Tropical Health Matters

These malaria and related news and abstracts stress the importance of sentinel surveillance systems, strong political and systems commitment to disease elimination, malachite green loop-mediated isothermal amplification for better malaria detection, and the threat of neglected fungal infections. An article from The Lancet shows that it is not just money that is needed to eliminate malaria, but better management and systems. Finally a bit of history from 18th Century North Carolina is shared. Click the links in each section to learn more about each topic.

Implementation of a malaria sentinel surveillance system in Togo: a pilot study

Since July 2017, 16 health facilities called sentinel sites, 4 hospitals and 12 peripheral care units located in 2 epidemiologically different health regions of Togo, have provided weekly data on malaria morbidity and mortality for the following 3 target groups:?<?5-years-old children,???5-years-old children and adults, and pregnant women. Data from week 29 in 2017 to week 13 in 2019 were analysed.

Each sentinel site provided complete data and the median time to data entry was 4 days. The number of confirmed malaria cases increased during the rainy seasons both in children under 5 years old and in children over 5 years old and adults. Malaria-related deaths occurred mainly in children under 5 years old and increased during the rainy seasons. The mean percentage of tested cases for malaria among suspected malaria cases was 99.0%. The mean percentage of uncomplicated malaria cases handled in accordance with national guidelines was 99.4%. The mean percentage of severe malaria cases detected in peripheral care units that were referred to a hospital was 100.0%. Rapid diagnostic tests and artemisinin-based combination therapies were out of stock several times, mainly at the beginning and end of the year. No hospital was out of stock of injectable artesunate or injectable artemether.

These indicators showed good management of malaria cases in the sentinel sites. Real-time availability of data requires a good follow-up of data entry on the online platform. The management of input stocks and the promptness of data need to be improved to meet the objectives of this malaria sentinel surveillance system.

Evaluation of the colorimetric malachite green loop-mediated isothermal amplification (MG-LAMP) assay …

… for the detection of malaria species at two different health facilities in a malaria endemic area of western Kenya. Prompt diagnosis and effective malaria treatment is a key strategy in malaria control. However, the recommended diagnostic methods, microscopy and rapid diagnostic tests (RDTs), are not supported by robust quality assurance systems in endemic areas. This study compared the performance of routine RDTs and smear microscopy with a simple molecular-based colorimetric loop-mediated isothermal amplification (LAMP) at two different levels of the health care system in a malaria-endemic area of western Kenya.

Patients presenting with clinical symptoms of malaria at Rota Dispensary (level 2) and Siaya County Referral Hospital (level 4) were enrolled into the study after obtaining written informed consent. Capillary blood was collected to test for malaria by RDT and microscopy at the dispensary and county hospital, and for preparation of blood smears and dried blood spots (DBS) for expert microscopy and real-time polymerase chain reaction (RT-PCR).

Results of the routine diagnostic tests were compared with those of malachite green loop-mediated isothermal amplification (MG-LAMP) performed at the two facilities.
A total of 264 participants were enrolled into the study. At the dispensary level, the positivity rate by RDT, expert microscopy, MG-LAMP and RT-PCR was 37%, 30%, 44% and 42%, respectively, and 42%, 43%, 57% and 43% at the county hospital. Using RT-PCR as the reference test, the sensitivity of RDT and MG-LAMP was 78.1% (CI 67.5–86.4) and 82.9% (CI 73.0–90.3) at Rota dispensary.

At Siaya hospital the sensitivity of routine microscopy and MG-LAMP was 83.3% (CI 65.3–94.4) and 93.3% (CI 77.9–99.2), respectively. Compared to MG-LAMP, there were 14 false positives and 29 false negatives by RDT at Rota dispensary and 3 false positives and 13 false negatives by routine microscopy at Siaya Hospital. MG-LAMP is more sensitive than RDTs and microscopy in the detection of malaria parasites at public health facilities and might be a useful quality control tool in resource-limited settings.

Terminating Trachoma. How Myanmar eliminated blinding trachoma.

Download the book  from WHO New Delhi: World Health Organization, Regional Office for South-East Asia; 2020. Licence: CC BY-NC-SA 3.0 IGO.  Myanmar’s three-phase approach to eliminating trachoma has been a great success, which will certainly continue. The country’s visionary National Eye Health Plan 2017-2021, which is closely aligned with international policies for prevention of blindness, gives confidence that Myanmar will maintain its elimination status. This book chronicles how a combination of good leadership, effective partnerships, health-care facilities and hardworking health-care personnel helped Myanmar eliminate trachoma as a public health problem.

Health sector spending and spending on HIV/AIDS, tuberculosis, and malaria, and development assistance for health, SDG Progress

Although the progress towards Sustainable Development Goal (SDG) 3, which aims to “ensure healthy lives and promote well-being for all at all ages”, has been assessed in various works, there is less research focusing on tracking spending towards this goal. In this study, spending estimates were used to determine progress in financing the priority areas of SDG3, examine the correlation between outcomes and financing, and identify where resource gains are most required to attain the SDG3 indicators for which data are available.

From 1995 to 2017, domestic health spending was determined, disaggregated by source (government, out-of-pocket, and prepaid private) for 195 countries and territories. Outcomes suggest a global rise in total health spending since the state of the SDGs in 2015, reaching $7·9 trillion (7·8–8·0) in 2017, and is estimated to rise to $11·0 trillion (10·7–11·2) by 2030, although with substantial disparity across countries. Per estimates, low-income and middle-income countries, in 2017, had an estimated spending of $20·2 billion on HIV/AIDS, $10·9 billion on tuberculosis, and $5·1 billion on malaria in endemic countries.

Although there is an increase in both domestic government and DAH spending, across these three diseases, variation in the accompanied changes in outcomes was observed. Malaria was noted to have the most consistent reductions in outcomes across countries as spending has raised. Findings thereby suggest mixed progress towards meeting the SDG3 targets; the progress varied by country and by target. The evidence on the scale-up of spending and improvements in health outcomes suggest a nuanced relationship, such that outcomes do not always improve with increases in spending.

Although more resources may be required by the countries to achieve SDG3, there will also be a necessity for addressing other constraints in the broader health system such as inefficient allocation of resources across interventions and populations, weak governance systems, human resource shortages, and drug shortages.

Ignored fungal infections kill more people annually than HIV and malaria combined

Carolina Pohl-Albertyn says that, “You may also know that there are other infections causing great concern, such as HIV (690 000 deaths/year), tuberculosis (1.5-million deaths/year), and malaria (405,000 deaths/year). But what would be your reaction if you knew that fungal infections (ranging from skin and mucosal infections (e.g. vaginal or oral thrush) to deadly systemic and organ infections (e.g. candidiasis, cryptococcal meningitis, and bronchopulmonary aspergillosis]) affect more than one-billion people each year, of which more than 150-million cases are severe and life-threatening and cause 1.7 million deaths per year?”

Malaria was once scourge in Chowan County, North Carolina

Nicole Bowman-Layton (Editor) provides some history of malaria. It’s fascinating to think that less than 100 years ago this disease was still a major scourge in Chowan County. I’ve wanted to write about this topic for a long time since the coronavirus popped up but was a bit concerned about writing about a somewhat depressing topic.

According to NCPedia malaria came to North Carolina in the 1500s from some of the first European explorers who were bitten by our friendly Anopheles mosquitoes and then transmitted to the native population. And as we well know, we live in a very damp environment surrounded by sitting water which certainly increases the harvest of mosquitos. Some of the most prominent Revolutionary Edentonians suffered from the “Ague” during their lives. Declaration signer Joseph Hewes suffered from “intermittent fever and ague” throughout his life which were certainly symptoms of malaria.

The German traveler Dr. Johan Schoepf wrote in his book Travels in the Confederation, 1783-1784, of “…the sickliness of the inhabitants, especially prevalent in the low, overflowed, and swampy parts of this country, and giving the people a pale, decayed, and prematurely old look. This is the case not only about Edenton, but along the entire low-lying coast, which this fall, from Virginia to South Carolina, was visited with numerous fevers.

Today we share news and abstracts concerning detecting malaria in pregnancy, news about the opening remarks from the WHO Director General at a special malaria and COVID-19 webinar, resumption of NTD activities after COVID-19 restrictions reduced, and mapping of Ebola carrying bats whose territory overlaps malaria in Africa. Click on the links to read more.

Prevalence and clinical impact of malaria infections detected with a highly sensitive HRP2 rapid diagnostic test in Beninese pregnant women

While sub-microscopic malarial infections are frequent and potentially deleterious during pregnancy, routine molecular detection is still not feasible. This study aimed to assess the performance of a Histidine Rich Protein 2 (HRP2)-based ultrasensitive rapid diagnostic test (uRDT, Alere Malaria Ag Pf) for the detection of infections of low parasite density in pregnant women.

This study demonstrates the higher performance of uRDT, as compared to cRDTs, to detect low parasite density P. falciparum infections during pregnancy, particularly in the 1st trimester. uRDT allowed the detection of infections associated with maternal anaemia.

The distribution range of Ebola virus carriers in Africa may be larger than previously assumed

Since Ebola overlaps both symptomatically and geographically with malaria in Africa, it is “Worrying that science has hitherto underestimated the range of Ebola-transmitting bat and fruit bat species. In this case, the models would provide a more realistic picture,” explains Dr. Lisa Koch

Based on ecological niche modeling, his team was able to show that the respective bat and fruit bat species are able to thrive in West and East Africa, including large parts of Central Africa. A wide belt of potential habitats extends from Guinea, Sierra Leone, and Liberia in the west across the Central African Republic, the Republic of the Congo and the Democratic Republic of the Congo to Sudan and Uganda in the East. A few of the studied bats and fruit bats may even occur in the eastern part of South Africa.

WHO Director-General’s Opening Remarks At the Webinar – Responding to the Double Challenge of Malaria and Covid-19

The WHO Director General is encouraged by efforts to maintain malaria services despite the COVID-19 outbreak, but says, “I would like to recognize and applaud all these efforts, and to thank all of you who have worked so hard to preserve and maintain those services to the greatest degree possible. However, despite these actions, it breaks my heart to report that we still expect to see an increase in cases and deaths from malaria.

“In a recent WHO survey of 105 countries, 46% of countries reported disruptions in malaria diagnosis and treatment. These disruptions threaten to set us back even further in realizing our shared vision for a malaria-free world.”

NTD Disease treatments restart in Africa as COVID-19 restrictions ease

It is not just malaria services that have been disrupted by COVID-19 responses. Treatment programmes that will reach millions of Africans at risk from debilitating neglected tropical diseases (NTDs) have restarted in a significant step towards COVID-19 recovery. Around one million people in Jigawa state, Nigeria have received antibiotics to treat the blinding eye disease trachoma and stop it from spreading.

Nigeria is the first country that Sightsavers and partners has supported to resume work on NTDs, which can have a devastating impact on some of the poorest communities in the world, with other African countries due to follow soon. In April, the threat of COVID-19 led the World Health Organization to recommend suspending mass treatment campaigns, which treat and prevent these diseases, but it has since provided guidance on restarting activities safely.

From time-to-time we will feature a collection of news and abstracts available “today.” Here are five stories available on 31st August 2020.

Med-tech on a leash: The many diseases that can be detected by dogs

Malaria, a parasitic disease, which is transmitted to humans by Anopheles mosquitoes, can also be detected by our canine friends. In 2019, English researchers presented the results of a study conducted in The Gambia, which involved training dogs with socks that had been worn by children infected with malaria, who otherwise had no symptoms.
The experiment proved to be so successful that researchers are now planning on using this method to test for asymptomatic cases of the disease….

New Malaria Transmission Patterns Emerge In Africa.

An international study reveals how future climate change could affect malaria transmission in Africa over the next century. Malaria is a climate sensitive disease; it thrives where it is warm and wet enough to provide surface water suitable for breeding by the mosquitoes that transmit it. For more than two decades now, scientists have suggested that climate change may alter the distribution and length of transmission seasons due to new patterns of temperature and rainfall. The burden of this disease falls primarily on Africa. In 2018, out of an estimated 228 million cases of malaria worldwide, 93% were in the African continent.
Detailed mapping of malaria transmission is vital for the distribution of public health resources and targeted control measures.

In the past, rainfall and temperature observations have been used in malaria climatic suitability models to estimate the distribution and duration of annual transmission, including future projections. But factors affecting how rainfall results in water for mosquito breeding are highly complex, for example how it is absorbed into soil and vegetation, as well as rates of runoff and evaporation. A new study, led by the Universities of Leeds and Lincoln in the UK, for the first time combined a malaria climatic suitability model with a continental-scale hydrological model that represents real-world processes of evaporation, infiltration and flow through rivers. This process-focused approach gives a more in-depth picture of malaria-friendly conditions across Africa….

Covid has spelt a lockdown for routine health services in India

Official data are now available to show the extent to which routine health services in India were unavailable and the scale of its impact. The number of fully immunised children fell by over 15 lakh in the three-month period from April to June compared to the same months last year. The number of institutional deliveries fell by about 13 lakh. The registered number of TB patients undergoing treatment fell to almost half of what it was last year. People seeking cancer treatment as outpatients fell by over 70%. Hard-won progress on several national health goals, including the programme to bring down infant and maternal mortality or those to treat TB, malaria and non-communicable diseases such as heart diseases, diabetes and cancer,

Insecticide resistance in indoor and outdoor-resting Anopheles gambiae in Northern Ghana

The overall results did not establish that there was a significant preference of resistant malaria vectors to solely rest indoors or outdoors, but varied depending on the resistant alleles present. Phenotypic resistance was higher in indoor than outdoor-resting mosquitoes, but genotypic and metabolic resistance levels were higher in outdoor than the indoor populations. Continued monitoring of changes in resting behaviour within An. gambiae s.l. populations is recommended.

Highlighting the burden of malarial infection and disease in the neonatal period: making sense of different concepts

Review of neonates from 14 malaria-endemic countries found pooled prevalence in this specific age group. Importantly, their results suggest a prevalence of congenital malaria of 40.4/1000, and a prevalence of neonatal malaria of 12/1000, Interestingly, the authors also confirmed congenital malaria to be more frequent in settings with unstable malaria transmission, a finding in line with the hypothesis of the importance of the immunity background in the risk of congenital malaria.

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

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.

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

Noella Umulisa, Veneranda Umubyeyi, Tharcisse Munyaneza, Ruzindana Emmanuel, Aline Uwimana, Stephen Mutwiwa, and Aimable Mbituyumuremyi presented “Assessment of Competence of Participants Before and After 6-day Intensive Malaria Microscopy Training in Rwanda” at the 68th Annual Meeting of the American Society of Tropical Medicines and Hygiene. (Affiliations: Maternal and Child Survival Program/Jhpiego, Malaria and Other Parasitic Diseases Division [Mal & OPDD], National Reference Laboratory, Rwanda Biomedical Centre [RBC]). Their findings are shared below.

WHO recommends prompt malaria diagnosis either by microscopy or malaria rapid diagnostic test (RDT) in all patients with suspected malaria before treatment is administered. Light Microscopy remains the mainstay of malaria diagnosis, allows the identification of different malaria-causing parasites (P. falciparum, P. vivax, P. malariae and P. ovale). It is estimated that a diagnostic test with 95% sensitivity and 95% specificity requiring minimal infrastructure would avert more than 100,000 deaths and about 400 million unnecessary treatments. Frequent delays occur since conventional microscopy methods are labour intensive, require skilled manpower and time

Sufficient training of laboratory staff is paramount for the correct microscopy diagnosis of malaria. In Rwanda, P. falciparum is by far the most common contributing 97-99% of the parasite population, followed by P. ovale with 0.5-2% and followed by P. malariae 0.5–1% as mono-infection.

Rwanda has 8 referral hospitals, 4 provincial hospitals, 36 district hospitals, 504 health centers, 818 health posts and 30,000 CHWs able to perform malaria diagnostics. Each of these health facilities has a laboratory able to perform malaria microscopy with at least 1 trained lab technician and 1 functioning microscope.

In May 2018, the Rwanda Biomedical Center and partners trained 1 lab technician per health center from 6 poor performing districts in malaria microscopy. The main objective was to evaluate the performance of laboratory technicians in detecting and quantifying malaria parasites from 75 health facilities within 6 districts in Rwanda. Information was collected at two points in time.

In Month 1 there were a Pre-Test for Theoretical and practical evaluation, a Practical session, Slides preparation practice, and detection of parasite’s density and species. This was followed by the Post-Test, again a Theoretical and practical evaluation

In Month 4 Post training follow up was conducted with 35 randomly selected trained lab technicians after 4 months. Observation of technicians’ Conduct visual inspection and maneuvers used in routine malaria diagnosis was done. Their ability to Detect parasites on a standardized pre-validated slide panel of five slides was determined. during this 4 Months Post-Training Species Detection Performance, P. Falciparum was identified correctly more often than P. ovale or P. malariae.

The attached charts show the results of training. During the training 75 technicians from 75 health centers in 6 districts were trained from May 28th–June 18th, 2018. 53% of the trained lab technicians were female and 47% male.

Correct Parasite Density was slightly higher just after training. Classic training improved the performance of lab technicians in parasite’s density from 53% to 87% immediately after training.

After 4 months of training, P. falciparum and P. ovalae were correctly detected by 93% and 79% of lab technicians, respectively. Also, after 4 months of training, P. malariae was detected only by 68% of evaluated lab technicians. Training: Sensitivity (99%) and specificity (85%) remain high. Performance of lab technicians assessed using standardized pre-validated slide panel as gold standard after >4 months

Trainings of lab technicians improves performance on malaria parasites density and species detection. P. falciparum is the most well detected species followed by P. ovale . The detection rate for P. malariae was the lowest, this can be explained by the fact is not often seen in Rwanda. Participants had high sensitivity and specificity in the detection of malaria parasites.

Continuous capacity building for lab staff is needed to ensure accurate malaria laboratory diagnosis for appropriate treatment. Malaria microscopy diagnosis quality control/assurance activities from central and district level to health center level should be strengthen for continuous capacity building of lab technicians

Acknowledgements: This poster was made possible by the generous support of the American people through the United States Agency for International Development (USAID), under the terms of the Cooperative Agreement AID-OAA-A-14-00028. The contents are the responsibility of the Maternal and Child Survival Program and do not necessarily reflect the views of USAID or the United States Government.

In the past week urban transmission in Goma, a city of at least 2 million inhabitants in eastern Democratic republic of Congo, was documented as a gold miner came home and infected his wife and child. To get a grip on the spread of the disease, DRC is considering another vaccine, not without some controversy. WHO provides detailed guidance on all aspects of response. On the malaria front we have learned more about malaria vectors, natural immunity and reactive case detection.

Ebola Challenges: Vaccines, Urban Transmission

The current Ebola vaccine being deployed to over 150,000 people in North Kivu and Ituri Provinces was itself an experimental intervention during 2016 when it was first used in the largest ever outbreak located in West Africa. BBC reports that, “World Health Organization (WHO) data show the Merck vaccine has a 97.5% efficacy rate for those who are immunised, compared to those who are not.”

The proposed addition of a Johnson and Johnson vaccine would be in that same experimental phase if introduced in DRC now. It has been proven safe as well as effective in other primates. The challenge is that even though the Merck vaccine supplies are near 500,000, this is not enough to cover the potential needs in an area with over 10 million people, although Merck is still producing more. At present, BBC says, “Those pushing for the use of the new Johnson & Johnson vaccine, had proposed using it to create a protective wall, vaccinating people outside the outbreak zone.” In addition, the new national response team is concerned that “Only about 50% of cases of Ebola in the Democratic Republic of Congo are being identified.”

Finally, there is the issue of community mistrust of government workers and challenging logistics. “There are also concerns that the new vaccine – which requires two injections 56 days apart – may be difficult to administer in a region where the population is highly mobile, and insecurity is rife.”

If efforts at vaccination are needed soon in Goma, up to 2 million doses might be needed. Reuters reports that, “Congolese authorities were racing to contain an Ebola epidemic on Thursday, after a gold miner with a large family contaminated several people in the east’s main city of Goma before dying of the hemorrhagic fever.” Readers may recall that the West Africa outbreak of 2014-16 in Guinea, Sierra Leone and Liberia accelerated greatly after infected people went to major cities in search of help.

The miner is the second ‘imported case into Goma, which borders Rwanda, but because his family lives there, he has already infected his wife and one of his 10 children. Contacts are being traced and monitored, but this urban and border threat is one of the factors that led WHO to finally declare the current outbreak a public health emergency.

Malaria

As we move toward malaria elimination Reactive Case Detection (RCD) has been proposed as an integral part of these efforts with the hopes that is can be conceived of as a way of gradually decreasing transmission, according to an article in Malaria Journal. In fact, the value of RCD may be limited as follows:

• RCD alone can eliminate malaria in only a very limited range of settings, where transmission potential is very low
• In other settings, it is likely to reduce disease burden and help maintain the disease-free state in the face of imported infections

Another article looks at “natural exposure to gametocytes that can result in the development of immunity against the gametocyte by the host as well as genetic diversity in the gametocyte.” The researchers learned that there can be variations in immune response depending on season and geography. This information is helpful in planning malaria elimination interventions.

On the vector front a baseline susceptibility testing was conducted in 16 countries in sub-Saharan Africa for neonicotinoids. “The target site of neonicotinoids represents a novel mode of action for vector control, meaning that cross-resistance through existing mechanisms is less likely.” The findings will help in the preparation for rollout of clothianidin formulations as part of national IRS rotation strategies by PMI and other partners.

Researchers also called on us to learn more about malaria vectors in other parts of the world. In order to eliminate Plasmodium falciparum from the Caribbean and Central America program planners should consider local vector characteristics such as An. albimanus. They found that, “House-screening and repellent IRS are potentially highly effective against An. albimanus if people are indoors during the evening.”

Vectors are also of concern on the edges of malaria transmission, particularly in South Africa, one of the ‘elimination eight’ countries of the Southern Africa Development Community. Researchers examined the, “potential role of Anopheles parensis and other Anopheles species in residual malaria transmission, using sentinel surveillance sites in the uMkhanyakude District of northern KwaZulu-Natal Province.” They found Anopheles parensis is a potential but minimal vector of malaria in South Africa “owing to its strong zoophilic tendency.” On the other hand, An. arabiensis was found to be the major vector responsible for residual malaria transmission in South Africa. Since these mosquitoes were found in outdoor-placed resting traps, interventions are needed to control outdoor-resting of vector populations.

NTDs of Concern

During the week, the member states of the African Union renewed their commitment to fight and permanently eliminate Neglected Tropical Diseases. Africa.com reported that, “Achievements to date include 1 billion people treated against at least one NTD and 37 countries have completed the removal of at least one NTD.”

Although some reports have discounted the idea of trachoma in Namibia, there may be reason to re-examine the situation. On Twitter Anthony Solomon notes that Namibia needs #trachoma prevalence surveys. A just-completed joint Ministry of Health & Social Services/@WHO mission found active trachoma & trichiasis in Zambezi & Kunene Regions.

The Times of India draws attention to snakebite. It says that “Under-reported and inadequately treated, fatalities in India are estimated at close to 50,000 a year, the world’s highest.”

Overall we can see that the concept of ‘neglect’ has several uses. There is neglect if half of Ebola cases are undetected. There is neglect if we do not understand malaria vectors in low transmission areas. Finally, there is neglect if we do not conduct up-to-date disease surveys to determine whether a disease is present or not. Elimination of tropical diseases is challenging when key processes are neglected.

This posting focuses on Malaria and Ebola, both of which have been the recent focus of some disturbing news. The malaria community has been disturbed by the clear documentation of resistance to drugs in Southeast Asia. Those working to contain Ebola in the northeast of the Democratic Republic of Congo saw a change in political leadership even in light of continued violence and potential cross-border spread.

Malaria Drug Resistance

Several sources reported on studies in the Lancet Infectious Diseases concerning the spread of Multidrug-Resistant Malaria in Southeast Asia. Reuters explained that by sing genomic surveillance, researchers concurred that “strains of malaria resistant to two key anti-malarial medicines are becoming more dominant” and “spread aggressively, replacing local malaria parasites,” becoming the dominant strains in Vietnam, Laos and northeastern Thailand.”

The focus was on “the first-line treatment for malaria in many parts of Asia in the last decade has been a combination of dihydroartemisinin and piperaquine, also known as DHA-PPQ,” and resistance had begun to spread in Cambodia between 2007 and 2013. Authors of the study noted that while, “”Other drugs may be effective at the moment, but the situation is extremely fragile, and this study highlights that urgent action is needed.” They further warned of an 9impending Global Health Emergency.

NPR notes that “Malaria drugs are failing at an “alarming” rate in Southeast Asia” and provided some historical context about malaria drug resistance arising in this region since the middle of the 20th century. “Somehow antimalarial drug resistance always starts in that part of the world,” says Arjen Dondorp, who leads malaria research at the Mahidol Oxford Tropical Medicine Research Unit in Bangkok and who was a lead author of the report about the randomized trial. Ironically, “one reason could have something to do with the relatively low levels of malaria there. When resistant parasites emerge, they are not competing against a dominant nonresistant strain of malaria and are possibly able to spread easier.

When we are talking about monitoring resistance in low resource and logistically and politically challenging areas, we need to think of appropriate diagnostic tools at the molecular level. Researchers in Guinea-Bissau conducted a proof of concept study and used malaria rapid diagnostic tests applied for parallel sequencing for surveillance of molecular markers. While they noted that, “Factors such as RDT storage prior to DNA extraction and parasitaemia of the infection are likely to have an effect on whether or not parasite DNA can be successfully analysed … obtaining the necessary data from used RDTs, despite suboptimal output, becomes a feasible, affordable and hence a justifiable method.”

A Look at Insecticide Treated Nets

On a positive note, Voice of America provides more details on the insecticide treated net (ITN) monitoring tool developed called “SmartNet” by Dr Krezanoski in collaboration with the Consortium for Affordable Medical Technologies in Uganda. The net uses strips of conductive fabric to detect when it’s in use. Dr. Krezanoski was happy to find that people given the net used it no differently that if they were not being observed. The test nets made it clear who what using and not using this valuable health investment and when it was in use. Such fine tuning will be deployed to design interventions to educate net users based on their real-life use patterns.

Another important net issue is local beliefs that may influence use. We can find out when people use nets, but we also need to determine why. In Tanzania, researchers found that people think mosquitoes that bite in the early evening when people are outside relaxing are harmless. As one community member said, “I only fear those that bite after midnight. We’ve always been told that malaria is spread by mosquitoes that bite after midnight.”

Even if people do use their ITNs correctly, we still need to worry about insecticide resistance. A study in Afghanistan reported that, “Resistance to different groups of insecticides in the field populations of An. stephensi from Kunar, Laghman and Nangarhar Provinces of Afghanistan is caused by a range of metabolic and site insensitivity mechanisms.” The authors conclude that vector control programs need to be better prepared to implement insecticide resistance management strategies.

Ebola Crisis Becomes (More) Political

Headlines such as “Congo health minister resigns over response to Ebola crisis” confronted the global health community this week. this happened after the DRC’s relatively new president took control of the response. The President set up a new government office to oversee the response to an outbreak outside of the Ministry of Health which was managing the current outbreak and the previous ones. The new board was set up without the knowledge of the Minister who was traveling to the effected provinces at the time.

The former Minister, Dr Oly Ilunga stated on Twitter that, “Suite à la décision de la @Presidence_RDC.  de gérer à son niveau l’épidémie d’#Ebola, j’ai remis ma démission en tant que Ministre de la Santé ce lundi. Ce fut un honneur de pouvoir mettre mon expertise au service de notre Nation pendant ces 2 années importantes de notre Histoire. (Following the decision of the @Presidence_RDC to manage the # Ebola outbreak, I resigned as Minister of Health on Monday. It was an honor to be able to put my expertise at the service of our Nation during these two important years of our History.)

The former Minister also warned that the “Multisectoral Ebola Response Committee would interfere with the ongoing activities of national and international health workers on the ground in North Kivu and Ituri provinces.” Part of the issue may likely have been “pressure to approve a new vaccine in addition to one that has already been used to protect more than 171,000 people.” People had warned about the potential confusion to the public as well as ethical issues if a second vaccine was used, especially one that did not have the strong accumulated evidence from both the current outbreak as well as the previous one in West Africa.

One might have thought that this would be a time when stability was needed since “The WHO earlier this month declared the outbreak a Public Health Emergency of International Concern, a rare step meant to highlight the urgency of the moment that has been used only four times before.” In addition, “the World Bank said it would release $300 million from a special fund set aside for crises like viral outbreaks to help cover the cost of the response.”

Unfortunately one of the msain impediments to successful Ebola control, violence in the region, continues. CIDRAP stated that. “the Allied Democratic Forces (ADF), a rebel group, attacked two villages near Beni, killing 12 people who live in the heart of the Democratic Republic of the Congo’s (DRC’s) ongoing Ebola outbreak. The terrorists killed nine in Eringeti and three in Oicha, according to Reuters. ADF has not publicly pledged allegiance to the Islamic state (ISIL), but that hasn’t stopped ISIL from claiming responsibility for the attacks.” It will take more than a change of structure in Kinshasa to deal with the realities on the ground.

CIDRAP also observed that since the resignation of the Health Minister, “DRC officials have provided no update on the outbreak, including statistics on the number of deaths, health workers infected, or suspected cases.” The last was seen on 21 July 2019.

ReliefWeb reports that, “Adding to the peril, the Ebola-affected provinces share borders with Rwanda and Uganda, with frequent cross-border movement for personal travel and trade, increasing the chance that the virus could spread beyond the DRC. There have already been isolated cases of Ebola reported outside of the outbreak zone.”

These are troubling times when parasites and mosquitoes are becoming more resistant to our interventions and when governments and communities are resistant to a clear and stable path to disease containment and control.

This week started with articles that drew attention to the challenges of malaria in low transmission areas and with low density infections. Malaria Journal has provided several insightful articles toward this end.

Being an island has certainly helped Zanzibar make progress toward malaria elimination as witness the fact that malaria prevalence has remained below 1% for the past decade. Not only does Zanzibar still face threats of infection from the mainland, it may also experience an upsurge locally if residual transmission and the role of human behavior and community actions are not well understood. April Monroe et al. conducted in-depth interviews with community members and local leaders across six sites on Unguja, Zanzibar as well as semi-structured community observations of night-time activities and special events to learn more.

While there was high reported ITN use, there were also times when people were exposed t mosquitoes while being outdoors during biting times. This could be around the house, or at special night events like such as weddings, funerals, and religious ceremonies. Men spent more time outdoors than women. Clearly appropriate interventions and needed and should be promoted in culturally appropriate ways in order to further reduce and eventually eliminate transmission.

Angela Early and colleagues presented findings on a diagnostic process of deep sequencing for understanding the dynamics and complexity of Plasmodium infections, but stress that knowing the lower limit of detection is challenging. They present “a new amplicon analysis tool, the Parallel Amplicon Sequencing Error Correction (PASEC) pipeline, is used to evaluate the performance of amplicon sequencing on low-density Plasmodium DNA samples.”

The authors learned that, “four state-of-the-art tools resolved known haplotype mixtures with similar sensitivity and precision.” They also cautioned that, “Samples with very low parasitemia and very low read count have higher false positive rates and call for read count thresholds that are higher than current default recommendations.” Better understanding of the genetic mix of plasmodium infections as countries move toward low transmission and elimination is crucial for selecting appropriate interventions and evaluating their outcomes.

Hannah Edwards and co-researchers examined conditions for malaria transmission along the Thailand-Myanmar border in areas approaching malaria elimination. While prevalence may be less than 1%, residual transmission still occurs. Transmission occurs not only around residences but in the forests where people work. The researchers therefore looked at the behavior of both humans and insects. Overall, they found that, “Community members frequently stayed overnight at subsistence farm huts or in the forest. Entomological collections showed higher biting rates of primary vectors in forested farm hut sites and in a more forested village setting compared to a village with clustered housing and better infrastructure.”

While mosquitoes preferred to bite inside huts, their threat was magnified by those who did not use long lasting insecticide-treated nets (LLINs). While out in the farms and forests, people tended to wake early and increase their likelihood of being bitten. The authors discuss the challenges of dual residences in terms of LLIN ownership and even concerning the potential access to indoor residual spraying. The definition for universal net coverage needs to expand from one net per two people to include adequate nets wherever people are located.

The Amazonian area of Brazil is another area working toward malaria elimination, in particular, Plasmodium vivax. Felipe Leão Gomes Murta et al. also looked at the human side of the equation and identified misperceptions by both community members and health workers that could inhibit elimination efforts. They found, “many myths regarding malaria transmission and treatment that may hinder the sensitization of the population of this region in relation to the use of current control tools and elimination strategies, such as mass drug administration (MDA),” and LLINs.

Problematic perceptions included mention by both groups that the use of insecticide-treated nets, may cause skin irritations and allergies. Both community members and health professionals said malaria is “an impossible disease to eliminate because it is intrinsically associated with forest landscapes.” They concluded that such perceptions can be a barrier to control and elimination.

Efforts to eliminate malaria from low transmission settings are an essential to the overall global goals. These four articles tell us that close attention to and better understanding of humans, parasites and mosquitoes is still needed to achieve these goals.