bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Three Immunoglobulin M Antibody Capture Enzyme-linked Immunosorbent Assays for Diagnosis of Japanese Encephalitis
Authors: Jacobson Julie A. , Hills Susan L. , Winkler Jennifer L. , Mammen Mammen , Thaisomboonsuk Butsaya , Marfin Anthony A. , Gibbons Robert V.
Published: September 2018

Japanese encephalitis (JE) virus is a major cause of neurologic infection in Asia, but surveillance has been limited. Three JE immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay kits have recently been developed. The aim of this study was to evaluate their sensitivity, specificity, and usability using 360 acute-phase serum samples containing JE, dengue, or neither IgM antibody. The kits, manufactured by Panbio Limited, Inbios International, Inc., and XCyton Diagnostics Ltd, had high sensitivities of 89.3%, 99.2%, and 96.7%, respectively. The specificities were 99.2%, 56.1%, and 65.3%, respectively. When dengue IgM-positive samples were excluded, the kits had specificities of 98.4%, 96.1%, and 96.1%, respectively. The Panbio kit includes both JE and dengue antigens and appears to have an advantage in settings where dengue virus co-circulates, although further assessments in clinical settings are needed. This information is helpful in considering options for strengthening the laboratory component of JE surveillance.
Protection against Snake Bites by Sleeping under a Bed Net in Southeastern Nepal
Authors: Chappuis François , Sharma Sanjib K. , Jha Nilhambar , Loutan Louis , Bovier Patrick A.
Published: September 2018

Snake bites in persons while they are asleep indoors are associated with a high risk of fatal outcome in southeastern Nepal. The preventive impact of sleeping under a bed net was assessed in four villages in a case-control study. A case was defined as a person with a history of snake bite that occurred indoors while asleep. Cases were matched with controls by village, type of household, sex, and age category. Of the 11,176 households visited, 56 cases, including 13 (23%) with a fatal outcome and 56 controls were included in the analysis. Sleeping under a bed net was a strong protective factor (odds ratio = 0.02, 95% confidence interval = 0.007–0.07, P < 0.0001), whereas the place of sleeping in the household and the use of a cot were not associated with the risk of snake bite. These findings provide further support for use of bed nets in this region.
Microbially Derived Artemisinin: A Biotechnology Solution to the Global Problem of Access to Affordable Antimalarial Drugs
Authors: Hale Victoria , Keasling Jay D. , Renninger Neil , Diagana Thierry T.
Published: September 2018

Despite considerable efforts by multiple governmental and nongovernmental organizations to increase access to artemisinin-based combination therapies (ACTs), these life-saving antimalarial drugs remain largely unaffordable to the most vulnerable populations. The cost of artemisinin derivatives, ACTs’ crucial active ingredients, contributes significantly to the high price of these therapies. With a grant from the Bill and Melinda Gates Foundation, a partnership between Amyris Biotechnologies, the Institute for OneWorld Health, and the University of California, Berkeley is using synthetic biology to help reduce the cost of artemisinin. This article presents a description of the technological platform the partnership—called the Artemisinin Project—is developing to manufacture a low-cost, semi-synthetic artemisinin through a fermentation process. By making life-saving ACTs affordable to the people who most need them, the Artemisinin Project hopes to show that the power of biotechnology can be harnessed to provide solutions to global health problems.
Antibodies among Men and Children to Placental-Binding Plasmodium falciparum-Infected Erythrocytes that Express var2csa
Authors: Beeson James G. , Ndungu Francis , Persson Kristina E. M. , Chesson Joanne M. , Kelly Greg L. , Uyoga Sophie , Hallamore Sandra L. , Williams Thomas N. , Reeder John C. , Brown Graham V. , Marsh Kevin
Published: September 2018

During pregnancy, specific variants of Plasmodium falciparum-infected erythrocytes (IEs) can accumulate in the placenta through adhesion to chondroitin sulfate A (CSA) mediated by expression of PfEMP1 encoded by var2csa-type genes. Antibodies against these variants are associated with protection from maternal malaria. We evaluated antibodies among Kenyan, Papua New Guinean, and Malawian men and Kenyan children against two different CSA-binding P. falciparum isolates expressing var2csa variants. Specific IgG was present at significant levels among some men and children from each population, suggesting exposure to these variants is not exclusive to pregnancy. However, the level and prevalence of antibodies was substantially lower overall than exposed multigravidas. IgG-binding was specific and did not represent antibodies to subpopulations of non-CSA-binding IEs, and some sera inhibited IE adhesion to CSA. These findings have significant implications for understanding malaria pathogenesis and immunity and may be significant for understanding the acquisition of immunity to maternal malaria.
Molecular Epidemiology of Malaria in Cameroon. XXVI. Twelve-Year In Vitro and Molecular Surveillance of Pyrimethamine Resistance and Experimental Studies to Modulate Pyrimethamine Resistance
Authors: Tahar Rachida , Basco Leonardo K.
Published: September 2018

In vitro pyrimethamine response of Plasmodium falciparum isolates and dihydrofolate reductase (dhfr) gene sequences were analyzed in 2004–2005 and compared with our previous data. Most isolates (n = 103, all dhfr mutants) had 50% inhibitory concentrations (IC50s) ≥ 119 nM, and six isolates had low IC50s (five wild-type or mixed dhfr, 0.04–1.37 nM; one triple mutant, 6.4 nM). Of 194 isolates, only 7 had the wild-type dhfr and 187 were mutants. The results of the two methods were highly concordant and indicated a significant increase (P < 0.05) in the prevalence of mutant, pyrimethamine-resistant P. falciparum between 1994 and 2005. The addition of probenecid or sulfinpyrazone to pyrimethamine resulted in a slight-to-moderate decrease in the level of in vitro pyrimethamine resistance without rendering the parasites susceptible to pyrimethamine. Analysis of molecular markers may be useful for the long-term surveillance of antifolate-resistant malaria.
Effects of Anticoagulants on Plasmodium vivax Oocyst Development in Anopheles albimanus Mosquitoes
Authors: Solarte Yezid , del Rosario Manzano Maria , Rocha Leonardo , Castillo Zuleyma , James Mark A. , Herrera Sócrates , Arévalo-Herrera Myriam
Published: September 2018

Artificial membrane feeding (AMF) assays are used to determine malaria transmission-blocking activity in Anopheles. The purpose of this study was to determine the effect of the most widely used anticoagulants, EDTA and heparin, on development of the Plasmodium vivax sporogonic cycle. Blood samples collected from 60 patients carrying P. vivax infections were used to feed An. albimanus using AMF. Seven days after feeding, mosquitoes were dissected to assess mosquito infection. Mosquitoes fed with blood containing EDTA showed a lower mean oocyst number as compared with those fed blood with heparin. However, this effect was minimized upon reduction of EDTA concentrations in the serum. This result may be explained by the fact that microgametocytes require Ca2+, Mn2+, and Mg+2 to activate enzymes important for exflagellation process and for motility of ookinetes. We therefore recommend that heparin be used as the anticoagulant of choice for blood used in AMF assays.
Treatment of Mucosal Leishmaniasis in Latin America: Systematic Review
Authors: Amato Valdir Sabbaga , Tuon Felipe Francisco , Siqueira Andre Machado , Nicodemo Antonio Carlos , Neto Vicente Amato
Published: September 2018

Mucosal leishmaniasis (ML) is an important endemic disease and public-health problem in underdeveloped countries because of its significant morbidity and mortality. Increases in ecological tourism have extended this problem to developed countries. This form of leishmaniasis, caused by reactivation after primary cutaneous lesion, has a natural history of progressive destruction of the nasal septa and soft and hard palates, causing facial disfiguration and leading to respiratory disturbances. Treatment of ML, based on several therapies, depends on use of toxic compounds, and few drugs have emerged over the past 40 years. Drug resistance has increased, and the cure rate is no better than 70% in the largest studies. Despite these data, there has been no systematic review of therapies used to treat this important tropical disease. The aim of this study is to determine the best drug management for treatment of ML in Latin America based on the best studies offered by the medical literature. The MEDLINE, LILACS, EMBASE, Web of Science, and Cochrane Library databases were searched to identify articles related to ML and therapy. The studies were independently selected by 2 authors. Articles with sufficient data for cure and treatment failures, internal and external validity information, and > 4 patients in each treatment were included. Validation of this systematic review was based on guidelines to guarantee quality; 22 articles met our inclusion criteria. Stibogluconate achieved a 51% cure rate (76/150 patients), and 88% of patients treated with meglumine were cured (121 patients). Pentamidine and amphotericin were as effective as meglumine. Use of itraconazole and other therapies (pentoxifylline, allopurinol, or interferon-γ) was controversial, and numbers of patients in some studies were insufficient for statistical analysis. Meglumine may be the drug of choice in the treatment of ML, as it offers similar cure rates when compared with amphotericin B and pentamidine. Cost, adverse effects, local experience, and availability of drugs to treat ML are strong points to be considered before determining the best management of this disease, especially in developing countries.
Kala-Azar Outbreak in Libo Kemkem, Ethiopia: Epidemiologic and Parasitologic Assessment
Authors: Alvar Jorge , Bashaye Seife , Argaw Daniel , Cruz Israel , Aparicio Pilar , Kassa Askal , Orfanos Giannos , Parreño Fernando , Babaniyi Olusegan , Gudeta Nigussu , Cañavate Carmen , Bern Caryn
Published: September 2018

In May 2005, visceral leishmaniasis (VL) was recognized for the first time in Libo Kemkem, Ethiopia. In October 2005, a rapid assessment was conducted using data from 492 patients with VL treated in the district health center and a household survey of 584 residents of four villages. One subdistrict accounted for 71% of early cases, but the incidence and number of affected subdistricts increased progressively throughout 2004–2005. In household-based data, we identified 9 treated VL cases, 12 current untreated cases, and 19 deaths attributable to VL (cumulative incidence, 7%). Thirty percent of participants were leishmanin skin test positive (men, 34%; women, 26%; P = 0.06). VL was more common in men than women (9.7% versus 4.5%, P < 0.05), possibly reflecting male outdoor sleeping habits. Molecular typing in splenic aspirates showed L. infantum (six) and L. donovani (one). Local transmission resulted from multiple introductions, is now well established, and will be difficult to eradicate.
Multilateral Initiative on Malaria: Justification, Evolution, Achievements, Challenges, Opportunities, and Future Plans
Authors: Rugemalila Joas B. , Ogundahunsi Olumide A. T. , Stedman Timothy T. , Kilama Wen L.
Published: September 2018

Malaria is a major public health problem; about half of the world’s populations live under exposure. The problem is increasing in magnitude and complexity because it is entwined with low socio-economic status, which makes African women and children particularly vulnerable. Combating malaria therefore requires concerted international efforts with an emphasis on Africa. The Multilateral Initiative on Malaria (MIM) was founded in 1997 to meet that need through strengthening research capacity in Africa, increasing international cooperation and communication, and utilization of research findings to inform malaria prevention, treatment, and control. The review undertaken in 2002 showed that through improved communication and science-focused institutional networks, MIM had brought African scientists together, opened up communication among malaria stakeholders, and provided Internet access to literature. The achievements were made through four autonomous constituents including the coordinating Secretariat being hosted for the first time in Africa by the African Malaria Network Trust (AMANET) for the period 2006–2010. The other constituents are the MIM TDR providing funding for peer-reviewed research; MIMCom facilitating Internet connectivity, access to medical literature, and communication between scientists inside and outside of Africa; and MR4 providing scientists access to research tools, standardized reagents, and protocols. Future plans will mostly consolidate the gains made under the MIM Strategic Plan for the period 2003–2005.
Clinico-Pathological Observations on the Pathogenesis of Severe Thrombocytopenia and Anemia Induced by Plasmodium vivax Infections During Antimalarial Drug Efficacy Trials in Aotus Monkeys
Authors: Obaldía Nicanor
Published: September 2018

During routine antimalarial drug efficacy trials, we observed, for the first time, severe thrombocytopenia developing in Aotus monkeys infected with Plasmodium vivax. Data obtained from 26 Aotus infected with the AMRU-1 strain showed that 77% developed severe thrombocytopenia, whereas only 15% had severe anemia, with hemorrhagic diathesis ensuing in 31%. In general, thrombocytopenic monkeys either failed primary treatment with experimental antimalarial drugs or were found to have higher-density parasitemias, longer patency duration, and lower hematocrits. In these monkeys, severe thrombocytopenia inversely correlated to parasitemia (R = −1.0), and animals that received a blood transfusion had significantly higher platelet counts (P < 0.05) by day 38 after inoculation. In conclusion, the AMRU-1 strain of P. vivax, was considered to be highly pathogenic to Aotus monkeys, and thrombocytopenia rather than anemia should be regarded an early indicator of drug treatment failure with this strain.
Spatial and Temporal Genetic Structure of Anopheles arabiensis in Southern Zambia over Consecutive Wet and Drought Years
Authors: Kent Rebekah J. , Mharakurwa Sungano , Norris Douglas E.
Published: September 2018

No studies have addressed the spatial complexity of Anopheles arabiensis populations in Zambia or the effects of drought on the genetic structure of this species. We genotyped approximately 420 An. arabiensis at 12 microsatellite loci representing 18 collections from the Southern Province of Zambia. Collections spanned three transmission seasons and covered a wet year–drought year–wet year cycle. Anopheles arabiensis within the 2,000 km2 of the Macha study region were panmictic, with high gene flow between Macha and Namwala, Zambia, which are 80 km apart. There was little evidence for genetic structuring among years, with no significant shifts in allele frequency distributions or observed heterozygosity, and no evidence for a genetic bottleneck despite a drastic reduction in mosquito numbers during the drought year. Anopheles arabiensis in southern Zambia has a large deme size, and the regional genetic structure of this species was little affected by an extended drought period.
Building to Collective Impact: The Global Fund Support for Measuring Reduction in the Burden of Malaria
Authors: Nahlen Bernard L. , Low-Beer Daniel
Published: September 2018

The Global Fund to Fight AIDS, Tuberculosis, and Malaria was established in 2002 to fund substantial scaling-up coverage of proven and effective interventions to reduce infection, illness, and deaths in those communities most at risk. As of December 2006 the Global Fund has committed $2.6 billion over 5 years to support malaria prevention and control in 85 countries. The Global Fund has worked closely with Roll Back Malaria partners to develop consensus on a set of outcome and impact indicators that have been incorporated into malaria grant agreements. Although the Global Fund has recommended that 5–10% of grant funds be invested in improving the capacity of the national monitoring and evaluation systems, an average of only 3.9% is invested in these systems. Several countries are already demonstrating reductions in the malaria burden. To sustain the scale-up in funding to support malaria interventions, countries must ensure that resources are used now to show robust, systematic, and regular measurement of impact on the burden of malaria.
A Newly Emergent Genotype of West Nile Virus Is Transmitted Earlier and More Efficiently by Culex Mosquitoes
Authors: Moudy Robin M. , Meola Mark A. , Morin Laura-Lee L. , Ebel Gregory D. , Kramer Laura D.
Published: September 2018

Studies examining the evolution of West Nile virus since its introduction into North America have identified the emergence of a new dominant genotype (WN02) that has displaced the introduced genotype (NY99). The mechanistic basis for this displacement, however, remains obscure. Although we found no detectable difference in vitro between the genotypes in either replication or fitness, there were significant differences in vivo in Culex mosquitoes. After peroral infection, the extrinsic incubation period (EIP) of the WN02 genotype was up to 4 days shorter than the EIP of the NY99 genotype; however, after intrathoracic inoculation, there was no difference in EIP between the genotypes, suggesting that differences in genotype interaction with the mosquito midgut are likely to play a role in this phenotype. These results suggest a model for the displacement of the NY99 genotype, where earlier transmission of WN02 viruses leads to higher WN02 infection rates in avian reservoir hosts.
Detection of Rickettsia africae in Rhipicephalus (Boophilus) decoloratus Ticks from the Republic of Botswana, South Africa
Authors: Portillo Aránzazu , Pérez-Martínez Laura , Santibáñez Sonia , Blanco José R. , Ibarra Valvanera , Oteo José A.
Published: September 2018

A total of 53 engorged adult ticks belonging to the species Rhipicephalus (Boophilus) decoloratus (N = 9), Rhipicephalus evertsi evertsi (N = 27), Rhipicephalus appendiculatus (N = 9), Amblyomma hebraeum (N = 5), and Hyalomma marginatum turanicum (N = 3), were removed from oryx in Botswana (South Africa). They were tested for the presence of spotted fever group (SFG) Rickettsia and Anaplasma phagocytophilum using polymerase chain reaction (PCR). Seventy-seven percent of R. decoloratus as well as twenty percent of A. hebraeum were positive for ompA, gltA and 16S rRNA SFG Rickettsia PCR assays. All nucleotide sequences were homologous to Rickettsia africae, the agent of African tick-bite fever (ATBF). None of the tested ticks was positive for 16S rRNA A. phagocytophilum PCR assays. These results suggest for the first time that R. decoloratus ticks may be reservoirs of R. africae, and support the ATBF risk in this area.
Prevalence of Antibodies Against Spotted Fever Group Rickettsiae in a Rural Area of Colombia
Authors: Hidalgo Marylin , Sánchez Ricardo , Orejuela Leonora , Hernández Jorge , Walker David H. , Valbuena Gustavo
Published: September 2018

We recently rediscovered Rocky Mountain spotted fever in Villeta, Colombia, near the same locality (Tobia) where it was first recognized in 1937. To have a better idea of the magnitude of this problem, sera from 392 randomly recruited healthy adults from Villeta were analyzed by indirect immunofluorescent antibody assay to detect IgG against Rickettsia rickettsii as antigen. The seropositivity rate for spotted fever group rickettsiae was 40.3%. We did not find any association between the presence of antibodies to spotted fever group rickettsiae and several demographic and epidemiologic variables, which could be a reflection of unique features of this area.
Malaria in Pregnancy Before and After the Implementation of a National IPTp Program in Gabon
Authors: Ramharter Michael , Schuster Katharina , Bouyou-Akotet Marielle K. , Adegnika Ayola A. , Schmits Kristen , Mombo-Ngoma Ghyslain , Agnandji Selidji T. , Nemeth Johannes , Afène Solange Nzenze , Issifou Saadou , Onnas Isabelle Ndombi , Kombila Maryvonne , Kremsner Peter G.
Published: September 2018

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine–pyrimethamine has recently been adopted by many African countries to reduce maternal and neonatal morbidity and mortality associated with malaria in pregnancy. We assessed the impact of a newly established national IPTp program on maternal and neonatal health in Gabon. Data on prevalence of maternal Plasmodium falciparum infection, anemia, premature birth, and birth weight were collected in cross-sectional surveys in urban and rural regions of Gabon before and after the implementation of IPTp in a total of 1403 women and their offspring. After introduction of IPTp, the prevalence of maternal Plasmodium falciparum infection decreased dramatically (risk ratio 0.16, P < 0.001). Whereas only a modest effect on the rate of anemia in pregnant women was observed, there was a marked benefit on the prevalence of low birth weight and premature birth for women adhering to national recommendations. These effects were most pronounced in primi- and secundigravid women.
Electrocardiographic Safety Evaluation of Dihydroartemisinin–Piperaquine in the Treatment of Uncomplicated falciparum Malaria
Authors: Mytton Oliver T. , Ashley Elizabeth A. , Peto Leon , Price Ric N. , La Yar , Hae Rae , Singhasivanon Pratap , White Nicholas J. , Nosten François
Published: September 2018

Dihydroartemisinin–piperaquine (DP) could become a leading fixed combination malaria treatment worldwide. Although there is accumulating evidence of efficacy and safety from clinical trials, data on cardiotoxicity are limited. In two randomized controlled trials in Thailand, 56 patients had ECGs performed before treatment, 4 hours after the first dose, and 4 hours after the last dose. The mean (95% CI) changes in QTc interval (Bazett’s correction) were 2 (−6 to 9) ms and 14 (7 to 21) ms, respectively. These small changes on the third day of treatment are similar to those observed elsewhere in the convalescent phase following antimalarial treatment with drugs known to have no cardiac effects and are therefore likely to result from recovery from acute malaria and not the treatment given. At therapeutic doses, DP does not have clinically significant effects on the electrocardiogram.
Development of a TaqMan®–Minor Groove Binding Protein Assay for the Detection and Quantification of Crimean-Congo Hemorrhagic Fever Virus
Authors: Garrison A. R. , Alakbarova S. , Kulesh D. A. , Shezmukhamedova D. , Khodjaev S. , Endy T. P. , Paragas J.
Published: September 2018

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus of the genus Nairovirus and the family Bunyaviridae. It is a negative-strand RNA virus comprised of small (S), medium (M), and large (L) genome segments. The S segment encodes for nucleocapsid protein, the M segment codes for envelope glycoproteins (Gn and Gc), and the L segment codes for the RNA-dependent RNA polymerase. Currently, there are a limited number of methods for rapidly diagnosing CCHFV infections. We developed a real-time, reverse transcription–polymerase chain reaction assay for the rapid detection of CCHFV by using the TaqMan®–minor groove binding protein probe technology. The primers and probes were designed to amplify and detect a region in the S segment of CCHFV that is conserved across multiple strains. The limit of detection of the assay was 10 genome copies of RNA. This primer and probe set was specific to 18 strains of CCHFV tested and did not cross-react with either a DNA panel of 78 organisms or a panel of 28 diverse RNA viruses. This will rapidly and specifically detect CCHFV, and it has been used to detect CCHFV infection in samples from humans, animals, and ticks.
Validation of a Diagnostic Algorithm for Adult Tuberculous Meningitis
Authors: Török M. Estee , Nghia Ho Dang Trung , Chau Tran Thi Hong , Mai Nguyen Thi Hoang , Thwaites Guy E. , Stepniewska Kasia , Farrar Jeremy J.
Published: September 2018

Tuberculous meningitis (TBM) remains difficult to diagnose. We prospectively evaluated a diagnostic algorithm for TBM in 205 HIV-negative patients with meningitis and a low CSF glucose. Patients were classified as having TBM or bacterial meningitis (BM) by two diagnostic methods: logistic regression method (LRM) and classification and regression tree (CART). We performed analyses of TBM versus BM and TBM versus non-TBM in all patients and in patients with microbiologically confirmed diagnoses. Diagnostic sensitivities for TBM were 99% (LRM) and 87% (CART). For BM, diagnostic sensitivities were 81.5% (LRM) and 86.5% (CART) in the primary analysis and 86.5% (LRM) and 74% (CART) in the secondary analysis. In microbiologically confirmed cases, similar rates were achieved. These figures are superior to microbiological confirmation rates in routine laboratories and support the use of this algorithm in high-prevalence TB settings with limited diagnostic facilities. Validation in an HIV-endemic setting is required.
Wilson Disease with Visceral Leishmaniasis: An Extremely Uncommon Presentation
Authors: Pandey K. , Sinha P. K. , Das V. N. R. , Kumar N. , Verma N. , Bimal S. , Lal C. S. , Topno R. K. , Singh D. , Verma R. B. , Bhattacharya S. K. , Das P.
Published: September 2018

Visceral leishmaniasis (VL), which is caused by the protozoa Leishmania donovani and transmitted by the bite of the female sand fly Phlebotomus argentipes, is common in Bihar, India. Wilson disease is an autosomal recessive disorder of copper metabolism in which copper is deposited in the brain and liver. We report a case of an extremely uncommon combination of these diseases in a patient. Treatment options for such a combination of diseases are limited and difficult.
Quantitative Analysis of Proliferation and Excretion of Bartonella quintana in Body Lice, Pediculus humanus L.
Authors: Seki Naomi , Kasai Shinji , Saito Noriko , Komagata Osamu , Mihara Minoru , Sasaki Toshinori , Tomita Takashi , Sasaki Tsuguo , Kobayashi Mutsuo
Published: September 2018

Although body louse is a well-known vector of trench fever, the growth kinetics of Bartonella quintana in body lice has not been fully understood. We performed a quantitative analysis of bacterial multiplication rate. B. quintana started proliferation in body lice 4 days after ingestion and was constantly excreted in the feces for at least 3 weeks. The number of bacteria in feces reached the maximum 107/louse per day on Day 15. The doubling time of B. quintana estimated from logistic regression formula was 21.3 hours. Scanning electron microscopy showed the presence of bacterial masses in feces. Immunofluorescent study using specific monoclonal antibody confirmed identification of B. quintana. Such an explosive multiplication rate and active excretion of B. quintana from the body lice could be related to epidemics of trench fever in developed countries.
Etiology of Acute Diarrhea in Children and Adults in Tunis, Tunisia, with Emphasis on Diarrheagenic Escherichia coli: Prevalence, Phenotyping, and Molecular Epidemiology
Authors: Al-Gallas Nazek , Bahri Olfa , Bouratbeen Aida , Ben Haasen Assia , Ben Aissa Ridha
Published: September 2018

A total of 271 stool specimens were collected from children (diarrheagenic, n = 115 and control, n = 54) and adults (diarrheagenic, n = 73 and control, n = 29) from Tunis, Tunisia, and processed to detect bacterial enteropathogens, parasites, and viruses. Diarrheagenic Escherichia coli (DEC) were identified by their virulence genes (polymerase chain reaction) and adherence patterns (tissue culture assays). The most frequently isolated enteric pathogens from diarrheagenic children were enterotoxigenic E. coli (ETEC, 32.3%), enteroaggregative E. coli (EAEC, 11.3%), enteroinvasive E. coli (EIEC, (11.3%), adenovirus (10.4%), enterohemorrhagic E. coli (EHEC, 10.4%), and Salmonella spp. (9.5%). For children in the control group, ETEC (37%), EAEC (15%), EHEC (11.1%), and typical enteropathogenic E. coli (EPEC, 11.1%) were the most common enteric pathogens. In adults in the diarrheagenic group, Salmonella spp. (34.2%), ETEC (12.3%), adenovirus (7%), and Shigella spp. (4%) were the most common enteric pathogens. In adults in the control group, ETEC (31%) was the most common enteric pathogen. Multiple pathogens were recovered from 22% of the diarrheagenic children and 7% of the diarrheagenic adults. Escherichia coli strains showed high resistance rates to tetracycline, streptomycin, and β-lactams. The most frequent combinations were ETEC-rotavirus and ETEC-adenovirus. Pulsed-field gel electrophoresis for DEC indicated a large number of DEC clones (five major clones) persistent in the community reservoir for a considerable period of time that caused diarrhea in the population. This suggests the confluence of small epidemics by clonally related DEC strains circulating in this region.
Prevalence and Associated Factors of Betel Quid Use in the Solomon Islands: A Hyperendemic Area for Oral and Pharyngeal Cancer
Authors: Tovosia Silent , Chen Ping-Ho , Ko Allen Min-Jen , Tu Hung-Pin , Tsai Pei-Chien , Ko Ying-Chin
Published: September 2018

Chewing betel quid is a popular habit in tropical areas. It is also a known fact that oral cancer is one of the most common cancers in the Solomon Islands, where betel quid chewing is prevalent. This study explores the prevalence of betel quid chewing in the Solomon Islands and related sociodemographic factors. A community-based survey was designed for the entire Solomon Islands people. Information on sociodemographic characteristics, habits of betel quid chewing, smoking, and drinking was collected by trained interviewers with a standard questionnaire. The prevalence of betel quid chewers, smokers, and drinkers was 76.8%, 53.0%, and 36.8%, respectively. Betel quid use was closely associated with smoking (aOR = 3.95; 95% CI: 1.87–8.33). Seventh-Day Adventist subjects were less likely to chew betel quid (aOR = 0.08; 95% CI: 0.04–0.18). Efforts to reduce habitual betel quid consumption and smoking might be of benefit in reduction of oral cancer incidence.
Effects of Malaria Heme Products on Red Blood Cell Deformability
Authors: Nuchsongsin Forradee , Chotivanich Kesinee , Charunwatthana Prakaykaew , Fausta Omodeo-Salè , Taramelli Donatella , Day Nicholas P. , White Nicholas J. , Dondorp Arjen M.
Published: September 2018

In falciparum malaria, the deformability of the entire erythrocyte population is reduced in proportion to disease severity, and this compromises microcirculatory blood flow through vessels partially obstructed by cytoadherent parasitized erythrocytes. The cause of rigidity of uninfected erythrocytes in not known but could be mediated by malaria heme products. In this study, we show that red blood cell deformability (RBC-D), measured by laser-assisted optical rotational cell analyzer, decreased in a dose-dependent manner after incubation with hemin and hydrogen peroxide but not with hemoglobin or β-hematin. Hemin also reduced mean red cell volume. Albumin decreased and N-acetylcysteine (NAC) both prevented and reversed rigidity induced by hemin. Hemin-induced oxidative damage of the membrane seems to be a more important contributor to pathology than cell shrinkage because the antioxidant NAC restored RBC-D but not red blood cell volume. The findings suggest novel approaches to the treatment of potentially lethal malaria.
Malaria Treatment Efficacy among People Living with HIV: The Role of Host and Parasite Factors
Authors: Laufer Miriam K. , van Oosterhout Joep J. G. , Thesing Phillip C. , Dzinjalamala Fraction K. , Hsi Teresa , Beraho Lorraine , Graham Stephen M. , Taylor Terrie E. , Plowe Christopher V.
Published: September 2018

Identification of an effect of HIV-associated immunosuppression on response to antimalarial therapy would help guide management of malaria infection in areas of high HIV prevalence. Therefore, we conducted an observational study of people living with HIV infection in Blantyre, Malawi. Participants who developed malaria were treated with sulfadoxine–pyrimethamine (SP) and followed for 28 days. Molecular markers for SP resistance were measured. One hundred seventy-eight episodes of malaria were assessed. The 28-day cumulative treatment failure rate was 29.1%. In univariate analysis, CD4 cell count was not associated with treatment failure (hazard ratio 0.6, 95% confidence interval 0.3–1.2). Among children, the risk of treatment failure increased with infection with SP-resistant parasites and anemia. Decreased CD4 cell count was not associated with impaired response to antimalarial therapy or diminished ability to clear SP-resistant parasites, suggesting that acquired immunity to malaria is retained in the face of HIV-associated immunosuppression.
Trypanocidal and Leishmanicidal Activities of Flavonoids from Argentine Medicinal Plants
Authors: Sülsen Valeria P. , Cazorla Silvia I. , Frank Fernanda M. , Redko Flavia C. , Anesini Claudia A. , Coussio Jorge D. , Malchiodi Emilio L. , Martino Virginia S. , Muschietti Liliana V.
Published: September 2018

In vitro trypanocidal and leishmanicidal activities of the flavonoids hispidulin, from Ambrosia tenuifolia, and santin, from Eupatorium buniifolium, are reported. A sensitive technique that takes advantage of (3H)thymidine uptake by dividing trypanosomatids has been adjusted for quantification of the parasiticidal effect of the natural products. The IC50 values for hispidulin and santin on Trypanosoma cruzi epimastigotes were 46.7 and 47.4 μM, respectively. On trypomastigotes, the IC50 values were 62.3 μM for hispidulin and 42.1 μM for santin. Hispidulin was more active than santin on promastigotes of Leishmania mexicana (IC50 = 6.0 μM versus 32.5 μM). No cytotoxic activity was observed on lymphoid cells, making hispidulin and santin potential lead compounds for the development of new natural drugs. This is the first report on the trypanocidal and leishmanicidal activities of these flavonoids and on the presence of santin in E. buniifolium.
The Immune Response to Toxocariasis Does Not Modify Susceptibility to Mycobacterium tuberculosis Infection in BALB/c Mice
Authors: Frantz Fabiani Gai , Rosada Rogério Silva , Turato Walter Miguel , Peres Camila Matias , Coelho-Castelo Arlete Aparecida Martins , Ramos Simone Gusmão , Aronoff David Michael , Silva Célio Lopes , Faccioli Lúcia Helena
Published: September 2018

Mycobacterium tuberculosis and helminth infections coincide geographically and are classically described as TH1 and TH2 pathologies. There is much interest in exploring how concurrent worm infections might alter immune responses to mycobacterial infection. To explore this issue, mice were infected with Toxocara canis and co-infected with M. tuberculosis. Mice infected with M. tuberculosis had high numbers of neutrophils and mononuclear cells within the alveolar spaces, with increased parenchymal interferon (IFN)-γ levels. However, in Toxocara-infected mice we detected increased eosinophil numbers in bronchoalveolar lavage fluid (BALF) and increased parenchymal levels of interleukin (IL)-5. In co-infected mice the BALF demonstrated enhanced eosinophil influx with decreased neutrophil and mononuclear cell accumulation. However, co-infected mice had similar mycobacterial proliferation in their lungs accompanied by similar histopathological changes and similar cytokine/nitric oxide production compared with Mycobacterium-only–infected mice. Our results suggest that T. canis infection does not necessarily lead to increased susceptibility to pulmonary tuberculosis.
Catarina Virus, an Arenaviral Species Principally Associated with Neotoma micropus (Southern Plains Woodrat) in Texas
Authors: Cajimat Maria N. B. , Milazzo Mary Louise , Bradley Robert D. , Fulhorst Charles F.
Published: September 2018

The purpose of this study was to define the taxonomic relationship of an arenavirus principally associated with the southern plains woodrat (Neotoma micropus) in southern Texas to other New World arenaviruses. The results of independent analyses of glycoprotein precursor amino acid sequences and nucleocapsid protein amino acid sequences indicated that the arenavirus in southern Texas is novel (proposed species name Catarina virus) and phylogenetically most closely related to Whitewater Arroyo virus, which is principally associated with the white-throated woodrat (Neotoma albigula) in northwestern New Mexico. Together, the close phylogenetic relationship between Catarina virus and Whitewater Arroyo virus and the association of these viral species with congeneric rodent species support the notion that the principal host relationships of some New World arenaviruses are a product of a long-term shared evolutionary relationship between the virus family Arenaviridae and the rodent family Cricetidae.
Detection of Four Adenovirus Serotypes within Water-Isolated Strains of Acanthamoeba in the Canary Islands, Spain
Authors: Lorenzo-Morales Jacob , Coronado-Álvarez Nieves , Martínez-Carretero Enrique , Maciver Sutherland K. , Valladares Basilio
Published: September 2018

We surveyed 236 potentially pathogenic Acanthamoeba strains, isolated from water sources in the Canary Islands, for the presence of human adenoviruses (HAdV) using a polymerase chain reaction (PCR)-based typing assay. A total of 34 of these strains were found to be positive for adenovirus belonging to four different HAdV serotypes (HAdV-1, 2, 8, and 37). We found that HAdV-2 was the most frequently encountered serotype amongst the Acanthamoeba strains, and their identification was confirmed by a nested PCR specific for this serotype. We showed that Acanthamoeba genotype T4 was highly associated with serotype HAdV-2, whereas Acanthamoeba genotype T3 was most often associated with adenovirus serotypes related to ocular diseases. Based on these data, we suggest that Acanthamoeba should be considered as a potential reservoir and perhaps even a transmitter of adenoviruses to human and other secondary hosts.
Spatial Analysis of Risk Factors for Childhood Morbidity in Nigeria
Authors: Kandala Ngianga-Bakwin , Ji Chen , Stallard Nigel , Stranges Saverio , Cappuccio Francesco P.
Published: September 2018

Recent Demographic and Health Surveys (DHS) from Sub-Saharan Africa (SSA) indicate a decline in childhood vaccination coverage but a high prevalence of childhood diarrhea, cough, and fever. We used Nigerian DHS data to investigate the impact of geographical factors and other important risk factors on diarrhea, cough, and fever using geoadditive Bayesian semiparametric models. A higher prevalence of childhood diarrhea, cough, and fever is observed in the northern and eastern states, while lower disease prevalence is observed in the western and southern states. In addition, children from mothers with higher levels of education and those from poor households had a significantly lower association with diarrhea; children delivered in hospitals, living in urban areas, or from mothers having received prenatal visits had a significantly lower association with fever. Our maps are a novel and relevant tool to help local governments to improve health-care interventions and achieve Millennium Development Goals (MDG4).
Transmission Dynamics of Cryptosporidium Infection in a Natural Population of Non-Human Primates at Polonnaruwa, Sri Lanka
Authors: Ekanayake Dilrukshi K. , Welch David Mark , Kieft Rudo , Hajduk Stephen , Dittus Wolfgang P. J.
Published: September 2018

Infections from Cryptosporidium parvum are of interest not only to public health, but also to wildlife conservation, particularly when humans and livestock encroach on nature and thereby increase the risk of cross-species transmissions. To clarify this risk, we used polymerase chain reaction to examine the hypervariable region of the C. parvum 18S rRNA gene in feces from three monkey species. Samples were isolated from regions where disease transmission between monkeys, livestock, and humans was likely (soiled habitat) or unlikely (clean habitat). Monkey individuals, their social groups, and different species shared multiple genotypes/isolates of C. parvum. Ecological and molecular analyses suggested that Cryptosporidium infection among Toque macaques in soiled habitats was mainly the bovine genotype C. parvum. Monkeys inhabiting clean habitat, particularly gray and purple-faced langurs, lacked Cryptosporidium species/types associated with bovines. Livestock apparently was a main source of infection for wild primates.
Prevalence of Chronic Symptoms of Ciguatera Disease in French Polynesian Adults
Authors: Chateau-Degat Marie-Ludivine , Huin-Blondey Marie-Odile , Chinain Mireille , Darius Taiana , Legrand Anne-Marie , Nguyen Ngoc Lam , Laudon François , Chansin René , Dewailly Eric
Published: September 2018

Ciguatera is a tropical disease caused by seafood poisoning, for which the duration of symptoms remains to be determined. The objectives of this prospective study were to determine the prevalence of symptoms at different time points and to identify factors associated with chronic symptoms observed in adults suffering from this disease. At the time of onset, we observed a dose–response relationship including a strong association between the delay of appearance of symptoms and a severity index (P < 0.001). Our results confirmed the key role of fish organs in the risk of contracting a more severe form of ciguatera. In the chronic stage, only the severity score based on information recorded in the acute phase is related to the persistence of symptoms (P < 0.001). Our findings suggest that several symptoms observed in the acute phase of the disease are still experienced 15 days after onset. This supports previous observations based on isolated case reports.
Toad Poisoning in Laos
Authors: Keomany Sommay , Mayxay Mayfong , Souvannasing Phouthalavanh , Vilayhong Chanthala , Stuart Bryan L. , Srour Leila , Newton Paul N.
Published: September 2018

We describe two patients who developed severe illness after eating the skin and eggs of a toad, probably Bufo melanostictus Schneider, in southeastern Laos. One boy died, and one developed a digoxin toxicity–like syndrome with bradycardia and heart failure but survived. A telephone survey of 16 Lao provincial hospitals suggested that toad poisoning occurs in at least six provinces. That 93% of villagers in three villages in southeastern Laos were aware that toads are poisonous but that 51% had encountered patients with toad toxicity suggests that the potential gravity is not appreciated. These data indicate that toad poisoning may be underestimated and that education on the seriousness of toad toxins could be a useful public health measure.
No Depletion of Wolbachia from Onchocerca volvulus after a Short Course of Rifampin and/or Azithromycin
Authors: Richards Frank O. , Amann Josef , Arana Byron , Punkosdy George , Klein Robert , Blanco Carlos , Lopez Beatriz , Mendoza Carlos , Domínguez Alfredo , Guarner Jeannette , Maguire James H. , Eberhard Mark
Published: September 2018

Endosymbionic Wolbachia bacteria inside adult Onchocerca volvulus worms (causing river blindness) are necessary for female worm fertility. We evaluated whether rifampin and/or azithromycin used in a five-day course could kill Wolbachia. In an open-label trial in Guatemala, 73 patients with 134 palpable onchocercal nodules were randomized into four treatment groups: rifampin, azithromycin, a combination of the two drugs, and controls (multivitamins). After five days of antibiotic treatment, all participants received a single dose of ivermectin on day 6. Nine months after treatment, the nodules were removed and the worms were examined. Skin snips to determine microfilariae were obtained at baseline and nine months. There were no significant differences between any of the treatment groups in the condition of the worms in the nodules, the presence of Wolbachia surface protein, or the number of microfilariae in skin. Short courses with these antibiotics will not clear Wolbachia from O. volvulus.
Treatment of Kala-Azar in Southern Sudan using a 17-Day Regimen of Sodium Stibogluconate Combined with Paromomycin: A Retrospective Comparison with 30-Day Sodium Stibogluconate Monotherapy
Authors: Melaku Yosef , Collin Simon M. , Keus Kees , Gatluak Francis , Ritmeijer Koert , Davidson Robert N.
Published: September 2018

Médecins sans Frontières-Holland has treated > 67,000 patients with kala-azar (KA) in southern Sudan since 1989. In 2002, we replaced the standard regimen of 30 days of daily sodium stibogluconate (SSG) with a 17-day regimen of daily SSG combined with paromomycin (PM). We analyzed data for 4,263 primary KA patients treated between 2002 and 2005 in southern Sudan to determine the relative efficacy of the combination therapy regimen (PM/SSG). The initial cure rate among patients treated with PM/SSG was 97.0% compared with 92.4% among patients treated with SSG monotherapy. Relative efficacy of PM/SSG compared with SSG increased over the study period: odds of death in the PM/SSG group were 44% lower (odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.37–0.84) in 2002, 78% lower (OR = 0.22, 95% CI = 0.10–0.50) in 2003, and 86% lower (OR = 0.14, 95% CI = 0.07–0.27) in 2004–2005. In remote field settings, 17 days of SSG combined with PM gives better survival and initial cure rates than 30 days of SSG monotherapy.
Yellow Fever 17-D Vaccine Is Neurotropic and Produces Encephalitis in Immunosuppressed Hamsters
Authors: Mateo Rosa I. , Xiao Shu-Yuan , da Rosa Amelia P. A. Travassos , Lei Hao , Guzman Hilda , Lu Liang , Tesh Robert B.
Published: September 2018

Immunosuppressed (cyclophosphamide) adult golden hamsters inoculated intraperitoneally (IP) with wild-type Asibi yellow fever virus (YFV) developed a rapidly fatal illness. Histopathologic and immunohistochemical studies of tissues from these animals showed typical hepatic changes of severe yellow fever (inflammation, hepatocyte necrosis, and steatosis) without brain involvement. In contrast, 50% of immunosuppressed hamsters receiving the YFV-17D–attenuated vaccine developed a slowly progressive encephalitic-type illness. Brain tissue from these latter animals revealed focal neuronal changes, inflammation, and YFV antigen–positive neurons; however, the liver and spleen appeared normal. YFV was isolated from brain cultures of many of these animals. Immunocompetent (non-immunosuppressed) hamsters inoculated with both viruses developed a subclinical infection. Results of this study indicate that wild-type YFV is hepatotropic in immunosuppressed hamsters, whereas the attenuated YFV-17 is primarily neurotropic. These findings support current recommendations against yellow fever vaccination of immunosuppressed/ immunocompromised people and suggest that this hamster model might be useful for monitoring the safety of other live-attenuated YFV vaccines.
Loop-Mediated Isothermal PCR (LAMP) for the Diagnosis of Falciparum Malaria
Authors: Paris Daniel H. , Imwong Mallika , Faiz Abul M. , Hasan Mahtabuddin , Yunus Emran Bin , Silamut Kamolrat , Lee Sue J. , Day Nicholas P. J. , Dondorp Arjen M.
Published: September 2018

A recently described loop-mediated isothermal polymerase chain reaction (LAMP) for molecular detection of Plasmodium falciparum was compared with microscopy, PfHRP2-based rapid diagnostic test (RDT), and nested polymerase chain reaction (PCR) as the “gold standard” in 115 Bangladeshi in-patients with fever. DNA extraction for LAMP was conducted by conventional methods or simple heating of the sample; test results were either assessed visually or by gel electrophoresis. Conventional DNA extraction followed by gel electrophoresis had the highest agreement with the reference method (81.7%, κ = 0.64), with a sensitivity (95% CI) of 76.1% (68.3–83.9%), comparable to RDT and microscopy, but a specificity of 89.6% (84.0–95.2%) compared with 100% for RDT and microscopy. DNA extraction by heat treatment deteriorated specificity to unacceptable levels. LAMP enables molecular diagnosis of falciparum malaria in settings with limited technical resources but will need further optimization. The results are in contrast with a higher accuracy reported in an earlier study comparing LAMP with a non-validated PCR method.