Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study.

BACKGROUND: COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. METHODS: Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. FINDINGS: In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics. INTERPRETATION: Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.

Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration.

Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance.

Assessment of the performance of small field of view gamma cameras for sentinel node imaging.

OBJECTIVE: To develop a method for the assessment of small field of view (SFOV) gamma cameras using a novel phantom designed to simulate the localization of sentinel nodes in the presence of a high-activity injection site. MATERIALS AND METHODS: The phantom consisted of a cube-shaped acrylic glass support frame. Sixteen acrylic glass plates and nine bars were stacked within the frame to allow a variable configuration of the simulated node depth and node-to-injection site separation. Syringes filled with Tc were used to simulate activity at the injection site and node. Scintigraphic imaging was carried out and the images were assessed subjectively and quantitatively through calculation of the contrast-to-noise ratio. The detection performance of an SFOV gamma camera was then compared with that of a large field of view gamma camera. RESULTS: The detectability studies showed that the SFOV gamma camera could detect low activity in nodes by visual examination of images and with contrast-to-noise ratios ranging from 3 to 62. In particular, the phantom showed the limits of node detection using an SFOV gamma camera over activity ratios less than 1 : 100 and at depths below 45 mm with 25 mm of node-to-injection site separation. Visual subjective assessment of images acquired under the same conditions showed that the SFOV gamma camera was superior to a large field of view camera for the detection of nodes at a node-to-injection site separation of 25 mm. CONCLUSION: A low-cost phantom has been designed and fabricated that provides a versatile method for the assessment of SFOV gamma cameras intended for sentinel node imaging.

The metabolic cost of incline locomotion in the Svalbard rock ptarmigan (Lagopus muta hyperborea): the effects of incline grade and seasonal fluctuations in body mass.

In a terrestrial environment animals must locomote over varying terrain; despite this, the majority of studies of animal locomotion focus on level locomotion. The influence moving up an inclined surface has on the metabolic cost of locomotion and the efficiency with which animals perform positive work against gravity is still not well understood. Generally speaking, existing data sets lack consistency in the use of grades, further compounded by differences between species in terms of morphology and locomotor gait. Here we investigated the metabolic cost of locomotion using respirometry in the Svalbard ptarmigan (Lagopus muta hyperborea). The Svalbard ptarmigan provides a unique opportunity to investigate the cost of incline locomotion as it undergoes a seasonal fluctuation in body mass, which doubles in winter, meaning the requirement for positive mechanical work also fluctuates with season. We demonstrate that at the same degree of incline, the cost of lifting 1 kg by 1 vertical metre remains relatively constant between seasons despite the large differences in body mass from summer to winter. These findings are consistent with the notion that positive mechanical work alone dictates the cost of lifting above a certain body mass. However, our data indicate that this cost may vary according to the degree of incline and gait.

Understanding sex differences in the cost of terrestrial locomotion.

Little is known regarding the physiological consequences of the behavioural and morphological differences that result from sexual selection in birds. Male and female Svalbard rock ptarmigans (Lagopus muta hyperborea) exhibit distinctive behavioural differences during the breeding season. In particular, males continuously compete for and defend territories in order to breed successfully, placing large demands on their locomotor system. Here, we demonstrate that male birds have improved locomotor performance compared with females, showing both a lower cost of locomotion (CoL) and a higher top speed. We propose that the observed sex differences in locomotor capability may be due to sexual selection for improved male performance. While the mechanisms underlying these energetic differences are unclear, future studies should be wary when pooling male and female data.

Reduced metabolic cost of locomotion in Svalbard rock ptarmigan (Lagopus muta hyperborea) during winter.

The Svalbard rock ptarmigan, Lagopus muta hyperborea experiences extreme photoperiodic and climatic conditions on the Arctic archipelago of Svalbard. This species, however, is highly adapted to live in this harsh environment. One of the most striking adaptations found in these birds is the deposition, prior to onset of winter, of fat stores which may comprise up to 32% of body mass and are located primarily around the sternum and abdominal region. This fat, while crucial to the birds' survival, also presents a challenge in that the bird must maintain normal physiological function with this additional mass. In particular these stores are likely to constrain the respiratory system, as the sternum and pelvic region must be moved during ventilation and carrying this extra load may also impact upon the energetic cost of locomotion. Here we demonstrate that winter birds have a reduced cost of locomotion when compared to summer birds. A remarkable finding given that during winter these birds have almost twice the body mass of those in summer. These results suggest that Svalbard ptarmigan are able to carry the additional winter fat without incurring any energetic cost. As energy conservation is paramount to these birds, minimising the costs of moving around when resources are limited would appear to be a key adaptation crucial for their survival in the barren Arctic environment.