Bed nets for malaria prevention under field conditions in Ethiopia: : Durability, use, and impact on spatial variation of malaria

Background: Despite a remarkable achievement in reducing malaria and in scaling up vector control intervention using long-lasting insecticidal nets (LLINs) in the last 15 years, malaria remains a significant public health problem in Ethiopia. To maximize the benefit of LLINs for malaria reduction, LLINs should provide a serviceable life, and people at risk for malaria should use them. However, field studies show considerable variation in both LLIN serviceable life and utilization in different settings. Moreover, malaria transmission is highly heterogeneous in different geographic locations and over time due to variations in risk factors. To further reduce the malaria burden, it is important to understand the factors that affect malaria clustering. For example, at a micro-geographic scale, it is crucial to target interventions in so-called hotspots (areas with a higher proportion of malaria cases than the overall population). In Ethiopia, several studies have evaluated the spatiotemporal clustering of malaria; however, with the exception of a single study in a southern Ethiopian village with a high malaria infection rate, none quantified the impact of malaria control interventions on the observed clustering. Hence, spatial variation in malaria transmission according to different intervention types in areas with low malaria transmission is not yet fully understood. To fill this knowledge gap, we examined the impact of LLIN use, indoor residual spraying (IRS), and combined LLIN and IRS use on spatial clustering of malaria in settings with low malaria transmission. In summary, evaluating the lifespan of LLINs, the extent of LLIN utilization by people at risk of malaria infection and the impacts of LLIN use alone, IRS use alone or the combination of LLINs and IRS on spatial clustering of malaria, could aid in designing efficient and effective malaria control strategies. General objective: The overall aim of this study was to assess LLINs in real-life field conditions and their impact on spatial variation of malaria in an area targeted for a cluster- randomized controlled trial for malaria prevention in southern-central Ethiopia. The specific objectives: 1) To determine the durability of LLINs under field conditions in terms of attrition, physical integrity, functional survival and bio-efficacy; 2) to assess LLIN ownership and use over time and identify factors associated with LLIN use; 3) to assess malaria infection clusters in areas with LLIN use; and 4) to assess malaria infection clusters in relation to IRS alone or a combination of LLIN and IRS interventions. Methods: We followed up a cohort of 1,532 LLINs every six months from October 2014 to November 2016 to assess their attrition, physical integrity and functional survival under field conditions. In addition, 120 randomly selected LLINs were tested for bio-efficacy (Paper I). In Paper II, we followed a cohort of 17,142 individuals via weekly home visits for 121 weeks to document their LLIN use. We also conducted a survey at 110 weeks after LLIN distribution to determine LLIN ownership. In Paper III, we followed a cohort of 34,548 persons every week from October 2014 to January 2017 and used active and passive case detection mechanisms to identify clinical malaria episodes. A discrete Poisson model was used to identify high rates of spatial, temporal and spatiotemporal clustering of malaria using SaTScan software v9.4.2 (Paper III). Results: In Paper I, we observed high attrition and low functional survival of LLINs in the study period. LLIN attrition was mainly due to disposal. The median functional survival time of the LLINs was only 12 months. The PermaNet ® 2.0 LLIN met the criteria of effective bio-efficacy up to 24 months after distribution. In Paper II, we observed low LLIN ownership and use during the study period. After 110 weeks, only 8% of households owned at least one LLIN. The median proportion of LLIN use per individuals was only 14%. More frequent LLIN use was reported by older age groups, compared with children under five years old. Similarly, people residing in houses whose heads of household had better educations reported more frequent LLIN use, compared with those with higher rates of illiteracy. Having a family size of more than five persons was associated with less frequent use of LLINs, compared with smaller family sizes. In Paper III, we observed spatial, temporal and spatiotemporal clustering of malaria infections in the study area and period. The spatial clustering of malaria at the household level was detected in all study arms (LLIN + IRS, LLIN alone, IRS alone and routine arms) with no significant difference in the risk of clustering between the arms. The risk of malaria clustering was high among households located closer to potential vector breeding sites. Moreover, an overlap was observed between clusters with low rates of LLIN use and clusters with high rates of malaria infection. The risk of malaria infection among people living in clusters with low LLIN use was 2.20 times higher than for people living in areas outside of these clusters (adjusted hazard ratio = 2.20, 95% confidence interval (CI): 1.80–2.60). Conclusion: The bed nets given for malaria prevention did not last long and were utilized as expected under field conditions in southern-central Ethiopia. Therefore, strategies are needed to address these problems and maximize malaria control efforts. We demonstrated variations in the risk of malaria infection across micro-geographic areas. None of the malaria control interventions (LLIN alone, IRS alone or combined LLIN and IRS) affected the occurrence of spatial clustering of malaria. The risk of malaria clustering was high in areas nearer to potential malaria vector breeding sites and thus prioritizing malaria control intervention in these locations could optimize resources. However, locations with low rates of LLIN use also exhibited high rates of malaria infection. Reducing variations in LLIN use in different locations thus also could reduce the risk of infection. Trial registration: PACTR 201411000882128 (8 September 2014)Doktorgradsavhandlin

Older children are at increased risk of Plasmodium vivax in south-central Ethiopia: a cohort study

Background Better understanding of the distribution of Plasmodium vivax and its risk factors could be used to prevent and control malaria infection. Therefore, the aim of this study was to characterize the distribution and risk factors of P. vivax, and to compare them with Plasmodium falciparum occurrence in south-central Ethiopia. Methods A cohort of 34,548 individuals were followed for 121 weeks between 2014 and 2016 as part of larger cluster randomized controlled trial to evaluate the effect of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) on malaria prevention in Ethiopia. Weekly home visit (active search) and patient self- report to health post (passive search) between the weekly home visits were used to register malaria cases. A blood sample was collected by finger prick and malaria was diagnosed using rapid diagnostic test (RDT). Generalized estimating equation (GEE) Poisson model that accounts for repeated measure of malaria episodes was applied to assess the risk factors of P. vivax episode. Results The overall incidence rate of P. vivax was 7.4 episodes per 1000 person-years of observation. The study showed households closer to the lake Zeway and Bulbula river (potential mosquito breeding sites) were more at risk of P. vivax infection (incidence rate ratio (IRR): 1.33; 95% CI = 1.23–1.45). Furthermore, the age group under 5 years (IRR: 1.40, 95% CI = 1.10–1.79), the age group 5–14 years (IRR: 1.27, 95% CI = 1.03–1.57), households with less educated household head (IRR: 1.63, 95% CI = 1.10–2.44) and house roof made of thatch/leaf (IRR: 1.35, 95% CI = 1.11–1.65) were at higher risk for P. vivax. Similar explanatory variables such as distance from the breeding sites, age group (under 5 years but not 5–14 years old), educational status and type of housing were also found to be the predictors of P. falciparum incidence. Conclusion Households living closer to a mosquito breeding site, age group under 15 years, less educated household heads and thatch/leaf roof housing were the risk factor for P. vivax. The result of this study can be used for tailored interventions for malaria control and prevention by prioritizing those living close to potential mosquito breeding site, enhancing bed net use of children less than 15 years of age, and improving housing.publishedVersio

Malaria increased the risk of stunting and wasting among young children in Ethiopia: Results of a cohort study.

INTRODUCTION: Given the high prevalence of malnutrition in a malaria-endemic setting, improving nutritional status could serve as a tool to prevent malaria. However, the relationship between the two conditions remains unclear. Therefore, this study assessed the association between under-nutrition and malaria among a cohort of children aged 6 to 59 months old. METHODS: Two cohorts of children were followed for 89 weeks in a rural Rift Valley area of Ethiopia. In the first approach (malaria-malnutrition), a cohort of 2,330 non-stunted and 4,204 non-wasted children were included to assess under-nutrition (outcome) based on their previous malaria status (exposure). In the second approach (malnutrition-malaria), a cohort of 4,468 children were followed-up to measure malaria (outcome), taking under-nutrition as an exposure. A weekly home visit was carried out to identify malaria cases. Four anthropometry surveys were conducted, and generalized estimating equation (GEE) method was used to measure the association between undernutrition and malaria. RESULTS: The prevalence of stunting was 44.9% in December 2014, 51.5% in August 2015, 50.7% in December 2015 and 48.1% in August 2016. We observed 103 cases with 118 episodes of malaria, 684 new stunting and 239 new wasting cases. The incidence rate per 10,000 weeks of observation was 3.8 for malaria, 50.4 for stunting and 8.2 for wasting. Children with malaria infection, [Adjusted Odds Ratio (AOR) = 1.9; 95% Confidence Interval (CI), 1.2-2.9)] and younger age (AOR = 1.3; 95% CI, 1.1-1.5) were more likely to be stunted. Furthermore, children with malaria infection (AOR = 8.5; 95% CI, 5.0-14.5) and young age group (AOR = 1.6; 95% CI, 1.2-2.1) were more likely to be wasted. However, stunting and wasting were not risk factors of subsequent malaria illness. CONCLUSIONS: Malaria infection was a risk factor for stunting and wasting, but stunting or wasting was not associated with subsequent malaria illness. As our study shows that malaria is a risk factor for stunting and wasting, a close follow-up of the nutritional status of such children may be needed. TRIAL REGISTRATION: PACT R2014 11000 882128 (8 September 2014)

Spatiotemporal clustering of malaria in southern-central Ethiopia: A community-based cohort study.

INTRODUCTION: Understanding the spatiotemporal clustering of malaria transmission would help target interventions in settings of low malaria transmission. The aim of this study was to assess whether malaria infections were clustered in areas with long-lasting insecticidal nets (LLINs) alone, indoor residual spraying (IRS) alone, or a combination of LLINs and IRS interventions, and to determine the risk factors for the observed malaria clustering in southern-central Ethiopia. METHODS: A cohort of 34,548 individuals residing in 6,071 households was followed for 121 weeks, from October 2014 to January 2017. Both active and passive case detection mechanisms were used to identify clinical malaria episodes, and there were no geographic heterogeneity in data collection methods. Using SaTScan software v 9.4.4, a discrete Poisson model was used to identify high rates of spatial, temporal, and spatiotemporal malaria clustering. A multilevel logistic regression model was fitted to identify predictors of spatial malaria clustering. RESULTS: The overall incidence of malaria was 16.5 per 1,000 person-year observations. Spatial, temporal, and spatiotemporal clustering of malaria was detected in all types of malaria infection (P. falciparum, P. vivax, or mixed). Spatial clustering was identified in all study arms: for LLIN + IRS arm, a most likely cluster size of 169 cases in 305 households [relative risk (RR) = 4.54, P<0.001]; for LLIN alone arm a cluster size of 88 cases in 103 households (RR = 5.58, P<0.001); for IRS alone arm a cluster size of 58 cases in 50 households (RR = 7.15, P<0.001), and for control arm a cluster size of 147 cases in 377 households (RR = 2.78, P<0.001). Living 1 km closer to potential vector breeding sites increased the odds of being in spatial clusters by 41.32 fold (adjusted OR = 41.32, 95% CI = 3.79-138.89). CONCLUSIONS: The risk of malaria infection varied significantly between kebeles, within kebeles, and even among households in areas targeted for different types of malaria control interventions in low malaria transmission setting. The results of this study can be used in planning and implementation of malaria control strategies at micro-geographic scale. TRIAL REGISTRATION: PACT R2014 11000 882128 (8 September 2014)

Anaemia among children in a drought affected community in south-central Ethiopia.

INTRODUCTION: As part of a field trial (PACTR201411000882128) to provide evidence on the combined use of long-lasting insecticidal nets and indoor residual spray for malaria prevention, we measured haemoglobin values among children aged 6 to 59 months. The aim of this study was to estimate the prevalence of anaemia, and to determine the risk factors of anaemia and change in haemoglobin value in Adami Tullu district in south-central Ethiopia. METHODS: Repeated cross-sectional surveys among 2984 children in 2014 and 3128 children in 2015; and a cohort study (malaria as exposure and anaemia as outcome variable) were conducted. The study area faced severe drought and food shortages in 2015. Anaemia was diagnosed using HemoCue Hb 301, and children with haemoglobin <11 g/dl were classified as anaemic. Multilevel and Cox regression models were applied to assess predictors of anaemia. RESULTS: The prevalence of anaemia was 28.2% [95% Confidence Interval (CI), 26.6-29.8] in 2014 and increased to 36.8% (95% CI, 35.1-38.5) in 2015 (P<0.001). The incidence of anaemia was 30; (95% CI, 28-32) cases per 100 children years of observation. The risk of anaemia was high (adjusted Hazard Ratio = 10) among children with malaria. Children from poor families [Adjusted Odds Ratio (AOR); 1.3; 95% CI, 1.1-1.6)], stunted children (AOR 1.5; 95% CI; 1.2-1.8), and children aged less than 36 months (AOR; 2.0; 95% CI, 1.6-2.4) were at risk of anaemia compared to their counterparts. There was no significant difference in risk of anaemia among the trial arms. CONCLUSIONS: Young age, stunting, malaria and poverty were the main predictors of anaemia. An increase in the prevalence of anaemia was observed over a year, despite malaria prevention effort, which could be related to the drought and food shortage. Therefore, conducting trials in settings prone to drought and famine may bring unexpected challenges

A qualitative study of use of long-lasting insecticidal nets (LLINs) for intended and unintended purposes in Adami Tullu, East Shewa Zone, Ethiopia.

BACKGROUND: Malaria poses a significant public health threat globally, across Africa and in Ethiopia. The use of long-lasting insecticidal nets (LLINs) is currently a proven prevention mechanism. Evidence is building on what happens to LLINs following mass distribution campaigns, with mixed results from different studies, some reporting very low use for intended purposes, others an encouraging level of using for intended purposes. In Ethiopia, between 2005 and 2015, about 64 million LLINs were distributed through periodic mass campaigns with the aims to achieve 100% coverage and 80% utilization. However, studies from rural Ethiopia showed variable LLINs coverage and utilization rate. The MalTrial Project, a collaborative venture between Hawassa University, Ethiopia and NROAID, Norway, has started a trial project in 2014 in Adami Tullu District of central Ethiopia. Quantitative surveys have established evidence on LLINs ownership and utilization, but the behavioural, sociocultural and socioeconomic dynamics of why LLINs' use for intended purposes is low or why they are employed for other purposes remained elusive. The present qualitative study, building on the quantitative findings and framework, therefore, attempted to fill gaps in these areas using qualitative methods in selected localities of the district. METHODS: The study employed 7 focus groups, 16 individual interviews and observation to undertake data collection in January 2017. The data were analysed using NVivo Version 11 (QSR International) to transcribe, code and identify themes using thematic analysis approach. RESULTS: The study found out that certain households were more likely to use nets for intended needs in proper ways; a range of factors, notably socio-cultural and poverty, highly influence users' ideas about the right ways and decisions to use and care for the nets; knowledge gaps and wrong perception exist regarding the purposes and life cycle of the nets; LLINs are employed for repurposed uses once they are considered non-viable, old, or lose their physical integrity; existence of misuse was acknowledged and understood as wrong; and values about gender roles further shape uses, misuses and repurposed use of the nets. CONCLUSIONS: Behavioural, socio-cultural, economic and ecological conditions coupled with deficiencies in perceived bed net design and distribution policies; weak education, communication and social support structures were important in understanding and accounting for why a low level of intended use and a rampant misuse and repurposed use in Adami Tullu community of Ethiopia. A major nexus to address in order to improve intended use of LLINs lies, first and foremost, in economic poverty and socio-cultural factors that underlie much of the misuse and repurposed use of the nets

Low use of long-lasting insecticidal nets for malaria prevention in south-central Ethiopia: A community-based cohort study.

INTRODUCTION: A decline in malaria morbidity and mortality has been documented in Ethiopia since 2005 following a scale-up of the distribution of long-lasting insecticidal nets (LLINs). However, universal access to LLINs ownership and use has not yet been achieved. This study aimed to determine ownership and use of LLINs over time in south-central Ethiopia. METHODS: A cohort of 17,142 individuals residing in 3,006 households was followed-up from October 2014 to January 2017 (121 weeks). New PermaNet2.0 LLINs were given to households in October 2014. Once per week, the LLIN use status was documented for each individual. A survey was conducted after 110 weeks of LLIN distribution to determine LLIN ownership. A multilevel negative binomial regression model was fitted to identify significant predictors of LLIN use. RESULTS: At baseline, the LLIN ownership was 100%. After 110 weeks only 233 (8%) of the households owned at least one LLIN. The median proportion of LLIN use per individuals during the study period was only 14%. During the first year (week 1-52) the average LLIN use per individuals was 36% and during the second year (week 53-104) it was 4.6%. More frequent LLIN use was reported among age group [5-14 years (adjusted IRR = 1.13, 95% CI 1.04-1.22), 15-24 years (adjusted IRR = 1.33, 95% CI 1.23-1.45), ≥25 years (adjusted IRR = 1.99, 95% CI 1.83-2.17)] compared to <5 years, and household head educational status [read and write (adjusted IRR = 1.17, 95% CI 1.09-1.26), primary (adjusted IRR = 1.20, 95% CI 1.12-1.27), secondary or above (adjusted IRR = 1.20, 95% CI (1.11-1.30)] compared to illiterate. Having a family size of over five persons (adjusted IRR = 0.78, 95% CI 0.73-0.84) was associated with less frequent use of LLINs compared to a family size of ≤5 persons. CONCLUSIONS: The study showed a low LLIN ownership after 110 weeks and a low LLIN use during 121 weeks of follow-up, despite 100% LLIN coverage at baseline. The study highlights the need to design strategies to increase LLIN ownership and use for setting similar to those studied here

Whole-Genome Resequencing Reveals Selection Signatures of Abigar Cattle for Local Adaptation

Over time, indigenous cattle breeds have developed disease resistance, heat tolerance, and adaptability to harsh environments. Deciphering the genetic mechanisms underlying adaptive traits is crucial for their improvement and sustainable utilization. For the first time, we performed whole-genome sequencing to unveil the genomic diversity, population structure, and selection signatures of Abigar cattle living in a tropical environment. The population structure analysis revealed that Abigar cattle exhibit high nucleotide diversity and heterozygosity, with low runs of homozygosity and linkage disequilibrium, suggesting a genetic landscape less constrained by inbreeding and enriched by diversity. Using nucleotide diversity (Pi) and population differentiation (FST) selection scan methods, we identified 83 shared genes that are likely associated with tropical adaption. The functional annotation analysis revealed that some of these genes are potentially linked to heat tolerance (HOXC13, DNAJC18, and RXFP2), immune response (IRAK3, MZB1, and STING1), and oxidative stress response (SLC23A1). Given the wider spreading impacts of climate change on cattle production, understanding the genetic mechanisms of adaptation of local breeds becomes crucial to better respond to climate and environmental changes. In this context, our finding establishes a foundation for further research into the mechanisms underpinning cattle adaptation to tropical environments.</p

Bed nets used to protect against malaria do not last long in a semi-arid area of Ethiopia: a cohort study.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are a key tool for malaria prevention and control. Currently, the recommended serviceable life of an LLIN is 3 years under field conditions. However, field studies show considerable variation in LLIN lifespan, from less than 2 years to more than 4 years. This study aimed to determine the attrition, physical integrity, functional survival, and bio-efficacy of LLINs under field conditions in south-central Ethiopia. METHODS: In October 2014, 7740 LLINs (PermaNet® 2.0) were distributed to 3006 households. Among the distributed LLINs, a cohort study involving 1532 LLINs in 659 households was carried out from October 2014 to November 2016. Data were collected every 6 months by observation, and through interviews with the heads of households. The proportional hole index was used to categorize LLINs as either serviceable or torn. In addition, 120 randomly selected LLINs were tested for bio-efficacy. RESULTS: The overall attrition of LLINs was 96% (n = 993) during the study period. The nets' attrition was mainly due to disposal (64.2%; n = 638). The proportion of LLINs with a hole size 0.5 cm or larger was 79.5% after 24 months. The use of the net on the previous night and having a clean net were associated with a good physical integrity. However, living in a household more than 1 km away from the mosquitoes' breeding site was associated with poor physical integrity. By the 24th month, only 4% of the nets met the criteria for functional survival. The median functional survival time of the nets was 12 months. A longer functional survival was associated with having a clean net, and shorter survival was associated with living in a household more than 1 km away from the mosquitoes' breeding site. The PermaNet® 2.0 met the criteria of effective bio-efficacy up to month 24 after distribution. CONCLUSIONS: The study showed that the median serviceable life of LLINs is only 12 months. However, the bio-efficacy of the LLINs is acceptable for at least 24 months. Therefore, stronger and more efficient LLINs need to be developed for conditions similar to those studied here

Long-lasting insecticidal nets and indoor residual spraying may not be sufficient to eliminate malaria in a low malaria incidence area: results from a cluster randomized controlled trial in Ethiopia.

BACKGROUND: Conflicting results exist on the added benefit of combining long-lasting insecticidal nets (LLINs) with indoor residual spraying (IRS) to control malaria infection. The main study objective was to evaluate whether the combined use of LLINs and IRS with propoxur provides additional protection against Plasmodium falciparum and/or Plasmodium vivax among all age groups compared to LLINs or IRS alone. METHODS: This cluster-randomized, controlled trial was conducted in the Rift Valley area of Ethiopia from September 2014 to January 2017 (121 weeks); 44 villages were allocated to each of four study arms: LLIN + IRS, IRS, LLIN, and control. Each week, 6071 households with 34,548 persons were surveyed by active and passive case detection for clinical malaria. Primary endpoints were the incidence of clinical malaria and anaemia prevalence. RESULTS: During the study, 1183 malaria episodes were identified, of which 55.1% were P. falciparum and 25.3% were P. vivax, and 19.6% were mixed infections of P. falciparum and P. vivax. The overall malaria incidence was 16.5 per 1000 person-years of observation time (PYO), and similar in the four arms with 17.2 per 1000 PYO in the LLIN + IRS arm, 16.1 in LLIN, 17.0 in IRS, and 15.6 in the control arm. There was no significant difference in risk of anaemia among the trial arms. CONCLUSIONS: The clinical malaria incidence and anaemia prevalence were similar in the four study groups. In areas with low malaria incidence, using LLINs and IRS in combination or alone may not eliminate malaria. Complementary interventions that reduce residual malaria transmission should be explored in addition to LLINs and IRS to further reduce malaria transmission in such settings. Trial registration PACTR201411000882128 (08 September 2014)