How prepared is the world? Identifying weaknesses in existing assessment frameworks for global health security through a One Health approach.

The COVID-19 pandemic has exposed faults in the way we assess preparedness and response capacities for public health emergencies. Existing frameworks are limited in scope, and do not sufficiently consider complex social, economic, political, regulatory, and ecological factors. One Health, through its focus on the links among humans, animals, and ecosystems, is a valuable approach through which existing assessment frameworks can be analysed and new ways forward proposed. Although in the past few years advances have been made in assessment tools such as the International Health Regulations Joint External Evaluation, a rapid and radical increase in ambition is required. To sufficiently account for the range of complex systems in which health emergencies occur, assessments should consider how problems are defined across stakeholders and the wider sociopolitical environments in which structures and institutions operate. Current frameworks do little to consider anthropogenic factors in disease emergence or address the full array of health security hazards across the social-ecological system. A complex and interdependent set of challenges threaten human, animal, and ecosystem health, and we cannot afford to overlook important contextual factors, or the determinants of these shared threats. Health security assessment frameworks should therefore ensure that the process undertaken to prioritise and build capacity adheres to core One Health principles and that interventions and outcomes are assessed in terms of added value, trade-offs, and cobenefits across human, animal, and environmental health systems.

Improving global health security through implementation of the National Action Plan for Health Security in Sierra Leone, 2018-2021: lessons from the field.

BACKGROUND: All countries are required to implement International Health Regulations (IHR) through development and implementation of multi-year National Action Plans for Health Security (NAPHS). IHR implementation requires annual operational planning which involves several tools such as NAPHS, State Party Annual Report (SPAR), Joint External Evaluation (JEE) and WHO IHR Benchmarks tool. Sierra Leone has successfully improved IHR capacities across the years through successful annual operational planning using the above tools. We conducted a study to document and share the country's unique approach to implementation of NAPHS. METHODS: This was an observational study where the process of implementing and monitoring NAPHS in Sierra Leone was observed at the national level from 2018 to 2021. Data was obtained through review and analysis of NAPHS annual operational plans, quarterly review reports and annual IHR assessment reports. Available data was supplemented by information from key informants. Qualitative data was captured as notes and analysed for various themes while quantitative data was analyzed mainly for means and proportions. RESULTS: The overall national IHR Joint External Evaluation self-assessment score for human health improved from 44% in 2018 to 51% in 2019 and 57% in 2020. The score for the animal sector improved from 32% in 2018 to 43% in 2019 and 52% in 2020. A new JEE tool with new indicators was used in 2021 and the score for both human and animal sectors declined slightly to 51%. Key enablers of success included strong political commitment, whole-of-government approach, annual assessments using JEE tool, annual operational planning using WHO IHR Benchmarks tool and real time online monitoring of progress. Key challenges included disruption created by COVID-19 response, poor health infrastructure, low funding and inadequate health workforce. CONCLUSION: IHR annual operational planning and implementation using evidence-based data and tools can facilitate strengthening of IHR capacity and should be encouraged.

The COVID-19 pandemic in the African continent.

In December 2019, a new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and associated disease, coronavirus disease 2019 (COVID-19), was identified in China. This virus spread quickly and in March, 2020, it was declared a pandemic. Scientists predicted the worst scenario to occur in Africa since it was the least developed of the continents in terms of human development index, lagged behind others in achievement of the United Nations sustainable development goals (SDGs), has inadequate resources for provision of social services, and has many fragile states. In addition, there were relatively few research reporting findings on COVID-19 in Africa. On the contrary, the more developed countries reported higher disease incidences and mortality rates. However, for Africa, the earlier predictions and modelling into COVID-19 incidence and mortality did not fit into the reality. Therefore, the main objective of this forum is to bring together infectious diseases and public health experts to give an overview of COVID-19 in Africa and share their thoughts and opinions on why Africa behaved the way it did. Furthermore, the experts highlight what needs to be done to support Africa to consolidate the status quo and overcome the negative effects of COVID-19 so as to accelerate attainment of the SDGs.

Innovative approach to monitor performance of integrated disease surveillance and response after the Ebola outbreak in Sierra Leone: lessons from the field.

BACKGROUND: Supervision of healthcare workers improves performance if done in a supportive and objective manner. Regular supervision is a support function of Integrated Disease Surveillance and Response (IDSR) strategy and allows systematic monitoring of IDSR implementation. Starting 2015, WHO and other development partners supported the Ministry of Health and Sanitation (MoHS) to revitalize IDSR in Sierra Leone and to monitor progress through supportive supervision assessments. We report on the findings of these assessments. METHODS: This was a cross-sectional study where six longitudinal assessments were conducted in randomly selected health facilities. Health facilities assessed were 71 in February 2016, 99 in July 2016, 101 in May 2017, 126 in August 2018, 139 in February 2019 and 156 in August 2021. An electronic checklist based on selected core functions of IDSR was developed and uploaded onto tablets using the Open Data Kit (ODK) platform. Supervision teams interviewed health care workers, reviewed documents and made observations in health facilities. Supervision books were used to record feedback and corrective actions. Data from the supervisory visits was downloaded from ODK platform, cleaned and analysed. Categorical data was summarized using frequencies and proportions while means and medians were used for continuous variables. Z test was used to test for differences in proportions. RESULTS: Completeness of IDSR reporting improved from 84.5% in 2016 to 96% in 2021 (11.5% points; 95% CI 3.6, 21.9; P-value 0.003). Timeliness of IDSR reports improved from 80.3 to 92% (11.7% points; 95% CI 2.4, 22.9; P-value 0.01). There was significant improvement in health worker knowledge of IDSR concepts and tools, in availability of IDSR standard case definition posters and reporting tools and in data analysis practices. Availability of vaccines and temperature monitoring tools in health facilities also improved significantly but some indicators dropped such as availability of IDSR technical guidelines and malaria testing kits and drugs. CONCLUSION: Supervision using electronic tool contributed to health systems strengthening through longitudinal tracking of core IDSR indicators and other program indicators such as essential malaria commodities and availability and status of routine vaccines. Supervision using electronic tools should be extended to other programs.

Evaluation of Early Warning, Alert and Response System for Ebola Virus Disease, Democratic Republic of the Congo, 2018-2020.

The 10th and largest Ebola virus disease epidemic in the Democratic Republic of the Congo (DRC) was declared in North Kivu Province in August 2018 and ended in June 2020. We describe and evaluate an Early Warning, Alert and Response System (EWARS) implemented in the Beni health zone of DRC during August 5, 2018-June 30, 2020. During this period, 194,768 alerts were received, of which 30,728 (15.8%) were validated as suspected cases. From these, 801 confirmed and 3 probable cases were detected. EWARS showed an overall good performance: sensitivity and specificity >80%, nearly all (97%) of alerts investigated within 2 hours of notification, and good demographic representativeness. The average cost of the system was US $438/case detected and US $1.8/alert received. The system was stable, despite occasional disruptions caused by political insecurity. Our results demonstrate that EWARS was a cost-effective component of the Ebola surveillance strategy in this setting.

The COVID-19 pandemic in the WHO African region: the first year (February 2020 to February 2021).

The World Health Organization African region recorded its first laboratory-confirmed coronavirus disease-2019 (COVID-19) cases on 25 February 2020. Two months later, all the 47 countries of the region were affected. The first anniversary of the pandemic occurred in a changed context with the emergence of new variants of concern (VOC) and growing COVID-19 fatigue. This study describes the epidemiological trajectory of COVID-19 in the region, summarises public health and social measures (PHSM) implemented and discusses their impact on the pandemic trajectory. As of 24 February 2021, the African region accounted for 2.5% of cases and 2.9% of deaths reported globally. Of the 13 countries that submitted detailed line listing of cases, the proportion of cases with at least one co-morbid condition was estimated at 3.3% of all cases. Hypertension, diabetes and human immunodeficiency virus (HIV) infection were the most common comorbid conditions, accounting for 11.1%, 7.1% and 5.0% of cases with comorbidities, respectively. Overall, the case fatality ratio (CFR) in patients with comorbid conditions was higher than in patients without comorbid conditions: 5.5% vs. 1.0% (P < 0.0001). Countries started to implement lockdown measures in early March 2020. This contributed to slow the spread of the pandemic at the early stage while the gradual ease of lockdowns from 20 April 2020 resulted in an upsurge. The second wave of the pandemic, which started in November 2020, coincided with the emergence of the new variants of concern. Only 0.08% of the population from six countries received at least one dose of the COVID-19 vaccine. It is critical to not only learn from the past 12 months to improve the effectiveness of the current response but also to start preparing the health systems for subsequent waves of the current pandemic and future pandemics.

COVID-19 in the WHO African region: using risk assessment to inform decisions on public health and social measures.

Successive waves of COVID-19 transmission have led to exponential increases in new infections globally. In this study, we have applied a decision-making tool to assess the risk of continuing transmission to inform decisions on tailored public health and social measures (PHSM) using data on cases and deaths reported by Member States to the WHO Regional Office for Africa as of 31 December 2020. Transmission classification and health system capacity were used to assess the risk level of each country to guide implementation and adjustments to PHSM. Two countries out of 46 assessed met the criteria for sporadic transmission, one for clusters of cases, and 43 (93.5%) for community transmission (CT) including three with uncontrolled disease incidence (Eswatini, Namibia and South Africa). Health system response's capacities were assessed as adequate in two countries (4.3%), moderate in 13 countries (28.3%) and limited in 31 countries (64.4%). The risk level, calculated as a combination of transmission classification and health system response's capacities, was assessed at level 0 in one country (2.1%), level 1 in two countries (4.3%), level 2 in 11 countries (23.9%) and level 3 in 32 (69.6%) countries. The scale of severity ranged from 0 to 4, with 0 the lowest. CT coupled with limited response capacity resulted in a level 3 risk assessment in most countries. Countries at level 3 should be considered as priority focus for additional assistance, in order to prevent the risk rising to level 4, which may necessitate enforcing hard and costly lockdown measures. The large number of countries at level 3 indicates the need for an effective risk management system to be used as a basis for adjusting PHSM at national and sub-national levels.

Monitoring and evaluation of COVID-19 response in the WHO African region: challenges and lessons learned.

Monitoring and evaluation (M&E) is an essential component of public health emergency response. In the WHO African region (WHO AFRO), over 100 events are detected and responded to annually. Here we discuss the development of the M&E for COVID-19 that established a set of regional and country indicators for tracking the COVID-19 pandemic and response measures. An interdisciplinary task force used the 11 pillars of strategic preparedness and response to define a set of inputs, outputs, outcomes and impact indicators that were used to closely monitor and evaluate progress in the evolving COVID-19 response, with each pillar tailored to specific country needs. M&E data were submitted electronically and informed country profiles, detailed epidemiological reports, and situation reports. Further, 10 selected key performance indicators were tracked to monitor country progress through a bi-weekly progress scoring tool used to identify priority countries in need of additional support from WHO AFRO. Investment in M&E of health emergencies should be an integral part of efforts to strengthen national, regional and global capacities for early detection and response to threats to public health security. The development of an adaptable M&E framework for health emergencies must draw from the lessons learned throughout the COVID-19 response.

Spatial and temporal distribution of infectious disease epidemics, disasters and other potential public health emergencies in the World Health Organisation Africa region, 2016-2018.

BACKGROUND: Emerging and re-emerging diseases with pandemic potential continue to challenge fragile health systems in Africa, creating enormous human and economic toll. To provide evidence for the investment case for public health emergency preparedness, we analysed the spatial and temporal distribution of epidemics, disasters and other potential public health emergencies in the WHO African region between 2016 and 2018. METHODS: We abstracted data from several sources, including: the WHO African Region's weekly bulletins on epidemics and emergencies, the WHO-Disease Outbreak News (DON) and the Emergency Events Database (EM-DAT) of the Centre for Research on the Epidemiology of Disasters (CRED). Other sources were: the Program for Monitoring Emerging Diseases (ProMED) and the Global Infectious Disease and Epidemiology Network (GIDEON). We included information on the time and location of the event, the number of cases and deaths and counter-checked the different data sources. DATA ANALYSIS: We used bubble plots for temporal analysis and generated graphs and maps showing the frequency and distribution of each event. Based on the frequency of events, we categorised countries into three: Tier 1, 10 or more events, Tier 2, 5-9 events, and Tier 3, less than 5 or no event. Finally, we compared the event frequencies to a summary International Health Regulations (IHR) index generated from the IHR technical area scores of the 2018 annual reports. RESULTS: Over 260 events were identified between 2016 and 2018. Forty-one countries (87%) had at least one epidemic between 2016 and 2018, and 21 of them (45%) had at least one epidemic annually. Twenty-two countries (47%) had disasters/humanitarian crises. Seven countries (the epicentres) experienced over 10 events and all of them had limited or developing IHR capacities. The top five causes of epidemics were: Cholera, Measles, Viral Haemorrhagic Diseases, Malaria and Meningitis. CONCLUSIONS: The frequent and widespread occurrence of epidemics and disasters in Africa is a clarion call for investing in preparedness. While strengthening preparedness should be guided by global frameworks, it is the responsibility of each government to finance country specific needs. We call upon all African countries to establish governance and predictable financing mechanisms for IHR implementation and to build resilient health systems everywhere.

Uganda's experience in Ebola virus disease outbreak preparedness, 2018-2019.

BACKGROUND: Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda's experience in EVD preparedness. RESULTS: On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms. CONCLUSION: As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significant and verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a "fire-fighting" approach during public health emergencies.

Institutionalized data quality assessments: a critical pathway to improving the accuracy of integrated disease surveillance data in Sierra Leone.

BACKGROUND: Public health agencies require valid, timely and complete health information for early detection of outbreaks. Towards the end of the Ebola Virus Disease (EVD) outbreak in 2015, the Ministry of Health and Sanitation (MoHS), Sierra Leone revitalized the Integrated Disease Surveillance and Response System (IDSR). Data quality assessments were conducted to monitor accuracy of IDSR data. METHODS: Starting 2016, data quality assessments (DQA) were conducted in randomly selected health facilities. Structured electronic checklist was used to interview district health management teams (DHMT) and health facility staff. We used malaria data, to assess data accuracy, as malaria was endemic in Sierra Leone. Verification factors (VF) calculated as the ratio of confirmed malaria cases recorded in health facility registers to the number of malaria cases in the national health information database, were used to assess data accuracy. Allowing a 5% margin of error, VF < 95% were considered over reporting while VF > 105 was underreporting. Differences in the proportion of accurate reports at baseline and subsequent assessments were compared using Z-test for two proportions. RESULTS: Between 2016 and 2018, four DQA were conducted in 444 health facilities where 1729 IDSR reports were reviewed. Registers and IDSR technical guidelines were available in health facilities and health care workers were conversant with reporting requirements. Overall data accuracy improved from over- reporting of 4.7% (VF 95.3%) in 2016 to under-reporting of 0.2% (VF 100.2%) in 2018. Compared to 2016, proportion of accurate IDSR reports increased by 14.8% (95% CI 7.2, 22.3%) in May 2017 and 19.5% (95% CI 12.5-26.5%) by 2018. Over reporting was more common in private clinics and not- for profit facilities while under-reporting was more common in lower level government health facilities. Leading reasons for data discrepancies included counting errors in 358 (80.6%) health facilities and missing source documents in 47 (10.6%) health facilities. CONCLUSION: This is the first attempt to institutionalize routine monitoring of IDSR data quality in Sierra Leone. Regular data quality assessments may have contributed to improved data accuracy over time. Data compilation errors accounted for most discrepancies and should be minimized to improve accuracy of IDSR data.

Revitalization of integrated disease surveillance and response in Sierra Leone post Ebola virus disease outbreak.

BACKGROUND: The Ministry of Health and Sanitation (MOHS) in Sierra Leone partially rolled out the implementation of Integrated Disease Surveillance and Response (IDSR) in 2003. After the Ebola virus disease outbreak in 2014-2015, there was need to strengthen IDSR to ensure prompt detection and response to epidemic-prone diseases. We describe the processes, successes and challenges of revitalizing public health surveillance in a country recovering from a protracted Ebola virus disease outbreak. METHODS: The revitalization process began with adaptation of the revised IDSR guidelines and development of customized guidelines to suit the health care systems in Sierra Leone. Public health experts defined data flow, system operations, case definitions, frequency and channels of reporting and dissemination. Next, phased training of IDSR focal persons in each health facility and the distribution of data collection and reporting tools was done. Monitoring activities included periodic supportive supervision and data quality assessments. Rapid response teams were formed to investigate and respond to disease outbreak alerts in all districts. RESULTS: Submission of reports through the IDSR system began in mid-2015 and by the 35th epidemiologic week, all district health teams were submitting reports. The key performance indicators measuring the functionality of the IDSR system in 2016 and 2017 were achieved (WHO Africa Region target ≥80%); the annual average proportion of timely weekly health facility reports submitted to the next level was 93% in 2016 and 97% in 2017; the proportion of suspected outbreaks and public health events detected through the IDSR system was 96% (n = 87) in 2016 and 100% (n = 85) in 2017. CONCLUSION: With proper planning, phased implementation and adequate investment of resources, it is possible to establish a functional IDSR system in a country recovering from a public health crisis. A functional IDSR system requires well trained workforce, provision of the necessary tools and guidelines, information, communication and technology infrastructure to support data transmission, provision of timely feedback as well as logistical support.

"We were being treated like the Queen": understanding trial factors influencing high paediatric malaria treatment adherence in western Kenya.

BACKGROUND: Adherence to anti-malarial medication is highly variable but frequently suboptimal. Numerous interventions with a variety of methodological approaches have been implemented to address the problem. A recently conducted, randomized, controlled trial in western Kenya evaluated the effects of short message service (SMS) reminders on paediatric adherence to artemether-lumefantrine (AL) and found over 97% adherence rates in both intervention and control arms. The current study was undertaken to explore participants' experiences in the trial and identify the factors contributing to the high adherence rates. METHODS: In July 2016, 5 months after the trial completion, focus group discussions (FGDs) were undertaken with caregivers of children who had been treated in the intervention (n = 2) or control (n = 2) arms and who, post-trial, had received malaria treatment from the same facilities. The FGDs explored similarities and differences in perceptions and experiences of the care they received during and after the trial. RESULTS: Intervention-arm participants reported that SMS messages were effective dosing reminders. Participants from both arms reported that trial instructions to keep empty AL packs for verification during a home visit by a health worker affected their dosing and adherence practices. Differences between trial and post-trial treatment experiences included: administration of the first AL dose by health workers with demonstration of dispersible tablets dilution; advice on what to do if a child vomited; clear instructions on timing of dosing with efforts made to ensure understanding; and, information that dose completion was necessary with explanation provided. Participants reported that after the trial AL was not available at facilities, constraining their ability to adhere to recommended malaria treatment. They emphasized receiving respectful and personal treatment from trial health workers contributing to perceptions of high quality care and enhanced readiness to adhere to dosing instructions. CONCLUSIONS: This study highlights the complex range of factors that influence AL adherence. The results suggest that in addition to standardized definitions and measurement of adherence, and the influence of enrolment procedures, AL adherence trials need to take account of how intervention impact can be influenced by differences in the quality of care received under trial and routine conditions.

A cross-sectional study of asymptomatic Plasmodium falciparum infection burden and risk factors in general population children in 12 villages in northern Uganda.

BACKGROUND: Plasmodium falciparum malaria is an important cause of morbidity in northern Uganda. This study was undertaken to assess village-, household-, and individual-level risk factors of asymptomatic falciparum malaria in children in 12 villages in northern Uganda. METHODS: Between 10/2011 and 02/2014, 1006 apparently healthy children under 16 years old were enrolled in 12 villages using a stratified, multi-stage, cluster survey design and assessed for P. falciparum malaria infection using the rapid diagnostic test (RDT) and thick film microscopy (TFM), and structured interviewer-administered questionnaires. Associations between weighted P. falciparum malaria prevalence (pfPR), based on RDT, and covariates were estimated as odds ratios and 95% confidence intervals (ORs, 95% CIs) using logistic models accounting for the survey design. RESULTS: Among 942 (93.5%) children successfully tested, pfPR was 52.4% by RDT and 32.7% by TFM. Overall pfPR was lower in villages where indoor residual insecticide spray (IRS) was, versus not, implemented (18.4% versus 75.2%, P < 0.0001). However, pfPR was heterogeneous both within IRS (10.6-34.8%) and non-IRS villages (63.6-86.2%). Elevated pfPR was associated with having a sibling who was RDT positive (OR 5.39, 95% CI 2.94-9.90, P = 0.0006) and reporting a fever at enrollment (aOR 4.80, 95% CI 1.94-11.9, P = 0.0094). Decreased pfPR was associated with living in an IRS village (adjusted OR 0.06, 95% CI 0.04-0.07, P < 0.0001), in a household with one (aOR 0.48, 95% CI 0.30-0.76) or more than one child below 5 years (aOR 0.23, 95% CI 0.12-0.44, Ptrend = 0.014), and reporting keeping a goat inside or near the house (aOR 0.42, 95% CI 0.29-0.62, P = 0.0021). CONCLUSIONS: The results show high but heterogeneous pfPR in villages in northern Uganda, confirm significantly decreased pfPR associated with IRS implementation, and suggest significant associations with some household characteristics. Further research is needed to elucidate the factors influencing malaria heterogeneity in villages in Uganda.

Efficacy of text-message reminders on paediatric malaria treatment adherence and their post-treatment return to health facilities in Kenya: a randomized controlled trial.

BACKGROUND: Short Message Service (SMS) reminders have been suggested as a potential intervention for improving adherence to medications and health facility attendance. METHODS: An open-label, randomized, controlled trial to test the efficacy of automated SMS reminders in improving adherence to artemether-lumefantrine (AL) and post-treatment attendance in comparison with standard care was conducted at four health facilities in western Kenya. Children below five years of age with uncomplicated malaria were randomized to intervention (SMS reminders) or control groups. Within each study group they were further randomized to three categories, which determined the timing of home visits to measure adherence to complete AL course and to individual AL doses. A sub-set of caregivers was advised to return to the facility on day 3 and all were advised to return after 28 days. The primary outcomes were adherence to medication and return on day 3. The primary analysis was by intention-to-treat. RESULTS: Between 9 June, 2014 and 26 February, 2016, 1677 children were enrolled. Of 562 children visited at home on day 3, all AL doses were completed for 97.6% (282/289) of children in the control and 97.8% (267/273) in the intervention group (OR = 1.10; 95% CI = 0.37-3.33; p = 0.860). When correct timing in taking each dose was considered a criteria for adherence, 72.3% (209/289) were adherent in the control and 69.2% (189/273) in the intervention group (OR = 0.82; 95% CI = 0.56-1.19; p = 0.302). Sending SMS reminders significantly increased odds of children returning to the facility on day 3 (81.4 vs 74.0%; OR = 1.55; 95% CI = 1.15-2.08; p = 0.004) and on day 28 (63.4 vs 52.5%; OR = 1.58; 95% CI = 1.30-1.92; p < 0.001). CONCLUSIONS: In this efficacy trial, SMS reminders increased post-treatment return to the health facility, but had no effect on AL adherence which was high in both control and intervention groups. Further effectiveness studies under the real world conditions are needed to determine the optimum role of SMS reminders. Trial registration ISRCTN39512726.

Age and geographic patterns of Plasmodium falciparum malaria infection in a representative sample of children living in Burkitt lymphoma-endemic areas of northern Uganda.

BACKGROUND: Falciparum malaria is an important risk factor for African Burkitt lymphoma (BL), but few studies have evaluated malaria patterns in healthy BL-age children in populations where both diseases are endemic. To obtain accurate current data, patterns of asymptomatic malaria were investigated in northern Uganda, where BL is endemic. METHODS: Between 2011 and 2015, 1150 apparently healthy children under 15 years old were sampled from 100 villages in northern Uganda using a stratified, multi-stage, cluster survey design. Falciparum malaria prevalence (pfPR) was assessed by questionnaire, rapid diagnostic test (RDT) and thick film microscopy (TFM). Weighted pfPR and unadjusted and adjusted associations of prevalence with covariates were calculated using logistic models and survey methods. RESULTS: Based on 1143 children successfully tested, weighted pfPR was 54.8% by RDT and 43.4% by TFM. RDT sensitivity and specificity were 97.5 and 77.8%, respectively, as compared to TFM, because RDT detect malaria antigens, which persist in peripheral blood after clinical malaria, thus results based on RDT are reported. Weighted pfPR increased from 40% in children aged under 2 years to 61.8% in children aged 6-8 years (odds ratio 2.42, 95% confidence interval (CI) 1.26-4.65), then fell slightly to 49% in those aged 12-15 years. Geometric mean parasite density was 1805.5 parasites/µL (95% CI 1344.6-2424.3) among TFM-positive participants, and it was higher in children aged <5 years at 5092.9/µL (95% CI 2892.7-8966.8) and lower in those aged ≥10 years at 983.8/µL (95% CI 472.7-2047.4; P = 0.001). Weighted pfPR was lower in children residing in sub-regions employing indoor residual spraying (IRS) than in those residing in non-IRS sub-regions (32.8 versus 65.7%; OR 0.26, 95% CI 0.14, 0.46). However, pfPR varied both within IRS (3.2-55.3%) and non-IRS sub-regions (29.8-75.8%; Pheterogeneity <0.001). pfPR was inversely correlated with a child's mother's income (P = 0.011) and positively correlated with being enrolled in the wet season (P = 0.076), but sex was irrelevant. CONCLUSIONS: The study observed high but geographically and demographically heterogenous patterns of asymptomatic malaria prevalence among children living in northern Uganda. These results provide important baseline data that will enable precise evaluation of associations between malaria and BL.

Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial.

BACKGROUND: Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence. METHODS: In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral artemisinin based combination therapy (ACT) in children living in a high malaria transmission setting in Eastern Uganda. RESULTS: We enrolled 300 participants and all were included in the intention to treat analysis. Baseline characteristics were similar across treatment arms. The median and interquartile range for number of days from baseline to parasite clearance was significantly lower among participants who received intravenous AS (2 (1-2) vs 3 (2-3), P < 0.001). Overall, 63.3% (178/281) of the participants had unadjusted parasitological treatment failure over the 42-day follow-up period. Molecular genotyping to distinguish re-infection from recrudescence was performed in a sample of 127 of the 178 participants, of whom majority 93 (73.2%) had re-infection and 34 (26.8%) had recrudescence. The 42 day risk of recrudescence did not differ with ACT administered. Adverse events were of mild to moderate severity and consistent with malaria symptoms. CONCLUSION: In this high transmission setting, we observed adequate initial treatment outcomes followed by very high rates of malaria re-infection post severe malaria treatment. The impact of recurrent antimalarial treatment on the long term efficacy of antimalarial regimens needs to be investigated and surveillance mechanisms for resistance markers established since recurrent malaria infections are likely to be exposed to sub-therapeutic drug concentrations. More strategies for prevention of recurrent malaria infections in the most at risk populations are needed. TRIAL REGISTRATION: The study was registered with the Pan African Clinical Trial Registry ( PACTR201110000321348 ).

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Development of a text-messaging intervention to improve treatment adherence and post-treatment review of children with uncomplicated malaria in western Kenya.

BACKGROUND: Patients' low adherence to artemisinin-based combination therapy has been reported in areas of Kenya bordering the Lake Victoria region, where the burden of malaria remains high. A randomized controlled trial is underway to determine the efficacy of short message service (SMS) text reminders on adherence to artemether-lumefantrine and post-treatment review of children under the age of five. This paper reports on the iterative process of intervention and delivery system development. METHODS: An intervention development workshop involving the research team and other stakeholders was held to determine the content of the text messages. Three focus group discussions were conducted to test caregivers' understanding of the messages developed during the workshop. The tested messages were refined and incorporated into an automated SMS distribution system and piloted with 20 caregivers drawn from facilities neighbouring the study sites. The automated SMS distribution system was repeatedly refined following the pilot and implemented at the start of the trial. RESULTS: The content of SMS messages underwent major revisions following the focus group discussions. Technical terms and abbreviations were replaced with simplified general terms. Message sign-off was modified to reflect the name of health facility, removing references to health workers. Day 3 post-treatment review visit reminder was modified to state the purpose of the visit while wording 'day 28' was added to the last post-treatment review visit reminder to help the caregiver recall the appointment date. The unscheduled visit prompt was modified to reflect flexibility and practicality of taking the child back to the facility if unwell. Reception of SMS reminders during the pilot was low with only 169/240 (70%) of scheduled messages delivered to the caregivers. The automated distribution system underwent major refinement and repeated testing following the pilot until effective delivery of all scheduled messages was achieved and sustained over a period of 3 months. CONCLUSIONS: Text message interventions should be carefully developed, tested and refined before implementation to ensure they are written in the most appropriate way for their target population. SMS distribution systems should be rigorously tested to ensure efficient delivery of the messages before they are deployed.