Characteristics and One Year Outcomes of Melioidosis Patients in Northeastern Thailand: A Prospective, Multicenter Cohort Study.

Background: Melioidosis is a neglected tropical infection caused by the environmental saprophyte Burkholderia pseudomallei. Methods: We conducted a prospective, observational study at nine hospitals in northeastern Thailand, a hyperendemic melioidosis zone, to define current characteristics of melioidosis patients and quantify outcomes over one year. Findings: 2574 individuals hospitalised with culture-confirmed melioidosis were screened and 1352 patients were analysed. The median age was 55 years, 975 (72%) were male, and 951 (70%) had diabetes. 565 (42%) patients presented with lung infection, 1042 (77%) were bacteremic, 442 (33%) received vasopressors/inotropes and 547 (40%) received mechanical ventilation. 1307 (97%) received an intravenous antibiotic against B. pseudomallei. 335/1345 (25%) patients died within one month and 448/1322 (34%) of patients died within one year. Most patients had risk factors for melioidosis, but patients without identified risk factors did not have a reduced risk of death. Of patients discharged alive, most received oral trimethoprim-sulfamethoxazole, which was associated with decreased risk of post-discharge death; 235/970 (24%) were readmitted, and 874/1015 (86%) survived to one year. Recurrent infection was detected in 17/994 patients (2%). Patients with risk factors other than diabetes had increased risk of death and increased risk of hospital readmission. Interpretation: In northeastern Thailand patients with melioidosis experience high rates of bacteremia, organ failure and death. Most patients discharged alive survive one year although all-cause readmission is common. Recurrent disease is rare. Strategies that emphasize prevention, rapid diagnosis and intensification of early clinical management are likely to have greatest impact in this and other resource-restricted regions. Funding: US NIH/NIAID U01AI115520.

Two success stories in the management of Guillain-Barré syndrome illustrate the challenges of intensive care unit care in Malawi.

The management of critical illness is especially challenging in low-resource environments, and early recognition and supportive care are essential, regardless of the ability to employ advanced or invasive therapy. In this report, we discuss two patients with Guillain-Barré syndrome who were managed successfully in the intensive care unit of a tertiary hospital in Malawi. Both patients recovered and were discharged home. The management and outcomes of these patients provide case-based lessons for improving intensive care unit medicine in low-resource contexts.

Prevalence, Etiology, and Outcome of Sepsis among Critically Ill Patients in Malawi.

There are scarce data describing the etiology and clinical sequelae of sepsis in low- and middle-income countries (LMICs). This study describes the prevalence and etiology of sepsis among critically ill patients at a referral hospital in Malawi. We conducted an observational prospective cohort study of adults admitted to the intensive care unit or high-dependency unit (HDU) from January 29, 2018 to March 15, 2018. We stratified the cohort based on the prevalence of sepsis as defined in the following three ways: quick sequential organ failure assessment (qSOFA) score ≥ 2, clinical suspicion of systemic infection, and qSOFA score ≥ 2 plus suspected systemic infection. We measured clinical characteristics and blood and urine cultures for all patients; antimicrobial sensitivities were assessed for positive cultures. During the study period, 103 patients were admitted and 76 patients were analyzed. The cohort comprised 39% male, and the median age was 30 (interquartile range: 23-40) years. Eighteen (24%), 50 (66%), and 12 patients (16%) had sepsis based on the three definitions, respectively. Four blood cultures (5%) were positive, two from patients with sepsis by all three definitions and two from patients with clinically suspected infection only. All blood bacterial isolates were multidrug resistant. Of five patients with urinary tract infection, three had sepsis secondary to multidrug-resistant bacteria. Hospital mortality for patients with sepsis based on the three definitions ranged from 42% to 75% versus 12% to 26% for non-septic patients. In summary, mortality associated with sepsis at this Malawi hospital is high. Bacteremia was infrequently detected, but isolated pathogens were multidrug resistant.

Treating Neonatal Abstinence Syndrome in a Rural Hospital: Lessons Learned.

OBJECTIVE: Our level 1 nursery and pediatric unit in a rural hospital adopted a family-centered, symptom-based oral morphine weaning protocol for neonatal abstinence syndrome (NAS) in 2009. Length of stay (LOS), treatment duration (TD), and hospital charges for infants treated for NAS were then compared to published data in neonatal intensive care units (NICUs) nationwide. METHODS: The electronic medical records of infants born January 1, 2011, to April 1, 2017, whose discharge diagnosis included an ICD-9 or ICD-10 code for NAS or prenatal drug exposure were paired with maternal electronic medical record and reviewed. TD was calculated by subtracting the last day morphine was provided from the day it was started, and LOS was calculated by subtracting the discharge date from the date of birth. Infant characteristics, maximum Finnegan score, breastfeeding, discharge disposition, maternal demographics, prenatal use of drugs or medications, and toxicology results were abstracted. Predictors of TD and LOS were analyzed, and hospital charges were enumerated. RESULTS: Chart review identified 167 infants with prenatal drug exposure, 33 of whom were treated for NAS. Median TD for infants with NAS was 18 days (range, 9-37 days) compared to 15 days (range, 9-25 days) in NICUs. Median LOS for infants treated for NAS was 22 days (range, 12-41 days) compared to 20 days (range, 12-32 days) in NICUs, but hospital charges were less. Maternal prenatal use of cocaine (P = .016) predicted LOS. CONCLUSIONS: Family-centered NAS treatment in a rural hospital lasted 2 to 3 days longer than in NICUs, largely as a result of social issues; however, hospital charges were less.

TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice.

Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3-4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.