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We conducted a prospective cohort study to determine the prevalence of leukotriene A4 hydrolase (LTA4H) polymorphisms in Zambian adults with tuberculous meningitis (TBM) and its association with mortality. We completed genotype testing on 101 definite cases of TBM and 119 consecutive non‐TBM controls. The distribution of genotypes among TBM patients was as follows: C/C (0.83), C/T (0.14), T/T (0.03). There was no significant difference in genotype distribution between TBM and non‐TBM patients. We found no relationship between LTA4H polymorphism and survival. Prospective studies are needed to determine the benefit of adjuvant steroids in TBM based upon population LTA4H genotype. ANN NEUROL 2021;90:994–998 [ABSTRACT FROM AUTHOR]

Objective: Interactions between enzyme‐inducing anti‐seizure medications (EI‐ASMs) and antiretroviral drugs (ARVs) can lead to decreased ARV levels and may increase the likelihood of viral resistance. We conducted a study to determine if co‐usage of ARVs and EI‐ASMs is associated with ARV‐resistant human immunodeficiency virus (HIV) among people living with HIV in Zambia. Methods: Eligible participants were ≥18 years of age and concurrently taking ASMs and ARVs for at least 1 month of the prior 6‐month period. Data were obtained regarding medication and HIV history. CD4 counts, plasma viral loads (pVLs), and HIV genotype and resistance profile in participants with a pVL >1000 copies/mL were obtained. Pearson's test of independence was used to determine whether treatment with EI‐ASM was associated with pVL >1000/mL copies. Results: Of 50 participants, 41 (82%) were taking carbamazepine (37 on monotherapy), and all had stable regimens in the prior 6 months. Among the 13 ARV regimens used, 68% had a tenofovir/lamivudine backbone. The majority (94%) were on a stable ARV regimen for >6 months. Median CD4 nadir was 205 cells/mm3 (interquartile range [IQR] 88‐389), and 60% of participants had commenced ARV treatment before advanced disease occurred. Mean CD4 count at enrollment was 464 cells/mm3 (SD 226.3). Seven participants (14%) had a CD4 count <200 cells/mm3. Four (8%) had a pVL >1000 copies/mL; all were on carbamazepine. Three participants with elevated pVL had a CD4 count <200 cells/mm3. None had documented adherence concerns by providers; however, two had events concerning for clinical failure. HIV genotype testing showed mutations in three participants. Carbamazepine was not found to correlate with elevated pVL (P =.58). Significance: EI‐ASMs are commonly used in sub‐Saharan Africa. Despite concurrent use of EI‐ASMs and ARVs, the majority of participants showed CD4 counts >200 cells/mm3 and were virally suppressed. Carbamazepine was not associated with an increased risk of virological failure or ARV‐resistant HIV. [ABSTRACT FROM AUTHOR]

Introduction: The re-emergence of vector borne diseases affecting millions of people in recent years has drawn attention to arboviruses globally. Here, we report on the sero-prevalence of chikungunya virus (CHIKV), dengue virus (DENV), mayaro virus (MAYV) and zika virus (ZIKV) in a swamp community in Zambia. Methods: We collected blood and saliva samples from residents of Lukanga swamps in 2016 during a mass-cholera vaccination campaign. Over 10,000 residents were vaccinated with two doses of Shanchol™ during this period. The biological samples were collected prior to vaccination (baseline) and at specified time points after vaccination. We tested a total of 214 baseline stored serum samples for IgG antibodies against NS1 of DENV and ZIKV and E2 of CHIKV and MAYV on ELISA. We defined sero-prevalence as the proportion of participants with optical density (OD) values above a defined cut-off value, determined using a finite mixture model. Results: Of the 214 participants, 79 (36.9%; 95% CI 30.5–43.8) were sero-positive for Chikungunya; 23 (10.8%; 95% CI 6.9–15.7) for Zika, 36 (16.8%; 95% CI 12.1–22.5) for Dengue and 42 (19.6%; 95% CI 14.5–25.6) for Mayaro. Older participants were more likely to have Zika virus whilst those involved with fishing activities were at greater risk of contracting Chikungunya virus. Among all the antigens tested, we also found that Chikungunya saliva antibody titres correlated with baseline serum titres (Spearman's correlation coefficient = 0.222; p = 0.03). Conclusion: Arbovirus transmission is occurring in Zambia. This requires proper screening tools as well as surveillance data to accurately report on disease burden in Zambia. [ABSTRACT FROM AUTHOR]

Regular plasma HIV-RNA testing for persons living with HIV on antiretroviral therapy (ART) is now the global standard, but as many as 60% of persons in Africa today on ART do not have access to standard laboratory HIV-RNA assays. As a result, patients in Zambia often receive treatment without any means of determining true virologic failure, which poses a risk of premature switch of ART regimens and widespread HIV drug resistance. Dry blood spots (DBS) on the other hand require unskilled personnel and less complex storage supply chain so are ideal to capture viral-load results from HIV patients outside clinic settings. We assess collection of DBS in the community using non-medically trained personnel (NMP) and documented challenges. We trained 23 NMP to collect DBS from lost to follow-up (LTFU) patients in 4 rural and urban Zambian districts. We developed a phlebotomy box to transport DBS without contamination at ambient temperature and concomitant training and standard operating procedures. We evaluated this through field observations, bi-weekly meetings, reports, and staff meetings. The laboratory assessed DBS quality for testing validity. We attempted to collect DBS from 357 participants in the community. Though individual reasons for refusal from the remaining 37% were not collected, NMPs reported privacy concerns, awkward box-size which drew attention in the community and fears of undisclosed uses of samples related to witchcraft and circulating narratives about past research. Successful DBS collection was not associated with patient gender, age, time on ART, enrolment CD4, facility. DBS viral-load collection by NMP is feasible in Zambia. Our training approach and assessments of NMP not part of the health system can be extended to patients by giving them more responsibility to manage their own differentiated care groups. Concerted efforts that compare collection of DBS by NMP to those collected by skilled-medical personnel are needed. [ABSTRACT FROM AUTHOR]

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Background: Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. Methods: We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. Results: Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1–9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3–13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192–8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22–5.53) and CD4 cell count below 200/μl (2.58, 1.20–5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir. Conclusion: One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults. [ABSTRACT FROM AUTHOR]