Incentivized recruitment of a population sample to a mobile HIV testing service increases the yield of newly diagnosed cases, including those in need of antiretroviral therapy.

OBJECTIVE: The aim of the study was to compare the yields of newly diagnosed cases of HIV infection and advanced immunodeficiency between individuals attending a mobile HIV counselling and testing (HCT) service as participants in a population-based HIV seroprevalence survey and those accessing the same service as volunteers for routine testing. METHODS: The study was conducted in a peri-urban township within the Cape Metropolitan Region, South Africa. Survey participants (recruited testers) were randomly selected, visited at home and invited to attend the mobile HCT service. They received 70 South African Rand food vouchers for participating in the survey, but could choose to test anonymously. The yield of HIV diagnoses was compared with that detected in members of the community who voluntarily attended the same HIV testing facility prior to the survey and did not receive incentives (voluntary testers). RESULTS: A total of 1813 individuals were included in the analysis (936 recruited and 877 voluntary testers). The prevalence of newly diagnosed HIV infection was 10.9% [95% confidence interval (CI) 9.0-13.1%] among recruited testers and 5.0% (3.7-6.7%) among voluntary testers. The prevalence of severe immune deficiency (CD4 count ≤ 200 cells/ µL) among recruited and voluntary testers was 17.8% (10.9-26.7%) and 4.6% (0.0-15.4%), respectively. Linkage to HIV care in recruited testers with CD4 counts ≤ 350 cells/ µL was 78.8%. CONCLUSION: Compared with routine voluntary HCT, selection and invitation in combination with incentives doubled the yield of newly diagnosed HIV infections and increased the yield almost fourfold of individuals needing antiretroviral therapy. This may be an important strategy to increase community-based HIV diagnosis and access to care.

Quality of induced sputum using a human-powered nebuliser in a mobile human immunodeficiency virus testing service in South Africa.

OBJECTIVES: To investigate the quality of induced sputum samples using a human-powered (HPN) and an electric-powered nebuliser (EPN). METHODS: For each participant two sputum samples were induced using the HPN and the EPN. The sequence of the two nebulisers was allocated at random. The proportion of good quality sputum according to different assessment criteria was compared using an exact McNemar test. The difference in time to expectoration was compared using the Wilcoxon matched-pairs signed-rank test. RESULTS: A total of 123 individuals were eligible for the study. Nine individuals refused to participate and five were unable to produce a sputum sample. The proportion of good quality sputum was higher among sputum samples induced by the HPN compared to those obtained using the EPN. The median time to produce a sputum sample was 2.2 min (IQR 1.13-4.1) for the HPN and 2.5 min (IQR 1.4-4.1) for the EPN. CONCLUSION: The HPN induced good quality sputum within 3 min. The device operates without electricity and is suitable not only for remote clinics with unreliable electricity, but also for mobile services and community-based intensified tuberculosis (TB) case finding. Further research needs to investigate the yield of TB in sputum samples induced by the HPN.

Earlier HIV diagnosis--are mobile services the answer?

OBJECTIVES: To assess the age and gender differences of clients accessing mobile HIV counselling and testing (HCT) compared with clients accessing facility-based testing, and to determine the difference in HIV prevalence and baseline CD4 counts. METHODS: This was a prospective observational cross-sectional study of 3 different HIV testing services in Cape Town. We compared data on age, sex, HIV status and CD4 counts collected between August and December 2008 from a mobile testing service (known as the Tutu Tester), a primary health care clinic, and a district hospital. RESULTS: A total of 3 820 individuals were tested: 2 499 at the mobile, 657 at the clinic, and 664 at the hospital. Age and sex distribution differed across services, with the mobile testing more men and older individuals. HIV prevalence was lowest at the mobile (5.9%) compared with the clinic (18.0%) and hospital (23.3%). Of the HIV-infected individuals from the mobile service, 75% had a CD4 count higher than 350 cells/µl compared with 48% and 32% respectively at the clinic and hospital. Age- and sex-adjusted risk for HIV positivity was 3.5 and 4.9 times higher in the clinic-based and hospital-based services compared with the mobile service. CONCLUSION: Mobile services are accessed by a different population compared with facility-based services. Mobile service clients were more likely to be male and less likely to be HIV-positive, and those infected presented with earlier disease.

Structure-activity relationships of tricyclic antidepressants and related compounds in the wing somatic mutation and recombination test of Drosophila melanogaster.

Four antidepressants and one neuroleptic drug were tested for genotoxicity using the somatic mutation and recombination test (SMART) in wing cells of Drosophila melanogaster. Three-day-old larvae trans-heterozygous for two linked recessive wing hair mutations (multiple wing hairs and flare) were fed the test compounds in water or solvents mixed with a standard dry food for 48 h. Wings of the emerging adult flies were scored for the presence of spots of mutant cells which can result from either somatic mutation or mitotic recombination. The tricyclic antidepressant clomipramine, which is closely related to imipramine (previously shown to be genotoxic in somatic cells of Drosophila), was clearly genotoxic at concentrations above 10 mM. The structurally related antidepressants lofepramine and mianserin were positive only at 100 mM which is the maximum tolerated dose. The antidepressant maprotiline and the antipsychotic chlorpromazine, which are distinguished from the other compounds by a 6-membered central ring instead of a 7-membered one, were not genotoxic in the same dose range. These results lend further support for the hypothesis that an N atom in the heterocyclic 7-membered ring of the tricyclic molecule is responsible for the genotoxic property of the compounds in Drosophila.

Improved high bioactivation cross for the wing somatic mutation and recombination test in Drosophila melanogaster.

The two tester strains of the high bioactivation (HB) cross for the wing somatic mutation and recombination test (SMART) in Drosophila melanogaster developed by Frölich and Würgler possess high metabolic capacity to activate promutagens. These strains contain chromosomes 1 and 2 of the DDT-resistant stock Oregon R(R) which exhibits a high constitutive level of cytochrome P450. However, they show several disadvantages for routine application, such as disturbed wing hair patterns in certain areas of the wing, making spot classification difficult, and a delay in development of the larvae. We have established and evaluated an improved HB cross (ORR; flr3 females and mwh males) producing ORR heterozygous individuals. These develop normally and have a normal, undisturbed wing hair pattern while exhibiting high bioactivation. The hybrid larvae of the improved HB cross show P450-dependent bioactivation capacity equal to or even slightly higher than those of the original HB cross. This was demonstrated by measuring the genotoxic activity of the promutagens diethylnitrosamine, 7,12-dimethylbenz[a]anthracene, N-nitrosopyrrolidine, and urethane. In addition, the improved HB cross has a sensitivity to the direct-acting alkylating agent ethyl nitrosourea equal to that of the standard cross. The main advantage of the improved HB cross is to combine the high bioactivation capacity with the ease of scoring the wings using the same criteria as for the standard cross.

Genotoxicity evaluation of five tricyclic antidepressants in the wing somatic mutation and recombination test in Drosophila melanogaster.

Five tricyclic antidepressants were tested for genotoxicity using the somatic mutation and recombination test (SMART) in wing cells of Drosophila melanogaster. Three-day-old larvae trans-heterozygous for 2 linked recessive wing hair mutants (multiple wing hairs and flare) were fed the test compounds in water mixed with a standard dry food for 48 h. Wings of the emerging adult flies were scored for the presence of spots of mutant cells which can be the consequence of either somatic mutation or mitotic recombination. Desipramine and imipramine were clearly genotoxic at concentrations above 1 mM whereas amitriptyline, nortriptyline and protriptyline were not genotoxic at concentrations up to 100 mM. This seems to implicate the nitrogen atom at position 5 in the 7-membered ring of the tricyclic molecule as being responsible for the genotoxic property of the compounds in Drosophila.

Somatic mutation in the wings of Drosophila melanogaster females dysgenic due to P elements when reared at 29 degrees C.

The possibility of somatic mobilisation of P elements in Drosophila melanogaster was investigated. Flies, trans-heterozygous for the genetic markers mwh and flr3, were obtained by crossing males containing transposition-competent P elements with females having M cytotype. The hybrid dysgenic flies were reared at 29 degrees C and their wings examined for mutant clones. The frequency of mutant spots found on the wings of the female flies was significantly higher than that of female control flies. We postulate that this increase in frequency may be due to P element mobilisation at high temperature in the wing cells of dysgenic hybrids. This is in direct contrast to the large body of research which indicates that P-transposition-mediated mutation is restricted to the germline.

On the use of excision repair defective cells in the wing somatic mutation and recombination test in Drosophila melanogaster.

Ten chemical mutagens were tested in the wing somatic mutation and recombination test in Drosophila melanogaster. This assay makes use of genetic markers expressed on the wing of adult flies. Larvae which are trans-heterozygous for mwh (multiple wing hairs) and flr (flare) were fed with the compounds either acutely (2, 4, or 6 hr) or chronically (48 or 72 hr), or were treated by inhalation (1 hr). Genetic changes induced in the somatic cells of the wing imaginal discs lead to the formation of mutant clones on the wing (mwh and/or flr). Single spots are produced by point mutation, chromosome breakage, and mitotic recombination; twin spots are produced exclusively by mitotic recombination. All 10 mutagens belonging to different chemical classes were clearly positive in this assay. However, the choice of the optimal treatment conditions (concentration of compound, duration of treatment, age of larvae at treatment) is essential. Eight of the compounds were also tested in excision repair defective cells by introducing the mei-9L1 mutation into the test system. This seems not to improve the detection capacity of the assay, mainly because only small spots are found in excision repair defective wings. In addition, the frequencies of spots in these wings are enhanced four to five times, which makes the scoring more tedious. For these and other practical reasons the use of this specific cross is not recommended in the wing spot test for routine screening purposes.