Colombian study to assess the use of noninvasive determination of the endothelium-mediated vasodilation (CANDEV) II: does location of the occlusion device affects the accuracy of the diagnosis?

Endothelial dysfunction (ED), which is often evaluated by flow-mediated vasodilation (FMV) in the brachial artery, has been postulated as a predictor of cardiac events. Although the upper and forearm location of the occlusion device have been used for FMV evaluation, currently there is no consensus whether they provide the same information. The main goal of this study was to evaluate if both techniques have the same accuracy to differentiate subjects with and without cardiovascular risk factors (CRFs). A cross-sectional study in 124 subjects was performed. The volunteers were divided in two groups: 62 subjects (20 women and 42 men) with at least one CRF and 62 (20 women and 42 men) healthy subjects without CRFs. FMV measurements using the cuff in the upper arm and forearm with intervals of 30 min were taken. In all subjects, %FMV with the cuff located in the upper arm was 10.13 +/- 4.5 and 9.8 +/- 4.1 with the cuff located below the elbow. In healthy subjects without CRFs the %FMV in the upper arm was 12.19 +/- 4.0 versus 12.31 +/- 3.4 in the upper forearm, in CRF subjects it was 8.08 +/- 4.0 vs 7.29 +/- 3.2., respectively. FMV was not affected by the location of the cuff in maintaining the test ability and accuracy to differentiate subjects with and without CRFs.

Diurnal biting periodicity of parous Simulium (Diptera: Simuliidae) vectors in the onchocerciasis Amazonian focus.

We describe the hourly patterns of parous biting activity of the three main simuliid vectors of human onchocerciasis in the Amazonian focus straddling between Venezuela and Brazil, namely, Simulium guianense s.l. Wise; S. incrustatum Lutz, and S. oyapockense s.l. Floch and Abonnenc. Time series of the hourly numbers of host-seeking parous flies caught in five Yanomami villages during dry, rainy, and their transition periods from 1995 to 2001 were investigated using harmonic analysis (assuming an underlying circadian rhythm) and periodic correlation (based on Spearman's r). Parous S guianense s.l. showed a bimodal activity pattern, with a minor peak in mid-morning and a major peak at 16:00 h. S. incrustatum exhibited mainly unimodal activity during either early morning or midday according to locality. S. oyapockense s.l. bit humans throughout the day mainly between 10:00 and 16:00 h but also showed bimodal periodicity in some localities. Superimposed on the endogenous, species-specific daily cycles, parous activity showed variation according to locality, season, air temperature and relative humidity, with biting being promoted by warmer and drier hours during wet seasons/periods and reduced during hotter times in dry seasons or transitions. The results are discussed in terms of their implications for blackfly biology and ecology as well as onchocerciasis epidemiology and control.

Human onchocerciasis in the Amazonian area of southern Venezuela: spatial and temporal variations in biting and parity rates of black fly (Diptera: Simuliidae) vectors.

We investigated some entomological factors underlying altitudinal prevalence variation in the Venezuelan Amazonia human onchocerciasis focus. Spatial and temporal variation in relative abundance, daily biting rate, proportion of parous flies, and monthly parous biting rate were studied for the three main simuliid vectors (based on their vectorial competence: Simulium oyapockense s.l. Floch & Abonnenc approximately = S. incrustatum Lutz << S. guianense s.l. Wise). Yanomami villages were selected among sentinel communities of the ivermectin control program, representing hypo- to hyperendemicity conditions of infection. Spatial variation was explored via increasing village altitude on two river systems (A: Ocamo-Putaco and B: Orinoco-Orinoquito). Temporal variation was studied between 1995 and 1999 by sampling the biting population during dry and rainy mouths. Environmental variables included monthly rainfall and maximum river height. Simuliid species composition itself varied along the altitudinal and prevalence gradient. S. oyapockense s.l. prevailed below 150 m. Above this altitude and up to 240 m, S. incrustatum and S. guianense s.l. became more frequently and evenly collected along A but not along B, where S. incrustatum remained absent. The daily biting rate of S. oyapockense s.l. was higher during the dry season along A, whereas the converse took place along B. Daily biting rate of S. incrustatum was lowest during early rains. By contrast, the daily biting rate of S. guianense s.l. was highest during this period. There was a significant negative cross-correlation between proportion of parous of S. oyapockense s.l. and river height (2 and 3 mo lagged), whereas this variable (1 and 2 mo lagged) was positively correlated with the proportion of parous flies for S. incrustatum. Monthly parous biting rate values suggest that the months contributing most to onchocerciasis transmission in the area are likely to be the dry season and the transition periods between seasons.

Phosphoglucomutase and trehalase isoenzymes of Venezuelan simulium vectors of Onchocerca volvulus.

Phosphoglucomutase (PGM) and trehalase (Tre) isoenzymes of five species of Simulium blackflies (Diptera: Simuliidae), vectors of onchocerciasis in Venezuela, were investigated by means of a portable electrophoresis field kit. Tre differed between S. incrustatum and S. oyapockense s.l. Electrophoretic variation of Tre in other members of the S. amazonicum and S. incrustatum groups merit further investigation. PGM appears to be more useful for separating populations within species complexes. Multiple populations and/or seasonal changes in population structure of S. guianense s.l., S. exiguum s.l. and S. metallicum s.l. were inferred from elecrophoretic variation of PGM.

Onchocerca-Simulium complexes in Venezuela: can human onchocerciasis spread outside its present endemic areas?

The compatibility between sympatric and allopatric combinations of Onchocerca volvulus-anthropophilic species of Simulium was studied in the north-eastern focus of human onchocerciasis as well as in a densely populated locality of the Amazonas State in Venezuela. The objectives were to test the conjecture that local adaptation exists between the parasite and its vectors (the Onchocerca-Simulium complex hypothesis), and assess the possibility of the infection spreading from its present distributional range. For the homologous combination, O. volvulus-S. metallicum cytospecies E in Anzoátegui State (north-eastern focus), parasite yield was 45% in contrast to 1% for the heterologous, southern parasite-S. metallicum infection. This was significantly lower than the parasite yield (4-10%) expected after allowing for the effect of density-dependent limitation of infective larval output described in this paper for S. metallicum. The population of S. exiguum s.l. from southern Venezuela allowed no larval development beyond the L1 stage of either northern or southern parasites. Mechanisms for such refractoriness probably operate at the level of the thoracic muscles, not affecting microfilarial uptake or migration out of the bloodmeal. The parasite yield of southern O. volvulus in S. oyapockense s.l. flies biting man at Puerto Ayacucho (Amazonas) was about 1%, in agreement with the figures recorded for highly compatible sympatric combinations such as O. volvulus-S. ochraceum s.l. in Guatemala. No infective larval development of the northern parasite was observed in southern S. oyapockense. These results, together with considerations of typical worm burdens in the human host, presence/absence of armed cibaria in the simuliids, parasite-induced vector mortality, and fly biting rates, suggest a lower potential for onchocerciasis to spread between the northern and southern endemic areas of Venezuela than that between Amazonian hyperendemic locations and settlements outside this focus with high densities of S. oyapockense s.l.

Onchocerciasis in the Amazonian focus of southern Venezuela: altitude and blackfly species composition as predictors of endemicity to select communities for ivermectin control programmes.

In preparation for an ivermectin distribution programme, the prevalence and intensity of infection due to Onchocerca volvulus as well as the species composition and abundance of Simulium vectors were investigated in 22 Yanomami communities situated along 2 altitudinal transects in the southern Venezuelan onchocerciasis focus. These transects corresponded to the Ocamo-Putaco and Orinoco-Orinoquito river systems, covering a range of elevation between 50 m and 740 m above sea level (asl). A total of 831 people underwent parasitological examination in this survey and an additional 196 patients from a previous study, at an altitude of 950 m, were included in the analysis. A total of 92,659 man-biting blackflies were collected and identified to morphospecies. S. oyapockense s.l. was the predominant simuliid up to 150 m asl, whereas S. guianense s.l. and S. incrustatum s.l. prevailed above 150 m. Communities located below 150 m were found to range from hypo- to mesoendemic; all villages above 150 m proved to be hyperendemic (> 60% microfilarial prevalence) and mass ivermectin treatment should be implemented. Age above 10-14 years, altitude of the village and biting rate of S. guianense s.l. up to 200 m asl were found to be statistically significant independent predictors of infection by multivariate logistic regression using a spline model. There were no differences in infection status according to sex. Above 200 m, microfilarial rate and density remained approximately constant, prevalence averaging 79% regardless of blackfly abundance. For the implementation of ivermectin-based onchocerciasis control programmes in the Amazonian focus, altitude and species composition of the blackfly population might be adopted as useful indicators aiding selection of the most affected communities. However, below 200 m additional parasitological indicators may also be necessary. As a direct result of this study, regular mass-ivermectin delivery to meso- and hyperendemic communities is now in progress.

Density-dependent processes in the transmission of human onchocerciasis: intensity of microfilariae in the skin and their uptake by the simuliid host.

The transmission success of Onchocerca volvulus is thought to be influenced by a variety of regulatory or density-dependent processes that act at various points in the two-host life-cycle. This paper examines one component of the life-cycle, namely, the ingestion of microfilariae by the simuliid vector, to assess the relationship between intake of larvae and the density of parasites in the skin of the human host. Analysis is based on data from three areas in which onchocerciasis is endemic and includes published information as well as new data collected in field studies. The three areas are: Guatemala (Simulium ochraceum s.l.), West and Central Africa (savanna members of the S. damnosum complex), and South Venezuela (S. guianense). The data record experimental studies of parasite uptake by flies captured in the field and fed to repletion on locally infected subjects who harboured varying intensities of dermal microfilarial infection. Regression analyses of log transformed counts of parasite burdens ingested by the flies plotted against log transformed counts of microfilariae per mg of skin revealed little evidence for saturation in parasite uptake by the flies as the intensity in the human host increased. There was a positive and highly significant rank correlation between both variables for the three blackfly species. In an alternative analysis a model was fitted to data on prevalence of flies with ingested microfilariae (mff) versus dermal mean intensities. The model assumed an overdispersed distribution of the number of mff/fly and a given functional relationship between intake and skin load. The results of both approaches were consistent. It is concluded that parasite ingestion by the vector host is not strongly density dependent in the three geographical areas and ranges of dermal loads examined. It therefore appears that this transmission process is of reduced importance as a regulatory mechanism in the dynamics of parasite population growth.