HIV-1 Genetic Diversity and Drug Resistance Mutations Among Treatment-Naive Adult Patients in Suriname

International audienceThe molecular epidemiologic profile of HIV-1 in Suriname was determined through protease (PR) and reverse transcriptase (RT) sequences obtained from HIV-1 strains collected from 100 drug-naive HIV-1-infected persons. Subtype determination revealed that most viruses were of subtype B (94.9%) in both PR and RT genomic regions, followed by B/D recombinants (5.1%). Analysis of drug resistance mutations showed only one transmitted dug resistance mutation (TDRM) (V75M) in a single strain. The genetic data obtained can serve as a baseline for Suriname to monitor emerging mutations. This study reveals that the HIV-1 epidemic in Suriname is still characterized by a low TDRM rate (1%) and a low level of subtype diversity. However, both genes display a high genetic polymorphism. This high polymorphism may ultimately lead to drug resistance. Continuous monitoring of the baseline resistance is therefore a prerequisite to safeguard effective long-term treatment for people living with HIV-1 in Suriname

First Chikungunya Outbreak in Suriname; Clinical and Epidemiological Features.

BACKGROUND:In June 2014, Suriname faced the first Chikungunya outbreak. Since international reports mostly focus on hospitalized patients, the least affected group, a study was conducted to describe clinical characteristics of mainly outpatients including children. In addition, the cumulative incidence of this first epidemic was investigated. METHODOLOGY:During August and September 2014, clinically suspected Chikungunya cases were included in a prospective follow-up study. Blood specimens were collected and tested for viral RNA presence. Detailed clinical information was gathered through multiple telephone surveys until day 180. In addition, a three stage household-based cluster with a cross-sectional design was conducted in October, December 2014 and March 2015 to assess the cumulative incidence. PRINCIPAL FINDINGS:Sixty-eight percent of symptomatic patients tested positive for Chikungunya virus (CHIKV). Arthralgia and pain in the fingers were distinctive for viremic CHIKV infected patients. Viremic CHIKV infected children (≤12 years) characteristically displayed headache and vomiting, while arthralgia was less common at onset. The disease was cleared within seven days by 20% of the patients, while 22% of the viremic CHIKV infected patients, mostly women and elderly reported persistent arthralgia at day 180. The extrapolated cumulative CHIKV incidence in Paramaribo was 249 cases per 1000 persons, based on CHIKV self-reported cases in 53.1% of the households and 90.4% IgG detected in a subset of self-reported CHIKV+ persons. CHIKV peaked in the dry season and a drastic decrease in CHIKV patients coincided with a governmental campaign to reduce mosquito breeding sites. CONCLUSIONS/SIGNIFICANCE:This study revealed that persistent arthralgia was a concern, but occurred less frequently in an outpatient setting. The data support a less severe pathological outcome for Caribbean CHIKV infections. This study augments incidence data available for first outbreaks in the region and showed that actions undertaken at the national level to mount responses may have positively impacted containment of this CHIKV outbreak

Differences in clinical manifestations of viremic CHIKV infected children and adults^a.

<p>Differences in clinical manifestations of viremic CHIKV infected children and adults<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004625#t003fn001" target="_blank">^a</a>.</p

Study participation profile of the Chikungunya cohort for the prospective study.

<p>Study participation profile of the Chikungunya cohort for the prospective study.</p

Clinical trend of arthralgia, skin rash, itching, nausea and myalgia from D0 to D7 of viremic CHIKV infected patients^a.

<p>Clinical trend of arthralgia, skin rash, itching, nausea and myalgia from D0 to D7 of viremic CHIKV infected patients<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004625#t002fn001" target="_blank">^a</a>.</p

Clinical symptoms of viremic CHIKV infected patients at onset, day 7, 14, 30 and 90.

<p>Data collected from the viremic CHIKV infected individuals enrolled in the telephone survey. Actual number of patients at each time point per symptom: 1) D0: fever (n = 98), arthralgia and rash (n = 96), back pain and vomiting (n = 93), myalgia (n = 92), itching (n = 87) and other symptoms (n = 90); 2) D7: arthralgia (n = 83), fever (n = 82), rash (n = 81), myalgia (n = 80), vomiting (n = 78), back pain (n = 77), eye pain (n = 74), itching (n = 73) and other symptoms (n = 75); 3) D14: arthralgia (n = 73), rash (n = 72) and other symptoms (n = 71); 4) D30: arthralgia and rash (n = 86) and other symptoms (n = 84), and 5) D90: rash (n = 86), itching (n = 84), arthralgia (n = 83) and other symptoms (n = 82). Presence of fever was only registered until 7 days after infection.</p

Number of reported CHIKV cases reported (July 2014-March 2015).

<p>Monthly rainfall (mm, obtained from the Meterological Center in Suriname) is also depicted; for weeks containing overlapping days from two months (<i>i</i>.<i>e</i>. week 31, 36, 40, 44 and 49), rainfall is depicted for the month with the most days in that week.</p

HDAC1 and HDAC2 collectively regulate intestinal stem cell homeostasis

Histone deacetylases (HDACs) are posttranslational modifiers that deacetylate proteins. Despite their crucial role in numerous biological processes, the use of broad-range HDAC inhibitors (HDACi), has shown clinical efficacy. However, undesired side effects highlight the necessity to better understand the biology of different HDACs and target the relevant HDACs. Using a novel mouse model, in which HDAC1 and HDAC2 can be simultaneously deleted in the intestine of adult mice, we show that the simultaneous deletion of HDAC1 and HDAC2 leads to a rapid loss of intestinal homeostasis. Importantly, this deletion cannot be sustained, and 8 days after initial ablation, stem cells that have escaped HDAC1 or HDAC2 deletion swiftly repopulate the intestinal lining. In vitro ablation of HDAC1 and HDAC2 using intestinal organoid cultures resulted in a down-regulation of multiple intestinal stem cell markers and functional loss of clonogenic capacity. Importantly, treatment of wild-type organoids with class I-specific HDACi MS-275 also induced a similar loss of stemness, providing a possible rationale for the gastrointestinal side effects often observed in HDACi-treated patients. In conclusion, these data show that HDAC1 and HDAC2 have a redundant function and are essential to maintain intestinal homeostasi