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Genotype and phylogenetic characterization of hepatitis B virus among multi-ethnic cohort in Hawaii.

AIM: Hepatitis B virus (HBV) genomes in carriers from Hawaii have not been evaluated previously. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Hawaii. METHODS: Genotyping of HBV among 61 multi-ethnic carriers in Hawaii was performed by genetic methods. Three complete genomes and 61 core promoter/precore regions of HBV were sequenced directly. RESULTS: HBV genotype distribution among the 61 carriers was 23.0% for genotype A, 14.7% for genotype B and 62.3% for genotype C. Genotypes A, B and C were obtained from the carriers whose ethnicities were Filipino and Caucasian, Southeast Asian, and various Asian and Micronesian, respectively. All cases of genotype B were composed of recombinant strains with genotype C in the precore plus core region named genotype Ba. HBeAg was detected more frequently in genotype C than in genotype B (68.4% vs 33.3%, P<0.05) and basal core promoter (BCP) mutation (T1762/A1764) was more frequently found in genotype C than in genotype B. Twelve of the 38 genotype C strains possessed C at nucleotide (nt) position 1858 (C-1858). However there was no significant difference in clinical characteristics between C-1858 and T-1858 variants. Based on complete genome sequences, phylogenetic analysis revealed one patient of Micronesian ethnicity as having C-1858 clustered with two isolates from Polynesia with T-1858. In addition, two strains from Asian ethnicities were clustered with known isolates in carriers from Southeast Asia. CONCLUSION: Genotypes A, B and C are predominant types among multi-ethnic HBV carriers in Hawaii, and distribution of HBV genotypes is dependent on the ethnic background of the carriers in Hawaii.

Adult↗

A polymerase chain reaction assay for the detection of Brugia malayi in blood.

There is need for sensitive, rapid, species-specific diagnosis of Brugia filarial parasites because traditional methods are tedious and time-consuming, with little guarantee of species specificity. A polymerase chain reaction (PCR)-based assay was developed using the Hha I family of highly repeated DNA sequences from Brugia. The assay was tested on 124 human blood samples collected in a field study in Indonesia. These included 66 microfilaria-positive samples from patients in an area endemic for Brugia, 30 from healthy individuals from the same endemic area, and 28 from healthy individuals from a nonendemic area. Twenty-eight blood samples collected in a village in French Polynesia endemic for Wuchereria bancrofti, but not B. malayi, were also tested. The blood samples were screened using the traditional blood smear and membrane filtration methods, which served as the gold standards to which the PCR assay was compared. The samples were digested with proteinase K, extracted with phenol and chloroform, and dialyzed. A fraction of the dialyzed product was used in PCRs using Hha I-specific primers. The PCR assay correctly identified all of the microfilaria-positive samples as PCR positive and all of the nonendemic samples as PCR negative. Additionally, 26 of 30 samples from healthy individuals in the endemic area were also identified as PCR negative, while four were PCR positive. It is likely that these four individuals had very low-level or cryptic infections, and that the PCR assay detected circulating DNA released from dead filariae. The results indicate that the Hha I PCR detection system is rapid, species-specific, and sensitive.

Animals↗

Meta-analysis of over 8,000 individuals from Hawai'i and Samoa for genetic associations to cardiometabolic phenotypes.

Although genome-wide association studies (GWAS) now routinely reveal genetic associations and biological insights in millions of individuals, underrepresentation of global populations, such as those from Polynesia, continue to persist. These exclusions, often driven by logistical challenges and lack of data, prevent systematic identification of population-enriched associations, such as the association of the missense variant at the CREBRF locus to BMI and type 2 diabetes discovered commonly occurring in Polynesian populations due to its rarity in global populations. Armed with the recently updated TOPMed imputation panel that could benefit studies in diverse populations that previously had poorer imputation performance, we performed the first GWAS of Native Hawaiians and largest to date of Polynesian-ancestry populations (combined N up to 8,461) to identify population-enriched associations for 13 adiposity and cardiometabolic traits available across both cohorts: BMI, fasting glucose, fasting insulin, HDL, height, hip circumference, HOMA-IR, LDL, T2D, total cholesterol, triglycerides, waist circumference, and waist-hip ratio. We found 25 trait-loci associations that met genome-wide significance: 20 previously reported or known associations and 5 associations newly confirmed via meta-analysis. In particular, with improved statistical power, we were able to confirm the suspected association between the missense CREBRF variant with fasting glucose levels. The remaining 4 potentially novel loci-trait associations for BMI, LDL, and waist-hip ratio, however, were not replicated in multi-ethnic datasets from All-of-Us despite having reasonable power to replicate. The lack of Polynesian-enriched findings outside of the CREBRF locus informs the bounds of the effect sizes or frequency of any enriched variants, and suggests that further expansion of cohort sizes from this region of the world and improved imputation references specific to these populations are needed to identify more population-enriched associations.

Journal Article↗

Parasitic infections. Treatment and developmental therapeutics. 1. Necatoriasis.

Necator americanus is a nematode hookworm of the family Ancylostomatidae, subfamily Necatorinae. This nematode parasite, which is distinguished by two chitinous cutting plates in the buccal cavity and fused male copulatory spicules, is the causative agent of necatoriasis, a hookworm disease prevalent in the Americas as well as in the tropical regions of Africa, southern Asia, and Polynesia. The adult parasites attached to the villi of the small intestines will suck blood causing abdominal discomfort, diarrhea and cramps, anorexia, wight loss, and in advanced disease, hypochromic microcytic anemia. Hookworm infections in man, especially in children, are one of the leading causes of iron-deficiency anemia resulting directly from intestinal capillary blood loss following the feeding activities of fourth-stage (L4) larva and adult worms. Another clinical manifestation often associated with hookworm infections is cutaneous larva migrans (CLM). It is a well recognized, usually self-limiting condition caused by the infectious larvae of nematodes. CLM is characterized by skin eruption and represents a clinical description rather than a definitive diagnosis. Of the hookworm parasites, the dog and cat worm Ancylostoma braziliense is the most common causing CLM, although many other species have been implicated. The major subject of this review article will be discussion of the evolution of therapies and treatment of human necatoriasis and the development of experimental infections with N. americanus. Difference in the clinical efficacies of mebendazole and albendazole will be discussed along with drug resistance of N. americanus.

Albendazole↗

[Survey of lymphatic filariasis on Ouvea Island in New Caledonia].

Several cases of Bancroftian filariasis were recently reported on Ouvea Island which is part of the archipelago of New Caledonia located in the south Pacific Ocean. Following these reports systematic screening was carried out in a group of 382 adult consultees at two medical dispensaries. Tests to detect microfilariae in the blood and antibodies in serum were performed at the Pasteur Institute in New Caledonia and the Malarde Institute in Papeete, French Polynesia, respectively. Of the two subjects with manifestations consistent with filariasis, one was seropositive but neither presented microfilariae. Overall 14 subjects (3.7 p. 100) presented microfilariae and 124 were seropositive (33.5 p. 100). The serologic index was significantly higher in men than in women (6.1 p. 100 vs 2.1 p. 100). Parasitic and serologic indexes were significantly higher (p < 0.001) in subjects living in the northern than southern part of the island. As in previous studies in New Caledonia, present data showed that Bancrofitian filariasis is asymptomatic on Ouvea Island. This finding contrasts with the symptomatic forms described on other islands in the south Pacific.

Adult↗

High and variable frequencies of CYP2C19 mutations: medical consequences of poor drug metabolism in Vanuatu and other Pacific islands.

Cytochrome P450 (CYP) 2C19 is polymorphic with poor metabolizers representing 3-6% of Europeans and Africans, and 13-23% of Asians. Greater than 99% of the poor metabolizer alleles in Asian populations are defined by two single base pair mutations (CYP2C19*2 and CYP2C19*3). We have recently reported an unprecedentedly high prevalence (71%) of CYP2C19-related poor metabolizer genotype individuals and poor metabolism of proguanil on two malarious islands of Vanuatu in eastern Melanesia. To elucidate this further, a total of 5538 individuals from 24 populations on 16 different islands of Vanuatu were genotyped. Of these, 61% had a poor metabolizer genotype (*2/*2, *2/*3 or *3/*3) with substantial variation among the populations (38-79%). The overall frequencies of CYP2C19*1 (wild-type), CYP2C19*2, and CYP2C19*3 were 0.223, 0.633, and 0.144, respectively. A significant linear correlation was observed between heterozygosity and South latitude (r = 0.552, P < 0.05). The genotype frequencies of 21 of the 24 populations were consistent with Hardy-Weinberg expectations (P > 0.05). Comparisons of genetic, linguistic and geographical patterns among populations suggest that short range gene flow is largely responsible for the current distribution of CYP2C19 alleles in Vanuatu. Taken together with previous studies of nuclear genetic loci of Pacific island populations, these data predict that the poor metabolizer genotype is common throughout Polynesia and Micronesia and may be even more prevalent in western Melanesia than in Vanuatu. This suggests that the majority of Pacific Islanders metabolize a wide variety of clinically important drugs to a significantly lower degree than the average European.

Antimalarials↗

Mating rendezvous in monogenean gill parasites of the humbug Dascyllus aruanus (Pisces: Pomacentridae).

The gills of the humbug, Dascyllus aruanus (Pomacentridae), were infected by a monogenean genus Haliotrema at a high prevalence (83%) but with a low mean intensity (5.6 worms/fish). All the gill arches of 365 fish, caught on the fringing reef of Moorea Island (French Polynesia), were examined for parasites. Each hemibranch was divided into 12 subequal sections. Monogeneans showing microhabitat overlap were defined as couples. Hosts with low intensity of infection (fewer than 5 monogeneans per gill) were selected and couples were recorded. Among the 37 hosts harboring 2 worms on their gills, 18 fish were infected with these 2 monogeneans on the same gill side of the body; 50% (n = 9) of these harbored monogeneans within the same gill arch and 55% (n = 5) of these last fish showed individual parasites within the same section of the gill. In the case of hosts with few monogeneans (3 and 4 individuals; n = 37) on the same arch, more than 40% (n = 16) harbored worms in couples. There may be some chemical communication that allowed these monogeneans to migrate toward each other and thus enhance mating success. Mating rendezvous appears to be a more important factor than site location for these gill monogeneans.

Animals↗

[Oral receptivity of Aedes aegypti formosus from Franceville (Gabon, central Africa) for type 2 dengue virus].

Dengue is widely distributed in the tropics but epidemic activity was rarely reported in Africa before the 1980's. In the past 15 years, increased epidemic dengue fever has been reported both in East and West Africa, raising concern about the ability of local populations of Aedes aegypti to transmit dengue viruses. Ae. aegypti is present in two forms in Africa: Ae. aegypti aegypti and Ae. aegypti formosus. This latter form, much darker, was not originally a local species but is now colonizing artificial breeding sites within cities. We have been able to demonstrate the oral susceptibility for dengue type 2 virus of Ae. aegypti formosus collected in Franceville, Gabon (Central Africa). However, these mosquitoes sampled exhibited lower infection rates than those of a control colony of Ae. aegypti aegypti originating from French Polynesia.

Aedes↗

Molecular heterogeneity of the Jk(null) phenotype: expression analysis of the Jk(S291P) mutation found in Finns.

Polymerase chain reaction genotyping of 32 unrelated Jk(null) individuals originating predominantly from Polynesia and Finland indicated that all were homozygous for the JK*B polymorphism and that 17 of 32, including the 14 Polynesians, carried a 3'-acceptor splice site mutation of intron 5 that resulted in the skipping of exon 6 (called mutation Jk delta 6). The remaining 15 Jk(null) donors from Finland were homozygous for a new T871C transition resulting in a S291P amino acid substitution at a consensus N-glycosylation site of the Jk polypeptide. Transcription-translation assays revealed that the Jk(S291P) mutant was translated into a glycosylated component as efficiently as the wild-type Jk polypeptide (wt Jk)] in the presence of microsomes, thus indicating that the S291P mutation has no effect on the N-glycosylation pattern of the Jk protein. Expression studies in Xenopus oocytes revealed that the Jk(S291P) polypeptide functions as a urea transporter, but the transport activity and the membrane expression level of the mutant protein was reduced to a similar extent. A substantial fraction of the mutant protein was retained intracellularly suggesting that the transit to the plasma membrane was reduced, presumably because of the S-->P mutation. After transfection in erythroleukemia K562 cells the wild-type, but not the mutant, protein was efficiently expressed at the cell surface. Because the Jk(S291P) mutant polypeptide was not present in human red cells from Jk(null) individuals, expression data in the erythroid context clearly indicates that the S-->P mutation is the molecular basis of the Finnish Jk(null) phenotype. (Blood. 2000;96:1566-1573)

Finland↗

Socioeconomic impacts and management ciguatera in the Pacific.

The inshore fisheries resource is important to the health and culture of many of the inhabitants of Pacific Island countries (PIC). Ciguateric fishes (mainly demersal reef fishes) cause a range of distressing and often debilitating gastrointestinal neurological and cardiovascular disturbances. Consequently, ciguatera limits the utilisation of this otherwise over-exploited resource. For many victims, the symptoms suffered during the chronic phase of ciguatera (lasting weeks, months and occasionally years) are exacerbated upon consumption of certain foods, particularly non-toxic fishes. After each outbreak, victims and members of their social-network experience a transient increase in perception of the risk of eating reef fish. The impact of ciguatera is greatest in atoll island countries where fish is the primary source of protein (it also has a major impact and to facilitate the management of ciguatera in PIC, regular information is required that quantifies: (i) the true incidence of ciguatera; (ii) the extent and way in which different communities avoid ciguatera; and (iii) the adverse impact ciguatera has on health, the workforce, trade and tourism. Over the last 15 years (based on SPEHIS data to 1990), some countries recorded a decrease in the ciguatera problem (New Caledonia, Marshall Is.), other countries an increase (Kirbati, Tuvalu, French Polynesia), while still other countries recorded an increase followed by a decrease in ciguatera (Tokelau, American Samoa, Western Samoa, Fiji and Vanuatu). There may also be seasonal trends in the incidence of ciguatera in some countries e.g. Fiji. Management options presently implementable in PIC include: (i) treatment with i.v. mannitol; (ii) provision of timely advise on the location and status of ciguatera "hot spots" in each country that would allow affected communities to react objectively to the risk posed by ciguatera; and (iii) modification of human behaviour and aspirations to reduce the impact of increasing population, pollution and development (e.g. causeways) pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ciguatera fish poisoning and fisheries development in the South Pacific Region.

Ciguatera fish poisoning represents an impediment to the development of fisheries based on shallow water reef fish stocks and to the food security of islands where agriculture is limited. Although fisheries development initiatives in the past 20 years in the Pacific have focused on the development of deep slope fisheries and fisheries for large pelagics such as tuna, shallow reef fisheries continue to be a major animal protein source for Pacific Islanders and a source of commercial revenue for fishermen. Statistics on ciguatera outbreaks in the Pacific are limited to local databases in Hawaii and French Polynesia, and to the compilation by the South Pacific Commission of "fish poisonings" reported by the medical departments of the countries of the region. A new database was established at the South Pacific Commission during 1990 to serve as a focus for detailed reporting of fish poisoning and ciguatera in the South Pacific. Some preliminary results from this database are presented and the importance of such information to the development of coastal reef fisheries is discussed.

Animals↗

HTLV-I infection in selected populations in Australia and the western Pacific region.

The prevalence of infection with human T lymphotropic virus type I (HTLV-I) in 19,975 blood samples from Australia and the western Pacific was determined by measuring the presence of specific antibody (anti-HTLV-I) by enzyme-linked immunosorbent assay (ELISA) with confirmation by western blot and/or radioimmunoprecipitation techniques. In Australia no evidence of HTLV-I infection was found in injecting drug users, patients with the acquired immunodeficiency syndrome (AIDS), subjects attending a sexually transmitted diseases clinic, female prostitutes, or transfusion recipients. A low prevalence of infection was detected in people with haemophilia (0.5%) and in male homosexuals (0.5%-1%). No antibody was detected in sera from Vanuatu, Kiribati, American Samoa, the Cook Islands, New Caledonia, the Federated States of Micronesia, French Polynesia and Fiji, but a low frequency of anti-HTLV-I was detected in sera from the Solomon Islands (1.2%) and Nauru (0.6%).

Acquired Immunodeficiency Syndrome↗

[Composition of renal stones currently observed in non-industrialized countries].

UNLABELLED: Up until relatively recently, renal stones in developing countries were considered to be very different from those observed in industrialized countries, essentially characterized by the predominance of phosphate and urate stones, while the predominant stones in industrialized countries are calcium oxalate stones. To verify whether this difference in the epidemiological profile is still observed today, we analysed renal stones collected in various regions of the globe and compared their composition to that of stones observed in France. MATERIAL AND METHOD: 1,042 stones were collected between 1991 and 2000 from 14 different countries or geographical zones: Sub-Saharan Africa (Cameroon, Mali, Senegal), North Africa (Algeria, Morocco, Tunisia), South America (Brazil, Paraguay), Asia Minor (Pakistan, Turkey), Far East (China, Laos, Vietnam) and French Polynesia (Tahiti). Stones were analysed by infrared spectrophotometry. The composition of these stones was compared to that of 24,706 stones collected in France over the same period and analysed according to the same protocol. RESULTS: Overall, the proportion of calcium oxalate stones was the same in adults in France and in developing countries (men: 75.7% contre 72%; women: 59.8% contre 56.3%), but was higher in children in non-industrialized countries (boys: 52.6% contre 31.8% in France; girls: 67.8% contre 48.8% in France, p<0.0001). The frequency of calcium phosphate stones was particularly low in boys in developing countries (8.3% contre 45.1% in France, p<0.0001) andfrequency of purine stones was higher in boys (21.3% contre 5.2% in France, p<0.0001) and in girls (13.6% contre 4.3% in France, p<0.05). Major differences were observed according to continent and region; struvite was present in 42.9% of stones in women in Sub-Saharan Africa contre 13% in South America and 2.7% in Asia Minor. Purines were 4 times more frequent in Tahitian men than in North African men. Calcium phosphate stones were 10 times less frequent in men in Asia Minor than in the Far East. CONCLUSION: The epidemiology of renal stones is continuing to change all over the world towards a predominance of calcium oxalate stones, which is now generalized. Major differences in the frequency of the other constituents, particularly purines and struvite, reflect particular eating habits and infectious risk factors specific to certain population.

Adult↗

Characterization of deltamethrin resistance in field populations of Aedes aegypti in Thailand.

Five field collections of adult Aedes aegypti mosquitoes from different areas in Bangkok and Pathum Thani provinces were subjected to susceptibility tests against deltamethrin. Low levels of resistance were detected among all populations tested (RR50 = 8-17.2) compared to the susceptible strain, Bora (French Polynesia). Among the five populations tested, the BKH (Bang Khen, Bangkok) and PSC (Phasicharoen, Bangkok) populations showed a higher level of deltamethrin resistance than the other three populations (RR50 of BKH = 17.2, and of PSC= 13.6) and cross-resistance to DDT was observed in these strains. Biochemical analysis showed a significant elevation of mixed function oxidases enzyme activity in all populations. There was an elevation of non-specific esterases in all populations except BKL, and there was no consistent association of glutathione S-transferases with deltamethrin and DDT resistance, although not all populations were bioassayed for DDT. The partial cDNA sequence of the para-type voltage-dependent sodium channel (IIS4-IIS6) was determined for BKH and PSC populations. Common amino acid substitution, leucine to phenylalanine in the IIS6 region, found for insects including Anopheles gambiae was not found in either the BKH or the PSC populations. However, two other amino acid substitutions (proline substituted with serine at position 64 in the PSC population and leucine with phenylalanine at position 69 in the BKH population) were found in the IIS5-IIS6 inter-segment region sequenced. The role these substitutions play in target site resistance is uncertain at this time.

Aedes↗

Modernisation, migration and nutritional health of Pacific Island populations.

The emergence of obesity and fatness across the second part of the 20th century has been documented for a number of Pacific Island populations. While dietary change and reduced physical activity levels associated with economic modernisation have been identified as the key factors fuelling the emergence of obesity, it is argued here that increasing numbers of Pacific Island migrants in the United States, New Zealand, France and Australia have provided the basis for the acceleration of the modernisation process by way of remittances, and the transmission of ideas of economic opportunity and change. Potential for migration for the Pacific Island nations is estimated from available data on population growth, total fertility rates and total mortality rates. Pacific Islander migrants form approximately one quarter of the total global Pacific Islander population, the majority of whom are from Tonga, Fiji, French Polynesia, and the Federated States of Micronesia. Per capita energy and fats and meat intake for the period 1961 to 2000 is described for five Pacific Island nations, showing that, in general, energy intakes have increased, as have the energy densities of the diets consumed. Thus the increase in mean body mass index observed in Pacific Islanders in the second half of the twentieth century can in general be attributed to dietary change associated with greater food and energy intake, and with increased consumption of fatty foods and meat, most of which are imports.

Activities of Daily Living↗

Measles outbreak and response--Fiji, February-May 2006.

In September 2005, the 37 countries and areas of the World Health Organization (WHO) Western Pacific Region (WPR) established a goal to eliminate measles in the region by 2012. After multiple outbreaks in 1996 and 1997, measles supplementary immunization activities (SIAs) in 1997 and 1998 resulted in apparent interruption of measles transmission in WPR. Since then, importations have resulted in limited outbreaks in French Polynesia and Guam, a large outbreak in the Marshall Islands in 2003, and an outbreak in Fiji during February-May 2006. This report describes the epidemiologic findings, public health response, and potential causes of the 2006 outbreak that produced 132 measles cases in Fiji (2006 estimated population: 832,432), the most populous country in the South Pacific.

Adolescent↗

Single versus repeated doses of ivermectin and diethylcarbamazine for the treatment of Wuchereria bancrofti var. pacifica microfilaremia. Results at 12 months of a double-blind study.

In October 1989, 58 apparently healthy Polynesian Wuchereria bancrofti carriers in whom microfilarial (mf) density was greater than or equal to 100 mf/ml were randomly allocated to treatment groups receiving single doses of either ivermectin at 100 mcg/kg or diethylcarbamazine (DEC) at 3 and 6 mg/kg. Six months later, half of the carriers initially treated with ivermectin 100 mcg/kg or DEC 3 mg/kg were given a second similar dose while the rest were given a placebo. By day 360 (6 months after retreatment), comparison of adjusted geometric mean mf counts per group indicated that (i) among the 3 treatments given once a year the DEC 6 mg/kg dose resulted in the highest efficacy, (ii) nevertheless, regarding either ivermectin 100 mcg/kg or DEC 3 mg/kg, 2 successive doses resulted in higher efficacy than one annual dose and (iii) though no significant difference could be evidenced between efficacy of ivermectin 100 mcg/kg and DEC 3 mg/kg given twice a year, DEC seemed to sustain the mf reduction for a longer period of time. During the 3 days following retreatment, adverse reactions (mild to moderate) were observed in 46% of carriers treated with microfilaricidal drugs and in 20% of those treated with placebo. These results suggest that single dose therapy with either DEC or ivermectin is safe and effective for prevention of lymphatic filariasis due to Wuchereria bancrofti in French Polynesia. The real impact on transmission by the vector, Aedes polynesiensis, of the complete negativation of microfilaremia observed during the previous part of the trial in carriers treated with ivermectin should be evaluated in a community-based trial including entomological study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diagnostic values of ELISA-IgG4 as compared to ELISA-IgG and indirect immunofluorescence, for the routine diagnosis of bancroftian filariasis in the South Pacific. Application on capillary blood collected on filter paper.

For the serodiagnosis of lymphatic filariasis, serological assays restricted to the detection of specific IgG4 antibodies enhanced the specificity. In French Polynesia, Wuchereria bancrofti is the sole human filaria and other pathogenic parasites are infrequent. In order to define a simple and cheap serological test, we have compared the diagnostic value of indirect immunofluorescence test (IFI-WBp), ELISA-IgG and ELISA-IgG4 assays. The specificity, sensitivity, R.O.C. curves of each test have been analyzed. No significant difference was found between those 3 tests, except that the reproducibility and the predictive value were lower using IFI-WBp than using the two ELISAs. Significant correlation was found between IgG and IgG4 anti-Brugia malayi antibody titers (r = 0.512, p less than 10(-5)). For large scale seropidemiological studies, ELISA-IgG can be performed with finger prick blood absorbed on filter paper, but not ELISA-IgG4. In conclusion, ELISA-IgG a less expensive and less time consuming method than ELISA-IgG4, can be used for the routine serodiagnosis as well as for seroepidemiological studies on bancroftian filariasis in the South Pacific islands.

Animals↗