Background Typhoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public-health threat in sub-Saharan Africa. We present phase 3 efficacy data from an African trial of a Vi-polysaccharide typhoid conjugate vaccine (Vi-TCV). Methods Children aged 9 months to 12 years in Blantyre, Malawi were randomized (1:1) in a double-blind trial to receive Vi-TCV (single dose) or group-A meningococcal control vaccine (MenA).The primary outcome was blood culture-confirmed typhoid fever. We present the primary vaccine efficacy (VE) and safety outcomes after 18–24 months of follow-up. Results This intention-to-treat (ITT) analysis included 28,130 children, comprising 14,069 children who received Vi-TCV and 14,061 children who received MenA. Blood culture-confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 per 100,000 person-years) and 62 children in the MenA group (243 per 100,000 person-years). Overall VE was 80.7% (95% confidence interval (CI): 64.2% to 89.6%) in an ITT analysis, and 83.7% (95% CI: 68.1%−91.6%) in a per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in Vi-TCV group and 78 in MenA group), including 6 deaths (all in MenA group). No serious adverse event was considered by the investigator as related to study vaccination. Conclusions Vi-TCV reduced blood culture-confirmed typhoid fever among Malawian children aged 9 months to 12 years. (Funded by the Bill & Melinda Gates Foundation; ClinicalTrials.gov number NCT03299426 .)

Background Non-typhoidal salmonella can cause serious, life-threatening invasive infections involving the bloodstream and other normally sterile sites. We aimed to systematically review the prevalence of complications and case-fatality ratio (CFR) of non-typhoidal salmonella invasive disease to provide contemporary global estimates and inform the development of vaccine and non-vaccine interventions. MethodsWe did a global systematic review and meta-analysis of studies investigating the complications and mortality associated with non-typhoidal salmonella invasive disease. We searched Embase, MEDLINE, Web of Science, and PubMed for peer-reviewed, primary research articles published from database inception up to June 4, 2021, with no restrictions on language, country, date, or participant demographics. Only studies reporting the proportion of complications or deaths associated with non-typhoidal salmonella invasive disease, confirmed by culture of samples taken from a normally sterile site (eg, blood or bone marrow) were included. We excluded case reports, case series, policy reports, commentaries, editorials, and conference abstracts. Data on the prevalence of complications and CFR were abstracted. The primary outcomes were to estimate the prevalence of complications and CFR of non-typhoidal salmonella invasive disease. We calculated an overall pooled CFR estimate and pooled CFR stratified by UN region, subregion, age group, and by serovar when available with a random-effects meta-analysis. A risk-of-bias assessment was done, and heterogeneity was assessed with Cochran's Q Test, I², and τ². This study was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and is registered with PROSPERO, CRD42020202293. FindingsThe systematic review returned a total of 8770 records. After duplicates were removed, 5837 titles and abstracts were screened, yielding 84 studies from 35 countries after exclusions. Of these included studies, 77 (91•7%) were hospital-based and 66 (78•6%) were located in Africa or Asia. Among 55 studies reporting non-typhoidal salmonella disease-associated complications, a total of 45 different complications were reported and 1824 complication events were identified among 6974 study participants. The most prevalent complication was septicaemia, occurring in 171 (57•2%) of 299 participants, followed by anaemia in 580 (47•3%) of 1225 participants. From 81 studies reporting the CFR of non-typhoidal salmonella invasive disease, the overall pooled CFR estimate was 14•7% (95% CI 12•2-17•3). When stratified by UN region, the pooled CFR was 17•1% (13•6-21•0) in Africa, 14•0% (9•4-19•4) in Asia, 9•9% (6•4-14•0) in Europe, and 9•6% (0•0-25•1) in the Americas. Of all 84 studies, 66 (78•6%) had an overall high risk of bias, 18 (21•4%) had a moderate risk, and none had a low risk. Substantial heterogeneity (I²>80%) was observed in most (15 [65•2%] of 23) CFR estimates. Interpretation Complications were frequent among individuals with non-typhoidal salmonella invasive disease ...

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Background Typhoid fever incidence and complications, including intestinal perforation, have declined significantly in high-income countries, with mortality rates \1%. However, an estimated 10.9 million cases still occur annually, most in low-and middle-income countries. With the availability of a new typhoid conjugate vaccine licensed for children and recommended by the World Health Organization, understanding severe complications, including associated mortality rates, is essential to inform country-level decisions on introduction of this vaccine. This scoping review summarizes over 20 years of the literature on typhoid intestinal perforation in sub-Saharan Africa. Methods We searched EMBASE, PubMed, Medline, and Cochrane databases for studies reporting mortality rates due to typhoid intestinal perforation in children, under 18 years old, in sub-Saharan Africa published from January 1995 through June 2019. Results Twenty-four papers from six countries were included. Reported mortality rates ranged from 4.6-75%, with 16 of the 24 studies between 11 and 30%. Thirteen papers included postoperative morbidity rates, ranging from 16-100%. The most documented complications included surgical site infections, intra-abdominal abscesses, and enterocutaneous fistulas. High mortality rates can be attributed to late presentation to tertiary centers, sepsis and electrolyte abnormalities requiring preoperative resuscitation, prolonged perforation-to-surgery interval, and lack of access to critical care or an intensive care unit postoperatively. Conclusions Current estimates of mortality related to typhoid intestinal perforation among children in sub-Saharan Africa remain unacceptably high. Prevention of typhoid fever is essential to reduce mortality, with the ultimate goal of a comprehensive approach that utilizes vaccination, improvements in water, sanitation, and hygiene, and greater access to surgical care.

The disease burden of typhoid fever remains high in endemic areas in Asia and Africa, especially in children. Recent clinical trials conducted by the Typhoid Vaccine Acceleration Consortium show typhoid conjugate vaccine (TCV) to be safe, immunogenic, and efficacious at preventing blood culture-confirmed typhoid fever in African and Asian children. Pakistan, Liberia, and Zimbabwe recently introduced TCV through campaigns and routine childhood immunizations, providing protection for this vulnerable population. It is essential to continue this momentum while simultaneously filling data gaps – including typhoid complications – to inform decision-making on TCV introduction. A multidisciplinary approach including surveillance, water, sanitation, and hygiene investments, and large-scale TCV introduction is needed to decrease the burden and mortality of typhoid fever.

The use of umbilical artery catheters is common in Neonatal Intensive Care Units, especially in low and very low birth weight neonates. Rarely, these can break or fracture, leading to a retained fragment, which can embolize or cause thrombosis. We pre sent a case of a very low birth weight, premature neonate, 940 grams, with a retained umbilical artery catheter that led to bilateral lower extremity ischemia. A laparotomy with aortotomy was per formed for retrieval of the catheter. Chronic occlusion of the aorta with collateralization is a long-term complication associated with this case.

No abstract

No abstract