Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe Agnandji, Selidji T; Huttner, Angela; Zinser, Madeleine E ...
New England journal of medicine/The New England journal of medicine,
04/2016, Volume:
374, Issue:
17
Journal Article
Peer reviewed
Open access
In this set of four phase 1 studies, a recombinant vesicular stomatitis virus (rVSV)–based Ebola vaccine induced Ebola virus–specific immune responses and was associated with side effects that ...included fever and transient arthritis, rash, and VSV viremia.
In August 2014, after the outbreak of Ebola virus disease was declared a public health emergency of international concern by the World Health Organization (WHO), the Canadian government donated 800 vials of the replication-competent recombinant vesicular stomatitis virus (rVSV)–vectored
Zaire ebolavirus
(rVSV-ZEBOV) candidate vaccine to the WHO. The VSV Ebola Consortium (VEBCON) was created under the auspices of the WHO to initiate phase 1 studies to facilitate rapid progression to phase 2 and 3 trials in affected countries.
1
Live replicating viral vaccines elicit humoral and cellular immune responses against viral pathogens.
2
,
3
A single injection of 10 million plaque-forming units . . .
Biological weapons achieve their intended target effects through the infectivity of disease-causing infectious agents. The ability to use biological agents in warfare is prohibited by the Biological ...and Toxin Weapon Convention. Bioterrorism is defined as the deliberate release of viruses, bacteria or other agents used to cause illness or death in people, but also in animals or plants. It is aimed at creating casualties, terror, societal disruption, or economic loss, inspired by ideological, religious or political beliefs. The success of bioterroristic attempts is defined by the measure of societal disruption and panic, and not necessarily by the sheer number of casualties. Thus, making only a few individuals ill by the use of crude methods may be sufficient, as long as it creates the impact that is aimed for. The assessment of bioterrorism threats and motives have been described before. Biocrime implies the use of a biological agent to kill or make ill a single individual or small group of individuals, motivated by revenge or the desire for monetary gain by extortion, rather than by political, ideological, religious or other beliefs. The likelihood of a successful bioterrorist attack is not very large, given the technical difficulties and constraints. However, even if the number of casualties is likely to be limited, the impact of a bioterrorist attack can still be high. Measures aimed at enhancing diagnostic and therapeutic capabilities and capacities alongside training and education will improve the ability of society to combat ‘regular’ infectious diseases outbreaks, as well as mitigating the effects of bioterrorist attacks.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Serological diagnosis of Zika virus (ZIKV) infections is challenging due to high cross-reactivity between flaviviruses. We evaluated the diagnostic performance of a novel anti-ZIKV ELISA based on ...recombinant ZIKV non-structural protein 1 (NS1). Assay sensitivity was examined using sera from 27 patients with reverse transcription (RT)-PCR-confirmed and 85 with suspected ZIKV infection. Specificity was analysed using sera from 1,015 healthy individuals. Samples from 252 patients with dengue virus (n = 93), West Nile virus (n = 34), Japanese encephalitis virus (n = 25), chikungunya virus (n = 19) or Plasmodium spp. (n = 69) infections and from 12 yellow fever-vaccinated individuals were also examined. In confirmed ZIKV specimens collected ≥ 6 days after symptom onset, ELISA sensitivity was 58.8% (95% confidence interval (CI): 36.0-78.4) for IgM, 88.2% (95% CI: 64.4-98.0) for IgG, and 100% (95% CI: 78.4-100) for IgM/IgG, at 99.8% (95% CI: 99.2-100) specificity. Cross-reactivity with high-level dengue virus antibodies was not detected. Among patients with potentially cross-reactive antibodies anti-ZIKV positive rates were 0.8% (95% CI: 0-3.0) and 0.4% (95% CI: 0-2.4) for IgM and IgG, respectively. Providing high specificity and low cross-reactivity, the NS1-based ELISA has the potential to aid in counselling patients, pregnant women and travellers after returning from ZIKV-endemic areas.
Leishmaniasis is increasingly reported among travellers. Leishmania species vary in sensitivity to available therapies. Fast and reliable molecular techniques have made species-directed treatment ...feasible. Many treatment trials have been designed poorly, thus developing evidence-based guidelines for species-directed treatment is difficult. Published guidelines on leishmaniasis in travellers do not aim to be comprehensive or do not quantify overall treatment success for available therapies. We aimed at providing comprehensive species-directed treatment guidelines.
English literature was searched using PubMed. Trials and observational studies were included if all cases were parasitologically confirmed, the Leishmania species was known, clear clinical end-points and time points for evaluation of treatment success were defined, duration of follow-up was adequate and loss to follow-up was acceptable. The proportion of successful treatment responses was pooled using mixed effects methods to estimate the efficacy of specific therapies. Final ranking of treatment options was done by an expert panel based on pooled efficacy estimates and practical considerations. 168 studies were included, with 287 treatment arms. Based on Leishmania species, symptoms and geography, 25 clinical categories were defined and therapy options ranked. In 12/25 categories, proposed treatment agreed with highest efficacy data from literature. For 5/25 categories no literature was found, and in 8/25 categories treatment advise differed from literature evidence. For uncomplicated cutaneous leishmaniasis, combination of intralesional antimony with cryotherapy is advised, except for L. guyanensis and L. braziliensis infections, for which systemic treatment is preferred. Treatment of complicated (muco)cutaneous leishmaniasis differs per species. For visceral leishmaniasis, liposomal amphotericin B is treatment of choice.
Our study highlights current knowledge about species-directed therapy of leishmaniasis in returning travellers and also demonstrates lack of evidence for treatment of several clinical categories. New data can easily be incorporated in the presented overview. Updates will be of use for clinical decision making and for defining further research.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this position paper, the European Society for Clinical Microbiology and Infectious Diseases, Study Group on Clinical Parasitology, summarizes main issues regarding the management of imported ...malaria cases. Malaria is a rare diagnosis in Europe, but it is a medical emergency. A travel history is the key to suspecting malaria and is mandatory in patients with fever. There are no specific clinical signs or symptoms of malaria although fever is seen in almost all non-immune patients. Migrants from malaria endemic areas may have few symptoms.Malaria diagnostics should be performed immediately on suspicion of malaria and the gold- standard is microscopy of Giemsa-stained thick and thin blood films. A Rapid Diagnostic Test (RDT) may be used as an initial screening tool, but does not replace urgent microscopy which should be done in parallel. Delays in microscopy, however, should not lead to delayed initiation of appropriate treatment. Patients diagnosed with malaria should usually be hospitalized. If outpatient management is preferred, as is the practice in some European centres, patients must usually be followed closely (at least daily) until clinical and parasitological cure. Treatment of uncomplicated Plasmodium falciparum malaria is either with oral artemisinin combination therapy (ACT) or with the combination atovaquone/proguanil. Two forms of ACT are available in Europe: artemether/lumefantrine and dihydroartemisinin/piperaquine. ACT is also effective against Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi, but these species can be treated with chloroquine. Treatment of persistent liver forms in P. vivax and P. ovale with primaquine is indicated after excluding glucose 6 phosphate dehydrogenase deficiency. There are modified schedules and drug options for the treatment of malaria in special patient groups, such as children and pregnant women. The potential for drug interactions and the role of food in the absorption of anti-malarials are important considerations in the choice of treatment.Complicated malaria is treated with intravenous artesunate resulting in a much more rapid decrease in parasite density compared to quinine. Patients treated with intravenous artesunate should be closely monitored for haemolysis for four weeks after treatment. There is a concern in some countries about the lack of artesunate produced according to Good Manufacturing Practice (GMP).
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract In low tuberculosis incidence regions, tuberculosis is mainly concentrated among hard-to-reach populations like migrants, homeless people, drug or alcohol abusers, prisoners and people ...living with HIV. To be able to eliminate tuberculosis from these low incidence regions tuberculosis screening and treatment programs should focus on these hard-to-reach populations. Here we discuss the barriers and facilitators of health care-seeking, interventions improving tuberculosis screening uptake and interventions improving treatment adherence in these hard-to-reach populations.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There are only limited data from resource-limited settings available on the prevalence of non-communicable diseases and associated risk factors of tuberculosis patients. This study investigated ...non-communicable disease co-morbidity in tuberculosis patients from Moyen Ogooué Province, Gabon.
All patients aged 18 years or older consulting for tuberculosis (TB) symptoms in Gabon's Moyen Ogooué province and neighbouring provinces from November 2018 to November 2020 were screened for diabetes mellitus, hypertension, and risk factors thereof (obesity, dyslipidaemia, smoking and alcohol consumption). Logistic regression was performed to identify factors associated with TB-diabetes and TB-hypertension co-morbidities.
Of 583 patients included, 227 (39%) were diagnosed with tuberculosis. In tuberculosis-confirmed patients, the prevalences of hypertension and diabetes were 16·3% and 12·8%, respectively. The prevalence of diabetes was twice as high in tuberculosis patients compared to non-tuberculosis patients. Factors independently associated with hypertension-tuberculosis co-morbidity were age >55 years (aOR=8·5, 95% CI 2·43, 32·6), age 45–54 years (aOR=4.9, 95%CI 1.3–19.8), and moderate alcohol consumption (aOR=2·4; 95% CI 1·02- 5·9), respectively. For diabetes-tuberculosis co-morbidity, age >55 years was positively (aOR=9·13; 95% CI 2·4–39·15), and moderate alcohol consumption inversely associated (aOR=0·26, 95% CI 0·08- 0·73). One-hundred-and-four (46%) of the tuberculosis patients had at least either dyslipidaemia, hypertension, diabetes, or obesity with a majority of newly-diagnosed hypertension and diabetes.
Integration of screening of non-communicable diseases and their risk factors during TB assessment for early diagnosis, treatment initiation and chronic care management for better health outcomes should be implemented in all tuberculosis healthcare facilities.
This study was supported by WHO AFRO/TDR/EDCTP (2019/893,805) and Deutsches Zentrum für Infektiologie (DZIF/ TTU 02.812).
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The early epidemiology of the 2022 monkeypox epidemic in non-endemic countries differs substantially from the epidemiology previously reported from endemic countries. We aimed to describe the ...epidemiological and clinical characteristics among individuals with confirmed cases of monkeypox infection.
We descriptively analysed data for patients with confirmed monkeypox who were included in the GeoSentinel global clinical-care-based surveillance system between May 1 and July 1 2022, across 71 clinical sites in 29 countries. Data collected included demographics, travel history including mass gathering attendance, smallpox vaccination history, social history, sexual history, monkeypox exposure history, medical history, clinical presentation, physical examination, testing results, treatment, and outcomes. We did descriptive analyses of epidemiology and subanalyses of patients with and without HIV, patients with CD4 counts of less than 500 cells per mm3 or 500 cells per mm3 and higher, patients with one sexual partner or ten or more sexual partners, and patients with or without a previous smallpox vaccination.
226 cases were reported at 18 sites in 15 countries. Of 211 men for whom data were available, 208 (99%) were gay, bisexual, or men who have sex with men (MSM) with a median age of 37 years (range 18–68; IQR 32–43). Of 209 patients for whom HIV status was known, 92 (44%) men had HIV infection with a median CD4 count of 713 cells per mm3 (range 36–1659; IQR 500–885). Of 219 patients for whom data were available, 216 (99%) reported sexual or close intimate contact in the 21 days before symptom onset; MSM reported a median of three partners (IQR 1–8). Of 195 patients for whom data were available, 78 (40%) reported close contact with someone who had confirmed monkeypox. Overall, 30 (13%) of 226 patients were admitted to hospital; 16 (53%) of whom had severe illness, defined as hospital admission for clinical care rather than infection control. No deaths were reported. Compared with patients without HIV, patients with HIV were more likely to have diarrhoea (p=0·002), perianal rash or lesions (p=0·03), and a higher rash burden (median rash burden score 9 IQR 6–21 for patients with HIV vs median rash burden score 6 IQR 3–14 for patients without HIV; p<0·0001), but no differences were identified in the proportion of men who had severe illness by HIV status.
Clinical manifestations of monkeypox infection differed by HIV status. Recommendations should be expanded to include pre-exposure monkeypox vaccination of groups at high risk of infection who plan to engage in sexual or close intimate contact.
US Centers for Disease Control and Prevention, International Society of Travel Medicine.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recently, following import by travel and migration, epidemic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has caused nosocomial outbreaks in Europe, sometimes with a ...fatal outcome. We describe clinico-epidemiological characteristics of CA-MRSA detected by the European Network for the Surveillance of imported S. aureus (www.staphtrav.eu) from May 2011 to November 2016.
Sentinel surveillance at 13 travel clinics enrolling patients with travel-associated skin and soft-tissue infection (SSTI) and analysing lesion and nose swabs at one central laboratory.
A total of 564 independent case-patients with SSTI were enrolled and had 374 (67%) S. aureus-positive lesions, of which 14% (51/374) were MRSA. The majority of CA-MRSA isolates from SSTI were Panton–Valentine leucocidin (PVL) -positive (43/51, 84%). The risk of methicillin-resistance in imported S. aureus varied by travel region (p <0.001) and was highest in Latin America (16/57, 28%, 95% CI 17.0–41.5) and lowest in Sub-Saharan Africa (4/121, 3%, 95% CI 0.9–8.3). Major epidemic clones (USA300 / USA300 Latin-American Variant, Bengal Bay, South Pacific) accounted for more than one-third (19/51, 37%) of CA-MRSA imports. CA-MRSA SSTI in returnees was complicated (31/51 multiple lesions, 61%; 22/50 recurrences, 44%), led to health-care contact (22/51 surgical drainage, 43%; 7/50 hospitalization, 14%), was transmissible (13/47 reported similar SSTI in non-travelling contacts, 28%), and associated with S. aureus nasal colonization (28 of 51 CA-MRSA cases, 55%; 24 of 28 colonized with identical spa-type in nose and lesion, 85%).
Travel-associated CA-MRSA SSTI is a transmissible condition that leads to medical consultations and colonization of the infected host.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To investigate the global occurrence of trimethoprim–sulfamethoxazole resistance and the genetic mechanisms of trimethoprim resistance, we analysed Staphylococcus aureus from travel-associated skin ...and soft-tissue infections treated at 13 travel clinics in Europe. Thirty-eight per cent (75/196) were trimethoprim-resistant and 21% (41/196) were resistant to trimethoprim–sulfamethoxazole. Among methicillin-resistant S. aureus, these proportions were 30% (7/23) and 17% (4/23), respectively. DfrG explained 92% (69/75) of all trimethoprim resistance in S. aureus. Travel to South Asia was associated with the highest risk of acquiring trimethoprim–sulfamethoxazole-resistant S. aureus. We conclude that globally dfrG is the predominant determinant of trimethoprim resistance in human S. aureus infection.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
