26 results on '"Kristina Elfving"'
Search Results
2. Physician’s conceptions of the decision-making process when managing febrile infants ≤ 60 days old: a phenomenographic qualitative study
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Ioannis Orfanos, Rose-Marie Lindkvist, Erik G. A. Eklund, Kristina Elfving, Tobias Alfvén, Tom J. de Koning, and Charlotte Castor
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Febrile infants ,Guidelines ,Adherence ,Lumbar puncture ,Pediatrics ,RJ1-570 - Abstract
Abstract Background The management of febrile infants aged ≤ 60 days and adherence to guidelines vary greatly. Our objective was to describe the process of decision-making when managing febrile infants aged ≤ 60 days and to describe the factors that influenced this decision. Methods We conducted 6 focus group discussions with 19 clinically active physicians in the pediatric emergency departments of 2 university hospitals in Skåne region, Sweden. We followed an inductive qualitative design, using a phenomenological approach. A second-order perspective was used, focusing on how physicians perceived the phenomenon (managing fever in infants) rather than the phenomenon itself. The transcribed interviews were analyzed using a 7-step approach. Results Performing a lumbar puncture (LP) was conceived as a complex, emotionally and mentally laden procedure and dominated the group discussions. Three central categories emerged as factors that influenced the decision-making process on whether to perform an LP: 1) a possible focus of infection that could explain the origin of the fever, 2) questioning whether the temperature at home reported by the parents was a fever, especially if it was ≤ 38.2°C, and 3) the infant’s general condition and questioning the need for LP in case of well-appearing infants. Around these 3 central categories evolved 6 secondary categories that influenced the decision-making process of whether to perform an LP or not: 1) the physicians’ desire to be able to trust their judgement, 2) fearing the risk of failure, 3) avoiding burdensome work, 4) taking others into account, 5) balancing guidelines and resources, and 6) seeing a need to practice and learn to perform LP. Conclusions The difficulty and emotional load of performing an LP were important factors that influenced the decision-making process regarding whether to perform an LP. Physicians highlighted the importance of being able to rely on their clinical judgment and make independent decisions. Guidelines may consider allowing a degree of flexibility and independent thinking to take into account patients’ characteristics and needs.
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- 2024
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3. Childhood stunting is highly clustered in Northern Province of Rwanda: A spatial analysis of a population-based study
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Albert Ndagijimana, Gilbert Nduwayezu, Clarisse Kagoyire, Kristina Elfving, Aline Umubyeyi, Ali Mansourian, and Torbjörn Lind
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Spatial ,Child ,Stunting ,Undernutrition ,Rwanda ,Sub-saharan africa ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Background: In Northern Province, Rwanda, stunting is common among children aged under 5 years. However, previous studies on spatial analysis of childhood stunting in Rwanda did not assess its randomness and clustering, and none were conducted in Northern Province. We conducted a spatial-pattern analysis of childhood undernutrition to identify stunting clusters and hotspots for targeted interventions in Northern Province. Methods: Using a household population-based questionnaire survey of the characteristics and causes of undernutrition in households with biological mothers of children aged 1–36 months, we collected anthropometric measurements of the children and their mothers and captured the coordinates of the households. Descriptive statistics were computed for the sociodemographic characteristics and anthropometric measurements. Spatial patterns of childhood stunting were determined using global and local Moran's I and Getis-Ord Gi* statistics, and the corresponding maps were produced. Results: The z-scores of the three anthropometric measurements were normally distributed, but the z-scores of height-for-age were generally lower than those of weight-for-age and weight-for-height, prompting us to focus on height-for-age for the spatial analysis. The estimated incidence of stunting among 601 children aged 1–36 months was 27.1 %. The sample points were interpolated to the administrative level of the sector. The global Moran's I was positive and significant (Moran's I = 0.403, p
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- 2024
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4. Pneumococcal concentration and serotype distribution in preschool children with radiologically confirmed pneumonia compared to healthy controls prior to introduction of pneumococcal vaccination in Zanzibar: an observational study
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Kristina Elfving, Lucia Gonzales Strömberg, Shadi Geravandi, Maria Andersson, Marc Bachelard, Mwinyi Msellem, Delér Shakely, Birger Trollfors, Rickard Nordén, Andreas Mårtensson, Anders Björkman, and Magnus Lindh
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Preschool child ,Immunization ,Serotypes ,Pneumococci ,Radiology ,Pneumonia ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background The World Health Organization recommends pneumococcal vaccination (PCV) in the first year of life. We investigated pneumococcal serotypes in children with clinical or radiologically confirmed pneumonia and healthy controls prior to PCV13 vaccine introduction in Zanzibar. Methods Children (n = 677) with non-severe acute febrile illness aged 2–59 months presenting to a health centre in Zanzibar, Tanzania April–July 2011 were included. Nasopharyngeal swabs collected at enrolment were analysed by real-time PCR to detect and quantify pneumococcal serotypes in patients (n = 648) and in healthy asymptomatic community controls (n = 161). Children with clinical signs of pneumonia according to the Integrated Management of Childhood illness guidelines (“IMCI pneumonia”) were subjected to a chest-X-ray. Consolidation on chest X-ray was considered “radiological pneumonia”. Results Pneumococcal DNA was detected in the nasopharynx of 562/809 (69%) children (70% in patients and 64% in healthy controls), with no significant difference in proportions between patients with or without presence of fever, malnutrition, IMCI pneumonia or radiological pneumonia. The mean pneumococcal concentration was similar in children with and without radiological pneumonia (Ct value 26.3 versus 27.0, respectively, p = 0.3115). At least one serotype could be determined in 423 (75%) participants positive for pneumococci of which 33% had multiple serotypes detected. A total of 23 different serotypes were identified. One serotype (19F) was more common in children with fever (86/648, 13%) than in healthy controls (12/161, 7%), (p = 0.043). Logistic regression adjusting for age and gender showed that serotype 9A/V [aOR = 10.9 (CI 2.0–60.0, p = 0.006)] and 14 [aOR = 3.9 (CI 1.4–11.0, p = 0.012)] were associated with radiological pneumonia. The serotypes included in the PCV13 vaccine were found in 376 (89%) of the 423 serotype positive participants. Conclusion The PCV13 vaccine introduced in 2012 targets a great majority of the identified serotypes. Infections with multiple serotypes are common. PCR-determined concentrations of pneumococci in nasopharynx were not associated with radiologically confirmed pneumonia. Trial registration Clinicaltrials.gov (NCT01094431).
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- 2022
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5. Oxygen saturation after birth in resuscitated neonates in Uganda: a video-based observational study
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Daniele Trevisanuto, Nicolas J Pejovic, Thorkild Tylleskär, Susanna Myrnerts Höök, Clare Lubulwa, Kristina Elfving, Allan Mpamize, and Mårten Larsson
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Pediatrics ,RJ1-570 - Published
- 2022
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6. Novel Biomarkers Differentiating Viral from Bacterial Infection in Febrile Children: Future Perspectives for Management in Clinical Praxis
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Samuel Rhedin, Kristina Elfving, and Anna Berggren
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biomarkers ,pediatric infectious diseases ,Pediatrics ,RJ1-570 - Abstract
Differentiating viral from bacterial infections in febrile children is challenging and often leads to an unnecessary use of antibiotics. There is a great need for more accurate diagnostic tools. New molecular methods have improved the particular diagnostics of viral respiratory tract infections, but defining etiology can still be challenging, as certain viruses are frequently detected in asymptomatic children. For the detection of bacterial infections, time consuming cultures with limited sensitivity are still the gold standard. As a response to infection, the immune system elicits a cascade of events, which aims to eliminate the invading pathogen. Recent studies have focused on these host–pathogen interactions to identify pathogen-specific biomarkers (gene expression profiles), or “pathogen signatures”, as potential future diagnostic tools. Other studies have assessed combinations of traditional bacterial and viral biomarkers (C-reactive protein, interleukins, myxovirus resistance protein A, procalcitonin, tumor necrosis factor-related apoptosis-inducing ligand) to establish etiology. In this review we discuss the performance of such novel diagnostics and their potential role in clinical praxis. In conclusion, there are several promising novel biomarkers in the pipeline, but well-designed randomized controlled trials are needed to evaluate the safety of using these novel biomarkers to guide clinical decisions.
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- 2021
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7. Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar - Aetiologies, Antibiotic Treatment and Outcome.
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Kristina Elfving, Deler Shakely, Maria Andersson, Kimberly Baltzell, Abdullah S Ali, Marc Bachelard, Kerstin I Falk, Annika Ljung, Mwinyi I Msellem, Rahila S Omar, Philippe Parola, Weiping Xu, Max Petzold, Birger Trollfors, Anders Björkman, Magnus Lindh, and Andreas Mårtensson
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Medicine ,Science - Abstract
BACKGROUND:Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission. METHODS:We prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated. FINDINGS:NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia. CONCLUSIONS:This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low.
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- 2016
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8. The usefulness of rapid diagnostic tests in the new context of low malaria transmission in Zanzibar.
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Delér Shakely, Kristina Elfving, Berit Aydin-Schmidt, Mwinyi I Msellem, Ulrika Morris, Rahila Omar, Xu Weiping, Max Petzold, Bryan Greenhouse, Kimberly A Baltzell, Abdullah S Ali, Anders Björkman, and Andreas Mårtensson
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Medicine ,Science - Abstract
We assessed if histidine-rich-protein-2 (HRP2) based rapid diagnostic test (RDT) remains an efficient tool for Plasmodium falciparum case detection among fever patients in Zanzibar and if primary health care workers continue to adhere to RDT results in the new epidemiological context of low malaria transmission. Further, we evaluated the performance of RDT within the newly adopted integrated management of childhood illness (IMCI) algorithm in Zanzibar.We enrolled 3890 patients aged ≥ 2 months with uncomplicated febrile illness in this health facility based observational study conducted in 12 primary health care facilities in Zanzibar, between May-July 2010. One patient had an inconclusive RDT result. Overall 121/3889 (3.1%) patients were RDT positive. The highest RDT positivity rate, 32/528 (6.1%), was found in children aged 5-14 years. RDT sensitivity and specificity against PCR was 76.5% (95% CI 69.0-83.9%) and 99.9% (95% CI 99.7-100%), and against blood smear microscopy 78.6% (95% CI 70.8-85.1%) and 99.7% (95% CI 99.6-99.9%), respectively. All RDT positive, but only 3/3768 RDT negative patients received anti-malarial treatment. Adherence to RDT results was thus 3887/3889 (99.9%). RDT performed well in the IMCI algorithm with equally high adherence among children
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- 2013
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9. Paediatric emergency departments should manage young febrile and afebrile infants the same if they have a fever before presenting
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Ioannis Orfanos, Jorge Sotoca Fernandez, Kristina Elfving, Tobias Alfvén, and Erik A. Eklund
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Fever ,Urinary Tract Infections ,Pediatrics, Perinatology and Child Health ,Humans ,Infant ,Bacteremia ,Bacterial Infections ,General Medicine ,Child ,Emergency Service, Hospital ,Meningitis, Bacterial ,Retrospective Studies - Abstract
Our aim was to evaluate the risk of bacterial meningitis, bacteremia, and urinary tract infection (UTI) in infants ≤60 days who presented to paediatric emergency departments (PEDs) after having fever at home. We also investigated any differences between infants who were afebrile or febrile on presentation.This was a multicenter retrospective study of infants ≤60 days presented to four Swedish PEDs during 2014-2020 with reported fever at home. We used relative risks (RR) to compare the prevalence of UTI, bacteremia, and bacterial meningitis between the infants who were afebrile and the infants who were still febrile when they presented to the PED.The cohort comprised 1926 infants, and 702 (36%) were afebrile on presentation. The prevalence of UTI in the afebrile and febrile infants was 6.1% [95% confidence interval (CI) 4.5-8.2] versus 14.2% (95% CI 12.3-16.2), corresponding to an RR of 0.43 (95% CI 0.31-0.59). In infants ≤28 days, the RR for meningitis was 1.05 (95% CI 0.18-6.23) for afebrile versus febrile infants. Five times more febrile infants underwent a lumbar puncture.Infants who were afebrile on presentation underwent fewer lumbar punctures, but they had similar rates of bacterial meningitis to febrile infants. Different management approaches are not justified.
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- 2022
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10. Age‐ and sex‐specific prevalence of serious bacterial infections in febrile infants ≤60 days, in Sweden
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Mattias Tenland, Erik A. Eklund, Jorge Sotoca Fernandez, Kristina Elfving, Maria Mossberg, Ioannis Orfanos, and Tobias Alfvén
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Male ,Sweden ,Pediatric emergency ,medicine.medical_specialty ,Fever ,business.industry ,Urinary system ,Significant difference ,Infant ,Retrospective cohort study ,Bacterial Infections ,General Medicine ,medicine.disease ,Age and sex ,Internal medicine ,Urinary Tract Infections ,Pediatrics, Perinatology and Child Health ,Prevalence ,medicine ,Humans ,Female ,Child ,business ,Meningitis ,Retrospective Studies - Abstract
Aim: The aim of the study was to describe age- and sex-specific prevalence of serious bacterial infections (SBI: urinary tract infection, bacteraemia, meningitis) among febrile infants ≤60 days in Sweden. Methods: This is a retrospective study in 4 Pediatric Emergency Departments from 2014 to 2017, in previously healthy, full-term infants ≤60 days with fever without a source. Results: Of the 1,701 included infants, 214 (12.6%; 95% CI, 11.1–14.3) had an SBI. Urinary tract infection (UTI) was diagnosed in 196 (11.5%; 95% CI, 10.0–13.1) patients. In the ≤28 and 29–60 days age-groups, meningitis prevalence was 0.9% (95% CI, 0.3–2.0) and 0.3% (95% CI, 0.1–0.8), whereas bacteraemia prevalence was 3.2% (95% CI, 1.9–4.9) and 0.6% (95% CI, 0.2–1.3). The SBI prevalence was higher in boys 16.0% (95% CI, 13.8–18.5) than girls 8.0% (95% CI, 6.2–10.2; p
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- 2021
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11. Management and Outcome of Febrile Infants ≤60 days, With Emphasis on Infants ≤21 Days Old, in Swedish Pediatric Emergency Departments
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Ioannis Orfanos, Kristina Elfving, Jorge Sotoca Fernandez, Lovisa Wennlund, Sofia Weiber, Erik A. Eklund, and Tobias Alfvén
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Microbiology (medical) ,Sweden ,Fever ,Infant ,Bacteremia ,Anti-Bacterial Agents ,Meningitis, Bacterial ,Infectious Diseases ,Cross-Sectional Studies ,Pediatrics, Perinatology and Child Health ,Humans ,Child ,Emergency Service, Hospital ,Retrospective Studies - Abstract
Management of febrile infants ≤60 days of age varies, and the age for routine investigations and antibiotic-treatment is debated. The American Academy of Pediatrics recommended age threshold for lumbar puncture (LP) is 21 days and for blood culture 60 days. We describe management and adverse outcome of febrile infants ≤60 days old, in Sweden.Retrospective cross-sectional study of infants ≤60 days of age with fever without source evaluated in 4 University pediatric emergency departments, between 2014 and 2017. Adverse outcome was defined as delayed-treated invasive bacterial infection (IBI: meningitis or bacteremia).We included 1701 infants. In infants ≤21 days old, LP was performed in 16% (95% CI: 12-20) and blood culture in 43% (95% CI: 38-48). Meningitis was diagnosed in 5 (1.3%; 95% CI: 0.4-3.0) and bacteremia in 12 (4.5%; 95% CI: 2.6-7.0) infants. Broad-spectrum antibiotics were not administered to 66% (95% CI: 61-71), of which 2 (0.8%; 95% CI: 0.1-2.8) diagnosed with IBI (1 meningitis and 1 bacteremia). In the 29-60 days age group, blood culture was performed in 21% (95% CI: 19-24), and broad-spectrum antibiotics were not administered to 84% (95% CI: 82-86), with no case of delayed-treated bacteremia.The rates of LP, blood culture and broad-spectrum antibiotics were low. Despite that, there were few delayed-treated IBIs, but 2 of the 17 infants ≤21 days of age with IBI were not timely treated, which prompts the need for a safer approach for this age group. Also, the utility of routine blood culture for all febrile infants 29-60 days old could be questioned.
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- 2022
12. Oxygen saturation after birth in resuscitated neonates in Uganda: A video-based observational study
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Mårten Larsson, Susanna Myrnerts Höök, Allan Mpamize, Thorkild Tylleskär, Clare Lubulwa, Daniele Trevisanuto, Kristina Elfving, and Nicolas J Pejovic
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fungi ,resuscitation ,Infant, Newborn ,neonatology ,physiology ,Pediatrics ,United States ,RJ1-570 ,Cross-Sectional Studies ,Oxygen Saturation ,Pediatrics, Perinatology and Child Health ,Humans ,Uganda ,Neonatology - Abstract
BackgroundMonitoring of peripheral capillary oxygen saturation (SpO2) during neonatal resuscitation is standard of care in high-resource settings, but seldom performed in low-resource settings. We aimed to measure SpO2 and heart rate during the first 10 min of life in neonates receiving positive pressure ventilation (PPV) according to the Helping Babies Breathe (HBB) protocol and compare results with SpO2 and heart rate targets set by the American Heart Association (AHA).MethodsA cross-sectional study was conducted at Mulago National Referral Hospital, Kampala, Uganda, as a substudy of the NeoSupra Trial. SpO2 and heart rate were measured on apnoeic neonates (≥34 weeks) who received PPV according to HBB (room air). Those who remained distressed after PPV received supplemental oxygen (O2). All resuscitations were video recorded and data were extracted by video review at 1 min intervals until 10 min post partum. Data were analysed for all observations and separately for only observations before and during PPV.Results49 neonates were analysed. Median SpO2 at 5 min (n=39) was 67% (49–88) with 59% of the observations below AHA target of 80%. At 10 min median SpO2 (n=44) was 93% (80–97) and 32% were below AHA target of 85%. When only observations before and during PPV were analysed, median SpO2 at 5 min (n=18) was 52% (34–66) and 83% were below AHA target. At 10 min (n=15), median SpO2 was 72% (57–89) and 67% were below AHA target. Median heart rates were above AHA target of 100 beats/min at all time intervals.ConclusionsA high proportion of neonates resuscitated with PPV after birth failed to reach the AHA SpO2 target in this small sample, implying an increased risk of hypoxic-ischaemic encephalopathy. Further studies in low-resource settings are needed to evaluate baseline data and the need for supplemental O2 and optimal SpO2 during PPV.Trial registration numberThis is a substudy to the trial ‘Neonatal Resuscitation with Supraglottic Airway Trial (NeoSupra)’; ClinicalTrials.gov Registry (NCT03133572).
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- 2022
13. Assessment of the FilmArray ME panel in 4199 consecutively tested cerebrospinal fluid samples
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Marie Studahl, Magnus Lindh, Johan Lindström, Kristina Elfving, and Johan Westin
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0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,viruses ,030106 microbiology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Central Nervous System Infections ,Internal medicine ,Streptococcus pneumoniae ,Multiplex polymerase chain reaction ,Enterovirus Infections ,Medicine ,Humans ,Clinical significance ,Meningitis ,030212 general & internal medicine ,Cerebrospinal Fluid ,business.industry ,Varicella zoster virus ,General Medicine ,medicine.disease ,Infectious Diseases ,Herpes simplex virus ,Viruses ,Enterovirus ,Encephalitis ,business ,Multiplex Polymerase Chain Reaction - Abstract
Objectives In central nervous system infections, early and correct management is of utmost importance. Rapid syndromic panel testing can potentially provide valuable guidance. The FilmArray meningitis/encephalitis (ME) panel detects 14 pathogens through multiplex PCR. Our study objectives were to assess its performance compared with established diagnostic procedures, especially real-time quantitative PCR for detection of viruses, and to determine the diagnostic and clinical significance of discrepant results. Methods All cerebrospinal fluid samples sent for viral diagnostics to our microbiological laboratory over 34 months were analysed with the ME panel and in-house real-time PCR for herpes simplex virus type 1 (HSV-1), HSV-2, varicella zoster virus and enteroviruses. Other pathogens detected by the panel were confirmed by routine diagnostic procedures. Discrepant results were analysed through interpretation of biological and clinical data, and performance data were calculated for individual pathogens. Results Altogether, 315 pathogens were detected by the ME panel in 4199 cerebrospinal fluid samples (7.5%) and an additional 21 viral targets were identified using real-time PCR. Thirty-four ME panel detections were not confirmed, totalling 55 discrepant results. After discrepancy analysis, 20 false-positive and 21 false-negative ME panel results remained. Performance varied between pathogens. Sensitivity for HSV-1 was calculated at 82.4% (59.0%–93.8%) with three false-negative results. Also noteworthy were 13 false-negative enterovirus and eight false-positive Streptococcus pneumoniae results. Conclusions Our analysis shows good performance for the ME panel in diagnosing central nervous system infection. The risk of false-negative HSV-1 results, however, warrants additional testing when encephalitis is suspected. Uncertainties in interpretation of enterovirus and S. pneumoniae results represent other limitations.
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- 2021
14. Pathogen Clearance and New Respiratory Tract Infections Among Febrile Children in Zanzibar Investigated With Multitargeting Real-Time Polymerase Chain Reaction on Paired Nasopharyngeal Swab Samples
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Delér Shakely, Max Petzold, Kimberly Baltzell, Kristina Elfving, Birger Trollfors, Andreas Mårtensson, Mwinyi I. Msellem, Magnus Lindh, Maria Andersson, and Anders Björkman
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Male ,0301 basic medicine ,Microbiology (medical) ,Mycoplasma pneumoniae ,Fever ,Rhinovirus ,viruses ,030106 microbiology ,medicine.disease_cause ,Tanzania ,Virus ,Measles virus ,03 medical and health sciences ,0302 clinical medicine ,Nasopharynx ,medicine ,Influenza A virus ,Humans ,Longitudinal Studies ,Prospective Studies ,030212 general & internal medicine ,Respiratory Tract Infections ,Respiratory tract infections ,biology ,Coinfection ,business.industry ,Infant ,biology.organism_classification ,Virology ,Infectious Diseases ,Chlamydophila pneumoniae ,Child, Preschool ,Respiratory Syncytial Virus, Human ,Viruses ,Pediatrics, Perinatology and Child Health ,Parechovirus ,Female ,business ,Multiplex Polymerase Chain Reaction - Abstract
Background New molecular methods have revealed frequent and often polymicrobial respiratory infections in children in low-income settings. It is not known whether presence of multiple pathogens is due to prolonged infections or to frequent exposure. The aim of this study was to analyze short-term pathogen clearance from nasopharynx and the rate of new respiratory tract infections in febrile preschool children. Methods Children (n = 207) with uncomplicated acute febrile illness 2-59 months of age presenting to a health center in Zanzibar, Tanzania, April-July 2011, were included. Paired nasopharyngeal swab samples, collected at enrolment and after 14 days, were analyzed by multiple real-time polymerase chain reaction for Adenovirus, bocavirus, Bordetella pertussis, Chlamydophila pneumoniae, Coronaviruses, Enterovirus, influenza A and B virus, metapneumovirus, measles virus, Mycoplasma pneumoniae, parainfluenza virus, Parechovirus, respiratory syncytial virus and Rhinovirus. An age-matched and geographically matched healthy control group (n = 166) underwent nasopharyngeal sampling on 1 occasion. Results At baseline, 157/207 (76%) patients had at least 1 pathogen detected, in total 199 infections. At follow-up (day 14), 162/199 (81%) of these infections were not detected, including >95% of the previously detected infections with Enterovirus, influenza A virus, influenza B virus, metapneumovirus or parainfluenza virus. Still 115 (56%) children were positive for at least 1 pathogen at follow-up, of which 95/115 (83%) were not found at baseline. Detection of influenza B on day 14 was significantly associated with fever during follow-up. Conclusion The results suggest that children with acute febrile illness in Zanzibar rapidly clear respiratory tract infections but frequently acquire new infections within 14 days.
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- 2018
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15. Rapid Clearance and Frequent Reinfection With Enteric Pathogens Among Children With Acute Diarrhea in Zanzibar
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Andreas Mårtensson, Mwinyi I. Msellem, Anders Björkman, Kristina Elfving, Birger Trollfors, Staffan Nilsson, Maria Andersson, Delér Shakely, and Magnus Lindh
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Diarrhea ,Microbiology (medical) ,030231 tropical medicine ,Cryptosporidium ,medicine.disease_cause ,Polymerase Chain Reaction ,Tanzania ,Asymptomatic ,Cohort Studies ,Feces ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Enterotoxigenic Escherichia coli ,Humans ,Medicine ,Shigella ,030212 general & internal medicine ,Bacteria ,biology ,business.industry ,Campylobacter ,Infant ,medicine.disease ,biology.organism_classification ,Gastroenteritis ,Malnutrition ,Infectious Diseases ,Socioeconomic Factors ,Child, Preschool ,Viruses ,Immunology ,Norovirus ,medicine.symptom ,business - Abstract
Background. Acute infectious gastroenteritis is an important cause of illness and death among children in low-income countries. In addition to rotavirus vaccination, actions to improve nutrition status, sanitation, and water quality are important to reduce enteric infections, which are frequent also among asymptomatic children. The aim of this study was to investigate if the high prevalence of these infections reflects that they often are not cleared properly by the immune response or rather is due to frequent pathogen exposure. Methods. Rectal swabs were collected at time of acute diarrhea and 14 days later from 127 children, aged 2-59 months and living in rural Zanzibar, and were analyzed by real-time polymerase chain reaction targeting multiple pathogens. Results. At baseline, detection rates >20% were found for each of enterotoxigenic Escherichia coli, Shigella, Campylobacter, Cryptosporidium, norovirus GII, and adenovirus. At follow-up, a large proportion of the infections had become cleared (34-100%), or the pathogen load reduced, and this was observed also for agents that were presumably unrelated to diarrhea. Still, the detection frequencies at follow- up were for most agents as high as at baseline, because new infections had been acquired. Neither clearance nor reinfection was associated with moderate malnutrition, which was present in 21% of the children. Conclusions. Children residing in poor socioeconomic conditions, as in Zanzibar, are heavily exposed to enteric pathogens, but capable of rapidly clearing causative and coinfecting pathogens.
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- 2017
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16. Distinct Biomarker Profiles Distinguish Malawian Children with Malarial and Non-malarial Sepsis
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Dumizulu L. Tembo, Tonney S. Nyirenda, Kimberly Baltzell, Teresa Bleakly Kortz, James Nyirenda, Gama Bandawe, Philip J. Rosenthal, Wilson Mandala, Kristina Elfving, and Sarah B. Macfarlane
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Male ,medicine.medical_specialty ,Malawi ,Fever ,030231 tropical medicine ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Von Willebrand factor ,Virology ,Internal medicine ,parasitic diseases ,medicine ,Humans ,Malaria, Falciparum ,Retrospective Studies ,biology ,business.industry ,Case-control study ,Infant ,Retrospective cohort study ,Articles ,medicine.disease ,Pathophysiology ,Infectious Diseases ,ROC Curve ,Case-Control Studies ,Child, Preschool ,biology.protein ,Biomarker (medicine) ,Cytokines ,Parasitology ,Tumor necrosis factor alpha ,Female ,business ,Malaria ,Biomarkers - Abstract
Presently, it is difficult to accurately diagnose sepsis, a common cause of childhood death in sub-Saharan Africa, in malaria-endemic areas, given the clinical and pathophysiological overlap between malarial and non-malarial sepsis. Host biomarkers can distinguish sepsis from uncomplicated fever, but are often abnormal in malaria in the absence of sepsis. To identify biomarkers that predict sepsis in a malaria-endemic setting, we retrospectively analyzed data and sera from a case-control study of febrile Malawian children (aged 6-60 months) with and without malaria who presented to a community health center in Blantyre (January-August 2016). We characterized biomarkers for 29 children with uncomplicated malaria without sepsis, 25 without malaria or sepsis, 17 with malaria and sepsis, and 16 without malaria but with sepsis. Sepsis was defined using systemic inflammatory response criteria; biomarkers (interleukin-6 [IL-6], tumor necrosis factor receptor-1, interleukin-1 β [IL-1β], interleukin-10 [IL-10], von Willebrand factor antigen-2, intercellular adhesion molecule-1, and angiopoietin-2 [Ang-2]) were measured with multiplex magnetic bead assays. IL-6, IL-1β, and IL-10 were elevated, and Ang-2 was decreased in children with malaria compared with non-malarial fever. Children with non-malarial sepsis had greatly increased IL-1β compared with the other subgroups. IL-1β best predicted sepsis, with an area under the receiver operating characteristic (AUROC) of 0.71 (95% CI: 0.57-0.85); a combined biomarker-clinical characteristics model improved prediction (AUROC of 0.77, 95% CI: 0.67-0.85). We identified a distinct biomarker profile for non-malarial sepsis and developed a sepsis prediction model. Additional clinical and biological data are necessary to further explore sepsis pathophysiology in malaria-endemic regions.
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- 2019
17. From high to low malaria transmission in Zanzibar-challenges and opportunities to achieve elimination
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Ulrika Morris, Berit Aydin-Schmidt, Andreas Mårtensson, Humphrey R. Mkali, A. K. Abbas, Chris Drakeley, Michael C. Sachs, R. Omar, J. Mcha, A-W Al-Mafazy, Jackie Cook, Max Petzold, Delér Shakely, Anders Björkman, Abdullah S. Ali, Mwinyi I. Msellem, Kristina Elfving, and K. A. Haji
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Male ,Infectious Medicine ,Adolescent ,Cross-sectional study ,lcsh:Medicine ,Infektionsmedicin ,Tanzania ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Environmental health ,parasitic diseases ,medicine ,Prevalence ,Humans ,030212 general & internal medicine ,Risk factor ,Malaria, Falciparum ,Child ,Rapid diagnostic test ,biology ,business.industry ,Incidence (epidemiology) ,Incidence ,lcsh:R ,1. No poverty ,Infant ,Plasmodium falciparum ,General Medicine ,biology.organism_classification ,medicine.disease ,3. Good health ,Transmission (mechanics) ,Cross-Sectional Studies ,Child, Preschool ,Female ,business ,030217 neurology & neurosurgery ,Malaria ,Research Article - Abstract
Background Substantial global progress in the control of malaria in recent years has led to increased commitment to its potential elimination. Whether this is possible in high transmission areas of sub-Saharan Africa remains unclear. Zanzibar represents a unique case study of such attempt, where modern tools and strategies for malaria treatment and vector control have been deployed since 2003. Methods We have studied temporal trends of comprehensive malariometric indices in two districts with over 100,000 inhabitants each. The analyses included triangulation of data from annual community-based cross-sectional surveys, health management information systems, vital registry and entomological sentinel surveys. Results The interventions, with sustained high-community uptake, were temporally associated with a major malaria decline, most pronounced between 2004 and 2007 and followed by a sustained state of low transmission. In 2015, the Plasmodium falciparum community prevalence of 0.43% (95% CI 0.23–0.73) by microscopy or rapid diagnostic test represented 96% reduction compared with that in 2003. The P. falciparum and P. malariae prevalence by PCR was 1.8% (95% CI 1.3–2.3), and the annual P. falciparum incidence was estimated to 8 infections including 2.8 clinical episodes per 1000 inhabitants. The total parasite load decreased over 1000-fold (99.9%) between 2003 and 2015. The incidence of symptomatic malaria at health facilities decreased by 94% with a trend towards relatively higher incidence in age groups > 5 years, a more pronounced seasonality and with reported travel history to/from Tanzania mainland as a higher risk factor. All-cause mortality among children
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- 2019
18. Coinfection with Enteric Pathogens in East African Children with Acute Gastroenteritis—Associations and Interpretations
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Tomas Bergström, Magnus Lindh, Kristina Elfving, Staffan Nilsson, Mwinyi I. Msellem, Jean-Claude Kabayiza, Maria Andersson, Anders Björkman, and Andreas Mårtensson
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0301 basic medicine ,Diarrhea ,Male ,030106 microbiology ,Biology ,medicine.disease_cause ,Real-Time Polymerase Chain Reaction ,Tanzania ,Microbiology ,03 medical and health sciences ,Feces ,0302 clinical medicine ,Virology ,Rotavirus ,medicine ,Humans ,Shigella ,030212 general & internal medicine ,Enteropathogenic Escherichia coli ,Pathogen ,Protozoan Infections ,Coinfection ,Campylobacter ,Rwanda ,Infant ,Articles ,Bacterial Infections ,medicine.disease ,Gastroenteritis ,Infectious Diseases ,Virus Diseases ,Case-Control Studies ,Child, Preschool ,Parasitology ,Female ,medicine.symptom - Abstract
Enteric coinfections among children in low-income countries are very common, but it is not well known if specific pathogen combinations are associated or have clinical importance. In this analysis, feces samples from children in Rwanda and Zanzibar less than 5 years of age, with (N = 994) or without (N = 324) acute diarrhea, were analyzed by real-time polymerase chain reaction targeting a wide range of pathogens. Associations were investigated by comparing co-detection and mono-detection frequencies for all pairwise pathogen combinations. More than one pathogen was detected in 840 samples (65%). A negative association (coinfections being less common than expected from probability) was observed for rotavirus in combination with Shigella, Campylobacter, or norovirus genogroup II, but only in patients, which is statistically expected for agents that independently cause diarrhea. A positive correlation was observed, in both patients and controls, between Ct (threshold cycle) values for certain virulence factor genes in enteropathogenic Escherichia coli (EPEC) (eae and bfpA) and toxin genes in enterotoxigenic E. coli (eltB and estA), allowing estimation of how often these genes were present in the same bacteria. A significant positive association in patients only was observed for Shigella and EPEC-eae, suggesting that this coinfection might interact in a manner that enhances symptoms. Although interaction between pathogens that affect symptoms is rare, this work emphasizes the importance and difference in interpretation of coinfections depending on whether they are positively or negatively associated.
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- 2018
19. The impact of introducing malaria rapid diagnostic tests on fever case management:A synthesis of ten studies from the ACT Consortium
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Frank Baiden, David Schellenberg, Anthony K. Mbonye, S. Patrick Kachur, Ismail Mayan, Katia Bruxvoort, Catherine Goodman, Heidi Hopkins, Toby Leslie, Seth Owusu-Agyei, Shunmay Yeung, Baptiste Leurent, Kristian S. Hansen, Mark Rowland, Siân E. Clarke, Clare I R Chandler, Delér Shakely, Bonnie Cundill, Anders Björkman, Lasse S Vestergaard, Mwinyi I. Msellem, Sham Lal, Debora D DiLiberto, Helen E. D. Burchett, Lindsay Mangham-Jefferies, Pascal Magnussen, Obinna Onwujekwe, Jayne Webster, Andreas Mårtensson, Kristina Elfving, Virginia Wiseman, Christopher J. M. Whitty, Evelyn K. Ansah, Sarah G. Staedke, and David G. Lalloo
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medicine.medical_specialty ,Pediatrics ,Fever ,Referral ,030231 tropical medicine ,MEDLINE ,wc_765 ,Antimalarials ,03 medical and health sciences ,0302 clinical medicine ,Virology ,parasitic diseases ,medicine ,Humans ,030212 general & internal medicine ,Medical prescription ,Artemisinin ,Intensive care medicine ,Africa South of the Sahara ,wc_770 ,Diagnostic Tests, Routine ,business.industry ,Afghanistan ,Diagnostic test ,Public Health, Global Health, Social Medicine and Epidemiology ,Articles ,Case management ,medicine.disease ,wa_243 ,wc_750 ,Malaria ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,Infectious Diseases ,Community health ,Parasitology ,business ,Case Management ,medicine.drug - Abstract
Since 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400–432,513). mRDTs were associated with significantly lower ACT prescription (range 8–69% versus 20–100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs.
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- 2017
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20. Real-Time PCR Threshold Cycle Cutoffs Help To Identify Agents Causing Acute Childhood Diarrhea in Zanzibar
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Mwinyi I. Msellem, Andreas Mårtensson, Kristina Elfving, Birger Trollfors, Max Petzold, Maria Andersson, Christina Welinder-Olsson, Anders Björkman, and Magnus Lindh
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Diarrhea ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Epidemiology ,Real-Time Polymerase Chain Reaction ,medicine.disease_cause ,Tanzania ,Gastroenterology ,Asymptomatic ,Rotavirus ,Enterotoxigenic Escherichia coli ,Internal medicine ,medicine ,Animals ,Humans ,Parasites ,Shigella ,Pathogen ,Bacteria ,biology ,Campylobacter ,Infant ,Cryptosporidium ,biology.organism_classification ,Virology ,Molecular Diagnostic Techniques ,Child, Preschool ,Viruses ,Female ,medicine.symptom - Abstract
Molecular assays might improve the identification of causes of acute diarrheal disease but might lead to more frequent detection of asymptomatic infections. In the present study, real-time PCR targeting 14 pathogens was applied to rectal swabs from 330 children aged 2 to 59 months in Zanzibar, including 165 patients with acute diarrhea and 165 asymptomatic control subjects. At least one pathogen was detected for 94% of the patients and 84% of the controls, with higher rates among patients for norovirus genogroup II (20% versus 2.4%; P < 0.0001), rotavirus (10% versus 1.8%; P = 0.003), and Cryptosporidium (30% versus 11%; P < 0.0001). Detection rates did not differ significantly for enterotoxigenic Escherichia coli (ETEC)- estA (33% versus 24%), ETEC- eltB (44% versus 46%), Shigella (35% versus 33%), and Campylobacter (35% versus 33%), but for these agents threshold cycle ( C T ) values were lower (pathogen loads were higher) in sick children than in controls. In a multivariate analysis, C T values for norovirus genogroup II, rotavirus, Cryptosporidium , ETEC- estA , and Shigella were independently associated with diarrhea. We conclude that this real-time PCR allows convenient detection of essentially all diarrheagenic agents and provides C T values that may be critical for the interpretation of results for pathogens with similar detection rates in patients and controls. The results indicate that the assessment of pathogen loads may improve the identification of agents causing gastroenteritis in children.
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- 2014
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21. Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing : analysis of observational and randomised studies in public and private healthcare settings
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Matthew Cairns, Pascal Magnussen, Kristian S. Hansen, Ismail Mayan, Anthony K. Mbonye, Christopher J. M. Whitty, Virginia Wiseman, Delér Shakely, Baptiste Leurent, Seth Owusu-Agyei, Evelyn K. Ansah, Mwinyi I. Msellem, Toby Leslie, Sham Lal, Lasse S Vestergaard, S. Patrick Kachur, Sarah G. Staedke, Hugh Reyburn, Clare I R Chandler, Obinna Onwujekwe, Kimberly Baltzell, Deborah DiLiberto, Katia Bruxvoort, Mark Rowland, Siân E. Clarke, Helen E. D. Burchett, Heidi Hopkins, Shunmay Yeung, David G. Lalloo, Anders Björkman, Andreas Mårtensson, David Schellenberg, Frank Baiden, Lindsay Mangham Jefferies, Kristina Elfving, Catherine Goodman, and Jayne Webster
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Pediatrics ,medicine.medical_specialty ,Infectious Medicine ,Asia ,wc_680 ,Fever ,medicine.drug_class ,030231 tropical medicine ,Antibiotics ,wa_395 ,Infektionsmedicin ,Corrections ,03 medical and health sciences ,Antimalarials ,0302 clinical medicine ,Ambulatory care ,qv_354 ,Internal medicine ,Epidemiology ,medicine ,Ambulatory Care ,Humans ,030212 general & internal medicine ,Medical prescription ,Practice Patterns, Physicians' ,Randomized Controlled Trials as Topic ,wc_770 ,business.industry ,Diagnostic Tests, Routine ,Public health ,General Medicine ,medicine.disease ,wc_750 ,Anti-Bacterial Agents ,Malaria ,Observational Studies as Topic ,Africa ,Observational study ,Reagent Kits, Diagnostic ,business ,qv_350.5 ,Program Evaluation - Abstract
Objectives\ud To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia. \ud Design\ud Analysisof nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study).\ud Setting\ud Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda.\ud Participants\ud 522 480 children and adults with acute febrile illness.\ud Interventions\ud Rapid diagnostic tests for malaria.\ud Main outcome measures\ud Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings.\ud Results\ud Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole.Conclusions Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials-a beneficial public health outcome-could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription.This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined. [Abstract copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.]
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- 2017
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22. Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar : Aetiologies, Antibiotic Treatment and Outcome
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Andreas Mårtensson, R. Omar, Max Petzold, Annika Ljung, Mwinyi I. Msellem, Kimberly Baltzell, Delér Shakely, Marc Bachelard, Weiping Xu, Abdullah S. Ali, Anders Björkman, Philippe Parola, Magnus Lindh, Kerstin I. Falk, Birger Trollfors, Maria Andersson, Kristina Elfving, Department of Infectious Diseases [Gothenburg, Sweden], Gothenburg University [Sweden], Department of Paediatrics [Gothenburg, Sweden], University of Gothenburg (GU), Department of Microbiology, Tumour and Cell biology [Stockholm, Sweden] (Malaria Research), Karolinska Institutet [Stockholm], Department of Medicine [Kungälv, Sweden], Kungälv Hospital [Sweden], Department of Family Health Care Nursing [San Francisco, USA], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Zanzibar Malaria Elimination Programme [Zanzibar, Tanzania], Ministry of Health [Zanzibar, Tanzania], Department of Microbiology, Tumor and Cell Biology [Stockholm] (MTC), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre for Applied Biostatistics, Occupational and Environmental Medicine [Gothenburg, Sweden] (Academic statistics), Centre for Clinical Research Sörmland [Uppsala, Sweden], Uppsala University, Department of Women and Children's Health, This work was supported by the ACT Consortium through an award from Bill and Melinda Gates Foundation., University of California [San Francisco] (UCSF), University of California-University of California, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Lin, Baochuan, and COMBE, Isabelle
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Male ,Medicin och hälsovetenskap ,Pulmonology ,Etiology ,lcsh:Medicine ,Fevers ,medicine.disease_cause ,Pathology and Laboratory Medicine ,Tanzania ,Medical and Health Sciences ,Pediatrics ,Dengue fever ,Families ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Antibiotics ,Medicine and Health Sciences ,030212 general & internal medicine ,Prospective Studies ,Rift Valley fever ,Child ,lcsh:Science ,Lung ,Children ,Pediatric ,Integrated Management of Childhood Illness ,screening and diagnosis ,Multidisciplinary ,Antimicrobials ,Drugs ,Pediatrik ,3. Good health ,Anti-Bacterial Agents ,Bacterial Pathogens ,Detection ,Treatment Outcome ,Infectious Diseases ,Medical Microbiology ,Child, Preschool ,Acute Disease ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Pneumonia & Influenza ,Female ,Rhinovirus ,medicine.symptom ,Pathogens ,Infection ,Human ,Research Article ,medicine.medical_specialty ,Fever ,Infectious Disease Control ,General Science & Technology ,030231 tropical medicine ,Respiratory Syncytial Virus Infections ,Asymptomatic ,Microbiology ,03 medical and health sciences ,Emerging and Re-emerging Infectious Diseases ,Rare Diseases ,Signs and Symptoms ,Clinical Research ,Diagnostic Medicine ,Internal medicine ,Microbial Control ,Influenza, Human ,medicine ,Humans ,Preschool ,Intensive care medicine ,Microbial Pathogens ,Pharmacology ,business.industry ,Prevention ,lcsh:R ,Infant ,Biology and Life Sciences ,Pneumonia ,medicine.disease ,Influenza ,4.1 Discovery and preclinical testing of markers and technologies ,Malaria ,Vector-Borne Diseases ,Emerging Infectious Diseases ,Good Health and Well Being ,Age Groups ,Case-Control Studies ,People and Places ,lcsh:Q ,Population Groupings ,business - Abstract
International audience; Background Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission. Methods We prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest Xray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q) PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated. Findings NPH-qPCR and GE-qPCR detected >= 1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia. Conclusions This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low.
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- 2016
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23. Improving prescribing practices with rapid diagnostic tests (RDTs): synthesis of 10 studies to explore reasons for variation in malaria RDT uptake and adherence
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Lasse S Vestergaard, Denise Roth Allen, Catherine Goodman, Kristina Elfving, Obinna Onwujekwe, Deborah DiLiberto, Baptiste Leurent, Clare I R Chandler, Pascal Magnussen, Heidi Hopkins, Wilfred Fon Mbacham, Virginia Wiseman, Christopher J. M. Whitty, Sarah G. Staedke, Anders Björkman, Anthony K. Mbonye, Delér Shakely, Siân E. Clarke, Frank Baiden, Kimberly Baltzell, Andreas Mårtensson, Katia Bruxvoort, Sham Lal, Marco Liverani, and Helen E. D. Burchett
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Pediatrics ,Time Factors ,Psychological intervention ,Infektionsmedicin ,Practice Patterns ,Health personnel ,0302 clinical medicine ,7.1 Individual care needs ,030212 general & internal medicine ,Practice Patterns, Physicians' ,Disease management (health) ,Diagnostics ,Prescription Drug Overuse ,Guideline adherence ,TROPICAL MEDICINE ,Disease Management ,Diagnostic test ,General Medicine ,Health Services ,Artemisinins ,Infectious Diseases ,Public Health and Health Services ,HIV/AIDS ,Reagent Kits ,Guideline Adherence ,Infection ,Infectious Medicine ,medicine.medical_specialty ,Fever ,Health Personnel ,Plasmodium falciparum ,Clinical Sciences ,030231 tropical medicine ,Drug Prescriptions ,Antimalarials ,03 medical and health sciences ,Rare Diseases ,Clinical Research ,Journal Article ,medicine ,Humans ,Serologic Tests ,Diagnostic ,Intensive care medicine ,Physicians' ,Other Medical and Health Sciences ,business.industry ,Research ,medicine.disease ,Malaria ,Vector-Borne Diseases ,Good Health and Well Being ,Reagent Kits, Diagnostic ,Management of diseases and conditions ,business - Abstract
OBJECTIVES: The overuse of antimalarial drugs is widespread. Effective methods to improve prescribing practice remain unclear. We evaluated the impact of 10 interventions that introduced rapid diagnostic tests for malaria (mRDTs) on the use of tests and adherence to results in different contexts.DESIGN: A comparative case study approach, analysing variation in outcomes across different settings.SETTING: Studies from the ACT Consortium evaluating mRDTs with a range of supporting interventions in 6 malaria endemic countries. Providers were governmental or non-governmental healthcare workers, private retail sector workers or community volunteers. Each study arm in a distinct setting was considered a case.PARTICIPANTS: 28 cases from 10 studies were included, representing 148 461 patients seeking care for suspected malaria.INTERVENTIONS: The interventions included different mRDT training packages, supervision, supplies and community sensitisation.OUTCOME MEASURES: Analysis explored variation in: (1) uptake of mRDTs (% febrile patients tested); (2) provider adherence to positive mRDTs (% Plasmodium falciparum positive prescribed/given Artemisinin Combination Treatment); (3) provider adherence to negative mRDTs (% P. falciparum negative not prescribed/given antimalarial).RESULTS: Outcomes varied widely across cases: 12-100% mRDT uptake; 44-98% adherence to positive mRDTs; 27-100% adherence to negative mRDTs. Providers appeared more motivated to perform well when mRDTs and intervention characteristics fitted with their own priorities. Goodness of fit of mRDTs with existing consultation and diagnostic practices appeared crucial to maximising the impact of mRDTs on care, as did prior familiarity with malaria testing; adequate human resources and supplies; possible alternative treatments for mRDT-negative patients; a more directive intervention approach and local preferences for ACTs.CONCLUSIONS: Basic training and resources are essential but insufficient to maximise the potential of mRDTs in many contexts. Programme design should respond to assessments of provider priorities, expectations and capacities. As mRDTs become established, the intensity of supporting interventions required seems likely to reduce.
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- 2017
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24. Febrile illness management in children under five years of age: a qualitative pilot study on primary health care workers’ practices in Zanzibar
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Shilpa Gulati, Kristina Elfving, Kimberly Baltzell, Mwinyi I. Msellem, Abdullah S. Ali, Delér Shakely, and Andreas Mårtensson
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Adult ,Male ,medicine.medical_specialty ,Non-malarial fevers ,030231 tropical medicine ,Human Resources ,MEDLINE ,Malaria elimination ,Pilot Projects ,Fever of Unknown Origin ,Tanzania ,Interviews as Topic ,03 medical and health sciences ,0302 clinical medicine ,parasitic diseases ,medicine ,Humans ,030212 general & internal medicine ,Fever of unknown origin ,Medical diagnosis ,Psychiatry ,Surveillance, monitoring, evaluation ,Primary Health Care ,biology ,Under-five ,Diagnostic Tests, Routine ,business.industry ,Research ,Rural health ,Public health ,Infant, Newborn ,1. No poverty ,Infant ,Middle Aged ,biology.organism_classification ,medicine.disease ,3. Good health ,Infectious Diseases ,Child, Preschool ,Family medicine ,Diagnostic decision-making ,Female ,Parasitology ,business ,Malaria - Abstract
Background In Zanzibar, malaria prevalence dropped substantially in the last decade and presently most febrile patients seen in primary health care facilities (PHCF) test negative for malaria. The availability of rapid diagnostic tests (RDTs) allows rural health workers to reliably rule out malaria in fever patients. However, additional diagnostic tools to identify alternative fever causes are scarce, often leaving RDT-negative patients without a clear diagnosis and management plan. This pilot study aimed to explore health workers’ practices with febrile children and identify factors influencing their diagnostic and management decisions in non-malarial fever patients. Methods Semi-structured key informant interviews were conducted with 12 health workers in six PHCFs in North A district, Zanzibar, April to June 2011. Interviews were coded using Atlas.ti to identify emerging themes that play a role in the diagnosis and management of febrile children. Results The following themes were identified: 1) health workers use caregivers’ history of illness and RDT results for initial diagnostic and management decisions, but suggest caregivers need more education to prevent late presentation and poor health outcomes; 2) there is uncertainty regarding viral versus bacterial illness and health workers feel additional point-of-care diagnostic tests would help with differential diagnoses; 3) stock-outs of medications and limited caregivers’ resources are barriers to delivering good care; 4) training, short courses and participation in research as well as; 5) weather also influences diagnostic decision-making. Conclusions This pilot study found that health workers in Zanzibar use caregiver history of fever and results of malaria RDTs to guide management of febrile children. However, since most febrile children test negative for malaria, health workers believe additional training and point-of-care tests would improve their ability to diagnose and manage non-malarial fevers. Educating caregivers on signs and symptoms of febrile illness, as well as the introduction of additional tests to differentiate between viral and bacterial illness, would be important steps to get children to PHCFs earlier and decrease unnecessary antibiotic prescribing without compromising patient safety. More research is needed to expand an understanding of what would improve fever management in other resource-limited settings with decreasing malaria.
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- 2013
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25. Prevalence of PCR Detectable Malaria Infection among Febrile Patients with a Negative Plasmodium falciparum Specific Rapid Diagnostic Test in Zanzibar
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R. Omar, Kristina Elfving, Anders Björkman, Jordan Kemere, Mwinyi I. Msellem, Abdullah S. Ali, Philip J. Rosenthal, Bryan Greenhouse, Michelle S. Hsiang, Kimberly Baltzell, Andreas Mårtensson, Delér Shakely, and Berit Aydin-Schmidt
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Male ,Plasmodium vivax ,Plasmodium malariae ,Medical and Health Sciences ,Polymerase Chain Reaction ,Tanzania ,Plasmodium ,law.invention ,law ,Surveys and Questionnaires ,Prevalence ,Child ,Polymerase chain reaction ,screening and diagnosis ,Microscopy ,Travel ,Rapid diagnostic test ,biology ,Articles ,Detection ,Infectious Diseases ,Real-time polymerase chain reaction ,Child, Preschool ,Protozoan ,HIV/AIDS ,Female ,4.4 Population screening ,Infection ,Biotechnology ,Adult ,Adolescent ,Plasmodium falciparum ,Young Adult ,Rare Diseases ,Tropical Medicine ,Virology ,parasitic diseases ,medicine ,Humans ,Preschool ,DNA Primers ,Infant ,DNA ,DNA, Protozoan ,biology.organism_classification ,medicine.disease ,4.1 Discovery and preclinical testing of markers and technologies ,Malaria ,Vector-Borne Diseases ,Good Health and Well Being ,Immunology ,Parasitology - Abstract
We screened for malaria in 594 blood samples from febrile patients who tested negative by a Plasmodium falciparum-specific histidine-rich protein-2-based rapid diagnostic test at 12 health facilities in Zanzibar districts North A and Micheweni, from May to August 2010. Screening was with microscopy, polymerase chain reaction (PCR) targeting the cytochrome b gene (cytbPCR) of the four major human malaria species, and quantitative PCR (qPCR). The prevalence of cytbPCR-detectable malaria infection was 2% (12 of 594), including 8 P. falciparum, 3 Plasmodium malariae, and 1 Plasmodium vivax infections. Microscopy identified 4 of 8 P. falciparum infections. Parasite density as estimated by microscopy or qPCR was > 4,000 parasites/μL in 5 of 8 cytbPCR-detectable P. falciparum infections. The infections that were missed by the rapid diagnostic test represent a particular challenge in malaria elimination settings and highlight the need for more sensitive point-of-care diagnostic tools to improve case detection of all human malaria species in febrile patients.
- Published
- 2013
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26. High effective coverage of vector control interventions in children after achieving low malaria transmission in Zanzibar, Tanzania
- Author
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Max Petzold, Anders Björkman, Mwinyi I. Msellem, Abdullah S. Ali, Abdul-wahiyd H Al-mafazy, Kristina Elfving, Karin Källander, Netta Beer, and Delér Shakely
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Adult ,medicine.medical_specialty ,Veterinary medicine ,Health Knowledge, Attitudes, Practice ,lcsh:Arctic medicine. Tropical medicine ,Mosquito Control ,Cross-sectional study ,lcsh:RC955-962 ,Psychological intervention ,Indoor residual spraying ,Tanzania ,lcsh:Infectious and parasitic diseases ,Interviews as Topic ,Environmental health ,parasitic diseases ,medicine ,Humans ,lcsh:RC109-216 ,Child ,Family Characteristics ,Surveillance, monitoring, evaluation ,biology ,business.industry ,Public health ,Research ,Health services research ,medicine.disease ,biology.organism_classification ,Vector control ,Malaria ,Mosquito control ,Cross-Sectional Studies ,Infectious Diseases ,Parasitology ,Health Services Research ,business - Abstract
Background Formerly a high malaria transmission area, Zanzibar is now targeting malaria elimination. A major challenge is to avoid resurgence of malaria, the success of which includes maintaining high effective coverage of vector control interventions such as bed nets and indoor residual spraying (IRS). In this study, caretakers' continued use of preventive measures for their children is evaluated, following a sharp reduction in malaria transmission. Methods A cross-sectional community-based survey was conducted in June 2009 in North A and Micheweni districts in Zanzibar. Households were randomly selected using two-stage cluster sampling. Interviews were conducted with 560 caretakers of under-five-year old children, who were asked about perceptions on the malaria situation, vector control, household assets, and intention for continued use of vector control as malaria burden further decreases. Results Effective coverage of vector control interventions for under-five children remains high, although most caretakers (65%; 363/560) did not perceive malaria as presently being a major health issue. Seventy percent (447/643) of the under-five children slept under a long-lasting insecticidal net (LLIN) and 94% (607/643) were living in houses targeted with IRS. In total, 98% (628/643) of the children were covered by at least one of the vector control interventions. Seasonal bed-net use for children was reported by 25% (125/508) of caretakers of children who used bed nets. A high proportion of caretakers (95%; 500/524) stated that they intended to continue using preventive measures for their under-five children as malaria burden further reduces. Malaria risk perceptions and different perceptions of vector control were not found to be significantly associated with LLIN effective coverage. Conclusions While the majority of caretakers felt that malaria had been reduced in Zanzibar, effective coverage of vector control interventions remained high. Caretakers appreciated the interventions and recognized the value of sustaining their use. Thus, sustaining high effective coverage of vector control interventions, which is crucial for reaching malaria elimination in Zanzibar, can be achieved by maintaining effective delivery of these interventions.
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