A considerable amount of disease is transmitted from animals to humans and many of these zoonoses are neglected tropical diseases. As outbreaks of SARS, avian influenza and Ebola have demonstrated, ...however, zoonotic diseases are serious threats to global public health and are not just problems confined to remote regions. There are two fundamental, and poorly studied, stages of zoonotic disease emergence: 'spillover', i.e. transmission of pathogens from animals to humans, and 'stuttering transmission', i.e. when limited human-to-human infections occur, leading to self-limiting chains of transmission. We developed a transparent, theoretical framework, based on a generalization of Poisson processes with memory of past human infections, that unifies these stages. Once we have quantified pathogen dynamics in the reservoir, with some knowledge of the mechanism of contact, the approach provides a tool to estimate the likelihood of spillover events. Comparisons with independent agent-based models demonstrates the ability of the framework to correctly estimate the relative contributions of human-to-human vs animal transmission. As an illustrative example, we applied our model to Lassa fever, a rodent-borne, viral haemorrhagic disease common in West Africa, for which data on human outbreaks were available. The approach developed here is general and applicable to a range of zoonoses. This kind of methodology is of crucial importance for the scientific, medical and public health communities working at the interface between animal and human diseases to assess the risk associated with the disease and to plan intervention and appropriate control measures. The Lassa case study revealed important knowledge gaps, and opportunities, arising from limited knowledge of the temporal patterns in reporting, abundance of and infection prevalence in, the host reservoir.
Diabetes is currently a crisis in sub-Saharan West Africa (SSWA) with dramatic implications for public health and national budgets prioritizing infectious diseases. There is limited recent literature ...about the prevalence, awareness, and risk factors for type 2 diabetes (T2D) in rural parts of SSWA. This study characterized T2D prevalence and risk factors for the rural Malian community of Nièna, which is situated in Mali's second-largest province of Sikasso. Between December 2020 and July 2021, a cross-sectional study of 412 participants was conducted in the Nièna community using clinical questionnaires and rapid diagnostic tests. Among 412 participants, there were 143 (34.7%) and 269 (65.3%) males and females, respectively. The overall prevalence of T2D in Nièna was 7.5% (31/412), and prevalence rates were 8.6% (23/269) and 5.6% (8/143) for females and males, respectively. Age, family history of diabetes, hypertension, waist circumference, and fetal macrosomia were significantly associated with T2D (p = 0.007, p < 0.001, p = 0.003, p = 0.013, and p < 0.001, respectively). Notably, 61.3% (19/31) of T2D subjects were unaware of their diabetic status before the study. Field surveys have considerable utility in driving T2D awareness in rural African settings.
Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to ...transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions.
Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost Formula: see text of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals ('super-spreaders'), as we found only Formula: see text of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) Formula: see text, with a maximum value up to Formula: see text.
This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.
Metabolic syndrome is known to predict outcomes in COVID-19 acute respiratory distress syndrome (ARDS) but has never been studied in non-COVID-19 ARDS. We therefore aimed to determine the association ...of metabolic syndrome with mortality among ARDS trial subjects.
Retrospective cohort study of ARDS trials' data.
An ancillary analysis was conducted using data from seven ARDS Network and Prevention and Early Treatment of Acute Lung Injury Network randomized trials within the Biologic Specimen and Data Repository Information Coordinating Center database.
Hospitalized patients with ARDS and metabolic syndrome (defined by obesity, diabetes, and hypertension) were compared with similar patients without metabolic syndrome (those with less than three criteria).
None.
The primary outcome was 28-day mortality. Among 4288 ARDS trial participants, 454 (10.6%) with metabolic syndrome were compared with 3834 controls (89.4%). In adjusted analyses, the metabolic syndrome group was associated with lower 28-day and 90-day mortality when compared with control (adjusted odds ratio aOR, 0.70 95% CI, 0.55-0.89 and 0.75 95% CI, 0.60-0.95, respectively). With each additional metabolic criterion from 0 to 3, adjusted 28-day mortality was reduced by 18%, 22%, and 40%, respectively. In subgroup analyses stratifying by ARDS etiology, mortality was lower for metabolic syndrome vs. control in ARDS caused by sepsis or pneumonia (at 28 d, aOR 0.64 95% CI, 0.48-0.84 and 90 d, aOR 0.69 95% CI, 0.53-0.89), but not in ARDS from noninfectious causes (at 28 d, aOR 1.18 95% CI, 0.70-1.99 and 90 d, aOR 1.26 95% CI, 0.77-2.06). Interaction p = 0.04 and p = 0.02 for 28- and 90-day comparisons, respectively.
Metabolic syndrome in ARDS was associated with a lower risk of mortality in non-COVID-19 ARDS. The relationship between metabolic inflammation and ARDS may provide a novel biological pathway to be explored in precision medicine-based trials.
Background The West African Ebola epidemic of 2013-2016 killed nearly 4,000 Sierra Leoneans and devastated health infrastructure across West Africa. Changes in health seeking behavior (HSB) during ...the outbreak resulted in dramatic underreporting and substantial declines in hospital presentations to public health facilities, resulting in an estimated tens of thousands of additional maternal, infant, and adult deaths per year. Sierra Leone's Kenema District, a major Ebola hotspot, is also endemic for Lassa fever (LF), another often-fatal hemorrhagic disease. Here we assess the impact of the West African Ebola epidemic on health seeking behaviors with respect to presentations to the Kenema Government Hospital (KGH) Lassa Ward, which serves as the primary health care referral center for suspected Lassa fever cases in the Eastern Province of Sierra Leone. Methodology/Principal findings Presentation frequencies for suspected Lassa fever presenting to KGH or one of its referral centers from 2011-2019 were analyzed to consider the potential impact of the West African Ebola epidemic on presentation patterns. There was a significant decline in suspected LF cases presenting to KGH following the epidemic, and a lower percentage of subjects were admitted to the KGH Lassa Ward following the epidemic. To assess general HSB, a questionnaire was developed and administered to 200 residents from 8 villages in Kenema District. Among 194 completed interviews, 151 (78%) of respondents stated they felt hospitals were safer post-epidemic with no significant differences noted among subjects according to religious background, age, gender, or education. However, 37 (19%) subjects reported decreased attendance at hospitals since the epidemic, which suggests that trust in the healthcare system has not fully rebounded. Cost was identified as a major deterrent to seeking healthcare. Conclusions/Significance Analysis of patient demographic data suggests that fewer individuals sought care for Lassa fever and other febrile illnesses in Kenema District after the West African Ebola epidemic. Re-establishing trust in health care services will require efforts beyond rebuilding infrastructure and require concerted efforts to rebuild the trust of local residents who may be wary of seeking healthcare post epidemic.
•We present the first data derived from audiometric exams of Lassa fever survivors.•17% of Lassa fever survivors reported hearing loss.•Bilateral hearing loss was most common among Lassa fever ...survivors.
Lassa fever (LF) a hemorrhagic fever endemic to Western has an incidence of approximately 500,000 cases per year. Here, we evaluate hearing loss and other sequelae following LF.
This case-control study enrolled laboratory confirmed LF survivors, non-LF Febrile controls and Matched Community controls with no history of LF or recent hospitalization for a febrile illness.
Study participants completed a symptom questionnaire. Pure-tone audiometry was completed by a subset of participants.
One hundred forty-seven subjects were enrolled aged from 3-66 years (mean = 23.3). LF survivors were significantly more likely to report balance difficulties (55% vs 20%, p < 0.001), hair loss (32% vs 7%, p < 0.001), difficulty speaking (19% vs 1%, p < 0.001), social isolation (50% vs 0%, p < 0.001), and hearing loss (17% vs 1%, p = 0.002) in comparison to Matched-Community Controls. Similar trends were noted in comparison to Febrile Controls, although these findings were non-significant. Fifty subjects completed audiometry. Audiometry found that LF survivors had significantly more bilateral hearing loss in comparison to Matched-Community Controls (30% vs 4%, p = 0.029).
This study characterizes the sequelae of LF and highlights the need for increased access to hearing care in West Africa.
Lassa fever is a viral hemorrhagic illness with a case fatality rate for hospitalized patients as high as 69%. Identifying cases before they progress to serious illness can lead to earlier treatment ...and improved clinical outcomes. Three existing clinical prediction tools were evaluated on their ability to predict the in-hospital mortality in Lassa fever: the quick Sequential Organ Failure Assessment (qSOFA), the Modified Early Warning System (MEWS), and the Universal Vital Assessment (UVA). This was a retrospective cohort study of patients admitted to the dedicated Lassa fever ward of the Kenema Government Hospital in Sierra Leone between May 2013 and December 2019. Data among three serology groups were analyzed: Lassa antigen-positive (Ag+) regardless of IgM status, Lassa Ag- and IgM+, and Lassa Ag- and IgM- cases. There were 123 cases of suspected Lassa fever included in this study. Abnormalities in respiratory rate, oxygenation status, mental status, and serum markers of kidney and liver dysfunction were more likely seen in the Ag+ group, which had an in-hospital mortality of 85.7%. For the Lassa Ag+ group, the sensitivity and positive predictive value of qSOFA ≥ 2 was 70.6% and 92.3%, MEWS ≥ 5 was 96.9% and 86.1%, and UVA ≥ 5 was 60.0% and 100.0%. The MEWS and UVA scores show potential for use in Lassa fever, but there is opportunity for future development of a tool that includes the clinical and laboratory markers specific to Lassa fever.
The quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score has not been well-evaluated in low- and middle-income countries (LMICs).
To assess the association of qSOFA with excess ...hospital death among patients with suspected infection in LMICs and to compare qSOFA with the systemic inflammatory response syndrome (SIRS) criteria.
Retrospective secondary analysis of 8 cohort studies and 1 randomized clinical trial from 2003 to 2017. This study included 6569 hospitalized adults with suspected infection in emergency departments, inpatient wards, and intensive care units of 17 hospitals in 10 LMICs across sub-Saharan Africa, Asia, and the Americas.
Low (0), moderate (1), or high (≥2) qSOFA score (range, 0 best to 3 worst) or SIRS criteria (range, 0 best to 4 worst) within 24 hours of presentation to study hospital.
Predictive validity (measured as incremental hospital mortality beyond that predicted by baseline risk factors, as a marker of sepsis or analogous severe infectious course) of the qSOFA score (primary) and SIRS criteria (secondary).
The cohorts were diverse in enrollment criteria, demographics (median ages, 29-54 years; males range, 36%-76%), HIV prevalence (range, 2%-43%), cause of infection, and hospital mortality (range, 1%-39%). Among 6218 patients with nonmissing outcome status in the combined cohort, 643 (10%) died. Compared with a low or moderate score, a high qSOFA score was associated with increased risk of death overall (19% vs 6%; difference, 13% 95% CI, 11%-14%; odds ratio, 3.6 95% CI, 3.0-4.2) and across cohorts (P < .05 for 8 of 9 cohorts). Compared with a low qSOFA score, a moderate qSOFA score was also associated with increased risk of death overall (8% vs 3%; difference, 5% 95% CI, 4%-6%; odds ratio, 2.8 95% CI, 2.0-3.9), but not in every cohort (P < .05 in 2 of 7 cohorts). High, vs low or moderate, SIRS criteria were associated with a smaller increase in risk of death overall (13% vs 8%; difference, 5% 95% CI, 3%-6%; odds ratio, 1.7 95% CI, 1.4-2.0) and across cohorts (P < .05 for 4 of 9 cohorts). qSOFA discrimination (area under the receiver operating characteristic curve AUROC, 0.70 95% CI, 0.68-0.72) was superior to that of both the baseline model (AUROC, 0.56 95% CI, 0.53-0.58; P < .001) and SIRS (AUROC, 0.59 95% CI, 0.57-0.62; P < .001).
When assessed among hospitalized adults with suspected infection in 9 LMIC cohorts, the qSOFA score identified infected patients at risk of death beyond that explained by baseline factors. However, the predictive validity varied among cohorts and settings, and further research is needed to better understand potential generalizability.
Situated in southeastern Sierra Leone, Kenema Government Hospital (KGH) maintains one of the world's only Lassa fever isolation wards and was a strategic Ebola virus disease (EVD) treatment facility ...during the 2014 EVD outbreak. Since 2006, the Viral Hemorrhagic Fever Consortium (VHFC) has carried out research activities at KGH, capturing clinical and laboratory data for suspected cases of Lassa fever. Here we describe the approach, progress, and challenges in designing and maintaining a data capture and management system (DCMS) at KGH to assist infectious disease researchers in building and sustaining DCMS in low-resource environments. Results on screening patterns and case-fatality rates are provided to illustrate the context and scope of the DCMS covered in this study. A medical records system and DCMS was designed and implemented between 2010 and 2016 linking historical and prospective Lassa fever data sources across KGH Lassa fever units and its peripheral health units. Data were captured using a case report form (CRF) system, enzyme-linked immunosorbent assay (ELISA) plate readers, polymerase chain reaction (PCR) machines, blood chemistry analyzers, and data auditing procedures. Between 2008 and 2016, blood samples for 4,229 suspected Lassa fever cases were screened at KGH, ranging from 219 samples in 2008 to a peak of 760 samples in 2011. Lassa fever case-fatality rates before and following the Ebola outbreak were 65.5% (148/226) and 89.5% (17/19), respectively, suggesting that fewer, but more seriously ill subjects with Lassa fever presented to KGH following the 2014 EVD outbreak (p = .040). DCMS challenges included weak specificity of the Lassa fever suspected case definition, limited capture of patient survival outcome data, internet costs, lapses in internet connectivity, low bandwidth, equipment and software maintenance, lack of computer teaching laboratories, and workload fluctuations due to variable screening activity. DCMS are the backbone of international research efforts and additional literature is needed on the topic for establishing benchmarks and driving goal-based approaches for its advancement in developing countries.
Peri-operative dexamethasone has been shown to effectively reduce post-operative nausea and vomiting and aide in analgesia after total joint arthroplasty (TJA); however, systemic glucocorticoid ...therapy has many adverse effects. The purpose of this study is to determine the effects of dexamethasone on prosthetic joint infection (PJI) and blood glucose levels in patients undergoing TJA.
A retrospective chart review of all patients receiving primary TJA from 2011 to 2015 (n = 2317) was conducted. Patients were divided into 2 cohorts: dexamethasone (n = 1426) and no dexamethasone (n = 891); these groups were subdivided into diabetic and non-diabetic patients. The primary outcome was PJI; secondary measures included glucose levels and pre-operative hemoglobin A1c (A1c) values. Statistics were carried out using logistic and regression models.
Of the 2317 joints, 1.12% developed PJI; this was not affected by dexamethasone (P = .166). Diabetics were found to have higher rate of infection (P < .001); however, diabetics who received dexamethasone were not found to have a significantly higher infection rate that non-diabetics (P = .646). Blood glucose levels were found to increase post-operatively, and dexamethasone did not increase this change (P = .537). Diabetes (P < .001) and increasing hemoglobin A1c (P < .001) were also associated with increased serum glucose levels; however, this was not influenced by dexamethasone (P = .595).
Although diabetic patients were found to have a higher infection rate overall, this was not affected by administration of intravenous dexamethasone, nor was the post-operative elevation in serum glucose levels. In this study population, peri-operative intravenous dexamethasone did not increase the rate of PJI and was safe to administer in patients undergoing TJA.
PDF
