In Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not known whether these deletions confer sufficient selective advantage to drive rapid population expansion. By studying blood samples from a cohort of 12,572 participants enroled in a prospective, cross-sectional survey along Ethiopia’s borders with Eritrea, Sudan and South Sudan using RDTs, PCR, an ultrasensitive bead-based immunoassay for antigen detection and next-generation sequencing, we estimate that histidine-rich protein 2-based RDTs would miss 9.7% (95% confidence interval 8.5–11.1) of P. falciparum malaria cases owing to pfhrp2 deletion. We applied a molecular inversion probe-targeted deep sequencing approach to identify distinct subtelomeric deletion patterns and well-established pfhrp3 deletions and to uncover recent expansion of a singular pfhrp2 deletion in all regions sampled. We propose a model in which pfhrp3 deletions have arisen independently multiple times, followed by strong positive selection for pfhrp2 deletion owing to RDT-based test-and-treatment. Existing diagnostic strategies need to be urgently reconsidered in Ethiopia, and improved surveillance for pfhrp2 deletion is needed throughout the Horn of Africa. A prospective, cross-sectional survey of 12,572 participants in Ethiopia reveals that malaria diagnostics miss almost 10% of cases owing to a gene deletion in Plasmodium falciparum that is under positive selection.

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Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia

Deletions in Plasmodium falciparum histidine rich protein 2(pfhrp2) gene threaten the usefulness of the most widely used HRP2-based malaria rapid diagnostic tests (mRDTs) that cross react with its structural homologue, PfHRP3. Parasites with deleted pfhrp2/3 genes remain undetected and untreated due to 'false-negative' RDT results. As Ethiopia recently launched malaria elimination by 2030 in certain selected areas, the availability of RDTs and the scale of their use have rapidly increased in recent years. Thus, it is important to explore the presence and prevalence of deletion in the target genes, pfhrp2 and pfhrp3. From a total of 189 febrile patients visited Adama Malaria Diagnostic centre, sixty-four microscopically-and polymerase chain reaction (PCR)-confirmed P. falciparum clinical isolates were used to determine the frequency of pfhrp2/3 gene deletions. Established PCR assays were applied to DNA extracted from blood spotted onto filter papers to amplify across pfhrp2/3 exons and flanking regions. However, analysis of deletions in pfhrp2, pfhrp3 and flanking genomic regions was successful for 50 of the samples. The pfhrp2 gene deletion was fixed in the population with all 50(100%) isolates presenting a deletion variant. This deletion extended downstream towards the Pf3D7 0831900 (MAL7PI.230) gene in 11/50 (22%) cases. In contrast, only 2/50 (4%) of samples had deletions for the Pf3D7 0831700 (MALPI.228) gene, upstream of pfhrp2. Similarly, the pfhrp3 gene was deleted in all isolates (100%), while 40% of the isolates had an extension of the deletion to the downstream flanking region that codes for Pf3D7 13272400 (MAL13PI.485).The pfhrp3 deletion also extended upstream to Pf3D7 081372100 (MAL13PI.475) region in 49/50 (95%) of the isolates, exhibiting complete absence of the locus. Although all samples showed deletions of pfhrp2 exon regions, amplification of an intron region was successful in five cases. Two different repeat motifs in the intron regions were observed in the samples tested. Pfhrp2/3 gene deletions are fixed in Ethiopia and this will likely reduce the effectiveness of PfHRP2-based mRDTs. It will be important to determine the sensitivity PfHRP 2/3-based RDTs in these populations and conduct a countrywide survey to determine the extent of these deletions and its effect on routine RDT-based malaria diagnosis.

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High prevalence and extended deletions in Plasmodium falciparum hrp2/3 genomic loci in Ethiopia

Background 
Ethiopia has shown incredible success in malaria morbidity, mortality, and control Community empowerment is a milestone to meet the ambitious plans of eliminating malaria by 2030


Objectives 
This study aimed to evaluate school-based malaria social behavior change communication (SBCC) in terms of community message exposure, acceptance, knowledge, and practices


Methods 
A community-based pre-posttest study was conducted in five districts of the Jimma Zone, Ethiopia 762 and 759 households were sampled for baseline and end-line, respectively The intervention engaged students from primary schools on participatory peer education within small groups, followed by exposing parents with malaria messages aimed to influencing ideation and preventive practices The data were analyzed using Statistical Package for Social Sciences (SPSS) version 200 Proportion/mean differences were computed to compare both surveys on exposure, knowledge, perceptions, and practices at p <005 Finally, a regression analysis was conducted between key changes and school-based exposure


Results 
The study revealed a sharp increase in exposure to malaria messages with effect size (ES) of 657%, p <0001 School specific exposure has grown to 578% (ES = 445%) Comprehensive knowledge about malaria increased to 391% (ES = 148%) Identifying mosquito bites as a cause of malaria was increased by ES = 208% A slight reduction in risk perception (ES = 33%) and attitude (ES = 38%) and a higher rise in self-efficacy (ES = 85%) were observed Community message acceptance in favor of malaria danger control was significantly improved by 10% ie an increase in rational decision making to uptake preventive practices Consistently, insecticide-treated nets (ITNs) usage was improved to 630% (ES = 258%) Giving priority to use ITNs for under five years old children and pregnant women grew by 163% and 248%, respectively Significant improvements were observed in treatment-seeking for fever (ES = 163%) and early treatment-seeking (ES = 155%) Not painting or plastering walls 6 months within spraying changed by ES = 61% No significant change was observed in drug adherence The school-based content intensity of exposure had effects on comprehensive knowledge, message acceptance, and ITN utilization


Conclusions 
Engaging school-aged children effectively advances community exposure, perception, and behaviors We recommend the inclusion of school-based SBCC in the national malaria control programs

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School-based social and behavior change communication (SBCC) advances community exposure to malaria messages, acceptance, and preventive practices in Ethiopia: A pre-posttest study

Background. Malaria is a severe parasitic disease that can progress to complications of the nervous system, respiratory distress, renal problems, metabolic acidosis, and hypoglycemia which can result in death in case of delay or absence of appropriate treatment. Even though health service facilities and vector control strategy in the community are implemented as control measures, variations in temperature and rainfall that can affect the life cycle of parasite are among the factors of malaria prevalence over the years. The aim of this trend analysis was to assess the prevalence and the impact of malaria over the seasons and years. Methods. A cross-sectional study using retrospective information was conducted at two health centers Gorgora and Chuahit in Dembia district. The data was collected from lab logbooks routinely diagnosed and registered for seven years. A systematic sampling technique was used by taking patient results from lab logbooks during the first ten days of every month. Data were entered directly into the EpiData Entry software version 3.1 and analysed with the SPSS software version 20. Moreover, a chi-square test with a level of significance set at less than 5% was used. Results. From a total of 11,879 clients that participated, 56.6% were males. The overall malaria prevalence in the last seven years was 21.8%, and the dominant parasite was P. falciparum which accounted for 15.6% of the participants which was threefold higher than P. vivax in the seven-year trend. Moreover, at Gorgora health center, the prevalence which was 15% at the beginning of the study (2012) rose to 33.9% and 30.5% in 2017 and 2018, respectively. In the analysis of the seven years, October and September in which the prevalence of malaria was 32.6% and 27.2%, respectively, constituted the peak months. High malaria prevalence was observed in autumn (September to November) season, and the least was observed in spring (March to May) with the prevalence of (17.8%) ( ). Malaria attack showed significant variability among different age groups, and the age group 15-29 and males were the most affected ( ). Conclusion. In this study, malaria transmission remained high, which affected males more than females. Thus, appropriate season-based bed net use, health education, immediate patient treatment, and stagnant water drainage methods are needed to alleviate the problem.

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A 7-Year Trend of Malaria at Primary Health Facilities in Northwest Ethiopia.

Ethiopia has made a significant progress of malaria control. Currently, the country has adopted and is implementing the World Health Organization very ambitious, but achievable, malaria elimination plan through extensive efforts. The regular evaluation of its performance is vital for plausible improvement. Thus, the aim of this study was to determine the trends of malaria infection in Boricha district, Southern Ethiopia. A retrospective study was conducted in all health facilities of the district. All malaria cases registered during 2010 to 2017 were reviewed to determine the trends of malaria morbidity. EpiData 3.1 was used for data entry and data were analysed using SPSS version 20.0. A total of 135,607 malaria suspects were diagnosed using microscopy and rapid diagnostic test over the last 8 years, of which 29,554 (21.8%) were confirmed positive cases. Plasmodium falciparum, Plasmodium vivax and mixed infections (both species) accounted for 56.3%, 38.4% and 5.2% of cases, respectively. Except in 2013 and 2014, Plasmodium falciparum was the dominant species over P. vivax. Of the total confirmed cases 51.6% were adults (≥ 15 years) followed by 24.5% of 5–14 years, and 23.9% of under 5 years. In general, malaria morbidity was significantly reduced over the last 8 years. The positivity rate declined from 54.6% to 5% during 2010 to 2017, and the case incidence rate per 1000 population at risk also declined from 18.9 to 2.2 during the same period. Malaria was reported in all months of the year, with peaks in November, followed by September and July. Malaria transmission has strong association with season (x2 = 303.955, df = 22, p < 0.0001). In general, a significant reduction of malaria morbidity was observed over the past 8 years. However, further investigation using advanced diagnostic tools is vital to determine the level of sub-microscopic infections to guide the elimination plan. In addition, eco-epidemiological analysis at fine-scale level is essential to devise area-specific interventions.

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Analysis of trends of malaria from 2010 to 2017 in Boricha District, Southern Ethiopia

Ethiopia is one of the African countries where Plasmodium falciparum and P. vivax co-exist. Monitoring and evaluation of current malaria transmission status is an important component of malaria control as it is a measure of the success of ongoing interventions and guides the planning of future control and elimination efforts. We evaluated changes in malaria control policy in Ethiopia, and reviewed dynamics of country-wide confirmed and clinical malaria cases by Plasmodium species and reported deaths for all ages and less than five years from 2001 to 2016. Districts level annual parasite incidence was analysed to characterize the malaria transmission stratification as implemented by the Ministry of Health. We found that Ethiopia has experienced major changes from 2003 to 2005 and subsequent adjustment in malaria diagnosis, treatment and vector control policy. Malaria interventions have been intensified represented by the increased insecticide treated net (ITN) and indoor residual spraying (IRS) coverage, improved health services and improved malaria diagnosis. However, countrywide ITN and IRS coverages were low, with 64% ITN coverage in 2016 and IRS coverage of 92.5% in 2016 and only implemented in epidemic-prone areas of > 2500 m elevation. Clinical malaria incidence rate dropped from an average of 43.1 cases per 1000 population annually between 2001 and 2010 to 29.0 cases per 1000 population annually between 2011 and 2016. Malaria deaths decreased from 2.1 deaths per 100 000 people annually between 2001 and 2010 to 1.1 deaths per 100 000 people annually between 2011 to 2016. There was shrinkage in the malaria transmission map and high transmission is limited mainly to the western international border area. Proportion of P. falciparum malaria remained nearly unchanged from 2000 to 2016 indicating further efforts are needed to suppress transmission. Malaria morbidity and mortality have been significantly reduced in Ethiopia since 2001, however, malaria case incidence is still high, and there were major gaps between ITN ownership and compliance in malarious areas. Additional efforts are needed to target the high transmission area of western Ethiopia to sustain the achievements made to date.

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Gezahegn Tesfaye

Papers

Malaria epidemiology and interventions in Ethiopia from 2001 to 2016.