bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiation between non-virulent and virulent Burkholderia pseudomallei with monoclonal antibodies to the Ara+ or Ara- biotypes.
Authors: Thepthai C , Dharakul T , Smithikarn S , Trakulsomboon S , Songsivilai S
Published: May 2017

Burkholderia pseudomallei is the causative agent of melioidosis, a fatal tropical infectious disease endemic in Southeast Asia. Environmental isolates of B. pseudomallei have two distinctive biotypes. Some soil isolates are arabinose-assimilators (Ara+ biotype) and are non-virulent in experimental animals. The others cannot assimilate arabinose (Ara- biotype) and are virulent in experimental animals. The Ara- biotype is found in almost all B. pseudomallei clinical isolates. In the present study, a panel of eight monoclonal antibodies that agglutinate the bacteria were produced and tested. The first group, Bps-D2, -D3, -D5, -L1, and -L2 agglutinated 100% of Ara+ clinical and soil isolates of B. pseudomallei. Another group Bps-A1, -A2, and -D1 agglutinated 92.9% and 90.9% of Ara- clinical and soil isolates, respectively. This panel of monoclonal antibodies may be useful for rapid differentiation between non-virulent Ara+ and virulent Ara- B. pseudomallei.
Short report: A practical technique for the cryopreservation of Dirofilaria immitis, Brugia malayi, and Wuchereria bancrofti microfilariae.
Authors: Bartholomay L C , Farid H A , El Kordy E , Christensen B M
Published: May 2017

A technique to cryopreserve microfilariae has been developed. This method was used to cryopreserve microfilariae of Dirofilaria immitis, Brugia malayi, and Wuchereria bancrofti at a controlled rate of 1 degree C/min by use of a freezing tank. Microfilariae of each of these species retained their ability to infect susceptible mosquito species and develop to the infective stage after cryopreservation. The method presented here is quickly and easily carried out with inexpensive equipment.
Resistance to treatment in Kala-azar: speciation of isolates from northeast India.
Authors: Sundar S , Pai K , Kumar R , Pathak-Tripathi K , Gam A A , Ray M , Kenney R T
Published: May 2017

Kala-azar in India is becoming increasingly difficult to treat, which may be due to the presence of species other than Leishmania donovani; Leishmania tropica was reported to cause the same clinical syndrome in the area. Over the past 3 years, we have collected samples from 241 patients with visceral leishmaniasis from across the region. Of the 189 isolates that grew on diphasic medium, 159 were successfully transferred to liquid medium for typing. Clinically, 80% of these were resistant to antimony. Lipophosphoglycan-specific monoclonal antibodies were used to distinguish the 2 species by agglutination of promastigotes; all 159 were shown to be L. donovani. Eighty-three isolates were confirmed to be L. donovani by isoenzyme analysis, by amplification of kinetoplast DNA, or both, in comparison with multiple reference strains; none were L. tropica. Thus, the rising incidence of clinical resistance to treatment is unlikely to be due to a different species causing kala-azar in north Bihar.
Experimental infections of pigs with Japanese encephalitis virus and closely related Australian flaviviruses.
Authors: Williams D T , Daniels P W , Lunt R A , Wang L F , Newberry K M , Mackenzie J S
Published: May 2017

The flavivirus Japanese encephalitis (JE) virus has recently emerged in the Australasian region. To investigate the involvement of infections with related enzootic flaviviruses, namely Murray Valley encephalitis (MVE) virus and Kunjin (KUN) virus, on immunity of pigs to JE virus and to provide a basis for interpretation of serologic data, experimental infections were conducted with combinations of these viruses. Antibody responses to primary and secondary infections were evaluated using panels of monoclonal antibody-based blocking enzyme-linked immunosorbent assays and microtiter serum neutralization tests (mSNTs). Identification of the primary infecting virus was possible only using the mSNTs. Following challenge, unequivocal diagnosis was impossible due to variation in immune responses between animals and broadened and/or anamnestic responses. Viremia for JE virus was readily detected in pigs following primary infection, but was not detected following prior exposure to MVE or KUN viruses. Boosted levels of existing cross-neutralizing antibodies to JE virus suggested a role for this response in suppressing JE viremia.
Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3'-untranslated region.
Authors: Durbin A P , Karron R A , Sun W , Vaughn D W , Reynolds M J , Perreault J R , Thumar B , Men R , Lai C J , Elkins W R , Chanock R M , Murphy B R , Whitehead S S
Published: May 2017

The recombinant dengue virus type-4 vaccine candidate 2AA30 was attenuated in rhesus monkeys due to an engineered 30-nucleotide deletion in the 3'-untranslated region of the viral genome. A clinical trial to evaluate the safety and immunogenicity of a single dose of 2Adelta30 was conducted with 20 adult human volunteers. The vaccine candidate was well tolerated and did not cause systemic illness in any of the 20 volunteers. Viremia was detectable in 14 volunteers at a mean level of 1.6 log10 plaque-forming units/ml of serum, although all 20 volunteers seroconverted with a seven-fold or greater increase in serum neutralizing antibody titer on day 28 post-vaccination (mean titer = 1:580). A mild, asymptomatic, macular rash developed in 10 volunteers, and a transient elevation in the serum level of alanine aminotransferase was noted in five volunteers. The low level of reactogenicity and high degree of immunogenicity of this vaccine candidate warrant its further evaluation and its use to create chimeric vaccine viruses expressing the structural genes of dengue virus types 1, 2, and 3.
Field prevalence of Wolbachia in the mosquito vector Aedes albopictus.
Authors: Kitrayapong Pattamaporn , Baimai Visut , O'Neill Scott L
Published: May 2017

The endosymbiotic bacteria in the genus Wolbachia have been proposed as a potential candidate to deliver pathogen-blocking genes into natural populations of medically important insects. The successful application of Wolbachia in insect vector control depends on the ability of the agent to successfully invade and maintain itself at high frequency under field conditions. Here, we evaluated the prevalence of Wolbachia infections in a field population of the Wolbachia-superinfected mosquito Aedes albopictus. A field prevalence of 100% (n = 1,016) was found in a single population in eastern Thailand via polymerase chain reaction (PCR) testing of Wolbachia both from individual parent females and their corresponding F1 offspring. This is the first report of accurate Wolbachia prevalence in a field population of an insect disease vector. The prevalence of superinfection was estimated to be 99.41%. All single-infected individual mosquitoes (n = 6) were found to harbor group A Wolbachia. For this particular population, none was found to be single-infected with group B Wolbachia. Our results also show that PCR testing of field materials alone without checking F1 offspring overestimated the natural prevalence of single infection. Thus, the confirmation of infection status by means of F1 offspring was critical to the accurate estimates of Wolbachia prevalence under field conditions.
Outbreak of vivax malaria in areas adjacent to the demilitarized zone, South Korea, 1998.
Authors: Lee Jong Soo , Lee Won Ja , Cho Shin Hyung , Ree Han-Il
Published: May 2017

Malaria had been eradicated in the Republic of Korea (South Korea) by the late 1970s. In 1993, a soldier was infected with Plasmodium vivax malaria in the Demilitarized Zone (DMZ; the border area between North and South Korea), and since then, the number of cases has been steadily increasing year after year. In 1998, 3,932 vivax malaria cases were microscopically confirmed, affecting 2,784 (70.8%) soldiers (including discharged soldiers) and 1,148 (29.2%) civilians. These cases occurred throughout the year, peaking in July (30.1%) and August (30.5%). Most of the patients were infected in areas in or near the DMZ. Taking into consideration entomologic, socioecologic, and epidemiologic factors, it is postulated that there has been an epidemic of malaria in North Korea since 1993, with the number of cases increasing yearly; the continuous infiltration across the DMZ from North Korea of infected female mosquitoes of the vector species Anopheles sinensis resulted in an outbreak of vivax malaria in the DMZ of South Korea.
Treatment of cutaneous leishmaniasis with a topical antileishmanial drug (WR279396): phase 2 pilot study.
Authors: Soto Jaime M , Toledo Julia T , Gutierrez Patricia , Arboleda Margarita , Nicholls Ruben S , Padilla Julio R , Berman Jonathan D , English Charles K , Grogl Max
Published: May 2017

We studied the efficacy of WR279396, a topical formulation of aminoglycosides that cures 100% of cutaneous leishmaniasis lesions in mice. We conducted what is to our knowledge the first controlled study of WR279396 therapy for clinical cutaneous leishmaniasis. A total of 45 Colombian soldiers, all men, were randomly assigned to treatment with WR279396 (33 patients) or placebo (12 patients). Each lesion was treated twice daily for 20 days. Lesions were measured at the end of therapy and at 45, 90, and 180 days after treatment began. A total of 17 (61%) of 28 assessable WR279396-treated patients were cured, and 5 (55%) of 9 assessable placebo-treated patients were cured (P = 0.9). For the 36 lesions treated with WR279396 that were cured, cure took a mean of 35 days, whereas for the 6 lesions that were cured in the group of patients receiving placebo, cure time took a mean of 56 days (P = 0.04). WR279396 is a nontoxic topical formulation that significantly accelerated cure time in patients with Leishmania panamensis cutaneous leishmaniasis.
Acute respiratory illness incidence and death among children under two years of age on Lombok Island, Indonesia.
Authors: Sutanto Agustinus , Gessner Bradford D , Djlantik Igg , Steinhoff Mark , Murphy Helen , Nelson Carib , Widjaya Anton , Arjoso Soemarjati
Published: May 2017

No childhood pneumonia incidence data for Indonesia exist, and few data exist for Asia as a whole. From February 1, 1998, to January 31, 1999, we conducted acute respiratory illness (ARI) surveillance among children < 24 months of age in 50 mainly rural villages on Lombok Island, Indonesia. The total number of child-years at risk during the study period was 17,015. The documented incidences of simple, severe, hospitalized, and radiologically confirmed alveolar pneumonia were 21, 8.3, 5.3, and 1.8 per 100 child-years of observation, respectively. For all outcomes, the incidence was higher among younger and rural children. All cause and ARI-specific infant mortality rates were 84 and 33 per 1,000 live births, respectively. More than 65% of deaths due to ARI occurred outside of a hospital setting. The incidence of pneumonia is high in Lombok. Interventions should include introducing vaccines to prevent infections leading to pneumonia and increasing the access of critically ill infants to the health care system.
Overexpression of vascular endothelial growth factor and its endothelial cell receptor KDR in type 1 leprosy reaction.
Authors: Fiallo Paolo , Clapasson Andrea , Favre Anna , Pesce Carlo
Published: May 2017

The sites of expression of vascular endothelial growth factor (VEGF) and of KDR, its endothelial cell receptor, were investigated in leprosy reaction Type 1, or reversal reaction (RR), by immunohistochemistry and in situ hybridization. In comparison with nonreactional leprosy, overexpression of both VEGF and KDR was seen in granuloma cells, especially epithelioid and foreign body-type giant cells, the epithelium and the vascular endothelium of RR specimens. In granuloma cells, hybridization for VEGF was stronger than immunostaining, a finding that may reflect the rapid turnover of VEGF in an immunologically dynamic situation such as RR. In the epidermis, double immunohistochemistry revealed VEGF overexpression in CDla-positive dendritic cells. The VEGF may not only be relevant for hyperpermeability and mononuclear cell differentiation (the key morphologic features in the acute, clinically evident phase of RR), but it could also be implicated in RR onset, when dendritic cells are activated in response to antigen stimulation.
Short report: concurrent Rocky Mountain spotted fever in a dog and its owner.
Authors: Paddock Christopher D , Brenner Ori , Vaid Chetan , Boyd D Barry , Berg Jason M , Joseph Richard J , Zaki Sherif R , Childs James E
Published: May 2017

A sequential occurrence of Rocky Mountain spotted fever (RMSF) in a dog and its owner is described. Diagnosis of RMSF in the animal guided subsequent testing for and diagnosis of the same disease in the human patient. Previous reports of concurrent RMSF in dogs and their owners are reviewed, and the epidemiologic significance of this occurrence is discussed.
Polymerase chain reaction-based identification and genotyping of Anopheles mosquitoes with a 96-pin bacterial replicator.
Authors: Rafferty Cristina S , Campbell Scott R , Wirtz Robert A , Benedict Mark Q
Published: May 2017

A simple method for rapid identification of large numbers of Anopheles mosquitoes was developed based on polymerase chain reaction (PCR) amplification of the rDNA intergenic spacer and internal transcribed spacer 2. By means of previously described primers for the Anopheles gambiae and An. quadrimaculatus species complexes, rDNA was amplified simultaneously from 96 whole mosquitoes or parts. No homogenization or individual DNA preparation was necessary, and transfer of 96 samples to PCR reactions was performed simultaneously with a bacterial replicator. Control reactions indicate that the level of cross-contamination is negligible, and false-negative findings are rare. The method was tested on larvae, pupae, adult heads, whole adult males and females, and single tarsi. All parts except tarsi provided satisfactory template. Fresh, ethanol-preserved, dried, and frozen adults were also tested with similar results. The method was also tested for amplification of a single-copy gene, white. Results were generally positive, although some false-negative findings were observed. This method allows rapid analysis of large numbers of mosquitoes without robotic equipment and should enable rapid and extensive PCR analysis of field-collected samples and laboratory specimens.
Molecular cloning and purification of Ac-TMP, a developmentally regulated putative tissue inhibitor of metalloprotease released in relative abundance by adult Ancylostoma hookworms.
Authors: Zhan Bin , Badamchian Mahnaz , Meihua Bo , Ashcom James , Feng Jianjun , Hawdon John , Shuhua Xiao , Hotez Peter J
Published: May 2017

A cDNA encoding a putative tissue inhibitor of metalloprotease was cloned from an Ancylostoma caninum adult hookworm cDNA library by immunoscreening with anti-hookworm secretory products antiserum. Ac-TMP (A. caninum tissue inhibitor of metalloproteinase) is encoded by a 480-bp mRNA with a predicted open reading frame of 140 amino acids (molecular weight, 16,100 Da) that contains one potential N-linked glycosylation site and an N-terminal Cys-X-Cys consensus sequence. The open reading frame corresponds to a putative hookworm tissue inhibitor of metalloproteases (TIMP) with 33% identity and 50% similarity to the N-terminal domain of human TIMP-2. Analysis by reverse transcriptase-polymerase chain reaction indicates that transcription of Ac-tmp is restricted to the adult stage. The protein was isolated from A. caninum adult secretory products by reverse-phase high-performance liquid chromatography and identified as one of the most abundant proteins released by the parasite. To our knowledge, this is the first description of a TIMP from a parasitic invertebrate.
Expression of filarial-specific IgG subclasses under different transmission intensities in a region endemic for loiasis.
Authors: Akue J P , Devaney E , Wahl G , Moukana H
Published: May 2017

Specific IgG subclasses were investigated in two villages (Okoumbi and Ndjokaye) in southeast Gabon with different Loa loa transmission intensities of approximately 9,000 and 1,300 infective larvae (L3) per person per year, respectively. IgG subclasses were measured by an enzyme-linked immunosorbent assay (ELISA) using extracts of L. loa L3, microfilariae (MF), or adult worms. Levels of L3-specific IgG3 were significantly higher in the village with low transmission (Ndjokaye) (P = 0.006). In contrast, MF-specific IgG2 was significantly higher in Okoumbi than in Ndjokaye (P = 0.0009). In the high-transmission village (Okoumbi), levels of both MF- and adult-specific IgG4 were significantly increased in MF carriers compared with amicrofilaremic subjects (P = 0.0015 and P = 0.003, respectively), while levels of L3- and MF-specific IgG1 were significantly higher in amicrofilaremic individuals compared with MF carriers (P = 0.04 and P = 0.03, respectively). Furthermore, among microfilaremic individuals, the level of the specific IgG1 subclass was much lower in Okoumbi than in Ndjokaye (P = 0.036). These results suggest that the expression of antigen-specific IgG3 and IgG2 is more likely to vary with transmission intensity, whereas antigen-specific IgG4 and IgG1 varies with adult worm and MF burden.
Effects of asymptomatic Giardia intestinalis infection on carbohydrate absorption in well-nourished Mexican children.
Authors: Moya-Camarena Silvia Y , Sotelo Norberto , Valencia Mauro E
Published: May 2017

The aim of this study was to evaluate carbohydrate absorption in well-nourished children with asymptomatic giardiasis. Two groups were selected based on results of stool examination of 211 children attending pre-school centers in Hermosillo, Sonora, Mexico: a control group of six non-infected children, and an infected group of seven children harboring Giardia intestinalis, without gastrointestinal symptoms of disease. Carbohydrate absorption was determined in the control group, before and after drug therapy in the infected group by the hydrogen breath test. Hydrogen production after lactose ingestion was higher in children with giardiasis compared with control group and after anti-parasite treatment; however, hydrogen production was not high enough to classify children as lactose malabsorbers by the cut-off criteria. Similar results were obtained for xylose absorption. None of the children had hydrogen increments high enough to be considered xylose malabsorbers. In conclusion, children asymptomatically infected with G. intestinalis showed significantly higher hydrogen production. However, the biological relevance is questionable since they did not exceed cut-off criteria to classify them as carbohydrate malabsorbers.
Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability.
Authors: Nagy J , Schipper H G , Koopmans R P , Butter J J , Van Boxtel C J , Kager P A
Published: May 2017

The assumed metabolic breakdown of albendazole by mucosal CYP3A4 enzymes was studied by coadministering albendazole (10 mg/kg) with grapefruit juice. Concentrations of albendazole sulfoxide (ABZSX), the active metabolite of albendazole, were compared with those after albendazole was administered with water, a fatty meal, or grapefruit juice plus cimetidine (10 mg/kg). In comparison to water, maximum ABZSX concentration (Cmax) was enhanced 6.5-fold by a fatty meal (from 0.24 +/- 0.09 mg/l to 1.55 +/- 0.30 mg/l; mean +/- SD; P < 0.001) and 3.2-fold by grapefruit juice (from 0.24 +/- 0.09 mg/l to 0.76 +/- 0.37 mg/L; P = 0.031). When grapefruit juice was combined with cimetidine, Cmax was significantly lower than with grapefruit juice alone (0.41 +/- 0.29 mg/l and 0.76 +/- 0.37 mg/l, respectively; P = 0.022). The area under the concentration-time curve from 0 to infinity (AUC(0-omega)) followed a comparable pattern. Half-life (T(1/2)) was 8.8 +/- 4.2 hr and 8.2 +/- 4.3 hr after administration with water or a fatty meal (P = 1.000). Grapefruit juice shortened T(1/2) by 46% (P = 0.026). We hypothesize that albendazole is metabolized by CYP3A4 enzymes in the intestinal mucosa. This process can be inhibited by grapefruit juice. Cimetidine decreased albendazole bioavailability.
Potential long-term toxicity of repeated orally administered doses of artemether in rats.
Authors: Xiao Shuhua , Yang Yuanqing , You Qiqing , Utzinger JÃ¼rg , Guo Huifang , Peiying Jiao , Mei Jinying , Guo Jian , Bergquist Robert , Tanner Marcel
Published: May 2017

Artemether, an efficacious antimalarial drug, effectively prevents patent schistosome infections and morbidity, as established in laboratory models and in clinical trials. In view of concern about the potential long-term toxicity, rats were treated orally with 80 mg/kg artemether once every 2 weeks for 5 months. After the final treatment, routine blood test results were normal except for reversible reductions of reticulocyte counts and reversible increases in hemoglobin levels. Liver and kidney function and histopathological examination showed no differences between treated and untreated rats. Administration of 400 mg/kg artemether resulted in transient focal vesicle degeneration of the liver or slight damage to the proprius layer lamina of intestinal villi. No damage to the central nervous system tissues, including cerebrum, cerebellum, midbrain, thalamus, pons, medulla oblongata, and spinal cord, was seen at either concentration. There were no alterations in electrocardiograms during the 6-month treatment period. We conclude that 80 mg/kg artemether administered once every 2 weeks is safe, and doses of 400 mg/kg do not result in evidence of neurotoxicology.
Control of aedes vectors of dengue in three provinces of Vietnam by use of Mesocyclops (Copepoda) and community-based methods validated by entomologic, clinical, and serological surveillance.
Authors: Kay Brian H , Nam Vu Sinh , Tien Tran Van , Yen Nguyen Thi , Phong Tran Vu , Diep Vu Thi Bich , Ninh Truong Uyen , Bektas Ahmet , Aaskov John G
Published: May 2017

We describe remarkable success in controlling dengue vectors, Aedes aegypti (L.) and Aedes albopictus (Skuse), in 6 communes with 11,675 households and 49,647 people in the northern provinces of Haiphong, Hung Yen, and Nam Dinh in Vietnam. The communes were selected for high-frequency use of large outdoor concrete tanks and wells. These were found to be the source of 49.6-98.4% of Ae. aegypti larvae, which were amenable to treatment with local Mesocyclops, mainly M. woutersi Van der Velde, M. aspericornis (Daday) and M. thermocyclopoides Harada. Knowledge, attitude, and practice surveys were performed to determine whether the communities viewed dengue and dengue hemorrhagic fever as a serious health threat; to determine their knowledge of the etiology, attitudes, and practices regarding control methods including Mesocyclops; and to determine their receptivity to various information methods. On the basis of the knowledge, attitude, and practice data, the community-based dengue control program comprised a system of local leaders, health volunteer teachers, and schoolchildren, supported by health professionals. Recycling of discards for economic gain was enhanced, where appropriate, and this, plus 37 clean-up campaigns, removed small containers unsuitable for Mesocyclops treatment. A previously successful eradication at Phan Boi village (Hung Yen province) was extended to 7 other villages forming Di Su commune (1,750 households) in the current study. Complete control was also achieved in Nghia Hiep (Hung Yen province) and in Xuan Phong (Nam Dinh province); control efficacy was > or = 99.7% in the other 3 communes (Lac Vien in Haiphong, Nghia Dong, and Xuan Kien in Nam Dinh). Although tanks and wells were the key container types of Ae. aegypti productivity, discarded materials were the source of 51% of the standing crop of Ae. albopictus. Aedes albopictus larvae were eliminated from the 3 Nam Dinh communes, and 86-98% control was achieved in the other 3 communes. Variable dengue attack rates made the clinical and serological comparison of control and untreated communes problematic, but these data indicate that clinical surveillance by itself is inadequate to monitor dengue transmission.
Molecular epidemiology of human T lymphotropic virus type 1 transmission in Okinawa, Japan.
Authors: Kakuda Kyoji , Ikematsu Hideyuki , Chong Wen Li Yong , Hayashi Jun , Kashiwagi Seizaburo
Published: May 2017

To clarify the route of human T lymphotropic virus type 1 (HTLV-1) transmission, we sequenced three proviral genome regions (gag, env, int) of HTLV-1 from 18 carriers in 7 families in Okinawa, Japan and compared the strains with isolates from other countries. The nucleotide substitution frequency among sequences derived from a single carrier was low; 0-0.24% in gag, 0-0.54% in env, and 0-0.34% in int. All sequences showed the closest identity to the Cosmopolitan strain, with differences of only 0-1.91%. All 8 mother/child pairs had identical nucleotide sequences. Of 3 pairs of spouses, 2 had identical sequences, with transmission probably from husband to wife. The mothers of both wives were HTLV-1-negative. The HTLV-1 sequence of the other wife showed three nucleotide differences from the sequence of her husband, but was identical to the sequence of her mother. These results support previous seroepidemiological studies that HTLV-1 transmission occurs from mother to children and also between spouses.
HIV infection, malaria, and pregnancy: a prospective cohort study in Kigali, Rwanda.
Authors: Ladner JoÃ«l , Leroy ValÃ©riane , Simonon Arlette , Karita Etienne , Bogaerts Joseph , De Clercq AndrÃ© , Van De Perre Philippe , Dabis FranÃ§ois , _ _
Published: May 2017

In order to study the relation between human immunodeficiency virus (HIV) infection and malaria in women, during and after pregnancy, a prospective cohort study was initiated at the Centre Hospitalier de Kigali in Rwanda through routine voluntary and confidential HIV screening in antenatal clinics. At inclusion in the cohort of all HIV-positive and an equivalent number of HIV-negative pregnant women, between 21 and 28 weeks of gestation, sociodemographic characteristics and medical history during the current pregnancy were collected; screening for malaria (tick blood smear) and anemia and a CD4 lymphocyte count were systematically performed. Each woman enrolled had a monthly follow-up until 6 months after delivery. A clinic was implemented that was accessible and free of charge to every woman during the study period between scheduled visits. Malaria infection was systematically screened in case of fever or other compatible symptoms. The cohort included 228 HIV-positive and 229 HIV-negative women. At inclusion, malaria prevalence was 8.0% in HIV-positive women and 3.5% in HIV-negative women (P < 0.04). Over the study period, the incidence of malaria was 6.2 per 100 women-months in the HIV-positive group and 3.5 in the HIV-negative group (relative risk [RR] = 1.7, 95% confidence interval [CI] = 1.4-2.3). The bulk of the difference occurred postpartum. The Kaplan-Meier 9-month probability of remaining free of malaria infection was 51.8% in HIV-positive women and 65.2% in HIV-negative women (P = 0.013). When taking account in the same multivariate model (including HIV infection, primiparity, CD4 lymphocytes, anemia, and education level), positive HIV serostatus remained the only factor significantly associated with malaria infection (RR = 1.4, CI = 1.1-1.6; P = 0.016). Our study prospectively documents the association between malaria and maternal HIV infection and highlights the increased risk of malaria occurrence in all HIV-infected women. Strategies to reduce the malaria morbidity during pregnancy should be reinforced in areas of high HIV seroprevalence.
Antibody responses to repetitive epitopes of the circumsporozoite protein, liver stage antigen-1, and merozoite surface protein-2 in infants residing in a Plasmodium falciparum-hyperendemic area of western Kenya. XIII. Asembo Bay Cohort Project.
Authors: Zhou Z , Xiao L , Branch O H , Kariuki S , Nahlen B L , Lal A A
Published: May 2017

The present study was initiated to characterize antibody responses to repetitive epitopes of the circumsporozoite protein (CSP), liver stage antigen-1 (LSA-1), and merozoite surface protein-2 (MSP-2) of Plasmodium falciparum in infants residing in a P. falciparum-hyperendemic area of western Kenya. In this study, development and maintenance of these antibody responses in 28 infants were studied longitudinally by use of monthly serum samples collected from birth to age 1 year. Mother plasma and infant umbilical cord plasma were also tested to assess the transplacental transfer of maternal antibodies. Results showed that antibodies passively transferred from mothers were detectable for CSP, LSA-1, and MSP-2 repeat epitopes. Infants were able to mount and maintain a strong antibody response against LSA-1 in their first year of life. Infants often responded to CSP repeats, but with a much lower antibody titer. Antibody responses in infants against Fc27 and 3D7 repeats of MSP-2 were low throughout their first year. In addition, 51 infants whose first detected infection occurred at > 4 months of age were selected to determine antibody responses to the antigens tested upon their first and second detected infections. Antibody responses to LSA-1 and, to a lesser degree, CSP increased in positivity rates and titer upon second infection. Antibody responses to Fc27-type and 3D7-type repeats of MSP-2 were low upon both infections. There was no association between maternally transferred anti-LSA-1, anti-CSP, or anti-MSP-2 antibodies and an infant's first detected infection. No significant correlation was found between an infant's antibody responses to the 4 antigen repetitive epitopes and protection against malarial parasitemia during the first year of life.
Outbreak of tick-borne relapsing fever at the north rim of the Grand Canyon: evidence for effectiveness of preventive measures.
Authors: Paul W S , Maupin G , Scott-Wright A O , Craven R B , Dennis D T
Published: May 2017

An outbreak of tick-borne relapsing fever (TBRF) originating at the North Rim of Grand Canyon National Park was investigated in 1990. To determine risk factors for the disease, almost 7,000 parties of visitors were surveyed; over half responded, representing > 10,000 people. Fifteen cases of confirmed or probable TBRF were identified in visitors and 2 in employees. All patients except one experienced symptoms after overnight stays in a group of cabins that had not been rodent-proofed after a TBRF outbreak in 1973 (relative risk for visitors [RR] 8.2, 95% confidence interval [CI] 1.1-62). Seven cases of TBRF were associated with a single cabin (RR 98, 95% CI 30-219). Structural flaws and rodent nests were common in the implicated cabins and rare in unaffected cabins. This investigation suggests that measures to rodent-proof cabins at sites where TBRF is endemic prevent reinfestation of cabins by infected rodents and tick vectors, thereby preventing the spread of disease in humans.
Prevalence of Rickettsia conorii and Rickettsia typhi infections in the population of northern Greece.
Authors: Daniel S Alexiou , Manika K , Arvanmdou M , Antoniadis A
Published: May 2017

Seroepidemical surveys concerning the prevalence of Rickettsia conorii and Rickettsia typhi have never been studied in northern Greece. We examined 1,584 sera samples from residents of northern Greece for the detection of antibodies to R. conorii and to R. typhi by means of immunofluorescence assay. In addition, we compared the prevalence of rickettsial infections among the demographic variables of sex, age, occupation, and area of residence. Antibodies to R. conorii and R. typhi were found in 125 (7.9%) and 31 (2.0%) of the examined subjects, respectively. The prevalence of antibodies to R. conorii correlated with increasing age and was statistically higher in men. Farmers had significantly higher prevalence of antibodies to both species of rickettsiae studied versus other professions. Residents of rural areas showed a statistically higher prevalence for R. conorii versus urban residents, although this difference was not demonstrated for R. typhi. We also detected differences in the prevalence of rickettsial infections among the different prefectures. Our data show the wide distribution of R. conorii in northern Greece and indicate the presence of R. typhi.
Susceptibility to dengue hemorrhagic fever in vietnam: evidence of an association with variation in the vitamin d receptor and Fc gamma receptor IIa genes.
Authors: Loke Hsin , Bethell Delia , Phuong Cao Xuan Thanh , Day Nick , White Nicholas , Farrar Jeremy , Hill Adrian
Published: May 2017

Dengue is an increasingly important cause of morbidity and mortality in the tropics, with more than a billion people at risk each year. Immunologic enhancement is thought to contribute to disease pathogenesis. Only a very small proportion of infected individuals develop life-threatening dengue hemorrhagic fever (DHF). In a large case-control study with 400 DHF patients and 300 matched controls, we have assessed five polymorphic non-HLA host genetic factors that might influence susceptibility to DHF. The less frequent t allele of a variant at position 352 of the vitamin D receptor (VDR) gene was associated with resistance to severe dengue (P = 0.03). Homozygotes for the arginine variant at position 131 of the Fc gammaRIIA gene, who have less capacity to opsonize IgG2 antibodies, may also be protected from DHF (one-tailed P = 0.03). No associations were found with polymorphisms in the mannose binding lectin, interleukin-1 (IL-4), and IL-1 receptor antagonist genes. Further studies to confirm these associations are warranted.
Pyrimethamine/sulfadoxine combination in the treatment of uncomplicated falciparum malaria: relation between dihydropteroate synthase/dihydrofolate reductase genotypes, sulfadoxine plasma levels, and treatment outcome.
Authors: Khalil Insaf , Alifrangis Michael , Rønn Anita M , Gabar Haythem A , Jelinek Tomas , Satti Gwiria M H , Bygbjerg Ib C
Published: May 2017

Several in vitro studies have shown the correlation between mutations in dhfr and dhps genes and resistance to pyrimethamine/sulfadoxine (PYR/SDX) combination, but the in vivo correlates of these mutations with PYR/ SDX efficacy have not been investigated fully. We assessed PYR/SDX efficacy in relation to the frequency of dhfr and dhps mutations in 37 Plasmodium falciparum isolates sampled before treatment. Plasma levels of SDX measured at days 0, 3, 7, and 14 ascertained drug absorption. Point mutations were detected only at codons 51 and 108 of dhfr and codon 436 of dhps. The frequency of dhfr 51/108 and dhps 436 mutations was 79% and 8%. The plasma levels of SDX indicated adequate drug absorption by all patients. The presence of Ile 51 and Asn 108 mutations among parasites that cleared after treatment indicates that these mutations alone are insufficient to cause in vivo resistance. In all recrudescent parasites, however, the presence of Ile 51/Asn 108 dhfr mutations was coupled with the dhps Ala 436. The findings suggest that the presence of Ile 51/Asn 108 dhfr mutations and Ala 436 dhps confers decreased susceptibility of P. falciparum to PYR/SDX in areas of low endemicity.
Monitoring the chromosome 2 intraerythrocytic transcriptome of Plasmodium falciparum using oligonucleotide arrays.
Authors: Le Roch Karine G , Zhou Yingyao , Batalov Sergei , Winzeler Elizabeth A
Published: May 2017

To test the feasibility of using short oligonucleotide probes to monitor transcript levels in Plasmodium falciparum, a microarray was manufactured containing 4,167 (25 base single-stranded) probes derived from the predicted coding region of P. falciparum chromosome 2. RNA samples from three asexual stages (rings, trophozoites, and schizonts) were labeled and hybridized to the arrays. These results were reproducible, and transcripts were detected for 69% of the 210 genes on chromosome 2. In addition, of the 145 expressed genes, 1/3 appeared to be differentially transcribed during the asexual cycle. Some regions of the chromosome appeared to be transcriptionally silent. Results were confirmed by Northern blot analysis and by quantitative reverse transcriptase-polymerase chain reaction. These data validate the use of relatively short 25-mers for monitoring the expression of a genome that is 82% AT rich.
Influence of host and larval habitat distribution on the abundance of African malaria vectors in western Kenya.
Authors: Minakawa Noboru , Seda Pamela , Yan Guiyun
Published: May 2017

The abundance of anopheline mosquitoes varies substantially among houses within the same villages. Anopheles gambiae sensu stricto is highly anthropophilic, and Anopheles arabiensis is zoophilic; thus, it is often hypothesized that the abundance of An. gambiae and An. arabiensis in a house is associated with the distribution of livestock and humans. In this paper we examined the influence of livestock and human host availability on the distribution and abundance of malaria vectors in the basin region of Lake Victoria in western Kenya. Larvae and adults of An. gambiae, An. arabiensis and Anopheles funestus were collected in the beginning and the end of the rainy season in 1999. Anopheles gambiae was the predominant species in both larval and adult samples. Multiple regression analyses found that the ratio of distance between houses and larval habitats to distance between cowsheds and larval habitats had a significant and negative association with the relative abundance of An. gambiae larvae for both sampling periods. The ratio of human density to cow density was positively correlated with the relative abundance of An. gambiae larvae in the late rainy period. For the adult samples, distance from a house to its nearest larval habitats was the only variable that showed a significant correlation with the An. gambiae density in houses in both sample periods. More than 90% of anopheline adults were found in the houses within 300 meters from the nearest larval habitats. Anopheline mosquito density was not correlated to the density of cows or humans, or the distance to cowsheds from houses. These results suggest that livestock and human host availability affect the relative abundance of An. gambiae larvae in aquatic habitats, but the distribution of anopheline adults in houses is determined by the distance from houses to larval habitats.
Contrasting sylvatic foci of Venezuelan equine encephalitis virus in northern South America.
Authors: Barrera Roberto , Ferro Cristina , Navarro Juan-Carlos , Freier Jerome , Liria Jonathan , Salas Rosalba , Ahumada Marta , Vasquez Clovis , Gonzalez Marta , Kang Wenli , Boshell Jorge , Weaver Scott C
Published: May 2017

The ecology of Venezuelan equine encephalitis (VEE) virus transmission was compared at three enzootic foci: two forest sites in the Catatumbo region of western Venezuela that have yielded small numbers of virus isolates since the 1970s, and another focus in the middle Magdalena Valley of Colombia that has consistently yielded many VEE virus isolates. Our results demonstrated dramatic differences in VEE virus isolation rates from sentinel hamsters, as well as differences in mosquito species composition and captured mammals with antibodies to VEE virus, between the Colombian and Venezuelan study sites. The higher isolation rate of enzootic VEE virus in the Colombian site was associated with a more abundant fauna of spiny rats (Proechimys spp.), known reservoir hosts of enzootic VEE virus. Mosquito collections demonstrated that the Colombian forest had a higher mosquito diversity and species evenness than either of the Venezuelan forests. The Colombian focus was especially richer in its Culex (Melanoconion) spp. fauna, a subgenus that includes all proven enzootic vectors for VEE virus. Our results suggest that the greater abundance, diversity, and stability of enzootic vector populations, combined with the greater density of rodent reservoir hosts, explains the higher levels of VEE virus circulation in the Colombian focus compared with the Venezuelan forests.
Role of hepatitis C infection in chronic liver disease in Egypt.
Authors: Strickland G Thomas , Elhefni Hanaa , Salman Tary , Waked Imam , Abdel-Hamid Mohamed , Mikhail Nabiel Nh , Esmat Gamal , Fix Alan
Published: May 2017

Hepatitis C virus (HCV) is considered the most common etiology of chronic liver disease (CLD) in Egypt, where prevalence of antibodies to HCV (anti-HCV) is approximately 10-fold greater than in the United States and Europe. Reported are results that show the role of HCV in both overt and occult CLD, the risk factors for CLD and for HCV infection, and the relative importance of chronic HCV, hepatitis B, or both in causing hepatic morbidity. Case patients included 237 new outpatients at the National Liver Institute. Controls comprised 212 sex- and age-matched neighbors without liver disease. Case patients were more likely than controls to report a history of blood transfusions, schistosomiasis, or parenteral therapy for schistosomiasis; to have anti-HCV, HCV RNA, hepatitis B surface antigen, and serum alanine aminotransferase (ALT) elevations; and to have abdominal ultrasound findings of cirrhosis, portal hypertension, and splenomegaly. Anti-HCV-positive case patients were more likely than anti-HCV-negative patients to be male, older, and farmers: to have received a blood transfusion or parenteral therapy for schistosomiasis; to have ALT elevations; and to have ultrasound findings of cirrhosis, portal hypertension, and spleen enlargement. Anti-HCV-positive controls were more likely than anti-HCV-negative controls to have received parenteral therapy for schistosomiasis. These data support the belief that HCV is the predominant cause of CLD in Egypt and suggest there is a large underlying reservoir of HCV-caused liver disease.
Detection of West Nile virus-infected mosquitoes and seropositive juvenile birds in the vicinity of virus-positive dead birds.
Authors: Nasci Roger S , Komar Nicholas , Marfin Anthony A , Ludwig George V , Kramer Laura D , Daniels Thomas J , Falco Richard C , Campbell Scott R , Brookes Kelsey , Gottfried Kristy L , Burkhalter Kristen L , Aspen Stephen E , Kerst Amy J , Lanciotti Robert S , Moore Chester G
Published: May 2017

Mosquitoes and wild birds were collected from three sites near locations in the New York City metropolitan area where single, West Nile (WN) virus-positive dead birds were found early in the 2000 transmission season. The mosquitoes were tested for the presence of infectious virus with a Vero cell culture assay and for WN viral RNA by using reverse transcriptase-polymerase chain reaction (RT-PCR) protocols. Serum samples from wild birds were tested for the presence of neutralizing antibodies against WN virus. Infectious WN virus and WN viral RNA were found in Culex species adult mosquitoes from each of the three sites, and a seropositive hatch-year house sparrow (Passer domesticus) was found in one of the three sites. Molecular techniques used to identify the species in the positive mosquito pools found that most of the pools contained a combination of Culex pipiens and Cx. restuans. The minimum infection rate in Culex species mosquitoes from the sites ranged from 0.2 to 6.0 per 1,000 specimens tested. The results demonstrated that, at least early in the transmission season, detection of a WN virus-positive dead bird indicates a local WN virus transmission cycle. This information is valuable in focusing subsequent surveillance and vector management programs. In addition, the RT-PCR procedure for detecting WN viral RNA in mosquito pools detected more positive pools than did the Vero cell plaque assay.
Comparative evaluation of selected diagnostic assays for the detection of IgG and IgM antibody to Orientia tsutsugamushi in Thailand.
Authors: Coleman Russell E , Sangkasuwan Vichai , Suwanabun Nantavadee , Eamsila Chirapa , Mungviriya Siriporn , Devine Peter , Richards Allen L , Rowland Denise , Ching Wei-Mei , Sattabongkot Jetsumon , Lerdthusnee Kriangkrai
Published: May 2017

We compared the performance of 2 commercially available dipstick assays, 2 enzyme-linked immunosorbent assays (ELISAs), and an indirect immunofluorescent antibody (IFA) assay for the diagnosis of scrub typhus, using the indirect immunoperoxidase (IIP) test as the reference standard. The dipstick assays were the Integrated Diagnostics (Baltimore, MD) Dip-S-Ticks Scrub Recombinant (r56) dipstick test (INDX assay) and the PanBio (Brisbane, Australia) Scrub Typhus IgM and IgG Rapid Immunochromatographic test (PanBio assay). One of the ELISAs used pooled cell lysates of Karp, Kato, and Gilliam strain Orientia tsutsugamushi as antigen (pooled-antigen ELISA), and the other used a recombinant r56 protein as the antigen (recombinant ELISA). With a panel of 123 positive and 227 negative sera, sensitivity and specificity of the assays were as follows: INDX assay, IgG, 60% and 95%, IgM, 60% and 97%; PanBio assay, IgG, 94% and 96%, IgM, 83% and 93%; IFA (1:400 cutoff), IgG, 91% and 96%, IgM, 85% and 98%; pooled-antigen ELISA, IgG (1:1600 cutoff), 97% and 89%, IgM (1:400 cutoff), 94% and 91%; recombinant ELISA, IgG (1:1600 cutoff), 97% and 92%, IgM (1:400 cutoff), 93% and 94%. Because of its excellent performance and use of a standardized, commercially available antigen, the recombinant ELISA is suitable for use in a diagnostic laboratory, where it may be able to replace the IFA and IIP assays. In contrast, the PanBio dipstick assay was easy to perform and did not require sophisticated equipment, making it suitable for use in rural areas where more sophisticated diagnostic tests such as the ELISA and IFA may not be available.
The effects of antimalarial drugs on ventricular repolarization.
Authors: Touze J E , Heno P , Fourcade L , Deharo J C , Thomas G , Bohan S , Paule P , Riviere P , Kouassi E , Buguet A
Published: May 2017

Cardiotoxicity has become a major concern during treatment with antimalarial drugs. Lengthening of the QTc and severe cardiac arrhythmia have been observed, particularly after treatment with halofantrine for chloroquine-resistant Plasmodium falciparum malaria. The purpose of this prospective study was to evaluate whether antimalarial agents alter dispersion of the QTc and ventricular repolarization dynamicity. Sixty patients with uncomplicated falciparum malaria were randomly allocated in four groups of 15 patients and treated with quinine, mefloquine, artemether, or halofantrine at recommended doses. Patients in treatment groups were compared with a group including 15 healthy controls with no history of malaria and/or febrile illness within the last month. QTc dispersion was measured on surface electrocardiograms. Repolarization dynamicity was analyzed from Holter recordings, which allow automatic beat-to-beat measurement of QT and RR intervals. Plasma drug concentration was determined by reversed-phase high-performance liquid chromatography. No change in QTc dispersion was observed after treatment with quinine, mefloquine, or artemether. Treatment with halofantrine was followed by a significant increase in QTc dispersion at 9 hours (P < 0.0001) and 24 hours (P < 0.01). Assessment of QT heart rate variability by QT/RR nychtohemeral regression slope demonstrated no significant difference between the artemether (mean +/- SEM = 0.170 +/- 0.048), mefloquine (0.145 +/- 0.044), and the control groups (0.172 +/- 0.039). A significant decrease in the Q-eT/RR slope was observed in the quinine group compared with the control and artemether groups (0.135 +/- 0.057; P < 0.04). With halofantrine, a significant increase in the QT/RR regression slope (0.289 +/- 0.118) was observed (P < 0.0002). QTc interval, QT dispersion, and QT regression slope were significantly correlated with halofantrine and quinine plasma concentration. Mefloquine and artemether did not alter ventricular repolarization. Quinine induced a significant decrease in QT/RR slope of the same order of magnitude as those previously observed with quinidine. Both QTc dispersion and QT/RR slope were significantly modified by halofantrine. These repolarization changes were related to a class-III antiarrhythmic drug effect and may explain the occurrence of ventricular arrhythmia and/or sudden deaths reported after halofantrine intake.