Anti-malaria drug treatment in Vietnam

Resistance to antimalarial drugs is increasing nearly everywhere in the tropical world, confounding global attempts to "Roll Back Malaria". Antimalarial treatment with artemisinin, artesunate, or artemether has proved rapidly effective in the treatment of non complicated and complicated malaria and remarkably nontoxic. However there is a number of important questions that still need urgent attention: Should artemisinin be deployed alone or in combination with other antimalarial drugs such mefloquine or other compound (s); which is the best regimen (s); can artemisinin and its derivatives (artesunate or artemether) reduce the mortality in severe malaria and which is the best drug(s); are there important neurotoxic side effects in patients treated with this group of antimalarial drugs. In order to answer those questions a series of studies were conducted in Vietnam and these form the basis of this thesis. The conclusion is 1/ Dihydroartemisinin-piperaquine is an inexpensive, safe, highly efficacious fixeddose antimalarial combination treatment that could make an important contribution to the control of multidrug-resistant fa1ciparum malaria for Vietnan1 and other countries. 2/ Artemether is a satisfactory alternative to quinine for the treatment of severe malaria in adults. The rectal administration of artemisinin would obviollsly constitute a useful therapeutic advance, in comparing with parenteral drugs such as artemether and artesunate, particularly in areas where parenteral administration is difficult. 3/ The artemisinin derivatives have an acceptable safety profile. 4/ Viet Nam has shown that it is possible to "Roll Back Malaria" assuming one has access to good drugs and a willingness to implement change. Those studies have helped to confirm that the qinghaosu (artemisinin) group of drugs is the most important new class of antimalarials developed in the last fifty years

Contribution to income inequality by income source: A comparison across ethnic groups in Vietnam

This study explores the dynamics of income and income inequality in Vietnam from 2004 to 2014. Two main sub-population groups are investigated: the ethnic majority, known as the Kinh people, and the minority group, which includes 53 minor ethnicities in Vietnam. The findings show that income gap among ethnic groups has increased over the last decade. The Gini index decomposition indicates that wages and nonfarm income are the two main determinants of income inequality. Cultivation and agricultural side-line incomes were relatively evenly distributed, despite their recent smaller equalizing effect. Both sub-population groups have experienced a decreasing contribution of the agricultural sector to overall household income. The changes in income inequality in Vietnam by income sources reflect the economic structure change of the economy from the agricultural reliance to non-agricultural economic activities

The Impact of Public Governance on Household Income: A Quantile Panel Analysis

This study investigated the role of provincial governance on the growth of per capita income of Vietnamese households, using a balanced panel dataset for the period 2012-2014. Whereas we found no evidence for the influence of provincial governance when a linear fixed-effect regression estimator was used, the results from a fixed-effect quantile regression estimator reveal that provincial governance has a positive effect on several groups (but not the poorest) and the effect tends to be greater for better-off households. In addition, we find that wage employment plays a larger role in the income growth of poorer households, while returns on education are higher for richer households. The findings suggest that a mean regression approach that looks only at the role of explanatory variables on mean household welfare and does not consider differences in the distribution of household welfare, may miss some heterogeneity that is of interest to policy makers

Kinetics of Viremia and NS1 Antigenemia Are Shaped by Immune Status and Virus Serotype in Adults with Dengue

Dengue is an acute viral disease that affects tens of millions of people annually in tropical and sub-tropical countries. In some cases, this infection happens to be severe and even life threatening. Severe cases have been associated with higher levels of virus in the blood. Several hypotheses have been proposed to explain the occurrence of these cases notably by involving the patient's history of previous DEN virus infection(s). Little is known about the relationships between the evolution over time of virus levels in the blood, the clinical outcome and the previous infection(s) history—a better understanding of these features could help in anti-viral drug development. To analyze these relationships, we studied well characterized patients who participated in a clinical trial. The majority of these patients were infected by DENV-1 serotype and had higher levels of virus than those infected by DENV-2 and sometimes DENV-3 serotypes. We also found that patients with more severe symptoms had higher levels of virus in the first days of their illness. We found as well that the virus was cleared faster and earlier from the blood of patients previously infected. These findings are of major importance for further anti-viral drug testing

Liver Involvement Associated with Dengue Infection in Adults in Vietnam

Globally, the number of adults hospitalized with dengue has increased markedly in recent years. It has been suggested that hepatic dysfunction is more significant in this group than among children. We describe the spectrum and evolution of disease manifestations among 644 adults with dengue who were prospectively recruited on admission to a major infectious disease hospital in southern Vietnam and compare them with a group of patients with similar illnesses not caused by dengue. Transaminase levels increased in virtually all dengue patients and correlated with other markers of disease severity. However, peak enzyme values usually occurred later than other complications. Clinically severe liver involvement was infrequent and idiosyncratic, but usually resulted in severe bleeding. Chronic co-infection with hepatitis B was associated with modestly but significantly increased levels of alanine aminotransferase, but did not otherwise impact the clinical picture

Glucose-6-phosphate dehydrogenase (G6PD) mutations and haemoglobinuria syndrome in the Vietnamese population

<p>Abstract</p> <p>Background</p> <p>In Vietnam the blackwater fever syndrome (BWF) has been associated with malaria infection, quinine ingestion and G6PD deficiency. The G6PD variants within the Vietnamese Kinh contributing to the disease risk in this population, and more generally to haemoglobinuria, are currently unknown.</p> <p>Method</p> <p>Eighty-two haemoglobinuria patients and 524 healthy controls were screened for G6PD deficiency using either the methylene blue reduction test, the G-6-PDH kit or the micro-methaemoglobin reduction test. The G6PD gene variants were screened using SSCP combined with DNA sequencing in 82 patients with haemoglobinuria, and in 59 healthy controls found to be G6PD deficient.</p> <p>Results</p> <p>This study confirmed that G6PD deficiency is strongly associated with haemoglobinuria (OR = 15, 95% CI [7.7 to 28.9], P < 0.0001). Six <it>G6PD </it>variants were identified in the Vietnamese population, of which two are novel (Vietnam1 [Glu³Lys] and Vietnam2 [Phe⁶⁶Cys]). G6PD Viangchan [Val²⁹¹Met], common throughout south-east Asia, accounted for 77% of the variants detected and was significantly associated with haemoglobinuria within G6PD-deficient ethnic Kinh Vietnamese (OR = 5.8 95% CI [114-55.4], P = 0.022).</p> <p>Conclusion</p> <p>The primary frequency of several <it>G6PD </it>mutations, including novel mutations, in the Vietnamese Kinh population are reported and the contribution of <it>G6PD </it>mutations to the development of haemoglobinuria are investigated.</p

Temporal fluctuation of multidrug resistant salmonella typhi haplotypes in the mekong river delta region of Vietnam.

BACKGROUND: typhoid fever remains a public health problem in Vietnam, with a significant burden in the Mekong River delta region. Typhoid fever is caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. Typhi), which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. We used a GoldenGate (Illumina) assay to type 1,500 single nucleotide polymorphisms (SNPs) and analyse the genetic variation of S. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005. PRINCIPAL FINDINGS: the population of S. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the S. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of S. Typhi haplotype H58-E2 in 2004. H58-E2-associated typhoid fever cases exhibited evidence of significant geo-spatial clustering along the Sông H u branch of the Mekong River. Multidrug resistance was common in the established clone H58-C but not in the outbreak clone H58-E2, however all H58 S. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the gyrA gene. SIGNIFICANCE: the H58 haplogroup dominates S. Typhi populations in other endemic areas, but the population described here was more homogeneous than previously examined populations, and the dominant clonal complex (H58-C, -E1, -E2) observed in this study has not been detected outside Vietnam. IncHI1 plasmid-bearing S. Typhi H58-C was endemic during the study period whilst H58-E2, which rarely carried the plasmid, was only transient, suggesting a selective advantage for the plasmid. These data add insight into the outbreak dynamics and local molecular epidemiology of S. Typhi in southern Vietnam

Lovastatin for adult patients with dengue: protocol for a randomised controlled trial.

BACKGROUND: Dengue is the most important vector-borne viral infection of man, with approximately 2 billion people living in areas at risk. Infection results in a range of manifestations from asymptomatic infection through to life-threatening shock and haemorrhage. One of the hallmarks of severe dengue is vascular endothelial disruption. There is currently no specific therapy and clinical management is limited to supportive care. Statins are a class of drug initially developed for lipid lowering. There has been considerable recent interest in their effects beyond lipid lowering. These include anti-inflammatory effects at the endothelium. In addition, it is possible that lovastatin may have an anti-viral effect against dengue. Observational data suggest that the use of statins may improve outcomes for such conditions as sepsis and pneumonia. This paper describes the protocol for a randomised controlled trial investigating a short course of lovastatin therapy in adult patients with dengue. METHODS/DESIGN: A randomised, double-blind, placebo-controlled trial will investigate the effects of lovastatin therapy in the treatment of dengue. The trial will be conducted in two phases with an escalation of dose between phases if an interim safety review is satisfactory. This is an exploratory study focusing on safety and there are no data on which to base a sample size calculation. A target sample size of 300 patients in the second phase, enrolled over two dengue seasons, was chosen based on clinical judgement and feasibility considerations. In a previous randomised trial in dengue, about 10% and 30% of patients experienced at least one serious adverse event or adverse event, respectively. With 300 patients, we will have 80% power to detect an increase of 12% (from 10% to 22%) or 16% (from 30% to 46%) in the frequency of adverse events. Furthermore, this sample size ensures some power to explore the efficacy of statins. DISCUSSION: The development of a dengue therapeutic that can attenuate disease would be an enormous advance in global health. The favourable effects of statins on the endothelium, their good safety profile and their low cost make lovastatin an attractive therapeutic candidate. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN03147572

Quantitative bacterial counts in the bone marrow of Vietnamese patients with typhoid fever

Background Bone marrow culture (BMC) is the reference standard for typhoid fever diagnosis. We studied the additional yield of BMC over blood culture (BC) and the relationship between quantitative BMC counts and severe disease. Methods Hospitalised Vietnamese patients with suspected typhoid fever were prospectively investigated with a BC, BMC, faecal culture and quantitative BMC counts. Results Salmonella typhi was isolated in 195 of 231 patients: from BC and BMC in 144 (73.8%), from BMC alone in 33 (16.9%), from BC alone in 12 (6.2%) and from faeces alone in 6 (3.1%). In 167 patients the median extracellular count of S. typhi was 2.5 cfu/mL (interquartile range [IQR] 0–10) and the intracellular count was 10.5 cfu/mL (IQR 2–42) with a ratio of 1.3 bacteria/cell (IQR 0.6–2.5). The median count of intracellular bacteria in 24 patients with severe disease was 46 bacteria/cell (IQR 9–105) compared with 6.5 bacteria/cell (IQR 2–34) in 143 with non-severe disease (p=0.005). The intracellular BMC count was negatively correlated with the peripheral white cell count and positively correlated with hepatomegaly, splenomegaly, aspartate transaminase, a positive BC and the fever clearance time following treatment with azithromycin, ofloxacin or a combination of the two. Conclusions BMC gave a moderate additional yield over BC. Intracellular BMC counts may reflect the bacterial load in typhoid fever