Ethiopia Trip Report

Project DIAMETER (Diagnostics for Malaria Elimination Toward Eradication) Submitted to: The Bill & Melinda Gates Foundation

March 26, 2014 MAIL ING ADDRESS PO Box 900922 Seattle, WA 98109 USA ADDRESS 2201 Westlake Avenue Suite 200 Seattle, WA 98121 USA TEL: 206.285.3500 FAX: 206.285.6619 www.path.org

PATH/Christine Clerk

Table of Contents Abbreviations ............................................................................................................... iii

Introduction ................................................................................................................... 1

Methods ........................................................................................................................ 4

Malaria diagnostic tests used in Ethiopia ....................................................................... 5

Malaria diagnostic scenarios in Ethiopia ........................................................................ 9

Malaria diagnostic settings in Ethiopia ........................................................................ 15

Challenges ................................................................................................................... 23

Summary ..................................................................................................................... 26

References ................................................................................................................... 27

Appendix A: List of stakeholders ................................................................................. A-1

Appendix B: Use scenarios for malaria diagnostic tests in Ethiopia ............................ B-1

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Abbreviations

AEIOU Activity, Environment, Interaction, Object, and User AFB acid-fast bacilli BF blood film BLA Bureau of Labor Affairs CBC complete blood count CDC Centers for Disease Control and Prevention DBS dried blood spot DIAMETER Diagnostics for Malaria Elimination Toward Eradication EDC Electronic Data Capture EHNRI Ethiopian Health and Nutrition Research Institute ELISA enzyme-linked immunosorbent assay EQA external quality assurance FMOH Federal Ministry of Health GPS global positioning system G6PD Glucose-6-phosphate dehydrogenase HC health center HEW health extension worker HF health facility HMIS health management information system HP health post HRP2 histidine-rich protein-2 ITN insecticide-treated net LED light-emitting diode MACEPA Malaria Control and Evaluation Partnership in Africa MDA mass drug administration MIS Malaria Indicator Survey MSAT mass screening and treatment NMCP National Malaria Control Program NGO nongovernmental organization OPD outpatient department PCD passive case detection PCR polymerase chain reaction PFSA Pharmaceutical Fund Supply Agency PHEM Public Health Emergency Management PMI President’s Malaria Initiative QA quality assurance QC quality control RACD reactive case detection RDT rapid diagnostic test RPHEM Regional Public Health Emergency Management TB tuberculosis TPP target product profiles USAID United States Agency for International Development WHO World Health Organization

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Ethiopia Trip Report

Introduction

Project DIAMETER

Recent progress in malaria control has enabled countries to reduce malaria transmission rates. Existing diagnostic technologies—microscopy and rapid diagnostic tests (RDTs)—have played a critical role in this success by enabling many regions to achieve transmission rates near the threshold that defines the elimination phase. However, it is not clear whether these same tests are the most efficient and cost-effective tools to achieve accurate infection detection at low levels of parasitemia, which is critical to achieving elimination goals. Furthermore, there is a lack of clarity and agreement on the use scenarios, target product profiles (TPPs), standardized methods of assay validation, and market potential for the malaria diagnostic tools best suited for cost-effective detection in elimination settings. The resulting ambiguity hinders the development of new infection detection technologies as well as strategic application of existing and nearly ready tools.

PATH has developed a rigorous approach to identifying the most promising solutions to diagnostic challenges in low-resource settings. This involves aggregating and analyzing user needs, market needs, and technical requirements to generate the comprehensive evidence base necessary to inform product development, commercialization, and strategic program operations. Thus, through extensive field research and collaboration with malaria elimination experts, the DIAMETER team will evaluate and hone the use scenarios and TPPs for infection detection in elimination settings. To this end, stakeholder interviews will be conducted in six to eight countries in Asia, Africa, and South America nearing malaria elimination. This information will be collated to inform product development of new diagnostics and areas where further research is required. This report presents findings from stakeholder interviews conducted in Ethiopia in December 2013.

Background on malaria in Ethiopia

Ethiopia has an estimated population of about 90 million. It is one of the least urbanized countries in the world, with almost 84% of its population living in rural areas.

Malaria transmission is largely determined by altitude and climate. Transmission typically occurs up to an altitude of 2,000m and rarely beyond 2,400m above sea level. The levels of malaria risk and transmission intensity within these geographical ranges, however, show marked seasonal, inter-annual, and spatial variations. This is due to the large differences in climate, topography, and human settlement patterns. Most malaria transmission occurs from September through December; some areas, mainly in the western and eastern parts of the country, experience a minor transmission period from March through May.1

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Five broad eco-epidemiological zones have been defined based on altitude and transmission intensity:

1. Endemic zones – These are hot, wet, and humid lowlands with altitudes less than 1,000m above sea level and constitute about 2.6% of the total population.

2. Epidemic-prone, high-risk zones – These constitute areas around water bodies located in semi-arid or dry lowland regions at altitudes ranging from 1,000m through 1,750m above sea level and cover about 31.4% of the population. Although malaria transmission is of high intensity, it is insufficient to prevent epidemics.

3. Epidemic-prone, moderate-risk zones – These are the midland zones with altitudes of 1751m through 1999m above sea level. Malaria transmission is relatively very low. These areas, which cover about 21.3% of the population, are liable to malaria epidemics.

4. Epidemic-prone, low-risk zones – These areas cover about 15.8% of the population and have been targeted for malaria elimination. They are the highland fringes with altitudes of 2001m through 2250m above sea level. The incidence of malaria is low but epidemics can result in high rates of mortality.

5. Malaria-free zones – These are the highlands with altitudes greater than 2250m above sea level and constitute 28.9% of the population.

Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) are the main parasite species in Ethiopia. Pf is the predominant species, accounting for about 65% to 75% of infections. Figures 1 and 2 show the estimated limits of Pf and Pv malaria transmission, respectively. Plasmodium malariae (Pm) and Plasmodium ovale (Po) together account for less than 1% of infections.1 An overall malaria prevalence of 0.7% was obtained during the 2011 malaria indicator survey (MIS), with 0.5% and 0.2% of the population tested (n=11,933) having Pf and Pv infections, respectively. A prevalence of 1.3% (1.0% Pf and 0.3% Pv) was reported in areas below an altitude of 2000m. A lower prevalence of 0.1% (all Pv infections) was reported for areas above an altitude of 2000m above sea level. Household ownership of insecticide-treated nets (ITNs) also varied with altitude, with 54.8% of households below 2000m owning ITNs compared to 37.9% of households in areas above 2000m above sea level.2

Figure 1. The spatial limits of Plasmodium falciparum malaria transmission map in 2010 in Ethiopia.3

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Figure 2. The spatial limits of Plasmodium vivax malaria transmission map in 2010 in Ethiopia.4

The goals of the National Strategic Plan for the period 2011–2015 are to achieve malaria elimination within specific geographic areas with historically low malaria transmission, and to achieve near-zero malaria deaths in all malarious areas of the country by 2015. These goals are to be achieved by ensuring that:

• All suspected malaria cases are diagnosed using RDTs or microscopy within 24 hours of the onset of fever.

• All persons with a positive diagnosis of malaria are treated according to national guidelines.

• All health posts in malarious villages provide the full malaria prevention and treatment package, including outreach services.

• A high-quality, broadly-based malaria infection detection, investigation, and response surveillance system is in place in all elimination-targeted malarious districts of the country.1

As of December 2013, the Federal Ministry of Health (FMOH) was in the process of revising its strategic plan and was unclear on the strategies it would use to achieve elimination. The government has partnered with various institutions for funding and implementing malaria control and elimination activities. Donor agencies include the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund); the President’s Malaria Initiative (PMI); the Bill & Melinda Gates Foundation; United States Agency for International Development (USAID); and Centers for Disease Control and Prevention (CDC), among others. Partners in delivering malaria interventions are Malaria Consortium, Columbia University’s ICAP, the Malaria

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Control and Evaluation Partnership in Africa (MACEPA), the Carter Center, and the United Nations Children’s Fund (UNICEF), as well as other groups. Each partner works closely with the government to ascertain its role and place within the framework of other partners’ activities.

Purpose of the report

1. To consolidate and document country-specific information derived from stakeholder interviews.

2. To disseminate summarized information to key informants who participated in the data collection process, to PATH staff in-country, and to other stakeholders.

Methods

In order to capture a complete picture of the current state of malaria elimination in each country, Project DIAMETER combines thorough desk research on malaria control and elimination efforts with theory-driven qualitative research targeting the opinions and actions of key players within the country’s malaria program.

Desk research

Prior to initiating the qualitative research component, a literature review of relevant documents was undertaken. This desk research helped the team to position where Ethiopia lies along the spectrum from control to elimination, clearly understand the strategies and priorities of the National Malaria Control Programme (NMCP), and gain perspective on previously completed and ongoing research in the country. Qualitative data collection tools were developed based on this desk research and key informants were identified.

Qualitative research with key informants

Twenty-one key informant interviews (46 interviewees) were conducted, along with visits to seven health facilities, a regional reference lab, six government agencies involved in malaria control, six nongovernmental organizations (NGOs), one donor agency, and an RDT manufacturing site (Appendix A). Interview guides and observation checklists were developed in advance to encourage systematic and uniform data-collection techniques within the tenets of Contextual Inquiry methodology and using a hybrid of two frameworks—Jobs-Outcomes-Constraints (JOC) and Activity, Environment, Interaction, Object, and User (AEIOU)—to organize concepts. Contextual Inquiry approaches qualitative data collection with the objective of describing how actors, objects, and rules influence and are influenced by the larger system in which they exist. This method exposes tacit knowledge that informants may not be aware of and encourages the informant (rather than the interviewer) to prioritize concepts.

Interview guides and observational checklists were used for each category of key informant: program manager, thought leader, laboratory personnel, clinician, and community health worker. The data collection tools were developed using a hybrid JOC-AEIOU framework, which prompted the

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interviewees to describe the main elements of the system (AEIOU) and then define the barriers to successfully achieving the intended objectives (JOC).

We made seven observational visits. Interviews were conducted at each of these sites, as well as with personnel from MACEPA, Public Health Emergency Management (PHEM), Amhara Regional Reference Lab, USAID/CDC/PMI, the FMOH NMCP, Bureau of Social Affairs, Regional Health Bureau-Pharmacy, Pharmaceutical Fund Supply Agency (PFSA), Ethiopian Health and Nutrition Research Institute (EHNRI), Malaria Consortium, Carter Center, UNICEF, World Health Organization (WHO), ICAP, and the Access Bio production facility. Following data collection, key concepts from each interview and site observation were summarized by the research team, mapped to the corresponding use scenarios and settings, and aggregated across all data. A spreadsheet mapping key concepts to use scenarios and settings is included as Appendix B.

Malaria diagnostic tests used in Ethiopia

Microscopy

Malaria case management should always be based on a confirmed infection, and microscopy is considered the gold standard for malaria diagnosis in Ethiopia. Thus, any health facility (HF) capable of performing microscopy must use these lab results to guide patient management. Tests such as RDTs are exclusively meant for community-level diagnosis at health posts (HP) by health extension workers (HEWs). Microscopy in Ethiopia is generally performed similarly to other countries visited by the DIAMETER team in 2013. Likewise, the microscopy constraints identified herein are comparable to those found in other Project DIAMETER country reports. In most circumstances, the patient is sent to the lab where a blood film (BF) is prepared by technicians, clinicians, or lab aides. Both thick and thin films are collected; in certain situations, only a thick film will be prepared initially; once it is read, a thin film will then be prepared, requiring a second finger-prick. Giemsa stain is usually delivered pre-made with the labs filtering it prior to use. Laboratories will stain smears as they come until higher volumes of patients require batch staining and reading. Variation in reading of fields and turnaround time was evident and expected. Results are always reported semi-quantitatively. Clinicians tend to trust results of microscopy and prefer the semi-quantitative results they provide. They are also aware of submicroscopic infections, particular at the tail end of an infection. Smear-negative patients will often receive an additional BF if fever persists. Microscopy can be performed in situations where power is temporarily unavailable or simply not present by use of solar mirrors and solar rechargeable light-emitting diode (LED) lights.

Constraints

Stockouts of reagents are uncommon, but in the past there were some reports of delivery of poor reagents. BF preparation was noted to be one of the major constraints for obtaining high-quality microscopy. Other

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common constraints involved microscope breakage, heavy workloads, lamp/oven drying of smears when pressed for time, and human resource issues.

Rapid diagnostic tests

Although RDTs are supposed to be used by HEWs at the lowest level of the health care system, they are also sometimes used in health centers. Health centers may use RDTs if they do not have microscopes or electricity, if they are too far from another microscopy center that they may refer patients to, or after regular lab hours. Ethiopia uses multispecies RDTs, and two brands were in use during our visit—First Response (Pf/Pan) and SD Bioline (Pf/Pv). The EHNRI and other partners usually provide technical input for RDT specifications, but the national procurement agency tends to prioritize cost, often opting for cheaper brands. They buy in large quantities and so tend to buy from multiple vendors. About 10 to 12 million tests are used annually. At the time of our visit, the FMOH was in the process of procuring about 20 million tests to be used over two years.

Constraints

A complaint with RDT use was the delivery of kits near the expiration date. This is not only a logistics delivery issue but also stems from the lengthy procurement process. Sometimes, kits enter the country a year after date of manufacture, and it takes another six months for them to be delivered to the HP. In addition to expired kits, there were common complaints of buffer packets missing or empty in the RDT kits. It was thought that this might be due to the nature of the tender process, where the cheapest-priced RDT that meets the technical standards is procured without taking into account the quality of the manufacturer. An additional problem identified was the discoloration of buffer, which was thought to lead to poor running of the sample on the strip as well as bubbles. Furthermore, false positive results were noted in lowland regions where temperatures often exceed 42°C to 45°C in March. It was noted that some 20% of RDTs from the Afar and Amhara regions were exposed to temperatures above the recommended storage temperatures. Storage of RDTs at HPs and by HEWs in these regions is a challenge—some of the structures have tin roofs, which make internal temperatures even greater than ambient temperatures. Other issues related to RDTs were: change in procedures when switching brands of RDT kit, inability to get blood from calloused fingers, false negatives, invalid test results when too much sample was added, and difficulty interpreting results under poor lighting conditions. One issue with the Pan test line is that it is recorded as Pv when positive (and Pf negative), when Po and Pm could be causing the Pan test to be positive. Finally, instructions in the RDT kits are in English, which many of the HEWs are unable to read.

Quality assurance

National guidelines are in place for quality assurance (QA) practices involving diagnosis of malaria via microscopy, as set forth by the EHNRI. However, the FMOH has noted that the existing system could be strengthened. A PMI/USAID-funded program implemented by ICAP, in collaboration with the government, has been initiated. The purpose of this program is to ensure that quality diagnosis of malaria occurs in select FMOH facilities, as they recognize that improving laboratory quality benefits patients by

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ensuring that clinicians trust results coming from their labs. The program began with a baseline assessment in HFs that identified major gaps in training, supply chain and storage, equipment, job aids/guidelines, support, and routine QA reporting directly to the central level. An action plan was then drafted and implemented to address the identified gaps. ICAP provides national and regional microscopy experts with internationally accredited training and continuing competency assessment. In addition, the program provides onsite training, in collaboration with the FMOH, in basic laboratory techniques for hospital and HF staff, as well as education for clinicians on fever management using algorithms based on laboratory results. ICAP provides selected clinics with equipment and reagents, such as Giemsa stain, to ensure that standards of quality are uniform. ICAP’s mandate is to ensure improvements are being made all the way up to the regional labs.

The quality assurance (QA) program involves blind BF re-checking of archived slides selected randomly from participating HF laboratories. Slides are sent to a central laboratory for re-reading, and feedback on agreement is sent back to the labs from which the slides originated. An improvement plan is then put into place if agreement does not meet a priori expectations, and retraining of the entire lab staff will follow. Ten slides from each clinic are sent each month, for a duration of 40 months. Control slides, with various species and densities, are also sent from the central level to clinic labs for assessment. Around 240 HFs have participated in the scheme, with an overall score of 85% agreement between the central and HF labs; those that have gone through eight rounds of evaluation have a 95% agreement score. Thus, the program is seen as highly successful.

However, there are challenges associated with moving to onsite evaluation. If 40 slides are taken from 100 HF labs, that means 4,000 slides have to be read at the central level. With plans to expand to more than 1,000 HF, the logistics and human resources required will be significant. There are more than 3,600 HFs in the country, and the program is unable to expand the services to meet all HFs in the country; thus, only high-burden areas are selected for participation. To address the scale-up of services, they will move the rechecking of slides to regional laboratories.

Reagents are supplied by ICAP, but the preparation is done by HF staff with support from the program. For HFs that do not have tap water, distilled water is bought or supplied by the regional reference lab. Each HF is supplied with a microscope with two solar mirrors and a solar rechargeable LED light so that microscopy can be performed in areas without power. Spare parts for microscopes are provided in addition to training in how to perform daily, weekly, and monthly maintenance to extend the life of the scope. The microscopes placed five years ago are still functional. If a microscope breaks down, there are HF and regional engineers available to fix it.

There are certain technologies that could improve the QA system. Digital image processing and transmission via cell phone to the regional center could improve the logistics issues. In addition, digital capture and analysis of many fields in low-density infections may be beneficial. In elimination settings, a fluorescent microscope may be useful for screening many slides with densities of 1 parasite/µl. However, molecular techniques, such as polymerase chain reaction (PCR), were noted to be too expensive for use in QA programs.

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The EHNRI, in partnership with the Foundation for Innovative New Diagnostics (FIND) and WHO, performs QA on RDTs intended for sale in Ethiopia. They have an archived repository of known positive and negative samples. Manufacturers send many RDTs to the EHNRI for evaluation, and the results of the testing are forwarded to the Ethiopian regulatory body responsible for approving RDTs. This information is instrumental in the tender process for bulk RDT procurement by the government. The EHNRI serially dilutes high parasitemic blood (2,000; 200; and 20 parasites/µl) with O or AB positive blood into 200 µl aliquots, which are stored at -80°C for future testing. Each lot of RDTs that enters the country will be tested with these samples and the results will be compared to the manufacturer’s claim. They keep more tests from the same lot and repeat testing every six months until expiration. They also perform testing at various temperatures, and follow WHO guidelines for testing protocols.

There is currently no national QA program for RDTs once they enter into the market, even though 70% of malaria diagnosis occurs by RDT at the community level. ICAP is currently undertaking a gap analysis in RDT use and treatment at the HP level. ICAP does provide training for hospital and HF staff in RDT use; these staff members in turn provide training in RDT use and case management for HEWs. The NMCP is currently working to develop a robust system for RDT QA; however, it is recognized that this is a very large weakness in the system that needs to be remedied. Currently, the CDC is evaluating dried tube specimens (control samples) intended for QA use by HEWs. If a new technology is developed for RDTs, the inclusion of QA samples should be considered. Because of reports from the field of a significant amount of kits without buffer, the EHNRI is planning a post-market study of RDTs already released into the market.

Constraints

Common problems observed that lead to discordance in slide reading include preparation of the thick film, staining, and skill gaps in speciation. Senior staff are able to differentiate species, although after extended time on the microscope they develop fatigue and their ability may slacken; even the most skilled technician cannot read 100 slides in a row without making mistakes. Patient volumes in clinics are very high, and placing limits on slide reading may work on paper but in reality it cannot be achieved. In the past, when malaria control was a vertical program, technicians were limited to reading 60 slides per day, but now there is no specified limit.

A difficulty identified by the program was that HFs have different brands of microscopes, which have different problems and fixes. Also, there is a shortage of spare microscopes for use when a microscope breaks down. Furthermore, some HFs are using scopes procured prior to this program; therefore, many obsolete models are in use.

Additional constraints thwarting improvement in lab quality are high workload, power outages, use of RDTs at the HF at night (RDT use should occur only at the HP level), and human resources issues. The country has an adequate number of trained microscopists, but there are not enough finances to hire the number of technicians required. Furthermore, the greatest need for microscopists occurs in rural areas,

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where it is difficult to retain qualified staff as technicians will transfer to the private-sector labs in urban areas.

As previously mentioned, the lack of a QA program for RDTs is a major constraint.

Malaria diagnostic scenarios in Ethiopia

Passive case detection

Passive case detection (PCD) occurs in public and private health facilities as well as by HEWs at the community level.

A. Private health facility

The private sector does not use RDTs because all RDT supplies in the country are dedicated for use by HEWs. Instead, private sector facilities rely solely on microscopy with Giemsa. The private sector hospitals work with the government to provide free malaria treatment and to conduct surveillance activities. Coartem is provided to private facilities for free and may be dispensed to microscopy-positive patients for no charge, although a lab fee may be required. If the patient is infected with Pv, then chloroquine is prescribed, but it is not free. Positive cases are reported to the Public Health Emergency Management (PHEM). Patients are given an identification card that includes name, sex, age, address, chief complaint, treatment history, physical exam results, assessment, and treatment provided. They also have an “index of suspicion”; when a number of cases come from one district in times where incidence is expected to be low, staff will send a report to the district and zonal health officer in charge of that district.

Constraints

RDTs are not available for use. There were no malaria-diagnostics-related constraints identified at the private facility we visited.

B. Public health facility

At the public health facility level, microscopy is typically used to diagnose malaria, as RDTs are usually reserved for community-level diagnosis at HPs by HEWs. In situations where a lab does not have a microscope, smears may be taken and read at the nearest microscopy center or RDTs will be used. Clinicians tend to trust results of microscopy and prefer the semi-quantitative results they provide. RDTs may be used as an alternative diagnostic method in situations where microscopy is not available, such as when electricity is not available, a microscope breaks, they are too far from another microscopy center, or after regular lab hours. Clinicians expressed that RDTs are helpful in ruling out other febrile illness and identifying species.

HFs participate in the FMOH reporting system. They may also collect information such as travel history of the patient. Additionally, public health facilities may collect reports on a weekly basis from the HPs in

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their catchment, aggregating data either by having each HEW deliver the data to the HF or by having a staff member from the facility visit each HP to collect the data.

Constraints

Power outages occur occasionally and, although some facilities have purchased backup generators, power outages still limit the functionality of the lab. Stockouts of RDTs and consumables occur occasionally. Additionally, problems were reported with facilities receiving RDTs that are near expiration or that have already expired by the time they arrive at the facility. Occasional problems with the buffer in the RDT kits were also reported. Staff find that patients may test negative with an RDT at a HP but test positive with microscopy at the health facility, suggesting poor sensitivity of RDTs. Heavy workloads on the microscopes can lead to delayed time-to-results or to alternative methods for drying slides to speed up the process.

It is challenging for HFs to get reports from the catchment HPs. It may take a long time (2 hours) for HEWs to deliver hard copies to the HF due to lack of transport. Additionally, because there is poor network service in the area, HEWs often have to travel to an area with better service in order to transmit data by mobile phone. As a result, HEWs are not always compliant in sending their reports on time. Mobile phones may need to be charged at the HF, because it is difficult to charge mobile phones at the HPs (due to unreliable or unavailable power). Newer phone batteries may last two days before needing to be recharged while a charge may only last one day in older batteries.

C. Community level

HPs are attached to HFs and are staffed by HEWs. The HEWs may receive training at a college to learn how to perform RDTs. They also receive hands-on practice using RDTs at the HCs. RDT brands may vary and HEWs may not receive additional training for changes in RDT brands. Sharps are disposed at the HF or may be buried locally. HEWs collect information on the patient and record date, name, age, sex, RDT result, treatment provided, and address of the patient. This information is reported to the HF on a weekly basis. When a patient comes in for testing, the HEW also asks if there is a sick person in their house. If so, they do not provide treatment or go to the index case house; rather, they request that the individual come to the HP for testing.

Constraints

Stockouts of RDTs occur occasionally. Additionally, RDTs may be near expiration by the time they arrive at the HP. Problems with the buffer in the RDT kits were also reported. RDT inserts may be in English, which the HEW may not be able to understand. Due to the burden on the HEW of traveling to the HF, waste may not be properly disposed of and there may be a delay in the delivery of weekly reports.

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Reactive case detection

In general, reactive case detection (RACD) is not currently done in Ethiopia. However, if a malaria patient at the HF reports a sick person in their house, the HF staff will mobilize HEWs near the patient’s house to visit and communicate by mobile phone. The malaria case officer will assist/support the HEWs for this exercise. If there is an increase in cases above the threshold level for the area, a committee is organized to investigate and coordinate with the outbreak response team from the regional PHEM office.

There was positive reception by HF staff to the concept of RACD along with an emphasis that increased investment in human resources would be needed to avoid compromising the HF service delivery. However, it was also noted that it would not take more than a few HF staff to do this activity.

Outbreak response Outbreaks of malaria in low-transmission settings in Ethiopia are common. The response to outbreaks falls under the auspices of the Regional Public Health Emergency Management (RPHEM) department. The RPHEM has in place a surveillance system for providing an early warning indicator of potential outbreaks and a rapid response team responsible for possible outbreak investigation. The surveillance system utilizes data collected from weekly HF/HP reports sent via telephone and later by hard copy. This data is aggregated at the zonal level prior to reaching RPHEM offices. The number of cases occurring per district is analyzed by RPHEM and compared to an established expected caseload for the season. This expected number is derived from the previous five years’ data on cases for the area. If the number of cases is greater than expected, the district surveillance officer will be called by RPHEM staff to confirm the numbers. If confirmed, a team will be formed to go to the district to look at the case report files and find out which areas within the district are affected.

Once an outbreak is confirmed, the community will be mobilized and an active case finding and treatment activity will occur, in addition to the deployment of environmental health technicians for the identification of larval breeding sites, indoor residual spraying, focal spraying, and bed net distribution. Case finding consists of an active search for febrile cases only, in house-to-house sweeps. The team consists of HF lab technicians and HEWs for testing with RDTs. In the past, if an area had greater than 30% BF positivity rate, they would not test and treat; rather, they would provide mass drug administration (MDA) for the afflicted community. With the roll-out of RDTs, they switched to the test and treat of febrile cases; therefore, the use of RDTs is now seen as crucial for a successful response to outbreaks.

The RDTs used for an outbreak response do not necessarily come from the district HF; instead, each zone and region keep supplies specifically for this purpose. There is a Global Fund–supported micro-planning system in place for the logistics of distribution of RDTs and drugs during an outbreak. Thus, stocks from the district can be used initially, with reserve supplies coming in to replenish the district in order to continue to supply the needs of the outbreak response teams. At the national level, 75% of supplies needed are sent to the regional level and less than 5% are reserved for epidemiological purposes.

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The population of Amhara is 20 million, and yet only three staff members are available to coordinate outbreaks at the RPHEM in Amhara: one is dedicated for neglected tropical diseases and two for malaria outbreaks. There are around 800 HFs and 3,000 HPs in seven districts, and micro-planning for such a large area can be difficult. The collection and analysis of surveillance information and the coordination of a response is challenging for such a small team to handle given the existing information technology (IT) infrastructure.

Historically, mapping technologies have not been used to assist in resource allocation or narrowing activities, although such systems are just beginning to be utilized. Mapping is occurring at the village and HP level at MACEPA demonstration sites, so the lessons learned can be shared with outbreak response coordinators. Currently, maps for outbreak response exist only at the HF level and are hand sketched. However, the FMOH is implementing a health management information system (HMIS) system in which each house will have a global positioning system (GPS) coordinate and number, which will feed into HEWs’ data collection folders.

In order to successfully implement and scale this system for data collection, significant improvements to infrastructure and equipment will be required throughout the region. An electronic data capture (EDC) system will be required, and computers and data entry will need to be integrated into the HFs. Power will be necessary to run the computers; therefore, investments must be made to either connect the HFs into the grid or to provide stand-alone solar/generator power. Furthermore, internet access will be required in order to access the HMIS system. More immediate concerns are improvement of network coverage for cell phone reporting as some HEWs live in areas where the network is poor, making reporting difficult. Improvement of the existing land lines is also prudent, as HF staff often need to use their personal cell phones to communicate with HPs because the connection is better than the landline they are using. Ultimately, a switch from monthly to weekly reporting within the improved HMIS system will be important in order to stay ahead of an outbreak; currently, the weekly reporting resides outside of the existing HMIS system.

Constraints

Constraints to effective outbreak response include the small size of the coordination team for malaria outbreaks. The lack of a system to enable effective collection, mapping, and analysis of data further inhibits efficient response. Poor phone networks for both mobile and landline phones also hinder the availability of data for planning.

Asymptomatic reservoirs that may fuel transmission may be missed in the search for febrile cases. In spite of a desire to provide mass screening and treatment (MSAT), the high cost of RDTs excludes testing non-febrile community members.

Difficulties associated with the storage of RDTs were identified. Notably, there are 10 districts within the region where the temperature can exceed 42°C. Some outbreak response staff theorize that the antigens in the RDTs denature at these temperatures. They have noticed a high false positive rate in these specific

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regions, whereas in cooler areas, performance of RDTs is unchanged. An evaluation of RDTS in these areas is being planned to determine the nature of the false positives. There is not a best practice in place for storage of RDTs, and there is concern about their storage by HEWs in these high-temperature regions. This problem is not new; HIV RDTS in this region also suffered from false positives in the past.

Outbreak response staff note that RDT kits have missing buffer—both missing containers and empty containers within the kit. There is also a perceived need to improve the quality of HF labs, as poor or missing reagents will generate poor microscopy results. In fact, in some areas that do not participate in the ICAP QA programs, diagnosis performed at the HP level will be superior to that found in the HF. Finally, the major challenge facing outbreak response staff is the migrant labor population that seeds outbreaks upon their return from endemic areas (see “Challenges” section below). Outbreak response staff suggest that point-of-care (POC) RDTs that detect recent IgG responses in addition to antigen capture could be beneficial in emergency situations or even situations such as screening at bus stations where migrant laborers return from the camps.

Mass screening and treatment of febrile cases Although there are no government-sponsored programs that undertake MSAT activities aside from outbreak response for active case detection, the Carter Center, in collaboration with the FMOH, has implemented a campaign of mass testing and treatment of febrile malaria cases during their trachoma MDA campaigns. These campaigns, called MALTRA (malaria-trachoma), occur every six months and are conducted over a one-week period in half of a region (about 75 districts). The goal is to reduce the prevalence of malaria and trachoma. All eligible members of the community are mobilized to benefit from MDA for trachoma using azithromycin and tetracycline ointment for some people. The purpose is to treat trachoma but, in the process, malaria interventions may also be coordinated when malaria cases are increasing. Activities are scheduled for November and May, corresponding to major and minor peak transmission seasons. In November, MALTRA campaign staff go to high-burden areas. In a one-week campaign they will treat 90,000 people for trachoma. These staff manage logistics to ensure that all districts/villages also receive diagnosis and treatment for malaria. Any remaining malaria doses will be left for future use in HFs and by HEWs.

To date, between six and ten million people have been mobilized during these campaigns. A team consists of one HEW and three non-professional staff, such as a member of the health development army or other volunteer. Each team sees about 300 to 350 people per day. Before providing MDA for trachoma for a villager, the team collects basic health information and checks for signs and symptoms of malaria. Those suspected of having malaria are separated from the rest of the group that receive MDA for trachoma. The suspected malaria cases get a clinical and lab (RDT) assessment, and treatment is provided for RDT-positive cases. Before a campaign begins, one month of training on the use of RDTs and malaria treatment is provided. This training is offered on a yearly basis.

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Constraints

Before MALTRA, the Carter Center did a baseline survey for malaria using microscopy and RDTs. Then, a Pf-only RDT (Paracheck) was used, but now they use a Pf/Pv combo test (Parascreen). They have observed (in the lab) that the sensitivity of Parascreen was low but that its specificity was comparable with microscopy. Once in the field, kits are not temperature controlled, which can affect the RDTs’ performance so they fail to detect cases. For example, in the field, the prevalence of malaria detected by microscopy was 4.5%, but by RDT it was only 1.3%. In clinical settings, RDTs performed better: RDTs had 85% to 95% sensitivity and 95% to 96% specificity, but these percentages went down when the RDTs were used at the community level.

Malaria indicator surveys In 2011, the FMOH conducted a national household survey to estimate the prevalence of malaria in Ethiopia. There were 10,444 households with 47,248 residents surveyed with thick and thin BFs, RDTs, and hemoglobin assessments of children under five years of age.3 In addition to the above indicators, 10,000 dried blood spots (DBS) were collected for the purpose of assessing Glucose-6-phosphate dehydrogenase (G6PD) prevalence in southern areas where Pv is prevalent and the potential use of primaquine is desired. These samples have yet to be analyzed by the EHNRI, but plans are in place to enhance the capability of the EHNRI lab for these genetic analyses. Currently, the EHNRI lab utilizes molecular methods, although primarily for drug-resistance studies. Staff members at the EHNRI fully recognize the utility of assessing DBS samples for assessing asymptomatic carriage in the population. In fact, a recent household study in the Rift Valley demonstrated a 19% prevalence of submicroscopic infections.

In addition to the national MIS, MACEPA is conducting a number of mini-surveys in their malaria elimination demonstration sites. The baseline assessment has been completed and more surveys are planned for evaluating their program impact. More than 8,000 people have been tested using microscopy and RDTs, as well as DBS for use in serology and nucleic acid amplification test (NAAT) assays. Of the 172 infections detected, 65% were asymptomatic. The assessment of submicroscopic infections via DBS/PCR in the parasite-negative samples is an attractive option for determining how impactful a test-and-treat strategy will be based on the use of RDTs for infection detection. At the time of this report, the DBS samples collected from this baseline are being assayed at the regional reference lab in Amhara for IgG immune responses via enzyme-linked immunosorbent assay (ELISA). The intent is to identify good markers for assessing transmission characteristics and, eventually, to document an area free of malaria based on lack of immune responses in sample populations. Therefore, as Ethiopia progresses in its elimination goals, the use of sophisticated techniques for centralized lab testing will become more apparent.

Constraints

Although the infrastructure is in place for these activities, funding and staffing are major constraints for decentralized introduction into regional programs. The volume of DBS samples from MIS surveys is

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beyond the capacity of one lab. Capability to perform PCR would need to be transferred to regional labs for this to be feasible. Although the infrastructure is in place in regional labs, the issue becomes finding and supporting the human resources that are qualified to perform these assays. The cost of such an endeavor is beyond what the current budget allocation would allow.

Malaria diagnostic settings in Ethiopia

We visited six health facilities. These included a regional hospital, a private teaching hospital, three health centers, and one health post. Additional meetings were held with government agencies and NGOs involved in malaria control. This section of the report will focus solely on health facilities, although comments from additional meetings have been incorporated into other parts of this document.

Amhara regional hospital laboratory This laboratory services the outpatient department (OPD) and inpatient wards for the regional referral hospital. In terms of malaria diagnosis, this lab relies solely on microscopy; no RDTs are performed at this level. Technicians perform thick smears and prepare thin films as needed when speciation is required. Hence, thin films are not prepared simultaneously with thick films; rather, a thick film is taken initially and a thin film is ordered later if desired. The technicians in this lab are highly skilled and are able to detect low-density infections and speciate competently. They report that it is very rare to encounter low-density infections; this is most likely due to the patient populations they serve, as many are referrals with severe disease from lower levels.

This lab uses both Giemsa and Wright’s stain, each of which are commercially prepared, although they filter the stain at the lab. Their slides are typically air-dried but they also have a drying oven to shorten the process when workload requires. They normally batch 10 to 15 slides at a time, and it takes around 40 minutes to produce results. Four or five microscopes are in operation at one time, but there is one scope that is dedicated for sputum microscopy (acid-fast bacilli [AFB] smears for tuberculosis [TB]). The lab is awaiting installment of a fluorescent microscope for use with sputum samples. It was stated that, for malaria, preference is given to Giemsa staining over possible fluorescent reading because the procedure is easier.

There are 17 lab technicians working at the lab, with 4 technicians per shift. They evaluate around 50 to 60 slides per day during the high season, with around 10 to 17 positive smears. During the low season, they read about 40 to 50 slides per day with around 6 positive results. Results are reported semi-quantitatively. Lab aides at the blood collection/registration station prepare smears, which are then taken to the lab for staining and reading. All slides are stored for internal and external QA schemes. If discordance is found between technicians or the hospital and reference lab, then teaching and retraining commences.

This lab does not perform any molecular methods such as PCR. They do have a range of other equipment, such as blood chemistry analyzer, a HemoCue®, and two hemotology machines (one is for back up).

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They therefore are capable of taking venous blood samples and have vacutainer blood collection tubes in stock. There is a CD4 machine within the hospital but it resides in another lab dedicated for HIV patients. This lab also has the ability to run bacterial cultures, with two incubators at different temperatures.

The lab is powered by central electricity and also has a generator that runs on Naphtha. There are power outages about twice per month and the generator has had problems, although the fuel source is in good supply. The hospital has service engineers who are trained to fix all equipment within their lab.

It was noted that it would be ideal to include malaria in the complete blood count (CBC) panel because it would be easier for the machine to automatically read the sample, and a printout was desired. If a hematology machine could include malaria in the panel, it would be preferable if the machine was capable of batching. It was also noted that a device larger than a HemoCue® device was desirable. A larger machine was deemed to be more trustworthy as it would be more likely to require daily calibration for quality control (QC) procedures; thus, they trust results generated from larger calibrated machines over smaller devices that do not have rigorous calibration functions.

Constraints

The heavy workload on lab technicians is a constraint at this facility. Occasionally, poor quality reagents are received and discarded. In the past, they have run out of stain when they had to discard 5 to 10 bottles through their QC program. Those particular bottles were received from the PFSA, who were informed of the poor quality.

Gamby teaching hospital (private) This is a medium-sized private hospital with inpatient wards, surgery, and various OPD clinics. They serve patients from urban areas as well as from outside the city. They use no RDTs for malaria diagnosis here; instead they rely solely on microscopy with Giemsa. They collect up to three BFs per patient to confirm a result. If the patient is initially smear-negative, they send them home and tell the patient to return if their fever persists. If the patient returns and is still smear-negative, no treatment is provided but further investigation into other causes will ensue. After a third negative test, other cause of the fever is highly probable, and the patient will be followed up for other tests. Empirical treatment is provided when the fever is not found to be caused by another organism and the patient does not respond to antibiotics in two to three days; in such cases, clinical acumen is used to guide treatment decisions. The BF collection is done in a separate area where erythrocyte sedimentation rate (ESR), blood chemistry, and serology centrifugation (Hct) are also performed. A drying lamp is used for BFs. Staining occurs at the parasitology station in the lab, which has two dedicated microscopes that are routinely disinfected. They keep reference and QA slides.

Coartem is dispensed to BF-positive cases without charge; however, patients are required to pay lab costs (approximately 10–12 Birr). If the patient is infected with Pv, chloroquine is prescribed (which is not free). The hospital has their own system to report their cases to the PHEM. There are two health officers and a nurse working daily to report weekly and monthly cases. They are currently adapting their system to

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the WHO codes and the HMIS system of the government. They expect to have a complete EDC by the end of the year, but they need to budget for this and there will be a user fee.

This lab is currently being registered for accreditation with the EHNRI. All documentation for accreditation of each station is kept in books in the lab, including a process control and improvement log and daily cleaning record. A Canadian accreditation body is assessing this system. They have a specimen tracking form (process control) and there is only a 1% error. They track and record turnaround times from sample collection to moving the sample from station to station, with an initial baseline used to measure times. In doing so, they can provide patients with the expected wait time depending on what tests they are seeking from the lab. Additional logs are kept for calibration, room and refrigerator temperatures, equipment failure, stockouts, customer satisfaction, productivity, and specimen rejection, to name a few. The specimen rejection log captures information such as clotting, unlabeled specimen, and old sample. They also have corrective action and prevention forms available for when problems arise.

The lab, which is open 24 hours, is divided into sections and by skill/certification level. There are stations for serology, urinalysis, hematology, microbiology, and parasitology. Each technician is specialized in a procedure and each station has its own dedicated equipment and documentation logs. The hematology station uses a ten-year-old Sysymex CBC. The lab has other standard equipment similar to equipment that may be found in a clinical laboratory in a high-resource setting, such as spectrophotometers, refrigerators/freezers, and a water distillation apparatus. They also have sophisticated instruments capable of running multiple parameters simultaneously, such as hormones and various sandwich ELISAs, providing the option of detecting 136 diseases. The use of these devices has cut the turnaround time to same-day results, compared to the past when it took up to a week for results from a lab in Addis Ababa. There is ventilation in place for sputum prep and reading for performing AFB microscopy. No TB cultures are done here, or by the private sector in general. However, they are proposing to acquire MGIT™ and GeneXpert® capabilities in the future. The lab runs on central electricity and also has a substantial generator system that powers the entire hospital during outages.

Constraints

Securing reagents and calibration samples for QA for their sophisticated machinery and hematology machines was difficult in the past. Currently, they are able to acquire QA samples sent from Canada, and procurement of reagents has been streamlined through distributors in Addis. Equipment breakdown is an issue; currently their back-up CBC and electrolyte machines are not functional. They have onsite engineers for servicing basic equipment, but when their more sophisticated equipment fails, servicing can be challenging. In the past, it was difficult to keep Geimsa and Wright’s stains in stock, but now they buy stain from a wholesaler/importer in Addis Ababa.

Mecha district health center (mid-level) This HF is the largest in the district and functions more like a district hospital than a health center. It is open 24 hours and has inpatient wards. They have a separate lab capable of microscopy and other clinical laboratory tests including AFB smears, urine analysis, Kato-Katz for stool, rapid plasma reagin (RPR) test

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for syphilis, hematocrit (Hct), HIV, Widal, Weil-Felix, and pregnancy tests. They have a fluorescent microscope for TB, but their technicians are not yet trained in its use.

This area has had malaria epidemics in the past two or three years, but lately the prevalence has decreased. People suspected of having malaria are seen by clinicians and, after a physical exam, patients are sent to the lab for a BF exam. Usually the patient will wait 30 to 60 minutes for the BF results. Because there are five separate OPDs in this HF, the lab can become congested, which may result in longer wait times for the patient.

The lab has three lab technicians, but in the past they had four; all three technicians are able to read BFs and one staff is available overnight. One technician prepares the smear and stains the slides, and another technician reads the slides. They prepare both thick and thin smears and results are reported semi-quantitatively (+, ++). When the lab becomes congested, about 10 to 15 BFs are batched for staining and reading. In the high season, they read about 100 slides per day and in the low season it is about 60. Eighty% of the time spent on a microscope is for malaria. There is no limit to the number of smears a technician can read in a day. If there is an increase in workload, they will respond by asking HR for additional assistance.

If the BF is positive, appropriate treatment is provided and is dependent on the species with which the patient is infected. If the patient has serious complications, they will be admitted to the wards and will be given pills on discharge. If the patient has severe malaria, they will be given a quinine drip. The clinicians generally trust the BF results, but they are aware of BF-negative results occurring at the tail end of an infection. In this scenario, they repeat testing every 12 hours. They also test for additional infectious agents such as the Widal test, Weil-Felix test (typhus), and relapsing fever. If they are not sure what the infection is and the symptoms are severe, they refer the patient.

They receive Giemsa stain from ICAP and they filter the stain themselves. They rarely run out of reagents, but there are some gaps of certain consumables such as capillary tubes and vacutainers; overall the supply is good. There is a refrigerator and freezer available for reagent storage and a log is kept daily on the temperature. The refrigerator houses the blood grouping reagents, Widal, and RPR, among other tests. The freezer houses reference material and QC smears. Staff from the regional lab come quarterly to pick up smears for QA. They randomly pick both positive and negative smears that the lab has stored.

Lab staff use water from the tap; they would prefer to use distilled water but it is not available (no distillation machine or money to buy distilled water). The tap does not run out of water. If rain water is used, it is not filtered and they do not check the pH of the water they use. They sometimes use a bulb for drying pre- and post-staining; they know this is not recommended, but they do it when workload requires.

The clinic bought its own generator because the power goes out about once a month for around two hours. They have to manually switch on the generator and it takes about five minutes to turn on the power. The generator, which runs on benzene, powers the whole facility, but clinic staff take noncritical instruments offline. This HC has a solar light mirror and LED light for when power is out, and they approve of this system.

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There are two microscopes but only one was working at the time of our visit; the other scope had been down for two months. The technicians report that if cases increase, the lack of the second scope will be a problem. If both scopes break, the technicians would switch to using RDTs until the clinic could use its own funds to buy a new scope. The only thing that the lab technicians disliked about microscopy is when the power goes out and patients complain about time to results. They see no areas where microscopy could be improved.

Constraints

Constraints identified were broken microscopes, heavy workload leading to longer turnaround times and non-air drying of BFs, power outages, and lack of distilled water. Stockouts of consumables not related to malaria diagnosis occasionally occur.

Rural health center in Mecha district (low-level) This HF lies in a high burden area for malaria as it is adjacent to an irrigation canal that provides ample breeding sites for malaria vectors. This HF is wired to accept central electricity, but it is not currently connected to the grid; hence, it functions without electricity.

There is one lab technician on staff, three OPD clinicians (nurses), and one health officer. The lab does not have a microscope. The lab technician collects AFB smears, which are taken to the nearest supporting microscopy center. If a malaria suspect comes to the HC, the clinician will test the patient with an RDT. The lab technician does not perform the RDTs for malaria, but does perform dipstick tests for urinalysis and hemoglobin and pregnancy tests. During the high season they use about 20 RDTs/day, and during the low season use fewer than 10.

They reported false-negative RDTs, but it wasn’t stated how this was determined. When a patient tests RDT-negative, lab staff ask the patient to come back the next day. The clinicians prefer managing patients based on microscopy results reported semi-quantitatively. Therefore, a microscope is desired here to handle the suspected RDT false-negatives from the HPs in the surrounding catchment area. False-positive results are also said to be a problem. If the RDT used is histidine-rich protein-2 (HRP2)–based, they will ask if the patient has recently taken malaria treatment. There are also concerns of false positives due to potential cross-reactivity with other malaria species or with relapsing fever, which is prevalent in this area.

The most common RDT used is from SD Bioline. Lab staff have problems with the buffer; the blister pack does not empty the buffer all the way. They report no problems with using the lancets or vendor switching/protocol changes. To avoid problems with the buffer, they compare the lot number on the buffer with that of the kit to make sure they match. They prefer the individual packaging to the bulk packaging.

This HF participates in the FMOH reporting system, and the data is posted on the clinic wall using a coded system. They collect information on the malaria patient’s travel history, and it is recorded in the patient’s file (not the registry).

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Constraints

Constraints identified include no power, no microscope, problems with the buffer packs, expired kits, and erroneous results of RDTs. Stockout of RDTs occurred at the time of our visit but the lab technician was preparing to be re-supplied later that day.

Kimbaba health center (mid-level) This is a rural HC that supports a number of surrounding HPs. It is part of the MACEPA step 1 program. This HC has a lab that uses microscopy to diagnose malaria. The turnaround time for results is approximately 30 to 40 minutes. They see around 10 patients with fevers per day in the low season, with around a 50% positivity rate. In the high season, they see more than 20 patients per day with a 75% positivity rate. Both thick and thin films are prepared. They batch up to 12 slides at a time and spend about three minutes viewing 100 fields. Reporting is semi-quantitative. When they doubt the results of the BF, they will take another sample in six hours or wait until the next day if fever persists. When the lab is closed at night and on weekends, the OPD uses RDTs. The lab is usually open eight hours a day, five days a week.

There are two lab technicians working at one time. All HC clinicians are trained to use RDTs, but it is usually the supervisor who performs RDTs when the lab is closed. The lab technicians spend more time on the microscope for TB diagnoses than for malaria because TB requires three slides to be read per patient. The lab technicians report that the workload is manageable for two technicians. If given a choice between using microscopy and RDTs, the technicians preferred RDTs because they are easier to use.

They perform QC procedures weekly and whenever there is a new reagent delivery. They keep all known positive and negative slides and perform repeat reads of slides for quality control. They keep both Pf and Pv slides. All slides are stored and are randomly selected to be sent to the regional lab. They send slides to the regional lab via ICAP. This happens every quarter in accordance with the national guidelines, although the process is new and at the time of our visit it had only occurred once.

They currently have malaria surveillance officers stationed here—one supervisor and two assistants—who handle the weekly reporting of the HC and HEW reports from their catchment HPs. Each HEW either brings the data to the HC or it is collected by HC staff going around to each of the HP. The supervisor (a nurse/midwife) aggregates all of the data and submits the weekly RDT reports collected from the HEWs via mobile phone.

The RDT currently in use is from SD Bioline. Lab staff report no problems with vendor switching and state that they have not had a vendor switch in the past two years. If a switch happens, they read the product insert for proper procedure and retrain HEWs on the new RDT format. In order to track time for an RDT run, lab technicians write the time to read on the cassette itself. They report that there is enough room to write the information they need on the cassette (medical record, patient ID, and time). They report no problems manipulating the blood transfer device. They do not suffer from stockouts, and they get their re-supply from the district as needed. They usually get re-supplied every two months from

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PFSA. They are able to balance the need for the HC use of RDTs with those needed at the HP, and re-supply can be obtained within a day.

In general, no major challenges related to microscopy were reported. Power is occasionally interrupted, typically for a four-hour time period once a month; however, in the past, the power supply was disrupted from the lab for a period of one month. They have a solar mirror and solar rechargeable light that they use to read slides on these occasions, and the light source works well if it is properly charged. They do not have problems with microscopes breaking, and the lab has a spare in case of maintenance issues. Giemsa is delivered to the lab pre-prepared and they filter it when needed. They air-dry slides, but have a lamp to dry slides pre- and post-staining only when there is no sun or when the patient load is heavy. Water for staining is obtained from a running water source that is brought to the lab by the cleaners.

Constraints

Several RDT-related constraints were reported by the staff. They reported that occasionally when they collect too much blood the test becomes invalid. Although adding blood to the cassette is not problematic, they reported problems with obtaining blood from a finger prick on calloused hands; they may only obtain a small sample and need to prick another finger. Some RDTs have buffer missing from the package, and when this happens they must use another RDT. This occurs about two or three times per box. One issue reported by the HEWs is that when the buffer in the kit is yellow, the test doesn’t run well. Because of this, they are planning an evaluation to compare RDTs with a matching DBS sample. They report that it is difficult to read the RDT results when the room is not well-lit and they need to use a light to interpret the results. Sometimes they find that a patient will test negative at the HP but test positive at the HC via BF.

Sometimes they receive kits that are within two months of the expiration date. When this happens, a committee is formed that includes members from the district headquarters to discard expired kits; they separate the expired kits from existing stock and place them in another storage area until they can be destroyed or buried on site. They dispose of RDTs in their HC incinerator “hole.” In the future, they plan to use a private organization to take the expired kits out and burn them elsewhere.

Communication with the HEWs at the HPs can be difficult. Reporting data by mobile phones was reported to be difficult as it takes a long time for the application on the phone to open. The clinic landline is broken and staff must often use their own credit on their personal phone. It is challenging for the HC to get the reports; because of a lack of transportation and poor phone service, the HEWs are not always compliant in sending their reports on time.

Kimbaba health post (community-level) This HP is attached to the Kimbaba HC and is open five days a week from 8:00 a.m. to 5:30 p.m. Two HEWs are stationed here. The RDTs in stock are First Response. During the high season, they run 20 to 25 RDTs in a day and about 10 are positive. In the low season they use 10 RDTs per day with around 1 to 3 positives (although occasionally all are positive). During busy times, a maximum of five tests are run at a time. They can get by with one box during the low season but they keep five or six boxes in stock

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during the high season. If they run out of RDTs, the HEW takes public transport (bus) to pick up a re-supply. This trip takes about half a day and the HEW uses a cart and plastic bag to carry them back to the HP.

To track time on the cassette the HEW either writes the time for reading on the cassette or uses a mobile phone to track time. There is adequate space on the cassette and no difficulty writing on it. For reporting requirements, the HEWs record the date, patient name, age, sex, RDT result, treatment provided, and address (the address consists of village and sub-village information only). When a patient comes in for testing, HEWs also ask if there is a sick person in the patient’s house. If there is, they do not provide treatment or visit the index case’s house; rather, they request that the sick person come to the HP for testing.

The HEWs fill out a weekly report and someone goes to the HF to deliver the report to the supervisor. If no one is available to deliver the data, the HEWs submit the report by phone. The surveillance officer does not come to the HP to get the data.

The HP has a fuel-operated refrigerator, but it was not functional during our visit. There is no power in the HP so the HEWs’ mobile phones are charged at a villager’s house for no fee or at their own homes. They get their water from a well or a local borehole. They burn plastics at the HP, and sharps are either carried to the HC by public transport (at the HEW’s personal expense) or buried at the HP.

There are no problems filling the blood transfer device to the calibration line. The First Response blood transfer device is preferred over the SD Bioline version because there are no problems with overfilling. There are no problems transferring blood onto the cassette.

Preference was expressed for individual packaging rather than bulk packaging in order to reduce contamination of the buffer. Even if house-to-house sweeps were done, individual packaging was still preferred. When the HEWs go house-to-house for outreach campaigns (vaccinations), they use an umbrella for protection from the rain and sun. On these campaigns, the HEW carries RDTs and drugs for opportunistic testing of febrile cases. One HEW usually carries 10 RDTs in a plastic shopping bag. For house-to-house testing of malaria, the HEW would need to carry up to three boxes of RDTs and would not be able to do that without help. Some houses are close together but some require significant walking (up to an hour). The HEWs expressed a preference for a backpack over the plastic shopping bag and reported that 5 kg is the maximum weight they could carry in a backpack. The HEWs expressed that most villagers would be amenable to house-to-house testing. However, the HEWs suggested that females may be reluctant to provide a urine or saliva sample.

Constraints

When performing an RDT, the HEWs report no problems taking a finger stick other than difficulties obtaining blood from children under five years of age because of the lancet they use; a trigger-style lancet would be preferred. Children cry whenever they see the HEW. Buffer is occasionally missing from the kit or the plastic bottle for the buffer is empty, so another package must be used. This has happened in both

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the SD Bioline and First Response kits, but it occurs more often with the First Response. When they switch kits, there is no retraining because the procedures between the two systems were stated to be identical. However, the HEWs report that problems arise because the product inserts are in English, which they do not understand. Sometimes the buffer is yellow, which results in poor flow on the cassette and air bubbles. In these cases, the HEW has to repeat tests. This has happened with both brands and the buffer in all kits in stock at the time of our visit was yellow. In addition, they receive kits that are very near the expiration date, sometimes with only two weeks left. Other constraints include stockouts, no cold-storage for RDTs, reporting challenges due to burdensome transport and poor mobile networks, lack of power, and no disposal for hazardous waste.

Challenges

Unknown strategies for elimination Ethiopia is a very ecologically diverse country and harbors many different epidemiological profiles for malaria transmission. In epidemic-prone areas there is significant heterogeneity in transmission risk, and as a result, elimination strategies will not be uniform throughout the country. Each area may require its own unique interventions, which in turn will be delivered progressively until elimination can be achieved. What exactly the strategies will be, and where and when they will be effective, remains to be determined. MACEPA has initiated demonstration studies that stratify various eco-epidemiological zones to identify what strategies may benefit the country in achieving their elimination goals. However, MACEPA is just entering the first phase of their program, which consists of implementing their rapid reporting system. They may find that alternative or modified strategies may be needed in certain areas.

Pf and Pv co-endemicity and G6PD Further complicating the issue is that current strategies are focusing on the elimination of Pf, and are mobilizing communities to assist with elimination campaign activities. However, from the community’s perspective, the concept of malaria elimination is not species specific. Even if Ethiopia is successful in eliminating the remaining pockets of asymptomatic carriers of Pf that are capable of rekindling transmission, many communities will still be afflicted with ongoing Pv transmission. Therefore, communities that are co-endemic with both species must be adequately sensitized to this possibility in order to avoid community fatigue with MDA or MSAT strategies requiring repetitive invasive blood sampling.

In addition, aside from the issue of identifying individuals at risk of hypnozoite carriage, there still remains the issue of achieving a successful radical cure for Pv, which requires the administration of 8-aminoquinoline-based medicines, which are potentially toxic to individuals with G6PD. Prior to the prescription of these drugs, individuals must be screened for G6PD or at the very least, population-based surveys of G6PD-prevalence must be undertaken to identify which areas will require individual screening for G6PD prior to drug administration. The FMOH and EHNRI should be applauded for the initial steps they have taken to analyze DBS samples collected during their MIS for G6PD. Furthermore, promising

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point-of-care screening tests for G6PD are close to entering the market, and guidelines for evaluating their performance have been developed.5 These tests will further assist future campaigns aimed at Pv control and elimination.

Despite the current focus on the development of more sensitive tools to identify sub-patent Pf infections, additional tools will be needed to identify Pv hypnozoite carriers. To date, no biomarkers capable of this have been identified, most notably because of the inability of the scientific community to study this sub-population of Pv parasites in vitro. However, a recent breakthrough in maintaining and activating cell cultures of hypnozoite-like parasites will allow scientists to possibly identify biomarkers capable of identifying carriers of dormant hepatic stages, and possibly to develop compounds capable of activating them so that they are susceptible to less toxic medicinal compounds.6 As promising as this new discovery is, it will require some time before such research efforts are underway, thus leaving Pv-endemic communities with gaps in technologies that can aid in the elimination of this species.

Heat exposure/storage/logistics of RDT delivery Although RDT exposure to extreme heat has been mentioned in reports from other DIAMETER country visits, only in Ethiopia was the problem so readily evident. In nearly every interview, the problem of poor performance of RDTs due to exposure to high temperatures was pointed out. In regions known to have extreme climate conditions, reports of up to 60% of RDT-positive results are called into question. Historical evidence of similar problems with HIV RDTs in the same regions highlights the need for strategies to minimize high heat exposure during transport and storage of RDTs within these regions. Perhaps providing HEWs with better options for kit storage is possible, but there are many reports of kits already being exposed to high heat prior to arrival at HPs (based on the buffer discoloration). One important aspect of any new diagnostic technology intended for use by HEWs is to improve the temperature stability of kits, as well as to provide protection from extreme temperature fluctuations that can occur during transport and storage prior to delivery to the end user.

Another challenging aspect is the timely delivery of kits to HPs. Logistics of delivery should be streamlined so that HPs do not receive kits near their expiration date. This is inherently a problem with the lengthy tender and procurement process; however, increased efficiency in delivery is an achievable goal. Lengthening the shelf-life of a new diagnostic test could mitigate the effects of the lengthy delivery process, so that HPs are not receiving kits that only have two weeks remaining before expiration.

Migrant populations As noted above, the issue of migrant laborers reseeding transmission in malaria-free areas with anophelism is a serious concern, especially as an elimination phase begins. In the north of the country, where malaria is endemic, there is a significant population of agricultural workers that hail from all over Ethiopia. The conditions the laborers work in are ideal for transmission and are very difficult for the delivery of an effective intervention. Conventional control measures are not amenable to these areas because of their remoteness and because the laborers reside outdoors, do not use and are unable to use bed nets, and work at night when exposure to infectious bites is high. There are roughly half a million migrant

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workers moving to these malaria-endemic areas annually and they move from site to site, so control measures aimed at sedentary populations are not feasible. There is a scarcity of water, a lack of nutritious food, and a dearth of health workers/chemists/medicine in these areas (even Coartem is not available), thus making these groups vulnerable to disease and transmission.

To respond to this pressing issue, the Bureau of Labor Affairs (BLA) wants to create awareness of these problems in both the workforce and among the investors/farm owners and to hire health care workers and experts to minimize disease in migrant workers. They hope to make medicines available at farm sites when an outbreak occurs. They feel this may be attractive to investors, as it will increase the productivity of the workforce. The laborers will also benefit, because they are not earning an income while sick from malaria. The BLA realizes they must pull together relevant stakeholders to design successful interventions. In addition, they would like to study the migration patterns of migrant workers to ensure that intervention access to laborers is maximized.

It will be important to determine the role and responsibilities of the investors in sustaining the health of the workforce. Under the current agreement with the Regional Health Authority, the investors have a responsibility to bring in the raw materials for their workers’ well-being, to protect their health, and to provide sanitary conditions for their workers to live in, as well as access to transportation (currently transportation is provided by tractor as there are no roads reaching these areas). At the moment malaria-related illness is not defined as a “work-related injury” and thus investors are not legally required to address malaria control under their current Certificate of Incorporation. Traditionally, the BLA has centered their focus on salary and weekend rest time for laborers; however, they now wish to engage the investors on malaria-related illness as well.

At an upcoming conference, they hope to gather the relevant stakeholders to identify necessary measures to mitigate the impact these laborers have on driving epidemics of malaria in Ethiopia. One possible solution is for the BLA to set up a central information center for workers when they arrive at the area prior to embarking for specific work camps. There they will register their name, where they are from, and their age into a computer system, and worker identification cards will be provided in addition to an orientation on expected employment conditions. This station will also serve as a disembarkation point, prior to their dispersal back to their community, and may serve as a potential test-and-treat location. The center could be staffed by workers who reside in the area on a permanent basis and currently participate in union activities such as resolving conflicts with investors and providing settlements for laborers. These workers could provide sensitization of malaria risk and proposed interventions directly to the laborers during their orientation.

Regardless of the delivery scheme, interventions for the health of laborers will need to be cross-cutting. Services must be offered for HIV, leishmaniasis, onchocerciasis, malaria, and prevention of human trafficking and cross-border migrations. Furthermore, the workers that come to the area each year will not be the same; therefore, repeated sensitization and interventions will be necessary. Additionally, the service centers will still be located 100 km away from many campsites, so outreach activities will be needed to maximize impact.

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Summary

Ethiopia has taken the initial steps in the elimination of malaria; national policies exist for elimination in certain areas by 2015. Strategies to achieve these areas of elimination are in development, and the FMOH has partnered with numerous donor agencies and NGOs for implementing interventions. Furthermore, the country has embarked on demonstration studies aimed to evaluate elimination tactics, has initiated and is scaling up strengthening of QA for PCD of malaria, has instituted a surveillance and reporting system for responding to outbreaks, and has mobilized large portions of the country for MSAT of febrile cases during trachoma MDA campaigns. The foundation for building a capable elimination force has been laid, yet the basic framework can be strengthened.

A strong external validation of imported RDTs exists, yet further integration of these results, aside from basic performance, into the RDT-tender process will prevent the procurement of RDTs from vendors with poor manufacturing histories. This problem may be alleviated with the recent registration of an RDT production facility outside of Addis Ababa. It is possible that this facility may produce affordable RDTs whose quality can be monitored more closely. The development and roll-out of QA strategies for RDT use in the field is warranted, and the NMCP is currently tackling this important issue. The government is fully aware of the risks that migrant workers pose for malaria transmission and the national BLA has taken steps to address the issue.

Technology constraints of the diagnostics used within Ethiopia are not unique; other countries we visited during this assessment share the same shortcomings. Of note was the exposure of RDTs to high temperatures in the lowland areas, which has widely affected the performance of tests in the field. Any new technologies under development should take heed of the stability requirements in areas like these. However, it is quite plausible to assume stability at these temperatures cannot be obtained without added cost or complexity; thus, the FMOH might consider putting strategies in place to mitigate such exposure by enabling HEWs to store RDTs adequately and to streamline transportation and sub-station storage. It was quite clear that any new, more-sensitive diagnostic tests must be placed into the hands of HEWs and, therefore, must take into consideration the technology constraints identified in this report, in particular those found at the HP level. Overall, Ethiopia is well aware of the problems facing their malaria control and elimination activities, and is taking appropriate steps to alleviate them given their current resources.

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References

1 Ethiopia Federal Ministry of Health (FMOH). National Strategic Plan for Malaria Prevention Control and Elimination in Ethiopia 2011–2015. Addis Ababa: FMOH; 2011. 2 Ethiopian Health and Nutrition Research Institute (EHNRI) and partners. Ethiopia National Malaria Indicator Survey 2011. Addis Ababa: EHNRI/FMOH; 2011. 3 Gething PW, Patil AP, Smith DL, et al. A new world malaria map: Plasmodium falciparum endemicity in 2010. Malaria Journal. 2011; 10(378). 4 Gething PW, Elyazar IRF, Moyes CL, et al. A long neglected world malaria map: Plasmodium vivax endemicity in 2010. Public Library of Science Neglected Tropical Diseases. 2012; 6(9):e1814. 5 Domingo GJ, Satyagraha AW, Anvikar A, et al. G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests. Malaria Journal. 2013;12:391. 6 Dembélé L, Franetich JF, Lorthiois A, et al. Persistence and activation of malaria hypnozoites in long-term primary hepatocyte cultures. Nature Medicine. 2014;20(3):307–312.

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Appendix A: List of stakeholders

Name Position

Dr. Adugna Woyessa Associate Researcher II, Federal Ministry of Health (FMOH)/ Ethiopian Health and Nutrition Research Institute (EHNRI)

Mr. Ashenafi Asefa Associate Researcher I, FMOH/EHNRI

Dr. Agonafer Tekalegne Country Director, Malaria Consortium

Dr. Zelalem Kebede Malaria Consortium

Dr. Josef Malone Medical Officer, Resident Advisor, Centers for Disease Control and Prevention (CDC)

Dr. Gunewardena Dissanayake Malaria Advisor, United States Agency for International Development /President’s Malaria Initiative (PMI)

Mr. Sheleme Chibsa Logistics Officer, CDC/PMI

Ms. Hiwot Solomon National Malaria Focal Point, FMOH

Dr. Hailemariam Lemma Malaria Control, FMOH

Dr. James McQuen Patterson Health Specialist, The United Nations Children’s Fund

Dr. Worku Bekele Malaria Cluster Lead, World Health Organization

Dr. Zerihun Tadesse Health Country Representative, The Carter Center

Dr. Tokola Endeshaw Staff, The Carter Center

Dr. Niway Hiruy Staff, The Carter Center

Dr. Tesfay Abraha Director Service Control & Quality Assurance, ICAP

Mr. Firew Bekele Representative, Access Bio. Inc. - Ethiopia

SeungHyeok Cha Supervisor, Access Bio. Inc. - Ethiopia

Endalew Bopale Quality Control, Access Bio. Inc. - Ethiopia

Jaehyeok Jang Supervisor, Access Bio. Inc. - Ethiopia

Belay Bezabih Core Process Owner, Amhara Regional Public Health Emergency Management (PHEM)

A-1

Name Position

Mulat Ademe Mecha District Director, Amhara Regional Health Bureau

Negestat Kone Mecha District Malaria Officer, Amhara Regional Health Bureau

Mulugeta Ademaychu

Mecha District Malaria Officer, Amhara Regional Health Bureau

Edmealem Admasu Core Process Owner, Pharmacist, Amhara Regional Health Bureau

Belaynew Refugee/migrant worker related issues, Bureau of Social Affairs

Abdissa Mengesha Tumie Procurement Specialist, Pharmaceutical Fund Supply Agency (PFSA)

Getacnew Ayenew

Branch Manager, PFSA

Dr. Mekonen Aychiluhem Hospital Director, Gamby Teaching & General Hospital

Sefialem Tadele Staff, Kimbaba Health Post

Mequanint Ayehu Staff, Kimbaba Health Center

Tsedal Eyasu Staff, Kimbaba Health Center

Lab Technician Kimbaba Health Center

Lab Technician Amhara Regional Hospital/Flelege Hiwot Hospital

Clinicians, Lab Technician Mecha Health Center 1 (Rural)

Lab Technician Mecha Health Center (Urban)

Woyneshet Gelaye Yalew Medical Parasitologist, Regional Health Research Laboratory Center

A-2

Appendix B: Use scenarios for malaria diagnostic tests in Ethiopia

B-1

Diagnostics Process Human Resources Infrastructure/SuppliesRural community Rapid

diagnostic tests (RDTs)

• Febrile patient presents to health extension worker (HEW) • RDT using fingerstick sample

• HEWs• General HEW training: One training session per year for RDT use and treatment (Tx) of malaria

• Slides/lancets/spirit/cotton swabs/band aids• Waste and sharps disposal• Phone (for results reporting and/or RDT time-keeping)• Public transport • Pen• Storage space in health post (HP) for RDT, Tx, and waste

• Tx of RDT positive (+) cases with species-specific drugs• Referral of RDT negative (-) cases• Weekly reporting of numbers tested and treated

• Receipt of expired kits• Buffer-related problems with RDTs (missing, discoloration, etc.)• No electricity• No running water• Use of public transport to resupply RDTs, reporting, and waste disposal• Recharge phone at villagers' homes• Young children fear lancet (difficult to get sample, child mistrusts HEW)• RDT product insert in English (only Amharic understood)• Recording Pan+ as Pv +• Long distance walks to houses during vaccination campaigns• Lack of backpack to carry RDTs

Health center (low-level infrastructure with lab)

RDTs • Febrile patient presents to health center • RDT used by clinicians in outpatient department (OPD)• Lab is used for other non-malaria related diagnoses (Dx)

• Lab technicians• Clinicians (nurses, others)

• RDTs• Separate lab used for acid-fast bacillus (AFB) smear collection and basic lab tests• OPD • No electricity (although wired to receive electricity)• Water (tap/rain/well)

• Tx of RDT + cases with species-specific drugs• Retesting of RDT- cases followed by referral if remaining RDT-• Weekly reporting of numbers tested and treated• Travel history taken of RDT+ cases

• No microscope in lab• No electricity despite being wired to receive electricity• RDT buffer packs not emptying all the way• False + and - RDT results• Stockouts require lab technician to use public transport for resupply (same day)

Health center (mid-level infrastructure)

Microscopy,RDTs

• Febrile patients present to OPD• Lab technician collects blood film (BF)• BF sent to lab • 30 minute turnaround time for results from collection• RDT used when lab is closed

• Lab technicians• Clinicians (nurses, others)

• Outpatient department (OPD)• Separate lab• Mains electricity• Microscope• Tap water• Solar mirror and light-emitting diode (LED) light (battery operated)

• Tx of RDT+ cases with species-specific drugs• Retesting of RDT- cases followed by referral of remaining RDT-• Weekly reporting of #s tested and treated• Travel history taken of RDT+ cases

• Broken landline• Long time to open mobile phone program• Network issues• Battery recharging issues• Use of personal phone/credit• Lack of transport to receive data from HP• RDT used when lab is closed• Patients referred to health center are initially RDT- at HP but BF + at health facility• Difficulty obtaining blood from calloused fingers• Too much blood placed onto RDT cassette results in invalid test results• Missing buffer from kit or empty buffer pouches• Buffer discoloration• Difficulty reading RDT results in dark settings (requires torch or LED light)• Receipt of kits near expiration date• Power disruption• Use of lamp to dry slides during adverse weather or heavy patient load• Water is brought to lab

Health center (high-level infrastructure)

Microscopy • Febrile patients present to OPD• Malaria suspects sent to lab• Lab technician collects BF at registration desk• BF sent to lab for staining and reading• 30-50 minute turnaround time for results from collection• Repeat BF testing if clinicians suspect tail end of infection• Differential Dx tests performed (Widal, relapsing fever, etc.)

• Lab technicians• Nurses• Physicians

• OPD and inpatient wards• Separate lab (open 24 hrs)• Tap water• Microscope (solar mirror and LED light)• Electricity (main and generator)• Refrigerators and freezers

• Tx of BF + cases with species-specific drugs• Weekly reporting of #s tested and treated• Severe cases will be admitted to ward• Quinine drip with pills Rx on discharge or referral

• Turnaround time for BF results increases with heavy patient load• One of two microscopes is broken• If both microscopes break down, then switch to RDTs or use own funds to buy another microscope• Stockouts of consumables such as capillary tubes/vacutainers• Preference to use distilled water but do not have access to distiller or funds to buy distilled water• pH of tap water not assessed• Use of bulb to dry slides during heavy patient loads• No limit on number of slides a technician can read in one day

Hospital (public referral)

Microscopy • Febrile patient presents to OPD• Malaria suspects sent to lab• Lab aides collect thick BF at registration desk• Inpatients have BF collected in ward and sent to lab• BF sent to lab for staining and reading• 40 minute turnaround time for results

• Clinicians• Lab aides• Lab technicians• Service engineers

• OPD and inpatient wards• Separate lab• Distilled water and tap water• Multiple microscopes (solar mirror and LED)• Electricity (central and generator)• Refrigerators and freezers• Sophisticated blood and chemistry analyzers

• Thin film BF taken on some thick BF+ slides when requested by physician• Tx of BF+ cases with species-specific drug (when thin film prepared)• Weekly reporting of tested and treated• Severe cases admitted to ward

• Thin films not routinely taken• Occasional use of oven to dry slides when patient load is high• Receipt of poor quality stain (in the past)• Power outages and generator problems• High volume lab so lab technicians are very busy

Hospital (private) Microscopy • Febrile patient presents to OPD• Malaria suspects sent to lab• Lab aides collect thick BF at registration desk• Inpatients have BF collected in ward and sent to lab• BF sent to lab for staining and reading• 40-minute turnaround time for results

• Clinicians• Lab aides• Lab technicians• Service engineers

• OPD and inpatient wards• Separate lab• Distilled water and tap water• Multiple microscopes • Electricity (central and generator)• Refrigerators and freezers• Sophisticated blood and chemistry analyzers

• Pf+ patients provided Tx free of charge• Pv+ patients pay for Tx• BF- patients get extensive work-up and two additional BF• Consistently BF- patients who do not have differential Dx and do not respond to antibiotics are treated empirically for malaria

• Poor reagent quality (in the past)• Poor access to reagents (in the past)

Pass

ive

Case

Det

ectio

nInputs

Use Scenario Setting Outcomes Constraints

B-2

Diagnostics Process Human Resources Infrastructure/Supplies

InputsUse Scenario Setting Outcomes Constraints

Reac

tive

Case

Det

ectio

n Outbreak response (household, central testing within community)

RDTs • Surveillance data from past weeks' surveillance report analyzed• If greater than threshold level, triggers investigative response • If data is accurate, the area is mobilized for active case detection of febrile cases• Community mobilized and people come to get tested at central area or house-to-house sweeps

• Lab technicians• HEWs• Clinicians• Environmental health technicians• Surveillance officers

• Vehicle• RDTs and supplies• Tx• Waste disposal

• Identification of larval breeding sites• Indoor residual spraying and focal spraying of insecticide• Assessment of bednet use • Distribution of new nets• Treat all RDT+ infections

• Small team to monitor and manage outbreaks for such a large area• Reporting system outside of existing health management information system • Labor and resource intensive• Poor network for mobile and landline phone reporting• Mapping software and geographic information system not used (yet)• Missing asymptomatic reservoirs when only testing febrile cases (high cost of RDTs prevents mass screening and treatment)• Exposure of RDTs to high temperature and resultant poor performance• Missing buffer or empty buffer packets in RDT kits