Safety and immunogenicity of two formulations of rotavirus vaccine in Vietnamese infants.

BACKGROUND AND AIMS: ROTAVIN-M1® (licensed, frozen vaccine) and ROTAVIN (second-generation, liquid candidate vaccine) are two rotavirus vaccine formulations developed from a live attenuated G1P8 (KH0118) strain by Center for Research and Production of Vaccines and Biologicals (POLYVAC), Vietnam. This study compared the safety and immunogenicity of these two formulations. METHODS: A Phase 3, randomized, partially double-blinded, active-controlled study was conducted in healthy infants aged 60-91 days in Vietnam. Infants received two doses of ROTAVIN or ROTAVIN-M1 in a ratio of 2:1 with an interval of 8 weeks. Solicited reactions were collected for 7 days after each vaccination. Blood samples were collected pre-vaccination and 4 weeks after the second vaccination in a subset of infants. Non-inferiority criteria required that the lower bound of 95% confidence intervals (CIs) of the post-vaccination anti-rotavirus IgA GMC (Geometric Mean Concentration) ratio of ROTAVIN/ROTAVIN-M1 should be >0.5. A co-primary objective was to compare the safety of the two vaccines in terms of solicited reactions. RESULTS: A total of 825 infants were enrolled. The post-vaccination GMC was 48.25 (95% CI: 40.59, 57.37) in the ROTAVIN group and 35.04 (95% CI: 27.34, 44.91) in the ROTAVIN-M1 group with an IgA GMC ratio of 1.38 (95% CI: 1.02, 1.86) thus meeting the pre-set criteria for non-inferiority. A total of 605 solicited reactions were reported in 297 (36.0%) participants with 35.4% in the ROTAVIN group and 37.2% in the ROTAVIN-M1 group. There were no cases of intussusception or death reported in the study. CONCLUSIONS: Based on the data generated, it can be concluded that ROTAVIN is immunologically non-inferior and has similar safety profile to ROTAVIN-M1 when administered to infants in a two-dose schedule. Therefore, it can be considered as a more suitable option for programmatic use to prevent rotavirus diarrhoea in Vietnam and the Mekong region. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT03703336, October 11, 2018.

Preparation of immuno-stimulating complexes (ISCOMs) by ether injection.

This study investigated the application of the solvent dispersion technique, specifically ether injection, which has been successfully used in the preparation of liposomes, as a new, continuous and potentially scaleable method for the preparation of ISCOMs. Phosphatidylcholine (PC) and cholesterol (Chol) were dissolved in ether, which was injected into an aqueous solution, maintained at 55 degrees C, containing Quil A. The influences of the following variables on ISCOM formation were investigated: ratio of PC:Quil A:Chol used, pumping rate, total lipid mass and concentration of buffer salts and Quil A in the aqueous phase. All samples were characterized by negative stain transmission electron microscopy, photon correlation spectroscopy and sucrose ultracentrifugation gradient. It was demonstrated that ISCOMs could be produced by this method but the homogeneity of the preparation was influenced by the conditions used. Homogeneous ISCOM preparations were consistently produced only when the weight ratio of PC:Quil A:Chol was 5:3:2 with a total lipid mass of 20 mg, the Quil A dissolved in a 0.01 M phosphate buffer at a concentration of 6 mg in 4 ml, and the ether solution injected into the warmed buffer solution at a rate of 0.2 ml/min. Changing any of these variables resulted in more heterogeneous preparations in which ISCOMs typically co-existed with other colloidal structures such as worm-like and helical micelles, liposomes, lamellae and lipidic particles.

99mTc labeled VIP analog: evaluation for imaging colorectal cancer.

Early and reliable diagnosis of colorectal cancer continues to be demanding and challenging. Colorectal cancer cells express Vasoactive Intestinal Peptide (VIP) receptors in high density. We have prepared a VIP analog (TP3654), labeled it with (99m)Tc, and evaluated it in experimental animals as an agent for imaging colorectal cancer. The tissue distribution of (99m)Tc-TP3654 has been compared with that of (111)In-DTPA-Octreotide and (99m)Tc-anti-CEA scan in nude mice bearing human colorectal cancer LS174T. Finally, pharmacokinetic and tissue distribution studies of (99m)Tc-TP3654 have been performed in four normal human volunteers. Data suggest that (99m)Tc-TP3654 can be prepared efficiently without loss of its receptor specificity and biological activity. Although the 24 hr tumor uptake of (99m)Tc-TP3654 in the animal model used was modest (0.21 +/- 0.07% I.D./g), the tissue distribution profile was more favorable than that of (111)In-DTPA-Octreotide or (99m)Tc-anti-CEA scan. Human studies indicated that (99m)Tc-TP3654 had no adverse effect in any subject. Within 24 hours, approximately 70% of the injected dose cleared through the kidneys, and approximately 20% through the hepatobiliary system. In these non-fasting volunteers hepatobiliary clearance was slow and in cancer patients tumor uptake was rapid. Data suggest that (99m)Tc-TP3654 is a promising agent for imaging colorectal cancer.

Imaging infection with LeuTech.

LeuTech is a 99Tcm labelled, anti-CD15, IgM, murine monoclonal antibody shown to have high affinity (Kd = 10(-11) M) for CD15 receptors (5.1 x 10(5)/cell) expressed on human neutrophils. LeuTech was injected directly, intravenously, and its efficacy in imaging infection in 46 consecutive patients was determined. Human anti-mouse antibody (HAMA) response was examined in 30 normal volunteers using a standard LeuTech dose reconstituted with decayed 99Tcm solution. There were 38 true positive, six true negative, and two false negative scans. Of the 38 positive images, 33 (92%) were positive within 10 min after injection of LeuTech. LeuTech accuracy in this group of patients was 96%, sensitivity 95%, specificity 100%, positive predictive value (PPV) 100%, and negative predictive value (NPV) 75%. No elevation of the HAMA titre was observed in any of the 30 normal volunteers and no adverse reaction was noted in any patient. LeuTech is a highly promising agent for rapid imaging of infectious foci.

Imaging tumors in humans with Tc-99m-VIP.

Vasoactive intestinal peptide (VIP) was modified at the C terminus with a spacer and four amino acids to serve as a chelating moiety. The modified peptide, TP 3654, was labeled with Tc-99m and evaluated in normal volunteers, as well as in patients with a history of cancer. Renal clearance (67%) was the primary route of excretion, with approximately 20% of the radioactivity clearing through the hepatobiliary system. No adverse reaction was noted in any of the subjects and all, except one small, of the known lesions as seen by CT, MRI, Tc-99m-MIBI, or mammography were correctly identified within a few minutes of an i.v. injection of approximately 10 mCi of Tc-99m-TP 3654 (specific activity 11.3 x 10(3) Ci/m mol). The scans were in concordance in nine patients. In the remaining two, one with a visible mass in the neck from high grade spindle cell sarcoma and the other with a palpable mass in a breast from ductal epithelial hyperplasia, were localized only with Tc-99m-TP 3654, but not with Tc-99m-MIBI. Both malignancies are known to express VIP receptors. The VIP analog promises to be a nontoxic and reliable agent for imaging cancers in humans that express VIP receptors.

Workforce requirements for a primary oral health care system.

AIM: To present the case for a primary health care (PHC) approach for dental care in Vietnam, and thereby contribute to a better understanding of the oral health problems that exist in many developing countries. METHODS: Information was obtained in Vietnam through discussions with dental and medical authorities of provincial health offices, educational institutions, hospitals, health centres and schools and by collecting data from record books and reports. FINDINGS: Dentistry lacks a PHC strategy and consequently urgent oral care and oral disease prevention and control are not available for the majority of the population in Vietnam. The curriculum of dental students and dental auxiliaries is not adequately directed to the oral health needs of the population. The present number of dental personnel is too low. CONCLUSION: A basic oral health care package (BOHCP) advocated by the WHO which could be incorporated into primary health services at sub-district level and in the school dental service would be most suitable to meet the oral health needs of the population in Vietnam. The oral health education component of the BOHCP may have more impact when it is conducted in close collaboration with non-dental health personnel and lay persons. The curriculum of dental personnel should be adjusted to meet the requirements of their future tasks. Dental auxiliaries, provided they are well trained can carry out the BOHCP. Consequently, there is a large need for this type of dental personnel in Vietnam.

111-indium-DTPA-IgG lung imaging in patients with pulmonary and HIV infection.

111-Indium-DTPA-IgG (111In-IgG) is a new radiopharmaceutical that has been evaluated for the detection of infection without the need for in vitro cell labeling. We prospectively studied this agent in 33 patients suspected of having lung infections, most of whom also had HIV infection, and three patients with HIV infection and diarrhea without lung disease. Anterior and posterior lung images in the upright position were obtained within 24 h after intravenous administration of 2 mCi of 111In-IgG and were read in a blinded fashion by two nuclear medicine physicians. Of 29 patients suspected to have Pneumocystis carinii pneumonia (PCP), the diagnosis was confirmed by bronchoalveolar lavage in 18. Diffusely increased lung uptake of 111In-IgG was found in 17 of 18 patients who had PCP and was normal in 10 of 11 patients without PCP. The intensity of 111In-IgG uptake was related to sever gas exchange abnormality. Two patients with apparent bacterial lung infections had focal accumulation of 111In-IgG while two patients with minor radiographic abnormalities had no increased uptake. Normal lung uptake also occurred in two of three HIV-positive patients who had diarrhea and no lung disease. 111In-IgG appears to be useful in the detection of PCP and other pulmonary infections.

Orthodontic silver brazing alloys.

Orthodontic silver brazing alloys suffer from the presence of cadmium, excessive flow temperatures, and crevice corrosion on stainless steel. Seven alloys were examined. Two alloys contained cadmium. The lowest flow temperature observed was 629 degrees C for a cadmium alloy and 651 degrees C for two cadmium free alloys. Three alloys had corrosion resistance superior to the other solders. Addition of low melting temperature elements gallium and indium reduced flow temperature in some cases but produced brittleness in the brazing alloy.