Perceptions of cancer in developing countries.
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Developing Countries↗
Biomedical subjects
J Saba
Publications and source records attributed to J Saba.
Is there a difference in the efficacy of peripartum antiretroviral regimens in reducing mother-to-child transmission of HIV in Africa?
BACKGROUND: Peripartum antiretroviral regimens have been shown to prevent mother-to-child transmission of HIV (MTCT) in randomized clinical trials; however, direct comparison of published results is impossible given methodological and population differences. OBJECTIVE: To directly compare the efficacy of different antiretroviral regimens in reducing the risk of 6-week MTCT rate in African breastfeeding populations. METHODS: Pooled analysis including all mother-infant pairs from any relevant trial: West African ZDV-placebo trials, Petra ZDV+3TC [two regimens A (pre/intra/post-partum) and B (intra/post-partum), placebo from Uganda and Tanzania], SAINT (NVP and Petra arm B), HIVNET012 (NVP, ultra short ZDV pp) and the Vitamin A trial (as placebo arm in South Africa). Peripartum HIV infection was any positive RNA or DNA polymerase chain reaction test < day 60. The MTCT risk was estimated at 6 weeks for each treatment arm and compared with placebo or single-dose NVP using logistic regression adjusting for maternal CD4 cell count, breastfeeding and birthweight. RESULTS: Overall, 4125 singleton live-births were included; 3629 (88%) were assessed for HIV status at 6 weeks of age. In comparison with placebo, zidovudine + lamivudine (ZDV+3TC) arm A [adjusted odds ratio (AOR), 0.23; P < 0.0001], ZDV+3TC arm B (AOR, 0.49; P < 0.001), antenatal ZDV short (AOR, 0.55; P = 0.006) and nevirapine (NVP) (AOR, 0.60; P = 0.0007) significantly reduced MTCT. In comparison with NVP, only the longest regimen of ZDV+3TC (AOR, 0.39, P < 0.0005) was significantly more effective. CONCLUSION: These results are in line with current World Health Organisation guidelines suggesting equivalence of choice between single-dose NVP and short-course ZDV, and confirm the greater efficacy of ZDV+3TC than with any single antiretroviral drug.
Adult↗
Cost-effectiveness of the female condom in preventing HIV and STDs in commercial sex workers in rural South Africa.
We assessed the cost-effectiveness of the female condom (FC) in preventing HIV infection and other STDs among commercial sex workers (CSWs) and their clients in the Mpumulanga Province of South Africa. The health and economic outcomes of current levels of male condom (MC) use in 1000 CSWs who average 25 partners per year and have an HIV prevalence of 50.3% was compared with the expected outcomes resulting from the additional provision of FCs to these CSWs. A simulation model calculated health and public sector cost outcomes assuming 5 years of HIV infectivity, 1 month of syphilis and gonorrhea infectivity, and FC use in 12% of episodes of vaginal intercourse. Delayed infections and interactions between STDs and HIV were modeled. The simulation was extended to non-CSWs with as few as one casual partner per year. We conducted multiple sensitivity analyses. The program would distribute 6000 FCs annually at a cost of $4002 and would avert 5.9 HIV, 38 syphilis, and 33 gonorrhea cases. This would save the public sector health payer $12,090 in averted HIV/AIDS treatment costs, and $1,074 in averted syphilis and gonorrhea treatment costs for a net saving of $9163. Sensitivity analyses indicate that the economic findings are robust across a wide range of values for key inputs. The program generates net savings of $5421 if HIV prevalence in CSWs is 25% rather than 50.3% and savings of S3591 if each CSW has an average of 10 clients per year rather than 25. A program focusing on non-CSWs with only one casual partner would save $199. We conclude that a well-designed FC program oriented to CSWs and other women with casual partners is likely to be highly cost-effective and can save public sector health funds in rural South Africa.
Condoms↗
Acceptability of the female condom among sex workers in Thailand: results from a prospective study.
BACKGROUND: The female condom may provide women with the first female-controlled barrier method that is effective against sexually transmitted diseases, including HIV infection. GOAL: This study evaluated the acceptability of the female condom among sex workers in Thailand. STUDY DESIGN: Data on use and acceptability of the female condom were collected using a structured questionnaire during an 8-week follow-up. RESULTS: Analyses included 148 women who were still in follow-up at week 8. Sex workers used, on average, 2.8 female condoms per week. The overall satisfaction rate with the female condom was 68%, although, among users, 31% had difficulties in device insertion, 37% had pain from the inner ring, and 22% reported itching sensations. The main reason for using the female condom in the future was its perceived safety, and the main reason for not using it would be the client's refusal. CONCLUSION: Two-thirds of the sex workers were satisfied with the female condom. Difficulties at insertion, discomfort during use, and clients' attitude were potential obstacles to the use of the female condom in the future.
Adult↗
A high-performance liquid chromatographic method to measure sphingosine 1-phosphate and related compounds from sphingosine kinase assays and other biological samples.
Sphingosine 1-phosphate is an intermediate of sphingosine catabolism as well as a potent signaling compound. Conditions were established for the extraction and analysis of sphingosine 1-phosphate and other sphingoid base 1-phosphates from in vitro sphingosine kinase assays and other biological samples. The sphingoid base 1-phosphates were extracted in high yield (85%) using small C-18 reverse-phase columns (LiChroprep RP-18). After the extracts were treated with 0.1 N KOH to remove glycerolipids, the sphingoid base 1-phosphates were converted to fluorescent o-phthalaldehyde derivatives that were separated by HPLC using C-18 columns with a mobile phase of methanol:10 mM potassium phosphate (pH 7.2):1 M tetrabutylammonium dihydrogen phosphate (in water) (83:16:1, v/v/v). The o-phthalaldehyde derivative of sphingosine 1-phosphate was reasonably stable (t(1/2) > or = 18 h) when EDTA was present and could be detected in picomole amounts. The HPLC retention time of the sphingoid base 1-phosphates could be shifted by adjusting the mobile phase to pH 5.5, which is useful in separating overlapping compounds (such as sphingosine 1-phosphate and 4-D-hydroxysphinganine) and in confirming the identity of sphingoid base 1-phosphates in biological samples. The extraction procedure and HPLC method facilitated assays of sphingosine kinase with different sphingoid bases as substrates and/or inhibitors and enabled the quantitation of sphingoid base 1-phosphates in human plasma, serum, and platelets as well as in strains of Saccharomyces cerevisae with mutations in sphingolipid metabolism.
Blood Platelets↗
Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice.
Each year, an estimated 590,000 infants acquire human immunodeficiency virus type 1 (HIV) infection from their mothers, mostly in developing countries that are unable to implement interventions now standard in the industrialized world. In resource-poor settings, the HIV pandemic has eroded hard-won gains in infant and child survival. Recent clinical trial results from international settings suggest that short-course antiretroviral regimens could significantly reduce perinatal HIV transmission worldwide if research findings could be translated into practice. This article reviews current knowledge of mother-to-child HIV transmission in developing countries, summarizes key findings from the trials, outlines future research requirements, and describes public health challenges of implementing perinatal HIV prevention interventions in resource-poor settings. Public health efforts must also emphasize primary prevention strategies to reduce incident HIV infections among adolescents and women of childbearing age. Successful implementation of available perinatal HIV interventions could substantially improve global child survival.
Adolescent↗
Induction of human cytotoxic T lymphocytes that preferentially recognise tumour cells bearing a conformational p53 mutant.
The tumour-suppressor gene p53 is pivotal in the regulation of apoptosis, and point mutations within p53 are the commonest genetic alterations in human cancers. Cytotoxic T lymphocytes (CTL) recognise peptide-MHC complexes on the surface of tumour cells and bring about lysis. Therefore, p53-derived peptides are potential candidates for immunisation strategies designed to induce antitumour CTL in patients. Conformational changes in the p53 protein, generated as a result of point mutations, frequently expose the 240 epitope, RHSVV (amino acids 212-217), which may be processed differently from the wild-type protein resulting in an altered MHC-associated peptide repertoire recognised by tumour-specific CTL. In this study 42 peptides (37 overlapping nonameric peptides, from amino acids 193-237 and peptides 186-194, 187-197, 188-197, 263-272, 264-272, possessing binding motifs for HLA-A2) derived from the wild-type p53 protein sequence were assayed for their ability to stabilise HLA-A2 molecules in MHC class I stabilisation assays. Of the peptides tested, 24 stabilised HLA-A2 molecules with high affinity (fluorescence ratio >1.5) at 26 degrees C, and five (187-197, 193-200, 217-224, 263-272 and 264-272) also stabilised the complexes at 37 degrees C. Peptides 188-197, 196-203 and 217-225 have not previously been identified as binders of HLA-A2 molecules and, of these, peptide 217-225 stabilised HLA-A2 molecules with the highest fluorescence ratio. Peptide 217-225 was chosen to generate HLA-A2-restricted CTL in vitro; peptide 264-272 was used as a positive control. The two primary CTL thus generated (CTL-217 using peptide 217 225; and CTL-264 using peptide 264-272) were capable of specifically killing peptide-pulsed T2 or JY cells. In order to determine whether these peptides were endogenously processed and to test the hypothesis that mutants expressing different protein conformations would generate an alternative peptide repertoire at the cell surface, a panel of target cells was generated. HLA-A2+ SaOs-2 cells were transfected with p53 cDNA containing point mutations at either position 175 (R-->H) or 273 (R-->H) (SaOs-2/175 and SaOs-2/273). Two HLA-A2-negative cell lines, A431 and SKBr3, naturally expressing p53 mutations at positions 273 and 175 respectively, were transfected with a cDNA encoding HLA-A2. The results showed that primary CTL generated in response to both peptides were capable of killing SaOs-2/175 and SKBr3-A2 cells, which possess the same mutation, but not SaOs-2/273, A431-A2 or SKBr3 cells transfected with control vector. This suggests that these peptides are presented on the surface of SaOs-2/175 and SKBr3-A2 cells in a conformation-dependent manner and represent potentially useful target peptides for immunotherapy.
CD8-Positive T-Lymphocytes↗
[Assessment of quality of life after antireflux surgery].
AIM OF THE STUDY: To assess the quality of life (QoL) of patients operated for gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: This prospective study included 82 consecutive patients submitted to antireflux surgery between October 1998 and January 1999. A new questionnaire was used to assess their QoL: the Gastrointestinal Quality of Life Index (GIQLI) that includes 36 items concerning 5 dimensions: symptoms, vitality, emotions, social relations and medical treatment. The series consisted of 44 men and 38 women with a mean age of 47 years (range: 18-78). QoL was assessed before and 6 months after surgery; the follow-up rate was 94% (77/82). The pre- and postoperative GIQLI scores of the study group and the GIQLY score of a control group of 110 healthy patients were compared. RESULTS: Before surgery, the GIQLI score (90 +/- 23) was greatly impaired compared to the score (123 +/- 13) observed in the control group (p < 0.001). After surgery, the GIQLI score (110 +/- 23) increased significantly (p < 0.001), but remained statistically lower than the score of the control group (p < 0.001). The postoperative score recorded in the symptoms dimension was lower than the control group score: 55 +/- 11 versus 66 +/- 6 (p < 0.001), while no significant difference was observed in the other 4 dimensions. Univariate statistical analysis revealed that the postoperative GIQLI score (y) was correlated with the preoperative GIQLI score (x) according to the formula: y = 0.43 x + 71 (p < 0.001) and the sex of the patients, as the postoperative GIQLI score was higher in male patients (115 +/- 19) than in female patients (103 +/- 23) (p < 0.02). CONCLUSION: The QoL of the patients was greatly improved after antireflux surgery, but remained lower than that of a control group of healthy subjects. Better patient selection should improve the results. In our series, male patients or patients with a high preoperative GIQLI score were the best candidates for antireflux surgery.
Adolescent↗
Accumulation of phosphorylated sphingoid long chain bases results in cell growth inhibition in Saccharomyces cerevisiae.
Sphingolipid metabolites in mammals can function as signaling molecules with cell-specific functions. In Saccharomyces cerevisiae, phosphorylated long chain bases, such as dihydrosphingosine 1-phosphate and phytosphingosine 1-phosphate, have also been implicated in stress responses. To further explore the biological roles of these molecules, we created disruption mutants for LCB4, LCB5, DPL1, YSR2, YSR3, and SUR2. LCB4 and LCB5 encode kinases that phosphorylate long chain bases. DPL1 and YSR2/YSR3 are involved in degradation of the phosphorylated long chain bases. SUR2 catalyzes conversion of dihydrosphingosine to phytosphingosine. We adapted an HPLC method to measure intracellular concentrations of the phosphorylated long chain bases. Double mutants of dpl1 and ysr2 were inviable, whereas dpl1 ysr2 lcb4 triple mutants were viable. Further, growth inhibition associated with accumulated phosphorylated long chain bases was observed in the triple mutant dpl1 ysr2 lcb4 overexpressing LCB4 or LCB5. These results indicate that phosphorylated long chain bases can inhibit cell growth. Mutants defective in both YSR2 and SUR2, which accumulated dihydrosphingosine 1-phosphate only, grew poorly. The phenotypes of the ysr2 sur2 mutants were suppressed by overexpression of DPL1. Our results clearly show that elevated levels of phosphorylated long chain bases have an antiproliferative effect in yeast.
Fungal Proteins↗
Prevention of mother-to-child transmission of HIV in developing countries: recommendations for practice. The Ghent International Working Group on Mother-To-Child Transmission of HIV.
OBJECTIVES: Different approaches to prevent mother-to-child transmission of HIV are being evaluated in developing countries. The first trials using a short regimen of zidovudine have been successful in Thailand, Côte d'Ivoire and Burkina Faso. International and local strategies are now being considered. The Ghent International Working Group on Mother-to-Child Transmission of HIV developed public health policy options to integrate these interventions into basic and maternal and child health (MCH) services. METHODS: The following tasks were undertaken: a critical review of randomized trials; an international pooled analysis of late postnatal transmission of HIV through breastfeeding; a review of the cost-effectiveness and cost-benefit of antiretroviral prophylaxis; a feasibility assessment of preventive strategies, including a postal survey on HIV voluntary counselling and testing (VCT) of pregnant women; the identification of requirements and research priorities for prenatal, obstetric and paediatric care. These projects provided the background for a three-day workshop in Ghent, Belgium, in November 1997. Conclusions were further refined, based on 1998 research findings. RESULTS: A summary of relevant evidence and ten public health recommendations are reported. VCT for pregnant women, a short regimen of zidovudine together with alternatives to breastfeeding currently represent the best option to reduce vertical transmission in most developing countries. The primary goal of the integrated package supporting these interventions is to alleviate overall maternal and infant morbidity and mortality. CONCLUSION: Prevention of mother-to-child transmission of HIV should now be considered for integration into basic health and MCH services of selected countries, with the involvement of governments and donor agencies.
Anti-HIV Agents↗
Ambulatory care transitioning for the rural hospital.
As rural community hospitals continue their transition of health care delivery to predominantly outpatient and ambulatory services, many factors are being considered in design, planning, and operations to enact this change both efficiently and effectively. The following examines strategies that allow these changes to be incorporated successfully while maintaining the flexibility for the continued transition that these organizations will experience in the future.
Ambulatory Care Facilities↗
Protection against sexually transmitted diseases by granting sex workers in Thailand the choice of using the male or female condom: results from a randomized controlled trial.
BACKGROUND: The male condom is the most effective barrier method available for protection against sexually transmitted diseases (STDs), including HIV infection. There is an urgent need to develop and evaluate other prevention methods, such as the female condom. This study estimated the additional protection against STDs offered to sex workers by giving them the option of using the female condom when clients refused to use a male condom. METHODS: Sex establishments in four cities in Thailand were randomized into two study groups: one in which sex workers were instructed to use male condoms consistently (male condom group); and one in which sex workers had the option of using the female condom if clients refused or were not able to use male condoms (male/female condom group). Randomization was done by sex establishments, and not by individuals, to minimize sharing of female condoms across study groups. The proportion of unprotected sexual acts (defined as sexual acts in which condoms were not used, tore, or slipped in or out) and incidence rate of STDs (gonorrhoea, chlamydial infection, trichomoniasis and genital ulcer disease) were measured over a 24-week period and compared between the two study groups. FINDINGS: Results are available from 34 sex establishments (249 women) in the male/female condom group, and 37 sex establishments (255 women) in the male condom group. Condom use was very high in both groups (97.9 and 97.3 % of all sexual acts, respectively, P > 0.05). Male condom use was lower in the male/female condom group when compared with the male condom group (88.2 and 97.5%, respectively, P < 0.001). However, this reduction in male condom use was counterbalanced by the use of female condoms in 12.0% of all sexual acts in the male/female condom group, contributing to a 17% reduction in the proportion of unprotected sexual acts in this group when compared to the male condom group (5.9 versus 7.1%, respectively, P = 0.16). Female condom use was sustained over the entire study period. There was also a 24% reduction in the weighted geometric mean incidence rate of STDs in the sex establishments of the male/female condom group compared to the male condom group (2.81 versus 3.69 per 100 person-weeks, P = 0.18).
Adolescent↗
Cost-effectiveness of antiviral drug therapy to reduce mother-to-child HIV transmission in sub-Saharan Africa.
OBJECTIVE: To assess the potential cost-effectiveness of short-course antiviral regimens to prevent mother-to-child transmission (MCT) of HIV in sub-Saharan Africa. DESIGN: Cost-effectiveness analysis. METHODS: No intervention was compared with three regimens of twice daily zidovudine and lamivudine: regimen A, starting at 36 weeks of gestation and continuing to 1 week postpartum; regimen B, from intrapartum through 1 week postpartum; and regimen C, intrapartum only. Model inputs were estimated from published and unpublished data. Absolute percentage reductions in HIV transmission extrapolated from zidovudine monotherapy trials were estimated at 12.4, 8.6 and 4.3% for regimens A, B, and C, respectively. Outcome measures were net costs to the public sector health-care system, cost per infection averted, and cost per disability-adjusted life-year (DALY) gained. Multiple sensitivity analyses were conducted. RESULTS: Based on the hypothetical efficacy estimates, regimen C was the most cost-effective. For a cohort of 100 women with 15% HIV prevalence, net costs to the public sector health-care systems were estimated at US$3617 for regimen A, US$ 1667 for regimen B, and US$351 for regimen C. Regimen C had a cost of US$ 1129 per HIV infection averted and a cost of US$60 per DALY. Regimens B and A cost US$2680 and 5134 per infection averted and US$143 and 274 per DALY, respectively. Cost-effectiveness declined rapidly at efficacy below 10% or HIV prevalence below 7%. Results were very sensitive to antiviral drug costs. For example, at 20% of current prices, the cost per DALY for regimen A fell to US$64, and to about US$42 for regimens B and C. CONCLUSION: Antiviral therapy may be cost-effective compared with other health interventions if HIV prevalence is high, if clinical trials confirm estimated efficacies, and if drug prices are reduced.
Africa South of the Sahara↗
Preventing mother-infant transmission worldwide: what is needed? Interview with Joseph Saba, M.D. Interview by John S. James.
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Anti-HIV Agents↗
Recognition of melanoma-associated peptides by peripheral blood mononuclear cells of ocular melanoma patients.
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Alleles↗
Pharmacokinetics and antiretroviral activity of lamivudine alone or when coadministered with zidovudine in human immunodeficiency virus type 1-infected pregnant women and their offspring.
The safety, pharmacokinetics, and antiretroviral activity of lamivudine alone and in combination with zidovudine was studied in pregnant women infected with human immunodeficiency virus type 1 (HIV-1) and their neonates. Women received the drugs orally from week 38 of pregnancy to 1 week after delivery. Neonate therapy began 12 h after delivery and continued for 1 week. Both treatment regimens were well-tolerated in women and newborns. Lamivudine and zidovudine pharmacokinetics in pregnant women were similar to those in nonpregnant adults. Lamivudine and zidovudine freely crossed the placenta and were secreted in breast milk. Neonatal lamivudine clearance was about half that in pediatric patients; zidovudine clearance was consistent with previous reports. HIV-1 RNA could be quantified in 17 of the 20 women. At the onset of labor/delivery, mean virus load had decreased by approximately 1.5 log10 copies/mL in both treatment cohorts. Although not definitive for HIV-1 infection status, all neonates had HIV-1 RNA levels below the limit of quantification at birth and at ages 1 and 2 weeks.
Administration, Oral↗
Identification of HIV infection in pregnancy: another era.
In order to be successfully implemented, some interventions to prevent vertical transmission of human immunodeficiency virus (HIV) will require prior identification of HIV-infected women. The testing and counselling of pregnant women should therefore be promoted. Promoting testing and counselling within prenatal clinics would be a good strategy; however, additional data on the social and economic implications of HIV testing are needed to demonstrate the relevance of such a strategy. Promotion of testing and counselling should be developed in collaboration with community-based organizations, non-governmental organizations and people living with HIV, in order to increase the involvement and understanding of the community at large.
AIDS Serodiagnosis↗
Sexually transmitted disease prevalence in brothel-based commercial sex workers in Chiang Mai, Thailand: impact of the condom use campaign.
One hundred and ninety five (195) brothel-based commercial sex workers (CSW) in Chiang Mai, Thailand, were screened for sexually transmitted disease (STD) between October 1994 and April 1995, prior to their enrollment in a multi-center comparative trial of the effectiveness of two strategies using male and female condoms. These CSW had a mean age of 22.2 (SD 4.3) years. Forty-seven per cent were Thai and 57.4 per cent had no formal education. Median duration of prostitution was 16 months and median cost for sexual service was 50 baht (US$ 2) per client. Ninety-four per cent of CSW reported always using condoms with clients. There were 63 (32.3%) CSW infected with at least one type of the STD screened. The prevalence of STD included chlamydial infection (16.9%), gonococcal infection (14.4%), condyloma accuminata (4.6%), moluscum contagiosum (2.6%) and trichomoniasis (1.0%). There was no statistically significant risk factor for STD found in this study. Despite an active programme for prevention of STD in CSW and the provision of free condoms, STD were diagnosed in one-third of the screened CSW in Chiang Mai. The programme needs to be strengthened by more intensive education and practice in the correct and consistent use of condoms and integrated with other STD prevention programmes.
Adult↗