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Little is known about major histocompatibility complex type I deficiency, a rare form of primary immunodeficiency. This report describes the presentation of a three-year-old Ethiopian boy with recurrent sinopulmonary infections and genetic analysis showing him having autosomal recessive major histocompatibility complex type I deficiency-the first such report in a child of black African descent-and follows it with a summary of existing literature on the epidemiology, presentation, and diagnosis as well as principles of management of this disorder.
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Doenças da Imunodeficiência Primária , Reinfecção , Masculino , Criança , Humanos , Pré-Escolar , Reinfecção/genética , Antígenos de Histocompatibilidade Classe II/genética , Complexo Principal de Histocompatibilidade , Doenças da Imunodeficiência Primária/genéticaRESUMO
Wiskott-Aldrich syndrome is an X-linked recessive primary immune-deficiency disorder very rarely reported from black African children. A 12-year old boy with recurrent sinopulmonary and diarrheal infections, eczema, thrombocytopenia, and low platelet volume was found by whole genome sequencing to harbor a predicted pathogenic c.1205dupC (p.Pro403Alafs*92) variant of a mutation in the WAS gene - confirming the diagnosis. This case report summarizes his presentation and management and provides a useful summary of the diagnosis and the responsible novel genetic mutation.
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Eczema , Trombocitopenia , Síndrome de Wiskott-Aldrich , Masculino , Criança , Humanos , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/genética , Proteína da Síndrome de Wiskott-Aldrich/genética , Mutação/genéticaRESUMO
Four in five children with inborn errors of immunity globally remain undiagnosed. These figures are disproportionally high in low-income countries like Ethiopia. Apart from the inclusion of basic overviews of these disorders in to postgraduate pediatric curricula, little effort has been placed in to establishing clinical immunology training programs. This report summarizes the existing epidemiology of inborn errors of immunity in Ethiopia, unique presentations in Ethiopian children, challenges faced in diagnosing them, and efforts to improve their management.
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Doenças Genéticas Inatas , Doenças do Sistema Imunitário , Criança , Humanos , Etiópia/epidemiologia , Doenças Genéticas Inatas/epidemiologia , Doenças Genéticas Inatas/imunologia , Doenças do Sistema Imunitário/epidemiologia , Doenças do Sistema Imunitário/genéticaRESUMO
BACKGROUND: Invasive candidiasis and/or candidemia (IC/C) is a common fungal infection leading to significant health and economic losses worldwide. Caspofungin was shown to be more effective than fluconazole in treating inpatients with IC/C. However, cost-effectiveness of caspofungin for treating IC/C in Ethiopia remains unknown. We aimed to assess the cost-utility of caspofungin compared to fluconazole-initiated therapies as primary treatment of IC/C in Ethiopia. METHODS: A Markov cohort model was developed to compare the cost-utility of caspofungin versus fluconazole antifungal agents as first-line treatment for adult inpatients with IC/C from the Ethiopian health system perspective. Treatment outcome was categorized as either a clinical success or failure, with clinical failure being switched to a different antifungal medication. Liposomal amphotericin B (L-AmB) was used as a rescue agent for patients who had failed caspofungin treatment, while caspofungin or L-AmB were used for patients who had failed fluconazole treatment. Primary outcomes were expected quality-adjusted life years (QALYs), costs (US$2021), and the incremental cost-utility ratio (ICUR). These QALYs and costs were discounted at 3% annually. Cost data was obtained from Addis Ababa hospitals while locally unavailable data were derived from the literature. Cost-effectiveness was assessed against the recommended threshold of 50% of Ethiopia's gross domestic product/capita (i.e.,US$476). Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the findings. RESULTS: In the base-case analysis, treatment of IC/C with caspofungin as first-line treatment resulted in better health outcomes (12.86 QALYs) but higher costs (US$7,714) compared to fluconazole-initiated treatment followed by caspofungin (12.30 QALYs; US$3,217) or L-AmB (10.92 QALYs; US$2,781) as second-line treatment. Caspofungin as primary treatment for IC/C was not cost-effective when compared to fluconazole-initiated therapies. Fluconazole-initiated treatment followed by caspofungin was cost-effective for the treatment of IC/C compared to fluconazole with L-AmB as second-line treatment, at US$316/QALY gained. Our findings were sensitive to medication costs, drug effectiveness, infection recurrence, and infection-related mortality rates. At a cost-effectiveness threshold of US$476/QALY, treating IC/C patient with fluconazole-initiated treatment followed by caspofungin was more likely to be cost-effective in 67.2% of simulations. CONCLUSION: Our study showed that the use of caspofungin as primary treatment for IC/C in Ethiopia was not cost-effective when compared with fluconazole-initiated treatment alternatives. The findings supported the use of fluconazole-initiated therapy with caspofungin as a second-line treatment for patients with IC/C in Ethiopia.
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Candidemia , Candidíase Invasiva , Adulto , Humanos , Caspofungina/uso terapêutico , Fluconazol/uso terapêutico , Candidemia/tratamento farmacológico , Análise Custo-Benefício , Equinocandinas/uso terapêutico , Etiópia , Lipopeptídeos/uso terapêutico , Candidíase Invasiva/tratamento farmacológico , Antifúngicos/uso terapêuticoRESUMO
Background: Cancer treatment is associated with variable degrees of myelosupression. Infection is often a life-threatening complication of chemotherapy-induced neutropenia, and it is also considered an oncologic emergency. Febrile neutropenia is a common, costly and potentially fatal complication in oncology. Objective: To assess factors affecting treatment outcome of cancer patients with chemotherapy induced febrile neutropenia. Method: We conducted a review of records of pediatric patients hospitalized and treated for chemotherapy-induced febrile neutropenia from January 1, 2013 to December 31, 2013 and met the selection criteria. Result: A total of 60 patients (36 males and 24 females) fulfilled the selection criteria. Twelve of them died while in hospital. The mean (SD) age of patients who died was 4.78 (±2.48) years and the mean (SD) hospital stay before death was 20.2 (±5.26) days. Ten children had hematologic malignancy and two had a solid tumor. Ten of the 12 patients had an absolute neutrophil count of less than 100/mm3 (p=0.008, OR=20.3) and a platelet count of less than 50,000/mm3. Six of the 10 children (10%) had sepsis. Patients with profound neutropenia, platelet count of less than 50,000 and sepsis were more likely to die (P=0.048, OR=7). Conclusion: The result of this study showed that absolute neutrophil count of less than 100/mm3, platelet count of less than 50,000/mm3 and a diagnosis of sepsis were factors affecting outcome patients with febrile neutropenia. Careful evaluation of these factors and assessing severity of patients' clinical condition at time of admission can be useful for triaging children with febrile neutropenia.
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Antibacterianos/uso terapêutico , Neutropenia Febril Induzida por Quimioterapia/terapia , Neoplasias/tratamento farmacológico , Sepse/terapia , Hemocultura , Neutropenia Febril Induzida por Quimioterapia/mortalidade , Criança , Pré-Escolar , Etiópia , Feminino , Humanos , Lactente , Contagem de Leucócitos , Masculino , Monócitos , Mortalidade , Neutrófilos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sepse/epidemiologia , Trombocitopenia/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Chronic hepatitis B affects close to 300 million people globally with 1.5 million new infections per year. It causes the highest numbers of cirrhosis and liver cancer diagnoses each year. In children, perinatal transmission and contact with infected blood or body fluids remain the main methods of transmission. There are increasing reports of breakthrough hepatitis B infections in fully vaccinated children born to hepatitis B-negative mothers, especially in low- and middle-income countries. Our study aimed to measure the adequacy of hepatitis B surface antibody levels among children and adolescents who received three rounds of hepatitis B vaccination during infancy and delivered to hepatitis B-negative mothers in Addis Ababa, Ethiopia. METHOD: This was a retrospective cohort study analyzing results of paired serology tests for hepatitis B surface antibody and antigen tests performed for children aged 1-18 years from July 2022 to June 2023. All recorded data were transferred to SPSS version 29.0. The prevalence of adequate hepatitis B surface antibody levels was determined and sub-group analysis conducted using descriptive statistics, frequencies and tables. The magnitude of association between different variables and vaccine-induced hepatitis B immunity was assessed using logistic regression. Statistically significant differences were taken at p < 0.05. RESULTS: A total of 256 children were included in the study (mean age: 7.53 years). Six children (2.3%) had breakthrough hepatitis B infections. Overall, 37 children (14.4%) were categorized as having optimal hepatitis B surface antibody levels (vaccine-induced antibody titers of >10 IU/mL), while 219 (85.6%) had low titers of <10 IU/mL. Nearly all (97.4%) of the sub-group aged 10 years and above had below-par antibody levels, with adolescents (11-18 years) being ten times more likely to have low seroprotection than those aged less than 5 years. CONCLUSIONS: Our study showed markedly low vaccine-induced hepatitis B surface antibody levels among the study population, especially adolescents. The presence of breakthrough infections may suggest a genuine lack of response and not just a mere drop in antibody titers and thus could highlight a significant public health problem in Ethiopia. Further immunologic studies and a thorough analysis of vaccine storage and administration should be conducted to inform prevention programs.
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Trisomy 21 (Down syndrome) is a chromosomal disorder associated with humoral and cellular immunologic impairments among other systemic manifestations. It occurs at a frequency of 1 in 750 live births. There are increasing reports of children with Down syndrome presenting signs of severe COVID-19. The literature from Africa on pediatric COVID-19 and risk stratification for severe disease is scant. A summary of the clinical features, complications, and treatment outcomes of three Ethiopian children with Trisomy 21 and severe COVID-19 along with a discussion of the correlation between trisomy 21 immunology and severe SARS CoV-2 infection is presented.
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Background: Fascioliasis is a zoonotic infection caused by Fasciola spp. (liver fluke). Although infrequently diagnosed, it is emerging as a helminth infection of public health importance in many parts of the world. There are few reports on human fascioliasis from Africa. Case report: This article reports a case of a 12-year-old Ethiopian boy who presented with left-sided abdominal pain and a history of frequent consumption of leafy vegetables. His work-up showed leukocytosis with marked eosinophilia, and increased serum amylase and lipase, and imaging confirmed multiple subcapsular hepatic masses as well as acute necrotizing pancreatitis. Upon serological testing for helminths, he tested positive on Fasciola hepatica enzyme-linked immunosorbent assay. Conclusions: Fascioliasis may present with acute pancreatitis, and should be considered as a possible diagnosis in people with acute biliary disease in endemic settings.
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Effective antimicrobial exposure is essential to treat infections and prevent antimicrobial resistance, both being major public health problems in low and middle income countries (LMIC). Delivery of drug concentrations to the target site is governed by dose and pharmacokinetic processes (absorption, distribution, metabolism and excretion). However, specific data on the pharmacokinetics of antimicrobials in children living in LMIC settings are scarce. Additionally, there are significant logistical constraints to therapeutic drug monitoring that further emphasize the importance of understanding pharmacokinetics and dosing in LMIC. Both malnutrition and diarrheal disease reduce the extent of enteral absorption. Multiple antiretrovirals and antimycobacterial agents, commonly used by children in low resource settings, have potential interactions with other antimicrobials. Hypoalbuminemia, which may be the result of malnutrition, nephrotic syndrome or liver failure, increases the unbound concentrations of protein bound drugs that may therefore be eliminated faster. Kidney function develops rapidly during the first years of life and different inflammatory processes commonly augment renal clearance in febrile children, potentially resulting in subtherapeutic drug concentrations if doses are not adapted. Using a narrative review approach, we outline the effects of growth, maturation and comorbidities on maturational and disease specific effects on pharmacokinetics in children in LMIC.
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Antimicrobial resistance is a global health threat and there is an urgent need to manage antibiotic use to slow its development. However, antimicrobial stewardship interventions in low- and middle-income countries (LMIC) have been limited in terms of their resourcing, feasibility and effectiveness in the face of greater challenges in child mortality. We sought to gather together examples of antibiotic use problems faced by clinicians in LMIC, many of which are unique to these settings, and real-world antimicrobial stewardship solutions identified, with the goal of learning broader lessons that might be applicable across LMIC.
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Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Países em Desenvolvimento , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/psicologia , Resolução de Problemas , Antibacterianos/efeitos adversos , Humanos , Pediatria , Sociedades MédicasRESUMO
BACKGROUND: Ethiopia launched free access for antiretroviral therapy in 2005. The number of patients on second line antiretroviral treatment has increased with each passing year. The objectives of this study were to describe the clinical, immunological and virologic outcomes of children and adolescents receiving second line anti-retroviral therapy in two referral hospitals, Yekatit 12 and Zewditu Memorial Hospitals, in Addis Ababa, Ethiopia. METHODS: This was a hospital based retrospective cohort study conducted among children and adolescents aged 18 years and less and receiving a second line antiretroviral drugs. Data was collected using structured questionnaires. Means and percentages were used for nominal variables. Statistical analysis was made using statistical software-SPSS 23.0. Kaplan Meier analysis, long rank test and multivariate Cox proportion model were used to identify factors affecting survival. RESULTS: A total of 75 children and adolescents were studied with a mean age of 13.28 years (SD: 4) with a mean treatment period on second line regimens of 35.2 months (SD: 21.8 months). Forty-eight participants were experiencing successful measures (in all three parameters) for their second line anti-retroviral treatment. Ten had virologic treatment failure while seven had died. Both treatment failure and death rates were higher within the first two years of treatment. Poor treatment adherence (Adjusted hazard ratio: 5.1 (95% CI: 1.1-23.2; p-value = 0.02)) and advanced World Health Organization clinical stage at start of the second line antiretrovirals (Adjusted hazard ratio: 7.51 (95% CI: 1.35-18.02; p-value = 0.002)) correlated significantly with survival of children and adolescents receiving treatment. CONCLUSIONS: The study describes clinical, immunological and virologic outcomes of second line antiretroviral treatment in a pediatric cohort under care in two hospitals in Addis Ababa, Ethiopia. Poor adherence and pre-treatment advanced clinical stages were predictors of survival.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Centros de Cuidados de Saúde Secundários/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Etiópia/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Estudos Retrospectivos , Falha de TratamentoRESUMO
Background. Congenital toxoplasmosis is a major sequela of untreated primary maternal infection. With or without symptoms, untreated infections eventually lead to multiple neurologic complications. Despite the high Toxoplasma gondii seroprevalence in the Ethiopian population, there are no reports of newborns diagnosed and treated for congenital toxoplasmosis. Presentation of Cases. The clinical presentation, evaluation, and management of three infants with congenital toxoplasmosis are described. Two were symptomatic at birth. All three had confirmed diagnoses using Toxoplasma serologic tests. Two completed their treatment with one infant developing complications of strabismus and seizure disorder. Discussion and Conclusions. There is little experience in managing congenital toxoplasmosis in Ethiopia due to constraints in diagnostics and therapy. The description of this first such report underscores the need for risk assessment and evaluation during antenatal care to obtain favorable fetal outcomes.
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OBJECTIVE: Antimicrobial stewardship (AMS) significantly reduces inappropriate antibiotic use and improves patient outcomes. In low-resource settings, AMS implementation may require concurrent strengthening of clinical microbiology capacity therefore additional investments. We assessed the cost-effectiveness of implementing AMS at Tikur Anbessa Specialised Hospital (TASH), a tertiary care hospital in Ethiopia. DESIGN: We developed a Markov cohort model to assess the cost-utility of pharmacist-led AMS with concurrent strengthening of laboratory capacity compared with usual care from a 'restricted societal' perspective. We used a lifetime time horizon and discounted health outcomes and cost at 3% annually. Data were extracted from a prospective study of bloodstream infections among patients hospitalised at TASH, supplemented by published literature. We assessed parameter uncertainty using deterministic and probabilistic sensitivity analyses. SETTING: Tertiary care hospital in Ethiopia, with 800 beds and serves over half a million patients per year. POPULATION: Cohort of adults and children inpatient population aged 19.8 years at baseline. INTERVENTION: Laboratory-supported pharmacist-led AMS compared with usual care. Usual care is defined as empirical initiation of antibiotic therapy in the absence of strong laboratory and AMS. OUTCOME MEASURES: Expected life-years, quality-adjusted life-years (QALYs), costs (US$2018) and incremental cost-effectiveness ratio. RESULTS: Laboratory-supported AMS strategy dominated usual care, that is, AMS was associated with an expected incremental gain of 38.8 QALYs at lower expected cost (incremental cost savings:US$82 370) per 1000 patients compared with usual care. Findings were sensitive to medication cost, infection-associated mortality and AMS-associated mortality reduction. Probabilistic sensitivity analysis demonstrated that AMS programme was likely to be cost-effective at 100% of the simulation compared with usual care at 1%-51% of gross domestic product/capita. CONCLUSION: Our study indicates that laboratory-supported pharmacist-led AMS can result in improved health outcomes and substantial healthcare cost savings, demonstrating its economic advantage in a tertiary care hospital despite greater upfront investments in a low-resource setting.
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Gestão de Antimicrobianos , Adulto , Criança , Análise Custo-Benefício , Etiópia/epidemiologia , Hospitais de Ensino , Humanos , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Centros de Atenção Terciária , Adulto JovemRESUMO
BACKGROUND: Wiskott Aldrich syndrome is a primary immunodeficiency notable for eczema, recurrent infections, bleeding diathesis and microcytic thrombocytopenia. CASE: A 4½ year old boy presented with recurrent sinopulmonary infections, repeated treatment for severe eczema since infancy, thrombocytopenia with low platelet volume. His brother and uncles died during childhood due to repeated illnesses. We outline ways to diagnose and manage children in resource limited settings. CONCLUSION: Wiskott Aldrich syndrome can be diagnosed by its clinical triad of syndromes. Mutation of the WASP gene confirms diagnosis. Increasing reports of primary immune deficiencies in Ethiopia call for improved education and care for clinical immunology.
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Trombocitopenia , Síndrome de Wiskott-Aldrich , Criança , Família , Humanos , Masculino , Mutação , Trombocitopenia/diagnóstico , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/genética , Proteína da Síndrome de Wiskott-Aldrich/genéticaRESUMO
Sub-Saharan Africa carries the largest burden of pediatric HIV infection. The success of second line anti-retroviral treatment and related factors among African children is not well-defined. Objectives: We aimed to identify the rate and determinants of second line anti-retroviral treatment failure among children and adolescents on follow-up at an Ethiopian tertiary teaching hospital. A retrospective observational cohort study was conducted at Tikur Anbessa Specialized Hospital, Addis Ababa. Structured forms were used to collect socio-demographic, clinical and diagnostic data. Descriptive statistics and bivariate analysis were used to describe the magnitude of the problem and its associations. A total of 76 children and adolescents taking second line anti-retroviral treatment were analyzed (mean age: 16.1 years). Failure of therapy was seen in 14/76 while four were eligible for a switch to third line anti-retrovirals. Mean duration on second line treatment till virologic failure was diagnosed was 17.6 months while mean viral load upon requiring a third line regimen was 82,131.3 copies/ml. Second line antiretroviral treatment virologic failure was significantly associated with the age of the child or adolescent. A high rate of virologic failure exists among the study population. Findings underline need for provision of third line anti-retroviral drugs in Ethiopia. Challenges for delivering a standard care were irregular viral load testing and delayed initiation of second line treatment after failure of first line regimens.
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Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Etiópia , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , HIV-1/fisiologia , Humanos , Estudos Retrospectivos , Centros de Atenção Terciária , Falha de Tratamento , Carga ViralRESUMO
BACKGROUND: Cellular primary immunodeficiencies are rarely reported from Africa. DiGeorge syndrome is a commonly recognized form of a congenital T-cell deficiency. The disorder is characterized by hypoplastic or aplastic thymus, hypocalcemia, recurrent infections, and other associated congenital defects. Case Report. We report an eleven-month-old infant presenting with recurrent chest and diarrheal infections, failure to thrive, lymphopenia, hypocalcemia, and hypoplastic thymus on imaging. A diagnosis of DiGeorge syndrome was confirmed after determining very low CD3 and CD4 levels. CONCLUSIONS: We describe the first case report of an Ethiopian child with a congenital T-cell immunodeficiency. We have outlined essentials for diagnosis and management of cellular primary immunodeficiency disorders in low resource settings.
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Background: Access to clinical bacteriology in low resource settings (LRS) is a key bottleneck preventing individual patient management of treatable severe infections, detection of antimicrobial resistance (AMR), and implementation of effective stewardship interventions. We sought to demonstrate the feasibility of a practical bundle of interventions aimed at implementing sustainable clinical bacteriology services at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia, and report on cost and intensity of supervision. Methods: Starting in Dec 2015, an intervention based on the CLSI QMS01-A guideline was established, consisting of (i) an initial needs assessment, (ii) development of key standard operating procedures, (iii) adaptation of processes for LRS, (iv) training and supervision of laboratory staff via consultant visits and existing online resources, and (v) implementation of a practical quality systems approach. A guiding principle of the bundle was sustainability of all interventions post implementation. Outcomes and challenges: An initial investment of ~US$ 26,200 for laboratory reagents, and a total of 50 visit-days per year from three Canadian and Norwegian microbiologists were committed. Twelve SOPs, including antimicrobial susceptibility testing, were adapted, and an automated blood culture platform was donated (bioMerieux). In the first 18 months of implementation of the intervention, the average volume of specimens analyzed in the lab went from 15/day to 75/day. The number of blood cultures tested increased from an average of 2/day to over 45/day. Antimicrobial susceptibility testing was introduced and cumulative antibiograms were generated for the institution. Quality control was implemented for all procedures and quality assurance tools implemented included external quality assurance and proficiency testing of six technologists with longitudinal follow-up. The laboratory is on the path toward SLIPTA accreditation by the African Society for Laboratory Medicine. Reagent costs, staff training and retention, and engagement of clinical personnel with the lab proved to be manageable challenges. Key external challenges include in-country supply-chain management issues, lack of competition among distributors, and foreign-currency exchange distortions. Conclusions: Using a relatively low-intensity intervention based on existing training tools and accreditation schemes, we demonstrate that establishment of reasonable-quality clinical bacteriology is not only within reach but also a critical step toward assessing the burden of AMR in settings like this one and implementing effective stewardship strategies.
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Gestão de Antimicrobianos , Bacteriologia , Laboratórios Hospitalares/normas , Pessoal de Laboratório/educação , Garantia da Qualidade dos Cuidados de Saúde , Acreditação , Bacteriologia/normas , Países em Desenvolvimento , Etiópia , Estudos de Viabilidade , Humanos , Laboratórios Hospitalares/economia , Técnicas Microbiológicas/normas , Técnicas Microbiológicas/estatística & dados numéricos , Encaminhamento e ConsultaRESUMO
Meningitis is one of the top ten causes of death among Ethiopian infants. Group B streptococcus (GBS) has emerged as a leading cause of meningitis in neonates and young infants, resulting in high mortality. Despite this, there is no report on GBS associated meningitis in Ethiopia where infant meningitis is common. Hence, the aim of this study was to determine the proportion of GBS associated meningitis among Ethiopian infants. PCR was prospectively used to detect GBS in culture-negative cerebrospinal fluid (CSF) samples, which were collected from infants suspected for meningitis, at Tikur Anbessa specialized hospital, Ethiopia, over a one-year period. GBS was detected by PCR in 63.9% of culture-negative CSF samples. Out of the 46 GBS positive infants, 10.9% (n = 5) of them died. The late onset of GBS (LOGBS) disease was noted to have a poor outcome with 3 LOGBS out of 5 GBS positive samples collected from patients with the final outcome of death. PCR was advantageous in the identification of GBS in culture-negative CSF samples. GBS was detected in 64% of the CSF samples from infants with meningitis compared with zero-detection rate by culture.
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Meningites Bacterianas , Reação em Cadeia da Polimerase , Infecções Estreptocócicas , Streptococcus agalactiae/genética , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/genética , Infecções Estreptocócicas/líquido cefalorraquidiano , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/genéticaRESUMO
Intense antibiotic consumption in Low- and Middle-Income Countries (LMICs) is fueled by critical gaps in laboratory infrastructure and entrenched syndromic management of infectious syndromes. Few data inform the achievability and impact of antimicrobial stewardship interventions, particularly in Sub-Saharan Africa. Our goal was to demonstrate the feasibility of a pharmacist-led laboratory-supported intervention at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia, and report on antimicrobial use and clinical outcomes associated with the intervention. Methods: This was a single-center prospective quasi-experimental study conducted in two phases: (i) an intervention phase (November 2017 to August 2018), during which we implemented weekly audit and immediate (verbal and written) feedback sessions on antibiotic prescriptions of patients admitted in 2 pediatric and 2 adult medicine wards, and (ii) a post-intervention phase (September 2018 to January 2019) during which we audited antibiotic prescriptions but provided no feedback to the treating teams. The intervention was conducted by an AMS team consisting of 4 clinical pharmacists (one trained in AMS) and one ID specialist. Our primary outcome was antimicrobial utilization (measured as days of therapy (DOT) per 1,000 patient-days and duration of antibiotic treatment courses); secondary outcomes were length of hospital stay and in-hospital all-cause mortality. A multivariable logistic regression model was used to explore factors associated with all-cause in-hospital mortality. Results: We collected data on 1,109 individual patients (707 during the intervention and 402 in the post-intervention periods). Ceftriaxone, vancomycin, cefepime, meropenem, and metronidazole were the most commonly prescribed antibiotics; 96% of the recommendations made by the AMS team were accepted. The AMS team recommended to discontinue antibiotic therapy in 54% of cases during the intervention period. Once the intervention ceased, total antimicrobial use increased by 51.6% and mean duration of treatment by 4.1 days/patient. Mean LOS stay as well as crude mortality also increased significantly in the post-intervention phase (LOS: 24.1 days vs. 19.8 days; in hospital death 14.7 vs. 6.9%). The difference in mortality remained significant after adjusting for potential confounders. Conclusions: A pharmacist-led AMS intervention focused on duration of antibiotic treatment was feasible and had good acceptability in our setting. Cessation of audit-feedback activities was associated with immediate and sustained increases in antibiotic consumption reflecting a rapid return to baseline (pre-intervention) prescribing practices, and worse clinical outcomes (increased length of stay and in-hospital mortality). Pharmacist-led audit-feedback activities can effectively reduce antimicrobial consumption and result in better-quality care, but require organizational leadership's commitment for sustainable benefits.