Clinical presentation and aetiologies of acute or complicated headache among HIV-seropositive patients in a Ugandan clinic

<p>Abstract</p> <p>Background</p> <p>We set out to define the relative prevalence and common presentations of the various aetiologies of headache within an ambulant HIV-seropositive adult population in Kampala, Uganda.</p> <p>Methods</p> <p>We conducted a prospective study of adult HIV-1-seropositive ambulatory patients consecutively presenting with new onset headaches. Patients were classified as focal-febrile, focal-afebrile, non-focal-febrile or non-focal-afebrile, depending on presence or absence of fever and localizing neurological signs. Further management followed along a pre-defined diagnostic algorithm to an endpoint of a diagnosis. We assessed outcomes during four months of follow up.</p> <p>Results</p> <p>One hundred and eighty patients were enrolled (72% women). Most subjects presented at WHO clinical stages III and IV of HIV disease, with a median Karnofsky performance rating of 70% (IQR 60-80).</p> <p>The most common diagnoses were cryptococcal meningitis (28%, n = 50) and bacterial sinusitis (31%, n = 56). Less frequent diagnoses included cerebral toxoplasmosis (4%, n = 7), and tuberculous meningitis (4%, n = 7). Thirty-two (18%) had other diagnoses (malaria, bacteraemia, etc.). No aetiology could be elucidated in 28 persons (15%). Overall mortality was 13.3% (24 of 180) after four months of follow up. Those without an established headache aetiology had good clinical outcomes, with only one death (4% mortality), and 86% were ambulatory at four months.</p> <p>Conclusion</p> <p>In an African HIV-infected ambulatory population presenting with new onset headache, aetiology was found in at least 70%. Cryptococcal meningitis and sinusitis accounted for more than half of the cases.</p

Vaccine value profile for Klebsiella pneumoniae

Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91–1.71) and 4.95 million (95% UI: 3.62–6.57) deaths were attributed to and associated with bacterial antimicrobial resistance (AMR), respectively. K. pneumoniae was the second leading pathogen in deaths attributed to AMR resistant bacteria. Furthermore, the rise of antimicrobial resistance in both community- and hospital-acquired infections is a concern for neonates and infants who are at high risk for invasive bacterial disease. There is a limited antibiotic pipeline for new antibiotics to treat multidrug resistant infections, and vaccines targeted against K. pneumoniae are considered to be of priority by the World Health Organization. Vaccination of pregnant women against K. pneumoniae could reduce the risk of invasive K. pneumoniae disease in their young offspring. In addition, vulnerable children, adolescents and adult populations at risk of K. pneumoniae disease with underlying diseases such as immunosuppression from underlying hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management are also potential target groups for a K. pneumoniae vaccine. A ‘Vaccine Value Profile’ (VVP) for K. pneumoniae, which contemplates vaccination of pregnant women to protect their babies from birth through to at least three months of age and other high-risk populations, provides a high-level, holistic assessment of the available information to inform the potential public health, economic and societal value of a pipeline of K. pneumoniae vaccines and other preventatives and therapeutics. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public–private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the WHO. All contributors have extensive expertise on various elements of the K. pneumoniae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information

Mapping the medical outcomes study HIV health survey (MOS-HIV) to the EuroQoL 5 Dimension (EQ-5D-3L) utility index

10.1186/s12955-019-1135-8Health and Quality of Life Outcomes1718

First-line antiretroviral therapy in Africa; how evidence-based are our recommendations?

According to the World Health Organization guidelines, a non-nucleoside reverse transcriptase inhibitor (NNRTI) along with two nucleoside reverse transcriptase inhibitors (NRTI) is the treatment of choice as first-line antiretroviral therapy. The results of the 2NN and different cohort studies performed in developed countries do not provide sufficient evidence by which to select between nevirapine and efavirenz as the first-line NNRTI for antiretroviral therapy in Africa. The current first-line NNRTI-containing antiretroviral therapy regimens used in Africa are certainly not ideal. Nevirapine interacts with rifampicin and therefore is not indicated in patients with tuberculosis. On the other hand, efavirenz should not be given to pregnant women. NNRTI-containing regimens may be less effective in women who received nevirapine monotherapy at delivery. Stavudine, used in the nucleoside backbone, may lead to lipoatrophy, lactic acidosis and polyneuritis. Zidovudine may cause serious anemia. Mainly because of cost considerations, the generic fixed-drug combination of nevirapine plus two NRTI seems at the moment to be the best choice. It is clear, however, that antiretroviral programs should not rely only on this combination for initial antiretroviral treatment. Most importantly, more HIV clinical trials need to be conducted in Africa, and African cohorts of patients on antiretroviral therapy need to be established in order to develop recommendations that are evidence based

Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in children and adolescents in Africa: A randomised, placebo-controlled, multicentre Phase II clinical trial

International audienceBackground : Reoccurring Ebola outbreaks in West and Central Africa have led to serious illness and death in thousands of adults and children. The objective of this study was to assess safety, tolerability, and immunogenicity of the heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimen in adolescents and children in Africa. Methods and findings : In this multicentre, randomised, observer-blind, placebo-controlled Phase II study, 131 adolescents (12 to 17 years old) and 132 children (4 to 11 years old) were enrolled from Eastern and Western Africa and randomised 5:1 to receive study vaccines or placebo. Vaccine groups received intramuscular injections of Ad26.ZEBOV (5 × 10 10 viral particles) and MVA-BN-Filo (1 × 10 8 infectious units) 28 or 56 days apart; placebo recipients received saline. Primary outcomes were safety and tolerability. Solicited adverse events (AEs) were recorded until 7 days after each vaccination and serious AEs (SAEs) throughout the study. Secondary and exploratory outcomes were humoral immune responses (binding and neutralising Ebola virus [EBOV] glycoprotein [GP]-specific antibodies), up to 1 year after the first dose. Enrolment began on February 26, 2016, and the date of last participant last visit was November 28, 2018. Of the 263 participants enrolled, 217 (109 adolescents, 108 children) received the 2-dose regimen, and 43 (20 adolescents, 23 children) received 2 placebo doses. Median age was 14.0 (range 11 to 17) and 7.0 (range 4 to 11) years for adolescents and children, respectively. Fifty-four percent of the adolescents and 51% of the children were male. All participants were Africans, and, although there was a slight male preponderance overall, the groups were well balanced. No vaccine-related SAEs were reported; solicited AEs were mostly mild/moderate. Twenty-one days post-MVA-BN-Filo vaccination, binding antibody responses against EBOV GP were observed in 100% of vaccinees (106 adolescents, 104 children). Geometric mean concentrations tended to be higher after the 56-day interval (adolescents 13,532 ELISA units [EU]/mL, children 17,388 EU/mL) than the 28-day interval (adolescents 6,993 EU/mL, children 8,007 EU/mL). Humoral responses persisted at least up to Day 365. A limitation of the study is that the follow-up period was limited to 365 days for the majority of the participants, and so it was not possible to determine whether immune responses persisted beyond this time period. Additionally, formal statistical comparisons were not preplanned but were only performed post hoc. Conclusions : The heterologous 2-dose vaccination was well tolerated in African adolescents and children with no vaccine-related SAEs. All vaccinees displayed anti-EBOV GP antibodies after the 2-dose regimen, with higher responses in the 56-day interval groups. The frequency of pyrexia after vaccine or placebo was higher in children than in adolescents. These data supported the prophylactic indication against EBOV disease in a paediatric population, as licenced in the EU. Trial registration : ClinicalTrials.gov NCT02564523