Diversity in the immunodominant determinants of the circumsporozoite protein of Plasmodium falciparum parasites from malaria-endemic regions of Papua New Guinea and Brazil.

To determine the nature and extent of variation in the T cell sites of the Plasmodium falciparum circumsporozoite (CS) protein, a candidate antigen in the development of a malaria vaccine, we cloned and sequenced 69 recombinant clones of the CS protein gene representing 18 and 17 P. falciparum isolates from infected individuals from Madang, Papua New Guinea (PNG), a holoendemic malaria region, and Paragaminos and Jacunda, Brazil, relatively low endemic regions, respectively. As previously known, the amino acid sequence polymorphism was restricted to the three immunodominant regions of the protein, Th1R-N1, Th2R, and Th3R. While some of the observed nonsilent mutations in the T cell determinants of the CS protein were similar to those previously identified, we have found new amino acid changes in each of the polymorphic sequences in parasites from PNG and Brazil. A comparison of the CS epitope sequences of parasites from PNG and Brazil with the previously known CS epitope sequences of parasites from Brazil and The Gambia showed the following: 1) polymorphism was found in the Th1R-N1, Th2R, and Th3R region; however, while amino acid substitutions in the Th1R-N1 and Th2R region tended to be conservative, the substitutions found in the Th3R region were not, suggesting that the Th3R epitope may be rapidly evolving to allow parasites to escape host antiparasite cytotoxic T cell-enforced immune responses, and 2) the CS proteins of P. falciparum from high malaria-transmission regions (PNG and The Gambia) appear more polymorphic than the CS proteins of parasites from relatively low malaria-endemic regions in Brazil, where P. falciparum infection has been recently established.

Polymorphism in the circumsporozoite protein of the human malaria parasite Plasmodium vivax.

The circumsporozoite (CS) protein that covers the surface of infectious sporozoites is a candidate antigen in malaria vaccine development. To determine the extent of B- and T-epitope polymorphism and to understand the mechanisms of antigenic variability, we have characterized the CS protein gene of Plasmodium vivax from field isolates representing geographically distant regions of Papua New Guinea (PNG) and Brazil. In the central repeat region of the CS protein, in addition to variation in the number of repeats, an array of mutations was observed which suggests that point mutations have led to the emergence of the variant CS repeat sequence ANGA(G/D)(N/D)QPG from GDRA(D/A)GQPA. Outside the repeat region of the protein, the nonsilent nucleotide substitutions of independent origin are localized in three domains of the protein that either harbor known T-cell determinants or are analogous to the Plasmodium falciparum immunodominant determinants, Th2R and Th3R. We have found that, with the exception of one CS clone sequence that was shared by one P. vivax isolate each from PNG and Brazil, the P. vivax CS protein types can be grouped into Papuan and Brazilian types. These results suggest that an in-depth study of parasite population dynamics is required before field trials for vaccine formulation based on polymorphic immunodominant determinants are conducted.

Blood pressure in four remote populations in the INTERSALT Study.

Four remote population samples (Yanomamo and Xingu Indians of Brazil and rural populations in Kenya and Papua New Guinea) had the lowest average blood pressures among all 52 populations studied in INTERSALT, an international cooperative investigation of electrolytes and blood pressure. Average systolic blood pressure was 103 versus 120 mm Hg in the remaining INTERSALT centers; diastolic blood pressure in these four population samples averaged 63 versus 74 mm Hg in the 48 other centers. There was little or no upward slope of blood pressure with age; hypertension was present in only 5% of the rural Kenyan sample and virtually absent in the other three centers. Also in marked contrast with the rest of the centers was level of daily salt intake, as estimated by 24-hour urinary sodium excretion. Median salt intake ranged from under 1 g to 3 g daily versus more than 9 g in the rest of INTERSALT populations. Average body weight was also low in these four centers, with no or low average alcohol intake, again unlike the other centers. The association within these four centers between the above variables and blood pressure was low, possibly reflecting their limited variability. While several other INTERSALT centers also had low average body weight or low prevalence of alcohol drinking, when this was accompanied by much higher salt intake (7-12 g salt or 120-210 mmol sodium daily), hypertension prevalence ranged from 8% to 19%. These findings confirm previous reports that in populations with a low salt intake, there is little or no hypertension or rise of blood pressure with age.(ABSTRACT TRUNCATED AT 250 WORDS)