CASE PRESENTATION: Here, we report two cases of melioidosis from Nepal. Both of them were diabetic male who presented themselves with fever, multiple abscesses and developed sepsis. They were treated with multiple antimicrobial agents including antitubercular drugs before being correctly diagnosed as melioidosis. Consistent with this, both patients were farmer by occupation and also reported travelling to Malaysia in the past. The diagnosis was made consequent to the isolation of B. pseudomallei from pus samples. Accordingly, they were managed with intravenous meropenem followed by oral doxycycline and cotrimoxazole.
CONCLUSION: The case reports raise serious concern over the existing unawareness of melioidosis in Nepal. Both of the cases were left undiagnosed for a long time. Therefore, clinicians need to keep a high index of suspicion while encountering similar cases. Especially diabetic-farmers who present with fever and sepsis and do not respond to antibiotics easily may turn out to be yet another case of melioidosis. Ascertaining the travel history and occupational history is of utmost significance. In addition, the microbiologist should be trained to correctly identify B. pseudomallei as it is often confused for other Burkholderia species. The organism responds only to specific antibiotics; therefore, correct and timely diagnosis becomes crucial for better outcomes.
METHODS: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site.
RESULTS: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person-years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow-up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co-infection, TB diagnosis, HIV VL, CD4 count and BMI.
CONCLUSIONS: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.
OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR.
METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia.
RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1).
CONCLUSION: This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.
OBJECTIVE: To evaluate immune-hematological profiles among HIV infected patients compared to HIV/malaria co-infected for ART management improvement.
METHODS: This was a cross sectional study conducted at Infectious Disease Hospital, Kano. A total of 761 consenting adults attending ART clinic were randomly selected and recruited between June and December 2015. Participants' characteristics and clinical details including two previous CD4 counts were collected. Venous blood sample (4ml) was collected in EDTA tube for malaria parasite diagnosis by rapid test and confirmed with microscopy. Hematological profiles were analyzed by Sysmex XP-300 and CD4 count by Cyflow cytometry. Data was analyzed with SPSS 22.0 using Chi-Square test for association between HIV/malaria parasites co-infection with age groups, gender, ART, cotrimoxazole and usage of treated bed nets. Mean hematological profiles by HIV/malaria co-infection and HIV only were compared using independent t-test and mean CD4 count tested by mixed design repeated measures ANOVA. Statistical significant difference at probability of <0.05 was considered for all variables.
RESULTS: Of the 761 HIV infected, 64% were females, with a mean age of ± (SD) 37.30 (10.4) years. Prevalence of HIV/malaria co-infection was 27.7% with Plasmodium falciparum specie accounting for 99.1%. No statistical significant difference was observed between HIV/malaria co-infection in association to age (p = 0.498) and gender (p = 0.789). A significantly (p = 0.026) higher prevalence (35.2%) of co-infection was observed among non-ART patients compared to (26%) ART patients. Prevalence of co-infection was significantly lower (20.0%) among cotrimoxazole users compared to those not on cotrimoxazole (37%). The same significantly lower co-infection prevalence (22.5%) was observed among treated bed net users compared to those not using treated bed nets (42.9%) (p = 0.001). Out of 16 hematology profiles evaluated, six showed significant difference between the two groups (i) packed cell volume (p = <0.001), (ii) mean cell volume (p = 0.005), (iii) mean cell hemoglobin concentration (p = 0.011), (iv) absolute lymphocyte count (p = 0.022), (v) neutrophil percentage count (p = 0.020) and (vi) platelets distribution width (p = <0.001). Current mean CD4 count cell/μl (349±12) was significantly higher in HIV infected only compared to co-infected (306±17), (p = 0.035). A significantly lower mean CD4 count (234.6 ± 6.9) was observed among respondents on ART compared to non-ART (372.5 ± 13.2), p<0.001, mean difference = -137.9).
CONCLUSION: The study revealed a high burden of HIV and malaria co-infection among the studied population. Co-infection was significantly lower among patients who use treated bed nets as well as cotrimoxazole chemotherapy and ART. Six hematological indices differed significantly between the two groups. Malaria and HIV co-infection significantly reduces CD4 count. In general, to achieve better management of all HIV patients in this setting, diagnosing malaria, prompt antiretroviral therapy, monitoring CD4 and some hematology indices on regular basis is critical.
METHODS: Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification.
RESULTS: Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity.
CONCLUSION: Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.
METHODS: Data from perinatally HIV-infected, antiretroviral-naïve patients initiated on NNRTI-based ART aged 10-19 years who had ≥6 months of follow-up were analyzed. Competing risk regression was used to assess predictors of NNRTI substitution and clinical failure (World Health Organization Stage 3/4 event or death). Viral suppression was defined as a viral load <400 copies/mL.
RESULTS: Data from 534 adolescents met our inclusion criteria (56.2% female; median age at treatment initiation 11.8 years). After 5 years of treatment, median height-for-age z score increased from -2.3 to -1.6, and median CD4+ cell count increased from 131 to 580 cells/mm(3). The proportion of patients with viral suppression after 6 months was 87.6% and remained >80% up to 5 years of follow-up. NNRTI substitution and clinical failure occurred at rates of 4.9 and 1.4 events per 100 patient-years, respectively. Not using cotrimoxazole prophylaxis at ART initiation was associated with NNRTI substitution (hazard ratio [HR], 1.5 vs. using; 95% confidence interval [CI] = 1.0-2.2; p = .05). Baseline CD4+ count ≤200 cells/mm(3) (HR, 3.3 vs. >200; 95% CI = 1.2-8.9; p = .02) and not using cotrimoxazole prophylaxis at ART initiation (HR, 2.1 vs. using; 95% CI = 1.0-4.6; p = .05) were both associated with clinical failure.
CONCLUSIONS: Despite late ART initiation, adolescents achieved good rates of catch-up growth, CD4+ count recovery, and virological suppression. Earlier ART initiation and routine cotrimoxazole prophylaxis in this population may help to reduce current rates of NNRTI substitution and clinical failure.
METHODS: Swabs from four body sites of 129 HIV-infected patients were cultured for S. aureus and identified by standard microbiological procedures. The isolates were subjected to antimicrobial susceptibility testing by disk diffusion against penicillin, erythromycin, clindamycin, and cotrimoxazole. PCR was used to detect the PVL gene and genetic relationship between the isolates was determined by using pulse field gel electrophoresis.
RESULTS: A total of 51 isolates of S. aureus were obtained from 40 (31%) of the patients. The majority (43.1%) of the isolates were obtained from the anterior nares. Thirteen (25.5%) of all the isolates were resistant to more than one category of antibiotics, with one isolate identified as MRSA. Thirty-eight (74.5%) isolates (including the MRSA isolate) carried PVL gene where the majority (44.7%) of these isolates were from the anterior nares. A dendogram revealed that the isolates were genetically diverse with 37 distinct pulsotypes clustered in 11 groups.
CONCLUSION: S. aureus obtained from multiple sites of the HIV patients were genetically diverse without any clonality observed.