Seasonal distribution of anti-malarial drug resistance alleles on the island of Sumba, Indonesia

Background: Drug resistant malaria poses an increasing public health problem in Indonesia, especially eastern Indonesia, where malaria is highly endemic. Widespread chloroquine (CQ) resistance and increasing sulphadoxine-pyrimethamine (SP) resistance prompted Indonesia to adopt artemisinin-based combination therapy (ACT) as first-line therapy in 2004. To help develop a suitable malaria control programme in the district of West Sumba, the seasonal distribution of alleles known to be\ud associated with resistance to CQ and SP among\ud Plasmodium falciparum isolates from the region was investigated.\ud Methods: Plasmodium falciparum isolates were collected during malariometric surveys in the wet and dry seasons in 2007 using two-stage cluster sampling. Analysis of pfcrt, pfmdr, pfmdr1 gene copy number, dhfr, and dhps genes were done using protocols described previously.\ud Results and Discussion: The 76T allele of the pfcrt gene is nearing fixation in this population. Pfmdr1 mutant alleles occurred in 72.8% and 53.3%, predominantly as 1042D and 86Y alleles that are mutuallyexclusive. The prevalence of amplified\ud pfmdr1 was found 41.9% and 42.8% of isolates in the wet and dryseasons, respectively. The frequency of dhfr mutant alleles was much lower, either as a single 108N mutation or paired with 59R. The 437G allele was the only mutant dhps allele detected and it was only found during dry season.\ud Conclusion: The findings demonstrate a slighly higher distribution of drug-resistant alleles during the wet season and support the policy of replacing CQ with ACT in this area, but suggest that SP might still be effective either alone or in combination with other anti-malarial

High risk behavior for HIV transmission among former injecting drug users: a survey from Indonesia

Contains fulltext : 88347.pdf (publisher's version ) (Open Access)BACKGROUND: Injecting drug use is an increasingly important cause of HIV transmission in most countries worldwide, especially in eastern Europe, South America, and east and southeast Asia. Among people actively injecting drugs, provision of clean needles and opioid substitution reduce HIV-transmission. However, former injecting drug users (fIDUs) are often overlooked as a high risk group for HIV transmission. We compared HIV risk behavior among current and former injecting drug users (IDUs) in Indonesia, which has a rapidly growing HIV-epidemic largely driven by injecting drug use. METHODS: Current and former IDUs were recruited by respondent driven sampling in an urban setting in Java, and interviewed regarding drug use and HIV risk behavior using the European Addiction Severity Index and the Blood Borne Virus Transmission Questionnaire. Drug use and HIV transmission risk behavior were compared between current IDUs and former IDUs, using the Mann-Whitney and Pearson Chi-square test. RESULTS: Ninety-two out of 210 participants (44%) were self reported former IDUs. Risk behavior related to sex, tattooing or piercing was common among current as well as former IDUs, 13% of former IDUs were still exposed to contaminated injecting equipment. HIV-infection was high among former (66%) and current (60%) IDUs. CONCLUSION: Former IDUs may contribute significantly to the HIV-epidemic in Indonesia, and HIV-prevention should therefore also target this group, addressing sexual and other risk behavior

Pseudomembranous Candidiasis Indicates High Level Drug Resistance among Patients on Antiretroviral Treatment in Nairobi East District, Kenya

Objectives: The aim of this study was to determine antiretroviral drug resistance patterns in patients on long-term antiretroviral therapy presenting with OPC.Methods: An exploratory survey was performed among HIV-infected patients on ART for minimum of 24 months presenting with OPC in Nairobi, Kenya. Type (pseudomembraneous or erythematous candidiasis, angular cheilitis) and previous episodes of OPC, CD4-cell counts, duration, regimen and adherence on ART were compared between patients with high (&gt;1000copies/ml) and low HIV-RNA levels. Genotypic resistance testing was performed on those with high viral loads.Results: Out of (n=45) patients with OPC, (n=28; 62%) had high HIV-RNA levels. The (n=28) patients who mostly presented with pseudomembraneuos candidiasis (n=26; p&lt;.0001), had significantly more previous episodes of OPC (55% versus 18%; P&lt;0.0373) lower median CD4 cell counts (74 versus 521; P&lt;.0001) and higher HIV-RNA median plasma levels (111,191 copies/ml versus &lt;20; P&lt;.0001). The sensitivity (0.96) and specificity (0.87) of pseudomebraneous candidiasis to predict virological failure was high. HIV genotyping performed in 22 of the 28 patients showed that most (18/22) had drug resistance mutations of which 12/18 had Lamivudine-associated M184V mutation, 14/18 had TAMS and 16/18 had NNRTI mutations. One patient had major PI mutations.Conclusion: Virological failure and drug resistance mutations including TAMs should be suspected in patients on long-term ART that present with pseudomembraneous candidiasis. We propose to include recurrent OPC in the WHO clinical criteria for ART failure as well as to establish clinical training sessions to build competences among health care providers.</p

Common genotypic polymorphisms in glutathione S-transferases in mild and severe falciparum malaria in Tanzanian children.

Malaria infection induces oxidative stress in the host cells. Antioxidant enzymes such as glutathione S-transferases (GSTs) are responsible for fighting reactive oxygen species and reduction of oxidative stress. Common GST polymorphisms have been associated with susceptibility to different diseases whose pathologies involve oxidative stress. In this study, we tested the hypothesis that GST polymorphisms that lead to reduced or lack of enzyme activity are associated with severe Plasmodium falciparum malarial anemia. We studied the genotypic distribution of GSTM1, GSTT1, and GSTP1 polymorphisms between mild malaria (N = 107) and severe malarial anemia (N = 50) in Tanzanian children. We did not find a significant relationship with the GSTT1 polymorphism. GSTM1-null was higher in the severe malaria anemia group but the difference was not significant (P = 0.08). However, a significant association of GSTP1 I105V genotype with severe malarial anemia was discovered (26.0% against 10.3% mild malaria, P = 0.004). We concluded that GSTP1 and possibly GSTM1 may protect against severe falciparum malaria in children

Characteristics of ART-naïve HIV-infected individuals in this study (n = 82).

<p>Heroin users: used heroin in the last 30 days. MMT: individuals receiving methadone maintenance treatment (MMT) in the last 30 days. Former users: used heroin or methadone over one year ago. Controls: never used heroin or methadone.</p><p>*All groups were compared using Kruskal-Wallis analyses. ART: antiretroviral therapy, IQR: interquartile range; Hb: haemoglobin</p><p>Characteristics of ART-naïve HIV-infected individuals in this study (n = 82).</p

The concentration of IL-1B (A), IL-6 (B), TNF-α (C), IFN-γ (D) and IL-10 (E) after ex vivo stimulation with Mycobacterium tuberculosis in various groups of ART-naïve HIV-infected individuals; individuals who used heroin in last 30 days (circles), individuals receiving methadone maintenance treatment (MMT: squares), individuals who used heroin over one year ago (former users: triangles) and those who never used opioids (controls: reversed triangles).

<p>The level of cytokines was corrected for baseline level and number of CD4 cells (and given in pictogram per 10⁵ cells). *Statistically significant difference (p< 0.016 after Bonferroni adjustment for multiple tests). MMT: methadone maintenance treatment; ART: antiretroviral therapy.</p

The concentration of IL-1B (A), IL-6 (B), TNF-α (C), IFN-γ (D) and IL-10 (E) after <i>ex vivo</i> stimulation with <i>Candida albicans</i> in various groups of ART-naïve HIV-infected individuals; individuals who used heroin in last 30 days (circles), individuals receiving methadone maintenance treatment (MMT: squares), individuals who used heroin over one year ago (former users: triangles) and those who never used opioids (controls: reversed triangles).

<p>The level of cytokines was corrected for baseline level and number of CD4 cells (and given in pictogram per 10⁵ cells). *Statistically significant difference (p< 0.016 after Bonferroni adjustment for multiple tests). MMT: methadone maintenance treatment; ART: antiretroviral therapy.</p