bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of a sentinel host system to study the questing behavior of Ixodes spinipalpis and its role in the transmission of Borrelia bissettii, human granulocytic ehrlichiosis, and Babesia microti.
Authors: Burkot T R , Maupin G O , Schneider B S , Denatale C , Happ C M , Rutherford J S , Zeidner N S
Published: May 2017

Ixodes spinipalpis maintains Borrelia bissettii spirochetes in Colorado in a cycle involving wood rats and deer mice. This tick has been described as nidicolous, remaining either attached to its rodent hosts or in the rodent nest. Nidicolous ticks pose little risk of pathogen transmission to humans if they do not actively quest for hosts. To investigate the questing potential of I. spinipalpis, sentinel mice were placed in an area where I. spinipalpis had been commonly found on wood rats and deer mice. Concurrently, wild rodent populations were trapped and analyzed for Lyme disease spirochetes, the agent of human granulocytic ehrlichiosis (aoHGE), and Babesia microti. A total of 122 I. spinipalpis larvae and 10 nymphs were found on 19% of 244 sentinel mice. In addition, 4 sentinel mice became infested with Malaraeus telchinus or Orchopeas neotomae fleas. Questing I. spinipalpis were positively associated with woody shrubs and negatively associated with sunny and grassy areas. Four sentinel mice became infected with aoHGE after having been fed upon only by I. spinipalpis larvae. One sentinel mouse became infected with B. bissettii after having an I. spinipalpis nymph feed on it, and one sentinel mouse became coinfected with aoHGE and B. bissettii after it was fed upon by a single I. spinipalpis nymph. These sentinel mouse conversions suggest the possibility that the aoHGE is transovarially transmitted by I. spinipalpis, and that I. spinipalpis is capable of simultaneously transmitting B. bissettii and the aoHGE. The findings that I. spinipalpis quest away from rodent nests and will attach to and infect sentinel mice may be of public health importance. It suggests the potential transmission of the agents of human granulocytic ehrlichiosis and Lyme disease to other hosts by I. spinipalpis, in regions of the western United States where Ixodes pacificus is not found.
Therapy of uncomplicated falciparum malaria: a randomized trial comparing artesunate plus sulfadoxine-pyrimethamine versus sulfadoxine-pyrimethamine alone in Irian Jaya, Indonesia.
Authors: Tjitra E , Suprianto S , Currie B J , Morris P S , Saunders J R , Anstey N M
Published: May 2017

Combining artesunate with existing antimalarial drugs may improve cure rates, delay emergence of resistance, and reduce transmission. We performed a randomized comparative trial to quantify the effect of adding artesunate to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in Indonesia. Using a modified 1997 World Health Organization protocol for assessment of therapeutic efficacy of antimalarial drugs, 105 patients (stratified by age/ethnic group) were randomized: 53 received artesunate orally, 4 mg/kg of body weight, a single daily dose for three days, plus sulfadoxine-pyrimethamine orally (1.25 mg of pyrimethamine/kg of body weight), a single dose on day 0, and 52 patients received sulfadoxine-pyrimethamine alone. Six from the combination group were withdrawn from analysis, as were six of the sulfadoxine-pyrimethamine group. Treatment failure rates on day 14 were 0% in the artesunate plus sulfadoxine-pyrimethamine group and 8.7% in the sulfadoxine-pyrimethamine group (P = 0.12). Treatment failure rates on day 28 were 4.4% and 15.2%, respectively (P = 0.16). Relative risk of treatment failure at 28 days was 0.3 (95% confidence interval [CI] = 0.1-1.3). Mean fever clearance time (1.3 versus 1.7 days) and mean parasite clearance time (1.4 versus 2.0 days) were both faster in the artesunate plus sulfadoxine-pyrimethamine group than in the sulfadoxine-pyrimethamine group (P = 0.08 and P < 0.0001, respectively). Only 20 (39.2%) of 51 patients treated with artesunate plus sulfadoxine-pyrimethamine were still parasitemic on day 1 compared with 45 (86.5%) of 52 patients treated with sulfadoxine-pyrimethamine alone (P = 0.000001, relative risk [RR] = 0.4, 95% CI = 0.3-0.6). Gametocyte carriage was lower following artesunate plus sulfadoxine-pyrimethamine than following sulfadoxine-pyrimethamine (RR = 0.5, 95% CI = 0.2-1.0 on day 7 and RR = 0.5, 95% CI = 0.2-1.1 on day 14). Mild diarrhea, rash, and itching resolved without treatment. Combined artesunate plus sulfadoxine-pyrimethamine resulted in more rapid fever and parasiteclearance, was well tolerated, reduced risk of treatment failure, and lowered gametocyte carriage.
Epidemiology of acute hepatitis in the Stann Creek District of Belize, Central America.
Authors: Bryan J P , Reyes L , Hakre S , Gloria R , Kishore G M , Tillett W , Engle R , Tsarev S , Cruess D , Purcell R H
Published: May 2017

Hepatitis is common in the Stann Creek District of southern Belize. To determine the etiologies, incidence, and potential risk factors for acute jaundice, we conducted active surveillance for cases. Cases of jaundice diagnosed by a physician within the previous 6 weeks were enrolled. Evaluation included a questionnaire and laboratory tests for hepatitis A, B, C, D, and E, a blood film for malaria, and a serologic test for syphilis. Etiologies of jaundice among 62 evaluable patients included acute hepatitis A, 6 (9.7%), acute hepatitis B, 49 (79.0%), hepatitis non-A-E, 2 (3.2%), and malaria, 5 (8.1%). There were no cases of acute hepatitis E. One patient each with antibody to hepatitis C and D were detected. The annualized incidence of hepatitis A was 0.26 per 1,000. All cases of hepatitis A were in children 4-16 years of age. The annualized incidence of hepatitis B, 2.17 per 1,000, was highest in adults aged 15-44 years (4.4 per 1,000) and was higher in men (36 cases; 3.09 per 1,000) than women (13 cases; 1.19 per 1,000). Four (31%) of the women with hepatitis B were pregnant. The annualized incidence was significantly higher in Mestizo (6.18 per 1000) and Maya (6.79 per 1,000) than Garifuna (0.38 per 1,000) or Creole (0.36 per 1,000). Persons with hepatitis B were significantly more likely to be born outside of Belize (82%), had been in Belize < 5 years (73%), and lived and worked in rural areas (96%) than was the general population. Of those > or = 14 years of age with hepatitis B, only 36% were married. Few persons admitted to transfusions, tattoos, IV drug use, multiple sexual partners, visiting prostitutes, or sexually transmitted diseases. Only 1 of 49 had a reactive test for syphilis. Six patients were hospitalized (including 3 with acute hepatitis B and one with hepatitis A), and none to our knowledge died. Acute hepatitis B is the most common cause of viral hepatitis in the Stann Creek District, but the modes of transmission remain obscure. Infants, women attending prenatal clinics, and new workers are potential targets for immunization with hepatitis B vaccine.
Invasive amebiasis: challenges in diagnosis in a non-endemic country (Kuwait).
Authors: Hira P R , Iqbal J , Al-Ali F , Philip R , Grover S , D'Almeida E , Al-Eneizi A A
Published: May 2017

Invasive zymodemes of the enteric protozoan Entamoeba histolytica infect the large intestine and cause extra-intestinal lesions such as amebic liver abscess (ALA). The clinical manifestations of ALA are protean, particularly in patients presenting in a non-endemic, desert country such as Kuwait, and diagnosis becomes problematic. In this study, we present cases of ALA to illustrate the clinical and diagnostic challenges. For serodiagnosis of ALA, we compared the sensitivity and specificity of the indirect hemagglutination assay (IHA) with the ImmunoTab assay and an enzyme-linked immunosorbent assay (ELISA) for this geographic region. We tested sera of 110 patients with ALA, 1,224 patients suspected of having invasive amebic infection, and 50 Europeans with no travel history to an amebic-endemic area. The IHA was simple, rapid, easy to perform, and reliable (sensitivity = 99%, specificity > 95%). The performance of the IHA in detecting ALA in suspected cases was significantly better than that of the ELISA and the ImmunoTab test. Compared with the IHA, both the ELISA and ImmunoTab assay detected relatively higher numbers of false-positive cases (4.7% and 3.6%, respectively). With the availability of ultrasound and computed tomography scans, the serology correlates excellently with the clinical presentation. In chronic cases where fibrosis may be present around the abscess, the IHA has limitations, as in the follow-up of treated patients. Pitfalls in diagnosis are highlighted by discussing the differential diagnosis of ALA from bacterial hepatic abscesses and infected hydatid cysts. Most importantly, the IHA in such cases was invariably at a titer that is considered not significant.
Development and optimization of polymerase chain reaction-based malaria diagnostic methods and their comparison with quantitative buffy coat assay.
Authors: Schindler H C , Montenegro L , Montenegro R , Carvalho A B , Abath F G , Jaureguiberry G
Published: May 2017

Polymerase chain reaction (PCR)-based assays targeting the small-subunit rRNA were developed and evaluated, allowing for the simultaneous diagnosis of Plasmodium falciparum and Plasmodium vivax DNA in human blood samples. The PCR methods and quantitative buffy coat (QBC) were compared in 402 patients. The heminested PCR method showed a sensitivity of 97.4%, which was superior to the sensitivity of the QBC method (91.7%, P < 0.05), to simple PCR (84.6%, P < 0.001), and to PCR with digoxigenin labeling (PCR-DIG) (88.5%, P < 0.001). The PCR-DIG and QBC analyses were more sensitive than simple PCR (P < 0.003 and P < 0.05, respectively). There was no significant difference between the sensitivities of the QBC assay and the PCR-DIG assay. The specificity for the 3 PCR-based methods was 100%, superior to the specificity calculated for the QBC assay (88.95%, P < 0.009). The frequency of a positive result in groups from endemic areas but without detectable parasitemia increased, in order, from simple PCR, QBC test, PCR-DIG, to heminested PCR. An association between a positive PCR result and a history of malaria was also found. Taken together, these data suggest that this technology could be further developed to screen people with oligoparasitemia and to monitor malaria treatment.
Sensitive and specific enzyme-linked immunosorbent assay for the diagnosis of Wuchereria bancrofti infection in urine samples.
Authors: Itoh M , Weerasooriya M V , Qiu G , Gunawardena N K , Anantaphruti M T , Tesana S , Rattanaxay P , Fujimaki Y , Kimura E
Published: May 2017

We developed an enzyme-linked immunosorbent assay (ELISA) that detects filaria-specific immunoglobulin G4 antibodies in unconcentrated urine. The ELISA was positive in 87 of 91 (95.6%) urine samples collected from people with Wuchereria bancrofti microfilariae, antigen, or both. Of 298 urine samples collected in Thailand, Lao People's Democratic Republic, and Japan, where no human filariasis is known, 295 (99.0%) were negative by ELISA. Various intestinal nematode and fluke infections did not interfere with the ELISA. Urine samples with sodium azide could be kept at 37 degrees C for 4 weeks, and the time of urine collection did not influence ELISA results. This ELISA can be used to identify endemic foci of filariasis.
A live attenuated recombinant dengue-4 virus vaccine candidate with restricted capacity for dissemination in mosquitoes and lack of transmission from vaccinees to mosquitoes.
Authors: Troyer J M , Hanley K A , Whitehead S S , Strickman D , Karron R A , Durbin A P , Murphy B R
Published: May 2017

2Adelta30 is a live dengue-4 virus vaccine candidate with a 30-nucleotide deletion in its 3'-untranslated region. To assess the transmissibility of 2Adelta30 by mosquitoes, we compared its in vivo replication in mosquitoes with that of its wild type DEN-4 parent. Both the vaccine candidate and wild type virus were equally able to infect the mosquito Toxorhynchites splendens after intrathoracic inoculation. Relative to its wild type parent, 2Adelta30 was slightly restricted in its ability to infect the midgut of Aedes aegypti mosquitoes fed on an artificial blood meal and was even more restricted in its ability to disseminate from the midgut to the salivary glands. Thus, the 30-nucleotide deletion rendered the vaccine candidate more sensitive than its wild type parent to the mosquito midgut escape barrier. Most significantly, 2Adelta30 was not transmitted to 352 Ae. albopictus mosquitoes fed on 10 vaccinees, all of whom were infected with the vaccine candidate.
Two-dimensional electrophoretic analysis of Aedes aegypti mosquito fat body proteins during a gonotropic cycle.
Authors: Shih K M , Fallon A M
Published: May 2017

We have used two-dimensional polyacrylamide gel electrophoresis to examine changes in the relative abundance and diversity of non-secreted proteins in Aedes aegypti fat body preparations during a reproductive cycle. Electrophoretic profiles were evaluated at four time points after eclosion, and at five time points after a blood meal. In contrast to the dramatic changes in abundance of specific secreted proteins such as vitellogenin, our results show that the complement of proteins internal to the fat body remains relatively constant during the mosquito reproductive cycle. Of the approximately 5-10% of proteins that do change in abundance, the majority undergo a dramatic decrease within 24 hours after eclosion.
Characterization of antibody responses to combinations of a dengue-2 DNA and dengue-2 recombinant subunit vaccine.
Authors: Simmons M , Murphy G S , Kochel T , Raviprakash K , Hayes C G
Published: May 2017

A dengue-2 (DEN-2) DNA vaccine coding for the premembrane and envelope (E) proteins and a recombinant fusion protein containing the B domain of the DEN-2 E protein fused to the maltose-binding protein (MBP) of Escherichia coli both elicited neutralizing antibody in mice. In order to achieve more rapid protective immunity as well as to increase the persistence of neutralizing antibody, we primed mice with the DNA vaccine (D), the recombinant MBP protein (R), or both (RD) given simultaneously, and then boosted twice with either the R (R/R/R or D/R/R) or D (D/D/D or R/D/D) constructs alone or the RD (RD/RD/RD) combination. All of the recombinant protein vaccines were given with alum as an adjuvant. The serum antibody response measured by enzyme-linked immunosorbent assay was highest in D/D/D mice and RD/RD/RD mice. The D/R/R mice showed an intermediate response, and the R/D/D and R/R/R showed the lowest response. The geometric mean (GM) 50% neutralizationtiter (50% plaque reduction neutralization, or PRNT50) was marginally higher for RD/RD/RD mice (891) at 9 months after priming than that for R/R/R mice (724). T he lowest GM PRNT50 titers were seen in the D/D/D mice (33) and R/D/D mice (40), and the D/R/R group had a slightly higher titer (156) than these 2 groups. The predominant antibody subclass for the D/D/D mice was immunoglobulin (Ig) G2a, similar to mice infected with live virus. The R/R/R mice showed an exclusive IgGI antibody response, and the RD/RD/RD response also was predominantly IgGI. The antibody subclass pattern of the R/D/D and D/R/R mice showed a more balanced distribution of both IgG1 and IgG2a. Investigating the neutralizing capacity of antibody subclasses suggested that both IgG1 and IgG2a could neutralize DEN-2 virus. Our observations indicate that the combination RD prime-boost regimen warrants further investigation as a vaccine strategy to prevent dengue infection.
In vitro susceptibility of Plasmodium falciparum isolates from Myanmar to antimalarial drugs.
Authors: Wongsrichanalai C , Lin K , Pang L W , Faiz M A , Noedl H , Wimonwattrawatee T , Laoboonchai A , Kawamoto F
Published: May 2017

In vitro drug susceptibility profiles were assessed in 75 Plasmodium falciparum isolates from 4 sites in Myanmar. Except at Mawlamyine, the site closest to the Thai border, prevalence and degree of resistance to mefloquine were lower among the Myanmar isolates as compared with those from Thailand. Geometric mean concentration that inhibits 50% (IC50) and 90% (IC90) of Mawlamyine isolates were 51 nM (95% confidence interval [CI], 40-65) and 124 nM (95% CI, 104-149), respectively. At the nearest Thai site, Maesod, known for high-level multidrug resistance, the corresponding values for mefloquine IC50 and IC90 were 92 nM (95% CI, 71-121) and 172 nM (95% CI, 140-211). Mefloquine susceptibility of P. falciparum in Myanmar, except for Mawlamyine, was consistent with clinical-parasitological efficacy in semi-immune people. High sensitivity to artemisinin compounds was observed in this geographical region. The data suggest that highly mefloquine-resistant P. falciparum is concentrated in a part of the Thai-Myanmar border region.
Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in Brazil: therapeutic response to meglumine antimoniate.
Authors: Romero G A , Guerra M V , Paes M G , MacÃªdo V O
Published: May 2017

We conducted a quasi-experimental study to compare the response to meglumine antimoniate in patients with localized cutaneous leishmaniasis from two endemic areas of Brazil that were infected by two Leishmania species. Sixty-one were infected by Leishmania (Viannia) braziliensis (group B) and 57 by L. (V.) guyanensis (group G). All had a parasitologically proven diagnosis and were treated with 20 mg of pentavalent antimonial (SbV)/kg/day given intravenously or intramuscularly for 20 days. Main outcomes were diagnosed using clinical criteria three months after treatment and patients were followed for six months. Intention-to-treat analysis showed a higher failure rate in group G (relative risk [RR] = 1.5, 95% confidence interval [CI] = 1.1-2.0, chi2 = 7.44, P = 0.006). The analysis using an explanatory approach including 52 patients from group B and 49 from group G, who were regularly treated and followed for six months, showed a low cure rate (50.8% in group B and 26.3% in group G) with a greater risk of failure in the latter group (RR = 1.7, 95% CI = 1.2-2.5, chi2 = 8.56, P = 0.003). The effect of the etiologic agent remained significant after adjusting for age, disease duration, and site and number of lesions that were identified as predictors of failure in a logistic regression model. We concluded that Leishmania species constitute an important factor in predicting the outcome of cutaneous leishmaniasis treated with a pentavalent antimonial.
Randomized, controlled, double-blind trial of topical treatment of cutaneous leishmaniasis with paromomycin plus methylbenzethonium chloride ointment in Guatemala.
Authors: Arana B A , Mendoza C E , Rizzo N R , Kroeger A
Published: May 2017

A double-blind, randomized trial was undertaken in Guatemala to determine the therapeutic efficacy of an ointment for the treatment of cutaneous leishmaniasis that contained 15% paromomycin and 12% methylbenzethonium chloride and that was applied twice a day for 20 days. The treatment group included 35 patients, and the placebo group included 33 patients. The initial clinical response rate (13 weeks after completing the treatment) was 91.4% in the treatment group and 39.4% in the placebo group. The final clinical response rate at the 12-month follow-up examination was 85.7% (31 of 35) in the treatment group and 39.4% (13 of 33) in the placebo group (P < or = 0.001). In general, the treatment was well tolerated and was never interrupted because of adverse effects. The number of adverse effects reported in the placebo group was lower than in the treatment group (16 events versus 30 events). All adverse effects reported by patients disappeared within 1 week of completing the treatment. Our findings show that the combination of paromomycin with methylbenzethonium chloride for 20 days is a good alternative for antimonial treatments of cutaneous leishmaniasis in Guatemala.
Binding of Plasmodium falciparum-infected erythrocytes to soluble platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): frequent recognition by clinical isolates.
Authors: Heddini A , Chen Q , Obiero J , Kai O , Fernandez V , Marsh K , Muller W A , Wahlgren M
Published: May 2017

Platelet-endothelial cell adhesion molecule-1 or CD31 (PECAM-1/CD31) is a receptor recognized by Plasmodium falciparum-parasitized erythrocytes (pRBCs). Fluorescence-labeled soluble recombinant PECAM-1/CD31 (sPECAM-1/CD31) is shown to bind to the surface of P. falciparum-infected erythrocytes on up to 70% of the cells. Binding is blocked by the addition of the unlabeled receptor in a dose-dependent fashion, but not by unrelated receptor-proteins. A significant correlation was found between the binding of sPECAM-1/CD31 to pRBCs and the binding to transfected L cells expressing the receptor as seen with six different P. falciparum lines or clones. Panning of cultures on PECAM-1/CD31 transfected L cells was paralleled by an increase in the binding of sPECAM-1/CD31. The pRBCs of 54% of fresh patient-isolates bound sPECAM-1/CD31 with a mean rate of 12.9% (range = 1.1-44%). The data suggest that PECAM-1/CD31 is a common receptor recognized by wild isolates and that the soluble PECAM-1/CD31 suspension assay is a sensitive and reliable way to study PECAM-1/CD31 binding.
Association of subtherapeutic dosages of a standard drug regimen with failures in preventing relapses of vivax malaria.
Authors: Duarte E C , Pang L W , Ribeiro L C , Fontes C J
Published: May 2017

This study evaluated the cure rate of the standard recommended regimen for Plasmodium vivax malaria in Brazil and assessed risk factors for failures. Fifty patients with vivax malaria given supervised medical treatment (standard dose of chloroquine: total dose = 1.5 g over a three-day period plus primaquine: total dose = 210 mg over a 14-day period) were followed for six months in a non-endemic area. Cox's regression was used to identify predictors of relapses. Among the 289 patient-months of follow-up, seven relapses were identified (2.4 relapses per 100 person-months) between 33 and 137 days after treatment initiation. Risk factors for relapses (P < or = 0.05) were female sex, higher parasitemia at baseline, shorter number of days with symptoms prior to baseline, and lower mg/kg dose of primaquine. Relapses following supervised vivax treatment is in principle a necessary, but not sufficient, component of in vivo parasite resistance. Results indicate that other factors, principally sub-therapeutic primaquine doses, may explain the occurrence of vivax treatment failures.
Impact of canine control on the epidemiology of canine and human visceral leishmaniasis in Brazil.
Authors: Palatnik-de-Sousa C B , dos Santos W R , FranÃ§a-Silva J C , da Costa R T , Reis A B , Palatnik M , Mayrink W , Genaro O
Published: May 2017

Brazil is the only country endemic for zoonotic visceral leishmaniasis (ZVL) that regularly conducts epidemiologic and prophylactic control programs that involve the treatment of human cases, insect vector control, and the removal of seropositive infected dogs. This report reviews 60 studies reporting data on the efficacy of these recommended control tools and concludes that in Brazil 1) eradication of the disease in Minas Gerais was achieved by the concomitant use of the three control methods, 2) although seropositivity by an immunofluorescent assay is not completely related to infectiousness, the removal of seropositive dogs leads to a significant reduction of canine and human incidence, 3) improvement of the sensitivity of the diagnostic tool used for canine control should optimize the efficacy of control, and 4) although difficult and expensive, the public health dog control campaigns performed in Brazil reduced the incidence of ZVL and should be maintained since treatment of dogs is an unrealistic intervention, both because of its prohibitive cost and relatively poor effectiveness.
Rickettsial infection in murine models activates an early anti-rickettsial effect mediated by NK cells and associated with production of gamma interferon.
Authors: Billings A N , Feng H M , Olano J P , Walker D H
Published: May 2017

Natural killer (NK) cell activity was significantly increased on days 2-6 of infection in the Rickettsia conorii-infected C3H/HeN mice and on day 2 in the Rickettsia typhi-infected C57BL/6 mice. Depletion of NK cell activity utilizing anti-NK1.1 monoclonal antibody enhanced the susceptibility of normally resistant C57BL/6 mice to infection with R. typhi, and depletion of NK cell activity with antibody to asialo GM1 enhanced the susceptibility of C3H/HeN mice to infection with R. conorii. Serum gamma interferon was increased in R. conorii-infected C3H/HeN mice compared with NK cell-depleted, infected mice during the early course of infection. Additionally, the NK cell activating cytokine IL-12 was elevated in the sera of infected mice during the time period representing enhanced NK cell activity compared with uninfected mice. Thus, it appears that NK cells contribute to the early anti-rickettsial immune response, likely via a mechanism involving gamma interferon.
Determination and geographical distribution of Orientia tsutsugamushi serotypes in Korea by nested polymerase chain reaction.
Authors: Ree H I , Kim T E , Lee I Y , Jeon S H , Hwang U W , Chang W H
Published: May 2017

Field rodents and chigger mites were collected at 30 locations in Korea in October and November 1997-1999 to determine the serotypes of Orientia tsutsugamushi and their geographical distribution. A nested polymerase chain reaction was performed with the spleen tissues from 546 field-striped mice (Apodemus agrarius) and 104 pools of chigger mites. The positivity rate of O. tsutsugamushi was 45.6% in A. agrarius and 39.4% in the chigger mite pools. Two serotypes, Boryong and Karp, were found in these samples; the former was predominant (78.3% in the mice and 82.9% in the chigger mite pools), with wide distribution throughout the country, including Cheju-do. The latter was confined to the middle of the Korean peninsula, with positivity rates of 15.7% in the mice and 12.2% in the chigger mite pools. The double infection of Karp and Boryong serotypes was found in 15 (6.0%) A. agrarius mice. Gilliam serotype was not detected at any of the study locations. The Boryong and Kuroki serotypes were identical in amino acid sequence of the 56-kDa protein, although they differed in virulence to BALB/c mice.
Lyme disease in New York State: spatial pattern at a regional scale.
Authors: Glavanakov S , White D J , Caraco T , Lapenis A , Robinson G R , Szymanski B K , Maniatty W A
Published: May 2017

Lyme disease occurs commonly in New York State, but its geographic distribution is heterogeneous. Over each of nine consecutive years, incidence rates from 57 New York State counties were subjected to spatial autocorrelation analysis. Although the epidemic advanced during the study period, the analyses reveal a consistent pattern of spatial dependence. The correlation distance, the distance over which incidence rates covary positively, remained near 120 km over the nine years. A local spatial analysis around Westchester County, a major disease focus, indicated that the global correlation distance matched the extent of the most intense local clustering; statistically weaker clustering extended to 200 km from Westchester. Analyzing the spatial character of the epidemic may reveal the epizootic processes underlying patterns in human infection, and may help identify a spatial scale for regional control of disease.
Focus of human trichinellosis in Papua New Guinea.
Authors: Owen I L , Pozio E , Tamburrini A , Danaya R T , Bruschi F , Gomez Morales M A
Published: May 2017

Human trichinellosis and teniasis (Taenia solium) are meat-borne helminthic infections with a wide distribution throughout the world. However, there is little information on the prevalence of these infections in Papua New Guinea. In 1999, serum samples were collected from 97 people in 6 villages in the remote Bensbach area of Papua New Guinea. Enzyme-linked immunosorbent assay and Western blot analyses were used to detect anti-Trichinella immunoglobulin (Ig) G and anti-cysticercus IgG in this population. The prevalence of Trichinella antibodies among inhabitants of the Bensbach area was 28.9% (28 of 97; 67.8% in men), suggesting a high consumption of poorly cooked meat. The higher prevalence of infection for Trichinella in men compared with women may be explained by the inclination of men to eat undercooked pork while hunting. All serum samples were negative for cysticercus antibodies. This is to our knowledge the first serosurvey showing anti-Trichinella antibodies in a human population living in Papua New Guinea (Australian region).
Pinworm control and risk factors of pinworm infection among primary-school children in Taiwan.
Authors: Sung J F , Lin R S , Huang K C , Wang S Y , Lu Y J
Published: May 2017

Longitudinal pinworm (Enterobius vermicularis) infection rates were estimated at a mass screening for first-grade children during 1991-1996; children were provided medication at the screening. This campaign was able to decrease the infection rates for the 1991 cohort from 16.3% to 0.6%. A case-control study was further conducted for the investigation of risk factors among fourth-graders. Cases comprised 429 children with at least one infection between September 1996 to June 1999, and controls were 280 randomly selected uninfected classmates. Parents were asked to complete a questionnaire survey to report students' personnel hygiene habits. The case-control study revealed that significant factors associated with the infection included playing on the floor (odds ratio [OR], 2.5), nail biting (OR, 2.1), failure to wash hands before meals (OR, 1.7) and living in nonapartment dwellings (OR, 1.6). Girls were at a higher, but not significant, risk (OR, 1.4), than boys. In conclusion, inadequate personal hygiene increases the risk for pinworm infection. The mass screening-medication campaign can be adapted to countries with a similar parasitic problem.
Skin test antigens for immediate hypersensitivity prepared from infective larvae of Strongyloides stercoralis.
Authors: Neva F A , Gam A A , Maxwell C , Pelletier L L
Published: May 2017

More rapid and simplified diagnostic procedures are needed for the diagnosis of strongyloidiasis. One approach is the use of an immediate hypersensitivity skin test that would reliably identify infected people. Accordingly, somatic and excretion/secretion (E/S) antigens were prepared from filariform larvae of Strongyloides stercoralis and were treated to remove possible adventitious agents. By use of a quantitative method for measurement of skin reactions, several preparations of the 2 antigens were tested in uninfected controls and in various groups of patients. Doses of 0.35 microg of E/S and 4 microg of somatic antigens elicited positive skin tests in 82-100% of infected people, depending on clinical status. A lower frequency of positive skin tests was found in strongyloidiasis patients also infected with human T-cell lymphotropic virus type 1. Cross-reactions, especially to somatic antigens, were frequently found in patients with filarial infections. Despite these limitations and the need for further study of specificity, these results provide a basis for future development of a diagnostic skin test antigen for strongyloidiasis.
Tissue diagnosis of Ehrlichia chaffeensis in patients with fatal ehrlichiosis by use of immunohistochemistry, in situ hybridization, and polymerase chain reaction.
Authors: Dawson J E , Paddock C D , Warner C K , Greer P W , Bartlett J H , Ewing S A , Munderloh U G , Zaki S R
Published: May 2017

In the United States, human ehrlichiosis is a complex of emerging tick-borne diseases caused by 3 distinct Ehrlichia species: Ehrlichia chaffeensis, Ehrlichia ewingii, and the human granulocytotropic ehrlichiosis agent. Ehrlichioses are characterized by a mild to severe illness, and approximately 4% of cases are fatal. Because these obligate intracellular bacteria are difficult to resolve with routine histologic techniques, their distribution in tissues has not been well described. To facilitate the visualization and detection of ehrlichiae, immunohistochemistry (IHC), in situ hybridization (ISH), and polymerase chain reaction (PCR) assays were developed by use of tissues from 4 fatal cases of E. chaffeensis infection. Evidence of E. chaffeensis via IHC, ISH, and PCR was documented in all 4 cases. Abundant immunostaining and in situ nucleic acid hybridization were observed in spleen and lymph node from all 4 patients. Significantly, in 2 of these patients, serologic evidence of infection was absent. Use of IHC, ISH, and PCR to visualize and detect Ehrlichia in tissues can facilitate diagnosis of ehrlichial infections.
Factors contributing to anemia after uncomplicated falciparum malaria.
Authors: Price R N , Simpson J A , Nosten F , Luxemburger C , Hkirjaroen L , ter Kuile F , Chongsuphajaisiddhi T , White N J
Published: May 2017

The factors contributing to anemia in falciparum malaria were characterized in 4,007 prospectively studied patients on the western border of Thailand. Of these, 727 patients (18%) presented with anemia (haematocrit < 30%), and 1% (55 of 5,253) required blood transfusion. The following were found to be independent risk factors for anemia at admission: age < 5 years, a palpable spleen, a palpable liver, recrudescent infections, being female, a prolonged history of illness (> 2 days) before admission, and pure Plasmodium falciparum infections rather than mixed P. falciparum and Plasmodium vivax infections. The mean maximum fractional fall in hematocrit after antimalarial treatment was 14.1% of the baseline value (95% confidence interval [CI], 13.6-14.6). This reduction was significantly greater in young children (aged < 5 years) and in patients with a prolonged illness, high parasitemia, or delayed parasite clearance. Loss of parasitized erythrocytes accounted for < 10% of overall red blood cell loss. Hematological recovery was usually complete within 6 weeks, but it was slower in patients who were anemic at admission (adjusted hazards ratio [AHR], 1.9, 95% CI, 1.5-2.3), and those whose infections recrudesced (AHR, 1.2, 95% CI, 1.01-1.5). Half the patients with treatment failure were anemic at 6 weeks compared with 19% of successfully treated patients (relative risk, 2.8, 95% CI, 2.0-3.8). Patients coinfected with P. vivax (16% of the total) were 1.8 (95% CI, 1.2-2.6) times less likely to become anemic and recovered 1.3 (95% CI, 1.0-1.5) times faster than those with P. falciparum only. Anemia is related to drug resistance and treatment failure in uncomplicated malaria. Children aged < 5 years of age were more likely than older children or adults to become anemic. Coinfection with P. vivax attenuates the anemia of falciparum malaria, presumably by modifying the severity of the infection.
Human immunodeficiency virus seropositivity and malaria as risk factors for third-trimester anemia in asymptomatic pregnant women in western Kenya.
Authors: van Eijk A M , Ayisi J G , ter Kuile F O , Misore A , Otieno J A , Kolczak M S , Kager P A , Steketee R W , Nahlen B L
Published: May 2017

To assess risk factors for anemia in late pregnancy, we studied healthy pregnant women with a singleton uncomplicated pregnancy of > or = 32 weeks attending the prenatal clinic in the Provincial Hospital in Kisumu, Kenya. Between June 1996 and December 1998, 4,608 pregnant women had a blood sample collected for hemoglobin (Hb) measurement, malaria smear, and testing for human immunodeficiency virus (HIV). The mean +/- standard deviation of Hb was 9.58 +/- 1.8 g/dL; 21% had malaria in their blood; and 25% of the women were HIV seropositive. Plasmodium falciparum parasitemia was more common among HIV-seropositive women in all gravidities compared with HIV-seronegative women (risk ratio, 1.71; 95% confidence interval, 1.53-1.92). In a multivariate analysis, for primi- and secundigravidae women, the factors malaria, belonging to the Luo tribe, and HIV seropositivity were significantly associated with any anemia (Hb < 11 g/dL), and HIV seropositivity and documented fever were associated with severe anemia (Hb < 7 g/dL). In women of higher gravidities, HIV seropositivity was the only statistically significant factor associated with any anemia or with severe anemia. Asymptomatic HIV seropositivity is an important risk factor to be considered in the differential diagnosis of maternal anemia, independent of P. falciparum parasitemia.
Multiplicity of Plasmodium falciparum infection in pregnancy.
Authors: Beck S , Mockenhaupt F P , Bienzle U , Eggelte T A , Thompson W N , Stark K
Published: May 2017

Little is known about the distribution and disease association of multiple Plasmodium falciparum infections in pregnant women. Genotyping of the merozoite surface protein-1 region was performed in 332 P. falciparum infected pregnant women in Ghana, and clinical and epidemiologic data were obtained. Overall, 68% of the women were infected with more than one strain (mean number of strains per carrier = 2.9). The multiplicity of infection decreased significantly with an increasing number of pregnancies, and infection with multiple P. falciparum strains was significantly associated with anemia. In logistic regression, women infected with four or more strains were 2.3 times more likely to be anemic than women harboring fewer strains. This association, however, was only observed in women with up to three pregnancies. The results suggest that with increasing gravidity and subsequent infections with multiple strains effective immune mechanisms against more and more strains develop. In pregnant women, the multiplicity of infection may be an important factor for the acquisition and maintenance of immunity against malaria.
Association of splenomegaly with cerebral malaria and decreased concentrations of reactive nitrogen intermediates in Thailand.
Authors: Nacher M , Singhasivanon P , Treeprasertsuk S , Chantachum Y , Vannaphan S , Traore B , Gay F , Looareesuwan S
Published: May 2017

The role of the spleen during Plasmodium falciparum malaria in humans is unclear. In Thailand, malaria transmission is low and splenomegaly is rarer than in high transmission areas. We compared the prevalence of splenomegaly between 52 cerebral malaria patients and 191 patients without complications despite a high parasite biomass. We also measured concentrations of reactive nitrogen intermediates (RNIs) in a fraction of these cases recruited in 1998 (24 cerebral malaria and 56 controls). Splenomegaly was significantly associated with cerebral malaria (adjusted odds ratio = 2.07 [95% confidence interval = 1-4.2]; P = 0.048). There was a linear trend for this association (P = 0.0003). After adjusting for potential confounders, concentrations of RNIs were significantly lower in the presence of splenomegaly (P = 0.01). These results suggest that in humans, as in animal models, the spleen may be involved in the pathogenesis of cerebral malaria. The relationship between RNI concentrations and the spleen suggest that nitric oxide may have a regulating role in the complex physiology of the spleen during malaria.
Short report: Prevalence of fecal Encephalitozoon sp. spores among hospitalized patients in Nepal.
Authors: Shrestha A K , Enriquez F J
Published: May 2017

During the months of June and July 1998, stool samples from 341 hospitalized patients (mean age, 32.7 +/- 16.3 years; range, 1-86 years) from Kathmandu, Nepal, were screened for the prevalence of Encephalitozoon sp. by use of anti-Encephalitozoon sp. monoclonal antibody 3B6-based immunofluorescence assay. The cross-sectional study revealed the presence of Encephalitozoon spores in 0.6% (2 of 341) patients. By use of direct microscopic examination, 27% (93 of 341) of patients were diagnosed with various gastrointestinal pathogens, among which Ascaris lumbricoides and Ancylostoma duodenale were the most commonly found, with prevalence rates of 8.8% (30 of 341) and 7.6% (26 of 341), respectively. To our knowledge, this is the first study to report the presence of Encephalitozoon sp. among humans in Nepal.
Pre-exposure anti-Campylobacter jejuni immunoglobulin a levels associated with reduced risk of Campylobacter diarrhea in adults traveling to Thailand.
Authors: Walz S E , Baqar S , Beecham H J , Echeverria P , Lebron C , McCarthy M , Kuschner R , Bowling S , Bourgeois A L , Scott D A
Published: May 2017

Diarrhea history questionnaires were administered to 369 U.S. military volunteers before and after deployment to Thailand. Additionally, blood samples obtained from a subset of 221 volunteers 1-3 weeks previously and 3-4 weeks after their deployment were tested by enzyme-linked immunosorbent assay for immunoglobulin A to Campylobacter jejuni. Stool samples from personnel (including volunteers) contracting diarrhea in Thailand were cultured for enteric pathogens. Overall, 35.2% (130 of 369) of questionnaire respondents reported one or more diarrhea episodes during their trip. Volunteers with pretravel anti-C. jejuni reciprocal titers < or = 450 were 1.6 times as likely to have had diarrhea during their stay in Thailand compared with those with pretravel titers > 450 (39.7% versus 25.3%; P = 0.05). The symptomatic seroconversion, or attributable Campylobacter diarrhea attack rate, for the 1-month exercise was 12.7% (28 of 221). The symptomatic seroconversion rate in nonimmune (titer < or = 450) volunteers was 17.1%, whereas that in immune volunteers was only 4.0% (P = 0.002). Campylobacter jejuni or C. coli were recovered from 32.9% (56 of 170) of stool samples cultured and were the most commonly identified enteropathogens. Campylobacter diarrhea was associated with elevated temperatures, fecal red cells, and fecal white blood cells. The results of this study show that Campylobacter continues to represent a significant health threat to Western travelers to Thailand, but many of these travelers have preexisting Campylobacter immunity that protects them from clinically significant Campylobacter enteritis.
Referral pattern of leptospirosis cases during a large urban epidemic of dengue.
Authors: Flannery B , Pereira M M , Velloso L de F , Carvalho C de C , De Codes L G , Orrico G de S , Dourado C M , Riley L W , Reis M G , Ko A I
Published: May 2017

During heavy seasonal rainfall in 1996, concurrent epidemics of dengue and leptospirosis occurred in an urban center in northeastern Brazil. We interviewed 110 cases of leptospirosis hospitalized a median of seven days after the onset of illness to evaluate the impact of the dengue epidemic on the triage of suspected leptospirosis from ambulatory clinics to the infectious disease reference hospital. Within the first three days of illness, 46 (42%) cases sought their first medical evaluation, and 28 (61% of 46) received a diagnosis of dengue. Dengue diagnoses were associated with a median of five days delay in referral to the infectious disease hospital. Patients who reported initial diagnoses of dengue were more likely than other patients to have required admission to the intensive care unit (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 0.8-9.5) and to have died during hospitalization (OR = 5.1, 95% CI = 0.8-55.0). These findings indicate that diagnostic confusion between the early symptoms of leptospirosis and dengue may have contributed to the high mortality observed during the leptospirosis epidemic.
Genomic sequencing of deer tick virus and phylogeny of powassan-related viruses of North America.
Authors: Kuno G , Artsob H , Karabatsos N , Tsuchiya K R , Chang G J
Published: May 2017

Powassan (POW) virus is responsible for central nervous system infection in humans in North America and the eastern parts of Russia. Recently, a new flavivirus, deer tick (DT) virus, related to POW virus was isolated in the United States, but neither its pathogenic potential in human nor the taxonomic relationship with POW virus has been elucidated. In this study, we obtained the near-full-length genomic sequence of the DT virus and complete sequences of 3 genomic regions of 15 strains of POW-related virus strains. The phylogeny revealed 2 lineages, one of which had the prototype POW virus and the other DT virus. Both lineages can cause central nervous system infection in humans. By use of the combination of molecular definition of virus species within the genus Flavivirus and serological distinction in a 2-way cross-neutralization test, the lineage of DT virus is classified as a distinct genotype of POW virus.
Artemisinin for treatment of uncomplicated falciparum malaria: is there a place for monotherapy?
Authors: Giao P T , Binh T Q , Kager P A , Long H P , Van Thang N , Van Nam N , de Vries P J
Published: May 2017

The efficacy of artemisinin monotherapy was studied in 227 patients with uncomplicated falciparum malaria. They all received artemisinin at t = 0 hr, t = 8 hr, and thereafter once daily; treatment was extended at random until they had taken either 5 days of artemisinin followed by 2 days of placebo (A5), or 7 days (A7) of artemisinin. The adult artemisinin dose was 500 mg; children aged < 15 years received 10 mg/kg per dose. The median (range) parasite clearance time was 39 (8-112) hr for A5 and 43 (38-104) hr for A7 (P = 0.085). The recrudescence rates were similar between the groups. The lowest parasite count achieved during treatment (Pterm) was associated with the occurrence of recrudescence (P = 0.046, Cox regression model); it was lower for patients with a radical cure or late recrudescence than for early recrudescence (P = 0.034, t-test). Artemisinin monotherapy may offer rapid recovery and fast parasite clearance, but recrudescence is frequent. Extending the duration of monotherapy from 5 days to 7 days does not reduce recrudescence.
In vivo-in vitro model for the assessment of clinically relevant antimalarial cross-resistance.
Authors: Noedl H , Wernsdorfer W H , Krudsood S , Wilairatana P , Viriyavejakul P , Kollaritsch H , Wiedermann G , Looareesuwan S
Published: May 2017

Cross-resistance may be considered one of the most important factors leading to decreased drug susceptibility of Plasmodium falciparum. The study aimed to determine whether clinically relevant cross-sensitivity of P. falciparum existed between artemisinin and mefloquine. Seventy-six patients with falciparum malaria were admitted and treated with artemisinin derivatives. Treatment response parameters were assessed and in vitro drug sensitivity tests were performed with artemisinin, mefloquine, quinine, and chloroquine. Distinct in vitro cross-sensitivity between artemisinin and mefloquine was observed (p = 0.604; P < 0.001). To assess the relevance of this finding for clinical cross-resistance, we used an analytical model based on the relation of in vivo treatment response parameters (fever, parasite and symptom clearance) to a single reference drug with in vitro drug sensitivity data of several other drugs. Artemisinin (R = 0.554; P = 0.009) and mefloquine (R = 0.615; P = 0.002) in vitro drug sensitivities were equally well reflected in the in vivo treatment response to artemisinin, thereby suggesting the clinical relevance of in vitro cross-sensitivity.