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Background:Abnormal childhood growth may affect future health. Maternal tenofovir (TFV) use was associated with lower body length and head circumference at 1 year of age in HIV-exposed uninfected (HEU) US children.Methods:We studied 509 HEU children in the US-based Surveillance Monitoring of Antiret

Human immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) have increased prevalence of hyperlipidemia and risk factors for cardiovascular disease. No studies have investigated the efficacy and safety of statins in this population. HIV-infected youth 10 to

Background. Sexually transmitted infections (STIs) are associated with adverse birth outcomes. Current prenatal STI screening guidelines define “risk” without explicit consideration of HIV status. Our objective was to test the hypothesis that HIV status is associated with bacterial STI in pregnant women.Methods. We designed a retrospective cohort study to identify pregnant women with HIV who delivered at our facility during 2000-2014. HIV+ women were compared to HIV- women with matching by year of delivery. Logistic regression was used to model adjusted odds of prevalent and incident STI. Prevalent STI was defined as chlamydia (CT), gonorrhea (GC), syphilis, or trichomoniasis detected on an initial prenatal screening test and incident STI as a newly positive result following a negative prenatal test.Results. The cohort included 432 women, 210 HIV+ and 222 HIV-. Most pregnant women were screened for STI (92% of HIV+ women and 74% of HIV- women). STI rates were high and particularly elevated in HIV+ women: 29% vs 18% (p=0.02), for prevalent STI and 11% vs 2% (pConclusion. Pregnant women who delivered in our center had high STI rates. Since HIV infection was independently associated with prevalent and incident STI, prenatal screening guidelines may need to incorporate HIV status as a high-risk group for repeat testing.

Mucoid bacteria, predominately Pseudomonas aeruginosa, are commonly associated with decline in pulmonary function in children with cystic fibrosis (CF), and are thought to persist at least in part due to a greater propensity toward forming biofilms. We isolated a higher frequency of mucoid Streptococcus pneumoniae (Sp) expressing high levels of capsular polysaccharides from sputa from children with CF, compared to those without CF. We compared biofilm formation and maturation by mucoid and non-mucoid isolates of Sp collected from children with and without CF. Non-mucoid Sp serotype 19A and 19F isolates had significantly higher levels of biofilm initiation and adherence to CF epithelial cells than did serotype 3 isolates. However, strains expressing high levels of capsule had significantly greater biofilm maturation, as evidenced by increased density and thickness in static and continuous flow assays via confocal microscopy. Finally, using a serotype 3 Sp strain, we showed that highly encapsulated mucoid phase variants predominate during late adherence and better colonize CFTR–/– as compared to wild-type mice in respiratory infection studies. These findings indicate that overexpression of capsule can enhance the development of mature pneumococcal biofilms in vitro, and may contribute to pneumococcal colonization in CF lung disease.

OBJECTIVE To evaluate the safety of in-utero antiretroviral exposure in children born to mothers with HIV, using a trigger-based design. DESIGN The Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites to evaluate safety of in-utero antiretroviral drug exposure in HIV-uninfected children born to HIV-infected mothers. Children meeting predefined clinical or laboratory thresholds have more intensive evaluations to determine whether they meet criteria for adverse events. METHODS Adverse event "cases" were defined for the following domains: growth, hearing, language, neurology, neurodevelopment, metabolic, hematologic/clinical chemistry and blood lactate. We used adjusted log-binomial models to calculate relative risks (RR) of case status overall and within individual domains for various antiretroviral exposures during pregnancy. RESULTS Among 2680 youth enrolled between 2007 and 2012 (48% female, 66% black, 33% Hispanic), 48% met a trigger and 25% were defined as a case in at least one domain. Language (13.2%) and metabolic (11.4%) cases were most common. After adjustment for birth cohort and other factors, there was no association of any antiretroviral regimen, drug class, or individual drug with meeting overall case criteria (case in any domain). Within individual domains, zidovudine (74% exposed) was associated with increased risk of metabolic case [RR = 1.69, 95%confidence interval (CI) 1.08-2.64] and didanosine plus stavudine (

Antiretroviral (ARV) therapy of pregnant women has dramatically reduced the transmission rate of HIV infection from mother to child. Monitoring for potential toxicities of individual ARVs and combinations of ARVs used during pregnancy is essential to allow judgments about the best regimens for reducing maternal-to-child transmission with the fewest adverse affects. Concern for possible mitochondrial toxicity associated with ARV medications has led investigators to study blood lactate concentrations in HIV-infected children and adults (1-7) and in infants exposed in utero to both HIV infection and ARV. (8-14) Because elevated blood lactate concentrations are often associated with mitochondrial dysfunction, this laboratory test has been used to screen for mitochondrial dysfunction in both clinical care and investigational studies. Obtaining accurate plasma lactate determinations in infants and children is difficult due to requirements that the patient be resting, that venous blood be obtained without use of a tourniquet, and that the sample be tested shortly after being obtained. (15) Technological developments have made analysis of capillary blood lactate at the point of care (POC) possible. The relative ease of POC testing and the reported high level of agreement with venous lactate measurements have led to the introduction of capillary blood POC lactate testing into a variety of clinical care settings, including for conditions unrelated to HIV infection (16-18) and in resource-constrained settings to monitor lactate concentrations in HIV-infected patients receiving ARVs. (19-22) We established a large US prospective surveillance study, the Surveillance Monitoring for Antiretroviral Therapy Toxicities (SMARTT) of the Pediatric HIV/AIDS Cohort Studies (PHACS), to look for evidence of possible mitochondrial toxicity in a large cohort of uninfected children born to HIV-infected mothers who used ARV medications during that pregnancy. The primary screening laboratory test selected to prompt further evaluation for possible mitochondrial abnormalities in this study was a blood lactate concentration above a threshold of 3mmol/L. Here we report the frequency of elevated POC lactate concentrations in US children born to HIV-infected women receiving ARVs during pregnancy but who remained uninfected. The associations between in utero ARV exposure and elevated POC lactate concentrations in these children were evaluated, controlling for other variables. This is the largest cohort study to date reporting lactate concentration in children using a POC testing device.

Mitochondrial dysfunction has been associated with both human immunodeficiency virus (HIV) infection and exposure to antiretroviral therapy. Mitochondrial dysfunction has not been widely studied in HIV-infected children. We estimated the incidence of clinically defined mitochondrial dysfunction among children with perinatal HIV infection.Children with perinatal HIV infection enrolled in a prospective cohort study (Pediatric AIDS Clinical Trials Group protocols 219 and 219C) from 1993 through 2004 were included. Two clinical case definitions of mitochondrial dysfunction, the Enquête Périnatale Française criteria and the Mitochondrial Disease Classification criteria, were used to classify signs and symptoms that were consistent with possible mitochondrial dysfunction. Adjusted odds ratios of the associations between single and dual nucleoside reverse-transcriptase inhibitor use and possible mitochondrial dysfunction were estimated using logistic regression.Overall, 982 (33.5%) of 2931 children met 1 or both case definitions of possible mitochondrial dysfunction. Mortality was highest among the 96 children who met both case definitions (20%). After adjusting for confounders, there was a higher risk of possible mitochondrial dysfunction among children who received stavudine regardless of exposure to other medications (odds ratio, 3.44 [95% confidence interval, 1.91-6.20]) or who received stavudine-didanosine combination therapy (odds ratio, 2.23 [95% confidence interval, 1.19-4.21]). Exposure to lamivudine and to lamivudine-stavudine were also associated with an increased risk of mitochondrial dysfunction.Receipt of nucleoside reverse-transcriptase inhibitors, especially stavudine and lamivudine, was associated with possible mitochondrial dysfunction in children with perinatal HIV infection. Further studies are warranted to elucidate potential mechanisms of nucleoside reverse-transcriptase inhibitor toxicities.

Background: There is equivocal evidence of in utero nucleoside reverse transcriptase inhibitor (NRTI) exposure and the occurrence of mitochondrial dysfunction (MD) in HIV-uninfected children born of HIV-infected women. Methods: The primary analysis included 1037 HIV-uninfected children born in 19912002 and enrolled in Pediatric AIDS Clinical Trials Group protocols 219/219C. Possible cases with unexplained signs of MD according to the Enquete Perinatale Francaise criteria were identified through retrospective review. Associations between overall in utero NRTI exposure, and trimester of first in utero NRTI exposure and possible MD were estimated with exact logistic regression. Results: Cases (n = 20) were significantly more likely to be male and to be born in earlier years than non-cases (n = 1017). There was no association between overal I in utero NRTI exposure and MD. In unadjusted models there were higher odds of first in utero exposure in the third trimester to lamivudine (3TC) [odds ratio (OR), 3.76 versus 3TC unexposed; 95% confidence interval (CI), 1.09-11.78] and to zidovudine (ZDV) and 3TC in combination (ZDV/3TC) (OR, 3.29 vs. ZDV/3TC unexposed; 95% CI, 0.96-10.25) among cases than noncases. When adjusted for year of birth the odds of first exposure in the third trimester to 3TC (OR, 10.57; 95% CI, 1.93-75.61) and ZDV/3TC (OR, 9.84; 95% CI, 1.77-71.68) were significantly higher among cases than non-cases. Incomplete data precluded control of possible confounding by maternal viral load and psychoactive drug use. Conclusions: Our study suggests that first exposure to 3TC or ZDV/3TC in the third trimester may be associated with the occurrence of possible MD. Further studies that rigorously assess MD and better control confounding are needed. (C) 2007 Lippincott Williams & Wilkins.

Background Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in human immunodeficiency virus (HIV)-related opportunistic infections and deaths in US youth, but both continue to occur. Methods We estimated the incidence of complications and deaths in IMPAACT P1074, a long-term US-based prospective multicenter cohort study conducted from April 2008 to June 2014. Incidence rates of selected diagnoses and trends over time were compared with those from a previous observational cohort study, P219C (2004-2007). Causes of death and relevant demographic and clinical features were reviewed. Results Among 1201 HIV-infected youth in P1074 (87% perinatally infected; mean [standard deviation] age at last chart review, 20.9 [5.4] years), psychiatric and neurodevelopmental disorders, asthma, pneumonia, and genital tract infections were among the most common comorbid conditions. Compared with findings in P219C, conditions with significantly increased incidence included substance or alcohol abuse, latent tuberculosis, diabetes mellitus, atypical mycobacterial infections, vitamin D deficiency or metabolic bone disorders, anxiety disorders, and fractures; the incidence of pneumonia decreased significantly. Twenty-eight deaths occurred, yielding a standardized mortality rate 31.5 times that of the US population. Those who died were older, less likely to be receiving cART, and had lower CD4 cell counts and higher viral loads. Most deaths (86%) were due to HIV-related medical conditions. Conclusions Opportunistic infections and deaths are less common among HIV-infected youth in the US in the cART era, but the mortality rate remains elevated. Deaths were associated with poor HIV control and older age. Emerging complications, such as psychiatric, inflammatory, metabolic, and genital tract diseases, need to be addressed.

Background. Children

This article is part of a series of papers presented at a symposium entitled "Antimicrobial Resistance in Streptococcus pneumoniae" at the 5th European Congress of Clinical Microbiology and Infectious Diseases in Oslo in September 1991., Examination of several hundred penicillin-resistant clinical isolates of Streptococcus pneumoniae has revealed extensive strain-to-strain variation in the number and molecular size of penicillin-binding proteins (PBPs), This polymorphism has been used to classify resistant isolates into groups (PBP families) that share distinct electrophoretic profiles, We describe herein properties of four such PBP families: two from Spain (and/or Ohio) and one each from Hungary and Alaska. We have discovered that representative isolates assigned to each PBP family also share capsular serotype, antibiotic resistance pattern, pneumococcal surface protein A type, and multilocus enzyme genotype. The results demonstrate independent clonal origin for strains assigned to each PBP family. Each resistant clone occurs with uniquely high incidence within specific geographic areas., These investigations were supported by the National Institute of Allergy and Infectious Diseases (RO I Al 16794, RO I AI33119, and PDI HD17812).

The relationships among capsular type, protein type, and penicillin resistance for capsular group 9 Streptococcus pneumoniae collected in northwestern Canada between 1974 and 1987 were examined. The group 9 relatively penicillin-resistant (RPR) isolates were of the rare 9L capsular type. Of 47 penicillin-susceptible (PS) group 9 isolates that were typed for capsule, only 1 was 9L. Among 29 PS group 9 isolates that were protein typed, 9 protein types were observed. Of the 70 RPR isolates, 51 were protein type P23, 1 was P19, and 18 could not be typed (P0). Protein types P23 differed from P0 by a single epitope on pneumococcal surface protein A. These results suggest that the Canadian P23 and P0 capsular group 9 isolates are likely subclones of a primordial 9L RPR strain.

Background: HIV protease inhibitors (PIs) are known to disturb lipid metabolism in adults, leading to hypercholesterolemia. A number of cross-sectional studies have also reported this phenomenon in perinatally HIV-infected children but differ greatly with respect to prevalence and/or methodology. Methods: The Pediatric AIDS Clinical Trials Group 219C (PACTG 219C) is a prospective cohort study designed to examine long-term outcomes in children born to HIV-infected women. The outcome of interest in this analysis was total cholesterol, and patients were classified as hypercholesterolemic if their total cholesterol was above the 95th percentile of US Third National Health and Nutrition Survey (NHANES III) standards for gender, race/ethnicity, and age. We hypothesized that hypercholesterolemia would be more common among older children receiving PI therapy who demonstrated excellent adherence and might be associated with hypertension and obesity. Information regarding treatment, adherence, and laboratory values was obtained using the date closest to the cholesterol measurement. Crude and adjusted effect measures were estimated using exposure odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) from univariate and multivariate logistic regression models. Results: Among 1812 HIV-infected participants between 4 and 19 years of age, 229 children had hypercholesterolemia (prevalence = 13.0%, 95% CI: 11.1-14.3) compared with 9 of 187 HIV-uninfected children (prevalence = 4.8%, 95% CI: 2.2-8.8). After adjusting for confounders, current PI use (OR = 5.3, 95% CI: 3.1-9.2), age from 4 to

BACKGROUND An aggressive therapeutic approach for treatment of HIV in adults consists of combining five or more concurrent antiretrovirals. The clinical benefits of this regimen are often accompanied by increased toxicities. We report the safety and tolerance of multiple drug therapy in HIV-infected children. METHODS A retrospective chart review was performed to identify HIV-infected children who received > or =5 concurrent antiretrovirals or 4 antiretrovirals plus hydroxyurea. Treatment success was defined as > or =1 log(10) decrease in plasma HIV RNA from baseline any time during multiple drug therapy. Toxicities were defined as a >Grade 2 change from baseline in laboratory values. RESULTS Twelve patients received multiple drug therapy for 6 months, and 42% of patients continued to receive therapy for at least 1 year. No Grade 3 or 4 toxicities or laboratory abnormalities were reported. Treatment success occurred in 8 (83%) of 12 patients. Adherence was a determining factor in treatment success or failure. CONCLUSIONS Treatment of HIV-infected children with multiple drug therapy was well-tolerated in this cohort. Treatment success occurred in most patients, with adherence affecting patients' likelihood of success. Larger controlled clinical trials in this patient population are necessary to determine whether the benefit of this therapeutic approach outweighs potential risks.

Thirty Streptococcus pneumoniae clinical isolates resistant to levofloxacin were analyzed for the quinolone resistance-determining DNA sequences to identify point mutations and were tested for in vitro susceptibility to multiple drug classes. Of these isolates, 29 had mutations in both gyrA and parC genes of DNA gyrase and topoisomerase IV, respectively. In GyrA, an amino acid change from Ser-81Phe was detected in 27 isolates and a Glu-85 Lys change was found in the remaining three. Of the 29 isolates for which ParC data were available, Ser-79 Tyr or Phe were the predominant mutations observed. MICs for levofloxacin were 4–16 mg/l, whereas those for moxifloxacin were 1–2 mg/l. Twenty-four (80%) isolates were susceptible to erythromycin, 25 (83%) to azithromycin, 26 (87%) to clarithromycin, 27 (90%) to clindamycin, 20 (67%) to penicillin, 21 (70%) to ceftriaxone and 30 (100%) to amoxycillin/clavulanate. These results confirm the presence of double mutations among clinical isolates of S. pneumoniae from diverse geographical regions of North America and also suggest that quinolone resistance may develop independently of resistance to other drug classes. © 2001 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.

To determine whether nasopharyngeal carriage isolates of Streptococcus pneumoniae are of the same genetic background as isolates that caused invasive disease in one community, IS1167 and boxA genotypes were obtained for 182 pneumococcal isolates from children living in central Tennessee. The isolates represented 70 combined IS1167-boxA genotypes. The genotypic diversity of the invasive isolates was significantly less than that of the total population ( ). Most of the carriage isolates belonged to genotypes unique to carriage, whereas P p .003 most of the invasive isolates belonged to genotypes common to carriage and disease (P p ). Monte Carlo simulations showed a greater number of genotypes unique to carriage than .02 can be explained by chance ( in all cases). Two genotypes were identified by multilocus P ! .05 sequence typing as members of globally disseminated clones, and one such genotype that was strictly carriage in this sample caused disease in other studies. Thus, clones can have different propensities for carriage and invasion. Streptococcus pneumoniae can be carried asymptomatically in the human nasopharynx, but little is known about the clones involved in carriage and their genetic relationships to clones associated with invasive disease. Invasion is correlated with at least transient carriage [1, 2]. Several studies have reported a link between carriage of pneumococci and the occurrence of acute otitis media [3–5]. Moreover, carriage isolates can exhibit the same capsule serotypes and genetic backgrounds as invasive isolates. For example, in a study by Takala et al. [6], the serotype 7 and 14 pneumococci were mostly clonal and invasive; however, there were 2 carriage isolates each of serotypes 7 and 14, and these belonged to the same genotypes as the isolates from disease. In a

Antimicrobial susceptibility, pneumococcal surface protein A (PspA) serotyping, and pulsed-field gel electrophoresis (PFGE) were used to evaluate clonal relatedness among 66 invasive isolates of Streptococcus pneumoniae serotype 6B collected during 1982-1996 from patients in Alaska. Thirty-seven (56%) of the isolates had penicillin minimal inhibitory concentration values >/=0.125 microgram/mL and were resistant to at least 1 other antibiotic. Fourteen PspA serotypes were observed; PspA 16 was the most common (35%). Forty-five (68%) of the 66 isolates shared common and highly related PFGE patterns using 3 enzymes. Twenty-six (58%) of the isolates with common PFGE patterns were from Native Alaskan children

These studies have identified a major genetic lineage of capsule serotype 12F Streptococcus pneumoniae, which has maintained two different types of the pneumococcal surface protein A (PspA) virulence factor and caused invasive disease in geographically disjoint locations. Twenty outbreak strains from a Texas jail and Maryland day care center and 16 reference strains from Texas, Maryland, Washington, Michigan, Oklahoma, Missouri, Alaska, and Australia were examined. Although the Texas and Maryland outbreak strains were indistinguishable by IS1167 and boxA genotyping procedures, all strains examined were members of a genetically similar lineage. The microevolutionary history of pspA differed from that of the overall genetic background of the strains. Taken together, these findings suggested that the Texas and Maryland outbreaks were caused by different clones of a major genetic lineage of serotype 12F pneumococci, within which at least one PspA has been acquired via localized genetic recombination.

SUMMARY Streptococcus pneumoniae is a problematic infectious agent, whose seriousness to human health has been underscored by the recent rise in the frequency of isolation of multidrug-resistant strains. Pneumococcal pneumonia in the elderly is common and often fatal. Young children in the developing world are at significant risk for fatal pneumococcal respiratory disease, while in the developed world otitis media in children results in substantial economic costs. Immunocompromised patients are extremely susceptible to pneumococcal infection. With 90 different capsular types thus far described, the diversity of pneumococci contributes to the challenges of preventing and treating S. pneumoniae infections. The current capsular polysaccharide vaccine is not recommended for use in children younger than 2 years and is not fully effective in the elderly. Therefore, innovative vaccine strategies to protect against this agent are needed. Given the immunogenic nature of S. pneumoniae proteins, these molecules are being investigated as potential vaccine candidates. Pneumococcal surface protein A (PspA) has been evaluated for its ability to elicit protection against S. pneumoniae infection in mouse models of systemic and local disease. This review focuses on immune system responsiveness to PspA and the ability of PspA to elicit cross-protection against heterologous strains. These parameters will be critical to the design of broadly protective pneumococcal vaccines.

Pneumococcal surface protein A (PspA) has been shown to be a serologically variable virulence factor of Streptococcus pneumoniae. In mice, PspA can elicit antibodies capable of protecting them against otherwise fatal infections with encapsulated pneumococci. In previous studies it has been reported that almost all isolates have two apparently unlinked genomic sequences that are highly homologous to the 5' and 3' halves of Rx1 pspA, although out MAbs to PspA have not detected more than one PspA in any given isolate of S. Pneumoniae. Recently, we have identified four isolates from a clone of capsular serotype 6B pneumococci (MC25-28) that simultaneously express two distinct PspAs. Each of the isolates (MC25-28) exhibited the same two Kpn I fragments (each containing a Hind III site) that hybridized with Rx1 pspA. MAbs specific for PspA detected two PspAs characterized by different molecular weights and different serologic patterns of reactivity (PspA type 6 detected by MAbs XiR278 and 2A4, and PspA type 34 detected only by MAb 7D2) in each of the four isolates. In previous studies XiR278 and 2A4 frequently have been observed to react with PspA epitopes of the same strain. Based on molecular weight data both epitopes were always present on the same molecule. Our present findings raise the possibility that pneumococci make a second serologically variable PspA which is generally not detected by currently available MAbs to PspA.

Previous studies have suggested that relatively penicillin-resistant (RPR) capsular group 9L strains in western Canada may be clonally related. To test this hypothesis, restriction fragment length polymorphisms (RFLPs) were examined using DNA probes for pspA and a newly recognized pneumococcal genetic element, IS1167. Penicillin-binding proteins (PBPs) and PBP genes from representative strains were also studied. All RPR type 9L strains demonstrated an identical RFLP when probed with IS1167, and 12 of 14 RPR strains had the same RFLP when examined with pspA. Amplification of pspA by polymerase chain reaction and restriction endonuclease digestion showed that the 9L strains had common DNA fragments not identified in any of the penicillin-susceptible strains. The 9L strains apparently have a low-affinity PBP 2B distinct from those of other capsular types. These data derived from new genetic markers and PBP analysis strongly support a clonal origin of RPR type 9L pneumococci of western Canada.

PspA is anchored to the surface of all pneumococci by the C-terminal end of the molecule. The N-terminal half of PspA is known to be serologically variable and to be able to elicit protective immune responses. Molecular analysis with DNA probes spanning different regions of pspA was carried out to identify homologous sequences among pneumococcal isolates. At high stringency, DNA probes derived from the 3'-half of pspA (encoding the C-terminal half of PspA) hybridized to all of 37 pneumococcal isolates tested, representing 20 capsular serotypes and 12 PspA serotypes. Most strains had two sequences highly homologous to this region of pspA. Using derivatives of strain Rx1, with insertion mutations in pspA, it was possible to identify the functional pspA sequence. At 50% stringency, the 3' pspA probes also detected lytA and additional sequences. lytA encodes autolysin and shares homology with the 3' portion of pspA. A probe derived from the 5'-half of pspA (encoding the N-terminal half of PspA) hybridized with only 75% of strains and generally detected only one of the two sequences recognized by the 3' probes. Thus, the 3'-half of pspA appears to contain more highly conserved sequences than the 5'-half of pspA and shares homology with several additional sequences, suggesting that the pneumococcus might make several proteins that interact with the surface by the same mechanism as PspA.

Previous studies have demonstrated that mouse antibodies to phosphocholine (PC) can protect mice against fatal infection caused by several, but not all, mouse-virulent laboratory strains of Streptococcus pneumoniae. Because the pneumococcal strains used in previous studies had been mouse passed and were propagated for many years outside of humans, it was not known whether antibody to PC would be able to protect mice against S. pneumoniae freshly isolated from humans. In the present study, we examined the ability of an immunoglobulin G (IgG) monoclonal antibody (MAb) to PC to protect against infections in mice caused by 14 pneumococcal strains of capsular types 3, 4, 6A, and 6B. Nine of these strains were selected as the most virulent strains for mice from a group of 69 fresh clinical isolates. Five were mouse-passed laboratory strains. Mouse IgG3 MAb to PC was able to exhibit protective effects (survival or increased time to death) against infection with virtually all of the strains injected intravenously and against infection with 70% of the strains injected intraperitoneally. The protective effects of antibody to PC appeared to be partially dependent on capsular type. MAb to PC was most effective against capsular type 3 strains and least effective against type 4 strains. With type 3 and type 4 strains, MAb to PC could frequently protect against larger numbers of CFU injected intravenously than intraperitoneally. For capsular type 6A and 6B strains the reverse was true.

The relationship between capsular type and virulence for mice was examined with 69 fresh human isolates of Streptococcus pneumoniae. These isolates represented eight capsular types or groups. Serologic and molecular weight differences in PspA (pneumococcal surface protein A) indicated that the strains were clonally distinct. Mice were infected intravenously with washed bacteria of all 69 isolates in sterile salt solutions. Twenty-eight of the isolates were also injected intraperitoneally to permit comparisons between the intravenous and intraperitoneal routes. With a few exceptions, there was concordance between the ability of strains to cause fatal infections by the two routes. About 30% of the 69 isolates were virulent for mice. The abilities of the isolates to kill mice and the length of time between inoculation and death were strongly associated with capsular type. All type 4 isolates, 40% of type 3 isolates, and 60% of group 6 isolates were virulent for mice; type 1 isolates were marginally virulent; and all type or group 14, 19, and 23 isolates were avirulent. Times to death were generally longer for mice infected with group 6 or type 1 than for those infected with type 3 or 4 pneumococci. There was no relationship between clinical diagnosis or tissue source of the isolates and virulence for mice.

Sixty-eight adults and nine children infected with human immunodeficiency virus type 1 (HIV-1) were evaluated consecutively for the presence and amount of cell-free infectious virus in their plasma. Viremia was detected in 18 of 68 adults and in five of nine children; titers ranged from 10 to 100,000,000 TCID/ml plasma. Among the adults, none of 19 asymptomatic patients, 4 of 34 AIDS-related complex patients, and 14 of 15 AIDS patients had cell-free infectious virus in their plasma. None of 35 adult subjects with CD4+ lymphocyte counts greater than 400/mm3 were viremic, whereas 3 of 17 with 200-400 CD4+ lymphocytes/mm3 and 15 of 16 individuals with less than 200 CD4+ lymphocytes/mm3 were plasma viremic. In contrast to adults, each of five children infected with HIV-1 in utero or during the perinatal period were plasma viremic regardless of their CD4+ lymphocytes counts (range, 42-2227/mm3), duration of infection, or clinical stage; however, children infected by HIV-1 at older ages were less frequently plasma viremic. Therapy with zidovudine led to a 10- to 10(6)-fold decline in plasma HIV-1 TCID in all eight subjects studied before and after treatment.

Naturally occurring antibodies reactive with the phosphocholine (PC) determinant of pneumococcal teichoic acids may be useful for evaluating the potential of patients to make antibodies to polysaccharides. Antibodies to PC are present in most adults under the age of 60 years, are absent in very young children, and are present at low levels in Wiscott-Aldrich patients and in IgG2-deficient adults. These last three groups respond very poorly to polysaccharide antigens. Antibodies to PC are also found at low levels in the elderly, a group that has previously been shown to have low levels of antibody to blood groups A and B carbohydrates. The levels of antibody to PC over time were constant in most individuals and, in adults, seemed to show slightly less variation than did titers of antibody to blood group B. Our findings suggest that titers of antibody to PC may be superior to titers of antibody to blood group A or B for monitoring responsiveness to carbohydrate antigens.