bluuebunny/crossref_metadata_2025 huggingface dataset:
MANIPULATION OF THE YELLOW FEVER VIRUS NON-STRUCTURAL GENES 2A AND 4B AND THE 3′NON-CODING REGION TO EVALUATE GENETIC DETERMINANTS OF VIRAL DISSEMINATION FROM THE AEDES AEGYPTI MIDGUT
Authors: McELROY KATE L. , TSETSARKIN KONSTANTIN A. , VANLANDINGHAM DANA L. , HIGGS STEPHEN
Published: September 2018

Although much is known about the ecology, epidemiology, and molecular biology of mosquito-borne viruses, the viral factors that allow transmission by mosquitoes to humans or animals remain unknown. Using infectious clones of disseminating (Asibi) and non-disseminating (17D) yellow fever viruses (YFV), we produced chimeric viruses to evaluate the role of different viral genes in dissemination. Previously, we showed that virus produced from an infectious clone containing the structural genes of 17D in Asibi disseminated from the mosquito midgut at a rate of 31%, indicating that some genetic determinants of dissemination must lie within the non-structural (NS) protein genes or 3′ non-coding region (NCR). We chose to investigate the roles of NS2A, NS4B, and the 3′NCR in YFV dissemination. Substitution of the 17D NS2A or NS4B into Asibi significantly attenuated YFV dissemination, demonstrating that this is a multigenic property. There was no difference in dissemination after substitution of the 17D 3′NCR.
MONITORING CHLOROQUINE RESISTANCE USING PLASMODIUM FALCIPARUM PARASITES ISOLATED FROM WILD MOSQUITOES IN TANZANIA
Authors: TEMU EMMANUEL A. , KIMANI ISSAC , TUNO NABUKO , KAWADA HITOSHI , MINJAS JAPHET N. , TAKAGI MASAHIRO
Published: September 2018

Monitoring antimalarial drug resistance is a useful epidemiologic tool and provides early detection of resistance foci. Using DNA extracted from the head/thorax of wild mosquitoes collected from Bagamoyo Coastal Tanzania, samples infected by Plasmodium falciparum (N = 89, in 2002 and N = 249 in 2004) were screened by nested polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay for mutations at Pfcrt76 and Pfmdr1-86 associated with chloroquine (CQ) resistance. The majority of isolates were of single infection (71%), and the prevalence of mutant alleles of Pfcrt76 decreased from 64.5% in 2002 to 16% in 2004; likewise, mutant Pfmdr1-86 alleles decreased from 46.6% to 2.7%. Overall, there was a decline of mutant isolates by a factor of 17 and 4 for Pfmdr1 and Pfcrt, respectively. In contrast, isolates with wild-type alleles increased significantly from < 20% in 2002 to 67.6% for Pfcrt76 and 83.5% for Pfmdr1-86 in 2004. This observation suggest a biologic trend of decrease of CQ mutants and a subsequent increase of CQ susceptible parasites in circulation after the discontinued use of CQ in 2001 as a first-line drug in Tanzania. High prevalence of susceptible P. falciparum found in circulation not only supports other reports of a decline of mutant parasites after a reduction of drug selection pressure but suggests that the fitness cost is high in mutant parasites. Typing parasite isolates from infected mosquitoes, an alternative means of data collection, has the potential to increase the spatial and temporal coverage, and this approach is practical in highly endemic regions of Africa.
IMPORTED NON–PLASMODIUM FALCIPARUM MALARIA: A FIVE-YEAR PROSPECTIVE STUDY IN A EUROPEAN REFERRAL CENTER
Authors: BOTTIEAU EMMANUEL , CLERINX JAN , VAN DEN ENDEN ERWIN , VAN ESBROECK MARJAN , COLEBUNDERS ROBERT , VAN GOMPEL ALFONS , VAN DEN ENDE JEF
Published: September 2018

From 2000 to 2005, we investigated prospectively 98 cases of imported non–Plasmodium falciparum malaria (48 Plasmodium vivax, 34 P. ovale, and 16 P. malariae). Latency period between return and clinical attack exceeded three months in 40% of the patients. It was longer in travelers who had taken chemoprophylaxis. Time to diagnosis was longer in patients with P. malariae infection and in those with late-onset first attack. Parasite density was often lower than 500/μL, especially in P. ovale malaria. Relapses were diagnosed in 18% of all malaria episodes. Eight (17%) P. vivax and 2 (6%) P. ovale malaria episodes were due to relapse despite standard primaquine therapy. Diagnosis of imported non-falciparum malaria is often challenged by long latency period and low parasite density. In addition, the substantial relapse rate despite standard primaquine therapy supports the use of a higher dose of primaquine to eradicate P. vivax and P. ovale malaria effectively.
HIGH PREVALENCE OF PLACENTAL MALARIA AND LOW BIRTH WEIGHT IN SAHELIAN PERIURBAN AREA
Authors: SARR DEMBA , MARRAMA LAURENCE , GAYE ALIOUNE , DANGOU JEAN M. , NIANG MAKHTAR , MERCEREAU-PUIJALON ODILE , LEHESRAN JEAN Y. , JAMBOU RONAN
Published: September 2018

The impact of placental malaria in African urban areas is poorly documented. We therefore conducted a study during the rainy season in Dakar, an area with low malaria transmission. Two groups of delivering women were enrolled according to the detection of PfHRP2 in placental blood. Ten percent of the women were positive for parasites in the placenta, and microscopic examination showed, respectively, 17%, 22%, and 44% of past, acute, and chronic infection. The mean birth weight decreased drastically with the infection of the placenta (2,684 ± 67 versus 3,085 ± 66 g for controls), particularly with chronic infection. Chronic infection was not linked with parasiteamia in maternal venous blood. Seventy-six percent of positive women were anemic (46% of the controls). Severe anemia was also associated with chronic infection. Long-lasting infections are the most deleterious to mother and infant and are most likely associated with drug resistance of parasites.
SERUM ANTIBODY LEVELS TO GLYCOSYLPHOSPHATIDYLINOSITOLS IN SPECIMENS DERIVED FROM MATCHED MALIAN CHILDREN WITH SEVERE OR UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA AND HEALTHY CONTROLS
Authors: CISSOKO YACOUBA , DAOU MODIBO , LYKE KIRSTEN E. , DICKO ALASSANE , DIARRA ISSA , KONE ABDOULAYE , GUINDO ANDO , TRAORE KARIM , KRISHNEGOWDA GOWDAHALLI , DIALLO DAPA A. , DOUMBO OGOBARA K. , PLOWE CHRISTOPHER V. , GOWDA D. CHANNE , SZTEIN MARCELO B.
Published: September 2018

Neutralizing antibodies to glycosylphosphatidylinositols (GPIs), which are Plasmodium falciparum surface protein anchor molecules implicated in malaria pathogenesis, are thought to protect against symptomatic malaria. Index cases of severe malaria in Malian children 3 months to 14 years of age were matched by age and residence to uncomplicated malaria and healthy controls. Serum antibodies to GPI (IgM and IgG) were measured at the time of severe malaria and after the malaria transmission season. The mean optical density values for IgM and IgG antibodies were higher in children with severe or uncomplicated malaria compared with healthy controls. Similarly, higher percentages of children with IgM and IgG antibodies to GPI were observed in the severe malaria group compared with matched healthy controls. IgG antibody levels to GPI were highest among children with cerebral malaria and children who died. The IgG antibody levels to GPI peaked during periods of malaria transmission and decreased after malaria transmission ended. A direct correlation between age and parasitemia and IgG antibodies to GPI was observed. In summary, higher levels of IgM and IgG antibodies to GPI in young children were associated with disease severity and were short-lived.
MALARIA PREVENTION DURING PREGNANCY: ASSESSING THE DISEASE BURDEN ONE YEAR AFTER IMPLEMENTING A PROGRAM OF INTERMITTENT PREVENTIVE TREATMENT IN KOUPÉLA DISTRICT, BURKINA FASO
Authors: SIRIMA SODIOMON B. , COTTE ANNETT H. , KONATÉ AMADOU , MORAN ALLISYN C. , ASAMOA KWAME , BOUGOUMA EDITH C. , DIARRA AMIDOU , OUÉDRAOGO ALPHONSE , PARISE MONICA E. , NEWMAN ROBERT D.
Published: September 2018

The World Health Organization recommends that pregnant women in malaria-endemic areas receive ≥ 2 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp/SP) in the second and third trimesters of pregnancy to prevent maternal anemia, placental parasitemia, and low birth weight (LBW). In 2001, a program evaluation in Koupéla District, Burkina Faso demonstrated that despite widespread use of chloroquine chemoprophylaxis, the burden of malaria during pregnancy remained high. In 2003, the Burkina Faso Ministry of Health piloted a program of IPTp/SP (three doses) and accelerated distribution of insecticide-treated nets (ITN) to pregnant women in Koupéla District. In 2004, a follow-up program evaluation was conducted. Coverage with ≥ 1 doses of IPTp/SP was high among women attending antenatal clinics (ANCs) (96.2%) and delivery units (DUs) (93.5%); ITN ownership was moderately high (ANC = 53.9%, DU = 61.6%). In multivariate analysis, ≥ 1 dose of IPTp/SP was associated with a significant reduction in the prevalence of peripheral parasitemia at ANCs (risk ratio [RR] = 0.49, P = 0.008), ≥ 2 doses of IPTp/SP were associated with a reduction in the prevalence of placental parasitemia (RR = 0.56, P = 0.02), and three doses of IPTp/SP were associated with a reduced risk of LBW (RR = 0.51, P = 0.04). The proportions of women at ANCs with peripheral parasitemia and anemia were significantly lower in 2004 than in 2001 (RR = 0.53, P = 0.001 and RR = 0.78, P = 0.003, respectively). The proportions of women at DUs with peripheral and placental parasitemia were also significantly lower in 2004 than in 2001 (RR = 0.66, P < 0.0001 and RR = 0.71, P = 0.0002, respectively). These data suggest that a package of IPTp/SP and ITNs is effective in reducing the burden of malaria during pregnancy in Burkina Faso.
TRICLABENDAZOLE AND ITS TWO MAIN METABOLITES LACK ACTIVITY AGAINST SCHISTOSOMA MANSONI IN THE MOUSE MODEL
Authors: KEISER JENNIFER , EL ELA NADIA ABOU , EL KOMY ENGY , EL LAKKANY NAGLAA , DIAB TAREK , CHOLLET JACQUES , UTZINGER JÜRG , BARAKAT RASHIDA
Published: September 2018

Some have claimed that triclabendazole, a safe and efficacious drug for the treatment of fascioliasis, also exhibits antischistosomal properties, but results are conflicting. We assessed the effect of triclabendazole and its two main metabolites against two different strains of Schistosoma mansoni harbored in mice. Low worm burden reductions (18.6–35.9%) were observed in mice infected with an Egyptian strain of S. mansoni and treated with a single dose of 120 mg/kg 3 days before infection or single/double doses of 120–200 mg/kg 7 weeks after infection. Triclabendazole failed to significantly reduce hepatic and intestinal tissue egg loads, and eggs of all developmental stages were observed. Administration of 400 mg/kg of either triclabendazole, triclabendazole sulphone, or triclabendazole sulfphoxide to mice infected with a Liberian strain of S. mansoni resulted in worm burden reductions < 10%. In comparison, high worm burden reductions (82–100%) were observed in S. mansoni–infected mice treated with single oral doses of 400, 500, or 500 mg/kg twice a day praziquantel, regardless of the S. mansoni strain. We conclude that triclabendazole and its main metabolites display weak and inconsistent schistosomicidal activities.
MYCOBACTERIUM ULCERANS DISEASE (BURULI ULCER) IN A RURAL HOSPITAL IN BAS-CONGO, DEMOCRATIC REPUBLIC OF CONGO, 2002–2004
Authors: PHANZU DELPHIN M. , BAFENDE ERIC A. , DUNDA BARTHELEMY K. , IMPOSO DESIRE B. , KIBADI ANATOLE K. , NSIANGANA SAMUEL Z. , SINGA JACKIE N. , MEYERS WAYNE M. , SUYKERBUYK PATRICK , PORTAELS FRANÇOISE
Published: September 2018

Buruli ulcer (BU), which is caused by Mycobacterium ulcerans, is an important disabling skin disease. Its prevalence is highest in west and central Africa. We report an apparent resurgence of BU in the Bas-Congo Province, Democratic Republic of Congo. During a 28-month period in 2002–2004, the rural hospital of the Institut Médical Evangélique at Kimpese admitted 51 patients suspected of having BU. Bacteriologic, molecular biologic, and histopathologic studies confirmed BU in 36 of these patients. Extensive clinical data, treatment outcomes, and socioeconomic correlations are summarized. Osteomyelitis was an important complication. A multidisciplinary approach to BU control in the Bas-Congo is proposed, aimed primarily at active case detection.
MOLECULAR EPIDEMIOLOGY OF MALARIA IN CAMEROON. XXII. GEOGRAPHIC MAPPING AND DISTRIBUTION OF PLASMODIUM FALCIPARUM DIHYDROFOLATE REDUCTASE (DHFR) MUTANT ALLELES
Authors: TAHAR RACHIDA , BASCO LEONARDO K.
Published: September 2018

Sulfadoxine-pyrimethamine (SP) is still a useful drug to combat chloroquine-resistant Plasmodium falciparum malaria in Cameroon. Because of several disadvantages of the in vivo test and in vitro drug sensitivity assays, molecular assays are an alternative laboratory tool to monitor the evolution of antifolate resistance, especially over the entire country that is characterized by several epidemiologic strata and malaria transmission patterns. In this study, 1,430 blood samples from either symptomatic children or asymptomatic carriers were collected from 14 sites throughout the country between 1999 and 2003 for the analysis of dihydrofolate reductase (dhfr) sequence. Of 1,368 samples (95.7%) that were successfully amplified, 1,180 were analyzed by direct sequencing of the polymerase chain reaction product, and 188 were analyzed by restriction enzymes. The prevalences of the wild-type, single Asn-108 mutation, double Arg-59/Asn-108 mutations, double Ile-51/Asn-108 mutations, triple Ile-51/Arg-59/Asn-108 mutations, and mixed alleles were 20.8%, 2.8%, 5.7%, 0.8%, 62.2%, and 7.6%, respectively. The proportions of triple dhfr mutations were > 60% at all study sites, with the exception of the eastern province (42% triple mutants in Bertoua in 1999) and the northern provinces (11–35% triple mutants in Ngaoundere, Garoua, and Maroua). In these two provinces, the proportion of mutant parasites increased significantly (P < 0.05) over the period of 2–4 years. Furthermore, there was a higher proportion (P < 0.05) of wild-type parasites in the northern provinces, compared with the rest of the country. The geographic mapping of molecular markers offers a novel tool for monitoring the epidemiology of drug-resistant malaria.
SIMPLIFIED MULTI-ORGAN DYSFUNCTION SCORE PREDICTS DISABILITY IN AFRICAN CHILDREN WITH PLASMODIUM FALCIPARUM MALARIA
Authors: HELBOK RAIMUND , ISSIFOU SAADOU , MATSIEGUI PIERRE B. , LACKNER PETER , MISSINOU MICHEL A. , KOMBILA DAVY , DENT WOLFGANG , SCHMUTZHARD ERICH , KREMSNER PETER G.
Published: September 2018

In this prospective study, we assessed the simplified multi-organ dysfunction score (sMODS) in 485 consecutive African children, hospitalized with Plasmodium falciparum malaria. Children were grouped according to their ability to walk unaided (Group 1, N = 414), sit unaided (Group 2, N = 63), or inability of both (Group 3, N = 8) before contracting malaria. The sMODS on admission to hospital was highly correlated with prolonged disease duration in Groups 1 and 2 (Spearman r = 0.79 and r = 0.78, respectively). A sMODS of ≥ 16 was indicative for prolonged disease duration in Group 1 (> 48 hours of inability to walk, sensitivity of 87%, specificity of 82%) and Group 2 (> 24 hours of inability to sit, sensitivity of 100%, and specificity of 78%.). The simplified MODS is a simple and sensitive measure merit of severity of illness in children with P. falciparum malaria and allows early prognostic evaluation.
HDV GENOTYPES IN THE WESTERN BRAZILIAN AMAZON REGION: A PRELIMINARY REPORT
Authors: PARANÁ RAYMUNDO , KAY ALAN , MOLINET FELIX , VIANA SEBASTIÃO , SILVA LUCIANO KALABRIC , SALCEDO JUAN MIGUEL , TAVARES-NETO JOSÉ , LOBATO CIRLEY , RIOS-LEITE MÁRCIO , MATTEONI LUCIANA , OLIVEIRA ARGEMIRO D’ , TAUIL PEDRO , TRÉPO CHRISTIAN
Published: September 2018

In Brazil, hepatitis delta virus (HDV) is only reported in Western Amazonia, where severe cases of acute and chronic HDV hepatitis have been described. The study area was chosen in the States of Acre and Rondonia where most cases of hepatitis B virus (HBV)/HDV are reported. From December 2003 to October 2004, 40 HBsAg carriers with anti-HDV IgM were selected. An epidemiologic questionnaire, including demographic and clinical/epidemiologic variables was filled out. HDV amplification and genotyping were performed. Genotype I was detected in 22 patients (55.0%), whereas genotype III was identified in 18 (45.0%). Patients who were infected with genotype I were older (45.1 ± 17.8 years) than patients infected with genotype III (32.8 ± 10.9 years; P = 0.01). No symptoms were reported by 21 (52.5%) patients. Otherwise, 19 (47.5%) had symptoms (fatigue, abdominal pain, weight loss, and decompensated liver disease) that motivated them to seek medical care. Genotype III carriers were more symptomatic, but no statistical significance was achieved. Our preliminary results show that HDV genotypes I and III are present in Brazilian Amazonia and that HDV genotype III is not limited to the Amerindian population.
SALIVARY GLAND EXTRACTS OF CULICOIDES SONORENSIS INHIBIT MURINE LYMPHOCYTE PROLIFERATION AND NO PRODUCTION BY MACROPHAGES
Authors: BISHOP JEANETTE V. , MEJIA J. SANTIAGO , DE LEÓN ADALBERTO A. PÉREZ , TABACHNICK WALTER J. , TITUS RICHARD G.
Published: September 2018

Culicoides biting midges serve as vectors of pathogens affecting humans and domestic animals. Culicoides sonorensis is a vector of several arboviruses in North American that cause substantial economic losses to the US livestock industry. Previous studies showed that C. sonorensis saliva, like the saliva of many hematophagous arthropods, contains numerous pharmacological agents that affect hemostasis and early events in the inflammatory response, which may enhance the infectivity of Culicoides-borne pathogens. This paper reports on the immunomodulatory properties of C. sonorensis salivary gland extracts on murine immune cells and discusses the possible immunomodulatory role of C. sonorensis saliva in vesicular stomatitis virus infection of vertebrate hosts. Splenocytes treated with C. sonorensis mitogens were significantly affected in their proliferative response, and peritoneal macrophages secreted significantly less NO. A 66-kDa glycoprotein was purified from C. sonorensis salivary gland extract, which may be in part responsible for these observations and may be considered as a vaccine candidate.
ROCKY MOUNTAIN SPOTTED FEVER HOSPITALIZATIONS AMONG AMERICAN INDIANS
Authors: DEMMA LINDA J. , HOLMAN ROBERT C. , MIKOSZ CHRISTINA A. , CURNS AARON T. , SWERDLOW DAVID L. , PAISANO EDNA L. , CHEEK JAMES E.
Published: September 2018

To describe the epidemiology of Rocky Mountain spotted fever (RMSF) among American Indians/Alaska Natives (AI/ANs), we conducted a retrospective analysis of hospitalization records with an RMSF diagnosis using Indian Health Service (IHS) hospital discharge data for calendar years 1980–2003. A total of 261 RMSF hospitalizations were reported among AIs, for an average annual hospitalization rate of 1.21 per 100,000 persons; two deaths were reported (0.8%). Most hospitalizations (88.5%) occurred in the Southern Plains region, where the rate was 4.23 per 100,000 persons. Children 1–4 years of age had the highest age-specific hospitalization rate of 2.50 per 100,000 persons. The overall annual RMSF hospitalization rate declined during the study period. Understanding the epidemiology of RMSF among AI/ANs and educating IHS/tribal physicians on the diagnosis of tick-borne diseases remain important for the prompt treatment of RMSF and the reduction of the disease occurrence among AI/ANs, particularly in high-risk areas.
PREVALENCE AND SPECIES DISTRIBUTION OF E. HISTOLYTICA AND E. DISPAR IN THE VENDA REGION, LIMPOPO, SOUTH AFRICA
Authors: SAMIE AMIDOU , OBI LARRY C. , BESSONG PASCAL O. , STROUP SUZANNE , HOUPT ERIC , GUERRANT RICHARD L.
Published: September 2018

The prevalence and species distribution of Entamoeba histolytica and E. dispar in the Venda region were determined in stool samples collected from public hospitals and primary schools by ELISA and a nested polymerase chain reaction (PCR). E. histolytica was detected in 37/197 (18.8%) and 1/47 (2.1%) samples, whereas 50/197 (25.3%) and 4/47 (8.5%) had E. dispar in the hospitals and schools, respectively. The age groups most infected were 0–2 (33%) years followed by 20–29 years (27%). E. histolytica was significantly associated with diarrhea (77.4% versus 22.6%; χ2 = 39.48, P < 0.05), and with the presence of lactoferrin (85.7% versus 14.2%) in the stools, indicating intestinal inflammation (χ2 = 29.605, P < 0.05). E. histolytica was found in 5 (16.12%) of the 31 HIV-positive individuals and in 33 (15.5%) of the 213 HIV-negative individuals. E. histolytica infections are common in the Venda region and are associated with diarrhea and intestinal inflammation.
ANTIBODIES TO PLASMODIUM VIVAX APICAL MEMBRANE ANTIGEN 1: PERSISTENCE AND CORRELATION WITH MALARIA TRANSMISSION INTENSITY
Authors: MORAIS CRISTIANE G. , SOARES IRENE S. , CARVALHO LUZIA H. , FONTES COR J. F. , KRETTLI ANTONIANA U. , BRAGA ÉRIKA M.
Published: September 2018

The antibody responses to the apical membrane antigen 1 of the Plasmodium vivax (PvAMA-1) were investigated in subjects living in areas of Brazil with different levels of malaria transmission. The prevalence and the levels of IgG to PvAMA-1 increased with the time of exposure. The frequency of a positive response and the mean IgG level were higher in areas where malaria prevalence was more intense, especially among non-infected subjects exposed to moderate transmission over a period of 20 years. The proportions and levels of IgG1and IgG3 isotypes were significantly higher among those subjects with long-term exposure. Antibodies, mainly IgG1, to PvAMA-1 persisted for seven years among subjects briefly exposed to malaria in an outbreak outside the Brazilian malaria-endemic area. These data show the highly immunogenic properties of PvAMA-1 and emphasize its possible use as a malaria vaccine candidate.
SPATIAL PATTERNS OF LYME DISEASE RISK IN CALIFORNIA BASED ON DISEASE INCIDENCE DATA AND MODELING OF VECTOR-TICK EXPOSURE
Authors: EISEN REBECCA J. , LANE ROBERT S. , FRITZ CURTIS L. , EISEN LARS
Published: September 2018

Ixodes pacificus, particularly the nymphal life stage, is the primary vector to humans of the Lyme disease agent Borrelia burgdorferi in California. During 2004, we collected I. pacificus nymphs from 78 woodland sites in ecologically diverse Mendocino County, which has a moderately high incidence of Lyme disease. Within this county, nymphal density was elevated in forested areas with a growing degree day range of 2,600–3,000 (10°C base). Using a geographic information systems approach, we identified all areas in California sharing these environmental characteristics and thus projected to pose high acarologic risk of exposure to host-seeking nymphal ticks. Such areas were most commonly detected in the northwestern part of the state and along the Sierra Nevada foothills in the northeast, but the analysis also identified isolated areas with high acarologic risk in southern California. This mirrors the spatial distribution of endemic Lyme disease during 1993–2005; most cases occurred in counties to the northwest (58%) or northeast (26%), whereas fewer cases were reported from southern California (16%). Southern zip-codes from which Lyme disease cases had been reported were commonly located in close proximity to areas with high projected acarologic risk. Overall, Lyme disease incidence in zip code areas containing habitat with high projected acarologic risk was 10-fold higher than in zip code areas lacking such habitat and 27 times higher than for zip code areas without this habitat type within 50 km. A comparison of spatial Lyme disease incidence patterns based on county versus zip code units showed that calculating and displaying disease incidence at the zip code scale is a useful method to detect small, isolated areas with elevated disease risk that otherwise may go undetected.
POPULATION DYNAMICS OF AN ENDOGENOUS MEIOTIC DRIVE SYSTEM IN AEDES AEGYPTI IN TRINIDAD
Authors: CHA SUNG-JAE , CHADEE DAVE D. , SEVERSON DAVID W.
Published: September 2018

An endogenous meiotic drive system was previously reported to be segregating in the yellow fever mosquito Aedes aegypti L. (Diptera: Culicidae) population in Trinidad. The meiotic driver (MD) is tightly linked to the male determining locus and selectively targets sensitive responders linked to the female determining allele, causing fragmentation of female gametes. This results in highly male-biased progeny. The MD system was initially studied as a genetic tool for population control with limited success, but recently interest has focused on its potential for population replacement. This study examines the distribution and dynamics of the MD system in Trinidad natural populations. We obtained ovitrap samples from seven geographically distinct regions and determined the allele frequencies of the driver (MD) and sensitive (ms) versus insensitive (mi) responders, respectively. Frequencies of the MD allele ranged from 0.1 to 0.5 and were low at the two major port cities, Port of Spain and San Fernando, suggesting the effects of frequent immigration by non-driving genotypes. Frequencies of the mi allele ranged from 0.4 to 0.7, suggesting the effects of strong selection by the driver. In addition, our results show that the driver and sensitivity of responders in the Trinidad populations are highly polymorphic. Continued studies of the dynamics of the MD system in natural populations are critical to considerations of its use in population replacement.
PRO-INFLAMMATORY CYTOKINES AND C-REACTIVE PROTEIN ARE ASSOCIATED WITH UNDERNUTRITION IN THE CONTEXT OF SCHISTOSOMA JAPONICUM INFECTION
Authors: COUTINHO HANNAH M. , LEENSTRA TJALLING , ACOSTA LUZ P. , SU LI , JARILLA BLANCA , JIZ MARIO A. , LANGDON GRETCHEN C. , OLVEDA REMIGIO M. , MCGARVEY STEPHEN T. , KURTIS JONATHAN D. , FRIEDMAN JENNIFER F.
Published: September 2018

Schistosomiasis is associated with undernutrition, but the mechanisms involved remain unknown. We analyzed baseline and follow-up data from a longitudinal treatment–reinfection study in N = 477 Schistosoma japonicum–infected subjects 7–20 years of age from Leyte, the Philippines. After baseline treatment with praziquantel, follow-up visits were scheduled every 3 months for 18 months; stool, venous blood, and anthropometric measurements were collected at each visit. Cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with specific S. japonicum antigens was measured once 4 weeks after treatment. After adjustment for confounders, S. japonicum intensity was associated with decreased serum albumin and Z-scores (all P < 0.05) and with increased serum C-reactive protein (CRP) and interleukin (IL)-6. CRP was associated with decreased albumin and Z-scores (all P < 0.01). Production of IL-1b and tumor necrosis factor (TNF)-α in response to worm antigen was associated with decreased albumin (both P < 0.005) and height-for-age Z-score (TNF-α only, P = 0.05). S. japonicum–associated undernutrition may, in part, result directly from inflammation.
A PROSPECTIVE STUDY OF THE EFFECTS OF SUSTAINED VECTOR SURVEILLANCE FOLLOWING COMMUNITY-WIDE INSECTICIDE APPLICATION ON TRYPANOSOMA CRUZI INFECTION OF DOGS AND CATS IN RURAL NORTHWESTERN ARGENTINA
Authors: CARDINAL MARTA V. , CASTAÑERA MÓNICA B. , LAURICELLA MARTA A. , CECERE MARÍA C. , CEBALLOS LEONARDO A. , VAZQUEZ-PROKOPEC GONZALO M. , KITRON URIEL , GÜRTLER RICARDO E.
Published: September 2018

Domestic dogs were used as natural sentinels to assess prospectively the long-term impact of selective, community-based spraying with pyrethroid insecticides after community-wide spraying on transmission of Trypanosoma cruzi in rural villages under surveillance between 1992 and 2002. In 2000 and 2002 light infestations by Triatoma infestans were recorded, and 523 dogs and cats were examined serologically or by xenodiagnosis. The prevalence of T. cruzi infection in dogs decreased from 65% at baseline to 8.9% and 4.7% at 7.5 and 10 years after sustained vector surveillance, respectively. The average annual force of infection dropped 260-fold from 72.7 per 100 dog-years at baseline to <0.3% in 2002, as determined prospectively and retrospectively from the age-prevalence curve of native dogs born during surveillance. Multiple logistic regression analysis showed that prevalent cases in dogs in 2000 and 2002 were associated positively and significantly with the peak number of T. infestans caught in domestic areas at the dog’s compound during its lifetime. The sustained decline in T. cruzi infections in dogs and cats is the result of selective, community-based insecticide spraying that kept the abundance of infected T. infestans at marginal levels, fast host population turnover, and low immigration rates from areas with active transmission.
MOLECULAR EPIDEMIOLOGY OF MALARIA IN CAMEROON. XXIII. EXPERIMENTAL STUDIES ON SERUM SUBSTITUTES AND ALTERNATIVE CULTURE MEDIA FOR IN VITRO DRUG SENSITIVITY ASSAYS USING CLINICAL ISOLATES OF PLASMODIUM FALCIPARUM
Authors: BASCO LEONARDO K.
Published: September 2018

Correlation studies on the in vitro drug response of field isolates of Plasmodium falciparum and molecular markers for drug resistance are becoming important as many malaria control programs abandon monotherapies and resort to combination therapies. The standardization and optimization of the in vitro drug sensitivity assay are one of the prerequisites for validating molecular markers in the field. The present study was designed to assess and compare the growth of freshly obtained isolates for at least the first erythrocytic cycle in various culture media and determine the in vitro response to chloroquine in alternative media. Parasite growth was consistently higher in Dulbecco’s modified Eagle’s medium (DME)–human serum, Iscove’s modified Dulbecco’s medium (IMDM)–human serum, RPMI 1640 medium–goat serum, and a serum-free medium containing 1:1 (v/v) mixture of IMDM and F-12 supplemented with an ammonium sulfate fraction of adult bovine serum than in RPMI 1640 medium–human serum mixture. The level of chloroquine response determined in human serum-supplemented DME, IMDM, and RPMI 1640 media did not differ significantly (P > 0.05) from the control (RPMI 1640–human serum). This study suggests that alternative media may be used to optimize parasite growth during the critical initial phase of transition from in vivo to in vitro conditions. The capacity of these media to support long-term cultivation of P. falciparum requires further investigation.
THE EVALUATION OF RADIOLABELED ARTESUNATE ON TISSUE DISTRIBUTION IN RATS AND PROTEIN BINDING IN HUMANS
Authors: LI QIGUI , XIE LISA H. , HAEBERLE ADAM , ZHANG JING , WEINA PETER
Published: September 2018

The present study reports the tissue distribution, pharmacokinetics, mass balance, and elimination of [14C] artesunate (AS) following single intravenous administration in rats. Protein binding was performed with rat and human plasma. Radioactivity and drug levels in blood, plasma, tissues, urine, and feces up to 192 hours were collected and measured. The mean terminal half-life of plasma (76 h) and blood (105 h) radioactivity was prolonged compared with that of unchanged AS (0.43 h) and dihydroartemisinin (0.75 h), an active metabolite of AS. Drug was widely distributed after 1 hour in select tissues. After 24 hours, the radioactivity rapidly declined in all tissues except spleen until 96 hours. Only 1% of total radioactivity was detected in brain tissue. AS revealed a higher binding capacity with human and rat plasma proteins (73–81%). The radioactivity in whole blood was higher (two to fourfold) than that in plasma throughout the period of the treatment, suggesting that AS binding to RBCs may relate to its powerful antimalarial activity.
CONGENITAL CHAGAS DISEASE IN BOLIVIA IS NOT ASSOCIATED WITH DNA POLYMORPHISM OF TRYPANOSOMA CRUZI
Authors: VIRREIRA MYRNA , ALONSO-VEGA CRISTINA , SOLANO MARCO , JIJENA JUAN , BRUTUS LAURENT , BUSTAMANTE ZULEMA , TRUYENS CARINE , SCHNEIDER DOMINIQUE , TORRICO FAUSTINO , CARLIER YVES , SVOBODA MICHAL
Published: September 2018

This study aims to typify the Trypanosoma cruzi (sub)lineage(s) in umbilical cord blood of congenitally infected Bolivian newborns, using PCR amplifications of “Region Markers”, mini-exon or kDNA fragments followed by hybridization or sequencing. New probes were also designed to distinguish three variants within the TcIId sublineage. The IIb, IId, or IIe T. cruzi sublineages, as well as different variants of the IId sublineage, were detected in infected neonates, whereas mixed infections were not found. The frequencies of the IId sublineage were similar in neonates (95.1%) and adults of the same area (94.1%). The IId-infected newborns displayed either asymptomatic, or severe and fatal clinical forms of congenital Chagas disease, as well as low or high parasitemia. Altogether these data show that T. cruzi DNA polymorphism, based on the presently available markers, is not associated with the occurrence of congenital infection or the development of severe clinical forms of congenital Chagas disease.
BIOCHEMICAL AND IMMUNOLOGIC PREDICTORS OF EFFICACY OF TREATMENT OR REINFECTION RISK FOR SCHISTOSOMA MANSONI
Authors: REIS ELIANA A. G. , REIS MITERMAYER G. , DE CÁSSIA R. SILVA RITA , CARMO THEOMIRA M. A. , ASSIS ANA MARLÚCIA O. , BARRETO MAURÍCIO L. , PARRAGA ISABEL M. , SANTANA MONICA LEILA P. , BLANTON RONALD E.
Published: September 2018

Most Schistosoma mansoni infections are egg-negative after a single dose of oxamniquine. A cohort of 661 infected children was treated at 6-month intervals and assessed for nutritional and parasitological status. Initial biochemical and immunologic markers were measured in a subset of 84 children. All were treated at the start of therapy and at 6 months. Immunoglobulins only served as markers for active infection. No markers were predictive of cure or reinfection, except initial infection intensity and serum low-density lipoprotein. Ten percent were persistently infected and had no change in infection intensity at any time-point. Several factors suggest that this group was biologically different. In addition to failing to reduce their worm burden, they had significantly higher initial intensity of infection (100 versus 65 eggs/g, P = 0.001) and significantly lower initial serum low-density lipoprotein (72 versus 104 mg/dL, P = 0.045). The biologic plausibility of this observation is discussed.
MODELING TARGETED IVERMECTIN TREATMENT FOR CONTROLLING RIVER BLINDNESS
Authors: POOLMAN ERIC M. , GALVANI ALISON P.
Published: September 2018

There is considerable host heterogeneity in exposure to onchocerciasis. We incorporate this heterogeneity into a model of onchocerciasis transmission that we use to evaluate intervention strategies targeting specific portions of the human population for treatment with ivermectin. Our model predicts that targeted allocation of ivermectin in a highly heterogeneous population will reduce the public health burden of onchocerciasis using 20–25% of the doses of untargeted allocation. Targeted allocation therefore poses significantly lower risk of adverse effects, while potentially delaying the emergence and spread of ivermectin resistance, relative to untargeted allocation.
UTILITY OF POLYMERASE CHAIN REACTION IN DIAGNOSIS OF TUBERCULOSIS FROM SAMPLES OF BONE MARROW ASPIRATE
Authors: SINGH URVASHI B. , BHANU N. VIJAYA , SURESH V. NAGA , ARORA JYOTI , RANA TANU , SETH PRADEEP
Published: September 2018

Fever of unknown origin (FUO) poses a diagnostic challenge to the clinicians, with a differential diagnosis as varied as neoplastic and infectious diseases. In developing countries, the infectious causes are responsible for more cases of FUO, with tuberculosis as one of the main causes of classic FUO. Disseminated tuberculosis with negative pulmonary findings is a diagnostic problem. This study examines the diagnostic utility of the polymerase chain reaction (PCR) in samples of bone marrow aspirate in 85 patients presenting with diverse clinical symptoms. Using primers specific for Mycobacterium tuberculosis, tubercular etiology was detected in 33% of patients clinically suspected of tuberculosis while culture on Lowenstein-Jensen medium grew M. tuberculosis in only one patient (2.5%). None of these patients had been diagnosed by microscopy. Clinical improvement with ATT was observed in 85% of the patients with positive PCR. PCR demonstrated much higher sensitivity and specificity, thereby facilitating early therapeutic decisions for suspected extrapulmonary tuberculosis.
DIHYDROARTEMISININ SUPPOSITORY IN MODERATELY SEVERE MALARIA: COMPARATIVE EFFICACY OF DIHYDROARTEMISININ SUPPOSITORY VERSUS INTRAMUSCULAR ARTEMETER FOLLOWED BY ORAL SULFADOXINE-PYRIMETHAMINE IN THE MANAGEMENT OF MODERATELY SEVERE MALARIA IN NIGERIAN CHILDREN
Authors: FALADE CATHERINE O. , FADERO FRANCIS F. , HAPPI CHRISTIAN T. , DADA-ADEGBOLA HANNAH O. , GBOTOSHO GRACE O. , AYEDE IDOWU , FALADE ADEGOKE G. , ODUOLA AYOADE M. J. , SALAKO LATEEF A.
Published: September 2018

We compared two dose forms of artemisinin derivatives, dihydroartemisinin suppository (DHA) and intramuscular artemether (ART), in children 6 months to 10 years of age with moderately severe malaria for which oral therapy was not appropriate. Children were randomly allocated to receive three daily doses of DHA or ART followed by a single oral dose of sulfadoxine-pyrimethamine on the third day of both treatment regimens and were monitored for parasitologic and clinical response for 14 days. At enrollment, parasite density was 1,640–523,333/μL (geometric mean parasite density [GMPD] = 58,129/μL) in patients treated with DHA, whereas that for children who received ART was 1,440–559,400/μL (GMPD = 60,387/μL). Mean parasite and fever clearance times were similar in both groups. Days 14 and 28 parasitologic cure rates were 100% (34 of 34) and 96.2% (25 of 26) versus 96.2% (25 of 26) and 91.7% (22 of 24) for children treated with DHA and ART, respectively. In conclusion, both treatment regimens were efficacious and well tolerated.
DIARRHEA PREVENTION IN A KENYAN SCHOOL THROUGH THE USE OF A SIMPLE SAFE WATER AND HYGIENE INTERVENTION
Authors: MIGELE JOHN , OMBEKI SAM , AYALO MARY , BIGGERSTAFF MATTHEW , QUICK ROBERT
Published: September 2018

To prevent diarrhea in rural Western Kenya, we implemented the Safe Water System (water treatment with bleach, safe storage, and behavior-change communications) in 2000. We implemented a pilot project in a school in May 2003. Teachers taught students about safe water and hygiene. Safe water storage vessels were placed between classrooms. Two large water tanks for handwashing were positioned by the kitchen and latrines. The vessels were filled daily with water, which was treated with bleach and monitored for free chlorine residuals. Daily student care logs at the local clinic were reviewed. Clinic visits for diarrhea peaked during the January through March period in 2002 at 130 and in 2003 at 71, but in 2004, after project implementation, only 13 diarrhea episodes were recorded. The project saved the school about $5.49 per student per year. The project has been expanded to 70 schools, and an evaluation is planned.
GEOGRAPHICAL DISTRIBUTION AND RISK FACTORS ASSOCIATED WITH ENTERIC DISEASES IN VIETNAM
Authors: KELLY-HOPE LOUISE A. , ALONSO WLADIMIR J. , THIEM VU DINH , ANH DANG DUC , CANH DO GIA , LEE HYEJON , SMITH DAVID L. , MILLER MARK A.
Published: September 2018

In Vietnam, shigellosis, typhoid fever, and cholera are important enteric diseases. To determine their magnitude and geographical distribution, and explore associated risk factors, we examined national surveillance data from 1991 to 2001 and potential ecological determinants. Average annual incidence rates were calculated and mapped for each province. Bivariate and multiple regression analyses were used to explore associations with selected environmental and human risk factors. Overall, shigellosis rates per 100,000 population (median, 41; mean, 70) were higher and more widespread than rates for typhoid fever (median, 7; mean, 23) and cholera (median, 0.3; mean, 2.7). Shigellosis was highest in the Central Highlands and was significantly associated with rainfall and urban poverty; typhoid fever prevailed in the Mekong River Delta and was most associated with vapor pressure and river/stream drinking water; and cholera predominated along the Central Coastal regions and correlated positively with rainfall and public well drinking water. The distinct geographical patterns of each disease appear to be driven by a combination of different ecological factors.
EXPLORATORY SPATIAL ANALYSIS OF SOCIAL AND ENVIRONMENTAL FACTORS ASSOCIATED WITH THE INCIDENCE OF ROSS RIVER VIRUS IN BRISBANE, AUSTRALIA
Authors: HU WENBIAO , TONG SHILU , MENGERSEN KERRIE , OLDENBURG BRIAN
Published: September 2018

We used geographic information systems and a spatial analysis approach to explore the pattern of Ross River virus (RRV) incidence in Brisbane, Australia. Climate, vegetation and socioeconomic data in 2001 were obtained from the Australian Bureau of Meteorology, the Brisbane City Council and the Australian Bureau of Statistics, respectively. Information on the RRV cases was obtained from the Queensland Department of Health. Spatial and multiple negative binomial regression models were used to identify the socioeconomic and environmental determinants of RRV transmission. The results show that RRV activity was primarily concentrated in the northeastern, northwestern, and southeastern regions in Brisbane. Multiple negative binomial regression models showed that the spatial pattern of RRV disease in Brisbane seemed to be determined by a combination of local ecologic, socioeconomic, and environmental factors.
PLASMODIUM FALCIPARUM GENOTYPES ASSOCIATED WITH CHLOROQUINE AND AMODIAQUINE RESISTANCE IN GUINEA-BISSAU
Authors: URSING JOHAN , KOFOED POUL-ERIK , RODRIGUES AMABELIA , ROMBO LARS , GIL JOSÉ PEDRO
Published: September 2018

Chloroquine is the most commonly used antimalarial in Guinea-Bissau and high doses are routinely prescribed. Blood from 497 patients treated with different doses of chloroquine or amodiaquine were genotyped. Pfcrt and pfmdr1 polymorphisms were identified. Pfmsp2 analysis identified recrudescent infections. The pfcrt 72–76 haplotypes were CVIET and CVMNK. The pfcrt 76T prevalence was 23% at day 0 and 96%, 83% and 100% at recrudescence following treatment with 25mg/kg and 50mg/kg of chloroquine and 15mg/kg of amodiaquine respectively. When treating pfcrt 76T carrying P. falciparum the efficacy of 50 mg/kg and 25mg/kg of chloroquine was 78% and 34% respectively (P = 0.007). The genetic basis of chloroquine resistance is probably the same in Guinea-Bissau as in the rest of Africa. The low pfcrt 76T prevalence suggests that resistance to normal dose chloroquine does not confer a major advantage to falciparum in Bissau and could be a result of treatment with high-dose chloroquine.
HIGH SPATIAL RESOLUTION MAPPING OF MALARIA TRANSMISSION RISK IN THE GAMBIA, WEST AFRICA, USING LANDSAT TM SATELLITE IMAGERY
Authors: BØGH CLAUS , LINDSAY STEVEN W. , CLARKE SIÂN E. , DEAN ANDY , JAWARA MUSA , PINDER MARGARET , THOMAS CHRISTOPHER J.
Published: September 2018

Understanding local variability in malaria transmission risk is critically important when designing intervention or vaccine trials. Using a combination of field data, satellite image analysis, and GIS modeling, we developed a high-resolution map of malaria entomological inoculation rates (EIR) in The Gambia, West Africa. The analyses are based on the variation in exposure to malaria parasites experienced in 48 villages in 1996 and 21 villages in 1997. The entomological inoculation rate (EIR) varied from 0 to 166 infective bites per person per rainy season. Detailed field surveys identified the major Anopheles gambiae s.l. breeding habitats. These habitats were mapped by classification of a LANDSAT TM satellite image with an overall accuracy of 85%. Village EIRs decreased as a power function based on the breeding areas size and proximity. We use this relationship and the breeding habitats to map the variation in EIR over the entire 2500-km2 study area.
DIFFERENTIATION OF SCHISTOSOMA HAEMATOBIUM FROM RELATED SCHISTOSOMES BY PCR AMPLIFYING AN INTER-REPEAT SEQUENCE
Authors: ABBASI IBRAHIM , KING CHARLES H. , STURROCK ROBERT F. , KARIUKI CURTIS , MUCHIRI ERIC , HAMBURGER JOSEPH
Published: September 2018

Schistosoma haematobium infects nearly 150 million people, primarily in Africa, and is transmitted by select species of local bulinid snails. These snails can host other related trematode species as well, so that effective detection and monitoring of snails infected with S. haematobium requires a successful differentiation between S. haematobium and any closely related schistosome species. To enable differential detection of S. haematobium DNA by simple polymerase chain reaction (PCR), we designed and tested primer pairs from numerous newly identified Schistosoma DNA repeat sequences. However, all pairs tested were found unsuitable for this purpose. Differentiation of S. haematobium from S. bovis, S. mattheei, S. curassoni, and S. intercalatum (but not from S. margrebowiei) was ultimately accomplished by PCR using one primer from a newly identified repeat, Sh110, and a second primer from a known schistosomal splice-leader sequence. For evaluation of residual S. haematobium transmission after control interventions, this differentiation tool will enable accurate monitoring of infected snails in areas where S. haematobium is sympatric with the most prevalent other schistosome species.
AN INVERSE RELATIONSHIP BETWEEN AUTOIMMUNE LIVER DISEASES AND STRONGYLOIDES STERCORALIS INFECTION
Authors: AOYAMA HAJIME , HIRATA TETSUO , SAKUGAWA HIROSHI , WATANABE TAKAKO , MIYAGI SATORU , MAESHIRO TATSUJI , CHINEN TAKAYUKI , KAWANE MARIKO , ZAHA OSAMU , NAKAYOSHI TOMOKUNI , KINJO FUKUNORI , FUJITA JIRO
Published: September 2018

A case-control study was undertaken to describe the prevalence of Strongyloides stercoralis infection among patients with autoimmune liver diseases, such as primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). This study covered 4,117 patients who were admitted to hospitals in Okinawa, Japan, between 1988 and 2006. During this period, 538 patients had the following chronic liver diseases: PBC, AIH, PSC, chronic viral hepatitis group, and alcoholic liver disease. The other 3,579 patients who were hospitalized and underwent parasitologic tests served as controls. The frequency of S. stercoralis infection in the autoimmune liver diseases group (1.0%) was lower than that found in the control group (7.0%; P = 0.0063). None of the female patients with PBC born before 1955 had S. stercoralis infection, which was also statistically significant (P = 0.045). We hypothesized that immunomodulation by S. stercoralis infection may lower the incidence of autoimmune liver disease.
Development of a Molecular Tool for the Identification of Leishmania Reservoir Hosts by Blood Meal Analysis in the Insect Vectors
Authors: Haouas Najoua , Pesson Bernard , Boudabous Raja , Dedet Jean-Pierre , Babba Hamouda , Ravel Christophe
Published: September 2018

The transmission of parasites of the genus Leishmania involves a large diversity of mammalian reservoir hosts. However, many of these are yet to be identified, mainly in isolated biotopes such as the Amazonian rain forest. Furthermore, the trophic preferences of insect vectors have major epidemiologic implications. In this study, we developed a molecular tool for the identification of blood meals of phlebotomine sand flies. This assay is based on specific amplification and sequencing of the blood meal–derived single copy prepronociceptin (PNOC) gene, which is used as a target in phylogenetic studies of mammals. Sand flies were identified simultaneously with the blood-meal identification, using molecular analysis of a ribosomal locus. After a systematic assessment of the sensitivity and specificity of polymerase chain reaction amplification of the PNOC gene using human fed sand flies, the assay was tested on wild-caught sand flies. This work has important implications for the discovery of new Leishmania reservoir hosts and for a better understanding of complex parasite life cycles.