bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of severe anemia and its association with malaria in young children of the Kassena-Nankana District of northern Ghana.
Authors: Owusu-Agyei Seth , Fryauff David J , Chandramohan Daniel , Koram Kwadwo A , Binka Fred N , Nkrumah Francis K , Utz Greg C , Hoffman Stephen L
Published: May 2017

Severe anemia is thought to be the principal underlying cause of malaria death in areas of intense seasonal malaria transmission such as the Kassena-Nankana District of northern Ghana. Factors associated with severe anemia in young children, 6-24 months old, were elucidated by analyzing results of 2 malaria-associated anemia surveys (1996, 2000), separated by 4 years, but conducted in the same community and at the same seasonal time point. Age-adjusted comparison confirmed that the proportion of severely anemic children and overall mean hemoglobin (Hb) levels in the November 2000 sample were significantly improved over those of the 1996 sample (17.5 versus 26.4%, P = 0.03; Hb 7.5 versus 6.9 g/dL, P = 0.002). Weight-for-age Z-scores also indicated a significant improvement in the 2000 sample (-1.93 versus -2.20, P < 0.05). Independently, each survey identified statistically significant associations between severe anemia and age, parasite rate, fever, and sex. Relative to children with Hb > or = 6.0 g/dL, those with severe anemia (Hb < 6.0 g/dL) were older, more frequently parasitemic (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.08-2.35), more often febrile (OR, 2.44; 95% CI, 1.71-3.48), and predominantly male (OR, 1.50; 95% CI, 1.05-2.13). An association was identified in both surveys between severe anemia and residence in the northern part of the district, but no clear link was observed in relation to irrigation. Blood transfusions, a likely surrogate index of severe anemia in young children, followed a distinct seasonal pattern. Evidence suggests that dramatic peaks and troughs of severe anemia are regular and possibly predictable events that may be used to gauge the health and survival of young children in this area.
Molecular epidemiology of malaria in Cameroon. XI. Geographic distribution of Plasmodium falciparum isolates with dihydrofolate reductase gene mutations in southern and central Cameroon.
Authors: Basco Leonardo K , Ndounga Mathieu , Tejiokem Mathurin , Ngane Vincent Foumane , Youmba Jean-Christian , Ringwald Pascal , Soula Georges
Published: May 2017

The DNA sequence of the dihydrofolate reductase (dhfr) gene, a molecular marker for pyrimethamine resistance, was determined for 178 field isolates of Plasmodium falciparum collected along the east-west axis in southern Cameroon. The proportion of isolates having the wild-type dhfr allele varied from 48.1% in the east (city of Bertoua) to 11.3-15.7% in central provinces (Yaounde and Eseka) and 0% in the littoral region (port city of Douala). Isolates with a single Asn-108 mutation or double mutations (Ile-51 or Arg-59 and Asn-108) constituted approximately 10% of the samples. Isolates with triple mutations (Ile-51, Arg-59, and Asn-108) were present in an equal proportion (48.1%) as the wild-type isolates in the east (Bertoua), while triple mutations predominated in Yaounde (62.3%), Eseka (62.7%), and Douala (78.9%). The distribution of triple dhfr mutations along the east-west axis in southern Cameroon suggests the presence of a decreasing gradient from the west coastal region to the central region and then to the east towards the interior of the country.
Molecular epidemiology of malaria in Cameroon. XII. In vitro drug assays and molecular surveillance of chloroquine and proguanil resistance.
Authors: Basco Leonardo K
Published: May 2017

Chloroquine-proguanil combination is one of the options for chemoprophylaxis. The rapid evolution of drug resistance status requires a constant upgrade of epidemiologic data. Due to various difficulties in conducting prospective clinical studies on the prophylactic efficacy of the drug combination, especially in highly chloroquine-resistant zones, in vitro drug sensitivity assays and specific molecular markers for chloroquine (Plasmodium falciparum chloroquine-resistance transporter, pfcrt) and cycloguanil (a biologically active metabolite of proguanil; dihydrofolate reductase, dhfr) resistance were evaluated as an alternative approach in this study. Of 116 isolates, 62 (53.4%) were doubly resistant in vitro to chloroquine (IC50 > or = 100 nM) and cycloguanil (IC50 > or = 15 nM). Likewise, 62 of 118 isolates (52.5%) carried both the mutant Thr-76 pfcrt allele and at least one dhfr mutant allele (1 with a single Asn-108 allele, 8 with double Arg-59 and Asn-108 mutations, and 53 with triple Ile-51, Arg-59, and Asn-108 mutations). The in vitro drug response corresponded with the presence or absence of key mutation(s) in the pfcrt and dhfr genes. These results suggest the high proportion of P. falciparum isolates in southern Cameroon that may not respond to chloroquine-proguanil combination.
Dracunculiasis eradication: and now, Sudan.
Authors: Hopkins Donald R , Ruiz-Tiben Ernesto , Diallo Nwando , Withers P Craig , Maguire James H
Published: May 2017

This paper summarizes the status of the global dracunculiasis eradication campaign as of early 2002. Of the 20 countries that were endemic when the campaign began, seven have already interrupted transmission, four countries reported less than 100 cases each, and only five countries reported more than 1,000 cases each in 2001. Only 14,000 cases remained outside Sudan in 2001. Sudan reported 78% of all cases of dracunculiasis in 2001, and virtually all of Sudan's cases were in the southern states, where the long-standing civil war limits accessibility to endemic areas. A political settlement of the war is now urgently needed, since it will be impossible to complete the eradication of dracunculiasis without peace in Sudan.
Neuropathologic toxicity of artemisinin derivatives in a mouse model.
Authors: Nontprasert Apichart , Pukrittayakamee Sasithon , Dondorp Arjen M , Clemens Ralf , Looareesuwan Sornchai , White Nicholas J
Published: May 2017

Intramuscular administration of high doses of artemether and arteether to experimental mammals produces selective damage to brain stem centers involved predominantly in auditory processing and vestibular reflexes. The relationship between clinical signs of neurotoxicity and neuropathologic toxicity was studied in the mouse. Intramuscular artemether (50-100 mg/kg/day for 28 days) caused dose-dependent neuropathologic damage to the brain stem. There was no pathologic evidence of neuronal death in mice receiving either oral artemether, or oral or intramuscular artesunate, in doses up to 300 mg/kg/day. The neurons in the lower brain stem trapezoid nucleus, the gigantocellular reticular nucleus, and the inferior cerebellar peduncle were the most sensitive to the toxic effects of artemether. All mice with neuropathologic changes also showed behavioral changes, whereas in some mice with gait disturbance, no corresponding histopathologic damage could be detected. Thus clinical assessment was a sensitive measure of neurotoxicity. There may be a reversible component to artemether neurotoxicity.
Potential of the Panama strain of Plasmodium vivax for the testing of malarial vaccines in Aotus nancymai monkeys.
Authors: Collins William E , Sullivan JoAnn S , Galland G Gale , Williams Allison , Nace Douglas , Williams Tyrone
Published: May 2017

Aotus monkeys were infected with a strain of Plasmodium vivax from Panama to determine its potential for the testing of malarial vaccines. After sporozoite inoculation, 3 splenectomized Aotus nancymai that had been infected previously with Plasmodium falciparum and P. vivax had prepatent periods of 13, 15, and 15 days with maximum parasite counts of 12,726/microl, 5,310/microl, and 9,180/microl. Three other A. nancymai previously infected with P. falciparum only had prepatent periods of 17, 15, and 15 days with maximum parasite counts of 44,460/microl, 31,500/microl, and 42,660/microl. One monkey with no previous history of infection had a prepatent period of 14 days after sporozoite inoculation, and a maximum parasite count of 100,000/microl; detectable parasitemia persisted for almost 500 days with 13 recognizable peaks in the parasite count. Anopheles dirus, Anopheles freeborni, Anopheles stephensi, and Anopheles quadrimaculatus mosquitoes were readily infected with the Panama strain.
Diuretic effect of sodium artesunate in patients with malaria.
Authors: Seguro Antonio Carlos , Campos Silvia Bernardete
Published: May 2017

Previously, we described a direct inhibitory effect of sodium artesunate on sodium chloride transport in the thick ascending limb of Henle's loop, indicating that artesunate acts as a diuretic agent. Here we present 2 cases of falciparum malaria treated with 4 intravenous 60-mg doses of sodium artesunate. Neither diuretics nor vasoactive drugs were administered. A rise in diuresis (6 L/24 hours) was accompanied by an increase in natriuresis, and both declined at the end of the treatment. This diuretic effect has not been reported previously in patients and may modify the course of renal failure and respiratory distress syndrome, both of which complicate severe malaria.
Molecular characterization of Lyme disease spirochetes (Borrelia burgdorferi sensu lato) isolated in Taiwan by restriction fragment length polymorphism analysis of 5S(rrf)-23S(rrl) intergenic spacer amplicons.
Authors: Chao Li-Lian , Shih Chien-Ming
Published: May 2017

We analyzed the 5S (rrf)-23S (rrl) intergenic spacer amplicon gene of Lyme disease spirochetes (Borrelia burgdorferi sensu lato) for the first time in Taiwan. The genetic identities of these Taiwan isolates (TWKM1-7) were clarified by comparing their restriction fragment length polymorphism patterns and sequence similarities of the polymerase chain reaction-amplified intergenic spacer amplicon genes with 3 major genospecies of Lyme disease spirochetes. Amplified-spacer DNAs were purified further and subjected to the cleavage by nuclease DraI or MseI. Differential fragment patterns in relation to different genospecies of Lyme disease spirochetes were observed among tested Borrelia isolates, and all of these Taiwan isolates were closely related to the genospecies of B. burgdorferi sensu stricto. The phylogenetic analysis also revealed that the sequence similarity of polymerase chain reaction-amplified spacer genes of these Taiwan isolates was highly homogeneous (95.7-100%) within the genospecies of B. burgdorferi sensu stricto and can be distinguished clearly from other genospecies of Lyme disease spirochetes with a 4.1% sequence divergence. Based on the differential fragment patterns and sequence similarity among these Taiwan isolates, the genetic identity of these Taiwan isolates should be classified into the genospecies of B. burgdorferi sensu stricto.
Domestic dog ownership in Iran is a risk factor for human infection with Leishmania infantum.
Authors: Gavgani A Samad Mazloumi , Mohite Hassan , Edrissian Gholan H , Mohebali Mehdi , Davies Clive R
Published: May 2017

One explanation proposed for the widespread failure to control zoonotic visceral leishmaniasis by culling infected domestic dogs is that wild canids or humans play significant roles in transmission. The aim of this study was to determine the importance of domestic dogs as the reservoir hosts of visceral leishmaniasis in northwest Iran. A random sample of 3,872 children and 199 dogs in 38 villages was surveyed by the direct agglutination test. Dog ownership details among these households were collected by questionnaire. Parasites isolated from 16 patients and 12 dogs were characterized as Leishmania infantum MON-1. Average seroprevalence in dogs (21.6%) was much higher than in children (7%). Child seropositivity increased significantly with village dog density in absolute terms (P < 0.001) and in relation to dog/human ratios (P = 0.028). Dog ownership within villages also was a significant risk factor for child seropositivity (P = 0.003).
Exacerbation of HIV viral load simultaneous with asymptomatic reactivation of chronic Chagas' disease.
Authors: Sartori Ana Marli C , Caiaffa-Filho HÃ©lio H , Bezerra Rita C , do S Guilherme Carmem , Lopes Marta H , Shikanai-Yasuda Maria Aparecida
Published: May 2017

Chronic Trypanosoma cruzi infection can reactivate in patients with immunosuppression related to human immunodeficiency virus (HIV) infection, resulting in severe meningoencephalitis or myocarditis and high parasitemia. The effects of T. cruzi on HIV infection are unknown. We describe an HIV-infected patient with chronic Chagas' disease who experienced an asymptomatic T. cruzi reactivation characterized by the finding of the parasite in direct microscopic examination of blood. The patient's HIV viral load had increased simultaneously with the exacerbation of T. cruzi parasitemia and decreased to previous levels after successful antiparasitic treatment. This otherwise unexplained finding suggests that T. cruzi infection might up-regulate HIV replication, which may affect HIV disease progression. Asymptomatic reactivation of Chagas' disease has not been reported before. This could mean that the severe clinical manifestations related to the reactivation of trypanosomiasis are just the tip of the iceberg.
Seroprevalence of rubella among women of childbearing age in Taiwan after nationwide vaccination.
Authors: Su Shih-Bin , Guo How-Ran
Published: May 2017

Taiwan initiated a nationwide program in 1986 to have all 15-year-old schoolgirls vaccinated against rubella and another program in 1992 to encourage all women of childbearing age to receive rubella vaccination. To assess the immunity among women after the implementation of these programs, we conduct a serosurvey. We recruited women who were 15-44 years old and received pre-employment health examinations at the clinic of an industrial park from January 1 to June 30, 2000. Anti-rubella antibody titers were determined by enzyme-linked immunoassays. All 1,087 women who fit the selection criteria agreed to participate, and the overall susceptible (seronegative) rate was 5.7%. The susceptible rate was much lower among women who were covered by both programs than women who were not (4% versus 23%, P < 0.001). The nationwide vaccination programs were effective, but a substantial proportion of childbearing-age women were still susceptible and need booster vaccination.
Outbreak of amebiasis in Tbilisi, Republic of Georgia, 1998.
Authors: Barwick Rachel S , Uzicanin Amra , Lareau Susan , Malakmadze Naile , Imnadze Paata , Iosava Merab , Ninashvili Nana , Wilson Marianna , Hightower Allen W , Johnston Stephanie , Bishop Henry , Petri William A , Juranek Dennis D
Published: May 2017

In 1998, we investigated a suspected outbreak of amebic liver abscesses caused by Entamoeba histolytica in the Republic of Georgia, using a case-control study. A questionnaire was administered and blood samples were obtained from cases and controls for serologic diagnosis. Medical records showed that E. histolytica infections were rarely diagnosed before 1998. However, from July through September 1998, 177 cases of suspected amebiasis were identified. Of 52 persons who had diagnosed liver abscesses, 37 (71%) were confirmed serologically to have antibodies against E. histolytica, compared with 11 of 53 persons (20.8%) diagnosed with intestinal amebiasis. In addition, 9-14% of asymptomatic controls were seropositive. Logistic regression identified the fact that interruptions in the water supply, decreases in water pressure, and increased water consumption were significantly associated with infection. The data support the hypothesis that drinking water was the source of infection, either because of inadequate municipal water treatment or contamination of municipal water in the distribution system.
Short report: Molecular evaluation of the efficacy of chloroquine treatment of uncomplicated Plasmodium falciparum malaria in East Timor.
Authors: Chen Nanhua , Baker Joanne , Ezard Nadine , Burns Matthew , Edstein Michael D , Cheng Qin
Published: May 2017

The efficacy of chloroquine treatment of uncomplicated Plasmodium falciparum malaria in East Timor was investigated via molecular tools. Genotyping of the polymorphic markers msp1 and msp2 was performed to investigate the number and type of parasite alleles in pre- and posttreatment blood samples collected from 48 patients. Patients were infected with a minimum of 8 msp1 and 14 msp2 allelic types of parasite, and 43% of the patients had more than one allelic type before treatment. The genotyping also revealed that 66.7% of the patients were infected with at least one identical allelic type of parasite before and after treatment and therefore were likely to have experienced recrudescence. All parasites in pre- and posttreatment blood samples carried the K76T mutation in pfcrt, regardless of the clinical response to chloroquine. The sequence polymorphism patterns in pfcrt in the majority of parasites examined were identical to those observed in Bougainville, Papua New Guinea.
A putative receptor for dengue virus in mosquito tissues: localization of a 45-kDa glycoprotein.
Authors: Yazi Mendoza MarÃ­a , Salas-Benito Juan Santiago , Lanz-Mendoza Humberto , HernÃ¡ndez-MartÃ­nez Salvador , del Angel Rosa M
Published: May 2017

Dengue virus (DENV) infects target cells by attaching to various cell receptors, many of which are still unknown. In C6/36 cells (Aedes albopictus cell line), DENV-4 bound to two glycoproteins of 40 and 45 kDa, located on the cell surface. Preincubation of cells with polyclonal antibody against the 45-kDa protein specifically blocked DENV-4 infection of C6/36 cells. The antibody and purified DENV-4 detected the 45-kDa molecule in total extracts from eggs, larvae, and pupae as well as from the midgut, ovary, and salivary glands from adult-stage Aedes aegypti mosquitoes, whereas in malphigian tubules it was absent. This suggests that the distribution of the 45-kDa protein correlates with tissue tropism of DENV infection in mosquitoes. The 45-kDa molecule was not detected in Anopheles albimanus mosquito. The relevance of our findings is discussed from the pathogenetic and vector competence viewpoints.
CALIFORNIA STATE MOSQUITO-BORNE VIRUS SURVEILLANCE AND RESPONSE PLAN: A RETROSPECTIVE EVALUATION USING CONDITIONAL SIMULATIONS
Authors: BARKER CHRISTOPHER M. , REISEN WILLIAM K. , KRAMER VICKI L.
Published: May 2017

The California Mosquito-Borne Virus Surveillance and Response Plan recently was developed to provide a semi-quantitative means for assessing risk for western equine encephalomyelitis (WEE) or St. Louis encephalitis (SLE) viruses and to provide intervention guidelines for mosquito control and public health agencies during periods of heightened risk for human infection. West Nile virus recently has arrived in California, and the response plan also will provide a baseline for assessing the risk for human and equine infection with this virus. In the response plan, overall risk is calculated by averaging risk due to 1) environmental conditions, 2) adult mosquito vector abundance, 3) vector infection rates, 4) sentinel chicken seroconversion rates, 5) equine cases (for WEE), 6) human cases, and 7) the proximity of virus activity to populated areas. Overall risk is categorized into three levels: normal season, emergency planning, or epidemic conditions. We evaluated this response plan using historical data from years with no, enzootic, and epidemic activity of WEE and SLE in several areas of California to determine whether calculated risk levels approximated actual conditions. Multiple methods of risk calculation were considered for both viruses. Assessed risk based on cumulative temperature, rainfall, and runoff levels over the entire season provided more or equally accurate assessments than biweekly assessments based solely on the previous half-month. For WEE, during years with enzootic activity or early-season periods of years with WEE epidemic activity, combining horse and human cases as a single risk factor improved the model’s ability to forecast pending WEE activity, but separating the two factors allowed a better indication of WEE activity during epidemics and periods with no activity. For SLE, assignment of higher risk to drier conditions as measured by rainfall and runoff yielded the most accurate representation of actual virus activity during all recent study periods.
INDOOR AND PERIDOMESTIC TRANSMISSION OF AMERICAN CUTANEOUS LEISHMANIASIS IN NORTHWESTERN ARGENTINA: A RETROSPECTIVE CASE-CONTROL STUDY
Authors: YADON ZAIDA E. , RODRIGUES LAURA C. , DAVIES CLIVE R. , QUIGLEY MARIA A.
Published: May 2017

A case-control study was carried out during 1990–1994 to identify risk factors associated with American cutaneous leishmaniasis (ACL) in Santiago del Estero, Argentina. The study subjects consisted of 171 cases and 308 controls matched by age, sex, and place of residence. The analysis was performed by conditional logistic regression. Risk factors found to be significantly associated with ACL were related to indoor transmission (few rooms in the house, dirt floor, and a permanent opening in lieu of a window); peridomestic transmission (presence of a pond or woodland within 150 m of the house and an agricultural area within 200 m of the house); and human behavior (sleeping in the backyard, collecting water, bathing, and performing agricultural activities). Most transmission appears to have occurred indoors and in the peridomicile. These environments should be included in further research and control policies.
SHORT REPORT: PERSISTENCE OF TUMOR NECROSIS FACTOR-α IN SITU AFTER LESION HEALING IN MUCOSAL LEISHMANIASIS
Authors: AMATO VALDIR S. , ANDRADE HEITOR F. , NETO VICENTE AMATO , DUARTE MARIA IRMA S.
Published: May 2017

Mucosal leishmaniasis (ML) is a disease characterized by intense activation of inflammatory cells and extensive tissue destruction. Among the cytokines involved in the immune response to ML, tumor necrosis factor-α (TNF-α) has attracted strong interest because of its roles in the modulation of the immune response. We studied 20 patients with ML who provided biopsy specimens before treatment and after lesion healing obtained by specific therapy. The biopsy specimens were subjected to immunohistochemical analysis for in situ quantification of cellular and extra-cellular TNF-α. The amount of TNF-α was significantly lower in the healed lesions compared with pretreatment biopsy specimens, although TNF-α persisted at the tissue level even after lesion healing. This relevant finding demonstrates for the first time an in situ tissue reduction of TNF-α after treatment and shows persistence of TNF-α in healed lesions may be related to the maintenance of an immunopathologic background for relapses observed in ML.
DIFFERENTIATING DENGUE VIRUS INFECTION FROM SCRUB TYPHUS IN THAI ADULTS WITH FEVER
Authors: WATT GEORGE , JONGSAKUL KRISADA , CHOURIYAGUNE CHAROEN , PARIS ROBERT
Published: May 2017

Dengue fever and scrub typhus are common infections in Asia that often present as acute febrile illness of unclear etiology. We prospectively evaluated febrile adults presenting to the outpatient department of a hospital in northern Thailand to attempt to identify distinguishing characteristics between the two infections. Fifty-four patients were infected with scrub typhus and 35 were infected with dengue virus. Dengue virus infection was associated with hemorrhagic manifestations, particularly bleeding from the gums, which was reported by 27% of the dengue patients, but by none of the scrub typhus patients (P < 0.001, by Fisher’s exact test). A low platelet count (< 140,000/mm3) and low white blood cell count (< 5,000/mm3) were strongly associated with dengue infections: odds ratio = 26.3 (95% confidence interval [CI] = 7.4–93.2) for platelet count and 8.2 (95% CI = 2.6–25.5) for leukocyte count. Prospective evaluations of the usefulness of these simple criteria to differentiate scrub typhus from dengue infection are needed in other areas, particularly where rapid confirmatory diagnostic tests are not available.
EFFICIENCY OF DENGUE SEROTYPE 2 VIRUS STRAINS TO INFECT AND DISSEMINATE IN AEDES AEGYPTI
Authors: ARMSTRONG PHILIP M. , RICO-HESSE REBECA
Published: May 2017

Dengue serotype 2 (DEN-2) viruses with the potential to cause dengue hemorrhagic fever have been shown to belong to the Southeast (SE) Asian genotype. These viruses appear to be rapidly displacing the American genotype of DEN-2 in the Western Hemisphere. To determine whether distinct genotypes of DEN-2 virus are better adapted to mosquito transmission, we classified 15 viral strains of DEN-2 phylogenetically and compared their ability to infect and disseminate in different populations of Aedes aegypti mosquitoes. Envelope gene nucleotide sequence analysis confirmed that six strains belonged to the American genotype and nine strains were of the SE Asian genotype. The overall rate of disseminated infection in mosquitoes from Texas was 27% for the SE Asian genotype versus 9% for the American genotype. This pattern of infection was similar in another population of mosquitoes sampled from southern Mexico (30% versus 13%). Together, these findings suggest that Ae. aegypti tends to be more susceptible to infection by DEN-2 viruses of the SE Asian genotype than to those of the American genotype, and this may have epidemiologic implications.
SHORT REPORT: ASSESSING FIELD VACCINE EFFICACY FOR MEASLES IN FAMINE-AFFECTED RURAL ETHIOPIA
Authors: TALLEY LEISEL , SALAMA PETER
Published: May 2017

Measles is a major cause of mortality in complex emergencies. Both high vaccination coverage and vaccine efficacy are required to prevent major epidemics of measles in such situations. Evaluation of field vaccine efficacy is a critical but underutilized component of program monitoring in emergencies, and is particularly important in rural areas where the integrity of the cold chain is difficult to guarantee. In July 2000, we evaluated the field vaccine efficacy for measles vaccination by comparing the incidence of cases in vaccinated and unvaccinated groups during a two-stage cluster survey of 563 children in Ethiopia. Approximately 30% of the measles cases occurred in vaccinated children. Estimated field vaccine efficacy for measles was 66.9% in children 9–36 months old. The finding of a field vaccine efficacy for measles less than 80% warrants formal assessment of measles vaccine efficacy, particularly in famine emergencies where measles is associated with a high case fatality rate.
OCCURRENCE OF BARTONELLA HENSELAE AND BARTONELLA QUINTANA IN A HEALTHY GREEK POPULATION
Authors: TEA A. , ALEXIOU-DANIEL S. , ARVANITIDOU M. , DIZA E. , ANTONIADIS A.
Published: May 2017

The purpose of this study was to determine the prevalence of IgM and IgG antibodies against Bartonella henselae and B. quintana in a healthy Greek population using a commercially available immunofluorescent test (Focus test). Five hundred healthy individuals were divided by sex into four age groups and three groups according to contact with cats. IgM antibodies were not detected in any of the subjects examined, while 99 (19.8%) and 75 (15%) were IgG seropositive to B. henselae and to B. quintana, respectively. No statistical difference in the seropositivity was observed among these groups. The IgG antibody titers ranged from 1/64 to 1/256 for B. henselae and from 1/64 to 1/512 for B. quintana. A high percentage (12.4%) of cross-reactivity between the two species was observed. Our data show that the prevalence of both Bartonella species in Greece is high. However, low IgG antibody levels are not sufficient evidence of active infection.
IN VITRO REACTIVATION OF HUMAN IMMUNODEFICIENCY VIRUS-1 UPON STIMULATION WITH SCRUB TYPHUS RICKETTSIAL INFECTION
Authors: MORIUCHI MASAKO , TAMURA AKIRA , MORIUCHI HIROYUKI
Published: May 2017

While a number of microbial infections induce a transient burst in viral load in individuals infected with human immunodeficiency virus-1 (HIV-1), a recent study has suggested that scrub typhus may suppress HIV-1 infection. We investigated the effects of Orientia tsutsugamushi on HIV-1 infection. In vitro HIV-1 infection experiments were conducted using peripheral blood mononuclear cells (PBMC) acutely infected with R5 and X4 HIV-1 or PBMC derived from patients receiving highly active antiretroviral therapy (HAART) whose plasma viral load was undetectable. Stimulation of PBMC with O. tsutsugamushi induced production of proinflammatory cytokines and β-chemokines, and markedly down-regulated expression of CCR5. Although pretreatment with O. tsutsugamushi rendered PBMC resistant to R5 HIV-1, it otherwise enhanced HIV-1 replication. Stimulation by O. tsutsugamushi induced HIV-1 replication in PBMC from patients receiving HAART. These findings suggest that scrub typhus does not necessarily suppress HIV-1 infection and does have potential to enhance HIV-1 replication.
DERMATOLOGIC LESIONS IN ASYMPTOMATIC BLOOD DONORS SEROPOSITIVE FOR HUMAN T CELL LYMPHOTROPIC VIRUS TYPE-1
Authors: GONÇALVES DENISE UTSCH , GUEDES ANTÔNIO CARLOS MARTINS , DE FREITAS CARNEIRO PROIETTI ANNA BÁRBARA , MARTINS MARINA LOBATO , PROIETTI FERNANDO AUGUSTO , LAMBERTUCCI JOSÉ ROBERTO , _ _
Published: May 2017

Dermatologic manifestations are quite common in patients with adult T cell leukemia/lymphoma and myelopathy/tropical spastic paraparesis associated with infection with human T cell lymphotropic virus type-1 (HTLV-1). In this study, we evaluated the dermatologic lesions of eligible blood donors in the state of Minas Gerais in Brazil who were seropositive but asymptomatic for infection with HTLV-1. The study population was composed of 128 HTLV-1-seropositive individuals and 108 seronegative controls. All individuals underwent a dermatologic evaluation. Biopsy specimens were obtained from abnormal and normal skin samples of seropositive individuals in an attempt to detect HTLV-1 in tissue samples by a polymerase chain reaction. Dermatologic alterations were observed more frequently in the seropositive group (adjusted odds ratio [OR] = 8.77, 95% confidence interval [CI] = 4.11–18.71). The most common skin diseases were dermatophytoses (adjusted OR = 3.32, 95% CI = 1.50–7.35), seborrheic dermatitis (OR = 3.53, 95% CI = 0.67–24.66), and acquired ichthyosis (P = 0.001). Virus was detected more frequently in abnormal skin samples. Dermatologic lesions probably related to HTLV-1 infection were diagnosed in eligible blood donors who were infected with this virus, who were previously considered to be asymptomatic carriers of HTLV-1.
CO-INFECTION WITH MALARIA AND LEPTOSPIROSIS
Authors: WONGSRICHANALAI CHANSUDA , MURRAY CLINTON K. , GRAY MICHAEL , MILLER R. SCOTT , MCDANIEL PHILIP , LIAO WILSON J. , PICKARD AMY L. , MAGILL ALAN J.
Published: May 2017

Malaria and leptospirosis are both common in the tropics. Simultaneous infections are possible, although not previously reported. We report two cases of malaria from an area of Thailand on the Thailand-Myanmar border with compelling serologic evidence of simultaneous acute leptospirosis. One was a case of infection with Plasmodium falciparum with acute and convalescent microscopic agglutination test (MAT) titers for Leptospira serovar icterohaemorrhagiae of 1:200 and 1:1,600, respectively. The other was a case of infection with P. vivax that seroconverted to a titer of 1:3,200 for Leptospira serovar bataviae. Additionally, there were five probable cases of leptospirosis with patent malaria parasitemia (three P. falciparum and two P. vivax) detected. Management of dual infections is complicated by their similar clinical presentations, and because the confirmatory diagnosis of malaria is readily available as opposed to that of leptospirosis. Treatment focusing on malaria mono-infections instead of dual infections could result in a delay of specific therapy for leptospirosis and possible consequences of serious complications.
FOREST MALARIA IN CHHINDWARA, MADHYA PRADESH, CENTRAL INDIA: A CASE STUDY IN A TRIBAL COMMUNITY
Authors: SINGH NEERU , MISHRA A. K. , SHUKLA M. M. , CHAND S. K.
Published: May 2017

Parasitologic and entomologic cross-sectional surveys were carried out during an outbreak of malaria between December 1998 and August 2000 in forest villages near the Mohkhed Primary Health Center in the Chhindwara District of Madhya Pradesh in central India. In December 1998, surveys showed that more than 70% of the fever cases had malaria, with 87% of the malaria caused by Plasmodium falciparum. The rate of enlarged spleens in children was 74.5%. In November 1999, 58% of the inhabitants were infected with malaria, with 80% of these cases caused by P. falciparum. Chloroquine resistance was seen in 23% of the cases. Anopheles culicifacies was the dominant mosquito species in all surveys (70–85%) and was resistant to DDT. The results indicate that the incidence of malaria in Chhindwara has increased gradually from 0.31 per 1,000 in 1990 to 6.75 per 1,000 in 2000. Improved access to treatment facilities, combination therapy, and vector control using an effective insecticide appear to be the most promising methods for controlling malaria in this region.
GENETIC DIVERSITY AND MULTIPLE INFECTIONS OF PLASMODIUM VIVAX MALARIA IN WESTERN THAILAND
Authors: CUI LIWANG , MASCORRO CARLYE N. , FAN QI , RZOMP KIMBERLY A. , KHUNTIRAT BENJAWAN , ZHOU GUOFA , CHEN HONG , YAN GUIYUN , SATTABONGKOT JETSUMON
Published: May 2017

Using two polymorphic genetic markers, the merozoite surface protein-3α (MSP-3α) and the circumsporozoite protein (CSP), we investigated the population diversity of Plasmodium vivax in Mae Sod, Thailand from April 2000 through June 2001. Genotyping the parasites isolated from 90 malaria patients attending two local clinics for the dimorphic CSP gene revealed that the majority of the parasites (77%) were the VK210 type. Genotyping the MSP3-α gene indicated that P. vivax populations exhibited an equally high level of polymorphism as those from Papua New Guinea, a hyperendemic region. Based on the length of polymerase chain reaction products, three major types of the MSP-3α locus were distinguished, with frequencies of 74.8%, 18.7%, and 6.5%, respectively. The 13 alleles distinguished by restriction fragment length polymorphism analysis did not show a significant seasonal variation in frequency. Genotyping the MSP-3α and CSP genes showed that 19.3% and 25.6% of the patients had multiple infections, respectively, and the combined rate was 35.6%. Comparisons of MSP-3α sequences from nine clones further confirmed the high level of genetic diversity of the parasite and also suggested that geographic isolation may exist. These results strongly indicate that P. vivax populations are highly diverse and multiple clonal infections are common in this malaria-hypoendemic region of Thailand.
THE EFFICACY OF COMBINED MEFLOQUINE-ARTESUNATE VERSUS MEFLOQUINE-PRIMAQUINE ON SUBSEQUENT DEVELOPMENT OF PLASMODIUM FALCIPARUM GAMETOCYTEMIA
Authors: SUPUTTAMONGKOL YUPIN , CHINDARAT SUPAT , SILPASAKORN SAOWALAK , CHAIKACHONPATD SUCHADA , LIM KIMHENG , CHANTHAPAKAJEE KITTIPORN , KAEWKAUKUL NAPARAT , THAMLIKITKUL VISANU
Published: May 2017

An open randomized controlled study of mefloquine-artesunate and mefloquine-primaquine for the treatment of uncomplicated Plasmodium falciparum malaria was carried out in Kanchanaburi in the Saiyok District in western Thailand. Weekly parasite counts from thick and thin blood films were done for six weeks. The gametocyte carriage rate was calculated and compared between the two treatment groups. Gametocytes on presentation, recrudescent infection, and reinfection were the significant factors associated with subsequent development of gametocytemia. It is the increased propensity of recrudescent infections to produce gametocytes that drives drug resistance. The results of this study confirmed that the complete eradication of asexual forms of P. falciparum by effective antimalarial treatment, but not by combination treatment with primaquine, is the most effective means to prevent subsequent gametocytemia.
PERFORMANCE OF THE OPTIMAL TEST FOR MALARIA DIAGNOSIS AMONG SUSPECTED MALARIA PATIENTS AT THE RURAL HEALTH CENTERS
Authors: IQBAL JAMSHAID , MUNEER ARIF , KHALID NABILA , AHMED MOHAMMED A.
Published: May 2017

The OptiMAL test detects both Plasmodium falciparum and P. vivax malaria infections. In this study, we evaluated the performance of the OptiMAL test at the Basic Health Units (BHUs) and the District Health Quarter (DHQ) Center in rural villages of Punjab, Pakistan that provide minimal health services. Two sets of blood specimens obtained from 930 suspected malaria patients attending these BHUs were tested at BHUs and the DHQ Center by microscopy and the OptiMAL test. At the BHUs, 231 (25%) of the patients were positive by microscopy and 278 (30%) patients tested positive by the OptiMAL test. At the DHQ Center, microscopic analysis of a second set of specimens from the same patients confirmed the malaria infection in 386 (42%) patients and the OptiMAL test result was positive in 300 (32%) patients. To determine the performance of OptiMAL test at the BHUs and the DHQ Center, all data were compared with microscopy results obtained at the DHQ Center. The OptiMAL test results for P. falciparum at the BHUs were comparable to those of the OptiMAL test at the DHQ Center. However, the sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of the OptiMAL test were considerably lower for P. vivax infections than for P. falciparum infections, irrespective of whether the test was performed at the BHUs or at the DHQ Center (P. falciparum: sensitivity = 78–85%, PPV = 89–97%, NPV = 96–98%; P. vivax: sensitivity = 61–76%, PPV = 88–95%, NPV = 90–93%). The OptiMAL test also detected a number of false-positive and false-negative results at both the BHUs and the DHQ Center. The false-positive results ranged from 1% to 2%; however, the number of false-negative results was much higher (BHUs: P. falciparum = 22%, P. vivax = 39%; DHQ Center: P. falciparum = 15%, P. vivax = 24%). In conclusion, these results, when combined with other advantages of the OptiMAL test, suggest that this test can be used by relatively inexperienced persons to diagnose malaria infection in rural areas where facilities for microscopy are not available.
APPLICATION OF MOLECULAR TOOLS IN THE CONTROL OF BLINDING TRACHOMA
Authors: MABEY DAVID , SOLOMON ANTHONY W.
Published: May 2017

The use of anti-chlamydial antibiotics for trachoma control is based on the assumption that most people with clinically active disease have conjunctival infection with Chlamydia trachomatis. In high prevalence areas, this is generally true. As prevalence decreases, however, the positive predictive value of clinical signs for C. trachomatis infection also decrease. In this paper, the case for using laboratory assays to guide trachoma control strategies is presented, molecular methods for diagnosis (such as a ligase chain reaction and a polymerase chain reaction [PCR]) are compared with earlier techniques, and recent findings of ongoing studies using a quantitative PCR are reviewed. In addition, the contribution of genotyping to our understanding of the epidemiology and biology of C. trachomatis is considered.
MODIFICATION OF DENGUE VIRUS STRAINS BY PASSAGE IN PRIMARY DOG KIDNEY CELLS: PREPARATION OF CANDIDATE VACCINES AND IMMUNIZATION OF MONKEYS
Authors: ECKELS KENNETH H. , DUBOIS DORIA R. , PUTNAK ROBERT , VAUGHN DAVID W. , INNIS BRUCE L. , HENCHAL ERIK A. , HOKE CHARLES H.
Published: May 2017

Dengue (DENV) virus strains for each of the four DENV serotypes were modified by passage in primary dog kidney (PDK) cell cultures with final manufacture of vaccine lots in fetal rhesus monkey diploid cell cultures. “Strain sets” consisting of serially-passaged DENV were inoculated in rhesus monkeys along with unmodified parent viruses for each strain. Vaccine candidates were compared with unmodified parent viruses by measuring viremia and immune responses. All except one DENV-1 strain demonstrated reduced infection in monkeys after PDK cell passage. A DENV-3 strain lost all monkey infectivity after PDK cell passage. Twelve vaccine candidates were selected for Phase 1 human trials through this selection process.
THE GLOBAL ELIMINATION OF BLINDING TRACHOMA: PROGRESS AND PROMISE
Authors: KUMARESAN JACOB A. , MECASKEY JEFFREY W.
Published: May 2017

Trachoma is the world’s leading cause of preventable blindness. It affects approximately 150 million people living in the world’s poorest, rural communities and causes an estimated loss of $2.9 billion in productivity annually. In 1985, the Edna McConnell Clark Foundation joined with the World Health Organization to support studies on trachoma epidemiology and control, resulting in the elaboration of the surgery, antibiotics, facial cleanliness and environmental improvement (SAFE) strategy as the basis for the elimination of this blinding disease. Founded in 1998 by the Clark Foundation and Pfizer, Inc., the International Trachoma Initiative (ITI) is the only organization dedicated to eliminating blinding trachoma through support to national control programs. The availability of donated Zithromax® (azithromycin) by Pfizer, Inc. has been paramount to the support of the ITI for implementation of SAFE in 10 country programs. The program has made considerable progress in four years. More than seven million individuals have received treatment, resulting in a cumulative reduction of 50% in active disease rates in children. More than 60,000 have also benefited from lid surgery that has halted progression to blindness. Morocco is expecting to attain the elimination of blinding trachoma by 2005. However, the challenges facing the goal of global elimination by 2020 involve a vital program expansion, increased financial and technical support, environmental improvement, and continued advocacy efforts.
ATYPICAL ANTIBODY RESPONSES IN DENGUE VACCINE RECIPIENTS
Authors: KANESA-THASAN N. , SUN W. , LUDWIG G. V. , ROSSI C. , PUTNAK J. R. , MANGIAFICO J. A. , INNIS B. L. , EDELMAN R.
Published: May 2017

Eight of 69 (12%) healthy adult volunteers vaccinated with monovalent live-attenuated dengue virus (DENV) vaccine candidates had atypical antibody responses, with depressed IgM:IgG antibody ratios and induction of high-titer hemagglutination-inhibiting and neutralizing (NT) antibodies to all four DENV serotypes. These features suggested flavivirus exposure prior to DENV vaccination, yet no volunteer had a history of previous flavivirus infection, flavivirus vaccination, or antibody to flaviviruses evident before DENV vaccination. Moreover, production of antibody to DENV by atypical responders (AR) was not accelerated compared with antibody responses in the 61 flavivirus-naive responders (NR). Further evaluation revealed no differences in sex, age, race, DENV vaccine candidate received, or clinical signs and symptoms following vaccination between AR and NR. However, viremia was delayed at the onset in AR compared with NR. A comparative panel of all AR and five randomly selected NR found flavivirus cross-reactive antibody after vaccination only in AR. Unexpectedly, six of eight AR had NT antibodies to yellow fever virus (YFV) > 1:10 before vaccination while NR had none (P = 0.04). The AR also universally demonstrated YFV NT antibody titers ≥ 1:160 after DENV vaccination, whereas four of five NR failed to seroconvert (P = 0.02). Yellow fever virus priming broadens the antibody response to monovalent DENV vaccination. The effect of flavivirus priming on the clinical and immunologic response to tetravalent DENV vaccine remains to be determined.
SEROTYPE-SPECIFIC TH1 RESPONSES IN RECIPIENTS OF TWO DOSES OF CANDIDATE LIVE-ATTENUATED DENGUE VIRUS VACCINES
Authors: GWINN WILLIAM , SUN WELLINGTON , INNIS BRUCE L. , CAUDILL JEFFREY , KING ALAN D.
Published: May 2017

As part of a larger vaccine study, peripheral blood mononuclear cells (PBMC) were collected from volunteers for analysis of vaccine- induced T cell responses. The PBMC were re-stimulated in vitro with live dengue virus and assayed for Th1 or Th2 memory cell responses. Re-stimulated PBMC from the volunteers predominantly secreted interferon-γ. Little interleukin-4 (IL-4) or IL-10 secretion was detected, indicating a Th1 type of T cell response. The interferon-γ response was primarily serotype-specific with some serotype cross-reactivity. T cell depletion studies showed that the interferon-γ was being secreted by CD4+ T lymphocytes and/or by cells other than CD8+ T lymphocytes that were being stimulated by the CD4+ T lymphocytes. CD3+ or CD8+ T cell depletion showed that granzyme B mRNA expression correlated with the presence of CD4+ T lymphocytes. However, depletion of CD4+ T cells after four days of stimulation indicated that the granzyme B mRNA was produced by cells in culture other than lymphocytes. In summary, an antigen-specific Th1 type T cell response was seen as a response to vaccination using live attenuated dengue virus.
PHASE I TRIAL OF 16 FORMULATIONS OF A TETRAVALENT LIVE-ATTENUATED DENGUE VACCINE
Authors: EDELMAN ROBERT , WASSERMAN STEVEN S. , BODISON SACARED A. , PUTNAK ROBERT J. , ECKELS KENNETH H. , TANG DOUGLAS , KANESA-THASAN NIRANJAN , VAUGHN DAVID W. , INNIS BRUCE L. , SUN WELLINGTON
Published: May 2017

Laboratory-attenuated strains of each of the four dengue serotypes previously tested as monovalent vaccines in volunteers were combined and tested for immunogenicity, safety, and reactogenicity in 16 dosage combinations. Tetravalent vaccines made using combinations of high (105–6 plaque-forming units [PFU]/dose) or low (103.5–4.5 PFU/dose) dosage formulations of each of the four viruses were inoculated in 64 flavivirus non-immune adult volunteers to determine which, if any, formulation raised neutralizing antibodies in at least 75% of volunteers to at least three of four dengue serotypes following one or two inoculations. Such formulations, if safe and sufficiently non-reactogenic, would be considered for an expanded Phase II trial in the future. Formulations 1–15 were each inoculated into three or four volunteers (total = 54) on days 0 and 28. Formulation 16 was tested in 10 volunteers, five volunteers inoculated on days 0 and 30, one volunteer on days 0 and 120, and four volunteers on days 0, 30, and 120. Blood was drawn for serologic assays immediately before and one month after each vaccination, and for viremia assay on day 10 after each vaccination. The 16 formulations were safe, but variably reactogenic after the first vaccination, and nearly non-reactogenic after the second and third vaccinations. Reactogenicity was positively correlated with immunogenicity. Similar proportions of volunteers seroconverted to dengue-1 (69%), dengue-2 (78%), and dengue-3 (69%), but significantly fewer volunteers seroconverted to dengue-4 (38%). The geometric mean 50% plaque reduction neutralization test titers in persons who seroconverted were significantly higher to dengue-1 (1:94) than to dengue-2 (1:15), dengue-3 (1:10), and dengue-4 (1:2). Seven formulations met the serologic criteria required for an expanded trial, and three of these were sufficiently attenuated clinically to justify further testing.
AOTUS LEMURINUS GRISEIMEMBRA MONKEYS: A SUITABLE MODEL FOR PLASMODIUM VIVAX SPOROZOITE INFECTION
Authors: JORDAN-VILLEGAS ALEJANDRO , ZAPATA JUDITH CONSTANZA , PERDOMO ANILZA BONELO , QUINTERO GUSTAVO E. , SOLARTE YEZID , ARÉVALO-HERRERA MYRIAM , HERRERA SÓCRATES
Published: May 2017

This study describes a successful Plasmodium vivax sporozoite infection in Aotus lemurinus griseimembra. Twenty-eight naive or previously infected monkeys, either splenectomized or spleen intact, were inoculated intravenously or subcutaneously with Plasmodium vivax sporozoites of the Salvador I strain or with two wild isolates (VCC-4 and VCC-5; Vivax-Cali-Colombia). The monkeys were successfully infected regardless of the parasite strain, spleen presence, or inoculation route and showed prepatent periods that ranged from 16 to 89 days. Only one monkey inoculated intravenously failed to develop parasitemia. Since immune protection against malaria pre-erythrocytic forms is mediated by both helper and cytolytic T cells that may home in the spleen and P. vivax cultures are not yet available; the use of spleen-intact A. lemurinus griseimembra, susceptible to both adapted and non-adapted strains of P. vivax sporozoites, is a valuable model for evaluation of pre-erythrocytic vaccine candidates.