement between these two modes of measurement. The saliva concentrations reflected the free concentrations very closely but were on average 34% higher. The Bland-Altman plots indicated that the discrepancy between saliva and plasma measures is consistent across the range of average NVP concentrations., Conclusions: Our study results strongly indicate agreement between saliva and plasma NVP concentrations in pediatric patients with HIV infection, on the basis of Bland-Altman analysis. Nonstimulated NVP saliva concentrations can be used as an alternative noninvasive, reliable, cost-effective method for direct measurement of adherence and application of therapeutic drug monitoring in NVP therapy.

Purpose: To assess the safety of a licensed anthrax vaccine (AVA) given to more than 500,000 US military personnel, through review and medical evaluation of adverse events (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS)., Methods: AEs were summarized by person, vaccine lot, type, frequency and impact. A Delphic approach was used to tentatively assess causality in an effort to detect serious AEs (SAEs) or other medically important AEs (OMIAEs) possibly attributable to AVA., Results: The Anthrax Vaccine Expert Committee (AVEC) reviewed 1841 reports describing 3991 AEs (9.4 reports/10,000 doses of AVA) that were submitted to VAERS from 1Q1998 through 4Q2001. One hundred forty-seven reports described an SAE or OMIAE, of which 26 were tentatively rated as possible, probable or certain consequences of vaccination (injection-site reaction [12], 'anaphylactic-like reaction' [5] and eight other systemic AEs [1-2 each])., Conclusions: This review produced no evidence for an unusual rate of any SAE or OMIAE attributable to AVA. It supported an earlier impression that AVA may cause significant local inflammation and should be administered over the deltoid rather than the triceps to avoid direct or compression injury to the ulnar nerve. The subjects of VAERS reports tended to be older than all recipients of AVA. Females generally had and/or reported AEs more often than males, but transient articular reactions were surprisingly more common in males. Variations in the frequency or severity (as judged by hospitalization and/or loss of duty) of reported AEs did not suggest a significant problem with (1) a particular lot of AVA, (2) recurrent AEs after multiple doses or (3) vaccination of persons with a concomitant illness or those given other vaccines or medications., (Copyright 2004 John Wiley & Sons, Ltd.)

This paper provides a brief overview of therapeutic drug monitoring (TDM) in patients with HIV infection. The manuscipt not only focuses on an update on TDM in HIV infection but also provides the latest information on tandem mass spectrometric methods for antiretroviral drug quantification. Also discussed are the preliminary new and original data on free antiretroviral drug measurement in both plasma and saliva.

On 20 December 2001, the Centers for Disease Control and Prevention (CDC) initiated the Anthrax Vaccine and Antibiotic Availability Program (hereafter, the "Program") under an investigational new drug application with the US Food and Drug Administration. This Program provided options for additional preventive treatment for persons at risk for inhalation anthrax as a result of recent bioterrorism attacks who had concluded or were concluding a 60-day course of antimicrobial prophylaxis. Participants were offered an additional 40 days of antibiotic therapy (with ciprofloxacin, doxycycline, or amoxicillin) or antibiotic therapy plus 3 doses of anthrax vaccine. By 11 February 2002, a total of 5420 persons had received standardized education about the Program and 1727 persons (32%) had enrolled. Twelve participants have been identified as having serious adverse events (SAEs). One SAE, which occurred in a participant with ciprofloxacin-induced allergic interstitial nephritis, was considered to be probably associated with treatment received in the Program. No SAEs were associated with anthrax vaccine. CDC will continue to monitor Program participants during the next 2 years.

Purpose: To assess the safety of a licensed anthrax vaccine given to nearly 400,000 US military personnel, reports of adverse events (AEs) submitted to the Vaccine Adverse Event Reporting System (VAERS) were reviewed and evaluated medically., Methods: The Anthrax Vaccine Expert Committee (AVEC), a civilian panel of private-sector physicians and other scientists, reviewed 602 VAERS reports using a Delphic approach (structured expert consensus) to assess the causal relationship between vaccination and the reported AEs and sought to identify unexpected patterns in the occurrence of medically important events. Reports were entered into a database and used to profile AEs with respect to person, type/location, relative frequency, severity/impact, concomitant illness or receipt of other drugs or vaccines, and vaccine lot., Results: Nearly half the reports noted a local injection-site AE, with more than one-third of these involving a moderate to large degree of inflammation. Six events qualified as serious AEs (SAEs), and all were judged to be certain consequences of vaccination. Three-quarters of the reports cited a systemic AE (most common: flu-like symptoms, malaise, rash, arthralgia, headache), but only six individual medically important events were judged possibly or probably due to vaccine (aggravation of spondyloarthropathy (2), anaphylactoid reaction, arthritis (2), bronchiolitis obliterans organizing pneumonia)., Conclusions: Since some cases of local inflammation involved distal paresthesia, AVEC recommends giving subcutaneous injections of AVA over the inferior deltoid instead of the triceps to avoid compression injury to the ulnar nerve. At this time, ongoing evaluation of VAERS reports does not suggest a high frequency or unusual pattern of serious or other medically important AEs.

Rotary International remains committed to the goal of global eradication of polio and certification by 2005. The reports of possible sources of virulent vaccine-derived poliovirus, which may persist after the global eradication of wild poliovirus, need to be investigated rapidly. If these sources are confirmed to be significant risks to global polio eradication, methods to eliminate these sources need to be identified and implemented. Final recommendations on the stopping of vaccination need to be made by WHO.

Objective: To determine the incidence of low birth weight infants born to HIV seropositive women and to demonstrate any effects of antiretroviral therapy on birth weight., Methods: Retrospective review of all obstetrical medical records from January 1, 1995 through June 30, 1998 to identify HIV seropositive women. We evaluated their antiretroviral therapy, CD4 counts, and birth weights of their newborns. We conducted detailed review of the clinical and laboratory findings for the HIV-infected untreated patients, women who received ZDV antepartum alone, and those who received PIs as part of antiretroviral treatment., Results: The frequency of low birth weight infants was significantly increased in HIV seropositive compared to HIV seronegative parturients. Low birth weight infants were more frequent among HIV infected women with lower CD4 counts but the association was not statistically significant. Women who received no antepartum treatment, antepartum only ZDV, and those treated with PIs had significantly more low birth weight infants than did comparison groups. HIV seropositive women also had high frequencies of several obstetrical risk factors for low birth weight infants., Conclusion: The present study showed a significantly increased frequency of low birth weight infants among HIV infected women and especially the subgroups of infected women who received no antepartum treatment, antepartum ZDV only, and those treated with PIs. This association, however, may be related to the presence of many other preterm obstetrical risk factors noted in this study. Increasing numbers of HIV seropositive women are being treated with PIs according to the Centers for Disease Control (CDC) guidelines. If PIs are a cause of low birth weight infants, women taking these drugs may have incremental risk of low birth weight.

Polymerase chain reaction (PCR) methodology was used to detect Epstein-Barr virus (EBV) DNA in peripheral blood mononuclear cells (PBMCs) from children and adults whose HIV status (i.e., infected or uninfected) is known. Initial EBV infections especially occurred in children between the ages of 7 and 24 months. EBV-positive children with vertically acquired HIV infection tended to have a detectable blood level of EBV DNA for a period of years, and their EBV DNA blood levels often exceeded 10,000 copies/0.1 ml of blood--hundreds of times higher than levels typically found in EBV-positive, HIV-uninfected children of the same age. EBV DNA was found in PBMCs in 26% of 49 HIV-infected mothers who were sampled during their pregnancy, but the median EBV DNA level in their EBV-positive samples was low--only 50 copies/0.1 ml blood. In limited tests with specimens from children infected with both HIV and EBV, high blood levels of EBV DNA unexpectedly appeared to be associated with decreased blood levels of HIV DNA (p = .063).

Blood levels of HIV DNA in our vertically infected pediatric patients typically followed a characteristic age-related pattern: continuously increasing with increasing age to a peak between ages 4 and 8 months, and thereafter rather steadily declining. Median HIV DNA levels peaked about 3 months earlier in children who by age 24 months developed more severe rather than less severe HIV disease. Children at particular risk of developing severe HIV disease by age 24 months commonly had > 800 HIV DNA copies per 0.1 ml of blood at age 3 weeks to 2 months, > 1,000 copies at 2 to 4 months, and > 2,500 copies at ages 4 to 6 months. Near the time of delivery mothers who transmitted HIV had significantly higher median blood levels of HIV DNA than mothers who did not transmit, but median HIV DNA levels in infected mothers as a group were low compared with those in pediatric patients > or = 1 month of age.

Objective: We studied 49 mother-infant pairs for human immunodeficiency virus (HIV) (a) to assess the virological and immunological status of HIV-infected mothers at delivery and their infants within the first 3 days of the infant's life, and (b) to correlate these findings with eventual infection outcome in the infant., Method: Maternal blood from women in labor and infant's blood within 3 days of life were tested for the titer of HIV immunoglobulin G (IgG) antibody, for presence of HIV by culture, for p24 antigen, for HIV DNA by polymerase chain reaction (PCR), and for absolute T-helper cell count (CD4)., Results: Eight infants were in the confirmed infected (CI) group, with a transmission rate of 21%. Thirty infants were in the confirmed uninfected (CU) group. In the mother, mean anti-HIV IgG titer was 1:2600 (CI group) and 1:3350 (CU group); in the infant, the mean titer was 1:3250 (CI group) and 1:2710 (CU group). Eighty-seven percent of the mothers were culture-positive in the CI group compared to 33% in the CU group (p = 0.005). Eighty-seven percent of CI infants were PCR-positive at birth; none was PCR-positive in the CU group (sensitivity = 87%; specificity = 100%). Sixty-two percent of CI infants were culture-positive at birth, whereas none was positive in the CU group (sensitivity = 62%; specificity = 100%). Of the uninfected infants, 23% were positive for p24 antigen at birth., Conclusions: HIV IgG antibody titers in mothers and their infants at birth were markedly elevated in both CI and CU groups but were not protective against infection. However, the high titers explain the long duration of this antibody in the blood of infants born to infected mothers. Culture positivity in the mother at delivery correlated highly with eventual infection in the infant (p = 0.005). HIV antigen, specifically p24 antigen, was detectable in uninfected infants when tested at birth.

About 25% of the children of untreated HIV-infected mothers are later determined to be HIV-infected. At birth, all of the children of HIV-infected mothers have HIV-IgG antibody, which is transferred transplacentally from the mothers to their children, and infected children produce HIV-IgG antibody in response to their infection. Most infected children have detectable HIV-IgA by 3 months of age. We have studied HIV antibody responses in three groups of children of HIV-infected mothers at 9 to 12 months and 15 to 24 months of age. The groups were classified by Centers for Disease Control and Prevention (CDC) criteria and included: (I) HIV seroreverters (SR); (II) HIV-infected; Non- to mildly symptomatic (N+A); and (III) HIV-infected; Moderately to Severely Symptomatic (B+C). HIV-IgG antibody was detected in some SR children at low titer levels (10 to 20) through 11 months of age but not at 12 or later. For both the N+A and B+C groups, there were no significant changes in the mean HIV-IgG titers from 9-12 to 15-24 months of age. Also, no significant difference in titers were found between the two infected groups for both age groups. HIV-IgA antibody responses were more frequently positive at 15 to 24 months for all seven antigens studied for the N+A than the B+C patients; however, statistical significance was attained only for gp41 (p < or = 0.01). N+A children showed more responses to the viral antigens at 15-24 months than at 9-12 months. This increase in HIV-specific IgA among the N+A children may be important in restricting their HIV infections. Total IgG levels were significantly higher in the HIV-infected groups than in the SR (p < or = 0.0001), but no differences were detected between the N+A and B+C groups. Total IgA increased over time in the N+A patients from 9-12 to 15-24 months. A similar trend was apparent in the B+C group, but did not reach statistical significance. Both N+A and B+C patients at 15-24 months had significantly higher total IgA levels than did the SR at 9-12 months of age. The B+C group had significantly lower CD4 counts for both age groups than did the N+A or SR groups (p < or = 0.0001).

Coinfection with herpesviruses in young children born to human immunodeficiency virus (HIV)-infected women was studied with blood samples from children who were 9-12 months and 15-24 months of age. Three groups of children were included: (I) HIV-uninfected, asymptomatic (HIV-); (II) polymerase chain reaction (PCR) and/or culture-positive and asymptomatic or mildly symptomatic (HIV+ asymptomatic); and (III) PCR and/or culture-positive and symptomatic (HIV+ symptomatic). Significantly more of the HIV+ symptomatic patients had cytomegalovirus (CMV) antibody than the HIV patients. In addition, CMV antibody levels were significantly higher in the HIV+ symptomatic patients than in either of the other two groups. Human herpesvirus 7 (HHV-7) antibody titers were significantly different among the three groups of patients; however, no pairwise comparisons were significant. No differences were found for HHV-6 or Epstein-Barr virus (EBV) antibody frequencies or titers. These findings suggest that infection with CMV is a cofactor or an opportunistic infection causing symptomatic HIV infections in young children.

The diagnosis of HIV infection in pregnant women is usually based on the detection of HIV-specific antibodies. These tests become positive a few weeks to months after infection. In the United States, it is recommended that tests be offered to all women and encouraged where the rate of infection is > or = 1/1,000 or the woman is at increased risk for infection. The great majority of infected pregnant women are asymptomatic, and questioning patients about risk behavior will identify only about one-half of the infected women. In Washington, D.C. about 1.5% of the pregnant women who reside in the city are HIV positive. The diagnosis of HIV in the child in the first month of life is difficult and requires the use of polymerase chain reaction tests and/or culture. Other tests become positive later. Immunological tests in most HIV-infected mothers in the USA are normal; however, about 12% of patients are symptomatic and show decreased CD4 T cell counts and 6% have AIDS. These patients may have other evidence of decreased T cell responses and are at increased risk for opportunistic infections. At birth, almost all children of HIV-infected mothers have normal immunological findings. However, about 50 of these children become ill by 1 year of age and many develop decreased T cell counts and other immunological changes.

Counseling for infections during pregnancy has traditionally focused on the clinical and laboratory findings of infection in the mother and the estimated risk of fetal damage associated with possible transmission of infection to the child. Now, with the use of techniques for fetal sampling, it is possible to diagnose infections of the fetus in utero and to correlate that information with the occurrence of fetal damage. The techniques that are available for sampling include amniocentesis, cordocentesis and chorionic villus sampling. The laboratory tests include: a) isolation of the organism in appropriate laboratory systems; b) detection of the DNA or RNA of the organism directly or with amplification with techniques such as PCR; c) detection of the organism by fluorescence or in situ hybridization; and d) identification of IgM or IgA fetal antibody to the organism by ELISA or similar methods. In utero infections can be documented for agents such as rubella, cytomegalovirus, parvovirus, Toxoplasma gondii and human immunodeficiency virus type 1. Further information is needed concerning the sensitivities and specificities of these methods for identifying fetal infection and predicting fetal damage.

Objective: To evaluate the clinical utility of a polymerase chain reaction (PCR) method for detecting human immunodeficiency virus (HIV) infection in infants 2 months of age or younger who were born to HIV-positive mothers., Design: Prospective, longitudinal study lasting 3 years. The PCR tests were performed with coded peripheral blood mononuclear cell lysates, and results were compared with findings using Centers for Disease Control and Prevention (CDC) (Atlanta, Ga) criteria defining HIV infection in children., Setting: Hospitals, particularly a pediatric hospital in Washington, DC., Patients: Newborns, young infants, and HIV-infected mothers., Outcome Measure: Presence or absence of pediatric HIV infection using CDC criteria compared with a diagnosis based on the detected presence or absence of HIV proviral DNA using PCR testing., Results: One or more blood samples obtained by 62 days of age from 30 (94%) of 32 HIV-infected infants were positive for HIV by routine PCR testing. Blood samples from 32 infants now confirmed to be uninfected tested negative for HIV. Human immunodeficiency virus DNA was detected in blood samples obtained within 48 hours of birth from eight of nine infected infants. In six of these newborns as well as most older infants, HIV DNA was present in such quantity that it was detectable in specimens equivalent to 0.01 mL or less of the original blood sample., Conclusions: Our PCR procedure can reliably detect the presence or absence of HIV infection during the first 2 months of life. The frequent presence and not uncommon high titer of HIV DNA within 48 hours of birth suggest that much of the transmission of HIV from mother to infant occurs well before birth.

The single-stranded DNA parvoviruses occur in humans and many species of animals. In general, they are species-specific and capable of producing disease at any stage of life. Parvoviruses have a requirement to replicate in cells in a permissive S-phase of DNA mitosis. The infections may be cytolytic to select cell groups resulting in specific developmental defects or may produce more generalized effects such as anemia, pancytopenia, or hemorrhage. The fetus is at particular risk for damage because of the vast number of cells in active mitosis. The teratogenic effects may be severe, often resulting in fetal death. Infections in childhood and adulthood are more frequently mild to subclinical. Some of the teratogenic effects recognized in animal species have been identified in humans. With increased knowledge of parvovirus effects in animals, more pathogenic effects may be related to human parvoviral disease. The need for vaccination, currently used annually in many domestic animal species, continues to be evaluated for humans.

Objective: To study a possible correlate of protection in mother-to-infant transmission of HIV infection. In particular, to determine whether lack of HIV-specific T-helper (TH) function as indicated by HIV and non-HIV antigen-stimulated interleukin (IL)-2 production of mother and/or newborn peripheral blood leukocytes (PBL) is associated with mother-to-infant transmission of HIV., Methods: PBL from 21 HIV-seropositive pregnant women and 23 cord blood leukocytes (CBL) from their offspring were studied for in vitro TH function by IL-2 production in response to HIV and non-HIV antigens. Polymerase chain reaction (PCR) and viral culture assays were performed to determine HIV infection of the infants., Results: PBL from 10 out of 21 (48%) mothers and from eight out of 23 (35%) CBL samples responded to two or more out of five synthetic gp 160 envelope (env) peptides. Three of the 23 (13%) offspring were shown to be HIV-infected by PCR and/or viral culture on follow-up. All three infected infants were from a subset whose CBL did not exhibit env-specific TH immunity., Conclusion: Our results demonstrate that fetal T cells can be primed to HIV env determinants in utero, suggest that HIV-specific TH immunity may be protective in newborns, and provide a possible means for identifying newborns who are at risk for HIV infection.

A matched case-control methodology was used to assess the risk for a wide range of abnormalities in children associated with serological evidence for 'TORCH' infections in the mothers. Specimens were selected from the large bank of sera from the approximately 54,000 pregnant women who participated in the Collaborative Perinatal Project. There was no clear association between any of the antigens studied and any specific damage to the child. These 'negative' findings are consistent with the absence of frequent significant effects due to these agents in the second and third trimesters of pregnancy.

Polymerase chain reaction (PCR) testing using up to four primer pairs and biotinylated probes was 97.9% sensitive (188 of 192 specimens positive) and 100% specific (267 of 267 specimens negative) for detecting the presence or absence of human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells from pediatric patients whose HIV status has been confirmed. SK38/39 and SK145/150 were the most sensitive primer pairs, respectively detecting HIV DNA in 95.6 and 95.9% of peripheral blood mononuclear cell specimens from HIV-infected children and collectively detecting all adequately tested PCR-positive specimens. Primer pairs SK29/30 and SK68/69 respectively detected HIV DNA in only 76.4 and 76.6% of HIV-positive specimens. Among infants born to HIV-seropositive mothers, 30 who subsequently were confirmed to be infected were sampled when they were less than or equal to 6 months of age; in all but one infant, HIV DNA was found in the first specimen collected. Among the nine youngest infected infants tested, all were PCR positive by 38 days of age. PCR methods thus have reliably detected vertically transmitted HIV infection early in life.

At present, the only well-standardized and widely available diagnostic techniques for HIV infection are detection of IgG HIV antibodies and HIV antigen. The antibody detection is sensitive, but is useful only in infants and children older than 15 months because of the presence of maternal antibodies. The utility of HIV antigen testing in neonates and young infants has not been established. A number of sensitive techniques, such as PCR, ELISPOT, and detection of HIV-specific IgM and IgA antibodies, are under development and promise to be very useful in the early diagnosis of vertical HIV infection. However, we will be able to accurately establish the sensitivity or specificity of the individual tests only when we have results of large prospective studies. These studies should compare different diagnostic methods and correlate the results of tests performed sequentially in neonates and young infants with the natural history of their disease process and eventual clinical outcome.

For hepatitis B, universal screening of pregnant women for HBsAg along with the combined use of hepatitis B vaccine and HBIG in infants of infected mothers appears to be the best way to detect and prevent vertically transmitted infection. Cytomegalovirus is the most common congenital viral infection, but the lack of a good screening test precludes its accurate and rapid diagnosis. For HPV-B19, larger and more controlled studies are needed to confirm the safety and effectiveness of fetal blood transfusions in the management of hydrops fetalis caused by this infection. Finally, the fact that most mothers of HSV- and toxoplasma-infected neonates have no history of infection, and are asymptomatic at the time of delivery, underscores the need for a high index of clinical suspicion in sick neonates.

Penicillin treatment and antibody response were studied using a rhesus monkey model for intraamniotic infection with type III group B streptococci (T3GBS). Acute and convalescent phase sera from mothers and their offspring were tested with a radioactive antigen-binding assay to determine the concentration of antibody to the capsular T3GBS antigen. The frequency of placentitis was significantly lower in penicillin-treated animals (3 of 8) than in controls (10 of 10; P less than .01). The penicillin group also had a significantly lower neonatal mortality (1 of 9) than controls (6 of 10; P less than .05). Both groups of rhesus mothers developed a significant increase in concentration of antibody to T3GBS, but the antibody response was of lesser magnitude in the penicillin-treated group. This experimental model appears to be useful for studying both therapy for intraamniotic infection and the humoral immune response to infection with T3GBS.

A group of 579 asymptomatic women from Jackson Memorial Hospital, Miami, Florida, and 207 from Kaiser Foundation Hospital in Honolulu, Hawaii, admitted in labor at 37 to 40 weeks of gestation had vaginal cultures for herpes simplex virus (HSV). No cultures were positive and no neonates developed HSV infection. Seven patients gave a history of previous HSV infection in the group from Florida and three from the group in Hawaii. Herpes appears to be a low incidence risk factor in both the populations studied.

The longitudinal study of approximately 60,000 pregnant women was conducted at 14 major medical centers throughout the United States. Clinical data was obtained under prescribed protocols for each of the study women throughout their pregnancy, at delivery, and through the postpartum period. The children were followed with uniform examinations from birth through seven years of age. In addition blood samples were taken from the pregnant women at registration, every two months through pregnancy, at delivery, and six weeks postpartum. Cord blood samples were also taken from the children during the last half of the study. We have used this material from the Collaborative Perinatal Project for the investigation of the role of infections in the production of damage to the fetus and newborn. The frequency of clinically recognizing infection during pregnancy was determined and geographic variation was demonstrated. Serological tests were used to document certain diseases. The frequency of confirmed clinical cases per 10,000 were: rubella, 8; rubeola, 0.6; mumps, 10; varicella-zoster, 5. The epidemiology and clinical findings associated with infections were studied using serological methods. This has provided data on the frequencies of infections such as cytomegalovirus, herpes simplex, mumps, rubeola, respiratory syncytial virus, and others. The study of abnormal pregnancies and matched controls is in progress using serological techniques. A number of specific studies have been reported on infections including rubella, neonatal meningitis, cytomegalovirus, maternal urinary tract infections, and toxoplasmosis. Further testing is now in progress employing more sophisticated laboratory methods and more complete data analysis.

Microsticks are machine-tooled or molded pegs of plastic or stainless steel which were developed as solid-phase carriers for the enzyme-linked immunosorbent assay (ELISA). They consist of a stem, which can be coated with plastic to be used as the reactive surface, and a shaft designed for easy handling and labeling and for positioning the sticks in microtiter wells and transfer plates. Microsticks permit a wide selection of coating materials and afford the user greater control over quality and standardization of the solid-phase surface. Polycarbonate and nitrocellulose coatings were tested in ELISAs for antibodies to measles virus, toxoplasma, and human gamma globulin. The Microsticks were found to give reproducible, sensitive, and specific ELISA results and minimized problems due to lot-to-lot and batch-to-batch variations found with other plastic carriers.

The enzyme-linked immunosorbent assay (ELISA) was compared with the enzyme-linked fluorescence assay (ELFA) for the detection of rubella antibody and herpes simplex virus antigen. Test parameters, specimens, antigen or antibody, and conjugates for the two types of assays were identical except that p-nitrophenyl phosphate was used as the substrate for the ELISA and 4-methylumbelliferyl phosphate was used as the substrate for ELFA. Automated readers were used for both assays. Antibody titers and sensitivity of antigen detection were quite similar for ELISA and ELFA. ELFA for rubella antibody, however, could be conducted with less antigen or shorter substrate incubation time (5 min for ELFA versus 30 min for ELISA). For herpes simplex virus antigen detection, ELFA could also be read after a shorter substrate incubation time (15 min for ELFA versus 30 min for ELISA). Clear polystyrene microtiter plates routinely used for ELISA could be used for ELFA, but clear polyvinyl chloride plates had high background fluorescence. Black polystyrene and polyvinyl chloride plates gave lower background fluorescence than did clear plates. ELFA is of particular value as a substitute for ELISAs in which long substrate incubations are required or antigens of only low titer are available.

Necropsies were performed on 25 rhesus monkeys, three cebus monkeys and three baboons which had been fed leaded paint or lead acetate at various doses up to 666 days. The 31 test primates and six controls ranged in age from five days to about eight years. In addition, the brains of 13 subadult squirrel monkeys fed lead oxide and two controls were studied grossly and microscopically. Lead content of liver, kidney and brain correlated with clinical outcome and typical histologic changes. Neuropathologic lesions, most severe in the young, occurred in 28 of 43 test primates despite a paucity of neurological signs. Brain lesions were similar to those occurring in human lead encephalopathy and included degenerative and proliferative changes of small vessels, ring hemorrhages, edema, perivascular hyalin droplets, rosette-like deposits of proteinaceous exudates, focal loss of myelin, astrogliosis and necrosis of hippocampal neurons.

Changes in clinical status and in two measures of immune function were followed for 21 months (median) in 106 multiple sclerosis (MS) patients and cohabitant controls. Antibody titers to measles, cytomegalovirus, and herpesvirus 1 and 2, and leukocyte migration inhibition indexes (LMIs) to measles and streptokinase/streptodornase (SKSD) were measured at 3- to 6-month intervals and at time of exacerbation in the index case. There were 36 exacerbations in 25 patients. Mean baseline antibody titers and LMI to measles were higher in cases than in controls. No consistent changes occurred in antibody titers to any of the viruses, non in LMI to SKSD. LMIs to measles were lower in most MS patients during exacerbations than before or after exacerbations. This apparent improvement in cell-mediated immune response to measles only during exacerbations may reflect aberrant immune regulation in MS patients, response to recrudescence of a latent agent, or some other phenomenon as yet undefined.