Short-course thymoglobulin induction and steroid-free immunosuppressive regimen in renal transplantation

Purpose: Optimal induction and maintenance immunosuppressive therapies in renal transplantation are still a matter of debate.Chronic corticosteroid usage is a major cause of morbidity but steroid-free immunosuppression (SF) can result in unacceptably high rates of acute rejection and even graft loss. Methods and materials: We have conducted a prospective openlabelled clinical trial in the Geneva-Lausanne Transplant Network from March 2005 to May 2008. 20 low immunological risk (<20% PRA, no DSA) adult recipients of a primary kidney allograft received a 4-day course of thymoglobulin (1.5 mg/kg/d) with methylprednisolone and maintenance based immunosuppression of tacrolimus and entericcoated mycophenolic acid (MPA). The control arm consisted of 16 matched recipients treated with basiliximab induction, tacrolimus, mycophenolate mofetil and corticosteroids. Primary endpoints were the percentage of recipients not taking steroids and the percentage of rejection-free recipients at 12 months.Secondary end points were allograft survival at 12 months and significant thymoglobulin and/or other drugs side effects. Results: In the SF group, 85% of the kidney recipients remained steroid-free at 12 months. The 3 cases of steroids introduction were due to one acute tubulo-interstitial rejection occurring at day 11, one tacrolimus withdrawal due to thrombotic microangiopathy and one MPA withdrawal because of multiple sinusitis and CMV reactivations. No BK viremia was detected nor CMV disease. The 6 CMV negative patients who received a positive CMV allograft had a symptomatic primoinfection after their 6-month course valgancyclovir prophylaxis. In the steroid-based group, 3 acute rejection episodes (acute humoral rejection, acute tubulointerstitial Banff IA and vascular Banff IIA) occurred in 2 recipients, 3 BK virus nephropathies were diagnosed between 45 and 135 days post transplant No side effects were associated with thymoglobulin infusion.In the SF group, 4 recipients presented severe leukopenia or agranulocytosis and one recipient had febrile hepatitis leading to transient MPA withdrawal. Discontinuation of MPA was needed in 2 patients for recurrent sinusitis and CMV reactivations. Patient and graft survival was 100% in both groups at 12 month follow-up. Conclusion: Steroid-free with short-course thymoglobulin induction therapy was a safe protocol in low-risk renal transplant recipients. Lower rates of acute rejection and BK virus infections episodes were seen compared to the steroid-based control group. A longer follow-up will be needed to determine whether this SF immunosuppressive regimen will result in higher graft and patient survival.

Ultrasonography in Schistosomiasis in Africa

Approximately 50 publications have become available in the international literature on ultrasonography in schistosomiasis in Africa. Geographically these cover Congo, Egypt, Kenya, Mali, Mauritius, Niger, Senegal, Sudan, Tanzania and East African Islands as well as Zimbabwe. Further studies are ongoing in many countries, such as Burundi, Ghana, Madagaskar and Uganda. It was shown that ultrasonography is useful in the detection of morbidity induced by schistosomiasis on an individual basis and on the community level. There is indication for varying morbidity patterns in different African foci. Post-treatment monitoring has provided evidence for reversibility of pathological lesions induced by Schistosoma (S.) haematobium and S. mansoni, even though evidence for reversibility of periportal fibrosis in adults is not yet satisfactorily substantiated. A standardized set of criteria for ultrasonographical observations has been worked out and is presently in the process of being refined. It is thus hoped that standardization will contribute to render studies in different endemic settings comparable on a global basis.

Methicillin-resistant Staphylococcus aureus infection after lung transplantation: 5-year review of clinical and molecular epidemiology.

BACKGROUND: Data on the epidemiology of MRSA infection in lung transplantation is limited. METHODS: We performed a 5-year retrospective study to assess the incidence and microbiologic and clinical characteristics of methicillin-resistant Staphylococcus aureus (MRSA) infection in a cohort of 163 lung transplant recipients. RESULTS: Seventeen patients with MRSA colonization and/or infection were identified, for a calculated incidence rate of 76.1 cases per 1,000 transplanted-years. Pulsed-field gel electrophoresis identified 3 different distinct MRSA profiles, all of them consistent with hospital-associated MRSA infection. CONCLUSION: Despite negative polymerase chain reaction (PCR) for the virulence factor Panton-Valentine leukocidin, MRSA infections resulted in significant disease and morbidity.

Schistosomiasis vaccine development: approaches and prospects

Mounting evidence for acquired immunity to schistosomiasis in humans supports the case for immunological intervention. On the other hand, rapid reinfection poses a threat to younger age groups due to the slow maturation of natural resistance. However, rational approaches, based on advances in immunology and molecular biology, have substantially increased the odds of producing an effective vaccine. Since the parasite cannot replicate in the human host and serious morbidity generally occurs only after a relatively long period of heavy worm burden, complete protection against infection is not essential. The chances of success would increase if more than one of the various host/parasite interphases were targeted, for example reducing morbidity through decreased worm loads as well as through suppression of egg production. Several promising schistosome antigens have now reached an advanced phase of development and are currently undergoing independent confirmatory testing according to a standardized protocol. A few molecules are being contemplated for scaled-up production but, so far, only one has reached the stage of industrial manufacture and safety testing. Since schistosomiasis cannot realistically be controlled by a single approach, vaccination is envisaged to be implemented in conjunction with other means of control, notably chemotherapy.

Control of schistosomiasis in Brazil: perspectives and proposals

Attempts to control schistosomiasis have hitherto involved the use of one or more of the following methods, either in isolation or in combination: (1) control of the intermediate host using molluscicides or biological methods; (2) basic sanitation and clean water supply; (3) health education; (4) individual or mass treatment; (5) protection of individuals in such a way as to prevent cercariae from penetrating the skin; (6) vaccine-based strategies against schistosomiasis. None of these methods is capable, on its own, of bringing about effective control of schistosomiasis, except in populations of a very limited size or under very special conditions. Molluscicides, besides expensive and toxic, have only a temporary effect. As for biological control, there is no effective method yet. Basic sanitation and clean water supply combined with health education potentially constitute the most effective approach, but only in the mid-to-long term. Mass treatment reduces morbidity, but does not control transmission. Protection of individuals has proved to be impracticable on a large scale. Vaccine-based strategies against schistosomiasis are still in the experimental stage. Experiments carried out in Brazil in the last 20 years have shown that mass treatment with single doses of oxamniquine or praziquantel can rapidly reduce levels of Shistosoma mansoni infection and morbidity in endemic areas. They have also shown that subsequent transmission and reinfection frequently occur in defined foci or "clusters", due to human contact with water, and in inverse proportion to the number and frequency of treatments carried out. On the basis of these experiments, the author suggests a multidisciplinary strategy for schistosomiasis control.

Immuno-epidemiology of Schistosoma mansoni infections in a recently exposed community in Senegal

The levels of IgE and IgG4 increased strongly between cohorts, indicating a dynamic immunological situation, but no immediate impact on infection levels. Morbidity was little specific abdominal discomfort was reported by 61%, diarrhoea by 33% of the subjects; mild hepatomegaly was found in 16%, splenomegaly in 0.5%. No relation to egg counts was observed for any symptom. This mild morbidity may be due to the recent nature of the focus. In the first cohort, the percentage of people with negative egg counts ten weeks after treatment was only 18%, though egg counts declined strongly. Antigen detection confirmed these results. Praziquantel treatment provoked transient but impressive side effects (colics, vomiting, urticaria, aedema), the occurrence of which correlated with intensity of infection. Cure rates in subsequent cohorts were followed up shorter after treatment but remained low. Reinfection nevertheless oppears limited. This lower drug efficacy may be due to very rapid reinfection and/or to the lack of immunity in the population, but also reduced susceptibility of the local parasite strain must be considered and studied.

Schistosomiasis control in China

After three decades' efforts, schistosomiasis japonica were controlled in one-third (4/12) of endemic provinces and 68.2 (259/380) of endemic counties throughout the country. The remaining 121 endemic counties are located primarily in the lake and mountainous regions. The epidemiological and ecological features of the lake and mountainous areas are different from the other endemic areas. The major schistosomiasis control efforts in China can be characterized as follows: (1) Application of centralized leadership and management, since schistosomiasis control is a task not only of the Ministry of Public Health, but also of all local governments in the endemic areas; (2) Integration of actions taken by various departments or bureaus, such as agriculture, water conservation and public health; (3) Promotion of mass participation; (4) Organization of strong professional teams; (5) Raising sufficient funds. Strategies on schistosomiasis control applied in different areas are divided into three levels: (1) In the areas where the schistosomiasis has been successfully controlled, surveillance must be maintained and immediate action should be taken where new infections occur and/or vector snails are found, so that control can be reestablished quickly; (2) In the areas where schistosomiasis has been partially controlled, any residents and/or live-stock infected should be examined and treated promptly with due care, and environment modifying and/or mollusciding must be used to eliminate the remaining snails; (3) In the areas where transmission has not been controlled, the main strategy is to control morbidity. Mass or selective chemotherapy with praziquental should be applied to both infected persosns and the live-stock, and environment modification for the snail-ridden areas should be taken but should be coordinated with agriculture where possible. Advance cases must be treated; and epidemics of Katayama fever prevented; water supply and sanitation shoud be improved and health education emphasized. Annual mass or selective chemotherapy with praziquental both reduces the prevalence rate and decreases the intensity of the infection for inhabitants and live-stock. As a consequence of the therapy a low prevalence rate can be obtained in a short time. The length of such arrangement period can be decided in accordance with the prevalence of the infection before the drug program is begun. Therefore,a maintenance phase is urgently needed. As China's ecomony expands and people's living standard rises, schistosomiasis will be controlled more effectively and successfully.

Schistosomiasis control in the State of São Paulo

The program of schistosomiasis control for the State of São Paulo, where only low endemicity areas occur, is discussed in this paper. Inclusion of schistosomiasis among the diseases due to obligatory notification is considered as a measure of great importance. Accordingly the search for passive cases conducted by the public health system acquired major importance in the disease surveillance. As from 1981 to 1992 only 11% of the detected cases were considered as autochthonous. The main transmission areas are located at the Litoral and Paraiba Valley regions. In the period of time under analysis, the epidemiological surveillance data suggest a decrease in the morbidity and in the autochthony tendency in the State of São Paulo.

Respiratory symptoms in preterm infants: burden of disease in the first year of life.

OBJECTIVE: While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors. METHODS: Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires. MAIN OUTCOME MEASURES: Cough and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy (severe outcomes). PATIENTS: 126 preterms (median gestational age 28.7 weeks; 78 with, 48 without BPD) hospitalised at the University Children's Hospital of Bern, Switzerland 1999-2006. RESULTS: Cough occurred in 80%, wheeze in 44%, re-hospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the preterm infants. Using logistic regression, the main risk factor for common symptoms was frequent contact with other children. Severe outcomes were associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR- and CRIB-Score. CONCLUSIONS: Cough in preterm infants is as common as in term infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more often. Severe outcomes are associated with perinatal risk factors. Preterm infants who did not qualify for BPD according to latest guidelines also showed a significant burden of respiratory disease in the first year of life.

Acute respiratory infections in children living in two low income communities of Rio de Janeiro, Brazil

Community studies of non-hospitalized children are essential to obtain a more thorough understanding of acute respiratory infections (ARI) and provide important information for public health authorities. This study identified a total ARI incidence rate (IR) of 4.5 per 100 child-weeks at risk and 0.78 for lower respiratory tract infections (LRI). Disease duration averaged less than one week and produced a total time ill with ARI of 5.8% and for LRI 1.2%. No clear seasonal variation was observed, the sex-specific IR showed a higher proportion of boys becoming ill with ARI and LRI and the peak age-specific IR occurred in infants of 6-11 months. Correlation with risk factors of the child (breastfeeding, vaccination, diarrheal disease, undernourishment) and the environment (crowding, living conditions, maternal age and education) showed marginal increases in the rate ratios, making it difficult to propose clear-cuts targets for action to lower the ARI and LRI morbidity. The importance of an integral maternal-child health care program and public education in the early recognition of LRI is discussed.

Gerdy tubercle osteotomy in surgical approach of posterolateral corner of the knee.

Posterolateral corner (PLC) injuries of the knee are uncommon injury patterns that may result in significant degrees of functional disability. When surgery is necessary to address this injury a good knowledge of anatomy and a good surgical exposure is the mainstay. This report reviews the complex anatomy of the posterolateral corner (PLC) of knee and describes the osteotomy of Gerdy tubercle as a technical variant to approach this anatomical region. This surgical step allowing a good mobilisation of the multiple layers of ilio-tibial tract from distal to proximal makes an excellent exposure of the PLC structures with absence of morbidity.

Nutrition dans la bronchopneumopathie chronique obstructive [Nutrition in chronic obstructive bronchopneumopathy]

The respiratory system and nutrition are linked. Obesity is sometimes seen in chronic obstructive pulmonary disease (COPD), but its prevalence, the morbidity and mortality induced by it are not known. In addition, the prevalence of malnutrition is high in COPD and the more severe the COPD is, the higher percentage of malnutrition is present. Emphysematous patients are more frequently undernourished than those suffering from chronic bronchitis. Malnutrition is the consequence of the hypermetabolism induced by the higher cost of breathing in emphysema. The survival rate of these patients is negatively affected by malnutrition. A careful assessment of nutritional status must be performed in all COPD patients, especially during an episode of acute respiratory failure. When signs of malnutrition are present, a nutritional intervention should be initiated rapidly. An amount of calories sufficient to meet the energy expenditure increased by the disease must be given. Excessive intake may overstress the respiratory system whose functional reserve is limited in COPD. The diet must include a well balanced percentage of fat, carbohydrates and proteins. Preservation of the fat-free mass is the minimum goal to reach in acute respiratory failure. After the resolution of the acute phase, a gain of weight should be attempted within a rehabilitation program.

A research agenda for malaria eradication: vaccines.

Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of "vaccines that interrupt malaria transmission" (VIMT), which includes not only "classical" transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented.

Lapband Versus SAGB for Morbid Obesity. Long-Term Results of a Prospective Randomized Trial

Background: Gastric banding is currently one of the most performed procedures for morbid obesity. Results are related in part to the surgical technique and the quality of follow-up. Several bands are currently on the market, and it may bethat the type of band also plays a role in long-term results. The aim of this prospective randomized study was to compare the long-term results of the Lapband and the SAGB.Patients and methods: In three institutions with a common bariatric surgeon, consecutive patients undergoing laparoscopic gastric banding for morbid obesity were randomized to receive either a Lapband or a SAGB. The Lapband was placed using the perigastric and the SAGB with the pars flaccida technique. All data were collected prospectively. The median duration of follow-up was 131 months (103-147). Patients who lost their band were excluded from analysis as of band removal.Results: 180 patients were included between December 1998 and June 2002, 90 in each group. Except for age, which was lower in SAGB patients, the pre-operative characteristics were similar in the two patient groups. Early band-related morbidity was higher in the SAGB group (6,6 vs 0 %, p=0,03). Patients with a Lapband lost weight quicker than those with SAGB (EBMIL 50,8 vs 39,8 after 12 months, p<0,001), but the two weight loss curves joined after 24 months, and no difference could be observed later on up to 12 years after surgery (EBMIL 53,7 vs 58,1 % after 10 years, P=0,68). Long-term complications developed in 91 patients (50,5 %). Severe complications leading to band removal±conversion to another procedure developed in 30 and 40 patients in the Lapband and SAGB group respectively (33,3 vs 44,4 %, p=0,16).Conclusions: This prospective randomized study shows no significant difference in the long-term results of gastric banding between the Lapband and the SAGB. Both bands were associated with significant long-term complication and band removal/conversion rates. Patients who retain their band have acceptable long-term weight loss. It is likely that the concept of gastric banding rather than the device itself plays the most important role in longterm results.

High number of CD56(bright) NK-cells and persistently low CD4+ T-cells in a hemophiliac HIV/HCV co-infected patient without opportunistic infections.

BACKGROUND: Both the human immunodeficiency virus (HIV) and hepatitis C virus (HCV), either alone or as coinfections, persist in their hosts by destroying and/or escaping immune defenses, with high morbidity as consequence. In some cases, however, a balance between infection and immunity is reached, leading to prolonged asymptomatic periods. We report a case of such an indolent co-infection, which could be explained by the development of a peculiar subset of Natural Killer (NK) cells. RESULTS: Persistently high peripheral levels of CD56+ NK cells were observed in a peculiar hemophiliac HIV/HCV co-infected patient with low CD4 counts, almost undetectable HIV viral load and no opportunistic infections. Thorough analysis of NK-subsets allowed to identify a marked increase in the CD56bright/dim cell ratio and low numbers of CD16+/CD56- cells. These cells have high levels of natural cytotoxicity receptors but low NCR2 and CD69, and lack both CD57 and CD25 expression. The degranulation potential of NK-cells which correlates with target cytolysis was atypically mainly performed by CD56bright NK-cells, whereas no production of interferon γ (IFN-γ) was observed following NK activation by K562 cells. CONCLUSIONS: These data suggest that the expansion and lytic capacity of the CD56bright NK subset may be involved in the protection of this « rare » HIV/HCV co-infected hemophiliac A patient from opportunistic infections and virus-related cancers despite very low CD4+ cell counts.