Presence of k13 561H artemisinin resistance mutations in Plasmodium falciparum infections from Rwanda

Aline Uwimana, Noella Umulisa, Meera Venkatesan, Eric S. Halsey, Tharcisse Munyaneza, Rafiki Madjid Habimana, Ryan Sandford, Leah F. Moriarty, Emily Piercefield, Zhiyong Zhou, Samaly Souza, Ira Goldman, Naomi Lucchi, Brian Ezema, Eldin Talundzic, Daniel Ngamije, Jean-Louis N Mangala, William Brieger, Venkatachalam Udhayakumar, and Aimable Mbituyumuremyi presented a poster on “Presence of k13 561H artemisinin resistance mutations in Plasmodium falciparum infections from Rwanda” at the 68th Annual Meeting of the American Society of Tropical Medicine and Hygiene. Their findings follow.

Artemisinin-based combination therapy (ACT) is the recommended first-line antimalarial for uncomplicated Plasmodium falciparum infection in Rwanda. With the emergence of artemisinin and partner drug resistance in the Greater Mekong sub-region, it is important to characterize the presence of polymorphisms in k13, a gene associated with artemisinin resistance, and in pfmdr1, a gene associated with susceptibility to partner drugs including lumefantrine.

To date, there have been sporadic reports of validated k13 markers in Africa. Adequate efficacy (94-97%) for the ACT artemether-lumefantrine (AL) was found in a therapeutic efficacy study (TES) conducted in three Rwandan sites (Masaka, Rukara and Bugarama) in 2018. TES clinical results are presented in poster LB-5134. Dried blood spots collected from the 2018 TES were characterized for artemisinin resistance-associated k13 molecular markers and 8 flanking microsatellites to assess genetic profile and diversity, along with mutations in pfmdr1.

Methods: DNA was isolated from day 0 and day of recurrence dried blood spots from a 2018 TES of AL conducted in 3 sites in Rwanda and analyzed by Sanger sequencing for resistance markers in the k13 and pfmdr1 genes.

Prevalence of k13 candidate and validated artemisinin resistance markers was calculated using day 0 samples. Presence of k13 markers post-treatment was determined using samples collected on the day of recurrence. 8 flanking microsatellite markers downstream and upstream of k13 were evaluated and compared with previously published results from samples from Thailand1.

Results of Prevalence of k13 561 were derived from HDNA from 219 of 228 day 0 samples and all 37 post-treatment samples were successfully isolated from dried blood spots. 26 of 219 day 0 samples showed presence of the 561H mutation in the k13 gene, a World Health Organization validated marker of artemisinin resistance (ref). 3 of the 26 were mixed infections with wild type (561R/H).

*WHO definitions2: Suspected endemic artemisinin resistance is defined as

  • • ? 10% of patients with a half-life of the parasite clearance slope ? 5 hours after treatment with ACT or artesunate monotherapy; or
  • • ? 5% of patients carrying k13 resistance-confirmed mutations; or
  • • ? 10% of patients with persistent parasitaemia by microscopy at 72 hours
    Confirmed endemic artemisinin resistance is defined as
  • • ? 5% of patients carrying k13 resistance-confirmed mutations, all of whom have been found to have either persistent parasitaemia by microscopy on day 3 or a half-life of the parasite clearance slope ? 5 hours after treatment

Additional k13 data found 8 of 37 post-treatment samples with k13 561H in 4 recrudescences (all also with 561H on day 0) and in 4 reinfections. Candidate k13 resistance marker 469F found in 3 day 0 samples (2 in Rukara, 1 in Bugarama) Candidate k13 resistance markers 441L and 449A found in 1 day 0 sample each (Masaka and Rukara, respectively)

In conclusion, k13 561H, a validated marker of artemisinin resistance, was found at a prevalence of 1-20% amongst 3 TES sites in Rwanda. This is the highest proportion of artemisinin resistance-confirmed k13 mutations reported to date in Africa. The overall efficacy of AL was high in all sites (>90%; see poster LB-5134). However, parasitemia on day 3, a proxy for delayed parasite clearance, ranged from 0-15% across sites. Together with the presence of k13 561H, our results indicate confirmed artemisinin resistance in one site, Masaka, and suspected resistance in another, Rukara.

Flanking microsatellites indicate that the k13 561H mutation likely arose locally as opposed to being introduced from Southeast Asia. k13 mutations are present against a high background prevalence of pfmdr1 N86 and D1246, associated with reduced susceptibility to lumefantrine4.

These results indicate that although AL remains an effective treatment of uncomplicated malaria in Rwanda, artemisinin resistance may be emerging. Continued monitoring and confirmation of suspected resistance is critical. Future studies will include an expansion of TES sites and frequent parasite sampling to assess parasite clearance rates, in addition to molecular analysis.

References

  1. Talundzic et al 2015. Selection and Spread of Artemisinin-Resistant Alleles in Thailand Prior to the Global Artemisinin Resistance Containment Campaign PLoS Pathogens 11(4)
  2. WHO 2017. Status report on artemisinin and ACT resistance
  3. Ishengoma et al 2019. Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria and prevalence of Pfk13 and Pfmdr1 polymorphisms after a decade of using artemisinin-based combination therapy in mainland Tanzania Malaria Journal 18(1):88.
  4. Venkatesan et al 2014 . Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine. AJTMH 91(4)

Contact information: Dr. Aline Uwimana <aline.uwimana@rbc.gov.rw> and Dr. Meera Venkatesan <mvenkatesan@usaid.gov>

Affiliations: Malaria and Other Parasitic Diseases Division, Rwanda Biomedical Centre, Kigali, Rwanda; Maternal and Child Survival Program/JHPIEGO, Baltimore MD, USA; US President’s Malaria Initiative, Washington DC, USA; US President’s Malaria Initiative, Atlanta, Georgia, USA; Malaria Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; National Reference Laboratory, Rwanda Biomedical Centre, Kigali, Rwanda; US Peace Corps, Kigali, Rwanda; US President’s Malaria Initiative, Kigali, Rwanda; WHO Rwanda Office, Malaria and Neglected Tropical Diseases Programs, Kigali, Rwanda; The Johns Hopkins University, Bloomberg School of Public Health, Department of International Health, Baltimore, MD, USA

Improving the Quality of Malaria Case Management and Malaria Prevention During Pregnancy in Public Health Facilities in Burkina Faso

Thierry D. A. Ouedraogo, Ousmane Badolo, Mathurin Dodo, Bonkoungou Moumouni, Youssouf Sawadogo, Dao Blami, and Stanislas Nébié presented a poster entitled “Improving the Quality of Malaria Case Management and Malaria Prevention During Pregnancy in Public Health Facilities in Burkina Faso” at the 68th Annual Meeting of the American Society of Tropical Medicine and Hygiene. Their findings are shared below.

Background: In 2017, malaria was the leading cause of medical consultation (43.34%), of hospitalization (44.05%) and of death (16.13%) in Burkina Faso. The disease mostly kills children under five years and pregnant women. One objective of the National Malaria Control Program (NMCP) is to contribute to improving the health of the population by reducing malaria mortality rate by at least 40% compared to 2015 in Burkina Faso by the end of 2020.

In order to achieve that, the NMCP revised the malaria treatment guidelines in 2014 to take into account WHO guidelines on malaria case management and conducted training in primary health care facilities. NMCP implemented a one-day orientation training in district and regional hospitals since 2015, with the support of the PMI Improving Malaria Care Project.

Health Care Providers Training: The training of health care providers was carried out in several 5-days sessions at health districts level. It was aimed at strengthening their skills in the prevention and management of malaria cases in Primary health centers (CSPSs) according to the revised guidelines. 1,819 providers (633 females, 1,186 males) have been trained on the updated malaria prevention and control guidelines in 53 districts during this period.

The training covered the definition and epidemiology of malaria, malaria drug prevention, biological diagnosis of malaria, of uncomplicated malaria cases management, severe malaria case management, healing assessment and health education, monitoring and evaluation. Clinical learning sessions on uncomplicated and severe malaria case management have allowed providers to practice treatment themselves.

The goal of the project was To assess the diagnosis and case management of uncomplicated and severe malaria according malaria guideline in the various health facilities in Burkina Faso in 2017. A cross-sectional study was conducted in 2017 to assess the quality of malaria treatment and prevention during pregnancy in public health facilities.

Submission of protocol Ethics Committee included Information of the surveyed structures and Information to respondents & verbal agreement. The team also worked to provide Quality assurance, Investigator training, Supervision of data collection and Development of guidelines for data collection.

Data processing began with Data review. Data entry used Epi Info input 7.2.2.6. The Data collection period ran from 17-30 September 2018. The assessment focused on the malaria diagnosis and treatment. A comparative analysis of 2015 and 2017 data was done to understand trends.

Challenges included The lack of regional and district regular supervision and
The treatment of presumptive cases without confirmation. The non-application of the treatment protocol for severe malaria occurred in some case and as were variations in doses and duration of treatment. There was some stock-out of drugs for the treatment of uncomplicated and severe malaria.

Overall there was an increase in correct procedures, and IMC project has strongly contributed to this success by training health care providers since 2015, by regularly monitoring the implementation of malaria control guidelines during supervision, and by ensuring the availability of supplies at all levels

Recommendations include Ensuring the effective implementation of national guidelines for malaria management according to levels of care and the availability of supplies for the diagnosis, treatment and prevention of malaria during pregnancy at all levels.

In Conclusion, The results of the evaluation show that all health centres surveyed (50/50) have the capacity to diagnose (confirm cases) and treat malaria cases. At the end of the study, the results indicate that progress has been made in the diagnosis and treatment of malaria from 2015 to 2017.

*Affiliation: PMI Improving Malaria Care Project; Jhpiego Burkina Faso. This poster was made possible by the generous support of the American people through the United States Agency for International Development (USAID) under Cooperative Agreement No. AID-624-A-13-00010 and the President’s Malaria Initiative (PMI). The contents are the responsibility of the authors and do not necessarily reflect the views of USAID, PMI or the United States Government.

Use of Malaria Service and Data Quality Improvement in Mwanza Tanzania

Emmanuel Lesilwa, Goodluck Tesha, Jasmine Chadewa, Agnes Kosia, Zahra Mkomwa, Bayoum Awadhi, Gaudiosa Tibaijuka, Rita Noronha, Dunstan Bishanga, Lusekelo Njonge, Frank Chacky, Abdallah Lusasi, Ally Mohamed, Chonge Kitojo, and Erik Reaves presented a poster entitled “Use of Malaria Service and Data Quality Improvement (MSDQI) Tool in Cascaded Supervision Approach Improved Quality of Malaria Services – Experience from Mwanza, Tanzania” at the 68th Annual Meeting of the American Society of Tropical Medicine and Hygiene. Their findings are shared below.

Inadequate quality of malaria service and data has been one of the problems in Mwanza region due to high malaria prevalence, inadequate knowledge of supervisors and standardized supervision tool. In 2017, NMCP and stakeholders developed malaria services and data quality improvement (MSDQI) tool to guide supervisors. The tool comprises of seven modules addressing performance of Malaria Case Management with indicators weighted against a standard score. Any facility scoring below 50% of the overall score is deemed poorly performing, 50%-75% moderate and above 75% good performance.

What is Malaria Service and Data Quality Improvement (MSDQI)? It is a checklist to guide supportive supervision teams in evaluating the quality of malaria services at the health facility level. MSDQI helps with the:-

  • Monitoring and evaluation
  • Facility-based malaria performance indicators
  • Provision of timely, accurate information and data for decision-making at district, regional, and national levels

In the attached graphs we present the Number of malaria test among OPD cases and the Number of malaria test among OPD cases which increased from 527,734 in 2016 to 1,241,990 in 2018 in Mwanza region. This resulted to the decrease of patients treated without malaria confirmatory test.

After intervention with MSDQI, there was a Decline in proportion of malaria cases clinically diagnosed and treated in Mwanza Regions reduced from 6.5% cases in 2016 to 0.1% cases in 2018

Good progress in IPTp2 and IPTp3 Coverage in Mwanza region was also documented. IPTp2 increased from 37.6% in 2016 to 72.3%, while PITp3 increased from 1.2% in 2016 to 48.5% in 2018.

There was Increased coverage of LLINs in pregnant women and infants.
Increased coverage of LLINs in Pregnant women went from 4.9% 2016 to 75.6% in 2018. Likewise that for Infants increased from 2.9% 2016 to 65% in 2018.

Several Lessons were Learned. Cascaded supervision approaches contribute to improved quality of malaria service provision and hence improved malaria indicators. The Way forward is to Continue using cascaded supervisors to improve quality of data and malaria services through MSDQI

*Affiliation: : USAID Boresha Afya Lake and Western Zone – PATH; USAID Boresha Afya Lake and Western Zone –Jhpiego; National Malaria Control Programme-Tanzania Ministry of Health, Community Development, Gender, Elderly and Children, Tanzania; US President’s Malaria Initiative-United States Agency for International Development

This presentation was made possible by the generous support of the American people through the United States Agency for International Development (USAID). The contents are the responsibility of the USAID Boresha Afya and do not necessarily reflect the views of USAID or the United States government

Systematic Approach to the Review of Malaria Management Guidelines Ghana, 2019

Mildred Komey Akosua,* James Sarkodie, Kezia Malm1 Raphael Ntumy, and Gladys Tetteh presented a poster entitled “Systematic Approach to the Review of Malaria Management Guidelines Ghana, 2019” at the 68th Annual Meeting of the American Society for Tropical Medicine and Hygiene.

The primary objective of the Ghana NMCP is to reduce morbidity & mortality due to malaria through effective strategies. Implementation of these effective malaria control strategies depends largely on the availability of up-to-date, evidence-based, and standardized reference materials to guide and improve practice. Guidelines for the management of malaria in Ghana, including the anti-malaria drug policy (ADP), guidelines for case management of malaria (CM) and guidelines for malaria in pregnancy (MiP) were last updated in 2014. The 2014 review took over six months and left behind no documented methodology to guide subsequent reviews.

The World Health Organization recommends a comprehensive review every five years. In order to make the 2019 review process concise, efficient and reproducible, the NMCP with support from the PMI Impact Malaria project outlined a methodical approach to the review.

The process established an oversight review committee; identified all stakeholders relevant to update the ADP and guidelines; prepared a reference package of technical resources and research findings; nominated experts and allocated them to topic-specific technical working groups (TWGs). (Fig 1)

Then, a series of TWG consultative meetings were held with clearly defined processes and outputs, and independent external experts and potential end users of the guidelines ratified the draft guidelines. (Fig 2 and Fig 3)

A final phase included development of training content, training manuals, and development of key job-aids. (Fig 4 and Fig 5) Costs for the review process were identified and funding obtained.

All components of the 2019 process were enhancements to the unrecorded 2014 review. The process resulted in a documented and costed methodological approach, an up-to-date ADP, MiP and CM guidelines, training curriculum, training manuals, and job aids; all developed in a timely and efficient manner over a three-month period.

It also resulted in an approach for achieving minor policy and guideline updates between comprehensive five-year reviews. Using a systematic well-defined comprehensive approach with clear expectations for inputs, process, outputs, roles, timelines, costs, and sequelae actions, results in up-to-date widely accepted policies and guidelines whose implementation can be easily operationalized, with mechanisms for minor guideline updates between comprehensive five-year reviews.

*Author affiliations: Ghana National Malaria Control Programme, PMI Impact Malaria Project, Jhpiego

TWITTER.COM/IMPACT_MALARIA; IMPACTMALARIA.ORG

Retention of malaria technical and training knowledge and skills by master mentors and general trainers in Myanmar

Ni Ni Aye,* San Kyawt Khine, May Aung Lin, Saw Lwin, Khin Than Win, Khin Lin, May Sandi Htin Aung, and Wyut Yi Shoon Lai Wai presented a poster on “Retention of technical and training knowledge and skills by master mentors and general trainers in three States/ Regions in Myanmar” at the 68 Annual Meeting of the American Society of Tropical Medicine and Hygiene. Their findings are shared below.

The National Malaria Control Program  of Myanmar aims to achieve malaria elimination through equitable and universal access to effective preventive and curative services to all at-risk populations in coordination with communities, national and international non-governmental organizations and other stakeholders.

The PMI-funded Defeat Malaria project supports the National Strategic Plan’s objective to reduce the malaria burden and contribute to malaria elimination in part through capacity development of integrated community malaria volunteers (ICMVs), a new type of cadre introduced in 2017.

Specifically, Defeat Malaria aims to improve this new cadre’s knowledge and skills in malaria epidemiology, prevention, and case management through a community-based intervention approach. 16 State/Regional (S/R) level master trainers (MTs) were trained from Kayin and Rakhine States and Tanintharyi Region, 13 of whom then trained 55 general trainers (GTs) in the same S/R to build the capacity of ICMVs.

Goals of the PMI Defeat Malaria Project (15 August 2016 – 14 August 2021) are to Reduce malaria burden, and to Control artemisinin-resistant malaria in target area Eliminate malaria in Myanmar. The Objectives of Defeat Malaria are to Ahieve universal coverage of at-risk populations, Strengthen malaria surveillance system, Enhance provider technical capacity and Promote community and public- and private-sector involvement in malaria control and elimination.

The specific Objectives of this study were To develop a cadre of core trainers with updated knowledge and skills in community based interventions to carry out cascade training of ICMVs in 3 S/R. It also aimed To evaluate the retention of knowledge and skills in malaria interventions and training techniques pre-training, immediately post-training, and at 9 months post-training, and in the process To improve training skills (facilitation, demonstration and coaching) during subsequent trainings.

Methodology For Master Mentors (MM) was a 5-day technical update session on malaria epidemiology, prevention and case management through a community-based intervention approach was conducted, followed by 5-day training skills course. For the general trainers (GT) a 5-day technical update and training skills course was provided.

Pre-training, immediate post-training and 9-month post-training malaria knowledge assessment was conducted using multiple choice questions. At the 9-month point a post-training assessment of training skills (facilitation, demonstration and coaching) using standardized checklists was undertaken.

In Conclusion, Master mentors who have basic knowledge of malaria technical and training skills became knowledgeable and competent on both skills (i.e. those from State/Regional level). Training modules on coaching skills need to be practiced more in TOT so that General Trainers can improve their skills. Project staff should emphasize why use of checklists to improve training skills is important, as this is a new element for local staff.

MM need continuous coaching to retain updated knowledge on malaria technical skills and their facilitation and coaching skills during the TOT and subsequent trainings. MM who are selected from district level and all General Trainers from Township level need even more practice and support. Project staff need to work with local NMCP staff as they learn coaching and mentoring in technical and training skills of GTs during their supervision visits to ICMVs at village level.

Actions taken in Project Year 3 (2018-2019) were based on assessment findings. MM and GT need more coaching after training to maintain knowledge and training skills. Selection of Master Mentors from State/Regional levels with knowledge of malaria and training skills improves retention of knowledge and skills post-training.

Township level NMCP staff had more time to conduct trainings than the Township Medical Officer so they will be prioritized for further trainings. Translations of knowledge tests for training skills were improved and were more understandable to participants. Project staff increased their support to local NMCP staff during supportive supervision visits to improve their coaching and mentoring skills, which are new skills for most.

Next Steps include Further assessments of knowledge and skills retention will be done for MM and GT 6 – 9 months post training. The project will continue support of NMCP staff as they support GT in subsequent trainings and supportive supervision for ICMV. Translation revisions of the training manuals, particularly knowledge assessments, will continue to ensure that language barriers are addressed.

*Affiliation: Jhpiego/Myanmar, PMI Defeat Malaria Project; University Research Co., Myanmar, PMI Defeat Malaria Project; Myanmar National Malaria Control Program

This poster is made possible by the generous support of the American people through the United States Agency for International Development (USAID) under the terms of its Cooperative Agreement No. AID-482-A-16-00003 and the USAID Defeat Malaria Project. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID, PMI or the United States Government.

Improved Uptake of Malaria in Pregnancy Indicators: A Case from USAID Boresha Afya Project, Lake & Western Zone, Tanzania

Zipporah Wandia,* Jasmine Chadewa, Agnes Kosia, Goodluck Tesha, Lusekelo Njoge, Zahra Mkomwa, Dunstan Bishanga, Rita Noronha, Bayoum Awadhi, Gaudiosa Tibaijuka, Chonge Kitojo, Erik Reaves, and Abdallah Lusasi presented a poster entitled “Improved Uptake of Malaria in Pregnancy Indicators: A Case from USAID Boresha Afya project, Lake & Western Zone, Tanzania” at the 68th Annual meeting of the American Society of Tropical Medicine and Hygiene. Their findings are seen below.

Magnitude of Malaria in Pregnancy: Malaria in pregnancy (MiP) has been recognized as a major public health concern. It is contributing to poor maternal and newborn health outcomes. In Sub-Saharan Africa, up to 20% of stillbirths are attributable to MiP and contributes to an estimated 10,000 maternal deaths and 100,000 infant deaths each year (Desai M. ter Kuile et al 2018).

Tanzania implements a three-pronged approach to prevent the adverse effect associated with MiP as recommended by WHO including 1)Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine, 2) Use of long-lasting insecticide-treated bed nets (LLINs), and 3) Strengthened Case management with Prompt diagnosis and treatment.

USAID Boresha Afya Lake and Western Zone Project supports Ministry of Health through the National Malaria Control Program to implements its strategies targeted to improve MiP in seven project supported regions. The Project uses the malaria data dashboard to identify facilities with gaps through:

  • Malaria Service Data Quality Improvement (MSDQI)
  • Supportive supervision
  • On job training and mentorship to capacitate health care providers to provide quality MiP services to improve indicators performanc

Results: USAID Boresha Afya Project in collaboration with the National Malaria Control Program(NMCP) and involvement regional and council health management teams improved uptake of IPTp and MiP indicators in seven regions supported by the project
Improved documentation in Health Management Information System Book 6  and the Antenatal care (ANC) register used in Tanzania’s health facilities. Quarterly follow-up and mentorship for health care workers at ANC were completed between 2016–2018 in 1817 (100%) health facilities.

Uptake of both IPTp2 and IPTp3 increased steadily as seen in the two graphs. The increase between 2016 and 2019 was from 50% to 80% for IPTp2. IPTp3 increased 0 to 63%. General support to antenatal care where IPTp is given resulted in an increase in those women attending for the first time in their first trimester: 15% to 34% over the same time period.

Testing of pregnant women for malaria rose from 75% to 99%. During the period an average of 10% of women tested positive and were given appropriate malaria treatment.

Lessons Learnt: The improvements in MiP indicators in the Project supported regions is partly attributed to:

  • Commitment among health care workers
  • Mentorship and proper documentation
  • Improved the overall quality of ANC services in the supported regions

*Affiliation: USAID Boresha Afya Project – Jhpiego Tanzania; USAID Boresha Afya Project – Path Tanzania; National Malaria Control Programme-Tanzania Ministry of Health, Community Development, Gender, Elderly and Children, Tanzania; US President’s Malaria Initiative-United States Agency for International Development

This presentation was made possible by the generous support of the American people through the United States Agency for International Development (USAID). The contents are the responsibility of the USAID Boresha Afya and do not necessarily reflect the views of USAID or the United States government.

Malaria Case Management Practice and Elimination Readiness in Five Elimination Districts of Madagascar, 2018

Anjoli Anand,* Favero Rachel, Catherine Dentinger, A. Ralaivaomisa, S. Ramamonjisoa, Elaine Razafimandimby, Jocelyn Razafindrakoto, Katherine Wolf, Laura C. Steinhardt, Julie Thwing, Bryan K. Kapella, M. Rabary, Sedera Mioramalala, Jean Pierre Rakotovao presented a poster on “Malaria Case Management Practice and Elimination Readiness in Five Elimination Districts of Madagascar, 2018” at the 68th Annual Meeting of the American Society of Tropical Medicine and Hygiene. Their findings are shared below.

Madagascar’s Malaria National Strategic Plan 2018-2022 calls for progressive malaria elimination beginning in low-incidence districts (< 1 case/1000). Although an elimination plan has not yet been developed, optimizing access to prompt diagnosis and quality treatment will be its foundation, along with improving outbreak detection and response, and developing an elimination plan.

There was need to understand current practices in preparation for elimination such as estimating current implementation readiness, documenting current diagnosis and treatment practices (case management), Assessing the use of data to inform decision-making and determining the availability of commodities, training and supervision. To assess this readiness and inform planning, we surveyed health facilities (HFs) and communities.

In September 2018, we randomly selected 35 HFs in 5 of the 8 districts identified for elimination, surveyed 41 HWs and 34 community health volunteers (CHVs), and observed 300 clinical encounters between HWs and patients of all ages. Quantitative and qualitative tools were used to collect data. There were a health facility checklist, an interview guide for health facility providers, a clinical observation guide, a community health volunteer CHV) interview guide, and a stakeholder interview guide.

To evaluate elimination readiness, a composite score was assigned to each HF catchment area that incorporates all survey responses based on commodity availability, malaria CM practices, data management, and supervision practices.

In preliminary results, 8 of 34 (24%) CHVs reported that they do not manage children under 5 years (CU5) with fever at the community level. Of 26 CHVs who care for CU5, 18 (69%) identified history of fever as a criterion for suspected malaria, 20 (77%) reported using a malaria rapid diagnostic test (RDT) when evaluating patients reporting fever, and 15 (58%) reported giving antimalarials for a positive RDT. Among treating CHVs, 13 (30%) reported having RDTs, and 11 (42%) reported having antimalarials currently available. A

Among facility-based HWs, 83% identified history of fever as a criterion for a suspected case. Of 120 patients with reported or recorded fever, 56 (47%) were tested with an RDT. Five RDTs were positive; a first-line antimalarial was prescribed to 4 of those patients. This evaluation is a baseline for CM performance as Madagascar establishes elimination targets. In the evaluated districts, CM could be improved by strategies to increase testing at CHV and HF levels and address availability of commodity stocks in the community.

*Affiliations: Epidemic Intelligence Service, Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, United States; Maternal Child Survival Program, Washington, DC, United States; US President’s Malaria Initiative; US Centers for Disease Control and Prevention, Antananarivo, Madagascar; Maternal Child Survival Program, Madagascar, Antananarivo, Madagascar; Maternal Child Survival Program, Antananarivo, Madagascar; US President’s Malaria Initiative, Antananarivo, Madagascar; Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, United States; National Malaria Control Program, Antananarivo, Madagascar

mMentoring, a New Approach to Improve Malaria Care in Burkina Faso

Moumouni Bonkoungou,* Ousmane Badolo, Youssouf Sawadogo, Stanislas Nebie, Thierry Ouedraogo, Yacouba Sawadogo, William Brieger, Gladys Tetteh, and Blami Dao presented their work on “mMentoring, a New Approach to Improve Malaria Care in Burkina Faso” at the 68th Annual Meeting of the American Society of Tropical Medicine and Hygiene as seen below.

Malaria is the leading cause of consultation (43.3%), hospitalization (44.1%) and death (16.1 %) in Burkina Faso. In the Sahel Region, the case fatality proportion due to malaria is 2% compared to 0.8% for the national average. This region is most affected by malaria than others. Also, the Sahel Region is currently experiencing high levels of insecurity making movement of health teams difficult and unsafe.

mMentoring is the use of mobile technology to ensure capacity building and continuing education among health staff. The process started by a workshop to develop messages, and briefing of the main actors.

Each week, messages and quizzes (An automatic answer is sent to each quiz) are sent to 753 providers (nurses, midwives, medical doctors) of the 115 health centers in the Sahel Region. Each month, messages are revised by a team at national level before being sent.

The messages sent were related to several key malaria prevention and control interventions, such as case definition, parasitological diagnosis, clinical case management of simple and severe cases, intermittent preventive treatment in pregnancy (IPTp), pre-referral treatment with rectal artesunate in children under 5 years, insecticide-treated bed nets.

After 10 months of implementation, 64 reinforcement messages on case management and prevention guideline and 63 quizzes were sent. Proportion of correct responses to the quizzes ranged from 43% and 96%. The lowest scores related to topics on management of severe cases while the highest were related to diagnosis of malaria.

The participation rate (number of respondents of the 753 targeted health workers) is on average 22% with 71% of participants from primary health facilities. Also, we notice IPT3 increased from 14.8% in the quarter 3 of 2017 to 45.6% in the same quarter of 2018 (with mMentoring).

The rate of performance of rapid diagnostic tests (RDTs) rose from 67.5% to 77.8%. The case fatality rate during this quarter of 2017 was 3.3% and 1.8% in 2018. As a real platform for continuing training, it would be wise to extend this approach to other regions of the country and also to other health actors like community health workers.

 

 

 

 

 

*Affiliations: PMI Improving Malaria Care Project, Ouagadougou, Burkina Faso, Ministry of Health, National Malaria Control Program, Ouagadougou, Burkina Faso, Johns Hopkins University, Baltimore, MD, United States, Jhpiego Baltimore, Baltimore, MD, United States

Reduction in malaria-attributable deaths following a rectal artesunate pre-referral treatment pilot in Burkina Faso, 2018

Ousmane Badolo,* Stanislas Nébié, Youssouf Sawadogo, Thierry Ouedraogo, Bonkoungou Moumouni, Mathurin Dodo, Lolade Oseni, Gladys Teteh, and William Brieger, presented a poster entitled, “Reduction in malaria-attributable deaths following a rectal artesunate pre-referral treatment pilot in Burkina Faso, 2018,” at the 68th Annual Meeting of the American Society of Tropical Medicine and Hygiene.

Background: In 2017, 4.32 percent of malaria cases were documented as severe malaria in Burkina Faso. The National Case Management Guidelines (August 2017) recommends that the First line treatment for severe malaria be injectable artesunate except in pregnancy where injectable quinine is used for the 1st trimester and injectable artesunate used for the 2nd and 3rd trimesters.

The guidelines recommend pre-referral treatment of severe disease at peripheral health facilities using rectal artesunate for children under 5, parenteral artesunate, artemether, or quinine for older children and adults. The guidelines also recommend pre-referral treatment of severe disease by community health workers with rectal artesunate for children under 5 only. The National Malaria Control Program is currently piloting pre-referral rectal artesunate for children under five years of age by CHWs in three districts in North and Sahel regions, where malaria mortality is the highest.

Results: Comparison Severe Malaria cases and death among <5 before and after the pre-referral treatment in Sahel region is seen in the Table. Pre-referral treatment was able to reduce fatality by 45%.

Comparison of monthly fatality of severe malaria among <5 year (October 16 to April 17; October 17 to April 18 and October 18 to April 19) in the Sahel region is seen in the Graph. This shows a substantial decline in severe malaria following introduction ofthe  pre-referral rectal artesunate pilot.

Several Lessons were Learned based on the Encouraging preliminary results. The involvement of the community in health activities allows good visibility of the intervention resulting in good acceptability and adherence. The community can take charge of its own health if it is well supervised. Good functionality of the “canary fridge” device when used in hot areas.  Ability to use other meeting and supervisory opportunities to implement the strategy.  Challenges identified can be corrected by close monitoring.

Insecurity in Northern Burkina Faso is a major constraint, but pre-referral treatment of severe malaria is needed to decrease mortality from malaria. Despite implementation difficulties, this experience has contributed to a reduction in deaths due to severe malaria in the Sahel region, which is also facing increasing insecurity.

An evaluation of the implementation with data collection for a one-year implementation period will provide lessons for the national scale up of pre-referral artesunate implementation.

*Affiliations: PMI Improving Malaria Care Project, Jhpiego Baltimore, MD, United States, Johns Hopkins University, Baltimore, MD, United States

This poster was made possible by the generous support of the American people through the United States Agency for International Development (USAID) under Cooperative Agreement No. AID-624-A-13-00010 and the President’s Malaria Initiative (PMI). The contents are the responsibility of the authors and do not necessarily reflect the views of USAID, PMI or the United States Government.

Efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum infection in Rwanda, 2018

The Efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum infection in Rwanda, 2018 was investigated by Aline Uwimana, Noella Umulisa, Eric S. Halsey, Meera Venkatesan, Tharcisse Munyaneza, Rafiki Madjid Habimana, Ryan Sandford, Leah Moriarty, Emily Piercefield, Zhiyong Zhou, Samaly Souza, Naomi Lucchi, Daniel Ngamije, Jean-Louis N Mangala, William Brieger, Venkatachalam Udhayakumar, Aimable Mbituyumuremyi.* The results were presented at the 68th Annual Meeting of the American Society of Tropical Medicine and Hygiene and are seen below.

Background: In Rwanda, there were 4,195,013 confirmed malaria cases and 341 malaria-related deaths in 2018[1]. Regular monitoring of artemisinin-based combination therapy efficacy is important to assess drug efficacy and for timely detection of the emergence of antimalarial drug resistance. In Rwanda, national policy is to routinely monitor the first-line antimalarial per World Health Organization (WHO) guidelines[2] The most recent therapeutic efficacy results in Rwanda showed an efficacy of the first-line antimalarial, artemether-lumefantrine (AL), of >97% in Masaka and Ruhuha in a study conducted from 2013 to 2015[3]

Methods: This was an Efficacy trial based on the standard WHO in vivo protocol[2]. Three sites (see map) were selected in Rwanda. Artemether-lumefantrine (AL) was given twice daily; each dose given under observation for 3 days. Participants were treated with AL and followed for 28 days from March 2018 to December 2018.

PCR correction, differentiating recrudescence from reinfection in late treatment failure samples, was performed using genotyping of seven neutral microsatellites. Microsatellite data were analyzed using a previously published algorithm that assigns each late treatment failure a posterior probability of recrudescence[4]

  • Primary Endpoint: 28-day PCR-corrected efficacy
  • Secondary Endpoints: 28-day uncorrected efficacy, day 3 parasitemia

PCR-corrected and uncorrected efficacies are seen to the left.  Kaplan Meier Curves are presented. Uncorrected (top) and PCR-corrected (bottom) survival functions for time until failure for a 2018 therapeutic efficacy study using artemether-lumefantrine in three Rwandan study sites; ACPR: adequate clinical and parasitological response. Day 3 Parasitemia was identified. Two sites, Masaka and Rukara, had > 10% of subjects with parasites detectable on day 3, a WHO criteria for suspected artemisinin resistance.

With PCR-corrected efficacies greater than the 90% cut-off recommended by WHO, AL remains an effective antimalarial to treat uncomplicated P. falciparum in Rwanda
More than 10% of subjects had day 3 parasitemia at two sites; the relationship with this finding and k13 mutations observed in this study was presented in ASTMH poster LB-5295 (Friday, November 22, 2019).

Periodic antimalarial efficacy monitoring in Rwanda should be maintained, and future studies should incorporate additional methods to assess parasite clearance times and presence of molecular markers of resistance. WHO algorithm indicating that, for this study, even with suspected artemisinin resistance in Rwanda, no change in ACT treatment policy is warranted at this time.

References

  1. Rwanda Malaria and Other Parasitic Diseases Division, Rwanda Biomedical Center, HMIS data, 2018.
  2. WHO, Methods for Surveillance of Antimalarial Drug Efficacy, 2009.
  3. Uwimana A, Efficacy of artemether–lumefantrine versus dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria among children in Rwanda: an open-label, randomized controlled trial, Trans R Soc Trop Med Hyg; doi:10.1093/trstmh/trz009; 2019.
  4. Plucinski MM, Morton L, Bushman M, Dimbu PR, Udhayakumar V. Robust algorithm for systematic classification of malaria late treatment failures as recrudescence or reinfection using microsatellite genotyping. Antimicrob Agents Chemother;59:6096–100; 2015.

Contact Information: Aline Uwimana, MD: aline.uwimana@rbc.gov.rw and Eric Halsey, MD: ycw8@cdc.gov

*Affiliations: Malaria and Other Parasitic Diseases Division, Rwanda Biomedical Centre, Kigali, Rwanda; Maternal and Child Survival Program/JHPIEGO, Baltimore MD, USA; The US President’s Malaria Initiative, Atlanta, Georgia, USA; Malaria Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; US President’s Malaria Initiative, Washington DC, USA; National Reference Laboratory, Rwanda Biomedical Centre, Kigali, Rwanda; US Peace Corps, Kigali, Rwanda; US President’s Malaria Initiative, Kigali, Rwanda; WHO Rwanda Office, Malaria and Neglected Tropical Diseases Programs, Kigali, Rwanda; The Johns Hopkins University, Bloomberg School of Public Health, Department of International Health, Baltimore, MD, USA