Earlier diagnoses and faster treatment of HIV in the District of Columbia: HIV surveillance analysis, 2006-2016.

To address high HIV prevalence, the District of Columbia (DC) Department of Health has implemented multiple strategies to increase routine HIV testing since 2006. Examination of delayed HIV diagnosis over time can demonstrate population-level impact of public health strategies to promote HIV testing. Using HIV surveillance data, we examined delayed HIV diagnosis in DC (stage 3 within 90 days of diagnosis), CD4 count at HIV diagnosis, linkage to HIV care, and time to viral suppression among DC residents age 13 and above who were diagnosed from 2006 to 2016.  We used the Cochran-Armitage test of trend, Cuzick's test of trend, and Chi-square for univariate analyses, and we examined factors associated with delayed HIV diagnosis using a log-binomial multivariate model. 7,937 DC residents were diagnosed with HIV and had available data.  Between 2006 and 2016, delayed HIV diagnoses declined from 36.4% to 25.5%, median CD4 count increased from 190 cells/µl to 426 cells/µl, and median time from HIV diagnosis to viral suppression declined from 1,136 days to 84 days.  Women, youth ages 13-29, and men who have sex with men had lower proportions with delayed HIV diagnosis. In the multivariate models, racial/ethnic disparities in delayed HIV diagnoses were apparent during 2006-2008 but not during 2009-2016. Continued efforts around earlier HIV testing are needed in DC.

Body fat differences by self-reported race/ethnicity in healthy term newborns.

BACKGROUND: Ethnic differences in total body fat (fat mass [FM]) have been reported in adults and children, but the timing of when these differences manifest and whether they are present at birth are unknown. OBJECTIVES: This study aimed to assess whether ethnic differences in body fat are present at birth in healthy infants born at term, where body fat is measured using air displacement plethysmography and fat distribution by skin-fold thickness. METHODS: Data were from a multiracial cross-sectional convenience sample of 332 term infants from four racial or ethnic groups based on maternal self-report (A, Asian; AA, non-Hispanic Black [African-American]; C, non-Hispanic White; and H, Hispanic). The main outcome measure was infant body fat at 1-3 days after birth, with age, birth weight, gestational age and maternal pre-pregnancy weight as covariates. RESULTS: Significant effects for race (P = 0.0011), sex (P = 0.0051) and a race by sex interaction (P = 0.0236) were found. C females had higher FM than C males (P = 0.0001), and AA females had higher FM than AA males (P = 0.0205). C males had less FM than A males (P = 0.0353) and H males (P = 0.0001). CONCLUSION: Race/ethnic and sex differences in FM are present in healthy term newborns. Although the implications of these differences are unclear, studies beginning in utero and birth set the stage for a life course approach to understanding disease later in life.

Efficacy of rHVT-AI vector vaccine in broilers with passive immunity against challenge with two antigenically divergent Egyptian clade 2.2.1 HPAI H5N1 strains.

In countries where avian influenza has become endemic, early vaccination of layer pullets or broilers with classical inactivated vaccines at the hatchery is no longer an option because of interference with passive immunity indirectly induced by the necessary vaccination of the breeders. On the other hand, injection of thousands of chicks from 7 to 10 days old on farms has been determined to be unreliable and, therefore, poorly efficacious. For these reasons, interest has arisen regarding a newly developed live recombinant vector vaccine based on a turkey herpesvirus (HVT) expressing the H5 gene from a clade 2.2 H5N1 highly pathogenic avian influenza virus (HPAIV) strain (rHVT-H5), which in theory is capable of breakthrough passive immunity to both the vector (HVT) and the insert (H5) and is consequently applicable at the hatchery. The objectives of this trial were to evaluate the impact of maternally derived antibodies (MDAs) specific to H5N1 on the immunity and the efficacy (protection and virus shedding) of different vaccination programs including rHVT-H5 and inactivated H5N1 and H5N2 vaccines applied alone or in combination. Therefore, broilers carrying MDAs against both HVT and Asian H5N1 HPAIV were vaccinated on the first day of age with rHVT-H5, with or without boosting vaccination by an inactivated vaccine after 10 days. The different groups were challenged with two antigenically highly divergent Egyptian dade 2.2.1 H5N1 HPAIVs at 4 wk of age. Protection against challenge was compared with unvaccinated birds or vaccinated birds without MDAs. Between 70% and 90% clinical protection could be observed in the vaccinated groups possessing MDAs, indicating no or very low interference of MDAs with vaccination. Results regarding clinical protection, humoral, cell-mediated, and mucosal immunity, as well as re-excretion of challenge virus are presented and discussed.

Further evidence of antigenic drift and protective efficacy afforded by a recombinant HVT-H5 vaccine against challenge with two antigenically divergent Egyptian clade 2.2.1 HPAI H5N1 strains.

In this study, we have compared the protection afforded by a recombinant turkey herpesvirus vaccine expressing the H5 gene from a clade 2.2 H5N1 strain (rHVT-H5) and a Mexican-origin H5N2 inactivated vaccine, alone or in combination, against two antigenically divergent H5N1 Egyptian strains isolated in 2007 and 2008. Our results confirm the existence of a major antigenic drift among the Egyptian H5N1 strains such that, although protection against the "classical" 2007 HPAI H5N1 Egyptian strain could be obtained with both types of vaccines, only vaccination with the rHVT-H5 vaccine protected against challenge with the "variant" 2008 HPAI H5N1 Egyptian strain.

Passive protection afforded by maternally-derived antibodies in chickens and the antibodies' interference with the protection elicited by avian influenza-inactivated vaccines in progeny.

Systematic vaccination can be applied when a disease has become enzootic in a country or region. The final goal of the approach is to control or eradicate the disease within the country. This is a long-term vaccination plan that could be applied nationwide to all commercial and backyard poultry. However, after several months of vaccination in enzootic areas, maternally derived antibody (MDA) is present in young chicks, providing some protection and/or interference with vaccination. The aim of this study was to evaluate the level of protection afforded by MDA against challenge with highly pathogenic avian influenza virus (HPAIV), and its suspected interference with current inactivated vaccines in broilers under controlled laboratory conditions. In the first set of experiments, broilers were vaccinated with inactivated vaccines containing H5N2 subtype antigens in the presence or absence of homologue MDAs and challenged with a clade 2.2 H5N1 HPAIV. In the second set of experiments, day-old broilers, either with or without avian influenza MDA, received a regular-type monovalent H5N2 AI vaccine (0.5 ml) or a concentrated (0.2 ml) AL-Newcastle disease virus combined inactivated vaccine subcutaneously. They were then challenged at 11 or 35 days of age. In conclusion, our results indicate that protection induced by day-old administration of inactivated vaccine (regular or concentrated) in the presence or absence of MDA to H5N2 AIV induces poor protection against challenge with H5N1 HPAIV and should not be recommended. Based on our results, vaccination of MDA-positive chickens at a later age (10 days) seems to be a valuable recommendation, although MDAs may still interfere with vaccination to a lesser extent because they are present up to 3 wk posthatch. Therefore, in areas with high infection pressure, when possible, two vaccinations are recommended for optimal protection. Also, it might be advisable to take into account day-old AI MDA titers when one is determining the optimal age of vaccination.

Comparative fecundity and survival rates of phlebotomus papatasi sandflies membrane fed on blood from eight mammal species.

Female sandflies, Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae), were fed via chicken membrane on heparinized blood from eight species of mammal (human, horse, cow, pig, dog, rabbit, guinea-pig, hamster) and their reproductive success rates were compared. No appreciable differences between those fed on human and animal blood were detected with respect to the proportion of flies that fed successfully, mortality-rate within 24h, number of eggs laid per blood-fed female or egg viability. When mass-rearing sandflies for research purposes, membrane-feeding avoids practical difficulties encountered if sandflies are allowed to feed on live hosts (i.e. anaesthesia, distress from handling and postfeeding inflammation) and reduction of sandfly fecundity due to host antibody interference. Use of animal blood also eliminates risks of accidental transmission of human blood-borne pathogens, e.g. hepatitis B and human immunodeficiency virus (HIV), and is less expensive than maintenance of animals and their preparation for sandfly feeding.

Retrospective analysis of infectious disease in patients who received recombinant human granulocyte-macrophage colony-stimulating factor versus patients not receiving a cytokine who underwent autologous bone marrow transplantation for treatment of lymphoid cancer.

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) significantly shortens the number of days required to achieve an absolute neutrophil count of >500/mm3 after autologous bone marrow transplantation (ABMT); however, the ability of rhGM-CSF to enhance neutrophil and macrophage function in vivo has been incompletely characterized. In this retrospective study, the authors compared the incidence of infection from the day of transplantation to 28 days posttransplantation between two groups of previously studied patients who underwent ABMT at the Fred Hutchinson Cancer Research Center. A control group that received no cytokine was compared with a study group that received rhGM-CSF while participating in phase I, II, or III trials. During the posttransplantation period when both study groups had severe neutropenia, 40% (38 of 95) of control patients were found to have an infection, whereas only 13% (6 of 46) of rhGM-CSF patients developed an infection (p = 0.001). Most infections occurred before an absolute neutrophil count of > 100/mm3 was achieved. There was a trend toward fewer fungal infections (14% vs. 4%; p = 0.093); gram-negative bacterial infections (6% vs. 0%; p = 0.083); pulmonary infections (12% vs. 2%; p = 0.062); fewer days of amphotericin B (p = 0.0305); and fewer days of intravenous antibiotics (p = 0.0791) in rhGM-CSF-treated patients. These results support in vivo findings that the function-enhancing effect of rhGM-CSF may reduce infection-related complications.

Syringoma resembling confluent and reticulated papillomatosis of Gougerot-Carteaud.

We report the case of a 31-year-old woman with a rare presentation of syringoma resembling confluent and reticulated papillomatosis of Gougerot-Carteaud. The lesions have been unresponsive to treatment with topical steroids and retinoic acid.

Comparing assessments of DSM-IV substance dependence disorders using CIDI-SAM and SCAN.

The main question addressed by this paper is whether DSM-IV substance dependence diagnoses obtained from two different instruments (the semi-structured WHO Schedules for Clinical Assessment in Neuropsychiatry, SCAN and the highly structured WHO Composite International Diagnostic Interview--Substance Abuse Module, SAM) are as consistent as diagnoses obtained from a single instrument (SAM) administered twice. Such comparisons of results from the two different instruments provide some measure of validity of the lay-administered SAM and of the underlying diagnostic concepts. Chance-corrected concordance was estimated using the kappa coefficient for SAM/SCAN (test/validation) and SAM/SAM (test/retest) comparisons. Analyses of agreement between SAM and SCAN for DSM-IV dependence diagnoses indicated good agreement for alcohol and cocaine, and fair agreement for opiates and cannabis. SAM/SAM (test/retest) agreement was excellent for alcohol and opiate dependence, good for cocaine dependence, and fair for cannabis dependence. Agreement on individual dependence criteria was generally consistent with overall diagnostic agreement though more variable. Notable was the poor agreement for cannabis criteria in the SAM/SCAN protocol. This may indicate that the dependence syndrome is less applicable to cannabis, while the consistency of agreement for alcohol, opiate, and cocaine dependence criteria supports the validity of these dependence syndromes. Finally, these data indicate that both the clinical (SCAN) and non-clinical (SAM) interviews can be used effectively for a variety of substances and dependence diagnoses.

Regulation of HIV-1 protease activity through cysteine modification.

The homodimeric protease of the human immunodeficiency virus 1 contains two cysteine residues per monomer which are highly conserved among viral isolates. However, these cysteine residues are not essential for catalytic activity which raises the question of why they are conserved. We have found previously that these cysteine residues are unusually susceptible to oxidation by metal ions, and this results in inhibition of protease activity. Recombinant protease mutants (C67A, C95A, and the double mutant C67A,C95A) were prepared to assess the possible role of these cysteines in redox regulation of the enzyme. Mixed disulfides were formed between the cysteine residues of the enzymes and low molecular weight thiols. Enzyme activity was lost when a mixed disulfide was formed between 5,5'-dithiobis(2-nitrobenzoic acid) and cysteine 95, while the same mixed disulfide at cysteine 67 reduced activity by 50%. This effect was reversible as normal activity could be restored when the enzyme was treated with dithiothreitol. The cysteines could also be modified with the common cellular thiol glutathione. Modification with glutathione was verified by mass spectrometry of the protein peaks obtained from HPLC separation. Glutathiolation of cysteine 95 abolished activity whereas modification at cysteine 67 increased the k(cat) by more than 2-fold with no effect on K(m). In addition, glutathiolation at cysteine 67 markedly stabilized the enzyme activity presumably by reducing autoproteolysis. These results demonstrate one possible mechanism for regulation of the HIV-1 protease through cysteine modification and identify additional targets for affecting protease activity other than the active site.

Cross talk in a fiber-optic Fabry-Perot sensor array with ring reflectors.

We demonstrate a fiber-optic interferometric sensor array based on the in-line Fabry-Perot configuration, which uses fiber ring reflectors to effect the low-reflectivity elements required between each sensor section. The intrinsic optical cross talk that occurs between the sensor sections owing to multiple reflections is analyzed and compared with experimental results obtained with a four-sensor system.

Histopathologic changes in condylomata acuminata after application of podophyllum.

The histologic changes of podophyllin-treated condylomata acuminata were studied at 24-hour, 48-hour, and 7-day intervals. The 24-hour specimens had scattered individual atypical cells, whereas 48-hour specimens demonstrated small focal areas of atypia. Seven-day specimens exhibited very mild atypia of cells. All treated specimens had inflammation-necrosis ranging from scattered inflammatory cells to degeneration of the squamous epithelium.