World Water Day: Water and Neglected Tropical Diseases

The United Nations introduces us to the challenges of water. “Water is the essential  building block of life. But it is more than just essential to quench thirst or protect health; water is vital for creating jobs and supporting economic, social, and human development.” Unfortunately, “Today, there are over 663 million people living without a safe water supply close to home, spending countless hours queuing or trekking to distant sources, and coping with the health impacts of using contaminated water.”

Haiti: Importance of Water to prevent STH

Many of the infectious health challenges known as Neglected Tropical Diseases (NTDs) have issues of water associated with their transmission. This may relate to scarcity of water and subsequent hygiene problems. It may relate to water quality and contamination. It may also relate to water in the lifecycle of vectors that carry some of the diseases.

Even though water is crucial to the control of many NTDs, it is not often the feature of large scale interventions. The largest current activity against five NTDs is mass drug administration (MDA) on an annual or more frequent basis to break the transmission cycle.  Known as diseases that respond to preventive chemotherapy (PCT) through MDA, these include lymphatic filariasis (LF), trachoma, onchocerciasis, schistosomiasis and soil transmitted helminths (STH) has been undertaken for over 10 years.

We have recently passed the Fifth Anniversary of the London Declaration on NTDs, which calls for the control of ten of the many these scourges The Declaration calls for “the elimination “by 2020 lymphatic filariasis, leprosy, sleeping sickness (human African trypanosomiasis) and blinding trachoma.” Another water-borne NTD, guinea worm, should be eradicated soon. Two of the elimination targets are part of MDA efforts, LF and trachoma.

Cameroon: mapping the community to detect NTD transmission sites

Ministries of Health and their donor and NGO partners who deliver MDA against the 5 diseases in endemic countries express interest in coordinating with water and sanitation for health (WASH) programs. People do recognize the value of collaboration between NTD MDA efforts and WASH projects, but these may be located in other ministries and organizations.

The long term implementation of WASH efforts is seen as a way to prevent resurgence of trachoma, for example, and  strongly compliment efforts to control STH and schistosomiasis. Hopefully before the 10th Anniversary of the London Declaration the vision of “ensuring access to clean water and basic sanitation,” can also be achieved.

Finally as a reminder our present tools for the control of Zika and Dengue fevers relies almost entirely on safe and protected household and community sources of water to prevent breeding of disease carrying Aedes aegypti mosquitoes. If we neglect water, we will continue to experience neglected tropical diseases. Hopefully the topic of water and NTDs will feature prominently at next months global partners meeting hosted by the World Health Organization.

 

Zika and Access to Reproductive Health Services in Brazil

Twice a year students in the Johns Hopkins Bloomberg School of Public Health write blog postings as part of the course “Social and Behavioral Foundations of Primary Health Care.” We often share blog posts that relate to tropical health issues.  Below is a posting by class members Linda Cho, Linda Chyr, Rebecca Earnest, and Sarah Rosenberg on Zika, family planning, and reproductive health in Brazil.


In the 1960s, the Brazilian government adopted a laissez-faire attitude, which lead to the predominance of private organizations in the provision of family planning services. Since then, Brazil has witnessed one of the most dramatic reductions in family size in modern history in part due to increased access to family planning services. (Photo New York Times: Members of the Union of Mothers of Angels.)

However, in early 2015, the widespread epidemic of the Zika fever caused by the Zika virus in Brazil caused persisting gaps in access to contraception to resurface. Since it was first detected it has instilled fear and uncertainty in pregnant women whose fetuses could be at risk of Zika-related birth defects like microcephaly should the virus be contracted during pregnancy. This makes access to comprehensive reproductive health services and education a critical need for women who are pregnant or considering becoming pregnant.

While contraceptive use is fairly high in Brazil with 75.2% of women using modern forms of contraception, barriers to access remain. Some women face challenges, some of which include but are not limited to incomplete insurance coverage or lack of reimbursement for long-acting reversible contraceptives (LARCs), high up-front costs, low number of contraceptive service sites, and/or a lack of supply of the implants in the public sector . This may be one driver behind why LARCs only make up 0.5% of all contraceptive sales. Furthermore, 55% of all pregnancies in Brazil estimated to be unplanned and 20% of all lives births are attributed to teenage girls, indicating that there may be substantial reproductive knowledge gaps  in how to effectively prevent pregnancy.

Amid the spread of a virus that poses unique health risks to pregnant women and their fetuses, there is an urgent need to address these gaps in reproductive health access and education. First, the Brazilian National Health System, which laudably provides most contraceptives free of charge to about 74% of the population, needs to reevaluate existing policies that may be still limiting access to contraceptive services. Secondly, organizations like the Brazilian Society for Family Welfare (BENFAM), which provides reproductive health services and education to underserved Brazilian communities, need greater financial and political support from policymakers, civil society, and even organizations traditionally opposed to such services like the Catholic Archdiocese.

Despite Brazil’s great strides to improve access to contraception and reproductive health education in recent years, Zika’s arrival highlighted gaps in the existing system that must be addressed through policy reform and greater political and financial support. Especially in the time of Zika, Brazilian women deserve no less.

What are national governments willing to pay for malaria control?

In 2013 national/domestic funding accounted for 20.4% of the US$2.6 billion in global support used to control and eliminate malaria, although it is not clear whether this is governmental, private or a mix.[i] The 2016 World Malaria Report (WMR) reports that, “Total funding for malaria control and elimination in 2015 is estimated at US$ 2.9 billion.[ii] This total represents just 46% of the Global Technical Strategy for Malaria 2016–2030 (GTS) 2020 milestone of US$ 6.4 billion.”

If domestic funding at the previous rate were to meet this milestone, endemic countries would need to put forward $US1.3 billion themselves, not to mention the fact that domestic funding may be needed even more as uncertainties increase in bilateral and multi-lateral sources. Of the coming from governments, US$ 612 million was direct expenditures through national malaria control programmes (NMCPs) while US$ 332 million was expenditures on malaria patient care. While domestic funding for malaria in African countries has increased in absolute terms over the years, it still remains a smaller proportion of total funding.[iii]

Governments in endemic countries characterized by a large portion of the poor, may in fact not contribute a fair share of malaria expenditure. Households are often said to bear the brunt of malaria financing through out-of-pocket expenditure for both treatment and prevention. While we do not have specific figures for malaria, we note that the overall out-of-pocket (OPP) expenditure by households in Nigeria for health care averaged 69.3% between 2010 and 2014.[iv]

Ghana has a national health insurance scheme that may reach up to two-thirds of the population. Costs of fever/malaria episodes therefore should covered by membership, although one is required to pay annual premiums.[v] Still a large portion of the population still pays out-of-pocket.

Although malaria funding from all sources has been increasing over the years, it has recently stagnated at a level approximately 45% of that level targeted to eventually eliminate the disease.  In many countries households still bear the brunt of malaria costs, both for treatment and prevention.

Benefits of investments in interventions like community health workers do help bring malaria care closer to the community at a cost people can afford.[vi] More financial support is needed to scale these up, especially by mobilizing in-country governmental, corporate and non-governmental resources.

[i] Kates J and Wexler A. Global Financing for Malaria: TRENDS & FUTURE STATUS.

Kaiser Family Foundation, December 2014 http://kff.org/report-section/global-financing-for-malaria-introduction/

[ii] World Health Organization. World Malaria Report 2016. ISBN 978-92-4-151171-1. Geneva: World Health Organization, 2016

[iii] Korenromp EL, Hosseini M, Newman RD, Cibulskis RE. Progress towards malaria control targets in relation to national malaria programme funding. Malaria Journal 2013, 12:18 Page 2 of 9 http://www.malariajournal.com/content/12/1/18

[iv] World Health Organization. Global Health Expenditure Database: Nigeria. Accessed 6 February 2017. http://apps.who.int/nha/database/Key_Indicators_by_Country/Index/en?COUNTRYKEY=84700

[v] Tawiah T, Asante KP, Dwommoh RA, Kwarteng A, Gyaase S, Mahama E, Abokyi L, Amenga-Etego S, Hansen K, Akweongo P, Owusu-Agyei S. Economic costs of fever to households in the middle belt of Ghana. Malar J. 2016 Feb 6;15:68. doi: 10.1186/s12936-016-1116-x.

[vi] Sunguya BF, Mlunde LB, Ayer R, Jimba M.. Towards eliminating malaria in high endemic countries: the roles of community health workers and related cadres and their challenges in integrated community case management for malaria: a systematic review. Malar J. 2017 Jan 3;16(1):10. doi: 10.1186/s12936-016-1667-x.

Malaria in Pregnancy Progress in Nigeria – the 2015 Malaria Indicator Survey

With an eye toward the future Nigeria’s National Malaria Control Program also refers to itself as the National Malaria Elimination Program (NMEP). Given that Nigeria has the highest burden of malaria in Africa, along with around one-quarter of sub-Saharan Africa’s population, the elimination goal will take a lot of work.

Recently the 2015 Malaria Information Survey (MIS) for Nigeria was released and gives a perspective on how far we have some and how far we need to go. We will focus on malaria in pregnancy (MIP) interventions today.

Intermittent Preventive Treatment for pregnant women (IPTp) using sulfadoxine-pyrimethamine (SP) remains the key MIP intervention due to the high and stable malaria transmission that still persists. There is always a challenge in delivering health interventions that require multiple contacts, and IPTp is not exception. The difficulty in achieving two doses when that was policy was clear. Now that WHO recommends monthly dosing from the second trimester forward (giving the possibility of 3, 4 or more doses), the service delivery challenge is heightened.

We can see in the attached graph from the MIS report that while there is progress, it remains well below the 2010 Roll back malaria Target of 80%. Part of the problem resides in the fact that the 2013 DHS showed only 61% of pregnant women attended even one antenatal care visit while 51% attended four or more.

The second lesson of the graph is missed opportunities. There is a gap between IPTp1 coverage of 37% and at least one ANC visit of 61%. Granted, 18% of women made their first visit in the first trimester when SP is not given, but not all of those stopped ANC then. The next evidence of missed opportunities is the gap between IPTp1 and IPTp2, almost a quarter of women who started IPTp did not get a second dose. We cannot say that the women’s own attendance gaps account for all the missed opportunities; some are likely due to health systems weaknesses such as stock-outs and health staff attention.

Key demographic factors are linked to receiving two or more IPTp doses. Only 30% or rural women received two or more compared to 50% of urban. There was a steady progression from 21% of the poorest women to 55% of those in the highest wealth quintile. A second chart also shows variation by section of the country. These access gaps are why we have advocated for supplementary distribution of IPTp through trained community health workers.

Use of insecticide treated bed nets by pregnant women shows a similar increase over time. The dip in 2013 probably related to fact that mass campaigns had occurred between 2009 and 2011 and thus by the time of the survey some nets had become damaged and abandoned. A major challenge in achieving net coverage is NOT relying on periodic distribution campaigns only, but ensuring regular and reliable supplies during routine services such as antenatal care. This again is a health systems problem that must be solved.

Net access is not only a health systems issue, bit may be factor of internal household dynamics. Even when the household possesses nets, only 63% of pregnant women therein slept under one the night before the survey. Community education needs strengthening – more than just telling people what to do but involving them is solving the problems of net use.

So as mentioned earlier, progress is being made, but more effort is needed. We are especially concerned because of the precariousness of global financial support for disease control. Nigeria needs to strategize how it can meet its own needs in protecting pregnant women and their unborn children from malaria, disability and death.

Malaria, Dengue, Mosquitoes – evolving in the urban environment

As the world increasingly urbanizes, we need to address the role of urban ecosystems and the evolution of disease vectors and organisms.  Marina Alberti and colleagues explained that …

“Recent studies show that cities might play a major role in contemporary evolution by accelerating phenotypic changes in wildlife, including animals, plants, fungi, and other organisms. Many studies of ecoevolutionary change have focused on anthropogenic drivers, but none of these studies has specifically examined the role that urbanization plays in ecoevolution or explicitly examined its mechanisms.”

In their own study they looked at “five types of urban disturbances including habitat modifications, biotic interactions, habitat heterogeneity, novel disturbances, and social interactions.” The researchers learned that, “clear urban signal; rates of phenotypic change are greater in urbanizing systems compared with natural and nonurban anthropogenic systems.” They concluded that there is need to continually “uncover insights for maintaining key ecosystem functions upon which the sustainability of human well-being depends.”

Of particular concern in the area of tropical health are the unique urban manifestations of diseases like yellow fever, dengue and malaria. Although Zika virus, for example, was first discovered in forests, it has adapted to an urban cycle involving humans and domestic mosquito vectors in tropical areas where dengue is endemic. Musso and Gubler in their review further explain that although there may be sylvatic cycles of Dengue, “Arboviruses such as DENV have adapted completely to humans and can be maintained in large tropical urban centers in a mosquito-human-mosquito transmission cycle that does not depend on nonhuman reservoirs.”

Weaver et al. note that Zika in spreading to Asia, “emerged on multiple occasions into urban transmission cycles involving Aedes (Stegomyia) spp. Mosquitoes.” In addition it can be hypothesized that phenotypic changes in Asian lineage ZIKV strains made rare disease outcomes such as congenital microcephaly and Guillain-Barré more common and visible.

According to Estelle Martin and co-researchers, “Puerto Rico, a major metropolitan center in the Caribbean, has experienced increasingly larger and clinically more severe epidemics following the introduction of all four dengue serotypes.” They found that Dengue serotype 4 replaced earlier strains and that “this epidemic strain progressed rapidly, suggesting that the epidemic strain was more fit, and that natural selection may have acted on these mutations to drive them to fixation.”

In addition to virus evolution, mosquito changes have been documented by Caroline Louise and colleagues in “One of the world’s largest urban agglomerations infested by Ae. aegypti … the Brazilian megalopolis of Sao Paulo.”  They detected microevolution despite a short observational period and stress the implications of the “rapid evolution and high polymorphism of this mosquito vector on the efficacy of control methods.”

“The adaptation of malaria vectors to urban areas is becoming a serious challenge for malaria control,” is a major concern of Antonio-Nkondjio and co-workers. They found, “rapid evolution of pyrethroid resistance in vector populations from the cities of Douala and Yaoundé,” Members of this team also learned that the M form of Anopheles gambiae predominated in the centre of urban agglomerates in Cameroon. Previously it was known that larval habitats polluted with decaying organic matter as found in densely populated urban agglomerates, were unsuitable for Anopheles gambiae. The recent study showed that the “M form showed greater tolerance to ammonia (arising from organic matter) compared to the S form. This trait may be part of the physiological machinery allowing forest populations of the M form to colonize polluted larval habitats.”

The evolutionary response of vectors and disease organisms to urban environments needs continued monitoring. Urban disease control and elimination efforts must adapt to such adaptations in the disease process.

Malaria Funding Allocations by the Global Fund and the Need to Mitigate Risk

The Global Fund Observer (aidspan) has provided information on the 2017-19 allocations by the Global Fund to Fight AIDS, TB and Malaria. Here we take a closer look at the malaria component.

Overall malaria grants account for $US 3.3b or 32% of total funding for the period. This includes 71 countries as follows:

  • 41 countries in WHO’s Africa Region
  • 6 in the Eastern Mediterranean Region
  • 7 in the Americas
  • 10 in Southeast Asia
  • 7 in the Western Pacific
malaria-fund-allocation-2017-19

2017-2019 GFATM Allocation

The Global Fund Observer also noted that the GFATM board is very much aware of risks to these grants. An example comes from the management pharmaceuticals. Risks can be found along the whole supply chain process. The GFATM found that, “artemisinin-based combination therapies (ACTs) are more commonly targeted for theft or illegal diversion than are antiretrovirals (ARVs) or medicines for opportunistic infections (OIs).”

In fact the GFATM has identified 40 high or very high risk countries, most of which overlap with the list receiving current grant allocations. Therefore while we praise the provision of needed malaria funds for the upcoming three years, we also call on the Global Fund managers, country coordinating mechanisms, grant recipients and watchdogs in civil society and the media to ensure these grants continue to save lives from malaria.

Leadership and Support for Malaria Pre-Elimination in Nepal

Emmanuel Le Perru, Jhpiego field staff in Nepal, shared his experiences in aiding the malaria pre-elimination efforts in the country during a retreat that preceded the 65th Annual Meeting of the American Society of Tropical Medicine and Hygiene in Atlanta. Here are some highlights of his talk.

risk-mapMalaria Pre-Elimination efforts are targeting 0 deaths as well as investigation of 100% of confirmed cases in Nepal. Systematic entomology investigation/interventions are required. Glucose-6-Phosphate Dehydrogenase deficiency (enzyme genetic defect causing hemolysis with primaquine) testing for Plasmodium vivax in high G6PDd prevalence communities is required. Cases should receive treatment within 72 hours of symptoms for Pf (to quickly prevent transmission and gametocyte reservoir). There is also a need to distinguish between indigenous and imported cases.

Jhpiego is providing technical assistance and capacity building for Nepal’s Ministry of Health pre-elimination efforts as follows:

  • Integrated Vector Management
  • Micro-stratification
  • Entomology curriculum to be conducted in medical college (need new positions)
  • Case-based Surveillance guidelines
  • Private-sector engagement (for increased reporting and product quality control/procurement such as Antigen RDTs)
  • Capacity Assessments in 9 health systems strengthening components at central and district levels (Jhpiego Malaria Implementation Guide)
  • Human resources: clear job descriptions and performance goals
  • Leadership & Management development program

gfatm-bednets-distProgram highlights include the fact that the Global Fund malaria grant rating improved from B2 (inadequate but demonstrating potential) in January 2016, but now A2 (meeting expectations) in November 2016. Concept note for operational research at 2 or 3 border check points has been developed in order to determine whether such intervention (communication & voluntary screening) is cost-effective and relevant to catch/target imported cases, raise awareness on malaria available services, detect/prevent sources of potential outbreaks. This will inform GFATM on the relevance to fund such intervention. A similar approach was done at the China-Myanmar border but was not recognized by not WHO.

Nepal's Global Fund Grant Indicators for Malaria Case Management

Nepal’s Global Fund Grant Indicators for Malaria Case Management

Although the National Malaria Strategic Plan refers to high risk groups (forest workers, national parks security personnel, refugees, prisoners, etc.) evidence is needed to back this up. A study or improved investigation forms are needed to identify such groups and use this information to design appropriate behavior change communications and other interventions.

Special Programming Highlights include proposing a focus on Closed/Isolated Settings/Foci (limited migration, duration and population) to WHO and GFATM. Considering a targeted mass drug administration (MDA) Plasmodium vivax (not yes recommended by WHO) with Primaquine/G6PD testing. Consideration is being given to new drugs in the pipeline such as Ivermectin. Molecular Testing using Polymerase Chain Reaction (PCR) to detect low parasitemia, asymptomatic or re-infection cases (Pv includes inactive/dormant sporozoites known as hypnozoites) is being proposed.

Community based testing as proposed in the Global Fund grant needs strengthening. Therefore RDT use by Female Community Health Volunteer is being considered. Active case detection is another possibility for those areas moving toward pre-elimination. As mentioned, there is also need for studies of asymptomatic infection.

Lessons learned so far for best practices for efforts in identifying specific pre-elimination interventions include the value of getting consensus at national level through the Malaria Technical Working Group. There is also need to challenge WHO recommendations and engage dialogue to get creative. At present there is a risk of a Catch 22 situation wherein the GFATM asks for innovative interventions but at the same time tries to adhere strictly WHO to existing guidance.

The Nepalese malaria program is in constant dialogue with the GFATM Fund Portfolio Manager and team on the local context and technical challenges in order to get them involved in looking for innovative solutions.

Challenges arise in malaria diagnostics. While systematic microscopy is the gold standard, quality can be poor because of low stain/re-agent quality, constant staff turnover and donor reluctance to fund additional training. Also microscopy confirmation and slide quality control are time consuming, and often this process is not clear or well followed. PCR require specific equipment, training and qualifications. Takes time to be operational.

There are opportunities moving forward.  Progress could be made if there were more “elimination experts” to position to influencer to WHO to seek and propose new interventions for the pre-elimination stage. Nepal provides an ideal opportunity to test new ideas. It will also be necessary for the national malaria program staff to receive regular technical updates on program issues such as new drugs (Ivermectin?) and on-going pilots of MDA.

Identifying a More Accurate Test for Schistosomiasis in The Gambia

During the recently concluded 65th Annual Meeting of the American Society of Tropical Meicine and Hygiene colleagues from The Gambian Ministry of Health and Social Welfare, the World Health Organization and the NTD Support Center presented a poster entitled, “Field Performance of a Circulating Cathodic Antigen Rapid Test at Point-Of-Care for Mapping Schistosomiasis-Endemic Districts in Gambia.” The authors included Bakary Sanneh, Kristen Renneker, Joof  Ebrima, Sanyang M. Abdoulie, Camara Yaya, Sambou M. Sana, Sey Alhagie Papa, Jagne Sherifo, Baldeh Ignacious, Louis-Albert Tchuem Tchuente, Patrick J Lammie, and Kisito Ogoussan. Their abstract appears below.

figureBackground: The traditional parasitological Kato Katz smears and urine filtration methods recommended by the World Health Organization (WHO) to implement mapping of schistosomiasis have been found to be less sensitive in the detection of light-intensity schistosomiasis infections. Field surveys in Sub-Sahara Africa have shown that the Circulating Cathodic Antigen (CCA) point-of-care (POC) test is more accurate for detecting Schistosoma mansonia than the microscopic Kato Katz technique.

Aim: To establish the field sensitivity and specificity of POC CCA as mapping tool to provide the endemicity of schistosomiasis in The Gambia.

Methods: A cross-section study …

  • Ten school per region in 4 regions with historical known risk
  • Fifty children aged 7 to 14 years: 25 boys and 25 girls (WHO Mapping sampling guide)
  • Stool, urine and finger pricks samples were examined for Schistosomiasis
  • Parasitological tests: 2 Kato-katz slides to read from each stool sample, and urine filtration technique, urine dip-stick and Circulating Cathodic Antigen (CCA) techniques,

table-1Discussion: The CCA prevalence in this study was 23.34% (95% CI, 21.51-25.26%) two times higher than the prevalence based on  egg-detection for S. haematobium and S.mansoni (10.13,95% CI 8.87-11.55; and 0.26%, (95% CI, 0.09-0.62, respectively).  Although The Gambia is thought to be endemic for only S. haematobium, yet 5 subjects were found to harbor S. mansoni. Three of the 5 individuals from the high endemic schistosomiasis regions were co-infected with S. haematobium and S. mansoni.

table-2The sensitivity of the POC-CCA proved to be relatively high (60.0%), using double Kato-Katz as a reference for S. mansoni detection, although few infections were found, 5 out 1954  tested. The specificity of the POC CCA was 76.8%, respectively.  Using urine filtration as reference standard for the detection of S. haematobium, the sensitivity of POC-CCA was 47.9% and the specificity was 79.4%.

Conclusion: The Gambia is endemic for both urinary and intestinal schistosomiasis although most of the infections are due to S. haematobium in the 4 regions investigated. The results of the study showed a low sensitivity of the POC-CCA test in detecting S. haematobium and therefore we conclude further research is needed  to develop an ideal rapid diagnosis tool for urinary schistosomiasis.

schisto-acknowledgementAcknowledgement: Thanks to the Mapping Team,  Consultants, MoHSW, WHO,  Task Force for Global Health (TFGH) for all their support. For questions please contact: Dr. Kisito Ogoussan, kogoussan@taskforce.org; or Mr. Bakary Sanneh, sheikbakary@yahoo.com

Malaria Mass Drug Administration: Ensuring Safe Care of Reproductive Age Women

The potential impact of mass malaria drug administration (MDA) on pregnant women was the focus of Symposium 146 at the recent 65th Annual Meeting of the American Society of Tropical Medicine and Hygiene in Atlanta. The symposium was co-chaired by Clara Menéndez and Larry Slutsker who opened the session with an overview.

mda-recommendations-whoAs malaria control interventions are scaled up and sustained and malaria transmission levels decline and prevalence falls, an increasing number of countries are starting to see elimination on the horizon. For pregnant women, the antimalarial antibodies that have provided some level of protection in moderate to high malaria transmission settings are reduced as malaria transmission declines.

Current evidence shows that as transmission levels decline, the consequences from P. falciparum malaria are even greater for pregnant women. As countries enter pre-elimination stage and move towards eventual elimination, it will be important to address the needs of pregnant women given their increased vulnerability.

To help achieve elimination, countries are exploring strategies involving widespread distribution of anti-malarials, primarily artemisinin-combination therapies (ACTs), to asymptomatic individuals, including both mass drug administration (MDA) and mass screen and treat (MSaT).

Animal studies have suggested potential embryo toxicity and teratogenic effects of artemisinin drugs in the first trimester of pregnancy.

Given the limited human data, ACTs are currently contraindicated in first trimester, except in documented cases of clinical malaria illness where quinine is unavailable. This poses a challenge in mass campaigns, as it requires the identification of women in early pregnancy who are not yet obviously pregnant. Screening including offering pregnancy tests and/or interview to ask a woman her pregnancy status directly may not work as many may not wish to reveal their pregnancy status.

Final Algorithm for Screening Prior to MDA in Mozambique

Final Algorithm for Screening Prior to MDA in Mozambique

While only about 5% of the population is pregnant at any given time, and only 1/3 of those are in the first trimester, approximately 20% of the population is comprised of women of reproductive age who may be pregnant. Thus, the number of women who need to be screened for pregnancy is substantial across countries. In addition to privacy issues, costs of screening processes are another barrier.

During the symposium Francisco Saúte from Mozambique and Samuel J. Smith from Sierra Leone shared experiences. Clara Menéndez addressed ethical issues involved in the potential risk of MDA with the ACT Dihydroartemisinin-Piperaquine (DHA-P). These two countries have addressed pregnant women in MDAs in two widely different contexts.

Mozambique is learning whether MDA is a valuable component to malaria elimination in the low transmission areas in the southern part of the country. In Sierra Leone MDA was seen as a lifesaving tool to prevent malaria deaths during the Ebola epidemic when taking blood samples for diagnosis was a major risk.

Over several rounds of MDA, Mozambique refined its pregnancy screening procedures over several rounds of MDA as seen in the attached slide.  Costs, confidentiality, convenience and efficiency entered into the equation that saw a greater focus on communicating with women rather that testing. Lessons learned from MDA in Mozambique included –

  • Screening for early pregnancy in the context of MDA is challenging, particularly among teenage girls where disclosing pregnancy can be problematic
  • Need to train field workers (preferably women) about the need to ensure confidentiality of pregnancy testing/results
  • Confidentiality is also crucial to ensure adherence to t
    MDA Rationale in Sierra Leone during Ebola Outbreak

    MDA Rationale in Sierra Leone during Ebola Outbreak

    he pregnancy testing

  • Women not accepting pregnancy test must be warned on risks/ benefits of ACTs in 1st trimester
  • Health authorities must understand that IPTp and MDA are not mutually exclusive

The Ebola epidemic in Sierra Leone and its neighbors, Liberia and Guinea, devastated the health workforce, and the availability of any sort of testing supplies was low.  The country experienced a major drop in utilization of clinic based MCH services including those for malaria during the period.

MDA Goals in Sierra Leons

MDA Goals in Sierra Leone

Because of initial similarities in presenting symptoms between Ebola and malaria, people were often fearful of going to the health center in case they were detained for Ebola care or were exposed to other patients who had Ebola. Community MDA seemed to be one way to protect the population from malaria in this emergency situation. The attached slide offers a rational for the MDA. A second slide explains Sierra Leone’s goal for MDA with Artesunate-Amodiaquine in the context of Ebola. Though not completely, the Sierra Leone MDAs were able to exclude pregnancy women in their first trimester.

Pregnant women excluded from MDA in Sierra Leone

Pregnant women excluded from MDA in Sierra Leone

In conclusion MDA is a tool conceived primarily for countries and areas of countries as part of the pre-elimination strategy. It presents a variety of logistical challenges, but a major concern should also be the ethical issues of giving a potentially toxic drug to women in their first trimester of pregnancy. Alternative strategies to protect these women, including insecticide treated nets, must be explored.

Mobile suitcase laboratory: A tool for the rapid detection of emerging and endemic infectious disease

Ahmed Abd El Wahed who is based at Georg-August University, Goettingen, Germany shares his experiences with development and use of field diagnostics that can fit in a suitcase. This work received support from the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, Geneva, Switzerland. He explains the concept here …

Laboratory diagnosis mainly depends on nucleic acid detection by real-time polymerase chain reaction (PCR), which is available in central laboratories and has a turnaround time of more than two hours. Since real-time RT-PCR assays are not suitable for on-site screening, samples collected from local hospitals, treatment center or at the site of an outbreak have to be sent to laboratories over long distances for testing.

In developing countries, the necessary equipment for diagnosis is only available in few central laboratories, which are not accessible and of limited capacity to test large numbers of incoming samples. Moreover, transport conditions of samples are inadequate and therefore lead to unreliable results.

lab-in-a-suitcaseFor decentralizing of the molecular diagnostics, there is a need for a simple molecular point-of-need test. We have developed a mobile suitcase laboratory (62+49+30 cm) containing all reagents and equipment for the detection of the nucleic acid of infectious agents using the recombinase polymerase amplification (RPA) technology. The RPA assay run at a constant temperature (42°C) for a maximum of 15 minutes.

Moreover, all reagents are cold-chain independent and the mobile laboratory is operated by a solar power battery. The nucleic acid extraction is performed by a magnetic bead based method, in which a simple fast lysis protocol is applied. In case of highly infectious agents such as Ebola virus, the inactivation step was performed in a glovebox.

The suitcase lab is designed to detect almost 30 pathogens such as Dengue, Zika, Chikungunya, Ebola, Coronaviruses as well as Tuberculosis, Leptospira, Salmonella typhi and paratyphi, malaria, avian influenza, and Leishmania.

The suitcase lab featured in a presentation at the 65th Annual Meeting of the American Society of Tropical Medicine in Atlanta under the title of “Novel Extraction Protocol and Recombinase Polymerase Amplification Assay for Detection of Leishmania Donovani In 30 Minutes.” Authors/presenters included Dinesh Mondal, Prakash Ghosh, Md. Anik Ashfaq Khan, Faria Hossain, Susanne Böhlken-Fascher, Greg Matlashewski, Axel Kroeger, Piero Olliaro, and Ahmed Abd El Wahed.

Their work highlighted Leishmania donovani (LD), a protozoan parasite transmitted to humans by sand flies, which causes Visceral Leishmaniasis (VL). Currently, diagnosis is based on presence of anti-LD antibodies and clinical symptoms. Molecular diagnosis would require real-time PCR, which is not easy to implement at field settings.

In this study, we report on the development and testing of a novel extraction protocol in combination with recombinase polymerase amplification (RPA) assay for the detection of LD. The LD RPA assay detected equivalent to one LD genomic DNA. The RPA assay was performed at constant temperature (42°C) and the total assay runtime including the extraction procedure was 30 minutes.

The RPA assay also detected other Leishmania species (L. major, L. aethiopica and L. infantum), but did not identify nucleic acid of other pathogens. Forty-eight samples from VL, asymptomatic and post-kala-azar dermal leishmaniasis subjects were detected positive and 48 LD negative samples were negative by both LD RPA and real-time PCR assays, which indicates 100% agreement.

To allow the use of the assay at field settings, a mobile suitcase laboratory (56+45.5+26.5 cm) was developed and operated at the local hospital in Mymensingh, Bangladesh by using a solar-powered battery. DNA extraction was performed by a novel magnetic bead based method, in which a simple fast lysis protocol was applied.