Monitoring trends in HIV prevalence among young people, aged 15 to 24 years, in Manicaland, Zimbabwe

BACKGROUND: In June 2001, the United Nations General Assembly Special Session (UNGASS) set a target of reducing HIV prevalence among young women and men, aged 15 to 24 years, by 25% in the worst-affected countries by 2005, and by 25% globally by 2010. We assessed progress toward this target in Manicaland, Zimbabwe, using repeated household-based population serosurvey data. We also validated the representativeness of surveillance data from young pregnant women, aged 15 to 24 years, attending antenatal care (ANC) clinics, which UNAIDS recommends for monitoring population HIV prevalence trends in this age group. Changes in socio-demographic characteristics and reported sexual behaviour are investigated. METHODS: Progress towards the UNGASS target was measured by calculating the proportional change in HIV prevalence among youth and young ANC attendees over three survey periods (round 1: 1998-2000; round 2: 2001-2003; and round 3: 2003-2005). The Z-score test was used to compare differences in trends between the two data sources. Characteristics of participants and trends in sexual risk behaviour were analyzed using Student's and two-tailed Z-score tests. RESULTS: HIV prevalence among youth in the general population declined by 50.7% (from 12.2% to 6.0%) from round 1 to 3. Intermediary trends showed a large decline from round 1 to 2 of 60.9% (from 12.2% to 4.8%), offset by an increase from round 2 to 3 of 26.0% (from 4.8% to 6.0%). Among young ANC attendees, the proportional decline in prevalence of 43.5% (from 17.9% to 10.1%) was similar to that in the population (test for differences in trend: p value = 0.488) although ANC data significantly underestimated the population prevalence decline from round 1 to 2 (test for difference in trend: p value = 0.003) and underestimated the increase from round 2 to 3 (test for difference in trend: p value = 0.012). Reductions in risk behaviour between rounds 1 and 2 may have been responsible for general population prevalence declines. CONCLUSIONS: In Manicaland, Zimbabwe, the 2005 UNGASS target to reduce HIV prevalence by 25% was achieved. However, most prevention gains occurred before 2003. ANC surveillance trends overall were an adequate indicator of trends in the population, although lags were observed. Behaviour data and socio-demographic characteristics of participants are needed to interpret ANC trends

Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours

BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users

Response rates for providing a blood specimen for HIV testing in a population-based survey of young adults in Zimbabwe

<p>Abstract</p> <p>Background</p> <p>To determine differences among persons who provided blood specimens for HIV testing compared with those who did not among those interviewed for the population-based Zimbabwe Young Adult Survey (YAS).</p> <p>Methods</p> <p>Chi-square analysis of weighted data to compare demographic and behavioral data of persons interviewed who provided specimens for anonymous testing with those who did not. Prevalence estimation to determine the impact if persons not providing specimens had higher prevalence rates than those who did.</p> <p>Results</p> <p>Comparing those who provided specimens with those who did not, there was no significant difference by age, residence, education, marital status, perceived risk, sexual experience or number of sex partners for women. A significant difference by sexual experience was found for men. Prevalence estimates did not change substantially when prevalence was assumed to be two times higher for persons not providing specimens.</p> <p>Conclusion</p> <p>When comparing persons who provided specimens for HIV testing with those who did not, few significant differences were found. If those who did not provide specimens had prevalence rates twice that of those who did, overall prevalence would not be substantially affected. Refusal to provide blood specimens does not appear to have contributed to an underestimation of HIV prevalence.</p

Non-functioning pituitary macroadenomas: factors affecting postoperative recurrence, and pre- and post-surgical endocrine and visual function

This is an accepted manuscript of a paper published by Springer on 06/04/2021, available online: https://doi.org/10.1007/s12020-021-02713-1 The accepted manuscript of the publication may differ from the final published version. For re-use please see the publisher's terms and conditions.Background: Non-functioning pituitary macroadenomas (NFPAs) with visual field defects are ideally managed by transsphenoidal tumour resection to improve vision, and long-term postsurgical follow up is necessary to monitor for tumour recurrence. Regular updates from global data are necessary for developing optimal management strategies of these tumours. Methods: Pre- and postoperative visual and endocrine profile, imaging characteristics and details of surgical interventions among patients with NFPAs managed between 2008 and 2019 in a UK regional centre were assessed. The radiological and surgical outcomes including postoperative complications, recurrence risk and the factors influencing outcomes also were assessed. Results: 105 cases with mean (SD) age 60.1 (14.3) years and follow-up duration 60 (37) months were studied. 67 (64%) patients were male. Five-year recurrence-free survival rate was 71.5% (95% confidence interval [CI] 62.7% to 81.6%) with 33 (31%) tumour recurrences of whom 20 (60%) received radiotherapy and 9 (27%) underwent further surgery. Younger age, tumour volume, and bilateral cavernous sinus extension were the predictors of recurrence on univariate analysis, while younger age was the only factor on multivariate analysis (Hazard ratio 0.95; 95% CI: 0.92, 0.97). 72/78 patients (92%) with preoperative visual field defects improved after surgery, of whom 27 (35%) had full recovery. 20 (24%) patients had recovery of an abnormal hormone axis. 15 patients (16%) developed perioperative complications such as cerebrospinal fluid leak (12 cases), meningitis (2 cases), and bleeding (2 cases). Conclusions: Five-year recurrence-free survival after transsphenoidal resection for NFPAs was 71.5% with older age at surgery conferring lower risk of recurrence. Visual recovery/ improvement occurred in 92% of cases with preoperative visual defects following surgery.Published versio

Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II) Protocol

<p>Abstract</p> <p>Background</p> <p>Within the spectrum of spontaneous intracerebral haemorrhage there are some patients with large or space occupying haemorrhage who require surgery for neurological deterioration and others with small haematomas who should be managed conservatively. There is equipoise about the management of patients between these two extremes. In particular there is some evidence that patients with lobar haematomas and no intraventricular haemorrhage might benefit from haematoma evacuation. The STICH II study will establish whether a policy of earlier surgical evacuation of the haematoma in selected patients will improve outcome compared to a policy of initial conservative treatment.</p> <p>Methods/Design</p> <p>an international multicentre randomised parallel group trial. Only patients for whom the treating neurosurgeon is in equipoise about the benefits of early craniotomy compared to initial conservative treatment are eligible. All patients must have a CT scan confirming spontaneous lobar intracerebral haemorrhage (≤1 cm from the cortex surface of the brain and 10-100 ml in volume). Any clotting or coagulation problems must be corrected and randomisation must take place within 48 hours of ictus. With 600 patients, the study will be able to demonstrate a 12% benefit from surgery (2p < 0.05) with 80% power.</p> <p>Stratified randomisation is undertaken using a central 24 hour randomisation service accessed by telephone or web. Patients randomised to early surgery should have the operation within 12 hours. Information about the status (Glasgow Coma Score and focal signs) of all patients through the first five days of their trial progress is also collected in addition to another CT scan at about five days (+/- 2 days). Outcome is measured at six months via a postal questionnaire to the patient. Primary outcome is death or severe disability defined using a prognosis based 8 point Glasgow Outcome Scale. Secondary outcomes include: Mortality, Rankin, Barthel, EuroQol, and Survival.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN22153967">ISRCTN22153967</a></p

Steep HIV prevalence declines among young people in selected Zambian communities: population-based observations (1995–2003)

BACKGROUND: Understanding the epidemiological HIV context is critical in building effective setting-specific preventive strategies. We examined HIV prevalence patterns in selected communities of men and women aged 15–59 years in Zambia. METHODS: Population-based HIV surveys in 1995 (n = 3158), 1999 (n = 3731) and 2003 (n = 4751) were conducted in selected communities using probability proportional to size stratified random-cluster sampling. Multivariate logistic regression and trend analyses were stratified by residence, sex and age group. Absence, <30% in men and <15% in women in all rounds, was the most important cause of non-response. Saliva was used for HIV testing, and refusal was <10%. RESULTS: Among rural groups aged 15–24 years, prevalence declined by 59.2% (15.7% to 6.4%, P < 0.001) in females and by 44.6% (5.6% to 3.1%, P < 0.001) in males. In age-group 15–49 years, declines were less than 25%. In the urban groups aged 15–24, prevalence declined by 47% (23.4% to 12.4%, P < 0.001) among females and 57.3% (7.5% to 3.2%, P = 0.001) among males but were 32% and 27% in men and women aged 15–49, respectively. Higher educated young people in 2003 had lower odds of infection than in 1995 in both urban [men: AOR 0.29(95%CI 0.14–0.60); women: AOR 0.38(95%CI 0.19–0.79)] and rural groups [men: AOR 0.16(95%CI 0.11–0.25), women: AOR 0.10(95%CI 0.01–7.34)]. Although higher mobility was associated with increased likelihood of infection in men overall, AOR, 1.71(95%CI 1.34–2.19), prevalence declined in mobile groups also (OR 0.52 95%CI 0.31–0.88). In parallel, urban young people with ≥11 school years were more likely to use condoms during the last casual sex (OR 2.96 95%CI 1.93–4.52) and report less number of casual sexual partners (AOR 0.33 95%CI 0.19–0.56) in the last twelve months than lower educated groups. CONCLUSION: Steep HIV prevalence declines in young people, suggesting continuing declining incidence, were masked by modest overall declines. The concentration of declines in higher educated groups suggests a plausible association with behavioural change

Blood cultures in ambulatory outpatients

BACKGROUND: Blood cultures are a gold standard specific test for diagnosing many infections. However, the low yield may limit their usefulness, particularly in low-risk populations. This study was conducted to assess the utility of blood cultures drawn from ambulatory outpatients. METHODS: Blood cultures drawn at community-based collection sites in the Calgary Health Region (population 1 million) in 2001 and 2002 were included in this study. These patients were analyzed by linkages to acute care health care databases for utilization of acute care facilities within 2 weeks of blood culture draw. RESULTS: 3102 sets of cultures were drawn from 1732 ambulatory outpatients (annual rate = 89.4 per 100,000 population). Significant isolates were identified from 73 (2.4%) sets of cultures from 51 patients, including Escherichia coli in 18 (35%) and seven (14%) each of Staphylococcus aureus and Streptococcus pneumoniae. Compared to patients with negative cultures, those with positive cultures were older (mean 49.6 vs. 40.1 years, p < 0.01), and more likely to subsequently receive care at a regional emergency department, outpatient antibiotic clinic, or hospital (35/51 vs. 296/1681, p < 0.0001). Of the 331 (19%) patients who received acute care treatment, those with positive cultures presented sooner after community culture draw (median 2 vs. 3 days, p < 0.01) and had longer median treatment duration (6 vs. 2 days, p < 0.01). CONCLUSION: Blood cultures drawn in outpatient settings are uncommonly positive, but may define patients for increased intensity of therapy. Strategies to reduce utilization without excluding patients with positive cultures need to be developed for this patient population

The incidence of HIV among women recruited during late pregnancy and followed up for six years after childbirth in Zimbabwe

<p>Abstract</p> <p>Background</p> <p>HIV incidence is a useful tool for improving the targeting of populations for interventions and assessing the effectiveness of prevention strategies. A study in Harare, Zimbabwe reported cumulative incidences of 3.4% (3.0-3.8) and 6.5% (5.7-7.4) among post-partum women followed for 12 and 24 months respectively between 1997 and 2001. According to a Government report on HIV the prevalence of HIV fell from about 30% in 1999 to 14% in 2008. The purpose of this study was to determine the incidence of HIV-1 among women enrolled during late pregnancy and followed for six years after childbirth and to identify risk factors associated with acquisition of HIV.</p> <p>Methods</p> <p>HIV-uninfected pregnant women around 36 weeks gestation were enrolled from primary health care clinics in peri-urban settlements around Harare and followed-up for up to six years after childbirth. At every visit a questionnaire was interview-administered to obtain socio-demographic data and sexual history since the previous visit. A genital examination was performed followed by the collection of biological samples.</p> <p>Results</p> <p>Of the 552 HIV-uninfected women 444 (80.4%) were seen at least twice during the six years follow-up and 39 acquired HIV, resulting in an incidence (95% CI) of 2.3/100 woman-years-at-risk (wyar) (1.1-4.1). The incidence over the first nine months post-partum was 5.7/100 wyar (3.3-8.1). A greater proportion of teenagers (15.3%) contributed to a high incidence rate of 2.9/100 (0.6-8.7) wyar. In multivariate analysis lower education of participant, RR 2.1 (1.1-4.3) remained significantly associated with HIV acquisition. Other risk factors associated with acquisition of HIV-1 in univariate analysis were young age at sexual debut, RR 2.3, (1.0-5.6) and having children with different fathers, RR 2.7(1.3-5.8). Women that knew that their partners had other sexual partners were about four times more likely to acquire HIV, RR 3.8 (1.3-11.2).</p> <p>Conclusion</p> <p>The incidence of HIV was high during the first nine months after childbirth. Time of seroconversion, age and educational level of seroconverter are important factors that must be considered when designing HIV intervention strategies.</p

Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS