Excluding pregnancy among women initiating antiretroviral therapy: efficacy of a family planning job aid

<p>Abstract</p> <p>Background</p> <p>Guidelines for initiating ART recommend pregnancy testing, typically a urine test, as part of the basic laboratory package. The principal reason for this recommendation is that Efavirenz, a first-line antiretroviral medication, has the potential of causing birth defects when used in the first trimester of pregnancy and is therefore contraindicated for use by pregnant women. Unfortunately, in many African countries pregnancy tests are not routinely provided or available in ART clinics, and, when available outside clinics, are often not affordable for clients.</p> <p>Recently, the World Health Organization added a family planning job aid called the 'pregnancy checklist,' developed by researchers at Family Health International, as a recommended tool for screening new ART clients to exclude pregnancy. Although the checklist has been validated for excluding pregnancy among family planning clients, there are no data on its efficacy among ART clients.</p> <p>This study was conducted to assess the clinical performance of a job aid to exclude pregnancy among HIV positive women initiating ART.</p> <p>Methods</p> <p>Non-menstruating women eligible for ART were enrolled from 20 sites in four provinces in Zambia. The pregnancy checklist was administered followed by a urine pregnancy test as a reference standard. Sensitivity, specificity, and positive and negative predictive values were estimated.</p> <p>Results</p> <p>Of the 200 women for whom the checklist ruled out pregnancy, 198 were not pregnant, for an estimated negative predictive value of 99%. The sensitivity of the checklist was 90.0%, and specificity was 38.7%. Among the women, 416 out of 534 (77.9%) did not abstain from sex since their last menses. Only 72 out of the 534 women (13.4%) reported using reliable contraception. Among the 416 women who did not abstain, 376 (90.4%) did not use reliable contraception.</p> <p>Conclusion</p> <p>The pregnancy checklist is effective for excluding pregnancy in many women initiating ART, but its moderate sensitivity and specificity precludes its use to completely replace pregnancy testing. Its use should be encouraged in low resource settings where pregnancy tests are unavailable or must be rationed. Family planning methods should be available and integrated into ART clinics.</p

Theoretical Model for Cellular Shapes Driven by Protrusive and Adhesive Forces

The forces that arise from the actin cytoskeleton play a crucial role in determining the cell shape. These include protrusive forces due to actin polymerization and adhesion to the external matrix. We present here a theoretical model for the cellular shapes resulting from the feedback between the membrane shape and the forces acting on the membrane, mediated by curvature-sensitive membrane complexes of a convex shape. In previous theoretical studies we have investigated the regimes of linear instability where spontaneous formation of cellular protrusions is initiated. Here we calculate the evolution of a two dimensional cell contour beyond the linear regime and determine the final steady-state shapes arising within the model. We find that shapes driven by adhesion or by actin polymerization (lamellipodia) have very different morphologies, as observed in cells. Furthermore, we find that as the strength of the protrusive forces diminish, the system approaches a stabilization of a periodic pattern of protrusions. This result can provide an explanation for a number of puzzling experimental observations regarding cellular shape dependence on the properties of the extra-cellular matrix

Effects of Transport Inhibitors on the Cellular Uptake of Carboxylated Polystyrene Nanoparticles in Different Cell Lines

Nanotechnology is expected to play a vital role in the rapidly developing field of nanomedicine, creating innovative solutions and therapies for currently untreatable diseases, and providing new tools for various biomedical applications, such as drug delivery and gene therapy. In order to optimize the efficacy of nanoparticle (NP) delivery to cells, it is necessary to understand the mechanisms by which NPs are internalized by cells, as this will likely determine their ultimate sub-cellular fate and localisation. Here we have used pharmacological inhibitors of some of the major endocytic pathways to investigate nanoparticle uptake mechanisms in a range of representative human cell lines, including HeLa (cervical cancer), A549 (lung carcinoma) and 1321N1 (brain astrocytoma). Chlorpromazine and genistein were used to inhibit clathrin and caveolin mediated endocytosis, respectively. Cytochalasin A and nocodazole were used to inhibit, respectively, the polymerisation of actin and microtubule cytoskeleton. Uptake experiments were performed systematically across the different cell lines, using carboxylated polystyrene NPs of 40 nm and 200 nm diameters, as model NPs of sizes comparable to typical endocytic cargoes. The results clearly indicated that, in all cases and cell types, NPs entered cells via active energy dependent processes. NP uptake in HeLa and 1321N1 cells was strongly affected by actin depolymerisation, while A549 cells showed a stronger inhibition of NP uptake (in comparison to the other cell types) after microtubule disruption and treatment with genistein. A strong reduction of NP uptake was observed after chlorpromazine treatment only in the case of 1321N1 cells. These outcomes suggested that the same NP might exploit different uptake mechanisms to enter different cell types

Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries

An integrative cell migration model incorporating focal adhesion (FA) dynamics, cytoskeleton and nucleus remodeling, actin motor activity, and lamellipodia protrusion is developed for predicting cell spreading and migration behaviors. This work is motivated by two experimental works: (1) cell migration on 2-D substrates under various fibronectin concentrations and (2) cell spreading on 2-D micropatterned geometries. These works suggest (1) cell migration speed takes a maximum at a particular ligand density (~1140 molecules/µm2) and (2) that strong traction forces at the corners of the patterns may exist due to combined effects exerted by actin stress fibers (SFs). The integrative model of this paper successfully reproduced these experimental results and indicates the mechanism of cell migration and spreading. In this paper, the mechanical structure of the cell is modeled as having two elastic membranes: an outer cell membrane and an inner nuclear membrane. The two elastic membranes are connected by SFs, which are extended from focal adhesions on the cortical surface to the nuclear membrane. In addition, the model also includes ventral SFs bridging two focal adhesions on the cell surface. The cell deforms and gains traction as transmembrane integrins distributed over the outer cell membrane bond to ligands on the ECM surface, activate SFs, and form focal adhesions. The relationship between the cell migration speed and fibronectin concentration agrees with existing experimental data for Chinese hamster ovary (CHO) cell migrations on fibronectin coated surfaces. In addition, the integrated model is validated by showing persistent high stress concentrations at sharp geometrically patterned edges. This model will be used as a predictive model to assist in design and data processing of upcoming microfluidic cell migration assays

Rabies trends and surveillance capabilities in Zambia

Tanzania Veterinary Journal, 2015; 30 (1): 21-32The main objective of this study was to assess the trends, distribution and positivity rate of rabies cases in Zambia. A retrospective study for the period of 10 years between 2004 and 2014, was conducted by using rabies case reports. The data were analyzed with descriptive statistics and geo- coded in Quantum Geographical Information System (QGIS) with the help of shape files. The geo- referenced data were then used to map the trend and spatial distribution of the disease on maps in a Geographical Information System (GIS) platform. The findings showed that 61.5% (462/751, 95% CI=57.9- 65.0) of the samples were positive. Canines accounted for 81.6% (95%, CI=77.7- 85) of the total positive samples followed by Bovines 9.1% (95%, CI= 6.7- 12.2). A mean monthly occurrence of canine rabies was 2.9. The average provincial positivity rate was 0.7. Positivity rates equal to or closer to one indicate poor surveillance; with rates equal to or closer to zero indicate good surveillance. One on one in-depth interview was conducted with one officer from each of these institutions i.e. The University of Zambia (UNZA), National Livestock and Epidemiological Information Center (NALEIC) and Central Veterinary Research Institute (CVRI) in order to familiarize with the current rabies surveillance systems in Zambia. The findings were that; sample submission is done by veterinarians and livestock officers and only UNZA and CVRI have capability for rabies diagnosis with NALEIC as a data storage institution. Rabies is endemic in Zambia and the dog is maintenance host for the disease in human and livestock populations. Therefore, controlling rabies in dogs indirectly overcomes the problem in human and livestock

Do peer educators make a difference? An evaluation of a youth-led HIV prevention model in Zambian schools

Restless Development's youth-led model places trained Volunteer Peer Educators (VPEs), aged 18-25 years, in schools to teach HIV prevention and reproductive health (RH). VPEs also run youth centers, extracurricular and community-based activities. This evaluation assesses (i) program effects on students' HIV/RH knowledge, attitudes and behaviors using a non-randomized quasi-experimental design among 2133 eighth and ninth grade students in 13 intervention versus 13 matched comparison schools and (ii) program costs. Intervention students had significantly higher levels of knowledge related to HIV [odds ratio (OR) 1.61, 95% confidence interval (CI) 1.18-2.19; P &lt; 0.01] and RH (OR 1.71; 95% CI 1.21-2.49; P &lt; 0.01), more positive attitudes toward people living with HIV and greater self-efficacy to refuse unwanted sex and access condoms. No evidence of differences in ever having had sex was found (28% in the intervention; 29% in the comparison schools). However, intervention students were more likely not to have had sex in the previous year (OR 1.26, 95% CI 1.03-1.56; P &lt; 0.05) and to have had only one sex partner ever (OR 1.43, 95% CI 1.00-2.03; P &lt; 0.05). The average annual cost of the program was US$21 per beneficiary. In conclusion, the youth-led model is associated with increased HIV and RH knowledge and self-efficacy and lowered levels of stigma and sexual risk-taking behaviors

Is single-dose NVP relevant in the era of more efficacious PMTCT regimens? Lessons from Zambia

For almost a decade, single-dose nevirapine (sdNVP) has been proven to be a safe and effective drug for the prevention of mother-to-child transmission (PMTCT) of HIV. With the advent of the use of more efficacious combination therapy strategy in reducing mother-to-child transmission, sdNVP has been relegated as a lower tier intervention. Availability of infrastructural capacity coupled with the practical reality that very few women attend an antenatal clinic more than once makes universal implementation of combination therapy a challenge. This retrospective review examined PMTCT programmatic indicators following the introduction of sdNVP at first contact in selected sites. Data from 79 PMTCT sites was reviewed from April 2006 to March 2007 (when sdNVP was offered only after 32 weeks) and compared to the period of April 2007–March 2008. In the pre-intervention period (April 2006–March 2007), the monthly average of pregnant women who received sdNVP per site was 5.02. Post-intervention (April 2007–March 2008), the monthly average increased by 59% to 7.97 (p-value&lt;0.05). In pre-intervention period when sdNVP was dispensed at 32 weeks, the average proportion of pregnant women who received antiretroviral prophylaxis was 59%. This increased to 82% after the intervention. Current systems for dispensing sdNVP may be used as a foundation for implementation of more efficacious PMTCT regimens. The sdNVP administered at first contact should be a safety net for women who are unable to receive more efficacious regimen

Infant feeding options, other nonchemoprophylactic factors, and mother-to-child transmission of HIV in Zambia

BACKGROUND: The role of antiretroviral drugs in the prevention of mother-to-child transmission (PMTCT) of HIV is well known. The objective of this study is to explore how nonchemoprophylactic factors, including infant feeding practices, mother's HIV status disclosure, mode and place of delivery, infant gender, and maternal age, are related to MTCT.METHODS: The study analyzed program data of DNA polymerase chain reaction (PCR) results from dried blood spot samples and selected client information from perinatally exposed infants aged 0 to 12 months.RESULTS: A total of 8237 samples were analyzed. In all, 84% of the mothers ever breast-fed their children. In instances where both mother and baby received intervention, the transmission rates of HIV were higher among those who are still breast-feeding after 6 to 12 months. Disclosure, location, and mode of delivery did not have an effect on the transmission rates of HIV when both mother and baby received prophylaxis.CONCLUSION: Nonchemoprophylaxis factors, especially breast-feeding, play a key role in perinatal transmission of HIV