Vaccination of pigs to control human neurocysticercosis

Taenia solium taeniasis/cysticercosis is a zoonotic disease complex in which the pig is an obligate intermediate host. The infection is widespread, particularly in the developing world, and neurocysticercosis is a major cause of human neurologic disease where the parasite is endemic. Despite easy availability, effective anti-parasitic drugs have not been deployed effectively to control disease transmission. We have investigated a vaccine strategy to prevent parasite infection of the pig intermediate host. Such a strategy would interrupt the parasite's life cycle and eliminate the source of infection for humans. Two recombinant antigens selected from the parasite oncosphere life cycle stage were tested in vaccination trials in pigs that were challenged orally with Taenia solium eggs. Both antigens were highly effective in protecting the pigs against infection with the parasite (98.6% and 99.9% protection, respectively). No viable cysts were found in eight pigs vaccinated with one of the antigens. A recombinant subunit vaccine based on oncosphere antigens has the potential to improve the available control measures for T. solium and thereby reduce or eliminate neurocysticercosis.     

Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS)

We did a case-control study in five Hong Kong hospitals, with 241 non-infected and 13 infected staff with documented exposures to 11 index patients with severe acute respiratory syndrome (SARS) during patient care. All participants were surveyed about use of mask, gloves, gowns, and hand-washing, as recommended under droplets and contact precautions when caring for index patients with SARS. 69 staff who reported use of all four measures were not infected, whereas all infected staff had omitted at least one measure (p=0.0224). Fewer staff who wore masks (p=0.0001), gowns (p=0.006), and washed their hands (p=0.047) became infected compared with those who didn't, but stepwise logistic regression was significant only for masks (p=0.011). Practice of droplets precaution and contact precaution is adequate in significantly reducing the risk of infection after exposures to patients with SARS. The protective role of the mask suggests that in hospitals, infection is transmitted by droplets.     

Taeniasis and cysticercosis in housemaids working in affluent neighborhoods in Lima, Peru

Taenia solium taeniasis/cysticercosis is endemic in most developing countries, where it is an important cause of epileptic seizures and other neurologic symptoms. In industrialized countries, cysticercosis results from travel or immigration of tapeworm carriers from endemic areas. In both endemic and nonendemic countries, housemaids commonly immigrate from cysticercosis-endemic areas and can transmit the infection if they carry the adult tapeworm. Between July 2001 and July 2002, 1,178 housemaids (961 of them work in the top five most affluent districts of Lima, a metropolis of 8 million inhabitants considered nonendemic for cysticercosis) were evaluated for serum antibodies to Taenia solium and stool microscopy for taeniasis and cysticercosis. The serosurvey revealed a prevalence of cysticercosis-specific antibodies of 14.6% (95% CI: 12.6-16.6%), and stool microscopy detected 12 T. solium tapeworm carriers, for a prevalence of taeniasis of 1.2% (95% CI: 0.6-1.8%). A nonrandom sample of 26 seropositive housemaids was examined by brain CT and 50% of them had brain lesions compatible with neurocysticercosis, mainly calcifications. From the families who used a tapeworm-carrier housemaid, cysticercosis antibodies were detected in 6 (23%) of 26 persons who agreed to participate. One seropositive member of the employer families was symptomatic for seizures and had brain calcifications. The prevalence of tapeworm infections in this housemaid group is similar to levels in endemic areas, constituting a source of neurocysticercosis infection.     

The occurrence of hyperaldosteronism in infants with congestive heart failure

Serum aldosterone and plasma renin were measured in 20 normal infants and 15 infants with congestive cardiac failure. Serum aldosterone was significantly increased (151 +/- 38 ng/dl mean +/- standard error of the mean) in patients before treatment when compared with aldosterone in normal infants (29 +/- 7 ng/dl). Increasing serum aldosterone was related to increasing plasma renin. The response to furosemide appeared to be inversely related to serum aldosterone concentrations. In four infants, administration of an aldosterone antagonist (spironolactone) resulted in improved diuresis and decreased serum aldosterone. Hyperaldosteronism is an important factor contributing to fluid and sodium retention in infants with heart failure.     

Mitral valve replacement in children: mortality, morbidity, and haemodynamic status up to medium term follow up

OBJECTIVE—To investigate the outcome of mechanical mitral valve replacement in children after up to 11 years of follow up.
DESIGN—Retrospective analysis of case records. Operative survivors underwent echocardiographic studies to define current haemodynamic status and prosthetic valve function.
SETTING—Tertiary referral centre.
PATIENTS—All 54 children who underwent mitral valve replacement between January 1987 and December 1997.
RESULTS—30 day mortality was 20.3% and was associated with small valve size and supra-annular position. The actuarial freedom from the following events at five years (70% confidence interval (CI)) was: death, including 30 day mortality and transplantation, 68% (70% CI 62% to 75%); bleeding, 89% (70% CI 84% to 94%); non-structural valve dysfunction and reoperation, 92% (70% CI 87% to 97%). The incidence of endocarditis and thromboembolism was low and there was no structural valve failure. Event-free survival was 52% (70% CI 45% to 60%). Low weight, young age, and small valve size increased the chance of death or reoperation. On echocardiography, left ventricular dilatation and wall motion abnormalities were often observed. A high mean gradient over the prosthesis was associated with small valve size but not with length of follow up.
CONCLUSIONS—With the use of mechanical prostheses for mitral valve replacement in children, the problem of structural valve failure is no longer an issue. However, the procedure is still associated with a high complication rate, both at surgery and during follow up, and should therefore be reserved for patients in whom valve repair is not technically feasible.


Keywords: mitral valve replacement; prosthetic mitral valve; child; outcome     

Diaminofluorene stain detects erythroid differentiation in immature haemopoietic cells treated with EPO,IL-3, SCF,TGFbeta1, MIP-1alpha and IFNgamma

We have combined in vitro clonogenic culture and a highly sensitive stain for haemoglobin to compare the influence of EPO, IL-3, SCF, TGFbeta1, MIP-1alpha and IFNgamma, to directly stimulate cells in the progenitor compartment to develop towards the erythroid lineage. Three cell lines were chosen, as they exist developmentally arrested in the progenitor compartment, yet in a pliant state of maturation. HEL (erythroleukaemia) and K562 (CML-derived) cell lines, may, under appropriate stimuli, develop erythroid characters, whilst the third, U937 (as control cell line), may be stimulated by DMSO to differentiate to myeloid cells. After in vitro semi-solid methylcellulose culture with these cytokines, resulting colonies were stained with 2,7-diaminofluorene (DAF), which sensitively stains haemoglobin blue. Haemoglobin production was low in HEL and K562 cells and absent in U937. Cytokine analysis showed varying levels of influence depending on the starting level of cell line maturation. EPO and TGFbeta1 maximally stimulated haemoglobin production in the HEL and K562 cell lines. This differential cytokine stimulation analysis combined with sensitive DAF haemoglobin detection could be applied in the study of many erythropoiesis-deficient patients or primitive erythropoiesis.     

Outcome of lamivudine-resistant hepatitis B virus is generally benign except in cirrhotics

AIM: We set to determine factors that determine clinical severity after the development of resistance. METHODS: Thirty-five Asian patients with genotypic lamivudine resistance were analyzed in three groups: 13/35 (37%) were non-cirrhotics with normal pre-treatment ALT (Group IA), 12/35 (34%) were non-cirrhotics with elevated pre-treatment ALT (Group IB), and 10/35 (29%) were cirrhotics (Group II). Patients were followed for a median of 98 wk (range 26-220) after the emergence of genotypic resistance. RESULTS: Group IA patients tended to retain normal ALT. Group IB patients showed initial improvement of ALT with lamivudine but 9/12 patients (75%) developed abnormal ALT subsequently. On follow-up however, this persisted in only 33%. Group II patients also showed improvement while on treatment, but they deteriorated with the emergence of resistance with 30% death from decompensated liver disease. Pretreatment ALT levels and CPT score (in the cirrhotic group) were predictive of clinical resistance and correlated with peak ALT levels and CPT score. CONCLUSION: The phenotype of lamivudine-resistant HBV correlated with the pretreatment phenotype. The clinical course was generally benign in non-cirrhotics. However, cirrhotics had a high risk of progression and death (30%) with the development of lamivudine resistance.     

Control of Taenia solium

Control or eradication of Taenia solium cysticercosis has been achieved to date only in Europe and North America. Significant improvements in sanitary conditions and developing functional slaughterhouse control systems were primarily responsible for control in these regions. Conversely, in endemic areas of developing countries control is limited by economic and sanitary conditions: the life cycle of T. solium is sustained because pigs have access to infected faeces, and cysticercosis-infested pork is available for consumption. Interventional trials with massive human cestocidal chemotherapy, treatment of both human and porcine populations with antihelminthic drugs and/or immunotherapy and health education have shown improvements in specific settings but not yet proven to be sustainable in the long-term. In order to ensure sustainability, any given control strategy towards elimination/eradication of porcine cysticercosis should incorporate economic incentives.     

Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden

Left ventricular (LV) diastolic dysfunction is prevalent in the community. Current assessment of diastolic function can be complex, involving Doppler evaluation of an array of hemodynamic data. The relation between left atrial (LA) volume and diastolic function, and between LA volume and cardiovascular risk and disease burden are not well known. In the present prospective study of 140 adults, mean age 58 ± 19 years, referred for a clinically-indicated echocardiogram and in sinus rhythm, with no history of atrial arrhythmias or valvular heart disease, we determined the LA volume, LV diastolic function status, cardiovascular risk score (based on age, gender, history of systemic hypertension, diabetes mellitus, hyperlipidemia, and smoking), and cardiovascular disease burden (based on confirmed vascular disease, congestive heart failure, and transient ischemic attack or stroke). LA volume was found to correlate positively with age, body surface area, cardiovascular risk score, LV end-diastolic and end-systolic dimensions, LV mass, diastolic function grade, tissue Doppler E/E′, tricuspid regurgitation velocity, and negatively with LV ejection fraction (all p <0.006). In a multivariate clinical model, LA volume indexed to body surface area (indexed LA volume) was independently associated with cardiovascular risk score (p <0.001), congestive heart failure (p = 0.014), vascular disease (p = 0.012), transient ischemic attack or stroke (p = 0.021), and history of smoking (p = 0.008). In a clinical and echocardiographic model, indexed LA volume was strongly associated with diastolic function grade (p <0.001), independent of LV ejection fraction, age, gender, and cardiovascular risk score. In patients without a history of atrial arrhythmias or valvular heart disease, LA volume expressed the severity of diastolic dysfunction and provided an index of cardiovascular risk and disease burden.