Presentation at 65th Annual meeting of the American Society of Tropical Medicine and Hygiene

Impact of combining Indoor Residual Spraying and Long-Lasting Insecticidal Nets on Anopheles arabiensis in Ethiopia: Preliminary findings of a randomized controlled trial

Oljira Kenea, Meshesha Balkew, Habte Tekie, Teshome Gebre-Michael, Wakgari Deressa, Eskindir Loha, Hans J. Overgaard, Bernt Lindtjørn

Abstract

The current malaria vector control interventions, indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) have been used in combination in sub-Saharan Africa with inconclusive evidence that the combined intervention is more effective than either IRS or LLINs alone. In Ethiopia, both interventions target Anopheles arabiensis, the sole primary malaria vector. This study compared the impact of combining IRS and LLINs with either intervention alone in south-central Ethiopia. Villages were randomly allocated 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 and 2015. 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 host-seeking density (HSD), indoor resting density (IRD), and outdoor resting density (ORD). Human landing catch (HLC) was performed in selected villages to monitor An. arabiensis biting behaviors. Mean densities were compared using incidence rate ratio (IRR) calculated by negative binomial regression. A total of 1786 female anophelines of four species was collected of which An. arabiensis (n=574) was highest in the control arm (51.4%) followed by LLIN (31.5%), IRS (9.2%), and IRS+LLIN (7.9%). The mean HSD of An. arabiensis in the IRS+LLIN arm was similar to either the IRS arm (0.03 vs. 0.03/ house/LTC/night) or the LLIN arm (0.03 vs. 0.10/house/LTC/night, p=0.07) and so was the difference in IRD and ORD between the IRS and LLIN compared to the IRS arm. However, both IRD and ORD were higher in LLIN compared to IRS+LLIN (p < 0.001 for indoors). In all study arms, An. arabiensis was actively biting indoors and outdoors throughout the night with an early night biting peak before the local people retire to bed. IRS+LLIN compared to IRS had equal powerful impact on resting density of An. arabiensis, but LLIN had the least impact.

Malaria control or elimination?

Malaria controlAbout ten years ago, the global health community was cautious about aiming at malaria eradication. The experiences from the 1960s and 1970s left some severe scars on such campaigns. Recently, the Gates Foundation has led the shift in approach and mobilised others to join efforts to end the disease. However, while malaria is preventable and treatable, eradication requires new tools (see figure).

A good vaccine would be highest on the agenda. Although vaccine trials show promising results, the vaccine efficacy is unfortunately too low to eradicate the disease.

Our recent study on the prevention of malaria in the Rift Valley of Ethiopia also shows some of the limited effects of insecticide-treated bed nets. In addition, we have observed that many of the mosquito bites take place at times when people do not use their bed nets. Our mosquito studies show that indoor residual spraying with insecticides can reduce the density of mosquitoes both inside the houses as well as outside the houses. Furthermore, a recent and unpublished study from south-west Ethiopia supporter previous findings that improving housing can reduce the entomological inoculation rates, which is a measure on how dangerous the mosquitoes are in transmitting malaria.

We, therefore, also support that several new tools are required. So, maybe the time is right to assess the combination of many interventions that would include active case finding, treatment, insecticide treated bed nets, indoor residual spraying, improved housing, and other vector control measures; such as reducing the out-door density of malaria mosquitoes.

Human-biting activities of Anopheles species in Ethiopia

Kenea O, Balkew M, Tekie H, Gebre-Michael T, Deressa W, Loha E, Lindtjørn B, Overgaard HJ: Human-biting activities of Anopheles species in south-central Ethiopia. Parasites & vectors 2016, 9(1):1-12.

Abstract

Background    Indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) are the key malaria vector control interventions in Ethiopia. The success of these interventions rely on their efficacy to repel or kill indoor feeding and resting mosquitoes. This study was undertaken to monitor human-biting patterns of Anopheles species in south-central Ethiopia.

Methods   Human-biting patterns of anophelines were monitored for 40 nights in three houses using human landing catches (HLC) both indoors and outdoors between July and November 2014, in Edo Kontola village, south-central Ethiopia. This time coincides with the major malaria transmission season in Ethiopia, which is usually between September and November. Adult mosquitoes were collected from 19:00 to 06:00 h and identified to species. Comparisons of HLC data were done using incidence rate ratio (IRR) calculated by negative binomial regression. The nocturnal biting activities of each Anopheles species was expressed as mean number of mosquitoes landing per person per hour. To assess malaria infections in Anopheles mosquitoes the presence of Plasmodium falciparum and P. vivax circumsporozoite proteins (CSP) were determined by enzyme-linked immunosorbent assay (ELISA).

Results   Altogether 3,408 adult female anophelines were collected, 2,610 (76.6 %) outdoors and 798 (23.4 %) indoors. Anopheles zeimanni was the predominant species (66.5 %) followed by An. arabiensis (24.8 %), An. pharoensis (6.8 %) and An. funestus (s.l.) (1.8 %).

The overall mean anopheline density was 3.3 times higher outdoors than indoors (65.3 vs19.9/person/night, IRR: 3.3, 95 % CI: 1.1–5.1, P = 0.001). The mean density of An. zeimanniAn. pharoensis and An. funestus (s.l.) collected outdoors was significantly higher than indoors for each species (P < 0.05). However, the mean An. arabiensis density outdoors was similar to that indoors (11.8 vs 9.4/person/night, IRR: 1.3, 95 % CI: 0.8–1.9, P = 0.335). The mean hourly human-biting density of An. arabiensis was greater outdoors than indoors and peaked between 21:00 and 22:00 h. However, An. arabiensis parous population showed high indoor man biting activities during bedtimes (22:00 to 05:00 h) when the local people were indoor and potentially protected by IRS and LLINs. All mosquito samples tested for CSP antigen were found negative to malaria parasites.

Conclusions   Results show much greater mosquito human-biting activities occurring outdoors than indoors and during early parts of the night, implying higher outdoor malaria transmission potential in the area. However, high bedtime (22:00 to 05:00 h) indoor biting activities of parous An. arabiensissuggest high potential intervention impact of IRS and LLINs on indoor malaria transmission.

Smallpox and eliminating other diseases

 Dr. Donald A. Henderson, who led the World Health Organization’s war on smallpox, administering a smallpox vaccination in Ethiopia, around 1972. The last known case was in 1977. (Photo WHO)

 

 

Dr. Donald A. Henderson was an American physician who coordinated the World Health Organisation’s efforts to eradicate smallpox. After smallpox had been declared eradicated in 1980, he returned to the US, and became the Dean of what is now the Johns Hopkins Bloomberg School of Public Health. Dr. Donald A. Henderson died this month and will be remembered as a great scientist and public health physician.

As a child in late 1950s I remember a smallpox epidemic in Dilla in Ethiopia. I was so fortunate to have met this remarkable man, and listen to a talk he had at WHO in Geneva. Because of the success in eradicating smallpox, many believe that it also should be possible to eliminate other diseases such as poliomyelitis, Guinea worm, measles, or even malaria. I find it interesting to read that Dr Henderson was rather skeptical about these new eradication initiatives. Both the characteristics of the diseases, as well as the efforts put into getting rid of the diseases differed from what was the strategy to eradicate smallpox.

The poor use bed nets less for malaria protection

Hailu A, Lindtjørn B, Deressa W, Gari T, Loha E, Robberstad B. Equity in long-lasting insecticidal nets and indoor residual spraying for malaria prevention in a rural South Central Ethiopia. Malaria Journal 2016; 15(1): 1-11.

Background: While recognizing the recent achievement in the global fight against malaria, the disease remains a challenge to health systems in low-income countries. Beyond widespread consensuses about prioritizing malaria prevention, little is known about the prevailing status of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) across different levels of wealth strata. The aim of this study was to evaluate the socioeconomic related dimension of inequalities in malaria prevention interventions.

Methods: This study was conducted in July–August 2014 in Adami Tullu district in the South-central Ethiopia, among 6069 households. A cross-sectional data were collected on household characteristics, LLIN ownership and IRS coverage. Principal component analysis technique was used for ranking households based on socioeconomic position. The inequality was measured using concentration indices and concentration curve. Decomposition method was employed in order to quantify the percentage contribution of each socioeconomic related variable on the overall inequality.

Results: The proportion of households with at least one LLIN was 11.6 % and IRS coverage was 72.5 %. The Erreygers normalized concentration index was 0.0627 for LLIN and 0.0383 for IRS. Inequality in LLIN ownership was mainly associated with difference in housing situation, household size and access to mass-media and telecommunication service.

Conclusion: Coverage of LLIN was low and significant more likely to be owned by the rich households, whereas houses were sprayed equitably. The current mass free distribution of LLINs should be followed by periodic refill based on continuous monitoring data.

Malaria in the Rift Valley in Ethiopia

Gari T, Kenea O, Loha E, Deressa W, Hailu A, Balkew M, Gebre-Michael T, Robberstad B, Overgaard HJ, Lindtjørn B: Malaria incidence and entomological findings in an area targeted for a cluster-randomized controlled trial to prevent malaria in Ethiopia: results from a pilot study. Malaria Journal 2016, 15.

Background  This study was part of the work to prepare for a cluster-randomized controlled trial to evaluate the effect of combining indoor residual spraying and long-lasting insecticidal nets on malaria incidence. A pilot study was done to estimate the variations of malaria incidence among villages, combined with entomological collections and an assessment of susceptibility to insecticides in malaria vectors.

Methods  A cohort of 5309 residents from four kebeles (the lowest government administrative unit) in 996 households was followed from August to December 2013 in south-central Ethiopia. Blood samples were collected by a finger prick for a microscopic examination of malaria infections. A multilevel mixed effect model was applied to measure the predictors of malaria episode. Adult mosquitoes were collected using light traps set indoors close to a sleeping person, pyrethrum spray sheet catches and artificial outdoor pit shelters. Enzyme-linked immunosorbent assays were used to detect the sources of mosquito blood meals, while mosquito longevity was estimated based on parity. The World Health Organization’s tube bioassay test was used to assess the insecticide susceptibility status of malaria vectors to pyrethroids and carbamates.

Results  The average incidence of malaria episode was 4.6 per 10,000 person weeks of observation. The age group from 5 to 14 years (IRR = 2.7; 95 % CI 1.1–6.6) and kebeles near a lake or river (IRR = 14.2, 95 % CI 3.1–64) were significantly associated with malaria episode. Only 271 (27.3 %) of the households owned insecticide-treated nets. Of 232 adult Anophelesmosquitoes collected, Anopheles arabiensis (71.1 %) was the predominant species. The average longevity of An. arabiensiswas 14 days (range: 7–25 human blood index days). The overall human blood index (0.69) for An. arabiensis was higher than the bovine blood index (0.38). Statistically significant differences in Anopheline mosquitoes abundance were observed between the kebeles (P = 0.001). Anopheles arabiensis was susceptible to propoxur, but resistant to pyrethroids. However, An. pharoensis was susceptible to all pyrethroids and carbamates tested.

Conclusions  This study showed a high variation in malaria incidence and Anopheles between kebeles. The observed susceptibility of the malaria vectors to propoxur warrants using this insecticide for indoor residual spraying, and the results from this study will be used as a baseline for the trial.

More malaria among wasted children

Shikur B, Deressa W, Lindtjørn B. Association between malaria and malnutrition among children aged under-five years in Adami Tulu District, south-central Ethiopia: a case–control study. BMC Public Health 2016; 16(1): 1-8.

Background: Malaria and malnutrition are the major causes of morbidity and mortality in under-five children in developing countries such as Ethiopia. Malnutrition is the associated cause for about half of the deaths that occur among under-five children in developing countries. However, the relationship between malnutrition and malaria is controversial still, and it has also not been well documented in Ethiopia. The aim of this study was to assess whether malnutrition is associated with malaria among under-five children.

Methods: A case–control study was conducted in Adami Tulu District of East Shewa Zone in Oromia Regional State, Ethiopia. Cases were all under-five children who are diagnosed with malaria at health posts and health centres. The diagnosis was made using either rapid diagnostic tests or microscopy. Controls were apparently healthy under-five children recruited from the community where cases resided. The selection of the controls was based on World Health Organization (WHO) cluster sampling method. A total of 428 children were included. Mothers/caretakers of under-five children were interviewed using pre-tested structured questionnaire prepared for this purpose. The nutritional status of the children was assessed using an anthropometric method and analyzed using WHO Anthro software. A multivariate logistic analysis model was used to determine predictors of malaria.

Results: Four hundred twenty eight under-five children comprising 107 cases and 321 controls were included in this study. Prevalence of wasting was higher among cases (17.8 %) than the controls (9.3 %). Similarly, the prevalence of stunting was 50.5 % and 45.2 % among cases and controls, respectively. Severe wasting [Adjusted Odds Ratio (AOR) =2.9, 95 % CI (1.14, 7.61)] and caretakers who had no education [AOR = 3, 95 % CI (1.27, 7.10)] were independently associated with malarial attack among under-five children.

Conclusion: Children who were severely wasted and had uneducated caretakers had higher odds of malarial attack. Therefore, special attention should be given for severely wasted children in the prevention and control of malaria.

Combining long-lasting insecticidal nets and indoor residual spraying for malaria prevention in Ethiopia: study protocol for a cluster randomized controlled trial

Wakgari-Trials-protocolDeressa W, Loha E, Balkew M, Hailu A, Gari T, Kenea O, Overgaard HJ, Gebremichael T, Robberstad B, and Lindtjørn B. Combining long-lasting insecticidal nets and indoor residual spraying for malaria prevention in Ethiopia: study protocol for a cluster randomized controlled trial. Trials 2016, 17:20

Background
Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the main malaria prevention interventions in Ethiopia. There is conflicting evidence that the combined application of both interventions is better than either LLINs or IRS used alone. This trial aims to investigate whether the combination of LLINs (PermaNet 2.0, Vestergaard Frandsen, Lausanne, Switzerland) with IRS using propoxur will enhance the protective benefits and cost-effectiveness of the interventions against malaria and its effect on mosquito behavior, as compared to each intervention alone.

Methods/Design
This 2 x 2 factorial cluster randomized controlled trial is being carried out in the Adami Tullu district in south-central Ethiopia for about 116 weeks from September 2014 to December 2016. The trial is based on four arms: LLINs + IRS, LLINs alone, IRS alone and control. Villages (or clusters) will be the unit of randomization. The sample size includes 44 clusters per arm, with each cluster comprised of approximately 35 households (about 175 people). Prior to intervention, all households in the LLINs + IRS and LLINs alone arms will be provided with LLINs free of charge. Households in the LLINs + IRS and IRS alone arms will be sprayed with carbamate propoxur once a year just before the main malaria transmission season throughout the investigation. The primary outcome of this trial will be a malaria incidence based on the results of the rapid diagnostic tests in patients with a fever or history of fever attending health posts by passive case detection. Community-based surveys will be conducted each year to assess anemia among children 5–59 months old. In addition, community-based malaria prevalence surveys will be conducted each year on a representative sample of households during the main transmission season. The cost-effectiveness of the interventions and entomological studies will be simultaneously conducted. Analysis will be based on an intention-to-treat principle.

Discussion
This trial aims to provide evidence on the combined use of LLINs and IRS for malaria prevention by answering the following research questions: Can the combined use of LLINs and IRS significantly reduce the incidence of malaria compared with the use of either LLINs or IRS alone? And is the reduced incidence justifiable compared to the added costs? Will the combined use of LLINs and IRS reduce vector density, infection, longevity and the entomological inoculation rate? These data are crucial in order to maximize the impact of vector control interventions on the morbidity and mortality of malaria.

Trial registration
PACTR201411000882128 (8 September 2014).

Highland malaria in Ethiopia

Abebe Animut Ayele defenAbebe [1]ds on Friday 15 January 2016 his PhD degree at the University of Bergen with a dissertation:

“Anopheles species and malaria transmission risk in a highland area, south-central Ethiopia.” 

Anopheles arabiensis is the primary malaria vector in the lowlands of Ethiopia. In the highland Butajira area, a typical area of highland Ethiopia, the entomological aspects of the disease remain poorly described.

The study describes the entomological aspects of malaria transmission by highlighting on the abundance, host feeding preferences, entomological inoculation rates (EIRs) and risk of households’ exposure to malaria infectious Anopheles bites over two years. The study was done at three different altitudes ranging from 1800 to 2300 m.

Ten species of larval stages and nine species of adult stages of anophelines occurred in the area. The streams were the main breeding habitats of the anophelines. Anopheles arabiensis was the most prevalent species, and was found to feed on human and cattle with a similar preference. Plasmodium falciparum and Plasmodium vivax infected Anopheles arabiensis and Plasmodium vivax infected Anopheles pharoensis were caught in the low- and mid-altitude villages. Also, houses with open eaves had higher density of malaria infectious Anopheles arabiensis.

Abebe Animut Ayele was born in 1968 in Gojjam in Ethiopia. He completed his bachelor’s degree in biology and his master’s degree in medical parasitology from Addis Ababa University where he works as a lecturer. He started his PhD training at the Centre for International Health, University of Bergen in 2008 with Professor Bernt Lindtjørn as main supervisor and Associate Professor Teshome Gebre-Michael as co-supervisor.

Abebe-coverThe thesis can be downloaded here 

The publications in his thesis include:

Animut A, Gebre-Michael T, Balkew M, Lindtjorn B. Abundance and dynamics of anopheline larvae in a highland malarious area of south-central Ethiopia. Parasit Vectors. 2012;5:117.

Animut A, Balkew M, Gebre-Michael T, Lindtjorn B. Blood meal sources and entomological inoculation rates of anophelines along a highland altitudinal transect in south-central Ethiopia. Malar J 2013; 12(1): 76.

Animut A, Balkew M, Lindtjorn B. Impact of housing condition on indoor-biting and indoor-resting Anopheles arabiensis density in a highland area, central Ethiopia. Malaria journal 2013;12(1):393.

Cattle and Control of Malaria

Massebo F, Balkew M, Gebre-Michael T, Lindtjorn B. Zoophagic behaviour of anopheline mosquitoes in southwest Ethiopia: opportunity for malaria vector control. Parasites & vectors 2015; 8(1): 645.

Background

Increased understanding of the feeding behaviours of malaria vectors is important to determine the frequency of human-vector contact and to implement effective vector control interventions. Here we assess the relative feeding preferences of Anopheles mosquitoes in relation to cattle and human host abundance in southwest Ethiopia.

Methods

We collected female Anopheles mosquitoes bi-weekly using Centers for Disease Control and prevention (CDC) light traps, pyrethrum spray catches (PSCs) and by aspirating from artificial pit shelters, and determined mosquito blood meal origins using a direct enzyme-linked immunosorbent assay (ELISA).

Results

Both Anopheles arabiensis Patton and An. marshalli (Theobald) showed preference of bovine blood meal over humans regardless of higher human population sizes. The relative feeding preference of An. arabiensis on bovine blood meal was 4.7 times higher than that of human blood. Anopheles marshalli was 6 times more likely to feed on bovine blood meal than humans. The HBI of An. arabiensis and An. marshalli significantly varied between the collection methods, whereas the bovine feeding patterns was not substantially influenced by collection methods. Even though the highest HBI of An. arabiensis and An. marshalli was from indoor CDC traps collections, a substantial number of An. arabiensis (65 %) and An. marshalli (63 %) had contact with cattle. Anopheles arabiensis (44 %) and An. marshalli (41 %) had clearly taken bovine blood meals outdoors, but they rested indoors.

Conclusion

Anopheles mosquitoes are zoophagic and mainly feed on bovine blood meals than humans. Hence, it is important to consider treatment of cattle with appropriate insecticide to control the zoophagic malaria vectors in southwest Ethiopia. Systemic insecticides like ivermectin and its member eprinomectin could be investigated to control the pyrethroid insecticides resistant vectors.