Evaluation of the clinical practice of aminoglycosides use in paediatric patients in Kenya : findings and implications to Low-middle Income Countries

Objectives To evaluate the practice of aminoglycoside use/monitoring in Kenya and explore healthcare worker (HCW) perceptions of aminoglycoside monitoring to identify gaps and opportunities for future improvements, given the low therapeutic index of aminoglycosides. Methods This was a two-phase study whereby we reviewed patients' medical records at Kenyatta National Hospital (October-December 2016) in Phase 1 and interviewed HCWs face to face in Phase 2. Outcome measures included describing and evaluating the practice of aminoglycoside use and monitoring and compliance to guidelines. Data were analysed using descriptive and inferential analysis. Results Overall, out of the 2318 patients admitted, 192 patients (8.3%) were prescribed an aminoglycoside, of which 102 (53.1%) had aminoglycoside doses that did not conform to national guidelines. Aminoglycoside-related adverse effects were suspected in 65 (33.9%) patients. Monitoring of aminoglycoside therapy was performed in only 17 (8.9%) patients, with no therapeutic drug monitoring (TDM), attributed mainly to knowledge and skill gaps and lack of resources. Out of the 28 recruited HCWs, 18 (64.3%) needed training in how to perform and interpret TDM results. Conclusions The practice of using and monitoring aminoglycosides was suboptimal, raising concerns around potential avoidable harm to patients. The identified gaps could form the basis for developing strategies to improve the future use of aminoglycosides, not only in Kenya but also in other countries with similar settings and resources

Epidemiological and clinical characteristics of patients hospitalised with COVID-19 in Kenya: a multicentre cohort study

Objectives: To assess outcomes of patients admitted to hospital with COVID-19 and to determine the predictors of mortality. Setting: This study was conducted in six facilities, which included both government and privately run secondary and tertiary level facilities in the central and coastal regions of Kenya. Participants: We enrolled 787 reverse transcriptase-PCRconfirmed SARS-CoV2-infected persons. Patients whose records could not be accessed were excluded. Primary and secondary outcome measures: The primary outcome was COVID-19-related death. We used Cox proportional hazards regressions to determine factors related to in-hospital mortality. Results: Data from patients with 787 COVID-19 were available. The median age was 43 years (IQR 30–53), with 505 (64%) being men. At admission, 455 (58%) were symptomatic with an additional 63 (9%) developing clinical symptoms during hospitalisation. The most common symptoms were cough (337, 43%), loss of taste or smell (279, 35%) and fever (126, 16%). Comorbidities were reported in 340 (43%), with cardiovascular disease, diabetes and HIV documented in 130 (17%), 116 (15%), 53 (7%), respectively. 90 (11%) were admitted to the Intensive Care Unit (ICU) for a mean of 11 days, 52 (7%) were ventilated with a mean of 10 days, 107 (14%) died. The risk of death increased with age (HR 1.57 (95% CI 1.13 to 2.19)) for persons \u3e60 years compared with thoseold; having comorbidities (HR 2.34 (1.68 to 3.25)) and among men (HR 1.76 (1.27 to 2.44)) compared with women. Elevated white cell count and aspartate aminotransferase were associated with higher risk of death. Conclusions: The risk of death from COVID-19 is high among older patients, those with comorbidities and among men. Clinical parameters including patient clinical signs, haematology and liver function tests were associated with risk of death and may guide stratification of high-risk patients

The COVID-19 pandemic and disruptions to essential health services in Kenya:A retrospective time-series analysis

Background: Public health emergencies can disrupt the provision of and access to essential health-care services, exacerbating health crises. We aimed to assess the effect of the COVID-19 pandemic on essential health-care services in Kenya. Methods: Using county-level data routinely collected from the health information system from health facilities across the country, we used a robust mixed-effect model to examine changes in 17 indicators of essential health services across four periods: the pre-pandemic period (from January, 2018 to February, 2020), two pandemic periods (from March to November 2020, and February to October, 2021), and the period during the COVID-19-associated health-care workers' strike (from December, 2020 to January, 2021). Findings: In the pre-pandemic period, we observed a positive trend for multiple indicators. The onset of the pandemic was associated with statistically significant decreases in multiple indicators, including outpatient visits (28·7%; 95% CI 16·0-43·5%), cervical cancer screening (49·8%; 20·6-57·9%), number of HIV tests conducted (45·3%; 23·9-63·0%), patients tested for malaria (31·9%; 16·7-46·7%), number of notified tuberculosis cases (26·6%; 14·7-45·1%), hypertension cases (10·4%; 6·0-39·4%), vitamin A supplements (8·7%; 7·9-10·5%), and three doses of the diphtheria, tetanus toxoid, and pertussis vaccine administered (0·9%; 0·5-1·3%). Pneumonia cases reduced by 50·6% (31·3-67·3%), diarrhoea by 39·7% (24·8-62·7%), and children attending welfare clinics by 39·6% (23·5-47·1%). Cases of sexual violence increased by 8·0% (4·3-25·0%). Skilled deliveries, antenatal care, people with HIV infection newly started on antiretroviral therapy, confirmed cases of malaria, and diabetes cases detected were not significantly affected negatively. Although most of the health indicators began to recover during the pandemic, the health-care workers' strike resulted in nearly all indicators falling to numbers lower than those observed at the onset or during the pre-strike pandemic period. Interpretation: The COVID-19 pandemic and the associated health-care workers' strike in Kenya have been associated with a substantial disruption of essential health services, with the use of outpatient visits, screening and diagnostic services, and child immunisation adversely affected. Efforts to maintain the provision of these essential health services during a health-care crisis should target the susceptible services to prevent the exacerbation of associated disease burdens during such health crises. Funding: Bill & Melinda Gates Foundation

Epidemiological and clinical characteristics of patients hospitalised with COVID-19 in Kenya:A multicentre cohort study

OBJECTIVES: To assess outcomes of patients admitted to hospital with COVID-19 and to determine the predictors of mortality. SETTING: This study was conducted in six facilities, which included both government and privately run secondary and tertiary level facilities in the central and coastal regions of Kenya. PARTICIPANTS: We enrolled 787 reverse transcriptase-PCR-confirmed SARS-CoV2-infected persons. Patients whose records could not be accessed were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was COVID-19-related death. We used Cox proportional hazards regressions to determine factors related to in-hospital mortality. RESULTS: Data from patients with 787 COVID-19 were available. The median age was 43 years (IQR 30–53), with 505 (64%) being men. At admission, 455 (58%) were symptomatic with an additional 63 (9%) developing clinical symptoms during hospitalisation. The most common symptoms were cough (337, 43%), loss of taste or smell (279, 35%) and fever (126, 16%). Comorbidities were reported in 340 (43%), with cardiovascular disease, diabetes and HIV documented in 130 (17%), 116 (15%), 53 (7%), respectively. 90 (11%) were admitted to the Intensive Care Unit (ICU) for a mean of 11 days, 52 (7%) were ventilated with a mean of 10 days, 107 (14%) died. The risk of death increased with age (HR 1.57 (95% CI 1.13 to 2.19)) for persons >60 years compared with those <60 years old; having comorbidities (HR 2.34 (1.68 to 3.25)) and among men (HR 1.76 (1.27 to 2.44)) compared with women. Elevated white cell count and aspartate aminotransferase were associated with higher risk of death. CONCLUSIONS: The risk of death from COVID-19 is high among older patients, those with comorbidities and among men. Clinical parameters including patient clinical signs, haematology and liver function tests were associated with risk of death and may guide stratification of high-risk patients

An Observational Cohort Comparison of Facilitators of Retention in Care and Adherence to Anti-Eetroviral Therapy at an HIV Treatment Center in Kenya

BACKGROUND: Most HIV treatment programs in resource-limited settings utilize multiple facilitators of adherence and retention in care but there is little data on the efficacy of these methods. We performed an observational cohort analysis of a treatment program in Kenya to assess which program components promote adherence and retention in HIV care in East Africa. METHODS: Patients initiating ART at A.I.C. Kijabe Hospital were prospectively enrolled in an observational study. Kijabe has an intensive program to promote adherence and retention in care during the first 6 months of ART that incorporates the following facilitators: home visits by community health workers, community based support groups, pharmacy counseling, and unannounced pill counts by clinicians. The primary endpoint was time to treatment failure, defined as a detectable HIV-1 viral load; discontinuation of ART; death; or loss to follow-up. Time to treatment failure for each facilitator was calculated using Kaplan-Meier analysis. The relative effects of the facilitators were determined by the Cox Proportional Hazards Model. RESULTS: 301 patients were enrolled. Time to treatment failure was longer in patients participating in support groups (448 days vs. 337 days, P<0.001), pharmacy counseling (480 days vs. 386 days, P = 0.002), pill counts (482 days vs. 189 days, P<0.001) and home visits (485 days vs. 426 days, P = 0.024). Better adherence was seen with support groups (89% vs. 82%, P = 0.05) and pill counts (89% vs. 75%, P = 0.02). Multivariate analysis using the Cox Model found significant reductions in risk of treatment failure associated with pill counts (HR = 0.19, P<0.001) and support groups (HR = 0.43, P = 0.003). CONCLUSION: Unannounced pill counts by the clinician and community based support groups were associated with better long term treatment success and with better adherence

A pragmatic randomized controlled trial of standard care versus steroids plus standard care for treatment of pneumonia in adults admitted to Kenyan hospitals (SONIA)

Background: It is unclear if adjunctive steroid therapy reduces mortality in community-acquired pneumonia, as very few studies have had mortality as a primary outcome. This question has become even more relevant following demonstration of a mortality benefit of dexamethasone when used in patients with COVID-19 who had severe disease. This has led to increased prescription of steroids in adults with community acquired pneumonia in low-resource settings even when their COVID-19 diagnosis is uncertain due to low testing rates. This pragmatic parallel randomised-controlled open-label trial will determine if adjunctive low-dose steroids for treatment of adults admitted to hospital with community acquired pneumonia whose SARS-CoV-2 status is either unknown or negative reduces mortality. Methods: We will enroll and randomize 2180 patients admitted with a clinical diagnosis of community acquired pneumonia into two arms; in Stratum A-participants will receive standard care for the treatment of community acquired pneumonia. In Stratum B-participants will receive a 10-day course of low-dose oral corticosteroids in addition to standard care. All participants will be followed up to 30 days post randomization and their final status recorded (alive or dead). An immunology sub study will be conducted on a subset of the trial participants (50 per arm) to determine the correlation of pre-existing and treatment induced immune and metabolic changes with study outcomes. Discussion: Mortality among adults admitted to hospital with community acquired pneumonia in resource-limited settings is high. Steroids are readily available in these settings. If the addition of steroids to standard care for community acquired pneumonia is found to be beneficial, this easily scalable intervention would significantly reduce the currently high mortality associated with the illness

The use of pill counts as a facilitator of adherence with antiretroviral therapy in resource limited settings.

Pill counts are often used to measure adherence to ART, but there is little data on how they affect adherence. We previously showed a bivariate relationship between clinicians counting pills and adherence in patients receiving HIV care in Kenya. We present a secondary analysis of the relationship between numbers of pill counts and clinical outcomes in resource limited settings.Patients initiating ART at Kijabe Hospital were monitored for the number of discretionary pill counts performed by their clinician in the first 6 months of ART. Subjects were followed for at least 1 year after enrollment. The number of clinician pill counts was correlated to ART adherence. The primary endpoints were time to treatment failure, defined as a detectable HIV-1 viral load, death; or loss to follow-up.Clinician pill counts were done at 68% of clinic visits for 304 subjects. There was a positive correlation between the number of clinician pill counts and ART adherence (r = 0.21, p <0.001). Patients were divided into 3 groups (0 counts, 1 to 3 counts, 4 to 7 counts) and exhibited adherence of 76%, 84%, and 92%, respectively (p = 0.004). Time to treatment failure for these groups was 220 days, 438 days, and 497 days (P<0.01), respectively. Time to virologic failure in living patients remaining in the cohort was longer in those with more pill count (P =0.02). Multi-variate analysis adjusting for co-variates affecting time to treatment failure found that that clinician pill counts were associated with a decreased risk of treatment failure (HR = 0.69, p =0.04).The number of clinician pill count performed was independently associated with better adherence and a decreased risk of treatment failure. The use of clinician pill counts should be further studied as an adherence promoter through a randomized clinical trial

MOESM1 of Isolated splenic tuberculosis with subsequent paradoxical deterioration: a case report

Additional file 1. Timeline of events

Infectious disease modelling for SARS-CoV-2 in Africa to guide policy:A systematic review

Applied epidemiological models have played a critical role in understanding the transmission and control of disease outbreaks. Their utility and accuracy in decision-making on appropriate responses during public health emergencies is however a factor of their calibration to local data, evidence informing model assumptions, speed of obtaining and communicating their results, ease of understanding and willingness by policymakers to use their insights. We conducted a systematic review of infectious disease models focused on SARS-CoV-2 in Africa to determine: a) spatial and temporal patterns of SARS-CoV-2 modelling in Africa, b) use of local data to calibrate the models and local expertise in modelling activities, and c) key modelling questions and policy insights. We searched PubMed, Embase, Web of Science and MedRxiv databases following the PRISMA guidelines to obtain all SARS-CoV-2 dynamic modelling papers for one or multiple African countries. We extracted data on countries studied, authors and their affiliations, modelling questions addressed, type of models used, use of local data to calibrate the models, and model insights for guiding policy decisions. A total of 74 papers met the inclusion criteria, with nearly two-thirds of these coming from 6% (3) of the African countries. Initial papers were published 2 months after the first cases were reported in Africa, with most papers published after the first wave. More than half of all papers (53, 78%) and (48, 65%) had a first and last author affiliated to an African institution respectively, and only 12% (9) used local data for model calibration. A total of 60% (46) of the papers modelled assessment of control interventions. The transmission rate parameter was found to drive the most uncertainty in the sensitivity analysis for majority of the models. The use of dynamic models to draw policy insights was crucial and therefore there is need to increase modelling capacity in the continent

Two-drug regimens for the treatment of HIV in Africa

Two-drug regimens (2DR) for the treatment of HIV are increasingly available. The oral regimen of dolutegravir and lamivudine is recommended as a preferred option in multiple national guidelines but is not currently included in WHO HIV treatment guidelines nor widely used in Africa. Long-acting injectable cabotegravir and rilpivirine is being rolled out in USA, Europe, and Australia but use in sub-Saharan Africa is currently limited to clinical trials. Given increasing life expectancy, rising prevalence of non-communicable diseases, and resulting polypharmacy among people living with HIV (PLWH), there are potential advantages to the use of 2DR in this setting. However, 2DR are not suitable for all. Data on the use of 2DR in PLWH in Africa are limited and further studies are needed to inform policy. In this article we review existing evidence and highlight the risks, benefits, and key knowledge gaps for the use of 2DR in programmatic care settings