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This study aims to empirically investigate the determinants of dollarization in Sierra. It uses quarterly data from 1992Q1 to 2017Q4 and autoregressive distributed lag Bound Testing technique. Both the long and short run results revealed that inflation, exchange rate depreciation, financial deepening and war dummy were the main determinants of dollarization in Sierra Leone during the study period. The error correction term depicts that 53 percent of any disequilibrium in dollarization will be corrected within a year. A key policy recommendation is that policy makers should implement prudent policies that will ensure broader macroeconomic stability (including price stability and exchange rate stability) as a recipe for de-dollarization in Sierra Leone.

The patterns of molecular evolution of the most diverse region of the apical membrane antigen 1 (AMA1) gene in Plasmodium falciparum from a Vietnamese subpopulation (Bao Loc) were investigated. Within the Bao Loc population, the sequenced gene region showed relatively high allelic and nucleotide diversity (0.985 and 0.02694, respectively). Further, the level of population recombination was substantial, resulting in a significant decay of linkage disequilibrium along the gene region. The results suggest that AMA1 is a useful genetic marker for studying the relationships between adaptation of parasite populations (to the human host immune system) and malaria epidemiology.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Africa is of high prevalence, although precise data are lacking in many individual nations. We investigated 129 unrelated subjects (71 male subjects, 58 female subjects) visiting a teaching hospital in Freetown, Sierra Leone, to collect baseline data on the distribution of G6PD deficiency among respective ethnic groups in the country. We confirmed eight G6PD-deficient male subjects by two formazan-based blood tests (11.3% of the male subjects examined), and also detected the common 376A > G mutation in 11 male subjects and eight female subjects by sequencing exons 3–5 of the G6PD gene. Selected samples were further sequenced for exons 2–13 and introns 5, 7, 8, and 11. Among the deficient male subjects, six were G6PD A- carrying the double mutations (202G > A and 376A > G), all of whom were in the Temne and Mende ethnic groups. Others included A- Betica, and a novel variant having double mutations in exon 5 (311G > A and 376A > G forming 104 Arg > His and 126 Asn > Asp, respectively), which we designate as G6PD Sierra Leone. Subsequent haplotype analysis linked this novel variant to the G6PD A- “family”.

As one of the most threatening tropical diseases, malaria continues to maintain its toll in the developing world and poses a heavy economic burden on many countries. Estimates show that 300 million to 500 million clinical cases occur per year, with at least a million deaths, most of which are seen among children under 5 years of age (8). Resistance to antimalarial drugs and insecticides, coupled with the lack of availability of an effective vaccine, is the leading factor behind the success of the parasite's continuing burden. Apart from its complex life cycle, which alternates between the human and the mosquito host, the malaria parasite also exhibits stages characterized by extensive genetic and antigenic diversity which may present adverse obstacles to antimalarial control measures. The Plasmodium falciparum circumsporozoite protein (CSP), a leading malaria vaccine candidate antigen, is predominantly distributed on the surface of the sporozoites (40) and has approximately 120 residues, with a molecular mass of about 58 kDa. The structure of CSP can be divided into a polymorphic central repeat region known to contain immunodominant B-cell epitopes (41) and flanked by a less variant 5′ and a highly polymorphic 3′ end where T-cell epitopes have been identified (19, 27). Clinical trials of Plasmodium falciparum CSP-based vaccines have shown that they induce both humoral and cellular immune responses (29, 39) and that the cellular immune responses are central in immunity against the exoerythrocytic stages of malaria. In an attempt to understand the nature and the extent of the polymorphism patterns of malaria parasites in a setting of malaria hypomesoendemicity, we have conducted a 5-year longitudinal study of the most variable terminal 3′ region of the CSP gene among Plasmodium falciparum field isolates collected from Bao Loc, southern Vietnam, over 5 years (1998 to 2003). We compare our data with the reported CSP sequences and also discuss the geographical patterns of polymorphism at this locus in Southeast Asia and globally. Our findings show that the genetic diversity of the Th2R and Th3R epitopes in this Bao Loc malaria setting is less than that in areas of hyperendemicity and that the variation patterns tend to correlate with malaria transmission intensity. Furthermore, the polymorphisms appear to be stable over time in this Bao Loc setting of relatively low malaria endemicity. Findings from our analyses involving worldwide CSP sequences seem to suggest that the sequence polymorphisms observed in the Th2R and Th3R epitopes of CSP not only appear to be geographically restricted but also may be a result of a balanced state(s) of interaction between the parasite and its hosts.

We conducted a survey of malaria diagnoses and glucose-6-phosphate dehydrogenase (G6PD) testing in remote areas of Cambodia. Blood specimens from 670 people were collected by the finger-prick method. Of these people, 24.9% were found to have malaria, and 7.0% of people were G6PD deficient. In the Khmer, the largest ethnical population in Cambodia, the G6PD deficiency rate of males was 12.6% (25/199) whereas the rates in the minorities of the Tum Pun and the Cha Ray were 1.1% (1/93) and 3.2% (2/63), respectively. Of the G6PD-deficient subjects, 97.9% (46/47) were G6PD Viangchan (871G>A), and only one case (2.1%) was G6PD Union (1360C>T). Since G6PD Mahidol (487G>A) is common in Myanmar according to our previous study, the current finding suggests that the Cambodian population is derived from homogeneous ancestries and is different from the Myanmar population. All G6PD Viangchan cases were linked to two other mutations of 1311C>T and IVS-11 nt93T>C in the G6PD gene.

We recently reported a new rapid screening method for glucose-6-phosphate dehydrogenase (G6PD) deficiency. This method incorporates a new formazan substrate (WST-8) and is capable of detecting heterozygous females both qualitatively and quantitatively. Here, we report its evaluation during field surveys at three malaria centres and in malaria-endemic villages of Myanmar and Indonesia, either alone or in combination with a rapid on-site diagnosis of malaria. A total of 57 severe (45 males and 12 females) and 34 mild (five males and 29 females) cases of G6PD deficiency were detected among 855 subjects in Myanmar whilst 30 severe (25 males and five females) and 23 mild (six males and 17 females) cases were found among 1286 subjects in Indonesia. In all cases, severe deficiency was confirmed with another formazan method but due to limitations in its detection threshold, mild cases were misdiagnosed as G6PD-normal by this latter method. Our results indicate that the novel method can qualitatively detect both severely deficient subjects as well as heterozygous females in the field. The antimalarial drug, primaquine, was safely prescribed to Plasmodium vivax-infected patients in Myanmar. Our new, rapid screening method may be essential for the diagnosis of G6PD deficiency particularly in rural areas without electricity, and can be recommended for use in malaria control programmes.

We conducted a survey of malaria diagnoses and treatments in remote areas of Myanmar. Blood specimens from more than 1,000 people were collected by the finger-prick method, and 121 (11%) of these people were found to be glucose-6-phosphate dehydrogenase (G6PD) deficient. Of these 121, 50 consented to analysis of the G6PD genome. We read the G6PD sequences of these subjects and found 45 cases of G6PD Mahidol (487G>A), two of G6PD Coimbra (592C>T), two of G6PD Union (1360C>T), and one of G6PD Canton (1376G>T). Taken together with data from our previous report, 91.3% (73/80) of G6PD variants were G6PD Mahidol. This finding suggests that the Myanmar population is derived from homogeneous ancestries and are different from Thai, Malaysian, and Indonesian populations.

In vitro growth of Plasmodium falciparum is restricted in glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes (RBC), as a result of oxidative stress. Bathocuproine disulphonate (BCS), a copper chelator, as well as cysteine have been shown to synergistically stimulate the in vitro growth of various mammalian cells and Trypanosoma under oxygenated conditions. We examined the effects of these two chemicals on the in vitro growth of P. falciparum in G6PD-deficient RBC, and found that addition of BCS and cysteine synergistically enhanced the growth of the P. falciparum FCR-3 strain in these RBC to the same level as in normal RBC. However, BCS or cysteine alone had no stimulatory effect. To explain this synergistic enhancement, changes in thiol, NADPH and glutathione contents were investigated. After addition of cysteine alone, thiol content in the medium decreased rapidly, but when BCS was added, it was maintained at about 35% at 24 hours after incubation, suggesting that BCS stimulates parasite growth in G6PD-deficient RBC by inhibiting copper-mediated oxidation of cysteine in the medium. In these RBC, no increase in NADPH level, but a slight increase in glutathione, was observed in the presence of both BCS and cysteine. The slight increase of glutathione, was probably due to incorporation of cysteine from the medium, although this could not fully explain the synergistic growth enhancement. These findings taken together suggest that cysteine incorporated into G6PD-deficient RBC may help maintain the thiol groups in many proteins, such as membrane proteins, hemoglobin and enzymes, and plays an important role in maintaining an appropriate culture state necessary for parasite growth. We also examined the effects of BCS and cysteine on adaptation of wild isolates of P. falciparum to in vitro cultivation using the candle jar method. Although there was no drastic effect on growth enhancement, the presence of BCS and cysteine accelerated the appearance of schizonts in many isolates.

BackgroundPandemic influenza A(H1N1) virus infection quickly circulated worldwide in 2009. In Japan, the first case was reported in May 2009, one month after its outbreak in Mexico. Thereafter, A(H1N1) infection spread widely throughout the country. It is of great importance to profile and understand the situation regarding viral mutations and their circulation in Japan to accumulate a knowledge base and to prepare clinical response platforms before a second pandemic (pdm) wave emerges.MethodologyA total of 253 swab samples were collected from patients with influenza-like illness in the Osaka, Tokyo, and Chiba areas both in May 2009 and between October 2009 and January 2010. We analyzed partial sequences of the hemagglutinin (HA) and neuraminidase (NA) genes of the 2009 pdm influenza virus in the collected clinical samples. By phylogenetic analysis, we identified major variants of the 2009 pdm influenza virus and critical mutations associated with severe cases, including drug-resistance mutations.Results and conclusionsOur sequence analysis has revealed that both HA-S220T and NA-N248D are major non-synonymous mutations that clearly discriminate the 2009 pdm influenza viruses identified in the very early phase (May 2009) from those found in the peak phase (October 2009 to January 2010) in Japan. By phylogenetic analysis, we found 14 micro-clades within the viruses collected during the peak phase. Among them, 12 were new micro-clades, while two were previously reported. Oseltamivir resistance-related mutations, i.e., NA-H275Y and NA-N295S, were also detected in sporadic cases in Osaka and Tokyo.

Sequence analyses of six isolates from Southeast Asia supports dividing species into types, Complete DNA sequences of the small subunit ribosomal RNA (SSUrRNA) gene and partial sequences of three other loci were obtained from three variant-type and three classic-type Plasmodium ovale isolates from Southeast Asia and compared with GenBank-available data. Three different SSUrRNA sequences (Pov 1–3) were found in each variant-type isolate, and two different SSUrRNA sequences (Poc 1–2) in each classic-type isolate. Pov 1–3 were closer to sequences previously found in the Cameroon and MAL/MAI isolates, whereas Poc 1–2 were closer to sequences previously found in two clones of the Nigerian I/CDC strain. The 3´ half of Pov 1–3 was identical to the partial sequence of the SSUrRNA gene from the London School (LS) strain. Results support grouping P. ovale into two groups, the classic type (including the Nigerian I/CDC strain) and the variant type (Cameroon, MAL/MAI, and LS isolates).