Cotrimoxazole Prophylaxis Research Articles

Drugs for Intermittent Preventive Treatment of Malaria in Pregnancy: Current Knowledge and Way Forward.

Malaria infection during pregnancy is an important driver of maternal and neonatal health in endemic countries. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention at each scheduled antenatal care visit, starting at the second trimester, in areas of high and moderate transmission. However, the increased resistance to SP in some endemic areas challenges its effectiveness. Furthermore, SP is contraindicated in the first trimester of pregnancy and in HIV-infected women on co-trimoxazole prophylaxis due to potential drug–drug interactions. Thus, in recent last decades, several studies evaluated alternative drugs that could be used for IPTp. A comprehensive literature review was conducted to summarize the evidence on the efficacy and safety of antimalarial drugs being evaluated for IPTp. Chloroquine, amodiaquine, mefloquine and azithromycin as IPTp have proven to be worse tolerated than SP. Mefloquine was found to increase the risk of mother-to-child transmission of HIV. Dihydroartemisin-piperaquine currently constitutes the most promising IPTp drug alternative; it reduced the prevalence of malaria infection, and placental and clinical malaria in studies among HIV-uninfected women, and it is currently being tested in HIV-infected women. Research on effective antimalarial drugs that can be safely administered for prevention to pregnant women should be prioritized. Malaria prevention in the first trimester of gestation and tailored interventions for HIV-infected women remain key research gaps to be addressed.

Treatment Outcomes of HIV Infected Children After Initiation of Antiretroviral Therapy in Southwest China: An Observational Cohort Study.

BackgroundThe number of HIV infected children receiving antiviral treatment in Guangxi is increasing. Understanding factors and trends of mortality and attrition in HIV-infected children under antiretroviral therapy (ART) was an urgent need to improve treatment outcomes. This study aimed to estimate mortality and attrition rates and identify factors that were associated with mortality and attrition after ART initiation among children with HIV in Guangxi, China between 2004 and 2018.MethodsCohort study data were extracted from the National Free Antiretroviral Treatment Program (NFATP) database, which has standard guidelines for core treatment indicators and other data at all HIV/AIDS treatment facilities in Guangxi. A total of 901 HIV-infected children who have started ART were included in the study. The study collected the following data: age, gender, WHO clinic stages before ART, CD4 cell count before ART, Cotrimoxazole prophylaxis (CTX) use before ART, initial ART regimen, malnutrition before ART, abnormal liver function before ART, abnormal kidney function before ART, severe anemia before ART, and the time lag between an HIV diagnosis and ART initiation.ResultsHIV-infected children under ART had a mortality rate of 0.87 per 100 person-years [95% Confidence Interval (CI) 0.63–1.11], and an attrition rate of 3.02 per 100 person-years (95% CI 2.57–3.47). Mortality was lower among children with a CD4 count between 200 and 500 copies/ml [Adjusted Hazard Ratio (AHR) 0.22, 95% CI 0.09–0.55], and CD4 count ≥500 copies/ml (AHR 0.10, 95% CI 0.03–0.29); but higher among children with late ART initiation at 1–3 months (AHR 2.30, 95% CI 1.07–4.94), and at ≥3 months (AHR 2.22, 95% CI 1.04–4.74). Attrition was lower among children with a CD4 count ≥500 copies/ml (AHR 0.62, 95% CI 0.41–0.95), but higher among children with late ART initiation at 1–3 months (AHR 1.55, 95% CI 1.05–2.30).ConclusionSupportive programs are needed to educate children's families and parents on early ART, link HIV-infected children to care and retain them in care among other programs that treat and manage the medical conditions of HIV-infected children before ART initiation.

Predictors of Dietary Diversity among HIV Clients in a Low-resource Tertiary Health Facility in Southeast Nigeria

Background: In a resource-limited setting where nutrient availability is a challenge, it may be necessary to determine factors that affect dietary diversity in people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) as addressing them could lead to better access to diversified diets in this group. Objective: The objective of this study was to determine the factors that influence dietary diversity among HIV clients attending the HIV clinic in a low-resource tertiary health facility. Materials and Methods: An institutional-based cross-sectional study was conducted among HIV clients receiving anti-retroviral therapy in Enugu state, Nigeria. A systematic random sampling technique was employed in selecting the study participants. Bivariate analysis was done using the chi-square test which was further subjected to multivariate logistic regression analyses to determine predictors of dietary diversity. Results: In this study, respondents who earned a family monthly income of 72.5 US dollars and below were 2.6 times less likely to have high dietary diversity (AOR = 0.378, CI = 0.180–0.792) compared to those who earned above 145 dollars. Also, HIV clients on cotrimoxazole prophylaxis were 2.3 times more likely to have high dietary diversity (AOR = 2.304, CI = 1.155–4.598) compared to those who were not on the prophylaxis. Conclusions: High family monthly income and being on cotrimoxazole prophylaxis were predictors of high dietary diversity in People living with HIV/AIDS. Therefore, there is a need to improve the income of PLWHA as well as ensure the ready availability of cotrimoxazole to reduce the rate of opportunistic infections thus leading to better consumption of diversified diets.

Safety and efficacy of Ibrutinib in Indian patients with chronic lymphocytic leukemia.

e19585 Background: Ibrutinib, an oral Bruton's tyrosine kinase inhibitor, is approved for the treatment of chronic lymphocytic leukemia (CLL) in both upfront and relapsed/refractory. The prevalence of CLL is very low in India compared to western countries. Hence, the real-world data regarding efficacy and safety of Ibrutinib among the Indian population is very scarce. In this study, we aim to examine the toxicity profile, treatment response, and survival outcomes among Indian patients with CLL treated with Ibrutinib. Methods: In this retrospective study, we recruited all consecutive patients diagnosed with CLL, both treatment naïve (TN) and relapsed/refractory (R/R) CLL, on Ibrutinib (daily dose of 420 mg), registered at the Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India between April 2016 and December 2021. Diagnosis of CLL, an indication of treatment, and response assessment were based on the recent guidelines (2018) from the International Workshop on CLL (iwCLL). Results: A total of 90 patients were recruited in this study, of which 33 were newly diagnosed and 57 had R/R CLL. Median age of the cohort was 60 years (range, 35–80 years) and male to female ratio was 3:1. The median total leukocyte count was 55x109/L and Del 17p was detected in 18% of cases. The R/R cases had received a median of 1(1-3) prior line of therapy. Overall response rate was observed in 76(84.4%), complete response was in 18 (20%) cases, partial response (PR) was in 49 (54.4%) cases, and in 9 (10%) cases PR with lymphocytosis (PR-L) was observed. With a median follow-up period of 15 months (4-60), 2-year progression-free survival (PFS) was 80% for the whole cohort. The median PFS was not reached in TN cases and was 18 months in R/R cases. Grade-3/4 adverse events (A/E) were seen in 17 (29.8%, n = 57) of R/R cases and in 3 (9.1%,n = 33) of TN cases. The most common Grade-3/4 A/E were infections in 19 (21.1%), (Varicella: 7, Pneumocystis: 6, Aspergilosis: 2, Mucormycosis: 1, Disseminated tuberculosis: 1, Encephalitis: 1, Others: 1) and cytopenias in 9 (10%) of cases. Other A/E were fatigue in 6 cases, arthralgia in 3, bleeding in 2, cutaneous rash in 2, reactivation of hepatitis-B in 2, diarrhea in 2, arrhythmia in 2, and autoimmune hemolytic anemia in one case. Ten patients (11.1%) had a dose reduction due to AE. The discontinuation rate was 27 (30%), due to progressive disease in 18 patients and due to adverse events in 9 patients. Twenty patients died, 14 due to disease progression or Richter's transformation, 5 due to infections, and 2 due to other reasons. Conclusions: This is the largest study of ibrutinib from India. Ibrutinib is safe and effective in upfront and R/R cases of CLL. Infections are the most common adverse event in R/R cases. Acyclovir and Co-trimoxazole prophylaxis can be considered in R/R cases of CLL in routine clinical practice . Arrhythmias were rare A/E as compared with the available literature.

Prevalence and risk factors for blood filariasis among HIV-infected adults in Gabon, Central Africa: a pilot study.

The level of blood filariasis parasitaemia as well as the frequency of and the relationship between cotrimoxazole prophylaxis (CTX-P), antiretroviral therapy (ART) intake and CD4 cell count among people living with human immunodeficiency virus (PLHIV) in rural areas of Gabon were being studied. Sociodemographic data and recent biological tests of PLHIV and HIV-negative participants were collected. Loa loa and Mansonella perstans microfilaria were detected by direct microscopy examination and leucoconcentration. Overall, 209 HIV-positive and 148 HIV-negative subjects were enrolled. The overall prevalence of microfilaria was comparable between PLHIV (19.9% [n=41/206]) and HIV-negative participants (14.8% [n=22/148]) (p=0.2). The L. loa infection rate was comparable between HIV-positive (9.2%) and HIV-negative participants (6.8%) (p=0.2), while the M. perstans infection rate was 14-fold higher among PLHIV (p<0.01). L. loa parasitaemia was 6-fold lower in PLHIV receiving CTX-P (median 150mf/mL [interquartile range {IQR} 125-350]) than in patients without (900 [550-2225]) (p<0.01). Among subjects with a CD4 cell count <200cells/μL, the prevalence of M. perstans was 7-fold higher than that of L. loa (20.6% vs 2.9%). This study suggests a similar exposure to L. loa infection of PLHIV and HIV-negative patients while M. perstans is more frequently found in HIV-positive individuals, notably those with a CD4 count <200cells/μL.

Retention in care and predictors of attrition among HIV-infected patients who started antiretroviral therapy in Kinshasa, DRC, before and after the implementation of the 'treat-all' strategy.

The retention of patients in care is a key pillar of the continuum of HIV care. It has been suggested that the implementation of a "treat-all" strategy may favor attrition (death or lost to follow-up, as opposed to retention), specifically in the subgroup of asymptomatic people living with HIV (PLWH) with high CD4 counts. Attrition in HIV care could mitigate the success of universal antiretroviral therapy (ART) in resource-limited settings. We performed a retrospective study of PLWH at least 15 years old initiating ART in 85 HIV care centers in Kinshasa, Democratic Republic of Congo (DRC), between 2010 and 2019, with the objective of measuring attrition and to define factors associated with it. Sociodemographic and clinical characteristics recorded at ART initiation included sex, age, weight, height, WHO HIV stage, pregnancy, baseline CD4 cell count, start date of ART, and baseline and last ART regimen. Attrition was defined as death or loss to follow-up (LTFU). LTFU was defined as "not presenting to an HIV care center for at least 180 days after the date of a last missed visit, without a notification of death or transfer". Kaplan-Meier curves were used to present attrition data, and mixed effects Cox regression models determined factors associated with attrition. The results compared were before and after the implementation of the "treat-all" strategy. A total of 15,762 PLWH were included in the study. Overall, retention in HIV care was 83% at twelve months and 77% after two years of follow-up. The risk of attrition increased with advanced HIV disease and the size of the HIV care center. Time to ART initiation greater than seven days after diagnosis and Cotrimoxazole prophylaxis was associated with a reduced risk of attrition. The implementation of the "treat-all" strategy modified the clinical characteristics of PLWH toward higher CD4 cell counts and a greater proportion of patients at WHO stages I and II at treatment initiation. Initiation of ART after the implementation of the 'treat all" strategy was associated with higher attrition (p<0.0001) and higher LTFU (p<0.0001). Attrition has remained high in recent years. The implementation of the "treat-all" strategy was associated with higher attrition and LTFU in our study. Interventions to improve early and ongoing commitment to care are needed, with specific attention to high-risk groups to improve ART coverage and limit HIV transmission.

Half-life time prediction of developing first-line antiretroviral treatment failure and its risk factors among TB and HIV co-infected children in Northwest Ethiopia; multi setting historical follow-up study

BackgroundEven though treatment failure is higher among TB and HIV infected children in a resource-limited setting, there is no prior evidence in general and in the study area in particular. Hence, this study was aimed at determining the half-life time prediction of developing first-line antiretroviral treatment failure and its risk factors among TB and HIV co-infected children.MethodsA historical follow-up study was employed among 239 TB and HIV co-infected children from January 2010-December 2020. The data was entered into Epi data version 4.2.2 and exported to STATA 14.0 Software for analysis. The Kaplan-Meier plot was used to estimate the half-life time to develop treatment failure. The required assumption was fulfilled for each predictor variable. Additionally, those variables having a p-value ≤0.25 in the bivariable analysis were fitted into a multivariable Cox-proportional hazards regression model. P-value, < 0.05 was used to declare a significant association.ResultsA total of 239 TB and HIV co-infected children were involved in this study. The overall half-life time to develop first treatment failure was found to be 101 months, with a total of 1027.8 years’ follow-up period. The incidence rate and proportion of developing first-line treatment failure were 5.5 per 100 PPY (Person-Year) [CI (confidence interval): 3.7, 6.9] 100 PPY and 23.8% (CI; 18.8, 29.7) respectively. Factors such as hemoglobin 10 mg/dl [AHR (Adjusted Hazard Ratio): 3.2 (95% CI: 1.30, 7.73), severe acute malnutrition [AHR: 3.8 (95% CI: 1.51, 79.65), World Health Organization stage IV [AHR: 2.4 (95% CI: 1.15, 4.93)], and cotrimoxazole prophylaxis non user [AHR: 2.3 (95% CI: 1.14, 4.47)] were found to be a risk factor to develop treatment failure.ConclusionIn this study, the half-life time to develop first-line treatment failure was found to be very low. In addition, the incidence was found to be very high. The presence of hemoglobin 10 mg/dl, severe acute malnutrition, World Health Organization stage, and non-use of cotrimoxazole prophylaxis were discovered to be risk factors for treatment failure. Further prospective cohort and qualitative studies should be conducted to improve the quality of care in paediatric ART clinics to reduce the incidence or burden of first line treatment failure among TB and HIV co-infected children.

HIV-related toxoplasma encephalitis: a tertiary care experience

Introduction: Toxoplasma encephalitis (TE) is the most commonly found in HIV patients who have no cotrimoxazole prophylaxis, especially when the CD count is &lt;100 / µL. Therapy is often based on a presumptive diagnosis because definitive diagnosis is difficult, and TE can be life threatening. Aim of this study is to provide a characteristic description of TE in HIV patients who admitted at Sanglah Hospital. Methods: This is a retrospective descriptive study of 43 adult patients admitted with diagnosis TE at the Sanglah Hospital, Indonesia between January 1st 2018 to December 31th 2018. Results: Most patients were male (69.8%), with the predominant age ranged 31-40 years old (39.5%). Among all patients; 14% on cotrimoxazole prophylaxis, and 23.3% on antiretroviral therapy. The most common clinical manifestation was headache (58.1%). Oral candidiasis was found in 67.4% of patients. CD4 levels &lt;100 cells / µL were found in 62.8% of patients, absolute lymphocytes &lt;500 / µL in 32.6% of patients. Anemia was found in 37.2% of patients. Multiple ring enhancement was the most common feature found on head CT scan, with the profound location was parietal lobe (46.5%). Pyrimethamine + clindamycin is used in 72.1% of cases. The TE mortality rate in HIV patients in this study was 11.6%. Conclusion: TE in HIV patients was more common on male, younger age and who are not receiving appropriate prophylaxis and/or without antiretroviral therapy. Laboratory study predominantly showed severe immunodeficiency. The most patients making a full recovery with pyrimethamine and clindamycin treatment.

Early diagnosis of Wiskott-Aldrich syndrome in the neonatal period and successful haematopoietic stem cell transplant in infancy

Wiskott-Aldrich syndrome (WAS) is a rare X-linked inborn error of immunity characterised by triad of eczema, microthrombocytopenia and recurrent infections. We herein report a case, where a male new-born with thrombocytopenia and no other symptoms was suspected of WAS in view of the significant family history of two previous sibling deaths. The diagnosis was confirmed by flowcytometry for WAS protein expression. He was initially managed with intravenous immunoglobulin replacement, regular cotrimoxazole prophylaxis, emollients and topical steroids for eczema (which child developed from the third month). The child underwent haematopoietic stem cell transplant (HSCT) at 8 months of age successfully and has remained asymptomatic at 5 years of follow-up. Early diagnosis of inborn error of immunity is extremely important for the prevention of complications and successful treatment including HSCT.

Effects of Cotrimoxazole Prophylaxis Initiation and Discontinuation on Mortality and Attrition Rates among HIV Patients Who Initiate ART in Southwest China: An Observational Cohort Study

Effects of Cotrimoxazole Prophylaxis Initiation and Discontinuation on Mortality and Attrition Rates among HIV Patients Who Initiate ART in Southwest China: An Observational Cohort Study

Cotrimoxazole versus sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria in HIV-infected pregnant women in Bangui, Central African Republic: A pragmatic randomised controlled trial.

The main objective of the MACOMBA (Maternity and Control of Malaria-HIV co-infection in Bangui) trial was to show that cotrimoxazole (CTX) is more effective than sulphadoxine-pyremethamine-IPTp (IPTp-SP) to prevent placental malaria infection (primary end point) among HIV-positive pregnant women with a CD4+ count ≥350cells/mm3 in Bangui, CAR. MACOMBA is a multicentre, open-label randomised trial conducted in four maternity hospitals in Bangui. Between 2013 and 2017, 193 women were randomised and 112 (59 and 53 in CTX and IPTp-SP arms, respectively) were assessed for placental infection defined by microscopic parasitaemia or PCR. Thirteen women had a placental infection: five in the CTX arm (one by microscopic placental parasitaemia and four by PCR) and eight by PCR in the SP-IPTp (8.5% vs. 15.1%, p=0.28). The percentage of newborns with low birthweight (<2500g) did not differ statistically between the two arms. Self-reported compliance to CTX prophylaxis was good. There was a low overall rate of adverse events in both arms. Although our results do not allow us to conclude that CTX is more effective, drug safety and good compliance among women with this treatment favour its widespread use among HIV-infected pregnant women, as currently recommended by WHO.

TCL-361: Bendamustine as Front-Line Therapy in T-Cell Prolymphocytic Leukemia: A Monocentric Experience

Introduction T-cell prolymphocytic leukemia (T-PLL) is a rare T-cell-neoplasm that is characterized by uncontrolled proliferation of mature T-cell lymphocytes with a very poor prognosis. Nowadays, alemtuzumab as a single agent is the best available option for both treatment-naive and relapsed/refractory patients; however, its efficacy is hampered by various adverse events (AEs) such as infusion-associated reactions, autoimmune AEs, and opportunistic infections. Objective We conducted a monocentric, retrospective study to evaluate the safety and efficacy of bendamustine, which is a bifunctional mechlorethamine derivative with alkylating and antimetabolite activities, as first-line therapy in patients unfit for alemtuzumab. Patients and Methods We collected clinical and biological data of 7 T-PLL patients treated with bendamustine between 2014 and 2020 in our institution. Four out of seven (57%) were males, the median age at diagnosis was 73 years (65–83 years). The median time from diagnosis to treatment was 15 months. Bendamustine was administered intravenously (90 mg/m2 on days one and two, every four weeks) for up to six cycles. Results Overall response rate was 57%, 3 patients achieved complete response (43%), and one partial response (14%). One patient experienced stable disease, and two patients progressed during treatment. Five patients (71%) experienced a relapse. Median overall survival (OS) was 63.7 months (19–108); median OS for responding patients was 187 months versus 24 months for non-responding patients (p=0.093). Median progression-free survival (PFS) was 12 months (11–13). Three patients received second-line therapy: one patient was treated with gemcitabine; the others received a second bendamustine course. Two patients received a third-line therapy with combination chemotherapy: COMP (prednisone, cyclophosphamide, vincristine, myocettm) and CVP (cyclophosphamide, vincristine, prednisone). Two patients experienced infusion-associated reactions. Four patients experienced hematological toxicities: one thrombocytopenia G3, 3 neutropenia G3 requiring G-CSF administration. Four patients received co-trimoxazole prophylaxis, one received acyclovir prophylaxis. One patient experienced herpetic retinitis. Premature termination ( Conclusions Our data are consistent with scientific literature. This treatment is feasible and safe, with an acceptable toxicity profile. Although alemtuzumab remains the standard of care of this rare disease, bendamustine might be a valid option either for unfit patients or for undeferrable disease.

The Etiology of Pneumonia in HIV-1-infected South African Children in the Era of Antiretroviral Treatment: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study.

HIV-1 infection predisposes to an increased burden of pneumonia caused by community-acquired and opportunistic pathogens. Within the context of the Pneumonia Etiology Research for Child Health case-control study of under 5 pneumonia, we investigated the etiology of World Health Organization-defined severe/very severe pneumonia requiring hospitalization in South African HIV-infected children. Nasopharyngeal-oropharyngeal swabs and blood, collected from cases and age- and season-matched HIV-infected controls attending outpatient antiretroviral therapy (ART) clinics, were analyzed using molecular diagnostic methods. Cases were also investigated for tuberculosis. Etiologic fractions among cases with radiologically confirmed pneumonia were derived using Bayesian analytic techniques. Of 115 HIV-infected cases, 89 (77.4%) had radiologically confirmed pneumonia. Severe immunosuppression (adjusted odds ratio, 32.60; 95% confidence interval, 7.25-146.64) was significantly associated with radiologically confirmed pneumonia. Cotrimoxazole prophylaxis (46.4% vs. 77.4%) and ART (28.2% vs. 83.1%) coverage were significantly lower in cases compared with ART-clinic controls. An etiologic agent was identified in 99.0% of the radiologically confirmed cases. The 'top 4' pathogens associated with radiologically confirmed pneumonia were Pneumocystis jirovecii [23.0%; 95% credible interval (CrI), 12.4%-31.5%], Staphylococcus aureus (10.6%; 95% CrI, 2.2%-20.2%), pneumococcus (9.5%; 95% CrI, 2.2%-18.0%) and respiratory syncytial virus (9.3%; 95% CrI, 2.2%-14.6%). Bacteremia (6.7%) and in-hospital death (10.1%) were frequent among those with radiologically confirmed disease. Pneumocystis jirovecii, S. aureus, pneumococcus and respiratory syncytial virus contribute a considerable burden of radiologically confirmed pneumonia in South African HIV-infected children under 5 years. Expediting access to ART and cotrimoxazole prophylaxis would decrease the burden of pneumonia in these children.

Intestinal Colonization with Tropheryma whipplei-Clinical and Immunological Implications for HIV Positive Adults in Ghana.

Background: Recent studies demonstrated higher prevalence rates of Tropheryma whipplei (T. whipplei) in HIV positive than in HIV negative subjects. However, associations with the immune status in HIV positive participants were conflicting. Methods: For this cross-sectional study, stool samples of 906 HIV positive and 98 HIV negative individuals in Ghana were tested for T. whipplei. Additionally, sociodemographic parameters, clinical symptoms, medical drug intake, and laboratory parameters were assessed. Results: The prevalence of T. whipplei was 5.85% in HIV positive and 2.04% in HIV negative participants. Within the group of HIV positive participants, the prevalence reached 7.18% in patients without co-trimoxazole prophylaxis, 10.26% in subjects with ART intake, and 12.31% in obese participants. Frequencies of clinical symptoms were not found to be higher in HIV positive T. whipplei carriers compared to T. whipplei negative participants. Markers of immune activation were lower in patients colonized with T. whipplei. Multivariate regression models demonstrated an independent relationship of a high CD4+ T cell count, a low HIV-1 viral load, and an obese body weight with the presence of T. whipplei. Conclusions: Among HIV positive individuals, T. whipplei colonization was associated with a better immune status but not with clinical consequences. Our data suggest that the withdrawal of co-trimoxazole chemoprophylaxis among people living with HIV on stable cART regimen may inadvertently increase the propensity towards colonization with T. whipplei.

Determinants of the uptake of intermittent preventive treatment of malaria in pregnancy with sulphadoxine pyrimethamine in Sabatia Sub County, Western Kenya

BackgroundAnnually, 125.2 million pregnant women worldwide risk contracting malaria, including 30.3 million and 1.5 million in Sub-Saharan Africa and Kenya respectively. At least three doses of sulphadoxine pyrimethamine for intermittent preventive treatment of malaria in pregnancy (IPTp-SP) is recommended for optimal benefit. Kenya recorded low IPTp-SP optimal uptake in 2015. This study investigated the prevalence of and factors influencing IPTp-SP optimal uptake in Sabatia Sub County, Western Kenya.MethodsA cross-sectional study was conducted in Sabatia Sub County from April to October 2020. Using a validated semi-structured questionnaire, data were obtained from 372 randomly sampled post-delivery women aged 15–49 years with live birth within one year preceding the study. Women on cotrimoxazole prophylaxis during pregnancy were excluded. Pearson Chi-square and Fisher’s Exact test were measures of association used. Binary logistic regression analysed predictors of optimal IPTp-SP uptake.ResultsOptimal IPTp-SP uptake was 79.6%, 95% CI 75.5%–83.7%. Predictors of IPTp-SP optimization were gestational age at first antenatal care (ANC) visit (P = 0.04), frequency of ANC visits (P < 0.001), maternal knowledge of IPTp-SP benefits (P < 0.001), maternal knowledge of optimal sulphadoxine pyrimethamine (SP) dose (P = 0.03) and SP administration at ANC clinic (P = 0.03). Late ANC initiators were less likely to receive optimal IPTp-SP (aOR = 0.4, 95% CI 0.2–0.9). Odds of optimizing IPTp-SP increased among women with ≥ 4 ANC visits (aOR = 16.7, 95% CI 7.9–35.3), good knowledge of IPTp-SP benefits (aOR = 2.4, 95% CI 1.3–4.5) and good knowledge of optimal SP dose (aOR = 1.9, 95% CI 1.1–3.4). Women who never missed being administered SP were highly likely to receive optimal IPTp-SP (aOR = 2.9, 95% CI 1.1–7.2)ConclusionsThis study has found high IPTp-SP optimal uptake in the study area. Efforts should be directed towards early and more frequent ANC visits. Intensive and targeted health education is required. It’s fundamental to adequately stock and consistently administer SP. Future studies considering larger samples and health workers’ perspectives of the health system delivery factors are recommended.Graphical abstract

Novel Heterozygous Mutation of CIITA Gene Presenting with Recurrent Infections and Systemic Lupus Erythematosus

Background: The expression of major histocompatibility complex (MHC) molecule is essential for homeostasis of the immune system. The expression of MHC-II is regulated by the master regulator for transcription, the Class II transactivator (CIITA) gene. Homozygous mutations affecting the CIITA gene result in bare lymphocyte syndrome type-II, but the clinical manifestations of heterozygous mutations are not well reported. Clinical Description: Herein, we describe the roller coaster course of a 6-year-old child who had presented with recurrent infections in infancy and systemic lupus erythematosus (SLE) in toddler age, who was later found to have heterozygous mutation in the CIITA gene. Management: The child was managed with immunosuppression for SLE and monthly intravenous immunoglobulin replacement therapy and daily cotrimoxazole prophylaxis for features of immunodeficiency. Conclusion: This case report aims to provide more insight into the clinical features associated with heterozygous mutations of CIITA.

P402 Is co-trimoxazole prophylaxis necessary for Inflammatory Bowel Disease patients receiving triple immunosuppression?

Abstract Background ECCO Guidelines (1) advocate Co-trimoxazole (TMP/SMX) prophylaxis against Pneumocystis jirovecii for patients with inflammatory bowel disease (IBD) on triple immunosuppression, although the evidence level is low and based on non-IBD patient data (2). We assessed adherence to this guidance and frequency of infection events among IBD patients at Imperial College Healthcare NHS Trust, London, UK. Methods Eligible patients were defined as those on a combination of 2 immunosuppressants (with one of those being a biologic) between December 2017 to December 2020, who received a course of high dose steroids (≥20mg prednisolone). Patient demographics, IBD treatment, TMP/SMX prophylaxis and infections (including hospitalisation) developed within 30-days of starting high dose steroids were recorded retrospectively using the hospital electronic patient records. Results In the cohort of 247 patients on concomitant biologic and immunosuppression dual therapy 176/247 (71%) were ≤ 49 years old and 136/247 (55%) were male. Over the three year observation period, 333 individual thiopurine-biologic combinations were prescribed; Of the biologics 157/333 (47%) were infliximab, 91/333 (27%) adalimumab, 50/333 (15%) vedolizumab, 27/333 (8%) ustekinumab and 8/333 tofacitinib (3%). All received azathioprine or 6MP concurrently. Steroids were prescribed on 75 occasions for 50 (20%) patients. Of 28/75 (37%) prescriptions where TMP/SMX was co-prescribed 4/28 (14%) developed infections with 1/28 (4%) requiring hospitalisation. There were no respiratory infections in this group. Of the 47/75 (63%) where TMP/SMX was not prescribed 7/47 (15%) developed infections (4/47 respiratory, 2/47 skin or bone, 2/47 [MZ1] gastrointestinal infections). One patient had 2 infections. The hospitalisation rate was 2/47 (4%). There were no confirmed cases of Pneumocystis jirovecii in either group. Conclusion Existing evidence for TMP/SMX prophylaxis in this setting is limited and is reflected in the varied clinical practice observed. However, no difference in clinically significant infection rates among individuals with and without TMP/SMX prophylaxis was observed in our setting. Further data are required to validate the utility of antibiotic prophylaxis in severely immunosuppressed IBD cohorts to better guide its use. References

Antibacterial Susceptibility Patterns of Bloodstream Isolates in 74 HIV-Infected Patients Hospitalized at the Clinic of Infectious and Tropical Diseases of Fann University Hospital, Dakar from 2013 to 2016

RésuméIntroductionLa bactériémie est associée à une létalité élevée chez les patients infectés par le VIH (PVVIH). La prophylaxie au cotrimoxazole et le mésusage des antibiotiques favorisent la résistance antibactérienne. Seules quelques études ont examiné ce problème chez les PVVIH. Ainsi, l'objectif de cette étude était de décrire le profil de résistance des germes responsables des bactériémies dans cette population.Matériel et méthodesIl s'agit d'une étude rétrospective transversale et descriptive menée à la clinique des maladies infectieuses et tropicales du CHU de Fann de mars 2013 à décembre 2016. Les données ont été collectées à partir des dossiers des patients grâce à un questionnaire d'enquête préétabli.RésultatsSoixante-quatorze cas de bactériémie ont été enregistrés, dont 51,4% chez les femmes. L'âge médian était de 45 ans [18-73 ans] et le taux moyen de CD4 de 83,3 cellules/μl. Les staphylocoques à coagulase négative étaient les plus isolés (14%) suivis d'Escherichia coli (10%) et de Klebsiella pneumoniae (10%). Les taux de résistance à la méthicilline pour les staphylocoques à coagulase négative et Staphylococcus aureus étaient respectivement de 35,7% (5/14) et 22% (2/9). Les souches productrices de BLSE étaient représentées par Escherichia coli 50% (5/10), Klebsiella pneumoniae 40% (4/10) et Enterobacter sp 25% (2/8). Les Pseudomonas sp étaient les principaux (22,2%) germes résistants aux carbapénèmes.ConclusionLes résultats de cette étude prônent la nécessité d'une surveillance continue de la résistance antibactérienne chez les PVVIH et l'antibiothérapie probabiliste s'appuyant sur les données de surveillance.

Asymptomatic malaria parasitaemia among HIV infected children and adolescents

Background: Malaria manifests with life-threatening manifestations resulting in hospital admissions and sometimes death may ensue. This is more devastating among children due to high susceptibility resulting from impaired immune system following severe malaria. Human immunodeficiency virus (HIV) coinfection with malaria further compromises the immune system and increases the vulnerability. The effect of co-trimoxazole prophylaxis in curtailing malaria has not being well evaluated in our environment where both malaria and HIV are endemic. This study sets out to determine the magnitude of asymptomatic malaria among HIV-infected children and adolescents receiving care at our facility. Study Design: This was a descriptive cross-sectional study. Materials and Methods: A prospective study among HIV-infected children aged 2–18 years was enrolled in our care. Nonprobability convenience sampling was used to recruit individuals who fulfilled the criteria. Questionnaire and patients' medical records were used to gather some data. A sample was taken for malaria parasite microscopy. The analysis was done using the Statistical Package for the Social Sciences version 20. Categorical variables were presented as percentages and association assessed using Chi-square test, whereas continuous variables were presented as mean and standard deviation, and the association between two means was checked using Student's t-test. Results: The mean age of the study population is 7.02 ± 2.97 years. Of the 420 participants in this study, 92 (45.7%) had confirmed malaria. There was no significant difference in the gender, age groups, and viral loads of patients with malaria. Conclusion: There is a high prevalence of malaria coinfection with HIV in this study.

Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial.

Daily co-trimoxazole is recommended for African adults living with human immunodeficiency virus (HIV) irrespective of antiretroviral treatment, immune status, or disease stage. Benefits of continued prophylaxis and whether co-trimoxazole can be stopped following immune reconstitution are unknown. We conducted a randomized controlled trial at 2 sites in Malawi that enrolled adults with HIV with undetectable viral load and CD4 count of >250/mm3 and randomized them to continue daily co-trimoxazole, discontinue daily co-trimoxazole and begin weekly chloroquine, or discontinue daily co-trimoxazole. The primary endpoint was the preventive effect of co-trimoxazole prophylaxis against death or World Health Organization (WHO) HIV/AIDS stage 3-4 events, using Cox proportional hazards modeling, in an intention-to-treat population. 1499 adults were enrolled. The preventive effect of co-trimoxazole on the primary endpoint was 22% (95% CI: -14%-47%; P = .20) versus no prophylaxis and 25% (-10%-48%; P = .14) versus chloroquine. When WHO HIV/AIDS stage 2 events were added to the primary endpoint, preventive effect increased to 31% (3-51%; P = .032) and 32% (4-51%; P = .026), respectively. Co-trimoxazole and chloroquine prophylaxis effectively prevented clinical malaria episodes (3.8 and 3.0, respectively, vs 28/100 person-years; P < .001). Malawian adults with HIV who immune reconstituted on ART and continued co-trimoxazole prophylaxis experienced fewer deaths and WHO HIV/AIDS stage 3-4 events compared with prophylaxis discontinuation, although statistical significance was not achieved. Co-trimoxazole prevented a composite of death plus WHO HIV/AIDS stage 2-4 events. Given poor healthcare access and lack of routine viral load monitoring, co-trimoxazole prophylaxis should continue in adults on ART after immune reconstitution in sub-Saharan Africa. Clinical Trials Registration. NCT01650558.