Rare Case of Cryptococcal Meningitis in Non-HIV Patient with Mantle Cell Lymphoma Associated with Acalabrutinib (Tyrosine Kinase Inhibitor)

Cryptococcus neoformans infections are more common among immunosuppressed individuals, causing the most widespread opportunistic CNS infection among HIV-positive patients [1]. Specifically, those with cellular immunosuppression, such as patients with HIV positive CD4 counts less than 100. When a patient presents with atypical symptoms, it can be difficult to diagnose due to its infrequent presentation in HIV negative patients. Due to the rarity of encounters in HIV-negative patients, when atypical symptoms are present, it poses a diagnostic challenge. Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin B-cell lymphoma that is known to be associated with cellular immunosuppression [2]. This demonstrates the need for early diagnosis and recognition of cryptococcal infections and as a physician should be vigilant to diagnose cryptococcal who is on Acalabrutinib with MCL [3]. CLL patients receiving ibrutinib should be evaluated for cryptococcal infection, which is potentially life threatening if overlooked [4]. Meningitis caused by Cryptococcus mainly presents with fever and altered mental status but in this case, our patient 78-year-old male with mantle cell lymphoma, undergoing a regimen of Rituximab-Bendamustine (BR) in combination with acalabrutinib (TKI), presented with hypotension to ED in June 2021. Cryptococcal infection in patient receiving ibrutinib were mostly reported in patients with Chronic lymphocytic leukemia, who have poor immune reconstitution. Here we are reporting case of cryptococcal meningoencephalitis in patient with MCL on acalabrutinib which is never reported before.

Outcomes in patients of pulmonary tuberculosis treated under RNTCP & follow up after 6 months

Tuberculosis (TB) is, one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent.This Prospective study was conducted at Santosh medical college Ghaziabad from 1 April 2018 to 30 September 2019. All diagnosed PTB patients above 12yrs were taken. Patients with EPTB, HIV positive, MDR TB, XDR TB were excluded from the study. At the end of study treatment outcome was evaluated.Total of 208 patients diagnosed as tuberculosis were enrolled in the study. 6 patients died during course of study, 10 were treatment failure, 4 were lost to follow-up, 3 transferred out & 1 shifted to private treatment. 184 patients completed treatment successfully. Out of 184, only 152 patients were available for interview at 6 months follow up after completion of treatment. 19 could not be traced, 11 patients refused and 2 died. Out of 152, 110 were asymptomatic, 1 relapsed & rest 41 patients were symptomatic. All symptomatic patients were subjected to Chest X-Ray. Fibrosis was seen on CXR of 30 patients, bronchiectasis was seen in 3 patients, 1 patient had destroyed lung, nothing abnormal detected in 7 patients.Even after successful treatment under RNTCP, these patients need to be followed up as many of them relapse or suffer from sequelae of tuberculosis.

Cost of integrating assisted partner services in HIV testing services in Kisumu and Homa Bay counties, Kenya: a microcosting study

Background HIV assisted partner services (aPS), or provider notification and testing for sexual and injecting partners of people diagnosed with HIV, is shown to be safe, effective, and cost-effective and was scaled up within the national HIV testing services (HTS) program in Kenya in 2016. We estimated the costs of integrating aPS into routine HTS within an ongoing aPS scale-up project in western Kenya. Methods We conducted microcosting using the payer perspective in 14 facilities offering aPS. Although aPS was offered to both males and females testing HIV-positive (index clients), we only collected data on female index clients and their male sex partners (MSP). We used activity-based costing to identify key aPS activities, inputs, resources, and estimated financial and economic costs of goods and services. We analyzed costs by start-up (August 2018), and recurrent costs one-year after aPS implementation (Kisumu: August 2019; Homa Bay: January 2020) and conducted time-and-motion observations of aPS activities. We estimated the incremental costs of aPS, average cost per MSP traced, tested, testing HIV-positive, and on antiretroviral therapy, cost shares, and costs disaggregated by facility. Results Overall, the number of MSPs traced, tested, testing HIV-positive, and on antiretroviral therapy was 1027, 869, 370, and 272 respectively. Average unit costs per MSP traced, tested, testing HIV-positive, and on antiretroviral therapy were $34.54, $42.50, $108.71 and $152.28, respectively, which varied by county and facility client volume. The weighted average incremental cost of integrating aPS was $7,485.97 per facility per year, with recurrent costs accounting for approximately 90% of costs. The largest cost drivers were personnel (49%) and transport (13%). Providers spent approximately 25% of the HTS visit obtaining MSP contact information (HIV-negative clients: 13 out of 54 min; HIV-positive clients: 20 out of 96 min), while the median time spent per MSP traced on phone and in-person was 6 min and 2.5 hours, respectively. Conclusion Average facility costs will increase when integrating aPS to HTS with incremental costs largely driven by personnel and transport. Strategies to efficiently utilize healthcare personnel will be critical for effective, affordable, and sustainable aPS.

Identifying barriers to ART initiation and adherence: An exploratory qualitative study on PMTCT in Zambia

Background Though antiretroviral therapy (ART) is widely available, HIV positive pregnant women in Zambia are less likely to start and remain on therapy throughout pregnancy and after delivery. This study sought to understand readiness to start ART among HIV pregnant women from the perspectives of both women and men in order to suggest more holistic programs to support women to continue life-long ART after delivery. Methods We conducted a qualitative study with HIV positive pregnant women before and after ART initiation, and men with female partners, to understand readiness to start lifelong ART. We conducted 28 in-depth interviews among women and 2 focus group discussions among male partners. Data were transcribed verbatim and analyzed in NVivo 12 using thematic analysis. Emerging themes from the data were organized using the social ecological framework. Results Men thought of their female partners as young and needing their supervision to initiate and stay on ART. Women agreed that disclosure and partner support were necessary preconditions to ART initiation and adherence and, expressed fear of divorce as a prominent barrier to disclosure. Maternal love and desire to look after one’s children instilled a sense of responsibility among women which motivated them to overcome individual, interpersonal and health system level barriers to initiation and adherence. Women preferred adherence strategies that were discrete, the effectiveness of which, depended on women’s intrinsic motivation. Conclusion The results support current policies in Zambia to encourage male engagement in ART care. To appeal to male partners, messaging on ART should be centered on emphasizing the importance of male involvement to ensure women remain engaged in ART care. Programs aimed at supporting postpartum ART adherence should design messages that appeal to both men’s role in couples’ joint decision-making and women’s maternal love as motivators for adherence.

High prevalence of sexually transmitted infections and risk factors among HIV-positive individuals in Yunnan, China

Background Yunnan has the highest rates of HIV in China. Other treatable sexually transmitted infections (STIs) are associated with accelerated HIV transmission and poor ART outcomes, but are only diagnosed by syndromic algorithms. Methods We recruited 406 HIV-positive participants for a cross-sectional study (204 ART-naive and 202 receiving ART). Blood samples and first-voided urine samples were collected. Real-time polymerase chain reaction methods were used for diagnosing Chlamydia trachomatis (CT), Neisseria gonorrhea (NG) and Mycoplasma genitalium (MG). Syphilis and herpes simplex virus type 2 (HSV-2) tests were also performed. Results Among the 406 participants, the overall prevalence of STIs was 47.0% and 45.1% in ART-naive individuals and 49.0% in individuals receiving ART, respectively. The testing frequencies were 11.6% (11.8% vs. 11.4%), 33.2% (29.4% vs. 37.1%), 3.2% (3.4% vs. 3.0%), 2.0% (3.4% vs. 0.5%) and 4.7% (6.4% vs. 3.0%) for active syphilis, HSV-2, CT, NG and MG, respectively. The percentage of multiple infections in both groups was 10.8% (22/204) in ART-naive participants and 9.9% (20/202) in participants receiving ART. Female sex, an age between 18 and 35 years, ever injecting drugs, homosexual or bisexual status, HIV/HBV coinfection, and not receiving ART were identified as risk factors. Self-reported asymptomatic patients were not eliminated from having a laboratory-diagnosed STI. Conclusions The STI prevalence was 47.0% (45.1% vs. 49.0%), and HSV-2, syphilis and MG were the most common STIs in HIV-infected individuals. We found a high prevalence (6.4%) of MG in ART-naive individuals. HIV-positive individuals tend to neglect or hide their genital tract discomfort; thus, we suggest strengthening STI joint screening and treatment services among HIV-infected individuals regardless of whether they describe genital tract discomfort.

Prevalence and Spectrum of Second Primary Malignancies among People Living with HIV in the French Dat’AIDS Cohort

Background: We aimed to describe the prevalence and spectrum of second primary cancer (SPC) in HIV-positive cancer survivors. Methods: A multicenter retrospective study was performed using longitudinal data from the French Dat’AIDS cohort. Subjects who had developed at least two primary cancers were selected. The spectrum of SPCs was stratified by the first primary cancer type and by sex. Results: Among the 44,642 patients in the Dat’AIDS cohort, 4855 were diagnosed with cancer between 1 December 1983 and 31 December 2015, of whom 444 (9.1%) developed at least two primary cancers. The most common SPCs in men were non-Hodgkin lymphoma (NHL) (22.8%), skin carcinoma (10%) and Kaposi sarcoma (KS) (8.4%), and in women the most common SPCs were breast cancer (16%), skin carcinoma (9.3%) and NHL (8%). The pattern of SPCs differed according to first primary cancer and by sex: in men, NHL was the most common SPC after primary KS and KS was the most common SPC after primary NHL; while in women, breast cancer was the most common SPC after primary NHL and primary breast cancer. Conclusion: The frequency and pattern of subsequent cancers among HIV-positive cancer survivors differed according to the first primary cancer type and sex.

Immune correlates of Mycobacterium Tuberculosis patients in Zambia stratified by HIV serostatus and level of immunity-a cross-sectional analytical laboratory based study

Background People living with HIV (PLHIV) co-infected with tuberculosis (TB) have a distinct clinical presentation and poorer treatment outcomes compared to HIV-seronegative TB patients. Excluding low CD4 count, innate immune factors associated with TB are not fully elucidated. We, therefore, characterised and compared the expression of IL-6, TNF-α, IFN-γ, and IL-10 in whole blood of treatment naïve TB patients stimulated with heat-killed Mycobacterium tuberculosis stratified by HIV status and the level of CD4 count. Results We recruited 39 HIV seropositive and 31 HIV seronegative TB patients. Median (IQR) age was 35(28–42) years and 31(25–36) years respectively, and a majority had pulmonary tuberculosis i.e. 38(95%) and 30(97%), respectively. The two groups were significantly different in the distribution of CD4 count, 563 [465–702.5 cells/mm3] vs 345 [157–483 cell/mm3] in HIV negative vs HIV positive respectively p = <0.001. Post stimulation, the expression of IL-6 in HIV negative TB patients was significantly higher than in the HIV positive 16,757366 [8,827–23,686 pg/ml] vs. 9,508 [5,514–15,008 pg/ml], respectively; p = 0.0360. TNF-α and IFN-γ were highly expressed in HIV negative TB patients compared to the HIV positive though not statistically significant. We only observed higher expression of IL-6 in HIV negative patients in comparison to the HIV positive when stratified by level of CD4 counts as < 500 and ≥ 500 cell/mm3 for both cohorts. 21,953 [8,990–24,206 pg/ml] vs 9,505 [5,400–15,313 pg/ml], p value = 0.0585 in patients with CD4 count < 500 cell/mm3 and 13,168 [7,087–22,584 pg/ml] vs 10,413 [7,397–14,806 pg/ml], p value = 0.3744 for patients with CD4 count of ≥ 500 cell/mm3 respectively. We found a positive pairwise correlation between TNF-α -alpha and IL-6 in both HIV positive and HIV negative patients, r = 0.61 (95% CI 0.36–0.72; p < 0.0001) and r = 0.48 (95% CI 0.15–0.68; p = 0.005) respectively. The IFNγ/IL-10 ratio was higher in HIV negative when compared to HIV positive individuals, 0.052 [0.0–0.28] vs 0.007 [0–0.32] respectively; p = 0.05759. IL-6 independently reduced the probability of TB/HIV, Adjusted odds ratio 0.99, p value 0.007. Conclusions This study suggests that HIV seronegative TB patients have a higher pro-inflammatory response to MTB than HIV seropositive TB patients. Further, it also shows that the level of CD4 influences immunomodulation. The findings suggest that the difference in cytokine expression may be responsible for the distinct patterns of TB presentation between HIV positive and HIV negative patient.