Positive-case follow up for lymphatic filariasis after a transmission assessment survey in Haiti

BackgroundLymphatic filariasis (LF) has been targeted for global elimination as a public health problem since 1997. The primary strategy to interrupt transmission is annual mass drug administration (MDA) for ≥5 years. The transmission assessment survey (TAS) was developed as a decision-making tool to measure LF antigenemia in children to determine when MDA in a region can be stopped. The objective of this study was to investigate potential sampling strategies for follow-up of LF-positive children identified in TAS to detect evidence of ongoing transmission.Methodology/Principle findingsNippes Department in Haiti passed TAS 1 with 2 positive cases and stopped MDA in 2015; however, 8 positive children were found during TAS 2 in 2017, which prompted a more thorough assessment of ongoing transmission. Purposive sampling was used to select the closest 50 households to each index case household, and systematic random sampling was used to select 20 households from each index case census enumeration area. All consenting household members aged ≥2 years were surveyed and tested for circulating filarial antigen (CFA) using the rapid filarial test strip and for Wb123-specific antibodies using the Filaria Detect IgG4 ELISA. Among 1,927 participants, 1.5% were CFA-positive and 4.5% were seropositive. CFA-positive individuals were identified for 6 of 8 index cases. Positivity ranged from 0.4–2.4%, with highest positivity in the urban commune Miragoane. Purposive sampling found the highest number of CFA-positives (17 vs. 9), and random sampling found a higher percent positive (2.4% vs. 1.4%).Conclusions/SignificanceOverall, both purposive and random sampling methods were reasonable and achievable methods of TAS follow-up in resource-limited settings. Both methods identified additional CFA-positives in close geographic proximity to LF-positive children found by TAS, and both identified strong signs of ongoing transmission in the large urban commune of Miragoane. These findings will help inform standardized guidelines for post-TAS surveillance.     

V˙O2peak and the gas-exchange anaerobic threshold during incremental arm cranking in able-bodied and paraplegic men

Resting energy expenditure, peak oxygen uptake (VO2peak) and the gas-exchange anaerobic threshold (Than) were measured during incremental arm cranking (15 W x min(-1)) in six able-bodied (AB) and six paraplegic (P) subjects. Only male subjects with traumatic spinal cord injuries in the area of the 10-12th thoracic segment were included in the P group. All AB and P subjects were physically active. Mean (SE) values for age and body mass were 28 (2) years and 78.9 (3.9) kg for the AB group and 32 (4) years and 70.8 (7.9) kg for the P group (P>0.05). Resting energy expenditure values were not found to be significantly different between AB [5.8 (0.2) kJ x min(-1)] and P [5.1 (0.3) kJ min(-1)] subjects. Mean VO2peak values were 29.3 (2.4) ml x kg(-1) min(-1) and 29.6 (2.2) ml x kg(-1) x min(-1) for the AB and P groups, respectively (P>0.05). Absolute oxygen uptake values measured at two gas-exchange anaerobic threshold (Than) were not significantly different between the two groups. However, the Than occurred at a significantly higher percentage of VO2peak in the P [58.9 (1.7)%] group than in the AB [50.0 (2.8)%] group (P<0.05). Moreover, respiratory exchange ratio (R) values obtained at the Than and at 15, 45, 60, 75 and 90 W of incremental exercise were significantly lower in the P group than in the AB group. Heart rates were significantly elevated at every submaximal work stage (15-120 W) in the P group compared to the AB group (P<0.05). These findings suggest that chronic daily wheelchair activity produces local adaptations in the functional upper-body musculature, which reduce glycogenolysis and increase the rate of lipid utilization (lower R) during arm exercise. These local adaptations may be in part responsible for the significantly higher Than observed for arm exercise in P subjects, even though VO2peak values were essentially the same for both groups.     

Response of a traplining hummingbird to changes in nectar availability

Theory predicts that nectarivores respond to changes in profitabilityof patches of flowers or feeders by adjusting visitation rateto increase reward size. We conducted a set of experiments inan outdoor enclosure with seven feeders to determine how Phaethornislongirostris, a traplining hummingbird, adjusts its visitationrates in response to changes in sucrose solution delivery rates.Each experiment tested the response of P. longirostris to thefollowing changes in the timing and volume of sucrose solutiondelivery: (1) increases in sucrose solution abundance at allfeeders (mimicking seasonal increases in numbers of open flowersor nectar output); (2) large changes in sucrose solution availabilityat one feeder (mimicking increases or decreases of patch profitability);and (3) sudden unexpected decreases in sucrose solution availabilityat one feeder (mimicking loss of nectar to competitors). Wefound that P. longirostris (1) decreased visitation rates whenthe sucrose solution delivery rate was higher at all feeders,(2) increased visitation rates to individual feeders when their profitabilityincreased for whole days but did not significantly decrease visitationrates when feeder output decreased; and (3) responded to sudden foodlosses at a feeder (due to simulated competition) by increasinguse of that feeder for 1 or 2 h after the loss.     

Diel movement of smallmouth yellowfish Labeobarbus aeneus in the Vaal River,South Africa

Diel movements of Orange–Vaal smallmouth yellowfish Labeobarbus aeneus (Burchell, 1822) in the Vaal River, South Africa, were determined by externally attaching radio transmitters to 11 adult fish and manually tracking them between March and May 2012. Twenty-four radio telemetry monitoring surveys produced 2 304 diel tracks. At night, yellowfish displayed a preference for slow shallow (<0.3?m s?1, <0.5?m) and fast shallow habitats (>0.3?m s?1, <0.3?m), whereas by day they avoided these habitats, preferring fast deep areas (>0.3?m s?1, >0.3?m). The average total distance of 272?m moved per 24-hour period was three times greater than the diel range, and the average maximum displacement per minute was significantly higher in daytime (4?m) than at night (1.5?m). These findings suggest that L. aeneus is active primarily during the day in fast-flowing, deeper waters, and relatively inactive at night, when it occupies shallower habitats. This behaviour should be further explored to identify causal mechanisms underlying the diel habitat shifts in this species such as water temperature, foraging tactics and/or predator avoidance.     

EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter leukodystrophy

Vanishing white matter disease (VWM) is a heritable leukodystrophy linked to mutations in translation initiation factor 2B (eIF2B). Although the clinical course of this disease has been relatively well described, the cellular consequences of EIF2B mutations on neural cells are unknown. Here we have established cell cultures from the brain of an individual with VWM carrying mutations in subunit 5 of eIF2B (encoded by EIF2B5). Despite the extensive demyelination apparent in this VWM patient, normal-appearing oligodendrocytes were readily generated in vitro. In contrast, few GFAP-expressing (GFAP+) astrocytes were present in primary cultures, induction of astrocytes was severely compromised, and the few astrocytes generated showed abnormal morphologies and antigenic phenotypes. Lesions in vivo also lacked GFAP+ astrocytes. RNAi targeting of EIF2B5 severely compromised the induction of GFAP+ cells from normal human glial progenitors. This raises the possibility that a deficiency in astrocyte function may contribute to the loss of white matter in VWM leukodystrophy.     

Onchocerciasis: Target product profiles of in vitro diagnostics to support onchocerciasis elimination mapping and mass drug administration stopping decisions

In June 2021, the World Health Organization (WHO), recognizing the need for new diagnostics to support the control and elimination of onchocerciasis, published the target product profiles (TPPs) of new tests that would support the two most immediate needs: (a) mapping onchocerciasis in areas of low prevalence and (b) deciding when to stop mass drug administration programs. In both instances, the test should ideally detect an antigen specific for live, adult O. volvulus female worms. The preferred format is a field-deployable rapid test. For mapping, the test needs to be ≥ 60% sensitive and ≥ 99.8% specific, while to support stopping decisions, the test must be ≥ 89% sensitive and ≥ 99.8% specific. The requirement for extremely high specificity is dictated by the need to detect with sufficient statistical confidence the low seroprevalence threshold set by WHO. Surveys designed to detect a 1–2% prevalence of a given biomarker, as is the case here, cannot tolerate more than 0.2% of false-positives. Otherwise, the background noise would drown out the signal. It is recognized that reaching and demonstrating such a stringent specificity criterion will be challenging, but test developers can expect to be assisted by national governments and implementing partners for adequately powered field validation.     

Genetic linkage relationships of eight enzyme/electromorph loci in Anopheles minimus

Two laboratory stocks of Anopheles minimus, each fixed for variant electromorphs of esterases, aspartate aminotransferase, hydroxyacid dehydrogenase, phosphogluconate dehydrogenase, mannose phosphate isomerase and glycerol dehydrogenase were used to assess linkage relationships between presumed gene loci controlling this variation. The two F₁, which had been obtained from crossing the stocks, were backcrossed to a parental stock. Three loci controlled the esterases and one locus each of the other enzymes. Mpi is sex-linked. The rest are autosomal and suggested relationships are: Pgd 2.3% recombination from Aat and unlinked to any other loci; Est-1-33.8%-Est-3-31.5%-Est-2-21.0%-Had. Gcd is unlinked to any other locus.There was evidence of strong interaction between the X chromosome of one stock and autosomes of the other in which individuals bearing the X chromosome of the one suffered relatively greater mortality and had delayed development with respect to other genotypic classes.     

A systems model approach to the ventilatory anaerobic threshold

An analogue systems model of whole-body human bioenergetics predicts a change in kinetics of VO2 time series values as a result of exercise levels above an anaerobic threshold. Plotted VO2 results from exercising subjects appear to confirm this change. The purpose of this study is to describe the background to the systems model analogue of the anaerobic threshold and a test procedure devised to estimate this threshold. The estimate so obtained has the dual advantages of being based on model theory and of not being subject to the sort of ambient variations inherent in a single-test determination. A non-homogeneous group of eight subjects comprising a full replicate of a 2(3) factorial experimental design, with factors age, sex and training status, took part in the study. On one hand the results indicate acceptance of the systems model theory. On the other, the analogue threshold measure possesses corresponding properties to the conventional anaerobic threshold. It is higher for trained (155-214 W) than for untrained subjects (108-158 W), higher for males (149-214 W) than for females (108-170 W), and displays no evident interaction effects. Results for the VO2 time constant and for the work efficiency, display similar effects except for an interaction in the latter between age and training status. These experimental findings are regarded as confirmatory of the nature of the analogue threshold measure.     

Longitudinal Monitoring of the Development of Antifilarial Antibodies and Acquisition of Wuchereria bancrofti in a Highly Endemic Area of Haiti

Antifilarial antibody testing has been established as a sensitive and specific method of diagnosing lymphatic filariasis. However, the development of serological responses to specific filarial antigens and their relationship to acquisition of infection is poorly understood. In order to evaluate whether the development of antigen specific antifilarial antibodies precedes microfilaremia and antigenemia, we compared the antibody responses of serum samples collected between 1990 and 1999 from a cohort of 142 Haitian children followed longitudinally. Antigen status was determined using the Og4C3 ELISA and the presence of microfilaremia was detected using microscopy. Antibody responses to Wb123, a Wuchereria bancrofti L3 antigen, were measured using a Luciferase Immunoprecipitation System (LIPS) assay. Antibody responses to Bm14 and Bm33, Brugia malayi antigens and to a major surface protein (WSP) from Wolbachia were analyzed using a multiplex bead assay. Over follow-up, 80 (56%) of the children became antigen-positive and 30 (21%) developed microfilaremia. Detectable antibody responses to Bm14, Bm33, Wb123, and WSP developed in 95%, 100%, 92%, and 29% of children, respectively. With the exception of WSP, the development of antibody responses generally preceded detection of filarial antigen. Our results show that antifilarial antibody responses can serve as an important epidemiological indicator in a sentinel population of young children and thus, may be valuable as tool for surveillance in the context of lymphatic filariasis elimination programs.     

Energy intake rates and nectar concentration preferences by hummingbirds

Summary In a series of daul choice tests with large volume feeders, rufous hummingbirds preferred sucrose concentrations near those that maximized their instantaneous rates of energy intake. As predicted on theoretical grounds, energy intake rates increased with increasing sucrose concentration to a maximum then decreased above this maximum. Earlier experimental studies suggested that hummingbirds always prefer the highest available concentration. Our results are consistent with the data of these studies, but by using a wider range of concentrations than previous workers, we found that the hummingbirds discriminated against very concentrated solutions.