Evaluation of effectiveness of the 23-valent pneumococcal capsular polysaccharide vaccine for HIV-infected patients.

BACKGROUND: We conducted a retrospective case-control study to evaluate effectiveness of pneumococcal vaccine against invasive disease among adults with human immunodeficiency virus (HIV) infection in San Francisco, Calif, and Atlanta, Ga. METHODS: Case patients were 18- to 55-year-old subjects with HIV infection who were admitted to selected hospitals in Atlanta or San Francisco from February 1992 to April 1995 from whom Streptococcus pneumoniae was isolated from a normally sterile site. Controls were HIV-infected patients of similar age matched to cases by hospital of admission and CD4 lymphocyte count (<0.20, 0.20-0.499, >/=0.50 x 10(9)/L [<200, 200-499, >/=500 cells/mm(3)]) or clinical stage of acquired immunodeficiency syndrome. Case and control subjects were restricted to persons known to have HIV infection before hospital admission. Analysis used matched univariate and conditional logistic regression. RESULTS: One hundred seventy-six case patients and 327 controls were enrolled. By univariate analysis, persons with pneumococcal disease were more likely to be black, be current smokers, and have close contact with children. Adjusted for these factors and CD4 cell count, pneumococcal vaccine effectiveness was 49% (95% confidence interval [CI], 12%-70%). Adjusting for all variables and key interaction terms, vaccine effectiveness among whites was 76% (95% CI, 35%-91%), whereas effectiveness among blacks was 24% (95% CI, -50% to 61%). Among controls, vaccination was significantly less common among blacks (29% vs 45%; P<.005). CONCLUSIONS: Pneumococcal vaccine demonstrated protection against invasive pneumococcal infections among white but not black HIV-infected adults. Failure to demonstrate effectiveness among blacks may be due to limited power because of low use of the vaccine in this population, immunization at more advanced stages of immunosuppression, or unmeasured factors. These data support current recommendations for use of pneumococcal vaccine in HIV-infected persons and highlight a clear need for strategies to improve vaccine-induced protection.

Diagnosis of Mycoplasma pneumoniae infection in autopsy and open-lung biopsy tissues by nested PCR.

A nested PCR specific for the Mycoplasma pneumoniae P1 gene was used to diagnose mycoplasma infection in two cohort patients with severe pneumonia within 24 h of tissue receipt. A postmortem diagnosis of M. pneumoniae infection was obtained for the first patient, who died without the collection of appropriate paired samples for serodiagnosis. An open-lung biopsy obtained from the second patient allowed a quick, definitive diagnosis and proper selection of therapy.

Community outbreak of Legionnaires' disease: an investigation confirming the potential for cooling towers to transmit Legionella species.

In August and September 1993, we investigated an outbreak of legionnaires' disease in Fall River, Massachusetts, that involved 11 persons; the attack rate was highest in Flint, a community of Fall River. All cases were infected with Legionella pneumophila serogroup 1 (Lp-1). A case-control study revealed that cases were more likely than matched controls to have visited sites in neighborhood A of Flint. Environmental sampling in Flint found that four of nine aerosol-producing devices sampled contained legionellae; only two, conjoined cooling towers on building A, contained Lp-1. Three independent methods of subtyping--monoclonal antibody subtyping, arbitrary primer polymerase chain reaction, and pulsed-field gel electrophoresis--revealed that Lp-1 isolates from three cases with culture-positive legionnaires' disease matched those from the cooling towers on building A. Water samples from the homes of cases with culture-positive legionnaires' disease contained no legionellae. The results of this epidemiologic and laboratory investigation indicate that the cooling towers on building A were the source of the outbreak of legionnaires' disease and confirm the importance of cooling towers in the transmission of legionnaires' disease.

Preventing bacterial respiratory tract infections among persons infected with human immunodeficiency virus.

Bacterial respiratory tract infections occur frequently in persons infected with human immunodeficiency virus (HIV) and may be caused by a wide variety of pathogens. Pneumonia is the most commonly diagnosed respiratory infection in HIV-infected persons and is more common in those persons than in non-HIV-infected ones. HIV-infected persons have a much higher risk of pneumococcal disease than do noninfected controls, and disease may occur relatively early in the course of HIV infection. While mortality associated with the disease does not seem to be high among HIV-infected persons, there is a higher rate of recurrence of the disease in that population. Risk factors for pneumococcal disease in HIV-infected persons are not well characterized. Though efficacy data are limited, the 23-valent polysaccharide pneumococcal vaccine is recommended for use early in the course of HIV infection. There are no data suggesting that HIV-infected persons should be revaccinated routinely. Antiretroviral agents may enhance the immunologic response to the polysaccharide vaccine. Prophylactic antibiotics may have a role in preventing recurrences of severe bacterial respiratory infections, and intravenous immunoglobulin may be useful in preventing serious bacterial infections in HIV-infected children. HIV-infected persons are also at greater risk for serious infections with Haemophilus influenzae than are non-HIV-infected persons. Vaccination against H. influenzae type b (Hib) is recommended for HIV-infected children but not for adults. Antimicrobial drug-resistant strains of Streptococcus pneumoniae and H. influenzae have become more prevalent recently and consequently have impacted on strategies for prevention and treatment of those infections.

Clinical assessment of anaerobic isolates from blood cultures.

Patients at two tertiary-care medical centers were evaluated to determine the clinical significance of anaerobic isolates from their blood specimens and to identify whether aerobic and/or anaerobic conditions were necessary for the detection of Streptococcus pneumoniae isolates. Significant anaerobes were isolated from only 0.1% and 0.4% of all blood cultures collected. The majority of patients with significant anaerobes had clinical conditions in which anaerobes are known to cause infections. Of the S. pneumoniae organisms, 83% were isolated only from the aerobic bottles of a blood culture set. These data lend support to the recommendations for the selective ordering of anaerobic blood cultures without compromising the isolation of S. pneumoniae.

Ovulation induction with low doses of clomiphene citrate.

Ovulation was induced with one-quarter tablet (12.5 mg) of clomiphene citrate given for five days to three oligoovulatory patients who had consistently formed functional ovarian cysts when given 50 and 25 mg of clomiphene citrate for five days. Two of the patients had polycystic ovary syndrome and the other had hypothalamic dysfunction associated with an eating disorder. On clomiphene citrate 12.5 mg for five days, one patient conceived, another produced inadequate cervical mucus but later conceived after in vitro fertilization and embryo transfer, and the third woman, who had concomitant fallopian tube disease, ovulated but has not conceived. Women oversensitive to clomiphene citrate can be effectively treated with very low doses of the drug. Perhaps other oligoovulatory patients may benefit from lower than currently recommended clomiphene citrate doses.

Pseudocorpus luteum insufficiency: a local defect of progesterone action on endometrial stroma.

A 23-yr-old woman whose initial complaint was infertility demonstrated glandular stromal dissociation with failure of the endometrial stroma to undergo pseudodecidualization in repeated endometrial biopsies taken late in the luteal phase. As the clinical presentation was consistent with the inadequate corpus luteum syndrome, hormone measurements were performed. The endometrial biopsy was abnormal during cycles in which the serum pattern of progesterone, estradiol, FSH, and LH was normal. Exogenous progesterone did not correct the abnormality. The patient, by in vitro studies, has approximately one half the number of high affinity progesterone-binding sites in the cytosol fraction of her endometrium compared to preparations from two normal control subjects. Since her cytosol-binding protein was qualitatively identical to two control subjects, the incomplete maturation of her endometrial stroma may represent an absence or reduced number of stromal cytosol receptors and/or a resistance to specific hormone action in an individual target tissue.

Free testosterone concentration in serum: a method for determination.

Two procedures for quantifying serum levels of testosterone-estradiol-binding globulin (TeBG) have been evaluated. Both procedures utilize indirect methods for assessing the extent of protein-steroid interaction for the purpose of devising a clinically feasible procedure for estimating serum free testosterone. In the first method serum protein concentration was varied by dilution until 50 per cent of steroid binding was obtained at a given concentration of steroid. Dextran-coated charcoal was used for separating TeBG-bound steroid from the unbound fraction. In the second procedure DEAE-cellulose filtration was used to isolate the TeBG-steroid complex for quantitation. Having a sufficiently accurate measure of TeBG levels together with a knowledge of the total endogenous testosterone permitted the estimation of serum free testosterone based on the binding affinities of serum proteins. The preferred DEAE-cellulose filtration method has proved useful for routine clinical evaluation of physiologically effective androgen levels.

Free testosterone concentration in serum: elevation is the hallmark of hirsutism.

A simple, reliable procedure for quantitating the concentration of free (not protein bound and thus biologically active) testosterone in serum has been applied to normal and hirsute patients. Each of 32 hirsute women studied had a significantly elevated level of free testosterone (that is, more than two standard deviations above the mean of that found in normal women), although half of them had a total serum testosterone level within normal limits. Suppression of free testosterone to within normal limits could be accomplished by dexamethasone alone in 47 per cent of the hirsute group. In the remainder of the hirsute group, suppression of free testosterone to within normal limits could be accomplished by addition of Enovid-E. Use of free serum testosterone concentration is clearly superior to the use of total serum testosterone concentration for the identification and rational therapy of simple hirsutism.

A rapid screening technic for detection of Y chromosomes.

A rapid, simple method for screening individuals at high risk for the presence of Y chromosomes is described. The correlation with actual sex using probability tables from Baye's formula have shown to be accurate, when used with a 99% confidence limit. This procedure can be utilized in the investigation of amenorrhea or may be used as a screening method prior to expensive and time-consuming karyotyping procedures.

Reversible norepinephrine binding to rabbit myometrium: relationship to sites of known biological significance.

Catecholamines bind specifically to several cell types and subcellular fractions. This binding is not consistent with binding to the adrenergic receptor. Catecholamines would be expected to bind to sites other than the adrenergic receptor (uptake 1, uptake 2, nerve vesicles, catecholamine-O-methyl transferase and serum albumin). We characterized the binding of 3H-norepinephrine to microsomes prepared from rabbit myometrium. In the presence of antioxidant binding was reversible and 3H-norepinephrine could be recovered bound to microsomes or free in incubation media. The binding was not characteristic of binding to any one known biological site. It may represent binding to a mixture of these sites or may be fortuitous binding to sites of unknown biological significance.

Artificial insemination with fresh donor semen.

A total of 141 patients received donor insemination during a 21/2-year period. Pregnancy was achieved by 57 per cent of these patients. When patients who were inseminated for less than three cycles are excluded, the pregnancy rate is 77 per cent. The mean conception time was three treatment cycles. In 69 pregnancies, the occurrence of abortion was that of the general population, and an increased male-to-female ratio was observed in the 36 live-born infants. Questionnaires sent to all couples and returned by 81 per cent indicated that donor insemination was not emotionally harmful to their marriage. Heterologous insemination is a safe, effective therapeutic alternative to adoption for selected couples.