bluuebunny/crossref_metadata_2025 huggingface dataset:
REDUCTION OF THE EFFICACY OF ANTIFOLATE ANTIMALARIAL THERAPY BY FOLIC ACID SUPPLEMENTATION
Authors: CARTER JANE Y. , LOOLPAPIT MORES P. , LEMA ORGENES E. , TOME JULIUS L. , NAGELKERKE NICO J. D. , WATKINS WILLIAM M.
Published: September 2018

Malaria and anemia are common conditions in patients presenting to outpatient clinics in Kenya. Anemia is usually due to malaria infection with underlying micronutrient deficiency. Iron therapy has been shown to enhance recovery from anemia in children with malaria, without affecting malaria treatment. Iron and folic acid are often prescribed together for anemic individuals. Until recently in Kenya, the drug of first choice for non-severe malaria was sulfadoxine-pyrimethamine (SP), an antifolate antimalarial drug. In this study, 303 patients of all ages with anemia and uncomplicated Plasmodium falciparum malaria attending an outpatient clinic in an area of seasonal malaria were treated with SP and iron, and were randomized to receive folic acid. Parasite clearance rates were measured using a survival analysis plot for both parasitologic and clinical failure. There was a significant reduction in the efficacy of SP in patients taking standard therapeutic doses of folic acid using the survival curve for parasitologic failure (P < 0.0001), but no difference for clinical failure (P = 0.7008). Folic acid supplementation did not enhance recovery from anemia.
RAPID AWARENESS AND TRANSMISSION OF SEVERE ACUTE RESPIRATORY SYNDROME IN HANOI FRENCH HOSPITAL, VIETNAM
Authors: NISHIURA HIROSHI , KURATSUJI TADATOSHI , QUY TRAN , PHI NGUYEN CHI , VAN BAN VO , HA LE DANG , LONG HOANG THUY , YANAI HIDEKI , KEICHO NAOTO , KIRIKAE TERUO , SASAZUKI TAKEHIKO , ANDERSON ROY M.
Published: September 2018

A case-control study was conducted to examine the relationship between severe acute respiratory syndrome (SARS) and the time-dependent precautionary behaviors taken during an outbreak of SARS in Hanoi French Hospital (HFH), Vietnam. Masks (odds ratio [OR] = 0.3; 95% confidence interval [CI]: 0.1, 0.7) and gowns (OR = 0.2; 95% CI: 0.0, 0.8) appeared to prevent SARS transmission. The proportion of doctors and nurses who undertook each measure significantly improved (χ2 = 9.8551, P = 0.043) after the onset of secondary cases. The impact of individual behaviors on an outbreak was investigated through mathematical approaches. The reproduction number decreased from 4.1 to 0.7 after notification. The basic reproduction number was estimated, and the use of masks alone was shown to be insufficient in containing an epidemic. Intuitive results obtained by means of stochastic individual-based simulations showed that rapid improvements in behavior and isolation would increase the probability of extinction.
USE OF RAINFALL AND SEA SURFACE TEMPERATURE MONITORING FOR MALARIA EARLY WARNING IN BOTSWANA
Authors: THOMSON MADELEINE C. , MASON SIMON J. , PHINDELA THANDIE , CONNOR STEPHEN J.
Published: September 2018

Improved prediction, prevention, and control of epidemics is a key technical element of the Roll Back Malaria partnership. We report a methodology for assessing the importance of climate as a driver of inter-annual variability in malaria in Botswana, and provide the evidence base for inclusion of climate information in a national malaria early warning system. The relationships of variability in rainfall and sea surface temperatures (SSTs) to malaria incidence are assessed at the national level after removing the impact of non-climatic trends and a major policy intervention. Variability in rainfall totals for the period December–February accounts for more than two-thirds of the inter-annual variability in standardized malaria incidence in Botswana (January–May). Both rainfall and annual malaria anomalies in December–February are significantly related to SSTs in the eastern Pacific, suggesting they may be predictable months in advance using seasonal climate forecasting methodologies.
DISTINGUISHING RECRUDESCENCES FROM NEW INFECTIONS IN ANTIMALARIAL CLINICAL TRIALS: MAJOR IMPACT OF INTERPRETATION OF GENOTYPING RESULTS ON ESTIMATES OF DRUG EFFICACY
Authors: SLATER MADELINE , KIGGUNDU MOSES , DOKOMAJILAR CHRIS , KAMYA MOSES R. , BAKYAITA NATHAN , TALISUNA AMBROSE , ROSENTHAL PHILIP J. , DORSEY GRANT
Published: September 2018

The use of molecular genotyping to distinguish recrudescence from new infections has become common in antimalarial clinical trials. However, methods used to interpret genotyping results have not been standardized. We analyzed data from 3,000 patients enrolled in clinical trials at seven sites in Uganda. Late treatment failure requiring genotyping occurred in 51% of the patients. Among samples successfully genotyped, 21% were definitive new infections (no recrudescent strains present on day of failure), 35% were definitive recrudescences (only recrudescent strains present), and 44% were mixed (new and recrudescent strains present). The probability of having a mixed genotyping result increased as transmission intensity increased. At the highest transmission site, the estimated risk of treatment failure increased from 34% to 84% for chloroquine plus sulfadoxine-pyrimethamine, from 18% to 45% for amodiaquine plus sulfadoxine-pyrimethamine, and from 12% to 57% for amodiaquine plus artesunate, depending on whether mixed genotyping results were classified as new infections or recrudescences, respectively. The method used to classify treatment outcomes can have a major impact on estimates of drug efficacy, especially in areas of high transmission intensity.
NO EVIDENCE OF CARDIOTOXICITY OF ATOVAQUONE-PROGUANIL ALONE OR IN COMBINATION WITH ARTESUNATE
Authors: GUPTA RAVINDRA K. , VAN VUGT MICHELE , PAIPHUN LUCY , SLIGHT THRA , LOOAREESUWAN SORNCHAI , WHITE NICHOLAS J. , NOSTEN FRANÇOIS
Published: September 2018

Combinations are set to become the mainstay in treatment and prophylaxis of malaria due to Plasmodium falciparum. Various antimalarials have been implicated in cardiotoxicity via prolongation of the QTc interval. Atovaquone-proguanil is an effective and increasingly popular antimalarial choice when used alone or with artesunate in areas of drug resistance. We report the results of an investigation carried out on the Thai-Burmese border in 42 patients randomized to receive either atovaquone-proguanil or atovaquone-proguanil-artesunate for three days. Electrocardiographic recordings were made at baseline and one hour after each dose. There was no statistically significant change in QTc interval between baseline and any subsequent readings in either treatment group or the cohort as a whole. We conclude that atovaquone-proguanil shows no evidence of cardiotoxicity either alone or when combined with artesunate.
EVALUATION OF METHODS TO ASSESS TRANSMISSION POTENTIAL OF VENEZUELAN EQUINE ENCEPHALITIS VIRUS BY MOSQUITOES AND ESTIMATION OF MOSQUITO SALIVA TITERS
Authors: SMITH DARCI R. , CARRARA ANNE-SOPHIE , AGUILAR PATRICIA V. , WEAVER SCOTT C.
Published: September 2018

Determining the dose of an arbovirus transmitted by a mosquito is important to design transmission and pathogenesis studies simulating natural infection. Several different artificial infection and transmission methods used to assess vector competence and to estimate the dose injected during mosquito feeding have not been fully evaluated to determine whether they accurately reflect natural transmission. Additionally, it is not known whether different mosquito vectors transmit similar amounts of a given virus. Therefore, we compared three traditional artificial transmission methods using Venezuelan equine encephalitis virus (VEEV) and Aedes albopictus and Ochlerotatus taeniorhynchus mosquitoes. Both the mosquito species and the infection route used affected the amount of virus detected in the saliva after a 10-day extrinsic incubation period. Median titers of virus detected in saliva of Ae. albopictus and Oc. taeniorhynchus mosquitoes ranged from 0.2 to 1.1 log10 (mean 0.7–1.4 log10) and 0.2 to 3.2 log10 (mean 1.0–3.6 log10) plaque-forming units, respectively. The results of this study will aid in the design of transmission and pathogenesis studies involving arboviruses.
HOSPITAL-BASED SURVEILLANCE FOR ACUTE FEBRILE ILLNESS IN EGYPT: A FOCUS ON COMMUNITY-ACQUIRED BLOODSTREAM INFECTIONS
Authors: AFIFI SALMA , EARHART KEN , AZAB MOHAMED A. , YOUSSEF FOUAD G. , SAKKA HAMMAM EL , WASFY MOMTAZ , MANSOUR HODA , OUN SAID EL , RAKHA MAGDA , MAHONEY FRANCIS
Published: September 2018

Acute febrile illness (AFI) is a common syndrome in Egypt. However its etiologies are not well characterized. To determine the relative frequency of pathogen etiologies and possibly improve diagnostic, clinical management and public health measures, we implemented laboratory-based surveillance in a network of infectious disease hospitals throughout Egypt. Admitted patients with AFI provided background details and a blood sample for bacterial culture and serologic analysis. Case definitions were based on laboratory results. Of 10,130 patients evaluated between 1999 and 2003, 5% were culture positive for Salmonella enterica serogroup Typhi, 3% for Brucella, and 2% for other pathogens. An additional 18% of patients had positive serologic results for typhoid and 11% for brucellosis. Risk factor analysis identified availability of municipal water to be significantly (P < 0.05) associated with protection against typhoid. Animal contact and consumption of raw dairy products were significantly associated with brucellosis. The surveillance network identified typhoid fever and brucellosis as the most common bacterial causes of AFI in Egypt, allowed better description of their epidemiology, and may lead to the development of targeted prevention strategies.
AGE-SPECIFIC SEROPREVALENCE OF HEPATITIS A AMONG SCHOOL CHILDREN IN CENTRAL TUNISIA
Authors: LETAIEF AMEL , KAABIA NAWFAL , GAHA RAFIKA , BOUSAADIA AMEL , LAZRAG FATMA , TRABELSI HALIM , GHANNEM HASSEN , JEMNI LETAIEF
Published: September 2018

Hepatitis A virus (HAV) has different epidemiologic and clinical patterns, depending on the level of endemicity in a given geographic area. Tunisia is considered a region of high endemicity for hepatitis. Improvement of socioeconomic conditions in this country has made a determination of the seroprevalence of this disease advisable. We assessed the seroprevalence of HAV in Sousse in central Tunisia. A total of 2,400 school children 5–20 years of age (mean ± SD age = 11.7 ± 3.5 years) were selected by two-stage cluster sampling and tested serologically for IgG antibody to HAV by using an enzyme-linked immunosorbent assay. The overall seroprevalence among this population was 60% (44%, in children < 10 years old, 58% in those 10–15 years of age, and 83% in those > 15 years of age. Seroprevalence also varied according to area of residence. At the age of 10, 21.3% of school children living in the urban areas and 87.7% of those living in rural areas had antibodies to HAV. Other factors that increased seroprevalence included non-potable water, crowding, and a low education level of parents with odds ratios of 4.37, 2.96, and 2.62, respectively. This study has shown an increase of seroprevalence with age, suggesting that transmission among younger children has decreased, particularly in urban areas. Programs to prevent hepatitis A may need to be modified based upon the changing age distribution of the disease and mass vaccination program could be indicated if additional incidence and prevalence data confirm the intermediate endemicity of HAV.
OUTBREAK OF SEVERE ACUTE RESPIRATORY SYNDROME IN SOUTHERN TAIWAN, 2003
Authors: LU SHENG-NAN , JIANG DONALD DAH-SHYONG , LIU JIEN-WEI , LIN MENG-CHIH , CHEN CHAO-LONG , SU IH-JEN , CHEN SHUN-SHENG
Published: September 2018

This study describes the epidemiologic features of the severe acute respiratory syndrome (SARS) outbreak in southern Taiwan in 2003. According to the official files of reported cases of SARS from February 21 to June 19, 2003, there were 586 cases in southern Taiwan. Symptom onset occurred between February 21 and June 19 in reported cases, between March 13 and May 30 in probable cases, and between March 17 and May 23 in polymerase chain reaction (PCR)–positive probable cases. Dates of symptom onset were earliest for six imported cases, followed by 53 cases related to nosocomial infections and 51 cases without known sources of infection. The positive rates of the PCR for these three groups decreased from 50.0% to 28.3% to 3.9% , respectively (P < 0.001, by chi-square test for linear trend). Three other cases resulted from exposure to contaminated hospitals in northern Taiwan, one of which was the index case of the nosocomial infection. Imported cases following nosocomial infection were the major cause of SARS infections in southern Taiwan. Due to the low positive rate of the PCR for SARS coronavirus, and the low positive predictive value of reported cases, the factuality of cases with unknown sources of infection should be further verified.
COMPARISON OF CLINICAL FEATURES AND HEMATOLOGIC ABNORMALITIES BETWEEN DENGUE FEVER AND DENGUE HEMORRHAGIC FEVER AMONG CHILDREN IN THE PHILIPPINES
Authors: CARLOS CELIA C. , OISHI KAZUNORI , CINCO MARIA T. D. D. , MAPUA CYNTHIA A. , INOUE SHINGO , CRUZ DEU JOHN M. , PANCHO MARY ANN M. , TANIG CAROL Z. , MATIAS RONALD R. , MORITA KOUICHI , NATIVIDAD FILIPINAS F. , IGARASHI AKIRA , NAGATAKE TSUYOSHI
Published: September 2018

To demonstrate the differences of clinical features and hematologic abnormalities between dengue fever (DF) and dengue hemorrhagic fever (DHF), 359 pediatric patients admitted St. Luke’s Medical Center in Quezon City, between 1999 and 2001 in Metro Manila, and adjoining provinces the Philippines, with a laboratory-confirmed dengue virus infection were evaluated. One third of the patients had DHF, and most of these patients were without shock. Restlessness, epistaxis, and abdominal pain were more associated with DHF. The platelet count was significantly lower in the DHF group than in the DF group before and after defervescence. In the DHF patients, the hematocrit was significantly increased before defervescence, and decreased the day after due to administration of intravenous fluid. Coagulation abnormalities associated with most DHF patients were thrombocytopenia and an increased fibrinolysis, but not disseminated intravascular coagulation. We present recent data on readily obtained clinical and laboratory data that can be used for early diagnosis and consequently earlier appropriate treatment of dengue virus infections.
DETECTION OF PLASMODIUM FALCIPARUM IN PREGNANCY BY LASER DESORPTION MASS SPECTROMETRY
Authors: NYUNT MYAING , PISCIOTTA JOHN , FELDMAN ANDREW B. , THUMA PHILIP , SCHOLL PETER F. , DEMIREV PLAMEN A. , LIN JEFFREY S. , SHI LIRONG , KUMAR NIRBHAY , SULLIVAN DAVID J.
Published: September 2018

Detection of Plasmodium falciparum malaria during pregnancy is complicated by sequestration of parasites in the placenta, which reduces peripheral blood microscopic detection. Laser desorption mass spectrometry (LDMS) has previously demonstrated sensitive detection of hemozoin from P. falciparum blood cultures and the ability to track parasitemia in a Plasmodium yoelii malaria mouse model. Here we use a simple, dilution in water, blood sample preparation protocol for LDMS detection of malaria in 45 asymptomatic, pregnant Zambian women. We compare LDMS to microscopy and polymerase chain reaction (PCR) analysis. All women were microscopy negative. LDMS detected P. falciparum hemozoin in 15 out of 45 women, while PCR results were positive in 25 women. Compared with PCR, which analyzed 20–30 μL of blood, the sensitivity of LDMS, which analyzed < 1 μL of blood, was 52%, with a specificity of 92%. LDMS is a potentially rapid and more sensitive alternate diagnostic method than microscopy.
USE OF AN IRON SUPEROXIDE DISMUTASE EXCRETED BY TRYPANOSOMA CRUZI IN THE DIAGNOSIS OF CHAGAS DISEASE: SEROPREVALENCE IN RURAL ZONES OF THE STATE OF QUERETARO, MEXICO
Authors: VILLAGRÁN MARÍA E. , MARÍN CLOTILDE , RODRÍGUEZ-GONZALEZ ISABEL , DE DIEGO JOSE A. , SÁNCHEZ-MORENO MANUEL
Published: September 2018

Four iron superoxide dismutase (SODI, SODII, SODIII, and SODIV) activities with pI values of 6.9, 6.8, 5.25, and 3.8, respectively, were isolated from epimastigote forms of the Maracay strain of Trypanosoma cruzi cultivated at 28°C in Grace’s medium supplemented with 10% heat-inactivated fetal bovine serum. The activity of SODe (pI 3.8), which coincides with that of SODIV, was detected in Grace’s medium without serum in which T. cruzi epimastigotes were cultivated for 24 hours at 28°C. SODe, which was excreted into the medium by the parasite, was immunogenic and antibodies to SODe were detected in serum to a dilution of 1:2,500 by Western blot. The role of SODe is related to the establishment of the parasite within the host, and its high immunogenicity and specificity make it a useful molecular marker in diagnosing infection with this parasite. To validate a Western blot result using SODe as a antigen fraction, 1,029 sera of individuals from 11 municipalities in the state of Queretaro, Mexico were analyzed. Sampling was done randomly and results were compared with those for the same sera with three conventional serologic methods: an enzyme-linked immunosorbent assay (ELISA), indirect hemagglutination (IHA), and an indirect immunofluorescence assay (IFA) to detect antibodies to T. cruzi SODe. Samples that were positive by these three techniques were also positive by the Western blot method. The seroprevalence values for SODe (8.16% by ELISA and Western blot) in Queretaro were considerably higher than those reported in regions of Mexico considered to be endemic for Chagas disease. These results support the use of SODe in the serodiagnosis of Chagas disease.
HABITAT-BASED MODELING OF IMPACTS OF MOSQUITO LARVAL INTERVENTIONS ON ENTOMOLOGICAL INOCULATION RATES, INCIDENCE, AND PREVALENCE OF MALARIA
Authors: GU WEIDONG , NOVAK ROBERT J.
Published: September 2018

Larval control of Anopheles mosquitoes has long been neglected in tropical Africa due to uncertainties about its impacts on incidence and prevalence of malaria. Population models of mosquitoes are a useful tool to provide qualitative and quantitative understandings of influences of larval interventions on malaria transmission. For these purposes, we develop a new modeling framework by conceiving a quantity of the total productivity in an area, which, in turn, can be partitioned into its constituent parts from individual habitats. Three scenarios of larval interventions were evaluated in relation to impacts on parasitological indicators of malaria transmission. Our results show that it is unnecessary to manage all aquatic habitats to obtain significant reductions in incidence and prevalence of malaria in situations of low and intermediate levels of transmission. We highlight that informed larval interventions featured by identifying and targeting prolific habitats can play a critical role in combating malaria in Africa.
AN OUTBREAK OF CHANDIPURA VIRUS ENCEPHALITIS IN THE EASTERN DISTRICTS OF GUJARAT STATE, INDIA
Authors: CHADHA MANDEEP S. , ARANKALLE VIDYA A. , JADI RAMESH S. , JOSHI MANOHAR V. , THAKARE JYOTSNA P. , MAHADEV P. V. M. , MISHRA A. C.
Published: September 2018

An outbreak of encephalitis with a case fatality rate of 78.3% was investigated among children in Gujarat State, India. Twenty-six cases were reported. Three patients had IgM antibodies to Chandipura virus. Virus was isolated from one patient with rhabdomyosarcoma in porcine stable cell lines and in suckling mice. Chandipura virus RNA was present in 9 of 20 acute-phase serum samples, and virus sequences from the present outbreak were closely related to prototype strain (1965) and Andhra Pradesh, India (2003) isolates. Serologic and molecular assays documented the absence of Japanese encephalitis virus, West Nile virus, dengue virus, and paramyxoviruses in clinical samples. The etiologic agent was Chandipura virus, which has become an important encephalitis-causing virus in India.
DISSEMINATED HISTOPLASMOSIS: A COMPARATIVE STUDY BETWEEN PATIENTS WITH ACQUIRED IMMUNODEFICIENCY SYNDROME AND NON-HUMAN IMMUNODEFICIENCY VIRUS–INFECTED INDIVIDUALS
Authors: TOBÓN ANGELA M. , AGUDELO CARLOS A. , ROSERO DAVID S. , OCHOA JUAN E. , DE BEDOUT CATALINA , ZULUAGA ALEJANDRA , ARANGO MYRTHA , CANO LUZ E. , SAMPEDRO JAIME , RESTREPO ANGELA
Published: September 2018

We studied 52 patients with disseminated histoplasmosis, 30 with the acquired immunodeficiency syndrome (AIDS) (cohort 1) and 22 not co-infected with the human immunodeficiency virus (cohort 2). Demographic, clinical, laboratory, mycologic findings, as well as antifungal therapy and highly active antiretroviral (HAART), were analyzed. Skin lesions were significantly higher in cohort 1 than in cohort 2 (P = 0.001). Anemia, leukopenia, and an elevated erythrocyte sedimentation rate were also more pronounced in cohort 1 than in cohort 2 (P < 0.001). Histoplasma capsulatum was isolated more often in cohort 1 than in cohort 2 (P < 0.05) patients, but antibodies to H. capsulatum were detected more frequently in cohort 2 than in cohort 1 (P < 0.05). Itraconazole treatment was less effective in cohort 1 than in cohort 2 (P = 0.012). In cohort 1 patients, HAART improved response to antifungals when compared with individuals not given HAART (P = 0.003), who exhibited higher mortality rates (P = 0.025). Cohort 1 patients who were given dual antifungal and anti-retroviral therapies responded as well as the non-HIV patients in cohort 2, who were treated only with itraconazole. These results indicate the need to promote restoration of the immune system in patients with AIDS and histoplasmosis.
OCCIPITAL INFARCTION REVEALED BY QUADRANOPSIA FOLLOWING SNAKEBITE BY BOTHROPS LANCEOLATUS
Authors: MERLE HAROLD , DONNIO ANGÉLIQUE , AYEBOUA LUCAS , PLUMELLE YVES , SMADJA DIDIER , THOMAS LAURENT
Published: September 2018

We report a case of snakebite in which envenomation was manifested through impairment of the visual field. The patient, a 46-year-old man, was bitten on the right thumb by Bothrops lanceolatus. Treatment with a specific equine antivenom (Bothrofav®) was administered one hour after the bite. With the exception of fang marks, the results of a clinical examination, particularly the neurologic component, were normal. The day after the bite, the patient developed an inferior left lateral homonymous quadranopsia with macular epargne. T2 magnetic resonance imaging showed a right occipital infarction. His condition improved clinically and biologically. This observation of snakebite is the first in which envenomation was accompanied exclusively by an impairment of the visual field. Envenomation by B. lanceolatus is distinct in its incidence of significant thrombotic complications at a distance from the site of the bite.
SOURCES OF VARIABILITY IN DETERMINING MALARIA PARASITE DENSITY BY MICROSCOPY
Authors: O’MEARA WENDY PRUDHOMME , MCKENZIE F. ELLIS , MAGILL ALAN J. , FORNEY J. RUSS , PERMPANICH BARNYEN , LUCAS CARMEN , GASSER ROBERT A. , WONGSRICHANALAI CHANSUDA
Published: September 2018

Enumeration of parasites by microscopic examination of blood smears is the only method available for quantifying parasitemia in infected blood. However, the sources and scale of error inherent in this technique have not been systematically investigated. Here we use data collected in outpatient clinics in Peru and Thailand to elucidate important sources of variation in parasite density measurements. We show that discrepancies between readings from two independent microscopists and multiple readings from a single microscopist are inversely related to the density of the infection. We present an example of how differences in reader technique, specifically the number of white blood cells counted, can contribute to the differences between readings. We discuss the implications of this analysis for field studies and clinical trials.
ASSOCIATION OF FAILURES OF SEVEN-DAY COURSES OF ARTESUNATE IN A NON-IMMUNE POPULATION IN BANGUI, CENTRAL AFRICAN REPUBLIC WITH DECREASED SENSITIVITY OF PLASMODIUM FALCIPARUM
Authors: MENARD DIDIER , MATSIKA-CLAQUIN MARCELLE DIANE , DJALLE DJIBRINE , YAPOU FERDINAND , MANIRAKIZA ALEXANDRE , DOLMAZON VIRGINIE , SARDA JACQUES , TALARMIN ANTOINE
Published: September 2018

We assessed the efficacy and safety of a seven-day course of artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in 55 non-immune patients living in Bangui, Central African Republic. The parasitologic cure rates were 100%, 95%, and 85% on days 14, 28, and 42, respectively. There were no significant differences in parasitemia density, 50% inhibitory concentration of dihydroartemisinin, and frequency of mutant P. falciparum multidrug resistance 1 codon 86 between patients who were cured and those who displayed recrudescence. However, the 90% inhibitory concentration for dihydroartemisinin and the number of genotypes isolated were both higher in the recrudescent patients (five- and two-fold, respectively). We found an association between recrudescence and decreased sensitivity. This suggests that the use of artemisinin compounds alone will select resistant strains. We conclude that artesunate should not be used in monotherapy even in seven-day courses, but only in combination with other anti-malarials to prevent the emergence of resistant P. falciparum.
LEPTOSPIROSIS AFTER RECREATIONAL EXPOSURE TO WATER IN THE YAEYAMA ISLANDS, JAPAN
Authors: NARITA MASASHI , FUJITANI SHIGEKI , HAAKE DAVID A. , PATERSON DAVID L.
Published: September 2018

Leptospirosis is a global zoonotic disease with a variety of clinical manifestations. We report an outbreak of leptospirosis in the Yaeyama Islands, Japan, in the summer of 1999 associated with heavy rainfall. Fourteen people were diagnosed with leptospirosis and required hospitalization. All cases were found to have exposure to contaminated soil or water. A history of recreational activities involving water sports was more frequent (71%) than occupational risk factors related to agriculture or construction (29%). Fever was the primary symptom in all cases, followed by chills (93%), headache (86%), myalgias (57%) and conjunctival suffusion (57%). All cases were successfully treated with antimicrobial therapy except one patient who improved spontaneously. Jarisch-Herxheimer reactions were seen in six cases (43%). The increasing incidence of leptospirosis related to recreational sports is an important public health problem in resort areas. A high-index of suspicion, early treatment, and prevention are crucial in this latently endemic area.
DRACUNCULIASIS ERADICATION: THE FINAL INCH
Authors: HOPKINS DONALD R. , RUIZ-TIBEN ERNESTO , DOWNS PHILIP , WITHERS P. CRAIG , MAGUIRE JAMES H.
Published: September 2018

This report summarizes the status of the Dracunculiasis Eradication Program as of early 2005. Nine of the 20 countries that were endemic for this disease when the program began have already interrupted transmission, Asia is free of Guinea worm, and five of the remaining disease-endemic countries reported less than 50 cases each in 2004. Ghana and Sudan each reported 45% of the 16,026 cases in 2004. Except for Sudan, whose reports are delayed, cases in the remaining disease-endemic countries were reduced by 61% during the first quarter of 2005 compared with the same period of 2004. With accelerating momentum towards zero cases in all countries, the recent settlement of Sudan’s north-south civil war, and a new challenge grant from the Bill & Melinda Gates Foundation, the way now seems clear to finish eradicating dracunculiasis by 2009 in Sudan and earlier elsewhere.

“The rule of the final inch . The work has been almost completed, the goal almost attained . In that moment of fatigue and self-satisfaction it is especially tempting to leave the work without having attained the apex of quality . In fact, the rule of the Final Inch consists in this: not to shirk this crucial work. Not to postpone it . And not to mind the time spent on it, knowing that one’s purpose lies . in the attainment of perfection.”

—Alexander Solzhenitzyn, The First Circle
ADVERSE PERINATAL OUTCOMES OF HIV-1–INFECTED WOMEN IN RELATION TO MALARIA PARASITEMIA IN MATERNAL AND UMBILICAL CORD BLOOD
Authors: VILLAMOR EDUARDO , MSAMANGA GERNARD , ABOUD SAID , URASSA WILLY , HUNTER DAVID J. , FAWZI WAFAIE W.
Published: September 2018

Malaria infection during pregnancy increases the risk of adverse birth outcomes among HIV-infected women. The role of umbilical cord parasitemia is not well characterized. We examined the risk of adverse perinatal outcomes in relation to maternal or umbilical cord Plasmodium falciparum parasitemia among 275 HIV-infected women from Tanzania, who participated in a randomized trial of zinc supplementation during pregnancy. Maternal parasitemia (≥1/μL) at the first antenatal visit was associated with increased risk of low birth weight < 2,500 g (adjusted relative risk [ARR] = 2.66; P = 0.01) and preterm delivery < 37 weeks (ARR = 1.87; P = 0.06). Maternal parasitemia at delivery was associated with preterm delivery (ARR = 2.27; P = 0.008), intrauterine growth retardation (ARR = 1.92; P = 0.03), and neonatal death (ARR = 3.22; P = 0.07). Cord parasitemia was associated with a large and significant increase in the risk of neonatal death (ARR = 8.75; P = 0.003). Maternal parasitemia at the first antenatal visit was strongly related to parasitemia at delivery, and the latter was associated with cord blood parasitemia. CD4 cell counts, parity, or assignment to the zinc arm (25 mg daily) were not associated with parasitemia in maternal or cord blood at delivery. Successful treatment of HIV-infected women who present to the first prenatal visit with malaria parasitemia and avoidance of reinfection are likely to decrease the risk of adverse outcomes during pregnancy and the early postpartum period. Cord blood parasitemia is a strong predictor of neonatal death. The potential effect of zinc supplementation on clinical malaria outcomes deserves future investigation.
COST-EFFECTIVENESS OF CHAGAS DISEASE INTERVENTIONS IN LATIN AMERICA AND THE CARIBBEAN: MARKOV MODELS
Authors: WILSON LESLIE S. , STROSBERG ARTHUR M. , BARRIO KIMBERLY
Published: September 2018

Chagas disease is a parasitic disease in Latin America. Despite vector control programs that have reduced incidence by 70%, there are at least 12–14 million prevalent cases. We used a Markov model to examine strategies for control and treatment of Chagas disease that compared annual costs, life expectancies, and cost-effectiveness of three vector control and drug treatment strategies. Vector control programs alone and vector control plus drug treatment are dominant over no vector control (i.e., less costly and save more lives), and vector control plus drug is highly cost-effective compared with vector control alone. We demonstrated expected changes in deaths over time resulting from various prevention approaches. Vector control affects primarily incidence, not decreasing deaths and prevalence for 30 years, while drug treatment affects prevalence and deaths immediately. The best strategy to combat Chagas disease is combinations of vector control and a potential new drug.
RAPID IDENTIFICATION OF LEISHMANIA COMPLEXES BY A REAL-TIME PCR ASSAY
Authors: WORTMANN GLENN , HOCHBERG LISA , HOUNG HUO-HSU , SWEENEY COLLEEN , ZAPOR MICHAEL , ARONSON NAOMI , WEINA PETER , OCKENHOUSE CHRISTIAN F.
Published: September 2018

A real-time PCR assay for the detection of four Leishmania complexes (L. Viannia, L. mexicana, L. donovani/infantum, and L. major) was developed and evaluated. The assay was developed to detect the glucosephosphate isomerase gene and capitalizes on DNA sequence variability within that gene for Leishmania complex identification. Primer/probe sets were created and tested against a panel of 21 known negative controls and on DNA extracted from cultured promastigotes or from tissue biopsies from patients with cutaneous leishmaniasis. The assay was highly specific, as no amplification products were detected in the negative control samples while simultaneously retaining a high degree of complex-specific diagnostic accuracy for cultured organisms and patient clinical samples. Real-time PCR offers rapid (within hours) identification of Leishmania to the complex level and provides a useful molecular tool to assist both epidemiologists and clinicians.
ULTRASOUND AND CLINICAL INVESTIGATION OF HEPATOSPLENIC SCHISTOSOMIASIS: EVALUATION OF SPLENOMEGALY AND LIVER FIBROSIS FOUR YEARS AFTER MASS CHEMOTHERAPY WITH OXAMNIQUINE
Authors: COTA GLÁUCIA FERNANDES , PINTO-SILVA ROGÉRIO AUGUSTO , ANTUNES CARLOS MAURÍCIO FIGUEIREDO , LAMBERTUCCI JOSÉ ROBERTO
Published: September 2018

The course of hepatosplenic schistosomiasis after mass chemotherapy with oxamniquine has been rarely reported. We report the effect of treatment in patients with advanced schistosomiasis mansoni living in area of Brazil highly endemic for this disease. A total of 739 inhabitants of a village were subjected to clinical and abdominal ultrasound examinations and were treated with oxamniquine. We have identified 84 individuals with hepatosplenic schistosomiasis. Alcohol abuse was associated with periportal thickening. Four years after treatment, 42 of the 84 individuals were re-examined and regression of splenomegaly was observed in 59% and of periportal thickening in 32%. Our data indicate that mass chemotherapy can lead to reduction of schistosomiasis morbidity but a significant group of patients (68%) will not improve. The association with alcohol abuse should be further evaluated. Thickening of the gallbladder wall can be a useful predictor of no involution of liver fibrosis after treatment.
DIARRHEAL EPIDEMICS IN DHAKA, BANGLADESH, DURING THREE CONSECUTIVE FLOODS: 1988, 1998, AND 2004
Authors: SCHWARTZ BRIAN S. , HARRIS JASON B. , KHAN ASHRAFUL I. , LAROCQUE REGINA C. , SACK DAVID A. , MALEK MOHAMMAD A. , FARUQUE ABU S.G. , QADRI FIRDAUSI , CALDERWOOD STEPHEN B. , LUBY STEPHEN P. , RYAN EDWARD T.
Published: September 2018

We examined demographic, microbiologic, and clinical data from patients presenting during 1988, 1998, and 2004 flood-associated diarrheal epidemics at a diarrhea treatment hospital in Dhaka, Bangladesh. Compared with non-flood periods, individuals presenting during flood-associated epidemics were older, more severely dehydrated, and of lower socioeconomic status. During flood-associated epidemics, Vibrio cholerae was the most commonly identified cause of diarrhea, and the only diarrheal pathogen whose incidence proportionally increased in each epidemic compared with seasonally matched periods. Rotavirus was the second most frequently identified flood-associated pathogen, although the proportion of cases caused by rotavirus infection decreased during floods compared with matched periods. Other causes of diarrhea did not proportionally change, although more patients per day presented with enterotoxigenic Escherichia coli, Shigella, and Salmonella species–associated diarrhea during floods compared with matched periods. Our findings suggest that cholera is the predominant cause of flood-associated diarrheal epidemics in Dhaka, but that other organisms spread by the fecal-oral route also contribute.
DEVELOPMENT OF ANTIBODIES TO BURKHOLDERIA PSEUDOMALLEI DURING CHILDHOOD IN MELIOIDOSIS-ENDEMIC NORTHEAST THAILAND
Authors: WUTHIEKANUN VANAPORN , CHIERAKUL WIRONGRONG , LANGA SAYAN , CHAOWAGUL WIPADA , PANPITPAT CHANATHIP , SAIPAN PENCHAN , THOUJAIKONG THAKSINAPORN , DAY NICHOLAS P. , PEACOCK SHARON J.
Published: September 2018

A cross-sectional serological survey of 2,214 children living in northeast Thailand was conducted to define the antibody response to Burkholderia pseudomallei from birth to 14 years. There was a sharp rise in detectable antibodies from birth to 4 years followed by reactivity in approximately 60–70% of children thereafter.
CYCLOOXYGENASE 2 EXPRESSION IN VESSELS AND NERVES IN REVERSAL REACTION LEPROSY
Authors: PESCE CARLO , GRATTAROLA MYRIAM , MENINI STEFANO , FIALLO PAOLO
Published: September 2018

Tissue expression of cyclooxygenase (COX)2, an inducible enzyme synthesizing eicosanoids in inflammation, was studied in reversal reaction (RR) leprosy in comparison with nonreactionary leprosy. COX2 was consistently expressed in cells of the mononuclear-macrophage lineage across the leprosy spectrum. Only in RR, the following two additional sites showed COX2 expression in the dermis and subcutis: 1) microvessels and 2) nerve bundles and isolated nerve fibers. The same sites also express vascular endothelial growth factor (VEGF). This is in keeping with experimental models relating VEGF to COX2 expression, with VEGF enhancing prostaglandin production through COX2 stimulation and prostaglandin synthase expression. We postulate that selective COX2 inhibitors, which are currently used in several inflammatory conditions, could be considered for RR treatment to reduce acute symptoms caused by tissue edema and possibly prevent long-term nerve damage, the main complication of RR.
CAUSES OF FEVER IN ADULTS ON THE THAI-MYANMAR BORDER
Authors: ELLIS RUTH D. , FUKUDA MARK M. , MCDANIEL PHILIP , WELCH KATHERINE , NISALAK ANANDA , MURRAY CLINTON K. , GRAY MICHAEL R. , UTHAIMONGKOL NICHAPAT , BUATHONG NILLAWAN , SRIWICHAI SABAITHIP , PHASUK RUNGNAPHA , YINGYUEN KRITSANAI , MATHAVARAT CHAIYAWAT , MILLER ROBERT S.
Published: September 2018

A hospital-based study was conducted along the Thai-Myanmar border to provide greater knowledge of the causes of febrile illness and to determine what zoonotic and vector-borne emerging infectious diseases might be present. A total of 613 adults were enrolled from June 1999 to March 2002. Cases were classified based on clinical findings and laboratory results. An etiologic diagnosis was made for 48% of subjects. Malaria was the most common diagnosis, accounting for 25% of subjects, with two-thirds Plasmodium falciparum. Serologic evidence for leptospirosis was found in 17% of subjects. Other etiologic diagnoses included rickettsial infections, dengue fever, and typhoid. The most frequent clinical diagnoses were nonspecific febrile illness, respiratory infections, and gastroenteritis. Clinical associations were generally not predictive of etiologic diagnosis. Apparent dual diagnoses were common, particularly for malaria and leptospirosis. Findings have been used to modify treatment of unspecified febrile illness in the area.
MODELING HANTAVIRUS RESERVOIR SPECIES DOMINANCE IN HIGH SEROPREVALENCE AREAS ON THE AZUERO PENINSULA OF PANAMA
Authors: SUZÁN GERARDO , GIERMAKOWSKI J. TOMASZ , MARCÉ ERIKA , SUZÁN-AZPIRI HUMBERTO , ARMIÉN BLAS , YATES TERRY L.
Published: September 2018

Habitat fragmentation commonly influences distribution of zoonotic disease reservoirs. In Panama, populations of rodent hosts of hantaviruses are favored by small habitat fragments isolated by agricultural lands. We expected a similar relationship between landscape characteristics and host distribution at fine geographical scales in southern Panama. The relative abundance of Zygodontomys brevicauda, the primary host for “Calabazo” virus, and other rodents was assessed at 24 sites within the Azuero Peninsula. We used satellite imagery to produce several spatial variables that described landscape; however, only slope was consistently related to abundances of the two most dominant rodent species. Using regression, we constructed a spatial model of areas of Z. brevicauda dominance, which in turn relates to higher infection rates. The model predicts highest abundances of Z. brevicauda in flat areas, where humans also dominate. These predictions have important ecological and conservation implications that associate diversity loss, topography, and human land use.
CORRELATION OF SERUM LEVELS OF MACROPHAGE MIGRATION INHIBITORY FACTOR WITH DISEASE SEVERITY AND CLINICAL OUTCOME IN DENGUE PATIENTS
Authors: CHEN LIEN-CHENG , LEI HUAN-YAO , LIU CHING-CHUAN , SHIESH SHU-CHU , CHEN SHUN-HUA , LIU HSIAO-SHENG , LIN YEE-SHIN , WANG SHAN-TAIR , SHYU HUEY-WEN , YEH TRAI-MING
Published: September 2018

Dengue virus infection can cause mild dengue fever (DF) or severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Cytokines are believed to be involved in the pathogenesis of dengue infection. However, the role of the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) in dengue infection is unclear. In this study, serum levels of MIF in adult dengue patients with different disease severity and clinical outcome were determined and compared with the levels of other cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10, and interferon gamma (IFN-γ), in the same patients. Serum levels of MIF, IL-6, and IL-10, but not IFN-γ or TNF-α, were higher in all DHF patients who died than in DHF survivors and DF patients. We conclude that in addition to IL-6 and IL-10, elevated levels of serum MIF are a potential predictor of disease severity and clinical outcome in dengue patients.
POINT MUTATIONS IN THE DIHYDROFOLATE REDUCTASE AND DIHYDROPTEROATE SYNTHASE GENES OF PLASMODIUM FALCIPARUM AND RESISTANCE TO SULFADOXINE-PYRIMETHAMINE IN SRI LANKA
Authors: HAPUARACHCHI HAPUARACHCHIGE C. , DAYANATH MEEGODA Y. D. , BANDARA KANDEYAYE BANDARALAGE A. T. , ABEYSUNDARA SUDUSINGHE , ABEYEWICKREME WIMALADHARMA , DE SILVA NILANTHI R. , HUNT SONIA Y. , SIBLEY CAROL HOPKINS
Published: September 2018

Sulfadoxine-pyrimethamine (SP) is the second-line treatment for Plasmodium falciparum malaria in Sri Lanka. Resistance to SP is caused by point mutations in the dihydrofolate reductase (Pf-dhfr) and dihydropteroate synthase (Pf-dhps) genes of P. falciparum. We determined the genotype of Pf-dhfr and Pf-dhps and the clinical response to SP in 30 field isolates of P. falciparum from Sri Lanka. All patients treated with SP had an adequate clinical response. Eighty-five percent (23 of 27) of pure field isolates carried parasites with double mutant alleles of Pf-dhfr (C59R + S108N) and showed about 200-fold higher levels of resistance to pyrimethamine than the wild type in a yeast system. None of the isolates had either known or novel mutations at other positions in the dhfr domain. In contrast, 67% (20 of 30) of the isolates carried parasites that were wild type for Pf-dhps. In Sri Lanka, detection of the triple mutant allele of Pf-dhfr will require tracking mutations at codon 51.
AOTUS NANCYMAAE AS A POTENTIAL MODEL FOR THE TESTING OF ANTI-SPOROZOITE AND LIVER STAGE VACCINES AGAINST PLASMODIUM FALCIPARUM
Authors: COLLINS WILLIAM E. , SULLIVAN JOANN S. , WILLIAMS ALLISON , NACE DOUGLAS , WILLIAMS TYRONE , GALLAND G. GALE , BARNWELL JOHN W.
Published: September 2018

The Santa Lucia strain of Plasmodium falciparum was transmitted to Aotus lemurinus griseimembra, A. azarae boliviensis, A. vociferans, and A. nancymaae monkeys by bite and by intravenous inoculation of sporozoites dissected from Anopheles freeborni, An. stephensi, An. gambiae, An. albimanus, and An. maculatus mosquitoes. The data obtained from these infections indicate that A. nancymaae can be considered a suitable host model when combined with the Santa Lucia strain of P. falciparum for the testing of candidate anti-sporozoite and liver stage vaccines.
DISTRIBUTION, DESCRIPTION, AND LOCAL KNOWLEDGE OF LARVAL HABITATS OF ANOPHELES GAMBIAE S.L. IN A VILLAGE IN WESTERN KENYA
Authors: MUTUKU FRANCIS M. , ALAII JANE A. , BAYOH M. NABIE , GIMNIG JOHN E. , VULULE JOHN M. , WALKER EDWARD D. , KABIRU EPHANTUS , HAWLEY WILLIAM A.
Published: September 2018

A sampling census revealed 104 aquatic habitats of 6 types for Anopheles gambiae s.l. larvae in a village in western Kenya, namely burrow pits, drainage channels, livestock hoof prints, rain pools, tire tracks, and pools in streambeds. Most habitats were created by human activity and were highly clustered in dispersion pattern within the village landscape. Landscape analysis revealed that six of forty-seven 0.09 km2 cells superimposed over the village harbored 65% of all habitats. Focus group discussions and in-depth interviews with villagers revealed the extent of knowledge of the village residents of larval habitats, mosquito sources in the local environment, and what might be done to prevent mosquito breeding. Participants did not associate specific habitats with anopheline larvae, expressed reluctance to eliminate habitats because they were sources of domestic water supply, but indicated willingness to participate in a source reduction program if support were available.
COGNITIVE EFFECTS OF DIARRHEA, MALNUTRITION, AND ENTAMOEBA HISTOLYTICA INFECTION ON SCHOOL AGE CHILDREN IN DHAKA, BANGLADESH
Authors: TARLETON JESSICA L. , HAQUE RASHIDUL , MONDAL DINESH , SHU JIANFEN , FARR BARRY M. , PETRI WILLIAM A.
Published: September 2018

Cognitive function was assessed in 191 Bangladeshi children 6–9 years of age using verbal and nonverbal tests. These scores were added to a health surveillance database that was compiled over the four previous years that includes incidence of diarrhea and Entamoeba histolytica infection and nutritional status. The associations of diarrhea, malnutrition, and social factors with cognitive scores were analyzed statistically, and associations between diarrhea and test scores were controlled for the influence of social factors. Cognitive scores were negatively associated with stunting during school age, as well as the height-for-age and weight-for-age scores at study enrollment. Incidence of diarrhea was associated with nonverbal test scores before, but not after, controlling for socioeconomic factors. Generally E. histolytica infection was not found to independently influence scores, except that E. histolytica-associated dysentery was associated with lower test scores while dysentery of any etiology was not. Thus, malnutrition during the school age years, but not diarrhea or E. histolytica infection, was associated with a lower level of cognitive functioning. This suggested that intervention during school age years may be able to mitigate the cognitive deficiencies associated with malnutrition.
PREVALENCE OF AND FACTORS ASSOCIATED WITH HELICOBACTER PYLORI INFECTION IN CHILDREN IN THE NORTH OF VIETNAM
Authors: NGUYEN BANG V. , NGUYEN KHANH G. , PHUNG CAM D. , KREMP ODILE , KALACH NICOLAS , DUPONT CHRISTOPHE , RAYMOND JOSETTE , VIDAL-TRECAN GWENAËLLE
Published: September 2018

The study aimed at evaluating the seroprevalence of and sociodemographic, health, lifestyle, and environmental hygiene conditions associated with Helicobacter pylori infection in Vietnamese children. Data from 824 children, aged from 6 months to 15 years and gastrointestinal symptom free when consulted, admitted to a university hospital, were collected using a structured questionnaire and ELISA test for H. pylori infection. The data were examined using univariate and multivariate analyses. H. pylori seroprevalence was 34.0%. Age groups from 3 to 6 years and older than 6, and number of offspring were positively and independently associated with H. pylori seropositivity [adjusted OR (95% CI): 2.9 (1.5–5.5); 1.9 (1.1–3.1) and 1.8 (1.1–2.6), respectively]. Breastfeeding more than 6 months was negatively and independently associated with H. pylori seropositivity [adjusted OR (95% CI): 0.5 (0.3–0.9)]. Mother’s age, history of allergy, gastro-duodenal disease history in the past, initiating collective life before 6 years, sharing bed with parents and time of bed sharing with parents > 24 months were positively but not independently associated with H. pylori seropositivity. None of the other environmental or lifestyle conditions examined was associated with H. pylori infection. Our results support person-to-person transmission and the role of sociodemographic factors in H. pylori infection.