bluuebunny/crossref_metadata_2025 huggingface dataset:
Further Biochemical Characterization of Chronic Trypanosoma Brucei Gambiense-Microtus Montanus Infection
Authors: Seed John Richard , Sechelski John , Hall James Edwin
Published: May 2017

Tyrosine aminotransferase (TAT), glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), and alkaline phosphatase (ALP) were measured in the serum and livers of Microtus montanus infected with Trypanosoma brucei gambiense. Only liver TAT and serum ALP showed significant changes. In addition, blood glucose, pyruvate and lactate, and liver glycogen levels were assayed. All four compounds showed significant changes, strongly suggesting increased glycogen mobilization and increased catabolic activity. Interestingly, the serum ketone levels were very low and no significant changes were observed. These chronically infected animals had an organic aciduria in which pyruvate, lactate, β-hydroxybutyrate, α-ketoglutarate, phenylpyruvate, and p-hydroxyphenylpyruvate were significantly increased. The possible significance of these observations is discussed.
Dirofilaria Ursi-Like Parasites Acquired by Humans in the Northern United States and Canada: Report of Two Cases and Brief Review
Authors: Beaver Paul C. , Wolfson John S. , Waldron Mary Ann , Swartz Morton N. , Evans George W. , Adler Jonathan
Published: May 2017

Two cases of subcutaneous dirofilariasis acquired in Ontario and Vermont are reported. The parasites in these and eight cases previously reported from the northern United States and Canada are classified as resembling Dirofilaria ursi, a primarily subcutaneous parasite of bears, or D. subdermata of porcupines, in the same region. A distinguishing morphological feature of the D. ursi-like group is the presence of distinct longitudinal cuticular ridges regularly and widely spaced on the outer surface, and usually evident even when the worms are necrotic. In the 10 known cases, all patients were women, and the usual location of nodules containing the worms was the scalp or a covered part of the upper body where blackfl.ies, the intermediate hosts of D. ursi, normally feed.
Modeling the transmission of schistosomiasis: an introductory view
Authors: Barbour A. D.
Published: May 2017

The transmission of schistosomiasis can be modeled at various levels of complexity in terms of systems of mathematical equations. This paper shows how such models can be set up, and stresses the importance of incorporating the right basic assumptions from the outset. The use of models for evaluating possible control strategies is illustrated in the context of a simple prevalence model of transmission. Some limitations and uncertainties involved in modeling schistosomiasis are also indicated.
Comparative clinical trial of artesunate suppositories and oral artesunate in combination with mefloquine in the treatment of children with acute falciparum malaria.
Authors: Sabchareon A , Attanath P , Chanthavanich P , Phanuaksook P , Prarinyanupharb V , Poonpanich Y , Mookmanee D , Teja-Isavadharm P , Heppner D G , Brewer T G , Chongsuphajaisiddhi T
Published: May 2017

A randomized pilot study to compare the safety and efficacy of artesunate suppositories (15 mg/kg/day for three days) versus oral artesunate (6 mg/kg/day for three days), both in combination with mefloquine (25 mg/kg), was conducted in 52 Thai children with uncomplicated multidrug-resistant falciparum malaria. Forty-five patients (87%) had a full 28-day follow-up in the hospital to assess efficacy and exclude reinfection. Mean [range] times to fever clearance of the two groups were similar (42 hr [15-104] versus 42 hr [6-119]). Artesunate suppositories resulted in significantly longer times to achieve 50% and 90% reductions of the initial parasite counts (17 and 26 hr versus 9 and 15 hr; P < 0.05 and P < 0.001). Time [range] to parasite clearance was longer in the artesunate suppositories group (42 hr [14-93] versus 35 hr [16-69]), but the difference was not significant. The cure rates by days 28 were not significantly different, 92% for artesunate suppository-treated patients and 100% for oral artesunate-treated patients. Both drug regimens are safe and effective. Further studies are needed to characterize the pharmacokinetic properties and the optimum regimen of artesunate suppositories for the treatment of severe malaria.
Enzyme-linked immunoelectrotransfer blot analysis of a cryptosporidiosis outbreak on a United States Coast Guard cutter.
Authors: Moss D M , Bennett S N , Arrowood M J , Wahlquist S P , Lammie P J
Published: May 2017

Symptoms consistent with an outbreak of cryptosporidiosis (diarrhea, vomiting, nausea, and abdominal cramps) occurred on a U.S. Coast Guard cutter within 0-18 days after the cutter filled its tanks with Milwaukee, Wisconsin city water in March 1993. At three-weeks postdocking (PD), the suspected water was removed, and serum samples and stool specimens were collected from 47 of the 58 crew members, as well as questionnaire data on their water consumption and symptoms aboard the cutter. At 10-weeks PD and/or at 28-weeks PD, additional serum specimens were collected. Intensitometric data from enzyme-linked immunoelectrotransfer blot (EITB) were obtained on IgA responses to a 17-kD antigen group, IgM responses to a 27-kD antigen group, and IgG responses to 27-, 17-, and 15-kD antigen groups extracted from oocysts. In addition, IgG responses to crude oocyst antigens were obtained by ELISA. Based on reported symptoms, EITB results, and stool examination, the crew members were classified as confirmed (10), probable (10), suspected (22), and noncases (16). Of the 10 confirmed cases (all symptomatic) and the 10 probable cases (eight symptomatic) whose stools were positive and negative, respectively, for Cryptosporidium oocysts by microscopy, all showed changes in EITB intensities to the antigen groups and were considered EITB positive. The remaining 38 crew members, 22 suspected cases (all symptomatic), and 16 noncases (all asymptomatic), if tested, had negative stool examinations and were considered EITB negative. Of the 10 confirmed cases, only four showed a significant change in IgG responses (P < 0.05) between three-weeks PD and follow-up serum specimens by ELISA. Crew members considered confirmed cases consumed significantly more water (P < or = 0.005) aboard the cutter than noncases. Crew members considered EITB positive consumed more water (P < or = 0.04) than crew members considered EITB negative while there was no significant difference in water consumption (P > or = 0.19) between crew members considered ELISA positive and ELISA negative. Using the EITB, the observation of changes in intensity of IgA responses to the 17-kD antigen group, IgM responses to the 27-kD antigen group, and IgG responses to the 27- 17-, and 15-kD antigen groups from C. parvum oocysts between acute and convalescent serum specimens appears useful for immunodiagnosis of Cryptosporidium infection and for prospective epidemiologic studies designed to monitor infection risk.
Cytokine responses in Trypanosoma cruzi-infected children in Paraguay.
Authors: Samudio M , Montenegro-James S , Cabral M , Martinez J , Rojas de Arias A , James M A
Published: May 2017

Both parasite and host immune factors may contribute to the development and progression of chronic chagasic cardiomyopathy during Trypanosoma cruzi infections. The present study targeted infected children (5-14 years of age) from an endemic area of Paraguay in an analysis of T. cruzi-specific cytokine profiles. This age group is characteristically the most affected by the early phases of infection. Trypanosoma cruzi-induced cytokine gene expression (interleukin-2 [IL-2], and interferon-gamma [IFN-gamma], IL-4, and IL-10) was studied in 25 seropositive children categorized as being either acute, symptomatic, with Romana's sign (n = 2), or early, indeterminate (postacute, n = 23). Acutely infected children showed a distinct T helper cell-1 (Th1)-type (IFN-gamma) cytokine response to infection. The cytokine pattern that was observed in the seropositive, asymptomatic (early, indeterminate) group was of the Th0 type (expression of both IFN-gamma and IL-4). We hypothesize that selective induction of a Th0-type cytokine pattern is important for development of cell-mediated and humoral immune responses that suppress parasite burden, thereby prolonging the onset or limiting the severity of chronic Chagas' disease later in life.
A simple dipstick assay for the detection of antibodies to phenolic glycolipid-I of Mycobacterium leprae.
Authors: BÃ¼hrer S S , Smits H L , Gussenhoven G C , van Ingen C W , Klatser P R
Published: May 2017

Among the many reported applications of the detection of antibodies to phenolic glycolipid-I (PGL-I) of Mycobacterium leprae, in particular, the use of seroprevalence as an indicator of the magnitude of the leprosy problem may turn out to be very useful in leprosy control programs. An operational function of serology within the leprosy control services requires a simple test system. We have developed a simple dipstick assay for the detection of antibodies to PGL-I and compared its performance with that of an ELISA. A high degree of agreement (97.2%) was observed between the ELISA and the dipstick assay when tested on 435 sera; the agreement beyond chance (Kappa value) was 0.92. No significant difference was found between the dipstick assay and the ELISA when seropositivity rates obtained in groups of leprosy patients, household contacts, and controls were compared. The interpretation of the dipstick results as positive or negative was unequivocal, as illustrated by the high agreement between different persons reading the test (Kappa values > 0.88). Storage of the only reagents required, the dipsticks and the stabilized detection reagent, up to three weeks under tropical conditions of high temperatures, high humidity, and exposure to light, did not influence the results of the assay. The dipstick assay described here is an easy-to-perform method for the detection of IgM antibodies to PGL-I of M. leprae; it does not require any special equipment and the highly stable reagents make the test robust and suitable for use in tropical countries. An internal control validates the performance of the assay. This dipstick assay may be the method of choice for epidemiologic mapping of leprosy.
Humoral response to Plasmodium falciparum Pf155/ring-infected erythrocyte surface antigen and Pf332 in three sympatric ethnic groups of Burkina Faso.
Authors: Modiano D , Chiucchiuini A , Petrarca V , Sirima B S , Luoni G , Perlmann H , Esposito F , Coluzzi M
Published: May 2017

The humoral immune response against synthetic peptides of two Plasmodium falciparum blood-stage antigens, Pf155/ring-infected erythrocyte surface antigen (RESA) (EENV)6 and Pf332 (SVTEEIAEEDK)2, in individuals belonging to three sympatric ethnic groups (Mossi, Rimaibe, and Fulani) living in the same conditions of hyperendemic transmission in a Sudan savanna area northeast of Ouagadougou, Burkina Faso were examined. The Mossi and Rimaibe are Sudanese Negroid populations with a long tradition of sedentary farming, while the Fulani are nomadic pastoralists partly settled and characterized by non-Negroid features of possible Caucasoid origin. A total of 764 subjects (311 Mossi, 273 Rimaibe, and 180 Fulani) were tested. A lower P. falciparum prevalence was observed in the Fulani of all age groups. The serologic results clearly indicate the existence of interethnic differences in the capacity to respond to these two P. falciparum antigens. The Mossi and Rimaibe showed similar responses, whereas the Fulani displayed consistently higher prevalences and levels of antibodies against both epitopes tested. The anti-(EENV)6 and anti-(SVTEEIAEEDK)2 seroprevalences were 29.9% and 38.9% in Mossi, 29.7% and 39.2% in Rimaibe, 86.1% and 76.1% in Fulani (all P values of Fulani-Mossi and Fulani-Rimaibe comparisons < 0.001). Anti-RESA and anti-Pf332 antibody levels were approximately 65% (P < 0.001) and 45% (P < 0.001), respectively, higher in seropositive Fulani than in seropositive Mossi and Rimaibe, who showed very similar values. The observed differences cannot be explained in terms of interethnic heterogeneity of malaria exposure since these communities have lived in the same area for more than 30 years and the P. falciparum inoculation rate, measured during two consecutive years, was substantially uniform for the three ethnic groups. The possibility of remarkable heterogeneities in the capacity to mount immune responses against P. falciparum antigens among populations with different genetic backgrounds must be taken into account in the development of anti-malaria vaccines.
Comparison of serum antibody responses to Giardia lamblia of symptomatic and asymptomatic patients.
Authors: Soliman M M , Taghi-Kilani R , Abou-Shady A F , El-Mageid S A , Handousa A A , Hegazi M M , Belosevic M
Published: May 2017

The circulating anti-parasite antibody response against Giardia lamblia in symptomatic and asymptomatic Egyptian children with confirmed giardiasis was examined. Symptomatic patients were identified using the following criteria: presence of only G. lamblia cysts in the feces, and one or more of the following symptoms, diarrhea, abdominal pain, loss of weight, vomiting and/or nausea, and abdominal distention. The anti-parasite humoral response was measured using indirect immunofluorescence (IFA), ELISA, and immunoblotting. There was a significant difference in the anti-parasite antibody response measured by IFA of asymptomatic and symptomatic patients, in which more than 34% of the asymptomatic patients had a titer equal to or less than 1:500, and more that 29% of the symptomatic patients had a titer of 1:8,000 or higher. The circulating anti-parasite total IgM and IgA but not IgG, measured by ELISA, was significantly higher in symptomatic than in asymptomatic patients, and were related to higher cyst output observed in symptomatic individuals. Although total anti-parasite IgG response was similar in symptomatic and asymptomatic patients, the analysis of the IgG isotype responses revealed that both IgG1 and IgG3 were significantly higher in symptomatic patients. The antigen recognition by anti-parasite IgM, IgA, IgG1, and IgG3 of symptomatic and asymptomatic individuals, determined by immunoblotting, was heterogeneous and revealed only minor differences in the response of the two groups.
La Untadita: a procedure for maintaining washbasins and drums free of Aedes aegypti based on modification of existing practices.
Authors: Sherman C , Fernandez E A , Chan A S , Lozano R C , Leontsini E , Winch P J
Published: May 2017

Chlorine bleach and detergent are routinely used by householders in El Progreso, Honduras in the process of cleaning washbasins and drums, the two most important larval habitats of Aedes aegypti in the city. The efficacy of these materials in eliminating eggs, larvae, and pupae of Ae. aegypti was assessed under controlled conditions. The promising results obtained led to trials using a combination of chlorine bleach and detergent to apply to the walls of washbasins and drums as a method for eliminating eggs. The bleach maintained its ovicidal properties when mixed with detergent, and the detergent gave the mixture consistency so that it could be applied as a thin film to the walls. This new procedure was named the little dab (Untadita in Spanish) and allows households to direct their efforts against a stage of the mosquito life cycle that has been ignored in the past: the egg.
The historical question of acquired immunodeficiency syndrome in the 1960s in the Congo River basin area in relation to cryptococcal meningitis.
Authors: Molez J F
Published: May 2017

In Europe before the advent of the acquired immunodeficiency syndrome (AIDS), fatal cases of infection with Cryptococcus neoformans resembling acute meningitis were rarely described and never in young adults. However, rapidly fatal cryptococcal meningitis in young Africans has been known to exist in central Africa for at least 30 years, mainly in the lower area of the Congo River basin. Cases have been reported in this area since 1953, particularly in young patients during the 1950s. It is also known that central African AIDS patients frequently suffer from cryptococcosis, and there is a possibility that earlier clinical reports of encephalitis were actually fatal cases of AIDS in young Africans. It appears possible that the central part of the African continent is the area where human immunodeficiency virus originated.
Exploratory space-time analysis of reported dengue cases during an outbreak in Florida, Puerto Rico, 1991-1992.
Authors: Morrison A C , Getis A , Santiago M , Rigau-Perez J G , Reiter P
Published: May 2017

The spatial and temporal distributions of dengue cases reported during a 1991-1992 outbreak in Florida, Puerto Rico (population = 8,689), were studied by using a Geographic Information System. A total of 377 dengue cases were identified from a laboratory-based dengue surveillance system and georeferenced by their residential addresses on digital zoning and U.S. Geological Survey topographic maps. Weekly case maps were generated for the period between June and December 1991, when 94.2% of the dengue cases were reported. The temporal evolution of the epidemic was rapid, affecting a wide geographic area within seven weeks of the first reported cases of the season. Dengue cases were reported in 217 houses; of these 56 (25.8%) had between two and six reported cases. K-function analysis was used to characterize the spatial clustering patterns for all reported dengue cases (laboratory-positive and indeterminate) and laboratory-positive cases alone, while the Barton and David and Knox tests were used to characterize spatio-temporal attributes of dengue cases reported during the 1991-1992 outbreak. For both sets of data significant case clustering was identified within individual households over short periods of time (three days or less), but in general, the cases had spatial pattern characteristics much like the population pattern as a whole. The rapid temporal and spatial progress of the disease within the community suggests that control measures should be applied to the entire municipality, rather than to the areas immediately surrounding houses of reported cases. The potential for incorporating Geographic Information System technologies into a dengue surveillance system and the limitations of using surveillance data for spatial studies are discussed.
Risk factors for primary pulmonary coccidioidomycosis hospitalizations among United States Navy and Marine Corps personnel, 1981-1994.
Authors: Gray G C , Fogle E F , Albright K L
Published: May 2017

Recent coccidioidomycosis outbreaks among military personnel have alarmed public health officials. We used computerized hospitalization records to identify risk factors for coccidioidomycosis hospitalizations among active-duty United States Navy and Marine Corps personnel for the years 1981 to 1994. Primary pulmonary disease was the most common form of disease, accounting for 82 (73%) of the 113 first admissions. Crude annual rates of primary pulmonary disease increased markedly in 1992 and 1993 in concert with an epidemic in the United States. Demographic data from the pulmonary admissions were combined with that of a 2% random sample of the entire Navy and Marine Corps population for multivariate risk factor modeling. Persons from junior paygrades, older age groups, and those reporting a race/ethnicity other than Caucasian or Hispanic were most likely to be hospitalized with this disease. These risk factor data should be considered in designing coccidioidomycosis surveillance and prevention programs.
Application of the enzyme-linked immunoelectrotransfer blot to filter paper blood spots to estimate seroprevalence of cysticercosis in Bolivia.
Authors: Jafri H S , Torrico F , Noh J C , Bryan R T , Balderrama F , Pilcher J B , Tsang V C
Published: May 2017

An enzyme-linked immunoelectrotransfer blot (EITB) assay was used to study the prevalence of cysticercosis in rural Bolivia. Dried blood spots on filter paper from fingersticks were used as assay samples. Before the serosurvey, experiments were performed to show that samples eluted from dried whole blood on filter paper exhibited no decrease in sensitivity when compared with the more traditional serum samples used in the EITB. Fingerstick blood dried on filter paper is a convenient, economical way of transporting and storing field samples for epidemiologic surveys of cysticercosis in developing countries. This report shows the utility of this sample collection method in underdeveloped countries where refrigeration is not possible and where venipuncture is a problem. Blood was obtained from randomly selected residents in three rural regions of Bolivia: Chuquisaca (n = 1,859), Cochabamba (n = 1,516), and Tarija (n = 1,010). The estimated seroprevalence on 10% of the sample collected for the three regions were 9%, 4.5%, and 2%, respectively.
Japanese encephalitis among hospitalized pediatric and adult patients with acute encephalitis syndrome in Hanoi, Vietnam 1995.
Authors: Lowry P W , Truong D H , Hinh L D , Ladinsky J L , Karabatsos N , Cropp C B , Martin D , Gubler D J
Published: May 2017

The etiologic spectrum of acute encephalitis syndrome (AES) has not been well defined in Vietnam. Cohort and case-control studies were performed on all adult and pediatric AES patients admitted to the Neurology Service of Bach Mai Hospital between June 5 and August 3, 1995. Among pediatric AES patients, 31 (67%) of 46 had acute Japanese encephalitis (JE), compared with only two (6%) of 33 adult AES patients (P < 0.0001). For confirmed JE cases, serum specimens obtained 15-21 days after symptom onset had the highest mean anti-JE IgM signal-to-noise (P/N) ratios (8.08 + 1.09 SE). A serosurvey of adult household members did not reveal any cases of recent subclinical JE infection, although 26% had evidence of past JE infection. The use of bed netting was nearly universal but did not appear to reduce the risk of AES or JE. Given the high incidence of JE, particularly among children, Vietnam seems well suited for the development of a targeted JE vaccination strategy.
Increase in asialoganglioside- and monosialoganglioside-reactive antibodies in chronic Chagas' disease patients.
Authors: Avila J L , Rojas M , Avila A
Published: May 2017

Antibodies reactive with the core glycan of asialoganglioside (GA1), monosialoganglioside (GM1), and disialoganglioside (GD1a) were studied in human sera. In healthy individuals, GA1-, GM1-, and GD1a-reactive antibodies were mainly of the IgM class, but also of the IgA and IgG classes, and were present at low titers in the serum of 68%, 79%, and 91% of the individuals studied, respectively. Levels of anti-GA1 and anti-GM1 antibodies, mainly of the IgA and IgG classes, were significantly elevated (P < 0.001) in 62% and 72% of subjects, respectively, chronically infected with Trypanosoma cruzi, with no association found with the degree of myocardial damage. No significant increase in anti-GA1 and anti-GM1 antibodies was found in dilated cardiomyopathy patients. The level of anti-GD1a antibody was not significantly different between healthy controls and chronic chagasic or dilatatory cardiomyopathy patients. Since the peripheral nervous system is very rich in gangliosides, it is possible that the increases in GA1- and GM1-specific antibodies that develop during chronic T. cruzi infection are involved in the pathology of peripheral neuropathy in Chagas' disease.
Effect of pentoxifylline on cytokine patterns in the therapy of complicated Plasmodium falciparum malaria.
Authors: Wenisch C , Looareesuwan S , Wilairatana P , Parschalk B , Vannapann S , Wanaratana V , Wernsdorfer W , Graninger W
Published: May 2017

The effect of pentoxifylline (PTX) was tested for its capacity to modulate cytokine responses during therapy of severe Plasmodium falciparum malaria in a placebo-controlled, randomized study in 45 adult patients in Bangkok, Thailand. The patients received standard antimalarial treatment with artesunate (120 mg intravenously given immediately, then 60 mg every 12 hr for a total dose of 600 mg). The patients received either low-dose PTX (20 mg/kg/day, n = 15), high-dose PTX (40 mg/kg/day, n = 15), or placebo (n = 15) as continuous infusion for the first three days of antimalarial treatment. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were markedly elevated in all patients prior to treatment. After 6 hr of high-dose PTX treatment, TNF and IL-6 levels significantly decreased while an increase in TNF and IL-6 levels was seen after 6 hr of low-dose PTX or placebo treatment (P < 0.01). After 12 and 24 hr of high-dose PTX infusion, TNF-receptor plasma concentrations were lower than in low-dose PTX- or placebo-treated patients (P < 0.01), whereas no differences between the groups with regard to IL-6 receptor levels were observed. We conclude that 40 mg/kg/day of PTX reduces plasma levels of TNF, IL-6, and TNF-receptor in patients with severe malaria. Whether this reduction improves clinical outcome remains to be determined.
In vitro activity of artemether against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial drugs.
Authors: Pradines B , Rogier C , Fusai T , Tall A , Trape J F , Doury J C
Published: May 2017

The in vitro activity of artemether against 56 African isolates of Plasmodium falciparum from Senegal was evaluated using an isotope-based drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0.8 to 15.2 nM (mean IC50 = 3.43 nM) and the 95% confidence interval (CI) was 2.50-4.36 nM. Artemether was equally effective on chloroquine-sensitive and chloroquine-resistant isolates (mean IC50 = 346 nM, 95% CI = 2.08-4.84 nM versus mean IC50 = 2.80 nM, 95% CI = 2.00-3.60 nM). There was a significant positive correlation between responses to artemether and mefloquine (r2 = 0.36, P < 0.001), artemether and quinine (r2 = 0.085, P < 0.05), artemether and halofantrine (r2 = 0.075, P < 0.05), quinine and mefloquine (r2 = 0.205, P < 0.01), quinine and halofantrine (r2 = 0.124, P < 0.05), and mefloquine and halofantrine (r2 = 0.801, P < 0.001). A positive correlation between these drugs suggests in vitro cross-resistance or at least in vitro cross-susceptibility.
Assessment of the effect of the oral iron chelator deferiprone on asymptomatic Plasmodium falciparum parasitemia in humans.
Authors: Thuma P E , Olivieri N F , Mabeza G F , Biemba G , Parry D , Zulu S , Fassos F F , McClelland R A , Koren G , Brittenham G M , Gordeuk V R
Published: May 2017

While the parenteral iron-chelating agent desferrioxamine B has anti-malarial activity in humans, the usefulness of an orally active chelator for this indication has not been investigated previously in vivo. We conducted a prospective, double-blind, placebo-controlled, cross-over trial of deferiprone (L1; CP20; 1,2-dimethyl-3-hydroxypyridin-4-one) in 25 adult Zambians with asymptomatic Plasmodium falciparum parasitemia. Deferiprone was administered daily for three or four days in divided doses of 75 or 100 mg/kg of body weight, dosages that are effective for treating iron overload. No reduction in asexual intra-erythrocytic parasites was observed during or after deferiprone treatment. The mean peak plasma concentration of deferiprone (108.9 +/- 24.9 micromol/L) achieved was within the range demonstrated to inhibit the growth of P. falciparum in vitro, but the systemic exposure as determined by the 24-hr plasma concentration-time curve would not be predicted inhibit growth in vivo. No evidence of deferiprone-associated hematological toxicity was noted in this short-term study of these subjects, all of whom had clinical evidence of normal body iron stores. Because of the risk of neutropenia and other adverse effects with higher doses or prolonged use of the chelator, additional trials of deferiprone as a sole anti-malarial agent would not seem to be justified. In contrast, further efforts are needed to develop other orally active iron-chelating agents specifically for their anti-malarial action.
Molecular epidemiology of malaria in Yaounde, Cameroon II. Baseline frequency of point mutations in the dihydropteroate synthase gene of Plasmodium falciparum.
Authors: Basco L K , Ringwald P
Published: May 2017

Sulfadoxine-pyrimethamine is one of the alternative antimalarial drugs used to treat chloroquine-resistant Plasmodium falciparum malaria. The molecular target of sulfadoxine, an analog of p-aminobenzoic acid that inhibits the folate biosynthetic pathway, is dihydropteroate synthase (DHPS). The nucleotide sequence of the DHPS gene was determined in 32 clinical isolates obtained in Yaounde, Cameroon, and compared with the sequence of reference clones and Cambodian strains of P. falciparum. Of the 32 Cameroonian isolates, 31 displayed one of the sulfadoxine-sensitive mutation patterns: Ala-436/Ala-437/Ala-581/Ala-613 (n = 20), Ser-436/Gly-437/Ala-581/Ala-613 (n = 6), Ser-436/Ala-437/Ala-581/Ala-613 (n = 4), and Ala-436/Gly-437/Ala-581/Ala-613 (n = 1). One isolate had a sulfadoxine-resistant profile characterized by a double mutation: Phe-436/Ala-437/Ala-581/Ser-613. Although the majority of the isolates had a sulfadoxine-sensitive genetic profile, further studies are needed to correlate the mutation patterns and in vitro and in vivo sulfadoxine sensitivity.
Evaluation of SPf66 malaria vaccine efficacy in Brazil.
Authors: Urdaneta M , Prata A , Struchiner C J , Tosta C E , Tauil P , Boulos M
Published: May 2017

This paper reports the efficacy results of the randomized, placebo-controlled, field trial of SPf66 malaria vaccine in Costa Marques, Rondonia, Brazil. This region is characterized by the seasonal distribution of Plasmodium falciparum and P. vivax infections, and the recent occupation by migrants from nonendemic areas. A total of 800 individuals of both sexes, ranging in age from seven to 60 years, were included in the study. Of the initial cohort, 572 participants completed the vaccination schedule. Clinical and parasitologic evaluations were obtained by active and passive searches on a periodic basis. The overall protective efficacy against P. falciparum infections was -1.6% (-32.9% to 22.4%), and 14.1% (-17.0% to 36.9%) for the first episode. The overall protective efficacy for P. vivax infections was -19.7% (-44.8% to 1.03%), and -10.8% (-41.1% to 12.8%) for the first episode. No statistical evidence of an overall significant protective effect of SPf66 malaria vaccine against P. falciparum and P. vivax malaria was obtained in this trial.
Identification and genetic analysis of Panama-genotype Venezuelan equine encephalitis virus subtype ID in Peru.
Authors: Oberste M S , Weaver S C , Watts D M , Smith J F
Published: May 2017

Venezuelan equine encephalitis (VEE) virus was isolated in 1993, 1994, and 1995 from human cases of acute, undifferentiated, febrile illness in the Peruvian Amazon Basin. Two virus isolates were recovered in 1994 from Peruvian soldiers at a jungle outpost near Pantoja in northern Peru, and 10 isolates were obtained from military personnel and civilians in 1993-1995 in Iquitos, an urban center in northeastern Peru. The genetic relationship of these isolates to other VEE virus strains was determined by sequencing 856-867 nucleotide reverse transcription-polymerase chain reaction fragments derived from the PE2 glycoprotein gene. The sequences were compared with those of other VEE virus strains, including representatives of the IAB, IC, ID, IE, II, and IIIC subtypes. The two Pantoja isolates were most closely related to subtype IC and ID viruses previously isolated in Colombia and Venezuela, and to the ID viruses isolated during the 1970s in Iquitos. All of the recent Iquitos isolates were similar to one another, but they were more closely related to Panamanian ID strains than to isolates previously obtained in Iquitos, Peru, or in Colombia and Venezuela. The recent Iquitos VEE viral isolates were the first Panama-genotype VEE ID virus strains identified outside of the Republic of Panama.
Epidemiologic characterization of American cutaneous leishmaniasis in an endemic region of eastern Venezuela.
Authors: Jorquera A , Ledezma E , De Sousa L , Garcia A , Sanchez J , Zerpa J , Gonzalez R , O'Daly J A
Published: May 2017

The status of American cutaneous leishmaniasis was investigated from 1985 to 1991 to provide an epidemiologic characterization of the disease in Bergantin, a rural community in the northeastern part of AnzoÃ¡tegui State, Venezuela. The study revealed the presence of the infection during the period analyzed, with an average incidence of 50.2 cases per 10,000 inhabitants and this number has increased 1.5 times during the last two years. Three villages where clinical cases had been recorded were selected for a comparison of their prevalence data. These villages comprise the human population in the high and low altitude limits of Bergantin. Immunologic assessment of the inhabitants used two different antigen preparations to examine responses to parasites associated with the cutaneous and visceral forms of the disease. The leishmanin skin test (LST) was used in a sample of 276 individuals (46.3% of the inhabitants) and resulted in an overall positivity of 16.7%. The percentage of LST positivity varied with age and sex, yet analysis of this response and the prevalence for each village reflected the specific characteristics of these localities. La MontaÃ±a, situated at 800 meters above sea level, had the highest prevalence (800 cases per 10,000 inhabitants) and the most positive LST response (21.2%) in comparison with the two other villages situated at a lower altitude (300 meters above sea level).
Risk factors associated with human cystic echinococcosis in Florida, Uruguay: results of a mass screening study using ultrasound and serology.
Authors: Carmona C , Perdomo R , Carbo A , Alvarez C , Monti J , Grauert R , Stern D , Perera G , Lloyd S , Bazini R , Gemmell M A , Yarzabal L
Published: May 2017

Sonographic evidence of asymptomatic Echinococcus granulosus lesions in the liver was found in 156 of 9,515 persons in the Department of Florida, Uruguay. The sensitivity of ELISA and latex agglutination serology compared with ultrasound was 47.6% and 28.1%, respectively, and specificity was > 85%. There was a significant positive association between positive sonography and a personal history of previous but treated Echinococcus infection while those that were seropositive but ultrasound-negative were significantly more likely to have a personal history of infection or a history of infection in their family. Prevalence of infection increased significantly with age. There was no correlation between echinococcosis and dog ownership or home slaughter of sheep but offal disposal was important, with an increased prevalence of infection of 3.2%, 2.8%, and 3.1%, respectively, in persons feeding offal to dogs or burying or burning it compared with a prevalence of 0.8-1.5% in those using other methods of disposal. Almost half the population, when questioned, seemed to have sound knowledge about E. granulosus and described correct treatment of E. granulosus in dogs but this did not affect prevalence. There was a significant positive association between infection and the presence of a fenced fruit/vegetable garden and use of rural waters, particularly the cachimba (a small dam) and the aljibe (a cistern or tank) that collect rainwater from the ground surface and roofs, respectively.
Evaluation of the protective efficacy of a recombinant dengue envelope B domain fusion protein against dengue 2 virus infection in mice.
Authors: Simmons M , Nelson W M , Wu S J , Hayes C G
Published: May 2017

A recombinant protein containing part of the dengue (DEN) 2 envelope protein was evaluated as a subunit immunogen for vaccination against DEN virus infection. A gene fragment encoding amino acids 298-400 (B domain) of the DEN-2 virus envelope was expressed as a fusion protein with the maltose binding protein (MBP) of Escherichia coli. This recombinant, DEN-2(B)/MBP, was purified and analyzed for its antigenicity, immunogenicity, and ability to protect mice against lethal challenge. The recombinant antigen reacted with a DEN-2 type-specific neutralizing monoclonal antibody (3H5), DEN-2 hyperimmune mouse ascitic fluid, and DEN-2 immune human sera. When administered to mice, DEN-2(B)/MBP elicited a DEN-2 virus neutralizing antibody response that conferred partial protection against challenge infection with a lethal dose of DEN-2 virus administered by intracranial inoculation. In addition, no replication of DEN-2 virus was detectable in the brains of the immunized mice as compared with control mice that were killed six days after challenge. Sera from immunized mice revealed no cross-neutralizing antibody to any of the other DEN serotypes in the plaque-reduction neutralization test. These findings warrant further studies with the DEN-2(B)/MBP antigen as a potential human vaccine candidate. An effective vaccine could prevent thousands of cases of illness and many deaths each year resulting from DEN virus infections.
Pathophysiology of fatal falciparum malaria in African children.
Authors: Newton C R , Taylor T E , Whitten R O
Published: May 2017

Children living in sub-Saharan Africa bear the brunt of the mortality from falciparum malaria, yet there is a dearth of relevant post-mortem data. Clinical studies from centers in Africa suggest that the pathophysiology of severe malaria is different in children and adults. Three overlapping clinical syndromes, metabolic acidosis manifesting as hyperpnea, cerebral malaria, and severe anemia, are responsible for nearly all the deaths in African children. Despite improvements in antimalarial treatment, there has not been a significant reduction in mortality. We review the pathology and pathophysiology of fatal falciparum malaria in African children. Many questions remain, the answers to which would facilitate the development and evaluation of new approaches to the management of this disease.
Intraspecific isozyme polymorphism of Anopheles gambiae in relation to environment, behavior, and malaria transmission in southwestern Burkina Faso.
Authors: Coosemans M , Smits A , Roelants P
Published: May 2017

A cellulose acetate electrophoresis system was used to study the isozyme polymorphism of the Anopheles gambiae complex in a rural village and a city in southwestern Burkina Faso. In both areas A. gambiae Giles was the dominant species (95%) whereas A. arabiensis Patton represented only 5%. Both species were separated readily by octanol dehydrogenase Odh and mannose phosphate isomerase (Mpi) even if they shared some alleles at these two loci. Polymorphism analysis (13 loci) at the intraspecific level of A. gambiae showed a significant difference between the specimens collected in the city from those collected in the village in their allelic and genotypic frequencies of isocitrate dehydrogenase-1 and malate dehydrogenase-1 and in their allelic frequencies for Mpi. No genetic difference was observed between the human biting A. gambiae collected inside or outside the houses in either the village or the city. The Plasmodium falciparum-infected A. gambiae differed from the noninfected ones in their allelic and genotypic frequencies at Mpi and acid phosphatase (Acp). A two-fold difference in infection rate was found for the genotype Mpi130/130 and Acp110/100 compared with other genotypes. However, infected anophelines were found in all genotypes that belonged to these two enzyme systems. Consequently, no refractory mechanism occurs in these natural populations.
A target for intervention in Plasmodium falciparum infections.
Authors: McKenzie F E , Bossert W H
Published: May 2017

We present a set of simple mathematical models to investigate interactions between malaria parasites and the human immune system and the differentiation of parasites from asexual, pathogenic into sexual, transmissible blood stages. Each model represents a different combination of empirically based hypotheses, and salient behaviors of each fit criteria developed from clinical data. In all models, however, higher gametocyte conversion rates result in lower peak asexual-form densities. Therefore, to the extent that asexual-form densities are associated with disease symptoms, interventions that stimulate gametocytogenesis should produce unexpected clinical benefits.
Prevention of Borrelia burgdorferi transmission in guinea pigs by tick immunity.
Authors: Nazario S , Das S , de Silva A M , Deponte K , Marcantonio N , Anderson J F , Fish D , Fikrig E , Kantor F S
Published: May 2017

We examined the effect of repeated infestation of guinea pigs with Ixodes scapularis on the capacity of ticks to transmit Borrelia burgdorferi infection. Repeated challenges with nymphs or larvae lead to a reduction in duration of nymphal tick attachment and weight of recovered ticks consistent with the development of tick immunity. Only one of 18 I. scapularis-immune guinea pigs challenged with B. burgdorferi-infected nymphal ticks became infected, whereas 10 of 18 naive guinea pigs similarly challenged became infected. We conclude that tick immunity interferes with borrelial transmission.
A single tissue culture system for the propagation of the agents of the human ehrlichioses.
Authors: Heimer R , Tisdale D , Dawson J E
Published: May 2017

Two newly emergent human diseases found in the United States, human monocytotropic ehrlichiosis (HME) and human granulocytotropic ehrlichiosis (HGE), are caused by pathogens of the genus Ehrlichia. The causative agent of HGE can be propagated in HL-60 human promyelocytic leukemia cells. Herein, we report the development of a method to propagate E. chaffeensis, the causative agent of HME, in HL-60 cells, thus providing a common system for the study of both species. The continuous propagation of E. chaffeensis requires the induction of HL-60 differentiation along the monocytic pathway toward phenotypically mature macrophages by the addition of 25-OH vitamin D3 to the growth medium.
Cutaneous scars in American tegumentary leishmaniasis patients: a site of Leishmania (Viannia) braziliensis persistence and viability eleven years after antimonial therapy and clinical cure.
Authors: Schubach A , Marzochi M C , Cuzzi-Maya T , Oliveira A V , Araujo M L , Oliveira A L , Pacheco R S , Momen H , Conceicao-Silva F , Coutinho S G , Marzochi K B
Published: May 2017

Two former patients treated for the cutaneous form of American tegumentary leishmaniasis were reviewed eight and 11 years, respectively, following clinical cure. We were able to isolate Leishmania parasites in a culture of material from the two scar biopsies, and in one of them the parasite was characterized as Leishmania (Viannia) braziliensis. In both cases, the histopathology revealed discreet hyperceratosis and a slight infiltrate of mononuclear cells surrounding and on the walls of the surface and deep dermal vessels. No amastigotes were seen on immunohistochemical or histopathologic examination. The Montenegro skin test result and the in vitro lymphoproliferative response to Leishmania antigen were positive, but no specific IgG and IgM antibodies were detected. Otorhinolaryngologic examination showed no macroscopic alteration in the mucosae. These findings are important for the evaluation and criteria of post-treatment cure.
Field evaluation of a dog owner, participation-based, bait delivery system for the oral immunization of dogs against rabies in Tunisia.
Authors: Ben Youssef S , Matter H C , Schumacher C L , Kharmachi H , Jemli J , Mrabet L , Gharbi M , Hammami S , El Hicheri K , Aubert M F , Meslin F X
Published: May 2017

We evaluated a dog owner, participation-based, bait delivery system for the oral immunization of dogs against rabies. In a field study in a semirural area of northern Tunisia, dog owners were asked to come to temporary bait delivery sites. A total of 314 baits were given to 178 dog owners in four sites. The experimental baits used consisted of a freeze-dried core unit containing sulfadimethoxine (SDM) as a biological marker and an aromatized paraffin envelope. No vaccine was used. Preliminary tests had shown that by using a rapid commercial card test, positive SDM serum levels were detected in more than 95% of dogs up to two days after bait ingestion. During the two days following bait delivery, we visited more than 95% of all households in the study area and took blood samples from as many owned dogs as possible. Unconsumed baits were recovered and human contacts with the bait matrix were recorded. The campaign required 7.6 person-min per bait and 13.5 person-min per dog owner for providing baits, gloves, and instructions. The estimated average cost effectiveness ratio per dog accepting a bait was 1.7 US dollars. From the indications given by the dog owners and the results of the SDM test, it was concluded that 85-90% of the owned dogs in the study area had consumed a bait at least partially. Of 314 baits delivered, 78.7% were fully consumed by dogs and 4.1% were recovered during the household survey. The remaining baits (17.2%) that were not recovered were either not consumed or only partially consumed by the target dogs (3.7 baits per 100 inhabitants). These baits probably remained within the highly populated areas and were potentially accessible to other domestic animals and other nontarget species, including humans. Twenty-five unprotected human contacts with baits were recorded (1.7% of all inhabitants). Our study has demonstrated the potential of dog owner based bait delivery. This technique is simple and efficient, particularly if the human population is accustomed to mass immunization in defined centers. Before applying this method on a large scale with live vaccine loaded baits, further studies should focus on minimizing the number of human contacts with the vaccine bait, systematizing contact identification and establishing structures in ensuring proper treatment if exposure to vaccine should occur.
Disseminated muscular cysticercosis with myositis induced by praziquantel therapy.
Authors: Takayanagui O M , Chimelli L
Published: May 2017

Cysticercosis, the infestation with the encysted larval stage of Taenia solium, is increasingly recognized as a major problem in most countries in Latin America, Asia, and Africa, involving mainly the central nervous system. Muscle involvement is also common, although it usually remains asymptomatic. We describe a case of disseminated muscular cysticercosis followed by myositis (fever, diffuse myalgia, weakness of the lower limbs, and inflammatory reaction around dying cysticerci) induced by praziquantel therapy, an event not described previously.
The relationship between asymptomatic human immunodeficiency virus infection and the prevalence and severity of anemia in pregnant Malawian women.
Authors: van den Broek N R , White S A , Neilson J P
Published: May 2017

The relationship between asymptomatic human immunodeficiency virus (HIV) infection and blood hemoglobin (Hb) concentration was examined in anemic pregnant women from a population with high prevalence of both anemia (60%) and HIV seropositivity (30%). Sera from 155 pregnant women with Hb levels < 10.5 g/dL were tested for HIV status, C-reactive protein (CRP), vitamin B12, retinol, and folate levels. The observed prevalence of HIV seropositivity in the group of women with anemia was 47.1% (95% confidence interval=39.2-55.0%). This is significantly higher than the HIV prevalence in the whole population (30.1%; P < 0.001). Median Hb values in HIV-seropositive and -seronegative women with anemia were 8.40 g/dL and 8.95 g/dL, respectively. Serum retinol, vitamin B12, and folate levels were not significantly different in the HIV-seropositive and -seronegative groups. In women who were HIV-seropositive with normal levels of CRP, a median decrease in Hb of 0.4 g/dL was observed. For those with serum CRP levels > 25 mg/l, the median decrease in Hb was 0.7 g/dL. Results indicate that asymptomatic HIV infection is associated with increased prevalence and severity of anemia in pregnancy in this population.