Cotrimoxazole prophylaxis prevents major infective episodes in patients with systemic lupus erythematosus on immunosuppressants: A non-concurrent cohort study

Background Prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) prevents pneumocystis jirovecii infection in SLE on immunosuppression. Its role in preventing other major infections in immuno suppressed SLE patients is unknown. Methods A non-concurrent cohort study was conducted on patients of SLE fulfilling SLICC and/or ACR 1997 criteria, who received tapering dose of steroid starting with ≥0.5 mg/kg/day of prednisolone or equivalent dose of deflazacort and mycophenolate mofetil ≥1 g/day (or equivalent dose of mycophenolate sodium) at least for the preceding 1 year. Interviewing patients & documenting relevant data from hospital electronic Medical records (EMR), followed by comparison of Incidence densities of major infections between those on prophylactic Trimethoprim 160 mg + Sulfamethoxazole 800 mg and those not on it, was done by student ‘t’ test. Multivariate logistic regression was performed for independent risk of any major infection between the two groups. Results Of 228 patients, 162 did not receive TMP-SMX prophylaxis, and 66 had received. The incidence density of major infection was found to be significantly lower in TMP-SMX group (1.25 per 100 person year) as compared to those not on TMP-SMX group (11.201 per 100 person year); P < 0.001 (95% CI 0.027 – 0.449) and odds ratio of 0.03 (CI 0 – 0.24). Conclusion Cotrimoxazole prophylaxis in SLE patients on immunosuppression prevents major infections.

Assessing the effectiveness of a Telemedicine Initiative in Clinical Management of Children Living with HIV/AIDS in Maharashtra, India

Aims: To evaluate the effectiveness of telemedicine in clinical management of children living with HIV/AIDS in resource limited settings. Background: Telemedicine is an important mechanism for service delivery in health care settings, both in resource rich and resource poor settings. Such service delivery mechanisms have shown to be associated with virologic suppression and higher CD4 counts. These services are also associated with improved access, shorter visiting times, and higher patient satisfaction. Objective: We designed the present two-group comparison study to compare the clinical evaluation and management of children in the antiretroviral therapy (ART) centres linked to telemedicine facility with those who are not linked to this facility in Maharashtra, India. Methods: We analysed clinical records from six ART centres in Maharashtra; of these 250 children were in the linked ART centres and 301 were in the non-linked ART centres. The outcomes were classified according to investigations, management, and monitoring. For management, we evaluated: 1) initiation of cotrimoxazole prophylaxis; 2) Children not initiated on ART when required; 3) ART regime after appropriate investigations; and 4) Change of regime (if immunologically indicated). For monitoring, we assessed the haematological monitoring of children on ART. Result: The mean (SD) ages of children in linked and non-linked ART centres were 10.8 (4.6) and 10.9 (4.6) years respectively (p=0.80). After adjusting for individual and structural level variables, physical examination (OR: 2.0, 95% CI; 1.2, 3.2), screening for tuberculosis (OR: 12.9, 95% CI: 2.0, 82.9) and cotrimoxazole prophylaxis was significantly more likely in the linked centres compared with non-linked centres (OR: 1.8, 95% CI: 1.4, 2.2). A higher proportion of children eligible for ART were not initiated on treatment in the non-linked centres compared with linked centres (26% vs. 8%, p=0.06). Children were less likely to be initiated on zidovudine-based regimens without baseline haemoglobin or with baseline haemoglobin of less than 9 gm% in linked centres (OR: 0.7, 95% CI: 0.6, 0.8). Similarly, children in the linked centres were less likely to have been started on nevirapine based regimens without baseline liver enzymes (OR: 0.8, 95% CI: 0.7, 0.9). Conclusions: Thus, the overall clinical management of Children Living with HIV/ AIDS (CLHA) was better in ART centres linked with the telemedicine initiative compared with those which were not linked. Children in the linked ART centres were more likely to have a complete baseline assessment (physical, hematological, radiological, and screening for TB), Presence of pediatrician in the centres was helpful.

Does cotrimoxazole prophylaxis in HIV patients increase the drug resistance of pneumococci? A comparative cross-sectional study in southern Ethiopia

Background Infections caused by antibiotic-resistant bacteria results in high rates of morbidity and mortality. Although the prolonged cotrimoxazole (CTX) prophylaxis is arguably associated with the risk of increasing drug resistance in the common pathogens, information regarding its impact on Streptococci pneumoniae / pneumococcus is very limited. Objective This study was conducted to investigate the effect of cotrimoxazole prophylaxis on nasopharyngeal colonization rate and antimicrobial resistance using Streptococci pneumoniae (pneumococcus) as an indicator organism among HIV patients in Arba Minch, Ethiopia. Materials and methods A comparative cross-sectional study was designed and conducted among HIV patients attending the Anti-Retroviral Treatment (ART) clinic of Arba Minch General Hospital (AMGH) from April 01 to August 31, 2018. A total of 252 participants were systematically selected and clustered into two study groups based on their CTX prophylaxis status, one taking CTX prophylaxis, and the second one, the control group (without prophylaxis). A structured questionnaire was used to collect socio-demographic and clinical data from patients. A nasopharyngeal swab was collected and cultured for pneumococcal isolation and identification in accordance with standard microbiological techniques. An antibiotics sensitivity test was performed according to the CLSI guidelines. Data were analyzed using the Statistical package for social science (SPSS) version 20. The primary outcome was determined using logistic regression analysis. Results Of the 252 enrolled HIV patients (mean age (37.38± 9.03 years), 144 (57.14%) were males. The overall, nasopharyngeal colonization rate of S. pneumoniae was 13.5% (95% CI: 8.4–15.6). Asymptomatic pneumococcal carriage rates among patients on CTX prophylaxis and the control group were 16.3%, and 10.3% respectively (p-value = 0.03). Regarding the risk factors analyzed, CTX prophylaxis (AOR: 2.2; 95% CI: 1.05–4.9) and gender (AOR: 2.5; 95% CI: 1.09–5.93) were significantly associated with pneumococcal colonization, showing a male preponderance. Cotrimoxazole-resistant pneumococci were 85.7% vs. 47.4% in the prophylaxis group and the control group respectively and it was statistically significant (AOR: 6.7; 95% CI: 1.3–36). Percentages of multi-drug resistant isolates in these two groups were 38.09 and 15.38 respectively (p-value = 0.04). Among the CTX resistant pneumococci isolates, 85% were also found to be co-resistant towards penicillin and was statistically significant. Conclusion The percentage prevalence of nasopharyngeal pneumococci colonization was higher in patients taking CTX prophylaxis. It was noted that CTX prophylaxis eventually results in the selection of cotrimoxazole resistance and multi-drug resistance in pneumococci. There is evidence of existing cross-resistance between cotrimoxazole and penicillin antibiotics. Therefore, CTX prophylaxis must be administered judiciously. Surveillance for antimicrobial susceptibility is warranted where the prophylaxis is common.

Determinants of HIV-malaria co-infection among people living with HIV on anti-retroviral therapy in Northeast Ethiopia: unmatched case control study

Background HIV and malaria are the leading causes of morbidity and mortality in the developing world including Ethiopia. Globally, HIV-malaria co-infection causes approximately 3 million deaths per year. However, both these infections are preventable if measures are taken on determinant factors. The objective of the study was therefore to assess factors associated with HIV-malaria co-infection among HIV-positive people who lived in Shewarobit district, northeast Ethiopia. Methods Unmatched case-control study was conducted among people living with HIV (PLWHA) in Shewarobit district from February 28, 2018, to April 30, 2018. The sample size was determined taking the assumption of 95% CI, 85% power, 3:1 control to case ratio, the proportion of PLWHA-malaria coinfection of 22.7%, OR 2.73, and 10% non-response rate. The final sample size was 262 (66 cases and 196 controls). Cases were adults on anti-retroviral therapy and diagnosed positive for malaria by microscopy while controls were adults on anti-retroviral therapy and diagnosed negative for malaria by microscopy in the previous 6 months before the survey. Result The median age of cases and controls in years was 35 (IQR = 19) and 38 (IQR = 19) respectively. Variables that had a significant association with HIV-malaria co-infection were non-in-door residual spraying (adjusted odds ratio (AOR) = 4.91; 95% CI 4.03, 15.13), poor perception on the health risk of HIV-malaria co-infections (AOR = 4.11; 95% CI 1.28, 10.17), non-use of insecticidal treated bed nets (AOR = 6.21; 95%CI 2.74, 14.11), non-use of cotrimoxazole prophylaxis (AOR = 2.42; 95% CI 1.11, 5.28), and not received health education on the risk of HIV-malaria interaction (AOR = 4.11; 95% CI 1.24, 4.84). Conclusion Provision of cotrimoxazole prophylaxis, sleeping under an insecticidal treated bed net, and indoor residual spraying help to reduce HIV-malaria co-infection-associated morbidity/mortality.

Usefulness of rapid diagnostic test in the diagnosis of asymptomatic malaria in HIV infected children on cotrimoxazole prophylaxis in Benin City, Nigeria

Background: Rapid diagnostic test (mRDT) is a useful tool in demonstrating parasitologically proven malaria. Its efficacy is however hampered when parasite density is low. Prophylactic use of cotrimoxazoleas in cases of HIV infected children can cause reduction in parasite count. It is doubtful if mRDT will retain its diagnostic usefulness among such individuals.Objectives: The study sought to evaluate the diagnostic value of mRDT in HIV infected children on cotrimoxazole prophylaxis in Benin City.Methods: In the prospective, cross sectional and descriptive study, we assessed malaria parasitaemia using standard methods in microscopy and parasite density and malaria antigenaemia using Care Start Pf (monoclonal antibodies specific to histidine rich protein – 2 antigen) in 221 each of HIV infected subjects on cotrimoxazole managed in a specialist clinic and HIV negative controls all seen at the University of Benin Teaching Hospital between April and June 2016.Results: Malaria antigenaemia rate MAr (20.8%) was lower than malaria parasitaemia rate MPr (24.4%) in subjects. MAr (20.8) and MPr (24.4%) in subjects were higher than MAr (18.10%) and MPr (17.7%) in controls. Mean (SEM) parasite count in subjects of was low (50.88 + 2.24 per μl). Using microscopy as gold standard the sensitivity, specificity, PPV and NPV of mRDT in subjects were 77.8%, 97.6%, 91.3% and 93.1%. Corresponding values in controls were 100.0%, 99.5%, 97.5% and 100.0%.Youden indices for subjects and controls were 0.75 and 0.99.Conclusions/Recommendations: Sensitivity of mRDT in HIV infected children on cotrimoxazole prophylaxis for opportunistic infections (OI) is reduced. However the indices of specificity, PPV and NPV are high enough to retain its value in the evaluation of HIV infected children for asymptomatic malaria and perhaps the clinical disease. Keywords: mRDT, Utility, HIVinfected Children, Cotrimoxazoleprophylaxis, Benin City

Benefits and Risks of Prolonged Cotrimoxazole Prophylaxis among People Living with HIV in Immune Reconstitution Phase: A Retrospective Cohort Study

Objectives. To determine the effect of prolonged cotrimoxazole prophylaxis (CP) in reducing hospitalization and opportunistic infection rates among people living with HIV (PLHIV) with CD4 count >200 cells/mm3. Methods. We retrospectively reviewed 349 medical charts of PLHIV with CD4 count (or T-cell count) of >200 cells/mm3 enrolled in an HIV treatment hub in Manila, Philippines, from January 2004 to July 2016. Demographic, clinical characteristics and outcomes were extracted. Descriptive statistics were generated. Chi-square test for two proportions was done to compare the difference in outcomes between the CP and non-CP groups. Results. Of the 349 patients, majority (96.6%) were male with a mean age of 28 years (SD 6.4) and mean CD4 count of 373 cells/mm3 (SD 148). CP was continued in 103 patients (29.5%) with mean duration of 1.7 (SD 1.9) years. The prolonged CP group had more events of adverse drug reactions (p<0.001), specifically minor cutaneous reactions (p<0.001) and immunologic failures (p<0.001), compared to the non-CP group. There were no statistically significant differences in the frequency of hospitalization, PJP (Pneumocystis jirovecii pneumonia), non-PJP, other respiratory illnesses, diarrhea, toxoplasmosis, tuberculosis, stage 3/4 events and mortality, between the prolonged CP and non-CP groups. Conclusion. We did not observe any additional benefit in giving prolonged CP among PLHIV with CD4 count >200 cells/mm3. More adverse effects were also seen in the CP group.

FRI0529 IS COTRIMOXAZOLE PROPHYLAXIS AGAINST PNEUMOCISTIS JIROVENCII PNEUMONIA RECOMMENDED IN PATIENTS WITH SYSTEMIC AUTOIMMUNE DISEASES REQUIRING IMMUNOSUPPRESSIVE THERAPIES? A SYSTEMATIC LITERATURE REVIEW.

Background:The incidence of Pneumocistis jirovencii pneumonia (PCP) has increased substantially during the past years in patients with systemic autoimmune diseases (SAD). Mortality associated to PCP was reported to be up to 20 to 58%, particularly in those receiving immunosuppressive therapy, such as tumoral necrosis antagonist factors or glucocorticoid therapy. Though, there is clear evidence of the effectiveness of Cotrimoxazole against PCP, the risk of adverse effects is important, increasing morbidity and mortality. Up to date, there is no consensus about the need of PCP prophylaxis in SAD patients with immunosuppressed therapies.Objectives:To analyse the efficacy and safety of Cotrimoxazole prophylaxis against PCP in SAD adult patients receiving immunosuppressive therapies.Methods:We performed a comprehensive literature search, screening different databases, MEDLINE, EMBASE and Cochrane Library up to April 2019. Outcomes covered prevention of PCP or other infections, morbidity, mortality and safety. All categories of studies were included. Two reviewers selected and extracted data from studies. The information obtained was summarized through a narrative review and results tabulated.Results:From the initial 340 identified references, 12 were finally included. Two were randomized controlled trials, six observational studies, and four case reports. The quality in the majority of studies resulted moderate or low, with limited level of evidence. Besides, all Cotrimoxazole prophylaxis regimens described in each study were distinct. Results were consistent to exhibit the efficacy of Cotrimoxazole prophylaxis, compared to non-prophylaxis in the prevention of PCP in patients receiving immunosupresor therapy, particularly, those taking high glucocorticoid dose above 20mg/day. In terms of efficacy, Cotrimoxazole 400mg/80mg/day, given three times per week, or 200mg/40mg/day or in dose escale exhibited a similar performance. In contrast, Cotrimoxazole 400mg/80mg/day displayed a higher incidence of adverse effects.Conclusion:Cotrimoxazole prophylaxis against PCP exhibited efficacy compared to non-prophylaxis, mainly in patients treated with high dose of glucocorticoids (≥20mg/day), causing a significant reduction in mortality. Positive efficacy results did not differ despite the diverse Cotrimoxazol regimens exposed. However, Cotrimoxazole adverse effects were observed after two months from initiation; particularly with daily dose of 400mg/80mg. In contrast, escalate dose or 200mg/40mg/day dose regimens appeared better tolerated.**This review is part of the Spanish Rheumatology Society –SER- recommendations on Systemic Autoimmune Diseases.References:[1] Utsunomiya, M., et al. (2017). “Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial.” Arthritis Res Ther 19(1): 7.[2] Yamamoto, T., et al. (2014). “A feasibility study assessing tolerability of daily versus twice weekly trimethoprim-sulfamethoxazole regimen for prophylaxis against pneumocystis pneumonia in patients with systemic autoimmune diseases on glucocorticoid therapy.” Japanese Journal of Clinical Pharmacology and Therapeutics 45(3): 89-92.Disclosure of Interests:None declared