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OUCRU researchers are proud to be involved in HECTOR – an interdisciplinary, multi-national research consortium which is investigating the genetic factors that contribute to antibiotic resistance.
Predictors of health workers’ knowledge about artesunate-based severe malaria treatment recommendations in government and faith-based hospitals in Kenya
Abstract Background Health workers’ knowledge deficiencies about artesunate-based severe malaria treatment recommendations have been reported. However, predictors of the treatment knowledge have not been examined. In this paper, predictors of artesunate-based treatment knowledge among inpatient health workers in two hospital sectors in Kenya are reported. Methods Secondary analysis of 367 and 330 inpatient health workers randomly selected and interviewed at 47 government hospitals in 2016 and 43 faith-based hospitals in 2017 respectively, was undertaken. Multilevel ordinal and binary logistic regressions examining the effects of 11 factors on five knowledge outcomes in government and faith-based hospital sectors were performed. Results Among respective government and faith-based health workers, about a third of health workers had high knowledge of artesunate treatment policies (30.8% vs 32.9%), a third knew all dosing intervals (33.5% vs 33.3%), about half knew preparation solutions (49.9% vs 55.8%), half to two-thirds knew artesunate dose for both weight categories (50.8% vs 66.7%) and over three-quarters knew the preferred route of administration (78.7% vs 82.4%). Eight predictors were significantly associated with at least one of the examined knowledge outcomes. In the government sector, display of artesunate administration posters, paediatric ward allocation and repeated surveys were significantly associated with more than one of the knowledge outcomes. In the faith-based hospitals, availability of artesunate at hospitals and health worker pre-service training were associated with multiple outcomes. Exposure to in-service malaria case-management training and access to malaria guidelines were only associated with higher knowledge about artesunate treatment policy. Conclusion Programmatic interventions ensuring display of artesunate administration posters in the wards, targeting of health workers managing adult patients in the medical wards, and repeated knowledge assessments are likely to be beneficial for improving the knowledge of government health workers about artesunate-based severe malaria treatment recommendations. The availability of artesunate and focus on improvements of nurses’ knowledge should be prioritized at the faith-based hospitals.
Trends in health workers’ compliance with outpatient malaria case-management guidelines across malaria epidemiological zones in Kenya, 2010–2016
Abstract Background Health workers' compliance with outpatient malaria case-management guidelines has been improving, specifically regarding the universal testing of suspected cases and the use of artemisinin-based combination therapy (ACT) only for positive results (i.e., ‘test and treat’). Whether the improvements in compliance with ‘test and treat’ guidelines are consistent across different malaria endemicity areas has not been examined. Methods Data from 11 national, cross-sectional, outpatient malaria case-management surveys undertaken in Kenya from 2010 to 2016 were analysed. Four primary indicators (i.e., ‘test and treat’) and eight secondary indicators of artemether-lumefantrine (AL) dosing, dispensing, and counselling were measured. Mixed logistic regression models were used to analyse the annual trends in compliance with the indicators across the different malaria endemicity areas (i.e., from highest to lowest risk being lake endemic, coast endemic, highland epidemic, semi-arid seasonal transmission, and low risk). Results Compliance with all four ‘test and treat’ indicators significantly increased in the area with the highest malaria risk (i.e., lake endemic) as follows: testing of febrile patients (OR = 1.71 annually; 95% CI = 1.51–1.93), AL treatment for test-positive patients (OR = 1.56; 95% CI = 1.26–1.92), no anti-malarial for test-negative patients (OR = 2.04; 95% CI = 1.65–2.54), and composite ‘test and treat’ compliance (OR = 1.80; 95% CI = 1.61–2.01). In the low risk areas, only compliance with test-negative results significantly increased (OR = 2.27; 95% CI = 1.61–3.19) while testing of febrile patients showed declining trends (OR = 0.89; 95% CI = 0.79–1.01). Administration of the first AL dose at the facility significantly increased in the areas of lake endemic (OR = 2.33; 95% CI = 1.76–3.10), coast endemic (OR = 5.02; 95% CI = 2.77–9.09) and semi-arid seasonal transmission (OR = 1.44; 95% CI = 1.02–2.04). In areas of the lowest risk of transmission and highland epidemic zone, none of the AL dosing, dispensing, and counselling tasks significantly changed over time. Conclusions There is variability in health workers' compliance with outpatient malaria case-management guidelines across different malaria-risk areas in Kenya. Major improvements in areas of the highest risk have not been seen in low-risk areas. Interventions to improve practices should be targeted geographically.
Determinants of improvement trends in health workers’ compliance with outpatient malaria case-management guidelines at health facilities with available “test and treat” commodities in Kenya
Background Health workers’ compliance with outpatient malaria case-management guidelines has been improving in Africa. This study examined the factors associated with the improvements. Methods Data from 11 national, cross-sectional health facility surveys undertaken from 2010–2016 were analysed. Association between 31 determinants and improvement trends in five outpatient compliance outcomes were examined using interactions between each determinant and time in multilevel logistic regression models and reported as an adjusted odds ratio of annual trends (T-aOR). Results Among 9,173 febrile patients seen at 1,208 health facilities and by 1,538 health workers, a higher annual improvement trend in composite “test and treat” performance was associated with malaria endemicity-lake endemic (T-aOR = 1.67 annually; p<0.001) and highland epidemic (T-aOR = 1.35; p<0.001) zones compared to low-risk zone; with facilities stocking rapid diagnostic tests only (T-aOR = 1.49; p<0.001) compared to microscopy only services; with faith-based/non-governmental facilities compared to government-owned (T-aOR = 1.15; p = 0.036); with a daily caseload of >25 febrile patients (T-aOR = 1.46; p = 0.003); and with under-five children compared to older patients (T-aOR = 1.07; p = 0.013). Other factors associated with the improvement trends in the “test and treat” policy components and artemether-lumefantrine administration at the facility included the absence of previous RDT stock-outs, community health workers dispensing drugs, access to malaria case-management and Integrated Management of Childhood Illness (IMCI) guidelines, health workers’ gender, correct health workers’ knowledge about the targeted malaria treatment policy, and patients’ main complaint of fever. The odds of compliance at the baseline were variable for some of the factors. Conclusions Targeting of low malaria risk areas, low caseload facilities, male and government health workers, continuous availability of RDTs, improving health workers’ knowledge about the policy considering age and fever, and dissemination of guidelines might improve compliance with malaria guidelines. For prompt treatment and administration of the first artemether-lumefantrine dose at the facility, task-shifting duties to community health workers can be considered.
Factors influencing health workers’ compliance with outpatient malaria ‘test and treat’ guidelines during the plateauing performance phase in Kenya, 2014–2016
Abstract Background Health workers’ compliance with outpatient malaria ‘test and treat’ guidelines has improved since 2010 but plateaued from 2014 at suboptimal levels in Kenya. This study examined the factors associated with high but suboptimal compliance levels at facilities with available malaria tests and drugs. Methods Data from four national, cross-sectional health facility surveys undertaken between 2014 and 2016 in Kenya were analysed. Association between 31 factors and compliance with malaria testing (survey range (SR): 65–69%) and no anti-malarial treatment for test negative patients (SR: 90–92%) were examined using multilevel logistic regression models. Results A total of 2,752 febrile patients seen by 594 health workers at 486 health facilities were analysed. Higher odds of malaria testing were associated with lake endemic (aOR = 12.12; 95% CI: 5.3–27.6), highland epidemic (aOR = 5.06; 95% CI: 2.7–9.5) and semi-arid seasonal (aOR = 2.07; 95% CI: 1.2–3.6) compared to low risk areas; faith-based (FBO)/ non-governmental organization (NGO)-owned compared to government-owned facilities (aOR = 5.80; 95% CI: 3.2–10.6); health workers’ perception of malaria endemicity as high-risk (aOR = 3.05; 95% CI: 1.8–5.2); supervision with feedback (aOR = 1.84; 95% CI: 1.2–2.9); access to guidelines (aOR = 1.96; 95% CI: 1.1–3.4); older patients compared to infants, higher temperature measurements and main complaints of fever, diarrhoea, headache, vomiting and chills. Lower odds of testing were associated with febrile patients having main complaints of a cough (aOR = 0.65; 95% CI: 0.5–0.9), a rash (aOR = 0.32; 95% CI: 0.2–0.7) or a running nose (aOR = 0.59; 95% CI: 0.4–0.9). Other factors associated with compliance with test negative results included the type of diagnostic test available at the facility, in-service training, health workers’ age, and correct knowledge of the targeted treatment policy. Conclusions To optimize outpatient malaria case-management, reduce testing compliance gaps and eliminate overtreatment of test negative patients, there is a need to focus on compliance within low malaria risk areas in addition to ensuring the universal and continuous availability of ‘test and treat’ commodities. Targeting of older and government health workers; dissemination of updated guidelines; and continuing with in-service training and supportive supervision with feedback is essential. Lastly, there is a need to improve health workers’ knowledge about malaria testing criteria considering their perceptions of endemicity.
Readiness of the Kenyan public health sector to provide pre‐referral care for severe paediatric malaria
AbstractObjectiveTo assess readiness among primary public health facilities in Kenya to provide pre‐referral antimalarials for severe malaria.MethodsNine national surveys of randomly selected primary public health facilities undertaken bi‐annually between 2017 and 2021 were analysed. The outcomes included the availability of pre‐referral antimalarial drugs at the health facilities and health worker knowledge of recommended pre‐referral treatment for severe malaria.ResultsA total of 1540 health workers from 1355 health facilities were interviewed. Injectable artesunate was available at 46%, injectable quinine at 7%, and artemether at 3% of the health facilities. None of the facilities had rectal artesunate suppositories in stock. A total of 960 (62%) health workers were trained on the use of injectable artesunate. 73% of the health workers who had ever referred a child with severe malaria were aware that artesunate was the recommended treatment, 49% said that intramuscular injection was the preferred route of administration, and 60% stated the correct dose. The overall knowledge level of the treatment policy was low at 21% and only slightly higher among trained than untrained health workers (24% vs 14%; p < 0.001) and those with access to guidelines versus those without access (29% vs 17%; p < 0.001).ConclusionsThe readiness of primary health facilities and health workers to deliver appropriate pre‐referral care to children with complicated malaria in Kenya is inadequate. Further investments are required to ensure (a) availability of nationally recommended pre‐referral antimalarials; (b) appropriate training and supervision in their administration, and (c) monitoring of the entire referral process.
Level and determinants of district primary healthcare system technical efficiency in Ghana: two-stage stochastic frontier analysis.
BackgroundPrimary healthcare (PHC) is critical towards achieving Universal Health Coverage (UHC). In Ghana, PHC is organised at the district level and plays a key role in the country's pursuit of UHC. However, many districts face challenges not only with limited resources but also with how effectively they are used. We examined how efficiently districts in Ghana use their health resources and what factors are associated with this efficiency.MethodsWe used a two-step stochastic frontier analysis model using data from 181 districts. The output variable was a composite coverage index derived from eight PHC service indicators for 2021, primarily reflecting maternal and child health and infectious disease services. Input variables included district health expenditure for 2020/2021 and the number of health facilities and clinical staff in 2021. We then assessed the associations between efficiency scores generated by the model and health systems, socioeconomic and demographic factors, such as health facility type, insurance coverage, literacy level, Gini coefficient, poverty incidence, urbanisation and population density.ResultsOn average, districts operated at 87% efficiency, with scores ranging from 65% to 99%. Two factors were associated with the efficiency. First, districts with a higher proportion of PHC facilities tended to use resources more efficiently (coeff=0.151; 95% CI=0.041 to 0.261). Second, districts with greater income inequality were less efficient, measured by the Gini coefficient (coeff=-0.858; 95% CI=-1.146 to -0.252).ConclusionDistricts in Ghana have the potential to improve PHC outputs by about 13% on average by better use of existing resources and addressing determinants of efficiency. Findings suggest that districts with a higher proportion of PHC facilities and lower income inequality tend to be more efficient. These patterns highlight the value of strengthening PHC infrastructure and pursuing equity-focused policies as part of strategies to enhance efficiency in district health systems.
Evaluating the impact, implementation experience and political economy of primary care networks in Kenya: protocol for a mixed methods study.
BackgroundPrimary care networks (PCNs) are increasingly being adopted in low- and middle-income countries (LMICs) to improve the delivery of primary health care (PHC). Kenya has identified PCNs as a key reform to strengthen PHC delivery and has passed a law to guide its implementation. PCNs were piloted in two counties in Kenya in 2020 and implemented nationally in October 2023. This protocol outlines methods for a study that examines the impact, implementation experience and political economy of the PCN reform in Kenya.MethodsWe will adopt the parallel databases variant of convergent mixed methods study design to concurrently but separately collect quantitative and qualitative data. The two strands will be mixed during data collection to refine questions, with findings triangulated during analysis and interpretation to provide a comprehensive understanding of PCN implementation. The quantitative study will use a controlled before and after study design and collect data using health facility and client exit surveys. The primary outcome measure will be the service delivery readiness of PHC facilities. We will use a random sample of 228 health facilities and 2560 clients in four currently implementing PCNs, four planning to implement and four control counties at baseline and post-implementation. We shall undertake a preliminary cross-sectional analysis of the data at baseline from October to December 2023, followed by a difference-in-difference analysis at the endline from October to December 2024 to compare the outcome differences between the intervention and control counties over a 12-month period. The qualitative study will include a cross-sectional process evaluation and political economy analysis (PEA) using document reviews and approximately 80 in-depth interviews with national and sub-national stakeholders. The process evaluation will assess the emergence of PCN reforms, the implementation experience, the mechanism of impact and how the context affects implementation and outcomes. The PEA will examine the interaction of structural factors, institutions and actors/stakeholders' interests and power relations in implementing PCNs. We will also examine the gendered effects of the PCNs, including power relations and norms, and their implications on PHC from the supply and demand sides. We shall undertake a thematic analysis of the qualitative data.DiscussionThis evaluation will contribute robust evidence on the impact, implementation experience, political economy and gendered implications of PCNs in a LMIC setting, as well as guide the refining of PCN implementation in Kenya and other LMICs implementing or planning to implement PCNs to enhance their effectiveness.
Antenatal care quality and detection of risk among pregnant women: An observational study in Ethiopia, India, Kenya, and South Africa.
BackgroundAntenatal care (ANC) is an essential platform to improve maternal and newborn health (MNH). While several articles have described the content of ANC in low- and middle-income countries (LMICs), few have investigated the quality of detection and management of pregnancy risk factors during ANC. It remains unclear whether women with pregnancy risk factors receive targeted management and additional ANC.Methods and findingsThis observational study uses baseline data from the MNH eCohort study conducted in 8 sites in Ethiopia, India, Kenya, and South Africa from April 2023 to January 2024. A total of 4,068 pregnant women seeking ANC for the first time in their pregnancy were surveyed. We built country-specific ANC completeness indices that measured provision of 16 to 22 recommended clinical actions in 5 domains: physical examinations, diagnostic tests, history taking and screening, counselling, and treatment and prevention. We investigated whether women with pregnancy risks tended to receive higher quality care and we assessed the quality of detection and management of 7 concurrent illnesses and pregnancy risk factors (anemia, undernutrition, obesity, chronic illnesses, depression, prior obstetric complications, and danger signs). ANC completeness ranged from 43% in Ethiopia, 66% in Kenya, 73% in India, and 76% in South Africa, with large gaps in history taking, screening, and counselling. Most women in Ethiopia, Kenya, and South Africa initiated ANC in second or third trimesters. We used country-specific multivariable mixed-effects linear regression models to investigate factors associated with ANC completeness. Models included individual demographics, health status, presence of risk factors, health facility characteristics, and fixed effects for the study site. We found that some facility characteristics (staffing, patient volume, structural readiness) were associated with variation in ANC completeness. In contrast, pregnancy risk factors were only associated with a 1.7 percentage points increase in ANC completeness (95% confidence interval 0.3, 3.0, p-value 0.014) in Kenya only. Poor self-reported health was associated with higher ANC completeness in India and South Africa and with lower ANC completeness in Ethiopia. Some concurrent illnesses and risk factors were overlooked during the ANC visit. Between 0% and 6% of undernourished women were prescribed food supplementation and only 1% to 3% of women with depression were referred to a mental health provider or prescribed antidepressants. Only 36% to 73% of women who had previously experienced an obstetric complication (a miscarriage, preterm birth, stillbirth, or newborn death) discussed their obstetric history with the provider during the first ANC visit. Although we aimed to validate self-reported information on health status and content of care with data from health cards, our findings may be affected by recall or other information biases.ConclusionsIn this study, we observed gaps in adherence to ANC standards, particularly for women in need of specialized management. Strategies to maximize the potential health benefits of ANC should target women at risk of poor pregnancy outcomes and improve early initiation of ANC in the first trimester.
Evaluating the effects, implementation experience and political economy of primary healthcare facility autonomy reforms within counties in Kenya: a mixed methods study protocol.
IntroductionThere is a growing emphasis on improving primary health care services and granting frontline service providers more decision-making autonomy. In October 2023, Kenya enacted legislation mandating nationwide facility autonomy. There is limited understanding of the effects of health facility autonomy on primary health care (PHC) facilities performance. It is recognized that stakeholder interests influence reforms, and gender plays a critical role in access to health and its outcomes. This protocol outlines the methods for a study that plans to evaluate the effects, implementation experience, political economy, and gendered effects of health facility autonomy reforms in Kenya.Methods and analysisThe research will use a before-and-after quasi-experimental study design to measure the effects of the reform on service readiness and service utilization, and a cross-sectional qualitative study to explore the implementation experience, political economy, and gendered effects of these reforms. Data to measure the effects of autonomy will be collected from a sample of 80 health facilities and 1600 clients per study arm. Qualitative interviews will involve approximately 83 facility managers and policymakers at the county level, distributed across intervening (36), and planning to intervene (36) counties. Additionally, 11 interviews will be conducted at the national level with representatives from the Ministry of Health, the National Treasury, the Controller of Budget, the Council of Governors, the Auditor General, and development partners. Given the uncertainty surrounding the implementation of the reforms, this study proposes two secondary designs in the event our primary design is not feasible - a cross-sectional study, and a quasi-experimental interrupted time series design. The study will use a difference-in-difference analysis for the quantitative component to evaluate the effects of the reforms, while using thematic analysis for the qualitative component to evaluate the political economy and the implementation experience of the reforms.Ethics and disseminationThis study was approved by the Kenya Medical Research Institute Scientific and Ethics Review Unit (KEMRI/SERU/CGMR-C/294/4708) and the National Commission for Science, Technology and Innovation (NACOSTI/P/23/28111). We plan to disseminate the findings through publications, policy briefs and dissemination workshops.
Factors associated with hospital length of stay in patients admitted with suspected malaria in Kenya: secondary analysis of a cross-sectional survey.
ObjectivesTo investigate factors associated with hospital length of stay (LOS) in patients admitted with suspected malaria using a competing risk approach.SettingCounty government referrals and major faith-based hospitals in Kenya in 2018.DesignSecondary analysis of a cross-sectional survey data.ParticipantsData were extracted from 2396 medical records of patients admitted with suspected malaria at 90 hospitals.Outcome measuresLOS, defined as time to discharge, was the primary event of interest, and time to death was the competing event against patient factors assessed during admission and hospitalisation.ResultsAmong the patients analysed, 2283 were discharged, 49 died and 64 were censored. The median LOS was 4 days (IQR: 3-6 days). The cumulative incidence of discharge significantly decreased (p<0.05) by 12.7% (subdistribution-HR (SDHR): 0.873; 95% CI 0.789 to 0.967) when the respiratory rate was assessed, by 14.1% (SDHR 0.859; 95% CI 0.754 to 0.978) when oxygen saturation was monitored, by 23.1% (SDHR 0.769; 95% CI 0.709 to 0.833) and 23.4% (SDHR 0.766; 95% CI 0.704 to 0.833) when haemoglobin/haematocrit and glucose/random blood sugar were performed, respectively, and by 30.4% (SDHR 0.696; 95% CI 0.626 to 0.774) when patients had at least one clinical feature of severe malaria. Conversely, patients with confirmed severe malaria and those treated with injectable artesunate had a significantly increased cumulative incidence of discharge by 21.4% (SDHR 1.214; 95% CI 1.082 to 1.362) and 33.9% (SDHR 1.339; 95% CI 1.184 to 1.515), respectively.ConclusionsFactors of inpatient clinical processes that influence hospital LOS were identified. These can be targeted during quality improvement interventions to enhance health service delivery in Kenya. Early recognition and appropriate management of the signs of malaria severity could greatly affect beneficial outcomes. Strengthening clinical practices and nursing care according to national case management guidelines should be a priority for malaria control managers in Kenya.
Cross-sectional study to predict subnational levels of health workers' knowledge about severe malaria treatment in Kenya.
ObjectivesThis study applied a Bayesian hierarchical ecological spatial model beyond predictor analysis to test for the best fitting spatial effects model to predict subnational levels of health workers' knowledge of severe malaria treatment policy, artesunate dosing, and preparation.SettingCounty referral government and major faith-based hospitals across 47 counties in Kenya in 2019.Design and participantsA secondary analysis of cross-sectional survey data from 345 health workers across 89 hospitals with inpatient departments who were randomly selected and interviewed.Outcome measuresThree ordinal outcome variables for severe malaria treatment policy, artesunate dose and preparation were considered, while 12 individual and contextual predictors were included in the spatial models.ResultsA third of the health workers had high knowledge levels on artesunate treatment policy; almost three-quarters had high knowledge levels on artesunate dosing and preparation. The likelihood of having high knowledge on severe malaria treatment policy was lower among nurses relative to clinicians (adjusted OR (aOR)=0.48, 95% CI 0.25 to 0.87), health workers older than 30 years were 61% less likely to have high knowledge about dosing compared with younger health workers (aOR=0.39, 95% CI 0.22 to 0.67), while health workers exposed to artesunate posters had 2.4-fold higher odds of higher knowledge about dosing compared with non-exposed health workers (aOR=2.38, 95% CI 1.22 to 4.74). The best model fitted with spatially structured random effects and spatial variations of the knowledge level across the 47 counties exhibited neighbourhood influence.ConclusionsKnowledge of severe malaria treatment policies is not adequately and optimally available among health workers across Kenya. The factors associated with the health workers' level of knowledge were cadre, age and exposure to artesunate posters. The spatial maps provided subnational estimates of knowledge levels for focused interventions.
Checklists to guide the supportive and critical care of tuberculous meningitis
The assessment and management of tuberculous meningitis (TBM) is often complex, yet no standardised approach exists, and evidence for the clinical care of patients, including those with critical illness, is limited. The roles of proformas and checklists are increasing in medicine; proformas provide a framework for a thorough approach to patient care, whereas checklists offer a priority-based approach that may be applied to deteriorating patients in time-critical situations. We aimed to develop a comprehensive assessment proforma and an accompanying ‘priorities’ checklist for patients with TBM, with the overriding goal being to improve patient outcomes. The proforma outlines what should be asked, checked, or tested at initial evaluation and daily inpatient review to assist supportive clinical care for patients, with an adapted list for patients in critical care. It is accompanied by a supporting document describing why these points are relevant to TBM. Our priorities checklist offers a useful and easy reminder of important issues to review during a time-critical period of acute patient deterioration. The benefit of these documents to patient outcomes would require investigation; however, we hope they will promote standardisation of patient assessment and care, particularly of critically unwell individuals, in whom morbidity and mortality remains unacceptably high.
Tuberculous meningitis: where to from here?
Purpose of reviewTuberculous meningitis (TBM) is associated with significant mortality and morbidity yet is difficult to diagnose and treat. We reviewed original research published in the last 2 years, since 1 January 2018, which we considered to have a major impact in advancing diagnosis, treatment and understanding of the pathophysiology of TBM meningitis in children and adults.Recent findingsStudies have sought to identify a high sensitivity diagnostic test for TBM, with new data on modified Ziehl--Neelsen staining, urinary and cerebrospinal fluid (CSF) lipoarabinomannan and GeneXpert Ultra. Recent studies on CSF biomarkers provide a better understanding of the detrimental inflammatory cascade and neuromarkers of brain damage and suggest potential for novel host-directed therapy. Tryptophan metabolism appears to affect outcome and requires further study. Increased clinical trials activity in TBM focuses on optimizing antituberculosis drug regimens and adjuvant therapy; however, there are few planned paediatric trials.SummaryTuberculous meningitis still kills or disables around half of sufferers. Although some progress has been made, there remains a need for more sensitive diagnostic tests, better drug therapy, improved management of complications and understanding of host-directed therapy if outcomes are to improve.
The Natural History and Transmission Potential of Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Abstract Background Little is known about the natural history of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods We conducted a prospective study at a quarantine center for coronavirus disease 2019 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with reverse-transcription polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrollment and daily nasopharyngeal/throat swabs (NTSs) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. Results Between 10 March and 4 April 2020, 14 000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13 (43%) never had symptoms and 17 (57%) were symptomatic. Seventeen (57%) participants imported cases. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS collected at enrollment (8/13 [62%] vs 17/17 [100%]; P = .02). SARS-CoV-2 RNA was detected in 20 of 27 (74%) available saliva samples (7 of 11 [64%] in the asymptomatic group and 13 of 16 [81%] in the symptomatic group; P = .56). Analysis of RT-PCR positivity probability showed that asymptomatic participants had faster viral clearance than symptomatic participants (P < .001 for difference over the first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit SARS-CoV-2 to 4 contacts. Conclusions Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTSs. The NTS viral loads fall faster in asymptomatic individuals, but these individuals appear able to transmit the virus to others.
A multi centre randomized open label trial of chloroquine for the treatment of adults with SARS-CoV-2 infection in Vietnam
Background: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or therapeutic agent to treat COVID-19. This clinical trial is designed to evaluate chloroquine as a potential therapeutic for the treatment of hospitalised people with COVID-19. We hypothesise that chloroquine slows viral replication in patients with COVID-19, attenuating the infection, and resulting in more rapid decline of viral load in throat/nose swabs. This viral attenuation should be associated with improved patient outcomes. Method: The study will start with a 10-patient prospective observational pilot study following the same entry and exclusion criteria as for the randomized trial and undergoing the same procedures. The main study is an open label, randomised, controlled trial with two parallel arms of standard of care (control arm) versus standard of care with 10 days of chloroquine (intervention arm) with a loading dose over the first 24 hours, followed by 300mg base orally once daily for nine days. The study will recruit patients in three sites in Ho Chi Minh City, Vietnam: the Hospital for Tropical Diseases, the Cu Chi Field Hospital, and the Can Gio COVID hospital. The primary endpoint is the time to viral clearance from throat/nose swab, defined as the time following randomization until the midpoint between the last positive and the first of the negative throat/nose swabs. Viral presence will be determined using RT-PCR to detect SARS-CoV-2 RNA. Discussion: The results of the study will add to the evidence-based guidelines for management of COVID-19. Given the enormous experience of its use in malaria chemoprophylaxis, excellent safety and tolerability profile, and its very low cost, if proved effective then chloroquine would be a readily deployable and affordable treatment for patients with COVID-19. Trial registration: Clinicaltrials.gov NCT04328493 31/03/2020
Xpert MTB/RIF Ultra for the Diagnosis of Tuberculous Meningitis: A Small Step Forward
AbstractThe delayed diagnosis of tuberculous meningitis (TBM) leads to poor outcomes, yet the current diagnostic methods for identifying Mycobacterium tuberculosis in cerebrospinal fluid (CSF) are inadequate. The first comparative study of the new GeneXpert MTB/RIF Ultra (Xpert Ultra) for TBM diagnosis suggested increased sensitivity of Xpert Ultra. Two subsequent studies have shown Xpert Ultra has improved sensitivity, but has insufficient negative predictive value to exclude TBM. Collecting and processing large volumes of CSF for mycobacterial testing are important for optimal diagnostic test performance. But clinical, radiological, and laboratory parameters remain essential for TBM diagnosis and empiric therapy is often needed. We therefore caution against the use of Xpert Ultra as a single diagnostic test for TBM; it cannot be used to “rule out” TBM.