Center for Tropical and Emerging Global Diseases
University of Georgia
Professor Emeritus Daniel Colley is the featured guest on the People, Parasites, and Plagues podcast. Learn more about his time spent with the CDC, becoming the director of the Center for Tropical and Emerging Global Diseases at UGA, and the research abroad that sparked his passion for schistosomes in this episode.
Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs.
Nathan C Lo, Fernando Schemelzer Moraes Bezerra, Daniel G Colley, Fiona M Fleming, Mamoun Homeida, Narcis Kabatereine, Fatma M Kabole, Charles H King, Margaret A Mafe, Nicholas Midzi, Francisca Mutapi, Joseph R Mwanga, Reda M R Ramzy, Fadjar Satrija, J Russell Stothard, Mamadou Souncalo Traoré, Joanne P Webster, Jürg Utzinger, Xiao-Nong Zhou, Anthony Danso-Appiah, Paolo Eusebi, Eric S Loker, Charles O Obonyo, Reginald Quansah, Song Liang, Michel Vaillant, M Hassan Murad, Paul Hagan, Amadou Garba. Lancet Infect Dis. 2022 May 17;S1473-3099(22)00221-3. doi: 10.1016/S1473-3099(22)00221-3.
Background: Over the past 20 years, schistosomiasis control has been scaled up. Preventive chemotherapy with praziquantel is the main intervention. We aimed to assess the effect of preventive chemotherapy on schistosomiasis prevalence in sub-Saharan Africa, comparing 2000-10 with 2011-14 and 2015-19.
Methods: In this spatiotemporal modelling study, we analysed survey data from school-aged children (aged 5-14 years) in 44 countries across sub-Saharan Africa. The data were extracted from the Global Neglected Tropical Diseases database and augmented by 2018 and 2019 survey data obtained from disease control programmes. Bayesian geostatistical models were fitted to Schistosoma haematobium and Schistosoma mansoni survey data. The models included data on climatic predictors obtained from satellites and other open-source environmental databases and socioeconomic predictors obtained from various household surveys. Temporal changes in Schistosoma species prevalence were estimated by a categorical variable with values corresponding to the three time periods (2000-10, 2011-14, and 2015-19) during which preventive chemotherapy interventions were scaled up.
Findings: We identified 781 references with relevant geolocated schistosomiasis survey data for 2000-19. There were 19 166 unique survey locations for S haematobium and 23 861 for S mansoni, of which 77% (14 757 locations for S haematobium and 18 372 locations for S mansoni) corresponded to 2011-19. Schistosomiasis prevalence among school-aged children in sub-Saharan Africa decreased from 23·0% (95% Bayesian credible interval 22·1-24·1) in 2000-10 to 9·6% (9·1-10·2) in 2015-19, an overall reduction of 58·3%. The reduction of S haematobium was 67·9% (64·6-71·1) and that of S mansoni 53·6% (45·2-58·3) when comparing 2000-10 with 2015-19.
Interpretation: Our model-based estimates suggest that schistosomiasis prevalence in sub-Saharan Africa has decreased considerably, most likely explained by the scale-up of preventive chemotherapy. There is a need to consolidate gains in the control of schistosomiasis by means of preventive chemotherapy, coupled with other interventions to interrupt disease transmission.
Funding: European Research Council and WHO.
Christos Kokaliaris, Amadou Garba, Martin Matuska, Rachel N Bronzan, Daniel G Colley, Ameyo M Dorkenoo, Uwem F Ekpo, Fiona M Fleming, Michael D French, Achille Kabore, Jean B Mbonigaba, Nicholas Midzi, Pauline N M Mwinzi, Eliézer K N’Goran, Maria Rebollo Polo, Moussa Sacko, Louis-Albert Tchuem Tchuenté, Edridah M Tukahebwa, Pitchouna A Uvon, Guojing Yang, Lisa Wiesner, Yaobi Zhang, Jürg Utzinger, Penelope Vounatsou. The Lancet Infectious Diseases, 2021, https://doi.org/10.1016/S1473-3099(21)00090-6.
Schistosomiasis, caused by several species of the parasitic worm Schistosoma, is a disease of poverty. The debilitating illness keeps people in a cycle of poverty due to missed educational and employment opportunities. In children, repeated infections often lead to anemia, malnutrition and learning disabilities. While there are no current preventive drug therapies or vaccines, annual mass drug administration (MDA) is often used to treat all elementary school children in countries where Schistosoma species are endemic.
“Treating with praziquantel through MDA programs is really successful in reducing schistosomiasis,” said Dan Colley, professor emeritus in the Franklin College of Arts and Sciences’ Department of Microbiology and former director of the Center for Tropical and Emerging Global Diseases. “However, in our studies we were seeing a few villages that didn’t really respond to annual MDA with lower numbers of infections. And it wasn’t just a few villages—in any given group of 25 study villages, we saw what we’re calling ‘persistent hotspots.’”
Through the work of the Schistosomiasis Consortium for Operational Research and Evaluation, researchers discovered that persistent hotspots (PHS) occurred in study sites in Cote d’Ivoire, Mozambique, Tanzania, Zanzibar and Kenya.
Schistosoma parasites develop in certain species of freshwater snails and are shed into the water where the form of the parasite that infects people can survive up to 24 hours. When an individual comes to the water to bathe, wash clothes, work or play, the parasites invade through the skin.
Several weeks after infection, the worms mature and begin to produce eggs that travel to the person’s bladder or intestines, where they are expelled through urine or stool. When freshwater sources are contaminated with human urine or fecal matter that contain these eggs, the life cycle begins again when the parasite eggs hatch and infect appropriate freshwater snails.
In a recent study published in PLOS ONE, Colley and his colleagues at the University of Georgia, Kenya Medical Research Institute (KEMRI), and Kenya’s Ministry of Health found high use of surface water and low use of latrines were factors associated with being a PHS and likely contributed to persistent levels of Schistosoma infection in these PHS villages—even in the face of annual MDA.
The study in western Kenya included both villages responding well to MDA (with a declining level of schistosomiasis) and those that are considered persistent hotspots. All the villages have fewer than 2,000 people, and most range between 500 and 1,500 residents. They often contain a crossroads that serves as the town center with a few shops. While the town center and the nearby houses have electricity, homes farther out might not. Villages considered PHS were located closer to open water sources, and more residents were employed in water-based jobs such as car washing and sand harvesting.
It was also found that these PHS villages had fewer latrines than villages that responded well to MDA, which likely led to more human fecal matter washing into the surface waters. The researchers believe that for these PHS villages, increasing latrine availability and use would reduce Schistosoma prevalence. However, it isn’t just a case of “if you build it, they will come.”
There are several barriers that would need to be overcome. Latrines, commonly called outhouses, are often smelly and attract flies and rats, which then attract snakes. In addition to issues of maintenance, there are social and educational components that need to be considered to change practices. But even when the people are willing, increased latrine use doesn’t always work.
Colley recounts the story of a group of car washers he and other colleagues at KEMRI and the Centers for Disease Control and Prevention worked with for over two decades. These men are well-versed on Schistosoma, and they decided to build a latrine.
“They knew the life cycle as well as we did, maybe better,” recalls Colley.
The car washers even made it an entrepreneurial pursuit by selling toilet paper for a shilling. However, when the rainy season came, the latrine was flooded, and all that waste was washed into the nearby lake where they worked daily.
This story illustrates just one of the challenges public health officials face in trying to incorporate wells and latrines into national programs to eliminate schistosomiasis. Studies like the one by Colley and his colleagues demonstrate the need to look beyond drug treatment when pushing to move from control to elimination of schistosomiasis.
“We can keep doing MDA, which is helpful, but eventually the worms may become drug resistant,” said Colley. “But with persistent hotspots now being found in everyone’s studies, we know we need to do better. That means we need to advocate for access to clean water sources, sanitation and perhaps ultimately vaccines, as well.”
Background: Evidence indicates that whereas repeated rounds of mass drug administration (MDA) programs have reduced schistosomiasis prevalence to appreciable levels in some communities referred to here as responding villages (R). However, prevalence has remained high or less than anticipated in other areas referred to here as persistent hotspot villages (PHS). Using a cross-sectional quantitative approach, this study investigated the factors associated with sustained high Schistosoma mansoni prevalence in some villages despite repeated high annual treatment coverage in western Kenya.
Method: Water contact sites selected based on observation of points where people consistently go to collect water, wash clothes, bathe, swim or play (young children), wash cars and harvest sand were mapped using hand-held smart phones on the Commcare platform. Quantitative cross-sectional surveys on behavioral characteristics were conducted using interviewer-based semi-structured questionnaires administered to assess water usage/contact patterns and open defecation. Questionnaires were administered to 15 households per village, 50 pupils per school and 1 head teacher per school. One stool and urine sample was collected from 50 school children aged 9-12 year old and 50 adults from both responding (R) and persistent hotspot (PHS) villages. Stool was analyzed by the Kato-Katz method for eggs of S. mansoni and soil-transmitted helminths. Urine samples were tested using the point-of-care circulating cathodic antigen (POC-CCA) test for detection of S. mansoni antigen.
Results: There was higher latrine coverage in R (n = 6) relative to PHS villages (n = 6) with only 33% of schools in the PHS villages meeting the WHO threshold for boy: latrine coverage ratio versus 83.3% in R, while no villages met the girl: latrine ratio requirement. A higher proportion of individuals accessed unprotected water sources for both bathing and drinking (68.5% for children and 89% for adults) in PHS relative to R villages. In addition, frequency of accessing water sources was higher in PHS villages, with swimming being the most frequent activity. As expected based upon selection criteria, both prevalence and intensity of S. mansoni were higher in the PHS relative to R villages (prevalence: 43.7% vs 20.2%; P < 0.001; intensity: 73.8 ± 200.6 vs 22.2 ± 96.0, P < 0.0001), respectively.
Conclusion: Unprotected water sources and low latrine coverage are contributing factors to PHS for schistosomiasis in western Kenya. Efforts to increase provision of potable water and improvement in latrine infrastructure is recommended to augment control efforts in the PHS areas.
Musuva RM, Odiere MR, Mwinzi PNM, Omondi IO, Rawago FO, Matendechero SH, Kittur N, Campbell Jr CH, Colley DG. (2021) Unprotected water sources and low latrine coverage are contributing factors to persistent hotspots for schistosomiasis in western Kenya. PLoS ONE 16(9): e0253115. https://doi.org/10.1371/journal.pone.0253115
Background: The prevalence of Schistosoma mansoni infection is usually assessed by the Kato-Katz diagnostic technique. However, Kato-Katz thick smears have low sensitivity, especially for light infections. Egg count models fitted on individual level data can adjust for the infection intensity-dependent sensitivity and estimate the ‘true’ prevalence in a population. However, application of these models is complex and there is need for adjustments that can be done without modelling expertise. This study provides estimates of the ‘true’ S. mansoni prevalence from population summary measures of observed prevalence and infection intensity using extensive simulations parametrized with data from different settings in sub-Saharan Africa.
Methodology: An individual-level egg count model was applied to Kato-Katz data to determine the S. mansoni infection intensity-dependent sensitivity for various sampling schemes. Observations in populations with varying forces of transmission were simulated, using standard assumptions about the distribution of worms and their mating behavior. Summary measures such as the geometric mean infection, arithmetic mean infection, and the observed prevalence of the simulations were calculated, and parametric statistical models fitted to the summary measures for each sampling scheme. For validation, the simulation-based estimates are compared with an observational dataset not used to inform the simulation.
Principal findings: Overall, the sensitivity of Kato-Katz in a population varies according to the mean infection intensity. Using a parametric model, which takes into account different sampling schemes varying from single Kato-Katy to triplicate slides over three days, both geometric and arithmetic mean infection intensities improve estimation of sensitivity. The relation between observed and ‘true’ prevalence is remarkably linear and triplicate slides per day on three consecutive days ensure close to perfect sensitivity.
Conclusions/significance: Estimation of ‘true’ S. mansoni prevalence is improved when taking into account geometric or arithmetic mean infection intensity in a population. We supply parametric functions and corresponding estimates of their parameters to calculate the ‘true’ prevalence for sampling schemes up to 3 days with triplicate Kato-Katz thick smears per day that allow estimation of the ‘true’ prevalence.
Bärenbold O, Garba A, Colley DG, Fleming FM, Assaré RK, Tukahebwa EM, et al. (2021) Estimating true prevalence of Schistosoma mansoni from population summary measures based on the Kato-Katz diagnostic technique. PLoS Negl Trop Dis 15(4): e0009310. https://doi.org/10.1371/journal.pntd.0009310
We assessed the feasibility of using a test, treat, track, test, and treat (5T) active surveillance strategy to identify and treat individuals with schistosomiasis in three very low-prevalence villages in Kafr El Sheikh Governorate, Egypt. Primary index cases (PICs) were identified using the point-of-care circulating cathodic antigen (POC-CCA) assay in schools, in rural health units (retesting individuals with positive Kato-Katz examinations over the previous 6 months), and at potential water transmission sites identified by PICs and field observations. Primary cases identified potential second-generation cases-people with whom they shared water activities-who were then tracked, tested, and treated if infected. Those sharing water activities with second-generation cases were also tested. The yield of PICs from the three venues were 128 of 3,576 schoolchildren (3.6%), 42 of 696 in rural health units (6.0%), and 83 of 1,156 at water contact sites (7.2%). There were 118 second- and 19 third-generation cases identified. Persons testing positive were treated with praziquantel. Of 388 persons treated, 368 (94.8%) had posttreatment POC-CCA tests 3-4 weeks after treatment, and 81.8% (301) became negative. The 67 persons remaining positive had negative results after a second treatment. Therefore, all those found positive, treated, and followed up were negative following one or two treatments. Analysis of efforts as expressed in person-hours indicates that 4,459 person-hours were required for these 5T activities, with nearly 65% of that time spent carrying out interviews, treatments, and evaluations following treatment. The 5T strategy appears feasible and acceptable as programs move toward elimination.
Reda M R Ramzy, Amal Rabiee, Khaled M Abd Elaziz, Carl H Campbell, Nupur Kittur, Daniel G Colley, Ayat A Haggag. Am J Trop Med Hyg. 2020 Jul 13. doi: 10.4269/ajtmh.20-0156.
It all began with a simple phone call and now, more than a decade later, the Schistosomiasis Consortium for Operational Control and Evaluation (SCORE) is preparing to pass the baton to new groups of investigators working on understanding and controlling schistosomiasis. Under the direction of Dan Colley, a member of the Center for Tropical and Emerging Global Diseases and professor emeritus of microbiology at the University of Georgia, SCORE has advanced the scientific understanding of how to control schistosomiasis and has moved us closer to the elimination of this devastating and sometimes deadly disease.
In January 2008, Colley received a phone call from Dr. Julie Jacobson of the Bill & Melinda Gates Foundation (BMGF). She wanted Colley to lead a program on how best to control and move towards elimination of schistosomiasis. This program would not be your typical research program.
First, it would involve national Neglected Tropical Disease (NTD) programs, the World Health Organization (WHO), and others around the globe who were pursuing ways to control morbidity due to Schistosoma mansoni and S. haematobium and their transmission.
“While there were and are now many individual research programs in academia, governments and NGOs working on how to control and eliminate schistosomiasis, SCORE was somewhat different in its size and complexity, allowing it to mount large-scale studies and do so comparatively across different countries,” said Colley.
Second, the program would not focus on basic research, but the results of their research would be more directly applicable to improving national NTD control programs.
“Julie made it clear that the BMGF was not interested, at this time, in funding basic research on either anti-schistosomal drug development or anti-schistosomal vaccine development,” said Colley.
While there are several Schistosoma spp. that infect humans worldwide, this program would focus only on two species, S. mansoni and S. haematobium. Furthermore, they would focus primarily on interventions to control these infections in Africa.
With the parameters laid out and the definition of what constitutes operational research, Colley agreed to gather together a consortium of scientists and SCORE was born: their mission – to undertake operational research that could support National NTD managers in making decisions about how to best control and/or eliminate schistosomiasis in their countries.
“The vision was that research findings would be useful to the WHO in revising current and developing new guidelines on how best to control and move towards elimination of schistosomiasis,” said Colley.
Over the past decade, their mission has not changed but how they pursued that mission evolved as situations change., such as the increased availability of praziquantel, made possible through a donation of the drug by Merck, AG; a more realistic vision of the integration of NTD programs; and the desire of funders to move more quickly from control of morbidity to elimination of the disease.
Over the past decade, SCORE has pursued a number of field and laboratory-based projects in 9 African countries. Several of these studies were included in the categories of gaining control, sustaining control of schistosomiasis, or eliminating its transmission.
The control projects compared how best to deliver Mass Drug Administration (MDA) of praziquantel. Gaining control projects were focused on areas with high prevalence of infection and included research related to subtle morbidity, snail infection, and schistosome population genetics. Sustaining control project focused on areas with moderate prevalence as these areas had already achieved a level of control or simply had lower levels of prevalence.
The original focus of the elimination research project was on Zanzibar and the elimination of S. haematobium. They hoped to inform effective strategies of moving an area of low infection prevalence to total elimination of schistosomiasis. In 2013, with supplemental funding, SCORE expanded its focus on elimination research to focus on S. mansoni in Africa. However, due to conflicts within the country where this research was implemented, SCORE and partners had to withdraw. Instead, SCORE identified another elimination priority on the impact of timed interventions on seasonally transmitted schistosomiasis. This research was conducted in Cote d’Ivoire in a large area with S. haematobium.
Another group of projects focused on tools needed to evaluate control and elimination efforts. They were able to field evaluate the point-of-care circulating cathodic antigen (POC-CCA) urine assay for its use as a mapping tool for S. mansoni infection in humans. They also conducted research and evaluation on highly sensitive and specific human diagnostic tests for schistosomiasis and developed and used tools for schistosome population genetics studies.
Keeping with their mission of supporting national NTD program managers in decision-making, SCORE provided critical information by analyzing and synthesizing existing data in a series of 7 Rapid Answers Projects. Each project resulted in a 2 page brochure providing essential information on a topic of interest to program managers. These brochures are available online at https://score.uga.edu/projects/rapid-answers-project/
And finally, in order to optimize the use of the data generated in these large studies, they collected and made them accessible to the scientific community and other stakeholders. SCORE worked with database programmers and statisticians at UGA to integrate the data from various study sites and conduct analyses of combined data, while providing them to all investigators by depositing them in an open database system, ClinEpiDB.
In July, the American Journal of Tropical Medicine and Hygiene published a supplement that summarizes many of the activities, lessons learned, and work that still needs to be done in 16 articles. This supplement is introduced with a guest editorial by N. Robert Bergquist.
Briefly the key findings and take away messages are summarized in Table 1 of the article “Contributions of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) to Schistosomiasis Control and Eliminations: Key Findings and Messages for Future Goals, Thresholds, and Operational Research” (https://doi.org/10.4269/ajtmh.19-0787).
“The impact of SCORE’s findings and messages will depend on their uptake by the WHO/NTD schistosomiasis guidelines development group in the formulation of revised and new guidelines for the control and elimination of schistosomiasis, and then whether national NTD programs consider them worthy of adoption and implementation,” said Colley.
Some of the findings from SCORE are already being implemented, such as the use of the POC-CCA rapid cassette test for mapping S. mansoni prevalence in low-to-moderate areas of schistosomiasis. Other findings, such as the occurrence of persistent hotspots in large-scale MDA programs, are now being considered by other research groups and national NTD programs.
SCORE was built on the foundation of a previously BMGF-funded program – the Schistosomiasis Control Initiative (SCI). The goal of SCI, which is now a private non-governmental organization, was to determine if preventive chemotherapy, as recommended by the WHO, could be implemented countrywide to control schistosomiasis.
“It was an ambitious undertaking that SCI accomplished in multiple African countries,” said Colley. “Now knowing that with the funding, persistence, and training, MDA countrywide could be done, the BMGF decided to fund a program to compare the frequency and platforms for MDA distribution.”
Of course, that program became SCORE. They took what SCI learned and asked additional questions about how best to conduct the preventive chemotherapy by MDA, and explore what tools were needed to do it better. Now that SCORE has fulfilled its mission, they are passing their findings and lessons learned, along with recommendations, to other groups. One of these, the recently established Global Schistosomiasis Alliance, which includes some of the same people involved with SCORE, has taken up the baton to help harmonize the continued fight to end schistosomiasis.
Background: World Health Organization guidelines recommend preventive chemotherapy with praziquantel to control morbidity due to schistosomiasis. The primary aim of this cross-sectional study was to determine if 4 years of annual mass drug administration (MDA) in primary and secondary schools lowered potential markers of morbidity in infected children 1 year after the final MDA compared to infected children prior to initial MDA intervention.
Methods: Between 2012 and 2016 all students in two primary and three secondary schools within three kilometers of Lake Victoria in western Kenya received annual mass praziquantel administration. To evaluate potential changes in morbidity we measured height, weight, mid-upper arm circumference, hemoglobin levels, abdominal ultrasound, and quality of life in children in these schools. This study compared two cross-sectional samples of Schistosoma mansoni egg-positive children: one at baseline and one at year five, 1 year after the fourth annual MDA. Data were analyzed for all ages (6-18 years old) and stratified by primary (6-12 years old) and secondary (12-18 years old) school groups.
Results: The prevalence of multiple potential morbidity markers did not differ significantly between the egg-positive participants at baseline and those at 5 years by Mann Whitney nonparametric analysis and Fisher’s exact test for continuous and categorical data, respectively. There was a small but significantly higher score in school-related quality of life assessment by year five compared to baseline by Mann Whitney analysis (P = 0.048) in 13-18 year olds where malaria-negative. However, anemia was not positively impacted by four annual rounds of MDA, but registered a significant negative outcome.
Conclusions: We did not detect differences in morbidity markers measured in a population of those infected or re-infected after multiple MDA. This could have been due to their relative insensitivity or a failure of MDA to prevent morbidity among those who remain infected. High malaria transmission in this area and/or a lack of suitable methods to measure the more subtle functional morbidities caused by schistosomiasis could be a factor. Further research is needed to identify and develop well-defined, easily quantifiable S. mansoni morbidity markers for this age group.
Bernard O. Abudho, Bernard Guyah, Bartholomew N. Ondigo, Eric M. Ndombi, Edmund Ireri, Jennifer M. Carter, Diana K. Riner, Nupur Kittur, Diana M. S. Karanja & Daniel G. Colley. Evaluation of morbidity in Schistosoma mansoni-positive primary and secondary school children after four years of mass drug administration of praziquantel in western Kenya. Infect Dis Poverty 9, 67 (2020). https://doi.org/10.1186/s40249-020-00690-7
