bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPARISON OF GOVERNMENT STATISTICS AND DEMOGRAPHIC SURVEILLANCE TO MONITOR MORTALITY IN CHILDREN LESS THAN FIVE YEARS OLD IN RURAL WESTERN KENYA
Authors: ARUDO JOHN , GIMNIG JOHN E. , TER KUILE FEIKO O. , KACHUR S. PATRICK , SLUTSKER LAURENCE , KOLCZAK MARGARETTE S. , HAWLEY WILLIAM A. , ORAGO ALLOYS S. S. , NAHLEN BERNARD L. , PHILLIPS-HOWARD PENELOPE A.
Published: September 2018

Estimates of mortality in children less than five years old using government civil registration statistics (passive surveillance) were compared against statistics generated by active demographic surveillance during a randomized controlled trial of permethrin-treated bed nets (ITNs) in western Kenya. Mortality rates were two-fold lower when estimated through civil registration compared with active prospective surveillance (rate ratio [RR] = 0.51, 95% confidence interval [CI] = 0.44–0.59). While civil registration underestimated deaths, particularly in the neonatal period, the age distribution of deaths in children 1–59 months of age was the same as with active surveillance. Seasonal mortality trends were also similar. There was no agreement between cause of death recorded by active and passive surveillance. Verbal autopsy estimated that half of all deaths were associated with malaria and pneumonia, but civil registration markedly under-reported these illnesses; incidence RR (95% CI) = 0.18 (0.14–0.24), and 0.05 (0.03–0.08), respectively, while over-reporting deaths due to measles (RR = 15.5 [95% CI = 7.3–33.2]). Government statistics under-represent mortality, particularly neonatal mortality, in children less than five years of age in rural areas of Kenya. They can provide accurate information on the age-distribution of deaths among children 1–59 months old, and on seasonal trends, but not on disease-specific mortality.
COMPARATIVE EVALUATION OF ELISAS BASED ON TEN RECOMBINANT OR PURIFIED LEISHMANIA ANTIGENS FOR THE SERODIAGNOSIS OF MEDITERRANEAN VISCERAL LEISHMANIASIS
Authors: MAALEJ IBTISSEM ABDMOULEH , CHENIK MEHDI , LOUZIR HECHMI , BEN SALAH AFIF , BAHLOUL CHOKRI , AMRI FETHI , DELLAGI KOUSSAY
Published: September 2018

This study compared a panel of 10 enzyme-linked immunosorbent assays (ELISAs) for the serodiagnosis of Mediterranean visceral leishmaniasis (MVL). The ELISAs were based on either one of the following Leishmania antigens: crude soluble Leishmania antigens (SLAs), recombinant (r) antigens (namely: rgp63, rK39, gene B protein, rH2A and rH2B histones proteins, rLACK, rPSA-2, r P20) and purified lipophosphoglycan. Most of the test antigens showed good performance (sensitivity > 85%, specificity > 80%). rK39 and SLA-based ELISA gave the best results in terms of sensitivity (100%) and predictive value of the negative (100%). The best specificity (97%) and the best predictive value of the positive (92%) were obtained with rK39. These results show that several Leishmania antigens are suitable to design a diagnostic ELISA of MVL. However, recombinant proteins add little to the classic crude SLA, which still represents a very good and less costly alternative.
PERFORMANCE OF RECOMBINANT K39 ANTIGEN IN THE DIAGNOSIS OF BRAZILIAN VISCERAL LEISHMANIASIS
Authors: GUIMARÃES CARVALHO SILVIO F. , LEMOS ELENICE MOREIRA , COREY RALPH , DIETZE REYNALDO
Published: September 2018

This study evaluated the performance of recombinant K39 (rK39) antigen in a immunochromatographic format (strip test) and a crude antigen enzyme-linked immunosorbent assay in the diagnosis of Brazilian visceral leishmaniasis (VL) in 128 consecutive patients with parasitologically proven infections (by microscopy and/or culture). For each patient, a medical history was obtained and a complete physical examination was performed. Controls included 10 healthy volunteers and 50 patients with other diseases: malaria (10), leprosy (9), Chagas’ disease (10), tuberculosis (10), and cutaneous leishmaniasis (11). The sensitivities of the rK39 antigen strip test and the ELISA were 90% and 89%, respectively, while the specificities were 100% and 98%, respectively. Our study confirms the accuracy of the rK39 antigen strip test in the diagnosis of VL in a high prevalence population.
INTERLEUKIN-8, TUMOR NECROSIS FACTOR-α, AND LACTOFERRIN IN IMMUNOCOMPETENT HOSTS WITH EXPERIMENTAL AND BRAZILIAN CHILDREN WITH ACQUIRED CRYPTOSPORIDIOSIS
Authors: ALCANTARA CIRLE S. , YANG CHANG-HUN , STEINER THEODORE S. , BARRETT LEAH J. , LIMA ALDO A. M. , CHAPPELL CYNTHIA L. , OKHUYSEN PABLO C. , WHITE A. CLINTON , GUERRANT RICHARD L.
Published: September 2018

To examine the importance of intestinal inflammation in the diagnosis and pathogenesis of human cryptosporidiosis, stools of healthy adult volunteers before and after experimental infection were tested for fecal lactoferrin, interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Stool samples of Brazilian children with well-defined Cryptosporidium infection, with or without diarrhea, were also tested for IL-8 and TNF-α. Only one of the 14 volunteers challenged with Cryptosporidium had increased fecal lactoferrin. However, of 17 stool specimens from children with only Cryptosporidium infection from a previous study, 12 had mild to moderately elevated lactoferrin despite negative work-up for inflammatory enteritides. One of 10 adult volunteers who developed diarrhea with experimental cryptosporidiosis and three of 11 children with cryptosporidiosis and diarrhea had detectable fecal IL-8. The level of TNF-α was increased only in one of 14 volunteers and in none of the children. Although considered relatively non-inflammatory, cryptosporidiosis is often associated with mild inflammation, especially in children in an endemic area.
GROWTH INHIBITORY EFFECT OF TRICLOSAN ON EQUINE AND BOVINE BABESIA PARASITES
Authors: BORK SABINE , YOKOYAMA NAOAKI , MATSUO TOMOHIDE , CLAVERIA FLORENCIA G. , FUJISAKI KOZO , IGARASHI IKUO
Published: September 2018

We evaluated the growth inhibitory effect of triclosan, which has recently been reported to inhibit the growth of Plasmodium species and Toxoplasma gondii, on bovine and equine Babesia parasites in in vitro cultures. The growth of Babesia bovis and B. bigemina was significantly inhibited in the presence of 100 μg/ml of triclosan, while B. caballi and B. equi were susceptible to as low as 50 μg/ml. Babesia bigemina and B. caballi were completely cleared as early as on the first and second day of the treatment, respectively. These parasites did not exhibit any growth in the subsequent five-day period of subculture without triclosan. Drug-treated parasites appeared pycnotic and atypically shaped, and ultrastructurally showed pronounced vacuolations, leading to complete destruction of parasites. Light microscopy showed that used concentrations of triclosan showed no toxicity against the host cells. The results suggest that triclosan can be used for chemotherapy of babesiosis.
ANALYSIS OF PFCRT, PFMDR1, DHFR, AND DHPS MUTATIONS AND DRUG SENSITIVITIES IN PLASMODIUM FALCIPARUM ISOLATES FROM PATIENTS IN VIETNAM BEFORE AND AFTER TREATMENT WITH ARTEMISININ
Authors: NGO THANH , DURAISINGH MANOJ , REED MICHAEL , HIPGRAVE DAVID , BIGGS BEVERLEY , COWMAN ALAN F.
Published: September 2018

We have analyzed artemisinin sensitivity in Plasmodium falciparum isolates obtained from patients in South Vietnam and show that artemisinin sensitivity does not differ before and after drug treatment. There was an increase in the level of mefloquine resistance in the isolates after drug treatment that was concomitant with a decrease in chloroquine resistance, suggesting that treatment with artemisinin has selected for increased mefloquine resistance. Mutations in the pfmdr1 gene, previously shown to be associated with sensitivity to mefloquine, were selected against. All isolates resistant to chloroquine encoded Thr-76 in the pfcrt gene consistent with an essential role in the mechanism of chloroquine resistance. Mutations in pfmdr1 also were linked to chloroquine resistance. High levels of mutation in dhfr and dhps genes, which have previously been associated with Fansidar resistance, also were found, suggesting that this drug would not be useful for malaria control in this part of Vietnam.
USE OF THE MULTI-ORGAN DYSFUNCTION SCORE AS A TOOL TO DISCRIMINATE DIFFERENT LEVELS OF SEVERITY IN UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA
Authors: HELBOK R. , DENT W. , NACHER M. , TREEPRASERTSUK S. , KRUDSOOD S. , WILAIRATANA P. , SILACHAMROON U. , LOOAREESUWAN S. , SCHMUTZHARD E.
Published: September 2018

The usual criteria for severe malaria are not always sufficient to identify patients who subsequently develop this disease. The multi-organ dysfunction score (MODS) was assessed in 22 patients with uncomplicated Plasmodium falciparum malaria to test its usefulness in discriminating different severity levels. The MODS on admission was highly correlated with the baseline concentration of tumor necrosis factor-α (r = 0.83, P < 0.001) and the duration of symptoms after admission (r = 0.54, P = 0.01). The MODS was also correlated with parasite count (r = 0.52, P = 0.014), parasite clearance time (r = 0.54, P = 0.009), and fever clearance time (r = 0.58, P = 0.005). The above correlations remained significant after controlling for the initial parasitemia (P = 0.03 and 0.005). The MODS is simple and easy to apply and needs a recording time of less than three minutes. Thus, this score might provide a quantitative approach for determining severity in Plasmodium falciparum malaria.
IMPACT OF PERMETHRIN-TREATED BED NETS ON THE INCIDENCE OF SICK CHILD VISITS TO PERIPHERAL HEALTH FACILITIES
Authors: PHILLIPS-HOWARD PENELOPE A. , NAHLEN BERNARD L. , WANNEMUEHLER KATHLEEN A. , KOLCZAK MARGARETTE S. , TER KUILE FEIKO O. , GIMNIG JOHN E. , OLSON KRIS , ALAII JANE A. , ODHACHA AMOS , VULULE JOHN M. , HAWLEY WILLIAM A.
Published: September 2018

During a randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) in an area with intense malaria transmission in western Kenya, we monitored 20,915 sick child visits (SCVs) by children less than five years of age visiting seven peripheral health facilities. The SCVs were monitored over a four-year period both before (1995–1996) and during the intervention (1997–1998). Results are used to estimate the effect of ITNs on the burden of malaria in this community and to evaluate the potential role of these facilities in assessment of the impact of large-scale public health interventions. Compared with baseline, a 27% greater reduction in the incidence of SCVs was seen in ITN villages than in control villages (37% versus 10%; P = 0.049). A similar reduction was observed in SCVs diagnosed as malaria (35% reduction in ITN villages versus 5% reduction in controls; P = 0.04). Two-hundred sixteen SCVs per 1,000 child-years were prevented; three-fourths of these were in children less than 24 months old. As a consequence of lack of laboratory facilities, severe anemia was rarely (< 2%) diagnosed, regardless of intervention status. No effect of ITNs on the incidence of respiratory tract infections, diarrhea, and other commonly diagnosed childhood illnesses was observed. The ITNs reduced the number of SCVs due to malaria, but had no effect on other illnesses. Routine statistics from these facilities provided useful information on trends in malaria incidence, but underestimated the burden of severe anemia.
EPIDEMIOLOGY AND CONTROL OF INTESTINAL PARASITES WITH NITAZOXANIDE IN CHILDREN IN MEXICO
Authors: DIAZ ELVIA , MONDRAGON JAIME , RAMIREZ ENRIQUE , BERNAL ROSAMARIA
Published: September 2018

The purpose of this study was to evaluate the efficacy and the tolerance of nitazoxanide in children as a single broad-spectrum antiparasitic agent in the treatment of mixed parasite infections with both intestinal protozoa and helminths. Two hundred seventy-two children (age range = 2–14 years) participated in this study. We systematically surveyed every household head using questionnaires designed to obtain information about household socioeconomic status and hygiene. Parasitic infections were confirmed by three stool examinations using direct smear, Ferreira concentration, and cold acid-fast Kinyoun staining methods. One hundred twenty-one (44%) children tested positive for protozoa such as Giardia lamblia (18%), Entamoeba histolytica/E. dispar (10%), Blastocystis hominis (7%), Cryptosporidium parvum (4%), and Cyclospora cayetanensis (3%), and helminths such as Hymenolepis nana (10%), Trichuris trichiura (6%), and Ascaris lumbricoides (6%). There were also two cases of infection with Enterobius vermicularis. After a complete physical examination was performed, 121 patients received treatment with nitazoxanide. Overall, 84% of the protozoa and 95% of the helminths were completely eliminated from the patients. Nitazoxanide was very well tolerated, with no serious adverse effects reported.
PRACTICAL ASPECTS OF IN VIVO ANTIMALARIAL DRUG EFFICACY TESTING IN THE AMERICAS
Authors: RUEBUSH TRENTON K. , MARQUIÑO WILMER , ZEGARRA JORGE , NEYRA DANIEL , VILLAROEL RODOLFO , AVILA JUAN CARLOS , DÍAZ CÉSAR , BELTRÁN EFRAÍN
Published: September 2018

The World Health Organization (WHO) has developed guidelines for in vivo antimalarial drug efficacy testing for Plasmodium falciparum and Plasmodium vivax in areas with low-to-moderate transmission, such as the Americas. These guidelines are used widely by ministries of health and national malaria control programs to assess the efficacy of their first-line and second-line drugs for the treatment of malaria and to provide the information necessary to update national malaria treatment policies. Following the WHO guidelines, we have conducted in vivo efficacy trials with a variety of drugs and drug combinations against P. falciparum and P. vivax at 13 sites in Peru, Bolivia, and Ecuador. Based on these experiences, we have identified several modifications that we believe should be made in the WHO recommendations to make them more suitable to the relatively low levels of P. falciparum transmission in the Americas and to the logistic challenges of carrying out such studies in sparsely populated areas, such as the Amazon Basin. These include changes in inclusion and exclusion criteria, in enrollment and follow-up procedures, and in the measurement of study outcomes.
REGULATION OF THE RATE OF ASEXUAL GROWTH AND COMMITMENT TO SEXUAL DEVELOPMENT BY DIFFUSIBLE FACTORS FROM IN VITRO CULTURES OF PLASMODIUM FALCIPARUM
Authors: DYER MIKE , DAY KAREN P.
Published: September 2018

The mechanism of switching to sexual differentiation (gametocytogenesis) of Plasmodium falciparum appears to be controlled by stochastic mechanisms that are sensitive to environmental conditions. In any given conditions, only a proportion of genetically identical parasites will become committed to sexual development. We used an experimental co-culture system to detect the presence of diffusible molecules from asexually replicating bloodstream stages of P. falciparum that were capable of influencing the growth and differentiation of the parasite. We cultured two populations of P. falciparum in a shared environment separated by a membrane that allowed free diffusion of molecules. The data presented show that P. falciparum parasites in culture stimulate their own growth and replication, and constitutively inhibit sexual conversion via diffusible molecules. These observations support the model that for P. falciparum, the sexual pathway of development is the default, and that constitutive repression of the sexual pathway permits asexual multiplication to occur in the bloodstream of the human host.
VERY HIGH RISK OF THERAPEUTIC FAILURE WITH CHLOROQUINE FOR UNCOMPLICATED PLASMODIUM FALCIPARUM AND P. VIVAX MALARIA IN INDONESIAN PAPUA
Authors: SUMAWINATA IWA W. , BERNADETA  , LEKSANA BUDHI , SUTAMIHARDJA AWALLUDIN , PURNOMO  , SUBIANTO BUDI , SEKARTUTI  , FRYAUFF DAVID J. , BAIRD J. KEVIN
Published: September 2018

Chloroquine remains the first-line therapy for uncomplicated malaria in Indonesia. Among a series of trials of chloroquine for malaria on this archipelago conducted since 1990, we now report the highest risk of therapeutic failure yet observed. A clinical trial of standard chloroquine therapy for uncomplicated malaria at Arso PIR V in northeastern Indonesian Papua was conducted during 1995. We enrolled 104 non-immune subjects infected with Plasmodium falciparum (n = 55), P. vivax (n = 29), or P. falciparum plus P. vivax (n = 20) and administered supervised standard chloroquine therapy (10 + 10 + 5 mg/kg at 24-hour intervals). The 28-day cumulative incidence of therapeutic failure was 95% for P. falciparum, 84% for P. vivax, and 100% for mixed infections. Only one subject each for P. falciparum and P. vivax remained free of parasites at day 28. All recurrent parasitemias occurred with whole blood levels of chloroquine plus desethylchloroquine exceeding 100 ng/ml. These findings document almost complete failure of chloroquine against P. falciparum or P. vivax near the northeastern coast of Indonesian Papua.
INCREASING HEALTH BURDEN OF HUMAN BABESIOSIS IN ENDEMIC SITES
Authors: KRAUSE PETER J. , MCKAY KATHLEEN , GADBAW JOSEPH , CHRISTIANSON DIANE , CLOSTER LINDA , LEPORE TIMOTHY , TELFORD SAM R. , SIKAND VIJAY , RYAN RAYMOND , PERSING DAVID , RADOLF JUSTIN D. , SPIELMAN ANDREW , _ _
Published: September 2018

Human infection due to Babesia microti has been regarded as infrequent and a condition primarily affecting the elderly or immunocompromised. To determine whether risk in endemic sites may be increasing relative to that of Borrelia burgdorferi and to define its age-related clinical spectrum, we carried out a 10-year community-based serosurvey and case finding study on Block Island, Rhode Island. Less intensive observations were conducted in nearby sites. Incidence of babesial infection on Block Island increased during the early 1990s, reaching a level about three-fourths that of borrelial infection. The sera of approximately one-tenth of Block Island residents reacted against babesial antigen, a seroprevalence similar to those on Prudence Island and in southeastern Connecticut. Although the number and duration of babesial symptoms in people older than 50 years of age approximated those in people 20 to 49 years of age, more older adults were admitted to hospital than younger adults. Few Babesia-infected children were hospitalized. Babesial incidence at endemic sites in southern New England appears to have risen during the 1990s to a level approaching that due to borreliosis.
URINARY TRACT PATHOLOGY ATTRIBUTED TO SCHISTOSOMA HAEMATOBIUM: DOES PARASITE GENETICS PLAY A ROLE?
Authors: BROUWER KIMBERLY C. , NDHLOVU PATRICIA D. , WAGATSUMA YUKIKO , MUNATSI ANDERSON , SHIFF CLIVE J.
Published: September 2018

Disease outcome in persons infected with Schistosoma haematobium varies dramatically, ranging from mild symptoms to severe damage of the kidneys and/or bladder. We used ultrasonography to characterize the extent of urinary tract pathology of infected children in Zimbabwe, and random genetic markers to examine the relationship between genetic diversity of S. haematobium and clinical outcome. One hundred thirty-three parasite isolates from 12 students with mild lesions and 13 with severe lesions were compared. Using four randomly amplified polymorphic DNA (RAPD) markers, we scored parasite allelic frequencies at 53 loci. Although parasite heterogeneity did not differ, allelic frequencies at eight loci differed significantly between the mild and severe groups. Parasite isolates were analyzed further using a modified cluster analysis that segregated the population into 13 clusters of associated genotypes. Three clusters were significantly over-represented in children with severe lesions. Our findings, although preliminary, suggest that parasite genetic associations may be important in clinical outcome.
PREVALENCE AND LEVELS OF FILARIA-SPECIFIC URINARY IgG4 AMONG CHILDREN LESS THAN FIVE YEARS OF AGE AND THE ASSOCIATION OFANTIBODY POSITIVITY BETWEEN CHILDREN AND THEIR MOTHERS
Authors: WEERASOORIYA M. V. , ITOH M. , ISLAM M. Z. , QIU X.-G. , FUJIMAKI Y. , KIMURA E.
Published: September 2018

An enzyme-linked immunosorbent assay (ELISA) to detect filaria-specific urinary IgG4 was tested in samples from 203 children less than five years old and their parents (165 mothers and 127 fathers) in Sri Lanka. There were four IgG4-positive children within 58 days after birth, suggesting the transfer of the antibody from mothers. No positive children were found between days 65 and 417. After day 1,000, the number of the positive individuals and the level of IgG4 increased quickly. The children of urinary IgG4-positive parents showed a higher IgG4 positive rate than those of negative parents. The children of positive mothers had a higher prevalence than those of negative mothers, whereas, the positivity of the fathers was not associated with that of their children. Collecting urine samples was easy to perform and well accepted because of its non-invasiveness. The ELISA will be useful for monitoring filarial infections in very young children, who are a sentinel population for evaluating the intensity of filariasis transmission and effectiveness of control measures.
VACCINATION OF RHESUS MACAQUES AGAINST DENGUE-2 VIRUS WITH A PLASMID DNA VACCINE ENCODING THE VIRAL PRE-MEMBRANE AND ENVELOPE GENES
Authors: PUTNAK ROBERT , FULLER JAMES , VANDERZANDEN LORNA , INNIS BRUCE L. , VAUGHN DAVID W.
Published: September 2018

A nucleic acid vaccine for dengue-2 virus was developed, consisting of a plasmid DNA vector with the pre-membrane (prM) and envelope (E) genes expressed from a cytomegalovirus promoter. The DNA was adsorbed onto gold microspheres for administration by a gene gun. Expression was demonstrated by transfection of mouse cells in culture where the prM and E antigens were detected intracellularly, and the E antigen was detected in the culture supernatant fluid, similar to a natural infection. The vaccine elicited neutralizing antibodies to dengue-2 virus and antigen-specific cytotoxic T lymphocyte responses in mice. Several vaccination regimens were evaluated in rhesus macaques for the ability to elicit neutralizing antibodies and protect against viremia after challenge with live dengue-2 virus. Neutralizing antibodies were measured in three of three animals that received four 2-μg doses of DNA and in two of six animals that received two 1-μg doses. No antibodies were detected in three animals that received a single 1-μg dose. When dengue virus challenge was performed one month after vaccination, the three animals that received four 2-μg doses exhibited 0, 0, and 1 day of viremia compared with unimmunized controls which exhibited 4, 4, and 6 days of viremia. Three animals that received two 1-μg doses also exhibited 0, 0, and 1 day of viremia, whereas three animals that received a single 1-μg dose exhibited 2, 3, and 5 days of viremia compared with unimmunized controls, which exhibited 4 days of viremia each. When challenge was performed 7 months after vaccination, three animals that received two 1-μg doses exhibited 0, 3, and 5 days of viremia compared with unimmunized controls, which exhibited 4, 5, and 9 days of viremia. These results suggest that a regimen consisting of two 1-μg doses of DNA can confer satisfactory protection at one month, but not at seven months, after vaccination. Long-term protection following DNA vaccination may require revaccination, higher doses of DNA, or a vaccine that contains additional epitopes or adjuvants.
PATHOGENICITY OF A VENEZUELAN EQUINE ENCEPHALOMYELITIS SEROTYPE IE VIRUS ISOLATE FOR PONIES
Authors: SAHU SUDHIR P. , PEDERSEN DOUGLAS D. , JENNY ALLEN L. , SCHMITT BEVERLY J. , ALSTAD ARNOLD D.
Published: September 2018

The enzootic or endemic strains of Venezuelan equine encephalomyelitis (VEE) virus (ID, IE, IF, and II-VI) are considered avirulent. In 1993 and 1996, outbreaks of encephalitis occurred in the horse populations in the Chiapas and Oaxaca provinces of Mexico, respectively. In both instances, enzootic VEE virus subserotype IE was isolated from brain tissues of dead horses. The present study investigated the pathogenicity of the Chiapas viral isolate (NVSL VEE IE 93-42124) in ponies. Three ponies were inoculated intradermally with 4, 5, and 6 logs, respectively, of the NVSL VEE IE 93-42124 viral isolate. All ponies showed fluctuations in body temperature, encephalitis, and other signs of infection with VEE virus. Virus was isolated only from the blood of ponies from day 1 to day 3 postinfection. Microscopic examination of hematoxylin and eosin–stained tissue sections showed mild to moderate nonsuppurative encephalitis, perivascular cuffing by mononuclear cells, gliosis, and meningoencephalitis. Antibody (IgM) to VEE virus IE was unable to differentiate between various subserotypes of VEE I viruses (serotypes IAB, IC, ID, and IF). Virus neutralizing antibody titers to heterologous VEE I viruses were 10–100-fold less than those for NVSL VEE IE 93-42124 virus and Mena II, a human isolate of VEE IE virus. The study confirmed that NVSL VEE IE 93-42124 virus, which was isolated from a brain of a horse during an outbreak of VEE in Chiapas, Mexico, was pathogenic for ponies.
REDUCTION OF MALARIA DURING PREGNANCY BY PERMETHRIN-TREATED BED NETS IN AN AREA OF INTENSE PERENNIAL MALARIA TRANSMISSION IN WESTERN KENYA
Authors: TER KUILE FEIKO O. , TERLOUW DIANNE J. , PHILLIPS-HOWARD PENELOPE A. , HAWLEY WILLIAM A. , FRIEDMAN JENNIFER F. , KARIUKI SIMON K. , SHI YA PING , KOLCZAK MARGARETTE S. , LAL ALTAF A. , VULULE JOHN M. , NAHLEN BERNARD L.
Published: September 2018

The impact of insecticide (permethrin)-treated bed nets (ITNs) on malaria in pregnancy was studied in a rural area in western Kenya with intense perennial malaria transmission. All households in 40 of 79 villages were randomized to receive ITNs by January 1997. The ITNs were distributed in control villages two years later. Complete data on birth outcome were available on 2,754 (89.6%) of 3,072 deliveries. Women (n = 780) were followed monthly throughout pregnancy in 19 of 79 villages. Among gravidae 1–4, ITNs were associated with reductions of 38% (95% confidence interval [CI] = 17–54%) in the incidence of malaria parasitemia and 47% (95% CI = 6–71%) in the incidence of severe malarial anemia (hemoglobin level < 8 g/dL with parasitemia) during pregnancy. At the time of delivery, mean hemoglobin levels were 0.6 g/dL (95% CI = 0.01–1.2 g/dL) higher, the prevalence of placental or maternal malaria was reduced by 35% (95% CI = 20–47%), and the prevalence of low birth weight was reduced by 28% (95% CI = 2–47%) in gravidae 1–4 from ITN villages. No beneficial impact was observed in gravidae five or higher. In areas of intense perennial malaria transmission, permethrin-treated bed nets reduce the adverse effect of malaria during the first four pregnancies.
INFECTION WITH HUMAN HERPESVIRUS-8 AND ITS CORRELATION WITH HEPATITIS B VIRUS AND HEPATITIS C VIRUS MARKERS AMONG RURAL POPULATIONS IN CAMBODIA
Authors: SARMATI LOREDANA , ANDREONI MASSIMO , SULIGOI BARBARA , BUGARINI ROBERTO , UCCELLA ILARIA , POZIO EDOARDO , REZZA GIOVANNI
Published: September 2018

Among 164 individuals in a rural population of Cambodia, antibodies to human herpesvirus-8 (HHV-8) were found among 56.6% of the women and 50.6% of the men. Seropositivity for HHV-8 tended to decrease with age (P < 0.001) and was not associated with exposure to hepatitis B virus (HBV) or HCV. Human herpesvirus-8, which shows a high rate of infection during childhood, does not seem to have the same pattern of transmission as HBV. This suggests very early acquisition of infection with HHV-8 in Cambodia.
COMPARISON OF A POLYMERASE CHAIN REACTION AND THE KATO-KATZ TECHNIQUE FOR DIAGNOSING INFECTION WITH SCHISTOSOMA MANSONI
Authors: PONTES LUIS A. , OLIVEIRA MARIA C. , KATZ NAFTALE , DIAS-NETO EMMANUEL , RABELLO ANA
Published: September 2018

Fecal samples from 194 individuals living in an area of Brazil endemic for Schistosoma mansoni were analyzed by a polymerase chain reaction (PCR) and the Kato-Katz parasitologic examination. Statistical analysis of the results showed a kappa index of 0.8 between the two methods. The prevalence of infection was 30.9% in three fecal samples examined by the Kato-Katz method, but 38.1% in one fecal sample examined by the PCR technique. Repeated survey of discordant results showed that five (41.6%) of 12 parasitologically negative cases for which PCR gave positive results were misdiagnosed by Kato-Katz examinations. The PCR technique showed a sensitivity of 96.7% and a specificity of 88% when the parasitologic examination was used as the reference test. The efficacy of cure with praziquantel was 87.8% in three parasitologic stool examinations and 75.6% in one PCR survey. These results demonstrate that the PCR assay might be a valuable alternative for diagnosing Schistosoma infections.
EPIDEMIOLOGY OF SPORADIC BLOODY DIARRHEA IN RURAL WESTERN KENYA
Authors: BROOKS JOHN T. , SHAPIRO ROGER L. , KUMAR LATA , WELLS JOY G. , PHILLIPS-HOWARD PENELOPE A. , SHI YA-PING , VULULE JOHN M. , HOEKSTRA ROBERT M. , MINTZ ERIC , SLUTSKER LAURENCE
Published: September 2018

We conducted laboratory-based surveillance and a case-control study to characterize the epidemiology of bloody diarrhea in rural Western Kenya. From May 1997 through April 2001, we collected stool from 451 persons with bloody diarrhea presenting to four rural clinics. Cultures of 231 (51%) specimens yielded 247 bacterial pathogens: 198 Shigella (97 S. flexneri, 41 S. dysenteriae type 1, 39 S. dysenteriae type non-1, 13 S. boydii, 8 S. sonnei), 33 Campylobacter, 15 non-typhoidal Salmonella, and 1 Vibrio cholerae O1. More than 90% of the isolates (excluding Campylobacter) were resistant to trimethoprim-sulfamethoxazole and tetracycline, and more than 80% were resistant to ampicillin. Most (74%) ill persons received medication to which their isolate was resistant. Drinking Lake Victoria water and sharing latrines between multiple households increased risk of bloody diarrhea. Washing hands after defecating was protective. Providing safe drinking water and more latrines, and promoting hand washing could reduce the burden of illness from bloody diarrhea while limiting injudicious antimicrobial use.
ACUTE UNDIFFERENTIATED FEVER CAUSED BY INFECTION WITH JAPANESE ENCEPHALITIS VIRUS
Authors: WATT GEORGE , JONGSAKUL KRISADA
Published: September 2018

To determine the proportion of acute undifferentiated fevers without neurologic deficits related to infection with Japanese encephalitis (JE) virus, flavivirus serology (dengue and JE) was performed in a cohort of 156 adults presenting to a hospital in Chiangrai, Thailand. Recent flavivirus infection was diagnosed for any individual with an IgM result > 40 units. A ratio of dengue virus IgM to JE virus IgM < 0.91 defined a JE virus infection. Diagnostic criteria for Japanese encephalitis were met in 22 individuals (14%), and were unequivocal in 8 patients. The admission findings in these eight subjects were similar to those described for other flavivirus infections. Thrombocytopenia was the most striking laboratory abnormality (median platelet count = 119,000/mm3, range = 44,000–236,000/mm3). Headache (75%), nausea (50%), myalgia (38%), rash (38%), and diarrhea (25%) were the most frequently encountered signs and symptoms. Infection with Japanese encephalitis virus is an underappreciated cause of acute undifferentiated fever in Asia.
CASE REPORT: GNATHOSTOMIASIS IN TWO TRAVELERS TO ZAMBIA
Authors: HALE DEVON C. , BLUMBERG LUCILLE , FREAN JOHN
Published: September 2018

Gnathostomiasis is a systemic infection caused by migrating nematode larvae of the genus Gnathostoma. It is a zoonosis involving a wide variety of animals as intermediate and definitive hosts, and consumption of raw fish is the main risk factor. The condition is most commonly seen in southeastern Asia, but has been described in a number of other countries, all outside Africa. We report the infection in two travelers returning from southcentral Africa, who presented with non-specific symptoms and marked eosinophilia, and in whom schistosomiasis was initially suspected. The typical migratory skin lesions of gnathostomiasis appeared later. The infections responded well to albendazole. The patients acquired the infection in western Zambia; this region of Africa appears to be a newly identified risk area for gnathostomiasis in tourists who indulge in eating raw freshwater fish.
SEXUAL TRANSMISSION OF HEPATITIS B VIRUS, HEPATITIS C VIRUS, AND HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 INFECTIONS AMONG MALE TRANSVESTITE COMERCIAL SEX WORKERS IN MONTEVIDEO, URUGUAY
Authors: RUSSI JOSE C. , SERRA MARGARITA , VIÑOLES JOSE , PÉREZ M. T. , RUCHANSKY D. , ALONSO G. , SANCHEZ JOSE L. , RUSSELL KEVIN L. , MONTANO SILVIA M. , NEGRETE MONICA , WEISSENBACHER MERCEDES
Published: September 2018

Prostitution may constitute a risk behavior for infection with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). We conducted a seroepidemiologic study among 200 male transvestite commercial sex workers (CSWs) in Montevideo, Uruguay in 1999. Evidence of exposure to HBV, HCV, and HIV was found in 101 (50.5%), 13 (6.5%), and 43 (21.5%) individuals, respectively. Positivity for HIV was correlated with both HBV (odds ratio [OR] = 2.15, 95% confidence interval [CI] = 1.01–4.67) and HCV (OR = 3.47, 95% CI = 0.90–12.79) infection. Predictors of infection were older age (≥ 26 years; P < 0.01) for all 3 viruses and time in CSW (≥5 years; P < 0.05) for HBV and HIV. Prior history of use of drugs (OR = 3.54, 95% CI = 1.09–11.52) and sexual contact with foreigners (OR = 9.2, 95% CI = 1.16–73.12) were found to be associated only with HCV infection. Sexual transmission of these viruses constitutes a significant problem among male transvestite CSWs.
LOW PREVALENCE AND INCREASED HOUSEHOLD CLUSTERING OF MYCOBACTERIUM TUBERCULOSIS INFECTION IN HIGH ALTITUDE VILLAGES IN PERU
Authors: OLENDER SUSAN , SAITO MAYUKO , APGAR JANE , GILLENWATER KARI , BAUTISTA CHRISTIAN T. , LESCANO ANDRES G. , MORO PEDRO , CAVIEDES LUZ , HSIEH EVELYN J. , GILMAN ROBERT H.
Published: September 2018

Anecdotal historical evidence suggests that tuberculosis was uncommon at high altitude, but whether transmission is affected by high altitude is not known. To test whether high altitude lowers infection by Mycobacterium tuberculosis, the prevalence of tuberculin skin test (TST) positivity was compared between two high altitude villages (3,340 meters [10,960 feet] and 3,500 meters [11,480 feet]) and three sea-level sites in Peru. High altitude villages had lower TST-positive prevalence rates (5.7% and 6.8%) than sea level areas (25–33%), and the difference remained significant (odds ratio = 4.5–6.0) after adjusting for age, education, bacille Calmette-Guérin vaccination, and contact with tuberculosis patients. The TST-positive individuals clustered within highland families more than within sea level families. These data suggest that prevention and control efforts targeted to families may be more effective at high altitude. The mechanism by which TST-positivity prevalence is decreased at high altitude is unknown, but may reflect relative hypoxia, low humidity, or an increased ultraviolet effect.
ANTIBODY-MEDIATED IN VITRO GROWTH INHIBITION OF FIELD ISOLATES OF PLASMODIUM FALCIPARUM FROM ASYMPTOMATIC CHILDREN IN BURKINA FASO
Authors: BOLAD AHMED , NEBIÉ ISSA , CUZIN-OUATTARA NADINE , TRAORE ALFRED , ESPOSITO FULVIO , BERZINS KLAVS
Published: September 2018

Antibody-mediated inhibition of Plasmodium falciparum parasites in vitro reflects the potential parasite-neutralizing activity of the antibodies in vivo. In this study, immunoglobulins and P. falciparum isolates were collected from children with asymptomatic malaria in Burkina Faso. We demonstrate a significantly lower in vitro growth inhibitory activity against the P. falciparum field isolates by autologous host immunoglobulin compared with that of immunoglobulin from other individuals. To gain further insight to possible mechanisms for the diverse sensitivity observed, analyses of consecutive isolates taken 14 days apart were performed with regard to polymerase chain reaction–based genotyping and sensitivity to growth inhibition in vitro. All the asymptomatic infections were composed of multiple, genotypically distinct parasite clones, and at least one new parasite clone appeared in most of the day 14 isolates compared with the corresponding day 0 isolates. Apparently persisting parasite clones, present in both the day 0 and day 14 isolates from the same person, were also frequently observed. The day 14 isolates were more effectively inhibited by autologous day 14 immunoglobulin than by the corresponding day 0 immunoglobulin in 57% of the cases. However, the frequent presence of persisting parasite clones in asymptomatic children indicates that the parasite may develop a relative resistance to neutralizing immune responses.
EFFICACY OF AMODIAQUINE ALONE AND COMBINED WITH SULFADOXINE-PYRIMETHAMINE AND OF SULFADOXINE PYRIMETHAMINE COMBINED WITH ARTESUNATE
Authors: RWAGACONDO CLAUDE E. , NIYITEGEKA FRANCOIS , SARUSHI JOSEPH , KAREMA CORINE , MUGISHA VERONIQUE , DUJARDIN JEAN-CLAUDE , VAN OVERMEIR CHANTAL , VAN DEN ENDE JEF , D’ALESSANDRO UMBERTO
Published: September 2018

The safety and the efficacy of amodiaquine (AQ) alone, AQ plus sulfadoxine-pyrimethamine (SP) (AQ plus SP), and artesunate (ART) plus SP (ART plus SP), three possible alternatives to chloroquine (CQ), were investigated in 379 Rwandan children 6–59 months old with uncomplicated Plasmodium falciparum malaria who visited one urban/peri-urban health center and two rural health centers. The three treatment regimens were well tolerated and no serious adverse effects were observed. Children treated with AQ plus SP had less clinical failures than those treated with ART plus SP (odds ratio [OR] = 0.25, 95% confidence interval [CI] = 0.06–0.81, P = 0.01) or AQ alone (OR = 0.33, 95% CI = 0.07–1.10, P = 0.08). Even after new infections were excluded, AQ plus SP was still significantly more efficacious than ART plus SP (P = 0.05). At day 14, the mean packed cell volume was significantly higher in the AQ plus SP group compared with the ART plus SP group (P = 0.02) and with the AQ alone group (P = 0.01). In Rwanda, AQ plus SP has been chosen to replace CQ as a first-line treatment. However, this is considered an interim measure and new combinations, possibly co-formulated, should be identified and tested.
ENHANCEMENT OF DEVELOPMENT OF LARVAL ANOPHELES ARABIENSIS BY PROXIMITY TO FLOWERING MAIZE (ZEA MAYS) IN TURBID WATER AND WHEN CROWDED
Authors: YE-EBIYO YEMANE , POLLACK RICHARD J. , KISZEWSKI ANTHONY , SPIELMAN ANDREW
Published: September 2018

To determine whether proximity to flowering maize enhances the development of larval anopheline mosquitoes breeding in turbid water and when crowded, we evaluated the development of larval Anopheles arabiensis under various conditions of turbidity, larval density, and proximity to pollen-shedding maize in simulated breeding puddles in a malaria-endemic site. In naturally formed puddles, water turbidity, as well as larval density, increased as the rainy season progressed. In sites remote from flowering maize, more pupae developed and the resulting adults were larger in relatively clear water than in turbid water, and larval crowding inhibited development. In close proximity to flowering maize, however, larval development was little affected by water turbidity and larval crowding. Larvae of this member of the African An. gambiae complex of mosquitoes develop readily in turbid water and when crowded, provided that their breeding sites are located where maize pollen is abundant.
IMPACT OF PERMETHRIN-TREATED BED NETS ON GROWTH, NUTRITIONAL STATUS, AND BODY COMPOSITION OF PRIMARY SCHOOL CHILDREN IN WESTERN KENYA
Authors: FRIEDMAN JENNIFER F. , PHILLIPS-HOWARD PENELOPE A. , HAWLEY WILLIAM A. , TERLOUW DIANNE J. , KOLCZAK MARGARETTE S. , BARBER MARLENE , OKELLO NORMAN , VULULE JOHN M. , DUGGAN CHRISTOPHER , NAHLEN BERNARD L. , TER KUILE FEIKO O.
Published: September 2018

Insecticide-treated bed nets (ITNs) have been demonstrated to reduce morbidity and mortality in children less than five years of age. They have also been shown to improve the nutritional status of these children, but little is known about their impact on the nutritional status of school-age children. We evaluated the impact of ITNs on growth, nutritional status, and body composition of primary schoolchildren less than 13 years of age living in an area of intense perennial malaria transmission in western Kenya. The ITNs did not have a significant impact on linear growth or summary measures of protein-energy malnutrition in this age group. This lack of efficacy most likely relates to the reduced burden of malaria in this age group in a setting of stable transmission pressure. Use of ITNs was associated with a change in body composition with an increase in percent lean body mass (1.2%; P = 0.04). This may be consequent to reduced exposure to malaria with subsequent reduced elaboration of pro-inflammatory cytokines known to promote muscle wasting.
TRANSPLACENTALLY TRANSFERRED MATERNAL-INFANT ANTIBODIES TO DENGUE VIRUS
Authors: WATANAVEERADEJ VEERACHAI , ENDY TIMOTHY P. , SAMAKOSES RUDIWILAI , KERDPANICH ANGKOOL , SIMASATHIEN SRILUCK , POLPRASERT NAPUSCHON , AREE CHANCHAI , VAUGHN DAVID W. , HO CYNTHIA , NISALAK ANANDA
Published: September 2018

Antibodies of all four dengue virus serotypes were detected by hemagglutination inhibition (HI) in 97% of 2,000 infants’ cord sera at the time of delivery. In comparison with 250 mother–infant’s paired sera, we found that 53% of the infants’ serum HI titers were higher than those of the mother’s. The mother/infant IgG subclasses 1, 2, 3, and 4 titers were 53.1/87.0, 8.4/11.7, 0.14/0.11, and 1.1/1.0 mg/dL, respectively. In 18 months of follow-up of 100 infants studied, we observed that antibody to dengue virus disappeared in 3% by two months of age, in 19% by four months of age, in 72% by six months of age, in 99% by nine months of age, and in 100% by 12 months of age, with a half-life of 41 days. We conclude that the antibodies to dengue virus disappeared in the first year of life. We suggest that the most appropriate age for vaccination with a live-attenuated dengue vaccine in an endemic area is one year of age.
INDUCTION OF NEUTRALIZING ANTIBODIES AND PARTIAL PROTECTION FROM VIRAL CHALLENGE IN MACACA FASCICULARIS IMMUNIZED WITH RECOMBINANT DENGUE 4 VIRUS ENVELOPE GLYCOPROTEIN EXPRESSED IN PICHIA PASTORIS
Authors: GUZMÁN MARÍA G. , RODRÍGUEZ RAYNER , RODRÍGUEZ ROSMARI , HERMIDA LISSET , ALVAREZ MAYLING , LAZO LAURA , MUNÉ MAYRA , ROSARIO DELFINA , VALDÉS KATIA , VÁZQUEZ SUSANA , MARTINEZ RAFAEL , SERRANO TERESITA , PAEZ JORGE , ESPINOSA RAÚL , PUMARIEGA TANIA , GUILLÉN GERARDO
Published: September 2018

A recombinant vaccine that expresses the envelope (E) gene of dengue virus type 4 was tested for immunogenicity and protection in Macaca fascicularis. One hundred micrograms of semipurified recombinant E protein (E4rec) expressed in Pichia pastoris was used to immunize three animals. Neutralizing antibodies to dengue 4 virus with a titer of 1:30 were detected in all immunized monkeys prior to challenge. Animals were challenged with 105 plaque-forming units of dengue 4 virus. One vaccine-immunized monkey was protected from viremia, while the other two were partially protected. Monkeys immunized with E4rec elicited the highest neutralizing antibody titers (P < 0.05) ranging from 1:85 to 1:640 at day 30. In both immunized and control animals, the longest duration of viremia correlated with earliest and highest level of IgM antibody to dengue virus. The vaccinated animals showed anamnestic antibody responses upon virus challenge, indicating successful priming by the recombinant vaccine. Our results suggest that E4rec expressed in P. pastoris can provide partial protection against viremia. However, the results were not effective enough to use it as a vaccine candidate. Further work is required to improve the quality of the immunogen.
OUTBREAK OF DENGUE FEVER IN PALAU, WESTERN PACIFIC: RISK FACTORS FOR INFECTION
Authors: ASHFORD DAVID A. , SAVAGE HARRY M. , HAJJEH RANA A. , MCREADY JILL , BARTHOLOMEW DAVID M. , SPIEGEL RICHARD A. , VORNDAM VANCE , CLARK GARY G. , GUBLER DUANE G.
Published: September 2018

Between January and June 1995, an outbreak of dengue fever occurred in Palau, an island nation of 32,000 inhabitants in the Western Pacific. To determine the magnitude of this outbreak and to determine modifiable risk factors to guide control strategies, we established active surveillance at the national hospital and private clinics, reviewed available clinical records, and conducted serologic and entomologic surveys. Between January 1 and July 1, 1995, 817 case-patients with acute febrile illness with body or joint aches and one of the following: headache, rash, nausea, vomiting, or hemorrhagic manifestations presented to health facilities in Palau. The epidemic peaked in the second week of April 1995. Of 338 case-patients tested, 254 (75%) had positive serologic results by an IgM capture enzyme-linked immunosorbent assay. Dengue 4 virus was isolated from 78 (51%) of 154 serum samples tested. Blood samples collected during a cross-sectional survey were tested for IgM antibody and yielded an attack ratio of 27% (95% confidence interval = 23–31%). Potential vectors included the introduced species Aedes aegypti and Ae. albopictus, and the native species Ae. hensilli. Significant risk factors (P ≤ 0.05) for infection included age < 20 years, the presence of food or water pans for animals on the property, taro farming, the presence of Ae. aegypti on the property, and presence of Ae. scutellaris group mosquitoes (Ae. Hensilli, Ae. albopictus, and a native species). This was the first outbreak of dengue 4 virus in the Western Pacific, and the first documented epidemic of dengue in Palau since 1988.
SHORT REPORT: A MAJOR GENOTYPE OF JAPANESE ENCEPHALITIS VIRUS CURRENTLY CIRCULATING IN JAPAN
Authors: MA SHAO-PING , YOSHIDA YASUKO , MAKINO YOSHIHIRO , TADANO MASAYUKI , ONO TETSURO , OGAWA MASAO
Published: September 2018

A 240-nucleotide sequence of the capsid/premembrane gene region of 23 Japanese encephalitis virus (JEV) strains isolated in Tokyo and Oita, Japan was determined and phylogenetic analyses were performed. All the strains clustered into two distinct genotypes (III and I). All strains isolated before 1991 belonged to genotype III, while those isolated after 1994 belonged to genotype I. In addition, the strains of the genotype I isolated in Japan showed a close genetic relationship with those from Korea and Malaysia.
MOLECULAR EPIDEMIOLOGY OF MALARIA IN CAMEROON. XVII. BASELINE MONITORING OF ATOVAQUONE-RESISTANT PLASMODIUM FALCIPARUM BY IN VITRO DRUG ASSAYS AND CYTOCHROME B GENE SEQUENCE ANALYSIS
Authors: BASCO LEONARDO K.
Published: September 2018

Atovaquone is a new broad-spectrum antiprotozoal drug with high in vitro activity against multidrug-resistant Plasmodium falciparum. Its specific action against protozoans is based on the inhibition of the parasite cytochrome bc1 complex of the mitochondrial electron transport system. Protozoans may develop atovaquone resistance by the selection of a mutant cytochrome b gene. With the increasing availability of atovaquone-proguanil combination for prophylaxis and treatment of malarial infections, it is necessary to establish baseline data on atovaquone sensitivity before the drug is introduced massively in an endemic region. For this purpose, the activity of atovaquone was assessed indirectly by in vitro drug sensitivity assays with several serum substitutes and DNA sequencing of the cytochrome b gene. Using the standard in vitro assay procedures with 10% human serum, the geometric mean 50% inhibitory concentration (IC50) for atovaquone was calculated to be 1.15 nM (range = 0.460–4.17 nM), while the use of 10% fetal calf serum resulted in lower IC50s (geometric mean = 0.575, range = 0.266–2.20 nM). The use of Albumax, a lipid-enriched bovine albumin, over the same concentration range (0.25–16 nM) showed poor results. None of the 37 isolates with an atovaquone IC50 < 4.17 nM displayed any mutation. Further monitoring of atovaquone-resistant P. falciparum is warranted for the rational use of this new antimalarial drug.