Tuberculosis along the continuum of HIV care in a cohort of adolescents living with HIV in Ethiopia.

SETTING: Eight health facilities in Ethiopia. OBJECTIVE: To determine tuberculosis (TB) incidence rates and associated factors among adolescents living with the human immunodeficiency virus (ALHIV). DESIGN: This was a retrospective cohort study. Adolescents enrolled in HIV care between January 2005 and 31 December 2013 constituted the study population. The main outcome variable was TB diagnosis during follow-up. Baseline World Health Organization (WHO) clinical stage, CD4 count, previous history of TB and use of isoniazid preventive therapy (IPT) were the main independent variables. We estimated TB incidence rates as incident cases per 100 person-years of observation (PYO). Cox regression analysis was used to control for confounders. RESULTS: Of the 1221 adolescents screened, 1072 were studied; 60.1% were girls. TB incidence rate was 16.32 per 100 PYO during pre-antiretroviral therapy (pre-ART) follow-up but declined to 2.25 per 100 PYO after initiation of ART. Advanced WHO clinical stage (adjusted hazard ratio [aHR] 2.71, 95%CI 1.69-4.33) and CD4 count <350 cells/µl (aHR 2.28, 95%CI 1.10-4.81) predicted TB incidence in the pre-ART cohort. IPT use was associated with a significant reduction in TB incidence in the ART cohort, but not in the pre-ART group. CONCLUSION: Although TB was a significant problem in ALHIV, timely administration of ART and IPT had a significant protective effect.

A whole cell biocatalyst for double oxidation of cyclooctane.

A novel whole cell cascade for double oxidation of cyclooctane to cyclooctanone was developed. The one-pot oxidation cascade requires only a minimum of reaction components: resting E. coli cells in aqueous buffered medium (=catalyst), the target substrate and oxygen as environmental friendly oxidant. Conversion of cyclooctane was catalysed with high efficiency (50% yield) and excellent selectivity (>94%) to cyclooctanone. The reported oxidation cascade represents a novel whole cell system for double oxidation of non-activated alkanes including an integrated cofactor regeneration. Notably, two alcohol dehydrogenases from Lactobacillus brevis and from Rhodococcus erythropolis with opposite cofactor selectivities and one monooxygenase P450 BM3 were produced in a coexpression system in one single host. The system represents the most efficient route with a TTN of up to 24363 being a promising process in terms of sustainability as well.

Short-term effects of large-dose vitamin A supplementation on viral load and immune response in HIV-infected women.

Vitamin A supplementation has been suggested for treatment and prevention of HIV infection. However, some in vitro data indicate that vitamin A may activate HIV. Randomly, 40 HIV-seropositive women of reproductive age were allocated to receive a single oral dose of 9900 micromol (300,000 IU) vitamin A or placebo. Plasma HIV-1 RNA concentration, total lymphocytes, selected lymphocyte subsets and activation markers, and in vitro lymphocyte proliferation to phytohemagglutinin (PHA) and Candida were measured before dosing and at various time points over an 8-week follow-up period. No differences were found between treatment groups in the frequency of signs or symptoms of acute vitamin A toxicity, nor were differences evident in any lymphocyte subset or activation marker at any time during follow-up. Mean and median viral load concentration at each time point and change in viral load from baseline to each follow-up point did not differ between treatment groups. No difference was measured between treatment groups in the proportion of women who responded to PHA or Candida. This study provides no evidence that high dose vitamin A supplementation of HIV-infected women is associated with significant clinical or immunologic adverse effects.

Cultural feasibility studies in preparation for clinical trials to reduce maternal-infant HIV transmission in Haiti.

A cultural feasibility study is defined as one that investigates scientific as well as ethical, behavioral, and social issues in the design of clinical trials. The value of such a broadly defined assessment is illustrated through the presentation of two case studies conducted to prepare for clinical trials to reduce maternal-infant HIV transmission on Cité Soleil, Haiti. The first study addressed issues surrounding a trial of breast-feeding and exclusive bottle-feeding among HIV seropositive mothers. The second study focused on the implementation of a double-blind trial of HIV immune globulin and standard immune globulin to be administered to infants of seropositive mothers shortly after birth. Both cases used focus group interviews with mothers and in-depth interviews with key informants to investigate AIDS-related beliefs, acceptability of trial participation, risks to subjects, and community reactions and repercussions to the trial. Findings point to the difficulties posed by attempts to conduct trial involving complex research designs in socially disadvantaged populations. Recommendations highlight the need to consider the community-wide impact of a trial, and the need to undertake extensive educational preparation of participants to ensure informed consent and adherence to protocols.

PIP: Cultural feasibility studies use ethnographic methods to explore ethical, behavioral, and social issues inherent in the design of proposed clinical trials. This approach was applied in advance of clinical trials aimed at reducing maternal-infant HIV transmission in Cite Soleil, Haiti. The first focused on conditions that would be necessary to conduct a trial of breast feeding versus exclusive bottle feeding by HIV-positive mothers; the second investigated the feasibility of a double-blind trial of administration of a high- titer antibody preparation--HIV immune globulin (HIVIG)--to infants of seropositive mothers shortly after birth. Study methods included focus group discussions with mothers and in-depth interviews with key informants about AIDS-related beliefs, acceptability of trial participation, risks to subjects, and community repercussions. Concerns identified included the potential negative effect on breast feeding promotion efforts in Haiti, the scarcity of economic means to sustain safe bottle feeding, the risk of being labeled HIV-positive by virtue of study participation, the potential for the HIVIG trial to reinforce the misconception that a vaccine effective against AIDS exists, and problems explaining the concept of a double-blind study and accepting random assignment to treatment and control groups. As a result of these studies, it was decided to conduct the infant feeding study in a community with higher rates of exclusive bottle feeding and lower infant mortality than exist in Cite Soleil. The HIVIG trial could be conducted, but only after extensive community education to ensure informed consent. An objective assessment of subject comprehension was developed for this purpose.

Parasitic infections of the central nervous system in children. Part III: Space-occupying lesions.

In the last part of this three-part review of parasitic infections of the central nervous system in children, we consider parasites which due to their size, distribution, or the nature of the host response, tend to cause focal lesions in the brain and spinal cord and therefore present as space-occupying lesions which occasionally mimic malignant tumors. As in Parts I and II, infections are grouped according to their predominant geographic area. Such infections include cysticercosis, one of the more common and important infections of the central nervous system.

Parasitic infections of the central nervous system in children. Part II: Disseminated infections.

In the second segment of this three-part review of parasitic infections of the central nervous system in children, we consider parasitic infections which typically involve various tissues and organs in addition to the brain and spinal cord. Parasites capable of dissemination in immunocompetent hosts are discussed first, and, as in Part I, organisms are grouped according to their predominant geographic location. This is followed by a discussion of the unique aspects of toxoplasmosis, strongyloidiasis and infection with microsporidia in immunocompromised patients, with an emphasis on the central nervous system.

Bacillus Calmette-Guérin complications in children born to HIV-1-infected women with a review of the literature.

OBJECTIVE: To compare the risk of complications following Bacillus Calmette-Guérin (BCG) vaccination among children by maternal and infant HIV-1 infection status as part of an investigation of an outbreak of BCG complications. METHODS: A nonconcurrent cohort study of BCG complications among 125 infants born to HIV-1 seropositive and 166 infants born to HIV-1 seronegative mothers was conducted in Cité Soleil, Haiti. Infants were examined at regular intervals until 15 months of age, and complications from BCG were documented. An investigation of BCG vaccination practices was conducted. RESULTS: Mild or moderate complications occurred among 16 of 166 (9.6%) infants born to HIV-1 seronegative mothers compared with 4 of 13 HIV-1-infected infants (30.8%, P = .04) and 10 of 75 (13.3%, P = .39) uninfected infants born to HIV-1-infected mothers. No serious complications were noted. The outbreak of complications was associated with administration of 2.0 to 2.5 times the recommended dose of BCG vaccine. CONCLUSIONS: This and five other cohort studies indicate that there may be a small increased risk of complications following BCG vaccination among HIV-1-infected children, but the reactions are usually mild and the risk does not outweigh the benefits of BCG vaccination in populations at high risk of tuberculosis during infancy and childhood.

Breastmilk, breastfeeding, and transmission of viruses to the neonate.

The benefits of breast milk have been well delineated, and breastfeeding should be encouraged whenever possible. However, the potential transmission of HIV-1, HTLV-1, and possibly HTLV-II warrant the recommendation that women in industrialized countries who are infected with these viruses not breastfeed their infants. These recommendations reflect what is currently known about the risks of viral transmission through breastfeeding; ongoing and future studies may provide additional data, enabling a better definition of the precise risks and factors associated with the transmission of viruses through breastfeeding.

HIV risk behavior and medical status of underprivileged youths in Belo Horizonte, Brazil.

METHODS: From June 1989 to April 1991, 394 adolescents aged 10-18 years randomly selected upon admission at a state shelter in Belo Horizonte, Brazil underwent health history interview, physical examination, serology for HIV, hepatitis B, and syphilis, and stool examination. Participants were classified as street-based youths (n = 195) or home-based youths (n = 199). The age distribution was similar in both groups, although males were overrepresented among street-based youths (79.5% versus 62.3%). RESULTS: Compared with home-based youths, street-based youths reported earlier onset (p = 0.009) and higher rates of sexual activity (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.4-3.3), sexual abuse (OR, 3.7; 95% CI, 1.2-10.1), and sexually transmitted diseases (OR, 2.9; 95% CI, 1.3-6.6). Overall condom use was low in both groups. Street-based youths were 7.8 times more likely to use drugs than home-based youths (95% CI, 4.9-12.7). Inhalants and marijuana were the more commonly used drugs. Intravenous drug use was low. CONCLUSIONS: Although chronic malnutrition and multiple parasitosis were common findings in both groups, street-based youths were more likely to present disorders related to trauma and poor hygienic conditions. Antibodies to HIV were detected in four (2%) street-based youths and in none of the home-based youths. This study confirms that street youths are at higher risk for HIV infection than their home-based peers and indicates a need for HIV prevention programs targeting this population.

Maternal IgG1 and IgA antibody to V3 loop consensus sequence and maternal-infant HIV-1 transmission.

Maternal-infant transmission of HIV-1 occurs in 13-40% of pregnancies. Studies on transmission of maternal immunity to HIV antigens have used antigens from viruses not representative of clinical isolates and have been conflicting. Using a consensus peptide sequence based on HIV isolates found in Haiti, we found that Haitian mothers who transmitted infection to their offspring had significantly higher mean concentrations of IgG1 antibodies to the V3 loop of the primary neutralising domain of the viral envelope (gp 160) than non-transmitters (p = 0.02). Concentrations of IgA antibody to this domain were similar in transmitters and non-transmitters.

Prevalence of HIV-1 DNA and p24 antigen in breast milk and correlation with maternal factors.

Breast milk specimens from human immunodeficiency virus type 1 (HIV-1)-seropositive and HIV-1-seronegative women were examined for the presence of HIV-1 p24 antigen by the antigen capture method and for viral DNA using the polymerase chain reaction. HIV-1 DNA was present in 70% of milk specimens collected from 47 HIV-seropositive women 0-4 days after delivery and in approximately 50% of specimens collected 6 and 12 months postpartum. p24 antigen, present in 24% of milk specimens collected from 37 seropositive women within the first 4 days postpartum, was not detected in any of the subsequent specimens. The presence of HIV-1 DNA or p24 antigen in milk was not significantly associated with maternal CD4 lymphocyte count, beta 2-microglobulin level, or fulfillment of the AIDS clinical case definition. Although the correlation of either HIV-1 proviral DNA or p24 antigen with the presence of infectious virus is not known, these data indicate the need for additional studies examining the role of breastfeeding in maternal-infant transmission of HIV-1.

The utility of verbal autopsies for identifying HIV-1-related deaths in Haitian children.

OBJECTIVE: To determine whether deaths among Haitian infants born to HIV-1-seronegative women could be distinguished from deaths among children born to HIV-1-seropositive women using the verbal autopsy technique. METHODS: Mothers of 315 Haitian children who died were interviewed about events leading to the child's death. Three physicians independently reviewed interview data and determined the probable cause of death without knowledge of maternal HIV-1 status or hospital records. The underlying causes of death assigned to the infants were analyzed to determine whether maternal HIV status could be predicted. RESULTS: There was good agreement among the physicians (kappa = 0.62) and 90% agreement between hospital records and the verbal autopsy diagnosis. Compared with children born to HIV-1-seronegative women, deaths in children born to HIV-1-seropositive mothers were more likely to be ascribed to a presumptive diagnosis of AIDS (37 versus 21%; P = 0.01). The sensitivity and specificity of verbal autopsies for identifying deaths associated with maternal HIV-1 infection ranged from 37 to 59% and from 69 to 79%, respectively, depending on the classification system used. The predictive positive value of a death believed to be consistent with pediatric HIV-1 infection was 26-30% and the predictive negative value was 85-90%. CONCLUSION: Verbal autopsies may be useful for distinguishing certain causes of death, but have limited utility for distinguishing deaths associated with maternal HIV-1 infection from deaths among children born to HIV-1-seronegative women.

Herpes simplex virus type 2 infection, syphilis, and hepatitis B virus infection in Haitian women with human immunodeficiency virus type 1 and human T lymphotropic virus type I infections. The Johns Hopkins University (JHU)/Centre pour le Developpement et la Santé (CDS) HIV Study Group.

Antibodies to herpes simplex virus type 2 (HSV-2), antibodies to hepatitis B virus (HBV) core antigen (anti-HBc), and VDRL antibodies (serologic evidence of syphilis) were evaluated in women known to be infected with human immunodeficiency virus type 1 (HIV-1) (n = 95) or human T lymphotropic virus type I (HTLV-I) (n = 45) and controls (n = 89). HIV-1-seropositive women were more likely than controls to have antibodies to HSV-2 (88% vs. 54%; P less than .001), anti-HBc (67% vs. 43%; P = .008), and VDRL antibodies (21% vs. 8%; P = .02). Similarly, HTLV-I-seropositive women were more likely than controls to have antibodies to HSV-2 (82% vs. 54%; P = .003) and anti-HBc (67% vs. 43%; P = .008). There was no evidence that HIV-1 or HTLV-I predisposed to chronic hepatitis B virus infection. The stronger associations between HIV-1 and HTLV-I with HSV-2 than the associations with syphilis or HBV are consistent with the hypothesis that recurrent disruptions of mucous membranes caused by HSV-2 infections predispose to sexual transmission of HIV-1 and HTLV-I.

Tuberculin skin test reactivity among adults infected with human immunodeficiency virus.

Infection with the human immunodeficiency virus type 1 (HIV-1) results in decreased cell-mediated immunity, which includes decreased delayed hypersensitivity to skin test antigens. HIV-1 seropositivity and skin test reactivity to purified protein derivative (PPD) were determined among 2042 healthy Haitian adults with normal chest radiographs. Among HIV-1-seropositive individuals, 52.3% (146/279) had PPD reactions greater than or equal to 10 mm compared with 67.2% (1184/1763) of the seronegative adults (P less than .001). However, the percentage of HIV-1-seropositive individuals with PPD reactions greater than or equal to 5 mm was similar to the percentage of seronegative adults with PPD reactions greater than or equal to 10 mm (180/279 [64.5%] vs. 1184/1763 [67.2%]). Assuming that the rate of prior infection with Mycobacterium tuberculosis was similar for HIV-1-seronegative and -seropositive populations, these data provide support for the recent recommendations to use induration of greater than or equal to 5 mm as evidence of past infection with M. tuberculosis in HIV-1 seropositive adults.

Failure of the H2 antagonist cimetidine to reverse parasite antigen-specific lymphocyte unresponsiveness in experimental filariasis.

Histamine is known to mediate potent immunosuppressive effects on lymphocyte function. In jirds infected with Brugia pahangi decreased mitogen and parasite antigen responsiveness are associated with the presence of histamine binding regulatory cells. The present study was thus designed to investigate the immunoregulatory role of histamine in experimental filariasis. Spleen cells from normal or B. pahangi infected jirds were incubated with BSA or histamine coupled Sepharose beads and the degree of cell-bead binding was quantitated. Cells from infected jirds demonstrated increased levels of histamine, but not BSA binding relative to normal cells, and this binding was blocked by soluble histamine or by the histamine receptor antagonist cimetidine. Cimetidine failed to restore the in vitro responsiveness of spleen cells from infected jirds to phytohemagglutinin or to a soluble extract of B. pahangi. Cimetidine did, however, reverse histamine-induced suppression of normal spleen cell responses to PHA. The present results suggest that histamine does not play a major role in the immunoregulatory alterations induced by B. pahangi infection.

Bancroftian filariasis in Haiti: preliminary characterization of the immunological responsiveness of microfilaremic individuals.

Patent infections with the lymphatic filariae, Wuchereria bancrofti and Brugia malayi, are associated with suppressed in vitro cellular responsiveness to filarial antigens. In studies of bancroftian filariasis in Haiti, a significant number of microfilaremic individuals can be characterized as "responders" to filarial antigens. Cells from 37/74 untreated microfilaremic subjects responded to B. pahangi antigen (stimulation ratio greater than 2) as detected by in vitro blastogenesis. A comparison of responders to nonresponders revealed a significant difference in mean B. pahangi reactivity (15,822 vs. 4,538 cpm, P less than 0.001), but no significant differences with respect to age, microfilaremia, PPD or PHA reactivity, or B. pahangi-specific antibody levels. Subtle differences may exist between these groups with respect to recognition of specific antigens on Western blots.