KRAS G12A somatic point mutation in adenocarcinomas is categorized clinically as ineligibility criteria for anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies. In this study, a modified G12A-K-ras epitope (139A) with sequence-specific modifications to improve immunogenicity was developed as a potential vaccine against G12A-mutant KRAS cancers. Additionally, coupling of the 139A epitope with a tetanus toxoid (TTD) universal T-cell epitope to improve antigenicity was also reported. To facilitate convenient oral administration, Lactococcus lactis, which possesses innate immunomodulatory properties, was chosen as a live gastrointestinal delivery vehicle. Recombinant L. lactis strains secreting a G12A mutated K-ras control and 139A with and without TTD fusion were generated for comparative immunogenicity assessment. BALB/c mice were immunized orally, and high survivability of L. lactis passage through the gastrointestinal tract was observed. Elevations in B-cell count with a concomitant titre of antigen-specific IgG and interferon-γ secreting T-cells were observed in the 139A treated mice group. Interestingly, an even higher antigen-specific IgA response and interferon-γ secreting T-cell counts were observed in 139A-TTD mice group upon re-stimulation with the G12A mutated K-ras antigen. Collectively, these results indicated that an antigen-specific immune response was successfully stimulated by 139A-TTD vaccine, and a TTD fusion was successful in further enhancing the immune responses.
Malaysian infants would have to receive nine injections during the first few months of life in order to be protected against disease caused by hepatitis B (HBV), diphtheria, tetanus, pertussis and Haemophilus influenzae type b (Hib) if single HBV and Hib vaccines were used. We evaluated a combined DTPw-HBV/Hib vaccine administered at 1.5, 3 and 5 months after a birth dose of hepatitis B vaccine (HBV). One month after completion of the primary vaccination, 99% of subjects had seroprotective anti-HBV antibody levels, and at least 98% had seroprotective antibodies against diphtheria, tetanus, and Hib, and were seropositive for pertussis antibodies. The immune response to the combined vaccine was comparable to that induced by separate injections with DTPw, HBV and Hib vaccines. Overall, the DTPw-HBV/Hib vaccine was as well tolerated as separate administration of DTPw, HBV and Hib vaccines. The combined DTPw-HBV/Hib vaccine induces protection against five diseases as recommended in the Malaysian routine vaccination schedule. Use of the combined DTPw-HBV/Hib vaccine can reduce the required number of injections from nine to four in the first few months of life.
Neonatal Tetanus is a severe disease with high fatality. It should no longer be present in a country with the development status of Malaysia. However, sporadic cases still occur and the disease has not been eradicated. This editorial summarises the disease pattern, incidence and suggests reasons for the continued persistence of the condition locally.
This study aims to study the demographics, clinical presentation, treatment and outcome of neonatal tetanus patients managed at Hospital Duchess of Kent from January 1st 2006 to December 31st 2006. Five neonates were studied. All presented with fever, poor sucking and limb stiffness, with a history of unsterile delivery and uncertain maternal tetanus immunity status. All were nursed in a minimal-stimuli environment and were given IV penicillin G, IM tetanus immunoglobulin and sedatives to control spasms. Nutrition and chest physiotherapy were rendered. Three patients required artificial ventilation. Duration of treatment ranged from 25 to 44 days. All survived. Inadequate maternal immunization, unsterile delivery and inappropriate umbilical cord care are major contributing factors of neonatal tetanus in our study. Supportive measures are the mainstay of treatment in our setting with very limited resources.
Matched MeSH terms: Tetanus/complications; Tetanus/diagnosis; Tetanus/drug therapy*; Tetanus/prevention & control
Tetanus is still widely prevalent in many parts of the world especially in the developing countries. This study was conducted to assess the demographic and clinical features, treatment and outcome of tetanus in adults with a special emphasis on identification of predictors of mortality. This was a retrospective study of all adult patients admitted with tetanus over a three-year period from 1998 to 2000 at Lok Nayak Hospital, New Delhi, India. The demography, clinical features, treatment and complications of the patients were assessed and were evaluated against two possible outcomes- survival or death, to identify the predictors of mortality. There were 217 adults (148 males, 69 females) admitted with generalized tetanus during the study period. The mean age of the patients was 36.08 +/- 18.84 years. In most instances (63.5%), wounds / injuries served as the source of infection. Overall 31.8% had mild, 21.7% had moderate and 46.5% had severe disease at presentation. Respiratory failure and dysautonomia were the frequently observed complications. Of the 217 patients, 82 died - a mortality rate of 37.78%. Parameters that were significantly associated with increased mortality were: age (especially > 60 years); shorter duration of symptoms - trismus, rigidity and dysphagia; severe disease at presentation and shorter period of onset. Tetanus is a preventable disease associated with a high fatality rate. Universal coverage of immunization programme and appropriate wound prophylaxis is the corner stone of tetanus eradication. The treatment of tetanus is difficult and requires specialized and intensive care. The presence of parameters indicating an adverse outcome at the beginning in the patients will help identify the subset of patients that need more intensive management especially in resource poor nations.
A 66-year-old man sustained an injury to his right foot while gardening. Despite receiving tetanus toxoid one hour later and adequate wound toilet, he developed severe tetanus complicated with autonomic dysfunction six days later. He died 20 days after admission. This case shows that tetanus toxoid alone may not be sufficient to prevent tetanus in wounded patients. Careful consideration must be given to the immune status of the patient and to the nature of the wound sustained. Incompletely immunised patients or patients with unknown immune status who sustain a tetanus prone wound should be protected with both tetanus toxoid and tetanus immunoglobulin.
A case of tetanus occurring after induced abortion is reported. The patient gave a history of low grade fever with chill and rigors, headache, neck pain and Trismus. She subsequently developed respiratory distress. However, incorrect information from the patient resulted in the delay to locate and eradicate the source of infection. Early referral to an intensive care unit for ventilatory assistance was the most appropriate step to save the patient. Complications which occurred during the course of the disease were sometimes difficult to overcome. These complications were probably related to the duration of stay in the intensive care unit. Their incidence could be reduced by more meticulous patient care.
There is a high incidence of tetanus in the Malaysian state of Kelantan. Out of 162 reported cases of tetanus in Peninsular Malaysia during 1979 - 1984, 62 cases were from Kelantan, i.e. 38% of the total reported cases in Peninsular Malaysia. Thus a retrospective study was carried out to analyse the possible factors responsible for this high incidence. 62 cases of tetanus admitted to the General Hospital, Kota Bharu, over a period of 1979 - 1984 were studied.
Neonatal tetanus, though still existing, had been considerably reduced compared to the preceding five-year period (1975-1979). There was notable absence of cases in the two months to four-year age group, 24% of the cases occurred in the 10 - 20 years, and 29% in the age group 25 - 40 years. Since tetanus is a disease preventable by active immunization. l every effort must be taken to improve immunization coverage and increase the public awareness to prevent unnecessary loss of lives.
Tetanus, especially tetanus neonatorum (T.N.) continues to be a significant medical and social problem in the developing countries. The case mortality rate remains very high even in the 'developed' countries, varying from 60-80 percent in various reports, and even higher in the case of tetanus neonatorum. Sanders et al had introduced the method of intrathecal injection of antitetanus serum (ATS) in 1976 and have achieved very encouraging results. As the conventional treatment of tetanus neonatorum had achieved very poor result, even in the very sophisticated centres, a case of tetanus neonatorum admitted to Cottage Hospital Semporna in Sabah had been treated with intrathecal ATS since June 1982. This paper reviews the results of this new approach to tetanus neonatorum treatment as compared to cases treated conventionally.
Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system (CNS) that is known to occur spontaneously in association with specific and non-specific viral illnesses and after vaccination against various pathogens. Although it is often a self-limited monophasic illness, the fatality rate is estimated to be as high as 20%, and many patients suffer residual neurologic impairment 1. The diagnosis is mainly based on clinical and radiological findings. The clinical presentation varies from merely, an asymptomatic condition to loss of consciousness, seizures, ataxia, optic neuropathy, cranial nerve palsies, and motor dysfunction. MRI of the brain is the single most important diagnostic radiological investigation and can facilitate early diagnosis and prompt treatment. This case report describes a patient with ADEM presenting with only seizures after vaccination with anti-tetanus toxin.
Immune Thrombocytopenia Purpura (ITP) secondary to vaccinations is rare, especially after autologous hematopoietic stem cell transplantation (HSCT). A 31-yearold female received autologous HSCT for relapsed Hodgkin Disease, with platelet engraftment at Day+14. One week after receiving second scheduled vaccinations, she developed severe thrombocytopenia (3x109/L) associated with pharyngeal hematoma. Bone marrow (BM) examinations were consistent with ITP, possibly secondary to Influenza vaccine. Platelet increment was poor despite high dose corticosteroids, intravenous immunoglobulin (IVIG), Danazol and Eltrombopag. A repeated BM biopsy was in agreement with ITP. Re-treatment with tapering doses of prednisolone resulted in stable platelet counts at 120x109/L a year later.
Report on 174 cases of tetanus neonatorum collected between 1946 and 1950 in the General Hospital, Singapore. There is a marked reduction in the incidence, which is attributed to a better maternity service. The results of treatment are bad – with a mortality of 90% of cases.