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Countries in the Indian subcontinent have committed to reducing the incidence of kala-azar, a clinical manifestation of visceral leishmaniasis, to below 1 in 10,000 by 2020. We address the role of timing of use and accuracy of diagnostics in kala-azar control and elimination. We use empirical data on health-seeking behaviour and health-system performance from the Indian state of Bihar, Bangladesh and Nepal to parameterize a mathematical model. Diagnosis of cases is key to case management, control and surveillance. Treatment of cases prevents onward transmission, and we show that the differences in time to diagnosis in these three settings explain the observed differences in incidence. Shortening the time from health-care seeking to diagnosis is likely to lead to dramatic reductions in incidence in Bihar, bringing the incidence down to the levels seen in Bangladesh and Nepal. The results emphasize the importance of maintaining population and health-system awareness, particularly as transmission and disease incidence decline. We explore the possibility of diagnosing patients before the onset of clinical kala-azar (before 14 days fever), and show that this could have a marked impact on incidence, even for a moderately sensitive test. However, limited specificity (that results in false positives) is a major barrier to such a strategy. Diagnostic tests of high specificity used at an early stage of active infection, even if sensitivity is only moderate, could have a key role in the control of kala-azar, and prevent its resurgence when paired with the passive health-care system and tests of high sensitivity, such as the test for rK39 antibody response.This article has not been written or reviewed by Nature editors. Nature accepts no responsibility for the accuracy of the information provided.

ABSTRACTCurrently, respiratory syncytial virus (RSV) infection is identified in epidemiological studies by virus antigen or nucleic acid detection in combination with serology. Oral-fluid specimens may provide a noninvasive alternative to blood, and oral fluid is more suitable for sampling outside of the clinic setting. We evaluated an indirect enzyme-linked immunosorbent assay for the detection of RSV-specific immunoglobulin G (IgG) and IgA by using oral-fluid samples collected from individuals with RSV infections confirmed by an immunofluorescent antibody test. For five children sampled repeatedly from birth, antibody profiles in oral fluid quite consistently tracked those in paired sera, and RSV infections were detected by rising titers of antibodies of at least one Ig class. Specific IgG responses were generally more reliable than IgA responses, except in early infancy, where the reverse was sometimes true. For a further five young children from whom oral fluid was collected weekly following RSV infection, boosted antibody responses, frequently of a transient nature, lasting a few weeks, were observed; specific IgG responses were of longer duration and more pronounced than specific IgA responses. Our data show significant promise for the use of oral fluid alone in RSV infection surveillance. The observed rapid dynamics of the antibody responses are informative in defining study sampling intervals.

Respiratory syncytial virus (RSV) causes significant burden of disease during infancy and childhood. This study examined the genetic relatedness of RSV positive samples from child inpatients and outpatients and a birth cohort from a rural coastal district of Kenya and also the distribution of strains between these three groups. Clinical samples were collected over a 4‐year period in Kilifi District, Kenya from community and hospital surveillance. Three hundred ninety seven of 1,044 nasal specimens from children (under 5 years old) attending Kilifi District Hospital, and from community‐monitored infants, were positive for RSV by multiplex RT‐PCR. Of these, 376 samples were analysed further by restriction fragment length polymorphisms (RFLP) of the nucleocapsid (N) and attachment (G) protein genes. The G gene was sequenced for 109 samples and phylogenetic analysis carried out. The group A samples from Kilifi fell into two clusters based on G gene sequences, while only one group B cluster was observed. One RSV‐B sample from 2003 demonstrated the presence of a 60‐nucleotide duplication within the G gene, clustering with similar isolates from Buenos Aries from 1999. All had similar sequences to isolates from the UK, USA, Spain, or Uruguay. The Kilifi District samples showed greater than 97% homology to isolates from South Africa and Mozambique and 91–94% homology to isolates from The Gambia. Samples from different sources, clearly differing in disease severity, did not differ in genotype characteristics, suggesting that disease causing variants are a general reflection of infections within this community. J. Med. Virol. 74:344–354, 2004. © 2004 Wiley‐Liss, Inc.

Many pathogens exhibit antigenic diversity and elicit strain–specific immune responses. This potential for cross–immunity structure in the host resource motivates the development of mathematical models, stressing competition for susceptible hosts in driving pathogen population dynamics and genetics. Here we establish that certain model formulations exhibit characteristics of prototype pattern–forming systems, with pathogen population structure emerging as three possible patterns: (i) incidence is steady and homogeneous; (ii) incidence is steady but heterogeneous; and (iii) incidence shows oscillatory dynamics, with travelling waves in strain–space. Results are robust to strain number, but sensitive to the mechanism of cumulative immunity.

Infection experiments provide a basis for understanding how epidemics propagate through individuals, emphasizing the importance of diagnostics.