The changing malaria trend and control efforts in Oromia Special zone, Amhara Regional State, North-East Ethiopia.

BACKGROUND: Countries in malaria endemic regions are determinedly making an effort to achieve the global malaria elimination goals. In Ethiopia, too, all concerned bodies have given attention to this mission as one of their priority areas so that malaria would be eradicated from the country. Despite the success stories from some areas in the country, however, malaria is still a major public health concern in most parts of Ethiopia. Therefore, this study is aimed at analysing the changing malaria trend and assessing the impact of malaria control efforts in one of the malaria endemic regions of Ethiopia. METHODS: Five years data on clinical malaria cases diagnosed and treated at all health facilities (including 28 Health Centres, 105 Health Posts and 2 Hospitals) in Oromia Special zone, Amhara Regional State, Ethiopia, were reviewed for the period from June 2014 to June 2019. Data on different interventional activities undertaken in the zone during the specified period were obtained from the Regional Health Bureau. RESULTS: The cumulative malaria positivity rate documented in the zone was 12.5% (n = 65,463/524,722). Plasmodium falciparum infection was the dominant malaria aetiology and accounted for 78.9% (n = 51,679). The age group with the highest malaria burden was found to be those aged above 15 years (54.14%, n = 35,443/65,463). The malaria trend showed a sharp decreasing pattern from 19.33% (in 2015) to 5.65% (in 2018), although insignificant increment was recorded in 2019 (8.53%). Distribution of long-lasting insecticidal nets (LLIN) and indoor residual spraying (IRS) were undertaken in the zone once a year only for two years, specifically in 2014 and 2017. In 2014, a single LLIN was distributed per head of households, which was not sufficient for a family size of more than one family member. Number of houses sprayed with indoor residual spray in 2014 and 2017 were 33,314 and 32,184 houses, respectively, leading to the assumption that, 151,444 (25.9%) and 141,641 (24.2%) population were protected in year 2014 and 2017, respectively. The analysis has shown that P. falciparum positivity rate was significantly decreased following the interventional activities by 3.3% (p = 0.009), but interventional efforts did not appear to have significant effect on vivax malaria, as positivity rate of this parasite increased by 1.49% (p = 0.0218). CONCLUSION: Malaria burden has shown a decreasing pattern in the study area, although the pattern was not consistent throughout all the years and across the districts in the study area. Therefore, unremitting surveillance along implementation of interventional efforts should be considered taking into account the unique features of Plasmodium species, population dynamics in the zone, seasonality, and malaria history at different districts of the zone should be in place to achieve the envisaged national malaria elimination goal by 2030.

In vivo efficacy of anti-malarial drugs against clinical Plasmodium vivax malaria in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Ethiopia is one of the few countries in Africa where Plasmodium vivax commonly co-exists with Plasmodium falciparum, and which accounts for ~ 40% of the total number of malaria infections in the country. Regardless of the growing evidence over many decades of decreasing sensitivity of this parasite to different anti-malarial drugs, there has been no comprehensive attempt made to systematically review and meta-analyse the efficacy of different anti-malarial drugs against P. vivax in the country. However, outlining the efficacy of available anti-malarial drugs against this parasite is essential to guide recommendations for the optimal therapeutic strategy to use in clinical practice. The aim of this study was to synthesize evidence on the efficacy of anti-malarial drugs against clinical P. vivax malaria in Ethiopia. METHODS: All potentially relevant, peer-reviewed articles accessible in PubMed, Scopus, Web of Science, and Clinical Trial.gov electronic databases were retrieved using a search strategy combining keywords and related database-specific subject terms. Randomized controlled trials (RCTs) and non-randomized trials aiming to investigate the efficacy of anti-malarial drugs against P. vivax were included in the review. Data were analysed using Review Manager Software. Cochrane Q (χ2) and the I2 tests were used to assess heterogeneity. The funnel plot and Egger's test were used to examine risk of publication bias. RESULTS: Out of 1294 identified citations, 14 articles that presented data on 29 treatment options were included in the analysis. These studies enrolled 2144 clinical vivax malaria patients. The pooled estimate of in vivo efficacy of anti-malarial drugs against vivax malaria in Ethiopia was 97.91% (95% CI: 97.29-98.52%), with significant heterogeneity (I2 = 86%, p < 0.0001) and publication bias (Egger's test = -12.86, p < 0.001). Different anti-malarial drugs showed varied efficacies against vivax malaria. The duration of follow-up significantly affected the calculated efficacy of any given anti-malarial drug, with longer duration of the follow-up (42 days) associated with significantly lower efficacy than efficacy reported on day 28. Also, pooled PCR-corrected efficacy and efficacy estimated from altitudinally lower transmission settings were significantly higher than PCR-uncorrected efficacy that estimated for moderate transmission settings, respectively. CONCLUSION: The overall efficacy of anti-malarial drugs evaluated for the treatment of vivax malaria in Ethiopia was generally high, although there was wide-ranging degree of efficacy, which was affected by the treatment options, duration of follow-up, transmission intensity, and the confirmation procedures for recurrent parasitaemia. Regardless of evidence of sporadic efficacy reduction reported in the country, chloroquine (CQ), the first-line regimen in Ethiopia, remained highly efficacious, supporting its continuous utilization for confirmed P. vivax mono-infections. The addition of primaquine (PQ) to CQ is recommended, as this is the only approved way to provide radical cure, and thus ensure sustained efficacy and longer protection against P. vivax. Continuous surveillance of the efficacy of anti-malarial drugs and clinical trials to allow robust conclusions remains necessary to proactively act against possible emergence and spread of drug-resistant P. vivax in Ethiopia.

A community-based cross-sectional study of the epidemiology of onchocerciasis in unmapped villages for community directed treatment with ivermectin in Jimma Zone, southwestern Ethiopia.

BACKGROUND: Human onchocerciasis is a neglected tropical parasitic disease caused by Onchocerca volvulus (O. volvulus) that may result in devastating skin and eye morbidity. Even though the disease is targeted for elimination, there was little or no information on the level of onchocerciasis endemicity for implementation of community directed treatment with ivermectin (CDTI) in the current study area. Thus, this study aimed at investigating the epidemiology of onchocerciasis and the level of awareness towards the disease among communities living close to CDTI area, Jimma Zone, southwestern Ethiopia. METHODS: A community based cross-sectional study was conducted from April 23 to May 22, 2012. Data on socio-demographic characteristics, knowledge, attitude and practice towards onchocerciasis were collected using semi-structured questionnaires. Clinical examination was undertaken for onchocercal skin diseases by experienced health professionals. Moreover, two skin snip samples were collected from the right and left gluteal folds. Study participants found positive for O. volvulus infection during the study were treated individually with standard dose of ivermectin as per WHO guideline. RESULTS: The overall prevalence of O. volvulus infection was 22.5 % while the prevalence of onchocercal skin diseases was 29.8 %. The community microfilarial (mf) load was 5.70 mf per skin snip. Age, sex, educational status, occupation and duration of stay in the villages showed significant association with onchocerciasis (P < 0.05). But sex (OR = 0.565, 95 % CI = 0.335, 0.952), educational status (OR = 0.545, 95 % CI = 0.310, 0.958) and duration of stay in the village (OR = 5.933, 95 % CI = 1.017, 34.626) were the independent predictors for O. volvulus infection. Three hundred eighty eight (88.2 %) of the study participants reported that they didn't know about onchocerciasis. CONCLUSIONS: There was moderate prevalence of onchocercal infection and onchocercial skin diseases (OSD) in the study area. Result of this study may suggest that the endemicity level of onchocerciasis in the study area was mesoendemic. Hence, intervention using ivermectin treatment should be implemented to reduce the burden of onchocerciasis. Since the majorities of the population had poor knowledge, attitude and practice towards onchocerciasis, inclusion of health education in the intervention package is crucial.

Plasmodium vivax epidemiology in Ethiopia 2000-2020: A systematic review and meta-analysis.

BACKGROUND: Ethiopia is one of the scarce African countries where Plasmodium vivax and P. falciparum co-exist. There has been no attempt to derive a robust prevalence estimate of P. vivax in the country although a clear understanding of the epidemiology of this parasite is essential for informed decisions. This systematic review and meta-analysis, therefore, is aimed to synthesize the available evidences on the distribution of P. vivax infection by different locations/regions, study years, eco-epidemiological zones, and study settings in Ethiopia. METHODS: This study was conducted in accordance with Preferred Reposting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Studies conducted and published over the last two decades (2000 to 2020) that reported an estimate of P. vivax prevalence in Ethiopia were included. The Cochrane Q (χ2) and the I2 tests were used to assess heterogeneity, and the funnel plot and Egger's test were used to examine publication bias. A p-value of the χ2 test <0.05 and an I2 value >75% were considered presence of considerable heterogeneity. Random effect models were used to obtain pooled estimate of P. vivax infection prevalence. This study is registered with PROSPERO (International Prospective Register of Systematic Reviews): ID CRD42020201761. RESULTS: We screened 4,932 records and included 79 studies that enrolled 1,676,659 confirmed malaria cases, from which 548,214 (32.69%) were P. vivax infections and 1,116,581 (66.59%) were due to P. falciparum. The rest were due to mixed infections. The pooled estimate of P. vivax prevalence rate was 8.93% (95% CI: 7.98-9.88%) with significant heterogeneity (I2 = 100%, p<0.0001). Regional differences showed significant effects (p<0.0001, and I2 = 99.4%) on the pooled prevalence of P. vivax, while study years (before and after the scaling up of interventional activities) did not show significant differences (p = 0.9, I2 = 0%). Eco-epidemiological zones considered in the analysis did show a significant statistical effect (p<0.001, I2 = 78.5%) on the overall pooled estimate prevalence. Also, the study setting showed significant differences (p = 0.001, and I2 = 90.3%) on the overall prevalence, where significant reduction of P. vivax prevalence (4.67%, 95%CI: 1.41-7.93%, p<0.0001) was observed in studies conducted at the community level. The studies included in the review demonstrated lack of publication bias qualitatively (symmetrical funnel plot) and quantitatively [Egger's test (coefficient) = -2.97, 95% CI: -15.06-9.13, p = 0.62]. CONCLUSION: The estimated prevalence of P. vivax malaria in Ethiopia was 8.93% with P. vivax prevailing in the central west region of Ethiopia, but steadily extending to the western part of the country. Its distribution across the nation varies according to geographical location, study setting and study years.

Relationship between exposure to malaria and haemoglobin level of children 2-9 years old in low malaria transmission settings.

In the context of reduced transmission of malaria, it is essential to examine the association between exposure to malaria and haemoglobin level. This study measured the Haemoglobin level of children 2-9 years of age and examined its association with malariometric indices. A cross sectional study was conducted, during June 2016, on 763 children 2-9 years old, recruited from ten sites representing different malaria transmission settings in Ethiopia. Haemoglobin concentration was determined using HemoCue analyzer. Malariometric indices (splenomegaly rate, parasite rate and serological marker) were measured. The overall prevalence of anaemia was 17.3% (95% CI: 14.6-19.9) in the study population. Mild, moderate and severe anaemia accounted for 7.3%, 7.2% and 2.8% respectively. Of the children with anaemia (132), only 7 (5.3%) had malaria parasitaemia. The prevalence of malaria parasitaemia was 3.6% (2/56), 9.1% (5/55) and 0.0% (0/21) among children with mild, moderate and severe anaemia, respectively. Malaria reactive antibody and anaemia co-occurred in 3.13% (21/672) of the samples. Seroprevalence and parasitaemia did not have significant association with anaemia (p>0.05). However, splenomegaly was significantly associated with increased risk of anaemia (AOR=14.93; p=0.001). Anaemia was significantly higher among children 2-4 years old (22.2%), and children living in households without any insecticide treated bed net (34.0%). The prevalence of anaemia was lower by 55.0% among children living in households with at least one net (AOR=0.45, 95% CI: 0.21-0.96). Repeated exposure to malaria infections (seropositive) and parasitaemia was less likely to contribute to development of anaemia among children 2-9 years in this study setting. Thus, in low malaria endemic settings, anaemia prevention and control program required to reconsider the historical evidence that suggests malaria is one of the major risk factor for anaemia.

Mapping insecticide resistance and characterization of resistance mechanisms in Anopheles arabiensis (Diptera: Culicidae) in Ethiopia.

BACKGROUND: The emergence and spread of insecticide resistance in the major African malaria vectors Anopheles gambiae (s.s.) and An. arabiensis may compromise the current vector control interventions and threatens the global malaria control and elimination efforts. METHODS: Insecticide resistance was monitored in several study sites in Ethiopia from 2013 to 2015 using papers impregnated with discriminating concentrations of DDT, deltamethrin, bendiocarb, propoxur, malathion, fenitrothion and pirimiphos-methyl, following the WHO insecticide susceptibility test procedure. Mosquitoes sampled from different localities for WHO bioassay were morphologically identified as An. gambiae (s.l.) using standard taxonomic keys. Samples were identified to species using species-specific polymerase chain reaction (PCR) and screened for the presence of target site mutations L1014F, L1014S and N1575Y in the voltage gated sodium channel (VGSC) gene and G119S in the acethylcholinesterase (AChE) gene using allele-specific PCR. Biochemical assays were performed to assess elevated levels of acetylcholinesterases, carboxylcholinesterases, glutathione-S-transferases (GSTs) and cytochrome P450s monooxygenases in wild populations of An. arabiensis, compared to the fully susceptible Sekoru An. arabiensis laboratory strain. RESULTS: Populations of An. arabiensis were resistant to DDT and deltamethrin but were susceptible to fenitrothion in all the study sites. Reduced susceptibility to malathion, pirimiphos-methyl, propoxur and bendiocarb was observed in some of the study sites. Knockdown resistance (kdr L1014F) was detected in all mosquito populations with allele frequency ranging from 42 to 91%. Elevated levels of glutathione-S-transferases (GSTs) were detected in some of the mosquito populations. However, no elevated levels of monooxygenases and esterases were detected in any of the populations assessed. CONCLUSIONS: Anopheles arabiensis populations from all surveyed sites in Ethiopia exhibited resistance against DDT and pyrethroids. Moreover, some mosquito populations exhibited resistance to propoxur and possible resistance to bendiocarb. Target site mutation kdr L1014F was detected in all mosquito populations while elevated levels of glutathione-S-transferases (GSTs) was detected in some mosquito populations. The reduced susceptibility of An. arabiensis to propoxur and bendiocarb, which are currently used for indoor residual spraying (IRS) in Ethiopia, calls for continuous resistance monitoring, in order to plan and implement evidence based insecticide resistance management.

Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Halaba district, South Ethiopia.

BACKGROUND: Chloroquine is an anti-malarial drug being used to treat Plasmodium vivax malaria cases in Ethiopia. However, emergence of chloroquine resistant strains of the parasite has challenged the current efficacy of the drug. Therefore, the aim of this study was to assess the effectiveness of chloroquine against P. vivax strains in one of the malaria endemic areas of Ethiopia, namely Halaba district, located in South Nations and Nationalities Peoples Region (SNNPR) of South Ethiopia RESULTS: Among 87 malaria patients enrolled in the study, only 80 of them completed the 28-days follow-up. Seven of them dropped from the study for different reasons. Among those study participants that completed their follow-up, 69 were classified under the category of adequate clinical and parasitological response (ACPR). However, the remaining 11 cases were considered as under treatment failure mainly due to recurrence of parasitemia on day 7 (four patients), day 14 (six patients), and day 21 (one patient). The age of all cases of treatment failures was found to be less than 20 years. The load of parasitemia of patients with treatment failure on day of admission (4709.4/µl) was higher than day of recurrence (372.37/µl). Parasite reduction ratio (PRR) of treatment failure cases was 12.6/µl. CONCLUSION: This report revealed the rise in treatment failure (13% [95% CI = 0.074 - 0.217]) as compared to earlier reports from Ethiopia. It signals the spreading of chloroquine resistant P. vivax (CRPv) strains to malaria endemic areas of Ethiopia. It is recommended that all concerned bodies should act aggressively before further expansion of the current drug resistant malaria.