Reanalysis of the Maltrials study

Our malaria prevention trial in Zeway was recently reanalysed. When analysing the trial results, we particularly questioned why the entomological data showed an effect of our interventions while the randomised cluster trial was negative.

In the last year, we have tried several new reanalysis methods, and we believe we had a negative trial because we needed to account for unequal community levels. In the future, we should pay much more attention to multi-level data structures.

As you may read from the paper, we postulate that visible and hidden layers could affect the analysis of such community studies. Thus, we are currently working with people familiar with remote sensing to evaluate if the distribution of, for example, maise fields plays an essential role in the variation of malaria in communities. In addition, we are trying to map the distribution of small and temporary ponds often seen as breeding sites for Anopheles arabiensis. We’re trying to use remote sensing by downloading high-resolution satellite data for our Hawassa and Arba Minch studies.

Is it time to recruit new students, master’s or PhD, with a keen interest and relevant educational background to do work on the interdisciplinary aspects of epidemiology, remote sensing and GIS?

You can read our paper by following this link,  where you will find related research papers.

South Ethiopia Network of Universities in Public Health II (SENUPH II)

The SENUPH II project represents a network of three universities in southern Ethiopia as well as the University of Bergen. The focus is on public health. Based on history of 20-year collaboration, we aim to strengthen the existing collaboration so to enhance efforts to improve capacity building, research, building independent senior researchers, and collaborate with the Ministry of Health with the relevant health information to improve the health of peoples in southern Ethiopia.

Project’s particular importance

Even if there has been a substantial economic growth in Ethiopia, the country remains among the 20 poorest countries. The population is in a transition with declining fertility, increasing life expectancy, heavy burdens of poverty-related diseases and increasing load of non-communicable diseases. Thus, the country needs evidence-based healthcare to improve health policy and improve the health of the population.

This project focuses on health challenges and priority setting. We believe universities in southern Ethiopia, can produce relevant information for policymakers to enhance public health work. By focusing on infectious diseases, malnutrition and the emerging burden of non-communicable diseases, we aim to build capacity in higher education both at universities and at the Ministry of health.

By the end of the project and through building strong research groups, we expect to have nine independent researchers capable of research leadership, supervising future PhD students, mentoring post docs, that further can develop their institutions when this project ends. Furthermore, we expect to have strengthened two PhD programs that would be sustainable in an Ethiopian context.

Building on a previous joint PhD degree programme between Hawassa University and the University of Bergen, and strengthening research at Dilla and Arba Minch University, we plan through PhD and post doc research, linked to training at the master’s level, strengthen the ownership, capability, and sustainability of the universities and of the Ministry of health to carry out evidence-based healthcare. The teaching, research, and implementation work will be interdisciplinary and integrated and involve disciplines such as epidemiology, medicine, priority setting and health economics, household economy, essential laboratory disciplines for emerging and existing epidemics.

Project goals

Through this six-year project, we aim to strengthen the institutional capacity for teaching, supervision and research by developing teams of researchers consisting of both senior (post docs) and junior researchers (PhD students and PhD holders) and thereby obtaining a critical mass needed for future sustainability of the institution. This will also focus on enhancing leadership capability of researchers so that they become independent researchers.

We shall strengthen research groups on thematic areas such as communicable diseases (malaria, emerging and re-emerging infections, and tuberculosis), nutrition, and priority setting on non-communicable diseases and health economics.

Relevant SDGs in the project

This project will deal with several of the sustainable development goals. The main goal is good health and well-being (SDG3). However, a large proportion of the efforts will be to reduce hunger in an area where chronic malnutrition is highly prevalent (SDG2). Our program will be based on quality teaching (DG4), and gender equality (SDG5).

Partner institutions

In Ethiopia, Hawassa University, Arba Minch University, and Dilla University, and the University of Bergen

New and important research from Arba Minch University

Arba Minch University has recently published three important papers. This work comes from the resaearch group on malaria and leishmaniasis. You will find the references with links to fulltext papers below:

Mekuriaw W, Balkew M, Messenger LA, Yewhalaw D, Woyessa A, Massebo F. The effect of ivermectin® on fertility, fecundity and mortality of Anopheles arabiensis fed on treated men in Ethiopia. Malaria Journal. 2019;18(1).

Pareyn M, Van den Bosch E, Girma N, van Houtte N, Van Dongen S, Van der Auwera G, et al. Ecology and seasonality of sandflies and potential reservoirs of cutaneous leishmaniasis in Ochollo, a hotspot in southern Ethiopia. PLoS Negl Trop Dis. 2019;13(8):e0007667

Pareyn M, Kochora A, Van Rooy L, Eligo N, Vanden Broecke B, Girma N, et al. Feeding behavior and activity of Phlebotomus pedifer and potential reservoir hosts of Leishmania aethiopica in southwestern Ethiopia. PLoS Negl Trop Dis. 2020;14(3):e0007947.

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

Solomon T, Loha E, Deressa W, Gari T, Lindtjørn B (2019) Spatiotemporal clustering of malaria in southern-central Ethiopia: A community-based cohort study. PLoS ONE 14(9): e0222986. https://doi.org/10.1371/journal.pone.0222986

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.

 

Bed nets, indoor spraying and malaria mosquitoes

Kenea O, Balkew M, Tekie H, Deressa W, Loha E, Lindtjørn B, et al. Impact of combining indoor residual spraying and long-lasting insecticidal nets on Anopheles arabiensis in Ethiopia: results from a cluster randomized controlled trial. Malaria Journal. 2019;18(1):182.

Background Indoor residual house spraying (IRS) and long-lasting insecticidal nets (LLINs) are the key front-line malaria vector interventions against Anopheles arabiensis, the sole primary malaria vector in Ethiopia. Universal coverage of both interventions has been promoted and there is a growing demand in combinations of interventions for malaria control and elimination. This study compared the impact on entomological outcomes of combining IRS and LLINs with either intervention alone in Adami Tullu district, south-central Ethiopia. The epidemiological outcomes were recently published on a separate paper.

Methods This factorial, cluster-randomized, controlled trial randomized villages to four study arms: IRS + LLIN, IRS, LLIN, and control. LLINs (PermaNet 2.0) were provided free of charge. IRS with propoxur was applied before the main malaria transmission season in 2014, 2015 and 2016. Adult mosquitoes were collected in randomly selected villages in each arm using CDC light trap catch (LTC) set close to a sleeping person, pyrethrum spray catch (PSC), and artificial pit shelter (PIT), for measuring mosquito host-seeking density (HSD), indoor resting density (IRD), and outdoor resting density (ORD), respectively. Human landing catch (HLC) was performed in a sub-set of villages to monitor An. arabiensis human biting rates (HBR). Mean vector densities and HBR were compared among study arms using incidence rate ratio (IRR) calculated by negative binomial regression.

Results  There were no significant differences in mean densities (HSD, IRD, ORD) and HBR of An. arabiensis between the IRS + LLIN arm and the IRS arm (p > 0.05). However, mean HSD, IRD, ORD, and HBR were significantly lower in the IRS + LLIN arm than in the LLIN alone arm (p < 0.05). All An. arabiensis tested for malaria infection were negative for Plasmodium species. For this reason, the entomological inoculation rate could not be determined.

Conclusions The IRS + LLIN were as effective as IRS alone in reducing densities and HBR of An. arabiensis. However, the effectiveness of the two interventions combined was higher than LLINs alone in reducing densities and HBR of the vector. Added impact of the combination intervention against malaria infectivity rates of An. arabiensis compared to either intervention alone remains unknown and warrants further research.

Trial registration PACTR201411000882128. Registered 8 September 2014, https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-016-1154-2

New PhD by Alemayehu Hailu: Economic evaluation of malaria prevention in Ethiopia

Thesis_UiB_Alemayehu_Hailu

Hailu A, D. Economic evaluation of malaria prevention in Ethiopia: Economic burden, equity, and cost-effectiveness analysis of malaria prevention in south-central Ethiopia [PhD]. Bergen: University of Bergen; 2018.

Summary
Background: Despite remarkable efforts in the global fight against malaria and achievements in the reduction of morbidity and mortality in the last decade, the disease remains to be a huge challenge to the health systems of malaria-endemic low-income countries in Africa and in all corners of the globe. Beyond the wide range of consensus on the disease burden and prioritization of malaria, the available evidence on the economic burden of malaria in Ethiopia is scanty. No clear evidence yet exists about the additional resources required for a combined implementation of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) with respect to the added protection afforded. In addition, little is known about the prevailing status of LLINs and IRS across different levels of wealth strata.

Objectives: The aims of this thesis were to estimate the economic burden of malaria; to evaluate the cost-effectiveness of a combined implementation malaria prevention interventions (LLINs and IRS); and analyse the distributional (equity) implications of the interventions in the Adami Tullu district, south-central Ethiopia.

Methods: Studies included in this thesis were conducted from 2014 – 2016 in the Adami Tullu district of Oromia Region, in south-central Ethiopia as part of and partly in conjunction with the MalTrials project. We conducted a cost of illness using 190 malaria patients in the first study. In Paper II, we carried out a combination of trial-based and literature-based cost-effectiveness analysis using Markov modelling. In the third study, using a cross-sectional data from 6069 households we did an inequality analysis of ownership of LLINs and IRS status. The principal component analysis technique was used for ranking households based on socioeconomic position. We measured the inequality in LLINs and IRS using concentration indices and concentration curve (Paper I&III).

Results: The median cost of malaria per episode to the household was USD 5.06 (IQR: 2.98 – 8.10) and the direct cost was significantly higher among the poor. The trial-based analysis had shown that the routine practice dominates both the combined intervention and singleton intervention while the literature-based analysis had indicated that combined intervention had an Incremental Cost-Effectiveness Ratio of USD 1403 per DALY averted. Immediately before we started the trial, the LLIN ownership was 11.6% and IRS coverage was 72.5%. We found a concentration index of 0.0627 for LLINs and – 0.0383 for the IRS. Inequality in LLIN ownership was mainly associated with a variability in a housing situation, the size of the household, and access to mass media and telecommunication service.

Conclusions: The economic burden of malaria to the rural households in Ethiopia is huge—mainly to the poor. Based on the trial-based cost-effectiveness analysis, we conclude that the combination of LLINs and IRS is not likely to be a cost-effective option compared with singleton intervention. However, based on the literature-based analysis, the combined intervention had potential to be a cost-effective alternative at 3 times GDP per capita per DALY averted. Furthermore, the ownership of LLIN was very low and significantly pro-rich, while IRS status was equitable across socioeconomic strata.

Taye Gari’s PhD thesis: Malaria, anaemia and undernutrition in Ethiopia

Taye Gari. Malaria, anaemia and undernutrition in a drought-affected area of the Rift Valley of Ethiopia: Experiences from a trial to prevent malaria.  PhD. University of Bergen, 2018. Bergen

Summary of PhD thesis

Background: In Ethiopia, malaria, anaemia and undernutrition are common childhood health problems. The country is planning to reduce these conditions to a level where they are not a public health problem. Meanwhile, for the success of this aim, a description of the occurrence and interaction of malaria, anaemia and undernutrition could help contribute to design tailored, efficient and effective control strategies. This study was done in the context of malaria prevention trial, which aimed to measure the effect of combining long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) in reducing the malaria incidence compared to LLINs or IRS alone. The study area was affected by a serious drought and famine during the first year of the study.

Objectives: The overall aim of this thesis is to improve our understanding of the effect of malaria prevention on anaemia, and to assess the association between malaria, anaemia and undernutrition among children in a drought-affected area in south-central, Ethiopia.

Methods: A cohort of 5309 residents was followed-up for 16 weeks to measure the variations in malaria incidence among villages (Paper I), and the results were used as a baseline to calculate the sample size needed for the trial. We followed a cohort of children aged 6 to 59 months for one year to describe anaemia and changes in haemoglobin (Hb) concentration (Paper II). A cohort of 4468 children was followed-up for 89 weeks to measure the relationship between malaria and undernutrition (Paper III). Weekly home visits and patient self-referral were also used to identify malaria cases. We conducted Hb concentration (once a year) and anthropometry (twice a year) surveys.

Results: In Paper I, we observed a variation in malaria incidence among villages. On the other hand, the insecticide-treated nets ownership was low (27%), with the distance from the lake or river and younger age being the main risk factors for malaria. The findings of this study were used as a baseline to calculate the sample size for the trial. In Paper II, despite the malaria prevention effort in the community, we observed an unexpected increase in anaemia prevalence over the period of a year, which could be due to the drought and famine that affected the area. A higher incidence of anaemia was observed among children with stunting, malaria infection, young age and in poor families. However, no significant difference in anaemia prevalence was observed among the different trial arms (LLIN+IRS, LLINs alone, IRS alone and routine arm). In Paper III, malaria infection was a risk factor for stunting and wasting, although undernutrition was not a risk for malaria infection. Furthermore, an increase in the prevalence of stunting, but no significant change in a prevalence of wasting was observed over time.

Conclusions: We showed a large variation in malaria incidence among villages. Conducting trials in a drought-prone area may bring an unexpected challenge. We observed an unexpected increase in anaemia prevalence over a year. There was no significant difference in anaemia prevalence among the trial arms. Moreover, a close follow-up of the nutritional status of children with malaria infection may be needed. There could hence be a need to prioritize villages nearer to the main mosquito breeding sites for malaria control.

Trial registration: PACTR 201411000882128 (8 September, 2014)

The Thesis can be downloaded here

Malaria, anaemia and undernutrition

On Friday June 22, 2018 Taye Gari Anaya will defend his PhD thesis at the University of Bergen. 

The title of his thesis is: “Malaria, anaemia and undernutrition in a drought-affected area of the Rift Valley of Ethiopia: Experiences from a trial to prevent malaria”.

Malaria, anaemia and malnutrition are interconnected, and often coexist in prevalent areas such as in sub-Saharan Africa, including Ethiopia. Although individuals in all ages of life are affected by these conditions, children under the age of 5 represent the most vulnerable group. Ethiopia is planning to reduce these conditions to a level where they are not public health problems Meanwhile, for the success of this aim, a description of the occurrence and interaction of malaria, anaemia and undernutrition could help to design tailored, efficient and effective control strategies.  

This thesis measures the effect of malaria prevention on anaemia reduction, and assesses the association between malaria, anaemia and undernutrition among a cohort of children aged 6 to 59 months old followed in a drought-affected rural area in south-central, Ethiopia.

The study showed a large variation in malaria incidence among villages in the same district. Despite community wide malaria prevention effort, an unexpected increase in anaemia prevalence was observed over a year. Malaria infection was a risk factor for undernutrition, although undernutrition was not a risk for malaria infection. There could be a need to prioritise villages nearer to the main mosquito breeding sites for malaria control. Moreover, a close follow-up of the nutritional status of children with malaria infection may be needed. 

Biographical

Taye Gari Ayana is from Hawassa in south Ethiopia. He completed Master degree in Public Health from Addis Ababa University in Ethiopia. From 2013 he has been affiliated with the Centre for International Health as a PhD candidate. Now he is a lecturer at the School of Public Health, at Hawassa University in Ethiopia. His supervisors were Professor Bernt Lindtjørn, Dr Eskindir Loha and Dr Wakgari Deressa. 

Improved housing reduces malaria

Getawen SK, Ashine T, Massebo F, Woldeyes D, Lindtjorn B. Exploring the impact of house screening intervention on entomological indices and incidence of malaria in Arba Minch town, southwest Ethiopia: A randomized control trial. Acta Trop. 2018;181:84-94. Epub 2018/02/17. doi: 10.1016/j.actatropica.2018.02.009. PubMed PMID: 29452110

House is the major site for malaria infection where most human-vector contact takes place. Hence, improving housing might reduce the risk of malaria infection by limiting house entry of vectors. This study aimed to explore the impact of screening doors and windows with wire meshes on density and entomological inoculation rate (EIR) of malaria vector, and malaria incidence, and assess the acceptability, durability, and cost of the intervention. The susceptibility status of malaria vector was also assessed.

A two-arm randomized trial was done in Arba Minch Town, southwest Ethiopia. 92 houses were randomly included in the trial. The baseline entomological and malaria prevalence data were collected. The mosquito sampling was done twice per household per month by Centers for Diseases Control and Prevention (CDC) light traps for six months. The baseline prevalence of malaria was assessed by testing 396 (83% of the 447 study participants) household members in all the eligible houses. The 92 houses were then randomized into control and intervention groups using mosquito and malaria prevalence baseline data to make the two groups comparable except the intervention. Then, we put wire-mesh on doors and windows of 46 houses. Post-screening mosquito collection was done in each household twice per month for three months. Each household member was visited twice per month for six months to assess malaria episodes. The frequency of damage to different structure of screening was measured twice. In-depth interview was conducted with 24 purposely selected household heads from intervention group. Speciation of Anopheles mosquito was done by morphological key, and the circum-sporozoite proteins (CSPs) analysis was done using enzyme-linked immunosorbent assay. A generalized estimating equation with a negative binomial distribution was used to assess the impact of the intervention on the indoor density of vectors. Clinical malaria case data were analyzed using Poisson regression with generalized linear model.

Screening doors and windows reduced the indoor density of An. arabiensis by 48% (mean ratio of intervention to control = 0.85/1.65; 0.52) (P = .001). Plasmodium falciparum CSP rate was 1.6% (3/190) in the intervention houses, while it was 2.7% (10/372) in the control houses. The protective efficacy of screening intervention from CSP positive An. arabiensis was 41% (mean ratio of intervention to control = 1.6/2.7; 0.59), but was not statistically significant (P = .6). The EIR of An. arabiensis was 1.91 in the intervention group, whereas it was 6.45 in the control group. 477 participants were followed for clinical malaria (50.1% from intervention and 49.9% from the control group). Of 49 RDT positive cases, 45 were confirmed to be positive with microscopy. 80% (n = 36) cases were due to P. falciparum and the rest 20% (n = 9) were due to P. vivax. The incidence of P. falciparum in the intervention group was lower (IRR: 0.39, 95% CI: 0.2-0.80; P = .01) than in the control group. Using incidence of P. falciparum infection, the protective efficacy of intervention was 61% (95% CI: 18-83; P = .007). 97.9% of screened windows and 63.8% of screened doors were intact after eleven months of installation. Malaria mosquito was resistance (mortality rate of 75%) to the insecticide used for bed nets treatment. Almost all participants of intervention arm were willing to continue using screened doors and windows.

Screening doors and windows reduced the indoor exposure to malaria vectors. The intervention is effective, durable and well-accepted. Hence, the existing interventions can be supplemented with house screening intervention for further reduction and ultimately elimination of malaria by reducing insecticide pressure on malaria vectors. However, further research could be considered in broad setting on different housing improvement and in the way how to scale-up for wider community.

 

Intended and non-intended use of bed nets for malaria protection

Doda Z, Solomon T, Loha E, Gari T and Lindtjørn B. A qualitative study of use of long-lasting insecticidal nets (LLINs) for intended and unintended purposes in Adami Tullu, East Shewa Zone, Ethiopia. Malaria Journal 2018;17:69  https://doi.org/10.1186/s12936-018-2209-5

Abstract

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.

Keywords  LLINs Malaria; Intended uses; Misuses; Repurposed uses; Collateral benefits of LLINs