bluuebunny/crossref_metadata_2025 huggingface dataset:
VIRGIN SOIL: THE SPREAD OF VISCERAL LEISHMANIASIS INTO UTTAR PRADESH, INDIA
Authors: BARNETT PAUL G. , SINGH S. P. , BERN CARYN , HIGHTOWER ALLEN W. , SUNDAR SHYAM
Published: September 2018

We conducted a cross-sectional study to determine the incidence of visceral leishmaniasis (VL) and risk factors in two villages in Uttar Pradesh, India reported to have had a recent outbreak. In 245 households with 2,203 people, we detected 3 current VL cases, 32 past cases, and 8 VL deaths since 2001 (annual incidence = 6 per 1,000). Risk factors included living in the same household as a VL case (odds ratio [OR] = 76, P < 0.0005 in one village and OR = 22, P < 0.0005 in the other village), sleeping downstairs and outside in the summer (OR = 4.7, P = 0.004), and an age ≥ 15 years old (OR = 2.9, P = 0.024). Increasing cattle density was a risk factor in one village but not the other. We were not able to determine the route by which VL entered the villages. Our data demonstrate a new spread of VL in previously unaffected areas. We recommend carefully supervised spraying with DDT, surveillance to pinpoint other affected villages, and efforts to increase availability of diagnostic and treatment facilities.
BODY COMPOSITION IN ADULTS INFECTED WITH HUMAN IMMUNODEFICIENCY VIRUS IN KHON KAEN, THAILAND
Authors: LUDY MARY-JON , HENDRICKS KRISTY , HOUSER ROBERT , CHETCHOTISAKD PLOENCHAN , MOOTSIKAPUN PIROON , ANUNNATSIRI SIRILUCK , PRICE ELIZABETH , WANKE CHRISTINE A.
Published: September 2018

A cross-sectional study of 77 patients infected with human immunodeficiency virus (HIV) in Khon Kaen, Thailand examined association of nutritional status with active opportunistic infections (AOIs)/HIV status and assessed degree of correlation between bioelectrical impedance analysis (BIA) and anthropometry. Many patients (41.3%) were malnourished using World Health Organization criteria for underweight, and malnutrition was associated with AOI status. Unconditional odds ratios (P < 0.05) for AOI as opposed to no AOI were 4.57 for underweight, 9.87 for severe underweight, 2.55 for triceps < 10th percentile, and 5.22 for mid-arm circumference < 10th percentile. Body fat composition from BIA, anthropometry, and body mass index were moderate to highly correlated (P < 0.001), with the highest correlation between BIA and subscapular skinfold (r = 0.86) and the lowest between BIA and triceps skinfold (r = 0.54). Insights were gained about relative value of using various measurements to assess nutritional status of HIV-infected populations.
HIGH PREVALENCE RATE OF ENTAMOEBA HISTOLYTICA ASYMPTOMATIC INFECTION IN A RURAL MEXICAN COMMUNITY
Authors: RAMOS FERNANDO , MORÁN PATRICIA , GONZÁLEZ ENRIQUE , GARCÍA GABRIELA , RAMIRO MANUEL , GÓMEZ ALEJANDRO , DE LEÓN MARÍA DEL CARMEN GARCÍA , MELENDRO EMMA I. , VALADEZ ALICIA , XIMÉNEZ CECILIA
Published: September 2018

The frequency of Entamoeba histolytica and Entamoeba dispar infection was analyzed in a rural community in the state of Morelos, Mexico, using polymerase chain reaction (PCR). Sociodemographic variables as risk factors for the infection were assessed. Results highlighted the number of individuals with intestinal parasites (43.1%) in the community, indicating extensive fecalism. A high frequency of E. histolytica asymptomatic infection, higher than E. dispar infection (13.8% versus 9.6%), was detected by PCR. Anti-amebic antibody levels (IgG) in serum and saliva (IgA) samples were not associated with E. histolytica intestinal infection. These findings suggest a predominant distribution of E. histolytica strains of low invasive potential in this community.
A PHASE II DOSE-INCREASING STUDY OF SITAMAQUINE FOR THE TREATMENT OF VISCERAL LEISHMANIASIS IN KENYA
Authors: WASUNNA MONIQUE K. , RASHID JUMA R. , MBUI JANE , KIRIGI GEORGE , KINOTI DEDAN , LODENYO HUDSON , FELTON J. MARK , SABIN ANTONY J. , HORTON JOHN
Published: September 2018

Sitamaquine (WR6026) is an 8-aminoquinoline in development for the oral treatment of visceral leishmaniasis (VL). This was an open-label, dose-increasing study to determine the dose-response and safety profile for sitamaquine in Kenyan patients with VL caused by Leishmania donovani. Patients (mean age 15.9 [range = 5–47] years) received sitamaquine daily for 28 days at one of four doses: 1.75 (n = 12), 2.0 (n = 61), 2.5 (n = 12), or 3.0 (n = 12) mg/kg/day. The primary efficacy outcome was cure (absence of parasites on splenic aspirate) in the intent-to-treat population at day 180. Cure was achieved in 79 (83%) of 95 patients overall, and in 11 (92%) of 12, 49 (80%) of 61, 9 (82%) of 11, and 10 (91%) of 11 patients at sitamaquine doses of 1.75, 2.0, 2.5, or 3.0 mg/kg/day, respectively. The most frequent adverse events during active treatment were abdominal pain (12 [12%] of 97) and headache (11 [11%] of 97), and one patient in each of the 2.5 mg/kg/day and 3.0 mg/kg/day dose groups had a severe renal adverse event. The effects of sitamaquine on the kidney need further investigation. Sitamaquine was efficacious and generally well tolerated in Kenyan patients with VL.
CRYPTOSPORIDIOSIS AND MICROSPORIDIOSIS IN UGANDAN CHILDREN WITH PERSISTENT DIARRHEA WITH AND WITHOUT CONCURRENT INFECTION WITH THE HUMAN IMMUNODEFICIENCY VIRUS
Authors: TUMWINE JAMES K. , KEKITIINWA ADDY , BAKEERA-KITAKA SABRINA , NDEEZI GRACE , DOWNING ROBERT , FENG XIAOCHUAN , AKIYOSHI DONNA E. , TZIPORI SAUL
Published: September 2018

Cryptosporidium spp. and Enterocytozoon bieneusi are enteric pathogens that have emerged as significant causes of persistent diarrhea (PD) in immunologically compromised individuals particularly in association with HIV/AIDS. We conducted a cross-sectional study on the clinical epidemiology of E. bieneusi and Cryptosporidium in children with PD, with and without HIV/AIDS, attending Uganda’s Mulago National Referral Hospital. Two hundred forty-three children aged < 60 months, admitted between November 2002 and May 2003 with PD (> 14 days), were analyzed for HIV status and CD4 lymphocyte counts, and stools were screened for the presence of E. bieneusi and Cryptosporidium by microscopy and positive samples genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Eighty (32.9%) of the children were excreting E. bieneusi, and 76 (31.3%) were excreting Cryptosporidium. Ninety-one of the 243 children had HIV, of who 70 (76.9%) had E. bieneusi, versus 10 (6.6%) of the 152 without (odds ratio = 47.33; 95% CI = 19.88 to 115.97), while 67 (73.6%) had Cryptosporidium, versus 9 (5.9%) without (odds ratio = 44.36; 95% CI = 18.39 to 110.40). Children with counts < 25% CD4 cells were more likely to have either E. bieneusi (odds ratio = 7.42; 95% CI = 3.77 to 14.69) or Cryptosporidium (odds ratio = 6.45; 95% CI = 3.28 to 12.76) than those with higher CD4 percentages. However, only HIV status was independently associated with either Cryptosporidium or E. bieneusi. Among the 243 children with PD, 67 (27.8%) were infected with both enteric pathogens, with HIV being the only independent predictor of coinfection. Finally, some 81% of HIV-infected children with PD excreted one or both organisms, compared with only 10% of children with PD testing negative for HIV. Seventy-four percent of isolates were C. hominis, the anthroponotic species, 17% were C. parvum, the zoonotic species, and 8% were a mixture of the two or others.
INCIDENCE OF TRYPANOSOMA CRUZI INFECTION AMONG CHILDREN FOLLOWING DOMESTIC REINFESTATION AFTER INSECTICIDE SPRAYING IN RURAL NORTHWESTERN ARGENTINA
Authors: GÜRTLER RICARDO E. , CECERE MARÍA C. , LAURICELLA MARTA A. , PETERSEN ROSARIO M. , CHUIT ROBERTO , SEGURA ELSA L. , COHEN JOEL E.
Published: September 2018

Following increasing reinfestation with Triatoma infestans after insecticide spraying, the household incidence of infection with Trypanosoma cruzi in children was positively related to the domestic abundance of infected T. infestans and the presence or proportion of infected dogs or cats in Amamá, a rural village in northwestern Argentina. Seven (12.1%) children seronegative for antibodies to T. cruzi at baseline, with no history of travel or blood transfusion, seroconverted after three years. Six incident cases lived in houses heavily infested with T. infestans, with high proportions of bugs infected with T. cruzi and having fed on humans or dogs. The remaining incident case occurred under a very light domestic infestation detected only at the endpoint, and most bugs had fed on humans. Dogs had a 17 times greater force of infection than children (4.3% per year). Sustained vector surveillance is crucially needed in high-risk areas for Chagas disease such as the Gran Chaco.
SPATIAL CLUSTERING AND EPIDEMIOLOGICAL ASPECTS OF VISCERAL LEISHMANIASIS IN TWO ENDEMIC VILLAGES, BARINGO DISTRICT, KENYA
Authors: RYAN JEFFREY R. , MBUI JANE , RASHID JUMA R. , WASUNNA MONIQUE K. , KIRIGI GEORGE , MAGIRI CHARLES , KINOTI DEDAN , NGUMBI PHILLIP M. , MARTIN SAMUEL K. , ODERA SHADRAK O. , HOCHBERG LISA P. , BAUTISTA CHRISTIAN T. , CHAN ADELINE S. T.
Published: September 2018

Visceral leishmaniasis (VL) seroprevalence in Kenya is unknown because of the lack of a practical and accurate diagnostic test or surveillance system. A novel serological assay was used to estimate the seroprevalence of Leishmania-specific antibodies, and Global Information System and spatial clustering techniques were applied to study the presence of spatial clusters in Parkarin and Loboi villages in Baringo District in 2001. VL seroprevalences were 52.5% in Parkarin and 16.9% in Loboi. Significant associations among seropositivity and house construction, age, and proximity to domestic animal enclosures were found. A significant spatial cluster of VL was found in Loboi. The spatial distribution of cases in the two villages was different with respect to risk factors, such as presence of domestic animals. This study suggests that disease control efforts could be focused on elimination of sand fly habitat, placement of domestic animal enclosures, and targeted use of insecticides.
MOLECULAR IDENTIFICATION OF A COLLECTION OF SPOTTED FEVER GROUP RICKETTSIAE OBTAINED FROM PATIENTS AND TICKS FROM RUSSIA
Authors: SHPYNOV STANISLAV N. , FOURNIER PIERRE-EDOUARD , RUDAKOV NIKOLAY V. , SAMOILENKO IRINA E. , RESHETNIKOVA TATJANA A. , YASTREBOV VLADIMER K. , SCHAIMAN MATVEY S. , TARASEVICH IRINA V. , RAOULT DIDIER
Published: September 2018

Thirty-one rickettsial isolates from ticks or patients in North Asian tick typhus (NATT) foci from the Ural region to the Russian Far East were obtained at the Omsk Research Institute of Natural Foci Infections between 1954 and 2001. Using citrate synthase (gltA) and outermenbrane protein a (ompA) gene sequencing, we identified these isolates as Rickettsia sibirica sensu stricto (25 isolates), R. sibirica strain BJ-90 (2 isolates), R. slovaca (1 isolate), and R. heilongjiangensis (3 isolates). We demonstrate that Ixodes persulcatus ticks should be considered potential vectors of NATT. We also demonstrate the presence of R. slovaca in Ural and R. heilongjiangensis in Siberia and Russian Far East, where they may cause human infections misdiagnosed as cases of NATT. Clinicians should be aware that several spotted fever rickettsioses with different prognoses coexist in Russia in areas where NATT was the only previously recognized rickettsiosis.
COST-EFFECTIVENESS OF HOME-BASED CHLORINATION AND SAFE WATER STORAGE IN REDUCING DIARRHEA AMONG HIV-AFFECTED HOUSEHOLDS IN RURAL UGANDA
Authors: SHRESTHA RAM K. , MARSEILLE ELLIOT , KAHN JAMES G. , LULE JOHN R. , PITTER CHRISTIAN , BLANDFORD JOHN M. , BUNNELL REBECCA , COUTINHO ALEX , KIZITO FRANCIS , QUICK ROBERT , MERMIN JONATHAN
Published: September 2018

Safe water systems (SWSs) have been shown to reduce diarrhea and death. We examined the cost-effectiveness of SWS for HIV-affected households using health outcomes and costs from a randomized controlled trial in Tororo, Uganda. SWS was part of a home-based health care package that included rapid diarrhea diagnosis and treatment of 196 households with relatively good water and sanitation coverage. SWS use averted 37 diarrhea episodes and 310 diarrhea-days, representing 0.155 disability-adjusted life year (DALY) gained per 100 person-years, but did not alter mortality. Net program costs were $5.21/episode averted, $0.62/diarrhea-day averted, and $1,252/DALY gained. If mortality reduction had equaled another SWS trial in Kenya, the cost would have been $11/DALY gained. The high SWS cost per DALY gained was probably caused by a lack of mortality benefit in a trial designed to rapidly treat diarrhea. SWS is an effective intervention whose cost-effectiveness is sensitive to diarrhea-related mortality, diarrhea incidence, and effective clinical management.
RISK FACTORS FOR FOLLOW-UP INTERRUPTION OF HIV PATIENTS IN FRENCH GUIANA
Authors: NACHER MATHIEU , EL GUEDJ MYRIAM , VAZ TANIA , NASSER VALÉRY , RANDRIANJOHANY ANDRY , ALVAREZ FERNAND , SOBESKY MILKO , MAGNIEN CHRISTIAN , COUPPIÉ PIERRE
Published: September 2018

French Guiana is the region of France where the HIV epidemic is most prevalent. To determine the risk factors for being lost for follow-up, we followed a cohort of 1,213 patients between 1992 and 2002 and determined which variables were related to two definitions of being lost to follow-up: permanently disappearing from HIV clinics and coming back after more than 1 year of missed appointments. The incidence rate for permanent follow-up interruption was 17.2 per 100 person-years. The median time to lost to follow-up was 4.3 years (interquartile range = 1.4–8.4 years). Cox modeling showed that the younger age groups, foreigners, patients with initial CD4 counts at the time of HIV diagnosis less than 500/mm3, and patients followed before the availability of highly active antiretroviral therapy (HAART) were significantly more likely to be permanently lost to follow-up, suggesting that some of the patients may have died. When looking at temporary loss to follow-up, younger age groups, untreated patients, patients consulting before the availability of HAART, and patients with CD4 counts more than 500/mm3 were more likely to not come back for a period of more than 1 year.
GENETIC DIVERSITY AND STRUCTURE OF AFRICAN PLASMODIUM FALCIPARUM POPULATIONS IN URBAN AND RURAL AREAS
Authors: BOGREAU HERVÉ , RENAUD FRANÇOIS , BOUCHIBA HOUSEM , DURAND PATRICK , ASSI SERGE-BRICE , HENRY MARIE-CLAIRE , GARNOTEL ERIC , PRADINES BRUNO , FUSAI THIERRY , WADE BOUBACAR , ADEHOSSI ERIC , PAROLA PHILIPPE , KAMIL MOHAMED ALI , PUIJALON ODILE , ROGIER CHRISTOPHE
Published: September 2018

The genetic variability and population structure of Plasmodium falciparum are key factors in malaria control strategies. Studies have suggested no P. falciparum population structure although linkage disequilibrium was observed in some African areas. We have assessed length polymorphism at 6–22 microsatellites in four urban and rural sites (Djibouti, Dakar, Niamey, and Zouan-Hounien, n = 240 blood samples). Results have shown a P. falciparum population structure in Africa (Fst = 0.17–0.24), lower genetic diversity in Djibouti (He = 0.53) than in the other sites (He = 0.73–0.76), and 3) significant linkage disequilibrium in Djibouti. These results could be related to geographic isolation and low flow of parasites between sites. They also suggest a potential effect of rural suburbs to generate genetic diversity in towns. This could affect the dispersal of selected drug resistance and should be considered when adapting urban malaria control strategies.
LACK OF INHIBITION OF THE ANTI-MALARIAL ACTION OF SULFADOXINE-PYRIMETHAMINE BY FOLIC ACID SUPPLEMENTATION WHEN USED FOR INTERMITTENT PREVENTIVE TREATMENT IN GAMBIAN PRIMIGRAVIDAE
Authors: MBAYE AMADOU , RICHARDSON KESHENA , BALAJO BABA , DUNYO SAM , SHULMAN CAROLINE , MILLIGAN PAUL , GREENWOOD BRIAN , WALRAVEN GIJS
Published: September 2018

Folic acid is frequently given to pregnant women at the same time as intermittent preventive treatment (IPTp) with sulfadoxine/pyrimethamine (SP), but it is not known if it interferes with the anti-malarial activity of SP. To investigate this concern, 1,035 Gambian primigravidae were randomized to receive either folic acid (500–1,500 μg/day) together with oral iron (522) or oral iron alone (513) for 14 days at the same time as they received IPTp with SP. On presentation, 261 women (25%) had Plasmodium falciparum asexual parasitemia. Prevalences of parasitemia on day 14 after treatment were similar in both groups: 5.7% (26 of 458) in the iron plus folic acid group and 4.9% (22 of 446) in the iron alone group (risk difference = 0.74%, 95% confidence interval [CI] = −2.2% to 3.7%). Parasitologic cure was observed in 116 (91%) of 128 of women who were parasitemic on presentation and who received iron and folic acid and in 122 (92%) of 133 women who received iron alone (difference = 1.1%, 95% CI = −5.6% to 8.0%). Women who received folic acid and iron had a slightly higher mean hemoglobin concentration at day 14 than women who had received iron alone (difference = 0.14 g/dL, 95% CI = 0.01–0.27 g/dL). The results of this study suggest that in an area of low SP resistance, administration of folic acid to pregnant women in a dose of 500–1,500 μg/day will not interfere with the protective effect of SP when used for IPTp.
PREVENTION AND TREATMENT STRATEGIES USED FOR THE COMMUNITY MANAGEMENT OF CHILDHOOD FEVER IN KAMPALA, UGANDA
Authors: KEMBLE SARAH K. , DAVIS JENNIFER C. , NALUGWA TALEMWA , NJAMA-MEYA DENISE , HOPKINS HEIDI , DORSEY GRANT , STAEDKE SARAH G.
Published: September 2018

To assess malaria-related prevention and treatment strategies in an urban parish of Kampala, Uganda, a questionnaire was administered to 339 randomly selected primary caregivers of children 1–10 years of age. Our study population was relatively stable and well educated, with better access to health services than many in Africa. Ownership of an insecticide-treated net (ITN) was reported by 11% of households and was predicted only by greater household wealth (highest quartile versus lowest quartile: odds ratio [OR] 21.8; 95% confidence interval [CI], 2.74–173). Among women, 5% reported use of an ITN and 11% used intermittent preventive therapy (IPT) during their last pregnancy. Use of appropriate IPT during pregnancy was predicted only by completion of secondary education or higher (OR, 2.87; 95% CI, 1.13–7.21). Children of 123 (36%) caregivers had experienced an episode of fever in the past 2 weeks. Of these, 22% received an anti-malarial that could be considered “adequate” (combination therapy or quinine). Only 1% of febrile children received adequate treatment at the correct dose within 24 hours of onset of fever. The only independent predictor of treatment with an adequate anti-malarial was accessing a clinic or hospital as the first source of care. In this urban area, use of appropriate malaria control measures occurs uncommonly.
RAPID DIAGNOSIS OF SCRUB TYPHUS IN RURAL THAILAND USING POLYMERASE CHAIN REACTION
Authors: SONTHAYANON PIENGCHAN , CHIERAKUL WIRONGRONG , WUTHIEKANUN VANAPORN , BLACKSELL STUART D. , PIMDA KRIANGSAK , SUPUTTAMONGKOL YUPIN , PUKRITTAYAKAMEE SASITHON , WHITE NICHOLAS J. , DAY NICHOLAS P. , PEACOCK SHARON J.
Published: September 2018

The aim of this study was to evaluate the use of polymerase chain reaction (PCR) amplification of the O. tsutsugamushi 16S rRNA gene for the diagnosis of scrub typhus in rural Thailand. A prospective study of acute febrile illness in Udon Thani, northeast Thailand, identified 183 patients as having scrub typhus on the basis of immunofluorescent antibody testing (IFA) of paired sera. A further 366 febrile patients admitted concurrently with a range of other diagnoses acted as negative controls. Diagnostic sensitivity and specificity of 16S rRNA PCR was 44.8% and 99.7%, respectively, compared with IFA. PCR positivity was related to duration of symptoms and presence of eschar (P < 0.001, both cases). PCR using primers to amplify a fragment of the 56-kd gene had a sensitivity and specificity of 29.0% and 99.2%, respectively. PCR has a high specificity but low sensitivity for the rapid diagnosis of scrub typhus in this endemic setting.
COMPETITION FOR RED BLOOD CELLS CAN ENHANCE PLASMODIUM VIVAX PARASITEMIA IN MIXED-SPECIES MALARIA INFECTIONS
Authors: MCQUEEN PHILIP G. , MCKENZIE F. ELLIS
Published: September 2018

We assess the consequences of competition for red blood cells (RBCs) in co-infections with the two major agents of human malaria, Plasmodium vivax and Plasmodium falciparum, using differential equations to model the population dynamics of RBCs and parasites. P. vivax parasitizes only the youngest RBCs, but this can reduce the broader RBC population susceptible to P. falciparum. We found that competition for RBCs typically causes one species to suppress the other, depending on their relative reproduction rates and timing of inoculation. However, if the species’ reproduction rates are nearly equal, transient increases in RBC production stimulated by the presence of P. falciparum may boost P. vivax parasitemia above its single-species infection level. Conversely, P. falciparum parasitemia is rarely enhanced above its single-species level. Furthermore, transients in RBC production can induce coupled oscillations in the parasitemia of both species. These results are remarkably robust to changes in model parameters.
URBAN MALARIA IN DAKAR, SENEGAL: CHEMOSUSCEPTIBILITY AND GENETIC DIVERSITY OF PLASMODIUM FALCIPARUM ISOLATES
Authors: HENRY MAUD , DIALLO IBRAHIMA , BORDES JULIEN , KA SIDY , PRADINES BRUNO , DIATTA BAKARY , M’BAYE PAPA SIALOU , SANE MOUHAMADOU , THIAM MASSAMBA , GUEYE PAPE MANDOUMBE , WADE BOUBACAR , TOUZE JEAN ETIENNE , DEBONNE JEAN-MARC , ROGIER CHRISTOPHE , FUSAI THIERRY
Published: September 2018

The chemosusceptibility and genetic polymorphism of Plasmodium falciparum populations from 48 patients hospitalized for malaria at the Hospital Principal in Dakar, Senegal were investigated during the 2002 malaria transmission season. Sixty-two percent of the isolates collected were from patients with severe malaria and 38% were from patients with mild malaria. In vitro activities of chloroquine, quinine, cycloguanil, atovaquone, mefloquine, halofantrine, and artesunate were evaluated. The prevalence of mutations in the Plasmodium falciparum dihydrofolate reductase (dhfr) and dihyropteroate synthetase (dhps) genes and the P. falciparum chloroquine resistance transporter (Pfcrt) gene associated with cycloguanil, pyrimethamine, sulfadoxine, and chloroquine resistance were estimated. The genetic polymorphism of the parasite populations was evaluated by analysis of the highly polymorphic regions of merozoite surface protein 1 (msp1) block 2 and msp2. Seventy percent of the isolates were assessed by an in vitro assay. Fifty-two percent of the isolates were chloroquine resistant, 45% were cycloguanil resistant, and 24% were atovaquone resistant. Four percent had low susceptibility to quinine. The Pfcrt and dhfr mutations were associated with in vitro chloroquine- and antimetabolic drug-resistant isolates, respectively. Approximately 70% of the isolates contained two or more clones. Genetic diversity of P. falciparum was high. The prevalence of allelic family K1 of msp1 was 68%. Isolates of P. falciparum were highly resistant to chloroquine, cycloguanil and atovaquone. The transmission rate of malaria in Dakar is low but a high degree of genetic polymorphism can increase severe malaria, as shown by persons coming to Dakar from areas highly endemic for malaria. Areas with urban malaria should use vector control measures and efficient chemoprophylaxis for non-immune populations.
DETECTION AND ISOLATION OF HIGHLY PATHOGENIC H5N1 AVIAN INFLUENZA A VIRUSES FROM BLOW FLIES COLLECTED IN THE VICINITY OF AN INFECTED POULTRY FARM IN KYOTO, JAPAN, 2004
Authors: SAWABE KYOKO , HOSHINO KEITA , ISAWA HARUHIKO , SASAKI TOSHINORI , HAYASHI TOSHIHIKO , TSUDA YOSHIO , KURAHASHI HIROMU , TANABAYASHI KIYOSHI , HOTTA AKITOYO , SAITO TAKEHIKO , YAMADA AKIO , KOBAYASHI MUTSUO
Published: September 2018

During the outbreak of highly pathogenic avian influenza that occurred in Tamba Town, Kyoto Prefecture in 2004, a total of 926 flies were collected from six sites within a radius of 2.3 km from the poultry farm. The H5 influenza A virus genes were detected from the intestinal organs, crop, and gut of the two blow fly species, Calliphora nigribarbis and Aldrichina grahami, by reverse transcription-polymerase chain reaction for the matrix protein (M) and hemagglutinin (HA) genes. The HA gene encoding multiple basic amino acids at the HA cleavage site indicated that this virus is a highly pathogenic strain. Based on the full-length sequences of the M, HA, and neuraminidase (NA) segments of virus isolates through embryonated chicken eggs, the virus from C. nigribarbis (A/blow fly/Kyoto/93/2004) was characterized as H5N1 subtype influenza A virus and shown to have > 99.9% identities in all three RNA segments to a strain from chickens (A/chicken/Kyoto/3/2004) and crows (A/crows/Kyoto/53/2004) derived during this outbreak period in Kyoto in 2004. Our results suggest it is possible that blow flies could become a mechanical transmitter of H5N1 influenza virus.
POLYMORPHISMS IN PFCRT, PFMDR1, DHFR GENES AND IN VITRO RESPONSES TO ANTIMALARIALS IN PLASMODIUM FALCIPARUM ISOLATES FROM BANGUI, CENTRAL AFRICAN REPUBLIC
Authors: MENARD DIDIER , YAPOU FERDINAND , MANIRAKIZA ALEXANDRE , DJALLE DJIBRINE , MATSIKA-CLAQUIN MARCELLE DIANE , TALARMIN ANTOINE
Published: September 2018

Drug resistance is probably the greatest challenge to most malaria-control programs. Given the limited resources for other malarial-control measures, rational drug used is crucial. Molecular markers for parasite resistance such as pfcrt, pfmdr-1, and dhfr have the potential to be used in an integrated fashion to provide timely information that is useful to policy makers. Therefore, we evaluated polymorphisms in these genes from Plasmodium falciparum and their association with in vitro antimalarial drug resistance to 135 parasites samples collected in Bangui in 2004. For the dhfr gene, we found a strong association between the dhfr genotype and chemosensitivity to pyrimethamine. For the pfcrt gene, we found that haplotypes with mutant-type alleles led to significant changes in the IC50 values for chloroquine, monodesethylamodiaquine, and quinine. We found no correlations for the pfmdr1 gene. These findings suggest that a regular monitoring and screening for resistance markers for antifolates and for chloroquine could act as an adjunct to in vivo trials.
PRIMAQUINE: REPORT FROM CDC EXPERT MEETING ON MALARIA CHEMOPROPHYLAXIS I
Authors: HILL DAVID R. , BAIRD J. KEVIN , PARISE MONICA E. , LEWIS LINDA S. , RYAN EDWARD T. , MAGILL ALAN J.
Published: September 2018

Primaquine phosphate has been used for preventing relapse of Plasmodium vivax and P. ovale malaria since the early 1950s, based on its ability to kill latent (hypnozoite) and developing liver stages of these parasites. There are three uses for primaquine in malaria: radical cure of established infection with P. vivax or P. ovale malaria; presumptive anti-relapse therapy (PART; terminal prophylaxis) in persons with extensive exposure to these parasites; and primary prophylaxis against all malaria species. All persons for whom primaquine is being considered must have a glucose-6-phosphate dehydrogenase (G6PD) enzyme level checked before use, and persons who have a deficiency of G6PD must not take primaquine for prophylaxis or PART. The recommended adult dose for PART based on clinical trials and expert opinion is 30 mg base daily for 14 days, started on return from a malarious region and overlapping with a blood schizonticide. The adult dose for primary prophylaxis is 30 mg daily begun 1 day before travel and continued for 7 days after return. This review will examine the evidence for these recommendations.
CLINICAL FEATURES OF 62 IMPORTED CASES OF DENGUE FEVER IN JAPAN
Authors: ITODA ICHIRO , MASUDA GOHTA , SUGANUMA AKIHIKO , IMAMURA AKIFUMI , AJISAWA ATSUSHI , YAMADA KEN-ICHIRO , YABE SADAO , TAKASAKI TOMOHIKO , KURANE ICHIRO , TOTSUKA KYOICHI , NEGISHI MASAYOSHI
Published: September 2018

To describe the clinical features of dengue cases in Japan, a retrospective study was conducted on 62 laboratory-confirmed Japanese dengue cases presented to Tokyo Metropolitan Komagome Hospital between 1985 and 2000. Age distribution was from 18 to 62 years old (mean, 31.5 years). All cases were imported from abroad and diagnosed as dengue fever. Clinical manifestations included fever (100%), headache (90%), and skin rash (82%). Laboratory examinations revealed leukocytopenia (71%), thrombocytopenia (57%), elevated levels of serum aspartate aminotransferase (78%), and lactate dehydrogenase (71%). Antibody responses were consistent with that of secondary flavivirus infection in 60% of cases. Severity of symptoms in patients with primary dengue antibody response and those with secondary flavivirus antibody responses didn’t show statistical significance. Dengue virus infection should be taken into consideration in the differential diagnosis of febrile patients who recently entered Japan from tropical or subtropical countries.
FALCIPARUM MALARIA WITH HEMOPHAGOCYTIC SYNDROME
Authors: OHNISHI KENJI , MITSUI KEIKO , KOMIYA NOBUHIRO , IWASAKI NORIAKI , AKASHI AKIKO , HAMABE YUICHI
Published: September 2018

A 30-year-old Japanese woman with falciparum malaria was hospitalized because of fever and renal failure, and prolonged anemia was identified despite the eradication of malaria parasites through anti-malaria therapy. Bone marrow aspiration revealed the presence of macrophages with hemophagocytosis, and serum interleukin (IL)-18 and tumor necrosis factor (TNF)-α levels were high in the anemic phase. Hemophagocytosis was confirmed for at least 3 weeks, and prolonged hemophagocytic syndrome is thought to be one of the causes of prolonged anemia in patients with falciparum malaria.
COMPARISON OF HRP2- AND pLDH-BASED RAPID DIAGNOSTIC TESTS FOR MALARIA WITH LONGITUDINAL FOLLOW-UP IN KAMPALA, UGANDA
Authors: HOPKINS HEIDI , KAMBALE WILSON , KAMYA MOSES R. , STAEDKE SARAH G. , DORSEY GRANT , ROSENTHAL PHILIP J.
Published: September 2018

Presumptive treatment of malaria results in significant overuse of antimalarials. Malaria rapid diagnostic tests (RDTs) may offer a reliable alternative for case management, but the optimal RDT strategy is uncertain. We compared the diagnostic accuracy of histidine-rich protein 2 (HRP2)- and plasmodium lactate dehydrogenase (pLDH)-based RDTs, using expert microscopy as the gold standard, in a longitudinal study of 918 fever episodes over an 8-month period in a cohort of children in Kampala, Uganda. Sensitivity was 92% for HRP2 and 85% for pLDH, with differences primarily due to better detection with HRP2 at low parasite densities. Specificity was 93% for HRP2 and 100% for pLDH, with differences primarily due to rapid clearance of pLDH antigenemia after treatment of a previous malaria episode. RDTs may provide an effective strategy for improving rational delivery of antimalarial therapy; in Kampala, either test could dramatically decrease inappropriate presumptive treatments.
ACUTE RESPIRATORY DISTRESS SYNDROME IN SCRUB TYPHUS
Authors: WANG CHIN-CHOU , LIU SHIH-FENG , LIU JIEN-WEI , CHUNG YU-HSIU , SU MAO-CHANG , LIN MENG-CHIH
Published: September 2018

Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi. Acute respiratory distress syndrome (ARDS) is a serious complication of scrub typhus. This study retrospectively reviewed the medical records of 72 patients diagnosed with scrub typhus from January 1998 to August 2006 in Kaohsiung Chang Gung Memorial Hospital in Taiwan. Eight of 72 scrub typhus patients with ARDS were included in the study; the other patients without ARDS were used as controls. The mortality rate for the scrub typhus patients with ARDS was 25%. The eight patients seldom had underlying diseases. Initial presentations of dyspnea and cough, white blood cell count, hematocrit, total bilirubin, and delayed used of appropriate antibiotics use were significant predictors of ARDS. Multivariate analysis showed that albumin, prothrombin time, and delayed use of appropriate antibiotics were independent predictors of ARDS. Identification of these relative risk factors may help clinicians evaluate clinical cases of scrub typhus with ARDS.
ATOVAQUONE-PROGUANIL: REPORT FROM THE CDC EXPERT MEETING ON MALARIA CHEMOPROPHYLAXIS (II)
Authors: BOGGILD ANDREA K. , PARISE MONICA E. , LEWIS LINDA S. , KAIN KEVIN C.
Published: September 2018

The fixed dose combination of atovaquone and proguanil hydrochloride, marketed under the trade name Malarone™, is the most recently approved agent in North America for the prevention and treatment of chloroquine- and multi-drug resistant Plasmodium falciparum malaria. In both adult and pediatric populations, atovaquone-proguanil demonstrates consistently high protective efficacy against P. falciparum, and in treatment trials, cure rates exceed 93%. Only a handful of genetically confirmed treatment failures have been reported to date. Atovaquone-proguanil has an excellent safety profile during both prophylaxis and treatment courses, with severe adverse events rarely reported. This topical review will examine the evidence behind the current indications for use of atovaquone-proguanil, and will summarize the current body of literature surrounding safety and tolerability.
ENDEMIC EASTERN EQUINE ENCEPHALITIS IN THE AMAZON REGION OF PERU
Authors: AGUILAR PATRICIA V. , ROBICH REBECCA M. , TURELL MICHAEL J. , O’GUINN MONICA L. , KLEIN TERRY A. , HUAMAN ALFREDO , GUEVARA CAROLINA , RIOS ZONIA , TESH ROBERT B. , WATTS DOUGLAS M. , OLSON JAMES , WEAVER SCOTT C.
Published: September 2018

Eastern equine encephalitis virus (EEEV) causes severe neurologic disease in North America, but only two fatal human cases have been documented in South America. To test the hypothesis that alphavirus heterologous antibodies cross-protect, animals were vaccinated against other alphaviruses and challenged up to 3 months later with EEEV. Short-lived cross-protection was detected, even in the absence of cross-neutralizing antibodies. To assess exposure to EEEV in Peru, sera from acutely ill and healthy persons were tested for EEEV and other alphavirus antibodies, as well as for virus isolation. No EEEV was isolated from patients living in an EEEV-enzootic area, and only 2% of individuals with febrile illness had EEEV-reactive IgM. Only 3% of healthy persons from the enzootic region had EEEV-neutralizing antibodies. Our results suggest that humans are exposed but do not develop apparent infection with EEEV because of poor infectivity and/or avirulence of South American strains.
INITIATION AND SPREAD OF TRAVELING WAVES OF PLAGUE, YERSINIA PESTIS, IN THE WESTERN UNITED STATES
Authors: ADJEMIAN JENNIFER ZIPSER , FOLEY PATRICK , GAGE KENNETH L. , FOLEY JANET E.
Published: September 2018

Yersinia pestis invaded the continental United States in 1900 and subsequently became established in wild rodent populations in several western states, traversing 2,250 km in approximately 40 years. However, the specific path of the eastward expansion of plague into the United States is poorly understood. We directly calculated velocities of disease spread and performed trend-surface analyses on spatio-temporally unique plague cases to clarify the route and speed of the initial spread of plague eastward. Velocities of disease spread were then analyzed using multiple linear regression models to identify environmental features that significantly impacted the rate of spread. Between one and three introductions of plague along the Pacific coast were observed, after which plague traveled from 45 to 87 km/year. In all regression models, the coast ranges of California were associated with slower spread, and the Southern Rockies were associated with a significant increase in the rate of disease spread. Additional climatic and environmental factors affecting the velocity of plague’s spread varied among the models. Maps were developed to graphically represent the traveling waves of plague over the United States landscape. These analyses identify important large-scale trends regarding the eastward invasion of plague into the continental United States that can be used to better understand the historical spread of plague, as well as how to manage threats from new or re-emerging diseases that might operate under similar spatio-temporal dynamics.
A COMPARISON OF METHODS FOR DETECTING THE EGGS OF ASCARIS, TRICHURIS, AND HOOKWORM IN INFANT STOOL, AND THE EPIDEMIOLOGY OF INFECTION IN ZANZIBARI INFANTS
Authors: GOODMAN DAVID , HAJI HAMAD J. , BICKLE QUENTIN D. , STOLTZFUS REBECCA J. , TIELSCH JAMES M. , RAMSAN MAHDI , SAVIOLI LORENZO , ALBONICO MARCO
Published: September 2018

This study compared five methods for detecting the eggs of the human parasitic geohelminths Ascaris, Trichuris, and hookworm in infant stool, and describes the epidemiology of infection in infants from a parasite-endemic area. A total of 424 infants 5–11 months old were enrolled from three villages on Pemba Island, Zanzibar. Methods used included the Kato-Katz technique, formol ethyl acetate sedimentation, modified formol ethyl acetate sedimentation, modified Wisconsin floatation, and simple gravity sedimentation. Of methods used alone, Wisconsin floatation and simple gravity sedimentation each provided the highest sensitivity for detecting eggs of these three geohelminths (89.6%). Of methods used in combination, the Kato-Katz technique/simple gravity sedimentation and Wisconsin floatation/simple gravity sedimentation each provided the highest sensitivity (99.0%). Prevalence of geohelminth infection was 26.5%. Between five and nine months of age the mean prevalence was 9.4%, while at 10 and 11 months of age the mean prevalence was 43.4%. Village prevalence varied from 3.6% to 43.8%. Infant geohelminth infection can occur at a high prevalence, and what method is best depends on research specifics.
EFFICACY OF THE ANTIPOXVIRUS COMPOUND ST-246 FOR TREATMENT OF SEVERE ORTHOPOXVIRUS INFECTION
Authors: SBRANA ELENA , JORDAN ROBERT , HRUBY DENNIS E. , MATEO ROSA I. , XIAO SHU-YUAN , SIIRIN MARINA , NEWMAN PATRICK C. , DA ROSA AMELIA P. A. TRAVASSOS , TESH ROBERT B.
Published: September 2018

Efficacy of the new antipoxvirus compound ST-246 was evaluated as treatment of monkeypox (MPX) virus infection in a ground squirrel model of the disease. Ground squirrels were given a lethal dose of MPX virus and were then treated orally at various times post-inoculation (pi) with 100 mg/kg/day of ST-246. Morbidity and mortality, clinical laboratory results, viral load, and pathology of placebo and treatment groups were compared. All animals that started treatment with ST-246 on days 0, 1, 2, and 3 pi survived lethal challenge with MPX virus; 67% of animals treated on day 4 pi also survived. In contrast, 100% of the placebo group died. Most of the ST-246-treated animals showed no evidence of clinical disease or alteration of baseline clinical laboratory values and had minimal histopathologic changes. These results suggest that ST-246 is a promising candidate for early treatment of severe orthopoxvirus infection.
Neurocysticercosis in the HIV Era: A Case Report and Review of the Literature
Authors: Serpa Jose A. , Moran Ana , Goodman Jerry C. , Giordano Thomas P. , White A. Clinton
Published: September 2018

The prevalence of HIV is increasing in countries where neurocysticercosis is endemic. Co-infection rates are expected to rise; however, no systematic reviews of the subject are available. We performed a literature review of neurocysticercosis (NCC) occurring in HIV-infected patients and described the clinical and immunophenotypic characteristics of a NCC case presenting with probable immune reconstitution inflammatory syndrome. We identified 27 cases of NCC-HIV co-infection. The most frequent presentation (61%) was with multiple parenchymal lesions. Seven patients (30%) had other concomitant neurologic infections (e.g., tuberculosis, toxoplasmosis). Thirteen patients received cysticidal therapy, and 85% responded to therapy. Only three patients died (12%). Immunohistochemistry of brain tissue in our case revealed abundant CD3+, CD8+, and CD68+ cells. NCC should be included in the differential diagnosis of neurologic infections in HIV patients in endemic populations. Consideration of the patient’s immune status should alert the clinician to potential atypical presentations.
Residence-Linked Human Plague in New Mexico: A Habitat-Suitability Model
Authors: Eisen Rebecca J. , Reynolds Pamela J. , Ettestad Paul , Brown Ted , Enscore Russell E. , Biggerstaff Brad J. , Cheek James , Bueno Rudy , Targhetta Joseph , Montenieri John A. , Gage Kenneth L.
Published: September 2018

Yersinia pestis, the causative agent of plague, has been detected in fleas and mammals throughout the western United States. This highly virulent infection is rare in humans, surveillance of the disease is expensive, and it often was assumed that risk of exposure to Y. pestis is high in most of the western United States. For these reasons, some local health departments in these plague-affected regions have hesitated to undertake surveillance and other prevention activities. To aid in targeting limited public health resources, we created a fine-resolution human plague risk map for New Mexico, the state reporting more than half the human cases in the United States. Our GIS-based model included three landscape features—a nonlinear relationship with elevation, distance to water, and distance to the ecotone between Rocky Mountain/Great Basin open and closed coniferous woodlands—and yielded an overall accuracy of ≈ 80%. The model classified 17.25% of the state as posing significant risk of exposure to humans on privately or tribally owned land, which suggests that resource requirements for regular surveillance and control of plague could be effectively focused on < 20% of the state.
Prevalence and Predictors of Maternal Peripheral Malaria Parasitemia in Central Mozambique
Authors: Brentlinger Paula E. , Montoya Pablo , Rojas Ana Judith Blanco , Correia Maria Ana Chadreque , Dgedge Martinho , Saúte Francisco , Gimbel-Sherr Kenneth , Mercer Mary Anne , Gloyd Stephen
Published: September 2018

Malaria infection during pregnancy (MiP) is heterogeneously distributed even in malaria-endemic countries. Program planners require data to facilitate identification of highest-priority populations for MiP control. Using data from two cross-sectional studies of 5,528 pregnant women in 8 neighboring sites in Mozambique, we described factors associated with maternal peripheral parasitemia by using logistic regression. Principal multivariate predictors of maternal peripheral parasitemia were gravidity (odds ratio [OR] = 2.29, 95% confidence interval [CI] = 1.60–3.26 for primigravidae and OR = 1.61, 95% CI = 1.29–2.01 for secundigravidae compared with gravidity ≥ 3); age (OR = 0.96 per year, 95% CI = 0.94–0.99); study site (OR = 1.45, 95% CI = 1.34–1.56 to 5.32, 95% CI = 4.92–5.75) for comparison with the reference site; and no maternal education (OR = 1.38, 95% CI = 1.15–1.66) compared with any education. Other predictors (in subgroups) were bed net use (OR = 0.49, 95% CI = 0.48–0.50); preventive sulfadoxine-pyrimethamine doses (OR = 0.25, 95% CI = 0.24–0.25); and infection with human immunodeficiency virus (HIV) (OR = 1.49, 95% CI = 1.11–2.00). Programmatic priorities should respond to heterogeneous distribution of multiple risk factors, including prevalance of malaria and infection with HIV, and maternal socioeconomic status.
Therapeutic Efficacy and Effects of Artemether-Lumefantrine and Amodiaquine-Sulfalene-Pyrimethamine on Gametocyte Carriage in Children with Uncomplicated Plasmodium falciparum Malaria in Southwestern Nigeria
Authors: Sowunmi Akintunde , Gbotosho Grace O. , Happi Christian T. , Adedeji Ahmed A. , Fehintola Fatai A. , Folarin Onikepe A. , Tambo Ernest , Fateye Babasola A.
Published: September 2018

The treatment efficacy and effects of artemether-lumefantrine (AL) and amodiaquine-sulfalene-pyrimethamine (ASP) on gametocyte carriage were evaluated in 181 children ≤ 10 years of age with uncomplicated Plasmodium falciparum malaria randomized to receive either drug combination. All children recovered clinically. Fever clearance times were similar. The rate of P. falciparum reappearance (recrudescence or re-infection) between two and six weeks after the start of therapy was significantly higher in AL-treated children (P = 0.01). Parasite clearance was significantly faster in children treated with AL (mean ± SD = 1.7 ± 0.6 days, 95% confidence interval = 1.58 – 1.83, P = 0.0001) but the polymerase chain reaction–corrected cure rate (90 of 91 versus 84 of 90) and the rate of resolution of malaria-related anemia two weeks after treatment began (45 of 50 versus 33 of 46) were higher in children treated with ASP. Gametocyte carriage rates were similar. Both regimens were well tolerated. Artemether-lumefantrine clears parasitemia more rapidly than ASP but both combinations are effective in treatment of uncomplicated P. falciparum malaria in Nigerian children.
Dichlorodiphenyltrichloroethane (DDT) for Indoor Residual Spraying in Africa: How Can It Be Used for Malaria Control?
Authors: Sadasivaiah Shobha , Tozan Yeşim , Breman Joel G
Published: September 2018

In 2006, the World Health Organization issued a position statement promoting the use of indoor residual spraying (IRS) with dichlorodiphenyltrichloroethane (DDT) for malaria vector control in epidemic and endemic areas. Other international organizations concurred because of the great burden of malaria and the relative ineffectiveness of current treatment and control strategies. Although the Stockholm Convention of 2001 targeted DDT as 1 of 12 persistent organic pollutants for phase-out and eventual elimination, it allowed a provision for its continued indoor use for disease vector control. Although DDT is a low-cost antimalarial tool, the possible adverse human health and environmental effects of exposure through IRS must be carefully weighed against the benefits to malaria control. This article discusses the controversy surrounding the use of DDT for IRS; its effective implementation in Africa; recommendations for deployment today, and training, monitoring, and research needs for effective and sustainable implementation. We consider the costs and cost effectiveness of IRS with DDT, alternative insecticides to DDT, and the importance of integrated vector control if toxicity, resistance, and other issues restrict its use.
Prevalence of Anti-Hantavirus Antibodies in Patients with Hypertransaminemia in Madrid (Spain)
Authors: Lledó Lourdes , Gegúndez María Isabel , Ledesma Juan , Domingo Cristina , González Rosario , Romanyk Juan , Saz José Vicente , Beltrán María
Published: September 2018

The hantaviruses are involved in a number of clinical syndromes of different severity and prognosis. Hantaviruses are widely distributed around the world, but the spectrum of illnesses they cause outside recognized endemic areas is unclear. A retrospective analysis was performed to detect anti-hantavirus antibodies in the serum of patients with hypertransaminemia of unknown etiology and in that of healthy members of the general population of Madrid (Spain). Antibodies were detected by indirect immunofluorescence and enzyme immunoassay; positive results were confirmed by Western blotting. Of the 182 patients with hypertransaminemia, 11 (6%) were positive for anti-hantavirus IgG antibodies; Western blotting using recombinant Puumala virus N antigen showed one of these patients to have hantavirus-specific IgM antibodies. Among the 146 healthy subjects from the general population, 3 (2%) were positive for anti-hantavirus IgG antibodies. These results show that anti-hantavirus antibodies are more commonly detected in patients with hypertransaminemia than in healthy people.