Importance and value of adjuvanted influenza vaccine in the care of older adults from a European perspective - A systematic review of recently published literature on real-world data.

BACKGROUND: There is an urgent need for improved influenza vaccines especially for older adults due to the presence of immunosenescence. It is therefore highly relevant to compare enhanced influenza vaccines with traditional influenza vaccines with respect to their effectiveness. OBJECTIVE: To compare vaccine efficacy and effectiveness of adjuvanted influenza vaccines (aTIV/aQIV) vs. non-adjuvanted standard-dose (TIV/QIV) and high-dose (TIV-HD/QIV-HD) influenza vaccines regarding influenza-related outcomes in older adults, complementing findings from the European Centre for Disease Prevention and Control (ECDC)'s systematic review of enhanced seasonal influenza vaccines from February 2020. METHODS: A systematic literature search was conducted in Embase and MEDLINE to identify randomised controlled trials, observational studies and systematic reviews, published since ECDC's systematic review (between 7 February 2020 and 6 September 2021). Included studies were appraised with either the Cochrane Risk of Bias tool, ROBINS-I or AMSTAR 2. RESULTS: Eleven analyses from nine real-world evidence (RWE) studies comprising ∼53 million participants and assessing the relative vaccine effectiveness (rVE) of aTIV vs. TIV, QIV and/or TIV-HD in adults aged ≥65 years over the 2006/07-2008/09 and 2011/12-2019/20 influenza seasons were identified. Nine analyses found that aTIV was significantly more effective than TIV and QIV in reducing influenza-related outcomes by clinical setting and suspected influenza outbreaks (rVE ranging from 7.5% to 25.6% for aTIV vs. TIV and 7.1% to 36.3% for aTIV vs. QIV). Seven analyses found similar effectiveness of aTIV vs. TIV-HD in reducing influenza-related medical encounters, inpatient stays and hospitalisations/emergency room visits. In three analyses, aTIV was significantly more effective than TIV-HD in reducing influenza-related medical encounters and office visits (rVE ranging from 6.6% to 16.6%). Risk of bias of identified studies was moderate to high. CONCLUSIONS: Our study suggests that both adjuvanted and high-dose vaccines are effective alternatives for vaccination programmes in older adults and preferable over conventional standard-dose vaccines.

Congenital infections with Trypanosoma cruzi or Toxoplasma gondii are associated with decreased serum concentrations of interferon-γ and interleukin-18 but increased concentrations of interleukin-10.

Little is known about the immune responses of newborns with congenital Chagas disease (CCD) or congenital toxoplasmosis (CT) but they probably differ to those seen in adults with Chagas disease or toxoplasmosis, leading to differences in pathology. The concentrations of interleukin-18 (IL-18), interferon-γ (IFN-γ) and interleukin 10 (IL-10) in the sera of infants with CCD or CT were determined and compared with those in the sera of uninfected controls (born to mothers who were seropositive or seronegative for Trypanosoma cruzi). The infants with CCD or CT were found to have lower IL-18 and IFN-γ concentrations but higher IL-10 concentrations than the uninfected controls. The IL-18 and IFN-γ concentrations were also significantly lower in the infants with CCD than in those with CT. Although the infants with symptomatic CT had significantly higher serum concentrations of IL-18 than those with asymptomatic infection with Toxoplasma, the infants with symptomatic CCD had similar serum concentrations of IL-18 to the infants with asymptomatic Tr. cruzi infection. Taken together, these results indicate that IL-10 contributes to the suppression of pro-inflammatory immune responses and therefore, perhaps, to clinically overt CCD and CT.

Prophylactic immunisation against traveller's diarrhoea caused by enterotoxin-forming strains of Escherichia coli and against cholera: does it make sense and for whom?

Traveller's diarrhoea (TD) constitutes the most common disease relevant to travel medicine with ETEC as the leading causative pathogen. Cholera is the most serious, but very rare form of TD. ETEC and cholera share pathogenic mechanisms by producing a toxin that has an 80% amino acid homology. A consensus of German-speaking experts sees the indication to use the whole cell/B subunit oral cholera vaccine (WC--BS) if cholera is a risk for aid workers or travellers with an anticipated threat of cholera who stay under poor hygienic conditions. The use of the vaccine should be considered in the indication to avoid ETEC TD for travellers with predisposing illness or medication or for travellers at risk to develop a serious course.

Mucosal abnormalities in microsporidiosis.

OBJECTIVE: To determine the prevalence of microsporidiosis in HIV-infected patients with and without diarrhoea and to characterize alterations in mucosal architecture and brush border enzyme activities in patients with microsporidiosis. PATIENTS: A total of 259 HIV-infected patients undergoing oesophago-gastroduodenoscopy because of diarrhoea (n = 123) or other symptoms (n = 136) were studied. METHODS: Patients were evaluated for the presence of microsporidia by electron microscopy of duodenal biopsies. Brush border enzyme activities were measured by histochemistry and mucosal architecture was determined by three-dimensional morphometry in biopsies from patients with microsporidiosis and compared with biopsies from a subgroup of HIV-infected patients with or without other enteropathogens. RESULTS: Enterocytozoon bieneusi was detected in 17 patients and Encephalitozoon intestinalis was detected in two patients. Microsporidiosis was significantly more frequent in patients with chronic diarrhoea (19.1%; P < 0.0001) or in patients with acute diarrhoea (7.2%; P = 0.04) than in patients without diarrhoea (1.5%). Microsporidiosis was associated with lactase deficiency (P = 0.03) and a reduced activity of alkaline phosphatase (P = 0.028) and alpha-glucosidase (P = 0.025) at the basal part of the villus compared with brush border enzymes in patients without enteropathogens. Patients with microsporidia had reduced villus height (P = 0.043) and a villus surface reduced by 40% (P = 0.004) compared with patients with enteropathogens other than microsporidia. CONCLUSIONS: Our study confirms the association between microsporidia and diarrhoea. The pathophysiologic mechanism by which microsporidia cause diarrhoea appears in part to be malabsorption, caused by a reduction of absorptive mucosal surface and impairment of enterocyte function.

Complicated tuberculosis and residual disease.

Complicated and extrapulmonary manifestations of tuberculosis (TB) may cause prolonged suffering for the individual patient and represent a high economic burden for the society concerned. Complications of pulmonary TB may be the consequence of reduced individual resistance, immunosuppression or specific immune defects. In HIV patients, pulmonary TB is often associated with extrapulmonary lesions, while the radiologic appearance of lung infiltrates may be less prominent compared to HIV negative persons. The present review summarizes data obtained during a 12-year study of extrapulmonary TB in Berlin, Germany, and outlines the role of residual TB lesions for disease reactivation in later life. Indications and limitations of INH preventive chemotherapy will be discussed.

The efficacy of halofantrine in the treatment of acute malaria in nonimmune travelers.

A multicenter prospective trial was performed to investigate the efficacy and the tolerability of halofantrine in nonimmune patients with malaria imported from areas with drug-resistant falciparum parasites (mainly Africa). Forty-five of the 74 subjects were treated with a one-day regimen (3 x 500 mg) of halofantrine, and the other 29 received the same regimen with an additional treatment on day 7. In the second group, a 100% efficacy rate was demonstrated, but in the group receiving the one-day regimen, four recrudescences were observed in patients with falciparum malaria. Only five mild adverse reactions were seen, which disappeared spontaneously after the end of the treatment. We conclude that halofantrine is highly effective in curing malaria in nonimmune subjects. The treatment scheme for such persons should include an additional treatment on day 7 for nonimmune individuals. This drug was well tolerated in our patients, indicating that halofantrine will be useful in the treatment of multidrug-resistant malaria in nonimmune persons.

Neuropsychiatric side effects after the use of mefloquine.

This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.

Cryptococcosis in AIDS patients: observations concerning CNS involvement.

The clinical course and response to therapy of seven patients with cryptococcosis and AIDS were reviewed. One patient was still in the primary stage of cryptococcosis in AIDS, i.e. the stage that is characterized by the sole cultural detection of Cryptococcus neoformans in the respiratory tract. The other six patients were in the secondary stage, where C. neoformans can be detected from the cerebrospinal fluid (CSF), blood, urine, faeces and other body sites. The main presenting features (headache, fever, nausea) were due to central nervous system involvement, although meningism and mental changes were rarely present, and CSF changes were very subtle. Treatment with amphotericin B and flucytosine was very effective, there being no more growth of fungi in cultures in most cases. Adverse reactions to the drugs used occurred frequently and consisted mainly of anaemia, hepatosis and fever. Diagnosis in the primary stage of cryptococcosis may improve the prognosis.

Listeria meningitis: report of ten recent cases and review of current therapeutic recommendations.

Ten cases of meningitis due to Listeria monocytogenes were admitted to three hospitals in Berlin between 1978 and 1983. One patient was a premature infant in whom meningitis was diagnosed as part of typical granulomatosis infantiseptica. Another presented with signs of brainstem encephalitis which was confirmed post mortem. Positive blood cultures were obtained from five of the patients. Two strains of listeria were resistant and one was only moderately sensitive to penicillin. The three most recently isolated strains were tested for sensitivity to the third generation cephalosporins. All were resistant to latamoxef, and two were resistant to cefotaxime. The implications of these findings for the empirical treatment of purulent meningitis are discussed.

A case of disseminated toxoplasmosis-value of PCR for the diagnosis.

Extracerebral toxoplasmosis has recently gained greater attention as a consequence of the AIDS epidemic. Serological techniques are unreliable, while isolation of the parasite is either time-consuming or insensitive. We here report a case of disseminated toxoplasmosis in a patient with AIDS. Diagnosis was suggested by serological tests and confirmed by PCR and Southern blot hybridisation or nested PCR. Detection of specific DNA was feasible in bronchoalveolar fluid, blood, serum and tissue samples. Direct detection of parasite-specific DNA by PCR and by nested PCR proved to be a promising, sensitive and rapid method for the diagnosis of disseminated toxoplasmosis, enabling us to promptly initiate specific treatment.

Malaria therapy in 452 patients, with special reference to the use of quinine.

We investigated the efficacy and toxic potential of antimalarial therapy regimens in 452 malaria patients treated between 1980 and 1990. Drug regimens in 330 non-immune travellers were compared with those of 122 semi-immunes with acute malaria; 71% patients acquired their infection in tropical Africa, and the 288 Plasmodium falciparum infections were the most prevalent species. Because of increasing drug resistance or toxicity of chloroquine, pyrimethamine-sulfadoxine and even mefloquine, quinine proved to be the most effective antimalarial against P. falciparum and the only one which did not lead to recrudescences. These occurred in 10% patients after chloroquine and 6% after mefloquine. Cinchonism occurred in 25% of those treated with quinine, but it was fully reversible and never necessitated withdrawal of the drug. We conclude that quinine is highly effective in the treatment of P. falciparum infection and is mandatory if the clinical condition requires a fast-acting blood schizonticide, in cases of hyper-parasitaemia and if multi-drug resistance occurs; its use should not be restricted by reversible side-effects such as cinchonism.

Comparison of three DOT-ELISA techniques in diagnosing Schistosoma haematobium infection.

The DOT-STRIP-ELISA was evaluated in the laboratory as a serodiagnostic tool for Schistosoma haematobium infection in order to assess the potential of introducing the technique under field conditions in the developing world. Out of 100 individuals with parasitologically confirmed Schistosoma haematobium, 87 reacted positively (sensitivity 87%), whereas 45 out of 50 sera from individuals from a non-endemic area reacted negatively (specificity 90%). Results were reproducible. Cross-reactions were observed with sera from individuals infected with Schistosoma mansoni, Echinococcus, Leishmania and Wuchereria. The DOT-STRIP-ELISA offers more advantages with regard to practicability and test-time when compared with the DOT-DISC-ELISA and DOT-MILLIPORE-ELISA.

[Ruptured splenic artery aneurysm--a rare cause of recurrent gastrointestinal hemorrhages]. / Rupturiertes Milzarterienaneurysma--eine seltene Ursache rezidivierender gastrointestinaler Blutungen.

HISTORY AND CLINICAL FINDINGS: A 51-year-old asthenic patient attended the hospital with syncope, head injury, tarry stool and severe anemia. There was a history of alcohol and nicotine abuse, but no known preceding diseases of the liver or gastrointestinal tract. Except hypotension, examination of the patient did not show any further abnormalities. DIAGNOSTIC PROCEDURE: An upper and lower endoscopy did not show any evidence of a bleeding source although the stomach was full of hematin. An abdominal ultrasound demonstrated signs of a chronic pancreatitis and a big cystic structure in the area of the pancreatic tail. Pulsed and color Doppler imaging followed by angiography led to the diagnosis of a pseudoaneurysm of the splenic artery. TREATMENT AND COURSE: After confirming the diagnosis, a laparotomy was performed. It revealed a pseudoaneurysm arising from the splenic artery that had penetrated the stomach and caused bleeding. Resection of the aneurysm, the stomach fundus, the left pancreas and the spleen was performed. 10 days after laparotomy, the patient was discharged from hospital in a good clinical condition. CONCLUSION: Pseudoaneurysms of the splenic artery are an uncommon cause of gastrointestinal bleeding. The most important factor in detecting a pseudoaneurysm is considering the diagnosis. It is necessary to check for a pseudoaneurysm secondary to pancreatitis with pulsed or color Doppler imaging especially if a pseudocyst was first diagnosed with abdominal ultrasound. Because of the high mortality of a pseudoaneurysm, surgical resection or interventional radiology should be done as early as possible.

[Travelers' diarrhea]. / Reisediarrhoe.

Travelers diarrhea affects millions of tourists each year. Most cases are caused by a variety of bacterial enteropathogens: toxigenic Escherichia coli, Campylobacter, Shigella, Salmonella, Aeromonas, Plesiomonas and non-cholera vibrios. Treatment may include antibacterial therapy with either ciprofloxacin, or azitrhomycin, or rifaximin. Viral pathogens such as norovirus usually cause short-term illness that typically resolves before travelers seek medical attention. Chronic gastrointestinal disease in returning travelers often is caused by parasitic pathogens like Giardia lamblia. The impact of prevention of travelers diarrhea is limited, therefore travelers should be informed about early self-treatment.

[Influenza and pneumococcal vaccination in adults]. / Grippe- und Pneumokokkenimpfung im Erwachsenenalter.

Seasonal influenza causes yearly increased morbidity and mortality especially in older adults and patients with a comorbidity. Vaccination coverage in Germany reaches 60 % in the age group of persons over 60 years, but fails to reach the WHO target of 75 %. Improved immunogenicity of vaccines is necessary because of the occurrence of immunosenescence. This can be achieved by improved adjuvants or by new routes of application like the intradermal vaccination which produces higher antibody levels. Invasive pneumococcal infections cause up to 10000 deaths in Germany every year. The polysaccharide vaccine prevents 60 - 80 % of invasive bacteremic pneumococcal infections and reduces the mortality and severity of invasive courses. Only 20 % of the target group is vaccinated: German physicians should stress the need for pneumococcal vaccination.

[Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: good prognosis with early detection]. / (Neuro-)Endokrine Tumoren des Magens sind auf dem Vormarsch: Gute Prognose bei frühem Nachweis.

Neuroendocrine tumors (NET) of the stomach are on the rise. In the United States they have increased about tenfold in the last 35 years. Prognosis has been much improved over the last three to four decades. Nowadays most of such NETs are diagnosed at an early stage. Quite often gastric NETs are found incidentally during a gastroscopy, performed for other reasons. Most of the asymptomatic, well differentiated gastric NETs are less than 2 cm in diameter. Conservative management and endoscopic surveillance is adequate for well differentiated, multifocal type 1 or type 2 gastric NETs (gastric carcinoids) of 10-20 mm , unless they are angio-invasive, have infiltrated into the muscularis propria or have metastasized. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is, however, indicated for all NETs larger than 20 mm. For optimal management tumor biology, type and stage of the neoplasm as well as the individual situation of the patient have to be taken into account. Most of the patients can be treated conservatively and be followed up with endoscopic surveillance.