Assessment of dose to functional sub-structures in the lower urinary tract in locally advanced cervical cancer radiotherapy.

PURPOSE: To provide an analysis of dose distribution in sub-structures that could be responsible for urinary toxicity after Image-Guided Adaptive BrachyTherapy (IGABT) in Locally Advanced Cervical Cancer (LACC). METHODS: 105 LACC patients treated with radiochemotherapy and IGABT were selected. Sub-structures (bladder wall, trigone, bladder neck, urethra) were contoured on IGABT-planning MRIs. D2cm3 and D0.1cm3, ICRU Bladder-Point (ICRU BP) and Posterior-Inferior Border of Symphysis points (PIBS, PIBS + 2 cm, PIBS - 2 cm) doses were extracted. Internal-Urethral-Ostium (IUO) and PIBS-Urethra (PIBS-U) points were defined as urethral dose surrogates. Finally, the Vaginal Reference Length (VRL) was extracted. Values were converted into total EBRT + BT equivalent dose in 2 Gy fractions using α/ß = 3 and T1/2 = 1.5 h. RESULTS: Median D2cm3 for bladder and trigone were 71.7[interquartile-range:66.5;74.1]Gy and 57.8[53.3;63.6]Gy, respectively, while median D0.1cm3 were 82.2[77.6;89.1]Gy and 70.7[62.0;76.7]Gy, respectively. Median ICRU BP dose was 63.7[56.5;70.5]Gy and correlated with trigone D2cm3 and D0.1cm3, while bladder and trigone D2cm3 had poor correlation (R2 = 0.492), as well as D0.1cm3 (R2 = 0.356). Bladder neck D0.1cm3 was always lower than trigone D0.1cm3 and higher than IUO. Correlation between PIBS + 2 cm and IUO was poor (R2 = 0.273), while PIBS and PIBS-U were almost equal (R2 = 0.990). VRL correlated with dose to bladder base. CONCLUSIONS: The study confirmed that ICRU BP and trigone doses correlate. Bladder D2cm3 is not representative of trigone dose because hotspots are often placed in the bladder dome. VRL is a good indicator for bladder base sparing. In addition to D2cm3 and D0.1cm3 for whole bladder, ICRU BP, trigone D2cm3 and D0.1cm3, IUO and PIBS are useful for lower urinary tract reporting.

Ultrasound-guided lumbar plexus block in volunteers; a randomized controlled trial.

Background: The currently best-established ultrasound-guided lumbar plexus block (LPB) techniques use a paravertebral location of the probe, such as the lumbar ultrasound trident (LUT). However, paravertebral ultrasound scanning can provide inadequate sonographic visibility of the lumbar plexus in some patients. The ultrasound-guided shamrock LPB technique allows real-time sonographic viewing of the lumbar plexus, various anatomical landmarks, advancement of the needle, and spread of local anaesthetic injectate in most patients. We aimed to compare block procedure outcomes, effectiveness, and safety of the shamrock vs LUT. Methods: Twenty healthy men underwent ultrasound-guided shamrock and LUT LPBs (2% lidocaine­adrenaline 20 ml, with 1 ml diluted contrast added) in a blinded randomized crossover study. The primary outcome was block procedure time. Secondary outcomes were procedural discomfort, number of needle insertions, injectate spread assessed with magnetic resonance imaging, sensorimotor effects, and lidocaine pharmacokinetics. Results: The shamrock LPB procedure was faster than LUT (238 [sd 74] vs 334 [156] s; P=0.009), more comfortable {numeric rating scale 0­10: 3 [interquartile range (IQR) 2­4] vs 4 [3­6]; P=0.03}, and required fewer needle insertions (2 [IQR 1­3] vs 6 [2­12]; P=0.003). Perineural injectate spread seen with magnetic resonance imaging was similar between the groups and consistent with motor and sensory mapping. Zero/20 (0%) and 1/19 (5%) subjects had epidural spread after shamrock and LUT (P=1.00), respectively. The lidocaine pharmacokinetics were similar between the groups. Conclusions: Shamrock was faster, more comfortable, and equally effective compared with LUT. Clinical trial registration: NCT02255591

Displacement of popliteal sciatic nerve catheters after major foot and ankle surgery: a randomized controlled double-blinded magnetic resonance imaging study.

BACKGROUND: Popliteal sciatic nerve catheters (PSNCs) are associated with a high frequency of displacement. We aimed to estimate the frequency of catheter displacement after 48 h with magnetic resonance imaging (MRI) in patients with PSNCs after major foot and ankle surgery randomized to catheter insertion either with a short-axis in-plane (SAX-IP) approach perpendicular to the nerve or with a short-axis out-of-plane (SAX-OOP) approach parallel to the nerve. METHODS: Forty patients were randomly allocated to SAX-IP or SAX-OOP PSNC. Ropivacaine 0.75% 20 ml was injected via the catheter followed by ropivacaine 0.2% 10 ml h(-)1 infusion. Correct primary catheter placement was ensured after initial injection of local anaesthetic via the catheter. Forty-eight hours after insertion, MRI was performed after injection of saline with added contrast (Dotarem) via the catheter. The primary outcome was catheter displacement estimated as the frequency of spread of contrast exclusively outside the paraneurium. RESULTS: All patients had correct primary catheter placement. The frequency of displacement 48 h after insertion of the PSNC was 40% when inserted perpendicular to the nerve vs 10% parallel to the nerve (difference was 30 percentage points, 95% CI: 3-53 percentage points). The relative risk of displacement was four times larger (95% CI: 0.8-10, P<0.028) in the SAX-IP vs the SAX-OOP group. The morphine consumption was 150% greater in the SAX-IP compared with the SAX-OOP group. CONCLUSION: Popliteal sciatic nerve catheters for major foot and ankle surgery inserted with ultrasound guidance parallel to the sciatic nerve have a significantly lower frequency of displacement compared with those inserted perpendicular to the nerve. CLINICAL TRIAL REGISTRATION: NCT02200016.

The suprasacral parallel shift vs lumbar plexus blockade with ultrasound guidance in healthy volunteers--a randomised controlled trial.

Surgical anaesthesia with haemodynamic stability and opioid-free analgesia in fragile patients can theoretically be provided with lumbosacral plexus blockade. We compared a novel ultrasound-guided suprasacral technique for blockade of the lumbar plexus and the lumbosacral trunk with ultrasound-guided blockade of the lumbar plexus. The objective was to investigate whether the suprasacral technique is equally effective for anaesthesia of the terminal lumbar plexus nerves compared with a lumbar plexus block, and more effective for anaesthesia of the lumbosacral trunk. Twenty volunteers were included in a randomised crossover trial comparing the new suprasacral with a lumbar plexus block. The primary outcome was sensory dermatome anaesthesia of L2-S1. Secondary outcomes were peri-neural analgesic spread estimated with magnetic resonance imaging, sensory blockade of dermatomes L2-S3, motor blockade, volunteer discomfort, arterial blood pressure change, block performance time, lidocaine pharmacokinetics and complications. Only one volunteer in the suprasacral group had sensory blockade of all dermatomes L2-S1. Epidural spread was verified by magnetic resonance imaging in seven of the 34 trials (two suprasacral and five lumbar plexus blocks). Success rates of the sensory and motor blockade were 88-100% for the major lumbar plexus nerves with the suprasacral technique, and 59-88% with the lumbar plexus block (p > 0.05). Success rate of motor blockade was 50% for the lumbosacral trunk with the suprasacral technique and zero with the lumbar plexus block (p < 0.05). Both techniques are effective for blockade of the terminal nerves of the lumbar plexus. The suprasacral parallel shift technique is 50% effective for blockade of the lumbosacral trunk.

Bancroftian filariasis: house-to-house variation in the vectors and transmission -- and the relationship to human infection -- in an endemic community of coastal Tanzania.

The house-to-house variation in Wuchereria bancrofti vector abundance and transmission intensity, and the relationship of these parameters to human infection, were investigated in an endemic community in coastal Tanzania. Vector mosquitoes were collected in light traps set up in 50 randomly selected households once weekly for 1 year. They were identified, dissected and checked for filarial larvae. Vector densities and transmission potentials varied markedly between households, both for all vectors combined and for the individual vector species (Anopheles gambiae s.1., An. funestus and Culex quinquefasciatus), even between households located close to each other. The variation in vector abundance was probably mainly attributable to differences in the distance to breeding sites, to specific household features likely to ease mosquito entry and hiding, and to the number of household inhabitants. Household annual biting rates (ABR) correlated positively with household annual transmission potentials (ATP), indicating that intense vector biting led to a high transmission intensity. Intriguingly, however, the human filarial-infection status (as indicated by microfilaraemia or circulating filarial antigenemia) did not differ significantly between households with relatively high and lower ABR or ATP. Possible reasons for this result include the long time required for W. bancrofti infection to establish in humans, human behaviour affecting exposure, the sharing of mosquito populations between households, and differential susceptibility of humans to infection. The marked heterogeneity in exposure between households, and the lack of immediate relationship between transmission and detectable human infection at household level, should be taken into account when considering the transmission pattern of lymphatic filariasis.

Rapid assessment of the geographical distribution of Mansonella perstans infections in Uganda, by screening schoolchildren for microfilariae.

The geographical distribution of Mansonella perstans infections in Uganda was assessed by day-time examination of school-aged children for microfilariae. Overall, 12,207 children from 76 sites representing the various topographical and ecological zones in the country were examined. Children with M. perstans microfilaraemia were detected at 47 (61.8%) of the study sites, with prevalences ranging from 0.4% to 72.8%. A broad, east-west-oriented belt of high endemicity was identified, stretching across the central part of the country from the southern end of Lake Albert to the north-western shores of Lake Victoria. To the north and south of this belt prevalences generally decreased, although high-prevalence foci were also identified in the far north-western and south-eastern corners of the country. Geostatistical interpolation was used to create a map showing the geographical distribution of M. perstans prevalences in Uganda (by ordinary kriging), and to assess the population exposed to M. perstans transmission. Estimates based on population data from 2002 indicated that 20.4 million people (82.6% of the national population) and 6.8 million people (27.5% of the national population) lived in areas where, respectively, >1% and >10% of the school-aged children had M. perstans microfilaraemias. Since the prevalence of M. perstans microfilaraemia is known to increase with age, the overall population prevalences are likely to be even higher than the prevalences observed in the school-aged children. More attention needs to be paid to the public-health implications of this wide-spread but neglected infection.

Rapid assessment of the geographical distribution of lymphatic filariasis in Uganda, by screening of schoolchildren for circulating filarial antigens.

To permit improvements in the targeting of control activities, the geographical distribution of lymphatic filariasis in Uganda was assessed by using a rapid immunochromatographic card test to check school-aged children for Wuchereria bancrofti-specific circulating filarial antigens (CFA). Survey sites were selected to represent the various ecological and topographical diversities in the country. Overall, 17,533 children from 76 sites were examined. CFA-positive cases were detected at 31 of the sites, with prevalences ranging from 0.4% to 30.7%. There appeared to be strikingly more lymphatic filariasis in the north of the country than in the south. The main focus was north of the Victoria Nile, where 27 (66%) of 41 sites had CFA-positive cases, often at high prevalences. Only four (11.4%) of the 35 sites south of the Victoria Nile had CFA-positive cases, and all four were along the western rift valley and had relatively low CFA prevalences. Geostatistical interpolation was used to create a map showing the geographical distribution of CFA prevalences in Uganda (by ordinary kriging), and to assess the population exposed to W. bancrofti transmission. Estimates based on population data from 2002 indicated that approximately 8.7 million people (35.3% of the national population) lived in areas where > 1% of the school-aged children were CFA-positive. CFA prevalences generally decreased with increasing altitude, and no CFA-positive cases were found at sites that were > 1300 m above sea level. Although it gives an under-estimate of the overall community prevalence (a fact that should be taken into account when interpreting the present results and comparing them with the results of other surveys), the screening of schoolchildren for CFA was found to be a simple and useful approach for mapping the geographical distribution of lymphatic filariasis.

Bancroftian filariasis: patterns of vector abundance and transmission in two East African communities with different levels of endemicity.

Intensive monitoring of Wuchereria bancrofti vector abundance and transmission intensity was carried out in two communities, one with high-level endemicity for bancroftian filariasis (Masaika, Tanzania) and the other with low-level (Kingwede, Kenya), on the East African coast. Mosquitoes were collected in light traps, from 50 randomly selected households in each community, once weekly for 1 year. They were identified, dissected and checked for parity and filarial larvae. Anopheles gambiae s. l., An. funestus and Culex quinquefasciatus transmitted W. bancrofti in the two communities but the importance of each of these taxa differed between the communities and by season. The overall vector densities and transmission intensities were significantly higher in Masaika than in Kingwede (the annual biting rate by 3.7 times and the annual transmission potential by 14.6 times), primarily because of differences in the available breeding sites for the vectors and in the vectorial capacity of the predominant vector species. A marked seasonal variation in vector abundance and transmission potential contributed to the complex transmission pattern in the communities. Generally, these indices were higher during and shortly after the rainy seasons than at other times of the year. Considerable differences in W. bancrofti transmission were thus observed between communities within a relatively small geographical area (mainly because of environmentally-determined differences in vector habitats), and these were reflected in the marked differences in infection level in the human populations. The variation in vector abundance, vector composition and transmission intensity in the two communities is discussed in respect to its cause, its effects, and its significance to those attempting to control bancroftian filariasis.

Bancroftian filariasis in 12 villages in Kwale district, Coast province, Kenya - variation in clinical and parasitological patterns.

As part of a larger study on the effects of permethrin-impregnated bednets on the transmission of Wuchereria bancrofti, subjects from 12 villages in the Coastal province of Kenya, south of Mombasa, were investigated. The aims were to update the epidemiological data and elucidate the spatial distribution of W. bancrofti infection. Samples of night blood from all the villagers aged i 1 year were checked for the parasite, and all the adult villagers (aged >/= 15 years) were clinically examined for elephantiasis and, if male, for hydrocele. Overall, 16.0% of the 6531 villagers checked for microfilariae (mff) were found microfilaraemic, although the prevalence of microfilaraemia in each village varied from 8.1%-27.4%. The geometric mean intensity of infection among the microfilaraemic was 322 mff/ml blood. At village level, intensity of the microfilaraemia was positively correlated with prevalence, indicating that transmission has a major influence on the prevalence of microfilaraemia. Clinical examination of 2481 adults revealed that 2.9% had elephantiasis of the leg and that 19.9% of the adult men (10.8%-30.1% of the men investigated in each village) had hydrocele. Although the overall prevalence of microfilaraemia in the study villages had not changed much since earlier studies in the 1970s, both prevalence and intensity varied distinctly between the study villages. Such geographical variation over relatively short distances appears to be a common but seldom demonstrated feature in the epidemiology of bancroftian filariasis, and the focal nature of the geographical distribution should be carefully considered by those mapping the disease.

Relationship between altitude and intensity of malaria transmission in the Usambara Mountains, Tanzania.

There is a consensus that malaria is a growing problem in African highlands. This is surprising because many parts of the highlands were considered too cold to support transmission. In this report, we examined how transmission of Plasmodium falciparum in six villages changed along an altitude transect in the Usambara Mountains, Tanzania, from 300 m to 1700 m. Routine entomological collections were made using spray catches and light traps for 15 mo. Direct estimates of entomological inoculation rates and indirect estimates of vectorial capacity suggested a >1000-fold reduction in transmission intensity between the holoendemic lowland and the hypoendemic highland plateau. Lowland transmission was perennial with a significant peak in the cool season after the long rains in May, when vectors densities were high. In the highlands, low temperatures prevented parasite development in mosquitoes during the cool season rains, and highland transmission was therefore limited to the warm dry season when vector densities were low. The primary effect of increasing altitude was a log-linear reduction in vector abundance and, to a lesser extent, a reduction in the proportion of infective mosquitoes. Highland malaria transmission was maintained at extraordinarily low vector densities. We discuss herein the implications of these findings for modeling malaria and suggest that process-based models of malaria transmission risk should be improved by considering the direct effect of temperature on vector densities. Our findings suggest that variation in the short rains in November and changes in agricultural practices are likely to be important generators of epidemics in the Usambaras.

Haemodynamic properties of PTFE femoropopliteal bypass grafts as determined by a new magnetic resonance technique.

OBJECTIVES: To apply the automatic three dimensional paraboloid (3DP) method for measurement of wall shear stress (WSS), blood flow, blood velocity, and cross sectional graft lumen area to magnetic resonance phase contrast velocity mapping data acquired from polytetrafluoroethylene (PTFE) suprageniculate 6 mm femoropopliteal bypass grafts to determine the biomechanical and haemodynamic properties immediately and three years after implantation. MATERIALS AND METHODS: Two patient cohorts, each of ten patients, with intermittent claudication were investigated by the 3DP method, one group (A) within 36 h after implantation of a femoropopliteal graft and the other group (B) 35 months after implantation. RESULTS: The mean blood flow was 5.9 ml/s (SD: 1.6), and WSS at peak systole was 2.2 N/m2 (SD: 0.6) 5 cm upstream to the distal anastomosis for group A, and 3.7 ml/s (SD: 1.9) and 1.9 N/m2 (SD: 0.4) for Group B. The WSS varied according to the angular position of the graft circumference. The implanted grafts were not circular but had a slightly elliptical circumference with a greater anterior/posterior diameter. CONCLUSION: The 3DP method is a precise tool with subpixel resolution for determining the biomechanical and haemodynamic properties of implanted PTFE grafts, and it can be used to assess graft function immediately after implantation. It is potentially applicable for routine graft surveillance.

Effects of exercise and respiration on blood flow in total cavopulmonary connection: a real-time magnetic resonance flow study.

BACKGROUND: Little is known about blood flow and its relationship to respiration during exercise in patients with total cavopulmonary connection (TCPC). METHODS AND RESULTS: We studied 11 patients 12.4+/-4.6 years (mean+/-SD) of age 5.9+/-2.8 years (mean+/-SD) after TCPC operation. Real-time MRI was used to measure blood flow in the superior vena cava (SVC), inferior vena cava (IVC), and ascending aorta under inspiration and expiration during supine lower-limb exercise (rest, 0.5 and 1.0 W/kg) on an ergometer bicycle. IVC and aortic flow increased from 1.60+/-0.52 and 2.99+/-0.83 L/min per m2 at rest to 2.58+/-0.71 and 3.97+/-1.20 L/min per m2 at 0.5 W/kg and to 3.25+/-1.23 and 4.62+/-1.49 L/min per m2 at 1.0 W/kg (P< or =0.05). SVC flow remained unchanged. Resting flow in the IVC was greater during inspiration (2.99+/-1.25 L/min per m2) than during expiration (0.83+/-0.44 L/min per m2) (inspiratory/mean flow ratio, 1.9+/-0.5), and retrograde flow was present during expiration (11+/-12% of mean flow). The predominance of inspiratory flow in IVC diminished with exercise to an inspiratory/mean flow ratio of 1.5+/-0.2 (P< or =0.05) and 1.4+/-0.3 at 0.5 and 1.0 W/kg, respectively. CONCLUSIONS: In the TCPC, circulation IVC and aortic but not SVC flows increase with supine leg exercise. Inspiration facilitates IVC flow at rest but less so during exercise, when the peripheral pump seems to be more important.

Flow during exercise in the total cavopulmonary connection measured by magnetic resonance velocity mapping.

OBJECTIVE: To measure caval and pulmonary flows at rest and immediately after exercise in patients with total cavopulmonary connection (TCPC). DESIGN: An observational study using the patients as their own controls. SETTING: Using a combination of magnetic resonance (MR) phase contrast techniques and an MR compatible bicycle ergometer, blood flow was measured in the superior vena cava, the tunnel from the inferior vena cava, and in the left and right pulmonary arteries during rest and on exercise (0.5 W/kg and 1.0 W/kg). PATIENTS: Eleven patients aged 11.4 (4.6) years (mean (SD)) were studied 6.3 (3.8) years after TCPC operation. MAIN OUTCOME MEASURES: Volume flow measured in all four branches of the TCPC connection during rest and exercise. RESULTS: Systemic venous return (inferior vena cava plus superior vena cava) increased from 2.5 (0.1) l/min/m2 (mean (SEM)) to 4.4 (0.4) l/min/m2 (p < 0.05) during exercise, with even distribution to the two pulmonary arteries. At rest, inferior vena caval flow was higher than superior vena caval flow, at 1.4 (0.1) v 1.1 (0.1) l/min/m2 (p < 0.05). During exercise, inferior vena caval flow doubled (to 3.0 (0.3) l/min/m2) while superior vena caval flow only increased slightly (to 1.4 (0.1) l/min/m2) (p < 0.05). The increased blood flow mainly reflected an increase in heart rate. The inferior vena caval to superior vena caval flow ratio was 1.4 (0.1) at rest and increased to 1.8 (0.1) (p < 0.05) at 0.5 W/kg, and to 2.2 (0.2) at 1.0 W/kg (p < 0.05). CONCLUSIONS: Quantitative flow measurements can be performed immediately after exercise using MR techniques. Supine leg exercise resulted in a more than twofold increase in inferior vena caval flow. This was equally distributed to the two lungs, indicating that pulmonary resistance rather than geometry decides flow distribution in the TCPC circulation.

Impact of insecticide-treated materials on filaria transmission by the various species of vector mosquito in Africa.

Nocturnally periodic bancroftian filariasis is maintained by three mainly endophilic vectors in East Africa: Culex quinquefasciatus, Anopheles funestus and the An. gambiae complex. Permethrin-impregnated bednets provide considerable protection against these mosquitoes, but the species respond differently. The degree of protection conferred by treated bednets was determined in Kenyan communities where all three vectors actively transmit Wuchereria bancrofti. The annual transmission potential in the communities (i.e. an estimate of the number of human infective, third-stage larvae of W. bancrofti inoculated into each villager each year) was reduced by 92%, through the nets' impact on vector biting rates (reduced by 22%) and their cumulative impact on the annual infective biting rate (reduced by 95%). Thus a modest reduction in the numbers of mosquitoes biting humans, attributable to the use of the insecticide-treated nets, strongly suppressed the risk of W. bancrofti transmission.

Serial magnetic resonance imaging of global and regional left ventricular remodeling during 1 year after acute myocardial infarction.

Biplane long-axis cine MRI was performed in 51 patients 1, 13, 26, and 52 weeks after their first AMI. LV mass index (LVMI) was significantly increased 1 week after AMI (84.3 +/- 16.9 vs. 68.1 +/- 11.4 g/m(2) controls, n = 48, p < 0.001), presumably owing to edema of the infarcted myocardium. Six months after AMI, LVMI decreased to 76.5 +/- 16.4 g/m(2), but had again augmented after 1 year (81.8 +/- 17.3 g/m(2), p < 0.05), suggesting late, compensatory left ventricular hypertrophy. In patients treated with primary percutaneous transluminal coronary angioplasty, LVMI decreased 5% over 1 year, while LVMI increased 10% in patients receiving thrombolysis (p < 0.05). In the entire population, the global increase in LVMI 1 year after AMI seemed to reflect global cavity dilatation with unchanged thickness of the vital myocardium. In conclusion, in patients receiving contemporary treatment, LV remodeling only partially complied with the classical patho-anatomical concept.

Aortic and mitral regurgitation: quantification using moving slice velocity mapping.

Comprehensive assessment of the severity of valvular insufficiency includes quantification of regurgitant volumes. Previous methods lack reliable slice positioning with respect to the valve and are prone to velocity offsets due to through-plane motion of the valvular plane of the heart. Recently, the moving slice velocity mapping technique was proposed. In this study, the technique was applied for quantification of mitral and aortic regurgitation. Time-efficient navigator-based respiratory artifact suppression was achieved by implementing a prospective k-space reordering scheme in conjunction with slice position correction. Twelve patients with aortic insufficiency and three patients with mitral insufficiency were studied. Aortic regurgitant volumes were calculated from diastolic velocities mapped with a moving slice 5 mm distal to the aortic valve annulus. Mitral regurgitant flow was indirectly assessed by measuring mitral inflow at the level of the mitral annulus and net aortic outflow. Regurgitant fractions, derived from velocity data corrected for through-plane motion, were compared to data without correction for through-plane motion. In patients with mild and moderate aortic regurgitation, regurgitant fractions differed by 60% and 15%, on average, when comparing corrected and uncorrected data, respectively. Differences in severe aortic regurgitation were less (7%). Due to the large orifice area of the mitral valve, differences were still substantial in moderate-to-severe mitral regurgitation (19%). The moving slice velocity mapping technique was successfully applied in patients with aortic and mitral regurgitation. The importance of correction for valvular through-plane motion is demonstrated.

Transmission intensity and the immunoepidemiology of bancroftian filariasis in East Africa.

Previous attempts to determine the interactions between filariasis transmission intensity, infection and chronic disease have been limited by a lack of a theoretical framework that allows the explicit examination of mechanisms that may link these variables at the community level. Here, we show how deterministic mathematical models, in conjunction with analyses of standardized field data from communities with varying parasite transmission intensities, can provide a particularly powerful framework for investigating this topic. These models were based on adult worm population dynamics, worm initiated chronic disease and two major forms of acquired immunity (larval- versus adult-worm generated) explicitly linked to community transmission intensity as measured by the Annual Transmission Potential (ATP). They were then fitted to data from low, moderate and moderately high transmission communities from East Africa to determine the mechanistic relationships between transmission, infection and observed filarial morbidity. The results indicate a profound effect of transmission intensity on patent infection and chronic disease, and on the generation and impact of immunity on these variables. For infection, the analysis indicates that in areas of higher parasite transmission, community-specific microfilarial rates may increase proportionately with transmission intensity until moderated by the generation of herd immunity. This supports recent suggestions that acquired immunity in filariasis is transmission driven and may be significant only in areas of high transmission. In East Africa, this transmission threshold is likely to be higher than an ATP of at least 100. A new finding from the analysis of the disease data is that per capita worm pathogenicity could increase with transmission intensity such that the prevalences of both hydrocele and lymphoedema, even without immunopathological involvement, may increase disproportionately with transmission intensity. For lymphoedema, this rise may be further accelerated with the onset of immunopathology. An intriguing finding is that there may be at least two types of immunity operating in filariasis: one implicated in anti-infection immunity and generated by past experience of adult worms, the other involved in immune-mediated pathology and based on cumulative experience of infective larvae. If confirmed, these findings have important implications for the new global initiative to achieve control of this disease.

Wuchereria bancrofti in a community with seasonal transmission: stability of microfilaraemia, antigenaemia and filarial-specific antibody concentrations.

The effect of seasonal transmission on microfilaraemia, antigenaemia and filarial-specific antibody levels in individuals infected with Wuchereria bancrofti was investigated in a follow-up study in an endemic community in north-eastern Tanzania. The subjects were 37 adult male residents who were found to be positive for circulating filarial antigen (CFA) at the beginning of the study (26 of whom were also found microfilaraemic with W. bancrofti at this time). Blood samples were collected from each subject in July 1998, January 1999 and July 1999, during the seasons when transmission intensity was high, low and high, respectively. The mean intensities of microfilaraemia and the mean concentrations of CFA were each slightly higher during the low-transmission season than during the two high-transmission seasons but the differences were not statistically significant (P > 0.05). Similarly, the mean levels of filarial-specific IgG1, IgG2, IgG3, IgG4 or IgE did not differ to a statistically significant degree between the three examination times. Microfilaraemias and the levels of CFA and filarial-specific antibodies all therefore appeared to be remarkably stable and largely unaffected by the seasonal variation in transmission. That no variation in the mean IgG4/IgE ratio was observed over the study period may indicate that the level of resistance to W. bancrofti infection in the study subjects was also unaffected by the transmission season.

Lymphatic filariasis in Uganda: baseline investigations in Lira, Soroti and Katakwi districts.

Baseline epidemiological investigations on lymphatic filariasis were conducted for the first time in Uganda in 3 communities in the districts of Lira (Alebtong area), Soroti (Lwala area) and Katakwi (Obalanga area), located to the north of Lake Kyoga at an altitude of 1000-1100 m above sea level. Individuals from the communities were examined, in April-August 1998, for Wuchereria bancrofti specific circulating antigen (by ICT card test), microfilaraemia (by counting chamber and stained blood-smear techniques) and chronic clinical manifestations of lymphatic filariasis. Endophilic mosquitoes were sampled and dissected for filarial larvae. Prevalences of circulating filarial antigen positivity were 29%, 18% and 30% in the Alebtong, Lwala and Obalanga communities, respectively. Microfilaria (mf) prevalences were 18%, 9% and 21%, and geometric mean mf intensities among mf-positive individuals were 306, 171 and 402 mf/mL blood, in the same communities. Examination of stained blood smears revealed mf of both W. bancrofti and Mansonella perstans, but more than 80% of mf-positive individuals harboured the first of these parasites. Prevalences of hydrocoele in adult (> or = 20 years) males were 28%, 7% and 17%, and prevalences of limb elephantiasis in adults were 9%, 4% and 4%, in the Alebtong, Lwala and Obalanga communities, respectively. Anopheles gambiae s.l. (mainly An. gambiae s.s.) and An. funestus were common in all 3 communities, and showed W. bancrofti infectivity rates of 1.1-1.7% and 1.3-2.9%, respectively. It is concluded that lymphatic filariasis is highly endemic in these high-altitude areas of Uganda, with An. gambiae s.l. and An. funestus being the main vectors.