Presence and distribution of mosquito larvae predators and factors influencing their abundance along the Mara River, Kenya and Tanzania.

Among all the malaria controlling measures, biological control of mosquito larvae may be the cheapest and easiest to implement. This study investigated baseline predation of immature mosquitoes by macroinvertebrate predators along the Mara River, determined the diversity of predators and mosquito larvae habitats and the range of their adaptive capacity to water physico-chemical parameters. Between July and August 2011, sampling sites (n=39) along the Mara River were selected and investigated for the presence of macroinvertebrate predators and mosquito larvae. The selected sampling sites were geocoded and each dipped 20 times using standard mosquito larvae dipper to sample mosquito larvae, while a D-frame dip net was used to capture the macroinvertebrate predators. Water physico-chemical parameters (dissolved oxygen, temperature, pH, conductivity, salinity and turbidity) were taken in situ at access points, while hardness and alkalinity were measured titrimetically. The influence of macroinvertebrate predator occurrence was correlated with mosquito larvae and water quality parameters using Generalized Linear Model (GLM). Predators (n=297) belonging to 3 orders of Hemiptera (54.2%), Odonata (22.9%) and Coleoptera (22.9%), and mosquito larvae (n=4001) belonging to 10 species, which included An.gambiae s.l (44.9%), Culex spp. (34.8%) and An. coustani complex (13.8%), An. maculipalpis (3.6%), An. phaorensis (1.2%), An. funestus group (0.5%), An. azaniae (0.4%), An. hamoni (0.3%), An. christyi (0.3%), An. ardensis (0.08%), An. faini (0.07%), An. sergentii (0.05%) and 0.05% of Aedes mosquito larvae which were not identified to species level, due to lack of an appropriate key, were captured from different habitats along the Mara river. It was established that invasion of habitats by the macroinvertebrate predators were partially driven by the presence of mosquito larvae (p < 0.001), and the prevailing water physico-chemical parameters (DO, temperature, and turbidity, p <0.001). Understanding abiotic and biotic factors which favour mosquitoes and macroinveterbrate co-occurrence may contribute to the control of malaria.

Distribution and abundance of schistosomiasis and fascioliasis host snails along the Mara River in Kenya and Tanzania.

We purposively selected 39 sampling sites along the Mara River and its two perennial tributaries of Amala and Nyangores and sampled snails. In addition, water physicochemical parameters (temperature, turbidity, dissolved oxygen, conductivity, alkalinity, salinity and pH) were taken to establish their influence on the snail abundance and habitat preference. Out of the 39 sites sampled, 10 (25.6%) had snails. The snail species encountered included Biomphalaria pfeifferi Krauss - the intermediate host of Schistosoma mansoni Sambon, Bulinus africanus - the intermediate host of Schistosoma haematobium, and Lymnaea natalensis Krauss - the intermediate host of both Fasciola gigantica and F. hepatica Cobbold. Ceratophallus spp., a non-vector snail was also encountered. Most (61.0%) of the snails were encountered in streamside pools. Schistosomiasis-transmitting host snails, B. pfeifferi and B. africanus, were fewer than fascioliasis-transmitting Lymnaea species. All the four different snail species were found to be attached to different aquatic weeds, with B. pfeifferi accounting for over half (61.1%) of the snails attached to the sedge, followed by B. africanus and Lymnaea spp., accounting for 22.2 and 16.7%, respectively. Ceratophallus spp. were non-existent in sedge. The results from this preliminary study show that snails intermediate hosts of schistosomiasis and fascioliasis exists in different habitats, in few areas along the Mara River, though their densities are still low to have any noticeable impacts on disease transmission in case they are infected. The mere presence of the vector snails in these focal regions calls for their immediate control and institution of proper regulations, management, and education among the locals that can help curtail the spread of the snails and also schistosomiasis and fascioliasis within the Mara River basin.

Should the law on anonymity of organ donation be changed? The perception of liver transplant recipients.

BACKGROUND: Belgian politicians submitted a proposal to rescind the law on anonymity of organ donation and transplantation and facilitate contact between donor families and recipients. It remains uncertain if recipients support this proposal. METHODOLOGY: One liver transplant patient organization (n = 176/249) answered and provided comments on two questions: (i) how satisfied are you with the current principle of anonymity of the identity of the donor and (ii) the law about anonymity should be changed to allow the donor family and the patient to meet. RESULTS: Seventy percent were satisfied/very satisfied with the present law, because of anxiety for emotional involvement or feeling obliged to do something in return, feelings of guilt, and out of mutual respect. Nineteen percent was dissatisfied/very dissatisfied and want to obtain some information about the donor, and directly express their gratitude. Forty-two percent disagreed with a change, because of anxiety for manipulation, feelings of guilt, respect for the privacy, and worry about the donor having a different background. Thirty-six percent wanted to change the law out of curiosity, to express their gratitude, or to facilitate their coping process. DISCUSSION: Prudence to change the law is warranted, as only a minority of patients are in favor of rescinding the anonymity.

Machine perfusion or cold storage in deceased-donor kidney transplantation.

BACKGROUND: Static cold storage is generally used to preserve kidney allografts from deceased donors. Hypothermic machine perfusion may improve outcomes after transplantation, but few sufficiently powered prospective studies have addressed this possibility. METHODS: In this international randomized, controlled trial, we randomly assigned one kidney from 336 consecutive deceased donors to machine perfusion and the other to cold storage. All 672 recipients were followed for 1 year. The primary end point was delayed graft function (requiring dialysis in the first week after transplantation). Secondary end points were the duration of delayed graft function, delayed graft function defined by the rate of the decrease in the serum creatinine level, primary nonfunction, the serum creatinine level and clearance, acute rejection, toxicity of the calcineurin inhibitor, the length of hospital stay, and allograft and patient survival. RESULTS: Machine perfusion significantly reduced the risk of delayed graft function. Delayed graft function developed in 70 patients in the machine-perfusion group versus 89 in the cold-storage group (adjusted odds ratio, 0.57; P=0.01). Machine perfusion also significantly improved the rate of the decrease in the serum creatinine level and reduced the duration of delayed graft function. Machine perfusion was associated with lower serum creatinine levels during the first 2 weeks after transplantation and a reduced risk of graft failure (hazard ratio, 0.52; P=0.03). One-year allograft survival was superior in the machine-perfusion group (94% vs. 90%, P=0.04). No significant differences were observed for the other secondary end points. No serious adverse events were directly attributable to machine perfusion. CONCLUSIONS: Hypothermic machine perfusion was associated with a reduced risk of delayed graft function and improved graft survival in the first year after transplantation. (Current Controlled Trials number, ISRCTN83876362.)

An international perspective: job satisfaction among transplant nurses.

CONTEXT: The high demand for transplant nurses across the world leads us to examine job design and job satisfaction because job satisfaction is linked to better outcomes for patients. OBJECTIVE: To describe international transplant nurses' perspectives of job design and job satisfaction by using Herzberg's theory of motivation. METHODS: Descriptive, correlational design. An electronic version of the Job Design and Job Satisfaction survey was mailed to all members of the International Transplant Nurses Society. RESULTS: A total of 331 members of the International Transplant Nurses Society responded to the survey. The mean age of respondents was 44.12 years, they had worked a mean of 19.12 years in nursing and 10.22 years in transplantation, and 50.6% of respondents were transplant nurse coordinators. Respondents were very satisfied overall with their jobs; they perceived that transplant nursing requires a high level of nonrepetitive, complex skills, autonomy in personal initiative and judgment, cooperation and collaboration with others, and that the job allows for completion of the work. Respondents were satisfied with pay, fringe benefits, and supervision. The feeling that the job could positively and significantly affect others was very strong. CONCLUSIONS: Results of this study provide empirical evidence supporting the perceived benefits and challenges of working in transplantation and support Herzberg's theory that motivators leading to job satisfaction include achievement, recognition, the work itself, responsibility, and advancement. Transplant nursing includes many of these motivators and desirable characteristics, including autonomy and working with a multidisciplinary team on a clear, patient-centered goal.

Rapid generation of an anthrax immunotherapeutic from goats using a novel non-toxic muramyl dipeptide adjuvant.

BACKGROUND: There is a clear need for vaccines and therapeutics for potential biological weapons of mass destruction and emerging diseases. Anthrax, caused by the bacterium Bacillus anthracis, has been used as both a biological warfare agent and bioterrorist weapon previously. Although antibiotic therapy is effective in the early stages of anthrax infection, it does not have any effect once exposed individuals become symptomatic due to B. anthracis exotoxin accumulation. The bipartite exotoxins are the major contributing factors to the morbidity and mortality observed in acute anthrax infections. METHODS: Using recombinant B. anthracis protective antigen (PA83), covalently coupled to a novel non-toxic muramyl dipeptide (NT-MDP) derivative we hyper-immunized goats three times over the course of 14 weeks. Goats were plasmapheresed and the IgG fraction (not affinity purified) and F(ab')2 derivatives were characterized in vitro and in vivo for protection against lethal toxin mediated intoxication. RESULTS: Anti-PA83 IgG conferred 100% protection at 7.5 mug in a cell toxin neutralization assay. Mice exposed to 5 LD50 of Bacillus anthracis Ames spores by intranares inoculation demonstrated 60% survival 14 d post-infection when administered a single bolus dose (32 mg/kg body weight) of anti-PA83 IgG at 24 h post spore challenge. Anti-PA83 F(ab')2 fragments retained similar neutralization and protection levels both in vitro and in vivo. CONCLUSION: The protection afforded by these GMP-grade caprine immunotherapeutics post-exposure in the pilot murine model suggests they could be used effectively to treat post-exposure, symptomatic human anthrax patients following a bioterrorism event. These results also indicate that recombinant PA83 coupled to NT-MDP is a potent inducer of neutralizing antibodies and suggest it would be a promising vaccine candidate for anthrax. The ease of production, ease of covalent attachment, and immunostimulatory activity of the NT-MDP indicate it would be a superior adjuvant to alum or other traditional adjuvants in vaccine formulations.

Implementation of an intervention plan designed to optimize donor referral in a donor hospital network.

CONTEXT: The shortage of donor organs remains the most important factor of waiting list mortality in organ transplantation worldwide. Donor detection is influenced by the legal system, family refusal, and underreporting caused by erroneous knowledge of donation criteria and lack of familiarity with the procedure. OBJECTIVE: To identify possible key factors of donor referral patterns within an existing cooperation with donor hospitals and donor units across the Dutch-speaking part of Belgium, an area of approximately 3 million inhabitants. An intervention plan to optimize the cooperation and procedure quality and efficiency was designed. DESIGN: The intervention plan was based on 3 essential principles in donor referral by donor reporters, information on donor criteria, facilitation of the donor procedure, and communication between donor reporters and the transplant center. The interventions were structured to optimize all 3 of these principles. Two successive periods of 4 years were retrospectively compared. PARTICIPANTS: Data were collected retrospectively on donor referral behavior from a total of 37 donor hospitals and donor units over an 8-year period. MAIN OUTCOME MEASURES: The referrals were reviewed for potential donors, effective donors, percentage of effective donors, refusal rate of relatives, number of tissue donors, impact on local and national transplant programs, and national donor numbers. RESULTS: Data showed a significant positive impact on donor referrals and donor referral behavior (+27% potential donors, +30% effective donors, +172.7% tissue donors, -7% family refusals rates, +9.63% national donors). The results stress the importance of reduced workload and optimization of communication and information availability in an existing donor hospital network.

Broad neutralization and complement-mediated lysis of HIV-1 by PEHRG214, a novel caprine anti-HIV-1 polyclonal antibody.

OBJECTIVES: To assess the potency, breadth of action, and mechanism of action of the polyclonal goat anti-HIV antibody, PEHRG214. DESIGN: Typical human antibody responses to HIV-1 infection are unable to neutralize virus efficiently, clear the infection, or prevent disease progression. However, more potent neutralizing antibodies may be capable of playing a pivotal role in controlling HIV replication in vivo. PEHRG214 is a polyclonal caprine antibody raised against purified HIV-associated proteins, such that epitopes that are immunologically silent in humans may potentially be recognized in another species. It has been administered safely to HIV-infected individuals in Phase I clinical trials. METHODS: The anti-HIV activity of PEHRG214 was assessed using neutralization and virion lysis assays. The target proteins for PEHRG214 activity were investigated using flow cytometry and by adsorption of anti-cell antibodies from the antibody cocktail. RESULTS: PEHRG214 strongly neutralized a diverse range of primary HIV-1 isolates, encompassing subtypes A to E and both CCR5 and CXCR4 phenotypes. Neutralization was enhanced by the presence of complement. PEHRG214 also induced complement-mediated lysis of all HIV-1 isolates tested, and recognized or cross-reacted with a number of host cell proteins. Lysis was abrogated by adsorption with T and/or B cells expressing GPI-linked proteins, but not by GPI-deficient B cells or red blood cells. CONCLUSIONS: PEHRG214 was found to potently neutralize and lyse HIV-1 particles. By targeting host cell proteins present in the viral envelope, which are conserved among all strains tested, PEHRG214 potentially opens up a highly novel means of eliminating circulating virus in infected individuals.

Combined 'en bloc' liver and pancreas transplantation in patients with liver disease and type 1 diabetes mellitus.

Liver disease alters the glucose metabolism and may cause diabetes, but this condition is potentially reversible with liver transplantation (LTx). Type 1 diabetes mellitus may be coincidentally present in a LTx candidate and immunosuppressive drugs will aggravate diabetes and make its management more difficult for posttransplant. In addition, diabetes negatively influences outcome after LTx. Therefore, the question arises as to why not transplanting the pancreas in addition to the liver in selected patients suffering from both liver disease and Type 1 diabetes. We report two cases of en bloc combined liver and pancreatic transplantation, a technique originally described a decade ago in the treatment of upper abdominal malignancies but rarely used for the treatment of combined liver disease and Type 1 diabetes. Both recipients are currently liver disease-free and insulin-free more than 2 and 4 years posttransplant, respectively. Surgical, medical and immunological aspects of combined liver-pancreas transplantation are discussed in the light of the existing relevant literature.

A phase I study of the pharmacokinetics and safety of passive immunotherapy with caprine anti-HIV antibodies, (PE)HRG214, in HIV-1-infected individuals.

PURPOSE: To establish the pharmacokinetics and safety of single-dose polyclonal caprine anti-HIV antibodies ((PE)HRG214)in HIV-1-infected individuals. DESIGN: A phase 1, open-label, nonrandomized, dose-escalating study. METHOD: HIV-1-infected patients with CD4+ T-cell counts of < or =200 cells/microL and plasma HIV viral load (VL)of > or =5,000 copies/mL received a single intravenous dose of HRG. Dosing began at 6,000 U/kg HRG with proposed step-wise escalation to 96,000 U/kg. RESULTS: Eleven males were enrolled; median CD4+T-cell count and VL were 96 cells/microL and 126,200 copies/mL, respectively. HRG exhibited linear pharmacokinetics across the dosing range studied. The mean terminal elimination half-life (t(1/2)) was 136.6 +/- 44.6 hours (range, 52.6-198 h). Serum sickness occurred in one 48,000 U/kg HRG recipient. One 6,000 U/kg and two 24,000 U/kg HRG recipients developed a mild rash. Between baseline and day 60, VL remained unchanged (n = 6), increased by 0.67 log(10) copies/mL (n = 1), or declined by 0.34-1.55 log(10) copies/mL (n = 4). CONCLUSION: Single-dose HRG exhibited linear kinetics and a long half-life. Although numbers in each dosing group were very small (n = 3), HRG was generally well tolerated in doses below 48,000 U/kg. Multiple dosing with HRG in the HIV-salvage setting may be complicated by immune-complex formation.

Tolerance of liver transplant patients to strenuous physical activity in high-altitude.

Physical functioning is improved after liver transplantation but studies comparing liver transplant recipients with normal healthy people are lacking. How liver (and other organ) transplant recipients tolerate strenuous physical activities is unknown. There are no data on the tolerance of transplant patients at high altitude. Six liver transplant subjects were selected to participate in a trek up Mount Kilimanjaro 5895 m, Tanzania. Physical performance and susceptibility to acute mountain sickness were prospectively compared with fifteen control subjects with similar profiles and matched for age and body mass index. The Borg-scale (a rating of perceived exertion) and cardiopulmonary parameters at rest were prospectively compared with six control subjects also matched for gender and VO2max. Immunosuppression in transplant subjects was based on tacrolimus. No difference was seen in physical performance, Borg-scales and acute mountain sickness scores between transplant and control subjects. Eight-three percent of transplant subjects and 84.6% of control subjects reached the summit (p=0.7). Oxygen saturation decreased whereas arterial blood pressure and heart rate increased with altitude in both groups. The only difference was the development of arterial hypertension in transplant subjects at 3950 m (p=0.036). Selected and well-prepared liver transplant recipients can perform strenuous physical activities and tolerate exposure to high altitude similar to normal healthy people.

Steroid-free immunosuppression during and after liver transplantation--a 3-yr follow-up report.

BACKGROUND/AIMS: Steroids are traditionally used in liver transplantation as a part of a triple or quadruple immunosuppressive regimen. Steroids act non-specifically and cause multiple side-effects. Most liver transplantation centers reduce the dosage of steroids and eventually withdraw them after various time intervals. A few steroid-free trials have been recently conducted after liver transplantation but long-term data are not yet available. In addition, in these trials steroids were usually given during surgery. We report the long-term (median = 40 months) follow-up data of a prospective pilot study designed to determine whether liver transplantation could be performed with no steroids at all (neither during nor after surgery). METHODS: Twenty-one consecutive liver transplantations in 20 adult patients between August 1998 and July 1999 were prospectively included in an ab initio steroid-free immunosuppressive protocol. Mean age was 54 yr (40-67 yr). Tacrolimus (through levels, 8-10 ng/mL) and azathioprine (1-2 mg/kg) were started after liver transplantation. Patients were not given steroids during or after liver transplantation except in the event of rejection or in case of tacrolimus or azathioprine toxicity requiring significant dose reduction and/or withdrawal. RESULTS: There has been no case of primary graft dysfunction or non-function. Eleven of 21 liver transplantations (52%) received no steroids throughout the whole study. Rejection developed in five of 21 liver transplantations (23.5%). These rejections responded to standard i.v. steroids (plus ATG in one patient), followed by an oral steroid taper stopped 3 months after rejection. Steroids were transiently given in six liver transplantations for non-immune reasons: two with tacrolimus-induced neurotoxicity, three cases where azathioprine was discontinued, and one for an allergic reaction; four of these six patients are off steroids at last follow-up. The 3-yr graft and patient survival is 95 and 100%, respectively. CONCLUSIONS: Steroids are not necessary in more than 50% of liver transplantations. Steroids were transiently needed to treat acute rejection in 23.5% liver transplantations and for toxicity of calcineurin inhibitors or azathioprine or other reason in 28%. Of the patients who received steroids, the majority (70%) was eventually taken off steroids. This prospective single-center pilot study shows that liver transplantation without steroids is feasible and yields no penalty in terms of acute and chronic rejection, immune graft loss, graft function, patient and graft survival.

A passive immunotherapy, (PE)HRG214, in patients infected with human immunodeficiency virus: a phase I study.

(PE)HRG214 (HRG) is a polyclonal antibody preparation produced by immunization of goats with purified human immunodeficiency virus (HIV) antigens. In this phase I study, HRG was administered intravenously as a single dose (1, 2, 4, 8, or 16 mg/kg) to 18 HIV-1-infected patients with CD4 cell counts >/=50 cells/microL and virus loads >/=500 copies/mL. The most frequent adverse event was a transient rash, which appeared to be both dose- and CD4 cell count-dependent. At the 16 mg/kg level, median half-life was 68.4 h, and median C(max) was 392 microg/mL, a level well above that which inhibits HIV in vitro. At that dose level, median and maximum decreases in HIV-1 RNA levels at day 8 were 0.24 log(10) and 0.58 log(10), respectively, and, at day 29, were 0.24 log(10 ) and 2.2 log(10), respectively. HRG, administered as a single dose, is reasonably well tolerated and achieves adequate plasma concentrations.