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M P Alpers

Publications and source records attributed to M P Alpers.

At least 19 recordsLinked to original sources
PubMed1992

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.

Amino Acid Sequence↗
PubMed1992

Subacute sclerosing panencephalitis (SSPE) in Papua New Guinea: a high incidence in young children.

Eighty-seven cases of subacute sclerosing panencephalitis (SSPE) were diagnosed from September 1988 to April 1991 in Papua New Guinea (PNG), by demonstration of high-titre measles-specific antibodies in cerebrospinal fluid (CSF). For 1990 the annual incidence of SSPE, for the study provinces, was calculated to be 56 cases per million under 20 years of age and it is expected that this figure will be higher in 1991. The mean age of presentation was 4.9 years, with a male to female ratio of 1.8:1. An elevation in the ratio of immunoglobulin G as a percentage of total protein in CSF and an increase in the CSF:serum immunoglobulin G ratio was shown in SSPE patients. The dramatic appearance and high frequency of the disease in PNG might relate to the early age of measles infection encountered in children in this country.

Child↗
PubMed1992

Placental Plasmodium falciparum parasitaemia in East Sepik (Papua New Guinea) women of different parity: the apparent absence of acute effects on mother and foetus.

The effects of malaria were studied in a group of parturient women of East Sepik Province, Papua New Guinea. Further information was gathered from a search of hospital records and interviews with village aid post orderlies. Examination of placental blood revealed a Plasmodium falciparum parasitaemia rate of 41% of the primiparae, 23% in parous 2, 25% in parous 3, and 3% in multiparae greater than 3. Approximately one-half of those with placental parasitaemia had a concomitant detectable peripheral parasitaemia. Placental parasitaemias were of relatively low density, averaging 1.6%. There were no instances in the observed series of births, hospital records, or village studies of the occurrence of severe malaria in the mother or its acute effects on the foetus. Neither birthweight nor maternal or cord blood haematocrit was related to the presence or absence of placental parasitaemia. Neonatal birthweight and risk of delivering a low birthweight (less than 2.5 kg) baby was statistically associated only with maternal parity. The possible reasons for the relatively benign effect of malaria in the pregnant women of this population are discussed.

Acute Disease↗
PubMed1992

Antigenicity of a protective recombinant filarial protein in human bancroftian filariasis.

A 92-kDa fusion protein that encodes amino acids 1-479 of a 62-kDa Brugia malayi antigen induces resistance to microfilariae in mice. The antigenicity of this recombinant protein was explored in asymptomatic residents of Wuchereria bancrofti-endemic areas of Papua New Guinea and Egypt. Unlike sera from individuals in nonendemic areas, sera from residents of endemic areas contained IgG3 antibodies (up to dilution 1:1280) reactive with the fusion protein. There was little or no recombinant antigen-specific IgG1, IgG2, IgG4, or IgE. The mean level of IgG3 antibodies to the amino acid 1-479 construct in sera of putatively "immune" adult Papua New Guineans and children in whom microfilaremia was < 4 parasites/mL of blood was not significantly different (P < .05) from those with > 1000 parasites/mL. These data indicate that the filarial antigen corresponding to the recombinant protein is highly immunogenic in naturally infected children and adults and that the isotype and magnitude of antibody reactivity with it do not correlate with the microfilaremic status of asymptomatic persons.

Adolescent↗
PubMed1992

The population dynamics in mosquitoes and humans of two Plasmodium vivax polymorphs distinguished by different circumsporozoite protein repeat regions.

The population dynamics of two Plasmodium vivax polymorphs were studied over a two-year period in a village in a hyperendemic area of Papua New Guinea in both the mosquito and human populations. Strains of P. vivax were distinguished by different circumsporozoite (CS) protein repeats, the VK210 (classic) and the VK247 (variant) polymorphs. In 1986, 34% of P. vivax CS protein-positive mosquitoes were of the VK247 type. Although the proportion of P. vivax sporozoite antigen-positive mosquitoes compared with all sporozoite-positive mosquitoes did not change from 1986 to 1987, the proportion of P. vivax-positive mosquitoes of the VK247 polymorph decreased significantly from 34% to 11% (5 of 45) in 1987. In 1986, 61% (47 of 77) of humans tested had IgGs that recognized the VK247 CS repeat, while only 26% (22 of 84) had IgGs that recognized the VK210 CS repeat. The observed fluctuation in the proportion of the two P. vivax CS protein polymorphs recorded in the mosquito population from 1986 to 1987 is consistent with a hypothesis of selection by humoral immune pressure on the VK247 strain.

Adolescent↗
PubMed1992

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.

Adolescent↗
PubMed1992

Markers of hepatitis B infection in Tari District, Southern Highlands Province, Papua New Guinea.

Serum samples collected from two groups in the Tari District of Southern Highlands Province were assayed for markers of hepatitis B virus (HBV) infection. 85% of women of childbearing age were found to have markers of HBV infection; 37% were positive for HBV surface antigen (HBsAg), indicative of the chronic carrier state, and 6.6% were positive for HBV e antigen (HBeAg), indicating the presence of actively replicating virus. 75% of women negative for HBsAg were positive for antibody to HBV core antigen (HBcAb), a marker of past infection. A group of children aged 6 to 18 years showed a significantly lower prevalence of markers of infection (66%) but higher rates of HBsAg positivity (46%) and HBeAg positivity (30%). Only 37% of the HBsAg-negative children in this group were positive for HBcAb. The results from this serosurvey suggest that the major route of HBV transmission in this population is horizontal, between older children, though significant transmission also occurs during the neonatal period.

Acute Disease↗
PubMed1992

Rotavirus diarrhoea in children in the highlands of Papua New Guinea.

Children from the highlands of Papua New Guinea, hospitalized for severe diarrhoea, were examined for clinical signs and the presence of rotaviruses. Rotavirus was detected in faecal samples from 68% (23/38) of patients examined. In contrast to other studies, an excess of respiratory symptoms was not observed and the infection rate of disease due to rotavirus was relatively high in children under 6 months of age. In an environment where pigs and humans share close contact a rotavirus strain infecting piglets was also demonstrated.

Animals↗
PubMed1992

Chemoprophylaxis against malaria in Papua New Guinea: a trial of amodiaquine and a combination of dapsone and pyrimethamine.

A placebo-controlled chemoprophylaxis trial was carried out in 1980 in 318 semi-immune school children in the Madang area of Papua New Guinea, where there was a high prevalence of strains of Plasmodium falciparum resistant to 4-aminoquinolines. Since prophylaxis with amodiaquine at 5 mg/kg weekly had failed, amodiaquine at a dose of 10mg/kg weekly and Maloprim (half a tablet or one tablet depending on body weight, which gave ranges of dapsone of 1.7-3.3mg/kg and pyrimethamine 0.2-0.4 mg/kg) weekly were tried. Neither regimen was completely successful in preventing parasitaemia, though after 13 weeks of prophylaxis the slide positivity rate was 16% for the amodiaquine group and 2% for the Maloprim group, which was in each case significantly lower than the normal baseline rate in the controls of 42%. Amodiaquine was completely successful in suppressing Plasmodium vivax infections. Breakthrough parasitaemia occurred, with either P. falciparum or P. vivax, in 5% of subjects on Maloprim at some time during the 13-week period of prophylaxis. Significantly more children in both the amodiaquine and Maloprim groups than in the placebo group showed a reduction in spleen size. All groups showed an unexplained fall in haemoglobin level over the study period but the fall was significantly less in both the prophylaxis groups. There was no adverse effect on white cell counts by either drug regimen. Chemoprophylaxis as a component of an integrated malaria control program should not be overlooked, provided that compliance can be maintained. However, in this particular case the principal purpose of the study had been to evaluate the proposed chemoprophylactic regimens in school children before embarking on an intervention study in young children. As a result of this study it was decided not to go ahead with the chemoprophylactic intervention in young children but to adopt an approach based on early presumptive treatment.

Antimalarials↗
PubMed1992

The Malaria Vaccine Epidemiology and Evaluation Project of Papua New Guinea: rationale and baseline studies.

The range of possible malaria vaccines, against different species of Plasmodium and various stages in the life cycle of the parasite in both human host and mosquito vector, is reviewed. The importance, in a malaria-endemic area, of protection by a malaria vaccine against disease rather than infection is emphasized, and the ways by which disease prevention may be achieved are discussed. Mechanisms of production and presentation of vaccines are considered, including the importance of appropriate and more effective adjuvants. The variety of immune responses to malaria is set out and linked to both human and plasmodial genetic factors. Host genetics may also modify susceptibility to malaria through mechanisms which are not immunological. There is a need for entomological studies of the Anopheles vectors, especially but not only in preparation for transmission-blocking vaccines. This overall complexity justifies a multidimensional approach to epidemiology and field-site preparation. An iterative procedure is proposed for initial field evaluation, through adult male volunteers to community studies in immune adults and then to semi-immune school children, before evaluation in the principal target population of nonimmune young children. The outcome variables for epidemiological evaluation are specified. After this brief review of malaria vaccines, the baseline studies being undertaken by the Malaria Vaccine Epidemiology and Evaluation Project of the Papua New Guinea Institute of Medical Research in the Wosera area of East Sepik Province are discussed in some detail, and their rationale linked to the range and complexity of the malaria vaccines that have been reviewed. These studies are described under the headings of their principal components of epidemiology, parasitology, immunology, genetics and entomology.

Animals↗
PubMed1992

Prenatal immune hypersensitization to malaria: Plasmodium falciparum-specific IgE antibody in paired maternal and cord sera from Papua New Guinea.

In a study of malaria and pregnancy in East Sepik Province of Papua New Guinea 45 maternal and cord serum pairs were tested for Plasmodium falciparum-specific IgE antibody. There were 17 positive sera: 6 cases of maternal serum alone, 5 cases of cord serum alone and 3 pairs of maternal and cord sera. IgE antibody positivity rates in the mothers increased with parity, whereas placental parasitaemia rates decreased. Cord serum positivity was not affected by parity. Immunoblots of the sera revealed a diversity of IgE antibodies to specific antigens of the P. falciparum lysate, but an IgE antibody to a 48kd antigen was present in all positive maternal and cord sera.

Animals↗
PubMed1992

Thyroid function in a formerly goitrous community on Karkar Island, Papua New Guinea.

During a survey of noncommunicable disease conducted on Karkar Island, Madang Province in 1986, measures of thyroid function were examined in adult residents of a formerly goitrous village (Gamog) and a neighbouring community (Marup) with no history of iodine deficiency or endemic goitre. In Gamog, almost 20% of males and almost 30% of females had palpable goitre (maximum prevalence at ages 35-54 years) but visible goitres were not encountered. However, thyroid function tests were generally similar in the two groups, suggesting that iodine deficiency is no longer an appreciable problem for adults in Gamog. The persistence of palpable goitre in this village is therefore likely to be a residual effect of previous iodine deficiency. Correction of the iodine deficiency in the Gamog community began with the program of iodized oil injections, which was undertaken in the 1970s. The current lack of iodine deficiency is probably due in the main to dietary change associated with the introduction of the cash economy. This effect may have occurred in many formerly goitrous communities in Papua New Guinea in recent years, although persistence of iodine deficiency in some parts of the country should not be discounted.

Adult↗
PubMed1991

Wide distribution of the variant form of the human malaria parasite Plasmodium vivax.

We have found polymorphism in the repetitive and nonrepetitive regions of the sporozoite vaccine antigen, the circumsporozoite (CS) protein, in Plasmodium vivax malaria parasites from two geographically distant malaria endemic regions of the world. Like the recently described variant repeat sequence of P. vivax from Thailand, the CS protein repeat sequence of the variant P. vivax parasites from Papua New Guinea and Brazil is ANGA(G/D)(N/D)QPG, which differs from the previously identified CS repeat sequence, GDRA(D/A)GQPA, of P. vivax parasites from South America, Central America, and North Korea. Comparison of the P. vivax CS protein outside the repeat region revealed restricted polymorphism in regions that have exhibited T-cell immune function and sequence heterogeneity in the CS protein of Plasmodium falciparum. Our results show that P. vivax malaria parasites with the variant CS repeat sequences are widespread in nature and that the polymorphism in the CS protein of P. vivax is also present in the nonrepeat region.

Amino Acid Sequence↗
PubMed1991

Characterization of a variant of human T-lymphotropic virus type I isolated from a healthy member of a remote, recently contacted group in Papua New Guinea.

We report the characterization of a variant of human T-lymphotropic virus type I (HTLV-I) isolated from an interleukin 2-dependent, CD8+ T-cell line derived from peripheral blood mononuclear cells of a healthy member of a remote, recently contacted hunter-horticulturalist group (Hagahai) in Madang province of Papua New Guinea. Antigenic characterization of this variant, designated PNG-1, by immunofluorescence, indicated no expression of gag-encoded proteins p19 and p24 (even after incubation with 5-bromo-2'-deoxyuridine), using monoclonal and polyclonal antibodies against HTLV-I gag gene products. Virus-specific proteins of 15, 19, 46, 53, and 61/68 kDa were demonstrated by Western blot analysis, using sera from patients with serologically and/or virologically confirmed HTLV-I myeloneuropathy, sera from HTLV-I-infected rabbits, and antibodies prepared against the C terminus of the major envelope glycoprotein gp46. Restriction endonuclease maps of PNG-1 proviral DNA differed from that of a prototype strain of HTLV-I (MT-2), but, as verified by polymerase chain reaction, PNG-1 was definitely HTLV-I, not HTLV-II. Nucleotide sequencing and further molecular genetic studies of this variant may provide insights into the origin and evolution of HTLV-I.

Cells, Cultured↗
PubMed1991

Effect of pneumococcal vaccine on morbidity from acute lower respiratory tract infections in Papua New Guinean children.

The effect of a 14-valent pneumococcal polysaccharide vaccine on morbidity from acute lower respiratory tract infection (ALRI) was determined in a randomized double-blind controlled trial in children under the age of 5 years living in the Paupa New Guinea highlands. The vaccine did not protect against mild ALRI. Vaccine efficacy in the study as a whole was 28% for moderate/severe ALRI, which was not statistically significant though consistent with the significant effect on mortality. Children entered the trial in five separate cohorts 4 months apart. The incidence of disease and vaccine efficacy varied between cohorts and with age. There was no vaccine effect in the first cohort, which had a much higher proportion of older children. The effect was greatest and statistically significant among those groups encountering an epidemic of moderate and severe ALRI at a young age. It was therefore in children at the most vulnerable age in times of greatest incidence of disease that the vaccine had its most potent effect. It is postulated that the efficacy of pneumococcal vaccine is dependent on the predominant invading serotypes in the period after vaccination, the age at which children develop immunocompetence to specific vaccine serotypes, and the levels of naturally acquired specific immunity already present in children at the time of vaccination, and that for all of these conditions there will be a cohort effect.

Acute Disease↗
PubMed1991

Relationships between growth and acute lower-respiratory infections in children aged less than 5 y in a highland population of Papua New Guinea.

One hundred fifty-six children in the highlands of Papua New Guinea aged less than 5 y, studied for a total of 7019 child-weeks, had an incidence of 1.3 episodes per child-year of acute lower-respiratory-tract infections (ALRIs). There was a marked age trend with an incidence of almost three times this average for children aged less than 6 mo. Those with low weight-for-age or low height-for-age had a higher ALRI incidence rate, with no evidence of cutoffs above which nutritional status had no effect; there was no association between low weight-for-height and increased risk of ALRI. A slow weight gain was not a significant risk factor in the short term but weight gain was reduced during episodes of ALRI.

Aging↗
PubMed1991

Antibodies to pneumococcal polysaccharides in pneumonia and response to pneumococcal vaccination in young children in Papua New Guinea.

Antibodies against pneumococcal polysaccharides were measured by ELISA in Papua New Guinean children with pneumonia aged 0-14 months, in age-matched healthy Papua New Guinean controls and in healthy expatriate children living in Papua New Guinea. At 0-5 months of age, the IgG antibody titres against six of the eight polysaccharides measured were significantly lower in pneumonia patients than in both control groups. Antibody titres in 6-14-month-old Papua New Guinean controls were significantly lower than in control Papua New Guineans aged 0-5 months for five of the eight polysaccharides tested. In the 6-14-months age group the antibody titre was significantly lower in pneumonia patients than in controls for only one polysaccharide. For seven of the eight serotypes tested, antibody levels in expatriate controls did not decline with age. Antibody responses of Papua New Guinean children aged 6-18 months to a 23-valent pneumococcal vaccine were serotype dependent. Fold increases in response to the vaccine were greatest for the IgA isotype. IgG antibody responses were greater than three fold to four of the eight serotypes tested.

Age Factors↗