Serum samples collected during 1978-79 from residents of the Chiniot and Changa Manga National Forest (CMF) areas of Punjab Province, Pakistan, had over-all neutralizing (N) antibody positive rates for West Nile (WN) virus of 32.8% (n = 192) and 38.5% (n = 239), respectively. Comparison of the age-specific antibody rates indicated that the pattern of exposure to infection was different in the two areas. Samples from a 1968 serosurvey of residents of the CMF area had an age-specific N antibody profile similar to the 1978 CMF sample, but both the over-all N and haemagglutination-inhibition (HI) antibody positive rates were much higher in the 1968 sample. When tested against antigen prepared from the Pakistan I-746 strain of WN virus, the percentage of sera HI antibody positive and the geometric mean titre of the sera were significantly higher than when tested against the Egypt-101 antigen. One of 124 and 11 of 50 sera from the 1978 and 1968 samples from CMF exhibited detectable HI antibody against dengue-3 virus, respectively, indicating cross-reacting flavivirus antibody was present. None of the positive sera had a higher titre against dengue-3 than against WN virus, but four of the 1968 sera reacted to equal titre against both antigens. During the 1978-79 CMF survey, serum samples from domestic and wild animals were tested for WN virus antibody. Of the 317 wild birds captured, 85 were N-antibody positive. The only frequently bled mammal was the Indian cow, from which 21 of 58 samples were positive for WN antibody.

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Mutant and geographical strains of Culex tritaeniorhynchus were compared for West Nile (WN) virus susceptibility by feeding on a high-titered blood-virus suspension. Eleven strains also were selected from 2-21 generations for an increase and/or a reduction of oral susceptibility using 90% and 10% infective virus doses, respectively. Only one of the 20 strains tested, e ma, was significantly less susceptible than the control strain. In the selection experiments, none of the strains showed a consistent decrease in susceptibility, but the Changa Manga II (CM) strain showed a sustained increase in susceptibility from generations F11-F21 when selection was discontinued. Reciprocal cross-matings and back-crosses were set up between the selected CM strain and two of the morphological mutant strains, e ma and re e ae, carrying homozygous recessive markers. The resulting progeny were tested for susceptibility to WN virus infection and the ability to replicate virus to high-titers after infection. These results suggest that the trait of increased susceptibility is dominant over resistance. The enhanced ability of infected mosquitoes to replicate WN virus showed partial dominance. Both of these traits appear to be polyfactorial, and are apparently associated with more than one chromosome in Cx. tritaeniorhynchus.

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Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism. Two polymorphisms, C677T and A1298C, were described leading to reduced enzyme activity. Methotrexate (MTX) is an antifolate agent of consolidation and maintenance therapy of acute lymphoblastic leukaemia (ALL). Despite its clinical success, MTX can be associated with serious toxicities resulting in treatment interruption or discontinuation, impacting disease outcome. There is evidence that MTX toxicity can be affected by polymorphisms in genes encoding for drug-metabolizing enzymes such as MTHFR. Therefore, we aimed to investigate the influence of MTHFR C677T and A1298C polymorphisms on the frequency of MTX-related toxicity, disease outcome and patients' survival. MTHFR polymorphisms were assessed in 50 adult patients with de novo ALL using real-time PCR. Patients were followed-up for the development of haematologic and/or nonhaematologic toxicity and assessment of clinical outcome. Frequency of C677T polymorphisms was 42% for TT, 24% for CT and 34% for CC; A1298C polymorphisms were 28, 6 and 66% for CC, AC and AA, respectively. MTX therapy was significantly associated with neutropaenia, hepatic and gastrointestinal toxicities, unfavourable response at day 14 of induction therapy, increased relapse and mortality rates and shorter survival in patients with 677 TT genotype than in those with CC and CT, whereas 1298 CC genotype patients had lower frequency of neutropaenia, hepatic toxicity and relapse than in those with AA and AC. Our study suggests MTHFR polymorphism as an attractive predictor of MTX-related toxicity in adult ALL, considering it a potential prognostic factor influencing disease outcome.