Ethiopia ICEMR (International Center of Excellence for Malaria Research)

Malaria Epidemiology and Vector Biology of Invasive Anopheles stephensi Across Rural and Urban Landscapes in Ethiopia

Source: National Institutes of Health

The overall goal of this project is to assess the impact of Anopheles stephensi invasion and spread on malaria epidemiology and transmission, develop efficient tools and methods for surveillance of An. stephensi, and identify cost-effective vector control methods that can be adapted to settings of varying urbanicities in Ethiopia.

An. stephensi is a major vector of urban malaria in South Asia and the Arabian Peninsula. Since its first detection on the African continent in Djibouti in 2012, the distribution of this vector species has expanded to Ethiopia, Sudan, Somalia, Kenya, Eritrea, Ghana, and Nigeria. The invasion and spread of An. stephensi in Africa pose serious challenges to malaria control and elimination efforts in fast-growing urban Africa. The biology of An. stephensi has been well characterized in its native range, South Asia and the Arabian Peninsula. However, its ecology, behavior, and population genetics are not well studied in Africa. An. stephensi invasion may cause a shift in the vectorial system and alter malaria transmission dynamics. Knowledge gaps in the newly invasive vector’s biology and the effectiveness of the available intervention methods have impeded An. stephensi control in Africa. Furthermore, lack of efficient surveillance tools and methods has also hindered efforts to effectively monitor the spread of An. stephensi population over time. The aim of the ICEMR project is to advance knowledge on the ecology and behavior of the invasive An. stephensi, develop new serology-based surveillance methods to assess human exposure to An. stephensi, and provide important information on the cost-effectiveness of urban vector control methods.

In close collaboration with the Ethiopian Ministry of Health and President’s Malaria Initiative, two interrelated research projects in four Ethiopia sites (urban center and surrounding rural areas) with contrasting An. stephensi abundance, malaria endemicities and different urbanicities will be conducted to:

• Examine the entomological drivers of malaria transmission along the rural-urban continuum.
• Elucidate the extent of spread of invasive An. stephensi in different eco-epidemiological settings.
• Develop and evaluate serological biomarkers for surveillance of human exposure to An. stephensi.
• Examine the impact of An. stephensi invasion on malaria risk.
• Evaluate the impact of larviciding on invasive An. stephensi and native malaria vectors larval density and malaria transmission dynamics.

The study designs of the Ethiopia ICEMR projects involve monitoring changes in land use, land cover, urbanization, and new settlements over time, quantifying the incidence of uncomplicated and severe malaria, entomological surveillance of malaria vectors, and geospatial analysis to determine malaria risk heterogeneity and association with An. stephensi and native vector’s distribution. A variety of malaria surveillance methods, including passive case detection at health centers and hospitals, cross-sectional sampling, reactive case detection and serological surveillance will be used to assess malaria risks. Entomological studies in each site include longitudinal entomological monitoring using various trapping methods, characterizing larval habitats, examination of population dynamics, biting and resting behaviors of invasive An. stephensi and native malaria vectors across the rural to urban landscapes. Observational studies will be carried out to assess the impact of ongoing microbial larviciding on malaria vectors and non-target organisms. Finally, peptide microarray technology will be used to identify biomarkers that can differentiate human exposure to An. stephensi from the native malaria vectors.

Study Sites

View Associated sites for the Ethiopia ICEMR in a larger map

Key Achievements

Previously, the ICEMR focused on assessing the impact of human-induced environmental modifications such as dam construction, irrigation, and shifting agricultural practices on the epidemiology, transmission, pathogenesis, and immunology of Plasmodium falciparum and P. vivax malaria in Kenya and Ethiopia. Below are outlined several notable accomplishments.

Understanding the impact of dams and irrigation on malaria in Africa

African countries are building dams to address the issues of food insecurity and increasing demand for electricity. A number of large and small dams are currently under construction in sub-Saharan Africa. While dams could solve economic problems, they may exacerbate others issue such as malaria. Mosquitoes that transmit malaria breed in shallow pools of water. Dams and irrigation canals provide shorelines that may contain many such shallow pools.

ICEMR investigators found that the number of people living within approximately three miles of large dam reservoirs in sub-Saharan Africa increased from around 14 million to about 19 million between 2000 and 2015. During these 15 years, the number of large dams increased from 884 to 919 in Africa based on the dams registered in the World Register of Dams database.

The relationship between dams and malaria is not entirely straightforward. Dams do not always result in an increase in malaria cases, and when they do, the degree of increase is not uniform. Multivariate analysis of the relationship between malaria incidence and environmental variables found the slope of the dam reservoir shoreline to be the most important predictor for the degree of malaria transmission surrounding the dam. ICEMR researchers have shown that in regions that are suitable for mosquito breeding, the slope of the reservoir shore plays the largest critical role in determining the occurrence of malaria in the vicinity of dams. Reservoirs with a lower slope at the shoreline have higher impacts on malaria. A gentle slope generally corresponds to poor drainage, promoting the persistence of surface water bodies and the formation of stable pools that are favorable habitats for mosquito breeding. Gentle slopes also provide suitable areas for cattle to drink water resulting in numerous hoof-prints that also are conducive for mosquito breeding. In contrast, a steeper slope facilitates drainage and reduces the likelihood that pools will form for periods long enough for mosquitoes to complete their aquatic development.

ICEMR researchers found that agricultural irrigation practices also play a key role in altering malaria vector populations. Observational studies at ICEMR sites in Ethiopia and Kenya showed that agricultural irrigation increased anopheline mosquito breeding habitat diversity, larval occurrence, and abundance, contributing to the proliferation of suitable breeding habitats for malaria vectors. Integration of a high-resolution hydrological model with remotely-sensed data in a study site in Ethiopia (Arjo-Dedessa irrigation development site) found that irrigation increased the probability of occurrence of larval habitats significantly during the dry and rainy seasons. The stability of the habitats was prolonged, with a significant shift from semi-permanent to permanent habitats. The high-risk window (June to September) for larval breeding was also extended by two months due to irrigation. Consequently, increased Anopheles species diversity, abundance, and density were found during both dry and wet seasons. The presence of such diversified malaria-transmitting Anopheles species could contribute to increased risk of year-round malaria transmission, and complicate disease prevention and control. Findings suggest that incorporating larval source management into routine vector control strategies could help reduce mosquito population density and malaria transmission around irrigation schemes.

The World Health Organization has set a target of reducing global malaria cases and mortality rates by at least 90% by 2030. However, ICEMR investigators caution that dam reservoirs will continue to be focal points for malaria transmission in sub-Saharan Africa, a continent that bears over 95% of the global malaria burden. Researchers urge that more rigorous impact prediction assessments must be done at the planning stages to determine the likely malaria impacts when considering new dams. Greater consideration must be given to the design of the dam reservoir, water management, and developing new malaria control tools suitable to dam and irrigation settings where larval breeding sites are very abundant.

Vector sampling tool development and evaluation

Surveillance of malaria vectors is critical to determine malaria transmission intensity and to evaluate the impact of vector control interventions. In most African countries, malaria vector surveillance activities have mainly relied on sampling host-seeking and indoor resting mosquitoes. The most commonly used methods for sampling host-seeking vectors are human landing catches (HLC) and CDC light traps. In addition, indoor-resting vectors are often sampled by pyrethrum spray catches (PSC) and aspirators. Over the past decade, there has been an increasing shift in vector species composition from anthropophagic (human biting), endophilic (indoor resting) vectors to zoophagic (animal biting), exophilic (outdoor resting) sibling species following the widespread use of insecticide-treated nets and indoor residual spraying. Yet, outdoor resting vector sampling is seldom included in the routine vector surveillance system due to lack of standardized and efficient traps.

The ICEMR aims to develop low-cost, exposure-free malaria vector surveillance methods. One tool ICEMR researchers have tested is the sticky pot, which is a sticky variant of a clay pot. Clay pots have been used previously to collect outdoor resting Anopheles mosquitoes. In a sticky pot, the internal surface of the clay pot is covered with waterproof black papers coated with Tangle-Trap sticky substance. The addition of this sticky substance allows for mosquitoes that rest within the pot to be continually trapped for surveillance, rather than only observing the fraction of mosquitoes that happen to be resting at the time of collection in a standard clay pot. Sticky pots are made using locally available clay pots, so they are low cost. Additionally, sticky pots do not require a battery like some alternative trapping methods. In ICEMR study sites, sticky pots collected about 58% more An. gambiae mosquitoes than clay pots and 19% fewer mosquitoes than CDC light traps.

ICEMR researchers also evaluated the human-odor baited CDC light trap (HBLT) and the human-baited double net/CDC light trap combination (HDNT) for outdoor host-seeking malaria vector surveillance. The HBLT consists of a CDC light trap baited with human-odor pumped from an ordinary sleeping room. HDNT is a variant of the previously designed double net trap with an integrated CDC light trap; mosquitoes attracted to the human-bait are collected by setting a CDC light trap between the two nets. These two trapping methods used human odor as an attractant, but they are exposure-free tools since the lured mosquitoes are captured by the CDC light trap rather than by the person acting as a bait and as a collector. In the ICEMR study sites, HBLT captured 2-3 times as many malaria vectors as the regular CDC light trap. HDNT caught 6 times as many malaria vectors as the CDC light trap, similar to the number of mosquitoes collected by the traditional human landing catch method.

These new alternative mosquito surveillance tools could be safer and effective complementary tools for outdoor resting and host-seeking malaria vector surveillance. For example, compared to the most commonly used CDC light trap method, sticky pots can be scaled up as an outdoor malaria vector surveillance method at a fraction of the cost of CDC light traps. Because mosquito collection using HDNT and HBLT does not expose human collectors to mosquito bites but requires more expensive CDC light traps, they can be used for malaria vector surveillance in sentinel sites.

Effectiveness of low-dose primaquine on Plasmodium vivax recurrence and P. falciparum transmission in Africa

Plasmodium vivax blood stage infection has the capacity to relapse weeks to years after mosquito transmission of sporozoites because of its dormant hypnozoite stage in the liver. Vivax malaria relapses can be prevented by eliminating hypnozoites using primaquine, currently the only licensed drug for this purpose. In Ethiopia, P. vivax is co-endemic with P. falciparum, with the former accounting for about 35% of all malaria cases. Recently, the Ethiopian National Malaria Strategic Plan added a 14-day course of low-dose primaquine to the chloroquine treatment regimen for radical cure of vivax malaria in low transmission areas to facilitate malaria elimination. Although randomized clinical trials in Ethiopia have documented the efficacy of primaquine in preventing P. vivax relapses under well supervised conditions, the effectiveness of primaquine in in actual settings where drug treatment adherence, stockouts and parasite species misdiagnosis are common is unknown. ICEMR researchers conducted an observational study to investigate the effectiveness of 14 days of low-dose primaquine to prevent blood stage P. vivax recurrence in a low transmission setting in Ethiopia. Results showed that 14-day full chloroquine-primaquine combination treatment reduced yearly P. vivax recurrence rate to 24% from 67% among those who did complete the treatment regime. Furthermore, ICEMR researchers showed that addition of a single low-dose primaquine to the artemisinin-based combination therapy (ACT) regime reduced P. falciparum infectiousness to mosquitoes by 92% in the field. These empirical findings support the scale-up of low-dose primaquine administration for treating P. vivax infections and reducing P. falciparum transmission in Africa.

Regional impact

Invasion of An. stephensi, an Asian malaria vector, into multiple countries in Africa poses a major threat to the malaria control and elimination efforts on the continent. To date only limited research has examined the biology of An. stephensi mosquitoes and the impact of An. stephensi invasion on malaria transmission in Africa. Many important questions remain unanswered, including where An. stephensi is likely to proliferate, the underlying factors driving its expansion, the development of new surveillance tools and techniques to monitor vector dispersal, and the implementation of cost-effective vector control methods suited for urban environments. Knowledge gained from this ICEMR and the development of new tools will be valuable in devising new surveillance tools and interventions to address the threat of An. stephensi invasion. These advancements will support malaria control and elimination efforts not just in Ethiopia but also in neighboring African countries facing the substantial public health risk posed by An. stephensi.

Staff

Principal Investigator

Guiyun Yan (PhD), University of California, Irvine, USA

Project Leads

• Delenasaw Yewhalaw, Jimma University, Ethiopia
• Ming Chieh Lee, University of California, Irvine, USA

Project Coordinator

• Chloe Wang (PhD), University of California, Irvine

Other Key Investigators

• Dawit Hawaria, Ph.D., Hawassa University, Ethiopia
• Harrysone Atieli, Ph.D., Dire Dawa University, Ethiopia
• Teshome Degefa, Ph.D., Jimma University, Ethiopia
• Guofa Zhou, Ph.D., University of California, Irvine, USA
• Werissaw Haileselassie, Ph.D., Addis Ababa University, Ethiopia
• Daibin Zhong, Ph.D., University of California, Irvine, USA
• James Kazura, M.D., Case Western Reserve University, USA
• Dejene Getachew, Ph.D., Dire Dawa University, Ethiopia
• Nigus Abay, Dire Dawa University, Ethiopia

Key Collaborating Institutions & Partners

• University of California, Irvine, USA
• Case Western Reserve University, USA
• Jimma University, Ethiopia
• Hawassa University, Ethiopia
• Addis Ababa University, Ethiopia
• Dire Dawa University, Ethiopia
• Semera University, Ethiopia
• Ethiopian Public Health Institute (EPHI)
• Ministry of Health (MoH) of Ethiopia
• U.S. President’s Malaria Initiative (PMI), Ethiopia

Key Lab Members and Collaborators