bluuebunny/crossref_metadata_2025 huggingface dataset:
CARD AGGLUTINATION TEST FOR TRYPANOSOMIASIS (CATT) END-DILUTION TITER AND CEREBROSPINAL FLUID CELL COUNT AS PREDICTORS OF HUMAN AFRICAN TRYPANOSOMIASIS (TRYPANOSOMA BRUCEI GAMBIENSE) AMONG SEROLOGICALLY SUSPECTED INDIVIDUALS IN SOUTHERN SUDAN
Authors: CHAPPUIS FRANÇOIS , STIVANELLO ELISA , ADAMS KAREN , KIDANE SOLON , PITTET ANNE , BOVIER PATRICK A.
Published: September 2018

The diagnosis of human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense relies on an initial serologic screening with the card agglutination test for trypanosomiasis (CATT) for T. b. gambiense, followed by parasitologic confirmation in most endemic areas. Unfortunately, field parasitologic methods lack sensitivity and the management of serologically suspected individuals (i.e., individuals with a positive CATT result but negative parasitology) remains controversial. In Kajo-Keji County in southern Sudan, we prospectively collected sociodemographic and laboratory data of a cohort of 2,274 serologically suspected individuals. Thirty-three percent (n = 749) attended at least one follow-up visit and HAT was confirmed in 64 (9%) cases. Individuals with lower initial CATT-plasma (CATT-P) end-dilution titers had lowest risks (10.4 and 13.8/100 person-years for 1:4 and 1:8 titers, respectively) that significantly increased for higher dilutions: relative risks = 5.1 (95% confidence interval [CI] = 2.6–9.5) and 4.6 (95% CI = 2.8–9.8) for 1:16 and 1:32 titers, respectively. The cumulative yearly risk was also high (76%) in individuals found with 11–20 cells in the cerebrospinal fluid, but this involved only eight patients. Adjustment for potential confounders did not affect the results. In conclusion, treatment with pentamidine should be considered for all serologically suspected individuals with a CATT-P end-dilution titer ≥ 1:16 in areas of a moderate to high prevalence of HAT.
GENE FLOW AMONG ANOPHELES ALBIMANUS POPULATIONS IN CENTRAL AMERICA, SOUTH AMERICA, AND THE CARIBBEAN ASSESSED BY MICROSATELLITES AND MITOCHONDRIAL DNA
Authors: MOLINA-CRUZ ALVARO , DE MÉRIDA ANA MARÍA P. , MILLS KATHERINE , RODRÍGUEZ FERNANDO , SCHOUA CAROLINA , YURRITA MARÍA MARTA , MOLINA EDUVIGES , PALMIERI MARGARITA , BLACK WILLIAM C.
Published: September 2018

Gene flow was examined among Anopheles albimanus populations from Cuba, Mexico, Guatemala, El Salvador, Nicaragua, Costa Rica, Panama, Colombia, and Venezuela by examining variation at four microsatellite (MS) loci and a mitochondrial DNA (mtDNA) marker. There was little variation among Central American populations and weak isolation by distance was only observed with the MS loci. There was moderate to large variation between Central and South American populations, suggesting a barrier to gene flow between Central and South America. However, Panamanian and Pacific Costa Rican populations differed with respect to western Central America, suggesting that there may be another barrier within Central America. There was small to moderate variation among Caribbean and continental populations. Phylogenetic and diversity analyses of mtDNA indicate that more ancestral and diverse haplotypes were present in the Caribbean population, suggesting that current continental An. albimanus populations may have originated from the Caribbean.
DETECTION OF RICKETTSIA AFRICAE IN PATIENTS AND TICKS ALONG THE COASTAL REGION OF CAMEROON
Authors: NDIP LUCY M. , FOKAM ERIC B. , BOUYER DONALD H. , NDIP ROLAND N. , TITANJI VINCENT P. K. , WALKER DAVID H. , MCBRIDE JERE W.
Published: September 2018

Rickettsia africae was identified in seven (6%) of 118 patients with acute fevers of unknown etiology proven not to be malaria or typhoid fever from clinics along the coastal region of Cameroon by polymerase chain reaction (PCR) amplification and sequencing of the citrate synthase (gltA) and outer membrane protein A (ompA) genes of Rickettsia. The majority (71%) of the patients were female. Clinical manifestations included fever (100%), headache (71%), myalgia (71%), arthralgia (43%), pulmonary involvement (29%), and diffuse rash (14%). Moreover, R. africae was detected by PCR amplification and sequence analysis of the gltA and ompA genes in 62 (75%) of 83 adult Amblyomma variegatum ticks collected from cattle in the same region. These results confirm the presence of a previously unrecognized infectious disease in the indigenous Cameroonian population, as well as extend the established range of R. africae.
DETECTION OF CYCLOSPORA CAYETANENSIS IN ANIMAL FECAL ISOLATES FROM NEPAL USING AN FTA FILTER-BASE POLYMERASE CHAIN REACTION METHOD
Authors: CHU DAN-MY T. , SHERCHAND JEEVAN B. , CROSS JOHN H. , ORLANDI PALMER A.
Published: September 2018

Cyclospora cayetanensis is an emerging protozoan parasite capable of causing a protracted diarrheal illness in both immunocompromised and immunocompetent individuals. Ingestion of fresh produce and water sources contaminated with mature sporulated oocysts results in acquisition of cyclosporiasis. Currently, no animal model exists for the study of this pathogenic parasite and the only confirmed reservoir host for C. cayetanensis in nature is humans. Previously, Cyclospora-like oocysts had been detected by microscopy in several animals including non-human primates. However, their phylogenetic relationship to C. cayetanensis remained uncertain due to the limited availability of molecular techniques to differentiate and speciate these isolates. In the present study, we examined a series of fecal isolates obtained from dogs, chickens, and monkeys collected between May and September 2002 from several geographic regions of Nepal. All samples were examined by microscopy and a polymerase chain reaction (PCR) for the presence of C. cayetanensis. Both microscopic and conventional PCR/restriction fragment length polymorphism (RFLP) analysis demonstrated the presence of Cyclospora sp. in the fecal samples of two dogs, one chicken, and one monkey. Application of a species-specific multiplex PCR assay confirmed the presence of both Eimeria sp. and C. cayetanensis in the positive chicken sample and only C. cayetanensis in the dog and monkey samples. However, in the absence of tissue analysis, the assignment of these animals as a natural reservoir host for C. cayetanensis remains to be determined.
SEROEPIDEMIOLOGIC STUDY OF LEISHMANIA INFANTUM INFECTION IN CASTILLA-LEON, SPAIN
Authors: GARROTE JOSÉ I. , GUTIÉRREZ M. PURIFICACION , IZQUIERDO RAÚL LÓPEZ , DUEÑAS M. ANA I. , ZARZOSA PILAR , CAÑAVATE CARMEN , BALI M. EL , ALMARAZ ANA , BRATOS MIGUEL A. , BERBEL CLARA , RODRÍGUEZ-TORRES ANTONIO , DOMINGO ANTONIO ORDUÑA
Published: September 2018

Leishmaniasis has increased in importance in recent years because infection with human immunodeficiency virus (HIV) has emerged as a risk factor for this disease. However, the actual prevalence of leishmaniasis in the general population of Spain is unknown. We present a study of the seroprevalence of infection with Leishmania infantum in the general population of Castilla-Leon, Spain. A random sample of individuals presenting to health care clinics (4,825 sera) and of HIV-infected patients in the autonomous community of Castilla-Leon was collected in 1996. The sero-prevalence of antibodies to L. infantum was determined by an indirect enzyme immunoassay and found to be 4.9% in the general population. There was a significant increase in seroprevalence with age (P = 0.001), from 3.96% in those 14–20 years old to 7.2% in those > 70 years old. There were no significant differences between women and men (5.0% versus 4.9%; P = 0.9534). Seroprevalence was significantly higher in people from rural areas than in those from cities (6.0% versus 3.4%; P = 0.001). Patients infected with HIV had a seroprevalence for L. infantum of 64.0%. No differences were observed between women and men, and prevalence did not increase with age.
A RANDOMIZED COMPARISON OF TWO ANEMIA TREATMENT REGIMENS IN TANZANIAN CHILDREN
Authors: SCHELLENBERG DAVID , KAHIGWA ELIZEUS , SANZ SERGI , APONTE JOHN J. , MSHINDA HASSAN , ALONSO PEDRO , MENENDEZ CLARA
Published: September 2018

We used a prospective, open-label randomized trial to evaluate two treatment regimens in Tanzanian children two months to four years of age presenting to a hospital with a packed cell volume (PCV) < 25%. Treatment was either standard (14 days of ferrous sulfate and an antimalarial) or extended (three months of ferrous sulfate and three antimalarial treatments). The prevalence of anemia was measured two weeks after completion of treatment and six months after recruitment. Two weeks after completing treatment, the prevalence of PCV < 33% was 58% in the standard treatment arm and 44% in the extended treatment group (P = 0.04), and the mean PCV was significantly higher in the extended treatment arm (32.1%, SD = 4.5% versus 30.8%, SD = 4.9%; P = 0.031). However, there was no difference in the prevalence of PCV < 25% in the first survey, and the benefits of extended therapy were only apparent six months after recruitment in children compliant with the extended treatment (odds ratio of PCV < 25% = 0.16, P = 0.06). Compliance was satisfactory in only 39% (82 of 209) of the children in the first week of treatment. Extending the duration of therapy and improving compliance may have health benefits for anemic children in malaria-endemic settings.
THE EFFECTS OF SHORT-TERM IRON SUPPLEMENTATION ON IRON STATUS IN INFANTS IN MALARIA-ENDEMIC AREAS
Authors: MENENDEZ CLARA , SCHELLENBERG DAVID , QUINTO LLORENÇ , KAHIGWA ELIZEUS , ALVAREZ LUISA , APONTE JOHN J. , ALONSO PEDRO L.
Published: September 2018

Iron deficiency and Plasmodium falciparum malaria are the two main causes of anemia in young children in region endemic for this disease. The impact on iron status of prophylactic oral iron supplementation (2 mg/kg/day from two to six months of age) and the duration of this effect were assessed in a group of 832 Tanzanian infants exposed to P. falciparum malaria. Iron parameters and red blood cell indices were assessed at 2, 5, 8, and 12 months of age. Infants who received iron supplements had a significantly lower prevalence of iron deficiency (P < 0.01 at 5 months and P < 0.001 at 8 and 12 months). Red blood cell indices (mean corpuscular volume, mean cell hemoglobin, and mean cell hemoglobin concentration) were increased in children receiving iron supplementation and they did not differ between those protected and unprotected against malaria. The prevalence of ferropenia was similar in children protected against malaria and in those who were not protected and did not receive iron supplements (34.7% versus 37.3% at 12 months of age). We concluded that iron supplementation between the ages of 2–6 months improves iron status at least up to 12 months of age. Malaria infection does not contribute to iron deficiency.
EPIDEMIOLOGY OF MALARIA TRANSMISSION AND DEVELOPMENT OF NATURAL IMMUNITY IN A MALARIA-ENDEMIC VILLAGE, SAN DULAKUDAR, IN ORISSA STATE, INDIA
Authors: SHARMA SURYA K. , CHATTOPADHYAY RANA , CHAKRABARTI KAUSIK , PATI SUDHANSHU S. , SRIVASTAVA VINOD K. , TYAGI PRAJESH K. , MAHANTY SANJIB , MISRA SAROJ K. , ADAK TRIDIBES , DAS BHABANI S. , CHITNIS CHETAN E.
Published: September 2018

We describe the epidemiology of malaria in San Dulakudar, a village in Sundargarh District in the state of Orissa in eastern India. Malaria transmission is perennial with Plasmodium falciparum, accounting for greater than 80% of malaria cases. Transmission intensity varies with season with high transmission after the monsoon rains in autumn and winter, low transmission in summer, and intermediate transmission in spring. The anthropophagic mosquito Anopheles fluviatilis was identified as the main vector for malaria transmission. Based on observations of spleen rates and supported by data on malaria parasite prevalence and malaria incidence, San Dulakudar can be classified as a hyperendemic area for P. falciparum malaria. Parasite prevalence and malaria incidence rates decrease with age, suggesting that residents of San Dulakudar develop immunity to malaria. The study demonstrates the presence of regions in the Indian subcontinent such as Sundargarh District where P. falciparum is the primary cause of malaria and where malaria transmission rates are comparable to those found in many parts of Africa.
THE IMPACT OF AGE, TEMPERATURE, AND PARASITE DENSITY ON TREATMENT OUTCOMES FROM ANTIMALARIAL CLINICAL TRIALS IN KAMPALA, UGANDA
Authors: DORSEY GRANT , GASASIRA ANNE F. , MACHEKANO RHODERICK , KAMYA MOSES R. , STAEDKE SARAH G. , HUBBARD ALAN
Published: September 2018

Antimalarial drug treatment policy in sub-Saharan Africa is generally guided by the results of clinical drug efficacy studies in patients with uncomplicated Plasmodium falciparum malaria. The selection criteria used to enroll these patients often vary and may have a significant impact on treatment outcomes. In Kampala, Uganda, we investigated the impact of age, baseline temperature, and pre-treatment parasite density on estimates of treatment efficacy using a statistical modeling approach in 2,138 patients enrolled in six clinical trials involving seven different treatment regimens. Decreasing age, increasing temperature, and increasing parasite density were all independent predictors of an increased risk of treatment failure across all treatment groups. Compared with an unrestrictive approach to subject selection, enrolling only patients fulfilling selection criteria recommended by the World Health Organization (age < 5 years old, documented fever, and parasite density < 200,000/μL) increased the risk of treatment failure by 25–60% for the different treatment regimens. Caution should be taken when comparing results from drug efficacy studies with different subject selection criteria.
ELEVATED PLASMA LEVELS OF INTERFERON (IFN)-γ, IFN-γ INDUCING CYTOKINES, AND IFN-γ INDUCIBLE CXC CHEMOKINES IN VISCERAL LEISHMANIASIS
Authors: HAILU ASRAT , VAN DER POLL TOM , BERHE NEGA , KAGER PIET A.
Published: September 2018

Interferon (IFN)- γ plays an important role during immune responses against leishmaniasis. Production of IFN-γ is regulated by interleukin (IL)-12, IL-18, and IL-15. Interferon-γ-inducible protein (IP)-10 and monokine induced by IFN-γ (Mig) are CXC chemokines, the production of which, at least in part, is IFN-γ dependent. A follow-up study of individuals infected with Leishmania donovani was undertaken in an area of Ethiopia endemic for visceral leishmaniasis (VL). Plasma levels of IFN-γ, IL-12p40, IL-18, IL-15, IP-10, and Mig were markedly elevated in symptomatic VL patients (n = 70) compared with individuals with asymptomatic Leishmania infections (n = 39), malaria patients (n = 13), and healthy controls from the endemic area (n = 12). A significant decrease of IFN-γ and all mediators was observed after treatment of VL patients (n = 33). These data show that increased plasma levels of IFN-γ, as well as the mediators involved in the production and the activity of this cytokine, are characteristic of active VL in humans, and may play an important immunopathogenic role. The data also suggest that in patients with VL, the production of type 1 cytokines is not depressed, but there appears to be an unresponsiveness to the stimuli of type 1 cytokines. The underlying causes of immunologic unresponsiveness remain a subject of further investigation.
GEOGRAPHIC DISTRIBUTION OF LYMPHATIC FILARIASIS IN HAITI
Authors: DE ROCHARS MADSEN V. E. BEAU , MILORD M. DENISE , JEAN YVAN ST. , DÉSORMEAUX ANNE M. , DORVIL JEAN J. , LAFONTANT JACK G. , ADDISS DAVID G. , STREIT THOMAS G.
Published: September 2018

Although lymphatic filariasis is known to have been endemic in Haiti since at least the mid 1700s, a national filariasis survey has never been conducted. As a first step in the national program to eliminate filariasis, we collected blood in January-April 2001 from 50–250 school children (6–11 years old) in all 133 communes of the country using an adaptation of the lot quality assurance sampling method. Of 22,365 children tested, 901 (4.0%) were positive for circulating Wuchereria bancrofti antigen. When weighted by commune population, the overall national antigen prevalence in this age group was 7.3%. Infected children were found in 117 (87.9%) communes, the most heavily affected areas being concentrated in the northern part of the country. In only 16 (12.1%) communes were all 250 children antigen negative. Thus, W. bancrofti infection in Haiti is much more widespread than previously realized; virtually the entire population of the country may be considered at risk of infection.
THE EFFECTS OF LONG-TERM COMMUNITY LEVEL TREATMENT WITH IVERMECTIN (MECTIZAN®) ON ADULT ONCHOCERCA VOLVULUS IN LATIN AMERICA
Authors: CUPP EDDIE W. , DUKE BRIAN O. , MACKENZIE CHARLES D. , GUZMÁN JOSE RUMBEA , VIEIRA JUAN CARLOS , MENDEZ-GALVAN JORGE , CASTRO JULIO , RICHARDS FRANK , SAUERBREY MAURICIO , DOMINGUEZ ALFREDO , EVERSOLE ROB R. , CUPP MARY S.
Published: September 2018

The objective of this study was to examine nodules from Mexico, Guatemala, and Ecuador collected over a one-year period (2001) to determine the effects of semi-annual ivermectin treatments on Onchocerca volvulus macrofilarial populations. Nodules were sectioned, stained with hematoxylin and eosin, and histologic findings were compared between countries and with historical data prior to the introduction of ivermectin into the region. Nodules from Ecuador had 10 times more dead or moribund worms than the historical control (66.6% versus 6.5%); nodules from patients from Mexico and Guatemala did not differ from the control. More than 80% of the female worms in each country were uninseminated and producing unfertilized oocytes. Nodules containing males differed in each country from the historical control (P < 0.0001), with presence of males ranging from 19.7% in Mexico to 13.6% in Ecuador versus 73% in the control. Nodules with females producing active microfilariae ranged from 7.8% (Mexico) to 2.7% (Ecuador) versus 60% in the historical control (P < 0.0001). Nodules from Ecuador and Mexico were significantly smaller in size than those from Guatemala or historical controls (P < 0.0005). These results depict a deteriorating condition of adult O. volvulus populations in Mexico, Guatemala and Ecuador, indicating that semi-annual ivermectin treatment of ≥6 years has had a profound effect on survival and reproduction of this species.
PREVALENCE OF HETEROPHYES NOCENS AND PYGYDIOPSIS SUMMA INFECTIONS AMONG RESIDENTS OF THE WESTERN AND SOUTHERN COASTAL ISLANDS OF THE REPUBLIC OF KOREA
Authors: CHAI JONG-YIL , PARK JAE-HWAN , HAN EUN-TAEK , SHIN EUN-HEE , KIM JAE-LIP , GUK SANG-MEE , HONG KWANG-SUN , LEE SOON-HYUNG , RIM HAN-JONG
Published: September 2018

To determine the distribution and prevalence of heterophyid fluke infections on coastal islands of the Republic of Korea, fecal specimens were collected from 4,179 people residing on 45 islands in the West (Yellow) and South Seas and examined using the formalin-ether and Kato-Katz techniques. Eggs of Heterophyes nocens were found in 459 (11.0%) residents of 42 islands, with an average number of eggs per gram (epg) of feces of 79.6. Eggs of Pygidiopsis summa were found in 49 (1.2%) on 12 islands, with an average epg of 253.0. The egg-positive rate for H. nocens was the highest on Chungdo (32.6%), followed by Imchado (27.3%); P. summa was most prevalent on Imchado (15.2%). The majority (78.9% [362 of 549] of those infected with H. nocens and 81.6% [40 of 49] of those infected with P. summa) of those infected were adults more than 40 years old. Adult flukes of these species were recovered from residents of Imchado by treatment with praziquantel and purgation. Our results indicate that H. nocens and P. summa are indigenous to the southern and western coastal islands of the Republic of Korea.
TREATMENT OF CUTANEOUS GNATHOSTOMIASIS WITH IVERMECTIN
Authors: KRAIVICHIAN KANYARAT , NUCHPRAYOON SURANG , SITICHALERNCHAI PRASERT , CHAICUMPA WANPEN , YENTAKAM SUTIN
Published: September 2018

In a randomized open study, we compared the efficacy of a single dose of oral ivermectin (200 μg/kg) and oral albendazole (400 mg/day for 21 days) for the treatment of cutaneous gnathostomiasis. Thirty-one patients were randomly assigned to receive ivermectin (n = 17) or albendazole (n = 14). Thirteen of 17 patients who received ivermectin responded, 3 relapsed, and 1 was unresponsive (cure rate = 76%). Thirteen of 14 patients who received albendazole responded very well and did not relapse. Only one patient was unresponsive (cure rate = 92%; P > 0.05). No major side effects were observed in both groups. We concluded that a single dose of ivermectin (200 μg/kg) is less effective than albendazole (400 mg/day for 21 days) for treatment of cutaneous gnathostomiasis, but there was no statistically significant difference (P > 0.05).
SPATIAL-TEMPORAL ANALYSIS OF ROSS RIVER VIRUS DISEASE PATTERNS IN QUEENSLAND, AUSTRALIA
Authors: GATTON MICHELLE L. , KELLY-HOPE LOUISE A. , KAY BRIAN H. , RYAN PETER A.
Published: September 2018

Ross River virus is the most common vector-borne disease in Australia, with the majority of notifications being in Queensland. This study describes a retrospective spatial analysis of Queensland Ross River virus disease notifications spanning a 10-year period. Notifications were mapped to the local government area (LGA) of the residence of the patient. Ross River virus disease outbreaks within each LGA were detected by applying a Poisson model. Estimates of the seasonal incidence rates indicated wide variation between seasons and LGAs. Positive spatial autocorrelation between LGAs experiencing outbreaks indicated that LGAs within the same region often experience outbreaks at the same time. A hierarchical cluster analysis of the outbreak data was used to group LGAs with similar temporal outbreak patterns. This analysis highlights the variability in Ross River virus disease notification rates across Queensland, and provides a robust method for identifying disease outbreaks.
RISK OF GIARDIA INTESTINALIS INFECTION IN CHILDREN FROM AN ARTIFICIALLY RECHARGED GROUNDWATER AREA IN MEXICO CITY
Authors: CIFUENTES ENRIQUE , SUÁREZ LETICIA , ESPINOSA MARTHA , JUÁREZ-FIGUEROA LUIS , MARTÍNEZ-PALOMO ADOLFO
Published: September 2018

The objective of this study was to assess the risk of infection with Giardia intestinalis in children living in an area with artificial groundwater recharge and potable water reuse in Mexico City. Eligible wells and surrounding homesteads were defined by using a geographic information system. Five wells were tested for G. intestinalis cysts per 400 liters of water. A total of 750 eligible households were visited during two cross-sectional surveys. Stool samples were provided by 986 children in the rainy season study and 928 children during the dry season survey for parasitologic tests. Their guardians provided information on water, sanitation, hygiene, and socioeconomic variables. The prevalence rates of G. intestinalis infection were 9.4% in the rainy season and 4.4% in the dry season. Higher rates of infection were observed in older individuals (9.5% and 10.6%) and girls had a lower risk of infection than boys (odds ratio [OR] =0.55, 95% confidence interval [CI] = 0.34, 0.88 in the rainy season and OR = 0.47, 95% CI = 0.25, 0.90 in the dry season). During the wet season survey, a health risk was detected among those storing water in unprotected receptacles (OR = 4.00, 4.69, and 5.34 for those using uncovered jars, cisterns or tanks, and buckets, respectively), and bathing outside the dwelling, i.e., using a tap (OR = 1.93, 95% CI = 1.10, 3.39). A health risk was also detected among children from households with unsafe food hygiene practices (OR =2.41, 95% CI =1.10, 5.30) and those with no hand-washing habits (OR = 2.27, 95% CI = 1.00, 5.20). Groundwater reserves are at risk of fecal pollution, as indicated by the presence of G. intestinalis cysts. However, the endemic pattern of intestinal infection reflects low standards of personal hygiene and unsafe drinking water storage and food-related practices at household level. Prevention activities must address health education and environmental protection policies.
TRIGGER EVENTS: ENVIROCLIMATIC COUPLING OF EBOLA HEMORRHAGIC FEVER OUTBREAKS
Authors: PINZON JORGE E. , WILSON JAMES M. , TUCKER COMPTON J. , ARTHUR RAY , JAHRLING PETER B. , FORMENTY PIERRE
Published: September 2018

We use spatially continuous satellite data as a correlate of precipitation within tropical Africa and show that the majority of documented Ebola hemorrhagic fever outbreaks were closely associated with sharply drier conditions at the end of the rainy season. We propose that these trigger events may enhance transmission of Ebola virus from its cryptic reservoir to humans. These findings suggest specific directions to help understand the sylvatic cycle of the virus and may provide early warning tools to detect possible future outbreaks of this enigmatic disease.
AGE-WISE EXPOSURE RATES TO HEPATITIS E VIRUS IN A SOUTHERN INDIAN PATIENT POPULATION WITHOUT LIVER DISEASE
Authors: DANIEL HUBERT DARIUS J. , WARIER ASWIN , ABRAHAM PRIYA , SRIDHARAN GOPALAN
Published: September 2018

To determine the age-stratified exposure to hepatitis E virus (HEV) in patients attending a tertiary care hospital in southern India, serum samples from 600 individuals were tested using a commercial HEV IgG enzyme-linked immunosorbent assay. Subjects were composed of blood donors, antenatal women, and pre-operative individuals who were negative for hepatitis B surface antigen and antibody to hepatitis C virus with no evidence of liver disease; 200 each were 1–5 and 6–15 years old and 100 each were 16–40 and ≥ 41 years old. One (0.5%) sample was positive in those 1–5 years old, two (1.0%) in those 6–15 years old, eight (8%) in those 16–40 years old, and 13 (13%) in those ≥ 41 years old. The overall seropositivity rate was 4%. However, there was an age-related increase in exposure to HEV that was statistically significant (P < 0.001), with a higher HEV seropositivity in urban individuals.
SHORT REPORT: EVALUATION OF A SIMPLE AND INEXPENSIVE PHOTOMETRIC DEVICE FOR THE MEASUREMENT OF HEMOGLOBIN
Authors: BORRMANN STEFFEN , OYAKHIROME SUNNY , ESSER GILBERT , TRINKLE CORDULA , ISSIFOU SAADOU , GROBUSCH MARTIN P. , KRISHNA SANJEEV , KREMSNER PETER G.
Published: September 2018

We have evaluated the accuracy of a simple and inexpensive photometric device (DHT) for the estimation of the blood concentration of hemoglobin by comparison with an automated, high-resolution, flow cytometry-based hematology analyzer (CellDyn 3000) and a centrifugal quantitative buffy coat hematology system (QBC I). We have analyzed the hemoglobin values of 163 individual blood samples. Bland-Altman analysis showed that the methods agreed only poorly: mean differences were 1.0 g/dL with limits of agreement (LOA) of −1.2 g/dL to 3.2 g/dL for the comparison of DHT and CellDyn measurements, 0.5 g/dL with LOA of -2.0 g/dL to 3.0 g/dL for the comparison of DHT with QBC measurements, and 0.5 g/dL with LOA of −1.1 g/dL to 2.1 g/dL for the comparison of QBC with CellDyn measurements. We conclude that the poor agreement of the DHT with the CellDyn does not permit the use of the DHT for critical hemoglobin measurements, particularly in transfusion services.
THERAPEUTIC EFFICACY OF SULFADOXINE-PYRIMETHAMINE AND PREVALENCE OF RESISTANCE MARKERS IN TANZANIA PRIOR TO REVISION OF MALARIA TREATMENT POLICY: PLASMODIUM FALCIPARUM DIHYDROFOLATE REDUCTASE AND DIHYDROPTEROATE SYNTHASE MUTATIONS IN MONITORING IN VIVO RESISTANCE
Authors: MUGITTU KEFAS , NDEJEMBI MODESTA , MALISA ALLEN , LEMNGE MARTHA , PREMJI ZULFIKAR , MWITA ALEX , NKYA WATOKY , KATARAIHYA JOHANNES , ABDULLA SALIM , BECK HANS-PETER , MSHINDA HASSAN
Published: September 2018

Prior to the 2001 malarial treatment policy change in Tanzania, we conducted trials to assess the efficacy of sulfadoxine-pyrimethamine (SP) and the usefulness of molecular markers in monitoring resistance. A total of 383 uncomplicated Plasmodium falciparum malaria patients (between 6 and 59 months old) were treated with SP and their responses were assessed. Mutations in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes in admission day blood samples were analyzed. Results indicated that 85.6% of the patients showed an adequate clinical response, 9.7% an early treatment failure, and 4.7% a late treatment failure. The quintuple mutant genotype (pfdhfr 51 Ile, 59 Arg, and 108 Asn and pfdhps 437 Gly and 540 Glu) showed an association with treatment outcome (odds ratio = 2.1; 95% confidence interval = 0.94–4.48, P = 0.045). The prevalence of the triple pfdhfr mutant genotype (51 Ile, 59 Arg, and 108 Asn) at a site of high SP resistance (23.6%) was four times higher compared with that observed at sites of moderate SP resistance (6.8–14.4%) (P = 0.000001). The genotype failure index calculated by using this marker was invariable (1.96–2.1) at sites with moderate SP resistance, but varied (3.4) at a site of high SP resistance. In conclusion, our clinical and molecular findings suggest that SP may have a short useful therapeutic life in Tanzania; thus, its adoption as an interim first-line antimalarial drug. The findings also point to the potential of the triple pfdhfr mutant genotype as an early warning tool for increasing SP resistance. These data form the baseline SP efficacy and molecular markers profile in Tanzania prior to the policy change.
SHORT REPORT: TREATMENT FAILURE DUE TO MIXED INFECTION BY DIFFERENT STRAINS OF THE PARASITE LEISHMANIA INFANTUM
Authors: ANTONIOU MARIA , DOULGERAKIS C. , PRATLONG F. , DEDET J. P. , TSELENTIS Y.
Published: September 2018

Therapeutic failure in a human immunodeficiency virus-negative patient with visceral leishmaniasis was due to mixed infection by two different Leishmania infantum zymodemes: L. infantum zymodeme MON-98, which is a rare zymodeme and is reported for the first time in Greece, and zymodeme MON-1, which is common in the Mediterranean region. The two strains were isolated from two samples of bone marrow from the patient obtained before the administration of treatment and 20 days later, since there was no improvement in the clinical signs. The zymodemes MON-98 and MON-1 exhibited different behaviors in vitro and showed different sensitivities to meglumine antimoniate in vitro and in vivo, as shown by clinical findings. Mixed infections with different Leishmania strains may explain the differences in the clinical course of leishmaniasis in many patients and may be the reason for treatment failures.
ADHERENCE TO ANTIMALARIAL COMBINATION THERAPY WITH SULFADOXINE-PYRIMETHAMINE AND ARTESUNATE IN RURAL TANZANIA
Authors: KACHUR S. PATRICK , KHATIB RASHID A. , KAIZER ELLEN , FOX SUSAN S. , ABDULLA SALIM M. , BLOLAND PETER B.
Published: September 2018

Artemisinin-containing antimalarial combination therapies are recommended to confront drug-resistant Plasmodium falciparum malaria. Among the questions surrounding whether these complex multidose treatments will be practical is to what extent patients complete the recommended doses. Combination therapy through coadministration of sulfadoxine-pyrimethamine plus artesunate was introduced as a first-line treatment for uncomplicated malaria in one district in Tanzania. Interventions to optimize correct use were also implemented. We observed 453 patient encounters at one health facility and recorded key practices as health workers dispensed the combination. A total of 253 patients were followed-up at 24 or 48 hours. Complete adherence measured at 48 hours reached 75.0%, based on self-report and tablet counts. This is substantially better than reported elsewhere and compares favorably with intervention studies to optimize adherence to chloroquine. Counseling about what to do if a patient vomits appears to have been an independent risk factor for nonadherence.
MALARIA MORBIDITY AMONG SCHOOL CHILDREN LIVING IN TWO AREAS OF CONTRASTING TRANSMISSION IN WESTERN KENYA
Authors: CLARKE SIÂN E. , BROOKER SIMON , NJAGI JOSEPH KIAMBO , NJAU ELIUD , ESTAMBALE BENSON , MUCHIRI ERIC , MAGNUSSEN PASCAL
Published: September 2018

Research in malaria-endemic areas is usually focused on malaria during early childhood. Less is known about malaria among older school age children. The incidence of clinical attacks of malaria was monitored, using active case detection in primary schools, in two areas of western Kenya that differ in the intensity of transmission. Clinical malaria was more common in schools in the Nandi highlands, with a six-fold higher incidence of malaria attacks during the malaria epidemic in 2002, compared with school children living in a holoendemic area with intense perennial transmission during the same period. The high incidence coupled with the high parasite densities among cases is compatible with a low level of protective immunity in the highlands. The malaria incidence among school children exposed to intense year-round transmission (26 per 100 school children per year) was consistent with reports from other holoendemic areas. Taken together with other published studies, the data suggest that malaria morbidity among school age children increases as transmission intensity decreases. The implications for malaria control are discussed.
INFLUENCE OF CHEMOTHERAPY ON THE PLASMODIUM GAMETOCYTE SEX RATIO OF MICE AND HUMANS
Authors: TALMAN ARTHUR M. , PAUL RICHARD E. L. , SOKHNA CHEIKH S. , DOMARLE OLIVIER , ARIEY FRÉDÉRIC , TRAPE JEAN-FRANÇOIS , ROBERT VINCENT
Published: September 2018

Plasmodium species, the etiologic agents of malaria, are obligatory sexual organisms. Gametocytes, the precursors of gametes, are responsible for parasite transmission from human to mosquito. The sex ratio of gametocytes has been shown to have consequences for the success of this shift from vertebrate host to insect vector. We attempted to document the effect of chemotherapy on the sex ratio of two different Plasmodium species: Plasmodium falciparum in children from endemic area with uncomplicated malaria treated with chloroquine (CQ) or sulfadoxine-pyrimethamine (SP), and P. vinckei petteri in mice treated with CQ or untreated. The studies involved 53 patients without gametocytes at day 0 (13 CQ and 40 SP) followed for 14 days, and 15 mice (10 CQ and 5 controls) followed for five days. During the course of infection, a positive correlation was observed between the time of the length of infection and the proportion of male gametocytes in both Plasmodium species. No effects of treatment (CQ versus SP for P. falciparum or CQ versus controls for P. vinckei petteri) on the gametocyte sex ratio were found for either Plasmodium species. This indicates that parasites do not respond to chemotherapy by altering their sex allocation strategy, even though, in the case of P. falciparum, they apparently increase their overall investment in sexual stages. This suggests that malaria parasite species respond to different environmental cues for their sex differentiation and sex determination.
ALLELIC DIMORPHISM IN THE MEROZOITE SURFACE PROTEIN-3α IN KOREAN ISOLATES OF PLASMODIUM VIVAX
Authors: HAN EUN-TAEK , SONG TAE-EUI , PARK JAE-HWAN , SHIN EUN-HEE , GUK SANG-MEE , KIM TAE-YUN , CHAI JONG-YIL
Published: September 2018

To study the genetic diversity of re-emerging Plasmodium vivax in the Republic of Korea, nucleotide sequence variations at the merozoite surface protein-3α (PvMSP-3α) locus were analyzed using 24 re-emerging isolates and 4 isolates from imported cases. Compared with the well known Belem strain (Brazil), a large number of amino acid substitutions, deletions, and insertions were found at the locus of the isolates examined. The Korean isolates were divided into two allelic types; type I (15 isolates), similar to the Belem strain, and type II (9), similar to the Chess strain (New Guinea). Isolates from imported cases were classified into three types; type III (1 from Malaysia), similar to type B from western Thailand, type IV (1 each from Indonesia and India), and type V (1 from Pakistan), both being new types. Our results have shown that the MSP-3α locus of re-emerging Korean P. vivax is dimorphic with two allelic types coexisting in the endemic area.
PRINCIPAL ROLE OF DIHYDROPTEROATE SYNTHASE MUTATIONS IN MEDIATING RESISTANCE TO SULFADOXINE-PYRIMETHAMINE IN SINGLE-DRUG AND COMBINATION THERAPY OF UNCOMPLICATED MALARIA IN UGANDA
Authors: DORSEY GRANT , DOKOMAJILAR CHRISTIAN , KIGGUNDU MOSES , STAEDKE SARAH G. , KAMYA MOSES R. , ROSENTHAL PHILIP J.
Published: September 2018

Antimalarial resistance to sulfadoxine-pyrimethamine (SP) is mediated by mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes. However, the relative importance of different mutations is incompletely understood and has not been studied with combination therapy. Samples from 812 patients treated for uncomplicated malaria in Kampala, Uganda were tested for the presence of mutations commonly found in Africa. The dhps Glu-540 mutation was the strongest independent predictor of treatment failure. The dhfr Arg-59 mutation was only predictive of treatment failure in the presence of the dhps Glu-540 mutation. Comparing combination regimens with SP monotherapy, the addition of chloroquine to SP did not improve efficacy, the addition of artesunate lowered the risk of treatment failure only for infections with both the dhfr Arg-59 and dhps Glu-540 mutations, and the addition of amodiaquine lowered this risk for all dhfr/dhps mutation patterns. The dhps Glu-540 mutation played a principal role and the dhfr Arg-59 mutation a secondary role in mediating resistance to SP alone and in combination.
LARGE-SCALE, POLYMERASE CHAIN REACTION–BASED SURVEILLANCE OF SCHISTOSOMA HAEMATOBIUM DNA IN SNAILS FROM TRANSMISSION SITES IN COASTAL KENYA: A NEW TOOL FOR STUDYING THE DYNAMICS OF SNAIL INFECTION
Authors: HAMBURGER JOSEPH , HOFFMAN ORIT , KARIUKI H. CURTIS , MUCHIRI ERIC M. , OUMA JOHN H. , KOECH DAVY K. , STURROCK ROBERT F. , KING CHARLES H.
Published: September 2018

Levels of prepatent Schistosoma haematobium infection were monitored in intermediate host snails (Bulinus nasutus) collected from transmission sites in coastal Kenya, using a polymerase chain reaction (PCR) assay amplifying the Dra I repeated sequence of S. haematobium. The timing and number of prepatent and patent infections were determined for each site and, where the time of first appearance was clear, the minimal prepatent period was estimated to be five weeks. High, persistent, prepatency rates (range = 28–54%), indicated a significant degree of repeated area contamination with parasite ova. In contrast, rates of cercarial shedding proved locally variable, and were either low (range = 0.14–3.4%) or altogether absent, indicating that only a small proportion of infected snails reach the stage of cercarial shedding. Given the apparently strong focal effects of environmental conditions, implications of these new data are discussed regarding the estimation of local force of transmission and the design of control activities.
EFFICACY OF PRAZIQUANTEL AGAINST SCHISTOSOMA HAEMATOBIUM INFECTION IN CHILDREN
Authors: TCHUENTÉ LOUIS-ALBERT TCHUEM , SHAW DARREN J. , POLLA LAURENT , CIOLI DONATO , VERCRUYSSE JOZEF
Published: September 2018

A study was performed to determine the efficacy of praziquantel (PZQ) against Schistosoma haematobium. Children (n = 592) infected with S. haematobium received either a single treatment with PZQ (40 mg/kg) or two or three treatments with PZQ at three-week intervals after the initial treatment and efficacy was monitored for nine weeks. Cure rates at three-weeks post-treatment were low (< 50%), suggesting either that worms are killed very slowly or, more likely, that eggs continue to be released from tissues after worm death. Interestingly, a single dose of PZQ showed high efficacy (cure rate > 83% and egg reduction rate > 98%) when assessed from six weeks post-treatment onward. There were no significant differences in cure rates or intensity of infection between the three cohorts at any point in the study, despite the different treatment regimens. Since children were in contact with transmission sites during the study period, the results suggest good efficacy of PZQ against all stages of S. haematobium, including the immature worms.
TREATMENT OF VISCERAL LEISHMANIASIS IN 2004
Authors: MURRAY HENRY W.
Published: September 2018

In 2004, visceral leishmaniasis (kala-azar) maintains its status as a neglected, if not “most neglected” disease. Lack of affordable new drugs, still a basic unsolved problem, has also been joined by additional therapeutic obstacles including large-scale resistance to pentavalent antimony (Sb) in India and coinfection with human immuno-deficiency virus in all endemic regions. Nevertheless, available treatment options have actually expanded because the energetic clinical trials effort of the past decade has yielded tangible advances. This progress includes successful application of less expensive generic Sb; rediscovery of the high-level efficacy of amphotericin B; implementation of short-course parenteral regimens (lipid formulations of amphotericin B); potential to replace Sb and amphotericin B with price-capped paromyomycin; and identification of the first effective oral agent (miltefosine). How to sustain and move this progress ahead, make new advances practical (e.g., affordable, and therefore, deployable), and how to translate promising experimental approaches into actual therapy remain difficult next steps in the treatment of kala-azar.
INTRASPECIFIC NUCLEOTIDE VARIATION IN ANOPHELES GAMBIAE: NEW INSIGHTS INTO THE BIOLOGY OF MALARIA VECTORS
Authors: MORLAIS ISABELLE , PONÇON NICOLAS , SIMARD FRÉDÉRIC , COHUET ANNA , FONTENILLE DIDIER
Published: September 2018

The Anopheles gambiae genome sequence, together with the recent development of molecular tools for genome-wide analysis, promises new insights into the biology of the malaria vector. These insights should help define the best possible breakdown point for interrupting transmission in the mosquito vector. A survey of the intraspecific nucleotide diversity in coding regions of three different mosquito strains showed an average of one single nucleotide polymorphism (SNP) every 125 coding base pairs. High levels of nucleotide polymorphism were observed in mosquito immune-related genes and pathogen recognition receptors harbored higher replacement substitutions. Genotyping at SNP loci in natural populations of An. gambiae from three malaria foci showed contrasting patterns. The distribution of mutation Y443H in the thioester-containing protein 3 (TEP3) gene suggested this mutational event has occurred under selective constraints. Our results show that SNP-based studies will be valuable in identifying the sequence variation associated with phenotypic traits shaping vector competence.
GENETICALLY MODIFIED, LIVE ATTENUATED DENGUE VIRUS TYPE 3 VACCINE CANDIDATES
Authors: BLANEY JOSEPH E. , HANSON CHRISTOPHER T. , FIRESTONE CAI-YEN , HANLEY KATHRYN A. , MURPHY BRIAN R. , WHITEHEAD STEPHEN S.
Published: September 2018

Three novel recombinant dengue type 3 (DEN3) virus vaccine candidates have been generated from a DEN3 virus isolated from a mild outbreak of dengue fever in the Sleman area of central Java in Indonesia in 1978. Antigenic chimeric viruses were prepared by replacing the membrane precursor and envelope (ME) proteins of recombinant DEN4 (rDEN4) virus with those from DEN3 Sleman/78 in the presence (rDEN3/4Δ30(ME)) and the absence (rDEN3/4(ME)) of the Δ30 mutation, a previously described 30-nucleotide deletion in the 3′ untranslated region. In addition, a full-length infectious cDNA clone was generated from the DEN3 isolate and used to produce rDEN3 virus and the vaccine candidate rDEN3Δ30. The chimeric viruses rDEN3/4(ME) and rDEN3/4Δ30(ME) appear to be acceptable vaccine candidates since they were restricted in replication in severe combined immune deficiency mice transplanted with human hepatoma cells, in rhesus monkeys, and in Aedes and Toxorynchites mosquitoes, and each was protective in rhesus monkeys against DEN3 virus challenge. The rDEN3/4(ME) and rDEN3/4Δ30(ME) viruses were comparable in all parameters evaluated, indicating that antigenic chimerization resulted in the observed high level of attenuation. Surprisingly, rDEN3Δ30 was not attenuated in any model tested when compared with wild-type rDEN3 and therefore, is not a vaccine candidate at present. Thus, the rDEN3/4(ME) and rDEN3/4Δ30(ME) antigenic chimeric viruses can be considered for evaluation in humans and for inclusion in a tetravalent dengue vaccine.
PARACOCCIDIOIDOMYCOSIS: AN EPIDEMIOLOGIC SURVEY IN A PEDIATRIC POPULATION FROM THE BRAZILIAN AMAZON USING SKIN TESTS
Authors: KALMAR E. M. N. , ALENCAR F. E. C. , ALVES F. P. , PANG L. W. , DEL NEGRO G. M. B. , CAMARGO Z. P. , SHIKANAI-YASUDA M. A.
Published: September 2018

Since Paracoccidioides brasiliensis and Histoplasma capsulatum are known to be present in similar environments, there have been many epidemiologic investigations regarding the prevalences of these two organisms. However, cross-reactivity can occur in paracoccidioidin and histoplasmin skin tests, and this usually results in the overestimation of the prevalence of P. brasiliensis.The prevalence of infection with P. brasiliensis was evaluated in a cross-sectional study of 298 asymptomatic school children in the Brazilian Amazon region (Mato Grosso State). In this investigation, the reactivity of children to two different P. brasiliensis antigen preparations, paracoccidioidin and a purified 43-kD glycoprotein (gp43), was compared with or without the co-administration of histoplasmin. In the group of individuals receiving paracoccidioidin who had a positive histoplasmin skin test result, the prevalence of exposure to P. brasiliensis was 44% (16 of 36). This reactivity to P. brasiliensis was significantly higher than that observed in other groups, which ranged from 4% to 6% (P < 5 × 10−4 for each). Overall prevalence was 4.6% (95% confidence interval = 2.5–7.7%). These data suggest that gp43 provides a better estimate of exposure to P. brasiliensis when the co-administration of histoplasmin is desired.
SHORT REPORT: INHIBITION BY TUMOR NECROSIS FACTOR-α–ACTIVATED MACROPHAGES OF THE TRANSITION OF PARACOCCIDIOIDES BRASILIENSIS CONIDIA TO YEAST CELLS THROUGH A MECHANISM INDEPENDENT OF NITRIC OXIDE
Authors: GONZALEZ ANGEL , ARISTIZÁBAL BEATRIZ H. , GÓMEZ ERIKA CARO , RESTREPO ANGELA , CANO LUZ E.
Published: September 2018

It is known that peritoneal murine macrophages activated with interferon-γ exert a fungicidal effect against Paracoccidioides brasiliensis conidia by a nitric oxide (NO)-mediated mechanism. This NO-mediated effect can also be induced by other cytokines such as tumor necrosis factor-α (TNF-α). The aim of this study was to determine if TNF-α-activated peritoneal murine macrophages infected with P. brasiliensis were able to show fungistatic/fungicidal effects mediated by NO. The results indicated that although macrophage activation with TNF-α did not result in NO production, these cells played an important role in inhibiting the conidia from becoming yeast cells. In vivo, the NO-independent inhibitory effect would prove of importance for the establishment of P. brasiliensis in host tissues.