Occupational hazards of traditional healers: repeated unprotected blood exposures risk infectious disease transmission.

OBJECTIVE: Healers provide support for acute and chronic illnesses in rural Mozambique, such as socially acceptable traditional 'vaccinations' (subcutaneous cuts in the skin to rub herbs directly into the bloody lesion). We aimed to document the frequency of blood exposure by traditional practitioners in Mozambique. METHODS: We conducted surveys with a simple random sample of 236 traditional healers in Zambézia province. Chi-square and Wilcoxon rank-sum tests were used to compare 'injection' behaviours across districts. RESULTS: Healers treated a median of eight patients in the past month (IQR: 4-15). About 75% conducted 'injections'. These healers 'injected' a median of four patients (IQR: 1-8), used a new razor a median of three times (IQR: 1-8), and almost never used gloves. Lifetime blood exposures among those who provided 'injections' during treatments were estimated to be 1758 over a healer's career. CONCLUSION: The majority of healers are exposed repeatedly to patient blood. Given the high prevalence of HIV, hepatitis B and C virus, and other blood-borne agents, specific healer practices are an occupational hazard and reuse of razors is risky for their clients.

Engagement of Men in Antenatal Care Services: Increased HIV Testing and Treatment Uptake in a Community Participatory Action Program in Mozambique.

Uptake of HIV testing and antiretroviral therapy (ART) services during antenatal care (ANC) in rural Mozambique is disappointing. To nurture supportive male engagement in ANC services, we partnered with traditional birth attendants and trained a new type of male-to-male community health agent, "Male Champions", who focused on counseling male partners to create new, male-friendly community norms around engagement in spousal/partner pregnancies. We assessed ANC service uptake using a pre-post intervention design. The intervention was associated with increases in: (1) uptake of provider-initiated counseling and testing among pregnant woman (81 vs. 92 %; p < 0.001); (2) male engagement in ANC (5 vs. 34 %; p < 0.001); and (3) uptake of ART (8 vs. 19 %; p < 0.001). When men accepted HIV testing, rates of testing rose markedly among pregnant women. With the challenges in scale-up of Option B+ in sub-Saharan Africa, similar interventions may increase testing and treatment acceptability during pregnancy.

Implementation and Operational Research: Age Distribution and Determinants of Invasive Cervical Cancer in a "Screen-and-Treat" Program Integrated With HIV/AIDS Care in Zambia.

BACKGROUND: Cervical cancer screening efforts linked to HIV/AIDS care programs are being expanded across sub-Saharan Africa. Evidence on the age distribution and determinants of invasive cervical cancer (ICC) cases detected in such programs is limited. METHODS: We analyzed program operations data from the Cervical Cancer Prevention Program in Zambia, the largest public sector programs of its kind in sub-Saharan Africa. We examined age distribution patterns by HIV serostatus of histologically confirmed ICC cases and used multivariable logistic regression to evaluate independent risk factors for ICC among younger (≤35 years) and older (>35 years) women. RESULTS: Between January 2006 and April 2010, of 48,626 women undergoing screening, 571 (1.2%) were diagnosed with ICC, including 262 (46%) HIV seropositive (median age: 35 years), 131 (23%) HIV seronegative (median age: 40 years), and 178 (31%) of unknown HIV serostatus (median age: 38 years). Among younger (≤35 years) women, being HIV seropositive was associated with a 4-fold higher risk of ICC [adjusted odds ratio = 4.1 (95% confidence interval: 2.8, 5.9)] than being HIV seronegative. The risk of ICC increased with increasing age among HIV-seronegative women and women with unknown HIV serostatus, but among HIV-seropositive women, the risk peaked around age 35 and nonsignificantly declined with increasing ages. Other factors related to ICC included being married (vs. being unmarried/widowed) in both younger and older women, and with having 2+ (vs. ≤1) lifetime sexual partners among younger women. CONCLUSIONS: HIV infection seems to have increased the risk of cervical cancer among younger women in Zambia, pointing to the urgent need for expanding targeted screening interventions.

Increased systemic inflammation is associated with cardiac and vascular dysfunction over the first 12 weeks of antiretroviral therapy among undernourished, HIV-infected adults in Southern Africa.

INTRODUCTION: Persistent systemic inflammation is associated with mortality among undernourished, HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa, but the etiology of these deaths is not well understood. We hypothesized that greater systemic inflammation is accompanied by cardiovascular dysfunction over the first 12 weeks of ART. METHODS: In a prospective cohort of 33 undernourished (body mass index <18.5 kg/m2) Zambian adults starting ART, we measured C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 and CD14 at baseline and 12 weeks. An EndoPAT device measured the reactive hyperemia index (LnRHI; a measure of endothelial responsiveness), peripheral augmentation index (AI; a measure of arterial stiffness), and heart rate variability (HRV; a general marker of autonomic tone and cardiovascular health) at the same time points. We assessed paired changes in inflammation and cardiovascular parameters, and relationships independent of time point (adjusted for age, sex, and CD4+ T-cell count) using linear mixed models. RESULTS: Serum CRP decreased (median change -3.5 mg/l, p=0.02), as did TNF-α R1 (-0.31 ng/ml, p<0.01), over the first 12 weeks of ART. A reduction in TNF-α R1 over 12 weeks was associated with an increase in LnRHI (p=0.03), and a similar inverse relationship was observed for CRP and LnRHI (p=0.07). AI increased in the cohort as a whole over 12 weeks, and a reduction in sCD163 was associated with a rise in the AI score (p=0.04). In the pooled analysis of baseline and 12 week data, high CRP was associated with lower HRV parameters (RMSSD, p=0.01; triangular index, p<0.01), and higher TNF- α R1 accompanied lower HRV (RMSSD, p=0.07; triangular index, p=0.06). CONCLUSIONS: Persistent inflammation was associated with impaired cardiovascular health over the first 12 weeks of HIV treatment among undernourished adults in Africa, suggesting cardiac events may contribute to high mortality in this population.

Population-level scale-up of cervical cancer prevention services in a low-resource setting: development, implementation, and evaluation of the cervical cancer prevention program in Zambia.

BACKGROUND: Very few efforts have been undertaken to scale-up low-cost approaches to cervical cancer prevention in low-resource countries. METHODS: In a public sector cervical cancer prevention program in Zambia, nurses provided visual-inspection with acetic acid (VIA) and cryotherapy in clinics co-housed with HIV/AIDS programs, and referred women with complex lesions for histopathologic evaluation. Low-cost technological adaptations were deployed for improving VIA detection, facilitating expert physician opinion, and ensuring quality assurance. Key process and outcome indicators were derived by analyzing electronic medical records to evaluate program expansion efforts. FINDINGS: Between 2006-2013, screening services were expanded from 2 to 12 clinics in Lusaka, the most-populous province in Zambia, through which 102,942 women were screened. The majority (71.7%) were in the target age-range of 25-49 years; 28% were HIV-positive. Out of 101,867 with evaluable data, 20,419 (20%) were VIA positive, of whom 11,508 (56.4%) were treated with cryotherapy, and 8,911 (43.6%) were referred for histopathologic evaluation. Most women (87%, 86,301 of 98,961 evaluable) received same-day services (including 5% undergoing same-visit cryotherapy and 82% screening VIA-negative). The proportion of women with cervical intraepithelial neoplasia grade 2 and worse (CIN2+) among those referred for histopathologic evaluation was 44.1% (1,735/3,938 with histopathology results). Detection rates for CIN2+ and invasive cervical cancer were 17 and 7 per 1,000 women screened, respectively. Women with HIV were more likely to screen positive, to be referred for histopathologic evaluation, and to have cervical precancer and cancer than HIV-negative women. INTERPRETATION: We creatively disrupted the 'no screening' status quo prevailing in Zambia and addressed the heavy burden of cervical disease among previously unscreened women by establishing and scaling-up public-sector screening and treatment services at a population level. Key determinants for successful expansion included leveraging HIV/AIDS program investments, and context-specific information technology applications for quality assurance and filling human resource gaps.

A 12 week longitudinal study of microbial translocation and systemic inflammation in undernourished HIV-infected Zambians initiating antiretroviral therapy.

BACKGROUND: Undernourished, HIV-infected adults in sub-Saharan Africa have high levels of systemic inflammation, which is a risk factor for mortality and other adverse health outcomes. We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses and mucosal integrity, contributes to heightened systemic inflammation in this population, and reductions in inflammation on antiretroviral therapy (ART) accompany reductions in translocation. METHODS: HIV-infected, Zambian adults with a body mass index <18.5 kg/m2 were recruited for a pilot study to assess the relationships between microbial translocation and systemic inflammation over the first 12 weeks of ART. To assess microbial translocation we measured serum lipopolysaccharide binding protein (LBP), endotoxin core IgG and IgM, and soluble CD14, and to assess intestinal permeability we measured the urinary excretion of an oral lactulose dose normalized to urinary creatinine (Lac/Cr ratio). Linear mixed models were used to assess within-patient changes in these markers relative to serum C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 over 12 weeks, in addition to relationships between variables independent of time point and adjusted for age, sex, and CD4+ count. RESULTS: Thirty-three participants had data from recruitment and at 12 weeks: 55% were male, median age was 36 years, and median baseline CD4+ count was 224 cells/µl. Over the first 12 weeks of ART, there were significant decreases in serum levels of LBP (median change -8.7 µg/ml, p = 0.01), TNF-α receptor 1 (-0.31 ng/ml, p < 0.01), and CRP (-3.5 mg/l, p = 0.02). The change in soluble CD14 level over 12 weeks was positively associated with the change in CRP (p < 0.01) and soluble CD163 (p < 0.01). Pooling data at baseline and 12 weeks, serum LBP was positively associated with CRP (p = 0.01), while endotoxin core IgM was inversely associated with CRP (p = 0.01) and TNF-α receptor 1 (p = 0.04). The Lac/Cr ratio was not associated with any serum biomarkers. CONCLUSIONS: In undernourished HIV-infected adults in Zambia, biomarkers of increased microbial translocation are associated with high levels of systemic inflammation before and after initiation of ART, suggesting that impaired gut immune defenses contribute to innate immune activation in this population.

Community stigma endorsement and voluntary counseling and testing behavior and attitudes among female heads of household in Zambézia Province, Mozambique.

BACKGROUND: Some aspects of HIV-related stigma have been shown to be a barrier to HIV services uptake and adherence to antiretroviral treatment (ART). Distinguishing which domains of stigma impact HIV services uptake can enhance the efficacy and efficiency of stigma-reduction interventions. METHODS: The relationships between use of voluntary counseling and testing (VCT) services and two domains of community stigma identified through factor analysis, negative labeling/devaluation and social exclusion, were investigated among 3749 female heads of household. Data were from a general household survey conducted in rural Mozambique. Multivariable logistic regression outcomes were: lifetime VCT use, past-6-months VCT use and VCT endorsement. RESULTS: Thirteen percent (13%) of the participants reported lifetime VCT use, 10% reported past-6-months VCT use and 63% endorsed VCT. A 25-point decrease (from 50 to 25) in the score for negative labeling and devaluation stigma was associated with increased lifetime VCT use (adjusted OR: 1.6, 95% CI: 1.1-2.3) and past-6-months VCT use (adjusted OR: 1.6, 95% CI: 1.1-2.4). A decrease from 50 to 25-points in the score for social exclusion stigma was associated with 1.5 and 1.3-fold increase in odds for past-6-months VCT use and endorsing VCT use, respectively (p < 0.001 for both). Compared with never-testers, considerably high endorsement of VCT use was observed among testers who did not receive HIV test results (adjusted OR: 2.7, 95% CI: 1.6-4.6) and much higher among testers who received results (adjusted OR: 7.3, 95% CI: 4.9-11.0). Distance from health facilities was associated with lower VCT use, but not lower endorsement of VCT. CONCLUSIONS: VCT use and endorsement might differ by domains of stigma held by individuals in the community. Greater uptake and favorable disposition towards use of VCT services in rural settings might be achieved by addressing stigma via domain-specific interventions and by improving the proximity of services and the dissemination of HIV test results.

Utilization of cervical cancer screening services and trends in screening positivity rates in a 'screen-and-treat' program integrated with HIV/AIDS care in Zambia.

BACKGROUND: In the absence of stand-alone infrastructures for delivering cervical cancer screening services, efforts are underway in sub-Saharan Africa to dovetail screening with ongoing vertical health initiatives like HIV/AIDS care programs. Yet, evidence demonstrating the utilization of cervical cancer prevention services in such integrated programs by women of the general population is lacking. METHODS: We analyzed program operations data from the Cervical Cancer Prevention Program in Zambia (CCPPZ), the largest public sector programs of its kind in sub-Saharan Africa. We evaluated patterns of utilization of screening services by HIV serostatus, examined contemporaneous trends in screening outcomes, and used multivariable modeling to identify factors associated with screening test positivity. RESULTS: Between January 2006 and April 2011, CCPPZ services were utilized by 56,247 women who underwent cervical cancer screening with visual inspection with acetic acid (VIA), aided by digital cervicography. The proportion of women accessing these services who were HIV-seropositive declined from 54% to 23% between 2006-2010, which coincided with increasing proportions of HIV-seronegative women (from 22% to 38%) and women whose HIV serostatus was unknown (from 24% to 39%) (all p-for trend<0.001). The rates of VIA screening positivity declined from 47% to 17% during the same period (p-for trend <0.001), and this decline was consistent across all HIV serostatus categories. After adjusting for demographic and sexual/reproductive factors, HIV-seropositive women were more than twice as likely (Odds ratio 2.62, 95% CI 2.49, 2.76) to screen VIA-positive than HIV-seronegative women. CONCLUSIONS: This is the first 'real world' demonstration in a public sector implementation program in a sub-Saharan African setting that with successful program scale-up efforts, nurse-led cervical cancer screening programs targeting women with HIV can expand and serve all women, regardless of HIV serostatus. Screening program performance can improve with adequate emphasis on training, quality control, and telemedicine-support for nurse-providers in clinical decision making.

ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate for operable malignant gastrointestinal stromal tumor: monitoring with 18F-FDG PET and correlation with genotype and GLUT4 expression.

UNLABELLED: We investigated the correlation between metabolic response by (18)F-FDG PET and objective response, glucose transporter type 4 (GLUT4) expression, and KIT/PDGFRA mutation status in patients with gastrointestinal stromal tumor undergoing neoadjuvant imatinib mesylate therapy. METHODS: (18)F-FDG PET was performed at baseline, 1-7 d, and 4 or 8 wk after imatinib mesylate initiation. Best objective response was defined by version 1.0 of the Response Evaluation Criteria in Solid Tumors (RECIST). Mutational analysis and tumor GLUT4 expression by immunohistochemistry were done on tissue obtained at baseline or surgery. RESULTS: (18)F-FDG PET showed high baseline tumor glycolytic activity (mean SUV(max), 14.2; range, 1.3-53.2), decreasing after 1 wk of imatinib mesylate (mean, 5.5; range, -0.5-47.7, P < 0.001, n = 44), and again before surgery (mean, 3.0; range, -0.5-36.1, P < 0.001, n = 40). At week 1, there were 3 patients with complete metabolic response (CMR), 33 with partial metabolic response (PMR), 6 with stable metabolic disease (SMD), and 2 with progressive metabolic disease (PMD). Before surgery, there were 3 with CMR, 33 with PMR, 4 with SMD, and none with PMD. The best response according to RECIST was 2 with partial response, 36 with stable disease, and 1 with progressive disease (n = 39). Of the patients with a posttreatment decrease in GLUT4 expression, 1 had CMR, 15 had PMR, 2 had SMD, and 1 had PMD at week 1, whereas before surgery 1 patient had CMR, 16 had PMR, 2 had SMD, and none had PMD. Among 27 patients with KIT exon 11 mutations, 1 had CMR, 22 had PMR, 3 had SMD, and 1 had PMD at week 1, whereas 1 had CMR, 22 had PMR, 2 had SMD, and 2 were unknown before surgery; among 4 patients with a wild-type genotype, 2 had PMR and 2 SMD at week 1, whereas 1 had CMR, 2 had PMR, and 1 had SMD before surgery. CONCLUSION: After imatinib mesylate initiation, metabolic response by (18)F-FDG PET was documented earlier (1-7 d) and was of much greater magnitude (36/44) than that documented by RECIST (2/39). Immunohistochemistry data suggest that GLUT4 may play a role in (18)F-FDG uptake in gastrointestinal stromal tumor, GLUT4 levels decrease after imatinib mesylate therapy in most patients with PMR, and the biologic action of imatinib mesylate interacts with glycolysis and GLUT4 expression. A greater than 85% metabolic response was observed as early as days 1-7 in patients with exon 11 mutations.

Acceptability of cervical cancer screening in rural Mozambique.

In Zambézia province, Mozambique, cervical cancer (CC) screening was introduced to rural communities in 2010. Our study sought to determine whether women would accept screening via pelvic examination and visual inspection with acetic acid (VIA) at two clinical sites near the onset of a new CC screening program. A cross-sectional descriptive study of 101 women was undertaken in two rural communities in north-central Mozambique. We assessed a woman's willingness to be screened, knowledge about CC symptoms and treatment, and her recommendations for best methods to deliver information to other women. After the interview, we offered CC screening. Fully 86% of women accepted VIA screening when it was offered, but uptake was 100% at one clinic and only 68% at another. The cause of CC was thought to be associated with promiscuous activity (49%) and curses placed on the woman (42%). All women in one rural Mozambique clinic and two-thirds at a second clinic underwent CC screening. Knowledge about CC screening was significantly associated with uptake, suggesting educational campaigns need to be undertaken. However, educators need to be cautious about linking screening with high-risk behaviors, as women who understood the link trended toward refusing screening.

National CT colonography trial (ACRIN 6664): comparison of three full-laxative bowel preparations in more than 2500 average-risk patients.

OBJECTIVE: The purpose of our study was to compare the effect of three different full-laxative bowel preparations on patient compliance, residual stool and fluid, reader confidence, and polyp detection at CT colonography (CTC). SUBJECTS AND METHODS: A total of 2531 patients underwent CTC followed by colonoscopy for the American College of Radiology Imaging Network (ACRIN) National CTC Trial. Of this total, 2525 patients used one of three bowel preparations with bisacodyl tablets and stool and fluid tagging: 4 L of polyethylene glycol (PEG); 90 mL of phosphosoda; or 300 mL of magnesium citrate. Patients reported percent compliance with the bowel preparation and radiologists graded each CTC examination for the amount of residual fluid and stool on a scale from 1 (none) to 4 (nondiagnostic). Reader confidence for true-positive findings was reported on a 5-point scale: 1 (low) to 5 (high). Sensitivity and specificity for detecting polyps ≥ 6 mm and ≥ 1 cm compared with colonoscopy were calculated for each preparation. RESULTS: The most commonly prescribed preparation was phosphosoda (n = 1403) followed by PEG (n = 1020) and magnesium citrate (n = 102). Phosphosoda had the highest patient compliance (p = 0.01), least residual stool (p < 0.001), and highest reader confidence versus PEG for examinations with polyps (p = 0.06). Magnesium citrate had significantly more residual fluid compared with PEG and phosphosoda (p = 0.006). The sensitivity and specificity for detecting colon polyps ≥ 6 mm and ≥ 1 cm did not differ significantly between preparations. CONCLUSION: Polyp detection was comparable for all three preparations, although phosphosoda had significantly higher patient compliance and the least residual stool.

ACRIN CT colonography trial: does reader's preference for primary two-dimensional versus primary three-dimensional interpretation affect performance?

PURPOSE: To determine whether the reader's preference for a primary two-dimensional (2D) or three-dimensional (3D) computed tomographic (CT) colonographic interpretation method affects performance when using each technique. MATERIALS AND METHODS: In this institutional review board-approved, HIPAA-compliant study, images from 2531 CT colonographic examinations were interpreted by 15 trained radiologists by using colonoscopy as a reference standard. Through a survey at study start, study end, and 6-month intervals, readers were asked whether their interpretive preference in clinical practice was to perform a primary 2D, primary 3D, or both 2D and 3D interpretation. Readers were randomly assigned a primary interpretation method (2D or 3D) for each CT colonographic examination. Sensitivity and specificity of each method (primary 2D or 3D), for detecting polyps of 10 mm or larger and 6 mm or larger, based on interpretive preference were estimated by using resampling methods. RESULTS: Little change was observed in readers' preferences when comparing them at study start and study end, respectively, as follows: primary 2D (eight and seven readers), primary 3D (one and two readers), and both 2D and 3D (six and six readers). Sensitivity and specificity, respectively, for identifying examinations with polyps of 10 mm or larger for readers with a primary 2D preference (n = 1128 examinations) were 0.84 and 0.86, which was not significantly different from 0.84 and 0.83 for readers who preferred 2D and 3D (n = 1025 examinations) or from 0.76 and 0.82 for readers with a primary 3D preference (n = 378 examinations). When performance by using the assigned 2D or 3D method was evaluated on the basis of 2D or 3D preference, there was no difference among those readers by using their preferred versus not preferred method of interpretation. Similarly, no significant difference among readers or preferences was seen when performance was evaluated for detection of polyps of 6 mm or larger. CONCLUSION: The reader's preference for interpretive method had no effect on CT colonographic performance.