Acceptability of the female condom in Zimbabwe: Positive but male-centred responses

An acceptability study of the female condom was carried out in Zimbabwe among sex workers (89), urban women attending a family planning clinic in Harare (84), and rural women (23). Their main reason for trying this new method was as protection from sexually transmitted infections, including HIV. Over 50 per cent of the women in all three groups said that they and their partners liked the condom very much and preferred it to the male condom. Less than 10 per cent did not like it. The main problems were with the inner ring and too much lubrication, but questions remain on sustainability, and cost is a major obstacle. Further, even though it did not interfere with the women's sexual pleasure, most of the reasons for liking the method were male-centred.     

The utility of preoperative serum thyroid-stimulating hormone level for predicting malignant nodular thyroid disease

Introduction

The aim of this study was to assess whether serum thyroid-stimulating hormone (TSH) levels are of value in predicting malignancy in patients with nodular thyroid disease (NTD).

Methods

Patients with NTD and a preoperative TSH level who underwent thyroidectomy between 1990 and 2008 were identified from a prospective database. Age, sex, TSH concentration, nodule size, and pathology were evaluated. Logistic regression analysis was used to determine which factors were predictive of malignancy.

Results

Six hundred fifty-three patients were analyzed. The overall rate of malignancy was 20%; the rate was highest in patients <30 years (32%). The mean TSH level was higher in the malignant group (5.5 μIU/mL vs 1.4 μIU/mL, P < .0001). The rate of malignancy was 65% in patients with TSH levels >5.5 μIU/mL. Logistic regression analysis revealed that TSH level was the only significant risk factor for malignancy.

Conclusion

The serum TSH level may be useful in predicting the probability of cancer and optimizing the extent of thyroidectomy in patients with NTD.     

Small cell lung carcinomas express shared and private tumor antigens presented by HLA-A1 or HLA-A2.

Tumor-derived peptides presented by MHC class I molecules are targets for tumor rejection by CD8+ CTLs. MHC-restricted CD8+ CTLs are required also for the identification and characterization of tumor antigens that will be useful for immune therapy. For many human solid tumors, however, tumor antigens remain undefined because of the difficulty of generating MHC-restricted, tumor-specific CTLs required for their analysis. CD8+ CTL responses are modulated by CD4+ helper T cells and by antigen-presenting cells. In this study, highly purified CD8+ T cells were mixed with tumor cells in primary cultures in the absence of any other cells to reduce the complexity of CTL generation. Tumor cells were transfected with HLA-A1 or HLA-A2 and used to stimulate partly matched HLA-A1- or HLA-A2-positive CD8+ T cells. Partial MHC class I matching of tumor and CD8+ T cells and omission of other cells in primary culture was highly effective in generating MHC class I-restricted CTL to poorly immunogenic small cell lung carcinomas (SCLCs). Cytotoxicity was further enhanced by cotransfection of tumor cells with B7.1 (CD80). ICAM-1 (CD54) was not as effective as costimulation. SCLC cells presented tumor-specific peptides with HLA-A1 and HLA-A2 and were lysed by A1- or A2-restricted CD8+ CTLs. A1- and A2-restricted CD8+ CTLs detected shared tumor antigens on unrelated SCLC tumor lines in addition to private antigens. The use of direct antigen presentation by MHC class I-transfected tumors to MHC class I-matched CD8+ T cells is an effective way to generate MHC class I-restricted CTLs toward poorly immunogenic tumors in vitro, permitting the molecular identification of their tumor antigens.     

Marijuana use and its association with adherence to antiretroviral therapy among HIV-infected persons with moderate to severe nausea

BACKGROUND: Adherence to antiretroviral therapy (ART) is essential to successful treatment of HIV infection. Two recent studies reported a negative correlation between marijuana use and adherence to ART. Some patients, however, report that smoking marijuana improves adherence to ART. This study therefore sought to identify which subgroups of patients may have differential adherence to ART in association with recent marijuana use. METHODS: Cross-sectional survey design within a public health care system for HIV/AIDS. RESULTS: With a 5% refusal rate, 252 patients completed the interview, 175 (69%) were on ART, and 168 (67%) provided ART adherence data. Forty-one subjects (24%), predominantly whites, used marijuana. In bivariate analysis, no association between ART adherence and marijuana use was found (odds ratio [OR] = 0.92, 95% CI = 0.4-1.9). Adherence was positively associated with undetectable plasma virus and negatively associated with alcohol and other illicit drug use. Examining subgroups of patients, among those with nausea, marijuana users were more likely to show an association with adherence than nonusers (OR = 3.3), while among those without nausea, marijuana use was lower associated with adherence (OR = 0.52, P for homogeneity 0.02). This relationship was confirmed in multivariate analyses controlling for the interactions between nausea and marijuana use, in which other illicit drug use remained a factor related to nonadherence. DISCUSSION: These data suggest that medicinal use of marijuana may facilitate, rather than impede, ART adherence for patients with nausea, in contrast to the use of other illicit substances, which were associated with lower rates of ART adherence. To demonstrate any causal relationship between marijuana and adherence would require a longitudinal or controlled study.     

Pathogenesis of a Pichinde Virus Strain Adapted to Produce Lethal Infections in Guinea Pigs

A model for studying the pathogenesis of virulent arenavirus infection was developed by adapting Pichinde virus to produce lethal infections of inbred guinea pigs. This adapted Pichinde virus retained low virulence for primates, thus potentially reducing the biohazard to investigators. Whereas all inbred (strain 13) guinea pigs were infected and killed by 3 plaque-forming units or more of adapted Pichinde virus injected subcutaneously, outbred (Hartley strain) guinea pigs were relatively resistant. All infected, inbred guinea pigs died at 13 to 19 days after inoculation, with viremias in excess of 5 log₁₀ plaque-forming units/ml, severe lymphopenia (<1,000/mm³), and elevated serum glutamic oxaloacetic acid transaminase levels. Immunofluorescent antibody examination of tissues and infectivity titrations of tissue homogenates obtained at 3- to 4-day intervals demonstrated significant viral replication in all visceral tissues examined, but not in brain. Livers of all moribund guinea pigs contained moderate to severe hepatocellular necrosis and diffuse fatty change. Splenic red pulp and adrenal cortical tissues were engorged with blood and contained necrotic foci. Pancreatic acinar tissues were atrophied and vacuolated; lung sections typically contained areas of moderate to severe interstitial pneumonia. Inflammatory cells were conspicuously absent from all lesions. The virological and pathological features of adapted Pichinde infection in guinea pigs are remarkably similar to those described for Lassa virus infections in rhesus monkeys and humans, suggesting that this model might provide insight into the pathogenesis and treatment of Lassa fever in humans.     

Report of sexually transmitted diseases by HIV infected men during follow up: time to target the HIV infected?

OBJECTIVES: To compare the rate of self reported sexually transmitted diseases (STDs) among HIV infected men with men who remained HIV negative during follow up of a Harare male factory cohort. METHODS: Male factory workers were offered enrolment and behavioural data were collected at entry then every 6 months, along with HIV testing. Self report of STDs was used to calculate incidence per 100 person years. Cox proportional hazards models examined independent risk factors for STDs, with hazard ratios (HRs). RESULTS: At entry 20% of men were HIV infected and 11% reported STDs in the previous year. A total of 2777 (82%) of 3383 men enrolled were followed at least once. Compared with men who remained HIV negative, seroconverters had the highest incidence of STDs (16.8 per 100 person years; IRR = 3.3, 95% CI = 2.5-4.3); men enrolled HIV positive also reported higher STD incidence (14.5 per 100 person years, IRR = 2.8; 95% CI 2.3-5.5). Among HIV positive men, the only independent risk factor for report of urethral discharge was history of multiple partners (HR = 10, 95% CI 1.4-73.2). CONCLUSION: HIV positive men reported threefold higher incidence of STDs than HIV negative men, many related to high risk sexual behaviour.     

Syphilis serology and HIV infection in Harare, Zimbabwe

OBJECTIVE: To determine the reliability of serological tests in detecting syphilis in a factory worker cohort and examine the impact of concurrent HIV infection on serological tests for syphilis. METHOD: Reactions to non-treponemal and treponemal antigens were tested using sera from a cohort of 3401 factory workers in Harare, Zimbabwe. The participants consented to regular testing for syphilis, by VDRL, and HIV using two ELISAs. All sera from men who were VDRL positive, and a random sample of VDRL negative sera, were tested by RPR, TPHA, and where appropriate FTA-Abs. From the results, men were defined as having no syphilis, active syphilis, incident syphilis, historic syphilis, or giving biological false positive reactions. RESULTS: 709 sera were examined from 580 men. There were 78 cases of active syphilis in the cohort, giving a prevalence of 2.3%, and the seroincidence was 0.25 per 100 person years of follow up. The prevalence of HIV in the cohort was 19.8%. There was a strong association between syphilis, whether active, incident or historic, and HIV seropositivity. With both HIV positive and negative sera the negative predictive values of VDRL and RPR were > 99.9% while the positive predictive value for VDRL (30%) was lower than for RPR (39%). Biological false positive reactions were detected in 0.5% of the cohort, with in most cases a transient rise in VDRL titres up to < 1/16. Higher false positive titres occurred in five men, each of whom was HIV positive. CONCLUSIONS: The VDRL is reliable in detecting possible cases of syphilis even in a community with a high prevalence of heterosexually transmitted HIV. There is need, however, for confirmatory tests. The prevalence of syphilis in this cohort is very low in comparison with other countries in southern Africa, but is consistent with recent data from Harare. Despite a strong association between syphilis and HIV it was clear that syphilis could not be counted as a major factor fueling the HIV epidemic in Zimbabwe.     

Geographic differences in antimalarial drug efficacy in Uganda are explained by differences in endemicity and not by known molecular markers of drug resistance

BACKGROUND: Recent clinical trials from Uganda have shown that the risk of failure following antimalarial therapy varies geographically. We tested the hypothesis that geographic differences in the response to therapy could be explained by differences in the prevalence of known molecular markers of drug resistance. METHODS: Samples from 2084 patients treated with chloroquine (CQ) plus sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) plus SP were tested for the presence of known molecular markers of resistance. Differences in the risk of treatment failure across 6 sites were compared, and age and complexity of infection were controlled for. RESULTS: The prevalence of molecular markers of drug resistance was high at all of the sites: 61%-91% of patients were infected with parasites containing the pfcrt Thr-76 mutation and dhfr/dhps quintuple mutation. The risk of treatment failure decreased with increasing transmission intensity for both CQ plus SP (73% to 19%) and AQ plus SP (38% to 2%). Restricting the analyses to patients infected with parasites containing all 6 mutations of interest did not affect these trends. CONCLUSIONS: The risk of treatment failure was inversely proportional to transmission intensity and was not explained by differences in molecular markers of antimalarial drug resistance. Our findings strongly suggest that geographic differences in response to antimalarial therapy in Uganda are primarily mediated by acquired immunity associated with malaria transmission intensity, rather than by parasite factors.