bluuebunny/crossref_metadata_2025 huggingface dataset:
QUANTITATIVE REAL-TIME POLYMERASE CHAIN REACTION FOR MALARIA DIAGNOSIS AND ITS USE IN MALARIA VACCINE CLINICAL TRIALS
Authors: ANDREWS LAURA , ANDERSEN RIKKE F. , WEBSTER DANIEL , DUNACHIE SUSANNA , WALTHER R. MICHAEL , BEJON PHILIP , HUNT-COOKE ANGELA , BERGSON GILLIAN , SANDERSON FRANCES , HILL ADRIAN V. S. , GILBERT SARAH C.
Published: September 2018

The demand for an effective malaria vaccine is high, with millions of people being affected by the disease every year. A large variety of potential vaccines are under investigation worldwide, and when tested in clinical trials, researchers need to extract as much data as possible from every vaccinated and control volunteer. The use of quantitative real-time polymerase chain reaction (PCR), carried out in real-time during the clinical trials of vaccines designed to act against the liver stage of the parasite’s life cycle, provides more information than the gold standard method of microscopy alone and increases both safety and accuracy. PCR can detect malaria parasites in the blood up to 5 days before experienced microscopists see parasites on blood films, with a sensitivity of 20 parasites/mL blood. This PCR method has so far been used to follow 137 vaccinee and control volunteers in Phase IIa trials in Oxford and on 220 volunteer samples during a Phase IIb field trial in The Gambia.
ECONOMIC EFFECTS OF ECHINOCOCCOSIS IN A DISEASE-ENDEMIC REGION OF THE TIBETAN PLATEAU
Authors: BUDKE CHRISTINE M. , JIAMIN QIU , QIAN WANG , TORGERSON PAUL R.
Published: September 2018

This report attempts to quantify the economic losses due to Echinococcus multilocularis and E. granulosus in Shiqu County, Sichuan, People’s Republic of China, as well as illustrate the cost effectiveness of dog anthelmintic prophylaxis combined with a sheep and goat vaccination program in terms of disability-adjusted life years (DALYs) saved. We evaluated human losses associated with treatment costs and loss of income due to morbidity and mortality, in addition to production losses in livestock due to E. granulosus infection. Annual combined human and animal losses (95% confidence interval) is estimated to reach U.S.$218,676 (U.S.$189,850–247,871) if only liver-related losses in sheep, goats, and yaks are taken into account. This equates to approximately U.S.$3.47 per person annually or 1.4% of per capita gross domestic product. However, total annual losses can be nearly U.S.$1,000,000 if additional livestock production losses are assumed. Eventual prevention of 65–95% of annual losses due to cystic echinococcosis is suggested with proposed biannual dog anthelmintic prophylaxis and a sheep and goat vaccination program. Prevention of 9–50% of human alveolar echinococcosis-associated losses is suggested based on stochastic models for the current epidemiologic situation. The median estimated cost of the program would be approximately $56,000 per year, which is a fraction of the estimated combined livestock and human financial losses due to the disease. Overall cost for the proposed control program is within the World Health Organization second most cost-effective band of less than U.S.$150 per DALY averted. However, cost per DALY averted would be less than U.S.$25 dollars for the human health sector if cost sharing was implemented between the public health and agricultural sectors based on proportional benefit from control.
PSEUDO-BORRELIOSIS IN PATIENTS WITH MALARIA
Authors: BERGER STEPHEN A. , DAVID LIORA
Published: September 2018

Malaria and relapsing fever are arthropod-borne infections characterized by fever, myalgia, headache, and a tendency to relapse. Both are diagnosed through examination of stained blood films, and both might respond to tetracycline therapy. In at least four published case reports, the presence of malarial microgametes possibly resulted in misdiagnosis of borreliosis in patients with malaria. An additional case is presented, and the mechanism of microgamete production in clinical specimens is discussed.
PLASMODIUM FALCIPARUM GENOTYPING BY MICROSATELLITES AS A METHOD TO DISTINGUISH BETWEEN RECRUDESCENT AND NEW INFECTIONS
Authors: NYACHIEO ATUNGA , VAN OVERMEIR CHANTAL , LAURENT THIERRY , DUJARDIN JEAN-CLAUDE , D’ALESSANDRO UMBERTO
Published: September 2018

In vivo tests for susceptibility to antimalarial drugs require molecular methods to distinguish recrudescence from new infection. The most commonly used DNA markers (merozoite surface proteins [MSPs]) are under immune selective pressure, which might lead to misclassification. We evaluated immunologically neutral microsatellite markers in blood samples collected during a drug efficacy trial in Rwanda. Fifty percent of the infections classified as recrudescent by MSP were classified as new by microsatellite markers. Reciprocally, 23.3% of infections classified as recrudescent by microsatellite markers were identified as new by MSP. In drug efficacy studies, microsatellite markers should complement MSP genotyping to distinguish a recrudescence from a new infection.
DETECTION OF BENZIMIDAZOLE RESISTANCE–ASSOCIATED MUTATIONS IN THE FILARIAL NEMATODE WUCHERERIA BANCROFTI AND EVIDENCE FOR SELECTION BY ALBENDAZOLE AND IVERMECTIN COMBINATION TREATMENT
Authors: SCHWAB ANNE E. , BOAKYE DANIEL A. , KYELEM DOMINIQUE , PRICHARD ROGER K.
Published: September 2018

The Global Program to Eliminate Lymphatic Filariasis has been implemented to reduce human microfilaremia to levels low enough to break the transmission of the disease by using single annual doses of albendazole in combination with diethylcarbamazine or ivermectin. Many veterinary helminth parasites have developed resistance against both albendazole and ivermectin. Resistance to albendazole in veterinary nematodes is known to be caused by either of two single amino acid substitutions from phenylalanine to tyrosine in parasite β-tubulin at position 167 or 200. We have developed assays capable of detecting these single nucleotide polymorphisms (SNPs) in Wuchereria bancrofti, and have applied them to microfilaria obtained from patients in Ghana and Burkina Faso. One of the SNPs was found in worms from untreated populations in both locations. Worms from treated patients had significantly higher frequencies of these mutations. These findings indicate that a β-tubulin allele associated with benzimidazole resistance is being selected in these populations.
DRUG-RESISTANT MALARIA IN BANGUI, CENTRAL AFRICAN REPUBLIC: AN IN VITRO ASSESSMENT
Authors: MENARD DIDIER , DJALLE DJIBRINE , MANIRAKIZA ALEXANDRE , YAPOU FERDINAND , SIADOUA VALERIE , SANA SERGE , MATSIKA-CLAQUIN MARCELLE DIANE , NESTOR MADJI , TALARMIN ANTOINE
Published: September 2018

We used an in vitro isotopic drug sensitivity assay to assess the sensitivity of Plasmodium falciparum isolates collected in Bangui, Central African Republic between March and July 2004. We tested antimalarials that are currently in use in this country (chloroquine, amodiaquine, quinine, and pyrimethamine), antimalarials that will become available in this region in the future (artemisinin and halofantrine), and prophylactic antimalarials (mefloquine, doxycycline, and atovaquone). The proportions of resistant isolates were 37% for chloroquine, 15.9% for amodiaquine, 0% for quinine, 0% for dihydroartemisinin, 1.6% for mefloquine, 3.8% for halofantrine, 4.0% for atovaquone, and 38.3% for pyrimethamine. No multi-resistant isolates (showing resistance to more than three drugs) were found. A positive correlation was found between the 50% inhibitory concentrations values for the following drugs: chloroquine and amodiaquine; quinine and halofantrine; chloroquine and dihydroartemisinin; chloroquine and halofantrine; amodiaquine and dihydroartemisinin; dihydroartemisinin and mefloquine; chloroquine and quinine; and quinine and dihydroartemisinin. These findings suggest that the Ministry of Health should recommend a interim policy with the amodiaquine plus sulfadoxine-pyrimethamine combination as the first-line antimalarial drug in Bangui until better alternative treatments such as artemisinin-based combination therapies become available at low prices in the Central African Republic.
EFFECTIVENESS OF QUININE MONOTHERAPY FOR THE TREATMENT OF PLASMODIUM FALCIPARUM INFECTION IN PREGNANT WOMEN IN LAMBARÉNÉ, GABON
Authors: ADEGNIKA AYÔLA A. , BREITLING LUTZ PH. , AGNANDJI SELIDJI T. , CHAI SANDERS K. , SCHÜTTE DANIELA , OYAKHIROME SUNNY , SCHWARZ NORBERT G. , GROBUSCH MARTIN P. , MISSINOU MICHEL A. , RAMHARTER MICHAEL , ISSIFOU SAADOU , KREMSNER PETER G.
Published: September 2018

Pregnant women participating in a longitudinal immuno-epidemiologic survey in Lambaréné, Gabon, and presenting with Plasmodium falciparum parasitemia at monthly blood smear examinations were offered treatment with oral 7-day quinine monotherapy according to national health guidelines. A total of 50 pregnant women were offered 7-day oral quinine sulfate 10 mg/kg thrice daily. Clinical examinations and laboratory tests were performed on Days 28 and 56 to assess the effectiveness of this standard regimen. By Day 28, the effectiveness of the 7-day quinine regimen was 60% (95% confidence interval: 46–72%). We conclude that a 7-day course of quinine has a poor effectiveness and that alternative treatment regimens for malaria in pregnant women should be assessed.
THE VALUE OF A NEW MICROCULTURE METHOD FOR DIAGNOSIS OF VISCERAL LEISHMANIASIS BY USING BONE MARROW AND PERIPHERAL BLOOD
Authors: ALLAHVERDIYEV ADIL M. , BAGIROVA MALAHAT , UZUN SONER , ALABAZ DERYA , AKSARAY NECMI , KOCABAS EMINE , KOKSAL FATIH
Published: September 2018

We have demonstrated that the microculture method (MCM) enables the diagnosis of visceral leishmaniasis (VL) with samples from both the bone marrow (BM) and peripheral blood (PB). The MCM is superior to the traditional culture method (TCM) as determined by its higher sensitivity in the detection of promastigotes and the more rapid time for emergence of promastigotes. The sensitivity of MCM (100% in BMs and 77.8–100% in PB) was considerably higher than that of the TCM (37.5–100% in BMs and 0–100% in PB) according to decreasing parasite density (P < 0.05). The concentration of parasites in buffy coats has increased the sensitivity of both methods, especially that of the MCM. Detection of promastigotes by MCM requires lower amounts of culture media (25–50 μL) and shorter incubation periods (2–7 days) than TCM (2.5–3.5 mL and 15–35 days, respectively). MCM was found to be valuable with the advantages of simplicity and sensitivity, in addition to being cost-effective in the routine diagnosis for VL in Adana Turkey.
APPLICATION OF AN ALTERNATIVE AEDES SPECIES (DIPTERA: CULICIDAE) SURVEILLANCE METHOD IN BOTUCATU CITY, SÃO PAULO, BRAZIL
Authors: NOGUEIRA LETÍCIA A. , GUSHI LETÍCIA T. , MIRANDA JOÃO E. , MADEIRA NEWTON G. , RIBOLLA PAULO E. M.
Published: September 2018

One of the main problems with dengue is the control of Aedes aegypti, its major vector. In Brazil, the current control program for Ae. aegypti and Aedes albopictus populations includes larval density surveys. An interesting alternative is the use of a distinct index, the Premise Condition Index (PCI). This tool relates conditions of property, such as houses and yards, and the degree of shade with the occurrence of Aedes sp. oviposition, and is calculated as scores from 3 to 9. The lowest score indicates property in good condition and an unfavorable breeding environment, while the highest score indicates property at high risk for infestation by Aedes sp. The present study is based on the application of the PCI in an urban area of Botucatu, Brazil to confirm its effectiveness.
HIGH RATES OF APOPTOSIS IN HUMAN MYCOBACTERIUM ULCERANS CULTURE-POSITIVE BURULI ULCER SKIN LESIONS
Authors: WALSH DOUGLAS S. , MEYERS WAYNE M. , PORTAELS FRANCOISE , LANE JOSHUA E. , MONGKOLSIRICHAIKUL DUANGRAT , HUSSEM KITTINUN , GOSI PANITA , MYINT KHIN SAW AYE
Published: September 2018

Buruli ulcer, a disease caused by Mycobacterium ulcerans, causes ulcerative skin disease likely generated by a toxin that mediates apoptosis. We analyzed paraffin-embedded sections of surgically excised Buruli ulcer lesions (two ulcers and one edematous plaque) and adjacent non-lesional skin samples (n = 9) for apoptosis by an indirect immunofluorescent terminal deoxynucleotide transferase–mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. All samples were stained for acid-fast bacilli (AFB) and cultured for mycobacteria, and most were analyzed with an M. ulcerans-specific diagnostic polymerase chain reaction (PCR). TUNEL (+) bodies were numerous in both ulcers and the plaque, and sparse or absent in adjacent non-lesional skin. The AFB tissue stains and cultures for M. ulcerans were positive only in the three lesions. The result of the PCR for M. ulcerans was positive in all three lesions and in four of six non-lesional tissue samples; three contained sparse TUNEL (+) bodies. An abundance of TUNEL (+) bodies in the three AFB stain (+), culture (+), and PCR (+) Buruli ulcer lesional samples, but not in nearby AFB stain (−), culture (−), and PCR (+) non-lesional skin samples, strengthen the evidence that apoptosis is an important tissue destruction mechanism in human lesions closely associated with viable M. ulcerans.
OCCURRENCE OF SHIGELLOSIS IN THE YOUNG AND ELDERLY IN RURAL CHINA: RESULTS OF A 12-MONTH POPULATION-BASED SURVEILLANCE STUDY
Authors: WANG XUAN-YI , DU LIN , VON SEIDLEIN LORENZ , XU ZHI-YI , ZHANG YING-LIN , HAO ZHI-YONG , HAN OAK-PIL , MA JING-CHEN , LEE HYE-JON , ALI MOHAMMAD , HAN CHANG-QUAN , XING ZHAN-CHUN , CHEN JI-CHAO , CLEMENS JOHN
Published: September 2018

In 2002, population- and treatment center–based surveillance was used to study the disease burden of shigellosis in rural Hebei Province in the People’s Republic of China. A total of 10,105 children with diarrhea or dysentery were enrolled. Infants were treated most frequently for diarrhea (1,388/1,000/year) followed by children ≤ 5 years old (618/1,000/year). Shigellosis was treated most often in children 3–4 years old (32/1,000/year) and people > 60 years of age (7/1,000/year). Fifty-six percent (184 of 331) Shigella isolates were detected in patients who had non-bloody diarrhea. Shigella flexneri was identified in 93% of 306 isolates. The most common S. flexneri serotypes were 1a (34%), X (33%), and 2a (28%). More than 90% of the Shigella isolates were resistant to cotrimoxazole and nalidixic acid, but remained susceptible to ciprofloxacin, norfloxacin, and gentamicin. Widespread resistance to antibiotics adds urgency to the development and use of vaccines to control shigellosis.
CRYPTOSPORIDIOSIS IN HIV-INFECTED VENEZUELAN ADULTS IS STRONGLY ASSOCIATED WITH ACUTE OR CHRONIC DIARRHEA
Authors: CERTAD GABRIELA , ARENAS-PINTO ALEJANDRO , POCATERRA LEONOR , FERRARA GIUSEPPE , CASTRO JULIO , BELLO ANDREINA , NÚÑEZ LUZ
Published: September 2018

A cross-sectional study was undertaken to determine the prevalence of cryptosporidiosis and its clinical and laboratory pattern in Venezuelan HIV-infected patients (N = 397). At enrollment, they underwent thorough clinical history and physical examination and provided stool specimens for the identification of Cryptosporidium sp. and other parasites. Cryptosporidium sp. was identified in 59 subjects (15%). This infection was strongly associated with acute and chronic diarrhea, weight loss, CD4+ counts below 100 cells/mm3, older age in patients with leukopenia, and more than 5 stools per day when CD4+ counts were below 100 cells/mm3. In addition, patients with Cryptosporidium infection were less likely to be coinfected with Isospora belli (OR = 0.05, P = 0.001). In fact, results of the current study confirm the worldwide importance of cryptosporidiosis as a clinically significant opportunistic infection associated with an advanced stage of immunosuppression.
DOES TRADITIONAL MEDICINE USE HAMPER EFFORTS AT TUBERCULOSIS CONTROL IN URBAN PERU?
Authors: OESER CLARISSA C. , ESCOMBE ADRIAN R. , GILMAN ROBERT H. , FRIEDLAND JON S. , EVANS CARLTON A. W. , MOORE DAVID A. J.
Published: September 2018

Decades of social and political unrest have contributed to the urbanization of the population of Peru with large-scale migration from rural Andean and Amazonian communities to overcrowded shantytowns around Lima. We administered a face-to-face survey questionnaire to 116 patients with suspected and proven tuberculosis (TB) in northern Lima to determine the extent to which the use of traditional therapies from indigenous regions persists and the impact of any such use on TB control. Sixty-three percent of participants reported some form of self-treatment prior to presentation to the National Tuberculosis Program; 52% of them used traditional remedies. Symptom duration was longer among self-remedy users than non-users (median = 25 versus 15 days; P = 0.07) and among those exclusively using western remedies rather than traditional remedies (median = 30 versus 15 days; P = 0.01). We thus found no evidence that use of traditional remedies has an appreciable effect on diagnostic delay in Lima.
PREDICTING CD4 COUNT USING TOTAL LYMPHOCYTE COUNT: A SUSTAINABLE TOOL FOR CLINICAL DECISIONS DURING HAART USE
Authors: MWAMBURI D. MKAYA , GHOSH MAYURIKA , FAUNTLEROY JIM , GORBACH SHERWOOD L. , WANKE CHRISTINE A.
Published: September 2018

Understanding the total lymphocyte count (TLC)-CD4 count relationship could aide design predictive instruments for making clinical decisions during antiretroviral therapy, especially in underserved resource-poor settings. We performed multiple regression analyses to assess the prediction of CD4 count using TLC on 771 participants with 4,836 visits. In linear and logistic regression TLC, hemoglobin, gender, history of AIDS, and weight predicted CD4 count and CD4 < 200, respectively, before and after highly active antiretroviral therapy (HAART) use. On HAART, the adjusted odds ratios (OR) for TLC < 1500 (optimal TLC cutoff) were 5.1 (95%CI 4.0, 6.5; P < 0.001), and off HAART, 4.6 (95%CI 3.4, 6.2: P < 0.001) with high predictive power. TLC predicts CD4 count and CD4 < 200 cells/μL well during HAART. Including the additional factors improves performance. TLC is simple and inexpensive and can be used in many ways to develop clinical decision-making tools in underserved resource-poor settings during HAART therapy.
THE NOVEL PLASMODIUM GALLINACEUM SPOROZOITE PROTEIN, PG93, IS PREFERENTIALLY EXPRESSED IN THE NUCLEUS OF OOCYST SPOROZOITES
Authors: LACRUE ALEXIS N. , JAMES ANTHONY A. , BEERNTSEN BRENDA T.
Published: September 2018

To study gene expression differences between oocyst and salivary gland sporozoites, cDNA libraries previously constructed from the two sporozoite populations of the avian malaria parasite, Plasmodium gallinaceum, were used in a subtractive hybridization protocol to isolate Pg93, a novel oocyst sporozoite gene. Pg93 encodes a putative ~76 kDa translated protein that was predicted to localize to the nucleus. Transcriptional analysis indicates that Pg93 is preferentially expressed in oocyst sporozoites versus salivary gland sporozoites. Immunolocalization assays confirm both the nuclear prediction and transcriptional analysis, suggesting that Pg93 is a nuclear protein. BLAST sequence analysis indicates that Pg93 represents a novel gene that has significant homology with a Plasmodium falciparum hypothetical protein and translated Plasmodium knowlesi and Plasmodium vivax nucleotide sequences. This is the first characterization of a Plasmodium nuclear protein that shows preferential expression in one sporozoite population as compared with the other population.
MILD, SELF-RESOLVING ACUTE LEPTOSPIROSIS IN AN HIV-INFECTED PATIENT IN THE PERUVIAN AMAZON
Authors: GANOZA CHRISTIAN A. , SEGURA EDDY R. , SWANCUTT MARK A. , GOTUZZO EDUARDO , VINETZ JOSEPH M.
Published: September 2018

We report a case of acute, self-resolving leptospirosis presenting in a HIV-positive patient from the Peruvian Amazon. The patient presented with an undifferentiated acute febrile illness that resolved without treatment, diagnosed retrospectively as leptospirosis by serology and real-time polymerase chain reaction. Five months later, he was admitted because of a febrile illness with jaundice, hepatosplenomegaly, peripheral edema, and oral candidiasis. Because of the clinical suspicion of AIDS, stored sera of the previous admission were tested, and HIV seropositivity was confirmed, proving that the condition was present at the first admission. Acute leptospirosis in HIV coinfection is not inevitably severe, and there is probably a wide variation in clinical manifestations similar to what occurs in immuno-competent hosts.
PRELIMINARY OBSERVATIONS ON THE EFFICACY OF A RECOMBINANT MULTISTAGE PLASMODIUM FALCIPARUM VACCINE IN AOTUS NANCYMAI MONKEYS
Authors: COLLINS WILLIAM E. , GALLAND G. GALE , BARNWELL JOHN W. , UDHAYAKUMAR VENKATACHALAM , SULLIVAN JOANN S. , NACE DOUGLAS , TONGREN JON ERIC , WILLIAMS TYRONE , ROBERTS JACQUELIN , SHI YA PING , LAL ALTAF A.
Published: September 2018

A vaccine trial was conducted to determine the efficacy of a multicomponent candidate vaccine, FALVAC-1, against Plasmodium falciparum in Aotus nancymai monkeys. After two immunizations, animals were challenged intravenously with parasites of the Vietnam Oak Knoll (FVO) strain of P. falciparum. The primary outcome was to determine the protective response of the monkeys to immunization with the FALVAC-1 antigen produced in baculovirus when combined with different adjuvants (alum, QS-21, ASO2a, CRL1005/oil, and CRL1005/saline) as compared with FALVAC-1 with FCA/FIA and antigen alone. When compared with the monkeys immunized with FALVAC-1 alone, FALVAC-1 with FCA/FIA reduced the mean parasite count (to Day 11), reduced the mean accumulated parasitemia (through Day 11), and extended the number of days to treatment. None of the other 5 antigen-adjuvant combinations were able to provide discernable levels of protection based on log(parasitemia) and log(cumulative parasitemia) to Day 11.
MALARIA AND NUTRITIONAL STATUS AMONG PRE-SCHOOL CHILDREN: RESULTS FROM CROSS-SECTIONAL SURVEYS IN WESTERN KENYA
Authors: FRIEDMAN JENNIFER F. , KWENA ARTHUR M. , MIREL LISA B. , KARIUKI SIMON K. , TERLOUW DIANNE J. , PHILLIPS-HOWARD PENELOPE A. , HAWLEY WILLIAM A. , NAHLEN BERNARD L. , SHI YA PING , KUILE FEIKO O. TER
Published: September 2018

Protein-energy malnutrition (PEM) affects millions of children in the developing world. The relationship between malaria and PEM is controversial. The goal of this study was to evaluate whether undernutrition is associated with increased or decreased malaria attributable morbidity. Three cross-sectional surveys were conducted using insecticide-treated bed nets (ITNs) among children aged 0–36 months living in an area with intense malaria transmission. Data were collected on nutritional status, recent history of clinical illness, socioeconomic status, current malaria infection status, and hemoglobin. In multivariate models, stunted children had more malaria parasitemia (odds ratio [OR] 1.98, P < 0.0001), high-density parasitemia (OR 1.84; P < 0.0001), clinical malaria (OR 1.77; P < 0.06), and severe malarial anemia (OR 2.65; P < 0.0001) than nonstunted children. The association was evident in children with mild-to-moderate (−3 < height-for-age Z-score [HAZ] < −2) and severe stunting (HAZ < −3). The cross-sectional nature of the study limits the interpretation of causality, but the data provide further observational support that the presence of undernutrition, in particular chronic undernutrition, places children at higher, not lower risk of malaria-related morbidity.
INHIBITORY EFFECT OF LACTOFERRIN ON IN VITRO GROWTH OF BABESIA CABALLI
Authors: IKADAI HIROMI , TANAKA TETSUYA , SHIBAHARA NONA , TANAKA HIROKO , MATSUU AYA , KUDO NOBORU , SHIMAZAKI KEI-ICHI , IGARASHI IKUO , OYAMADA TAKASHI
Published: September 2018

Lactoferrin (LF) is an important biologic molecule with many functions, one of which is antimicrobial defense. We evaluated the growth-inhibiting effects of four types of LF (native LF, Fe+3-bound [holo] LF, Fe+3-free [apo] LF, and LF hydrolyzate) on the in vitro growth of Babesia caballi and B. equi. The growth of B. caballi was significantly suppressed in media containing apo LF, but was not inhibited in media containing native LF, holo LF, or LF hydrolyzate. The growth of B. equi was not inhibited by media containing native LF, holo LF, or apo LF. These data indicate that apo LF had the strongest inhibitory effect on B. caballi. This may have been caused by inactivation or inhibition of a growth factor in the culture medium.
MICROSATELLITE AND MITOCHONDRIAL GENETIC DIFFERENTIATION OF ANOPHELES ARABIENSIS (DIPTERA: CULICIDAE) FROM WESTERN KENYA, THE GREAT RIFT VALLEY, AND COASTAL KENYA
Authors: TEMU EMMANUEL A. , YAN GUIYUN
Published: September 2018

The population genetic structure of the African malaria vector Anopheles arabiensis from western Kenya, the Great Rift Valley, and coastal Kenya was investigated using 12 microsatellite loci and a partial sequence of mtDNA dehydrogenase gene subunit 5 (ND5). The mean number of alleles and the observed heterozygosity were similar for the mosquito populations from the three regions as revealed by the microsatellite data. A total of 30 polymorphic sites in the ND5 gene defined 39 haplotypes. Six haplotypes were shared among four populations from the three distinct ecological conditions, and they constituted 92% of the total number of individuals sequenced. Mitochondrial haplotype and nucleotide diversity were high. Microsatellite markers within polymorphic inversions revealed a level of genetic differentiation (FST = 0.116) four to seven times higher than markers outside inversions (FST = 0.016) or inside fixed inversions (FST = 0.027). Mitochondrial ND5 gene sequences did not reveal significant genetic differentiation for the same four populations (ΦST = −0.008). The contrasts in the level of genetic differentiation between microsatellite markers inside polymorphic inversions, the mitochondrial ND5 gene, and microsatellite markers outside inversions suggest that the level of genetic differentiation in An. arabiensis populations across the Great Rift Valley varies significantly among different areas of the genome. Variations in the degree of genetic differentiation with respect to the chromosomal location of microsatellite markers may result from intrinsic characteristics of the markers, demographic or historic factors affecting these populations, and the possible adaptive significance of chromosomal inversions to climatic conditions.
HOUSEHOLD-BASED CERAMIC WATER FILTERS FOR THE PREVENTION OF DIARRHEA: A RANDOMIZED, CONTROLLED TRIAL OF A PILOT PROGRAM IN COLOMBIA
Authors: CLASEN THOMAS , PARRA GLORIA GARCIA , BOISSON SOPHIE , COLLIN SIMON
Published: September 2018

Household water treatment is increasingly recognized as an effective means of reducing the burden of diarrheal disease among low-income populations without access to safe water. Oxfam GB undertook a pilot project to explore the use of household-based ceramic water filters in three remote communities in Colombia. In a randomized, controlled trial over a period of six months, the filters were associated with a 75.3% reduction in arithmetic mean thermotolerant coliforms (TTCs) (P < 0.0001). A total of 47.7% and 24.2% of the samples from the intervention group had no detectible TTCs/100 mL or conformed to World Health Organization limits for low risk (1–10 TTCs/100 mL), respectively, compared with 0.9% and 7.3% for control group samples. Overall, prevalence of diarrhea was 60% less among households using filters than among control households (odds ratio = 0.40, 95% confidence interval = 0.25, 0.63, P < 0.0001). However, the microbiologic performance and protective effect of the filters was not uniform throughout the study communities, suggesting the need to consider the circumstances of the particular setting before implementing this intervention.
EVALUATION OF LYMPH NODE AND BONE MARROW CYTOLOGY IN THE DIAGNOSIS OF CANINE LEISHMANIASIS (LEISHMANIA INFANTUM) IN SYMPTOMATIC AND ASYMPTOMATIC DOGS
Authors: SARIDOMICHELAKIS MANOLIS N. , MYLONAKIS MATHIOS E. , LEONTIDES LEONIDAS S. , KOUTINAS ALEXANDER F. , BILLINIS CHARALAMBOS , KONTOS VASSILIOS I.
Published: September 2018

The sensitivity and specificity of lymph node and bone marrow smear microscopy for the diagnosis of Leishmania infantum–infected dogs was evaluated in 79 dogs with leishmaniasis (Group A), 52 asymptomatically infected dogs (Group B), and 44 healthy noninfected dogs (Group C). Light microscopy examination included 10 to 1,000 oil immersion fields, and the density of Leishmania amastigotes was scored by a 0 to +6 scale. Using polymerase chain reaction as the gold standard, the specificity of lymph node and bone marrow cytology was 100%, whereas sensitivity ranged from 7.8% to 92.6%, being significantly higher in Group A compared with Group B. The amastigote scores were also significantly higher in Group A compared with Group B. These results indicate that lymph node and bone marrow cytology is a highly sensitive and specific method for the diagnosis of canine patent leishmaniasis, whereas its sensitivity is relatively low in asymptomatic infections.
DETECTION OF EXCRETORY/SECRETORY COPROANTIGENS IN EXPERIMENTAL HOOKWORM INFECTION
Authors: BUNGIRO RICHARD D. , CAPPELLO MICHAEL
Published: September 2018

This report describes the detection of hookworm excretory/secretory (ES) antigens in soluble hamster fecal extracts by an enzyme-linked immunosorbent assay (ELISA). A rabbit polyclonal IgG antibody against Ancylostoma ceylanicum ES was used to capture hookworm coproantigens that were then detected using pooled, high-titer, infected hamster serum. The ELISA was capable of detecting ES proteins over a range of 10 ng/mL to 10 μg/mL when the antigens were diluted in buffer or uninfected fecal extract, and ES could be detected in infected hamster feces at dilutions up to 1:256. Examination of the kinetics of coproantigen production demonstrated that detectable amounts of ES were produced as early as four days after A. ceylanicum infection, whereas fecal eggs were not observed until day 17. Moreover, fecal ES levels correlated well with intestinal worm burden and could be detected in wet or dry stool samples stored for 14 days over a temperature range of −80°C to 37°C. The fecal ELISA was then adapted to analyze the excretion of AceES-2, a novel immunogenic ES protein recently cloned from A. ceylanicum cDNA. AceES-2 was found to be excreted in feces with kinetics similar to that of whole ES. Examination of individual hookworm antigens by this method will provide new insights into the molecular host-parasite interaction and may form the basis for future diagnostic methods.
AMEBIC COLITIS IN ASYMPTOMATIC SUBJECTS WITH POSITIVE FECAL OCCULT BLOOD TEST RESULTS: CLINICAL FEATURES DIFFERENT FROM SYMPTOMATIC CASES
Authors: OKAMOTO MAKOTO , KAWABE TAKAO , OHATA KEN , TOGO GOUICHI , HADA TETSUYA , KATAMOTO TETSUROU , TANNO MASATAKA , MATSUMURA MASAYUKI , YAMAJI YUTAKA , WATABE HIROTSUGU , IKENOUE TSUNEO , YOSHIDA HARUHIKO , OMATA MASAO
Published: September 2018

Amebiasis is a common parasitic infectious disease in developing countries. In developed countries, it is occasionally encountered in travelers to the tropics and in homosexual males. During the past eight years, we detected four cases of amebic colitis among 5,193 subjects who underwent colonoscopy because of positive fecal occult blood test results in a mass screening. All four cases did not have any abdominal symptoms. Ulcerative lesions were observed only in the cecum and ascending colon; another portion of the colon and rectum appeared normal. We may encounter amebic colitis during colonoscopic examination even in subjects who are asymptomatic.
EVALUATION OF A NEW RAPID IMMUNOCHROMATOGRAPHIC ASSAY FOR SERODIAGNOSIS OF ACUTE HEPATITIS E INFECTION
Authors: MYINT KHIN S. A. , GUAN MING , CHEN HSIAO YING , LU YANG , ANDERSON DAVID , HOWARD TERESA , NOEDL HARALD , MAMMEN MAMMEN P.
Published: September 2018

A rapid and reliable diagnostic assay for acute hepatitis E virus (HEV) infection is needed. We evaluated a rapid, immunochromatographic assay for IgM antibodies to HEV (ASSURE™ HEV IgM Rapid Test) using acute-phase HEV samples (n = 200) from Indonesia and Nepal and convalescent-phase HEV samples (n = 70) from Nepal. Blood donors in Thailand (n = 100), individuals with hepatitis A (n = 80), hepatitis B (n = 45), and hepatitis C (n = 50) in Thailand and Nepal, acute-phase sera of individuals with Epstein-Barr virus infection (n = 20), and rheumatoid factor–positive blood (n = 26) served as negative controls. The assay had a sensitivity of 93% (95% confidence interval [CI] = 88.5–96.1%) and a specificity of 99.7% (95% CI = 98.3–100%). The positive and negative predictive values were 99.5% (95% CI = 97.1–100%) and 95.8% (95% CI = 93.1–97.7%), respectively. These results suggest that this assay is a sensitive and specific tool for the rapid diagnosis of acute HEV infection.
FIELD EVALUATION OF THE MEADE READIVIEW HANDHELD MICROSCOPE FOR DIAGNOSIS OF INTESTINAL SCHISTOSOMIASIS IN UGANDAN SCHOOL CHILDREN
Authors: STOTHARD J. RUSSELL , KABATEREINE NARCIS B. , TUKAHEBWA EDRIDAH M. , KAZIBWE FRANCIS , MATHIESON WILLIAM , WEBSTER JOANNE P. , FENWICK ALAN
Published: September 2018

A novel, inexpensive handheld microscope, the Meade Readiview, was evaluated for field diagnosis of intestinal schistosomiasis by comparison of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) against conventional compound microscopy as part of a parasitologic survey in nine sentinel schools and a rapid mapping survey across 22 schools in Uganda. Fecal smears from 685 primary school children were examined and the overall prevalence of Schistosoma mansoni was 45%. However, prevalence by school ranged widely from 0% to 100%. For individual diagnosis the Readiview had a sensitivity of 85%, a specificity of 96%, a PPV of 95%, and an NPV of 88%. Due to the poorer movement control of the glass slide on the Readiview stage, fecal smears with less than four eggs could be overlooked. At the highest magnification (160×), egg-like objects could be confounding. Estimating prevalence by school was usually within ± 7% of that of conventional microscopy. Since the Readiview is more robust and portable, both in size and weight, and one-tenth as expensive as the traditional compound microscope, a change in the logistics and costs associated with field infection surveillance is possible. This inexpensive microscope is a pragmatic alternative to the compound microscope. It could play an important role in the collection of prevalence data to better guide anthelmintic drug delivery and also empower the diagnostic capacity of peripheral health centers where compound microscopes are few or absent.
RESPONSES TO LEISHMANIA DONOVANI IN MICE DEFICIENT IN BOTH PHAGOCYTE OXIDASE AND INDUCIBLE NITRIC OXIDE SYNTHASE
Authors: MURRAY HENRY W. , XIANG ZHAOYING , MA XIAOJING
Published: September 2018

Mice deficient in phagocyte oxidase (phox) and inducible nitric oxide synthase (iNOS), which are primary macrophage killing mechanisms, generated tissue granulomas but showed unrestrained Leishmania donovani visceral replication and suboptimal initial responsiveness to antimony treatment. Nevertheless, visceral infection was controlled post-treatment and did not recur. A phox/iNOS-independent macrophage mechanism, which was not triggered by L. donovani, emerges after chemotherapy.
EXPERIMENTAL YELLOW FEVER VIRUS INFECTION IN THE GOLDEN HAMSTER (MESOCRICETUS AURATUS) III. CLINICAL LABORATORY VALUES
Authors: SBRANA ELENA , XIAO SHU-YUAN , POPOV VSEVOLOD L. , NEWMAN PATRICK C. , TESH ROBERT B.
Published: September 2018

Using a recently described hamster model of yellow fever (YF), we compared the hematologic and clinical chemistry changes that occur in blood with the histopathologic alternations observed in liver and other organs. Inflammatory foci and necroapoptotic hepatocytes were first observed in the liver three days after YF infection. This was accompanied by a rapid increase in serum transaminase and bilirubin values, elevation of prothrombin times, thrombocytopenia, and leukocytosis. Maximum liver pathology was observed on the sixth and seventh days post-infection; this corresponded to the peak alternations in clinical chemistry and hematologic values. In surviving hamsters, regenerating hepatocytes began to appear on the eighth day post-infection; this was accompanied by a corresponding return to baseline levels of most of the aforementioned clinical laboratory values. The histopathologic and clinical laboratory findings in the hamster model were very similar to those observed in severe human cases of YF. These results provide further validation of the utility of the hamster model for studying the pathogenesis and treatment of YF.
HEPATITIS C INFECTION AMONG DRUG USERS IN NORTHERN THAILAND
Authors: JITTIWUTIKARN JAROON , THONGSAWAT SATAWAT , SURIYANON VINAI , MANEEKARN NIWAT , CELENTANO DAVID , RAZAK MYAT HTOO , SRIRAK NAMTIP , VONGCHAK TASSANAI , KAWICHAI SURINDA , THOMAS DAVID , SRIPAIPAN TEERADA , NETSKI DALE , ANANTHAKRISHNAN ASHWIN , NELSON KENRAD E.
Published: September 2018

Illicit drug users are commonly infected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). We evaluated the prevalence, incidence, and risk behaviors associated with HCV infection in 1,859 drug users in northern Thailand. The HCV prevalence was 27.3%: 86.0% among drug injectors (IDUs) and 5.3% among those who did not inject. Sexual behavior was not significantly associated with HCV among IDUs or drug users who used but didn’t inject illicit drugs; only injection behaviors were independently associated with HCV in multivariate analysis. Among men, a history and increasing frequency of injecting drugs, older age, and a history of incarceration were associated with HCV infection. Among 514 opiate users who were HCV and HIV seronegative at baseline, 41 incident HCV infections and 6 HIV infections occurred on follow-up; the HCV incidence was 5.43/100 person-years; it was 44.3/100 person-years in IDUs and 1.9/100 person-years in non-injectors. HCV and HIV among drug users in Thailand are common and primarily associated with injection behavior.
TREATMENT OF EOSINOPHILIC MENINGITIS WITH A COMBINATION OF PREDNISOLONE AND MEBENDAZOLE
Authors: CHOTMONGKOL VERAJIT , SAWADPANITCH KOOKWAN , SAWANYAWISUTH KITTISAK , LOUHAWILAI SITICHOKE , LIMPAWATTANA PANITA
Published: September 2018

To study the efficacy of the combination of prednisolone and mebendazole for the treatment of eosinophilic meningitis, we conducted a pilot study among Thai patients with eosinophilic meningitis. Patients were given a two-week course of prednisolone, 60 mg/day, and mebendazole, 10 mg/kg/day. The primary observation parameter was the number of patients who still had headaches after the two-week course of treatment. Forty-one patients were enrolled in the study. Four (10%) patients still had headaches after the two-week course of treatment and the median length of time until complete disappearance of headaches was three days. Serious side effects were not detected. Treatment for two weeks with the combination regimen of prednisolone and mebendazole is safe and beneficial in relieving headaches in patients with eosinophilic meningitis.
SEROLOGICAL EVIDENCE OF INFECTION WITH RICKETTSIA TYPHI AND RICKETTSIA FELIS AMONG THE HUMAN POPULATION OF CATALONIA, IN THE NORTHEAST OF SPAIN
Authors: NOGUERAS MARÍA MERCEDES , CARDEÑOSA NEUS , SANFELIU ISABEL , MUÑOZ TOMÁS , FONT BERNAT , SEGURA FERRAN
Published: September 2018

Murine typhus (MT) is a cause of fever of intermediate duration in the south of Spain. Rickettsia typhi has been described as the MT etiological agent. Rickettsia felis produces an infection similar to MT. The aim of the study is to determine their seroprevalence in humans in Catalonia. Antibodies to Rickettsia typhi and Rickettsia felis from 217 serum samples were examined by indirect immunofluorescence assay (IFA). Age, gender, residence area, contact with animals, and occupation were surveyed. Rickettsia typhi and Rickettsia felis seroprevalences were 8.8% and 3.2%, respectively. Rickettsia typhi was present in 7.6% of the samples in urban, 8.5% in semirural, and in 21.4% in rural areas, whereas Rickettsia felis was present in 3.5% in urban, 1.7% in semirural, and 7.1% in rural area. The only statistically significant association observed was that between Rickettsia felis seropositivity and age. Our data seem to indicate the presence of Rickettsia typhi and Rickettsia felis in humans in Catalonia.
AN OUTBREAK OF LEPTOSPIROSIS AMONG ISRAELI TROOPS NEAR THE JORDAN RIVER
Authors: HADAD E. , PIROGOVSKY A. , BARTAL C. , GILAD J. , BARNEA A. , YITZHAKI S. , GROTTO I. , BALICER R. D. , SCHWARTZ E.
Published: September 2018

An outbreak of leptospirosis that involved 7 of a team of 27 Israeli troops occurred following a military exercise in northern Israel near the Jordan River. The organism implicated in the outbreak was Leptospira interrogans serovar Hardjo. The clinical course was uncomplicated and all patients fully recovered. There were no cases of asymptomatic infection. Military personnel should be recognized as having an occupational risk for contracting leptospirosis, especially when military activity takes place near natural water sources inhabited by cattle, taking into account the local epidemiology of this disease. Moreover, outbreaks among military personnel may serve as a sentinel for leptospiral illness in areas in which civilian exposure takes place, such as the Jordan River, which is an important site that involves immersion in the context of both pilgrimage and civilian recreational activities.

“Bathe and you will become clean. So he went down and immersed himself seven times in the Jordan, as Elisha had told him to do. And his flesh became clean once more like the flesh of a small child.”

II Kings 5:14
CLINIC-BASED SURVEILLANCE FOR BACTERIAL- AND ROTAVIRUS-ASSOCIATED DIARRHEA IN EGYPTIAN CHILDREN
Authors: WIERZBA THOMAS F. , ABDEL-MESSIH IBRAHIM ADIB , ABU-ELYAZEED REMON , PUTNAM SHANNON D. , KAMAL KARIM A. , ROZMAJZL PATRICK , AHMED SALWA F. , FATAH ABDEL , ZABEDY KHALED , SHAHEEN HIND I. , SANDERS JOHN , FRENCK ROBERT
Published: September 2018

To identify enteropathogens for vaccine development, we implemented clinic-based surveillance for severe pediatric diarrhea in Egypt’s Nile River Delta. Over 2 years, a physician clinically evaluated and obtained stool samples for microbiology from patients with diarrhea and less than 6 years of age. In the first (N = 714) and second clinic (N = 561), respectively, 36% (N = 254) and 46% (N = 260) of children were infected with rotavirus, enterotoxigenic Escherichia coli (ETEC), Campylobacter, or Shigella. When excluding mixed rotavirus-bacterial infections, for the first and second clinic, 23% and 10% had rotavirus-associated diarrhea, and 14% and 17% had ETEC-associated diarrhea, respectively. Campylobacter-associated diarrhea was 1% and 3%, and Shigella-associated diarrhea was 2% and 1%, respectively, for the two clinics. Rotavirus-associated diarrhea peaked in late summer to early winter, while bacterial agents were prevalent during summer. Rotavirus-associated cases presented with dehydration, vomiting, and were often hospitalized. Children with Shigella- or Campylobacter-associated diarrhea reported as watery diarrhea and rarely dysentery. ETEC did not have any clinically distinct characteristics. For vaccine development and/or deployment, our study suggests that rotavirus is of principle concern, followed by ETEC, Shigella, and Campylobacter.
DELAYED-TYPE HYPERSENSITIVITY SKIN TEST REACTIVITY AND SURVIVAL IN HIV-INFECTED PATIENTS IN UGANDA: SHOULD ANERGY BE A CRITERION TO START ANTIRETROVIRAL THERAPY IN LOW-INCOME COUNTRIES?
Authors: JONES-LÓPEZ EDWARD C. , OKWERA ALPHONSE , MAYANJA-KIZZA HARRIET , ELLNER JERROLD J. , MUGERWA ROY D. , WHALEN CHRISTOPHER C. , _ _
Published: September 2018

Access to antiretroviral (ARV) drugs is improving in sub-Saharan Africa but still constrained by several clinical and logistical obstacles. There is a need to develop affordable markers to guide initiation of treatment. We present a prospective cohort study of 779 patients participating in a TB prophylaxis trial. We performed separate analyses for anergic and nonanergic subjects. Prognostic factors for anergic and nonanergic subjects differed between groups. Individuals with anergy and constitutional symptoms were at the highest risk of death. Incident tuberculosis and CD4 < 200 cells/μL at enrollment were the strongest risk factors for death. HIV disease is associated with substantial morbidity and mortality in this population. The burden caused by tuberculosis is particularly high. Anergy is a strong and independent predictor of death. World Health Organization criteria to start ARV may be strengthened with the addition of DTH testing, an inexpensive and readily available tool in sub-Saharan Africa.
HIGH TITERS OF IgG ANTIBODIES AGAINST PLASMODIUM FALCIPARUM SERINE REPEAT ANTIGEN 5 (SERA5) ARE ASSOCIATED WITH PROTECTION AGAINST SEVERE MALARIA IN UGANDAN CHILDREN
Authors: OKECH BRENDA , MUJUZI GODFREY , OGWAL ALEX , SHIRAI HIROKI , HORII TOSHIHIRO , EGWANG THOMAS G.
Published: September 2018

Plasmodium falciparum serine repeat antigen (SERA5) is a promising asexual blood stage malaria candidate vaccine. However, there is a paucity of information about natural immune responses to SERA5 in children from malaria-endemic regions. We undertook a hospital-based case-control study of severe malaria in Apac District, Northern Uganda, in children 6–59 months of age. The commonest symptoms observed in children with severe malaria (SM) were respiratory distress (53.4%) and prostration (40.4%) followed by circulatory collapse (7.4%), severe anemia (Hb < 5 g/dL, 7.0%), and seizures (2.6%). None of the SM children had impaired consciousness, coma, or cerebral malaria. We measured serum IgG antibodies using a recombinant construct of SERA5 (SE36) in enzyme-linked immunosorbent assays. High titers of IgG anti-SE36 were associated with protection against severe malaria in children under 5 years old.
A CASE-CONTROL AUDITORY EVALUATION OF PATIENTS TREATED WITH ARTEMETHER-LUMEFANTRINE
Authors: HUTAGALUNG ROBERT , HTOO HSAR , NWEE PAW , ARUNKAMOMKIRI JARUWAN , ZWANG JULIEN , CARRARA VERENA I. , ASHLEY ELIZABETH , SINGHASIVANON PRATAP , WHITE NICHOLAS J. , NOSTEN FRANÇOIS
Published: September 2018

Artemether-lumefantrine is the first registered, fixed, artemisinin-based combination treatment. Artemisinin derivatives are highly effective antimalarials with a favorable safety profile. Concerns remain over their potential neurotoxicity, although there has been no clinical evidence of this in humans. In animals (rats, dogs, and monkeys) artemether, a derivative of artemisinin is associated with an unusual toxicity pattern in specific brain nuclei involving the auditory and vestibular pathways. A recent report from Mozambique described a small but significant and irreversible hearing loss in patients exposed to artemether-lumefantrine. To explore this issue, we conducted a case-control study using tympanometry, audiometry and auditory brain-stem responses. We assessed 68 subjects who had been treated with artemether-lumefantrine within the previous five years and 68 age- and sex-matched controls living in the malarious region along the Thailand-Myanmar border. There were no differences in the test results between cases and controls. There was no neurophysiologic evidence of auditory brainstem toxicity that could be attributed to artemether-lumefantrine in this study population.