Usability of pulse oximeters used by community health and primary care workers as screening tools for severe illness in children under five in low resource settings: A cross-sectional study in Cambodia, Ethiopia, South Sudan, and Uganda.

Timely recognition and referral of severely ill children is especially critical in low-resource health systems. Pulse-oximeters can improve health outcomes of children by detecting hypoxaemia, a severity indicator of the most common causes of death in children. Cost-effectiveness of pulse-oximeters has been proven in low-income settings. However, evidence on their usability in community health settings is scarce.This study explores the usability of pulse-oximeters for community health and primary care workers in Cambodia, Ethiopia, South Sudan, and Uganda. We collected observational data, through a nine-task checklist, and survey data, using a five-point Likert scale questionnaire, capturing three usability aspects (effectiveness, efficiency, and satisfaction) of single-probe fingertip and multi-probe handheld devices. Effectiveness was determined by checklist completion rates and task completion rates per checklist item. Efficiency was reported as proportion of successful assessments within three attempts. Standardized summated questionnaire scores (min = 0, max = 100) determined health worker's satisfaction. Influencing factors on effectiveness and satisfaction were explored through hypothesis tests between independent groups (device type, cadre of health worker, country). Checklist completion rate was 78.3% [CI 72.6-83.0]. Choosing probes according to child age showed the lowest task completion rate of 68.7% [CI 60.3%-76.0%]. In 95.6% [CI 92.7%-97.4%] of assessments a reading was obtained within three attempts. The median satisfaction score was 95.6 [IQR = 92.2-99.0]. Significantly higher checklist completion rates were observed with single-probe fingertip devices (p<0.001) and children 12-59 months (p<0.001). We found higher satisfaction scores in South Sudan (p<0.001) and satisfaction varied slightly between devices. From a usability perspective single-probe devices for all age groups should be prioritized for scaled implementation. Further research on easy to use and accurate devices for infants is much needed.

A non-randomized controlled trial to assess the protective effect of SMC in the context of high parasite resistance in Uganda.

BACKGROUND: Until recently, due to widespread prevalence of molecular markers associated with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) resistance in east and southern Africa, seasonal malaria chemoprevention (SMC) has not been used at scale in this region. This study assessed the protective effectiveness of monthly administration of SP + AQ (SPAQ) to children aged 3-59 months in Karamoja sub-region, Uganda, where parasite resistance is assumed to be high and malaria transmission is seasonal. METHODS: A two-arm quasi-experimental, open-label prospective non-randomized control trial (nRCT) was conducted in three districts. In two intervention districts, 85,000 children aged 3-59 months were targeted to receive monthly courses of SMC using SPAQ during the peak transmission season (May to September) 2021. A third district served as a control, where SMC was not implemented. Communities with comparable malaria attack rates were selected from the three districts, and households with at least one SMC-eligible child were purposively selected. A total cohort of 600 children (200 children per district) were selected and followed using passive surveillance for breakthrough confirmed malaria episodes during the five-month peak transmission season. Malaria incidence rate per person-months and number of malaria episodes among children in the two arms were compared. Kaplan-Meier failure estimates were used to compare the probability of a positive malaria test. Other factors that may influence malaria transmission and infection among children in the two arms were also assessed using multivariable cox proportional hazards regression model. RESULTS: The malaria incidence rate was 3.0 and 38.8 per 100 person-months in the intervention and control groups, respectively. In the intervention areas 90.0% (361/400) of children did not experience any malaria episodes during the study period, compared to 15% (29/200) in the control area. The incidence rate ratio was 0.078 (95% CI 0.063-0.096), which corresponds to a protective effectiveness of 92% (95% CI 90.0-94.0) among children in the intervention area. CONCLUSION: SMC using SPAQ provided high protective effect against malaria during the peak transmission season in children aged 3-59 months in the Karamoja sub-region of Uganda.

A hybrid effectiveness-implementation study protocol to assess the effectiveness and chemoprevention efficacy of implementing seasonal malaria chemoprevention in five districts in Karamoja region, Uganda.

Background: The World Health Organization (WHO) recommends seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SPAQ) for children aged 3 to 59 months, living in areas where malaria transmission is highly seasonal. However, due to widespread prevalence of resistance markers, SMC has not been implemented at scale in East and Southern Africa. An initial study in Uganda showed that SMC with SPAQ was feasible, acceptable, and protective against malaria in eligible children in Karamoja region. Nonetheless, exploration of alternative regimens is warranted since parasite resistance threats persist. Objective: The study aims to test the effectiveness of SMC with Dihydroartemisinin-piperaquine (DP) or SPAQ (DP-SMC & SPAQ-SMC), chemoprevention efficacy as well as the safety and tolerability of DP compared to that of SPAQ among 3-59 months old children in Karamoja region, an area of Uganda where malaria transmission is highly seasonal. Methods: A Type II hybrid effectiveness-implementation study design consisting of four components: 1) a cluster randomized controlled trial (cRCT) using passive surveillance to establish confirmed malaria cases in children using both SPAQ and DP; 2a) a prospective cohort study to determine the chemoprevention efficacy of SPAQ and DP (if SPAQ or DP clears sub-patent infection and provides 28 days of protection from new infection) and whether drug concentrations and/or resistance influence the ability to clear and prevent infection; 2b) a sub study examining pharmacokinetics of DP in children between 3 to <6 months; 3) a resistance markers study in children 3-59 months in the research districts plus the standard intervention districts to measure changes in resistance marker prevalence over time and finally; 4) a process evaluation. Discussion: This study evaluates the effects of SPAQ-SMC versus DP-SMC on clinical malaria in vulnerable children in the context of high parasite SP resistance, whilst informing on the best implementation strategies. Conclusion: This study will inform malaria policy in high-burden countries, specifically on utility of SMC outside the sahel, and contribute to progress in malaria control.

District-led malaria surveillance and response as an effective way to manage malaria upsurges following the withdrawal of indoor residual spraying: a case study from Nwoya District, northern Uganda.

BACKGROUND: Malaria remains the number one cause of morbidity and mortality in Uganda. In 2009, the United States President's Malaria Initiative (PMI) funded an indoor residual spraying (IRS) project in 10 mid-northern districts, resulting in marked reductions in malaria prevalence over 5 years, from 62.5 percent to 7.2 percent. When the project ended and IRS withdrawn, malaria prevalence increased exponentially to pre-IRS level of 63 percent in 2016 and was characterized by frequent life-threatening upsurges that were exacerbated by a weak national led malaria surveillance system with delayed and piece meal responses. Malaria Consortium, in collaboration with Nwoya district local government implemented a district led malaria surveillance and response system. This study was conducted to compare the impact of District led and national led surveillance and response systems on overall malaria burden in two sub-counties in Nwoya district, Northern Uganda. METHODS: The assessment was conducted between week 41 of 2018 and week 10 of 2019 in Anaka and Alero sub counties following the shift from the national to district led malaria surveillance and response system. A district multi-sectoral malaria response taskforce team, known as the District Malaria Surveillance and Response Team (DMSRT), was formed by the Nwoya District Health Team (DHT). The DMSRT was trained and equipped with new surveillance tools for early detection of and response to malaria upsurges within the district, and were mandated to develop a costed district specific malaria response plan. RESULTS: All (18) targeted health facilities provided weekly malaria reports and continuously updated the malaria normal channel graphs. There was an overall reduction in weekly new malaria cases from 12.9 in week 41 of 2018 to 6.2 cases in week 10 of 2019. Malaria positivity rates (TPR) for Alero and Anaka sub-counties reduced from 76.0 percent and 69.3 percent at week 42 of 2018 to 28 percent and 30.3 percent, respectively at week 10 of 2019. CONCLUSIONS: Malaria surveillance and response, with precisely targeted multipronged activities, when led and implemented by local district health authorities is an effective, efficient, and sustainable approach to prevent malaria upsurges and associated morbidity and mortality.

Current malaria infection, previous malaria exposure, and clinical profiles and outcomes of COVID-19 in a setting of high malaria transmission: an exploratory cohort study in Uganda.

BACKGROUND: The potential effects of SARS-CoV-2 and Plasmodium falciparum co-infection on host susceptibility and pathogenesis remain unknown. We aimed to establish the prevalence of malaria and describe the clinical characteristics of SARS-CoV-2 and P falciparum co-infection in a high-burden malaria setting. METHODS: This was an exploratory prospective, cohort study of patients with COVID-19 who were admitted to hospital in Uganda. Patients of all ages with a PCR-confirmed diagnosis of SARS-CoV-2 infection who had provided informed consent or assent were consecutively enrolled from treatment centres in eight hospitals across the country and followed up until discharge or death. Clinical assessments and blood sampling were done at admission for all patients. Malaria diagnosis in all patients was done by rapid diagnostic tests, microscopy, and molecular methods. Previous P falciparum exposure was determined with serological responses to a panel of P falciparum antigens assessed using a multiplex bead assay. Additional evaluations included complete blood count, markers of inflammation, and serum biochemistries. The main outcome was overall prevalence of malaria infection and malaria prevalence by age (including age categories of 0-20 years, 21-40 years, 41-60 years, and >60 years). The frequency of symptoms was compared between patients with COVID-19 with P falciparum infection versus those without P falciparum infection. The frequency of comorbidities and COVID-19 clinical severity and outcomes was compared between patients with low previous exposure to P falciparum versus those with high previous exposure to P falciparum. The effect of previous exposure to P falciparum on COVID-19 clinical severity and outcomes was also assessed among patients with and those without comorbidities. FINDINGS: Of 600 people with PCR-confirmed SARS-CoV-2 infection enrolled from April 15, to Oct 30, 2020, 597 (>99%) had complete information and were included in our analyses. The majority (502 [84%] of 597) were male individuals with a median age of 36 years (IQR 28-47). Overall prevalence of P falciparum infection was 12% (95% CI 9·4-14·6; 70 of 597 participants), with highest prevalence in the age groups of 0-20 years (22%, 8·7-44·8; five of 23 patients) and older than 60 years (20%, 10·2-34·1; nine of 46 patients). Confusion (four [6%] of 70 patients vs eight [2%] of 527 patients; p=0·040) and vomiting (four [6%] of 70 patients vs five [1%] of 527 patients; p=0·014] were more frequent among patients with P falciparum infection than those without. Patients with low versus those with high previous P falciparum exposure had a increased frequency of severe or critical COVID-19 clinical presentation (16 [30%] of 53 patients vs three [5%] of 56 patients; p=0·0010) and a higher burden of comorbidities, including diabetes (12 [23%] of 53 patients vs two [4%] of 56 patients; p=0·0010) and heart disease (seven [13%] of 53 patients vs zero [0%] of 56 patients; p=0·0030). Among patients with no comorbidities, those with low previous P falciparum exposure still had a higher proportion of cases of severe or critical COVID-19 than did those with high P falciparum exposure (six [18%] of 33 patients vs one [2%] of 49 patients; p=0·015). Multivariate analysis showed higher odds of unfavourable outcomes in patients who were older than 60 years (adjusted OR 8·7, 95% CI 1·0-75·5; p=0·049). INTERPRETATION: Although patients with COVID-19 with P falciparum co-infection had a higher frequency of confusion and vomiting, co-infection did not seem deleterious. The association between low previous malaria exposure and severe or critical COVID-19 and other adverse outcomes will require further study. These preliminary descriptive observations highlight the importance of understanding the potential clinical and therapeutic implications of overlapping co-infections. FUNDING: Malaria Consortium (USA).

Correction to: Monitoring changes in malaria epidemiology and effectiveness of interventions in Ethiopia and Uganda: Beyond Garki Project baseline survey.

Please be advised that one of the author names is incorrectly spelled in the published article: 'Irene Kyomuhagi' should be 'Irene Kyomuhangi'.

Community dialogues for child health: results from a qualitative process evaluation in three countries.

BACKGROUND: Across the developing world, countries are increasingly adopting the integrated community case management of childhood illnesses (iCCM) strategy in efforts to reduce child mortality. This intervention's effectiveness is dependent on community adoption and changes in care-seeking practices. We assessed the implementation process of a theory-driven community dialogue (CD) intervention specifically designed to strengthen the support and uptake of the newly introduced iCCM services and related behaviours in three African countries. METHODS: A qualitative process evaluation methodology was chosen and used secondary project data and primary data collected in two districts of each of the three countries, in purposefully sampled communities. The final data set included 67 focus group discussions and 57 key informant interviews, totalling 642 respondents, including caregivers, CD facilitators community leaders, and trainers. Thematic analysis of the data followed the 'Framework Approach' utilising both a deduction and induction process. RESULTS: Results show that CDs contribute to triggering community uptake of and support for iCCM services through filling health information gaps and building cooperation within communities. We found it to be an effective approach for addressing social norms around child care practices. This approach was embraced by communities for its flexibility and value in planning individual and collective change. CONCLUSIONS: Regular CDs can contribute to the formation of new habits, particularly in relation to seeking timely care in case of child sickness. This study also confirms the value of process evaluation to unwrap the mechanisms of community mobilisation approaches in context and provides key insights for improving the CD approach.

How Do Patients and Health Workers Interact around Malaria Rapid Diagnostic Testing, and How Are the Tests Experienced by Patients in Practice? A Qualitative Study in Western Uganda.

BACKGROUND: Successful scale-up in the use of malaria rapid diagnostic tests (RDTs) requires that patients accept testing and treatment based on RDT results and that healthcare providers treat according to test results. Patient-provider communication is a key component of quality care, and leads to improved patient satisfaction, higher adherence to treatment and better health outcomes. Voiced or perceived patient expectations are also known to influence treatment decision-making among healthcare providers. While there has been a growth in literature on provider practices around rapid testing for malaria, there has been little analysis of inter-personal communication around the testing process. We investigated how healthcare providers and patients interact and engage throughout the diagnostic and treatment process, and how the testing service is experienced by patients in practice. METHODS: This research was conducted alongside a larger study which explored determinants of provider treatment decision-making following negative RDT results in a rural district (Kibaale) in mid-western Uganda, ten months after RDT introduction. Fifty-five patients presenting with fever were observed during routine outpatient visits at 12 low-level public health facilities. Observation captured communication practices relating to test purpose, results, diagnosis and treatment. All observed patients or caregivers were immediately followed up with in-depth interview. Analysis followed the 'framework' approach. A summative approach was also used to analyse observation data. RESULTS: Providers failed to consistently communicate the reasons for carrying out the test, and particularly to RDT-negative patients, a diagnostic outcome or the meaning of test results, also leading to confusion over what the test can detect. Patients appeared to value testing, but were frustrated by the lack of communication on outcomes. RDT-negative patients were dissatisfied by the absence of information on an alternative diagnosis and expressed uncertainty around adequacy of proposed treatment. CONCLUSIONS: Poor provider communication practices around the testing process, as well as limited inter-personal exchange between providers and patients, impacted on patients' perceptions of their proposed treatment. Patients have a right to health information and may be more likely to accept and adhere to treatment when they understand their diagnosis and treatment rationale in relation to their perceived health needs and visit expectations.

Exposure to deltamethrin affects development of Plasmodium falciparum inside wild pyrethroid resistant Anopheles gambiae s.s. mosquitoes in Uganda.

BACKGROUND: Pyrethroid resistance in African vector mosquitoes is a threat to malaria control. Resistant mosquitoes can survive insecticide doses that would normally be lethal. We studied effects of such doses on Plasmodium falciparum development inside kdr-resistant Anopheles gambiae s.s. in Uganda. METHODS: We collected An. gambiae s.s. homozygous for kdr-L1014S mutation, fed them on blood samples from 42 P. falciparum-infected local patients, then exposed them either to nets treated with sub-lethal doses of deltamethrin or to untreated nets. After seven days, we dissected 692 mosquitoes and examined their midguts for oocysts. Prevalence (proportion infected) and intensity of infection (number of oocysts per infected mosquito) were recorded for each group. RESULTS: Both prevalence and intensity of infection were significantly reduced in deltamethrin-exposed mosquitoes, compared to those exposed to untreated nets. With low doses (2.5-5.0 mg/m(2)), prevalence was reduced by 59% (95% CI = 22%-78%) and intensity by 41% (95% CI = 25%-54%). With high doses (10-16.7 mg/m(2)), prevalence was reduced by 80% (95% CI = 67%-88 %) and intensity by 34 % (95 % CI = 20%-46%). CONCLUSIONS: We showed that, with locally-sampled parasites and mosquitoes, doses of pyrethroids that are sub-lethal for resistant mosquitoes can interfere with parasite development inside mosquitoes. This mechanism could enable pyrethroid-treated nets to prevent malaria transmission despite increasing vector resistance.

What drives the consistent use of long-lasting insecticidal nets over time? A multi-method qualitative study in mid-western Uganda.

BACKGROUND: The distribution of long-lasting insecticidal nets (LLINs) through universal coverage campaigns is a widely adopted approach for the prevention of malaria at scale. While post-distribution surveys play a valuable role in determining cross-sectional levels of LLIN retention and use, as well as frequently cited reasons for non-use, few studies have explored the consistency of LLIN use over time, within the expected lifespan of the net, and the factors which may drive this. METHODS: In this qualitative study, 74 in-depth interviews were conducted with (male) household heads and (female) caregivers of children in LLIN recipient households, as well as community health workers, in Buliisa, Hoima and Kiboga districts in Uganda, 25-29 months following a LLIN mass campaign distribution. A triangulation approach to data analysis was taken, incorporating thematic analysis, most significant change and positive deviance. RESULTS: The factors found to be most influential in encouraging long-term LLIN use were positive experience of net use prior to the distribution, and appreciation or awareness of a range of benefits arising from their use, including protection from malaria as well as importantly, other health, lifestyle, social and economic benefits. Social support from within the community was also identified as an important factor in determining continued use of LLINs. Net use appeared to be more consistent amongst settled urban and rural communities, compared with fishing, pastoralist, refugee and immigrant communities. CONCLUSIONS: A multitude of interplaying factors encouraged consistent LLIN use in this setting. Whilst the protection of malaria remains a powerful motivator, social and behaviour change (SBC) strategies should also capitalize on the non-malaria benefits of net use that provide a long-term rationale for consistent use. Where supplies are available, SBC campaigns should promote replacement options, emphasizing ongoing net care and replacement as a household responsibility, thus reducing dependence on free distributions. The triangulation approach to qualitative data analysis enabled increased confidence in the validity of findings and an enhanced contextual understanding of the factors promoting consistent net use in mid-western Uganda. The approach should be considered when designing future studies to explore factors driving net retention and use trends.

Why do health workers give anti-malarials to patients with negative rapid test results? A qualitative study at rural health facilities in western Uganda.

BACKGROUND: The large-scale introduction of malaria rapid diagnostic tests (RDTs) promises to improve management of fever patients and the rational use of valuable anti-malarials. However, evidence on the impact of RDT introduction on the overprescription of anti-malarials has been mixed. This study explored determinants of provider decision-making to prescribe anti-malarials following a negative RDT result. METHODS: A qualitative study was conducted in a rural district in mid-western Uganda in 2011, ten months after RDT introduction. Prescriptions for all patients with negative RDT results were first audited from outpatient registers for a two month period at all facilities using RDTs (n = 30). Facilities were then ranked according to overall prescribing performance, defined as the proportion of patients with a negative RDT result prescribed any anti-malarial. Positive and negative deviant facilities were sampled for qualitative investigation; positive deviants (n = 5) were defined ex post facto as <0.75% and negative deviants (n = 7) as >5%. All prescribing clinicians were targeted for qualitative observation and in-depth interview; 55 fever cases were observed and 22 providers interviewed. Thematic analysis followed the 'framework' approach. RESULTS: 8344 RDT-negative patients were recorded at the 30 facilities (prescription audit); 339 (4.06%) were prescribed an anti-malarial. Of the 55 observed patients, 38 tested negative; one of these was prescribed an anti-malarial. Treatment decision-making was influenced by providers' clinical beliefs, capacity constraints, and perception of patient demands. Although providers generally trusted the accuracy of RDTs, anti-malarial prescription was driven by perceptions of treatment failure or undetectable malaria in patients who had already taken artemisinin-based combination therapy prior to facility arrival. Patient assessment and other diagnostic practices were minimal and providers demonstrated limited ability to identify alternative causes of fever. Provider perceptions of patient expectations sometimes appeared to influence treatment decisions. CONCLUSIONS: The study found high provider adherence to RDT results, but that providers believed in certain clinical exceptions and felt they lacked alternative options. Guidance on how the RDT works and testing following partial treatment, better methods for assisting providers in diagnostic decision-making, and a context-appropriate provider behaviour change intervention package are needed.

Monitoring changes in malaria epidemiology and effectiveness of interventions in Ethiopia and Uganda: Beyond Garki Project baseline survey.

BACKGROUND: Scale-up of malaria interventions seems to have contributed to a decline in the disease but other factors may also have had some role. Understanding changes in transmission and determinant factors will help to adapt control strategies accordingly. METHODS: Four sites in Ethiopia and Uganda were set up to monitor epidemiological changes and effectiveness of interventions over time. Here, results of a survey during the peak transmission season of 2012 are reported, which will be used as baseline for subsequent surveys and may support adaptation of control strategies. Data on malariometric and entomological variables, socio-economic status (SES) and control coverage were collected. RESULTS: Malaria prevalence varied from 1.4 % in Guba (Ethiopia) to 9.9 % in Butemba (Uganda). The most dominant species was Plasmodium vivax in Ethiopia and Plasmodium falciparum in Uganda. The majority of human-vector contact occurred indoors in Uganda, ranging from 83 % (Anopheles funestus sensu lato) to 93 % (Anopheles gambiae s.l.), which is an important factor for the effectiveness of insecticide-treated nets (ITNs) or indoor residual spraying (IRS). High kdr-L1014S (resistance genotype) frequency was observed in A. gambiae sensu stricto in Uganda. Too few mosquitoes were collected in Ethiopia, so it was not possible to assess vector habits and insecticide resistance levels. ITN ownership did not vary by SES and 56-98 % and 68-78 % of households owned at least one ITN in Ethiopia and Uganda, respectively. In Uganda, 7 % of nets were purchased by households, but the nets were untreated. In three of the four sites, 69-76 % of people with access to ITNs used them. IRS coverage ranged from 84 to 96 % in the three sprayed sites. Half of febrile children in Uganda and three-quarters in Ethiopia for whom treatment was sought received diagnostic tests. High levels of child undernutrition were detected in both countries carrying important implications on child development. In Uganda, 7-8 % of pregnant women took the recommended minimum three doses of intermittent preventive treatment. CONCLUSION: Malaria epidemiology seems to be changing compared to earlier published data, and it is essential to have more data to understand how much of the changes are attributable to interventions and other factors. Regular monitoring will help to better interpret changes, identify determinants, modify strategies and improve targeting to address transmission heterogeneity.