Category Archives: Diagnosis

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

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.

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

Intensive Malaria Microscopy Training in Rwanda

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.

Tropical Health Update 2019-08-04: Ebola, Malaria Vectors, Snakebite and Trachoma

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.

Tropical Health Update 2019-07-28: Ebola and Malaria Crises

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.

The Weekly Tropical Health News 2019-07-06: Eliminating Malaria in Low Transmission Settings

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.

The Weekly Tropical Health News 2019-06-29

Below we highlight some of the news we have shared on our Facebook Tropical Health Group page during the past week.

Polio Persists

If all it took to eradicate a disease was a well proven drug, vaccine or technology, we would not be still reporting on polio, measles and guinea worm, to name a few. In the past week Afghanistan reported 2 wild poliovirus type 1 (WPV1) cases, and Pakistan had 3 WPV1 cases. Circulating vaccine-derived poliovirus type 2 (cVDPV2) was reported in Nigeria (1), DRC (4) and Ethiopia (3) from healthy community contacts.

Continued Ebola Challenges

In the seven days from Saturday to Friday (June 28) there were 71 newly confirmed Ebola Cases and 56 deaths reported by the Democratic Republic of Congo’s Ministry of Health. As Ebola cases continue to pile up in the Democratic Republic of the Congo (DRC), with 12 more confirmed Thursday and 7 more Friday, a USAID official said four major donors have jump-started a new strategic plan for coordinating response efforts. To underscore the heavy toll the outbreak has caused, among its 2,284 cases, as noted on the World Health Organization Ebola dashboard today, are 125 infected healthcare workers, including 2 new ones, DRC officials said.

Pacific Standard explained the differences in Ebola outbreaks between DRC today and the West Africa outbreak of 2014-16. On the positive side are new drugs used in organized trials for the current outbreak. The most important factor is safe, effective vaccine that has been tested in 2014-16, but is now a standard intervention in the DRC. While both Liberia and Sierra Leone had health systems and political weaknesses as post-conflict countries, DRC’s North Kivu and Ituri provinces are currently a war zone, effectively so for the past generation. Ebola treatment centers and response teams are being attacked. There are even cultural complications, a refusal to believe that Ebola exists. So even with widespread availability of improved technologies, teams may not be able to reach those in need.

To further complicate matters in the DRC, Doctors Without Borders (MSF) “highlighted ‘unprecedented’ multiple crises in the outbreak region in northeastern DRC. Ebola is coursing through a region that is also seeing the forced migration of thousands of people fleeing regional violence and is dealing with another epidemic. Moussa Ousman, MSF head of mission in the DRC, said, ‘This time we are seeing not only mass displacement due to violence but also a rapidly spreading measles outbreak and an Ebola epidemic that shows no signs of slowing down, all at the same time.’”

NIPAH and Bats

Like Ebola, NIPAH is zoonotic, and also involves bats, but the viruses differ. CDC explains that, “Nipah virus (NiV) is a member of the family Paramyxoviridae, genus Henipavirus. NiV was initially isolated and identified in 1999 during an outbreak of encephalitis and respiratory illness among pig farmers and people with close contact with pigs in Malaysia and Singapore. Its name originated from Sungai Nipah, a village in the Malaysian Peninsula where pig farmers became ill with encephalitis.

A recent human outbreak in southern India has been followed up with a study of local bats. In a report shared by ProMED, out of 36 Pteropus species bats tested for Nipah, 12 (33%) were found to be positive for anti-Nipah bat IgG antibodies. Unlike Ebola there are currently no experimental drugs or vaccines.

Climate Change and Dengue

Climate change is expected to heighten the threat of many neglected tropical diseases, especially arboviral infections. For example, the New York Times reports that increases in the geographical spread of dengue fever. Annually “there are 100 million cases of dengue infections severe enough to cause symptoms, which may include fever, debilitating joint pain and internal bleeding,” and an estimated 10,000 deaths. Dengue is transmitted by Aedes mosquitoes that also spread Zika and chikungunya. A study, published Monday in the journal Nature Microbiology, found that in a warming world there is a strong likelihood for significant expansion of dengue in the southeastern United States, coastal areas of China and Japan, as well as to inland regions of Australia. “Globally, the study estimated that more than two billion additional people could be at risk for dengue in 2080 compared with 2015 under a warming scenario.”

Schistosomiasis – MDA Is Not Enough, and Neither Are Supplementary Interventions

Schistosomiasis is one of the five neglected tropical diseases (NTDs) that are being controlled and potentially eliminated through mass drug administration (MDA) of preventive chemotherapy (PCT), in this case praziquantel. In The Lancet Knopp et al. reported that biannual MDA substantially reduced Schistosomiasis haematobium prevalence and infection intensity but was insufficient to interrupt transmission in Zanzibar. In addition, neither supplementary snail control or behaviour change activities did not significantly boost the effect of MDA. Most MDA programs focus on school aged children, and so other groups in the community who have regular water contact would not be reached. Water and sanitation activities also have limitations. This raises the question about whether control is acceptable for public health, or if there needs to be a broader intervention to reach elimination?

Trachoma on the Way to Elimination

Speaking of elimination, WHO has announced major “sustained progress” on trachoma efforts. “The number of people at risk of trachoma – the world’s leading infectious cause of blindness – has fallen from 1.5 billion in 2002 to just over 142 million in 2019, a reduction of 91%.” Trachoma is another NTD that uses the MDA strategy.

The news about NTDs from Dengue to Schistosomiasis to Trachoma is complicated and demonstrates that putting diseases together in a category does not result in an easy choice of strategies. Do we control or eliminate or simply manage illness? Can our health systems handle the needs for disease elimination? Is the public ready to get on board?

Malaria Updates

And concerning being complicated, malaria this week again shows many facets of challenges ranging from how to recognize and deal with asymptomatic infection to preventing reintroduction of the disease once elimination has been achieved. Several reports this week showed the particular needs for malaria intervention ranging from high burden areas to low transmission verging on elimination to preventing re-introduction in areas declared free from the disease.

In South West, Nigeria Dokunmu et al. studied 535 individuals aged from 6 months were screened during the epidemiological survey evaluating asymptomatic transmission. Parasite prevalence was determined by histidine-rich protein II rapid detection kit (RDT) in healthy individuals. They found that, “malaria parasites were detected by RDT in 204 (38.1%) individuals. Asymptomatic infection was detected in 117 (57.3%) and symptomatic malaria confirmed in 87 individuals (42.6%).

Overall, detectable malaria by RDT was significantly higher in individuals with symptoms (87 of 197/44.2%), than asymptomatic persons (117 of 338/34.6%)., p = 0.02. In a sub-set of 75 isolates, 18(24%) and 14 (18.6%) individuals had Pfmdr1 86Y and 1246Y mutations. Presence of mutations on Pfmdr1 did not differ by group. It would be useful for future study to look at the effect of interventions such as bednet coverage. While Southwest Nigeria is a high burden area, the problem of asymptomatic malaria will become an even bigger challenge as prevalence reduces and elimination is in sight.

Sri Lanka provides a completely different challenge from high burden areas. There has been no local transmission of malaria in Sri Lanka for 6 years following elimination of the disease in 2012. Karunasena et al. report the first case of introduced vivax malaria in the country by diagnosing malaria based on microscopy and rapid diagnostic tests. “The imported vivax malaria case was detected in a foreign migrant followed by a Plasmodium vivax infection in a Sri Lankan national who visited the residence of the former. The link between the two cases was established by tracing the occurrence of events and by demonstrating genetic identity between the parasite isolates. Effective surveillance was conducted, and a prompt response was mounted by the Anti Malaria Campaign. No further transmission occurred as a result.”

Bangladesh has few but focused areas of malaria transmission and hopes to achieve elimination of local transmission by 2030. A particular group for targeting interventions is the population of slash and burn cultivators in the Rangamati District. Respondents in this area had general knowledge about malaria transmission and modes of prevention and treatment was good according to Saha and the other authors. “However, there were some gaps regarding knowledge about specific aspects of malaria transmission and in particular about the increased risk associated with their occupation. Despite a much-reduced incidence of malaria in the study area, the respondents perceived the disease as life-threatening and knew that it needs rapid attention from a health worker. Moreover, the specific services offered by the local community health workers for malaria diagnosis and treatment were highly appreciated. Finally, the use of insecticide-treated mosquito nets (ITN) was considered as important and this intervention was uniformly stated as the main malaria prevention method.”

Kenya offers some lessons about low transmission areas but also areas where transmission may increase due to climate change. A matched case–control study undertaken in the Western Kenya highlands. Essendi et al. recruited clinical malaria cases from health facilities and matched to asymptomatic individuals from the community who served as controls in order to identify epidemiological risk factors for clinical malaria infection in the highlands of Western Kenya.

“A greater percentage of people in the control group without malaria (64.6%) used insecticide-treated bed nets (ITNs) compared to the families of malaria cases (48.3%). Low income was the most important factor associated with higher malaria infections (adj. OR 4.70). Houses with open eaves was an important malaria risk factor (adj OR 1.72).” Other socio-demographic factors were examined. The authors stress the need to use local malaria epidemiology to more effectively targeted use of malaria control measures.

The key lesson arising from the forgoing studies and news is that disease control needs strong global partnerships but also local community investment and adaptation of strategies to community characteristics and culture.

The Weekly Tropical Health News Update 2019-06-22

For almost 20 years we have been maintaining an email list where current news and articles have been shared with those interested in tropical health and malaria. The listserve host we have been using is changing to a paid model. While there are still some free listserve options, these are cumbersome to produce. Since we are already maintaining this blog, we thought it best to provide a weekly summary of key news events through this medium.

Mapping Plasmodium Vivax

The Malaria Atlas Project has published in The Lancet a global burden of Plasmodium Vivax mapping study. The authors describe the contribution of this study as: “Our study highlights important spatial and temporal patterns in the clinical burden and prevalence of P vivax. Amid substantial progress worldwide, plateauing gains and areas of increased burden signal the potential for challenges that are greater than expected on the road to malaria elimination. These results support global monitoring systems and can inform the optimisation of diagnosis and treatment where P vivax has most impact.”

Ebola Spread from DRC to Uganda

Since the major ongoing outbreak of Ebola Virus Disease in North Kivu and Ituri Provinces of the Democratic Republic of Congo (DRC) started nearly a year ago, there has been concern that the disease might spread to neighboring countries like Uganda, Rwanda, South Sudan and the Central African Republic. This fear same true recently when a family affected by Ebola crossed from DRC into Uganda to connect with relatives in Kasese District Uganda. Uganda has had many years’ experience dealing with Ebola and was able to contain the situation.

A press release this week noted that, “As of today (21 June 2019), Uganda has not registered any new confirmed Ebola Virus Disease (EVD) case in Kasese District or any other part of Uganda since the last registered case one week ago. There are no new suspect cases under admission. Currently, 110 contacts to the confirmed Ebola cases in Kagando and Bwera are being followed up daily. A total of 456 individuals have been vaccinated against EVD using the Ebola-rVSV vaccine in Kasese District, Western Uganda.”

Although many people expected that the meeting of the “International Health Regulations (2005) Emergency Committee} for Ebola virus disease in the Democratic Republic of the Congo would finally declare the current outbreak a Public Health Emergency of International Concern (PHEIC) because it crossed a border, the result was noting that the challenge was still an emergency only for DRC. WHO did note that there were serious funding gaps and support from other countries for the DRC’s predicament. Ironically, such gaps make it more likely that Ebola can spread more widely.

As of 21 June 2019, the DRC reported a total of 2,211 cases since the start of the epidemic last year, of which 2,117 have been confirmed and 94 are probable. There have been 1,489 deaths. To date 139,027 persons have been vaccine with the Merck rVSV-ZEBOV vaccine.

Progress toward Eliminating Malaria – the E-2020 Countries

The process of eliminating malaria from the world needs to start in a step-by-step fashion. WHO explained that, “Creating a malaria-free world is a bold and important public health and sustainable development goal. It is also the vision of the Global technical strategy for malaria 2016-2030, which calls for the elimination of malaria in at least 10 countries by the year 2020.”

Actually, WHO identified 21 countries, spanning 5 regions, that could defeat malaria by 2020. The progress report charts the effort. During the recent World Health Assembly two countries received recognition for being certified malaria-free, Argentina and Algeria. This week WHO also announced that 5 more countries have not had malaria cases in the past year. There was also release of a downloadable report on progress toward the 2020 target for selected countries.

Reconsidering Yaws Eradication

In the 1950s and 1960s the world focused on the possibility of eradicating Yaws through screening and treatment interventions. Like the early malaria eradication programs from the same period, the Yaws effort slowed, stopped and experienced a resurgence. The Telegraph reported that, “Between 1952 and 1964, Unicef and the WHO screened some 300 million people for the illness, in a coordinated programme which treated more than 50 million cases. Yaws was on the brink of being wiped out and reports of the disease dropped by 95 per cent.” WHO continues to work on treatment strategies with azithromycin and for resistant cases, benzathine benzylpenicillin injection.

WHO noted that there were 80,472 cases reported in 2018, although this figure is likely to be much higher in actuality. The challenge of case detection exists but may be overcome, according to the Telegraph with a new molecular rapid diagnostic test which detects yaws within 30 minutes, and thus could allow on-the-spot diagnosis in remote regions.

Measles Cases Continue to Increase

The problem of measles in the DRC may not be receiving much attention because of the Ebola epidemic. Ironically, Outbreak News Today reports that, “In a follow-up on the measles outbreak in the Democratic Republic of the Congo (DRC), UN health officials report an additional 7500 suspect cases in the past 2 weeks, bringing the total cases since the beginning of the year to 106,870. The death toll due to the measles outbreak has reached 1815 deaths (case fatality ratio 1.7%).”

Vaccine coverage challenges in the DRC result from health systems weaknesses. Unfortunately, a global study has shown that increasing cases in the Global North are not due to weak systems, but ‘vaccine hesitancy.’ The Guardian reports that a global survey has revealed the scale of the crisis of confidence in vaccines in Europe, “showing that only 59% of people in western Europe and 50% in the east think vaccines are safe, compared with 79% worldwide.” The Guardian observes that, “In spite of good healthcare and education systems, in parts of Europe there is low trust in vaccines. France has the highest levels of distrust, at 33%.”

For more news and daily updates check our other services, a closed/private Facebook Group and a Twitter feed. For those who do not use social media, please check here each weekend to find a summary of some of the stories we have shared during the week.

Zero Malaria Starts with Universal Coverage: Part 2 Preventive and Curative Treatments

April hosts several important global health days or observances. On World Health Day 2019 WHO stressed that, “Universal health coverage (UHC) is WHO’s number one goal. Key to achieving it is ensuring that everyone can obtain the care they need, when they need it, right in the heart of the community.” Nationwide monitoring through the Demographic and Health Surveys (DHS), the Malaria Indicator Surveys (MIS) and the Multi-Indicator Cluster Surveys (MICS) can document the status of appropriate malaria treatment and intermittent preventive treatment in pregnant women (IPTp).

Definitions of indicators have evolved for treatment-related malaria interventions. When Intermittent Preventive Treatment for pregnant women (IPTp) began in the early 2000s, the recommended dosing was twice during pregnancy after the first trimester one month apart in high and/or stable transmission areas. Due to lessening efficacy of sulfadoxine-pyrimethamine (SP), the dosage recommendation has changed to at least three times, still a month apart from the beginning of the second trimester.

This updated policy was broadcast widely between 2012 and 2013, but it took countries some time to build capacity and scale up for the expanded coverage goals. UNICEF Data5 again show that between 2014 and 2017 coverage was far below either 80% of pregnant women, let alone reaching them universally (Figure 2). Most countries achieved 30% or less coverage. Zambia at 50% was the highest. Low coverage leaves both pregnant women and the unborn child at risk for anemia and death in the former and low birth weight, still birth or miscarriage for the latter. The World Malaria Report of 2018 estimates that three doses of IPTp were received by only 22% of pregnant women in the target countries in 2017.

The concept of IPT was investigated for infants and children during by a consortium of researchers in several African Countries. It was found that IPTi with SP could have a positive effect on preventing malaria. To operationalize this concept, the World Health Organization developed what is known as Seasonal Malaria Chemoprevention (SMC) that would be delivered in the Sahel region of West Africa where malaria transmission itself is seasonal and where there are some countries with very low transmission with implications for malaria elimination.

The SMC delivery process was not linked to immunization but provided by community health workers and volunteers. SP and Amodiaquine (SP-AQ) were used in combination and provided monthly, three or four times during the rainy/high transmission season. Coverage was targeted at children below school age. It is only recently that SMC has been scaled up to reach all eligible countries or states and regions within designated countries.

WHO states that SMC focuses on, “children aged 3–59 months (and) reduces the incidence of clinical attacks and severe malaria by about 75%.” In some countries the coverage is extended to primary school aged children, making comparisons and calculations of coverage (universal por otherwise) challenging.

The World Malaria Report of 2018 notes that, “In 2017, 15.7 million children in 12 countries in Africa’s Sahel subregion were protected through seasonal malaria chemoprevention (SMC) programs. However, about 13.6 million children who could have benefited from this intervention were not covered, mainly due to a lack of funding.” This implies that 54% of eligible children were reached.  Coverage of SMC can refer to receiving any of the doses or as having received all the monthly doses offered by a nation’s malaria control program. Specifically, the World Malaria Report 2018 drew on surveys in 7 countries that provided 4 monthly doses to determine that 53% of children received all doses.

Determining coverage for malaria treatment for sick people is not as straightforward as finding out the numbers who slept under an ITN or swallowed IPTp doses, and even those are not simple. As defined, correct treatment first consists of parasitological diagnosis, which at the primary care level could be by microscopy or rapid diagnostic test (RDT). The next issue is treating only those with positive tests. Finally, the treatment must consist of age- or weight-specific doses of an approved artemisinin-based combination therapy (ACT) drug. Very few clinic records or surveys document whether the treatment given is ‘correct’ by these standards.

WHO addresses the need for achieving universal access to malaria diagnostic testing and notes this will not be easy. They provide a successful example of Senegal, where following the introduction of malaria RDTs in 2007, malaria diagnostic testing rates rose rapidly from 4% to 86% (by 2009). Logistics, funding, training and supportive supervision complicate implementation.

UNICEF Data report that performance of malaria diagnostics in febrile children in surveys between 2014-17 was approximately 30% on average for countries with national surveys within that time frame (Figure 3). Only 4 countries achieved 50% or better. Most surveys then go on to report the number of febrile children who received ACTs, but do not necessary indicate how many who were correctly diagnoses were given ACTs vs those who received ACT but did not receive a test or tested negative.

The Nigeria 2015 Malaria Indicator Survey Illustrates this dilemma. Among 2600 children who reported having a fever in the two weeks preceding the survey, 66.1% sought advice (or care). Overall, 12.6% of febrile children received a diagnostic test as defined in the question as to whether the child was stuck on the finger or heel to obtain blood. Among the febrile children 37.6% reportedly were given some type of antimalarial drug. Overall 15.5% of febrile children were given an ACT. Even if ACTs were given only to tested children, not all tests would have been positive.

The overall implication of measuring treatment without a link to testing is that if more children receive any, let alone the correct drugs, is that evidence for actual presence of disease. We have a long way to go to measure malaria treatment coverage correctly, not to mention achieving universal coverage with appropriate treatment. Different malaria treatment-related interventions with different steps and different target groups in different regions of Africa and the World make defining, no less achieving UHC, a huge challenge.