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INTRODUCTION: Following the coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, vaccination became the main strategy against disease severity and even death. Healthcare workers were considered high-risk for infection and, thus, were prioritised for vaccination. METHODS: A follow-up to a SARS-CoV-2 seroprevalence study among clinical and non-clinical HCWs at the Aga Khan University Hospital, Nairobi, we assessed how vaccination influenced SARS-CoV-2 anti-spike IgG antibody responses and kinetics. Blood samples were drawn at two points spanning 6 to 18 months post-vaccination, and SARS-CoV-2 spike antibody levels were determined by enzyme-linked immunosorbent assay. RESULTS: Almost all participants, 98% (961/981), received a second vaccine dose, and only 8.5% (83/981) received a third dose. SARS-CoV-2 spike IgG antibodies were detected in 100% (961/961) and 92.7% (707/762) of participants who received two vaccine doses, with the first and second post-vaccine test, respectively, and in 100% (83/83) and 91.4% (64/70) of those who received three vaccine doses at the first and second post-vaccine test, respectively. Seventy-six participants developed mild infections, not requiring hospitalisation even after receiving primary vaccination. Receiving three vaccine doses influenced the anti-spike S/Co at both the first (p<0.001) and second post-vaccination testing (p<0.001). Of those who tested SARS-CoV-2 positive, the anti-spike S/Co ratio was significantly higher than those who were seronegative at the first post-vaccine test (p = 0.001). Side effects were reported by almost half of those who received the first dose, 47.3% (464/981), 28.9% (278/961) and 25.3% (21/83) of those who received the second and third vaccine doses, respectively. DISCUSSION AND CONCLUSION: Following the second dose of primary vaccination, all participants had detectable anti-spike antibodies. The observed mild breakthrough infections may have been due to emerging SARS-CoV-2 variants. Findings suggest that although protective antibodies are induced, vaccination protected against COVID-19 disease severity and not necessarily infection.
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COVID-19 , Vacinas , Humanos , Quênia/epidemiologia , Formação de Anticorpos , SARS-CoV-2 , Estudos Soroepidemiológicos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação , Anticorpos Antivirais , Pessoal de Saúde , Imunoglobulina GRESUMO
BACKGROUND: The burden of central line-associated bloodstream infections is significant and has negative implications for healthcare, increasing morbidity and mortality risks, increasing inpatient hospital stays, and increasing the cost of hospitalization. Efforts to reduce the incidence of central line-associated bloodstream infections have utilized quality improvement projects that implement, measure, and monitor outcomes. However, variations in location, healthcare organization, patient risks, and practice gaps are key to the success of interventions and approaches. This study aims to evaluate interventions of a quality improvement project on the reduction of central line-associated bloodstream infection rates at a university teaching hospital. METHODS: This was a retrospective review of a quality improvement project that was implemented using the Plan-Do-Study-Act quality improvement cycle. Active surveillance of processes and outcomes was performed in the critical care areas; compliance to central line care bundles, and central line-associated bloodstream infections. Interrupted time series was used to analyze trends pre and post-intervention and regression modeling to estimate data segments preceding and succeeding the interventions. RESULTS: There were 350 central line insertions, 3912 catheter days, and 20 central line-associated bloodstream infection events during the intervention period. Compliance with central line care bundles was at 94%. There was a trend in the reduction of central line-associated bloodstream infections by 18% that did not reach statistical significance (p = 0.252). CONCLUSIONS: Improvement projects to reduce central line-associated bloodstream infections face challenges and complexities associated with implementing interventions in real-world healthcare settings. There is a great need to continuously monitor, evaluate, readjust, and adapt interventions to achieve desired results, sustain improvements in patient outcomes, and investigate reasons for non-adherence as keys to achieving desired outcomes.
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Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Infecção Hospitalar , Sepse , Humanos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/etiologia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Infecções Relacionadas a Cateter/complicações , Melhoria de Qualidade , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Hospitais de Ensino , Sepse/complicaçõesRESUMO
INTRODUCTION: Acute uncomplicated urinary tract infections are common in outpatient settings but are not treated optimally. Few studies of the outpatient use of antibiotics for specific diagnoses have been done in sub-Saharan Africa, so little is known about the prescribing patterns of medical officers in the region. METHODS: Aga Khan University has 16 outpatient clinics throughout the Nairobi metro area with a medical officer specifically assigned to that clinic. A baseline assessment of evaluation and treatment of suspected UTI was performed from medical records in these clinics. Then the medical officer from each of the 16 clinics was recruited from each clinic was recruited with eight each randomized to control vs. feedback groups. Both groups were given a multimodal educational session including locally adapted UTI guidelines and emphasis on problems identified in the baseline assessment Each record was scored using a scoring system that was developed for the study according to adequacy of history, physical examination, clinical diagnosis matching recorded data, diagnostic workup and treatment. Three audits were done for both groups; baseline (audit 1), post-CME (audit 2), and a final audit, which was after feedback for the feedback group (audit 3). The primary analysis assessed overall guideline adherence in the feedback group versus the CME only group. RESULTS: The overall scores in both groups showed significant improvement after the CME in comparison to baseline and for each group, the scores in most domains also improved. However, audit 3 showed persistence of the gains attained after the CME but no additional benefit from the feedback. Some deficiencies that persisted throughout the study included lack of workup of possible STI and excess use of non-UTI laboratory tests such as CBC, stool culture and H. pylori Ag. After the CME, the use of nitrofurantoin rose from only 4% to 8% and cephalosporin use increased from 49 to 67%, accompanied by a drop in quinolone use. CONCLUSION: The CME led to modest improvements in patient care in the categories of history taking, treatment and investigations, but feedback had no additional effect. Future studies should consider an enforcement element or a more intensive feedback approach.
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Helicobacter pylori , Infecções Urinárias , Humanos , Retroalimentação , Quênia , Pacientes Ambulatoriais , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico , NitrofurantoínaRESUMO
BACKGROUND: Preterm birth is a global problem with about 12% of births in sub-Saharan Africa occurring before 37 weeks of gestation. Several studies have explored a potential association between vaginal microbiota and preterm birth, and some have found an association while others have not. We performed a study designed to determine whether there is an association with vaginal microbiota and/or placental microbiota and preterm birth in an African setting. METHODS: Women presenting to the study hospital in labor with a gestational age of 26 to 36 weeks plus six days were prospectively enrolled in a study of the microbiota in preterm labor along with controls matched for age and parity. A vaginal sample was collected at the time of presentation to the hospital in active labor. In addition, a placental sample was collected when available. Libraries were constructed using PCR primers to amplify the V6/V7/V8 variable regions of the 16S rRNA gene, followed by sequencing with an Illumina MiSeq machine and analysis using QIIME2 2022.2. RESULTS: Forty-nine women presenting with preterm labor and their controls were enrolled in the study of which 23 matched case-control pairs had sufficient sequence data for comparison. Lactobacillus was identified in all subjects, ranging in abundance from < 1% to > 99%, with Lactobacillus iners and Lactobacillus crispatus the most common species. Over half of the vaginal samples contained Gardnerella and/or Prevotella; both species were associated with preterm birth in previous studies. However, we found no significant difference in composition between mothers with preterm and those with full-term deliveries, with both groups showing roughly equal representation of different Lactobacillus species and dysbiosis-associated genera. Placental samples generally had poor DNA recovery, with a mix of probable sequencing artifacts, contamination, and bacteria acquired during passage through the birth canal. However, several placental samples showed strong evidence for the presence of Streptococcus species, which are known to infect the placenta. CONCLUSIONS: The current study showed no association of preterm birth with composition of the vaginal community. It does provide important information on the range of sequence types in African women and supports other data suggesting that women of African ancestry have an increased frequency of non-Lactobacillus types, but without evidence of associated adverse outcomes.
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Microbiota , Trabalho de Parto Prematuro , Nascimento Prematuro , Humanos , Feminino , Recém-Nascido , Gravidez , Lactente , RNA Ribossômico 16S/genética , Nascimento Prematuro/microbiologia , Estudos de Casos e Controles , Quênia , Placenta , Vagina/microbiologia , Trabalho de Parto Prematuro/microbiologia , Microbiota/genéticaRESUMO
BACKGROUND: Healthcare workers and nonclinical staff in medical facilities are perceived to be a high-risk group for acquiring SAR-CoV-2 infection, and more so in countries where COVID-19 vaccination uptake is low. Serosurveillance may best determine the true extent of SARS-CoV-2 infection since most infected HCWs and other staff may be asymptomatic or present with only mild symptoms. Over time, determining the true extent of SARS-CoV-2 infection could inform hospital management and staff whether the preventive measures instituted are effective and valuable in developing targeted solutions. METHODS: This was a census survey study conducted at the Aga Khan University Hospital, Nairobi, between November 2020 and February 2021 before the implementation of the COVID-19 vaccination. The SARS-CoV-2 nucleocapsid IgG test was performed using a chemiluminescent assay. RESULTS: One thousand six hundred thirty-one (1631) staff enrolled, totalling 60% of the workforce. The overall crude seroprevalence was 18.4% and the adjusted value (for assay sensitivity of 86%) was 21.4% (95% CI; 19.2-23.7). The staff categories with higher prevalence included pharmacy (25.6%), outreach (24%), hospital- based nursing (22.2%) and catering staff (22.6%). Independent predictors of a positive IgG result after adjusting for age, sex and comorbidities included prior COVID-19 like symptoms, odds ratio (OR) 2.0 [95% confidence interval (CI) 1.3-3.0, p = 0.001], a prior positive SARS-CoV-2 PCR result OR 12.0 (CI: 7.7-18.7, p<0.001) and working in a clinical COVID-19 designated area, OR 1.9 (CI 1.1-3.3, p = 0.021). The odds of testing positive for IgG after a positive PCR test were lowest if the antibody test was performed more than 2 months later; OR 0.7 (CI: 0.48-0.95, p = 0.025). CONCLUSIONS: The prevalence of anti- SARS-CoV-2 nucleocapsid IgG among HCWs and nonclinical staff was lower than in the general population. Staff working in clinical areas were not at increased risk when compared to staff working in non-clinical areas.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Estudos Soroepidemiológicos , Centros de Atenção Terciária , Censos , Vacinas contra COVID-19 , Quênia/epidemiologia , Pessoal de Saúde , Anticorpos Antivirais , Imunoglobulina G , NucleocapsídeoRESUMO
Background Acute COVID-19-related myocardial, pulmonary, and vascular pathology and how these relate to each other remain unclear. To our knowledge, no studies have used complementary imaging techniques, including molecular imaging, to elucidate this. We used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID-19. Specifically, we investigated the presence of myocardial inflammation and its association with coronary artery disease, systemic vasculitis, and pneumonitis. Methods and Results Consecutive patients presenting with acute COVID-19 were prospectively recruited during hospital admission in this cross-sectional study. Imaging involved computed tomography coronary angiography (identified coronary disease), cardiac 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/computed tomography (identified vascular, cardiac, and pulmonary inflammatory cell infiltration), and cardiac magnetic resonance (identified myocardial disease) alongside biomarker sampling. Of 33 patients (median age 51 years, 94% men), 24 (73%) had respiratory symptoms, with the remainder having nonspecific viral symptoms. A total of 9 patients (35%, n=9/25) had cardiac magnetic resonance-defined myocarditis. Of these patients, 53% (n=5/8) had myocardial inflammatory cell infiltration. A total of 2 patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with and without myocarditis (8.4 ng/L [interquartile range, IQR: 4.0-55.3] versus 3.5 ng/L [IQR: 2.5-5.5]; P=0.07) or myocardial cell infiltration (4.4 ng/L [IQR: 3.4-8.3] versus 3.5 ng/L [IQR: 2.8-7.2]; P=0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR: 5%-31%) and 11% (IQR: 7%-18%), respectively. Neither were associated with the presence of myocarditis. Conclusions Myocarditis was present in a third patients with acute COVID-19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is nonischemic and not attributable to a vasculitic process. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN12154994.
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COVID-19 , Doença da Artéria Coronariana , Miocardite , Biomarcadores , COVID-19/complicações , Doença da Artéria Coronariana/diagnóstico , Estudos Transversais , Feminino , Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/diagnóstico por imagem , TroponinaRESUMO
Giardia duodenalis captured the attention of Leeuwenhoek in 1681 while he was examining his own diarrheal stool, but, ironically, it did not really gain attention as a human pathogen until the 1960s, when outbreaks were reported. Key technological advances, including in vitro cultivation, genomic and proteomic databases, and advances in microscopic and molecular approaches, have led to an understanding that this is a eukaryotic organism with a reduced genome rather than a truly premitochondriate eukaryote. This has included the discovery of mitosomes (vestiges of mitochondria), a transport system with many of the features of the Golgi apparatus, and even evidence for a sexual or parasexual cycle. Cell biology approaches have led to a better understanding of how Giardia survives with two nuclei and how it goes through its life cycle as a noninvasive organism in the hostile environment of the lumen of the host intestine. Studies of its immunology and pathogenesis have moved past the general understanding of the importance of the antibody response in controlling infection to determining the key role of the Th17 response. This work has led to understanding of the requirement for a balanced host immune response that avoids the extremes of an excessive response with collateral damage or one that is unable to clear the organism. This understanding is especially important in view of the remarkable ranges of early manifestations, which range from asymptomatic to persistent diarrhea and weight loss, and longer-term sequelae that include growth stunting in children who had no obvious symptoms and a high frequency of postinfectious irritable bowel syndrome (IBS).
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Giardia lamblia , Giardíase , Síndrome do Intestino Irritável , Diarreia , Humanos , Masculino , ProteômicaRESUMO
BACKGROUND: Lower respiratory tract infections continue to contribute significantly to morbidity and mortality across all age groups globally. In sub-Saharan Africa, many studies of community acquired pneumonia in adults have focused on HIV-infected patients and little attention has been given to risk factors and etiologic agents in an urban area with a more moderate HIV prevalence. METHODS: We prospectively enrolled 77 patients admitted to a 280 bed teaching hospital in Kenya with radiographically confirmed community acquired pneumonia from May 2019 to March 2020. The patients were followed for etiology and clinical outcomes. Viral PCR testing was performed using the FTD respiratory pathogen-21 multiplex kit on nasopharyngeal or lower respiratory samples. Additional microbiologic workup was performed as determined by the treating physicians. RESULTS: A potential etiologic agent(s) was identified in 57% including 43% viral, 5% combined viral and bacterial, 5% bacterial and 4% Pneumocystis. The most common etiologic agent was Influenza A which was associated with severe clinical disease. The most common underlying conditions were cardiovascular disease, diabetes and lung disease, while HIV infection was identified in only 13% of patients. Critical care admission was required for 24, and 31% had acute kidney injury, sometimes in combination with acute respiratory distress or sepsis. CONCLUSION: Viruses, especially influenza, were commonly found in patients with CAP. In contrast to other studies from sub-Saharan Africa, the underlying conditions were similar to those reported in high resource areas and point to the growing concern of the double burden of infectious and noncommunicable diseases.
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Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/virologia , Pneumonia Viral/epidemiologia , Adulto , Idoso , Feminino , Infecções por HIV/epidemiologia , Hospitalização , Hospitais de Ensino , Humanos , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Orthomyxoviridae/isolamento & purificação , Orthomyxoviridae/patogenicidade , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Occult hepatitis B virus (HBV) infection (OBI) is a phase of HBV infection characterised by the presence of HBV DNA in the absence of detectable hepatitis B surface antigen (HBsAg). OBI is of concern in the HIV-infected due to high prevalence and risk of HBV reactivation. The prevalence and clinico-demographic characteristics of OBI in anti-retroviral therapy (ART) naïve HIV infected adults in Kenya is unknown. METHODS: A cross sectional study carried was out at three sites in Kenya. HIV infected ART naïve adults were enrolled and demographic data collected. Blood samples were assayed for HBsAg, HBV DNA, alanine aminotransferase, aspartate aminotransferase, antibodies to hepatitis B surface antigen (anti-HBs) and hepatitis B core antigen (anti-HBc). Data on CD4 count, HIV viral load and platelet count were obtained from medical records. RESULTS: Of 208 patients, 199 (95.7%) did not report HBV vaccination, 196 (94.2%) were HBsAg negative, 119 (57.2%) had no HBV markers, 58 (27.9%) had previous HBV infection (anti-HBc positive) and 11 (5.3%) had OBI. All 11 (100%) OBI patients were anti-HBc positive. OBI patients comprised 19.0% of HBsAg negative, anti-HBc positive patients. There was no difference in clinico-demographic characteristics between the overt HBV, OBI and HBV negative patients. CONCLUSION: This was the first study on OBI in ART naïve HIV infected adults in Kenya. The lower OBI prevalence compared to other sub-Saharan African countries could be attributed to lower HBV exposure. Most patients were HBV unexposed and unimmunized, outlining the need to implement guideline recommended immunization strategies.
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Infecções Assintomáticas/epidemiologia , Coinfecção/epidemiologia , Infecções por HIV/complicações , Hepatite B/complicações , Adulto , Coinfecção/virologia , Estudos Transversais , Feminino , Infecções por HIV/virologia , Hepatite B/epidemiologia , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Humanos , Quênia/epidemiologia , Masculino , PrevalênciaRESUMO
BACKGROUND: Outcomes in well-resourced, intensive care units (ICUs) in Kenya are thought to be comparable to those in high-income countries (HICs) but risk-adjusted mortality data is unavailable. We undertook an evaluation of the Aga Khan University Hospital, Nairobi ICU to analyze patient clinical-demographic characteristics, compare the performance of Sequential Organ Failure Assessment (SOFA), delta-SOFA at 48 hours and Mortality Prediction Model-III (MPM-III) mortality prediction systems, and identify factors associated with increased risk of mortality. METHODS: A retrospective cohort study was conducted of adult patients admitted to the ICU between January 2015 and September 2017. SOFA and MPM-III scores were determined at admission and SOFA repeated at 48 hours. RESULTS: Approximately 33% of patients did not meet ICU admission criteria. Mortality among the population of critically ill patients in the ICU was 31.7%, most of whom were male (61.4%) with a median age of 53.4 years. High adjusted odds of mortality were found among critically ill patients with leukemia (aOR 6.32, p<0.01), tuberculosis (aOR 3.96, p<0.01), post-cardiac arrest (aOR 3.57, p<0.01), admissions from the step-down unit (aOR 3.13, p<0.001), acute kidney injury (aOR 2.97, p<0.001) and metastatic cancer (aOR 2.45, p = 0.04). The area under the receiver-operating characteristic (ROC) curve of admission SOFA was 0.77 (95% CI, 0.73-0.81), MPM-III 0.74 (95% CI, 0.69-0.79), delta-SOFA 0.69 (95% CI, 0.63-0.75) and 48-hour SOFA 0.83 (95% CI, 0.79-0.87). The difference between SOFA at 48 hours and admission SOFA, MPM-III and delta-SOFA was statistically significant (chi2 = 17.1, 24.2 and 26.5 respectively; p<0.001). Admission SOFA, MPM-III and 48-hour SOFA were well calibrated (p >0.05) while delta-SOFA was borderline (p = 0.05). CONCLUSION: Mortality among the critically ill was higher than expected in this well-resourced ICU. 48-hour SOFA performed better than admission SOFA, MPM-III and delta-SOFA in our cohort. While a large proportion of patients did not meet admission criteria but were boarded in the ICU, critically ill patients stepped-up from the step-down unit were unlikely to survive. Patients admitted following a cardiac arrest, and those with advanced disease such as leukemia, stage-4 HIV and metastatic cancer, had particularly poor outcomes. Policies for fair allocation of beds, protocol-driven admission criteria and appropriate case selection could contribute to lowering the risk of mortality among the critically ill to a level on par with HICs.
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Estado Terminal/mortalidade , Escores de Disfunção Orgânica , Adulto , Idoso , Estado Terminal/epidemiologia , Feminino , Mortalidade Hospitalar , Hospitais Privados , Humanos , Unidades de Terapia Intensiva , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Many studies have shown that Staphylococcus aureus is a leading cause of both community onset and hospital onset bloodstream infections. However, relatively little is known about the occurrence and outcome of S. aureus bacteremia in sub-Saharan Africa. A previous report indicated that S. aureus accounts for 16% of community onset and 6% of hospital onset bloodstream infections at Aga Khan University Hospital Nairobi (AKUHN). Data about the etiology of S. aureus bacteremia in sub-Saharan Africa will help optimize recognition and treatment. This study was performed in order to understand the etiologies and risk factors for S. aureus bacteremia in a sub-Saharan location. MATERIALS AND METHODS: A review of the electronic record of laboratory results from September 2010 through December 2018 identified 201 patients seen at AKUHN with S. aureus bacteremia. The source and/or focus of infection was identified and in-hospital mortality was determined. Cases with bacteremia after three days of hospitalization were considered hospital acquired. Community onset cases were divided into community acquired and health care associated. RESULTS: Most cases (71%; 143/201) were community onset, but only 41% (83/201) of these cases were community acquired. The most commonly identified foci of infection for community acquired bacteremia were musculoskeletal (25%; 21/83) and skin and soft tissue (24%; 20/83). The majority of health care associated (70%; 40/57) and hospital acquired cases (74%; 43/58) were associated with invasive vascular devices, with peripheral IVs being the most common for hospital acquired and dialysis catheters being the most common for health care associated infections. In-hospital mortality rates were 23% (19/83) for community acquired, 19% (11/57) for health care associated and 33% (19/58) for hospital acquired infections. CONCLUSION: Invasive vascular devices were associated with a substantial portion of cases of S. aureus bacteremia and provide an important target for infection control efforts.
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Bacteriemia/epidemiologia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/isolamento & purificação , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Infecções Relacionadas a Cateter/sangue , Infecções Relacionadas a Cateter/microbiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Centros de Cuidados de Saúde Secundários/estatística & dados numéricos , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/microbiologia , Adulto JovemRESUMO
Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. aurisIMPORTANCE In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.
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Candida , Farmacorresistência Fúngica/genética , Antifúngicos/farmacologia , Azóis/farmacologia , Evolução Biológica , Candida/classificação , Candida/efeitos dos fármacos , Candida/genética , Candida/isolamento & purificação , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/epidemiologia , Equinocandinas/farmacologia , Fluconazol/farmacologia , Genes Fúngicos , Genética Populacional/métodos , Genoma Fúngico , Humanos , Metagenômica , Epidemiologia Molecular , Mutação , Filogenia , Filogeografia , Sequenciamento Completo do GenomaRESUMO
OBJECTIVES: Candida auris emerged as a human pathogen in 2009 and has subsequently been identified around the world as a cause of invasive candidiasis. We did an analysis from a single institution in order to analyze risk factors and outcomes for C. auris candidemia. METHODS: Patients with candidemia were identified by the electronic medical record and reviewed for risk factors and outcome. Candida isolates were identified by Vitek2 as Candida haemulonii, but species determinations for 21 of the isolates using published molecular and proteomic methods identified all as C. auris. FINDINGS: From September 2010 to December 2016, C. auris accounted for 38% of 201 patients with candidemia, while C. albicans contributed 25%. C. auris patients had been hospitalized longer (mean 32 days vs. 13 days; p<0.001), were more likely to have central lines preceding candidemia than C. albicans patients (84% vs. 54%; p=<0.001) and had more commonly been treated with carbapenems (83% vs 61% for C. albicans [p=0.01]). The crude mortality was 29%, compared to 36% for C. albicans. CONCLUSIONS: These findings suggest an opportunistic pathogen that may be less virulent, but difficult to eradicate and that control efforts should focus on antimicrobial usage.
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Candidemia/microbiologia , Adulto , Idoso , Antifúngicos/uso terapêutico , Candida/isolamento & purificação , Candida albicans/isolamento & purificação , Candidemia/tratamento farmacológico , Candidemia/mortalidade , Feminino , Humanos , Quênia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemAssuntos
Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Citodiagnóstico , Pneumonia/microbiologia , Criptococose/microbiologia , Criptococose/mortalidade , Criptococose/urina , Cryptococcus neoformans/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/mortalidadeRESUMO
BACKGROUND: Relevant seroprevalence data for endemic pathogens in a given region provide insight not only into a population's susceptibility to acute infection or risk for reactivation disease but also into the potential need for policy initiatives aimed at reducing these risks. Data from sub-Saharan Africa are sparse and since Aga Khan University Hospital Nairobi is an internationally accredited hospital equipped with a laboratory electronic medical record system, analysis of pertinent local seroprevalence data has been made possible. METHODS: We have analyzed serology data from laboratory electronic records at a 300 bed tertiary private teaching hospital in Kenya for the dates, 2008 to 2017 for Toxoplasma gondii, cytomegalovirus, and rubella, which were used primarily for antenatal screening. We also analyzed the data from hepatitis A and amebiasis serologies, which were used primarily for diagnostic purposes. RESULTS: For T. gondii, cytomegalovirus, and rubella, we used IgG serology to determine seroprevalence, finding rates of 32%, 86%, and 89%, respectively. There was no significant age-related difference in the 20 to 49 year old age range for any of these three pathogens. Of the Hepatitis A IgM tests that were ordered, 33% were positive with a peak positive rate of 70% in the five to nine year old age range. The seroprevalence of amebiasis was 4% and all cases of seropositivity were accompanied by compatible clinical illness (hepatic abscess). CONCLUSIONS: These data provide insight into seroprevalence rates of selected pathogens that can be used to guide screening and diagnostic laboratory testing as well as private and public immunization practices.
Assuntos
Citomegalovirus/imunologia , Entamoeba histolytica/imunologia , Hepatite A/imunologia , Complicações Infecciosas na Gravidez/epidemiologia , Rubéola (Sarampo Alemão)/imunologia , Toxoplasma/imunologia , Adolescente , Adulto , Anticorpos Antiprotozoários/sangue , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Registros Eletrônicos de Saúde , Feminino , Hospitais Privados/normas , Hospitais de Ensino/estatística & dados numéricos , Humanos , Lactente , Quênia/epidemiologia , Pessoa de Meia-Idade , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Diagnóstico Pré-Natal , Estudos Soroepidemiológicos , Adulto JovemRESUMO
BACKGROUND: Remifentanil and dexmedetomidine are common agents used in general anaesthesia, monitored anaesthesia care and critical care. When combined with inhaled or intravenous anaesthetic agents intra-operatively, they provide analgesia, lower general anaesthetic requirements and provide sedation and analgesia in the peri-operative period if indicated. Pharmacodynamically, they cause hypotension and bradycardia which are reversible if well managed. Past studies of these drugs have shown a significant proportion of patients with hypotension when compared with similar agents or in isolation. This study compares these two drugs on the effect of hypotension when used as adjuncts to general anaesthesia at low dose standard rate of infusions. OBJECTIVE: To compare the proportion of hypotension episodes in a group of adult patients receiving dexmedetomidine infusion at 0.4mcg/kg/hr versus a group receiving remifentanil infusion at 0.2mcg/kg/min, severity of hypotension and physician interventions in each group. METHODS: One hundred and four patients scheduled for elective surgery under general anaesthesia were randomized into two groups: Control group; received remifentanil infusion at 0.2mcg/kg/minIntervention group; received dexmedetomidine at 0.4mcg/kg/hr.General anaesthesia was standardized in both groups. The patients were blinded to the study. Baseline blood pressures of all patients were determined prior to induction. The patient's demographic characteristics were recorded. The number of patients who developed hypotension, the frequency of hypotension and the physician interventions were recorded and analysed. RESULTS: The age and gender characteristics were different between the two groups (p values <0.023 and 0.05 respectively) however they did not affect the proportion of patients with hypotension. The weight, baseline pressures and ASA status of the patients within the groups were similar. The operative procedures varied within the groups. General surgery did not influence the outcome of hypotension in both arms. The duration of surgery in remifentanil group exceeded that of Dexmedetomidine p value<0.0005 however the time to the first episode of hypotension was similar between the groups. The episodes of hypotension were fewer in the dexmedetomidine arm and the proportion of patients with hypotension were higher in the remifentanil arm, p value<0.001, R.R 0. = 0.5938, 95% C.I= 0.329-0.819 The physician interventions administered were similar between the two groups except the use of ephedrine between the groups. CONCLUSION: Among this population, at standard infusion rates, the proportion of patients that risk hypotension was greater in those undergoing elective surgery receiving remifentanil at 0.2mcg/kg/min than in dexmedetomidine at 0.4mcg/kg/hr under isoflurane based anaesthesia.
Assuntos
Analgésicos/efeitos adversos , Anestesia Geral/métodos , Dexmedetomidina/efeitos adversos , Hipotensão/induzido quimicamente , Remifentanil/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Analgésicos/administração & dosagem , Pressão Sanguínea , Dexmedetomidina/administração & dosagem , Feminino , Frequência Cardíaca , Hospitais Universitários , Humanos , Quênia , Masculino , Pessoa de Meia-Idade , Remifentanil/administração & dosagem , Fatores Sexuais , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to determine the prevalence of liver fibrosis in patients with human immunodeficiency virus (HIV) monoinfection versus those with HIV hepatitis-B virus (HBV) co-infection as assessed with shear wave elastography (SWE) in a tertiary sub-Saharan Africa hospital. MATERIALS AND METHODS: A total of 105 consecutive patients, 70 with HIV monoinfection and 35 with HIV-HBV co-infection, had liver elastography obtained using SWE to assess for the presence of liver fibrosis the cutoff of which was 5.6 kPa. Assessment of aspartate aminotransferase-to-platelet ratio index (APRI) score (a noninvasive serum biomarker of liver fibrosis) in these patients was also done. RESULTS: The prevalence of liver fibrosis was significantly higher (P < 0.0001) in patients with HIV-HBV co-infection, 25.7%, compared to those with HIV monoinfection, 7.1%. APRI score was greater in patients with HIV-HBV co-infection than those with HIV monoinfection. HIV co-infection with HBV accelerates progression to liver fibrosis. Association of a low cluster of differentiation 4 (CD-4) count with advanced fibrosis supports earlier starting of antiretroviral therapy to prevent rapid progression of liver disease in HIV-positive patients. CONCLUSION: In view of the high prevalence of liver fibrosis in patients with HIV-HBV co-infection, regular monitoring of the disease progression is recommended.
RESUMO
BACKGROUND: Accurate local prevalence of microbial diseases and microbial resistance data are vital for optimal treatment of patients. However, there are few reports of these data from developing countries, especially from sub-Saharan Africa. The status of Aga Khan University Hospital Nairobi as an internationally accredited hospital and a laboratory with an electronic medical record system has made it possible to analyze local prevalence and antimicrobial susceptibility data and compare it with other published data. METHODS: We have analyzed the spectrum of microbial agents and resistance patterns seen at a 300 bed tertiary private teaching hospital in Kenya using microbial identity and susceptibility data captured in hospital and laboratory electronic records between 2010 and 2014. RESULTS: For blood isolates, we used culture collection within the first three days of hospitalization as a surrogate for community onset, and within that group, Escherichia coli was the most common, followed by Staphylococcus aureus. In contrast, Candida spp. and Klebsiella pneumoniae were the most common hospital onset causes of bloodstream infection. Antimicrobial resistance rates for the most commonly isolated Gram negative organisms was higher than many recent reports from Europe and North America. In contrast, Gram positive resistance rates were quite low, with 94% of S. aureus being susceptible to oxacillin and only rare isolates of vancomycin-resistant enterococci. CONCLUSIONS: The current report demonstrates high rates of antimicrobial resistance in Gram negative organisms, even in outpatients with urinary tract infections. On the other hand, rates of resistance in Gram positive organisms, notably S. aureus, are remarkably low. A better understanding of the reasons for these trends may contribute to ongoing efforts to combat antimicrobial resistance globally.
Assuntos
Candidíase/epidemiologia , Infecção Hospitalar/epidemiologia , Infecções por Klebsiella/epidemiologia , Infecções Estafilocócicas/epidemiologia , Antibacterianos/uso terapêutico , Candida/isolamento & purificação , Doenças Transmissíveis , Farmacorresistência Bacteriana , Hospitais Privados , Hospitais de Ensino , Humanos , Quênia , Klebsiella/isolamento & purificação , Testes de Sensibilidade Microbiana , Staphylococcus aureus/isolamento & purificaçãoRESUMO
OBJECTIVES: As part of the ISO 15189:2007 accreditation process, the Aga Khan University Hospital Nairobi laboratory became the first internationally accredited hospital laboratory in sub-Saharan Africa outside South Africa in 2011 through the South Africa National Accreditation System. METHODS: Seven preanalytic, 10 analytic, eight postanalytic, and five administrative performance parameters were monitored from 2009 to 2012 to measure the impact of the accreditation process. RESULTS: Most measures in all four categories showed substantial improvement. The seven preanalytic measures all showed major improvement-between a quarter and a half sigma. Real but less dramatic improvement appeared in analytic and postanalytic measures, but greater than one sigma decrease in analytic "procedure violations" and a three-quarter sigma decrease in excessive turnaround time were noted in these categories. Administrative improvements included dramatic decreases in misdirected and missing reports and complaints. CONCLUSIONS: This study demonstrates the correlation of the accreditation process with improvement in quality measures in a low-resource region.