Vulnerability of populations to malaria after indoor residual spraying is withdrawn from areas where its use has previously been sustained: a protocol for a systematic review.

INTRODUCTION: With its proven effectiveness, indoor residual spraying (IRS) as a malaria vector control strategy forms one of the reliable vector control strategies, especially when at least 80% of the population is covered. However, to date, there is uncertainty regarding the consequences of IRS withdrawal on malaria control when there is no clear exit strategy in place. Therefore, there is a need to comprehensively update literature regarding malaria burden indicators when IRS is withdrawn following sustained use. METHODS AND ANALYSIS: This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic search of studies published between 2000 and 2022 will be performed in CINAHL, Embase, MEDLINE, ProQuest, PsychInfo, Scopus and OpenGrey. Preset eligibility criteria will be used to identify studies for inclusion by two independent reviewers. Title/abstracts will first be screened and potentially eligible ones screened using their full-text publications. Any conflicts/discrepancies at the two stages will be resolved through regular discussion sessions. Included studies will be extracted to capture study and patient characteristics and relevant outcomes (malaria incidence and malaria vector abundance). Relevant tools will be used to assess the risk of bias in the studies measuring the impact of withdrawal. A meta-analysis will be performed if sufficient homogeneity exists; otherwise, data arising will be presented using tables and by employing narrative synthesis techniques. Heterogeneity will be assessed using a combination of visual inspection of the forest plot along with consideration of the χ2 test and I2 statistic results. ETHICS AND DISSEMINATION: Ethics approval is not applicable for this study since no original data will be collected. The results will be disseminated through peer-reviewed publications and conference presentations. Furthermore, this systematic review will inform the design of exit strategies for IRS-based programmes in malaria-endemic areas. PROSPERO REGISTRATION NUMBER: CRD42022310655.

Paper 1: Demand-driven rapid reviews for health policy and systems decision-making: lessons from Lebanon, Ethiopia, and South Africa on researchers and policymakers' experiences.

BACKGROUND: Rapid reviews have emerged as an approach to provide contextualized evidence in a timely and efficient manner. Three rapid review centers were established in Ethiopia, Lebanon, and South Africa through the Alliance for Health Policy and Systems Research, World Health Organization, to stimulate demand, engage policymakers, and produce rapid reviews to support health policy and systems decision-making. This study aimed to assess the experiences of researchers and policymakers engaged in producing and using rapid reviews for health systems strengthening and decisions towards universal health coverage (UHC). METHODS: Using a case study approach with qualitative research methods, experienced researchers conducted semi-structured interviews with respondents from each center (n = 16). The topics covered included the process and experience of establishing the centers, stimulating demand for rapid reviews, collaborating between researchers and policymakers, and disseminating and using rapid reviews for health policies and interventions and the potential for sustaining and institutionalizing the services. Data were analyzed using thematic analysis. RESULTS: Major themes interacted and contributed to shape the experiences of stakeholders of the rapid review centers, including the following: organizational structural arrangements of the centers, management of their processes as input factors, and the rapid reviews as the immediate policy-relevant outputs. The engagement process and the rapid review products contributed to a final theme of impact of the rapid review centers in relation to the uptake of evidence for policy and systems decision-making. CONCLUSIONS: The experiences of policymakers and researchers of the rapid review centers determined the uptake of evidence. The findings of this study can inform policymakers, health system managers, and researchers on best practices for demanding, developing and using rapid reviews to support decision- and policymaking, and implementing the universal healthcare coverage agenda.

Accuracy and Incremental Yield of the Chest X-Ray in Screening for Tuberculosis in Uganda: A Cross-Sectional Study.

The WHO END TB strategy requires ≥90% case detection to combat tuberculosis (TB). Increased TB case detection requires a more sensitive and specific screening tool. Currently, the symptoms recommended for screening TB have been found to be suboptimal since up to 44% of individuals with TB are asymptomatic. The chest X-ray (CXR) as a screening tool for pulmonary TB was evaluated in this study, as well as its incremental yield in TB diagnosis using a cross-sectional study involving secondary analysis of data of 4512 consented/assented participants ≥15 years who participated in the Uganda National TB prevalence survey between 2014 and 2015. Participants with a cough ≥2 weeks, fever, weight loss, and night sweats screened positive for TB using the symptoms screening method, while participants with a TB defining abnormality on CXR screened positive for TB by the CXR screening method. The Löwenstein-Jensen (LJ) culture was used as a gold standard for TB diagnosis. The CXR had 93% sensitivity and 65% specificity compared to LJ culture results, while symptoms had 76% sensitivity and 31% specificity. The screening algorithm involving the CXR in addition to symptoms led to a 38% increment in the yield of diagnosed tuberculosis. The number needed to screen using the CXR and symptoms screening algorithm was 32 compared to 45 when the symptoms are used alone. Therefore, the CXR in combination with symptoms is a good TB screening tool and increases the yield of diagnosed TB.

Adherence to the MDR-TB intensive phase treatment protocol amongst individuals followed up at central and peripheral health care facilities in Uganda - a descriptive study.

BACKGROUND: Following initiation of MDR-TB treatment, patients have a choice to receive follow up DOT supervision at either the central initiating facility or at a peripheral facility. OBJECTIVES: We describe the adherence patterns of MDR-TB patients undergoing DOT supervision at the two health facility categories during intensive phase of treatment. METHODS: We used a retrospective cohort of patients initiated on MDR TB treatment at Mulago National Referral Hospital between 2014 and 2016. We extracted data from the National Tuberculosis and Leprosy Program records and analysed these using STATA V14. RESULT: Majority (84.01%) of the patients received their DOT supervision from the peripheral facilities. Males made up 62.1% of patients, and 91.2% had had their household contacts screened for MDR-TB. 26.5% of the patients on peripheral DOT supervision had good adherence to treatment protocol compared to 0% among patients on central initiating health facility DOT supervision. Among the patients with good adherence, 24.1% had contacts screened for MDR-TB as compared to 3.6% with poor adherence. CONCLUSION: More patients preferred MDR-TB DOT supervision at peripheral facilities, which had better adherence to the treatment protocol compared to the central initiating facility. Younger people and those with household contacts screened had better adherence to the treatment protocol, highlighting areas for targeted interventional programs for MDR-TB in resource limited settingsMore patients preferred MDR-TB DOT supervision at peripheral facilities, which had better adherence to the treatment protocol compared to the central initiating facility. Younger people and those with household contacts screened had better adherence to the treatment protocol, highlighting areas for targeted interventional programs for MDR-TB in resource limited settings.

Pre-diagnostic drop out of presumptive TB patients and its associated factors at Bugembe Health Centre IV in Jinja, Uganda.

BACKGROUND: Drop out of presumptive TB individuals before making a final diagnosis poses a danger to the individual and their community. We aimed to determine the proportion of these presumptive TB drop outs and their associated factors in Bugembe Health Centre, Jinja, Uganda. METHODS: We used data from the DHIS2, presumptive and laboratory registers of Bugembe Health Centre IV for 2017. Descriptive statistics were used to summarize the population characteristics. A modified Poisson regression model via the generalized linear model (GLM) with log link and robust standard errors was used for bivariate and multivariate analysis.We used data from the DHIS2, presumptive and laboratory registers of Bugembe Health Centre IV for 2017. Descriptive statistics were used to summarize the population characteristics. A modified Poisson regression model via the generalized linear model (GLM) with log link and robust standard errors was used for bivariate and multivariate analysis. RESULT: Among the 216 registered presumptive TB patients who were less than 1% of patients visiting the outpatients' department, 40.7% dropped out before final diagnosis was made. Age and HIV status were significantly associated with pre-diagnostic drop out while gender and distance from the health center were not. CONCLUSION: A high risk to individuals and the community is posed by the significant proportion of presumptive TB patients dropping out before final diagnosis. Health systems managers need to consider interventions targeting young persons, male patients, HIV positive persons.

The natural history of nodding syndrome.

Nodding syndrome is a poorly understood acquired disorder affecting children in sub-Saharan Africa. The aetiology and pathogenesis are unknown, and no specific treatment is available. Affected children have a distinctive feature (repeated clusters of head nodding) and progressively develop many other features. In an earlier pilot study, we proposed a five-level clinical staging system. The present study aimed to describe the early features and natural history of nodding syndrome and refine the proposed clinical stages. This was a retrospective study of the progressive development of symptoms and complications of nodding syndrome. Participants were a cohort of patients who had been identified by community health workers and were referred for treatment. A detailed history was obtained to document the chronological development of symptoms before and after onset of head nodding and a physical examination and disability assessment performed by a team of clinicians and therapists. A total of 210 children were recruited. The mean age at the onset of head nodding was 7.5 (SD: 3.0) years. Five overlapping clinical stages were recognised: prodromal, head nodding, convulsive seizures, multiple impairments, and severe disability stages. Clinical features before the onset of head nodding (prodromal features) included periods of staring blankly or being inattentive, complaints of dizziness, excessive sleepiness, lethargy, and general body weakness, all occurring two weeks to 24 months before nodding developed. After the onset of head nodding, patients progressively developed convulsive seizures, cognitive and psychiatric dysfunction, physical deformities, growth arrest, and eventually, in some patients, severe disability. The description of the natural history of nodding syndrome and especially the prodromal features has the potential of providing a means for the early identification of at-risk patients and the prompt initiation of interventions before extensive brain injury develops. The wide spectrum of symptoms and complications emphasises the need for multi-disciplinary investigations and care.

Asymptomatic malaria parasitaemia and seizure control in children with nodding syndrome; a cross-sectional study.

OBJECTIVE: Plasmodium falciparum is epileptogenic and in malaria endemic areas, is a leading cause of acute seizures. In these areas, asymptomatic infections are common but considered benign and so, are not treated. The effects of such infections on seizures in patients with epilepsy is unknown. This study examined the relationship between P. falciparum infection and seizure control in children with a unique epilepsy type, the nodding syndrome. DESIGN: This cross-sectional study was nested in an ongoing trial 'Doxycycline for the treatment of nodding syndrome (NCT02850913)'. We hypothesised that, in patients with epilepsy, infection by P. falciparum, including asymptomatic infections, increases the risk of seizures and impairs seizure control. SETTING AND PARTICIPANTS: Participants were Ugandan children with nodding syndrome, age ≥8 years, receiving sodium valproate. All had standardised testing including documentation of the number of seizures in the past month, a rapid malaria test and if positive, the peripheral blood parasite density. OUTCOMES: The primary outcome was the number of seizures in the past month (30 days). RESULTS: A total of 164/240 (68%) had malaria. Asymptomatic infections (without fever) were seen in 160/240 (67%) and symptomatic infections in 4/240 (2.7%). In participants without malaria, the median (IQR) number of seizures in the past month was 2.0 (1.0-4.0) and it was 4.0 (2.0-7.5) in participants with malaria, p=0.017. The number of seizures in asymptomatic persons was 3.0 (IQR 2.0-7.3) and 6.0 (IQR 4.0-10.0) in symptomatic individuals, p=0.024. Additionally, in asymptomatic patients, a positive correlation was observed between the parasite density and number of seizures, r=0.33, p=0.002. CONCLUSION: In patients with nodding syndrome, both asymptomatic and symptomatic malaria are associated with an increased risk of seizures and poorer seizure control. Similar effects should be examined in other epilepsy disorders. Malaria prevention should be strengthened for these patients and chemotreatment and prevention studies considered to improve seizure control.