bluuebunny/crossref_metadata_2025 huggingface dataset:
ASSOCIATION OF VIRULENCE FACTOR-POSITIVE AND -NEGATIVE ENTEROAGGREGATIVE ESCHERICHIA COLI AND OCCURRENCE OF CLINICAL ILLNESS IN TRAVELERS FROM THE UNITED STATES TO MEXICO
Authors: HUANG DAVID B. , JIANG ZHI-DONG , DUPONT HERBERT L.
Published: September 2018

The objective of the study was to determine if the presence or absence of virulence factor-positive and -negative enteroaggregative Escherichia coli (EAEC) determined the occurrence of illness or sub-clinical EAEC infection in travelers from the United States to Mexico. Sixty-five newly arrived college students from the United States submitted weekly stool samples for a four-week period of time. Among EAEC-infected subjects, diarrhea occurred in those with a defined virulence factor with the following frequency: aggA, 5 of 15 (33%); aggR, 3 of 11 (27%); aafA, 3 of 8 (38%); and aspU, 1 of 6 (17%). Twenty-two of 31 students (71%) had two or more EAEC infections. After the initial EAEC infection, only 4 (11%) of 31 students had a subsequent symptomatic EAEC infection. Our study suggests that clinical illness by EAEC is not explained by presence of a defined EAEC virulence factors, and we provide suggestive evidence that EAEC infection protects against future symptomatic infection.
INDUCIBLE NITRIC OXIDE SYNTHASE (NOS2) PROMOTER CCTTT REPEAT POLYMORPHISM: RELATIONSHIP TO IN VIVO NITRIC OXIDE PRODUCTION/NOS ACTIVITY IN AN ASYMPTOMATIC MALARIA-ENDEMIC POPULATION
Authors: BOUTLIS CRAIG S. , HOBBS MAURINE R. , MARSH ROBYN L. , MISUKONIS MARY A. , TKACHUK ARIANA N. , LAGOG MOSES , BOOTH JENNIFER , GRANGER DONALD L. , BOCKARIE MOSES J. , MGONE CHARLES S. , LEVESQUE MARC C. , WEINBERG J. BRICE , ANSTEY NICHOLAS M.
Published: September 2018

Polymorphisms in the inducible nitric oxide synthase gene (NOS2) promoter have been associated with clinical outcome from malaria. These include a CCTTT repeat (CCTTTn) 2.5 kilobases upstream from the NOS2 transcription start site, and two single nucleotide substitutions: G→ C at position -954 (G-954C), and C→ T at position -1173 (C-1173T). Although hypothesized to influence NO production in vivo, the functional relevance of (CCTTT)n and G-954C is uncertain because disease association studies have yielded inconsistent results. This study found no association between CCTTT repeat number and levels of plasma NO metabolites or peripheral blood mononuclear cell NOS activity in a cohort of asymptomatic malaria-exposed coastal Papua New Guineans 1–60 years old. This suggests that (CCTTT)n does not independently influence NOS2 transcription in vivo. Neither the G-954C nor the C-1173T polymorphisms were identified in this population, indicating the variability and complexity of selection for NOS2 promoter polymorphisms in different malaria-endemic populations.
A SURVEY FOR SPOTTED FEVER GROUP RICKETTSIAE AND EHRLICHIAE IN AMBLYOMMA VARIEGATUM FROM ST. KITTS AND NEVIS
Authors: KELLY PATRICK J. , FOURNIER PIERRE-EDOUARD , PAROLA PHILIPPE , RAOULT DIDIER
Published: September 2018

Eighty-nine Amblyomma variegatum ticks were collected from the islands of St. Kitts and Nevis in the Caribbean and preserved in 70% ethanol or local rum. After being washed in sterile water, their DNA was extracted and analyzed by a polymerase chain reaction (PCR) for DNA of spotted fever group rickettsiae and ehrlichiae. None of the tested ticks was positive in a PCR assay using the primers 16S EHRD and 16S EHRR for the 16S rRNA gene of Ehrlichia spp. Forty-one percent of the A. variegatum (36 of /89 of which 34 [47%] of 72 were adult males, 2 (13%) of 16 were adult females, and 0 (0%) of 1 were nymphs) were positive in a PCR assay using the primer pair 190-70 and 190-701 for the outer membrane protein A (ompA) gene of spotted fever group rickettsiae. All PCR amplification products obtained had 100% sequence homology with Rickettsia africae, the agent of African tick-bite fever.
HIGH SEASONAL VARIATION IN ENTOMOLOGIC INOCULATION RATES IN ERITREA, A SEMI-ARID REGION OF UNSTABLE MALARIA IN AFRICA
Authors: SHILILU JOSEPHAT , GHEBREMESKEL TEWOLDE , MENGISTU SOLOMON , FEKADU HELEN , ZEROM MEHARI , MBOGO CHARLES , GITHURE JOHN , NOVAK ROBERT , BRANTLY EUGENE , BEIER JOHN C.
Published: September 2018

Entomologic studies were conducted in eight villages to investigate the patterns of malaria transmission in different ecologic zones in Eritrea. Mosquito collections were conducted for 24 months between September 1999 and January 2002. The biting rates of Anopheles arabiensis were highly seasonal, with activity concentrated in the wet season between June and October in the highlands and western lowlands, and between December and March in the coastal region. The biting rates in the western lowlands were twice as high as in the western escarpment and 20 times higher than in the coastal region. Sporozoite rates were not significantly different among villages. The risk of infection ranged from zero on the coast to 70.6 infective bites per year in the western lowlands. The number of days it would take for an individual to receive an infective bite from an infected An. arabiensis was variable among villages (range = 2.8–203.1 days). The data revealed the presence of only one main malaria transmission period between July and October for the highlands and western lowlands. Peak inoculation rates were recorded in August and September (range = 0.29–43.6 infective bits/person/month) at all sites over the two-year period. The annual entomologic inoculation rates (EIRs) varied greatly depending on year. The EIR profiles indicated that the risk of exposure to infected mosquitoes is highly heterogeneous and seasonal, with high inoculation rates during the rainy season, and with little or no transmission during the dry season. This study demonstrates the need to generate spatial and temporal data on transmission intensity on smaller scales to guide targeted control of malaria operations in semi-arid regions. Furthermore, EIR estimates derived in the present study provide a means of quantifying levels of exposure to infected mosquitoes in different regions of the country and could be important for evaluating the efficacy of vector control measures, since Eritrea has made significant steps in reducing the burden of malaria based on the Roll Back Malaria initiative of the World Health Organization.
A LARGE OUTBREAK OF HISTOPLASMOSIS AMONG AMERICAN TRAVELERS ASSOCIATED WITH A HOTEL IN ACAPULCO, MEXICO, SPRING 2001
Authors: MORGAN JULIETTE , CANO MARIA V. , FEIKIN DANIEL R. , PHELAN MAUREEN , VELAZQUEZ MONROY OSCAR , KURI MORALES PABLO , CARPENTER JOSEPH , WELTMAN ANDRE , SPITZER PETER G. , LIU HANS H. , MIRZA SARA A. , BRONSTEIN DAVID E. , MORGAN DANIEL J. , KIRKMAN LAURA A. , BRANDT MARY E. , IQBAL NAUREEN , LINDSLEY MARK D. , WARNOCK DAVID W. , HAJJEH RANA A. , _ _
Published: September 2018

During spring 2001, college students from Pennsylvania reported an acute febrile respiratory illness after returning from spring break vacation in Acapulco, Mexico. Acute pulmonary histoplasmosis was presumptively diagnosed and the cluster of illness was reported to the Centers of Disease Control and Prevention. A large investigation then ensued, which included finding student-travelers for interviews and requesting sera for histoplasmosis testing. We defined a clinical case by fever and at least one of the following: cough, shortness of breath, chest pain, or headache, in an Acapulco traveler during March–May 2001. A laboratory-confirmed case had positive serology. An initial study determined that the likely site of histoplasmosis exposure was Hotel H; we therefore performed a large cohort study among travelers who stayed at Hotel H. Of 757 contacted, 262 (36%) met the clinical case definition. Of 273 serum specimens tested, 148 (54%) were positive. Frequent use of Hotel H’s stairwells, where construction was ongoing, was associated with increased risk of illness (relative risk = 10.5, 95% confidence interval = 3.7–30.5; P < 0.001). This is the first histoplasmosis outbreak associated with a hotel undergoing construction. Hotels in endemic areas should consider construction precaution measures to prevent histoplasmosis among their guests.
A NEW FOCUS OF SCHISTOSOMA MANSONI IN YORO VILLAGE, MBAM AND INOUBOU DIVISION, CAMEROON
Authors: MOYOU-SOMO ROGER , KOUEMENI LYSETTE ELISABETH , NDJAMEN BLAISE , NGOGANG JEANNE , DONGLA ROGER , LONGANG-TCHATCHOUANG VIRGINIE , HASSIMI MOHAMADOU
Published: September 2018

Investigations on intestinal schistosomiasis were carried out in Yoro, a small village located in the transitional zone between forest and savannah, in the Mbam and Inoubou Division of Cameroon. Four human-water contact points were identified in the village and sampled for snails, and the inhabitants underwent parasitologic and clinical surveys to search for signs and symptoms of intestinal schistosomiasis. The results indicated the presence of two freshwater snails, both potential intermediate hosts of Schistosoma sp: Biomphalaria pfeifferi and Bulinus forskalii. However, only the former species was incriminated in the transmission of the disease, with the prevalence of snail infection being 10% (1 of 10) and 14.3% (2 of 14), respectively, during surveys 1 (in the dry season) and 2 (in the rainy season). The overall prevalence of Schistosoma mansoni eggs in stool samples was 54.4% (98 of 180). The mean ± SD intensity of infection was 100.3 ± 114.7 eggs per gram of stool. Eggs of S. intercalatum were not detected during parasitologic examination of stool specimens. In Cameroon, it appears that unlike the distribution of S. mansoni, which usually follows that of B. pfeifferi, B. forskalii is commonly found where S. intercalatum does not exist due to competitive exclusion through introgressive hybridization. Of the 180 people included in the study, 52.3% reported abdominal pain and 37.5% had bloody stools. Splenomegaly and hepatomegaly were noted in 11.7% and 3.9%, respectively, of the subjects examined. Three foci of S. mansoni were previously described in the Mbam and Inoubou Division, including Bafia town, Makenene, and Kinding Djabi villages. With the present focus in Yoro, the Mbam and Inoubou Division appears to be the most important endemic zone of S. mansoni in southern Cameroon.
GEOGRAPHIC AND ECOLOGIC DISTRIBUTIONS OF THE ANOPHELES GAMBIAE COMPLEX PREDICTED USING A GENETIC ALGORITHM
Authors: LEVINE REBECCA S. , PETERSON A. TOWNSEND , BENEDICT MARK Q.
Published: September 2018

The distribution of the Anopheles gambiae complex of malaria vectors in Africa is uncertain due to under-sampling of vast regions. We use ecologic niche modeling to predict the potential distribution of three members of the complex (A. gambiae, A. arabiensis, and A. quadriannulatus) and demonstrate the statistical significance of the models. Predictions correspond well to previous estimates, but provide detail regarding spatial discontinuities in the distribution of A. gambiae s.s. that are consistent with population genetic studies. Our predictions also identify large areas of Africa where the presence of A. arabiensis is predicted, but few specimens have been obtained, suggesting under-sampling of the species. Finally, we project models developed from African distribution data for the late 1900s into the past and to South America to determine retrospectively whether the deadly 1929 introduction of A. gambiae sensu lato into Brazil was more likely that of A. gambiae sensu stricto or A. arabiensis.
A NOVEL DNA-BASED MICROFLUORIMETRIC METHOD TO EVALUATE ANTIMALARIAL DRUG ACTIVITY
Authors: CORBETT YOLANDA , HERRERA LIURIS , GONZALEZ JOSE , CUBILLA LUIS , CAPSON TODD L. , COLEY PHYLLIS D. , KURSAR THOMAS A. , ROMERO LUZ I. , ORTEGA-BARRIA EDUARDO
Published: September 2018

This paper describes the development of a novel microfluorimetric assay to measure the inhibition of Plasmodium falciparum based on the detection of parasitic DNA by intercalation with PicoGreen®. The method was used to determine parasite inhibition profiles and 50% inhibitory concentration values of known or potential antimalarial drugs. Values for parasite inhibition with known antimalarial drugs using the PicoGreen® assay were comparable with those determined by the standard method based upon the uptake of 3H-hypoxanthine and the Giemsa stain microscopic technique. The PicoGreen® assay is rapid, sensitive, reproducible, easily interpreted, and ideally suited for screening of large numbers of samples for antimalarial drug development.
EFFICACY OF SULFADOXINE/PYRIMETHAMINE IN THE TREATMENT OF UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA IN REPUBLIC OF CONGO
Authors: NSIMBA BASILE , MALONGA DAVID A. , MOUATA ANDRE M. , LOUYA FREDERIC , KIORI JEANNINE , MALANDA MAURICE , YOCKA DOMINIQUE , OKO-OSSHO JOSEPH , EBATA-MONGO STANISLAS , LE BRAS JACQUES
Published: September 2018

Congo is facing frequent failures of treatment of Plasmodium falciparum malaria with chloroquine (CQ), which is still recommended and used as a first-line drug. In Pointe-Noire and Brazzaville, the two largest cities that contain approximately 60% of the population of Congo, we compared the efficacy of CQ versus sulfadoxine/pyrimethamine (SP) for treatment of uncomplicated malaria in children 6–59 months old (mean = 33 months) using the standard World Health Organization (WHO) 14-day in vivo test in two phases between 1999 and 2002. Patients enrolled were randomly assigned to receive SP (25 mg/kg of sulfadoxine and 1.25 mg/kg of pyrimethamine) or CQ (25 mg/kg). In the first phase of the study, 46 patients were assigned to the CQ (n = 23) or SP (n = 23) groups in Pointe-Noire and 52 children were assigned to the CQ (n = 26) or to SP (n = 26) groups in Brazzaville. Results were interpreted according to the WHO lot quality assurance sampling method, and treatment failure rates for SP versus CQ were < 25% versus > 25% in both cities. In the second phase of the study, we accurately determined the actual proportion of treatment failures for SP in Brazzaville. Thus, in 75 of the 80 children enrolled and followed-up until day 14, no clinical or parasitologic failure was recorded and no serious adverse reaction was observed. Since the CQ treatment failure rate exceeds the unacceptable upper limit, SP seems well to be an appropriate alternative for the first-line treatment of uncomplicated P. falciparum malaria, at least in the settings of the present study.
FIELD DETECTION OF EASTERN EQUINE ENCEPHALITIS VIRUS IN THE AMAZON BASIN REGION OF PERU USING REVERSE TRANSCRIPTION-POLYMERASE CHAIN REACTION ADAPTED FOR FIELD IDENTIFICATION OF ARTHROPOD-BORNE PATHOGENS
Authors: O’GUINN MONICA L. , LEE JOHN S. , KONDIG JOHN P. , FERNANDEZ ROBERTO , CARBAJAL FAUSTINO
Published: September 2018

In support of efforts to develop rapid diagnostic assays for use in the field, reverse transcription-polymerase chain reaction (RT-PCR) assays were developed to detect arboviruses circulating in the Amazon Basin region of Peru. Previous knowledge of arthropod/pathogen relationships allowed a focused evaluation to be conducted in November 2000 that assessed the feasibility and reliability of a mobile, rapid, field-expedient RT-PCR diagnostic system aimed at detecting eastern equine encephalitis virus (EEEV) in Culex (Melanoconion) pedroi mosquitoes. Modifications were made to a commercially available mobile molecular laboratory kit and assay procedures were tailored for use under harsh environmental conditions with field-collected and field-processed mosquitoes. From CO2 baited mosquito light traps, 3,227 Cx. (Mel.) pedroi mosquitoes were collected and sorted into 117 pools. The pools were processed and assayed in the field by RT-PCR and five of those pools were found positive for EEEV. Laboratory sequence analysis confirmed the presence of two distinct subtypes of EEEV.
MOLECULAR EPIDEMIOLOGY OF MALARIA IN CAMEROON. XIX. QUALITY OF ANTIMALARIAL DRUGS USED FOR SELF-MEDICATION
Authors: BASCO LEONARDO K.
Published: September 2018

Substandard and counterfeit pharmaceutical products are increasingly circulating and distributed around the world, in particular in less developed countries. These low-quality or counterfeit products often involve drugs that are in high demand for the prevention and treatment of highly prevalent diseases, such as antimalarial drugs in endemic countries. Self-medication for presumed malarial infections with drugs purchased from unofficial drug vendors is a common practice in Africa. The aim of the study was to investigate the quality of chloroquine, quinine, and sulfadoxine-pyrimethamine obtained from illegitimate sector in urban and rural areas in Cameroon and analyze the impact of these drugs on patients. We collected 284 samples of three antimalarial drugs from 132 different sources in 16 villages and cities throughout the country. We also collected antimalarial drugs that were used for self-medication by malaria-infected patients. Drug quality was assessed by a simple color reaction test and semi-quantitative thin-layer chromatography. Fifty (38%) of 133 chloroquine, 52 (74%) of 70 quinine, and 10 (12%) of 81 antifolates had either no active ingredient, an insufficient active ingredient, the wrong ingredient, or unknown ingredient(s). Self-medication with antimalarial drugs purchased from unofficial vendors is not a reliable strategy to diminish morbidity and mortality. These counterfeit drugs contribute to the spread of drug-resistant malaria parasites and may lead to increasing therapeutic failure and medical expense.
A SENSITIVE NEW MICROCULTURE METHOD FOR DIAGNOSIS OF CUTANEOUS LEISHMANIASIS
Authors: ALLAHVERDIYEV ADIL M. , UZUN SONER , BAGIROVA MALAHAT , DURDU MURAT , MEMISOGLU HAMDI R.
Published: September 2018

A sensitive microcapillary culture method (MCM) was developed for rapid diagnosis of cutaneous leishmaniasis (CL). The MCM is superior to the traditional culture method (TCM) as determined by the smaller inoculum size, the higher sensitivity for detection of promastigotes, and the more rapid time for emergence of promastigotes. With lesion amastigote loads from grade III to 0, the positive rates and the periods for promastigote emergence were 3–4-fold higher and faster with the MCM than with the TCM, e.g., 83–97% positive in 4–7 days versus 20–40% positive in 15–30 days (P = 0.0001). The higher Pco2 and lower Po2 and pH presumably encourage a rapid amastigoteto-promastigote differentiation and/or the survival or growth of the latter. This MCM has the advantage of simplicity, and may be suitable for diagnostic use and for parasite retrieval in many other endemic sites where parasites are known to be difficult to grow.
PREVALENCE OF ANTIBODIES TO HANTAVIRUS AMONG FAMILY AND HEALTH CARE WORKER CONTACTS OF PERSONS WITH HANTAVIRUS CARDIOPULMONARY SYNDROME: LACK OF EVIDENCE FOR NOSOCOMIAL TRANSMISSION OF ANDES VIRUS TO HEALTH CARE WORKERS IN CHILE
Authors: CASTILLO CONSTANZA , VILLAGRA ELIECER , SANHUEZA LIGIA , FERRES MARCELA , MARDONES JOVITA , MERTZ GREGORY J.
Published: September 2018

Nosocomial transmission of Andes virus has been documented in Argentina, but has not yet been proven in Chile. We studied 215 contacts (106 family member contacts and 109 health care worker contacts) of 20 index cases of hantavirus cardiopulmonary syndrome (HCPS) in Chile. The seroprevalence of IgG antibodies against Andes virus was 1.9% (95% confidence interval [CI] = 0.34–6.3%) among the family members and 0.0% (95% CI = 0–3.2%) among the health care workers. Our data suggest that there is no evidence for nosocomial transmission of Andes virus in region IX of Chile.
RAPID DIAGNOSIS OF TYPHOID FEVER BY ENZYME-LINKED IMMUNOSORBENT ASSAY DETECTION OF SALMONELLA SEROTYPE TYPHI ANTIGENS IN URINE
Authors: FADEEL MOUSTAFA ABDEL , CRUMP JOHN A. , MAHONEY FRANK J. , NAKHLA ISABELLE A. , MANSOUR ADEL M. , REYAD BAHEIA , EL MELEGI DAWLAT , SULTAN YEHIA , MINTZ ERIC D. , BIBB WILLIAM F.
Published: September 2018

We developed and evaluated an enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies to capture somatic antigen 9 (O9), flagellar antigen d (Hd), and the Vi capsular polysaccharide antigen (Vi) from the urine of persons with and without typhoid fever. Sequential urine samples were collected from 44 patients with blood culture-confirmed typhoid fever and from two control groups. The first control group included patients with brucellosis (n = 12) and those with clinically diagnosed, non-typhoid, acute, febrile illness (n = 27). The second control group was a sample of healthy volunteer laboratory workers (n = 11). When assessed relative to date of fever onset, sensitivity was highest during the first week for all three antigens: Vi was detected in the urine of nine (100%) patients, O9 in 4 (44%) patients, and Hd in 4 (44%) patients. Sequential testing of two urine samples from the same patient improved test sensitivity. Combined testing for Vi with O9 and Hd produced a trend towards increased sensitivity without compromising specificity. The specificity for Vi exceeded 90% when assessed among both febrile and healthy control subjects, but was only 25% when assessed among patients with brucellosis. Detection of urinary Vi antigen with this ELISA shows promise for the diagnosis of typhoid fever, particularly when used within the first week after fever onset. However, positive reactions for Vi antigen in patients with brucellosis must be understood before urinary Vi antigen detection can be developed further as a useful rapid diagnostic test.
TRYPANOSOMA BRUCEI GAMBIENSE TRYPANOSOMIASIS IN TEREGO COUNTY, NORTHERN UGANDA, 1996: A LOT QUALITY ASSURANCE SAMPLING SURVEY
Authors: HUTIN YVAN J. F. , LEGROS DOMINIQUE , OWINI VINCENT , BROWN VINCENT , LEE EVAN , MBULAMBERI DAWSON , PAQUET CHRISTOPHE
Published: September 2018

We estimated the pre-intervention prevalence of Trypanosoma brucei gambiense (Tbg) trypanosomiasis using the lot quality assurance sampling (LQAS) methods in 14 parishes of Terego County in northern Uganda. A total of 826 participants were included in the survey sample in 1996. The prevalence of laboratory confirmed Tbg trypanosomiasis adjusted for parish population sizes was 2.2% (95% confidence interval =1.1−3.2). This estimate was consistent with the 1.1% period prevalence calculated on the basis of cases identified through passive and active screening in 1996–1999. Ranking of parishes in four categories according to LQAS analysis of the 1996 survey predicted the prevalences observed during the first round of active screening in the population in 1997–1998 (P < 0.0001, by chi-square test). Overall prevalence and ranking of parishes obtained with LQAS were validated by the results of the population screening, suggesting that these survey methods may be useful in the pre-intervention phase of sleeping sickness control programs.
FUNICULITIS DUE TO SCHISTOSOMA HAEMATOBIUM: UNCOMMON DIAGNOSIS USING PARASITOLOGIC ANALYSIS OF SEMEN
Authors: DURAND F. , BRION J.-P. , TERRIER N. , PINEL C. , PELLOUX H.
Published: September 2018

Schistosomal funiculitis is one of the rare localizations of longstanding chronic infection with schistosomiasis. We report a case of a 24-year-old-man who experienced iliac fossa pain and weight loss eight years after his last trip to Mali. Clinical diagnosis of lesions in the genitourinary tract due to schistosomiasis and biologic analysis are required to diagnose this uncommon localization of schistosomiasis.
EVALUATION OF A MALARIA RAPID DIAGNOSTIC TEST FOR ASSESSING THE BURDEN OF MALARIA DURING PREGNANCY
Authors: SINGER LAUREN M. , NEWMAN ROBERT D. , DIARRA AMIDOU , MORAN ALLISYN C. , HUBER CURTIS S. , STENNIES GAIL , SIRIMA SODIOMON B. , KONATE AMADOU , YAMEOGO MATHIAS , SAWADOGO ROMIAL , BARNWELL JOHN W. , PARISE MONICA E.
Published: September 2018

Plasmodium falciparum infection during pregnancy may cause placental malaria and subsequently low birth weight, primarily through the placental sequestration of infected red blood cells. Measuring the burden of malaria during pregnancy usually involves determining the prevalence of placental malaria infection through microscopic examination of placental blood films, a difficult and error-prone process. A number of rapid diagnostic tests (RDTs) for malaria have been developed, most of them immunochromatographic dipstick assays. However, none have been tested for the direct determination of malaria antigen in placental blood. We undertook an evaluation of the Malaria Rapid Test (MAKROmed®) in determining placental malaria infection. The prevalence of placental parasitemia was 22.6% by microscopy, 51.0% by a polymerase chain reaction (PCR), and 43.1% by RDT. When the PCR was used as the gold standard, RDTs had a sensitivity of 89% and a specificity of 76%. The MAKROmed RDT was highly sensitive in the detection of placental malaria, but had lower than expected specificity.
BALAMUTHIA MANDRILLARIS MENINGOENCEPHALITIS: THE FIRST CASE IN SOUTHEAST ASIA
Authors: INTALAPAPORN POJ , SUANKRATAY CHUSANA , SHUANGSHOTI SHANOP , PHANTUMCHINDA KAMMANT , KEELAWAT SOMBOON , WILDE HENRY
Published: September 2018

We present a case of 23-year-old man with acute meningoencephalitis, accompanied by inflammation of a nasal ulcer. He had been healthy until six months prior to admission to the hospital when he had a motorcycle accident. A star-shaped wound at his nose was incurred after falling into a swamp. A computed tomogram of the brain showed two nonenhancing hypodense lesions at the left caudate nucleus and the right parietal lobe, ependymitis and leptomeningeal enhancement. A skin biopsy showed chronic noncaseous granulomatous inflammation without demonstrated microorganisms. The patient did not respond to the empirical treatment with cloxacillin, ceftriaxone, and amphotericin B, and eventually died on the thirteenth day of hospitalization. At autopsy, hematoxylin and eosin–stained brain sections showed a chronic necrotizing inflammation with numerous amebic trophozoites and rare cysts. Definitive identification of Balamuthia mandrillaris was made by fluorescent immunohistochemical analysis. There were 10 Naegleria fowleri primary amebic meningoencephalitis, eight Acanthamoeba granulomatous amebic encephalitis, and three Acanthamoeba meningitis in Thailand. To our knowledge, this case is the first reported case of B. mandrillaris in Southeast Asia.
A COMPARATIVE STUDY OF THE EFFECTIVENESS OF DIAGNOSTIC TESTS FOR VISCERAL LEISHMANIASIS
Authors: BOELAERT MARLEEN , RIJAL SUMAN , REGMI SUDHIR , SINGH RUPA , KARKI BALMANSINGH , JACQUET DIANE , CHAPPUIS FRANÇOIS , CAMPINO LENEA , DESJEUX PHILIPPE , LE RAY DOMINIQUE , KOIRALA SHEKHAR , VAN DER STUYFT PATRICK
Published: September 2018

We compared the validity of pancytopenia, the formol-gel test (FGT), the indirect fluorescence antibody test (IFAT), the direct agglutination test (DAT), and the rK39 dipstick test as diagnostic criteria for visceral leishmaniasis (VL) in Nepal. Between September 2000 and January 2002, 310 clinical suspects had a bone marrow aspirate, and if negative, a spleen aspirate smear examined for Leishmania donovani. Sensitivity and specificity of all tests were determined compared with parasitology and by latent class analysis (LCA). Compared with parasitology, the sensitivities of the other tests were as follows: pancytopenia = 16.3% (95% confidence interval [CI] = 11.3–22.5%), FGT = 39.9% (95% CI = 32.7–47.4%), IFAT = 28.4% (95% CI = 22.0–35.5%), DAT = 95.1% (95% CI = 90.8–97.7%), and the rK39 dipstick test = 87.4% (95% CI = 81.7–91.9%). Sensitivity estimates obtained by LCA were similar, but specificity estimates were substantially higher (DAT = 93.7% versus 77.8%; rK39 dipstick test = 93.1% versus 77.0%). The DAT or the rK39 dipstick test can replace parasitology as the basis of a decision to treat VL in Nepalese peripheral health services.
ANTIBODIES TO RIFIN: A COMPONENT OF NATURALLY ACQUIRED RESPONSES TO PLASMODIUM FALCIPARUM VARIANT SURFACE ANTIGENS ON INFECTED ERYTHROCYTES
Authors: ABDEL-LATIF MOHAMED S. , CABRERA GERARDO , KÖHLER CARSTEN , KREMSNER PETER G. , LUTY ADRIAN J. F.
Published: September 2018

We used a pool of recombinant rifin proteins to pre-adsorb antibodies to rifin in the plasma of semi-immune African (Gabonese) adults and showed that this results in a reduction in the level of IgG antibody reactivity to variant surface antigens (VSA) measured in a standardized flow cytometric assay with a panel of heterologous parasite isolates. The same methods demonstrated a similar but less-marked contribution of antibodies to the duffy binding-like 1α (DBL-1α ) domain to the overall anti-VSA response. Thus, we conclude that both antibodies to rifin and, to a lesser extent, antibodies directed to conserved regions of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) DBL-1α domain contribute to the overall antibody response to VSA. We also assessed the associations between these different antibody responses in a cohort of Gabonese children. We found marked differences related to the childrens’ history of presentation with either mild or severe malaria, but no consistent pattern that would indicate a specific role or influence of antibody responses to rifin.
TESTING VACCINES IN HUMAN EXPERIMENTAL MALARIA: STATISTICAL ANALYSIS OF PARASITEMIA MEASURED BY A QUANTITATIVE REAL-TIME POLYMERASE CHAIN REACTION
Authors: HERMSEN CORNELUS C. , DE VLAS SAKE J. , VAN GEMERT GEERT JAN A. , TELGT DENISE S. C. , VERHAGE DANIELLE F. , SAUERWEIN ROBERT W.
Published: September 2018

Clinical trials are an essential step in evaluation of safety and efficacy of malaria vaccines, and human experimental malaria infections have been used for evaluation of protective immunity of Plasmodium falciparum malaria. In this study, a quantitative real-time polymerase chain reaction was used to measure P. falciparum malaria parasitemia in non-immune volunteers who had been experimentally infected by mosquito bites. Based on a remarkably small variation in the kinetics of parasitemia, a statistical model was developed that provides detailed estimates of pre-patent periods and parasite multiplication of blood stages. Using this model, we could predict results on vaccine efficacy for 1) pre-erythrocytic vaccines in the asymptomatic incubation period and 2) asexual stage vaccines after a limited number of multiplication cycles. The model shows that stage-specific vaccines even with limited efficacy can be highly efficacious when used in combination. This P. falciparum challenge method significantly adds to the potential to evaluate efficacy of candidate malaria vaccines before going into field trials.
IMPREGNATED NETS OR DDT RESIDUAL SPRAYING? FIELD EFFECTIVENESS OF MALARIA PREVENTION TECHNIQUES IN SOLOMON ISLANDS, 1993–1999
Authors: OVER MEAD , BAKOTE’E BERNARD , VELAYUDHAN RAMAN , WILIKAI PETER , GRAVES PATRICIA M.
Published: September 2018

The incidence of malaria in Solomon Islands has been decreasing since 1992. The control program used a combination of methods including DDT residual house spraying and insecticide-treated mosquito nets. To determine how much each method contributed to malaria control, data were analyzed on monthly incidence and on control activities for 41 of 110 malaria zones over the same time period (January 1993 to August 1999). After correction for endogeneity, then spraying, insecticide treatment of nets, and education about malaria are all independently associated with reduction in incident cases of malaria or fever, while larviciding with temephos is not. The evidence suggests that although impregnated bed nets cannot entirely replace DDT spraying without substantial increase in incidence, their use permits reduced DDT spraying. The paper shows that non-experimental data can be used to infer causal links in epidemiology, provided that instrumental variables are available to correct for endogeneity.
POLICY CHALLENGES IN MALARIA VACCINE INTRODUCTION
Authors: MOREE MELINDA , EWART SARAH
Published: September 2018

Recently licensed life-saving vaccines have experienced slow introduction and gradual uptake in the developing world. Policy challenges at the national level contribute to the delay in making new vaccines accessible to people in poor countries. The hurdles that delayed the introduction of other vaccines can provide guidance for navigating the policy challenges that face the introduction of a new malaria vaccine. When a malaria vaccine is licensed, national leaders will rely on available data and analyses to draw conclusions about which malaria interventions have the greatest potential for public health impact. Epidemiologic and economic analyses can help facilitate their decision-making. This article draws attention to the importance of research to inform policy decisions and to minimize delays in the introduction of a new malaria vaccine.
EPIDEMIOLOGY OF SHIGELLA-ASSOCIATED DIARRHEA IN RURAL EGYPTIAN CHILDREN
Authors: ABU-ELYAZEED REMON R. , WIERZBA THOMAS F. , FRENCK ROBERT W. , PUTNAM SHANNON D. , RAO MALLA R. , SAVARINO STEPHEN J. , KAMAL KARIM A. , PERUSKI LEONARD F. , ABD-EL MESSIH IBRAHIM A. , EL-ALKAMY SAHAR A. , NAFICY ABDOLLAH B. , CLEMENS JOHN D.
Published: September 2018

During the period from February 1995 to February 1998, the epidemiology of Shigella diarrhea was studied among children less than three years of age residing in Egypt’s Nile Delta. Children were visited twice a week and a stool sample was collected from any of them with diarrhea. The incidence of Shigella-associated diarrhea was 0.2 episodes/child-year, with S. flexneri being the most common serogroup isolated (55% of Shigella episodes). Younger age and the warm months increased the risk of developing Shigella-associated diarrhea, while breastfeeding was protective. Children with Shigella were ill for a mean of four days and passed a mean of six stools per day. Common symptoms included fever (35%), vomiting (19%), and dehydration (16%). Dysentery, however, was unusual, occurring in only 11% of the cases. In conclusion, Shigella-associated diarrhea remains relatively common in Egyptian children and supports the need for additional control measures including vaccine development.
DELAYED EFFECTIVENESS OF HOME-BASED INTERVENTIONS IN REDUCING CHILDHOOD DIARRHEA, KARACHI, PAKISTAN
Authors: LUBY STEPHEN P. , AGBOATWALLA MUBINA , HOEKSTRA ROBERT M. , RAHBAR MOHAMMAD H. , BILLHIMER WARD , KESWICK BRUCE H.
Published: September 2018

We introduced home drinking water disinfection and handwashing with soap in Karachi squatter settlements to evaluate their effect on diarrhea. In April 2000, 150 households received soap, 76 received dilute bleach and a water storage vessel, and 76 were enrolled as controls. In 2000, among households wealthy enough to own a refrigerator, children in households that received bleach and a vessel had a 73% lower incidence of diarrhea than controls; those that received soap had a 56% lower incidence. There was no reduction in diarrhea in intervention households without a refrigerator. In 2001, households that received bleach and a vessel had a 71% lower incidence of diarrhea and children in households that received soap had a 35% lower incidence than controls. In 2001, the interventions were equally effective in households that had a refrigerator and those that did not. Both of these home-based interventions were ultimately effective in preventing diarrhea, but only households of slightly higher socioeconomic status changed their behavior quickly enough to benefit during the first summer.
DUPLEX DOPPLER SONOGRAPHIC ASSESSMENT OF THE EFFECTS OF DIETHYLCARBAMAZINE AND ALBENDAZOLE THERAPY ON ADULT FILARIAL WORMS AND ADJACENT HOST TISSUES IN BANCROFTIAN FILARIASIS
Authors: HUSSEIN OMAR , SETOUHY MAGED EL , AHMED EHAB S. , KANDIL AMR M. , RAMZY REDA M. R. , HELMY HANAN , WEIL GARY J.
Published: September 2018

We used duplex Doppler sonography to assess effects of diethylcarbamazine and albendazole therapy (DEC/ALB) on adult Wuchereria bancrofti in vivo. The study was performed in clinically normal Egyptian adults with blood microfilaria counts > 80/mL. Motile adult worms were observed before treatment in dilated scrotal lymphatic vessels in 28 of 36 men (78%) and over the proximal extremities in 5 of 22 women (23%). Most worm nests were inactivated in the months following treatment (90% at 12 months). Circulating filarial antigen levels (a marker for living adult worms) also fell dramatically following treatment. Some men had intrascrotal calcifications and/or non-palpable hydroceles detectable by ultrasound before they were treated. New hydroceles and intrascrotal calcifications appeared after treatment in many cases. However, most of these were transient and of no clinical significance. Prevelance rates for hydrocele and intrascrotal calcifications 24 months after treatment were essentially the same as those prior to treatment. These results show that DEC/ALB is highly active against adult W. bancrofti. They also suggest that host responses to dying adult worms are important in the pathogenesis of filarial hydroceles.
INTRODUCTION OF THE AMERICAN/ASIAN GENOTYPE OF DENGUE 2 VIRUS INTO THE YUCATAN STATE OF MEXICO
Authors: LOROÑO-PINO MARÍA A. , FARFÁN-ALE JOSÉ A. , ZAPATA-PERAZA ALICIA L. , ROSADO-PAREDES ELSY P. , FLORES-FLORES LUIS F. , GARCÍA-REJÓN JULIÁN E. , DÍAZ FRANCISCO J. , BLITVICH BRADLEY J. , ANDRADE-NARVÁEZ MANUEL , JIMÉNEZ-RÍOS EUSEBIO , BLAIR CAROL D. , OLSON KEN E. , BLACK WILLIAM , BEATY BARRY J.
Published: September 2018

A dengue (DEN) outbreak occurred in the Yucatan State of Mexico in 2002. Three isolates were obtained from patients presenting with DEN-like symptoms, and examined by partial nucleotide sequencing and phylogenetic analysis. The isolates were identified as DEN-2 viruses of the American-Asian genotype; this is the first report of this genotype in the Yucatan State. The DEN-2 viruses of the American-Asian genotype have been associated with more severe disease outcomes. Thus, its introduction into the Yucatan State presents a serious problem to public health authorities. During this outbreak, DEN virus infection was confirmed in 18% (282 of 1,560) of the patients who presented with DEN-like symptoms. Of these, 87 (31%) patients met the World Health Organization criteria for dengue hemorrhagic fever, including two patients who died. The majority (77%) of the patients experienced secondary infections in this epidemic.
MIXED DOMESTIC INFESTATION BY RHODNIUS PROLIXUS STÄL, 1859 AND PANSTRONGYLUS GENICULATUS LATREILLE, 1811, VECTOR INCRIMINATION, AND SEROPREVALENCE FOR TRYPANOSOMA CRUZI AMONG INHABITANTS IN EL GUAMITO, LARA STATE, VENEZUELA
Authors: FELICIANGELI M. DORA , CARRASCO HERNÁN , PATTERSON JAMES S. , SUAREZ BENNY , MARTÍNEZ CLARA , MEDINA MEHUDY
Published: September 2018

Mixed infestation of nymphs and adults of Rhodnius prolixus Stäl, 1859 and Panstrongylus geniculatus Latreille, 1811 was detected in 3 (15%) of 20 dwellings in El Guamito, an endemic focus of Chagas disease in Lara State, Venezuela. In one of the houses, both species were positive for Trypanosoma cruzi: 14.3% (R. prolixus) and 20% (P. geniculatus ). The overall infection rate in 143 of 352 R. prolixus was 16.1%. Parasites isolated from R. prolixus were identified as T. cruzi I by random amplified polymorphic DNA analysis. Dot–enzyme-linked immunosorbent assays of 36 R. prolixus showed that 58.3% of the R. prolixus had fed on humans. The gut contents of one fifth-instar nymph of P. geniculatus that was positive for T. cruzi also reacted with anti-human serum. A questionnaire was used to gather data on the demographic and socioeconomic characteristics of the population. An indirect immunofluorescent test, an indirect hemaglutination test, and an ELISA were used to detect the presence of antibodies against T. cruzi in 84 of 86 inhabitants and in 15.5% of people more than 20 years old. The relative risk (RR) of infection was greater in men than in women (RR = 1.61, 95% confidence interval = 0.54–4.80). Of the people more than 15 years old, 36.6% had no formal education. All respondents recognized triatomine bugs, but they did not relate them to Chagas disease transmission. A total of 85.7% of the houses were “ranchos” suitable for the colonization of triatomine bugs. The possible domiciliation of P. geniculatus and the implications of competition with R. prolixus for resources are discussed. Since there is no clear separation of food sources, abiotic factors such as microclimatic variation within houses may be critical to predict the outcome of the process of competition and potential domestication of this generally sylvatic species.
RAPID DETECTION OF MALARIA INFECTION IN VIVO BY LASER DESORPTION MASS SPECTROMETRY
Authors: SCHOLL PETER F. , KONGKASURIYACHAI DARIN , DEMIREV PLAMEN A. , FELDMAN ANDREW B. , LIN JEFFREY S. , SULLIVAN DAVID J. , KUMAR NIRBHAY
Published: September 2018

Rapid diagnosis leading to effective treatment is essential to control escalating infectious diseases such as malaria. Malaria pigment (hemozoin) detection by laser desorption mass spectometry (LDMS) was recently shown to be a sensitive (<10 parasites/μL) technique for detecting Plasmodium falciparum parasites cultured in human blood. To examine the use of LDMS in a rapid new malaria screening assay, we followed the time course of P. yoelii infections in mice in parallel with light microscopy and a colorimetric hemozoin assay. Hemozoin was detected by LDMS in 0.3 μL of blood within two days of infection independently of the inoculating dose of 106, 104, or 102 parasite-infected erythrocytes. Microscopy and colorimetric hemozoin determinations lagged the LDMS detection of infections by 2–4 and 3–5 days, respectively, except at the highest inoculation dose. The LDMS detection of hemozoin is a potentially more rapid screen than light microscopy for detecting malaria infection in this mouse model at parasitemias <0.1%.
CHARACTERIZATION OF THE EARLY CELLULAR IMMUNE RESPONSE TO LEISHMANIA MAJOR USING PERIPHERAL BLOOD MONONUCLEAR CELLS FROM LEISHMANIA-NAIVE HUMANS
Authors: ROGERS KATHLEEN A. , TITUS RICHARD G.
Published: September 2018

While the response to Leishmania major is well characterized in mice, there is much less known about the human immune response, particularly early after exposure to the parasite. Therefore, we developed a primary in vitro (PIV) system that allowed us to address these questions. We co-cultured peripheral blood mononuclear cells from Leishmania-naive donors with L. major parasites and found that the responding PIV cells produced interferon-γ and interleukin-12 (IL-12). When restimulated, these PIV cells also occasionally produced IL-5. Both CD4 and CD8 cells and both HLA class I and II cell activation pathways appeared to play a role in the PIV system, and cell activation was dependent upon the presence of antigen-presenting cells. Moreover, PIV cells generated with L. major showed considerable cross-reactivity with other species of Leishmania. Finally, the PIV cells augmented intracellular killing of L. major when they were co-cultured with macrophages infected with the parasite.
EPIDEMIOLOGIC AND ENVIRONMENTAL INVESTIGATION OF A RECREATIONAL WATER OUTBREAK CAUSED BY TWO GENOTYPES OF CRYPTOSPORIDIUM PARVUM IN OHIO IN 2000
Authors: MATHIEU ELS , LEVY DEBORAH A. , VEVERKA FRAN , PARRISH MARY-KAY , SARISKY JOHN , SHAPIRO NANCY , JOHNSTON STEPHANIE , HANDZEL THOMAS , HIGHTOWER ALLEN , XIAO LIHUA , LEE YEUK-MUI , YORK STEVE , ARROWOOD MICHAEL , LEE ROBIN , JONES JEFFREY L.
Published: September 2018

In August 2000, the Ohio Department of Health requested assistance to investigate a cryptosporidiosis outbreak with more than 700 clinical case-patients. An epidemiologic and environmental investigation was conducted. Stool specimens, pool water, and sand filter samples were analyzed. A community-based case-control study showed that the main risk factor was swimming in pool A (odds ratio [OR] = 42, 95% confidence interval [CI] = 12.3–144.9). This was supported by results of polymerase chain reaction (PCR) analysis, which showed the presence of both the human and bovine genotypes of Cryptosporidium parvum in case-patients and samples from the filter of pool A. A pool-based case-control study indicated that the highest risk was related to exposure to pool water via the mouth (OR = 5.1, 95% CI = 2.1–12.5) or to pool sprinklers (OR = 2.5, 95% CI = 1.3–4.7). Fecal accidents at the pool were documented. Records indicated that the pool met local health regulations. The outbreak, caused by co-infection with two C. parvum genotypes (human and bovine), underscores the need for concerted action to improve public health policies for recreational water facilities and enhanced education regarding the potential for disease transmission through pools.
THE BURDEN OF THE NEUROCOGNITIVE IMPAIRMENT ASSOCIATED WITH PLASMODIUM FALCIPARUM MALARIA IN SUB-SAHARAN AFRICA
Authors: MUNG’ALA-ODERA VICTOR , SNOW ROBERT W. , NEWTON CHARLES R. J. C.
Published: September 2018

The burden of Plasmodium falciparum malaria has been estimated traditionally in terms of infections and mortality. Neurocognitive sequelae have recently been identified that add to the burden caused by this parasite. We have attempted to provide estimates of the neurocognitive burden based upon more recent estimates of the population at risk and a detailed review of published studies in sub-Saharan Africa. There is little data on which to estimate the burden, and considerable limitations in extracting the data from the published studies to provide these estimates. However, we estimate that at least 1,300–7,800 children will have neurologic sequelae following cerebral malaria in stable endemic areas per year. The figure is likely to be considerably higher, since these estimates do not include neurocognitive impairment following non-cerebral malaria in children or adults in stable endemic areas, or populations in low stable or epidemic areas.
OXIDATIVE STRESS IN ADULT DENGUE PATIENTS
Authors: GIL LIZETTE , MARTÍNEZ GREGORIO , TÁPANES ROLANDO , CASTRO OSVALDO , GONZÁLEZ DANIEL , BERNARDO LIDICE , VÁZQUEZ SUSANA , KOURÍ GUSTAVO , GUZMÁN MARÍA G.
Published: September 2018

An association between viral diseases and increased oxidative stress has been suggested. The time course of serum levels of total antioxidant status (TAS), peroxidation potential (PP), glutathione (GSH), lipid peroxidation measured as hydroperoxides, and malondyaldehyde and 4-hydroxyalkenals (MDA + 4-HDA), as well as antioxidant enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx), were measured in 22 serologically confirmed dengue patients. Most of the patients had dengue fever and three of them had dengue hemorrhagic fever. The redox parameters were compared with those of age- and sex- matched controls. No significant difference was observed for levels of GSH and TAS between patients and controls. Levels of PP, MDA + 4-HDA, and SOD were significantly higher. Levels of GPx and total hydroperoxides were significantly lower in patients in comparison with controls. These findings suggest that the alteration in redox status could result of increased oxidative stress and it may play a role in the pathogenesis of the disease.
A HISTIDINE-RICH PROTEIN 2–BASED MALARIA DRUG SENSITIVITY ASSAY FOR FIELD USE
Authors: NOEDL HARALD , ATTLMAYR BERNHARD , WERNSDORFER WALTHER H. , KOLLARITSCH HERWIG , MILLER ROBERT S.
Published: September 2018

With the spread of antimalarial drug resistance, simple and reliable tools for the assessment of antimalarial drug resistance, particularly in endemic regions and under field conditions, have become more important than ever before. We therefore developed a histidine-rich protein 2 (HRP2)–based drug sensitivity assay for testing of fresh isolates of Plasmodium falciparum in the field. In contrast to the HRP2 laboratory assay, the field assay uses a procedure that further simplifies the handling and culturing of malaria parasites by omitting centrifugation, washing, the use of serum, and dilution with uninfected red blood cells. A total of 40 fresh Plasmodium falciparum isolates were successfully tested for their susceptibility to dihydroartemisinin, mefloquine, quinine, and chloroquine (50% inhibitory concentration [IC50] = 3.43, 61.89, 326.75, and 185.31 nM, respectively). Results very closely matched those obtained with a modified World Health Organization schizont maturation assay (R2 = 0.96, P < 0.001; mean log difference at IC50 = 0.054).