Insecticide Resistance in East Africa — History, Distribution and Drawbacks on Malaria Vectors and Disease Control

Malaria is a major contributor to the global disease burden and a significant impediment to socio-economic development in resource-poor countries. In contrast to improved trends of malaria morbidity and mortality in some parts of the world, malaria has remained a life threatening disease in many other regions including East Africa because of factors such as weak health systems, growing drug and insecticide resistance, ecological change, climate anomalies, socio-economic factors and changes in land use patterns. Ongoing malaria vector control strategies rely mainly on the use of indoor residual spraying (IRS) and insecticide treated nets (ITNs) which are the primary intervention strategies to reduce malaria burden. The current success in reducing malaria related morbidity and mortality has led to the optimism that elimination of the disease as a public health problem may be a realistic objective. Efforts during the last decades enabled access to ITNs in sub-Saharan Africa protecting millions of people at risk of malaria. The number of countries that employed IRS as a vector control strategy increased almost by two fold and the percentage of households owing at least one ITN in sub-Saharan Africa is estimated to increase from time to time. Currently, all ITNs are treated with pyrethroids while IRS depends on pyrethroids, DDT and recently on carbamates. Despite IRS and ITNs are known in reducing malaria incidence, insecticide resistance in malaria vectors threatens the success of malaria control program. Resistance to insecticides has occurred in most arthropod vectors with different mechanisms. If the current trends of increased insecticide resistance continue, it may jeopardise the efficacy of current vector control tools. Given the limited choice of available insecticides, i.e., only 12 insecticides belonging to 4 classes of insecticides (organochlorines, organophosphates, pyrethroids and carbamates), resistance to these insecticides has become a limiting factor for current efforts to sustain control. Currently, no other insecticide class with similar efficacy has been approved by WHOPES. The development of insecticide resistance in malaria vectors has been attributed to the prolonged use of insecticides for IRS and high coverage of ITNs/LLINs. The recent use of pyrethroids for indoor residual spraying is likely to have enhanced the selection pressure for insecticide resistance alleles among East African vector populations. Moreover, mosquitoes breeding in agricultural habitats are exposed to sub lethal doses of pesticides used in agriculture. Since currently recommended insecticides for IRS or ITNs were developed with similar active ingredients of pesticides used for agricultural pest control, their extensive and widespread use to boost agricultural productivity is believed to foster insecticide resistance in mosquito populations. There is strong evidence on the emergence of resistance to DDT and pyrethroids in the major malaria vectors in East Africa however, current information on resistance status of the malaria vectors in different areas of the sub-region is scarce. Genes conferring resistance to malaria vectors, including kdr, super kdr and acetylcholinesterase mutations and metabolic resistance are not mapped. The frequency and spatial distribution of East and West African kdr mutations and their association with the phenotypic resistance in East Africa is less understood. The bioassay results after WHO diagnostic tests in different East African malaria vector populations against insecticides used in public health is not well documented. In conclusion, planning and implementing insecticide resistance monitoring and management strategy should be part of the vector control program either for pre-emptive action without waiting for the development of resistance or to slowdown the spread of resistance in malaria vectors in the sub-region

Zooprophylaxis as a control strategy for malaria caused by the vector Anopheles arabiensis (Diptera: Culicidae) : a systematic review

Background: Zooprophylaxis is the use of wild or domestic animals, which are not the reservoir host of a given disease, to divert the blood-seeking malaria vectors from human hosts. In this paper, we systematically reviewed zooprophylaxis to assess its efficacy as a malaria control strategy and to evaluate the possible methods of its application. Methods: The electronic databases, PubMed Central®, Web of Science, Science direct, and African Journals Online were searched using the key terms: “zooprophylaxis” or “cattle and malaria”, and reports published between January 1995 and March 2016 were considered. Thirty-four reports on zooprophylaxis were retained for the systematic review. Results: It was determined that Anopheles arabiensis is an opportunistic feeder. It has a strong preference for cattle odour when compared to human odour, but feeds on both hosts. Its feeding behaviour depends on the available hosts, varying from endophilic and endophagic to exophilic and exophagic. There are three essential factors for zooprophylaxis to be effective in practice: a zoophilic and exophilic vector, habitat separation between human and host animal quarters, and augmenting zooprophylaxis with insecticide treatment of animals or co-intervention of long-lasting insecticide-treated nets and/or indoor residual spraying. Passive zooprophylaxis can be applied only in malaria vector control if cattle and human dwellings are separated in order to avoid the problem of zoopotentiation. Conclusions: The outcomes of using zooprophylaxis as a malaria control strategy varied across locations. It is therefore advised to conduct a site-specific evaluation of its effectiveness in vector control before implementing zooprophylaxis as the behaviour of Anopheles arabiensis mosquitoes varies across localities and circumstances

Bio-efficacy of selected long-lasting insecticidal nets against pyrethroid resistant Anopheles arabiensis from South-Western Ethiopia.

The emergence and spread of insecticide resistance in the major African malaria vectors Anopheles gambiae s.s. and Anopheles arabiensis may compromise control initiatives based on insecticide-treated nets (ITNs) or indoor residual spraying (IRS), and thus threaten the global malaria elimination strategy. We investigated pyrethroid resistance in four populations of An. arabiensis from south-western Ethiopia and then assessed the bio-efficacy of six World Health Organization recommended long lasting insecticidal nets (LLINs) using these populations. For all four populations of An. arabiensis, bottle bioassays indicated low to moderate susceptibility to deltamethrin (mortality at 30 minutes ranged between 43 and 80%) and permethrin (mortality ranged between 16 and 76%). Pre-exposure to the synergist piperonylbutoxide (PBO) significantly increased the susceptibility of all four populations to both deltamethrin (mortality increased between 15.3 and 56.8%) and permethrin (mortality increased between 11.6 and 58.1%), indicating the possible involvement of metabolic resistance in addition to the previously identified kdr mutations. There was reduced susceptibility of all four An. arabiensis populations to the five standard LLINs tested (maximum mortality 81.1%; minimum mortality 13.9%). Bio-efficacy against the four populations varied by net type, with the largest margin of difference observed with the Jimma population (67.2% difference). Moreover, there were differences in the bio-efficacy of each individual standard LLIN against the four mosquito populations; for example there was a difference of 40% in mortality of Yorkool against two populations. Results from standard LLINs indicated reduced susceptibility to new, unused nets that was likely due to observed pyrethroid resistance. The roof of the combination LLIN performed optimally (100% mortality) against all the four populations of An. arabiensis, indicating that observed reductions in susceptibility could be ameliorated with the combination of PBO with deltamethrin, as used in PermaNet® 3.0. Our results suggest that bio-efficacy evaluations using local mosquito populations should be conducted where possible to make evidence-based decisions on the most suitable control products, and that those combining multiple chemicals such as PBO and deltamethrin should be considered for maintaining a high level of efficacy in vector control programmes

The effect of dams and seasons on malaria incidence and anopheles abundance in Ethiopia

Background: Reservoirs created by damming rivers are often believed to increase malaria incidence risk and/or stretch the period of malaria transmission. In this paper, we report the effects of a mega hydropower dam on P. falciparum malaria incidence in Ethiopia. Methods: A longitudinal cohort study was conducted over a period of 2 years to determine Plasmodium falciparum malaria incidence among children less than 10 years of age living near a mega hydropower dam in Ethiopia. A total of 2080 children from 16 villages located at different distances from a hydropower dam were followed up from 2008 to 2010 using active detection of cases based on weekly house to house visits. Of this cohort of children, 951 (48.09%) were females and 1059 (51.91%) were males, with a median age of 5 years. Malaria vectors were simultaneously surveyed in all the 16 study villages. Frailty models were used to explore associations between time-to-malaria and potential risk factors, whereas, mixed-effects Poisson regression models were used to assess the effect of different covariates on anopheline abundance. Results: Overall, 548 (26.86%) children experienced at least one clinical malaria episode during the follow up period with mean incidence rate of 14.26 cases/1000 child-months at risk (95% CI: 12.16 -16.36). P. falciparum malaria incidence showed no statistically significant association with distance from the dam reservoir (p = 0.32). However, P. falciparum incidence varied significantly between seasons (p < 0.01). The malaria vector, Anopheles arabiensis, was however more abundant in villages nearer to the dam reservoir. Conclusions: P. falciparum malaria incidence dynamics were more influenced by seasonal drivers than by the dam reservoir itself. The findings could have implications in timing optimal malaria control interventions and in developing an early warning system in Ethiopia

Household level spatio-temporal analysis of Plasmodium falciparum and Plasmodium vivax malaria in Ethiopia

Background: The global decline of malaria burden and goals for elimination has led to an increased interest in the fine-scale epidemiology of malaria. Micro-geographic heterogeneity of malaria infection could have implications for designing targeted small-area interventions. Methods: Two-year longitudinal cohort study data were used to explore the spatial and spatio-temporal distribution of malaria episodes in 2040 children aged < 10 years in 16 villages near the Gilgel-Gibe hydropower dam in Southwest Ethiopia. All selected households (HHs) were geo-referenced, and children were followed up through weekly house-to-house visits for two consecutive years to identify febrile episodes of P. falciparum and P. vivax infections. After confirming the spatial dependence of malaria episodes with Ripley's K function, SatScan(TM) was used to identify purely spatial and space-time clusters (hotspots) of annual malaria incidence for 2 years follow-up: year 1 (July 2008-June 2009) and year 2 (July 2009-June 2010). Results: In total, 685 P. falciparum episodes (in 492 HHs) and 385 P. vivax episodes (in 290 HHs) were identified, representing respectively incidence rates of 14.6 (95% CI: 13.4-15.6) and 8.2 (95% CI: 7.3-9.1) per 1000 child-months at risk. In year 1, the most likely (128 HHs with 63 episodes, RR = 2.1) and secondary (15 HHs with 12 episodes, RR = 5.31) clusters of P. vivax incidence were found respectively in southern and north-western villages; while in year 2, the most likely cluster was located only in north-western villages (85 HHs with 16 episodes, RR = 4.4). Instead, most likely spatial clusters of P. falciparum incidence were consistently located in villages south of the dam in both years: year 1 (167 HHs with 81 episodes, RR = 1.8) and year 2 (133 HHs with 67 episodes, RR = 2.2). Space-time clusters in southern villages for P. vivax were found in August-November 2008 in year 1 and between November 2009 and February 2010 in year 2; while for P. falciparum, they were found in September-November 2008 in year 1 and October-November 2009 in year 2. Conclusion: Hotspots of P. falciparum incidence in children were more stable at the geographical level and over time compared to those of P. vivax incidence during the study period

Correction to: Ten years malaria trend at Arjo-Didessa sugar development site and its vicinity, Southwest Ethiopia: a retrospective study.

Following publication of the original article [1], it came to the authors' attention that unfortunately the last name of one of the authors is spelled incorrectly in the published article

Malaria and water resource development: the case of Gilgel-Gibe hydroelectric dam in Ethiopia

<p>Abstract</p> <p>Background</p> <p>Ethiopia plans to increase its electricity power supply by five-fold over the next five years to fulfill the needs of its people and support the economic growth based on large hydropower dams. Building large dams for hydropower generation may increase the transmission of malaria since they transform ecosystems and create new vector breeding habitats. The aim of this study was to assess the effects of Gilgel-Gibe hydroelectric dam in Ethiopia on malaria transmission and changing levels of prevalence in children.</p> <p>Methods</p> <p>A cross-sectional, community-based study was carried out between October and December 2005 in Jimma Zone, south-western Ethiopia, among children under 10 years of age living in three 'at-risk' villages (within 3 km from dam) and three 'control' villages (5 to 8 km from dam). The man-made Gilgel-Gibe dam is operating since 2004. Households with children less than 10 years of age were selected and children from the selected households were sampled from all the six villages. This included 1,081 children from 'at-risk' villages and 774 children from 'control' villages. Blood samples collected from children using finger prick were examined microscopically to determine malaria prevalence, density of parasitaemia and identify malarial parasite species.</p> <p>Results</p> <p>Overall 1,855 children (905 girls and 950 boys) were surveyed. A total of 194 (10.5%) children were positive for malaria, of which, 117 (60.3%) for <it>Plasmodium vivax</it>, 76 (39.2%) for <it>Plasmodium falciparum </it>and one (0.5%) for both <it>P. vivax </it>and <it>P. falciparum</it>. A multivariate design-based analysis indicated that, while controlling for age, sex and time of data collection, children who resided in 'at-risk' villages close to the dam were more likely to have <it>P. vivax </it>infection than children who resided farther away (odds ratio (OR) = 1.63, 95% CI = 1.15, 2.32) and showed a higher OR to have <it>P. falciparum </it>infection than children who resided in 'control' villages, but this was not significant (OR = 2.40, 95% CI = 0.84, 6.88). A classification tree revealed insights in the importance of the dam as a risk factor for malaria. Assuming that the relationship between the dam and malaria is causal, 43% of the malaria occurring in children was due to living in close proximity to the dam.</p> <p>Conclusion</p> <p>This study indicates that children living in close proximity to a man-made reservoir in Ethiopia are at higher risk of malaria compared to those living farther away. It is recommended that sound prevention and control programme be designed and implemented around the reservoir to reduce the prevalence of malaria. In this respect, in localities near large dams, health impact assessment through periodic survey of potential vectors and periodic medical screening is warranted. Moreover, strategies to mitigate predicted negative health outcomes should be integral parts in the preparation, construction and operational phases of future water resource development and management projects.</p

Isolation of Intestinal Parasites of Public Health Importance from Cockroaches (Blattella germanica) in Jimma Town, Southwestern Ethiopia

Cockroaches are claimed to be mechanical transmitters of disease causing microorganisms such as intestinal parasites, bacteria, fungi, and viruses. This study assessed the potential of the German cockroach Blattella germanica in the mechanical transmission of intestinal parasites of public health importance. A total of 2010 cockroaches were collected from 404 households in Jimma Town, southwestern Ethiopia. All the collected cockroaches were identified to species as B. germanica. The contents of their gut and external body parts were examined for the presence of intestinal parasites. Overall, 152 (75.6%) of the 210 batches were found to harbor at least one species of human intestinal parasite. Ascaris lumbricoides, Trichuris trichiura, Taenia spp, Strongyloideslike parasite, Entamoeba histolytica/dispar/moshkovski, Giardia duodenalis and Balantidium coli were detected from gut contents. Moreover, parasites were also isolated from the external surface in 22 (10.95%) of the batches. There was significant difference in parasite carriage rate of the cockroaches among the study sites ( = 0.013). In conclusion, B. germanica was found to harbor intestinal parasites of public health importance. Hence, awareness on the potential role of cockroaches in the mechanical transmission of human intestinal parasites needs to be created. Moreover, further identification of the Strongyloides-like worm is required using molecular diagnostics

Bio-control of anopheles mosquito larvae using invertebrate predators to support human health programs in Ethiopia

Mosquitoes have been a nuisance and health threat to humans for centuries due to their ability to transmit different infectious diseases. Biological control methods have emerged as an alternative or complementary approach to contain vector populations in light of the current spread of insecticide resistance in mosquitoes. Thus, this study aimed to evaluate the predation efficacy of selected potential predators against Anopheles mosquito larvae. Potential invertebrate predators and Anopheles larvae were collected from natural habitats, mainly (temporary) wetlands and ponds in southwest Ethiopia and experiments were conducted under laboratory conditions. Optimal predation conditions with respect to larval instar, water volume and number of predators were determined for each of the seven studied predators. Data analyses were carried out using the Poisson regression model using one way ANOVA at the 5% significant level. The backswimmer (Notonectidae) was the most aggressive predator on Anopheles mosquito larvae with a daily mean predation of 71.5 larvae (95% CI: [65.04;78.59]). Our study shows that larval instar, water volume and number of predators have a significant effect on each predator, except for dragonflies (Libellulidae), with regard to the preference of the larval instar. A selection of mosquito predators has the potential to control Anopheles mosquito larvae, suggesting that they can be used as complementary approach in an integrated malaria vector control strategy

Prevalence and distribution of G6PD deficiency: implication for the use of primaquine in malaria treatment in Ethiopia.

BackgroundG6PD enzyme deficiency is a common enzymatic X-linked disorder. Deficiency of the G6PD enzyme can cause free radical-mediated oxidative damage to red blood cells, leading to premature haemolysis. Treatment of Plasmodium vivax malaria with primaquine poses a potential risk of mild to severe acute haemolytic anaemia in G6PD deficient people. In this study, the prevalence and distribution of G6PD mutations were investigated across broad areas of Ethiopia, and tested the association between G6PD genotype and phenotype with the goal to provide additional information relevant to the use of primaquine in malaria treatment.MethodsThis study examined G6PD mutations in exons 3-11 for 344 febrile patient samples collected from seven sites across Ethiopia. In addition, the G6PD enzyme level of 400 febrile patient samples from Southwestern Ethiopia was determined by the CareStart™ biosensor. The association between G6PD phenotype and genotype was examined by Fisher exact test on a subset of 184 samples.ResultsMutations were observed at three positions of the G6PD gene. The most common G6PD mutation across all sites was A376G, which was detected in 21 of 344 (6.1%) febrile patients. Thirteen of them were homozygous and eight were heterozygous for this mutation. The G267+119C/T mutation was found in 4 (1.2%) individuals in South Ethiopia, but absent in other sites. The G1116A mutation was also found in 4 (1.2%) individuals from East and South Ethiopia. For the 400 samples in the south, 17 (4.25%) were shown to be G6PD-deficient. G6PD enzyme level was not significantly different by age or gender. Among a subset of 202 febrile patients who were diagnosed with malaria, 11 (5.45%) were G6PD-deficient. These 11 infected samples were diagnosed with Plasmodium vivax by microscopy. Parasitaemia was not significantly different between the G6PD-deficient and G6PD-normal infections.ConclusionsThe prevalence of G6PD deficiency is modest among febrile patients in Ethiopia. G6PD deficiency testing is thus recommended before administrating primaquine for radical cure of P. vivax infected patients. The present study did not indicate a significant association between G6PD gene mutations and enzyme levels