Last data update: Mar 21, 2025. (Total: 48935 publications since 2009)
Records 1-30 (of 43 Records) |
Query Trace: Roy SL[original query] |
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Slaying the serpent: A research agenda to expand intervention development and accelerate guinea worm eradication efforts
Delea MG , Sack A , Eneanya OA , Thiele E , Roy SL , Sankara D , Ijaz K , Hopkins DR , Weiss AJ . Am J Trop Med Hyg 2024 Dracunculiasis, also known as Guinea worm disease, is targeted to become the second human disease and first parasitic infection to be eradicated. The global Guinea Worm Eradication Program (GWEP), through community-based interventions, reduced the burden of disease from an estimated 3.5 million cases per year in 1986 to only 13 human cases in 2022. Despite progress, in 2012 Guinea worm disease was detected in domesticated dogs and later in domesticated cats and baboons. Without previous development of any Guinea worm therapeutics, diagnostic tests to detect pre-patent Guinea worm infection, or environmental surveillance tools, the emergence of Guinea worm disease in animal hosts-a threat to eradication-motivated an assessment of evidence gaps and research opportunities. This gap analysis informed the refinement of a robust research agenda intended to generate new evidence and identify additional tools for national GWEPs and to better align the global GWEP with a 2030 Guinea worm eradication certification target. This paper outlines the rationale for the development and expansion of the global GWEP Research Agenda and summarizes the results of the gap analysis that was conducted to identify Guinea worm-related research needs and opportunities. We describe five work streams informed by the research gap analysis that underpin the GWEP Research Agenda and address eradication endgame challenges through the employment of a systems-informed One Health approach. We also discuss the infrastructure in place to disseminate new evidence and monitor research results as well as plans for the continual review of evidence and research priorities. |
Reply to: Rethinking disease eradication: putting countries first
Hopkins DR , Ijaz K , Weiss A , Roy SL , Ross DA . Int Health 12/28/2021 13 (6) 648-649 In a recent article, Gebre1 suggests that endemic countries should lead in deciding on disease eradication initiatives and asserts that ‘elimination as a public health problem’ is the preferred option because eradication occurs at the expense of other health programs and weakens fragile health systems. The author's primary example is dracunculiasis (Guinea worm) eradication, but he fails to take into account that vertical disease elimination and eradication programs also strengthen health systems overall. Eradication means permanent reduction to an incidence of zero of a disease worldwide, while elimination as a public health problem means minimal disease incidence but control measures are still necessary. |
Epidemiological and molecular investigations of a point-source outbreak of Dracunculus medinensis infecting humans and dogs in Chad: a cross-sectional study.
Guagliardo SAJ , Thiele E , Unterwegner K , Narcisse Nanguita N , Dossou L , Tchindebet Ouakou P , Zirimwabagabo H , Ruiz-Tiben E , Hopkins DR , Roy SL , Cama V , Bishop H , Sapp S , Yerian S , Weiss AJ . Lancet Microbe 2022 3 (2) e105-e112 ![]() BACKGROUND: Dracunculiasis (also known as Guinea worm disease), caused by the Dracunculus medinensis nematode, is progressing towards eradication, with a reduction in cases from 3·5 million cases in the mid-1980s to only 54 human cases at the end of 2019. Most cases now occur in Chad. On April 19, 2019, a 19-year-old woman presented with D medinensis in an area within the Salamat region of Chad, where the disease had not been previously reported. We aimed to investigate the connection between this case and others detected locally and elsewhere in Chad using a combination of epidemiological and genetic approaches. METHODS: In this cross-sectional field study, we conducted household case searches and informal group interviews in the Bogam, Liwi, and Tarh villages in Chad. All community members including children were eligible for participation in the outbreak investigation. Adult female D medinensis associated with this outbreak were collected for genetic analysis (18 from humans and two from dogs). Four mitochondrial genes and 22 nuclear microsatellite markers were used to assess relatedness of worms associated with the outbreak in comparison with other worms from elsewhere in Chad. FINDINGS: Between April 12 and Sept 6, 2019, we identified 22 human cases and two canine cases of dracunculiasis associated with 15 households. Six (40%) of the 15 affected households had multiple human or canine cases within the household. Most cases of dracunculiasis in people were from three villages in Salamat (21 [95%] of 22 cases), but one case was detected nearly 400 km away in Sarh city (outside the Salamat region). All people with dracunculiasis reported a history of consuming fish and unfiltered water. Worms associated with this outbreak were genetically similar and shared the same maternal lineage. INTERPRETATION: Molecular epidemiological results suggest a point-source outbreak that originated from a single female D medinensis, rather than newly identified sustained local transmission. The failure of the surveillance system to detect the suspected canine infection in 2018 highlights the challenge of canine D medinensis detection, particularly in areas under passive surveillance. Human movement can also contribute to dracunculiasis spread over long distances. FUNDING: The Carter Center. |
An evaluation of water, sanitation, and hygiene status and household assets and their associations with soil-transmitted helminthiasis and reported diarrhea in Nueva Santa Rosa, Guatemala
Rao G , Blackstock AJ , Derado G , Cuéllar VM , Juliao P , Alvarez M , López B , Muñoz F , Thornton A , Patel JC , Lopez G , Rivera JG , Reyes L , Arvelo W , Lindblade KA , Roy SL . J Water Sanit Hyg Dev 2021 11 (3) 362-373 Soil-transmitted helminth (STH) infections and diarrheal illness affect billions of people yearly. We conducted a cross-sectional survey in Nueva Santa Rosa, Guatemala to identify factors associated with STH infections and diarrhea using univariable and multivariable logistic regression models. On multivariable analyses, we found associations between STH infections and two factors: school-aged children (odds ratio (OR) vs. adults: 2.35, 95% CI 1.10–4.99) and household drinking water supply classified as ‘other improved’ (OR vs. ‘improved’: 7.00, CI 1.22–40.14). Finished floors in the household vs. natural floors were highly protective (OR 0.16, CI 0.05–0.50) for STH infection. In crowded households (>2.5 people/bedroom), observing water present at handwashing stations was also protective (OR 0.32, CI 0.11–0.98). When adjusted for drying hands, diarrhea was associated with preschool-age children (OR vs. adults: 3.33, CI 1.83–6.04), spending >10 min per round trip collecting water (OR 1.90, CI 1.02–3.56), and having a handwashing station ≤10 m near a sanitation facility (OR 3.69, CI 1.33–10.21). Our study indicates that familiar WASH interventions, such as increasing drinking water quantity and water at handwashing stations in crowded homes, coupled with a hygiene intervention like finished flooring may hold promise for STH and diarrhea control programs. © 2021 The Authors. |
Progress Toward Global Eradication of Dracunculiasis, January 2020-June 2021
Hopkins DR , Weiss AJ , Roy SL , Yerian S , Cama VA . MMWR Morb Mortal Wkly Rep 2021 70 (44) 1527-1533 Dracunculiasis (Guinea worm disease), caused by the parasite Dracunculus medinensis, is traditionally acquired by drinking water containing copepods (water fleas) infected with D. medinensis larvae, but in recent years also appears increasingly to be transmitted by eating fish or other aquatic animals. The worm typically emerges through the skin on a lower limb of the host 1 year after infection, causing pain and disability (1). There is no vaccine or medicine to prevent or medicine to treat dracunculiasis; eradication relies on case containment* to prevent water contamination and other interventions to prevent infection: health education, water filtration, treatment of unsafe water with temephos (an organophosphate larvicide), and provision of safe drinking water (1,2). The eradication campaign began in 1980 at CDC (1). In 1986, with an estimated 3.5 million cases(†) occurring annually in 20 African and Asian countries(§) (3), the World Health Assembly called for dracunculiasis elimination (4). The Guinea Worm Eradication Program (GWEP), led by The Carter Center and supported by the World Health Organization (WHO), UNICEF, CDC, and other partners, began assisting ministries of health in countries with endemic disease. With 27 cases in humans reported in 2020, five during January-June 2021, and only six countries currently affected by dracunculiasis (Angola, Chad, Ethiopia, Mali, South Sudan, and importations into Cameroon), achievement of eradication appears to be close. However, dracunculiasis eradication is challenged by civil unrest, insecurity, and epidemiologic and zoologic concerns. Guinea worm infections in dogs were first reported in Chad in 2012. Animal infections have now overtaken human cases, with 1,601 reported animal infections in 2020 and 443 during January-June 2021. Currently, all national GWEPs remain fully operational, with precautions taken to ensure safety of program staff and community members in response to the COVID-19 pandemic. Because of COVID-19, The Carter Center convened the 2020 and 2021 annual GWEP Program Managers meetings virtually, and WHO's International Commission for the Certification of Dracunculiasis Eradication met virtually in October 2020. Since 1986, WHO has certified 199 countries, areas, and territories dracunculiasis-free. Six countries are still affected: five with endemic disease and importations into Cameroon. Seven countries (five with endemic dracunculiasis, Democratic Republic of the Congo, and Sudan) still lack certification (4). The existence of infected dogs, especially in Chad, and impeded access because of civil unrest and insecurity in Mali and South Sudan are now the greatest challenges to interrupting transmission. This report describes progress during January 2020-June 2021 and updates previous reports (2,4,5). |
Assessment of the Chad guinea worm surveillance information system: A pivotal foundation for eradication
Karki S , Weiss A , Dcruz J , Hunt D , Haigood B , Ouakou PT , Chop E , Zirimwabagabo H , Rubenstein BL , Yerian S , Roy SL , Kamb ML , Guagliardo SAJ . PLoS Negl Trop Dis 2021 15 (8) e0009675 BACKGROUND: In the absence of a vaccine or pharmacological treatment, prevention and control of Guinea worm disease is dependent on timely identification and containment of cases to interrupt transmission. The Chad Guinea Worm Eradication Program (CGWEP) surveillance system detects and monitors Guinea worm disease in both humans and animals. Although Guinea worm cases in humans has declined, the discovery of canine infections in dogs in Chad has posed a significant challenge to eradication efforts. A foundational information system that supports the surveillance activities with modern data management practices is needed to support continued program efficacy. METHODS: We sought to assess the current CGWEP surveillance and information system to identify gaps and redundancies and propose system improvements. We reviewed documentation, consulted with subject matter experts and stakeholders, inventoried datasets to map data elements and information flow, and mapped data management processes. We used the Information Value Cycle (IVC) and Data-Information System-Context (DISC) frameworks to help understand the information generated and identify gaps. RESULTS: Findings from this study identified areas for improvement, including the need for consolidation of forms that capture the same demographic variables, which could be accomplished with an electronic data capture system. Further, the mental models (conceptual frameworks) IVC and DISC highlighted the need for more detailed, standardized workflows specifically related to information management. CONCLUSIONS: Based on these findings, we proposed a four-phased roadmap for centralizing data systems and transitioning to an electronic data capture system. These included: development of a data governance plan, transition to electronic data entry and centralized data storage, transition to a relational database, and cloud-based integration. The method and outcome of this assessment could be used by other neglected tropical disease programs looking to transition to modern electronic data capture systems. |
Surveillance of Human Guinea Worm in Chad, 2010-2018
Guagliardo SAJ , Ruiz-Tiben E , Hopkins DR , Weiss AJ , Ouakou PT , Zirimwabagabo H , Unterwegner K , Tindall D , Cama VA , Bishop H , Sapp SGH , Roy SL . Am J Trop Med Hyg 2021 105 (1) 188-195 The total number of Guinea worm cases has been reduced by 99.9% since the mid-1980s when the eradication campaign began. Today, the greatest number of cases is reported from Chad. In this report, we use surveillance data collected by the Chad Guinea Worm Eradication Program to describe trends in human epidemiology. In total, 114 human cases were reported during the years 2010-2018, with highest rates of containment (i.e., water contamination prevented) in the years 2013, 2014, 2016, and 2017 (P < 0.0001). Approximately half of case-patients were female, and 65.8% of case-patients were aged 30 years or younger (mean: 26.4 years). About 34.2% of case-patients were farmers. Cases were distributed across many ethnicities, with a plurality of individuals being of the Sara Kaba ethnicity (21.3%). Most cases occurred between the end of June and the end of August and were clustered in the Chari Baguirmi (35.9%) and Moyen Chari regions (30.1%). Cases in the northern Chari River area peaked in April and in August, with no clear pattern in the southern Chari River area. History of travel within Chad was reported in 7.0% of cases, and male subjects (12.5%) were more likely than female subjects (1.7%) to have reported a history of travel (P = 0.03). Our findings confirm that human Guinea worm is geographically disperse and rare. Although the proportion of case-patients with travel history is relatively small, this finding highlights an additional challenge of surveillance in mobile populations in the final stages of the global eradication campaign. |
Community-based Guinea worm surveillance in Chad: Evaluating a system at the intersection of human and animal disease
Rubenstein BL , Roy SL , Unterwegner K , Yerian S , Weiss A , Zirimwabagabo H , Chop E , Romero M , Ouakou PT , Moundai T , Guagliardo SAJ . PLoS Negl Trop Dis 2021 15 (3) e0009285 BACKGROUND: Guinea worm is a debilitating parasitic infection targeted for eradication. Annual human cases have dropped from approximately 3,500,000 in 1986 to 54 in 2019. Recent identification of canine cases in Chad threatens progress, and therefore detection, prevention, and containment of canine cases is a priority. We investigated associations between disease knowledge, community engagement, and canine cases in Chad to identify opportunities to improve active surveillance. METHODS: We surveyed 627 respondents (villagers, local leaders, community volunteers, and supervisors) across 45 villages under active surveillance. Descriptive statistics were analyzed by respondent category. Logistic regression models were fitted to assess the effects of volunteer visit frequency on villager knowledge. RESULTS: Knowledge increased with respondents' associations with the Guinea worm program. Household visit frequency by community volunteers was uneven: 53.0% of villagers reported visits at least twice weekly and 21.4% of villagers reported never being visited. Villagers visited by a volunteer at least twice weekly had better knowledge of Guinea worm symptoms (OR: 1.71; 95% CI: 1.04-2.79) and could name more prevention strategies (OR: 2.04; 95% CI: 1.32-3.15) than villagers visited less frequently. The primary motivation to report was to facilitate care-seeking for people with Guinea worm. Knowledge of animal "containment" to prevent contamination of water, knowledge of rewards for reporting animal cases, and ability to name any reasons to report Guinea worm were each positively correlated with village canine case counts. CONCLUSIONS: Community volunteers play crucial roles in educating their neighbors about Guinea worm and facilitating surveillance. Additional training and more attentive management of volunteers and supervisors could increase visit frequency and further amplify their impact. Emphasizing links between animal and human cases, the importance of animal containment, and animal rewards might improve surveillance and canine case detection. The surveillance system should be evaluated routinely to expand generalizability of data and monitor changes over time. |
Certifying Guinea worm eradication in humans and animals
Hopkins DR , Ijaz K , Weiss AJ , Roy SL . Lancet 2021 397 (10276) 793-794 The Viewpoint by David Molyneux and colleagues,1 members of the International Commission for the Certification of Dracunculiasis Eradication, notes the special challenges they face in preparing to certify that there are no Guinea worms remaining in humans or animals in the final seven countries that have not yet been certified as free of transmission, since eradication programmes detected the sustained transmission of Dracunculus medinensis among domestic dogs in Chad, Ethiopia, and Mali. We believe a comprehensive approach to evidence for certification might include a range of actions. |
Correlates of variation in Guinea worm burden among infected domestic dogs
Guagliardo SAJ , Wiegand R , Roy SL , Cleveland CA , Zirimwabagabo H , Chop E , Tchindebet Ouakou P , Ruiz-Tiben E , Hopkins D , Weiss A . Am J Trop Med Hyg 2021 104 (4) 1418-1424 The Guinea Worm Eradication Program has been extraordinarily successful-in 2019, there were 53 human cases reported, down from the estimated 3.5 million in 1986. Yet the occurrence of guinea worm in dogs is a challenge to eradication efforts, and underlying questions about transmission dynamics remain. We used routine surveillance data to run negative binomial regressions predicting worm burden among infected dogs in Chad. Of 3,371 infected dogs reported during 2015-2018, 38.5% had multiple worms. A multivariable model showed that the number of dogs in the household was negatively associated with worm burden (adjusted incidence rate ratio [AIRR] = 0.95, 95% CI: 0.93-0.97, P < 0.0001) after adjusting for dog age (AIRR = 0.99, 95% CI: 0.96-1.01, P > 0.1). This could relate to the amount of infective inocula (e.g., contaminated food or water) shared by multiple dogs in a household. Other significant univariable associations with worm burden included dog history of guinea worm infection (IRR = 1.30, 95% CI: 1.18-1.45) and dog owners who were hunters (IRR = 0.78, 95% CI: 0.62-0.99, P < 0.05) or farmers (IRR = 0.83, 95% CI: 0.77-0.90, P < 0.0001). Further analysis showed that the number of dogs in the household was significantly and positively correlated with nearly all other independent variables (e.g., owner occupation: farmer, fisherman, or hunter; dog age, gender, and history of guinea worm). The associations we identified between worm burden and dogs per household, and dogs per household and owner characteristics should be further investigated with more targeted studies. |
Investigation of dracunculiasis transmission among humans, Chad, 2013-2017
Liu EW , Sircar AD , Matchanga K , Mahamat AM , Ngarhor N , Ouakou PT , Zirimwabagabo H , Ruiz-Tiben E , Sankara D , Wiegand R , Roy SL . Am J Trop Med Hyg 2020 104 (2) 724-730 Dracunculiasis, slated for global eradication, typically is acquired by drinking stagnant water containing microscopic crustaceans (copepods) infected with Dracunculus medinensis larvae, causing clusters of case persons with worms emerging from the skin. Following a 10-year absence of reported cases, 9-17 sporadic human cases with few epidemiologic links have been reported annually in Chad since 2010; dog infections have also been reported since 2012. We conducted an investigation of human cases in Chad to identify risk factors. We conducted a case-control study using a standardized questionnaire to assess water and aquatic animal consumption, and links to dog infections. Case persons had laboratory-confirmed D. medinensis during 2013-2017. Each case person was matched to one to three controls without history of disease by age, gender, and residency in the village where the case person was likely infected. We estimated odds ratios (ORs) using simple conditional logistic regression. We enrolled 25 case persons with 63 matched controls. Dracunculiasis was associated with consumption of untreated water from hand-dug wells (OR: 13.4; 95% CI: 1.7-108.6), but neither with consumption of aquatic animals nor presence of infected dogs in villages. Unsafe water consumption remains associated with dracunculiasis. Education of populations about consuming safe water and using copepod filters to strain unsafe water should continue and expand, as should efforts to develop and maintain safe drinking water sources. Nevertheless, the peculiar epidemiology in Chad remains incompletely explained. Future studies of dogs might identify other risk factors. |
Development of a multiplex bead assay for the detection of canine IgG(4) antibody responses to guinea worm
Priest JW , Ngandolo BNR , Lechenne M , Cleveland CA , Yabsley MJ , Weiss AJ , Roy SL , Cama V . Am J Trop Med Hyg 2020 104 (1) 303-312 Increased levels of guinea worm (GW) disease transmission among dogs in villages along the Chari River in Chad threaten the gains made by the GW Eradication Program. Infected dogs with preemergent worm blisters are difficult to proactively identify. If these dogs are not contained, blisters can burst upon submersion in water, leading to the contamination of the water supply with L1 larvae. Guinea worm antigens previously identified using sera from human dracunculiasis patients were coupled to polystyrene beads for multiplex bead assay analysis of 41 non-endemic (presumed negative) dog sera and 39 sera from GW-positive dogs from Chad. Because commercially available anti-dog IgG secondary antibodies did not perform well in the multiplex assay, dog IgGs were partially purified, and a new anti-dog IgG monoclonal antibody was developed. Using the new 4E3D9 monoclonal secondary antibody, the thioredoxin-like protein 1-glutathione-S-transferase (GST), heat shock protein (HSP1)-GST, and HSP2-GST antigen multiplex assays had sensitivities of 69-74% and specificities of 73-83%. The domain of unknown function protein 148 (DUF148)-GST antigen multiplex assay had a sensitivity of 89.7% and a specificity of 85.4%. When testing samples collected within 1 year of GW emergence (n = 20), the DUF148-GST assay had a sensitivity of 90.0% and a specificity of 97.6% with a receiver-operating characteristic area under the curve of 0.94. Using sera from two experimentally infected dogs, antibodies to GW antigens were detected within 6 months of exposure. Our results suggest that, when used to analyze paired, longitudinal samples collected 1-2 months apart, the DUF148/GST multiplex assay could identify infected dogs 4-8 months before GW emergence. |
Progress toward global eradication of dracunculiasis, January 2019-June 2020
Hopkins DR , Weiss AJ , Roy SL , Yerian S , Sapp SGH . MMWR Morb Mortal Wkly Rep 2020 69 (43) 1563-1568 Dracunculiasis (Guinea worm disease) is caused by the parasite Dracunculus medinensis and is acquired by drinking water containing copepods (water fleas) infected with D. medinensis larvae. The worm typically emerges through the skin on a lower limb approximately 1 year after infection, resulting in pain and disability (1). There is no vaccine or medicine to treat the disease; eradication efforts rely on case containment* to prevent water contamination. Other interventions to prevent infection include health education, water filtration, chemical treatment of unsafe water with temephos (an organophosphate larvicide to kill copepods), and provision of safe drinking water (1,2). The worldwide eradication campaign began in 1980 at CDC (1). In 1986, with an estimated 3.5 million cases(†) occurring each year in 20 African and Asian countries(§) (3), the World Health Assembly (WHA) called for dracunculiasis elimination (4). The global Guinea Worm Eradication Program (GWEP), led by the Carter Center and supported by the World Health Organization (WHO), United Nations Children's Fund, CDC, and other partners, began assisting ministries of health in countries with dracunculiasis. This report, based on updated health ministry data (4), describes progress made during January 2019-June 2020 and updates previous reports (2,4,5). With only 54 human cases reported in 2019, 19 human cases reported during January 2019-June 2020, and only six countries currently affected by dracunculiasis (Angola, Chad, Ethiopia, Mali, South Sudan, and importations into Cameroon), the achievement of eradication is within reach, but it is challenged by civil unrest, insecurity, and lingering epidemiologic and zoologic concerns, including 2,000 reported animal cases in 2019 and 1,063 animal cases in 2020, mostly in dogs. All national GWEPs remain fully operational, with precautions taken to ensure safety of program staff members and community members in response to the coronavirus disease 2019 (COVID-19) pandemic. |
Development of a multiplex bead assay for the detection of IgG antibody responses to Guinea worm
Priest JW , Stuchlik O , Reed M , Soboslay P , Cama V , Roy SL . Am J Trop Med Hyg 2020 103 (6) 2294-2304 The success of the Guinea Worm (GW) Eradication Program over the past three decades has been tempered by the persistence of GW disease in a few African nations and the potential for a future resurgence in cases. Domestic dogs are now a major concern as a disease reservoir as large numbers of cases of canine GW disease are now reported each year, mainly along the Chari River in Chad. As a first step toward the development of a serologic assay for dogs, archived human plasma samples from dracunculiasis-positive donors from Togo were used to select adult female GW antigens for peptide sequencing and cloning. Eight protein sequences of interest were expressed as recombinant glutathione-S-transferase (GST) fusion proteins, and the most promising proteins were coupled to carboxylated microspheres for use in multiplex assays. A thioredoxin-like protein (TRXL1) and a domain of unknown function (DUF148) were assessed for total IgG and IgG(4) reactivities using a panel of specimens from GW cases, uninfected donors, and individuals infected with various nematode worms, including Onchocerca volvulus. Both the DUF148-GST and the TRXL1-GST assays cross-reacted with O. volvulus sera, but the latter assay was always the more specific. The IgG(4) and total IgG TRXL1-GST assays both had sensitivities > 87% and specificities > 90%. Maximum specificity (> 96%) was obtained with the total IgG assay when reactivity to both antigens was used to define a positive case. Given the good performance of the human assay, we are now working to modify the assay for dog assessments. |
Guinea worm in domestic dogs in Chad: A description and analysis of surveillance data
Guagliardo SAJ , Roy SL , Ruiz-Tiben E , Zirimwabagabo H , Romero M , Chop E , Ouakou PT , Hopkins DR , Weiss AJ . PLoS Negl Trop Dis 2020 14 (5) e0008207 After a ten-year absence of reported Guinea worm disease in Chad, human cases were rediscovered in 2010, and canine cases were first recorded in 2012. In response, active surveillance for Guinea worm in both humans and animals was re-initiated in 2012. As of 2018, the Chad Guinea Worm Eradication Program (CGWEP) maintains an extensive surveillance system that operates in 1,895 villages, and collects information about worms, hosts (animals and humans), and animal owners. This report describes in detail the CGWEP surveillance system and explores epidemiological trends in canine Guinea worm cases during 2015-2018. Our results showed an increased in the number of canine cases detected by the system during the period of interest. The proportion of worms that were contained (i.e., water contamination was prevented) improved significantly over time, from 72.8% in 2015 to 85.7% in 2018 (Mantel-Haenszel chi-square = 253.3, P < 0.0001). Additionally, approximately 5% of owners of infected dogs reported that the dog had a Guinea worm-like infection earlier that year; 12.6% had a similar worm in a previous year. The proportion of dogs with a history of infection in a previous year increased over time (Mantel-Haenszel chi-square = 18.8, P < 0.0001). Canine cases were clustered in space and time: most infected dogs (80%) were from the Chari Baguirmi (38.1%) and Moyen Chari Regions (41.9%), and for each year the peak month of identified canine cases was June, with 78.5% occurring during March through August. Findings from this report evoke additional questions about why some dogs are repeatedly infected. Our results may help to target interventions and surveillance efforts in terms of space, time, and dogs susceptible to recurrent infection, with the ultimate goal of Guinea worm eradication. |
Progress toward global eradication of dracunculiasis - January 2018-June 2019
Hopkins DR , Weiss AJ , Roy SL , Zingeser J , Guagliardo SAJ . MMWR Morb Mortal Wkly Rep 2019 68 (43) 979-984 Dracunculiasis (also known as Guinea worm disease) is caused by the parasite Dracunculus medinensis and is acquired by drinking water containing copepods (water fleas) infected with D. medinensis larvae. The worm typically emerges through the skin on a lower limb approximately 1 year after infection, resulting in pain and disability (1). There is no vaccine or medicine to treat the disease; eradication efforts rely on case containment* to prevent water contamination and other interventions to prevent infection, including health education, water filtration, chemical treatment of unsafe water with temephos (an organophosphate larvicide to kill copepods), and provision of safe drinking water (1,2). In 1986, with an estimated 3.5 million cases(dagger) occurring each year in 20 African and Asian countries( section sign) (3), the World Health Assembly called for dracunculiasis elimination (4). The global Guinea Worm Eradication Program (GWEP), led by The Carter Center and supported by the World Health Organization (WHO), CDC, the United Nations Children's Fund, and other partners, began assisting ministries of health in countries with dracunculiasis. This report, based on updated health ministry data, describes progress to eradicate dracunculiasis during January 2018-June 2019 and updates previous reports (2,4,5). With only five countries currently affected by dracunculiasis (Angola, Chad, Ethiopia, Mali, and South Sudan), achievement of eradication is within reach, but it is challenged by civil unrest, insecurity, and lingering epidemiologic and zoologic questions. |
Progress toward global eradication of dracunculiasis - January 2017-June 2018
Hopkins DR , Ruiz-Tiben E , Weiss AJ , Roy SL , Zingeser J , Guagliardo SAJ . MMWR Morb Mortal Wkly Rep 2018 67 (45) 1265-1270 Dracunculiasis (Guinea worm disease), caused by the parasite Dracunculus medinensis, is acquired by drinking water containing copepods (water fleas) infected with its larvae. The worm typically emerges through the skin on a lower limb approximately 1 year after infection, causing pain and disability (1). The worldwide eradication campaign began at CDC in 1980. In 1986, the World Health Assembly called for dracunculiasis elimination, and the global Guinea Worm Eradication Program (GWEP), led by the Carter Center in partnership with the World Health Organization (WHO), United Nations Children's Fund (UNICEF), CDC, and others, began assisting ministries of health in countries with dracunculiasis. There is no vaccine or medicine to treat the disease; the GWEP relies on case containment* to prevent water contamination and other interventions to prevent infection, including health education, water filtration, chemical treatment of water, and provision of safe drinking water (1,2). In 1986, an estimated 3.5 million cases(dagger) occurred each year in 20( section sign) African and Asian countries (3,4). This report, based on updated health ministry data (3), describes progress during January 2017-June 2018 and updates previous reports (1,4). In 2017, 30 cases were reported from Chad and Ethiopia, and 855 infected animals (mostly dogs) were reported from Chad, Ethiopia, and Mali, compared with 25 cases and 1,049 animal infections reported in 2016. During January-June 2018, the number of cases declined to three cases each in Chad and South Sudan and one in Angola, with 709 infected animals reported, compared with eight cases and 547 animal infections during the same period of 2017. With only five affected countries, the eradication goal is near, but is challenged by civil unrest, insecurity, and lingering epidemiologic and zoologic questions. |
Association of water quality with soil-transmitted helminthiasis and diarrhea in Nueva Santa Rosa, Guatemala, 2010
Matanock A , Lu X , Derado G , Cuellar VM , Juliao P , Alvarez M , Lopez B , Munoz F , Thornton A , Patel JC , Lopez G , Reyes L , Arvelo W , Blackstock AJ , Lindblade KA , Roy SL . J Water Health 2018 16 (5) 724-736 Improved water quality reduces diarrhea, but the impact of improved water quality on Ascaris and Trichuris, soil-transmitted helminths (STH) conveyed by the fecal-oral route, is less well described. To assess water quality associations with diarrhea and STH, we conducted a cross-sectional survey in households of south-eastern Guatemala. Diarrhea was self-reported in the past week and month. STH was diagnosed by stool testing using a fecal parasite concentrator method. We explored associations between Escherichia coli-positive source water (water quality) and disease outcomes using survey logistic regression models. Overall, 732 persons lived in 167 households where water was tested. Of these, 79.4% (581/732) had E. coli-positive water, 7.9% (58/732) had diarrhea within the week, 14.1% (103/732) had diarrhea within the month, and 6.6% (36/545) tested positive for Ascaris or Trichuris, including 1% (6/536) who also reported diarrhea. Univariable analysis found a statistically significant association between water quality and STH (odds ratio [OR] = 5.1, 95% confidence interval [CI] = 1.1-24.5) but no association between water quality and diarrhea. Waterborne transmission and effects of water treatment on STH prevalence should be investigated further. If a causal relationship is found, practices such as household water treatment including filtration might be useful adjuncts to sanitation, hygiene, and deworming in STH control programs. |
The epidemiology and clinical features of Balamuthia mandrillaris disease in the United States, 1974 - 2016
Cope JR , Landa J , Nethercut H , Collier SA , Glaser C , Moser M , Puttagunta R , Yoder JS , Ali IK , Roy SL . Clin Infect Dis 2018 68 (11) 1815-1822 Background: Balamuthia mandrillaris is a free-living ameba that causes rare, nearly always fatal disease in humans and animals worldwide. B. mandrillaris has been isolated from soil, dust, and water. Initial entry of Balamuthia into the body is likely via the skin or lungs. To date, only individual case reports and small case series have been published. Methods: The Centers for Disease Control and Prevention (CDC) maintains a free-living ameba (FLA) registry and laboratory. To be entered into the registry, a Balamuthia case must be laboratory-confirmed. Several sources were used to complete entries in the registry, including case report forms, CDC laboratory results, published case reports, and media information. SAS(c) version 9.3 software was used to calculate descriptive statistics and frequencies. Results: We identified 109 case reports of Balamuthia disease between 1974 and 2016. Most (99%) had encephalitis. The median age was 36 years (range 4 months to 91 years). Males accounted for 68% of the case patients. California had the highest number of case reports followed by Texas and Arizona. Hispanics constituted 55% for those with documented ethnicity. Exposure to soil was commonly reported. Among those with a known outcome, 90% of patients died. Conclusions: Balamuthia disease in the United States is characterized by a highly fatal encephalitis that affects patients of all ages. Hispanics were disproportionately affected. The southwest region of the U.S. reported the most cases. Clinician awareness of Balamuthia as a cause of encephalitis might lead to earlier diagnosis and initiation of treatment, resulting in better outcomes. |
Dracunculiasis eradication: Are we there yet
Hopkins DR , Ruiz-Tiben E , Eberhard ML , Weiss A , Withers PC , Roy SL , Sienko DG . Am J Trop Med Hyg 2018 99 (2) 388-395 This report summarizes the status of the global Dracunculiasis Eradication Program as of the end of 2017. Dracunculiasis (guinea worm disease) has been eliminated from 19 of 21 countries where it was endemic in 1986, when an estimated 3.5 million cases occurred worldwide. Only Chad and Ethiopia reported cases in humans, 15 each, in 2017. Infections of animals, mostly domestic dogs, with Dracunculus medinensis were reported in those two countries and also in Mali. Insecurity and infections in animals are the two main obstacles remaining to interrupting dracunculiasis transmission completely. |
Risk factors for sporadic Giardia infection in the USA: a case-control study in Colorado and Minnesota
Reses HE , Gargano JW , Liang JL , Cronquist A , Smith K , Collier SA , Roy SL , Vanden Eng J , Bogard A , Lee B , Hlavsa MC , Rosenberg ES , Fullerton KE , Beach MJ , Yoder JS . Epidemiol Infect 2018 146 (9) 1-8 Giardia duodenalis is the most common intestinal parasite of humans in the USA, but the risk factors for sporadic (non-outbreak) giardiasis are not well described. The Centers for Disease Control and Prevention and the Colorado and Minnesota public health departments conducted a case-control study to assess risk factors for sporadic giardiasis in the USA. Cases (N = 199) were patients with non-outbreak-associated laboratory-confirmed Giardia infection in Colorado and Minnesota, and controls (N = 381) were matched by age and site. Identified risk factors included international travel (aOR = 13.9; 95% CI 4.9-39.8), drinking water from a river, lake, stream, or spring (aOR = 6.5; 95% CI 2.0-20.6), swimming in a natural body of water (aOR = 3.3; 95% CI 1.5-7.0), male-male sexual behaviour (aOR = 45.7; 95% CI 5.8-362.0), having contact with children in diapers (aOR = 1.6; 95% CI 1.01-2.6), taking antibiotics (aOR = 2.5; 95% CI 1.2-5.0) and having a chronic gastrointestinal condition (aOR = 1.8; 95% CI 1.1-3.0). Eating raw produce was inversely associated with infection (aOR = 0.2; 95% CI 0.1-0.7). Our results highlight the diversity of risk factors for sporadic giardiasis and the importance of non-international-travel-associated risk factors, particularly those involving person-to-person transmission. Prevention measures should focus on reducing risks associated with diaper handling, sexual contact, swimming in untreated water, and drinking untreated water. |
Transitioning from river blindness control to elimination: steps toward stopping treatment
Cantey PT , Roy SL , Boakye D , Mwingira U , Ottesen EA , Hopkins AD , Sodahlon YK . Int Health 2018 10 i7-i13 The transition from onchocerciasis control to elimination requires country programmes to rethink their approach to a variety of activities as they move from addressing morbidity to addressing transmission of the parasite. Although the 2016 WHO guidelines provide extensive recommendations, it was beyond the scope of the document to provide guidance on all aspects of the transition. This paper will discuss some of the important issues that programmes are grappling with as they transition to elimination and provide some potential approaches that programmes can use to address them. Although there are some data to support some aspects of the suggested approaches, operational research will be needed to generate data to support these approaches further and to determine how programmes could best tailor them to their own unique epidemiological challenges. Good communication between the national programmes and the broader global programme will facilitate the clear articulation of programmatic challenges and the development of the evidence to support programme decision-making. |
Progress toward global eradication of dracunculiasis, January 2016-June 2017
Hopkins DR , Ruiz-Tiben E , Eberhard ML , Roy SL , Weiss AJ . MMWR Morb Mortal Wkly Rep 2017 66 (48) 1327-1331 Dracunculiasis (Guinea worm disease) is caused by Dracunculus medinensis, a parasitic worm. Approximately 1 year after a person acquires infection from contaminated drinking water, the worm emerges through the skin, usually on a lower limb (1). Pain and secondary bacterial infection can cause temporary or permanent disability that disrupts work and schooling. The campaign to eradicate dracunculiasis worldwide began in 1980 at CDC. In 1986, the World Health Assembly called for dracunculiasis elimination,* and the global Guinea Worm Eradication Program, led by the Carter Center and supported by the World Health Organization (WHO), United Nations Children's Fund, CDC, and other partners, began assisting ministries of health in countries with endemic dracunculiasis. In 1986, an estimated 3.5 million cases occurred each year in 20 countries in Africa and Asia (2). Since then, although the goal of eradicating dracunculiasis has not been achieved, considerable progress has been made. Compared with the 1986 estimate, the annual number of reported cases in 2016 has declined by >99%, and cases are confined to three countries with endemic disease. This report updates published (3-4) and unpublished surveillance data reported by ministries of health and describes progress toward dracunculiasis eradication during January 2016-June 2017. In 2016, a total of 25 cases were reported from three countries (Chad [16], South Sudan [six], Ethiopia [three]), compared with 22 cases reported from the same three countries and Mali in 2015 (Table 1). The 14% increase in cases from 2015 to 2016 was offset by the 25% reduction in number of countries with indigenous cases. During the first 6 months of 2017, the overall number of cases declined to eight, all in Chad, from 10 cases in three countries (Chad [four], South Sudan [four] and Ethiopia [two]) during the same period of 2016. Continued active surveillance, aggressive detection, and appropriate management of cases are essential eradication program components; however, epidemiologic challenges, civil unrest, and insecurity pose potential barriers to eradication. |
Risk factors for Acanthamoeba keratitis-a multistate case-control study, 2008-2011
Brown AC , Ross J , Jones DB , Collier SA , Ayers TL , Hoekstra RM , Backensen B , Roy SL , Beach MJ , Yoder JS . Eye Contact Lens 2017 44 Suppl 1 S173-S178 OBJECTIVE: To identify modifiable risk factors contributing to Acanthamoeba keratitis (AK) infection. METHODS: A case-control investigation was conducted. Case patients were soft contact lens wearers with laboratory-confirmed AK. Control were soft contact lens wearers ≥12 years of age, with no history of AK. Case patients were recruited from 14 ophthalmology referral centers and a clinical laboratory. Control were matched on state of residence and type of primary eye care provider (ophthalmologist or optometrist). Participants were interviewed using a standardized questionnaire. Univariable and multivariable conditional logistic regression analyses were conducted. Matched odds ratios (mORs) were calculated. RESULTS: Participants included 88 case patients and 151 matched control. Case patients were more likely to be aged <25 years (unadjusted mOR 2.7, 95% confidence interval 1.3-5.5) or aged >53 years (mOR 2.5, 1.1-5.7), and more likely to be men (mOR 2.6, 1.4-4.8). Unadjusted analyses identified multiple risk factors: rinsing (mOR 6.3, 1.3-29.9) and storing lenses in tap water (mOR 3.9, 1.2-12.3), topping off solution in the lens case (mOR 4.0, 2.0-8.0), having worn lenses ≤5 years (mOR 2.4, 1.3-4.4), rinsing the case with tap water before storing lenses (mOR 2.1, 1.1-4.1), and using hydrogen peroxide (mOR 3.6, 1.1-11.7) versus multipurpose solution. Significant risk factors in multivariable modeling included age >53 years, male sex, topping off, and using saline solution. CONCLUSIONS: Numerous modifiable risk factors for AK were identified, mostly involving hygiene practices. To reduce the risk of AK, lens wearers should observe recommended lens care practices. |
Progress toward global eradication of dracunculiasis - January 2015-June 2016
Hopkins DR , Ruiz-Tiben E , Eberhard ML , Roy SL , Weiss AJ . MMWR Morb Mortal Wkly Rep 2016 65 (40) 1112-1116 Dracunculiasis (Guinea worm disease) is caused by Dracunculus medinensis, a parasitic worm. Approximately 1 year after a person acquires infection from drinking contaminated water, the worm emerges through the skin, usually on the leg. Pain and secondary bacterial infection can cause temporary or permanent disability that disrupts work and schooling. The campaign to eradicate dracunculiasis worldwide began in 1980 at CDC. In 1986, the World Health Assembly called for dracunculiasis elimination (1), and the global Guinea Worm Eradication Program, led by the Carter Center and supported by the World Health Organization (WHO), United Nations Children's Fund (UNICEF), CDC, and other partners, began assisting ministries of health in countries where dracunculiasis was endemic. In 1986, an estimated 3.5 million cases were occurring each year in 20 countries in Africa and Asia (1,2). Since then, although the goal of eradicating dracunculiasis has not been achieved, substantial progress has been made. Compared with the 1986 estimate, the annual number of reported cases in 2015 has been reduced by >99%, and cases are confined to four countries with endemic disease. This report updates published (3-5) and unpublished surveillance data reported by ministries of health and describes progress toward dracunculiasis eradication during January 2015-June 2016. In 2015, a total of 22 cases were reported from four countries (Chad [nine cases], Mali [five], South Sudan [five], and Ethiopia [three]), compared with 126 cases reported in 2014 from the same four countries (Table 1). The overall 83% reduction in cases from 2014 to 2015 is the largest such annual overall reduction ever achieved during this global campaign. During the first 6 months of 2016, however, cases increased 25% compared with the same period in 2015. Continued active surveillance and aggressive detection and appropriate management of cases are essential eradication program components; however, epidemiologic challenges and civil unrest and insecurity pose potential barriers to eradication. |
A cross-sectional study of water, sanitation, and hygiene-related risk factors for soil-transmitted helminth infection in urban school- and preschool-aged children in Kibera, Nairobi
Worrell CM , Wiegand RE , Davis SM , Odero KO , Blackstock A , Cuellar VM , Njenga SM , Montgomery JM , Roy SL , Fox LM . PLoS One 2016 11 (3) e0150744 Soil-transmitted helminth (STH) infections affect persons living in areas with poor water, sanitation, and hygiene (WASH). Preschool-aged children (PSAC) and school-aged children (SAC) are disproportionately affected by STH infections. We aimed to identify WASH factors associated with STH infection among PSAC and SAC in Kibera, Kenya. In 2012, households containing a PSAC or SAC were randomly selected from those enrolled in the International Emerging Infections Program, a population-based surveillance system. We administered a household questionnaire, conducted environmental assessments for WASH, and tested three stools from each child for STH eggs using the Kato-Katz method. WASH factors were evaluated for associations with STH infection using univariable and multivariable Poisson regression. Any-STH prevalence was 40.8% among 201 PSAC and 40.0% among 475 SAC enrolled. Using the Joint Monitoring Programme water and sanitation classifications, 1.5% of households reported piped water on premises versus 98.5% another improved water source; 1.3% reported improved sanitation facilities, while 81.7% used shared sanitation facilities, 13.9% had unimproved facilities, and 3.1% reported no facilities (open defecation). On univariable analysis, STH infection was significantly associated with a household toilet located off-premises (prevalence ratio (PR) = 1.33; p = 0.047), while always treating water (PR = 0.81; p = 0.04), covering drinking water containers (PR = 0.75; p = 0.02), using clean towels during hand drying (PR = 0.58; p<0.01), having finished household floor material (PR = 0.76; p<0.01), having electricity (PR = 0.70; p<0.01), and increasing household elevation in 10-meter increments (PR = 0.89; p<0.01) were protective against STH infection. On multivariable analysis, usually versus always treating water was associated with increased STH prevalence (adjusted prevalence ratio (aPR) = 1.52; p<0.01), while having finished household floor material (aPR = 0.76; p = 0.03), reported child deworming in the last year (aPR = 0.76; p<0.01), and 10-meter household elevation increases (aPR = 0.89; p<0.01) were protective against infection. The intersection between WASH and STH infection is complex; site-specific WASH interventions should be considered to sustain the gains made by deworming activities. |
Population density, poor sanitation, and enteric infections in Nueva Santa Rosa, Guatemala
Jarquin C , Arnold BF , Munoz F , Lopez B , Cuellar VM , Thornton A , Patel J , Reyes L , Roy SL , Bryan JP , McCracken JP , Colford JM Jr . Am J Trop Med Hyg 2016 94 (4) 912-919 Poor sanitation could pose greater risk for enteric pathogen transmission at higher human population densities because of greater potential for pathogens to infect new hosts through environmentally mediated and person-to-person transmission. We hypothesized that incidence and prevalence of diarrhea, enteric protozoans, and soil-transmitted helminth infections would be higher in high-population-density areas compared with low-population-density areas, and that poor sanitation would pose greater risk for these enteric infections at high density compared with low density. We tested our hypotheses using 6 years of clinic-based diarrhea surveillance (2007-2013) including 4,360 geolocated diarrhea cases tested for 13 pathogens and a 2010 cross-sectional survey that measured environmental exposures from 204 households (920 people) and tested 701 stool specimens for enteric parasites. We found that population density was not a key determinant of enteric infection nor a strong effect modifier of risk posed by poor household sanitation in this setting. |
Diagnosis, clinical course, and treatment of primary amoebic meningoencephalitis in the United States, 1937-2013
Capewell LG , Harris AM , Yoder JS , Cope JR , Eddy BA , Roy SL , Visvesvara GS , Fox LM , Beach MJ . J Pediatric Infect Dis Soc 2015 4 (4) e68-75 BACKGROUND: Primary amoebic meningoencephalitis (PAM) is a rapidly progressing waterborne illness that predominately affects children and is nearly always fatal. PAM is caused by Naegleria fowleri, a free-living amoeba found in bodies of warm freshwater worldwide. METHODS: We reviewed exposure location, clinical signs and symptoms, diagnostic modalities, and treatment from confirmed cases of PAM diagnosed in the United States during 1937-2013. Patients were categorized into the early (ie, flu-like symptoms) or late (ie, central nervous system signs) group on the basis of presenting clinical characteristics. Here, we describe characteristics of the survivors and decedents. RESULT: The median age of the patients was 12 years (83% aged ≤18 years); males (76%) were predominately affected (N = 142). Most infections occurred in southern-tier states; however, 4 recent infections were acquired in northern states: Minnesota (2), Kansas (1), and Indiana (1). Most (72%) of the patients presented with central nervous system involvement. Cerebrospinal fluid analysis resembled bacterial meningitis with high opening pressures, elevated white blood cell counts with predominantly neutrophils (median, 2400 cells/muL [range, 5-26 000 cells/muL]), low glucose levels (median, 23 mg/dL [range, 1-92 mg/dL]), and elevated protein levels (median, 365 mg/dL [range, 24-1210 mg/dL]). Amoebas found in the cerebrospinal fluid were diagnostic, but PAM was diagnosed for only 27% of the patients before death. Imaging results were abnormal in approximately three-fourths of the patients but were not diagnostic for amoebic infection. Three patients in the United States survived. CONCLUSIONS: To our knowledge, this is the first comprehensive clinical case series of PAM presented in the United States. PAM is a fatal illness with limited treatment success and is expanding into more northern regions. Clinicians who suspect that they have a patient with PAM should contact the US Centers for Disease Control and Prevention at 770-488-7100 (available 24 hours/day, 7 days/week) to discuss diagnostic testing and treatment options (see cdc.gov/naegleria). |
Progress toward global eradication of Dracunculiasis, January 2014-June 2015
Hopkins DR , Ruiz-Tiben E , Eberhard ML , Roy SL . MMWR Morb Mortal Wkly Rep 2015 64 (41) 1161-1165 Dracunculiasis (Guinea worm disease) is caused by Dracunculus medinensis, a parasitic worm. Approximately 1 year after a person acquires infection from contaminated drinking water, the worm emerges through the skin, usually on the lower limb. Pain and secondary bacterial infection can cause temporary or permanent disability that disrupts work and schooling. The campaign to eradicate dracunculiasis worldwide began in 1980 at CDC. In 1986, the World Health Assembly called for dracunculiasis elimination, and the global Guinea Worm Eradication Program, led by the Carter Center and supported by the World Health Organization (WHO), United Nations Children's Fund (UNICEF), CDC, and other partners, began assisting ministries of health in countries where dracunculiasis was endemic. In 1986, an estimated 3.5 million cases occurred each year in 20 countries in Africa and Asia. Since then, although the goal of eradicating dracunculiasis has not been achieved, considerable progress has been made. Compared with the 1986 estimate, the annual number of reported cases in 2015 has been reduced by 99% and cases are confined to four endemic countries. This report updates published and unpublished surveillance data reported by ministries of health and describes progress toward dracunculiasis eradication from January 2014 through June 2015. During 2014, a total of 126 cases were reported from four countries (Chad [13 cases], Ethiopia [three], Mali [40], and South Sudan [70]), compared with 148 cases reported in 2013, from the same four countries. The overall 15% reduction in cases during 2013-2014 was less than that experienced in recent years, but the rate of decline increased again to 70% in the first 6 months of 2015 compared with the same period during 2014. Continued active surveillance with aggressive detection and appropriate management of cases are essential program components; however, epidemiologic challenges and civil unrest and insecurity pose potential barriers to eradication. |
Assessment of blood-brain barrier penetration of miltefosine used to treat a fatal case of granulomatous amebic encephalitis possibly caused by an unusual Balamuthia mandrillaris strain
Roy SL , Atkins JT , Gennuso R , Kofos D , Sriram RR , Dorlo TP , Hayes T , Qvarnstrom Y , Kucerova Z , Guglielmo BJ , Visvesvara GS . Parasitol Res 2015 114 (12) 4431-9 Balamuthia mandrillaris, a free-living ameba, causes rare but frequently fatal granulomatous amebic encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid (CSF) and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine. Brain biopsy specimens, CSF, and sera were tested for B. mandrillaris using multiple techniques, including culture, real-time polymerase chain reaction, immunohistochemical techniques, and serology. CSF and serum miltefosine levels were determined using a liquid chromatography method coupled to tandem mass spectrometry. The CSF miltefosine concentration on hospital admission day 12 was 0.4 mug/mL. The serum miltefosine concentration on day 37, about 80 h post-miltefosine treatment, was 15.3 mug/mL. These are the first results confirming some blood-brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation. Further evaluation of brain parenchyma penetration is required to determine optimal miltefosine dosing for Balamuthia GAE, balanced with the drug's toxicity profile. Additionally, the Balamuthia isolate was evaluated by real-time polymerase chain reaction (PCR), demonstrating genetic variability in 18S ribosomal RNA (18S rRNA) sequences and possibly signaling the first identification of multiple Balamuthia strains with varying pathogenicities. |
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