bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission I. Description of study site, general methodology, and study population.
Authors: Bloland P B , Ruebush T K , McCormick J B , Ayisi J , Boriga D A , Oloo A J , Beach R , Hawley W , Lal A , Nahlen B , Udhayakumar V , Campbell C C
Published: May 2017

A large-scale longitudinal cohort project was initiated in western Kenya in June 1992. The primary purpose of the project was to study Plasmodium falciparum malaria in a highly endemic area using a comprehensive and multidisciplinary approach, which included epidemiology, entomology, and immunology. Between June 1992 and July 1994, pregnant women living in 15 rural villages were identified during a monthly census and 1,164 were enrolled. The women were followed-up throughout their pregnancy and they, along with their newborn infants and direct siblings of the infants' less than 15 years of age, were monitored over time. As of May 1995, 1,017 infants had been born to these women. This paper presents the design and general methodology used in this study and describes the initial experience with intense monitoring of a large population over a prolonged period.
Increased frequency of Th2-type cytokine-producing T cells in microfilaremic loiasis.
Authors: Winkler S , Willheim M , Baier K , Aichelburg A , Kremsner P G , Graninger W
Published: May 2017

The frequency of cytokine-producing peripheral blood mononuclear cells was assessed in 28 subjects with microfilaremic loiasis and in 14 amicrofilaremic individuals. In addition, a subgroup of seven microfilaremic individuals coinfected with Plasmodium malariae was evaluated. By using flow cytometry for the intracellular detection of cytokines, a more pronounced T helper (Th)2 cell-type response with the expansion of interleukin (IL)-4, IL-10, and IL-13 expressing CD4+ cells in the microfilaremic compared with the amicrofilaremic group was noted. Expression of IL-5 was equivalent in both groups as was the frequency of Th2-type cytokines expressing CD8+ cells and of Th1-type cytokines (interferon [IFN]-gamma, IL-2, IFN-gamma/IL-2) producing CD4+ and CD8+ cells. Th0-type cytokine-expressing cells, represented by IL-4/IFN-gamma, IL-10/IFN-gamma, and IL-13/IFN-gamma, were equally distributed within groups. Coinfection of P. malariae did not significantly alter the cytokine expression compared with microfilaremic individuals without P. malariae infections. By identifying a large panel of cytokine-producing T cell subpopulations, a Th2-driven immune response in microfilaremic Loa loa patients was noted.
Rapid serologic diagnosis of dengue virus infection using a commercial capture ELISA that distinguishes primary and secondary infections.
Authors: Vaughn D W , Nisalak A , Solomon T , Kalayanarooj S , Nguyen M D , Kneen R , Cuzzubbo A , Devine P L
Published: May 2017

A commercial capture ELISA for specific IgM and IgG antibodies produced during dengue infection (PanBio Dengue Duo) showed excellent sensitivity (99%, n = 78) using sera collected at hospital discharge compared with established ELISA and hemagglutination inhibition (HAI) assays. Furthermore, the ELISA was able to diagnose 79% of the dengue cases using sera collected at hospital admission. The ELISA also showed high specificity (92%) in paired sera from patients without flavivirus infection (n = 26), although 45% of the patients with Japanese encephalitis (n = 20) showed elevation of IgG but not IgM. The IgG capture ELISA showed good correlation with the HAI assay (r = 0.83, P < 0.0001), and IgG levels could be used to distinguish between primary and secondary infection, with 100% of primary infections and 96% of secondary infections being correctly classified. This ELISA should prove useful in the clinical diagnosis of dengue infections.
Population genetics and phylogenetic analysis of Colorado Borrelia burgdorferi.
Authors: Norris D E , Johnson B J , Piesman J , Maupin G O , Clark J L , Black W C
Published: May 2017

Borrelia burgdorferi is transmitted in an enzootic cycle in Colorado between the tick Ixodes spinipalpis and the woodrat Neotoma mexicana. The genetic relationship of Colorado isolates to other B. burgdorferi isolates is unknown nor have relationships among various Colorado isolates been determined. Portions of the flagellin (fla), 66-kD protein, and outer surface protein A (ospA) genes were amplified from 71 Colorado isolates, screened for genetic variability using single strand conformation polymorphism analysis, and unique alleles were sequenced. Colorado isolates were most similar to tick isolates from California and New York isolate 25015. Genetic distances among Colorado ospA sequences were the same or higher than distances among other isolates whereas distances among fla sequences tended to be the same or lower. The index of association (I(A)) was calculated among all loci as a measure of clonality. The I(A) among Colorado isolates was similar to I(A) previously estimated among other United States isolates.
Stimulation of Plasmodium falciparum gametocytogenesis by conditioned medium from parasite cultures.
Authors: Williams J L
Published: May 2017

Plasmodium falciparum gametocyte development was examined in erythrocyte monolayer cultures prepared with Cell-Tak, a cell and tissue adhesive. The monolayers, which were stable for up to 10 days in culture, supported multiple cycles of asexual growth and the development of clusters of stage IV gametocytes. Small numbers of chicken erythrocytes incorporated into the monolayers served as internal reference standards for parasite counts. This permitted quantitative assessment of gametocyte formation under different culture conditions. Gametocyte formation was limited in monolayers grown in standard culture medium but it increased slightly in monolayers cocultured with suspensions of parasitized erythrocytes. The number of gametocytes increased significantly in monolayers grown in parasite-conditioned medium. In both cases the changes resulted from increased numbers of stage II and III gametocytes in the monolayers. These results suggest that parasite conditioned medium contains a factor(s) that stimulates sexual development.
Genetic variation among isolates of western equine encephalomyelitis virus from California.
Authors: Kramer L D , Fallah H M
Published: May 2017

The mechanism for long-term maintenance of western equine encephalomyelitis (WEE) virus in California was investigated by studying genetic variation in the E2 portion of the genome of 55 strains of WEE virus isolated since 1938 from different locations in California. Four major lineages were evident: virus strains isolated from the Central Valley since 1993 and Los Angeles in 1991 formed lineage A; southern California strains isolated since 1978 and isolates from the Central Valley from 1978 to 1987 formed lineage B; northern California isolates from 1968 to 1971 formed lineage C; and early isolates from 1938 to 1961 formed a fourth lineage, D. The separation of strains from north and south of the Tehachapi and San Bernardino Mountains (i.e., the Central Valley and southern California, respectively) since 1991 indicates that there has been little recent movement of virus between the two regions and recent strains from these two locations appear to be evolving independently. However, within the Central Valley and within southern California, virus appears to circulate freely, perhaps by movement of birds or mosquito vectors. Although the current virus lineage in the Central Valley may have been introduced from an unknown source in 1991, introduction and establishment of new viral genotypes from outside California do not seem to occur regularly. It appears most likely that virus is maintained in separate geographic areas of California through local persistence in enzootic foci.
Hepatocellular carcinoma in Egyptians with and without a history of hepatitis B virus infection: association with hepatitis C virus (HCV) infection but not with (HCV) RNA level.
Authors: Yates S C , Hafez M , Beld M , Lukashov V V , Hassan Z , Carboni G , Khaled H , McMorrow M , Attia M , Goudsmit J
Published: May 2017

The aim of this study was to analyze the association of hepatocellular carcinoma (HCC) with hepatitis C virus (HCV) in Egypt, using hepatitis B virus (HBV) and hepatitis E virus (HEV) as virus controls. In addition, the association of HCC with HCV RNA levels among persons seropositive for HCV was analyzed. We compared 131 patients with proven HCC, 247 with bladder cancer, and 466 healthy hospital employees. Age, sex, and place of residence were recorded to study confounding factors. Among the healthy controls, 16% were seropositive for HCV, 21% for HBV, and 31% for HEV. When healthy controls were age-matched with HCC patients, the latter were significantly (P < 0.001) more often HCV seropositive (67%) than were the controls (30%). The seropositivity for HBV and HEV did not differ significantly in frequency between the two groups. The seropositivity for HCV was also significantly (P < 0.001) more often found in HCC patients (76%) than in BC patients (47%), with seroprevalences for HBV and HEV not differing significantly in these age-matched groups. In HBV-negative HCC and bladder cancer patients, seroprevalence for HCV was significantly (P = 0.002) higher in HCC patients (68%) than in bladder cancer patients (36%). This difference was even more pronounced (P < 0.001) in HBV-positive HCC and bladder cancer patients (78% versus 52%, respectively). Of HCV-seropositive individuals, 49% were HCV RNA positive by branched DNA assay, and of these, 96% were infected by HCV genotype 4. No correlation between HCV RNA load and seropositivity of HBV or age or disease state was found. Infection with HCV and HCV-HBV double infection, but not HBV or HEV infection alone, is strongly correlated with HCC in Egypt.
Myocardial parasite persistence in chronic chagasic patients.
Authors: AÃ±ez N , Carrasco H , Parada H , Crisante G , Rojas A , Fuenmayor C , Gonzalez N , Percoco G , Borges R , Guevara P , Ramirez J L
Published: May 2017

The persistence of Trypanosoma cruzi tissue forms was detected in the myocardium of seropositive individuals clinically diagnosed as chronic chagasic patients following endomyocardial biopsies (EMBs) processed by immunohistochemical (peroxidase-anti-peroxidase [PAP] staining) and molecular (polymerase chain reaction [PCR]) techniques. An indirect immunofluorescent technique revealed antigenic deposits in the cardiac tissue in 24 (88.9%) of 27 patients. Persistent T. cruzi amastigotes were detected by PAP staining in the myocardium of 22 (84.6%) of 26 patients. This finding was confirmed with a PCR assay specific for T. cruzi in 21 (91.3%) of 23 biopsy specimens from the same patients. Statistical analysis revealed substantial agreement between PCR and PAP techniques (k = 0.68) and the PCR and any serologic test (k = 0.77). The histopathologic study of EMB specimens from these patients revealed necrosis, inflammatory infiltrates, and fibrosis, and made it possible to detect heart abnormalities not detected by electrocardiogram and/or cineventriculogram. These indications of myocarditis were supported by the detection of T. cruzi amastigotes by the PAP technique or its genome by PCR. They suggest that although the number of parasites is low in patients with chronic Chagas' disease, their potential for heart damage may be comparable with those present during the acute phase. The urgent necessity for testing new drugs with long-term effects on T. cruzi is discussed in the context of the present results.
Short report: Diagnosis of tick-borne relapsing fever by the quantitative buffy coat fluorescence method.
Authors: Chatel G , Gulletta M , Matteelli A , Marangoni A , Signorini L , Oladeji O , Caligaris S
Published: May 2017

The quantitative buffy coat (QBC) parasite detection method is a sensitive and specific tool for the diagnosis of malaria parasites. It is also useful for the diagnoses of other hemoparasites, including Trypanosoma, Babesia, and Leptospira. We report a case of relapsing fever diagnosed by this technique in a short-term traveler from Senegal. The diagnosis was confirmed by the standard Giemsa hemoscopy and by the identification of significant titers of antibodies to Borrelia spp. of tick-borne relapsing fevers by specific immunofluorescence and Western blot tests. The QBC technique seems to be useful in the diagnosis of tick-borne relapsing fever in blood samples and should be included in the management of fever in the traveler returning from tropical regions.
Short report: Diagnosis of human fascioliasis: detection of anti-cathepsin L antibodies in blood samples collected on filter paper.
Authors: Strauss W , O'Neill S M , Parkinson M , Angles R , Dalton J P
Published: May 2017

We have developed an ELISA for the diagnosis of human fascioliasis based on the detection of IgG4 antibodies to Fasciola hepatica cathepsin LI cysteine protease. Use of this assay in the Bolivian Altiplano, a region with a high prevalence of the disease, was hampered by the reluctance of the indigenous population to provide blood. To overcome this problem, we have investigated the method of collecting small quantities of blood from the finger onto filter paper, followed by the elution of antibodies for use in the diagnostic assay. Serum samples and blood samples collected onto filter paper were obtained from 57 individuals living in the village of Cutusuma in 1987 and from 11 individuals in Chijipata in 1996. Analysis of the IgG4-ELISA results revealed that there is highly significant linear relationship (P < 0.001) between the two methods of sampling. Most importantly, a reliable diagnosis was made with the blood-filter samples from Cutusuma, which had been stored for 10 years at 40 degrees C. While some deterioration of the blood-filter samples from Cutusuma had occurred over the 10-year storage period, no deterioration occurred with the Chijipata samples, which were stored for one year. Therefore, the method of collecting blood onto filter paper should prove useful for large-scale epidemiologic studies on human fascioliasis in the Bolivian Altiplano and in other regions where this disease is prevalent.
No serologic evidence of an association found between Gulf War service and Mycoplasma fermentans infection.
Authors: Gray G C , Kaiser K S , Hawksworth A W , Watson H L
Published: May 2017

Occult occupational infection with Mycoplasma fermentans has been proposed as a cause for illness among Persian Gulf War veterans. Symptom data and sera from a 1994-1995 cross-sectional survey of Navy Seabees were used to select symptomatic and asymptomatic Gulf War veterans and nondeployed veterans to evaluate this hypothesis. Survey sera from 96 Seabees were matched to prewar (before September 1990) archived sera. Immunoblot serologic analyses were performed for M. fermentans in a controlled, blinded fashion. Both Gulf War veterans and nondeployed veterans had prewar and postwar serologic evidence of M. fermentans infection consistent with natural infection data. Among study subjects collectively, and stratified by Gulf War service, none of the immunoblot banding profiles (prewar or postwar) or their changes over time were associated with postwar symptoms. These serologic data do not support the hypothesis that Gulf War veterans have experienced Gulf War-related morbidity from M. fermentans infection.
Effect of chemotherapy on malaria transmission among Yanomami Amerindians: simulated consequences of placebo treatment.
Authors: Freeman J , Laserson K F , Petralanda I , Spielman A
Published: May 2017

To determine whether chemotherapy effectively reduces Plasmodium falciparum malaria transmission in isolated human populations, we followed two abrupt sequential outbreaks of malaria infection among Yanomami Amerindians and modeled the effect of chemotherapy and the consequences if no drug was available. A Macdonald-type mathematical model demonstrated that both outbreaks comprised a single epidemic event linked by an invisible outbreak in vector mosquitoes. The basic reproductive number, R0, from fitted values based on the treated epidemic was 2 during the initial phase of the epidemic, and waned as vector density decreased with the onset of the dry season. In the observed epidemic, 60 (45%) of 132 village residents were affected, and the treated outbreak ended after two months. Although the initial chemotherapy regimen was only marginally effective, the duration of human infectivity was reduced from an expected nine months to two weeks. In the absence of this intervention, the initial R0 value would have been 40, more than 60% of the population would have been infected, and more than 30% would have remained parasitemic until the next rainy season (about six months later). Another outbreak would then have ensued, and malaria probably would have remained endemic in this village. Our simulated placebo treatment permits us to conclude that even partially effective chemotherapeutic interventions, such as those in our study, interrupt serial transmission of P. falciparum among isolated human populations that are exposed to infection seasonally.
Vector-related case-control study of severe malaria in Kilifi District, Kenya.
Authors: Mbogo C N , Kabiru E W , Glass G E , Forster D , Snow R W , Khamala C P , Ouma J H , Githure J I , Marsh K , Beier J C
Published: May 2017

A case-control study examined vector-related and environmental parameters associated with severe malaria in Kilifi District along the coast of Kenya. Over an 11-month period, 119 children identified with severe malaria infections at the Kilifi District Hospital were matched by age with control children who reported to the outpatient clinic with nonsevere infections. Intensive mosquito sampling was done in each of the case-control houses over a four-day period, beginning within a week of index case admission. A total of 109 environmental, demographic, behavioral, and animal husbandry variables were characterized for each household. Vector species (Anopheles gambiae s.l. and An. funestus) were detected in 40.1% and 36.1% of case and control houses, respectively. The relative abundance of vectors in individual houses was stable over the two-week resampling periods (r = 0.9). Both the overall abundance of anopheline mosquitoes (odds ratio [OR] = 1.5) and P. falciparum sporozoite rates (OR = 1.5) were not significantly different between case and control houses. In a matched analysis, 11 of 109 house variables associated significantly with severe malaria were also associated with vector abundance, as determined by chi-square linear trend analysis. Under conditions of year-round, low-level transmission on the coast of Kenya, the risk of severe disease in children is multifactorial and not governed strictly by transmission intensity or environmental heterogeneity affecting vector abundance and distributions. This suggests that current interventions that appear to be achievable only in areas where transmission is already low to moderate should be appropriate. However, such interventions should be monitored so that inappropriate and possibly disastrous control activities can be avoided in Africa.
Rickettsia serosurvey in Kimberley, Western Australia.
Authors: Graves S , Wang L , Nack Z , Jones S
Published: May 2017

To determine if antibodies to rickettsiae (scrub typhus, spotted fever, and typhus group rickettsiae) occur among persons living in the Kimberley (northern tropical) region of Western Australia, 920 sera collected in a non-random manner in 1996 from patients in Kununurra, Broome, Fitzroy Crossing, Wyndham, Derby, and Halls Creek were tested by micro-immunofluorescence for antibodies to a panel of rickettsial antigens. Of 920 sera examined, 52 (5.6%) were positive for antibodies to one or more of the three groups of rickettsial microorganisms. The largest group of sera (24; 2.6%) were positive for scrub typhus (Orientia tsutsugamushi). Eleven other sera (1.2%) were positive for scrub typhus and spotted fever group rickettsiae and four (0.4%) were positive for scrub typhus, spotted fever group, and typhus group rickettsiae. In addition 13 sera (1.4%) were positive only for spotted fever group rickettsiae. In this study, only titers > or = 1:256 were considered significant. Thus, there is serologic evidence for scrub typhus and spotted fever group rickettsial infections in the Kimberley region of Western Australia. Because of the method of serum collection, it is not possible to determine the prevalence of seropositivity, but the data support the need for a proper epidemiologic study of rickettsial diseases in this region of Australia.
Failure of amphotericin B colloidal dispersion in the treatment of paracoccidioidomycosis.
Authors: Dietze R , Fowler V G , Steiner T S , Pecanha P M , Corey G R
Published: May 2017

Although amphotericin B desoxycholate is considered the most effective treatment for disseminated Paracoccidioides brasiliensis infections, little is known about the efficacy of lipid-based formulations of amphotericin B in this infection. In this study, we treated four adults with the juvenile form of paracoccidioidomycosis with 3 mg/kg/day of amphotericin B colloidal dispersion for at least 28 days. Although all of the patients initially responded by clinical observation, all four patients relapsed within six months. The use of amphotericin B colloidal dispersion for the initial induction of paracoccidioidomycosis failed to cure this infection. Possible reasons for failure include dose, duration, or reduced efficacy of this lipid preparation. For many fungal infections, lipid-based preparations have been shown to have a therapeutic-toxic advantage, but our experience with Paracoccidioides infections suggests that more careful studies will need to be performed before they can be recommended for use in this mycosis.
Phlebotomine sand fly (Diptera: Psychodidae) seasonal distribution and infection rates in a defined focus of Leishmania tropica.
Authors: Johnson R N , Lawyer P G , Ngumbi P M , Mebrahtu Y B , Mwanyumba J P , Mosonik N C , Makasa S J , Githure J I , Roberts C R
Published: May 2017

A two-year study was conducted of phlebotomine sand fly fauna in a defined focus of Leishmania tropica. A total of 17,947 sand flies representing 10 species were collected from the location. Phlebotomus guggisbergi, a vector of L. tropica in Kenya, was the most prevalent species through the entire period, representing about 80% of the total catch. There was marked seasonal fluctuation in the populations of the three most common species, with highest population levels reached in December and lowest levels reached in July and August. Leishmania-like infections were encountered in 489 P. guggisbergi. No flagellate infections were observed in any other species of sand fly. Although infected P. guggisbergi were collected during each month of the year, the percent parous infected flies was highest (27.5%) during the November through January time period. These data show that the greatest risk of transmission to humans at this focus occurs during December, when the vector is prevalent and infections are common.
Automated measurement of oxygen consumption by the yellow fever mosquito, Aedes aegypti.
Authors: Diarra G M , Roberts T W , Christensen B M
Published: May 2017

Oxygen consumption of single mosquitoes was measured using a differential pressure transducer (DPT) connected to two small chambers. A mosquito was placed in the experimental chamber (P1) and was separated from NaOH by 4 cm2 of marquisette mesh. The reference chamber (P2) contained the same amount of NaOH and the marquisette mesh but without a mosquito. When these two chambers were sealed, removed O2 from P1 resulted in a pressure decrease with respect to P2. This pressure differential was transduced into an output voltage that was directly proportional to the amount of O2 consumed by the mosquito. An array of eight DPTs was interfaced with an IBM 486 PC using an ADAC 5500MF analog to digital converter and software from ADAC (Direct View) to automate the recording procedure. We determined that our apparatus was sensitive enough to detect subtle differences in O2 consumption in mosquitoes subjected to different physiologic conditions.
Reduced soluble transferrin receptor concentrations in acute malaria in Vanuatu.
Authors: Williams T N , Maitland K , Rees D C , Peto T E , Bowden D K , Weatherall D J , Clegg J B
Published: May 2017

Soluble transferrin receptor (sTfR) concentration is a sensitive index of iron deficiency when used in conjunction with ferritin measurements in adults. One advantage of this assay is that unlike ferritin it does not appear to be affected by a range of infectious and inflammatory conditions or by pregnancy, rendering it a promising adjunct to the diagnosis of iron deficiency in tropical populations. We have measured plasma sTfR concentrations in a group of malaria patients (n = 21) and asymptomatic (18) and aparasitemic (76) controls in Vanuatu. Plasma sTfR concentration was significantly reduced in individuals with acute malaria (P = 0.003). While this observation provides evidence that erythropoeitic suppression may be an important etiologic component in malarial anemia, it also suggests that malaria may be a confounding factor when interpreting sTfR concentrations in such populations. The role of sTfR in the diagnosis of iron deficiency in tropical populations remains to be established.
Identification of a novel strain of Borrelia hermsii in a previously undescribed northern California focus.
Authors: Cleary M , Theis J
Published: May 2017

An epizootiologic investigation testing for the presence of tick-borne relapsing fever spirochetes in rodent and tick hosts was conducted at Eagle Lake in Lassen County, California. Six of 211 O. hermsii ticks and none of 180 rodents were polymerase chain reaction (PCR)-positive for Borrelia spirochetes. Sequencing of the PCR-amplified flagellin gene fragment suggests that the spirochetes from Eagle Lake represent a previously undescribed strain of Borrelia hermsii.
Serologic evidence of rickettsialpox (Rickettsia akari) infection among intravenous drug users in inner-city Baltimore, Maryland.
Authors: Comer J A , Tzianabos T , Flynn C , Vlahov D , Childs J E
Published: May 2017

We tested single serum samples from 631 intravenous (i.v.) drug users from inner-city Baltimore, Maryland for serologic evidence of exposure to spotted fever group rickettsiae. A total of 102 (16%) individuals had titers > or = 64 to Rickettsia rickettsii by an indirect immunofluorescence assay. Confirmation that infection was caused by R. akari was obtained by cross-adsorption studies on a subset of serum samples that consistently resulted in higher titers to R. akari than to R. rickettsii. Current i.v. drug use, increased frequency of injection, and shooting gallery use were significant risk factors for presence of group-specific antibodies reactive with R. rickettsii. There was a significant inverse association with the presence of antibodies reactive to R. rickettsii and antibodies reactive to the human immunodeficiency virus. This study suggests that i.v. drug users are at an increased risk for R. akari infections. Clinicians should be aware of rickettsialpox, as well as other zoonotic diseases of the urban environment, when treating i.v. drug users for any acute febrile illness of undetermined etiology.
Outbreak of histoplasmosis among cavers attending the National Speleological Society Annual Convention, Texas, 1994.
Authors: Ashford D A , Hajjeh R A , Kelley M F , Kaufman L , Hutwagner L , McNeil M M
Published: May 2017

In June 1994, 18 people developed serologically confirmed histoplasmosis following cave exploration associated with the annual National Speleological Society Convention in Bracketville, Texas. Six others had an undiagnosed illness suspected to be histoplasmosis. Two persons were hospitalized. We conducted a survey of convention attendees and a nested case-control study of those entering caves. We also conducted a histoplasmin skin test survey of a subgroup of the society, the Texas Cavers Association, who were attending a reunion in October 1994. Among the national convention attendees, exposure to two caves was identified as responsible for 22 (92%) of the 24 cases; 12 (75%) of 16 people exploring one cave (Cave A) and 10 (77%) of 13 exploring a separate cave (Cave B) developed acute histoplasmosis. Additional risk-factors included fewer years of caving experience, longer time spent in the caves, and entering a confined crawl space in Cave A. Of 113 participants in the separate skin test survey, 68 (60%) were found to be skin test positive, indicating previous exposure to Histoplasma capsulatum. A positive skin test was significantly associated with male sex and more years of caving experience. Those less experienced in caving associations should be taught about histoplasmosis, and health care providers should pursue histories of cave exposure for patients with bronchitis or pneumonia that does not respond to initial antibiotic therapy.
Evaluation of malaria surveillance using retrospective, laboratory-based active case detection in four southwestern states, 1995.
Authors: Barat L M , Barnett B J , Smolinski M S , Espey D K , Levy C E , Zucker J R
Published: May 2017

The global resurgence of malaria has raised concerns of the possible reintroduction of indigenous transmission in the United States. The Centers for Disease Control and Prevention's National Malaria Surveillance System, using data supplied by state and local health departments (SLHDs), is maintained to detect local malaria transmission and monitor trends in imported cases. To determine the completeness of reporting of malaria cases to SLHDs, cases identified by local surveillance systems were compared with those identified through active case detection conducted at all laboratories that receive clinical specimens from 11 metropolitan areas in Arizona, California, New Mexico, and Texas. Of the 61 malaria cases identified through either local surveillance or active case detection, 43 (70%) were identified by SLHDs (range by metropolitan area = 50-100%) and 56 (92%) through active case detection. High percentages of cases were identified by SLHDs in New Mexico (80%) and San Diego County (88%), where laboratories are required to send positive blood smears to the SLHD laboratory for confirmation. Completeness of reporting, calculated using the Lincoln-Peterson Capture-Recapture technique, was 69% for SLHD surveillance systems and 89% for laboratory-based active case detection. The high percentage of cases identified by the 11 SLHDs suggests that the National Malaria Surveillance System provides trends that accurately reflect the epidemiology of malaria in the United States. Case identification may be improved by promoting confirmatory testing in SLHD laboratories and incorporating laboratory-based reporting into local surveillance systems.
Genetic analysis of susceptibility to infection with Ascaris lumbricoides.
Authors: Williams-Blangero S , Subedi J , Upadhayay R P , Manral D B , Rai D R , Jha B , Robinson E S , Blangero J
Published: May 2017

Epidemiologic studies of helminthic infections have shown that susceptibility to these parasites frequently aggregates in families, suggesting the possible involvement of genetic factors. This paper presents a genetic epidemiologic analysis of Ascaris lumbricoides infection in the Jirel population of eastern Nepal. A total of 1,261 individuals belonging to a single pedigree were assessed for intensity of Ascaris infection at two time points. Following an initial assessment in which all individuals were treated with albendazole, a follow-up examination was performed one year later to evaluate reinfection patterns. Three measures of worm burden were analyzed, including eggs per gram of feces, direct worm counts, and worm biomass (weight). For all traits, variance component analysis of the familial data provided unequivocal evidence for a strong genetic component accounting for between 30% and 50% of the variation in worm burden. Shared environmental (i.e., common household) effects account for between 3% and 13% of the total phenotypic variance.
Efficacy of six doses of artemether-lumefantrine (benflumetol) in multidrug-resistant Plasmodium falciparum malaria.
Authors: Vugt M V , Wilairatana P , Gemperli B , Gathmann I , Phaipun L , Brockman A , Luxemburger C , White N J , Nosten F , Looareesuwan S
Published: May 2017

The new oral fixed combination artemether-lumefantrine (CGP 56697) has proved to be an effective and well-tolerated treatment of multi-drug resistant Plasmodium falciparum malaria, although cure rates using the four-dose regimen have been lower than with the currently recommended alternative of artesunate-mefloquine. Two six-dose schedules (total adult dose = 480 mg of artemether and 2,880 mg of lumefantrine) were therefore compared with the previously used four-dose regimen (320 mg of artemether and 1,920 mg of lumefantrine) in a double-blind trial involving 359 patients with uncomplicated multidrug-resistant falciparum malaria. There were no differences between the three treatment groups in parasite and fever clearance times, and reported adverse effects. The two six-dose regimens gave adjusted 28-day cure rates of 96.9% and 99.12%, respectively, compared with 83.3% for the four-dose regimen (P < 0.001). These six-dose regimens of artemether-lumefantrine provide a highly effective and very well-tolerated treatment for multidrug-resistant falciparum malaria.
Induction of histamine release in parasitized individuals by somatic and cuticular antigens from Onchocerca volvulus.
Authors: GonzÃ¡lez-MuÃ±oz M , GÃ¡rate T , Puente S , Subirats M , Moneo I
Published: May 2017

The host immune response in onchocerciasis is believed to contribute to the clinical manifestations of infection. Mazzotti and chronic inflammatory reactions might be mediated by mechanisms involving specific IgE and reactivity of mast cells and basophils to the parasite antigens. In this report, we show that Onchocerca volvulus antigens are capable of inducing histamine release. Three types of extracts were prepared from the parasite: soluble total, surface, and cuticular collagen. Soluble extracts released histamine in all individuals with onchocerciasis at significantly higher levels (P < 0.05) than those found in endemic controls, but similar levels to those found in patients with mansonellosis. However, cuticular collagen induced significantly (P < 0.01) higher histamine release in patients with onchocerciasis than in those with mansonellosis. No reactivity against human type IV collagen was observed. Implications derived from the presence of sensitized basophils in the pathogenesis of onchocerciasis are discussed.
Genetic polymorphism of falciparum malaria vaccine candidate antigen genes among field isolates in India.
Authors: Ranjit M R , Sharma Y D
Published: May 2017

The present study was designed to investigate the genetic diversity of Plasmodium falciparum among field isolates from India. A total of 71 clinical isolates were analyzed by the polymerase chain reaction (PCR) for the amplification of repeat regions of malaria vaccine candidate antigen genes, i.e., merozoite surface antigen-1 (MSA-1), MSA-2, and circumsporozoite protein (CSP). All three genes showed variation; MSA-2 has the maximum number of 10 variant forms while MSA-1 and CSP had 8 and 6 variants, respectively. Some variant forms were more common than others among the clinical isolates. There were mixed alleles for each gene in several (27 of 71) cases. The MSA-2 gene showed the maximum number of cases with mixed alleles (22 of 65 [33.85%]) compared with MSA-1 (10 of 68 [14.7%]) and CSP (10 of 65 [15.38%]). Fifty-five (88.7%) of 62 clinical isolates of P. falciparum showed a different genotype. The malaria hyperendemic region (Orissa) not only showed the maximum number of variant forms of each gene but also the maximum number of cases with mixed alleles compared with the non-hyperendemic regions (Madhya Pradesh and Rajasthan). The presence of such large numbers of P. falciparum strains in India should be taken into account in future malaria vaccine programs.
Short report: entomologic inoculation rates and Plasmodium falciparum malaria prevalence in Africa.
Authors: Beier J C , Killeen G F , Githure J I
Published: May 2017

Epidemiologic patterns of malaria infection are governed by environmental parameters that regulate vector populations of Anopheles mosquitoes. The intensity of malaria parasite transmission is normally expressed as the entomologic inoculation rate (EIR), the product of the vector biting rate times the proportion of mosquitoes infected with sporozoite-stage malaria parasites. Malaria transmission intensity in Africa is highly variable with annual EIRs ranging from < 1 to > 1,000 infective bites per person per year. Malaria control programs often seek to reduce morbidity and mortality due to malaria by reducing or eliminating malaria parasite transmission by mosquitoes. This report evaluates data from 31 sites throughout Africa to establish fundamental relationships between annual EIRs and the prevalence of Plasmodium falciparum malaria infection. The majority of sites fitted a linear relationship (r2 = 0.71) between malaria prevalence and the logarithm of the annual EIR. Some sites with EIRs < 5 infective bites per year had levels of P. falciparum prevalence exceeding 40%. When transmission exceeded 15 infective bites per year, there were no sites with prevalence rates < 50%. Annual EIRs of 200 or greater were consistently associated with prevalence rates > 80%. The basic relationship between EIR and P. falciparum prevalence, which likely holds in east and west Africa, and across different ecologic zones, shows convincingly that substantial reductions in malaria prevalence are likely to be achieved only when EIRs are reduced to levels less than 1 infective bite per person per year. The analysis also highlights that the EIR is a more direct measure of transmission intensity than traditional measures of malaria prevalence or hospital-based measures of infection or disease incidence. As such, malaria field programs need to consider both entomologic and clinical assessments of the efficacy of transmission control measures.
Chemotherapy of malaria and resistance to antimalarial drugs in Guayana area, Venezuela.
Authors: Caraballo A , Rodriguez-Acosta A
Published: May 2017

Resistance to antimalarial chemotherapy is one of the greatest difficulties for the control of malaria transmission. Seventy patients with Plasmodium falciparum malaria were included in a study of resistance to chloroquine and sulfadoxine-pyrimethamine therapy. Resistance levels RI, RII, and RIII were established. Eighteen infections (51%) cleared after chloroquine treatment and did not recur within 28 days of follow-up; these were classified as sensitive. Ten infections (29%) were resistant at the RI level. Resistance at level RII was observed in 5 (14%) cases, and RIII resistance was demonstrated in 2 infections (6%). With sulfadoxine-pyrimethamine, 28 (80%) infections were classified as sensitive. Six infections (17%) showed resistance at level RII, and 1 (3%) infection was resistant at the RI level. Resistance at level RIII was not observed. In a microtest for chloroquine and sulfadoxine-pyrimethamine sensitivity in vitro, schizont development was accomplished successfully in 70 blood samples. In vitro resistance to chloroquine was demonstrated in 15 of 70 (21%) of all isolates. Eight of 70 (11%) of all isolates showed resistance to sulfadoxine-pyrimethamine. Diversity of response of P. falciparum to the studied antimalarial drugs in the Guayana area of Venezuela is considered a problem restricting the control of malaria in this geographical area. A constant evaluation program monitoring P. falciparum drug sensitivity is necessary for preserving the efficacy of the established treatment.
Identification and analysis of dihydrofolate reductase alleles from Plasmodium falciparum present at low frequency in polyclonal patient samples.
Authors: Mookherjee S , Howard V , Nzila-Mouanda A , Watkins W , Sibley C H
Published: May 2017

As resistance to chloroquine spreads in sub-Saharan Africa, pyrimethamine plus sulfadoxine (PSD) is increasingly used as a first-line treatment for falciparum malaria. Populations of Plasmodium falciparum (Pf) resistant to PSD have been selected quickly in other regions. The resistance is strongly correlated with point mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), the two targets of the drug. It is critical to identify drug-resistant Pf-DHFR alleles that are present at a low frequency in these populations since alleles that confer drug resistance will be quickly selected by PSD use. It is difficult to identify these rare alleles by standard molecular techniques. We have designed a yeast expression system that facilitates the identification and rapid analysis of Pf-DHFR alleles that confer PSD resistance, even when they are present at very low frequency in polyclonal patient samples. We analyzed samples from patients in Kilifi, Kenya collected between 1992 and 1995. We determined the prevalence of the drug-sensitive and drug-resistant alleles in patient samples analyzed in parallel by an allele-specific enzyme digestion (ASED) assay. We identified a pyrimethamine-resistant allele (S108N) present at a frequency of < 1% in a sample that was scored as only S108 by ASED. In addition, a novel pyrimethamine-resistant allele (1164M) was isolated twice, once each from two different patient samples. This approach will allow determination of the prevalence of Pf-DHFR alleles that confer pyrimethamine resistance in particular regions, and the rapid identification of novel alleles that confer drug resistance.
Temporal recruitment of neutrophils and eosinophils to the skin in a murine model for onchocercal dermatitis.
Authors: Pearlman E , Garhart C A , Grand D J , Diaconu E , Strine E R , Hall L R
Published: May 2017

The parasitic helminth Onchocerca volvulus causes ocular onchocerciasis (river blindness) and onchocercal skin disease. To understand the immunologic basis for early stage skin disease, we developed a model in which C57B1/6 mice were immunized subcutaneously and injected intradermally (in the ear) with soluble O. volvulus antigens (OvAg). We found that ear thickness increased significantly after intradermal injection of OvAg and remained elevated for at least 7 days. Dermatitis was dependent on prior immunization, and was associated with an intense cellular infiltrate in the dermis. Neutrophils were the predominant inflammatory cells in the dermis 12 hr after intradermal injection, with only occasional eosinophils present. Conversely, increased ear thickness at later time points was associated with eosinophils, and neutrophils were only rarely detected. Both cell types were present at intermediate time points. These data indicate that recruitment of neutrophils and eosinophils to the skin is temporally regulated.
Epidemic O'Nyong-Nyong fever in southcentral Uganda, 1996-1997: entomologic studies in Bbaale village, Rakai District.
Authors: Lutwama J J , Kayondo J , Savage H M , Burkot T R , Miller B R
Published: May 2017

Entomologic studies were conducted between January 27 and February 2, 1997, in Bbaale village in southcentral Uganda during an o'nyong-nyong (ONN) virus epidemic, which began in mid 1996 and continued into 1997. The objectives were to confirm the role of anophelines in ONN virus transmission and to examine other mosquito species as epidemic vectors of ONN virus. Of 10,050 mosquitoes collected using light traps and pyrethrum knockdown sprays, Anopheles (Cellia) funestus Giles was presumed to be the principal vector because it was the most abundant mosquito species from which a strain of ONN virus was isolated. This virus was isolated for the first time from a culicine species, Mansonia (Mansonioides) uniformis Theobald. Bwamba virus and Nyando virus were also isolated from An. funestus.
Susceptibility of Panamanian Aotus lemurinus lemurinus to sporozoite-induced Plasmodium falciparum (Santa Lucia) infection.
Authors: Gramzinski R A , Obaldia N , Jones T R , Rossan R N , Collins W E , Garrett D O , Lal A A , Hoffman S L
Published: May 2017

Aotus monkeys are good models for erythrocyte-induced Plasmodium falciparum and P. vivax infections and have been extensively used in malarial drug and vaccine development. Recently, it has been shown that certain species of Aotus can be infected with sporozoites, and that the degree of susceptibility varies among species. We demonstrate here that Panamanian Aotus lemurinus lemurinus are susceptible to a sporozoite-induced infection, opening the possibility that this species of Aotus could be used as models for testing the efficacy of pre-erythrocytic P. falciparum vaccines and drug candidates directed at the pre-erythrocytic stages of P. falciparum and P. vivax malaria. In this species, we compared sporozoite infection rates. Two of four animals splenectomized prior to infection with sporozoites developed patent parasitemias. Seven of eight animals splenectomized either 7 or 35 days after infection became parasitemic. Additionally, we used a P. falciparum-specific polymerase chain reaction (PCR) method to detect the early appearance of parasitized erythrocytes in the blood prior to detection by conventional microscopy, and found that the parasitemia was detected first in five animals by the PCR method, first in three animals by blood film, with one parasitemia detected simultaneously. We also demonstrated the feasibility of infecting monkeys located in Panama with sporozoites isolated at an insectary in Atlanta, thus documenting the feasibility of similar studies where the insectary and monkey colony are not in the same location. A subsequent attempt to infect these monkeys using sporozoites was not successful, suggesting that this model of human malaria is not yet ready for routine use in vaccine or drug efficacy screening. This model merits further study because of the importance of testing pre-erythrocytic P. falciparum malaria vaccines and drugs in animals.
In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections.
Authors: Yardley V , Croft S L
Published: May 2017

The activities of four amphotericin B formulations, Fungizone, AmBisome, Amphocil, and Abelcet, were compared in vitro and in vivo against Trypanosoma cruzi infections. In vitro, Fungizone and Amphocil were highly active against T. cruzi Y strain amastigotes in macrophages with 50% effective dose (ED50) values of 0.027-0.028 microg/ml, which were 7-fold and 42-fold more active than AmBisome and Abelcet, respectively. In vitro activities of all formulations against T. cruzi amastigotes in Vero cells were similar, with ED50 values in the range of 2.0-4.2 microg/ml. Acute infections of the T. cruzi Y strain in BALB/c mice were suppressed in all animals by a single 25 mg/kg dose of the liposomal formulation AmBisome. At the same dose, the two other lipid formulations, Amphocil and Abelcet, increased the survival rate but did not suppress infection in all animals.
Clinical analysis and parasite genetic diversity in human immunodeficiency virus/Chagas' disease coinfections in Brazil.
Authors: Perez-Ramirez L , BarnabÃ© C , Sartori A M , Ferreira M S , Tolezano J E , Nunes E V , Burgarelli M K , Silva A C , Shikanai-Yasuda M A , Lima J N , Da-Cruz A M , Oliveira O C , Guilherme C , Bastrenta B , Tibayrenc M
Published: May 2017

To evaluate the possible role of parasitemia on Chagas' disease reactivation in Chagas' disease/human immunodeficiency virus (HIV) coinfection cases and the impact of HIV coinfection on Trypanosoma cruzi genetic diversity, 71 patients with Chagas' disease (34 HIV+ and 37 HIV-) were surveyed. Moreover, 92 T. cruzi stocks from 47 chronic chagasic patients (29 HIV+ and 18 HIV-) were isolated and analyzed by multilocus enzyme electrophoresis and a random amplified polymorphic DNA procedure. High parasitemia appeared to play a major role in cases of Chagas' disease reactivation. In HIV+ patients, the genetic diversity and population structure (clonality) of T. cruzi was similar to that previously observed in HIV- patients, which indicates that immunodepression does not modify drastically genotype repartition of the parasite. There was no apparent association between given T. cruzi genotypes and specific clinical forms of Chagas' disease/HIV associations.