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					Papua New Guinea Medical Journal                                                         Volume 48, No 1-2, Mar-Jun 2005


                                       MEDLARS BIBLIOGRAPHY

                     PUBLICATIONS OF RELEVANCE TO PAPUA NEW GUINEA AND MELANESIA

                       Bibliographic Citation List generated from MEDLARS

1   Aghanwa HS.                                                         significantly lower in the blanket group (P = 0.031).
    Attitude toward and knowledge about mental illness                  No difference was found between the contact and
    in Fiji islands.                                                    the control groups (P = 0.93). Whether this apparent
    Int J Soc Psychiatry 2004 Dec;50(4):361-375.                        reduced leprosy incidence in the first three years in
         BACKGROUNDS: There is a dearth of                              the blanket group is due to a delayed development
    information on the extent of knowledge about mental                 of leprosy or a complete clearance of infection needs
    illness and attitudes toward the mentally ill in Fiji.              to be determined.
    AIMS: This study aimed to explore these aspects,
    and also to determine the factors influencing them.             5   Bakker MI, Hatta M, Kwenang A, Faber WR, van
    METHOD: Market vendors, peri-urban dwellers,                        Beers SM, Klatser PR, Oskam L.
    white-collar and health workers from Greater Suva                   Population survey to determine risk factors for
    were interviewed. The interview schedule used                       Mycobacterium leprae transmission and infection.
    elicited socio-demographic characteristics,                         Int J Epidemiol 2004 Dec;33(6):1329-1336. Epub
    knowledge of, and attitudes toward, mental illness.                 2004 Jul 15.
    RESULTS: A majority of the subjects attributed the                       BACKGROUND: Not every leprosy patient is
    cause of mental illness to substance abuse, believed                equally effective in transmitting Mycobacterium
    in the diversity of mental illness, considered hospital             leprae. We studied the spatial distribution of infection
    as an important source of help and acknowledged                     (using seropositivity as a marker) in the population
    the effectiveness of medication. Less than one-fifth                to identify which disease characteristics of leprosy
    of the subjects were willing to marry or employ                     patients are important in transmission. METHODS:
    mentally ill persons. About 42% of the sample would                 Clinical data and blood samples for anti-M. leprae
    be deterred by embarrassment from seeking help.                     ELISA were collected during a cross-sectional survey
    Educational attainment was correlated with                          on five Indonesian islands highly endemic for leprosy.
    knowledge about mental illness, except with                         A geographic information system (GIS) was used to
    knowledge about early mental symptoms (p < 0.01).                   define contacts of patients. We investigated spatial
    Prestigious occupation, single marital status, female               clustering of patients and seropositive people and
    gender, younger age and urban dwelling were                         used logistic regression to determine risk factors for
    associated with positive disposition toward the                     seropositivity. RESULTS: Of the 3986 people
    mentally ill (p < 0.01). Race was not significantly                 examined for leprosy, 3271 gave blood.
    influential on almost all attitudinal variables.                    Seroprevalence varied between islands (1.7-8.7%)
    CONCLUSION: Health education is capable of                          and correlated significantly with leprosy prevalence.
    positively influencing knowledge about, and attitudes               Five clusters of patients and two clusters of
    toward, mental illness in Fiji.                                     seropositives were detected. In multivariate
                                                                        analysis, seropositivity significantly differed by
2   Allen L, Shrimpton R.                                               leprosy status, age, sex, and island. Serological
    The International Research on Infant                                status of patients appeared to be the best
    Supplementation Study: implications for programs                    discriminator of contact groups with higher
    and further research.                                               seroprevalence: contacts of seropositive patients had
    J Nutr 2005 Mar;135(3):666S-669S.                                   an adjusted odds ratio (aOR) of 1.75 (95% CI 0.922-
                                                                        3.31). This increased seroprevalence was strongest
3   Andrade AL, Martelli CM.                                            for contact groups living < or =75 m of two
    Globalisation of Hib vaccination – how far are we?                  seropositive patients (aOR = 3.07; 95% CI 1.74-
    Lancet 2005 Jan 1-7;365(9453):5-7.                                  5.42). CONCLUSIONS: In this highly endemic area
                                                                        for leprosy, not only household contacts of
4   Bakker MI, Hatta M, Kwenang A, Van Benthem                          seropositive patients, but also people living in the
    BH, Van Beers SM, Klatser PR, Oskam L.                              vicinity of a seropositive patient were more likely to
    Prevention of leprosy using rifampicin as                           harbour antibodies against M. leprae. Through
    chemoprophylaxis                                                    measuring the serological status of patients and
    Am J Trop Med Hyg 2005 Apr;72(4):443-448.                           using a broader definition of contacts, higher risk
        An intervention study was implemented on five                   groups can be more specifically identified.
    Indonesian islands highly endemic for leprosy to
    determine whether rifampicin can be used as                     6   Baravilala WR, Moulds RF.
    chemoprophylaxis to prevent leprosy. The                            A Fijian perspective on providing a medical
    population was actively screened before the                         workforce.
    intervention and subsequently once a year for three                 Med J Aust 2004 Dec 6-20;181(11-12):602.
    years. In the control group, no chemoprophylaxis
    was given. In the contact group, chemoprophylaxis               7   Beadell JS, Gering E, Austin J, Dumbacher JP,
    was only given to contacts of leprosy patients and in               Peirce MA, Pratt TK, Atkinson CT, Fleischer RC.
    the blanket group to all eligible persons. The cohort               Prevalence and differential host-specificity of two
    consisted of 3,965 persons. The yearly incidence                    avian blood parasite genera in the Australo-Papuan
    rate in the control group was 39/10,000; the                        region.
    cumulative incidence after three years was                          Mol Ecol 2004 Dec;13(12):3829-3844.


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Papua New Guinea Medical Journal                                                          Volume 48, No 1-2, Mar-Jun 2005

         The degree to which widespread avian blood                  9   Berlioz-Arthaud A, Barr IG.
    parasites in the genera Plasmodium and                               Laboratory-based influenza surveillance in New
    Haemoproteus pose a threat to novel hosts depends                    Caledonia, 1999-2003.
    in part on the degree to which they are constrained                  Trans R Soc Trop Med Hyg 2005 Apr;99(4):290-300.
    to a particular host or host family. We examined the                      We aimed to evaluate the annual incidence of
    host distribution and host-specificity of these                      influenza in New Caledonia and to identify the
    parasites in birds from two relatively understudied                  circulating viral types and subtypes in order to gather
    and isolated locations: Australia and Papua New                      information for the local vaccination programme and
    Guinea. Using polymerase chain reaction (PCR),                       regional influenza surveillance. A surveillance
    we detected infection in 69 of 105 species,                          network was set up in 1999; it included sentinel
    representing 44% of individuals surveyed (n = 428).                  practitioners in Noumea and the virology department
    Across host families, prevalence of Haemoproteus                     of the Pasteur Institute. Influenza circulated in New
    ranged from 13% (Acanthizidae) to 56%                                Caledonia every year, regularly during the southern
    (Petroicidae) while prevalence of Plasmodium                         hemisphere winter and occasionally during March-
    ranged from 3% (Petroicidae) to 47%                                  May. Isolates were generally consistent with world
    (Ptilonorhynchidae). We recovered 78 unique                          surveillance, except in 1999, when a new A/H1N1
    mitochondrial lineages from 155 sequences.                           variant was identified. This study emphasises the
    Related lineages of Haemoproteus were more likely                    need for regular influenza surveillance, even when
    to derive from the same host family than predicted                   performed on a limited scale. Importantly the optimal
    by chance at shallow (average LogDet genetic                         time for local vaccination was found to be in
    distance = 0, n = 12, P = 0.001) and greater depths                  December or January each year.
    (average distance = 0.014, n = 11, P < 0.001) within
    the parasite phylogeny. Within two major                         10 Billo M, Fournet A, Cabalion P, Waikedre J, Bories
    Haemoproteus subclades identified in a maximum                      C, Loiseau P, Prina E, deArias AR, Yaluff G,
    likelihood phylogeny, host-specificity was evident up               Fourneau C, Hocquemiller R.
    to parasite genetic distances of 0.029 and 0.007                    Screening of New Caledonian and Vanuatu
    based on logistic regression. We found no significant               medicinal plants for antiprotozoal activity.
    host relationship among lineages of Plasmodium by                   J Ethnopharmacol 2005 Jan 15;96(3):569-575. Epub
    any method of analysis. These results support                       2004 Dec 1.
    previous evidence of strong host-family specificity                     Sixty-seven extracts of 30 medicinal plants
    in Haemoproteus and suggest that lineages of                        traditionally used in New Caledonia or Vanuatu by
    Plasmodium are more likely to form evolutionarily-                  healers to treat inflammation, fever and in cicatrizing
    stable associations with novel hosts.                               remedies were evaluated in vitro for their
                                                                        antiprotozoal activity against Leishmania donovani,
8   Becker AE, Gilman SE, Burwell RA.                                   Leishmania amazonensis and Trypanosoma cruzi.
    Changes in prevalence of overweight and in body                     Among the selected plants, Pagiantha cerifera was
    image among Fijian women between 1989 and 1998.                     the most active against both Leishmania species;
    Obes Res 2005 Jan;13(1):110-117.                                    four extracts were active against promastigotes of
         OBJECTIVE: To investigate changes in                           Leishmania donovani at EC(50) values inferior to 5
    prevalence of overweight and obesity and in body                    microg/ml. Garcinia pedicillata extract had an
    image among ethnic Fijian women in Fiji during a                    EC(50) value of 12.5 microg/ml against intracellular
    period of rapid social change and the relationship                  amastigotes of Leishmania amazonensis. Alone
    between changes in body image and BMI.                              Amborella trichopoda reduced by more of 80% the
    RESEARCH METHODS AND PROCEDURES: The                                trypomastigotes of Trypanosoma cruzi in the blood.
    study design was a multiwave cohort study of BMI
    in a traditional Fijian village over a 9.5-year period           11 Billo M, Cabalion P, Waikedre J, Fourneau C,
                                                                        Bouttier S, Hocquemiller R, Fournet A.
    from 1989 to 1998. Cohorts were identified in 1989
                                                                        Screening of some New Caledonian and Vanuatu
    (n=53) and in 1998 (n=50). Selection criteria                       medicinal plants for antimycobacterial activity.
    included Fijian ethnicity, female gender, age of at                 J Ethnopharmacol 2005 Jan 4;96(1-2):195-200.
    least 18 years, and residence in a specific coastal                      Twenty plants, belonging to sixteen families,
    Fijian village in 1989 and 1998, respectively.                      used in traditional New Caledonian and Vanuatu
    Assessments consisted of measurement of height                      medicine for treatment of symptoms potentially
    and weight, collection of demographic data by written               related to tuberculosis (cough, fever or inflammation)
    survey, and administration of the Nadroga Language                  were screened for antimycobacterial activity. We
    Body Image Questionnaire. RESULTS: The                              also screened an original endemic plant, Amborella
    prevalence of overweight and obesity was                            trichopoda, only member of the monogeneric family
    significantly different between the cohorts, increasing             Amborellaceae and considered the most primitive
    from 60% in 1989 to 84% in 1998 (p=0.014). In                       living angiosperm. In total, 55 extracts were
    addition, the age-adjusted mean BMI was                             evaluated for inhibitory activity against
    significantly higher in 1998 compared with 1989                     Mycobacterium bovis BCG strain at a concentration
    (p=0.011). Finally, there were significant between-                 of 100 microg/ml. Methanolic and dichloromethane
    cohort differences in multiple measures of body                     extracts of Amborella trichopoda, Codiaeum
    image, which were mostly independent of BMI.                        peltatum, Myristica fatua, and essential oils
                                                                        Myoporum crassifolium showed an activity at this
    DISCUSSION: At 84%, the prevalence of overweight
                                                                        concentration. Methanolic extract of Amborella
    and obesity in this community sample of Fijian                      trichopoda fruits presented a significant activity with
    women is among the highest in the world. The                        a minimal inhibitory concentration included between
    dramatically increased prevalence over the 9.5-year                 1 and 2.5 microg/ml. In the same conditions, this
    period studied corresponds with rapid social change                 activity was comparable with those of the reference
    in Fiji and significant shifts in prevailing traditional            drugs pyrazynamide and ethambutol, at 20 and 2.5
    attitudes toward body shape.                                        microg/ml, respectively.


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Papua New Guinea Medical Journal                                                           Volume 48, No 1-2, Mar-Jun 2005

12 Boutlis CS, Weinberg JB, Baker J, Bockarie MJ,                         available in the literature were analyzed.
   Mgone CS, Cheng Q, Anstey NM.                                          Phylogenetic studies using different algorithms
   Nitric oxide production and nitric oxide synthase                      (minimum evolution, neighbour joining, maximum
   activity in malaria-exposed Papua New Guinean                          parsimony, and maximum likelihood) gave the same
   children and adults show longitudinal stability and                    clear-cut results. Newly sequenced HTLV-I isolates
   no association with parasitemia                                        described in this report allocated in three well-defined
        Infect Immun 2004 Dec;72(12):6932-6938.                           subtypes: Cosmopolitan, Central African, and a new
       Individuals in areas of intense malaria                            distinct one that we termed ‘Maroni’ subtype (present
   transmission exhibit resistance (or tolerance) to                      in the Maroni Basin, French Guiana, and West
   levels of parasitemia in their blood that would                        Indies). Clearly, the most divergent PTLV-I strains
   normally be associated with febrile illness in malaria-                present in Asia- Australo-Melanesia as well as
   naive subjects. The resulting level of parasitemia                     African and Asian STLV-I derived from the same
   associated with illness (the pyrogenic threshold) is                   node in the phylogenetic tree as isolates of the
   highest in childhood and lowest in adulthood. Clinical                 Central African subtype. In addition, we showed that
   parallels between malarial and bacterial endotoxin                     within each PTLV-I subtype, groups of isolates may
   tolerance have led to the supposition that both share                  be characterized by nonrandom and systematically
   common physiological processes, with nitric oxide                      associated mutations.
   (NO) proposed as a candidate mediator. The
   hypotheses that NO mediates tolerance and blood                    16 Cassar O, Capuano C, Meertens L, Chungue E,
   stage parasite killing in vivo were tested by                         Gessain A.
   determining its relationship to age and parasitemia                   Human T-cell leukemia virus type 1 molecular
   cross-sectionally and longitudinally in a population                  variants, Vanuatu, Melanesia.
   of 195 children and adults from Papua New Guinea                      Emerg Infect Dis 2005 May;11(5):706-710.
   encountering intense malaria exposure. Despite                            Four of 391 Ni-Vanuatu women were infected
   pharmacological clearance of asymptomatic                             with variants of human T-cell leukemia virus type 1
   parasitemia, NO production and mononuclear cell                       (HTLV-1) Melanesian subtype C. These strains had
   NO synthase (NOS) activity were remarkably stable                     env nucleotide sequences approximately 99% similar
   within individuals over time, were not influenced by                  to each other and diverging from the main molecular
   parasitemia, and varied little with age. These results                subtypes of HTLV-1 by 6% to 9%. These strains
   contrast with previous smaller cross-sectional                        were likely introduced during ancient human
   studies. Baseline NO production and NOS activity                      population movements in Melanesia.
   did not protect against recurrent parasitemia,
   consistent with previous data suggesting that NO                   17 Chen N, Wilson DW, Pasay C, Bell D, Martin LB,
   does not have antiparasitic effects against blood                     Kyle D, Cheng Q.
   stage infection in vivo. The NO indices studied were                  Origin and dissemination of chloroquine-resistant
   markedly higher in specimens from study subjects                      Plasmodium falciparum with mutant pfcrt alleles in
   than in samples from Australian controls, and NOS                     the Philippines.
   activity was significantly associated with plasma                     Antimicrob Agents Chemother 2005 May;49(5):2102-
   immunoglobulin E levels, consistent with induction                    2105.
   of NO by chronic exposure to other infections and/                         The pfcrt allelic type and adjacent microsatellite
   or host genetic factors. These results suggest that                   marker type were determined for 82 Plasmodium
   NO is unlikely to mediate killing of blood stage                      falciparum isolates from the Philippines. Mutant pfcrt
   parasites in this setting and is unlikely to be the                   allelic types P1a and P2a/P2b were dominant in
   primary mediator in the acquisition or maintenance                    different locations. Microsatellite analysis revealed
   of malarial tolerance.                                                that P2a/P2b evolved independently in the
                                                                         Philippines, while P1a shared common ancestry with
13 Brown H.                                                              Papua New Guinea chloroquine-resistant parasites.
   Treating the injured and burying the dead.
   Lancet 2005 Jan 15-21;365(9455):204-205.                           18 Cortés A.
                                                                         A chimeric Plasmodium falciparum Pfnbp2b/Pfnbp2a
14 Cameron J.                                                            gene originated during asexual growth.
   Caring for mama and pikinini in Papua New Guinea.                     Int J Parasitol 2005 Feb;35(2):125-130. Epub 2004
   Pract Midwife 2005 Feb;8(2):14-16.                                    Dec 15.
                                                                              The Plasmodium falciparum line 3D7-A has an
15 Capdepont S, Londos-Gagliardi D, Joubert M,                           unusual invasion phenotype, such that it can invade
   Correze P, Lafon ME, Guillemain B, Fleury HJ.                         enzyme-treated and mutant red blood cells that are
   New insights in HTLV-I phylogeny by sequencing and                    resistant to invasion by other parasite lines. 3D7-A
   analyzing the entire envelope gene.                                   has a chimeric Pfnbp2b gene that contains part of
   AIDS Res Hum Retroviruses 2005 Jan;21(1):28-42.                       the repeat region of the paralogous gene Pfnbp2a.
       The HTLV-I envelope plays a major role in the                     This chimeric gene originated by spontaneous gene
   process of target cell infection. It is implied in the                conversion during normal maintenance in culture,
   recognition of the viral receptor(s), penetration of the              indicating that ectopic recombination and gene
   viral genetic material, and induction of host immunity                conversion during asexual growth are potentially
   to the virus. It is thus important to study the genetic               important mechanisms participating in the evolution
   variability of the viral env gene as well as its variation            of paralogous genes in Plasmodium. However, the
   in terms of evolution. In a new approach to these                     presence of the chimeric Pfnbp2b gene in 3D7-A
   features, we sequenced the entire env gene of 65                      was not associated with its peculiar invasion
   HTLV-I isolates originating from Gabon, French                        phenotype.
   Guiana, West Indies, and Iran, such isolates
   representing all major HTLVI phylums but the                       19 Cortés A, Mellombo M, Masciantonio R, Murphy
   Australo-Melanesian one. The sequences obtained                       VJ, Reeder JC, Anders RF.
   and all PTLV-I (HTLV-I and STLV-I) env sequences                      Allele specificity of naturally acquired antibody


                                                                129
Papua New Guinea Medical Journal                                                         Volume 48, No 1-2, Mar-Jun 2005

    responses against Plasmodium falciparum apical                      to be the causative etiology, with serotype 1
    membrane antigen 1.                                                 predominating.
    Infect Immun 2005 Jan;73(1):422-430.
         Antibody responses against proteins located on             22 d’Arcangues C, Piaggio G, Brache V, Aissa RB,
    the surface or in the apical organelles of merozoites              Hazelden C, Massai R, Pinol A, Subakir SB, Su-
    are presumed to be important components of                         juan G; Study Group on Progestogen-induced
    naturally acquired protective immune responses                     Vaginal Bleeding Disturbances.
    against the malaria parasite Plasmodium falciparum.                Effectiveness and acceptability of vitamin E and low-
    However, many merozoite antigens are highly                        dose aspirin, alone or in combination, on Norplant-
    polymorphic, and antibodies induced against one                    induced prolonged bleeding.
    particular allelic form might not be effective in                  Contraception 2004 Dec;70(6):451-462.
    controlling growth of parasites expressing alternative                 A study (ISRCTN 77665712) was undertaken to
    forms. The apical membrane antigen 1 (AMA1) is a                   test the effectiveness and the acceptability of vitamin
    polymorphic merozoite protein that is a target of                  E and low-dose aspirin, alone or in combination, as
    naturally acquired invasion-inhibitory antibodies and              treatment for prolonged vaginal bleeding induced by
    is a leading asexual-stage vaccine candidate. We                   Norplant. A total of 486 Norplant users who were
    characterized the antibody responses against AMA1                  requesting treatment for bleeding lasting longer than
    in 262 individuals from Papua New Guinea exposed                   7 days were enrolled in five centers: Beijing, China;
    to malaria by using different allelic forms of the full            Jakarta, Indonesia; Santiago, Chile; Santo Domingo,
    AMA1 ectodomain and some individual subdomains.                    Dominican Republic; and Tunis, Tunisia. They were
    The majority of individuals had very high levels of                randomized to one of four different 10-day oral
    antibodies against AMA1. The prevalence and titer                  treatments: 200 mg vitamin E daily, 80 mg aspirin
    of these antibodies increased with age. Although                   daily, both or a placebo. Treatment packs were
    antibodies against conserved regions of the molecule               designed to ensure blinding of both the subjects and
    were predominant in the majority of individuals, most              the clinical staff. Neither vitamin E nor low-dose
    plasma samples also contained antibodies directed                  aspirin nor their combination was found to have any
    against polymorphic regions of the antigen. In a few               effect on reducing the length of the bleeding episode
    individuals, predominantly from younger age groups,                for which treatment was taken or on the vaginal
    the majority of antibodies against AMA1 were                       bleeding patterns these women experienced during
    directed against polymorphic epitopes. The D10                     the year of follow-up.
    allelic form of AMA1 apparently contains most if not
    all of the epitopes present in the other allelic forms
    tested, which might argue for its inclusion in future           23 Dale P, Sipe N, Anto S, Hutajulu B, Ndoen E,
    AMA1-based vaccines to be tested. Some important                   Papayungan M, Saikhu A, Prabowa YT.
    epitopes in AMA1 involved residues located in                      Malaria in Indonesia: a summary of recent research
    domain II or III but depended on more than one                     into its environmental relationships.
    domain.                                                            Southeast Asian J Trop Med Public Health 2005
                                                                       Jan;36(1):1-13.
                                                                           A review of the literature was carried out to
20 Cortés A, Mellombo M, Mgone CS, Beck HP,
                                                                       evaluate malaria and its environmental relationships.
   Reeder JC, Cooke BM.                                                Research, in 6 parts of Indonesia, addressed the
   Adhesion of Plasmodium falciparum-infected red                      relationship between malaria incidence and physical
   blood cells to CD36 under flow is enhanced by the                   and socioeconomic environmental factors, using
   cerebral malaria-protective trait South-East Asian                  longitudinal and cross-sectional approaches.
   ovalocytosis.                                                       Physical factors, which are generally important for
       Mol Biochem Parasitol 2005 Aug;142(2):252-                      malaria, included rainfall, mosquito breeding and
   257. Epub 2005 Apr 15.                                              resting sites, their distance from human habitation,
                                                                       and elevation, though the latter was not statistically
21 Corwin AL, Subekti D, Sukri NC, Willy RJ, Master                    significant. Housing conditions were occasionally
   J, Priyanto E, Laras K.                                             important. Social and economic factors of
   A large outbreak of probable rotavirus in Nusa                      importance were income, education, use of bednets
   Tenggara Timur, Indonesia.                                          and pattern of outdoor activities, especially at night.
   Am J Trop Med Hyg 2005 Apr;72(4):488-494.                           Use of repellents, mosquito coils and sleeping
       An outbreak of acute diarrheal disease was                      arrangements were significant in some of the studies.
   reported in Kupang, Nusa Tenggara, Indonesia, in
   August 2002. An investigative team carried out a                 24 De Boer MA, Peters LA, Aziz MF, Siregar B,
   retrospective historical review of records, and a case-             Cornain S, Vrede MA, Jordanova ES, Fleuren GJ.
   control study involving data and specimen                           Human papillomavirus type 18 variants:
   collections. Etiologic determination involving stool                histopathology and E6/E7 polymorphisms in three
   specimens was based on an enzyme-linked                             countries.
   immunosorbent assay, with a reverse transcriptase-                  Int J Cancer 2005 Apr 10;114(3):422-425.
   polymerase chain reaction performed for serotyping                       In cervical cancer, human papillomavirus type
   purposes. Two thousand six hundred probable cases                   18 (HPV 18) and HPV 16 are predominantly related
   were identified from hospital records during the                    to adenocarcinomas (ADCs) and squamous cell
   outbreak months of June, July, August, and                          carcinomas (SCCs), respectively. Here, we studied
   September 2002. Previous enteric outbreaks were                     whether the geographically distributed HPV intratypic
   recognized from the same months in the preceding                    variants are also associated with histologically
   years and all annual outbreak episodes following a                  different tumors. A total of 44 HPV 18-positive and
   period of prolonged, low rainfall. In contrast to                   91 HPV 16-positive cervical carcinomas from
   previous outbreaks discerned from trend analysis,                   Indonesian, Surinamese and Dutch patients were
   the overwhelming burden of disease fell upon the                    histologically classified using hematoxilin and eosin,
   pediatric population versus the young and old in                    periodic acid Schiff plus and Alcian Blue staining.
   previous outbreak instances. Rotavirus was found                    Samples were sequenced and intratypic variants

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Papua New Guinea Medical Journal                                                          Volume 48, No 1-2, Mar-Jun 2005

    were classified into the known phylogenetic                           haplogroups P and Q.
    branches. The Asian Amerindian HPV 18 variant                         Mol Biol Evol 2005 Jun;22(6):1506-1517. Epub 2005
    was observed in 56% of ADCs compared to 15% of                        Apr 6.
    SCCs (p < 0.006). The African HPV 18 variant was                          Modern humans have occupied New Guinea and
    exclusively found in SCCs. By sequencing the HPV                      the nearby Bismarck and Solomon archipelagos of
    18 E6 and E7 open reading frames, we found                            Island Melanesia for at least 40,000 years. Previous
    predicted amino acid changes only in 8 samples.                       mitochondrial DNA (mtDNA) studies indicated that
    Two amino acid changes were consistent throughout                     two common lineages in this region, haplogroups P
    the African branch. In HPV 16-positive tumors, we                     and Q, were particularly diverse, with the
    did not find a specific linkage between intratypic                    coalescence for P considered significantly older than
    variants and histopathology. We conclude that HPV                     that for Q. In this study, we expand the definition of
    18 intratypic variants are differentially associated with             haplogroup Q so that it includes three major
    adenocarcinoma and squamous cell carcinoma of                         branches, each separated by multiple mutational
    the cervix. The findings described here stress the                    distinctions (Q1, equivalent to the earlier definition
    biologic significance of intratypic HPV variants and                  of Q, plus Q2 and Q3). We report three whole-
    might help explaining differences in the pathogenesis                 mtDNA genomes that establish Q2 as a major Q
    of cervical ADCs and SCCs.                                            branch. In addition, we describe 314 control region
                                                                          sequences that belong to the expanded haplogroups
25 Duke T.                                                                P and Q from our Southwest Pacific collection. The
   Slow but steady progress in child health in Papua                      coalescence dates for the largest P and Q branches
   New Guinea.                                                            (P1 and Q1) are similar to each other (approximately
   J Paediatr Child Health 2004 Dec;40(12):659-663.                       50,000 years old) and considerably older than prior
                                                                          estimates. Newly identified Q2, which was found in
26 Duke T, Oa O, Mokela D, Oswyn G, Hwaihwanje I,                         Island Melanesian samples just to the east, is
   Hawap J.                                                               somewhat younger by more than 10,000 years. Our
   The management of sick young infants at primary                        coalescence estimates should be more reliable than
   health centres in a rural developing country.                          prior ones because they were based on significantly
   Arch Dis Child 2005 Feb;90(2):200-205.                                 larger samples as well as complete mtDNA-coding
       AIMS: To investigate the epidemiology of illness                   region sequencing. Our estimates are roughly in
   among young infants at remote health clinics in a                      accord with the current suggested dates for the first
   rural developing country and to determine risk factors                 settlement of New Guinea-Sahul.                   The
   for mortality that might be used as triggers for                       phylogeography of P and Q indicates almost total
   emergency treatment or referral. METHODS: Multi-                       (female) isolation of ancient New Guinea-Island
   site 12 month observational study of consecutive                       Melanesia from Australia that may have existed from
   presentations of infants less than 2 months, and an                    the time of the first settlement. While Q subsequently
   investigation of neonates who died in one district                     diversified extensively in New Guinea-Island
   without accessing health care. RESULTS: Forty per                      Melanesia, it has not been found in Australia. The
   cent of 511 young infant presentations occurred in                     only shared mtDNA haplogroup between Australia
   the first week of life and most of these in the first 24               and New Guinea identified to date remains one minor
   hours. Twenty five deaths were recorded: 18 in the                     branch of P.
   health facilities and seven in villages. In addition
   there were eight stillbirths. Clinical signs predicting            29 Gessner BD, Sutanto A, Linehan M, Djelantik IG,
   death were: not able to feed, fast respiratory rate,                  Fletcher T, Gerudug IK, Ingerani, Mercer D,
   apnoea, cyanosis, ‘too small’, ‘skin-cold’, and severe                Moniaga V, Moulton LH, Moulton LH, Mulholland
   abdominal distension. Signs indicating severe                         K, Nelson C, Soemohardjo S, Steinhoff M,
   respiratory compromise were present in 25% of                         Widjaya A, Stoeckel P, Maynard J, Arjoso S.
   young infants; failure to give oxygen therapy was a                   Incidences of vaccine-preventable Haemophilus
   modifiable factor in 27% of deaths within health                      influenzae type b pneumonia and meningitis in
   facilities. A high proportion of seriously ill young                  Indonesian children: hamlet-randomised vaccine-
   infants were discharged from health facilities early
                                                                         probe trial.
   without adequate follow up. A common reason for
   not seeking care for fatally ill neonates was the                     Lancet 2005 Jan 1-7;365(9453):43-52.
   perception by parents that health staff would respond                      BACKGROUND: Most studies of Haemophilus
   negatively to their social circumstances.                             influenzae type b (Hib) disease in Asia have found
   CONCLUSIONS: Clinical signs with moderate                             low rates, and few Asian countries use Hib vaccine
   positive predictive value for death may be useful                     in routine immunisation programmes. Whether Hib
   triggers for emergency treatment and longer                           disease truly is rare or whether many cases remain
   observation or urgent referral. The results of this                   undetected is unclear. METHODS: To estimate
   study may be useful in planning strategies to address                 incidences of vaccine-preventable Hib pneumonia
   high neonatal mortality rates in developing countries.                and meningitis among children younger than 2 years
                                                                         in Lombok, Indonesia, during 1998-2002, we
27 Duke T, Tefuarani N, Baravilala W.                                    undertook a hamlet-randomised, controlled, double-
   Getting the most out of health education in Papua                     blind vaccine-probe study (818 hamlets). Children
   New Guinea. Report from the 40th Annual Papua                         were immunised (WHO schedule) with diphtheria,
   New Guinea Medical Symposium.                                         tetanus, pertussis (DTP) or DTP-PRP-T (Hib
                                                                         conjugate) vaccine. Vaccine-preventable disease
   Med J Aust 2004 Dec 6-20;181(11-12):606-607.                          incidences were calculated as the difference in rates
                                                                         of clinical outcomes between DTP and DTP-PRP-T
28 Friedlaender J, Schurr T, Gentz F, Koki G,                            groups. Analyses included all children who received
   Friedlaender F, Horvat G, Babb P, Cerchio S,                          at least one vaccine dose. FINDINGS: We enrolled
   Kaestle F, Schanfield M, Deka R, Yanagihara R,                        55073 children: 28147 were assigned DTP-PRP-T
   Merriwether DA.                                                       and 26926 DTP. The proportion of pneumonia
   Expanding southwest pacific mitochondrial                             outcomes prevented by vaccine ranged from less


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    than 0 to 4.8%. Calculated incidences of vaccine-                    94.25%. The results of the statistical analysis of the
    preventable Hib disease (per 10(5) child-years of                    data obtained in this study revealed that the
    observation) for outcome categories were:                            diagnostic specificity, the diagnostic positive
    substantial alveolar consolidation or effusion, less                 predictive value and the diagnostic efficiency of the
    than zero (-43 [95% CI -185 to 98]); all severe                      TB-Dot test were significantly higher (p < 0.05) than
    pneumonia, 264 (95% CI less than zero to 629); all                   those of the ICT-TB test. However, the diagnostic
    clinical pneumonia, 1561 (270 to 2853); confirmed                    sensitivity and the negative predictive value of both
    Hib meningitis, 16 (1.4 to 31); meningitis with                      tests did not differ significantly (p > 0.05). Viewed
    cerebrospinal-fluid findings consistent with a                       from the point of their practicability, it can be justified
    bacterial aetiology, 67 (22 to 112); and admission                   that the ICT-TB test is a very practicable test, which
    for suspected meningitis or presenting to a clinic with              needs only 15 minutes and does not require special
    convulsions, 158 (42 to 273). INTERPRETATION:                        instruments to perform the test, but is more
    Hib vaccine did not prevent the great majority of                    expensive than the TB-Dot test. On the other hand,
    pneumonia cases, including those with alveolar                       though the TB-Dot test is not very practicable and
    consolidation. These results do not support a major                  relatively time consuming, it has a significantly higher
    role for Hib vaccine in overall pneumonia-prevention                 degree of diagnostic value and is much cheaper
    programmes. Nevertheless, the study identified high                  when compared to the ICT-TB test.
    incidences of Hib meningitis and pneumonia;
    inclusion of Hib vaccine in routine infant                       32 Hastings MD, Maguire JD, Bangs MJ,
    immunisation programmes in Asia deserves                            Zimmerman PA, Reeder JC, Baird JK, Sibley CH.
    consideration.                                                      Novel Plasmodium vivax dhfr alleles from the
                                                                        Indonesian Archipelago and Papua New Guinea:
30 Han ET, Song TE, Park JH, Shin EH, Guk SM,                           association with pyrimethamine resistance
   Kim TY, Chai JY.                                                     determined by a Saccharomyces cerevisiae
   Allelic dimorphism in the merozoite surface protein-                 expression system.
   3alpha in Korean isolates of Plasmodium vivax.                       Antimicrob Agents Chemother 2005 Feb;49(2):733-
   Am J Trop Med Hyg 2004 Dec;71(6):745-749.                            740.
       To study the genetic diversity of re-emerging                        In plasmodia, the dihydrofolate reductase
   Plasmodium vivax in the Republic of Korea,                           (DHFR) enzyme is the target of the pyrimethamine
   nucleotide sequence variations at the merozoite                      component of sulfadoxine-pyrimethamine (S/P).
   surface protein-3alpha (PvMSP-3alpha) locus were                     Plasmodium vivax infections are not treated
   analyzed using 24 re-emerging isolates and 4                         intentionally with antifolates. However, outside
   isolates from imported cases. Compared with the                      Africa, coinfections with Plasmodium falciparum and
   well known Belem strain (Brazil), a large number of                  P. vivax are common, and P. vivax infections are
   amino acid substitutions, deletions, and insertions                  often exposed to S/P. Cloning of the P. vivax dhfr
   were found at the locus of the isolates examined.                    gene has allowed molecular comparisons of dhfr
   The Korean isolates were divided into two allelic                    alleles from different regions. Examination of the
   types; type I (15 isolates), similar to the Belem strain,            dhfr locus from a few locations has identified a very
   and type II (9), similar to the Chesson strain (New                  diverse set of alleles and showed that mutant alleles
   Guinea). Isolates from imported cases were                           of the vivax dhfr gene are prevalent in Southeast
   classified into three types; type III (1 from Malaysia),             Asia where S/P has been used extensively. We have
   similar to type B from western Thailand, type IV (1                  surveyed patient isolates from six locations in
   each from Indonesia and India), and type V (1 from                   Indonesia and two locations in Papua New Guinea.
   Pakistan), both being new types. Our results have                    We sequenced P. vivax dhfr alleles from 114 patient
   shown that the MSP-3alpha locus of re-emerging                       samples and identified 24 different alleles that
   Korean P. vivax is dimorphic with two allelic types                  differed from the wild type by synonymous and
   coexisting in the endemic area.                                      nonsynonymous point mutations, insertions, or
                                                                        deletions. Most importantly, five alleles that carried
31 Handojo I, Arifin MZ.                                                four or more nonsynonymous mutations were
   The immunoserological diagnosis of tuberculosis: a                   identified. Only one of these highly mutant alleles
   comparison of two tests.                                             had been previously observed, and all carried the
   Southeast Asian J Trop Med Public Health 2005                        57L and 117T mutations. P. vivax cannot be cultured
   Jan;36(1):141-144.                                                   continuously, so we used a yeast assay system to
        A comparative study of the diagnostic value of                  determine in vitro sensitivity to pyrimethamine for a
   the ICT-TB test and the TB-Dot test, based on                        subset of the alleles.           Alleles with four
   laboratory examination, was carried out in 39 patients               nonsynonymous mutations conferred very high
   suffering from sputum positive pulmonary                             levels of resistance to pyrimethamine. This study
   tuberculosis (25 males and 14 females, aged 16-50                    expands significantly the total number of novel dhfr
   years) and in 48 patients (27 males and 21 females,                  alleles now identified from P. vivax and provides a
   aged 17-55 years) suffering from non-tuberculosis                    foundation for understanding how antifolate
   pulmonary diseases, that had attended the                            resistance arises and spreads in natural P. vivax
   Tembagapura Hospital and the TB Control Health                       populations.
   Center Timika-Mimika, Papua. The diagnostic
   sensitivity of the ICT-TB test was 87.18%, the                    33 Hiawalyer G.
   diagnostic specificity was 81.25%, the diagnostic                    A surveillance information system as a management
   positive predictive value was 79.07%, the negative                   tool: a report from Papua New Guinea.
   predictive value was 88.64%, and the diagnostic                      Soz Praventivmed 2005;50 Suppl 1:S31-S32.
   efficiency was 83.91%. The diagnostic sensitivity                        To have a very good surveillance system, it is
   of the TB-Dot test was 93.31%, the diagnostic                        paramount important to have a functional health
   specificity was 95.83%, the diagnostic positive                      information system that could be easily used for
   predictive value was 94.74%, the negative predictive                 monitoring and investigation of disease outbreaks.
   value was 93.85%, and the diagnostic efficiency was                  In Papua New Guinea (PNG) a national health


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    information system was developed, trialed and                      Jan 24.
    implemented nationwide. Furthermore to have the                         A field-applicable assay for testing anthelmintic
    system working linked to it must be the local health               sensitivity is required to monitor for anthelmintic
    system for sustainability and control. A public health             resistance. We undertook a study to evaluate the
    manual for disease surveillance in PNG was                         ability of three in vitro assay systems to define drug
    developed and is now being used for surveillance.                  sensitivity of clinical isolates of the human hookworm
    This paper describes how the health information                    parasite Necator americanus recovered from
    system, particularly surveillance system was                       children resident in a village in Madang Province,
    developed and implemented on the national scale,                   Papua New Guinea. The assays entailed
    how it was integrated with other management                        observation of drug effects on egg hatch (EHA), larval
    information systems and how information has been                   development (LDA), and motility of infective stage
    used to support management decision-making and                     larvae (LMA). The egg hatch assay proved the best
    informed policy decision. It will highlight some of                method for assessing the response to benzimidazole
    the hurdles that it has encountered while trying to                anthelmintics, while the larval motility assay was
    implement the system. PNG has one of the best                      suitable for assessing the response to ivermectin.
    national health information systems as compared                    The performance of the larval development assay
    to many developing countries but limited information               was unsatisfactory on account of interference caused
    generated from the system. There was also less                     by contaminating bacteria. A simple protocol was
    feedback from all levels of the health sector. We                  developed whereby stool samples were subdivided
    need to improve surveillance on the basic principles               and used for immediate egg recovery, as well as for
    of integration, focus, and sharing of work. There                  faecal culture, in order to provide eggs and infective
    must be an appropriate and timely response and                     larvae, respectively, for use in the egg hatch assay
    feedback. We need to improve on the current system                 and larval motility assay systems. While the assays
    rather than building a new one.                                    proved effective in quantifying drug sensitivity in
                                                                       larvae of the drug-susceptible hookworms examined
34 Hombhanje FW, Hwaihwanje I, Tsukahara T,                            in this study, their ability to indicate drug resistance
   Saruwatari J, Nakagawa M, Osawa H, Paniu MM,                        in larval or adult hookworms remains to be
   Takahashi N, Lum JK, Aumora B, Masta A, Sapuri                      determined.
   M, Kobayakawa T, Kaneko A, Ishizaki T.
   The disposition of oral amodiaquine in Papua New                38 Laman M, Ripa P, Vince J, Tefuarani N.
   Guinean children with falciparum malaria.                          Can clinical signs predict hypoxaemia in Papua New
   Br J Clin Pharmacol 2005 Mar;59(3):298-301.                        Guinean children with moderate and severe
       AIMS: We assessed the disposition of oral                      pneumonia?
   amodiaquine (AQ) and CYP2C8 polymorphism in                        Ann Trop Paediatr 2005 Mar;25(1):23-27.
   20 children with falciparum malaria. METHODS: AQ                        Pulse oximetry was performed on 77 children
   and DEAQ concentrations were determined with                       admitted with acute lower respiratory tract infections
   SPE-HPLC method. CYP2C8 genotypes were                             (ALRI) to the children’s ward in Port Moresby General
   assessed by PCR-RFLP method. RESULTS: AQ                           Hospital, Papua New Guinea over a 4-month period
   was not detectable beyond day 3 postdose. Cmax                     in 2002. Clinical findings were correlated with
   for DEAQ was reached in 3.0 days. The mean                         different levels of hypoxaemia, <93%, <90% and
   values for t1/2, MRT, and AUCtotal were 10.1 days,                 <85%. Cyanosis, head nodding and drowsiness
   15.5 days and 4512.6 microg l(-1) day, respectively.               were good predictors of hypoxia but lacked
   All the children were CYP2C8* homozygous.                          sensitivity. Decisions to use oxygen based on these
   CONCLUSION: Our data are consistent with those                     signs would therefore result in a significant number
   previously reported, and the AQ regimen seems                      of children with hypoxia not receiving oxygen. Pulse
   pharmacokinetically adequate in the absence of                     oximetry is the best indicator of hypoxaemia in
   CYP2C8 polymorphism.                                               children with ALRI and, although relatively expensive,
                                                                      its use might be cost-effective in controlling oxygen
35 Kevau IH, Vince JD, McPherson JV.                                  requirements.
   Tailoring medical education in Papua New Guinea
   to the needs of the country.                                    39 Lawrence G, Leafasia J, Sheridan J, Hills S, Wate
   Med J Aust 2004 Dec 6-20;181(11-12):608-610.                       J, Wate C, Montgomery J, Pandeya N, Purdie D.
                                                                      Control of scabies, skin sores and haematuria in
36 Klapsing P, MacLean JD, Glaze S, McClean KL,                       children in the Solomon Islands: another role for
   Drebot MA, Lanciotti RS, Campbell GL.                              ivermectin.
   Ross River virus disease reemergence, Fiji, 2003-                  Bull World Health Organ 2005 Jan;83(1):34-42. Epub
   2004.                                                              2005 Jan 21.
   Emerg Infect Dis 2005 Apr;11(4):613-615.                               OBJECTIVE: To assess the effects of a 3-year
       We report 2 clinically characteristic and                      programme aimed at controlling scabies on five small
   serologically positive cases of Ross River virus                   lagoon islands in the Solomon Islands by monitoring
   infection in Canadian tourists who visited Fiji in late            scabies, skin sores, streptococcal skin
   2003 and early 2004. This report suggests that Ross                contamination, serology and haematuria in the island
   River virus is once again circulating in Fiji, where it            children. METHODS: Control was achieved by
   apparently disappeared after causing an epidemic                   treating almost all residents of each island once or
   in 1979 to 1980.                                                   twice within 2 weeks with ivermectin (160-250
                                                                      microg/kg), except for children who weighed less
37 Kotze AC, Coleman GT, Mai A, McCarthy JS.                          than 15 kg and pregnant women, for whom 5%
   Field evaluation of anthelmintic drug sensitivity using            permethrin cream was used. Reintroduction of
   in vitro egg hatch and larval motility assays with                 scabies was controlled by treating returning residents
   Necator americanus recovered from human clinical                   and visitors, whether or not they had evident scabies.
   isolates.                                                          FINDINGS: Prevalence of scabies dropped from
   Int J Parasitol 2005 Apr 1;35(4):445-453. Epub 2005                25% to less than 1% (P < 0.001); prevalence of sores


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    from 40% to 21% (P < 0.001); streptococcal                         two-locus haplotypes were examined in 367
    contamination of the fingers in those with and without             unrelated Melanesians living on the islands of
    sores decreased significantly (P = 0.02 and 0.047,                 Vanuatu and New Caledonia. Diversity at all HLA
    respectively) and anti-DNase B levels decreased (P                 class-I and class-II loci was relatively limited. In
    = 0.002). Both the proportion of children with                     class-I loci, three HLA-A allelic groups (HLA-A*24,
    haematuria and its mean level fell (P = 0.002 and P                HLA-A*34 and HLA-A*11), seven HLA-B alleles or
    < 0.001, respectively). No adverse effects of the                  allelic groups (HLA-B*1506, HLA-B*5602, HLA-B*13,
    treatments were seen. CONCLUSION: The results                      HLA-B*5601, HLA-B*4001, HLA-B*4002 and HLA-
    show that ivermectin is an effective and practical                 B*2704) and four HLA-C alleles or allelic groups
    agent in the control of scabies and that control                   (HLA-Cw*04, HLA-Cw*01, HLA-Cw*0702 and HLA-
    reduces the occurrence of streptococcal skin disease               Cw*15) constituted more than 90% of the alleles
    and possible signs of renal damage in children.                    observed. In the class-II loci, four HLA-DRB1 alleles
    Integrating community-based control of scabies and                 (HLA-DRB1*15, HLA-DRB1*11, HLA-DRB1*04 and
    streptococcal skin disease with planned                            HLA-DRB1*16), three HLA-DRB3-5 alleles (HLA-
    programmes for controlling filariasis and intestinal               DRB3*02, HLA-DRB4*01 and HLA-DRB5*01/02)
    nematodes could be both practical and produce great                and five HLA-DQB1 alleles (HLA-DQB1*0301, HLA-
    health benefits.                                                   DQB1*04, HLA-DQB1*05, HLA-DQB1*0601 and
                                                                       HLA-DQB1*0602) constituted over 93, 97 and 98%
40 Lehmann D, Vail J, Firth MJ, de Klerk NH, Alpers                    of the alleles observed, respectively. Homozygosity
   MP.                                                                 showed significant departures from expected levels
   Benefits of routine immunizations on childhood                      for neutrality based on allele frequency (i.e. excess
   survival in Tari, Southern Highlands Province, Papua                diversity) at the HLA-B, HLA-Cw, HLA-DQB1 and
   New Guinea.                                                         HLA-DRB3/5 loci on some islands. The locus with
   Int J Epidemiol 2005 Feb;34(1):138-148. Epub 2004                   the strongest departure from neutrality was HLA-
   Nov 23.                                                             DQB1, homozygosity being significantly lower than
        BACKGROUND: Non-specific beneficial as well                    expected on all islands except New Caledonia. No
   as deleterious effects of childhood immunizations                   consistent pattern was demonstrated for any HLA
   have been reported in areas of high mortality. This                 locus in relation to malaria endemicity.
   study aimed to determine the effects of diphtheria-
   tetanus-whole-cell-pertussis (DTP), BCG, hepatitis              42 McGain F, Limbo A, Williams DJ, Didei G, Winkel
   B, and measles vaccines on mortality in the                        KD.
   highlands of Papua New Guinea (PNG). METHODS:                      Snakebite mortality at Port Moresby General
   Demographic events for children born in 1989-1994                  Hospital, Papua New Guinea, 1992-2001.
   who were under monthly demographic surveillance                    Med J Aust 2004 Dec 6-20;181(11-12):687-691.
   in Tari were recorded from birth until age 2 years,                    OBJECTIVE: Fatal snakebites at Port Moresby
   out-migration, death, or the end of the study period.              General Hospital (PMGH), Papua New Guinea
   Data on BCG, hepatitis B, DTP, measles and                         (PNG), were examined to identify interventions that
   pneumococcal polysaccharide vaccination were                       may improve patient survival.                 DESIGN:
   collected monthly from clinic records. To allow for                Retrospective case series. SUBJECTS AND
   different characteristics of immunized and non-                    SETTING: Inpatients at PMGH who presented with
   immunized children, analysis included conditioning                 snakebite, had evidence of envenomation, and died
   on a propensity score for vaccination, adjusting for               as inpatients between 1 January 1992 and 31
   differences in children’s background characteristics.              December 2001. OUTCOME MEASURES: Number
   RESULTS: In all, 101/3502 children (3%) who had                    and cause of fatalities; ventilation bed-days;
   at least one vaccine died between ages 29 days and                 antivenom timing, dose and price. RESULTS: 87
   24 months were compared to 112/546 (21%) who                       deaths occurred among 722 snakebite admissions
   had none. BCG was associated with lower mortality                  to the intensive care unit (ICU). Of these 722
   in the 1-5 month age group (hazard ratio [HR] = 0.17,              patients, 82.5% were ventilated, representing 45%
   95% CI: 0.09, 0.34), measles vaccine with lower                    of all ventilated ICU patients and 60% (3430/5717)
   mortality at age 6-11 months (HR = 0.42, 95% CI:                   of all ICU ventilator bed-days. The median duration
   0.17, 1.01), and pneumococcal polysaccharide                       of ventilation in fatal snakebite cases was
   vaccine with lower mortality at age 12-23 months                   significantly less than in non-fatal cases for children
   (HR = 0.42, 95% CI: 0.19, 0.93). One or more doses                 (3.0 v. 4.5 days) and adults (3.0 v. 5.0 days). The
   of DTP was associated with lower overall mortality                 case-fatality rate for children (14.6%) was
   (HR = 0.27, 95% CI: 0.16, 0.44), particularly in the               significantly greater than that for adults (8.2%). Sixty
   1-5 month age group (HR = 0.19, 95% CI: 0.10,                      fatalities were examined in detail: 75% received
   0.34), and also in those who had had prior BCG (HR                 blood products; 53% received antivenom (mostly a
   = 0.45, 95% CI: 0.22, 0.91). CONCLUSION: Routine                   single ampoule of polyvalent), but only 5% received
   immunizations are effective in reducing overall                    antivenom < or = 4 hours post-bite. Major causes
   mortality in young children in an area of high                     of death included respiratory complications (50%),
   mortality. In particular, DTP, whether considered                  probable intracerebral haemorrhage (17%), and
   separately or in addition to BCG, was associated                   renal failure (10%). Antivenom unit costs increased
   with a lowering of overall mortality, in contrast to               significantly over the decade; in 2000 an ampoule
   findings reported from Guinea-Bissau.                              of polyvalent antivenom was 40-fold more expensive
                                                                      in PNG than in Australia on a gross domestic product
41 Maitland K, Bunce M, Harding RM, Barnardo MC,                      (A dollars) per capita basis. CONCLUSIONS:
   Clegg JB, Welsh K, Bowden DK, Williams TN.                         Management of severe snakebite is a major
   HLA class-I and class-II allele frequencies and two-               challenge for PMGH. Improved antivenom
   locus haplotypes in Melanesians of Vanuatu and New                 procurement and use policies (including increased
   Caledonia.                                                         use of appropriate monovalent antivenoms),
   Tissue Antigens 2004 Dec;64(6):678-686.                            combined with targeted snakebite education
       HLA class-I and class-II allele frequencies and                interventions (community- and hospital-based), are


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    key interventions to reduce the ongoing toll from                 (hemoglobin level < 7.5 g/dL) from 0.0-3.3% to 3.8-
    snakebite.                                                        18.4%. These massive increases in morbidity have
                                                                      devastating impact on the affected communities and
43 Mosley LM, Sharp DS, Singh S.                                      highlight that malaria epidemics are a serious and
   Effects of a tropical cyclone on the drinking-water                increasing public health problem in the highlands of
   quality of a remote Pacific island.                                Papua New Guinea.
   Disasters 2004 Dec;28(4):405-417.
        The effect of a cyclone (Ami, January 2003) on            45 Owen IL.
   drinking-water quality on the island of Vanua Levu,               Parasitic zoonoses in Papua New Guinea.
   Fiji was investigated. Following the cyclone nearly               J Helminthol 2005 Mar;79(1):1-14.
   three-quarters of the samples analysed did not                         Relatively few species of zoonotic parasites have
   conform to World Health Organisation (WHO)                        been recorded in humans in Papua New Guinea. A
   guideline values for safe drinking-water in terms of              greater number of potentially zoonotic species,
   chlorine residual, total and faecal coliforms, and                mostly nematodes, occur in animals but are yet to
   turbidity. Turbidity and total coliform levels                    be reported from humans. Protozoa is the best
   significantly increased (up 56 and 62 per cent,                   represented group of those infecting man, with
   respectively) from pre-cyclone levels, which was                  Giardia duodenalis, Cryptosporidium parvum,
   likely due to the large amounts of silt and debris                Cyclospora cayetanesis, Toxoplasma gondii,
   entering water-supply sources during the cyclone.                 Sarcocystis spp., Entamoeba polecki, Balantidium
   The utility found it difficult to maintain a reliable             coli and, possibly, Blastocystis hominis. The only
   supply of treated water in the aftermath of the                   zoonotic helminths infecting humans include the
   disaster. Communities were unaware they were                      trematode Paragonimus westermani, the cestodes
   drinking water that had not been adequately treated.              Hymenolepis nana, H. diminuta and the sparganum
   Circumstances permitted this cyclone to be used as                larva of Spirometra erinacea, and the nematodes
   a case study to assess whether a simple paper-strip               Trichinella papuae and Angiostrongylus cantonensis
   water-quality test (the hydrogen sulphide, H(2)S) kit             and, possibly, Ascaris suum. Other groups
   could be distributed and used for community-based                 represented            are         Acanthocephala
   monitoring following such a disaster event to better              (Macracanthorhynchus hirudinaceus)), insects
   protect public health. The H(2)S test results                     (Chrysomya bezziana, Cimex sp., Ctenocephalides
   correlated well with faecal and total coliform results            spp.), and mites (Leptotrombidium spp. and, possibly
   as found in previous studies. A small percentage of               Sarcoptes scabiei, and Demodex sp.). One leech
   samples (about 10 per cent) tested positive for faecal            (Phytobdella lineata) may also be considered as
   and total coliforms but did not test positive in the              being zoonotic. The paucity of zoonotic parasite
   H(2)S test. It was concluded that the H(2)S test                  species can be attributed to long historical isolation
   would be well suited to wider use, especially in the              of the island of New Guinea and its people, and the
   absence of water-quality monitoring capabilities for              absence until recent times of large placental
   outer island groups as it is inexpensive and easy to              mammals other than pig and dog. Some zoonotic
   use, thus enabling communities and community                      helminths have entered the country with recent
   health workers with minimal training to test their own            importation of domestic animals, in spite of
   water supplies without outside assistance. The                    quarantine regulations, and a few more (two
   importance of public education before and after                   cestodes, one nematode and one tick) are poised
   natural disasters is also discussed.                              to enter from neighbouring countries, given the
                                                                     opportunity. Improvement in water supplies, human
44 Mueller I, Namuigi P, Kundi J, Ivivi R, Tandrapah                 hygiene and sanitation would reduce the prevalence
   T, Bjorge S, Reeder JC.                                           of many of these parasites, and thorough cooking
   Epidemic malaria in the highlands of Papua New                    of meat would lessen the risk of infection by some
   Guinea.                                                           others.
   Am J Trop Med Hyg 2005 May;72(5):554-560.
       As part of a larger study into the epidemiology            46 Poka H.
   of malaria in the highlands of Papua New Guinea,                  Practising in rural Papua New Guinea.
   outbreak investigations were carried out at the end               Med J Aust 2004 Dec 6-20;181(11-12):609.
   of the 2002 rainy season in 11 villages situated
   between 1,400 and 1,700 meters above sea level                 47 Pozio E, Owen IL, Marucci G, La Rosa G.
   that had reported epidemics. Locations and timing                 Inappropriate feeding practice favors the
   of these epidemics corresponded largely to those                  transmission of Trichinella papuae from wild pigs to
   reported in the pre-control era of the 1960s and                  saltwater crocodiles in Papua New Guinea.
   1970s. On average, 28.8% (range = 10.3-63.2%)                     Vet Parasitol 2005 Feb 28;127(3-4):245-251. Epub
   of people in each of the 11 villages were found to be             2004 Dec 16.
   infected with malaria. Plasmodium falciparum                          The recent discovery of Trichinella zimbabwensis
   accounted for 59% of all identified infections and P.             in farmed crocodiles (Crocodilus niloticus) of
   vivax for 34%. The majority (53%) of infections were              Zimbabwe and its ability to infect mammals, and the
   symptomatic. Although symptomatic infections were                 development of both T. zimbabwensis and Trichinella
   most common in children 2-9 years of age (36%),                   papuae in experimentally infected reptiles led to an
   even in adults a prevalence of 20% was observed.                  investigation of Trichinella infection in saltwater
   A comparison with earlier non-epidemic data in three              crocodiles (Crocodylus porosus) and in wild pigs
   of the villages without easy access to health care                (Sus scrofa) of Papua New Guinea, to see if T.
   showed markedly increased levels of morbidity, with               papuae also, is present in both cold- and warm-
   6-10-fold increases in parasite prevalence, a 3-fold              blooded animals. Of 222 crocodiles examined, 47
   increase in both measured and reported fevers, and                animals (21.2%), all from Kikori, Gulf Province, were
   a 12-fold increase in enlarged spleens. The average               positive for non-encapsulated larvae in the muscles.
   hemoglobin levels were reduced by 2.3-3.5 g/dL, with              The greatest number of larvae was found usually in
   a concurrent increase in moderate to severe anemia                the biceps, with an average of 7 larvae/g. One


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Papua New Guinea Medical Journal                                                         Volume 48, No 1-2, Mar-Jun 2005

    isolate from a crocodile infected successfully both                 in Mozambique, 10 in Indonesia, and 9 in South
    laboratory rats and mice. Of 81 wild pigs examined,                 Africa. At all study sites, the majority of RSV cases
    9 from Bensbach river area (Western Province) and                   occurred in infants. CONCLUSION: These studies
    1 from Kikori area (Gulf Province) were positive for                demonstrate that RSV contributes to a substantial
    non-encapsulated larvae in the muscles. Trichinella                 but quite variable burden of LRI in children aged < 5
    larvae from both saltwater crocodiles and wild pigs                 years in four developing countries. The possible
    have been identified by multiplex-PCR analysis as                   explanations for this variation include social factors,
    T. papuae. The sequence analysis of the region                      such as family size and patterns of seeking health
    within the large subunit ribosomal DNA, known as                    care; the proportion of children infected by human
    the expansion segment V, has shown the presence                     immunodeficiency syndrome (HIV); and differences
    of a molecular marker distinguishing T. papuae                      in clinical definitions used for obtaining samples. The
    isolates of Bensbach river area from those of Kikori                age distribution of cases indicates the need for an
    area. This marker could be useful to trace back the                 RSV vaccine that can protect children early in life.
    geographical origin of the infected animal. The
    epidemiological investigation carried out in the Kikori         51 Rodgers-Bird QM.
    area has shown that local people catch young                       Challenges of Solomon Island medical students: a
    crocodiles in the wild and keep them in holding pens               graduation vote of thanks. Letter
    for several months, before sending them to the                     Aust J Rural Health 2005 Apr;13(2):128.
    crocodile farm in Lae (Morobe Province). They feed
    the crocodiles primarily with wild pig meat bought at
    the local market and also with fish. These results              52 Sa JM, Nomura T, Neves J, Baird JK, Wellems
    stress the importance of using artificial digestion for            TE, del Portillo HA.
    routinely screening of swine and crocodiles, and of                Plasmodium vivax: allele variants of the mdr1 gene
    adopting measures for preventing the spread of                     do not associate with chloroquine resistance among
    infection, such as the proper disposal of carcasses                isolates from Brazil, Papua, and monkey-adapted
    and the adequate freezing of meat.                                 strains.
                                                                       Exp Parasitol 2005 Apr;109(4):256-259.
48 Ratu Sade K.                                                            We describe here the sequence of the
   The status of emergency medicine in Makira Ulawa                    Plasmodium vivax mdr1 gene from 10 different
   Province, Solomon Islands.                                          isolates differing in chloroquine sensitivity. The
   Emerg Med Australas 2005 Apr;17(2):167-169.                         deduced amino acid sequence of PvMDR1 shares
        This Perspective reports on the challenges that                more than 70% similarity with other malarial MDR
   face a solo doctor in a provincial hospital in the                  proteins and it displays consensus motifs of an ABC
   Solomon Islands following the civil disturbances of                 family transporter including two transmembrane
   1998-2003. The Health Service is seriously                          domains and two ATP binding cassettes. Similarity
   constrained by a paucity of funding, supplies and                   and dendrogram analyses revealed that sequences
   personnel. In spite of that, a rudimentary service                  could be grouped according to their geographical
   can be provided and lives can be saved using simple                 origin. Within each geographical group however,
   techniques and basic resources. Further training of                 no correlation was found between chloroquine
   nurses, midwives and doctors is required.                           resistance and specific mutations.
   Emergency medicine, as a generalist discipline,
   provides a foundation to improve the delivery of care            53 Schultz R.
   to the acutely ill and injured in these circumstances.              A two-year placement in the Solomon Islands.
                                                                       Med J Aust 2004 Dec 6-20;181(11-12):604-605.
49 Reeder JC.
   Papua New Guinea: targeting research to things that              54 Suligoi B, Danaya RT, Sarmati L, Owen IL, Boros
   matter.                                                             S, Pozio E, Andreoni M, Rezza G.
   Med J Aust 2004 Dec 6-20;181(11-12):610-611.                        Infection with human immunodeficiency virus, herpes
                                                                       simplex virus type 2, and human herpes virus 8 in
50 Robertson SE, Roca A, Alonso P, Simoes EA,                          remote villages of southwestern Papua New Guinea.
   Kartasasmita CB, Olaleye DO, Odaibo GN,                             Am J Trop Med Hyg 2005 Jan;72(1):33-36.
   Collinson M, Venter M, Zhu Y, Wright PF.                                To investigate the spread of human
   Respiratory syncytial virus infection: denominator-                 immunodeficiency virus (HIV) and other sexually
   based studies in Indonesia, Mozambique, Nigeria                     transmitted viruses, two serosurveys (the first in 1999
   and South Africa.                                                   among 56 adults and the second in 2001 among
   Bull World Health Organ 2004 Dec;82(12):914-922.                    351 adults) were conducted in remote villages of
   Epub 2005 Jan 5.                                                    the southwestern part of Papua New Guinea. Only
       OBJECTIVE: To assess the burden of respiratory                  one individual was positive for antibodies to HIV. In
   syncytial virus (RSV)-associated lower respiratory                  2001, the seroprevalence of human herpes virus 8
   infections (LRI) in children in four developing                     (HHV-8) was 32.2%, and the seroprevalence of
   countries. METHODS: A WHO protocol for                              herpes simplex virus type 2 (HSV-2) was 27.4%.
   prospective population-based surveillance of acute                  Both prevalence rates increased with age, and were
   respiratory infections in children aged less than 5                 lower in the villages near the Bensbach River. The
   years was used at sites in Indonesia, Mozambique,                   seropositivity of HSV-2 was independently correlated
   Nigeria and South Africa. RSV antigen was identified                with HHV-8 infection. Our data show that the
   by enzyme-linked immunosorbent assay performed                      inhabitants of the southwestern region of Papua New
   on nasopharyngeal specimens from children                           Guinea currently experience an extremely low
   meeting clinical case definitions. FINDINGS: Among                  circulation of HIV. However, the high prevalence of
   children aged < 5 years, the incidence of RSV-                      infectious agents that can be sexually transmitted,
   associated LRI per 1000 child-years was 34 in                       such as HSV-2 and to a lesser extent HHV-8,
   Indonesia and 94 in Nigeria. The incidence of RSV-                  indicates the presence of behavioral patterns that
   associated severe LRI per 1000 child-years was 5                    may facilitate the spread of HIV in this area of

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Papua New Guinea Medical Journal                                                       Volume 48, No 1-2, Mar-Jun 2005

    currently low endemicity.                                         discharge and 41 were lost to follow-up. Major
                                                                      neurological sequelae were found in 50 (63 per cent)
55 Temple V, Mapira P, Adeniyi K, Sims P.                             of surviving children, and 27 (34 percent) had multiple
   Iodine deficiency in Papua New Guinea (sub-clinical                severe complications. In rural Papua New Guinea
   iodine deficiency and salt iodization in the highlands             meningitis causes high rates of mortality and severe
   of Papua New Guinea).                                              long-term disability in a high proportion of survivors.
   J Public Health (Oxf) 2005 Mar;27(1):45-48. Epub                   High-level resistance to chloramphenicol is likely to
   2004 Nov 25.                                                       be part of the reason for this, but widespread
        Data on the status about iodine nutrition in                  availability of third-generation cephalosporins for the
   children in Papua New Guinea (PNG) are scarce.                     treatment of meningitis, although urgently required,
   This study attempts to determine the mean daily per                will not overcome the other problems of delayed
   capita consumption of salt, the iodine content of salt             presentation with established complications. There
   in the households and retail shops and the urinary                 is a need for the introduction of conjugate
   iodine concentration in children (6-12 years) in Hella             Haemophilus influenzae vaccine, and affordable
   Region, Southern Highland Province (SHP), PNG.                     vaccination strategies against Streptococcus
   The mean daily consumption of salt was 2.62 +/-                    pneumoniae. Richer countries could sponsor these
   1.29 g. The iodine content of salt was >30 p.p.m. in               vaccines in developing countries, and apply pressure
   95 per cent of households and 100 per cent of retail               on vaccine producers to lower the costs.
   shops. The median urinary iodine concentration of
   48.0 mg/l for all the children indicates moderate              58 Wood DM, Alsahaf H, Streete P, Dargan PI, Jones
   iodine deficiency. The median urinary iodine                      AL.
   concentrations for the male (67.0 mg/l) and female                Fatality after deliberate ingestion of the pesticide
   (44.0 mg/l) children indicate mild and moderate                   rotenone: a case report.
   iodine deficiency, respectively. 68.42 per cent of the            Crit Care 2005 Jun;9(3):R280-284. Epub 2005 Apr
   male and 81.82 per cent of the female children have               29.
   urinary iodine concentration <100 mg/l, indicating                     Rotenone is a pesticide derived from the roots
   that iodine deficiency is a potential public health               of plants from the Leguminosae family. Poisoning
   problem in the Hella region. These results indicate               following deliberate ingestion of these plant roots
   a need for further assessment of the implementation               has commonly been reported in Papua New Guinea.
   of the universal salt iodization strategy for the                 However, poisoning with commercially available
   elimination of iodine deficiency in the SHP, PNG.                 rotenone in humans has been reported only once
                                                                     previously following accidental ingestion in a 3.5-
56 Tokudome S, Soeripto, Triningsih FX, Ananta I,                    year-old child. Therefore, the optimal management
   Suzuki S, Kuriki K, Akasaka S, Kosaka H,                          of rotenone poisoning is not known. After deliberate
   Ishikawa H, Azuma T, Moore MA.                                    ingestion of up to 200 ml of a commercially available
   Rare Helicobacter pylori infection as a factor for the            0.8% rotenone solution, a 47-year-old female on
   very low stomach cancer incidence in Yogyakarta,                  regular metformin presented with a reduced level of
   Indonesia.                                                        consciousness, metabolic acidosis and respiratory
   Cancer Lett 2005 Feb 28;219(1):57-61.                             compromise. Metformin was not detected in
       To elucidate factors associated with the very low             premortem blood samples obtained. Despite
   risk of gastric neoplasia in Yogyakarta, Indonesia,               intensive supportive management, admission to an
   approximately 1/50 of the level in Japan, we recruited            intensive care unit, and empirical use of N-
   52 male and 39 female participants from the general               acetylcysteine and antioxidant therapy, she did not
   populace in the city of Yogyakarta in October 2003.               survive. Poisoning with rotenone is uncommon but
   Helicobacter pylori IgG antibodies were found in only             is potentially fatal because this agent inhibits the
   5% (0-13) (95% confidence interval) and 4% (0-9)                  mitochondrial respiratory chain. In vitro cell studies
   for Javanese males and females, respectively, and                 have shown that rotenone-induced toxicity is reduced
   were statistically lower than the 62% (58-65) and                 by the use of N-acetylcysteine, antioxidants and
   57% (53-60), respectively, in Japanese.                           potassium channel openers. However, no animal
   Furthermore, positive findings of pepsinogen test                 studies have been reported that confirm these
   were only 0 and 2% (0-6) for males and females, in                findings, and there are no previous reports of
   Yogyakarta, and were again significantly lower than               attempted use of these agents in patients with acute
   the 23% (22-25) and 22% (20-23), in Japan. The                    rotenone-induced toxicity.
   very low incidence of stomach cancer in Yogyakarta
   may be due to a low prevalence of H. pylori infection          59 Wuster W, Dumbrell AJ, Hay C, Pook CE, Williams
   and chronic atrophic gastritis.                                   DJ, Fry BG.
                                                                     Snakes across the Strait: trans-Torresian
57 Wandi F, Kiagi G, Duke T.                                         phylogeographic relationships in three genera of
   Long-term outcome for children with bacterial                     Australasian snakes (Serpentes: Elapidae:
   meningitis in rural Papua New Guinea.                             Acanthophis, Oxyuranus, and Pseudechis).
   J Trop Pediatr 2005 Feb;51(1):51-53. Epub 2004 Dec                Mol Phylogenet Evol 2005 Jan;34(1):1-14.
   15.                                                                   We analyze the phylogeny of three genera of
       This study was undertaken to evaluate the long-               Australasian elapid snakes (Acanthophis-death
   term neurological outcome for survivors of bacterial              adders; Oxyuranus-taipans; Pseudechis-
   meningitis in rural Papua New Guinea. Children who                blacksnakes), using parsimony, maximum likelihood,
   were discharged from Nonga Base Hospital in                       and Bayesian analysis of sequences of the
   Rabaul with a diagnosis of bacterial meningitis                   mitochondrial cytochrome b and ND4 genes. In
   between 1992 and 2000 were evaluated in their                     Acanthophis and Pseudechis, we find evidence of
   home villages or on review at hospital. Neurological              multiple trans-Torresian sister-group relationships.
   and developmental complications were documented.                  Analyses of the timing of cladogenic events suggest
   The outcomes for 80 of 121 eligible children were                 crossings of the Torres Strait on several occasions
   determined; eight had died following hospital                     between the late Miocene and the Pleistocene.


                                                            137
Papua New Guinea Medical Journal                                                  Volume 48, No 1-2, Mar-Jun 2005

    These results support a hypothesis of repeated land          kavalactone, kawain, in kava extracts as causing
    connections between Australia and New Guinea in              strong antiproliferative and apoptotic effect in human
    the late Cenozoic. Additionally, our results reveal          bladder cancer cells. Flavokawain A results in a
    undocumented genetic diversity in Acanthophis and            significant loss of mitochondrial membrane potential
    Pseudechis, supporting the existence of more                 and release of cytochrome c into the cytosol in an
    species than previously believed, and provide a              invasive bladder cancer cell line T24. These effects
    phylogenetic framework for a reinterpretation of the         of flavokawain A are accompanied by a time-
    systematics of these genera. In contrast, our                dependent decrease in Bcl-x(L), a decrease in the
    Oxyuranus scutellatus samples from Queensland                association of Bcl-x(L) to Bax, and an increase in
    and two localities in New Guinea share a single              the active form of Bax protein. Using the primary
    haplotype, suggesting very recent (late Pleistocene)         mouse embryo fibroblasts Bax knockout and wild-
    genetic exchange between New Guinean and                     type cells as well as a Bax inhibitor peptide derived
    Australian populations.                                      from the Bax-binding domain of Ku70, we showed
                                                                 that Bax protein was, at least in part, required for
60 Zi X, Simoneau AR.                                            the apoptotic effect of flavokawain A. In addition,
   Flavokawain A, a novel chalcone from kava extract,            flavokawain A down-regulates the expression of X-
   induces apoptosis in bladder cancer cells by                  linked inhibitor of apoptosis and survivin. Because
   involvement of Bax protein-dependent and                      both X-linked inhibitor of apoptosis and survivin are
   mitochondria-dependent apoptotic pathway and                  main factors for apoptosis resistance and are
   suppresses tumor growth in mice.                              overexpressed in bladder tumors, our data suggest
   Cancer Res 2005 Apr 15;65(8):3479-3486.                       that flavokawain A may have a dual efficacy in
        Consumption of the traditional kava preparation          induction of apoptosis preferentially in bladder
   was reported to correlate with low and uncustomary            tumors. Finally, the anticarcinogenic effect of
   gender ratios (more cancer in women than men) of              flavokawain A was evident in its inhibitory growth of
   cancer incidences in three kava-drinking countries:           bladder tumor cells in a nude mice model (57% of
   Fiji, Vanuatu, and Western Samoa. We have                     inhibition) and in soft agar.
   identified flavokawain A, B, and C but not the major




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