Predictors of low CD4 count in resource-limited settings: based on an antiretroviral-naive heterosexual thai population

A barrier to the appropriate provision of antiretroviral therapy to treat immunosuppressed HIV-infected persons in resource-poor countries is identifying who requires treatment. The World Health Organization (WHO) has suggested using a clinical algorithm combined with a total lymphocyte count (TLC) < 1200 cells/mm as a surrogate for a CD4 count less than 200 cells/mm when it is not possible to measure the CD4 count. We evaluated various TLC levels, anemia, and body mass index and compared our data with the WHO criteria to develop a more sensitive algorithm to predict CD4 counts of < 200 cells/mm and < 350 cells/mm in 839 men and women from Thailand infected with HIV-1 subtype E (CRF01_AE). The December 2003 WHO guidelines had a sensitivity of 34.1% in men and 31.8% in women to detect persons with a CD4 count < 200 cells/mm in this HIV-infected population from Thailand. The use of a TLC < 1500 cells/mm or TLC < 2000 cells/mm combined with anemia or WHO stage II infection doubled the sensitivity to detect persons with a CD4 count < 200 (63.0% in men, 68.2% in women) with less than a 6% decrease in specificity.     

Efficacy of acitretin in the treatment of reactive neutrophilic dermatoses in adult-onset immunodeficiency due to interferon-gamma autoantibody

Reactive neutrophilic dermatoses in adult-onset immunodeficiency due to interferon-γ autoantibody (AOID) are usually associated with concomitant active opportunistic infections. Data focusing on the treatment of these dermatoses with non-immunosuppressive drugs are still lacking. The aim of this study was to assess the efficacy and safety of acitretin treatment of reactive neutrophilic dermatoses in AOID. We conducted a retrospective review of all patients with AOID who had reactive neutrophilic dermatoses and had been treated with acitretin from January 2008 to December 2018. In total, 23 patients had been diagnosed with AOID, with 27 episodes of reactive neutrophilic dermatoses (20 episodes of Sweet syndrome and seven episodes of generalized pustular eruption) and treated with acitretin. The median effective dose of acitretin was 10 mg/day. The mean initial response was 5.6 ± 2.3 days. The rash had almost or completely cleared within 2 weeks in 70.4% of patients. One case had developed a reversible acitretin-induced liver injury with hepatocellular pattern. The median total duration of treatment was 3 months. In conclusion, this study demonstrates the potential role of acitretin as one of the treatments of choice for reactive neutrophilic dermatoses in AOID, attributable to its favorable response and good tolerability.     

Drug Use, Increasing Incarceration Rates, and Prison-Associated HIV Risks in Thailand

Background: Incarceration is a known risk for HIV infection in Thai drug users. Through the 1990s, incarceration rates for drug-related offenses rose sharply, whereas HIV prevention and drug treatment in prisons remained limited. Methods: We assessed HIV and incarceration risks for injection drug users (IDU) and non-IDU in a large treatment center cohort in northern Thailand to investigate HIV and prison risks in this period. We used Thai Bureau of Corrections data to assess incarceration and prevention funds in prisons, 1992–2000. Results: Among 1,865 drug user in the treatment cohort, 503 (27.0%) had ever been jailed. Men (OR 3.3, 95% CI 2.1, 5.2), IDU (OR 6.3, 95% CI 5.1, 7.9), and men who have sex with men (MSM) (OR 3.4, 95% CI 1.8, 6.3) were more likely to have been jailed. Among male IDU who had ever been jailed (N = 272), 15.8% had used drugs in prison. In a multivariate model, incarceration and ever IDU remained independently associated with HIV infection; IDU, MSM behaviors, and harmful traditional practices remained independently associated with having been jailed. From 1992 to 2000, overall alleged narcotics offenses increased from 117,000 to 276,000/year. The number of persons incarcerated for narcotics offenses increased fivefold from 1992 to 1999, from 12,860 to 67,440. For FY 2000, narcotics treatment accounted for 0.06% of the Thai corrections budget, whereas HIV programs in prisons were 0.017%. Conclusions: Incarceration rates for narcotics offenses have increased sharply in Thailand, whereas prevention has lagged. Having been jailed is an important independent risk for HIV infection among Thai male drug users, especially IDU and MSM. HIV prevention and drug treatment are urgently needed in Thai prisons.     

Designing the epitope flanking regions for optimal generation of CTL epitopes

The flanking amino acids that surround epitopes are critical for effective antigen processing and maintenance of epitope integrity. In the present study, the frequency and characteristics of each amino acid that flanked the peptides generated from the proteasomal degradation of three different subtypes of HIV-1 Gag-p24 were determined. Synthetic flanking regions were designed based on the highest and the lowest frequencies of amino acid with the ideal characteristics at positions upstream and downstream of the proteasomal cleavage site. Peptides were synthesized that contained known CD8+ CTL-epitopes from HIV-1 Gag, CMV pp65, and vaccinia proteins HRP-2, and C16, flanked by amino acid sequences specifically designed to either generate or inhibit the known CD8+ CTL-epitopes. As predicted, the known CD8+ CTL-epitopes were effectively generated from the peptides with synthetic flanking regions specifically designed to promote epitope generation in a proteasome-dependent manner. The majority of the proteasome-generated epitopes were cleaved immediately after the C-terminal amino acid of the specific CTL-epitope. The synthetic peptide sequences containing known CD8+ CTL-epitopes with the flanking regions that promote epitope generation were effectively processed and presented to epitope specific CD8+ T-cells resulting in the production of IFN-γ. These results highlight the importance of flanking regions in promoting efficient antigen processing and presentation. This concept can have important implications in vaccine design and development strategies.     

Heterosexually acquired CRF01_AE/B recombinant HIV type 1 found in Thailand

CRF01_AE and subtype B are circulating in Thailand and the strains have become intermixed in some high-risk groups, establishing the possibility of intersubtype recombination. The first such recombinant, mostly B with gp120 from CRF01_AE, was recently identified. Here we report a heterosexually acquired recombinant of different structure, with most of the genome from CRF01_AE but almost the entire envelope from subtype B. Surveillance by V3 serotype and genotype in multiple regions, followed by full-genome sequencing, was used to identify this strain. Pending vaccine trials in Thailand require knowledge of the presence of such strains in the population, and these recombinants provide valuable reagents for the laboratory evaluation of cross-subtype immunity. Studies are underway to determine whether either recombinant is circulating widely.     

Nutritional factors and thalassaemia major

Abnormal growth is a common feature of thalassaemia major in children. In an attempt to determine whether it has a nutritional cause, 12 children aged 1 to 3 years with thalassaemia major were studied under metabolic ward conditions. Nutritional status was assessed by anthropometry and biochemistry before and after an intensive nutrition regimen. Five children had wasting or stunting on admission. As a result of the nutrition intervention, mean weight for height improved significantly. The mean height increase of 0.4 cm after one month was not significant. Plasma zinc, depressed in half the children on admission, improved, as did alpha tocopherol, while copper decreased. Plasma insulin-like growth factor-I also increased commensurate with improved growth. Fat absorption was normal in all children. Undernutrition is an important cause of associated growth disturbances in children with thalassaemia major. Malnutrition was primarily caused by inadequate nutrient intake, as indicated by the capacity to gain weight appropriately when provided with nutrition support, and by the absence of intestinal malabsorption. While long term studies are required to determine if nutritional support will prevent stunting, these results underscore its central role in preventing nutritional deficiencies and in promoting normal growth in thalassaemic children.     

Effects of the injectable contraceptive depot medroxyprogesterone acetate in Thai women with liver fluke infestation: final results.

The effect of the 3-monthly injectable contraceptive depot medroxyporgesterone acetate (DMPA) on liver function and lipids was assessed in Thai women both with and without liver fluke (Ophisthorchis viverrini) infestation. DMPA administration was started in the immediate postpartum period and women who accepted immediate postpartum IUD insertion of sterilization were recruited as a control group. Complete 18-month followup results were obtained for 108 DMPA and 106 control fluke-positive subjects and for 89 DMPA and 74 fluke-negative subjects. No woman in any of the groups developed signs or symptoms of hepatic disease and the DMPA users had fewer health-related complaints during followup than the control subjects. Over 80% of both groups of users were amenorrheic 18 months postpartum, compared with about 15% of those in the control group. A large majority of subjects in each group continued to breastfeed for the entire study period without complaint. Weight change was small and similar in both the DMPA and control groups. Total bilirubin, aspartate aminotransferase, alanine aminotransferase, dehydrogenase, and alkaline phosphatase levels at 6, 12, and 18 months in the DMPA groups were generally equivalent to or lower than those in the corresponding control groups. Cholesterol levels were significantly decreased in the fluke-positive DMPA subjects while serum triglycerides were significantly decreased in both DMPA groups compared with their controls throughout the followup period. We conclude that during 18 months of use, DMPA did not cause any deleterious effects on health or on the metabolic factors studied in women with and without liver fluke infestation.     

Serum prolactin and cortisol levels after suckling for varying periods of time and the effect of a nipple shield

Plasma prolactin and cortisol levels were measured in mothers breast feeding with or without the use of a thin latex nipple shield, and in mothers wearing a nipple shield but who were not nursing. Suckling duration and milk transfer were also recorded. Suckling duration ranged between 6 and 31 min, being significantly correlated with prolactin levels 40 to 120 min after the feed started. At the latter time, baseline prolactin level and time spent nursing accounted together for most of the variance in prolactin levels: R2 was 0.79 and 0.82 at 90 min and 120 min respectively. Prolactin was released as usual when the shield was in place: levels were not significantly different from levels without the shield. Suckling duration was also unaffected by the shield, but milk transfer was significantly reduced. Cortisol was not released by using the shield, and the shield alone (without suckling) did not release prolactin. The thin latex nipple shield has therefore no untoward effect on the release of these hormones during nursing.