Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 39 Records) |
Query Trace: Fox LM[original query] |
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Geospatial analysis of Plasmodium falciparum serological indicators: school versus community sampling in a low-transmission malaria setting
Jaramillo-Underwood A , Herman C , Jean SE , Nace D , Elder ES , Robinson K , Knipes A , Worrell CM , Fox LM , Desir L , Fayette C , Javel A , Monestime F , Mace KE , Udhayakumar V , Won KY , Chang MA , Lemoine JF , Rogier E . BMC Med 2024 22 (1) 31 BACKGROUND: Due to low numbers of active infections and persons presenting to health facilities for malaria treatment, case-based surveillance is inefficient for understanding the remaining disease burden in low malaria transmission settings. Serological data through the detection of IgG antibodies from previous malaria parasite exposure can fill this gap by providing a nuanced picture of where sustained transmission remains. Study enrollment at sites of gathering provides a potential approach to spatially estimate malaria exposure and could preclude the need for more intensive community-based sampling. METHODS: This study compared spatial estimates of malaria exposure from cross-sectional school- and community-based sampling in Haiti. A total of 52,405 blood samples were collected from 2012 to 2017. Multiplex bead assays (MBAs) tested IgG against P. falciparum liver stage antigen-1 (LSA-1), apical membrane antigen 1 (AMA1), and merozoite surface protein 1 (MSP1). Predictive geospatial models of seropositivity adjusted for environmental covariates, and results were compared using correlations by coordinate points and communes across Haiti. RESULTS: Consistent directional associations were observed between seroprevalence and environmental covariates for elevation (negative), air temperature (negative), and travel time to urban centers (positive). Spearman's rank correlation for predicted seroprevalence at coordinate points was lowest for LSA-1 (ρ = 0.10, 95% CI: 0.09-0.11), but improved for AMA1 (ρ = 0.36, 95% CI: 0.35-0.37) and MSP1 (ρ = 0.48, 95% CI: 0.47-0.49). CONCLUSIONS: In settings approaching P. falciparum elimination, case-based prevalence data does not provide a resolution of ongoing malaria transmission in the population. Immunogenic antigen targets (e.g., AMA1, MSP1) that give higher population rates of seropositivity provide moderate correlation to gold standard community sampling designs and are a feasible approach to discern foci of residual P. falciparum transmission in an area. |
Spatial, environmental, and individual associations with Anopheles albimanus salivary antigen IgG in Haitian children
Jaramillo-Underwood A , Herman C , Impoinvil D , Sutcliff A , Knipes A , Worrell CM , Fox LM , Desir L , Fayette C , Javel A , Monestime F , Mace KE , Chang MA , Lemoine JF , Won K , Udhayakumar V , Rogier E . Front Cell Infect Microbiol 2022 12 1033917 IgG serology can be utilized to estimate exposure to Anopheline malaria vectors and the Plasmodium species they transmit. A multiplex bead-based assay simultaneously detected IgG to Anopheles albimanus salivary gland extract (SGE) and four Plasmodium falciparum antigens (CSP, LSA-1, PfAMA1, and PfMSP1) in 11,541 children enrolled at 350 schools across Haiti in 2016. Logistic regression estimated odds of an above-median anti-SGE IgG response adjusting for individual- and environmental-level covariates. Spatial analysis detected statistically significant clusters of schools with students having high anti-SGE IgG levels, and spatial interpolation estimated anti-SGE IgG levels in unsampled locations. Boys had 11% (95% CI: 0.81, 0.98) lower odds of high anti-SGE IgG compared to girls, and children seropositive for PfMSP1 had 53% (95% CI: 1.17, 2.00) higher odds compared to PfMSP1 seronegatives. Compared to the lowest elevation, quartiles 2-4 of higher elevation were associated with successively lower odds (0.81, 0.43, and 0.34, respectively) of high anti-SGE IgG. Seven significant clusters of schools were detected in Haiti, while spatially interpolated results provided a comprehensive picture of anti-SGE IgG levels in the study area. Exposure to malaria vectors by IgG serology with SGE is a proxy to approximate vector biting in children and identify risk factors for vector exposure. |
Spatial cluster analysis of Plasmodium vivax and P. malariae exposure using serological data among Haitian school children sampled between 2014 and 2016
Oviedo A , Herman C , Knipes A , Worrell CM , Fox LM , Desir L , Fayette C , Javel A , Monestime F , Mace KE , Chang MA , Lemoine JF , Won K , Udhayakumar V , Rogier E . PLoS Negl Trop Dis 2022 16 (1) e0010049 BACKGROUND: Estimation of malaria prevalence in very low transmission settings is difficult by even the most advanced diagnostic tests. Antibodies against malaria antigens provide an indicator of active or past exposure to these parasites. The prominent malaria species within Haiti is Plasmodium falciparum, but P. vivax and P. malariae infections are also known to be endemic. METHODOLOGY/PRINCIPAL FINDINGS: From 2014-2016, 28,681 Haitian children were enrolled in school-based serosurveys and were asked to provide a blood sample for detection of antibodies against multiple infectious diseases. IgG against the P. falciparum, P. vivax, and P. malariae merozoite surface protein 19kD subunit (MSP119) antigens was detected by a multiplex bead assay (MBA). A subset of samples was also tested for Plasmodium DNA by PCR assays, and for Plasmodium antigens by a multiplex antigen detection assay. Geospatial clustering of high seroprevalence areas for P. vivax and P. malariae antigens was assessed by both Ripley's K-function and Kulldorff's spatial scan statistic. Of 21,719 children enrolled in 680 schools in Haiti who provided samples to assay for IgG against PmMSP119, 278 (1.27%) were seropositive. Of 24,559 children enrolled in 788 schools providing samples for PvMSP119 serology, 113 (0.46%) were seropositive. Two significant clusters of seropositivity were identified throughout the country for P. malariae exposure, and two identified for P. vivax. No samples were found to be positive for Plasmodium DNA or antigens. CONCLUSIONS/SIGNIFICANCE: From school-based surveys conducted from 2014 to 2016, very few Haitian children had evidence of exposure to P. vivax or P. malariae, with no children testing positive for active infection. Spatial scan statistics identified non-overlapping areas of the country with higher seroprevalence for these two malarias. Serological data provides useful information of exposure to very low endemic malaria species in a population that is unlikely to present to clinics with symptomatic infections. |
COVID-19 Vaccination Coverage Among Adults - United States, December 14, 2020-May 22, 2021.
Diesel J , Sterrett N , Dasgupta S , Kriss JL , Barry V , Vanden Esschert K , Whiteman A , Cadwell BL , Weller D , Qualters JR , Harris L , Bhatt A , Williams C , Fox LM , Meaney Delman D , Black CL , Barbour KE . MMWR Morb Mortal Wkly Rep 2021 70 (25) 922-927 The U.S. COVID-19 vaccination program launched on December 14, 2020. The Advisory Committee on Immunization Practices recommended prioritizing COVID-19 vaccination for specific groups of the U.S. population who were at highest risk for COVID-19 hospitalization and death, including adults aged ≥75 years*; implementation varied by state, and eligibility was gradually expanded to persons aged ≥65 years beginning in January 2021. By April 19, 2021, eligibility was expanded to all adults aged ≥18 years nationwide.(†) To assess patterns of COVID-19 vaccination coverage among U.S. adults, CDC analyzed data submitted on vaccinations administered during December 14, 2020-May 22, 2021, by age, sex, and community-level characteristics. By May 22, 2021, 57.0% of persons aged ≥18 years had received ≥1 COVID-19 vaccine dose; coverage was highest among persons aged ≥65 years (80.0%) and lowest among persons aged 18-29 years (38.3%). During the week beginning February 7, 2021, vaccination initiation among adults aged ≥65 years peaked at 8.2%, whereas weekly initiation among other age groups peaked later and at lower levels. During April 19-May 22, 2021, the period following expanded eligibility to all adults, weekly initiation remained <4.0% and decreased for all age groups, including persons aged 18-29 years (3.6% to 1.9%) and 30-49 years (3.5% to 1.7%); based on the current rate of weekly initiation (as of May 22), younger persons will not reach the same levels of coverage as older persons by the end of August. Across all age groups, coverage (≥1 dose) was lower among men compared with women, except among adults aged ≥65 years, and lower among persons living in counties that were less urban, had higher social vulnerabilities, or had higher percentages of social determinants of poor health. Continued efforts to improve vaccination confidence and alleviate barriers to vaccination initiation, especially among adults aged 18-49 years, could improve vaccination coverage. |
Acquisition of ciprofloxacin resistance among an expanding clade of β-lactamase positive, serogroup Y Neisseria meningitidis in the United States.
Potts CC , Retchless AC , McNamara LA , Marasini D , Reese N , Swint S , Hu F , Sharma S , Blain AE , Lonsway D , Karlsson M , Hariri S , Fox LM , Wang X . Clin Infect Dis 2021 73 (7) 1185-1193 BACKGROUND: Penicillin and ciprofloxacin are important for invasive meningococcal disease (IMD) management and prevention. IMD cases caused by penicillin- and ciprofloxacin-resistant Neisseria meningitidis containing a ROB-1 β-lactamase gene (blaROB-1) and a mutated DNA gyrase gene (gyrA), have been recently reported in the USA. METHODS: We examined 2097 meningococcal genomes collected through US population-based surveillance from January 2011-February 2020 to identify IMD cases caused by strains with blaROB-1 or gyrA-mediated resistance. Antimicrobial resistance was confirmed phenotypically. The US isolate genomes were compared to non-US isolate genomes containing blaROB-1. Interspecies transfer of ciprofloxacin resistance was assessed by comparing gyrA among Neisseria species. RESULTS: Eleven penicillin- and ciprofloxacin-resistant isolates were identified after December 2018; all were serogroup Y, sequence type 3587, clonal complex (CC) 23, and contained blaROB-1 and a T91I-containing gyrA allele. An additional 22 penicillin-resistant, blaROB-1-containing US isolates with wild-type gyrA were identified from 2013-2020. All 33 blaROB-1-containing isolates formed a single clade, along with 12 blaROB-1-containing isolates from six other countries. Two-thirds of blaROB-1-containing US isolates were from Hispanic individuals. Twelve additional ciprofloxacin-resistant isolates with gyrA T91 mutations were identified. Ciprofloxacin-resistant isolates belonged to six CCs and contained 10 unique gyrA alleles; seven were similar or identical to alleles from N. lactamica or N. gonorrhoeae. CONCLUSIONS: Recent IMD cases caused by a dual resistant serogroup Y suggest changing antimicrobial resistance patterns in the USA. The emerging dual-resistance is due to acquisition of ciprofloxacin resistance by β-lactamase-containing N. meningitidis. Routine antimicrobial resistance surveillance will effectively monitor resistance changes and spread. |
Molecular diagnostic assays for the detection of common bacterial meningitis pathogens: A narrative review.
Diallo K , Feteh VF , Ibe L , Antonio M , Caugant DA , du Plessis M , Deghmane AE , Feavers IM , Fernandez K , Fox LM , Rodrigues CMC , Ronveaux O , Taha MK , Wang X , Brueggemann AB , Maiden MCJ , Harrison OB . EBioMedicine 2021 65 103274 Bacterial meningitis is a major global cause of morbidity and mortality. Rapid identification of the aetiological agent of meningitis is essential for clinical and public health management and disease prevention given the wide range of pathogens that cause the clinical syndrome and the availability of vaccines that protect against some, but not all, of these. Since microbiological culture is complex, slow, and often impacted by prior antimicrobial treatment of the patient, molecular diagnostic assays have been developed for bacterial detection. Distinguishing between meningitis caused by Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Streptococcus agalactiae and identifying their polysaccharide capsules is especially important. Here, we review methods used in the identification of these bacteria, providing an up-to-date account of available assays, allowing clinicians and diagnostic laboratories to make informed decisions about which assays to use. |
Investigation of a Large Diphtheria Outbreak and Co-circulation of Corynebacterium pseudodiphtheriticum among Forcibly Displaced Myanmar Nationals, 2017-2019.
Weil LM , Williams MM , Shirin T , Lawrence M , Habib ZH , Aneke JS , Tondella ML , Zaki Q , Cassiday PK , Lonsway D , Farrque M , Hossen T , Feldstein LR , Cook N , Maldonado-Quiles G , Alam AN , Muraduzzaman AKM , Akram A , Conklin L , Doan S , Friedman M , Acosta AM , Hariri S , Fox LM , Tiwari TSP , Flora MS . J Infect Dis 2020 224 (2) 318-325 BACKGROUND: Diphtheria, a life-threatening respiratory disease, is caused mainly by toxin-producing strains of Corynebacterium diphtheriae, while nontoxigenic Corynebacteria, such as C. pseudodiphtheriticum rarely causes diphtheria-like illness. Recently several global diphtheria outbreaks have resulted from the breakdown of healthcare infrastructures particularly in countries experiencing political conflict. This report summarizes a laboratory and epidemiological investigation of a diphtheria outbreak among Forcibly Displaced Myanmar Nationals in Bangladesh. METHODS: Specimens and clinical information were collected from patients presenting at Diphtheria Treatment Centers. Swabs were tested for toxin-gene (tox) bearing C. diphtheriae by real-time (RT) PCR and culture. The isolation of another Corynebacterium species prompted further laboratory investigation. RESULTS: Among 382 patients; 153 (40%) tested tox-positive for C. diphtheriae by RT-PCR; 31 (20%) PCR-positive swabs were culture-confirmed. RT-PCR revealed 78% (298/382) of patients tested positive for C. pseudodiphtheriticum. Of patients positive for only C. diphtheriae, 63% (17/27) had severe disease compared to 55% (69/126) positive for both Corynebacterium species, and 38% (66/172) for only C. pseudodiphtheriticum. CONCLUSIONS: We report the confirmation of a diphtheria outbreak and identification of a co-circulating Corynebacterium species. The high proportion of C. pseudodiphtheriticum co-detection may explain why many suspected patients testing negative for C. diphtheriae presented with diphtheria-like symptoms. |
Evaluation of a facility-based inspection tool to assess lymphedema management services in Vietnam
Dung DT , Binh VTL , Worrell CM , Brady M , Walsh V , Yajima A , Sifri Z , Fox LM . PLoS Negl Trop Dis 2020 14 (10) e0008773 Assuring availability of services for patients with lymphedema is required for countries to be validated as having achieved elimination of lymphatic filariasis (LF). A direct inspection protocol (DIP) tool, designed to measure the readiness to provide quality lymphedema management services, has recently been developed. The DIP tool includes 14 indicators across six quality themes: trained staff, case management and education materials, water infrastructure, medications and commodities, patient tracking system, and staff knowledge. We evaluated the use of the tool in Vietnam, where data were needed to inform validation efforts. To apply the tool in Vietnam, we compiled a list of 219 commune health stations (CHS) with known lymphedema patients and conducted a cross-sectional survey in 32 CHS; including 24 in Red River Delta region, 2 in the North Central region, and 6 in the South Central Coast region. The mean facility score, calculated by assigning 1 point per indicator, was 8.8 of 14 points (63%, range 4[29%]-13[93%]). Percentage of surveyed facilities with staff trained in last two years was 0%; availability of lymphedema management guidelines (56%); availability of information, education, and communication materials (16%); reliable improved water infrastructure (94%); availability of antiseptics (81%), antifungals (44%), analgesics or anti-inflammatories (97%), antibiotics (94%); supplies for lymphedema and acute attack management (100%); lymphedema patients recorded in last 12 months (9%); staff knowledge about lymphedema signs/symptoms (63%), lymphedema management strategies (72%), signs/symptoms of acute attacks (81%), and acute attack management strategies (75%). The tool allowed standardized assessment of readiness to provide quality services. Lack of trained health staff, limited patient tracking, and depletion of education materials were identified as challenges and addressed by the national program. Survey data were included in the validation dossier, providing evidence necessary for WHO to validate Vietnam as having eliminated lymphatic filariasis in 2018. |
Next generation rapid diagnostic tests for meningitis diagnosis
Feagins AR , Ronveaux O , Taha MK , Caugant DA , Smith V , Fernandez K , Glennie L , Fox LM , Wang X . J Infect 2020 81 (5) 712-718 Rapid diagnostic tests (RDTs) are increasingly recognized as valuable, transformative tools for the diagnosis of infectious diseases. Although there are a variety of meningitis RDTs currently available, certain product features restrict their use to specific levels of care and settings. For this reason, the development of meningitis RDTs for use at all levels of care, including those in low-resource settings, was included in the "Defeating Meningitis by 2030" roadmap. Here we address the limitations of available meningitis RDTs and present test options and specifications to consider when developing the next generation of meningitis RDTs. |
Detection of Ciprofloxacin-Resistant, β-Lactamase-Producing Neisseria meningitidis Serogroup Y Isolates - United States, 2019-2020.
McNamara LA , Potts C , Blain AE , Retchless AC , Reese N , Swint S , Lonsway D , Karlsson M , Lunquest K , Sweitzer JJ , Wang X , Hariri S , Fox LM . MMWR Morb Mortal Wkly Rep 2020 69 (24) 735-739 Meningococcal disease is a sudden-onset, life-threatening illness caused by the bacterium Neisseria meningitidis. Prompt empiric antibiotic treatment can reduce morbidity and mortality among patients, and antibiotic prophylaxis can prevent secondary disease in close contacts. Historically, N. meningitidis isolates in the United States have largely been susceptible to the antibiotics recommended for treatment and prophylaxis, including penicillin and ciprofloxacin. This report describes detection of penicillin-resistant and ciprofloxacin-resistant N. meningitidis serogroup Y (NmY) isolates in the United States. NmY isolates containing a blaROB-1 beta-lactamase enzyme gene conferring resistance to penicillins (1) were recovered from 33 cases reported during 2013-2020. Isolates from 11 of these cases, reported during 2019-2020, harbored a ciprofloxacin resistance-associated mutation in a chromosomal gene (gyrA). Cases were reported from 12 geographically disparate states; a majority of cases (22 of 33, 67%) occurred in Hispanic persons. These cases represent a substantial increase in penicillin-resistant and ciprofloxacin-resistant meningococci in the United States since 2013. Ceftriaxone and cefotaxime, the recommended first-line agents for empiric bacterial meningitis treatment, can continue to be used for treatment, but health care providers should ascertain susceptibility of meningococcal isolates to penicillin before switching to penicillin or ampicillin. Ongoing monitoring for antimicrobial resistance among meningococcal isolates and prophylaxis failures will be important to inform treatment and prophylaxis recommendations. |
Combination of Serological, Antigen Detection, and DNA Data for Plasmodium falciparum Provides Robust Geospatial Estimates for Malaria Transmission in Haiti.
Oviedo A , Knipes A , Worrell C , Fox LM , Desir L , Fayette C , Javel A , Monestime F , Mace K , Chang MA , Udhayakumar V , Lemoine JF , Won K , Lammie PJ , Rogier E . Sci Rep 2020 10 (1) 8443 Microscopy is the gold standard for malaria epidemiology, but laboratory and point-of-care (POC) tests detecting parasite antigen, DNA, and human antibodies against malaria have expanded this capacity. The island nation of Haiti is endemic for Plasmodium falciparum (Pf) malaria, though at a low national prevalence and heterogenous geospatial distribution. In 2015 and 2016, serosurveys were performed of children (ages 6-7 years) sampled in schools in Saut d'Eau commune (n = 1,230) and Grand Anse department (n = 1,664) of Haiti. Children received malaria antigen rapid diagnostic test and provided a filter paper blood sample for further laboratory analysis of the Pf histidine-rich protein 2 (HRP2) antigen, Pf DNA, and anti-Pf IgG antibodies. Prevalence of Pf infection ranged from 0.0-16.7% in 53 Saut d'Eau schools, and 0.0-23.8% in 56 Grand Anse schools. Anti-Pf antibody carriage exceeded 80% of students in some schools from both study sites. Geospatial prediction ellipses were created to indicate clustering of positive tests within the survey areas and overlay of all prediction ellipses for the different types of data revealed regions with high likelihood of active and ongoing Pf malaria transmission. The geospatial utilization of different types of Pf data can provide high confidence for spatial epidemiology of the parasite. |
Toward a Global Genomic Epidemiology of Meningococcal Disease.
Retchless AC , Fox LM , Maiden MCJ , Smith V , Harrison LH , Glennie L , Harrison OB , Wang X . J Infect Dis 2019 220 S266-s273 Whole-genome sequencing (WGS) is invaluable for studying the epidemiology of meningococcal disease. Here we provide a perspective on the use of WGS for meningococcal molecular surveillance and outbreak investigation, where it helps to characterize pathogens, predict pathogen traits, identify emerging pathogens, and investigate pathogen transmission during outbreaks. Standardization of WGS workflows has facilitated their implementation by clinical and public health laboratories (PHLs), but further development is required for metagenomic shotgun sequencing and targeted sequencing to be widely available for culture-free characterization of bacterial meningitis pathogens. Internet-accessible servers are being established to support bioinformatics analysis, data management, and data sharing among PHLs. However, establishing WGS capacity requires investments in laboratory infrastructure and technical knowledge, which is particularly challenging in resource-limited regions, including the African meningitis belt. Strategic WGS implementation is necessary to monitor the molecular epidemiology of meningococcal disease in these regions and construct a global view of meningococcal disease epidemiology. |
Future directions for meningitis surveillance and vaccine evaluation in the meningitis belt of sub-Saharan Africa
Novak RT , Ronveaux O , Bita AF , Ake HF , Lessa FC , Wang X , Bwaka AM , Fox LM . J Infect Dis 2019 220 S279-s285 In sub-Saharan Africa, bacterial meningitis remains a significant public health problem, especially in the countries of the meningitis belt, where Neisseria meningitidis serogroup A historically caused large-scale epidemics. In 2014, MenAfriNet was established as a consortium of partners supporting strategic implementation of case-based meningitis surveillance to monitor meningitis epidemiology and impact of meningococcal serogroup A conjugate vaccine (MACV). MenAfriNet improved data quality through use of standardized tools, procedures, and laboratory diagnostics. MenAfriNet surveillance and study data provided evidence of ongoing MACV impact, characterized the burden of non-serogroup A meningococcal disease (including the emergence of a new epidemic clone of serogroup C), and documented the impact of pneumococcal conjugate vaccine. New vaccines and schedules have been proposed for future implementation to address the remaining burden of meningitis. To support the goals of "Defeating Meningitis by 2030," MenAfriNet will continue to strengthen surveillance and support research and modeling to monitor the impact of these programs on meningitis burden in sub-Saharan Africa. |
Invasive meningococcal disease in Africa's meningitis belt: More than just meningitis
Reese HE , Ronveaux O , Mwenda JM , Bita A , Cohen AL , Novak RT , Fox LM , Soeters HM . J Infect Dis 2019 220 S263-s265 Since the progressive introduction of the meningococcal serogroup A conjugate vaccine within Africa's meningitis belt beginning in 2010, the burden of meningitis due to Neisseria meningitidis serogroup A (NmA) has substantially decreased. Non-A serogroups C/W/X are now the most prevalent. Surveillance within the belt has historically focused on the clinical syndrome of meningitis, the classic presentation for NmA, and may not adequately capture other presentations of invasive meningococcal disease (IMD). The clinical presentation of infection due to serogroups C/W/X includes nonmeningeal IMD, and there is a higher case-fatality ratio associated with these non-A serogroups; however, data on the nonmeningeal IMD burden within the belt are scarce. Expanding surveillance to capture all cases of IMD, in accordance with the World Health Organization's updated vaccine-preventable disease surveillance standards and in preparation for the anticipated introduction of a multivalent meningococcal conjugate vaccine within Africa's meningitis belt, will enhance meningococcal disease prevention across the belt. |
Phylogenetic relationships and regional spread of meningococcal strains in the meningitis belt, 2011-2016.
Topaz N , Caugant DA , Taha MK , Brynildsrud OB , Debech N , Hong E , Deghmane AE , Ouedraogo R , Ousmane S , Gamougame K , Njanpop-Lafourcade BM , Diarra S , Fox LM , Wang X . EBioMedicine 2019 41 488-496 BACKGROUND: Historically, the major cause of meningococcal epidemics in the meningitis belt of sub-Saharan Africa has been Neisseria meningitidis serogroup A (NmA), but the incidence has been substantially reduced since the introduction of a serogroup A conjugate vaccine starting in 2010. We performed whole-genome sequencing on isolates collected post-2010 to assess their phylogenetic relationships and inter-country transmission. METHODS: A total of 716 invasive meningococcal isolates collected between 2011 and 2016 from 11 meningitis belt countries were whole-genome sequenced for molecular characterization by the three WHO Collaborating Centers for Meningitis. FINDINGS: We identified three previously-reported clonal complexes (CC): CC11 (n=434), CC181 (n=62) and CC5 (n=90) primarily associated with NmW, NmX, and NmA, respectively, and an emerging CC10217 (n=126) associated with NmC. CC11 expanded throughout the meningitis belt independent of the 2000 Hajj outbreak strain, with isolates from Central African countries forming a distinct sub-lineage within this expansion. Two major sub-lineages were identified for CC181 isolates, one mainly expanding in West African countries and the other found in Chad. CC10217 isolates from the large outbreaks in Nigeria and Niger were more closely related than those from the few cases in Mali and Burkina Faso. INTERPRETATIONS: Whole-genome based phylogenies revealed geographically distinct strain circulation as well as inter-country transmission events. Our results stress the importance of continued meningococcal molecular surveillance in the region, as well as the development of an affordable vaccine targeting these strains. FUND: Meningitis Research Foundation; CDC's Office of Advanced Molecular Detection; GAVI, the Vaccine Alliance. |
Outbreak of Neisseria meningitidis serogroup C outside the meningitis belt-Liberia, 2017: an epidemiological and laboratory investigation.
Bozio CH , Vuong J , Dokubo EK , Fallah MP , McNamara LA , Potts CC , Doedeh J , Gbanya M , Retchless AC , Patel JC , Clark TA , Kohar H , Nagbe T , Clement P , Katawera V , Mahmoud N , Djingarey HM , Perrocheau A , Naidoo D , Stone M , George RN , Williams D , Gasasira A , Nyenswah T , Wang X , Fox LM . Lancet Infect Dis 2018 18 (12) 1360-1367 BACKGROUND: On April 25, 2017, a cluster of unexplained illnesses and deaths associated with a funeral was reported in Sinoe County, Liberia. Molecular testing identified Neisseria meningitidis serogroup C (NmC) in specimens from patients. We describe the epidemiological investigation of this cluster and metagenomic characterisation of the outbreak strain. METHODS: We collected epidemiological data from the field investigation and medical records review. Confirmed, probable, and suspected cases were defined on the basis of molecular testing and signs or symptoms of meningococcal disease. Metagenomic sequences from patient specimens were compared with 141 meningococcal isolate genomes to determine strain lineage. FINDINGS: 28 meningococcal disease cases were identified, with dates of symptom onset from April 21 to April 30, 2017: 13 confirmed, three probable, and 12 suspected. 13 patients died. Six (21%) patients reported fever and 23 (82%) reported gastrointestinal symptoms. The attack rate for confirmed and probable cases among funeral attendees was 10%. Metagenomic sequences from six patient specimens were similar to a sequence type (ST) 10217 (clonal complex [CC] 10217) isolate genome from Niger, 2015. Multilocus sequencing identified five of seven alleles from one specimen that matched ST-9367, which is represented in the PubMLST database by one carriage isolate from Burkina Faso, in 2011, and belongs to CC10217. INTERPRETATION: This outbreak featured high attack and case fatality rates. Clinical presentation was broadly consistent with previous meningococcal disease outbreaks, but predominance of gastrointestinal symptoms was unusual compared with previous African meningitis epidemics. The outbreak strain was genetically similar to NmC CC10217, which caused meningococcal disease outbreaks in Niger and Nigeria. CC10217 had previously been identified only in the African meningitis belt. FUNDING: US Global Health Security. |
A Delphi consultation to assess indicators of readiness to provide quality health facility-based Lymphoedema management services
Walsh VL , Fox LM , Brady M , King J , Worrell CM . PLoS Negl Trop Dis 2018 12 (9) e0006699 BACKGROUND: The World Health Organization (WHO) in collaboration with partners is developing a toolkit of resources to guide lymphatic filariasis (LF) morbidity management and disability prevention (MMDP) implementation and evaluation. Direct health facility inspection is the preferred method for documenting the readiness of a country programme to provide quality lymphoedema management services, one of the three MMDP criteria used to demonstrate the elimination of LF as a public health problem. METHODOLOGY/PRINCIPAL FINDINGS: As component of tool development, a Delphi consultation was implemented to gain consensus on six proposed domains and fourteen proposed tracer indicators to measure national programme readiness to provide quality health facility-based lymphoedema management services. A seven-point Likert-type scale was used to rank the importance of proposed domains and tracer indicators. Consensus for inclusion of the indicator was defined a priori as 70% or more of respondents ranking the proposed indicator in the top three tiers (5-7). Purposive sampling was used to select 43 representative experts including country representatives, programme implementers, and technical experts. A 55.8% response rate (n = 24) was achieved for the survey. Analysis of the responses demonstrated that consensus for inclusion had been reached for all proposed domains including trained staff (mean = 6.9, standard deviation (SD) = 0.34), case management and education materials (mean = 6.1, SD = 0.65), water infrastructure (mean = 6.3, SD = 0.81), medications and commodities (mean = 6.3, SD = 0.69), patient tracking system (mean = 6.3, SD = 0.85), and staff knowledge (mean = 6.5, SD = 0.66). SIGNIFICANCE: The Delphi consultation provided an efficient and structured method for gaining consensus among lymphatic filariasis experts around key lymphoedema management quality indicators. The results from this analysis were used to refine the indicators included within the direct inspection protocol tool to ensure its ability to assess health facility readiness to provide quality lymphoedema management services. |
The effect of a regimen of antifungal cream use on episodes of acute adenolymphangitis (ADL) among lymphedema patients: An application using marginal structural models
Mues KE , Klein M , Kleinbaum DG , Flanders WD , Fox LM . J Epidemiol Glob Health 2017 8 176-182 Episodes of adenolymphangitis (ADL) are a recurrent clinical aspect of lymphatic filariasis (LF) and a risk factor for progression of lymphedema. Inter-digital entry lesions, often found on the web spaces between the toes of those suffering from lymphedema, have been shown to contribute to the occurrence of ADL episodes. Use of antifungal cream on lesions is often promoted as a critical component of lymphedema management.Our objective was to estimate the observed effect of antifungal cream use on ADL episodes according to treatment regimen among a cohort of lymphedema patients enrolled in a morbidity management program. We estimated this effect using marginal structural models for time varying confounding.In this longitudinal study, we estimate that for every one-unit increase in the number of times one was compliant to cream use through 12 months, there was a 23% (RR = 0.77 (0.62, 0.96)) decrease in the number of ADL episodes at 18 months, however the RR's were not statistically significant at other study time points. Traditionally adjusted models produced a non-significant RR closer to the null at all time points.This is the first study to estimate the effect of a regimen of antifungal cream on the frequency of ADL episodes. This study also highlights the importance of the consideration and proper handling of time-varying confounders in longitudinal observational studies. |
Rapid laboratory identification of Neisseria meningitidis serogroup C as the cause of an outbreak - Liberia, 2017
Patel JC , George J , Vuong J , Potts CC , Bozio C , Clark TA , Thomas J , Schier J , Chang A , Waller JL , Diaz MH , Whaley M , Jenkins LT , Fuller S , Williams DE , Redd JT , Arthur RR , Taweh F , Vera Walker Y , Hardy P , Freeman M , Katawera V , Gwesa G , Gbanya MZ , Clement P , Kohar H , Stone M , Fallah M , Nyenswah T , Winchell JM , Wang X , McNamara LA , Dokubo EK , Fox LM . MMWR Morb Mortal Wkly Rep 2017 66 (42) 1144-1147 On April 25, 2017, a cluster of unexplained illness and deaths among persons who had attended a funeral during April 21-22 was reported in Sinoe County, Liberia (1). Using a broad initial case definition, 31 cases were identified, including 13 (42%) deaths. Twenty-seven cases were from Sinoe County (1), and two cases each were from Grand Bassa and Monsterrado counties, respectively. On May 5, 2017, initial multipathogen testing of specimens from four fatal cases using the Taqman Array Card (TAC) assay identified Neisseria meningitidis in all specimens. Subsequent testing using direct real-time polymerase chain reaction (PCR) confirmed N. meningitidis in 14 (58%) of 24 patients with available specimens and identified N. meningitidis serogroup C (NmC) in 13 (54%) patients. N. meningitidis was detected in specimens from 11 of the 13 patients who died; no specimens were available from the other two fatal cases. On May 16, 2017, the National Public Health Institute of Liberia and the Ministry of Health of Liberia issued a press release confirming serogroup C meningococcal disease as the cause of this outbreak in Liberia. |
Assessment of U.S. pediatrician knowledge of toxocariasis
Woodhall DM , Garcia AP , Shapiro CA , Wray SL , Shane AL , Mani CS , Stimpert KK , Fox LM , Montgomery SP . Am J Trop Med Hyg 2017 97 (4) 1243-1246 Toxocariasis, one of a group of parasitic diseases known as neglected parasitic infections, is a disease caused by the larvae of two species of Toxocara roundworms, Toxocara canis, from dogs, and less commonly Toxocara cati, from cats. Although most infected individuals are asymptomatic, clinical manifestations may include fever, fatigue, coughing, wheezing, or abdominal pain (visceral toxocariasis) or vision loss, retina damage, or eye inflammation (ocular toxocariasis). To assess U.S. pediatrician knowledge of toxocariasis, we conducted an electronic survey of American Academy of Pediatrics members. Of the 2,684 respondents, 1,120 (47%) pediatricians correctly selected toxocariasis as the diagnosis in an unknown case presentation with findings typical for toxocariasis; overall 1,695 (85%) stated they were not confident that their knowledge of toxocariasis was current. This knowledge gap suggests a need for improved toxocariasis awareness and education for U.S. pediatricians, especially those caring for children at risk for infection. |
First evidence of Angiostrongyliasis caused by Angiostrongylus cantonensis in Guadeloupe, Lesser Antilles
Dard C , Piloquet JE , Qvarnstrom Y , Fox LM , M'Kada H , Hebert JC , Mattera D , Harrois D . Am J Trop Med Hyg 2017 96 (3) 692-697 Infection by the rat lungworm Angiostrongylus cantonensis represents the most common cause of infectious eosinophilic meningitis in humans, causing central nervous system (CNS) angiostrongyliasis. Most of CNS angiostrongyliasis cases were described in Asia, Pacific Basin, Australia, and some limited parts of Africa and America. CNS angiostrongyliasis has been reported in the Caribbean but never in the Lesser Antilles. The primary objectives of this study were to depict the first case of CNS angiostrongyliasis in the Lesser Antilles and investigate the environmental presence of A. cantonensis in Guadeloupe, Lesser Antilles. In December 2013, a suspected case of CNS angiostrongyliasis in an 8-month-old infant in Guadeloupe was investigated by real-time polymerase chain reaction (PCR) testing on cerebral spinal fluid (CSF). The environmental investigation was performed by collecting Achatina fulica molluscs from different parts of Guadeloupe and testing the occurrence of A. cantonensis by real-time PCR. CSF from the suspected case of angiostrongyliasis was positive for A. cantonensis by real-time PCR. Among 34 collected snails for environmental investigation, 32.4% were positive for A. cantonensis In conclusion, we report the first laboratory-confirmed case of CNS-angiostrongyliasis in the Lesser Antilles. We identified the presence and high prevalence of A. cantonensis in A. fulica in Guadeloupe. These results highlight the need to increase awareness of this disease and implement public health programs in the region to prevent human cases of angiostrongyliasis and improve management of eosinophilic meningitis patients. |
Evaluation of lymphatic filariasis and onchocerciasis in three Senegalese districts treated for onchocerciasis with ivermectin
Wilson NO , Badara Ly A , Cama VA , Cantey PT , Cohn D , Diawara L , Direny A , Fall M , Feeser KR , Fox LM , Kabore A , Seck AF , Sy N , Ndiaye D , Dubray C . PLoS Negl Trop Dis 2016 10 (12) e0005198 In Africa, onchocerciasis and lymphatic filariasis (LF) are co-endemic in many areas. Current efforts to eliminate both diseases are through ivermectin-based mass drug administration (MDA). Years of ivermectin distribution for onchocerciasis may have interrupted LF transmission in certain areas. The Kedougou region, Senegal, is co-endemic for LF and onchocerciasis. Though MDA for onchocerciasis started in 1988, in 2014 albendazole had not yet been added for LF. The objective of this study was to assess in an integrated manner the LF and onchocerciasis status in the three districts of the Kedougou region after ≥10 years of ivermectin-based MDA. The study employed an African Programme for Onchocerciasis Control (APOC) onchocerciasis-related methodology. In the three districts, 14 villages close to three rivers that have Simulium damnosum breeding sites were surveyed. Convenience sampling of residents ≥5 years old was performed. Assessment for LF antigenemia by immunochromatographic testing (ICT) was added to skin snip microscopy for onchocerciasis. Participants were also tested for antibodies against Wb123 (LF) and Ov16 (onchocerciasis) antigens. In two districts, no participants were ICT or skin snip positive. In the third district, 3.5% were ICT positive and 0.7% were skin snip positive. In all the three districts, Wb123 prevalence was 0.6%. Overall, Ov16 prevalence was 6.9%. Ov16 prevalence among children 5-9 years old in the study was 2.5%. LF antigenemia prevalence was still above treatment threshold in one district despite ≥10 years of ivermectin-based MDA. The presence of Ov16 positive children suggested recent transmission of Onchocerca volvulus. This study showed the feasibility of integrated evaluation of onchocerciasis and LF but development of integrated robust methods for assessing transmission of both LF and onchocerciasis are needed to determine where MDA can be stopped safely in co-endemic areas. |
Evaluating the burden of lymphedema due to lymphatic filariasis in 2005 in Khurda district, Odisha state, India
Walsh V , Little K , Wiegand R , Rout J , Fox LM . PLoS Negl Trop Dis 2016 10 (8) e0004917 BACKGROUND: Over 1.1 billion people worldwide are at risk for lymphatic filariasis (LF), and the global burden of LF-associated lymphedema is estimated at 16 million affected people, yet country-specific estimates are poor. METHODOLOGY/PRINCIPAL FINDINGS: A house-to-house morbidity census was conducted to assess the burden and severity of lymphedema in a population of 1,298,576 persons living in the LF-endemic district of Khurda in Odisha State, India. The burden of lymphedema in Khurda is widespread geographically, and 1.3% (17,036) of the total population report lymphedema. 51.3% of the patients reporting lymphedema were female, mean age 49.4 years (1-99). Early lymphedema (Dreyer stages 1 & 2) was reported in two-thirds of the patients. Poisson regression analysis was conducted in order to determine risk factors for advanced lymphedema (Dreyer stages 4-7). Increasing age was significantly associated with advanced lymphedema, and persons 70 years and older had a prevalence three times greater than individuals ages 15-29 (aPR: 3.21, 95% CI 2.45, 4.21). The number of adenolymphangitis (ADL) episodes reported in the previous year was also significantly associated with advanced lymphedema (aPR 4.65, 95% CI 2.97-7.30). This analysis is one of the first to look at potential risk factors for advanced lymphedema using morbidity census data from an entire district in Odisha State, India. SIGNIFICANCE: These data highlight the magnitude of lymphedema in LF-endemic areas and emphasize the need to develop robust estimates of numbers of individuals with lymphedema in order to identify the extent of lymphedema management services needed in these regions. |
Economic analysis of the impact of overseas and domestic treatment and screening options for intestinal helminth infection among US-bound refugees from Asia
Maskery B , Coleman MS , Weinberg M , Zhou W , Rotz L , Klosovsky A , Cantey PT , Fox LM , Cetron MS , Stauffer WM . PLoS Negl Trop Dis 2016 10 (8) e0004910 BACKGROUND: Many U.S.-bound refugees travel from countries where intestinal parasites (hookworm, Trichuris trichuria, Ascaris lumbricoides, and Strongyloides stercoralis) are endemic. These infections are rare in the United States and may be underdiagnosed or misdiagnosed, leading to potentially serious consequences. This evaluation examined the costs and benefits of combinations of overseas presumptive treatment of parasitic diseases vs. domestic screening/treating vs. no program. METHODS: An economic decision tree model terminating in Markov processes was developed to estimate the cost and health impacts of four interventions on an annual cohort of 27,700 U.S.-bound Asian refugees: 1) "No Program," 2) U.S. "Domestic Screening and Treatment," 3) "Overseas Albendazole and Ivermectin" presumptive treatment, and 4) "Overseas Albendazole and Domestic Screening for Strongyloides". Markov transition state models were used to estimate long-term effects of parasitic infections. Health outcome measures (four parasites) included outpatient cases, hospitalizations, deaths, life years, and quality-adjusted life years (QALYs). RESULTS: The "No Program" option is the least expensive ($165,923 per cohort) and least effective option (145 outpatient cases, 4.0 hospitalizations, and 0.67 deaths discounted over a 60-year period for a one-year cohort). The "Overseas Albendazole and Ivermectin" option ($418,824) is less expensive than "Domestic Screening and Treatment" ($3,832,572) or "Overseas Albendazole and Domestic Screening for Strongyloides" ($2,182,483). According to the model outcomes, the most effective treatment option is "Overseas Albendazole and Ivermectin," which reduces outpatient cases, deaths and hospitalization by around 80% at an estimated net cost of $458,718 per death averted, or $2,219/$24,036 per QALY/life year gained relative to "No Program". DISCUSSION: Overseas presumptive treatment for U.S.-bound refugees is a cost-effective intervention that is less expensive and at least as effective as domestic screening and treatment programs. The addition of ivermectin to albendazole reduces the prevalence of chronic strongyloidiasis and the probability of rare, but potentially fatal, disseminated strongyloidiasis. |
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. |
Experiences of a community-based lymphedema management program for lymphatic filariasis in Odisha State, India: an analysis of focus group discussions with patients, families, community members and program volunteers
Cassidy T , Worrell CM , Little K , Prakash A , Patra I , Rout J , Fox LM . PLoS Negl Trop Dis 2016 10 (2) e0004424 BACKGROUND: Globally 68 million people are infected with lymphatic filariasis (LF), 17 million of whom have lymphedema. This study explores the effects of a lymphedema management program in Odisha State, India on morbidity and psychosocial effects associated with lymphedema. METHODOLOGY/PRINCIPAL FINDINGS: Focus groups were held with patients (eight groups, separated by gender), their family members (eight groups), community members (four groups) and program volunteers (four groups) who had participated in a lymphedema management program for the past three years. Significant social, physical, and economic difficulties were described by patients and family members, including marriageability, social stigma, and lost workdays. However, the positive impact of the lymphedema management program was also emphasized, and many family and community members indicated that community members were accepting of patients and had some improved understanding of the etiology of the disease. Program volunteers and community members stressed the role that the program had played in educating people, though interestingly, local explanations and treatments appear to coexist with knowledge of biomedical treatments and the mosquito vector. CONCLUSIONS/SIGNIFICANCE: Local and biomedical understandings of disease can co-exist and do not preclude individuals from participating in biomedical interventions, specifically lymphedema management for those with lymphatic filariasis. There is a continued need for gender-specific psychosocial support groups to address issues particular to men and women as well as a continued need for improved economic opportunities for LF-affected patients. There is an urgent need to scale up LF-related morbidity management programs to reduce the suffering of people affected by LF. |
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). |
Real-Time Polymerase Chain Reaction Detection of Angiostrongylus cantonensis DNA in Cerebrospinal Fluid from Patients with Eosinophilic Meningitis.
Qvarnstrom Y , Xayavong M , Aramburu da Silva AC , Park SY , Whelen AC , Calimlim PS , Sciulli RH , Honda SA , Higa K , Kitsutani P , Chea N , Heng S , Johnson S , Graeff-Teixeira C , Fox LM , da Silva AJ . Am J Trop Med Hyg 2015 94 (1) 176-81 Angiostrongylus cantonensis is the most common infectious cause of eosinophilic meningitis. Timely diagnosis of these infections is difficult, partly because reliable laboratory diagnostic methods are unavailable. The aim of this study was to evaluate the usefulness of a real-time polymerase chain reaction (PCR) assay for the detection of A. cantonensis DNA in human cerebrospinal fluid (CSF) specimens. A total of 49 CSF specimens from 33 patients with eosinophilic meningitis were included: A. cantonensis DNA was detected in 32 CSF specimens, from 22 patients. Four patients had intermittently positive and negative real-time PCR results on subsequent samples, indicating that the level of A. cantonensis DNA present in CSF may fluctuate during the course of the illness. Immunodiagnosis and/or supplemental PCR testing supported the real-time PCR findings for 30 patients. On the basis of these observations, this real-time PCR assay can be useful to detect A. cantonensis in the CSF from patients with eosinophilic meningitis. |
Changes in antibody levels during and following an episode of acute adenolymphangitis (ADL) among lymphedema patients in Leogane, Haiti
Mues KE , Lammie PJ , Klein M , Kleinbaum DG , Addiss D , Fox LM . PLoS One 2015 10 (10) e0141047 INTRODUCTION: Episodes of acute adenolymphangitis (ADL) are often the first clinical sign of lymphatic filariasis (LF). They are often accompanied by swelling of the affected limb, inflammation, fever, and general malaise and lead to the progression of lymphedema. Although ADL episodes have been studied for a century or more, questions still remain as to their etiology. We quantified antibody levels to pathogens that potentially contribute to ADL episodes during and after an episode among lymphedema patients in Leogane, Haiti. We estimated the proportion of ADL episodes hypothesized to be attributed to specific pathogens. METHODS: We measured antibody levels to specific pathogens during and following an ADL episode among 41 lymphedema patients enrolled in a cohort study in Leogane, Haiti. We calculated the absolute and relative changes in antibody levels between the ADL and convalescent time points. We calculated the proportion of episodes that demonstrated a two-fold increase in antibody level for several bacterial, fungal, and filarial pathogens. RESULTS: Our results showed the greatest proportion of two-fold changes in antibody levels for the carbohydrate antigen Streptococcus group A, followed by IgG2 responses to a soluble filarial antigen (BpG2), Streptococcal Pyrogenic Exotoxin B, and an antigen for the fungal pathogen Candida. When comparing the median antibody level during the ADL episode to the median antibody level at the convalescent time point, only the antigens for Pseudomonas species (P-value = 0.0351) and Streptolysin O (P-value = 0.0074) showed a significant result. CONCLUSION: Although our results are limited by the lack of a control group and few antibody responses, they provide some evidence for infection with Streptococcus A as a potential contributing factor to ADL episodes. Our results add to the current evidence and illustrate the importance of determining the causal role of bacterial and fungal pathogens and immunological antifilarial response in ADL episodes. |
Unprogrammed deworming in the Kibera slum, Nairobi: implications for control of soil-transmitted helminthiases
Harris JR , Worrell CM , Davis SM , Odero K , Mogeni OD , Deming MS , Mohammed A , Montgomery JM , Njenga SM , Fox LM , Addiss DG . PLoS Negl Trop Dis 2015 9 (3) e0003590 BACKGROUND: Programs for control of soil-transmitted helminth (STH) infections are increasingly evaluating national mass drug administration (MDA) interventions. However, "unprogrammed deworming" (receipt of deworming drugs outside of nationally-run STH control programs) occurs frequently. Failure to account for these activities may compromise evaluations of MDA effectiveness. METHODS: We used a cross-sectional study design to evaluate STH infection and unprogrammed deworming among infants (aged 6-11 months), preschool-aged children (PSAC, aged 1-4 years), and school-aged children (SAC, aged 5-14 years) in Kibera, Kenya, an informal settlement not currently receiving nationally-run MDA for STH. STH infection was assessed by triplicate Kato-Katz. We asked heads of households with randomly-selected children about past-year receipt and source(s) of deworming drugs. Local non-governmental organizations (NGOs) and school staff participating in school-based deworming were interviewed to collect information on drug coverage. RESULTS: Of 679 children (18 infants, 184 PSAC, and 477 SAC) evaluated, 377 (55%) reported receiving at least one unprogrammed deworming treatment during the past year. PSAC primarily received treatments from chemists (48.3%) or healthcare centers (37.7%); SAC most commonly received treatments at school (55.0%). Four NGOs reported past-year deworming activities at 47 of >150 schools attended by children in our study area. Past-year deworming was negatively associated with any-STH infection (34.8% vs 45.4%, p = 0.005). SAC whose most recent deworming medication was sourced from a chemist were more often infected with Trichuris (38.0%) than those who received their most recent treatment from a health center (17.3%) or school (23.1%) (p = 0.05). CONCLUSION: Unprogrammed deworming was received by more than half of children in our study area, from multiple sources. Both individual-level treatment and unprogrammed preventive chemotherapy may serve an important public health function, particularly in the absence of programmed deworming; however, they may also lead to an overestimation of programmed MDA effectiveness. A standardized, validated tool is needed to assess unprogrammed deworming. |
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