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The global burden of malaria has been substantially reduced over the past two decades. Future efforts to reduce malaria further will require moving beyond the treatment of clinical infections to targeting malaria transmission more broadly in the community. As such, the accurate identification of asymptomatic human infections, which can sustain a large proportion of transmission, is becoming a vital component of control and elimination programmes. We determined the relationship across common diagnostics used to measure malaria prevalence - polymerase chain reaction (PCR), rapid diagnostic test and microscopy - for the detection of Plasmodium falciparum infections in endemic populations based on a pooled analysis of cross-sectional data. We included data from more than 170,000 individuals comparing the detection by rapid diagnostic test and microscopy, and 30,000 for detection by rapid diagnostic test and PCR. The analysis showed that, on average, rapid diagnostic tests detected 41% (95% confidence interval = 26-66%) of PCR-positive infections. Data for the comparison of rapid diagnostic test to PCR detection at high transmission intensity and in adults were sparse. Prevalence measured by rapid diagnostic test and microscopy was comparable, although rapid diagnostic test detected slightly more infections than microscopy. On average, microscopy captured 87% (95% confidence interval = 74-102%) of rapid diagnostic test-positive infections. The extent to which higher rapid diagnostic test detection reflects increased sensitivity, lack of specificity or both, is unclear. Once the contribution of asymptomatic individuals to the infectious reservoir is better defined, future analyses should ideally establish optimal detection limits of new diagnostics for use in control and elimination strategies.

Mass-screen-and-treat and targeted mass-drug-administration strategies are being considered as a means to interrupt transmission of Plasmodium falciparum malaria. However, the effectiveness of such strategies will depend on the extent to which current and future diagnostics are able to detect those individuals who are infectious to mosquitoes. We estimate the relationship between parasite density and onward infectivity using sensitive quantitative parasite diagnostics and mosquito feeding assays from Burkina Faso. We find that a diagnostic with a lower detection limit of 200 parasites per microlitre would detect 55% of the infectious reservoir (the combined infectivity to mosquitoes of the whole population weighted by how often each individual is bitten) whereas a test with a limit of 20 parasites per microlitre would detect 83% and 2 parasites per microlitre would detect 95% of the infectious reservoir. Using mathematical models, we show that increasing the diagnostic sensitivity from 200 parasites per microlitre (equivalent to microscopy or current rapid diagnostic tests) to 2 parasites per microlitre would increase the number of regions where transmission could be interrupted with a mass-screen-and-treat programme from an entomological inoculation rate below 1 to one of up to 4. The higher sensitivity diagnostic could reduce the number of treatment rounds required to interrupt transmission in areas of lower prevalence. We predict that mass-screen-and-treat with a highly sensitive diagnostic is less effective than mass drug administration owing to the prophylactic protection provided to uninfected individuals by the latter approach. In low-transmission settings such as those in Southeast Asia, we find that a diagnostic tool with a sensitivity of 20 parasites per microlitre may be sufficient for targeted mass drug administration because this diagnostic is predicted to identify a similar village population prevalence compared with that currently detected using polymerase chain reaction if treatment levels are high and screening is conducted during the dry season. Along with other factors, such as coverage, choice of drug, timing of the intervention, importation of infections, and seasonality, the sensitivity of the diagnostic can play a part in increasing the chance of interrupting transmission.

Evidence for asteroidal satellites (moons) has been sought for decades, because the relative frequency of such satellites will bear on the collisional history of the asteroid belt and the Solar System, yet only one has been detected unambiguously1,2,3. Here we report the discovery of a satellite of the asteroid 45 Eugenia, using an adaptive optics system on a ground-based telescope. The satellite has a diameter of about 13 km, and an orbital period of about 4.7 days with a separation of 1,190 km from Eugenia. Using a previously determined4 diameter for Eugenia, we estimate that its bulk density is about 1.2 g cm-3, which is similar to that of the C-type asteroid Mathilde5,6. This implies that Eugenia, also a low-albedo C-type asteroid, may be a rubble pile, or composed of primitive, icy materials of low bulk density.

IT is well established that some of the toxic effects of sulphonamides on animals fed purified diets are caused by inhibition of bacterial synthesis of some B vitamins in the intestine, with consequent development of deficiency states. Few attempts have been made, however, to determine if the sulphonamides have a more fundamental effect on the metabolism of the B vitamins in the animal body. The purpose of the present communication is to make a preliminary report on experiments which suggest that sulphadiazine has an effect on the metabolism of aneurin in the animal body.

Utilization of High-Energy Intermediates of Oxidative Phosphorylation and the Proposed Function of Imidazole Phosphate as an Intermediate in Oxidative Phosphorylation

BASED on his observation that mitochondrial protein-bound phosphohistidine becomes maximally labelled with added radioactive inorganic phosphate before maximum labelling of the mitochondrial ATP is reached, Prof. Boyer concluded in 1963 that protein-bound phosphohistidine is an intermediate in respiratory-chain phosphorylation1. By the summer of 1964, it was generally accepted that phosphohistidine is not on the main pathway of synthesis of mitochondrial ATP, but on the relatively slow side-path catalysed by succinyl-CoA synthetase and nucleosidediphosphate kinase. We had already pointed out early in 1964 that the kinetics of the incorporation were inconsistent with Boyer's theory and supported phosphohistidine as an intermediate on a slow side-path2.

DURING radiobiological work on bacteria it was found by one of us (H. L.) that the effect of ionizing radiation (X-rays) is greatly potentiated if the bacteria are irradiated in a medium in which water is replaced by heavy water1. Thus, for example, with Escherichia coli B and Pseudomonas 6009 the dose-reduction factor was approximately 2, that is, the X-ray dose required to produce a given reduction in the number of colony-forming bacteria on irradiation in deuterium oxide was one half that in water. This effect, however, occurred only if the bacteria were irradiated in presence of oxygen, but not, or only insignificantly, after irradiation under anaerobic conditions.

AMNESIC agents, such as electroconvulsive stimulation, can cause loss of memory for events that occurred before treatment1. Usually as the interval between learning and convulsive treatment is increased, the resulting retrograde amnesia is diminished1–3. This temporal gradient of retrograde amnesia can sometimes cover several years4. Clinical descriptions of the amnesic syndrome suggest that information about the temporal sequence of events can be more severely impaired than other aspects of memory5,6. Thus, an amnesic patient may describe a past event accurately but be unable to report when the event occurred. We have administered a new remote memory test based on former one-season television programmes to psychiatric patients receiving bilateral electroconvulsive therapy (ECT), and report here that memory for temporal order is markedly affected by ECT. ECT caused retrograde amnesia for order information about programmes broadcast from 1 to ∼7 yr before treatment, but not for programmes broadcast from 8–;17 yr before treatment.

SUB-MITOCHONDRIAL particles prepared from horse or ox heart contain two species of cytochrome b in equal amounts, one (bi) affected by antimycin and the other (b) not affected1–3. In addition to its well known inhibitory effect on the respiratory chain, acting between cytochromes b and c1, antimycin brings about an increased reduction of the total cytochrome b present in sub-mitochondrial particles and causes a shift in absorption of 1–2 nm towards longer wavelengths of the b band. This “redshift” is best studied with the wavelength pair 566–560 nm, for the absorption maximum of ferrocytochrome b is at 563 nm, and A566–560 nm is not affected by the redox state of cytochrome b (ref. 1). Sigmoidal curves for the antimycin effect are found with sub-mitochondrial particles4 and with intact white potato (W. D. Bonner and E. C. S., unpublished) or rat heart (H. J. W., J. A. B. and E. C. S., unpublished) mitochondria in the presence of uncoupler, and linear (or hyperbolic) with energized mitochondria (state 4). To explain these antimycin effect curves, it is proposed that antimycin, a multi-site inhibitor in particles, reacts preferentially with and stabilizes a high-energy form of cytochrome bi (bi∼X) (refs. 4 and 5).

Phosphorylation Coupled with the Reduction of Cytochrome C by α-Ketoglutarate in Heart Muscle Granules

THE possible role of vitamin E in respiratory enzyme systems has often been suggested; but supporting evidence of the actual presence of vitamin E in active enzyme preparations has not been published. We have now found appreciable amounts in heart sarcosomal (mitochondrial) fragments (Keilin and Hartree heart-muscle preparation).

Nielsen and Lehninger1 have recently demonstrated the incorporation of phosphorus-32 into organic phosphate during the aerobic oxidation of ferrocytochrome c by rat-liver mitochondria in the presence of adenosine diphosphate, magnesium, versene, antimycin A and inorganic phosphate labelled with phosphorus-32. In the present communication, a net phosphorylation is shown to accompany the same reaction catalysed by rat-heart sarcosomes (mitochondria).

BANDS in the spectra of neutral and ionised nitrogen show unexplained alternating intensities, and the bands of helium are best interpreted if one assumes that only half the lines are observed, the alternate lines being not merely weak but missing altogether (Mecke, Zeits. f. Phys. 26, 227, 1925; 31, 709, 1925). A similar effect seems to be present in oxygen, although the interpretation is less certain. All these molecules are symmetrical, composed of two like atoms. I wish to suggest that the alternations may be connected with the well-known difficulty of assigning the proper period in quantising the rotation of a symmetrical system (Ehrenfest and Tolman, Phys. Rev. 24, 287, 1924).

FRESHLY prepared suspensions of the granular components of heart-muscle (sarcosomes1, interstitial granules2 or mitochondria3) are able to oxidize a number of intermediary metabolites, and to couple this oxidation with the synthesis of adenosine triphosphate from adenosine diphosphate and inorganic phosphate (oxidative phosphorylation)4,5. In agreement with the experience of other workers using preparations from different tissues, it has been found that the heart-muscle sarcosomes rapidly lose their ability to carry out oxidative phosphorylation, especially at temperatures above 0° C. Such aged preparations oxidize succinate at practically unimpaired rate, but the accompanying phosphorylation is lost. The ability to oxidize α-ketoglutarate is lost to about the same extent as the phosphorylation associated with this oxidation, so that the P : O ratio (the number of atoms of inorganic phosphate esterified per atom of oxygen consumed) is not greatly affected. The lability of rat heart sarcosomes is indicated by the following percentages of inactivation of the α-keto-glutaric oxidase system (the enzyme complex required for the aerobic oxidation of α-ketoglutarate to succinate) : 10 min. standing at 15.5° C., 52 per cent inactivation ; 15 min. at 25° C., 94 per cent inactivation. Cat preparations are somewhat more stable (15 min. standing at 25° C., 71 per cent inactivation).

IN the attempts to interpret theoretically the interaction between radiation and matter, two apparently contradictory aspects of the mechanism have been disclosed. On one hand, interference and dispersion demand a continuity similar to that of the classical theory of optics. On the other, the exchange of energy and momentum between radiation and matter presents discontinuous features which have even led to the introduction of the theory of light quanta, denying in its most extreme form the wave constitution of light. The two aspects must be really consistent, but the discontinuous side is apparently the more fundamental, and for this reason any attempt at a consistent interpretation in the present state of science must inevitably appear rather formal. Nevertheless, on the basis of Bohr's correspondence principle, it seems possible to build up a more adequate picture of optical phenomena than has previously existed, by associating the essentially continuous radiation field with the continuity of existence in stationary states, and the discontinuous changes of energy and momentum with the discontinuous transitions from one state to another.

The Succinic Oxidase and Dihydrocozymase Oxidase Systems in Heart Muscle and Kidney Preparations

BOTHE and Geiger have recently performed an experiment on the Compton effect (Die Naturwissenschaften, 13, p. 440, May 15, 1925; Zs. f. Phys., 32, p. 639, 1925) indicating that the recoil electron, and the photoelectron emitted by the scattered radiation, appear simultaneously. Prof. A. H. Compton has made another experiment (Proc. Nat. Acad. Sci., 11, p. 303, 1925), showing that the direction in which the scattered radiation acts in producing ionisation, and the direction of the recoil electron, are related. The natural interpretation of these experiments is in terms of a corpuscular theory of radiation, in which a corpuscular quantum, glancing off a scattering atom with emission of a recoil electron, very soon hits another atom and emits a photoelectron. This contradicts the suggestion, discussed by Bohr, Kramers, and the writer (Phil. Mag., 47, p. 785, 1924), that there was a virtual field, like the ordinary fields of optical theory, emitted during the stationary states of the atom, the function of which was to induce a probability of transition; for on that view the probabilities of ejection of electrons by the scattering and absorbing atoms would be independent, both being induced by a radiation field existing continuously, and the two electrons would be in general ejected at different times and in unrelated directions. I wish to point out, however, that a corpuscular theory still is not in conflict with the main part of the idea of virtual fields.

GOUDSMIT and Uhlenbeck have suggested that the structure of multiple lines in spectra can be made much more comprehensible if it is assumed that the electron itself has a magnetic moment of one Bohr magneton (eh/4mc) and an angular momentum of one-half unit (h/4), which can orient itself in various ways with respect to the normal to the electron orbits. Goudsmit and Uhlenbeck point out (Naturwissenschaften, Nov. 20, 1925) that to obtain such a magnetic moment from the rotation of a Lorentz electron about its axis, there would have to be a peripheral velocity greatly exceeding the speed of light. It can also be easily seen that the magnetic energy with its resulting mass would be much greater than the electrical energy. These difficulties do not seem to be easy to overcome by any small modification of the classical model of the electron. It appears, however, that an entirely different picture of electronic structure, based on the idea of light quanta, is capable of giving a consistent explanation of the energy of the electron, and also of predicting the values of some of the electronic constants.

IN an experiment with a phosphorylating kidney -cyclophorase preparation Loomis and Lipmann1 discovered that 2,4-dinitrophenol could replace the inorganic phosphate necessary for a maximal rate of oxygen uptake with glutamate as the substrate. This observation was confirmed by Teply2 and Judah and Williams-Ashman3, using the same type of enzyme preparation, but the experiment has never been repeated, to our knowledge, with the purer and more tightly coupled mitochondrial preparations that have become available in the last few years. Since the observation of Loomis and Lipmann is of fundamental importance for present-day concepts of respiratory-chain phosphorylation (cf.ref. 4), we have re-investigated the problem with fresh rat-liver mitochondria using a medium with adenosine diphos-phate, glucose and hexokinase to exhaust the endogenous inorganic phosphate of the mitochondria (cf. ref. 5). The result of one of our experiments is given in Fig. 1 and the mean figures obtained in eight experiments have been summarized in Table 1. It can be seen that under our conditions dinitrophenol gives only a small stimulation of the basal oxygen uptake and that phosphate is necessary to obtain maximal oxidation rates.

SIR OLIVER LODGE's letter in NATURE of November 7 on the winding of rivers in plains has induced me to measure the velocity of flow in different parts of a bend in the river Wey near here. A short line—17 feet—was measured on the bank at the bend, and marks set up at right angles to it, and the time taken by blocks of wood to naove between the marks measured with a stop-watch. The distances of the blocks from the inner bank were estimated in terms of the breadth of the river, with the following results:—