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Summary: Introduction: Intensive care personnel in countries prone to outbreaks of high-consequence infectious diseases (HCIDs), such as Ebola virus disease, stand at the forefront of caring for affected patients. This study describes the knowledge, attitudes and practices (KAP) of intensive care personnel in Rwanda on the management and infection prevention and control (IPC) of HCIDs. Methods: A cross-sectional survey was carried out among staff working in the 4 operational intensive care units in September 2022. The self-administered questionnaire collected information on participants' background and their KAP on critical care (CC), HCIDs and IPC. Results: Of the 107 participants, 67 (62.6%) had less than 4 years' work experience in CC. 41 (38.3%) of them had attended trainings on IPC since 2020. In univariate analyses, a higher knowledge score was associated with being a physician, years of working in CC and differed by hospital. A large proportion perceived their knowledge on CC as good or very good (58.0%) and their everyday risk of acquiring an infection as at least high (48.6%). Overall, 72.9% reported compliance with hand hygiene measures. However, around a quarter of participants reported rarely or never avoiding recapping of needles or never or rarely taking additional precautions during aerosol-generating procedures. Conclusions: Staff had a moderate knowledge base and might benefit from continuous learning on CC and HCIDs. The perception of high risk of infection at work stands in contrast with lack of compliance with basic IPC practices which should be reinforced to avoid preventable and potentially fatal infections.

INTRODUCTION:Since 2011 Médecins sans Frontières together with the eSwatini Ministry of Health have been managing patients with multi-drug resistant tuberculosis (MDR-TB) at Matsapha and Mankayane in Manzini region. This analysis describes the model of care and outcomes of patients receiving a 20 months MDR-TB treatment regimen between 2011 and 2013. METHOD:We conducted a retrospective observational cohort study of MDR-TB patients enrolled for treatment between May 2011 and December 2013. An extensive package of psychological care and socio-economic incentives were provided including psychological support, paid treatment supporters, transport fees and a monthly food package. Baseline demographic details and treatment outcomes were recorded and for HIV positive patient's univariate analysis as well as a cox regression hazard model were undertaken to assess risk factors for unfavorable outcomes. RESULTS:From the 174 patients enrolled, 156 (89.7%) were HIV co-infected, 102 (58.6%) were female, median age 33 years old (IQR: 28-42), 55 (31.6%) had a BMI less than 18 and 86 (49.4%) had not been previously treated for any form of TB. Overall cohort outcomes revealed a 75.3% treatment success rate, 21.3% mortality rate, 0.6% failure and 0.6% lost to follow-up rate. In the adjusted multivariate analysis, low BMI and low CD4 count at treatment initiation were associated with an increased risk of unfavorable outcome. CONCLUSIONS:A model of care that included psychosocial support and patient's enablers led to a high level of treatment success with a very low lost to follow up rate. Limiting the overall treatment success was a high mortality rate which was associated with advanced HIV and a low BMI at presentation. These factors will need to be addressed in order to improve upon the overall treatment success rate in future.

Introduction: Intensive care personnel in countries prone to outbreaks of high-consequence infectious diseases (HCIDs), such as Ebola virus disease, stand at the forefront of caring for affected patients. This study describes the knowledge, attitudes and practices (KAP) of intensive care personnel in Rwanda on the management and infection prevention and control (IPC) of HCIDs., Methods: A cross-sectional survey was carried out among staff working in the 4 operational intensive care units in September 2022. The self-administered questionnaire collected information on participants' background and their KAP on critical care (CC), HCIDs and IPC., Results: Of the 107 participants, 67 (62.6%) had less than 4 years' work experience in CC. 41 (38.3%) of them had attended trainings on IPC since 2020. In univariate analyses, a higher knowledge score was associated with being a physician, years of working in CC and differed by hospital. A large proportion perceived their knowledge on CC as good or very good (58.0%) and their everyday risk of acquiring an infection as at least high (48.6%). Overall, 72.9% reported compliance with hand hygiene measures. However, around a quarter of participants reported rarely or never avoiding recapping of needles or never or rarely taking additional precautions during aerosol-generating procedures., Conclusions: Staff had a moderate knowledge base and might benefit from continuous learning on CC and HCIDs. The perception of high risk of infection at work stands in contrast with lack of compliance with basic IPC practices which should be reinforced to avoid preventable and potentially fatal infections., (© 2024 The Authors.)

Rwanda is a country in East Africa, a region characterized by highly mobile populations and outbreaks of high-consequence infectious diseases occurring on a regular basis. To increase the level of outbreak preparedness in the region, the Rwandan government and the German Ministry of Health signed a joint agreement to construct a new high-level isolation unit in Rwanda, the first in East Africa, and implement a training program for Rwandan healthcare workers to equip them with the necessary skills and knowledge for medical management of patients under high-level isolation conditions, including intensive care treatment. To better understand the scope and format of the planned training program, a needs assessment was performed based on findings from a standardized survey of 4 intensive care units in Rwanda as well as observations from 2 members of a German high-level isolation unit who completed clinical internships at Rwandan hospitals. In this case study, we describe the necessary steps to promote the sustainability and capabilities of the new high-level isolation unit in Kigali and ensure the successful implementation of the training program.

Background: Millions of people are bitten by venomous snakes annually, causing high mortality and disability, but the true burden of this neglected health issue remains unknown. Since 2015, Médecins Sans Frontières has been treating snakebite patients in a field hospital in north-west Ethiopia. Due to the poor market situation for effective and safe antivenoms for Sub-Saharan Africa, preferred antivenom was not always available, forcing changes in choice of antivenom used. This study describes treatment outcomes and the effectiveness and safety of different antivenoms used., Methodology / Principal Findings: This retrospective observational study included 781 snakebite patients presenting at the field hospital between 2015 and 2019. Adjusted odds ratios, 95%-CI and p-values were used to compare the treatment outcome of patients treated with Fav-Afrique (n = 149), VacSera (n = 164), and EchiTAb-PLUS-ICP (n = 156) antivenom, and to identify the risk of adverse reactions for each antivenom. Whereas only incidental snakebite cases presented before 2015, after treatment was made available, cases rapidly increased to 1,431 in 2019. Envenomation was mainly attributed to North East African saw-scaled viper (Echis pyramidum) and puff adder (Bitis arietans). Patients treated with VacSera antivenom showed lower chance of uncomplicated treatment outcome (74.4%) compared to Fav-Afrique (93.2%) and EchiTAb-PLUS-ICP (90.4%). VacSera and EchiTAb-PLUS-ICP were associated with 16- and 6-fold adjusted odds of treatment reaction compared to Fav-Afrique, respectively, and VacSera was weakly associated with higher odds of death., Conclusions / Significance: Snakebite frequency is grossly underreported unless treatment options are available. Although EchiTAb-PLUS-ICP showed favorable outcomes in this retrospective analysis, prospective randomized trials are needed to evaluate the effectiveness and safety of the most promising antivenoms for Sub-Saharan Africa. Structural investment in sustained production and supply of antivenom is urgently needed., Competing Interests: The authors have declared that no competing interests exist.

Background: Provision of antiretroviral therapy (ART) during conflict settings is rarely attempted and little is known about the expected patterns of mortality. The Central African Republic (CAR) continues to have a low coverage of ART despite an estimated 110,000 people living with HIV and 5000 AIDS-related deaths in 2018. We present results from a cohort in Zemio, Haut-Mboumou prefecture. This region had the highest prevalence of HIV nationally (14.8% in a 2010 survey), and was subject to repeated attacks by armed groups on civilians during the observed period., Methods: Conflict from armed groups can impact cohort mortality rates i) directly if HIV patients are victims of armed conflict, or ii) indirectly if population displacement or fear of movement reduces access to ART. Using monthly counts of civilian deaths, injuries and abductions, we estimated the impact of the conflict on patient mortality. We also determined patient-level risk factors for mortality and how the risk of mortality varies with time spent in the cohort. Model-fitting was performed in a Bayesian framework, using logistic regression with terms accounting for temporal autocorrelation., Results: Patients were recruited and observed in the HIV treatment program from October 2011 to May 2017. Overall 1631 patients were enrolled and 1628 were included in the analysis giving 48,430 person-months at risk and 145 deaths. The crude mortality rate after 12 months was 0.92 (95% CI 0.90, 0.93). Our model showed that patient mortality did not increase during periods of heightened conflict; the odds ratios (OR) 95% credible interval (CrI) for i) civilian fatalities and injuries, and ii) civilian abductions on patient mortality both spanned unity. The risk of mortality for individual patients was highest in the second month after entering the cohort, and declined seven-fold over the first 12 months. Male sex was associated with a higher mortality (odds ratio 1.70 [95% CrI 1.20, 2.33]) along with the severity of opportunistic infections (OIs) at baseline (OR 2.52; 95% CrI 2.01, 3.23 for stage 2 OIs compared with stage 1)., Conclusions: Our results show that chronic conflict did not appear to adversely affect rates of mortality in this cohort, and that mortality was driven predominantly by patient-specific risk factors. The risk of mortality and recovery of CD4 T-cell counts observed in this conflict setting are comparable to those in stable resource poor settings, suggesting that conflict should not be a barrier in access to ART., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

A high incidence of bacterial meningitis was observed in the Central African Republic (CAR) from December 2015 to May 2017 in three hospitals in the northwest of the country that are within the African meningitis belt. The majority of cases were caused by Streptococcus pneumoniae (249/328; 75.9%), which occurred disproportionately during the dry season (November-April) with a high case-fatality ratio of 41.6% (95% confidence interval [CI] 33.0, 50.8%). High rates of bacterial meningitis during the dry season in the meningitis belt have typically been caused by Neisseria meningitidis (meningococcal meningitis), and our observations suggest that the risk of contracting S. pneumoniae (pneumococcal) meningitis is increased by the same environmental factors. Cases of meningococcal meningitis (67/328; 20.4%) observed over the same period were predominantly group W and had a lower case fatality rate of 9.6% (95% CI 3.6, 21.8%). Due to conflict and difficulties in accessing medical facilities, it is likely that the reported cases represented only a small proportion of the overall burden. Nationwide vaccination campaigns in the CAR against meningitis have been limited to the use of MenAfriVac, which targets only meningococcal meningitis group A. We therefore highlight the need for expanded vaccine coverage to prevent additional causes of seasonal outbreaks., Competing Interests: No competing interests were disclosed.

A high incidence of bacterial meningitis was observed in the Central African Republic (CAR) from December 2015 to May 2017 in three hospitals in the northwest of the country that are within the African meningitis belt. The majority of cases were caused by Streptococcus pneumoniae (249/328; 75.9%), which occurred disproportionately during the dry season (November-April) with a high case-fatality ratio of 41.6% (95% confidence interval [CI] 33.0, 50.8%). High rates of bacterial meningitis during the dry season in the meningitis belt are typically caused by Neisseria meningitidis (meningococcal meningitis), and our observations suggest that the risk of contracting S. pneumoniae (pneumococcal) meningitis is increased by the same environmental factors. Cases of meningococcal meningitis (67/328; 20.4%) observed over the same period were predominantly type W and had a lower case fatality rate of 9.6% (95% CI 3.6, 21.8%). Due to conflict and difficulties in accessing medical facilities, it is likely that the reported cases represented only a small proportion of the overall burden and that there is high underlying prevalence of S. pneumoniae carriage in the community. Nationwide vaccination campaigns in the CAR against meningitis have been limited to the use of MenAfriVac, which targets only meningococcal meningitis type A. We therefore highlight the need for expanded vaccine coverage to prevent additional causes of seasonal outbreaks., Competing Interests: No competing interests were disclosed.

Introduction: Since 2011 Médecins sans Frontières together with the eSwatini Ministry of Health have been managing patients with multi-drug resistant tuberculosis (MDR-TB) at Matsapha and Mankayane in Manzini region. This analysis describes the model of care and outcomes of patients receiving a 20 months MDR-TB treatment regimen between 2011 and 2013., Method: We conducted a retrospective observational cohort study of MDR-TB patients enrolled for treatment between May 2011 and December 2013. An extensive package of psychological care and socio-economic incentives were provided including psychological support, paid treatment supporters, transport fees and a monthly food package. Baseline demographic details and treatment outcomes were recorded and for HIV positive patient's univariate analysis as well as a cox regression hazard model were undertaken to assess risk factors for unfavorable outcomes., Results: From the 174 patients enrolled, 156 (89.7%) were HIV co-infected, 102 (58.6%) were female, median age 33 years old (IQR: 28-42), 55 (31.6%) had a BMI less than 18 and 86 (49.4%) had not been previously treated for any form of TB. Overall cohort outcomes revealed a 75.3% treatment success rate, 21.3% mortality rate, 0.6% failure and 0.6% lost to follow-up rate. In the adjusted multivariate analysis, low BMI and low CD4 count at treatment initiation were associated with an increased risk of unfavorable outcome., Conclusions: A model of care that included psychosocial support and patient's enablers led to a high level of treatment success with a very low lost to follow up rate. Limiting the overall treatment success was a high mortality rate which was associated with advanced HIV and a low BMI at presentation. These factors will need to be addressed in order to improve upon the overall treatment success rate in future., Competing Interests: The authors have declared that no competing interests exist.

The development of rapid serodiagnostic tests for sleeping sickness and other diseases caused by kinetoplastids relies on the affordable production of parasite-specific recombinant antigens. Here, we describe the production of recombinant antigens from Trypanosoma brucei gambiense (T.b. gambiense) in the related species Leishmania tarentolae (L. tarentolae), and compare their diagnostic sensitivity and specificity to native antigens currently used in diagnostic kits against a panel of human sera. A number of T.b. gambiense protein antigen candidates were chosen for recombinant expression in L. tarentolae based on current diagnostics in field use and recent findings on immunodiagnostic antigens found by proteomic profiling. In particular, the extracellular domains of invariant surface glycoprotein 65 (ISG65), variant surface glycoproteins VSG LiTat 1.3 and VSG LiTat 1.5 were fused with C-terminal histidine tags and expressed as soluble proteins in the medium of cultured, recombinant L. tarentolae. Using affinity chromatography, on average 10 mg/L of recombinant protein was purified from cultures and subsequently tested against a panel of sera from sleeping sickness patients from controls, i.e. persons without sleeping sickness living in HAT endemic countries. The evaluation on sera from 172 T.b. gambiense human African trypanosomiasis (HAT) patients and from 119 controls showed very high diagnostic potential of the two recombinant VSG and the rISG65 fragments with areas under the curve between 0.97 and 0.98 compared to 0.98 and 0.99 with native VSG LiTat 1.3 and VSG LiTat 1.5 (statistically not different). Evaluation on sera from 78 T.b. rhodesiense HAT patients and from 100 controls showed an acceptable diagnostic potential of rISG65 with an area under the curve of 0.83. These results indicate that a combination of these recombinant antigens has the potential to be used in next generation rapid serodiagnostic tests. In addition, the L. tarentolae expression system enables simple, cheap and efficient production of recombinant kinetoplatid proteins for use in diagnostic, vaccine and drug discovery research that does not rely on animal use to generate materials.

Background: Due to unacceptably high mortality with pentavalent antimonials, Médecins Sans Frontières in 2006 began using liposomal amphotericin B (AmBisome) for visceral leishmaniasis (VL) patients in Ethiopia who were severely ill or positive for human immunodeficiency virus (HIV)., Methods: We used clinical data obtained from January 2007 to January 2009 to compare outcomes by HIV status and VL episode (primary vs relapse) and to identify risk factors for treatment failure among patients treated with AmBisome monotherapy at a total dose of 30 mg/kg in 6 doses on alternate days, a higher dose than recommended by the World Health Organization (20 mg/kg)., Results: Among 94 HIV-negative severely ill VL patients, 93% had initial cure and 6% died. Among 195 HIV-positive patients (116 primary, 79 relapse VL), 60% had initial cure, 7% died, and 32% were parasitological failures. AmBisome was less effective in the 79 HIV-positive VL relapse patients (38% initial cure, 5% mortality, 56% parasitological failure) than in the 116 HIV-positive primary VL patients (74% initial cure, 8% mortality, 16% parasitological failure). Sodium stibogluconate (SSG) rescue treatment increased the overall cure rate among all HIV-positive VL patients from 60% to 83%, but 16% (9 of 59) of rescue treatment patients died, mainly due to SSG toxicity., Conclusions: High-dose AmBisome for VL is safe and effective in severely ill HIV-negative patients, and safe but less effective in HIV-positive patients. Combining AmBisome with another drug may enhance its effectiveness in HIV-positive VL patients. SSG should be avoided for treatment of VL in HIV-positive patients.

Substantial neurologic morbidity occurs in survivors of premature birth. Premature infants are exposed to partial oxygen pressures that are fourfold higher compared to intrauterine conditions, even if no supplemental oxygen is administered. Here we report that short exposures to nonphysiologic oxygen levels can trigger apoptotic neurodegeneration in the brains of infant rodents. Vulnerability to oxygen neurotoxicity is confined to the first 2 weeks of life, a period characterized by rapid growth, which in humans expands from the sixth month of pregnancy to the third year of life. Oxygen caused oxidative stress, decreased expression of neurotrophins, and inactivation of survival signaling proteins Ras, extracellular signal-regulated kinase (ERK 1/2), and protein kinase B (Akt). The synRas-transgenic mice overexpressing constitutively activated Ras and phosphorylated kinases ERK1/2 in the brain were protected against oxygen neurotoxicity. Our findings reveal a mechanism that could potentially damage the developing brain of human premature neonates.