The Uganda housing modification study - association between housing characteristics and malaria burden in a moderate to high transmission setting in Uganda.

Background: Scale up of proven malaria control interventions has not been sufficient to control malaria in Uganda, emphasizing the need to explore innovative new approaches. Improved housing is one such promising strategy. This paper describes housing characteristics and their association with malaria burden in a moderate to high transmission setting in Uganda.

LLIN Evaluation in Uganda Project (LLINEUP)-effects of a vector control trial on Plasmodium infection prevalence and genotypic markers of insecticide resistance in Anopheles vectors from 48 districts of Uganda.

Pyrethroid bednets treated with the synergist piperonyl butoxide (PBO) offer the possibility of improved vector control in mosquito populations with metabolic resistance. In 2017-2019, we conducted a large-scale, cluster-randomised trial (LLINEUP) to evaluate long-lasting insecticidal nets (LLINs) treated with a pyrethroid insecticide plus PBO (PBO LLINs), as compared to conventional, pyrethroid-only LLINs across 104 health sub-districts (HSDs) in Uganda. In LLINEUP, and similar trials in Tanzania, PBO LLINs were found to provide greater protection against malaria than conventional LLINs, reducing parasitaemia and vector density.

LLIN Evaluation in Uganda Project (LLINEUP): modelling the impact of COVID-19-related disruptions on delivery of long-lasting insecticidal nets on malaria indicators in Uganda.

Background: Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3-4 years, but the 2020-2021 campaign was altered because of COVID-19 restrictions so that the timing of delivery of new nets was different from the original plans made by the National Malaria Control Programme.

Methods: A transmission dynamics modelling exercise was conducted to explore how the altered delivery of LLINs in 2020-2021 impacted malaria burden in Uganda.

House modifications as a malaria control tool: how does local context shape participants' experience and interpretation in Uganda?

Background: Evidence that house design can provide protection from malaria is growing. Housing modifications such as screening windows, doors, and ceilings, and attaching insecticide-impregnated materials to the eaves (the gap between the top of the wall and bottom of the roof), can protect against malaria. To be effective at scale, however, these modifications must be adopted by household residents.

LLIN Evaluation in Uganda Project (LLINEUP) - infection prevalence and genotypic markers of insecticide resistance in vectors from 48 districts of Uganda.

Background: In 2017-2019, we conducted a large-scale, cluster-randomised trial (LLINEUP) to evaluate long-lasting insecticidal nets (LLINs) treated with a pyrethroid insecticide plus the synergist piperonyl butoxide (PBO LLINs), as compared to conventional, pyrethroid-only LLINs across 104 health sub-districts (HSDs) in Uganda. In LLINEUP, and similar trials in Tanzania, PBO LLINs were found to provide greater protection against malaria than conventional LLINs, reducing parasitaemia and vector density. In the LLINEUP trial, cross-sectional entomological surveys were carried out at baseline and then every 6 months for two years.

Effect of long-lasting insecticidal nets with and without piperonyl butoxide on malaria indicators in Uganda (LLINEUP): final results of a cluster-randomised trial embedded in a national distribution campaign.

Background: Long-lasting insecticidal nets (LLINs) are the foundation of malaria control but resistance of mosquito vectors to pyrethroids threatens their effectiveness. We embedded a cluster-randomised trial into Uganda's 2017-18 campaign to distribute LLINs. LLINs with piperonyl butoxide (PBO) reduced parasite prevalence more effectively than conventional LLINs (without PBO) for 18 months.

LLIN evaluation in Uganda project (LLINEUP): The fabric integrity, chemical content and bioefficacy of long-lasting insecticidal nets treated with and without piperonyl butoxide across two years of operational use in Uganda.

Long-lasting insecticidal nets (LLINs) supplemented with the synergist piperonyl butoxide have been developed in response to growing pyrethroid resistance; however, their durability in the field remains poorly described. A pragmatic cluster-randomised trial was embedded into Uganda's 2017-2018 LLIN distribution to compare the durability of LLINs with and without PBO. A total of 104 clusters (health sub-districts) were included with each receiving one of four LLIN products, two with pyrethroid + PBO (Olyset Plus and PermaNet 3.

Validity of caregivers' reports on prior use of antibacterials in children under five years presenting to health facilities in Gulu, northern Uganda.

Introduction: Given the frequent initiation of antibacterial treatment at home by caregivers of children under five years in low-income countries, there is a need to find out whether caregivers' reports of prior antibacterial intake by their children before being brought to the healthcare facility are accurate. The aim of this study was to describe and validate caregivers' reported use of antibacterials by their children prior to seeking care at the healthcare facility.

Methods: A cross sectional study was conducted among children under five years seeking care at healthcare facilities in Gulu district, northern Uganda.

Antibiotic use among children under five years with diarrhea in rural communities of Gulu, northern Uganda: a cross-sectional study.

Background: Diarrhea is the second leading cause of mortality in children under 5 years of age globally, and the risk of death increases with practices such as restriction of fluid intake and inappropriate use of antibiotics. We determined the prevalence of antibiotic use in managing diarrhea in children under 5 years of age in rural communities of Gulu district, northern Uganda.

Method: A cross-sectional study among children under 5 years with diarrhea, from households selected using multi-stage sampling.

Alcohol consumption, hypertension and obesity: Relationship patterns along different age groups in Uganda.

The prevalence of non-communicable diseases including hypertension and obesity is rising and alcohol consumption is a predisposing factor. This study explored the effect of alcohol consumption patterns on the hypertension-age group and obesity-age group relationships. The data were extracted from the 2014 National NCD Survey of adults aged 18-69 years.

Use of antibacterials in the management of symptoms of acute respiratory tract infections among children under five years in Gulu, northern Uganda: Prevalence and determinants.

Inappropriate use of antibacterials is a major public health challenge as it can promote emergence of resistance, wastage of financial resources, morbidity and mortality. In this study, we determined the prevalence and factors associated with antibacterial use in managing symptoms of acute respiratory tract infections (ARIs) in households in rural communities of Gulu district, northern Uganda. A cross-sectional study was conducted among households selected using multi-stage sampling.

Effect of long-lasting insecticidal nets with and without piperonyl butoxide on malaria indicators in Uganda (LLINEUP): a pragmatic, cluster-randomised trial embedded in a national LLIN distribution campaign.

Background: Long-lasting insecticidal nets (LLINs) are the primary malaria prevention tool, but their effectiveness is threatened by pyrethroid resistance. We embedded a pragmatic cluster-randomised trial into Uganda's national LLIN campaign to compare conventional LLINs with those containing piperonyl butoxide (PBO), a synergist that can partially restore pyrethroid susceptibility in mosquito vectors.

Methods: 104 health sub-districts, from 48 districts in Uganda, were randomly assigned to LLINs with PBO (PermaNet 3.

Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study.

Background: Multiple red blood cell (RBC) variants appear to offer protection against the most severe forms of Plasmodium falciparum malaria. Associations between these variants and uncomplicated malaria are less clear.

Methods: Data from a longitudinal cohort study conducted in 3 sub-counties in Uganda was used to quantify associations between three red blood cell variants Hb [AA, AS, S (rs334)], alpha thalassaemia 3.

LLIN Evaluation in Uganda Project (LLINEUP): factors associated with childhood parasitaemia and anaemia 3 years after a national long-lasting insecticidal net distribution campaign: a cross-sectional survey.

Background: Recent reductions in malaria burden have been attributed largely to long-lasting insecticidal nets (LLINs). In March-June 2017, approximately 3 years after a national LLIN distribution campaign, a cross-sectional community survey was conducted to investigate factors associated with malaria parasitaemia and anaemia, in advance of Uganda's 2017-2018 LLIN campaign.

Methods: Households from 104 clusters in 48 districts were randomly selected using two-staged cluster sampling; 50 households were enrolled per cluster.

LLIN Evaluation in Uganda Project (LLINEUP): a cross-sectional survey of species diversity and insecticide resistance in 48 districts of Uganda.

Background: Long-lasting insecticidal nets (LLINs) are the principal tool for malaria control in Africa and are presently treated with a single class of insecticide; however, increasing levels of insecticide resistance threaten their success. In response to this threat nets have been developed that incorporate the synergist, piperonyl butoxide (PBO), which inhibits the activity of cytochrome P450s which is one main mechanisms of insecticide resistance, allowing resistance to pyrethroids to be reversed. However, data on the value and cost effectiveness of these nets is lacking.

LLIN Evaluation in Uganda Project (LLINEUP): factors associated with ownership and use of long-lasting insecticidal nets in Uganda: a cross-sectional survey of 48 districts.

Background: Long-lasting insecticidal nets (LLINs) are a key malaria control intervention. To investigate factors associated with ownership and use of LLINs in Uganda, a cross-sectional community survey was conducted in March-June 2017, approximately 3 years after a national Universal Coverage Campaign (UCC).

Methods: Households from 104 clusters (health sub-districts) in 48 districts were randomly selected using two-staged cluster sampling; 50 households were enrolled per cluster.

Association Between Recent Overnight Travel and Risk of Malaria: A Prospective Cohort Study at 3 Sites in Uganda.

Background: Human movement can undermine malaria control efforts. However, understanding of the association between travel and malaria infection in Africa is limited. We evaluated the association between recent overnight travel and malaria incidence in Uganda.

Rapid improvements to rural Ugandan housing and their association with malaria from intense to reduced transmission: a cohort study.

Background: Rapid population growth in Africa requires an urgent expansion and improvement of housing options. Improving housing presents a promising opportunity for malaria control by reducing indoor exposure to mosquitoes. We measured recent changes in house design in rural Uganda and evaluated their association with malaria in relation to a mass scale-up of control efforts.

Both inflammatory and regulatory cytokine responses to malaria are blunted with increasing age in highly exposed children.

Background: Young children are at greatest risk for malaria-associated morbidity and mortality. The immune response of young children differs in fundamental ways from that of adults, and these differences likely contribute to the increased susceptibility of children to severe malaria and to their delayed development of immunity. Elevated levels of pro-inflammatory cytokines and chemokines in the peripheral blood during acute infection contribute to the control of parasitaemia, but are also responsible for much of the immunopathology seen during symptomatic disease.

Vδ2+ T cell response to malaria correlates with protection from infection but is attenuated with repeated exposure.

Vδ2 γδ T cells are semi-innate T cells that expand markedly following P. falciparum (Pf) infection in naïve adults, but are lost and become dysfunctional among children repeatedly exposed to malaria. The role of these cells in mediating clinical immunity (i.

Measures of Malaria Burden after Long-Lasting Insecticidal Net Distribution and Indoor Residual Spraying at Three Sites in Uganda: A Prospective Observational Study.

Background: Long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) are the primary vector control interventions used to prevent malaria in Africa. Although both interventions are effective in some settings, high-quality evidence is rarely available to evaluate their effectiveness following deployment by a national malaria control program. In Uganda, we measured changes in key malaria indicators following universal LLIN distribution in three sites, with the addition of IRS at one of these sites.

Characterizing microscopic and submicroscopic malaria parasitaemia at three sites with varied transmission intensity in Uganda.

Background: Parasite prevalence is a key metric used to quantify the burden of malaria and assess the impact of control strategies. Most published estimates of parasite prevalence are based on microscopy and likely underestimate true prevalence.

Methods: Thick smear microscopy was performed in cohorts of children (aged 6 month to 10 years) and adults every 90 days over 2 years, at three sites of varying transmission intensity in Uganda.

Associations between urbanicity and malaria at local scales in Uganda.

Background: Sub-Saharan Africa is expected to show the greatest rates of urbanization over the next 50 years. Urbanization has shown a substantial impact in reducing malaria transmission due to multiple factors, including unfavourable habitats for Anopheles mosquitoes, generally healthier human populations, better access to healthcare, and higher housing standards. Statistical relationships have been explored at global and local scales, but generally only examining the effects of urbanization on single malaria metrics.

Decline of FoxP3+ Regulatory CD4 T Cells in Peripheral Blood of Children Heavily Exposed to Malaria.

FoxP3+ regulatory CD4 T cells (Tregs) help to maintain the delicate balance between pathogen-specific immunity and immune-mediated pathology. Prior studies suggest that Tregs are induced by P. falciparum both in vivo and in vitro; however, the factors influencing Treg homeostasis during acute and chronic infections, and their role in malaria immunopathogenesis, remain unclear.

Verbal Autopsy: Evaluation of Methods to Certify Causes of Death in Uganda.

To assess different methods for determining cause of death from verbal autopsy (VA) questionnaire data, the intra-rater reliability of Physician-Certified Verbal Autopsy (PCVA) and the accuracy of PCVA, expert-derived (non-hierarchical) and data-driven (hierarchal) algorithms were assessed for determining common causes of death in Ugandan children. A verbal autopsy validation study was conducted from 2008-2009 in three different sites in Uganda. The dataset included 104 neonatal deaths (0-27 days) and 615 childhood deaths (1-59 months) with the cause(s) of death classified by PCVA and physician review of hospital medical records (the 'reference standard').