bluuebunny/crossref_metadata_2025 huggingface dataset:
Flares in Rheumatoid Arthritis Patients with Low Disease Activity: Predictability and Association with Worse Clinical Outcomes
Authors: Bechman Katie , Tweehuysen Lieke , Garrood Toby , Scott David L. , Cope Andrew P. , Galloway James B. , Ma Margaret H.Y.
Published: September 2018

Objective.

To investigate predictors of flare in rheumatoid arthritis (RA) patients with low disease activity (LDA) and to evaluate the effect of flare on 12-month clinical outcomes.

Methods.

Patients with RA who were taking disease-modifying antirheumatic drugs and had a stable 28-joint count Disease Activity Score (DAS28) < 3.2 were eligible for inclusion. At baseline and every 3 months, clinical (DAS28), functional [Health Assessment Questionnaire–Disability Index (HAQ-DI), EQ-5D, Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-F), Medical Outcomes Study Short Form-36 (SF-36)], serum biomarkers [multibiomarker disease activity (MBDA) score, calprotectin, CXCL10], and imaging data were collected. Flare was defined as an increase in DAS28 compared with baseline of > 1.2, or > 0.6 if concurrent DAS28 ≥ 3.2. Cox regression analyses were used to identify baseline predictors of flare. Biomarkers were cross-sectionally correlated at time of flare. Linear regressions were performed to compare clinical outcomes after 1 year.

Results.

Of 152 patients, 46 (30%) experienced a flare. Functional disability at baseline was associated with flare: HAQ-DI had an unadjusted HR 1.82 (95% CI 1.20–2.72) and EQ-5D had HR 0.20 (95% CI 0.07–0.57). In multivariate analyses, only HAQ-DI remained a significant independent predictor of flare (HR 1.76, 95% CI 1.05–2.93). At time of flare, DAS28 and its components significantly correlated with MBDA and calprotectin, but correlation coefficients were low at 0.52 and 0.49, respectively. Two-thirds of flares were not associated with a rise in biomarkers. Patients who flared had significantly worse outcomes at 12 months (HAQ-DI, EQ-5D, FACIT-F, SF-36, and radiographic progression).

Conclusion.

Flares occur frequently in RA patients with LDA and are associated with worse disease activity, quality of life, and radiographic progression. Higher baseline HAQ-DI was modestly predictive of flare, while biomarker correlation at the time of flare suggests a noninflammatory component in a majority of events.
Canadian Rheumatology Association Recommendations for the Assessment and Monitoring of Systemic Lupus Erythematosus
Authors: Keeling Stephanie O. , Alabdurubalnabi Zainab , Avina-Zubieta Antonio , Barr Susan , Bergeron Louise , Bernatsky Sasha , Bourre-Tessier Josiane , Clarke Ann , Baril-Dionne Alexandra , Dutz Jan , Ensworth Stephanie , Fifi-Mah Aurore , Fortin Paul R. , Gladman Dafna D. , Haaland Derek , Hanly John G. , Hiraki Linda T. , Hussein Sara , Legault Kimberly , Levy Deborah , Lim Lily , Matsos Mark , McDonald Emily G. , Medina-Rosas Jorge , Pardo Pardi Jordi , Peschken Christine , Pineau Christian , Pope Janet , Rader Tamara , Reynolds Jen , Silverman Earl , Tselios Konstantinos , Suitner Manon , Urowitz Murray , Touma Zahi , Vinet Evelyne , Santesso Nancy
Published: September 2018

Objective.

To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada.

Methods.

Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online.

Results.

There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination.

Conclusion.

These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.
L’irrationnalité doxastique
Authors: Bandini Aude
Published: September 2018

Les articles ici réunis offrent une réflexion croisée sur différentes variétés de ce que l’on nomme l’irrationalité doxastique. En s’intéressant à des phénomènes tels que les biais cognitifs, la duperie de soi, le doute excessif ou encore l’aveuglement volontaire, qui constituent des processus d’acquisition, de rétention ou de révision de croyances défaillants, voire viciés, ces articles contribuent à éclairer notre compréhension de ce en quoi consistent les croyances irrationnelles, ce qui les motive, les explique, et les rend blâmables ou non.
L’évaluation de la duperie de soi : Butler, Clifford et la philosophie contemporaine
Authors: Meylan Anne
Published: September 2018

Une partie de la réflexion philosophique contemporaine s’est attachée, dans le monde anglophone, au problème de la duperie de soi ( self-deception ), lequel a connu un remarquable regain d’intérêt de la part des épistémologues au cours des vingt dernières années. Il s’agit de savoir pourquoi la duperie de soi paraît spontanément blâmable, quelque chose à éviter, et si ce jugement de valeur est toujours bien fondé, tant sur le plan épistémologique que sur le plan moral. S’engage alors une réflexion conceptuelle et normative, qui s’intéresse aux croyances en général, et aux croyances irrationnelles en particulier, dans leur rapport constitutif aux raisons et aux justifications.
Mastectomias em cadelas no Hospital Veterinário da Universidade Paranaense
Authors: Kaiser Correa Bruna Gabriela , Oliveira Dhiego Henrique de , Trentim Mayara Da Silva , Bastos Gabriela Lupepsa , Bessi Wellington Henrique , Rodrigues Nhirneyla Marques , Quessada Ana Maria
Published: September 2018

A incidência de tumores mamários em cadelas é alta no Brasil. Grande parte ocorre em cadelas idosas e o uso de progestágenos para prevenir o estro aumenta ainda mais o número de casos, devido a etiologia hormonal destes tumores. O tratamento de eleição é a mastectomia. O objetivo deste estudo foi registrar os tipos de mastectomias realizadas (uni ou bilaterais, acompanhadas ou não de ovariohisterectomia) em cadelas no Hospital Veterinário da Universidade Paranaense (campus de Umuarama), bem como dados epidemiológicos dos tumores de mama referentes à idade e raça durante o ano de 2015. Realizou-se 61 mastectomias no ano de 2015, sendo a maioria unilateral acompanhada de ovariohisterectomia (OH). Dados epidemiológicos foram obtidos de 31 cadelas sendo em maior número animais sem raça definida e com idade superior a seis anos. A maior parte dos tumores não eram ulcerados. Devido a quantidade de casos atendidos, concluiu-se que os tumores mamários em cadelas foram de alta incidência na região de Umuarama no ano de 2015, sendo de grande importância a realização de maiores pesquisas para identificação dos agentes causadores e prevenção de tais neoplasias, e principalmente programas de conscientização populacional sobre o uso de anticoncepcionais para evitar o estro, elucidando os problemas oriundos desta prática. Neste estudo, predominaram as mastectomias unilaterais, levando-se em conta o número, tamanho e presença de ulcerações dos tumores para escolha do lado a ser operado, e acompanhadas de OH.
DIAGNÓSTICO DERMATOPATOLÓGICO EM CÃES
Authors: Ramos Afonso Marcos Vinícius , Cardoso Jacyara Pereira , Barreto Silene Maria Prates
Published: September 2018

Na rotina da clínica médica veterinária, destaca-se a área dermatológica, sendo responsável pela maior parte da casuística, destacando-se o setor da dermatopatologia, sendo a pele é o maior órgão do organismo, revestindo toda a superfície externa do corpo.  Para a obtenção de diagnósticos mais precisos, foram utilizados exames específicos (teste de luz de Wood, teste com fita de acetato, teste com hidróxido de potássio, raspado de pele, coloração de Gram, tricograma e citologia). As dermatopatologias encontradas foram de origem bacteriana (23,08%), parasitária (23,08%), fúngicas (23,08%), de cunho imunológico (12,82%), de origem infecciosa (30,77%) e outras causas diversas (7,69%). Tais resultados possuem extrema relevância para a rotina da clínica médica de pequenos animais, uma vez que podem direcionar o atendimento pelo médico veterinário, proporcionando um tratamento com maior acurácia para as dermatopatologias.
PLACENTAL MONOCYTE INFILTRATES IN RESPONSE TO PLASMODIUM FALCIPARUM MALARIA INFECTION AND THEIR ASSOCIATION WITH ADVERSE PREGNANCY OUTCOMES
Authors: ROGERSON STEPHEN J. , POLLINA ELENA , GETACHEW ABERA , TADESSE EYOB , LEMA VALENTINO M. , MOLYNEUX MALCOLM E.
Published: September 2018

Maternal anemia and low birth weight (LBW) may complicate malaria in pregnancy, and placental monocyte infiltrates have been associated with LBW, and anecdotally with anemia. We examined placental pathology from 357 Malawian women. Intervillous monocyte infiltrates were frequent in placental malaria and were not seen in uninfected placentas. Histology was grouped according to a 5-point scale. Dense monocyte infiltrates and presence of intramonocytic malaria pigment were associated with anemia and LBW. Of factors associated with LBW and/or anemia in univariate analysis, gravidity (P = 0.002), number of antenatal clinic (ANC) visits (P < 0.001), malaria pigment in fibrin (P = 0.03), and monocyte malaria pigment (P = 0.0001) remained associated with lower birth weight by multivariate analysis. Associated with maternal anemia were HIV infection (P < 0.0001), intervillous monocyte numbers (P < 0.0001), number of ANC visits (P = 0.002), and recent febrile symptoms (P = 0.0001). Pigment-containing placental monocytes are associated with anemia and LBW due to malaria, and may have a causative role in their development.
IMPACT OF PERMETHRIN-TREATED BED NETS ON MALARIA AND ALL-CAUSE MORBIDITY IN YOUNG CHILDREN IN AN AREA OF INTENSE PERENNIAL MALARIA TRANSMISSION IN WESTERN KENYA: CROSS-SECTIONAL SURVEY
Authors: TER KUILE FEIKO O. , TERLOUW DIANNE J. , PHILLIPS-HOWARD PENELOPE A. , HAWLEY WILLIAM A. , FRIEDMAN JENNIFER F. , KOLCZAK MARGARETTE S. , KARIUKI SIMON K. , SHI YA PING , KWENA ARTHUR M. , VULULE JOHN M. , NAHLEN BERNARD L.
Published: September 2018

Information on the impact of insecticide (permethrin)-treated bed nets (ITNs) from randomized controlled trials in areas of intense perennial malaria transmission is limited. As part of a large-scale, community-based, group-randomized controlled trial of the effect of ITNs on childhood mortality in a holoendemic area in western Kenya, we conducted three cross-sectional surveys in 60 villages to assess the impact of ITNs on morbidity in 1,890 children less than three years old. Children in ITN and control villages were comparable pre-intervention, but after the introduction of ITNs, children in intervention villages were less likely to have recently experienced illness requiring treatment (protective efficacy [95% confidence intervals] = 15% [1–26%]), have an enlarged spleen (32% [20–43%]), be parasitemic (19% [11–27%]), have clinical malaria (44% [6–66%]), have moderately severe anemia (hemoglobin level < 7.0 g/dL; 39% [18–54%]), or have a pruritic body rash, presumably from reduced nuisance insect bites (38% [24–50%]). Use of ITNs was also associated with significantly higher mean weight-for-age Z-scores and mid-upper arm circumferences. There was no evidence, however, that ITNs reduced the risk of helminth infections, diarrhea, or upper or lower respiratory tract infections. The ITNs substantially reduced malaria-associated morbidity and improved weight gain in young children in this area of intense perennial malaria transmission.
PREVENTION OF THE TRANSMISSION OF CHAGAS’ DISEASE WITH PYRETHROID-IMPREGNATED MATERIALS
Authors: KROEGER AXEL , VILLEGAS ELCI , ORDOÑEZ-GONZÁLEZ JOSÉ , PABON EULIDES , SCORZA JOSÉ VICENTE
Published: September 2018

Interrupting the transmission of Chagas’ disease using insecticide-treated materials could be a cost-effective option, particularly for sylvatic vectors, which enter houses at night. A randomized trial was undertaken that included all houses in two communities in regions endemic for this disease, one in Venezuela (50 houses) and one in Colombia (47 houses). After a baseline study (including a short questionnaire survey, entomologic assessment, and Chagas’ disease serology), each household was randomly allocated to either the intervention group, which used pyre-throid-impregnated bed nets, or the control group, which used unimpregnated bed nets. Serologic analysis of children in the baseline study showed active transmission of Chagas’ disease in the Venezuelan community (10.7% of 103 children were positive), but none in the Colombian community (0% of 100 children were positive). Vectors were sylvatic and bugs entered the houses at night in both communities. The efficacy of pyrethroids against triatomine vectors was tested in Venezuela by exposing Rhodnius prolixus to lambdacyhalothrin-impregnated fabrics and in Colombia by residual house spraying with deltamethrin. This randomized trial showed that in both countries users of impregnated bed nets were well protected from vector bites (immediate benefit). The long-term effect on the community was high vector mortality. In Venezuela, all 62 vectors detected (mainly R. robustus) died within 72 hours of contact with impregnated bed nets. In houses that used unimpregnated nets, only 24.5% (13 of 53) of the vectors died (P < 0.001). The vectors most likely came from infested palm trees and they maintained transmission of the disease in this community (28.1% of 629 R. robustus were positive for Trypanosoma cruzi). Bioassays showed that the mortality rate of R. prolixus was 100% on lambdacyhalothrin-impregnated materials. In addition, in Colombia (the main vector was R. prolixus), the effect of repellent on vectors (driving them away from impregnated nets) was significant. Thus, users of impregnated bed nets are well protected from transmission of Chagas’ disease, and vector reduction or elimination can potentially be achieved in areas infested with R. prolixus and R. robustus.
FACTORS INFLUENCING THE DISTRIBUTION OF LARVAL BLACKLEGGED TICKS ON RODENT HOSTS
Authors: SHAW MARGARET T. , KEESING FELICIA , MCGRAIL ROBERT , OSTFELD RICHARD S.
Published: September 2018

Because of differences among hosts in reservoir competence for tick-borne diseases, the distribution of larval blacklegged ticks on hosts might determine tick infection prevalence and disease risk to humans. We conducted a three-part study to determine the factors responsible for greater burdens of larval blacklegged ticks on white-footed mice than on eastern chipmunks. A microhabitat study indicated that questing ticks have higher encounter rates with mice than with chipmunks. Laboratory experiments demonstrated that ticks oriented more strongly toward mice. However, larval ticks fed more successfully from chipmunks. Our results strongly suggest that mice are both more likely to use larval tick-infested microhabitats and to attract questing larvae than are chipmunks, leading to a dramatically higher initial infestation rate, which is then reduced by greater grooming activity by mice. The high mortality rate of larvae that were experimentally introduced onto mice suggests that grooming is a significant cause of mortality to larval blacklegged ticks.
CHRONIC CHAGAS’ DISEASE IN RHESUS MONKEYS (MACACA MULATTA): EVALUATION OF PARASITEMIA, SEROLOGY, ELECTROCARDIOGRAPHY, ECHOCARDIOGRAPHY, AND RADIOLOGY
Authors: CARVALHO CRISTIANO MARCELO ESPINOLA , ANDRADE MÁRCIA CRISTINA RIBEIRO , XAVIER SÉRGIO SALLES , MANGIA REGINA HELENA RICCIOPPO , BRITTO CONSTANÇA CARVALHO , JANSEN ANA MARIA , FERNANDES OCTAVIO , LANNES-VIEIRA JOSELI , BONECINI-ALMEIDA MARIA DA GLÓRIA
Published: September 2018

Severe chronic damage to the heart and gastrointestinal tract in patients with Chagas’ disease are often observed 10–20 years after the acute phase. The course of long-lasting infection with the Colombian strain of Trypanosoma cruzi was studied in seven rhesus monkeys infected for 15–19 years. Subpatent parasitemia was detected in all studied animals, using hemoculture (two of seven), artificial xenodiagnosis (three of seven), and a polymerase chain reaction PCR (six of six). High titers of specific IgG antibody to T. cruzi persisted throughout the chronic phase of infection. Abnormal electrocardiographic (three of six) and echocardiographic (one of six) patterns detected in the T. cruzi-infected monkeys were possibly related to parasite-triggered myocardial damage. The results suggest that rhesus monkeys experimentally infected with T. cruzi, besides reproducing the acute phase of Chagas’ disease, also develop chronic chagasic cardiomyopathy.
A RANDOMIZED CONTROLLED TRIAL OF HOUSEHOLD-BASED FLOCCULANT-DISINFECTANT DRINKING WATER TREATMENT FOR DIARRHEA PREVENTION IN RURAL GUATEMALA
Authors: RELLER MEGAN E. , MENDOZA CARLOS E. , LOPEZ M. BEATRIZ , ALVAREZ MARICRUZ , HOEKSTRA ROBERT M. , OLSON CHRISTY A. , BAIER KATHLEEN G. , KESWICK BRUCE H. , LUBY STEPHEN P.
Published: September 2018

We conducted a study to determine if use of a new flocculant-disinfectant home water treatment reduced diarrhea. We randomly assigned 492 rural Guatemalan households to five different water treatment groups: flocculant-disinfectant, flocculant-disinfectant plus a customized vessel, bleach, bleach plus a vessel, and control. During one year of observation, residents of control households had 4.31 episodes of diarrhea per 100 person-weeks, whereas the incidence of diarrhea was 24% lower among residents of households receiving flocculant-disinfectant, 29% lower among those receiving flocculant-disinfectant plus vessel, 25% lower among those receiving bleach, and 12% lower among households receiving bleach plus vessel. In unannounced evaluations of home drinking water, free chlorine was detected in samples from 27% of flocculant-disinfectant households, 35% of flocculant-disinfectant plus vessel households, 35% of bleach households, and 43% of bleach plus vessel households. In a setting where diarrhea was a leading cause of death, intermittent use of home water treatment with flocculant-disinfectant decreased the incidence of diarrhea.
CLINICAL DIAGNOSIS AND ASSESSMENT OF SEVERITY OF CONFIRMED DENGUE INFECTIONS IN VIETNAMESE CHILDREN: IS THE WORLD HEALTH ORGANIZATION CLASSIFICATION SYSTEM HELPFUL?
Authors: PHUONG CAO XUAN THANH , NHAN NGO THI , KNEEN RACHEL , THUY PHAM THI THU , VAN THIEN CHU , NGA NGUYEN THI THUY , THUY TRAN THANH , SOLOMON TOM , STEPNIEWSKA KASIA , WILLS BRIDGET , _ _
Published: September 2018

Classification of dengue using the current World Health Organization (WHO) system is not straightforward. In a large prospective study of pediatric dengue, no clinical or basic laboratory parameters clearly differentiated between children with and without dengue, although petechiae and hepatomegaly were independently associated with the diagnosis. Among the 712 dengue-infected children there was considerable overlap in the major clinical features. Mucosal bleeding was observed with equal frequency in those with dengue fever and dengue hemorrhagic fever (DHF), and petechiae, thrombocytopenia, and the tourniquet test differentiated poorly between the two diagnostic categories. Fifty-seven (18%) of 310 with shock did not fulfill all four criteria considered necessary for a diagnosis of DHF by the WHO, but use of the WHO provisional classification scheme resulted in considerable over-inflation of the DHF figures. If two separate entities truly exist rather than a continuous spectrum of disease, it is essential that some measure of capillary leak is included in any classification system, with less emphasis on bleeding and a specific platelet count.
PARALLEL ASSESSMENT OF 24 MONTHLY DOSES OF RIFAMPIN, OFLOXACIN, AND MINOCYCLINE VERSUS TWO YEARS OF WORLD HEALTH ORGANIZATION MULTI-DRUG THERAPY FOR MULTI-BACILLARY LEPROSY
Authors: VILLAHERMOSA LAARNI G. , FAJARDO TRANQUILINO T. , ABALOS RODOLFO M. , CELLONA ROLAND V. , BALAGON MARIA V. , DELA CRUZ EDUARDO C. , TAN ESTERLINA V. , WALSH GERALD P. , WALSH DOUGLAS S.
Published: September 2018

Monthly doses of rifampin, ofloxacin, and minocycline (ROM) are expected to be effective treatment for multi-bacillary leprosy. Patients with MB leprosy received ROM (n = 10) or World Health Organization multi-drug therapy (MDT) (n = 11). Treatment with ROM was given as 24 consecutive monthly observed doses of rifampin (600 mg), ofloxacin (400 mg), and minocycline (100 mg). Treatment with MDT was given as 24 consecutive monthly observed doses of rifampin (600 mg) and clofazimine (300 mg), and unobserved daily dapsone (100 mg) and clofazimine (50 mg). Twenty patients completed the 24-month regimens with > 99% compliance. Treatments with ROM and MDT were safe, tolerable, and caused similar improvements in lesions, bacterial indices, and histology. All MDT recipients developed clofazimine-induced pigmentation. Six ROM and nine MDT recipients assessed at five or more years after completion of treatment had no evidence of relapse. Twenty-four months of treatment with ROM is a safe, well-tolerated, and convenient regimen that may provide an alternate therapy to MDT for MB leprosy. Larger trials with sufficient follow-up would better define the role of ROM.
HUMAN CYSTIC ECHINOCOCCOSIS: EVALUATION OF POST-TREATMENT SEROLOGIC FOLLOW-UP BY IgG SUBCLASS ANTIBODY DETECTION
Authors: LAWN STEPHEN D. , BLIGH JOHN , CRAIG PHILIP S. , CHIODINI PETER L.
Published: September 2018

Assessment of post-treatment disease activity among patients with cystic echinococcosis (CE) is insensitive using detection of CE-specific total IgG antibody. This study investigated whether serum concentrations of CE-specific IgG subclasses 1–4 correlate better with disease activity than total IgG. We studied a cohort of patients (n = 28) with symptomatic CE treated with anthelminthic drugs and surgery and who were followed up clinically and radiologically for a mean of 5.6 years (range = 3–12 years). Serial archived sera collected during follow-up were retrospectively analyzed by enzyme-linked immunosorbent assays using crude horse hydatid cyst fluid as antigen. Changes in concentrations of antibodies were correlated with clinical and radiologic outcome. At diagnosis, concentrations of CE-specific total IgG, IgG1, and IgG2 antibodies were significantly elevated in a greater proportion of patients compared with IgG3 and IgG4 antibodies. During post-treatment follow up, the IgG2 antibody response provided the best correlate of disease activity.
DEVELOPMENT OF A QUANTITATIVE REAL-TIME POLYMERASE CHAIN REACTION ASSAY SPECIFIC FOR ORIENTIA TSUTSUGAMUSHI
Authors: JIANG JU , CHAN TEIK-CHYE , TEMENAK JOSEPH J. , DASCH GREGORY A. , CHING WEI-MEI , RICHARDS ALLEN L.
Published: September 2018

Two specific and sensitive polymerase chain reaction (PCR) assays were developed to detect and quantitate Orientia tsutsugamushi, the agent of scrub typhus, using a portion of the 47-kD outer membrane protein antigen/ high temperature requirement A gene as the target. A selected 47-kD protein gene primer pair amplified a 118-basepair fragment from all 26 strains of O. tsutsugamushi evaluated, but it did not produce amplicons when 17 Rickettsia and 18 less-related bacterial nucleic acid extracts were tested. Similar agent specificity for the real-time PCR assay, which used the same primers and a 31-basepair fluorescent probe, was demonstrated. This sensitive and quantitative assay determination of the content of O. tsutsugamushi nucleic acid used a plasmid containing the entire 47-kD gene from the Kato strain as a standard. Enumeration of the copies of O. tsutsugamushi DNA extracted from infected tissues from mice and monkeys following experimental infection with Orientia showed 27-5,552 copies/μL of mouse blood, 14,448-86,012 copies/μL of mouse liver/spleen homogenate, and 3-21 copies/μL of monkey blood.
EVIDENCE OF RICKETTSIAL AND LEPTOSPIRA INFECTIONS IN ANDEAN NORTHERN PERU
Authors: BLAIR PATRICK J. , SCHOELER GEORGE B. , MORON CECILIA , ANAYA ELIZABETH , CACEDA ROXANA , CESPEDES MANUEL , CRUZ CHRISTOPHER , FELICES VIDAL , GUEVARA CAROLINA , HUAMAN ALFREDO , LUCKETT RICKY , MENDOZA LEONARDO , RICHARDS ALLEN L. , RIOS ZONIA , SUMNER JOHN W. , VILLASECA PABLO , OLSON JAMES G.
Published: September 2018

Between May and October 2002, a cluster of acute febrile illnesses occurred in the subtropical Andean foothills of Peru. Serologic evidence in villages where disease had been documented showed that the prevalence of IgM antibody to Leptospira ranged from 6% to 52%, that of IgM antibody to spotted fever group (SFG) rickettsia ranged from 10% to 19%, and that of IgM antibody to Coxiella burnetii from 1% to 15%. Measurement of IgG antibodies for SFG rickettsiae suggested that this disease was endemic. In contrast, IgG antibodies against C. burnetii were largely absent. In humans, microagglutination tests identified pathogenic variants of Leptospira. The presence of an SFG rickettsial infection was confirmed in four febrile patients following polymerase chain reaction and sequencing of the conserved 17-kD common antigen gene (htrA). Collectively, these analyses indicated that Rickettsia sp., C. burnetii, and Leptospira sp. were circulating in the region during the time of disease outbreak and implicate the involvement of an as yet undetermined SFG rickettsia in northwestern Peru.
FATAL AUTOCHTHONOUS EOSINOPHILIC MENINGITIS IN A JAMAICAN CHILD CAUSED BY ANGIOSTRONGYLUS CANTONENSIS
Authors: LINDO J. F. , ESCOFFERY C. T. , REID B. , CODRINGTON G. , CUNNINGHAM-MYRIE C. , EBERHARD M. L.
Published: September 2018

A fatal case of infection with Angiostrongylus cantonensis is reported in a 14-month-old Jamaican boy. Although infection with Angiostrongylus was not considered initially, sections of multiple worms were observed in the brain and lungs at autopsy and confirmed the infection. This is the first reported fatality due to this infection in the Western Hemisphere, and follows shortly after an outbreak of eosinophilic meningitis among a group of travelers to Jamaica. The source of infection in this case could not be determined.
HISTOPLASMOSIS ASSOCIATED WITH EXPLORING A BAT-INHABITED CAVE IN COSTA RICA, 1998–1999
Authors: LYON GEORGE M. , BRAVO ANA V. , ESPINO ARACELLY , LINDSLEY MARK D. , GUTIERREZ ROSA E. , RODRIGUEZ ISABEL , CORELLA ANA , CARRILLO FLORA , MCNEIL MICHAEL M. , WARNOCK DAVID W. , HAJJEH RANA A.
Published: September 2018

Between October 1998 and April 1999, 51 persons belonging to two separate groups developed acute pulmonary histoplasmosis after visiting a cave in Costa Rica. The first group consisted of 61 children and 14 adults from San Jose, Costa Rica; 44 (72%) were diagnosed with acute histoplasmosis. The second group comprised 14 tourists from the United States and Canada; 9 (64%) were diagnosed with histoplasmosis. After a median incubation time of 14 days, the most common symptoms were headache, fever, cough, and myalgias. Risk factors for developing histoplasmosis included crawling (odds ratio [OR] = 17.5, 95% confidence interval [CI] = 2.3–802) and visiting one specific room (OR = 3.4, 95% CI = 1.0–12.3) in the cave. Washing hands (OR = 0.1, 95% CI = 0.01–0.6) after exiting the cave was associated with a decreased risk of developing histoplasmosis. Histoplasma capsulatum was isolated from bat guano collected from inside the cave. Persons who explore caves, whether for recreation or science, should be aware of the risk bat-inhabited caves pose for developing histoplasmosis, especially if they are immunocompromised in any way.
SAFETY AND IMMUNOGENICITY OF RTS,S+TRAP MALARIA VACCINE, FORMULATED IN THE AS02A ADJUVANT SYSTEM, IN INFANT RHESUS MONKEYS
Authors: WALSH DOUGLAS S. , PICHYANGKUL SATHIT , GETTAYACAMIN MONTIP , TONGTAWE PONGSRI , SIEGRIST CLAIRE-ANNE , HANSUKJARIYA PRANEE , KESTER KENT E. , HOLLAND CAROLYN A. , VOSS GERALD , COHEN JOE , STEWART ANN V. , MILLER R. SCOTT , BALLOU W. RIPLEY , HEPPNER D. GRAY
Published: September 2018

Malaria vaccine RTS,S combined with thrombospondin-related anonymous protein (TRAP) and formulated with AS02A (RTS,S+TRAP/AS02A) is safe and immunogenic in adult humans and rhesus monkeys (Macaca mulatta). Here, RTS,S+TRAP/AS02A was administered on a 0-, 1-, and 3-month schedule to three cohorts of infant monkeys, along with adult comparators. Cohort 1 evaluated 1/5, 1/2, and full adult doses, with the first dose administration at one month of age; cohort 2 monkeys received full adult doses, with the first dose administration at one versus three months of age; and, cohort 3 compared infants gestated in mothers with or without previous RTS,S/AS02A immunization. Immunization site reactogenicity was mild. Some infants, including the phosphate-buffered saline only recipient, developed transient iron-deficiency anemia, which is considered a result of repeated phlebotomies. All RTS,S+TRAP/AS02A regimens induced vigorous antibody responses that persisted through 12 weeks after the last vaccine dose. Modest lymphoproliferative and ELISPOT (interferon-γ and interleukin-5) responses, particularly to TRAP, approximated adult comparators. RTS,S+TRAP/AS02A was safe and well tolerated. Vigorous antibody production and modest, selective cell-mediated immune responses suggest that RTS,S+TRAP/AS02A may be immunogenic in human infants.
DETECTION OF LEISHMANIA INFANTUM KINETOPLAST DNA IN PERIPHERAL BLOOD FROM ASYMPTOMATIC INDIVIDUALS AT RISK FOR PARENTERALLY TRANSMITTED INFECTIONS: RELATIONSHIP BETWEEN POLYMERASE CHAIN REACTION RESULTS AND OTHER LEISHMANIA INFECTION MARKERS
Authors: MARTÍN-SÁNCHEZ JOAQUINA , PINEDA JUAN A. , MORILLAS-MÁRQUEZ FRANCISCO , GARCÍA-GARCÍA JOSÉ A. , ACEDO CARMEN , MACÍAS JUAN
Published: September 2018

Individuals with frequent exposures to agents spread through the parenteral route show a high prevalence of Leishmania seropositivity in Spain. However, the frequency of positive polymerase chain reaction (PCR) results for Leishmania in blood in this setting remains unknown. In this study, L. infantum kinetoplast DNA (kDNA) was found in blood from 23 (24%) of 95 asymptomatic individuals with a serum Leishmania antibody titer ≥ 1:20 and in none of 44 seronegative individuals. The greater the antibody titer, the greater the proportion of PCR-positive samples, but 16 (20%) of 81 individuals with antibody titers ≤ 1:40 tested positive by PCR. Nine (37%) PCR-positive and 22 (19%) (P = 0.03) PCR-negative individuals showed a positive leishmanin skin test result. This results show that a remarkable proportion of asymptomatic Leishmania-seropositive individuals at risk for parenterally transmitted infections carry Leishmania kDNA in blood. This is more common in subjects with a high serum Leishmania antibody level and a positive leishmanin skin test result.
C-REACTIVE PROTEIN IN THE DIAGNOSIS OF MELIOIDOSIS
Authors: CHENG ALLEN C. , O’BRIEN MATTHEW , JACUPS SUSAN P. , ANSTEY NICHOLAS M. , CURRIE BART J.
Published: September 2018

Previous work suggested that C-reactive protein (CRP) may be a useful test in the diagnosis of melioidosis, the infection caused by Burkholderia pseudomallei. We reviewed patients with culture-confirmed melioidosis to define the role of this inflammatory marker in the diagnosis of melioidosis. In 175 patients, we found that the admission CRP level may be normal or only mildly elevated, including patients with severe sepsis, fatal cases, and in relapsed melioidosis. In a multivariate analysis, sepsis and bacteremia were more strongly associated with mortality than CRP. Admission levels of CRP are not a sensitive marker for the presence of melioidosis and a normal level cannot be used to exclude acute, chronic, or relapsed melioidosis in febrile patients in or from endemic regions.
IMPORTED SPOTTED FEVER RICKETTSIOSES IN UNITED STATES TRAVELERS RETURNING FROM AFRICA: A SUMMARY OF CASES CONFIRMED BY LABORATORY TESTING AT THE CENTERS FOR DISEASE CONTROL AND PREVENTION, 1999–2002
Authors: MCQUISTON JENNIFER H. , PADDOCK CHRISTOPHER D. , SINGLETON JOSEPH , WHEELING JOHN T. , ZAKI SHERIF R. , CHILDS JAMES E.
Published: September 2018

The increasing popularity of foreign travel and ecotourism places travelers at increased risk for certain tick-borne diseases. From 1999 through 2002, 31 cases of imported spotted fever-group rickettsioses (SFGR) in United States residents reporting travel to Africa were confirmed by laboratory testing at the Centers for Disease Control and Prevention. Nineteen patients (61%) reported visiting South Africa prior to illness onset. Most patients reported fever and one or more eschars; rash was reported for only 26% of the patients. Twelve patients had an initial non-reactive acute-phase serum sample obtained a median of three days after illness onset, and were confirmed by testing a second convalescent-phase serum sample obtained a median of 32 days after illness onset. Five patients were confirmed positive through immunohistochemical staining of skin biopsies, including three patients with acute-phase serum samples that tested negative for SFGR. This study emphasizes the importance of evaluating convalescent-phase serum specimens 28 days or more after illness onset or examining skin biopsies by immunohistochemical staining during early infection to confirm a diagnosis of imported SFGR.
ANTIMALARIAL DRUG RESISTANCE, ARTEMISININ-BASED COMBINATION THERAPY, AND THE CONTRIBUTION OF MODELING TO ELUCIDATING POLICY CHOICES
Authors: YEUNG SHUNMAY , PONGTAVORNPINYO WIRICHADA , HASTINGS IAN M. , MILLS ANNE J. , WHITE NICHOLAS J.
Published: September 2018

Increasing resistance of Plasmodium falciparum malaria to antimalarial drugs is posing a major threat to the global effort to “Roll Back Malaria”. Chloroquine and sulfadoxine-pyrimethamine (SP) are being rendered increasingly ineffective, resulting in increasing morbidity, mortality, and economic and social costs. One strategy advocated for delaying the development of resistance to the remaining armory of effective drugs is the wide-scale deployment of artemisinin-based combination therapy. However, the cost of these combinations are higher than most of the currently used monotherapies and alternative non-artemisinin-based combinations. In addition, uncertainty about the actual impact in real-life settings has made them a controversial choice for first-line treatment. The difficulties in measuring the burden of drug resistance and predicting the impact of strategies aimed at its reduction are outlined, and a mathematical model is introduced that is being designed to address these issues and to clarify policy options.
THE SPATIAL-TEMPORAL DISTRIBUTION OF DROUGHT, WETTING, AND HUMAN CASES OF ST. LOUIS ENCEPHALITIS IN SOUTHCENTRAL FLORIDA
Authors: SHAMAN JEFFREY , DAY JONATHAN F. , STIEGLITZ MARC
Published: September 2018

Using a dynamic hydrology model, we simulated land surface wetness conditions at 42 sites in 28 counties in southcentral Florida from 1990 to 1998 and compared these simulations with the incidence of human cases of St. Louis encephalitis (SLE) within these counties. Within counties, drought four months prior and wetting one-half month prior were significantly associated with human cases of SLE. Simulated land surface wetness conditions resolved transmission loci in both space and time, and May drought was significantly associated with the subsequent occurrence of human SLE cases. These findings are consistent with previous results associating simulated land surface wetness conditions with the transmission of SLE virus as measured in sentinel chickens, and support our working hypothesis that springtime drought facilitates SLE virus amplification in mosquito and wild bird populations.
ENHANCING THE APPLICATION OF EFFECTIVE MALARIA INTERVENTIONS IN AFRICA THROUGH TRAINING
Authors: IJUMBA JASPER N. , KITUA ANDREW Y.
Published: September 2018

Africa bears more than 90% of the entire global malaria disease burden. Surprisingly, even with the current renewed interest in malaria prevention and control and the enabling environment resulting from the Roll Back Malaria initiative and the political commitment made by the African Presidents at the Abuja Summit, there are still no significant initiatives for strengthening capacity for malaria control through training within the African continent itself. The Center for Enhancement of Effective Malaria Interventions (CEEMI) has been established in Dar es Salaam, Tanzania for results-oriented training. It is intended to provide the needed skills for identifying and solving malaria control problems and providing incentives to malaria control workers in their work performance. The intention is to produce implementers with leadership skills for planning and managing malaria control activities and who can use strategic thinking in improving their work performance. To sustain political commitment and support and to sensitize the community on malaria issues, the CEEMI, in collaboration with the Ministry of Health (National Malaria Control Program), the Institute of Journalism and Mass Communication of the University of Dar es Salaam, and the Commonwealth Broadcasting Association have already conducted malaria seminars for Tanzanian Members of Parliament and journalists from Kenya, Malawi, Tanzania, and Uganda. Additionally, a diploma course in health communication is being developed for journalists and for the same purpose. Also being developed is a training module for “Council Malaria Focal Person.” This is aimed at complementing the Roll Back Malaria initiative to meet the Abuja targets of reducing morbidity and mortality due to malaria by 50% by 2010.
DESCRIBING THE BURDEN OF MALARIA ON CHILD DEVELOPMENT: WHAT SHOULD WE BE MEASURING AND HOW SHOULD WE BE MEASURING IT?
Authors: HOLDING PENNY A. , KITSAO-WEKULO PATRICIA K.
Published: September 2018

There are a number of pathways, both direct and indirect, through which malaria infection could impact the course of child development, causing impairment and disability and adding to the burden of malaria. We present an overview of relevant studies that illustrate these pathways, updating the evidence previously presented. We conclude that before the mechanisms and numbers of affected children can be adequately defined, a wider range of potential pathways to impaired development need to be investigated. Only then can the calculation of the burden be evidence-based, rather than merely speculative. Priorities for future research are described. The calculation of the impact of malaria on child development also requires a degree of uniformity in the definition of outcome across studies. This is currently lacking, and suggestions are made for a common approach to the reporting of results.
LARGE-SCALE CANDIDATE GENE STUDY OF TUBERCULOSIS SUSCEPTIBILITY IN THE KARONGA DISTRICT OF NORTHERN MALAWI
Authors: FITNESS JODENE , FLOYD SIAN , WARNDORFF DAVID K. , SICHALI LIFTED , MALEMA SIMON , CRAMPIN AMELIA C. , FINE PAUL E. M. , HILL ADRIAN V. S.
Published: September 2018

Twenty-seven polymorphisms from 12 genes have been investigated for association with tuberculosis (TB) in up to 514 cases and 913 controls from Karonga district, northern Malawi. Homozygosity for the complement receptor 1 (CR1) Q1022H polymorphism was associated with susceptibility to TB in this population (odds ratio [OR] = 3.12, 95% Confidence interval [CI] = 1.13–8.60, P = 0.028). This association was not observed among human immunodeficiency virus (HIV)–positive TB cases, suggesting either chance association or that HIV status may influence genetic associations with TB susceptibility. Heterozygosity for a newly studied CAAA insertion/deletion polymorphism in the 3′-untranslated region of solute carrier family 11, member 1 (SLC11A1, formerly NRAMP1) was associated with protection against TB in both HIV-positive (OR = 0.70, 95% CI = 0.49–0.99, P = 0.046) and HIV-negative (OR = 0.65, 95% CI = 0.46–0.92, P = 0.014) TB cases, suggesting that the SLC11A1 protein may have a role in innate TB immune responses that influence susceptibility even in immunocompromised individuals. However, associations of other variants of SCLA11A with TB reported from other populations were not replicated in Malawi. Furthermore, associations with vitamin D receptor, interferon-γ, and mannose-binding lectin observed elsewhere were not observed in this Karonga study. Genetic susceptibility to TB in Africans appears polygenic. The relevant genes and variants may vary significantly between populations, and may be affected by HIV infection status.
ASSESSING WATER-RELATED RISK FACTORS FOR BURULI ULCER: A CASE-CONTROL STUDY IN GHANA
Authors: AIGA HIROTSUGU , AMANO TAKAYUKI , CAIRNCROSS SANDY , DOMAKO JOSEPH A. , NANAS OFOSU-KWABI , COLEMAN SUSAN
Published: September 2018

To assess water-related risk factors of Buruli ulcer, a case-control study of 102 patients (51 cases and 51 controls) was undertaken by matching age group, sex, and bacille Calmette-Guérin (BCG) vaccination history in Ghana. The factors used here for matching have previously been implicated as factors of Buruli ulcer, an emerging infectious disease. This is the first study to delineate a set of previously suspected, water-related risk factors, in a case-control study matching for age group, sex, and BCG vaccination status. The results of both bivariate and multivariate analyses presented a significantly high odds ratio (OR) only for swimming in rivers on a habitual basis (OR = 18.00, P < 0.01) among the major water-related risk factors. Use of water from rivers and ponds for drinking, cooking, bathing, and washing purposes were not significant risk factors. Our data suggest that swimming, or activities on riverbanks associated with it, is a risk factor.
THE BURDEN OF CO-INFECTION WITH HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 AND MALARIA IN PREGNANT WOMEN IN SUB-SAHARAN AFRICA
Authors: TER KUILE FEIKO O. , PARISE MONICA E. , VERHOEFF FRANCINE H. , UDHAYAKUMAR VENKATACHALAM , NEWMAN ROBERT D. , VAN EIJK ANNE M. , ROGERSON STEPHEN J. , STEKETEE RICHARD W.
Published: September 2018

In sub-Saharan Africa, human immunodeficiency virus (HIV) and malaria are among the leading causes of morbidity during pregnancy. We reviewed available information collected since the first report 15 years ago that HIV impaired the ability of pregnant women to control malaria parasitemia. Results from 11 studies showed that HIV-infected women experienced consistently more peripheral and placental malaria (summary relative risk = 1.58 and 1.66, respectively), higher parasite densities, and more febrile illnesses, severe anemia, and adverse birth outcomes than HIV-uninfected women, particularly in multigravidae. Thus, HIV alters the typical gravidity-specific pattern of malaria risk by shifting the burden from primarily primigravidae and secundigravidae to all pregnant women. The proportional increase of malaria during pregnancy attributable to HIV was estimated to be 5.5% and 18.8% for populations with HIV prevalences of 10% and 40%, respectively. Maternal malaria was associated with a two-fold higher HIV-1 viral concentrations. Three studies investigating whether placental malaria increased mother-to-child HIV-1 transmission showed conflicting results, possibly reflecting a complex balance between placental malarial immune responses and stimulation of HIV-1 viral replication. Further investigations of interactions between antiretroviral drugs, prophylaxis with cotrimoxazole, and antimalarial drugs in pregnant women are urgently needed. Although much has been learned in the past 15 years about the interaction between malaria and HIV-1 during pregnancy, many issues still require further information to improve our understanding. There is a clear need to strengthen the deployment of existing malaria and HIV prevention and intervention measures for pregnant women.
CARBOXYHEMOGLOBIN LEVELS IN KENYAN CHILDREN WITH PLASMODIUM FALCIPARUM MALARIA
Authors: CUNNINGTON AUBREY J. , KENDRICK STUART F. W. , WAMOLA BETTY , LOWE BRETT , NEWTON CHARLES R. J. C.
Published: September 2018

Heme oxygenase (HO) is thought to be induced in severe malaria, but the pathophysiologic consequences have not been examined. It is induced by hemolysis, oxidative stress, and inflammation. It degrades heme, producing carbon monoxide (CO), which causes elevated levels of carboxyhemoglobin (COHb). In a prospective study of 1,520 children admitted to a Kenyan district hospital, COHb levels were no higher in children with malaria than with other infections. The COHb levels in children with severe malarial anemia were higher than in other children with malaria, but significantly lower than in children with other causes of severe anemia such as sickle cell disease. Levels of COHb were not significantly higher in children with cerebral malaria or in those dying of malaria. These results do not support a systemic increase in HO activity in malaria compared with other infectious diseases, but the roles of HO and CO in malaria require further study.
USE OF DISABILITY ADJUSTED LIFE YEARS IN THE ESTIMATION OF THE DISEASE BURDEN OF ECHINOCOCCOSIS FOR A HIGH ENDEMIC REGION OF THE TIBETAN PLATEAU
Authors: BUDKE CHRISTINE M. , JIAMIN QIU , ZINSSTAG JAKOB , QIAN WANG , TORGERSON PAUL R.
Published: September 2018

Shiqu County, located on the Tibetan plateau of western China, has an extremely high prevalence of both human alveolar echinococcosis (AE), and cystic echinococcosis (CE). The short form 12 version 2 quality of life survey, which was used to evaluate the extent to which morbidity associated with echinococcosis should be accounted, verified that there was a significant reduction in the mean health scores in all categories for individuals diagnosed with abdominal echinococcosis compared with an age and sex cross-matched population. Results of a larger ultrasound survey, which screened 3135 subjects, demonstrated that the prevalence rates of AE and CE were both approximately 6% with a combined prevalence rate of 11.4%. Prevalence rates adjusted for the age and sex structure of Shiqu County were 4.6% for AE and 4.9% for CE with an estimated overall adjusted prevalence rate of 9.5%. The burden of disease associated with echinococcosis was calculated using disability adjusted life years (DALYs) based on these estimated prevalence rates. Monte-Carlo techniques were used to model the uncertainty in the prevalence estimates and the disability weights. Using these methods, we estimated that the total numbers of DALYs lost due echinococcosis was 50,933 (95% confidence interval [CI] = 41,995–61,026). The DALYs lost consisted of approximately 32,978 (95% CI = 25,019–42,422) due to AE and 17,955 (95% CI = 14,268–22,128) due to CE and suggests an average of approximately 0.81 DALY lost per person. This study has clearly shown that the impact of DALYs lost due to echinococcosis, in terms of medical treatment costs, lost income, and physical and social suffering, is likely to be substantial in this highly endemic region of China.