The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host–pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8+ T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection1. Mutation within these epitopes can allow viral escape from CD8+ T-cell recognition. Here we analysed viral sequences and HLA alleles from >2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128–135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8+ T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P < 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.

Abstract. The annual incidence of leptospirosis in Barbados is approximately 13 severe cases/100,000. The peak incidence occurs in October to December of each year, coinciding with the months of heaviest rainfall. During the second half of 1995, an epidemic of dengue type 1 infection produced almost 1,000 laboratory-confirmed cases. During the same period, leptospirosis mortality was twice the average, suggesting that some cases of leptospirosis were being misdiagnosed and treated inappropriately. Sera from patients investigated for dengue or leptospirosis were analyzed retrospectively to determine the extent of misdiagnosis. During 1995 and 1996, 31 of 139 and 29 of 93 patients, respectively, were confirmed as having leptospirosis. Sera from the remaining leptospirosis-negative patients were tested for IgM antibodies to dengue virus. During 1995 and 1996, 48 of 108 patients and 21 of 64 patients, respectively, were found to have dengue. In 1997, sera from all patients investigated for leptospirosis were also tested prospectively for IgM antibodies to dengue: 38 of 92 leptospirosis-negative patients (41%) were dengue IgM-positive, while 2 of 25 leptospirosis cases also had serologic evidence suggesting acute dengue infection. A second large outbreak of dengue caused by serotype 2 occurred in 1997. During the 1995 and 1997 dengue epidemics in Barbados, dengue cases outnumbered leptospirosis cases investigated in the leptospirosis diagnostic protocol. During 1997, patients investigated but negative for dengue were also tested for anti-leptospiral IgM: 7.3% (19 of 262) were IgMpositive. Substantial misdiagnosis of both dengue and leptospirosis can occur and greater public awareness and clinical suspicion of the similar presentations of these two diseases are necessary.Dengue fever is included within the group of emerging or re-emerging infectious diseases of public health significance.

Leptospirosis is a common and underdiagnosed zoonosis. Two rapid assays for serological diagnosis of acute leptospirosis in diagnostic laboratories, the immunoglobulin M (IgM)-dipstick assay and the indirect hemagglutination assay (IHA), were evaluated and compared with standard assays. Sera were examined from 104 patients admitted to a hospital for investigation in a leptospirosis diagnostic protocol. Specimens for serology were taken on days 1 and 4 of the patients' hospital stay. Antibodies were detected using an IgM-enzyme-linked immunosorbent assay (ELISA), microscopic agglutination test (MAT), an IgM-dipstick assay, and an IHA. Fifty-one patients were found to have leptospirosis. The sensitivity of the IgM-dipstick assay was 98%, its specificity was 90.6%, its positive predictive value was 90.9%, and its negative predictive value was 98%. The sensitivity of the IHA was 92.2%, its specificity was 94.4%, its positive predictive value was 95.9%, and its negative predictive value was 92.7%. The standard IgM-ELISA and MAT, were positive in the first samples tested from 67 and 55% of the cases, respectively, and the rapid IgM-dipstick assay and IHA were positive in 71 and 49%, respectively, in the first sample tested. Both rapid assays are highly sensitive and specific. Neither requires specialized equipment, and both are suitable for use in diagnostic laboratories.

Abstract. Leptospirosis is a common zoonosis of worldwide distribution. Diagnosis of leptospirosis is usually accomplished by serology, but the microscopic agglutination test (MAT) generally requires paired sera for detection of seroconversion and is considered too complex for routine use. A number of rapid assays have been developed in recent years. In the present study, 2 immunoglobulin (Ig) M enzyme-linked immunosorbent assay (ELISA) methods were evaluated for the early diagnosis of acute leptospirosis in Barbados. A total of 103 patients admitted to the Queen Elizabeth Hospital for diagnosis of suspected leptospirosis were investigated. A case of leptospirosis was confirmed by a 4-fold rise in titer between 2 sera tested by MAT, an initial titer of Ն 800 in the MAT, or by isolation of leptospires from blood or urine. A total of 48 cases of leptospirosis were confirmed. In 33 cases, both commercial assays were positive in the first sample, taken at admission, a mean of 6.7 days after onset of symptoms, whereas seroconversion was detected in a further 9 cases. Both assays were negative in 5 cases, and the remaining case gave discordant results in the 2 assays. False-positive IgM results were detected in 4 patients without leptospirosis. The sensitivity of the 2 assays was 89.6 and 97.5%, respectively, and specificities were 92.7 and 96.4%, respectively. The positive predictive values were 87.8 and 95.5%, and the negative predictive values were 90.7 and 89.5%, respectively. Either of these assays can be used for early diagnosis of leptospirosis, particularly in laboratories that cannot perform more specialized leptospiral serology.

Leptospirosis is a febrile zoonosis of worldwide distribution. A latex agglutination assay was evaluated in two studies, the first using a panel of well-characterized sera from patients with leptospirosis and from patients with other disease states and the second, a prospective hospital-based study, evaluating sera from 186 consecutive patients admitted to hospital with acute febrile illness. The confirmed leptospirosis serum panel included paired acute-and convalescent-phase specimens from 40 cases, of which 34 gave positive latex tests (case sensitivity, 85%; 95% confidence interval [95% CI], 70 to 94%). The other diseases represented in the panel of 112 specimens from nonleptospirosis patients included autoimmune diseases, brucellosis, dengue, melioidosis, malaria, syphilis, toxoplasmosis, viral hepatitis, and a number of other viral infections. The specificity of latex agglutination using this panel was 81% (95% CI, 73 to 87%). Among the patients with acute febrile illness, there were 25 cases of leptospirosis and 161 patients with other diagnoses. The sensitivity and specificity of latex agglutination in this group were 88% (95% CI, 72 to 97%) and 98% (95% CI, 95 to 100%), respectively. In this evaluation, the two distinct groups of specimens gave similar results for sensitivity, but specificity was different in each study. The sensitivity and specificity observed for the hospital study were similar to those obtained in evaluations of other rapid tests in the same population. The results of this study suggest that multiple evaluations of new diagnostic assays should be performed, because performance characteristics may vary in different populations.