Communication regarding routine childhood vaccination.

Vaccine hesitancy is an emerging problem in South Africa (SA), which threatens to erode the country's immunisation achievements. Communication interventions may be an effective strategy for addressing vaccine hesitancy. We highlight a Cochrane review of qualitative evidence that explored parents' views and experiences of communication regarding childhood vaccinations, and provide implications for practice that are relevant to the SA context. The findings suggest that healthcare providers (HCPs) play a central role in childhood vaccination attitudes and decision-making. Therefore, capacitating HCPs to promote vaccination with confidence is key to effective communication to address vaccine hesitancy in SA.

Human papillomavirus vaccination acceptance and hesitancy in South Africa: Research and policy agenda.

Cervical cancer is responsible for one-quarter of a million deaths per year worldwide. In South Africa (SA), cervical cancer is the leading cause of cancer deaths among women aged 15 - 44 years. Human papillomavirus (HPV) vaccines provide a safe and highly effective means to reduce the burden of cervical cancer. The World Health Organization initiated a plan for the elimination of cervical cancer; the programme's success relies on the introduction and high uptake of HPV vaccines globally. SA introduced a school-based HPV vaccination programme in 2014, but uptake is not as high as expected. Suboptimal HPV vaccination coverage may result from various factors, including vaccine hesitancy. Vaccine-hesitant parents may delay or refuse HPV vaccination for their daughters. Tailored interventions are needed to address this. However, knowledge regarding vaccine hesitancy and policies to address this hesitancy in SA are currently limited. While SA has taken commendable steps in cervical cancer prevention by implementing and financing the HPV vaccination programme, it is imperative that there are clear policies in place to help strengthen the programme. These policies need to clarify areas of uncertainty that may lead to mistrust, and pre-empt factors that will cause hesitancy. Equally important is that local research should be conducted to better understand HPV vaccination hesitancy and other determinants of uptake to further inform and shape national policies.

Need for a comprehensive, consistently applied national hepatitis B vaccination policy for healthcare workers in higher educational institutions: a case study from South Africa.

BACKGROUND: Hepatitis B virus (HBV) is transmitted by infected blood and other body fluids, placing healthcare workers (HCWs) and student HCWs at increased risk of HBV infection through occupational exposure. AIM: To establish the existence, content and implementation of hepatitis B (HB) vaccination policies for student HCWs being trained at higher educational institutions (HEIs) in South Africa. METHODS: Self-administered structured questionnaires were sent to 23 nursing colleges and 11 universities in South Africa that train doctors, nurses or dentists. FINDINGS: Twelve (35%) questionnaires were returned. Ten HEIs had a policy consisting mainly of recommendations given to students at registration. Nine HEIs made HB vaccinations available, with four HEIs covering the cost through student fees. Seven HEIs did not require a record of previous vaccination. Six HEIs did not accept non-responders (NRs), three HEIs would only accept an NR after receiving a second three-dose vaccination series and counselling, six HEIs regarded an HBV carrier as infectious, and 10 HEIs would accept HBV carriers as students. The low response rate makes it difficult to generalize the results, but may suggest a lack of an HB vaccination policy for student HCWs at non-responding HEIs. CONCLUSIONS: Policies of responding HEIs regarding HB vaccination, HBV carriage and response to HB vaccination were variable, sometimes inappropriate and not sufficiently comprehensive to protect student HCWs against occupationally acquired HBV. This emphasizes the need for a comprehensive, consistently applied, nationally coordinated vaccination policy to ensure that student HCWs receive proper protection against HBV infection.

Increased exposure to hepatitis B virus infection in HIV-positive South African antenatal women.

The prevalence of markers for hepatitis B virus (HBV) exposure and active infection in HIV-positive (n=710) and HIV-negative (n=710) pregnant South African women was investigated. The following statistically significant increases in the HIV-positive group were found: anti-hepatitis B core antigen (anti-HBc) (37.3% versus 28.6%; odds ratio [OR]: 1.49); anti-hepatitis B surface antigen (anti-HBs) (29.5% versus 20.1%; OR: 1.66); exposure based on hepatitis B surface antigen (HBsAg) and anti-HBc (39.2% versus 30.1%; OR: 1.49); and exposure based on anti-HBs, anti-HBc and HBsAg (37.1% versus 24.5%; OR: 1.82). However, there was no increase in active HBV infections, with 2.4% of the HIV positives and 2.2% of the HIV negatives being HBV DNA positive. Although the impact that HIV has had on the prevalence of HBV in this population group is not as pronounced as that found in areas of low endemicity (where up to seven-fold increases have been reported), there is a statistically significant increased exposure to HBV.

Hepatitis B virus and human immunodeficiency virus co-infection in sub-Saharan Africa: a call for further investigation.

A growing body of evidence indicates that human immunodeficiency virus (HIV)-positive individuals are more likely to be infected with hepatitis B virus (HBV) than HIV-negative individuals, possibly as a result of shared risk factors. There is also evidence that HIV-positive individuals who are subsequently infected with HBV are more likely to become HBV chronic carriers, have a high HBV replication rate, and remain hepatitis Be antigen positive for a much longer period. In addition, it is evident that immunosuppression brought about by HIV infection may cause reactivation or reinfection in those previously exposed to HBV. Furthermore, HIV infection exacerbates liver disease in HBV co-infected individuals, and there is an even greater risk of liver disease when HIV and HBV co-infected patients are treated with highly active anti-retroviral therapy (HAART). Complicating matters further, there have been several reports linking HIV infection to 'sero-silent' HBV infections, which presents serious problems for diagnosis, prevention, and control. In sub-Saharan Africa, where both HIV and HBV are endemic, little is known about the burden of co-infection and the interaction between these two viruses. This paper reviews studies that have investigated HIV and HBV co-infection in sub-Saharan Africa, against a backdrop of what is currently known about the interactions between these two viruses.

The first five years of universal hepatitis B vaccination in South Africa: evidence for elimination of HBsAg carriage in under 5-year-olds.

South Africa implemented a vaccine against hepatitis B virus (HBV) into the Expanded Programme on Immunisation (EPI) in April 1995. The HBV vaccine is given at 6, 10, and 14 weeks, in parallel with OPV, DTP and Hib vaccines. This study assessed the impact of universal childhood HBV vaccination programme in reducing HBsAg carriage, in the first five years (1995--1999) since its implementation. In parallel, we investigated the current burden of HBV infection in mothers of vaccinees and the adult general population. A total of 598 babies (mean age=23.3 months) who received 3 doses of 1.5 microg/0.5 ml Hepaccine-B (Cheil) were recruited from the Northern Province (one of the nine provinces in South Africa). HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe were tested using the IMx or Axsym kits (Abbott Laboratories). PCR assays were performed following established protocols. The overall seroprotection rate (i.e. anti-HBs titre> or =10 mIU/ml) was 86.8% (519/598) in vaccinated babies, while 13.2% had anti-HBs levels<10 mIU/ml. Seroprotection rates and geometric mean titres (GMT) decreased significantly with increasing age, possibly reflecting waning anti-HBs titre over time. Total HBV exposure (positive for either HBsAg, anti-HBs, or anti-HBc) was 31.0% (58/187) in mothers of vaccinees and 40% (72/180) in the adult general population. HBsAg carrier rate was virtually similar in both groups (3.2% in mothers of vaccinees vs. 3.3% in the general population). Against this background, no vaccine failures resulting in HBsAg and HBV DNA positivity were seen in vaccinated babies, including 6 babies born to HBsAg positive carrier mothers (one carrier mother was positive for HBeAg and HBV DNA). However, 0.9% (5/582) babies, aged between 8--11 months, tested positive for anti-HBc, all of whom had anti-HBs titres>10 mIU/ml and were negative for HBV DNA. Anti-HBc positivity was probably maternal in origin, or may represent sub-clinical averted HBV infections. It can be concluded that the HBV vaccine is highly effective within the framework of the South African EPI and already shows a positive impact in the elimination of HBsAg carrier rate in children<5 years.

Opaque2 modifiers alter transcription of the 27-kDa gamma-zein genes in maize.

Opaque2 modifier genes cause a two- to three-fold increase in the amount of gamma-zein RNA and protein in maize kernels, and can convert the soft, starchy endosperm of an opaque2 mutant to a hard, vitreous phenotype. We analyzed several aspects of transcriptional and post-transcriptional regulation of gamma-zein gene expression in wild-type, opaque2 and modified opaque2 genotypes to investigate the molecular mechanisms by which opaque2 modifiers influence the expression of gamma-zein genes. We found that the poly(A) tails of the gamma-zein RNAs A and B were of similar length in normal, opaque2 and modified opaque2 genotypes. Multiple poly(A) addition sites were detected for the gamma-zein A and B RNAs, but no evidence was obtained that o2 modifiers influence the selection of these sites. Nucleotide sequence analysis of gamma-zein A and B cDNAs derived from 18-DAP endosperm from normal, opaque2, and modified opaque2 kernels confirmed the use of eight different poly(A) addition sites for gamma-zein A transcripts and six different sites for the gamma-zein B transcripts. It also revealed that the A/B gamma-zein RNA ratio in modified opaque2 was at least 40:1, compared to 1:1 in wild type and 3:1 in opaque2. Nuclear run-on transcription assays showed a dramatic shift in the transcription rate of the gamma-zein A gene relative to the B gene in the modified opaque2 genotype. These results are consistent with a model in which the two opaque2 modifier loci influence gamma-zein gene expression through different mechanisms: one affects transcription of the gamma-zein locus and the other influences the steady state level of gamma-zein RNA.

The new lung cancer staging system: what does it mean?

Staging now provides the basis for any cancer treatment, determining prognosis and treatment and allowing for comparison of clinical outcomes. Changes in the lung cancer staging system have been implemented to represent our evolving knowledge and expanding diagnostic and therapeutic modalities. Current changes are designed to be minimally disruptive to historical staging systems, but new methods of treatment and better understanding of tumor biology may revolutionize our current staging classification in the future.

Implementation of a clinical pathway decreases length of stay and hospital charges for patients undergoing total colectomy and ileal pouch/anal anastomosis.

BACKGROUND: Clinical pathways are increasingly being used by hospitals to improve efficiency in the care of certain patient populations; however, little prospective data are available to support their use. This study examined whether using a clinical pathway for patients undergoing ileal pouch/anal anastomosis, a complex procedure in which we had extensive practical experience, affected hospital charges or length of stay (LOS). METHODS: A clinical pathway was developed to serve patients undergoing elective total colectomy and ileal pouch/anal anastomosis. All operations were performed by two attending physicians (J.E.F., M.S.N.). Before implementation, 10 pilot patients were prospectively monitored to ensure that hospital charges were accurately generated. In addition, charge audits were performed by an outside agency to verify the accuracy of the hospital bills. The pathway was then implemented, and 14 patients were prospectively analyzed. RESULTS: In all patients the principal diagnosis was ulcerative colitis, with the exception of three patients with familial polyposis. Mean external audit charges were within 2% of the hospital bills; therefore the hospital bills were used in all calculations. The mean LOS decreased from 10.3 days to 7.5 days (p = 0.046) for patients on the pathway versus pilot patients. Mean hospital charges also decreased significantly, from $21,650 to $17,958 per patient (p = 0.005). CONCLUSIONS: Implementation of a clinical pathway, even for an operation in which the surgeon has much experience, is an effective method for reducing LOS and charges for patients. This is likely the result of interdisciplinary cooperation, elimination of unnecessary interventions, and streamlined involvement of ancillary services. These results support the development of clinical pathways for procedures that involve routine preoperative and postoperative care. In addition, the benefits of clinical pathways should increase proportionally with increasing case volume for a particular procedure.

A maize cDNA encoding a member of the retinoblastoma protein family: involvement in endoreduplication.

Retinoblastoma (RB-1) is a tumor suppressor gene that encodes a 105-kDa nuclear phosphoprotein. To date, RB genes have been isolated only from metazoans. We have isolated a cDNA from maize endosperm whose predicted protein product (ZmRb) shows homology to the "pocket" A and B domains of the Rb protein family. We found ZmRb behaves as a pocket protein based on its ability to specifically interact with oncoproteins encoded by DNA tumor viruses (E7, T-Ag, E1A). ZmRb can interact in vitro and in vivo with the replication-associated protein, RepA, encoded by the wheat dwarf virus. The maize Rb-related protein undergoes changes in level and phosphorylation state concomitant with endoreduplication, and it is phosphorylated in vitro by an S-phase kinase from endoreduplicating endosperm cells. Together, our results suggest that ZmRb is a representative of the pocket protein family and may play a role in cell cycle progression. Moreover, certain plant monopartite geminiviruses may operate similarly to mammalian DNA viruses, by targeting and inactivating the retinoblastoma protein, which otherwise induces G1 arrest.

Mononuclear cell line THP-1 internalizes bactericidal/permeability-increasing protein by a non-receptor-mediated mechanism consistent with pinocytosis.

BACKGROUND: Bactericidal/permeability-increasing protein (BPI) binds lipopolysaccharide and neutralizes its toxic effects in vitro and in endotoxemic animals. Our recent work identified physiologically significant interactions between BPI, lipopolysaccharide, and mononuclear cells. OBJECTIVE: To determine whether the interaction between BPI and mononuclear cells is receptor mediated. DESIGN: Labeled BPI was incubated with THP-1 cells in the presence of up to 100-fold excess of unlabeled BPI. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting were performed to evaluate competitive binding and total uptake of BPI. Crosslinking was performed to determine whether BPI binds to a single protein entity. Acid washing experiments and flow cytometric analysis were performed to determine whether BPI remains on the cellular surface. Finally, flow cytometry analysis was used to determine whether BPI incubation with THP-1 cells affects the surface expression of the lipopolysaccharide-binding protein-lipopolysaccharide receptor CD14. RESULTS: Labeled BPI uptake was not inhibited by the presence of 100-fold excess of unlabeled BPI at 37 degrees C or 4 degrees C in the presence of azide. Uptake was not saturable under either condition with incubation concentrations up to 10 microgram/mL. Cross-linking did not show BPI bound to a single entity. Acid washing and flow cytometry experiments disclosed rapid internalization of BPI. Finally, BPI uptake by THP-1 cells had no effect on the surface expression of CD14. CONCLUSIONS: Bactericidal/permeability-increasing protein is rapidly internalized by mononuclear cells in a nonspecific fashion not saturable at very high doses, which is consistent with pinocytosis. This process may represent a disposal mechanism for lipopolysaccharide in closed-space infections and may be partially responsible for the rapid clearance of BPI from the peripheral circulation.

Molecular analysis of a new member of the opium poppy tyrosine/3,4-dihydroxyphenylalanine decarboxylase gene family.

An aromatic amino acid decarboxylase DNA fragment was generated from opium poppy (Papaver somniferum L.) genomic DNA by the PCR using primers designed from conserved amino acid sequences of other aromatic amino acid decarboxylase genes. Using this fragment as a probe, a genomic clone was isolated that encodes a new member of the opium poppy tyrosine/3,4-dihydroxyphenylalanine decarboxylase gene family (TyDC5). The predicted TyDC5 amino acid sequence shares extensive identity with other opium poppy tyrosine/3,4-dihydroxyphenylalanine decarboxylases (84%), and when expressed in Escherichia coli, it is active against tyrosine and to a lesser extent against 3,4-dihydroxyphenylalanine. Ribonuclease protection assays indicate that TyDC5 is expressed primarily in the roots of mature poppy plants. A peak of TyDC5 expression was also observed during germination, coincident with the emergence of the radicle from the seed coat. Parallel results were obtained in transgenic tobacco using a TyDC5 promoter fragment (-2060) translationally fused to the beta-glucuronidase reporter gene (GUS). IN TyDC5::GUS tobacco, GUS activity transiently appeared in all parts of the seedling during germination, but was limited to the roots in older plants. These results indicate that TyDC5 expression is transcriptionally regulated and suggest that the TyDC5 enzyme may play an important role in providing precursors for alkaloid synthesis in the roots and germinating seedlings of opium poppy.

Current uses and abuses of total parenteral nutrition.

Total parenteral nutrition remains a vital medical intervention, and in our institution it is considered as basic as intravenous fluids, antibiotics, and blood transfusions. As is true of most treatments, there are specific indications as well as associated risks and costs which mandate justification of its use. It is clear that the indications for TPN are diminishing as basic science and clinical studies continue to find increased benefits associated with enteral feeding, and as techniques for initiating enteral nutrition improve. Because of unproven benefits and/or increased complication rates, TPN has lost favor in the treatment of conditions that were previously thought to require parenteral alimentation, such as acute pancreatitis, pediatric and adult burns, critical care, and preoperative use in patients with mild or moderate malnutrition. Despite diminishing indications, TPN continues to generate excitement in some areas as its immunological effects become better defined. The use of TPN in patients with cancer before certain therapies, as well as in the transplant population, remains hopeful. New uses of TPN will result from a better understanding of the cellular and molecular effects of parenteral feeding. In the future, TPN may well be used as a pharmacologic agent rather than as nutritional intervention.

Definition of the role of enterococcus in intraabdominal infection: analysis of a prospective randomized trial.

BACKGROUND: The role of enterococcus in intraabdominal infection is controversial. This study examines the contribution of enterococcus to adverse outcome in a large intraabdominal infection trial. METHODS: A randomized prospective double-blind trial was performed to compare two different antimicrobial regimens in combination with surgical or percutaneous drainage in the treatment of complicated intraabdominal infections. A total of 330 valid patients was enrolled from 22 centers in North America. RESULTS: In 330 valid patients, 71 had enterococcus isolated from the initial drainage of an intraabdominal focus of infection. This finding was associated with a significantly higher treatment failure rate than that of patients without enterococcus (28% versus 14%, p < 0.01). In addition, only Acute Physiology and Chronic Health Evaluation II score and presence of enterococcus were significant independent predictors of treatment failure when stepwise logistic regression was performed (p < 0.01 and < 0.03). Risk factors for the presence of enterococcus include age, Acute Physiology and Chronic Health Evaluation II, preinfection hospital length of stay, postoperative infections, and anatomic source of infection. There was no difference between the clinical trial treatment regimens with regard to overall failure, failure associated with enterococcus, or frequency of enterococcal isolation. CONCLUSIONS: This study is the first to report enterococcus as a predictor of treatment failure in complicated intraabdominal infections. This trial also identifies several significant risk factors for the presence of enterococcus in such infections.

Expression of a 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from Camptotheca acuminata is differentially regulated by wounding and methyl jasmonate.

We have isolated a gene, hmg1, for 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) from Camptotheca acuminata, a Chinese tree that produces the anti-cancer monoterpenoid indole alkaloid camptothecin (CPT). HMGR supplies mevalonate for the synthesis of the terpenoid component of CPT as well as for the formation of many other primary and secondary metabolites. In Camptotheca, hmg1 transcripts were detected only in young seedlings and not in vegetative organs of older plants. Regulation of the hmg1 promoter was studied in transgenic tobacco using three translational fusions (-1678, -1107, -165) with the beta-glucuronidase (GUS) reporter gene. Histochemical analysis of plants containing each of the three promoter fusions showed similar developmental and spatial expression patterns. In vegetative tissues, GUS staining was localized to the epidermis of young leaves and stems, particularly in glandular trichomes. Roots showed intense staining in the cortical tissues in the elongation zone and light staining in the cortex of mature roots. hmg1::GUS expression was also observed in sepals, petals, pistils, and stamens of developing flowers, with darkest staining in the ovary wall, ovules, stigmas, and pollen. Leaf discs from plants containing each of the translational fusions showed a 15- to 20-fold wound induction of hmg1::GUS expression over 72 h; however, this increase in GUS activity was completely suppressed by treatment with methyl jasmonate. Taken together, these data show that a 165-bp fragment of Camptotheca hmg1 promoter is sufficient to confer developmental regulation as well as wound induction and methyl jasmonate suppression of GUS expression in transgenic tobacco.