Relationship Between Viremia and Specific Organ Damage in Ebola Patients: A Cohort Study.

Background: Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant determination of routine laboratory biomarkers and Ebola viremia to explore the potential role of viral replication in specific organ damage. Methods: We recruited patients with detectable Ebola viremia admitted to the EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilità Sociale (ONG ONLUS) Ebola Treatment Center in Sierra Leone. Repeated measure of Ebola viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), activated prothrombin time (aPTT), international normalized ratio (INR), creatinine, and blood urea nitrogen (BUN) were recorded. Patients were followed up from admission until death or discharge. Results: One hundred patients (49 survivors and 51 nonsurvivors) were included in the analysis. Unadjusted analysis to compare survivors and nonsurvivors provided evidence that all biomarkers were significantly above the normal range and that the extent of these abnormalities was generally higher in nonsurvivors than in survivors. Multivariable mixed-effects models provided strong evidence for a biological gradient (suggestive of a direct role in organ damage) between the viremia levels and either ALT, AST, CPK LDH, aPTT, and INR. In contrast, no direct linear association was found between viremia and either creatinine, BUN, or bilirubin. Conclusions: This study provides evidence to support that Ebola virus may have a direct role in muscular damage and imbalance of the coagulation system. We did not find strong evidence suggestive of a direct role of Ebola virus in kidney damage. The role of the virus in liver damage remains unclear, but our evidence suggests that acute severe liver injury is not a typical feature of Ebola virus disease.

Measles Cases during Ebola Outbreak, West Africa, 2013-2106.

The recent Ebola outbreak in West Africa caused breakdowns in public health systems, which might have caused outbreaks of vaccine-preventable diseases. We tested 80 patients admitted to an Ebola treatment center in Freetown, Sierra Leone, for measles. These patients were negative for Ebola virus. Measles virus IgM was detected in 13 (16%) of the patients.

Exploring barriers to access to care following the 2021 socio-political changes in Afghanistan: a qualitative study.

BACKGROUND: Following the change of government in August 2021, the social and economic landscape of Afghanistan deteriorated into an economic and humanitarian crisis. Afghans continue to struggle to access basic healthcare services, making Universal Health Coverage (UHC) in the country a major challenge. The aim of this study was to perform a qualitative investigation into the main access to care challenges in Afghanistan and whether these challenges have been influenced by the recent socio-political developments, by examining the perspectives of health professionals and hospital directors working in the country. METHODS: Health professionals working in facilities run by an international non-government organisation, which has maintained continuous operations since 1999 and has become a key health reference point for the population, alongside the public health system, and hospital directors working in government hospitals were recruited to participate in an in-depth qualitative study using semi-structured interviews. RESULTS: A total of 43 participants from ten provinces were interviewed in this study. Four issues were identified as critical barriers to achieving UHC in Afghanistan: (1) the lack of quality human resources; (2) the suboptimal management of chronic diseases and trauma; (3) the inaccessibility of necessary health services due to financial hardship; (4) the unequal accessibility of care for different demographic groups. CONCLUSIONS: Health professionals and hospital directors shed light on weaknesses in the Afghan health system highlighting chronic issues and issues that have deteriorated as a result of the 2021 socio-political changes. In order to improve access to care, future healthcare system reforms should consider the perspectives of Afghan professionals working in the country, who are in close contact with Afghan patients and communities.

Access to care in Afghanistan after august 2021: a cross-sectional study exploring Afghans' perspectives in 10 provinces.

BACKGROUND: The Taliban takeover in August 2021 ended a decades-long conflict in Afghanistan. Yet, along with improved security, there have been collateral changes, such as the exacerbation of the economic crisis and brain drain. Although these changes have altered the lives of Afghans in many ways, it is unclear whether they have affected access to care. This study aimed to analyse Afghans' access to care and how this access has changed after August 2021. METHODS: The study relied on the collaboration with the non-governmental organisation EMERGENCY, running a network of three hospitals and 41 First Aid Posts in 10 Afghan provinces. A 67-item questionnaire about access to care changes after August 2021 was developed and disseminated at EMERGENCY facilities. Ordinal logistic regression was used to evaluate whether access to care changes were associated with participants' characteristics. RESULTS: In total, 1807 valid responses were returned. Most respondents (54.34%) reported improved security when visiting healthcare facilities, while the ability to reach facilities has remained stable for the majority of them (50.28%). Care is less affordable for the majority of respondents (45.82%). Female respondents, those who are unmarried and not engaged, and patients in the Panjshir province were less likely to perceive improvements in access to care. CONCLUSIONS: Findings outline which dimensions of access to care need resource allocation. The inability to pay for care is the most relevant barrier to access care after August 2021 and must therefore be prioritised. Women and people from the Panjshir province may require ad hoc interventions to improve their access to care.

Treating Children With Advanced Rheumatic Heart Disease in Sub-Saharan Africa: The NGO EMERGENCY's Project at the Salam Centre for Cardiac Surgery in Sudan.

Rheumatic heart disease is endemic in Sub-Saharan Africa and while efforts are under way to boost prophylaxis and early diagnosis, access to cardiac surgery is rarely affordable. In this article, we report on a humanitarian project by the NGO EMERGENCY, to build and run the Salam Centre for Cardiac Surgery in Sudan. This hospital is a center of excellence offering free-of-charge, high-quality treatment to patients needing open-heart surgery for advanced rheumatic and congenital heart disease. Since it opened in 2007, more than 8,000 patients have undergone surgery there; most of them Sudanese, but ~20% were admitted from other countries, an example of inter-African cooperation. The program is not limited to surgical procedures. It guarantees long-term follow-up and anticoagulant treatment, where necessary. By way of example, we report clinical features and outcome data for the pediatric cohort: 1,318 children under the age of 15, operated on for advanced rheumatic heart disease between 2007 and 2019. The overall 5-year survival rate was 85.0% (95% CI 82.7-87.3). The outcomes for patients with mitral valves repaired and with mitral valves replaced are not statistically different. Nevertheless, observing the trend of patients undergoing valve repair, a better outcome for this category might be assumed. RHD in children is an indicator of poor socio-economic conditions and an inadequate health system, which clearly will not be cured by cardiac surgery alone. Nevertheless, the results achieved by EMERGENCY, with the crucial involvement and participation of the Sudanese government over the years, show that building a hospital, introducing free cardiac surgery, and offering long-term post-operative care may help spread belief in positive change in the future.

Inflammatory and Humoral Immune Response during Ebola Virus Infection in Survivor and Fatal Cases Occurred in Sierra Leone during the 2014⁻2016 Outbreak in West Africa.

Ebola virus (EBOV) infection is characterized by an excessive inflammatory response, a loss of lymphocytes and a general paralysis of the immune system, however pathophysiological mechanisms are not fully understood. In a cohort of 23 fatal and 21 survivors of ebola virus disease (EVD) cases admitted to the Emergency Ebola-Treatment-Center in Goderich (Freetown, Sierra Leone) during the 2014 to 2016 EBOV epidemic in Western Africa, we analyzed the pathway-focused gene expression profile of secreted proteins involved in the immune response and the levels of specific anti-EBOV IgM and IgG from the time of admission till discharge or death. We observed a dysregulated inflammatory response in fatal patients as compared to survivors, mainly consisting of the upregulation of inflammatory mediators, whose extent directly correlated with viremia levels. The upregulation persisted and intensified during the late phase of infection. Relevant differences were also found in humoral immunity, as an earlier and more robust EBOV antibody response was observed in survivor patients.

Intensive care support and clinical outcomes of patients with Ebola virus disease (EVD) in West Africa.

PURPOSE: We investigate the impact on outcome of different levels of supportive treatment in Ebola virus disease (EVD). The NGO EMERGENCY delivered care sequentially at two Ebola Treatment Centres (ETC) in Sierra Leone: first at Lakka (fluids, symptomatic, antibiotic, antimalaria treatment, and hospital level medical care), and thereafter in Goderich, adding organ support in the only African ETC with an equipped and staffed intensive care unit (ETC-ICU). METHODS: The primary outcome in this retrospective cohort study was in-ETC mortality. Secondarily, we used multivariable logistic regression to investigate the independent impact of the IC on mortality by comparing patients in two ETCs, adjusting for potential confounders, including the viral load (base-10 logarithm in copies/ml) (LVL), modelled as a piecewise linear function. Mortality was plotted versus LVL. Confidence bands were constructed by a bootstrap technique. The number of hospital-free days within 28 was computed to assess the burden of EVD. RESULTS: Data from 229 EVD patients were analysed (123 in Lakka, 106 in Goderich). Crude analysis showed a non-statistically significant difference in mortality (57.7% in Lakka vs 50.0% in Goderich; p = 0.19). Age and LVL were associated with mortality. Adjusted mortality was lower at the Goderich ICU-ETC (p = 0.055). This difference was observed with 80% confidence for patients with LVL between 7.5 and 8.5 copies/ml. Hospital-free days (of 28 days) were greater (7.7 vs 5.5; p = 0.03) for patients treated in the ICU-ETC. CONCLUSIONS: Provision of critical care to patients with EVD is feasible in resource-limited settings and was associated with improved survival and less time in hospital.

Molecular Signature of the Ebola Virus Associated with the Fishermen Community Outbreak in Aberdeen, Sierra Leone, in February 2015.

We report the complete genome sequence of Ebola virus from a health worker linked to a cluster of cases occurring in the fishing community of Aberdeen, Sierra Leone (February 2015), which were characterized by unusually severe presentation. The sequence, clustering in the SL subclade 3.2.4, harbors mutations potentially relevant for pathogenesis.

Blood kinetics of Ebola virus in survivors and nonsurvivors.

BACKGROUND: Infection with Ebola virus (EBOV) results in a life-threatening disease, with reported mortality rates between 50%-70%. The factors that determine patient survival are poorly understood; however, clinical observations indicate that EBOV viremia may be associated with fatal outcome. We conducted a study of the kinetics of Zaire EBOV viremia in patients with EBOV disease (EVD) who were managed at an Ebola Treatment Centre in Sierra Leone during the recent West African outbreak. METHODS: Data from 84 EVD patients (38 survivors, 46 nonsurvivors) were analyzed, and EBOV viremia was quantified between 2 and 13 days after symptom onset. Time since symptom onset and clinical outcome were used as independent variables to compare EBOV viral kinetics in survivors and nonsurvivors. RESULTS: In all patients, EBOV viremia kinetics was a quadratic function of time; however, EBOV viremia was 0.94 logarithm (log) copies per ml (cp/ml) (P = 0.011) higher in nonsurvivors than in survivors from day 2 after the onset of symptoms. Survivors reached peak viremia levels at an earlier time after symptom onset than nonsurvivors (day 5 versus day 7) and had lower mean peak viremia levels compared with nonsurvivors (7.46 log cp/ml; 95% CI, 7.17-7.76 vs. 8.60 log cp/ml; 95% CI, 8.27-8.93). Before reaching peak values, EBOV viremia similarly increased both in survivors and nonsurvivors; however, the decay of viremia after the peak was much stronger in survivors than in nonsurvivors. CONCLUSION: Our results demonstrate that plasma concentrations of EBOV are markedly different between survivors and nonsurvivors at very early time points after symptom onset and may be predicative of outcome. Further studies focused on the early phase of the disease will be required to identify the causal and prognostic factors that determine patient outcome. FUNDING: Italian Ministry of Health; Italian Ministry of Foreign Affairs; EMERGENCY's private donations; and Royal Engineers for DFID-UK.