Early uptake of HIV counseling and testing among pregnant women at different levels of health facilities - experiences from a community-based study in Northern Vietnam

<p>Abstract</p> <p>Background</p> <p>HIV counselling and testing for pregnant women is a key factor for successful prevention of mother to child transmission of HIV. Women's access to testing can be improved by scaling up the distribution of this service at all levels of health facilities. However, this strategy will only be effective if pregnant women are tested early and provided enough counselling.</p> <p>Objective</p> <p>To assess early uptake of HIV testing and the provision of HIV counselling among pregnant women who attend antenatal care at primary and higher level health facilities.</p> <p>Methods</p> <p>A community based study was conducted among 1108 nursing mothers. Data was collected during interviews using a structured questionnaire focused on socio-economic background, reproductive history, experience with antenatal HIV counselling and testing as well as types of health facility providing the services.</p> <p>Results</p> <p>In all 91.0% of the women interviewed had attended antenatal care and 90.3% had been tested for HIV during their most recent pregnancy. Women who had their first antenatal checkup at primary health facilities were significantly more likely to be tested before 34 weeks of gestation (OR = 43.2, CI: 18.9-98.1). The reported HIV counselling provision was also higher at primary health facilities, where women in comparison with women attending higher level health facilities were nearly three or and four times more likely to receive pre-test (OR = 2.7; CI:2.1-3.5) and post-test counseling (OR = 4.0; CI: 2.3-6.8).</p> <p>Conclusions</p> <p>The results suggest that antenatal HIV counseling and testing can be scaled up to primary heath facilities and that such scaling up may enhance early uptake of testing and provision of counseling.</p

Number and timing of antenatal HIV testing: Evidence from a community-based study in Northern Vietnam

<p>Abstract</p> <p>Background</p> <p>HIV testing for pregnant women is an important component for the success of prevention of mother-to-child transmission of HIV (PMTCT). A lack of antenatal HIV testing results in loss of benefits for HIV-infected mothers and their children. However, the provision of unnecessary repeat tests at a very late stage of pregnancy will reduce the beneficial effects of PMTCT and impose unnecessary costs for the individual woman as well as the health system. This study aims to assess the number and timing of antenatal HIV testing in a low-income setting where PMTCT programmes have been scaled up to reach first level health facilities.</p> <p>Methods</p> <p>A cross-sectional community-based study was conducted among 1108 recently delivered mothers through face-to-face interviews following a structured questionnaire that focused on socio-economic characteristics, experiences of antenatal care and HIV testing.</p> <p>Results</p> <p>The prevalence of women who lacked HIV testing among the study group was 10% while more than half of the women tested had had more than two tests during pregnancy. The following factors were associated with the lack of antenatal HIV test: having two children (aOR 2.1, 95% CI 1.3-3.4), living in a remote rural area (aOR 7.8, 95% CI 3.4-17.8), late antenatal care attendance (aOR 3.6, 95% CI 1.3-10.1) and not being informed about PMTCT at their first antenatal care visits (aOR 7.4, 95% CI 2.6-21.1). Among women who had multiple tests, 80% had the second test after 36 weeks of gestation. Women who had first ANC and first HIV testing at health facilities at primary level were more likely to be tested multiple times (OR 2.9 95% CI 1.9-4.3 and OR = 4.7 95% CI 3.5-6.4), respectively.</p> <p>Conclusions</p> <p>Not having an HIV test during pregnancy was associated with poor socio-economic characteristics among the women and with not receiving information about PMTCT at the first ANC visit. Multiple testing during pregnancy prevailed; the second tests were often provided at a late stage of gestation.</p

Modeling tuberculosis dynamics with the presence of hyper-susceptible individuals for Ho Chi Minh City from 1996 to 2015

Background The depletion of CD4 cell is the underlying reason for TB hyper-susceptibility among people with HIV. Consequently, the trend of TB dynamics is usually hidden by the HIV outbreak. Methods Here, we aim to evaluate the trend of TB dynamics quantitatively by a simple mathematical model using the known prevalence of hyper-susceptible individuals in the population. In order to estimate the parameters governing transmission we fit this model in a maximum likelihood framework to both reported TB cases and data from samples tested with Interferon Gamma Assay from Ho Chi Minh City - a city with high TB transmission and strong synchronization between HIV/AIDS and TB dynamics. Results Our results show that TB transmission in HCMC has been declining among people without HIV; we estimate a 18% (95% CI: 9–25%) decline in the transmission parameter between 1996 and 2015. Furthermore, we show that co-infected patients have limited contribution to the transmission process. For hyper-susceptible individuals, our model suggests that the risk of a new active TB infection occurring is significantly higher than the risk of relapsed active TB, while this is not the case for people without hyper-susceptibility. Conclusions The increase of TB notifications in Ho Chi Minh City from 1996 to 2008 is evitable when, as occurred, the number of hyper-susceptible individuals increased faster than the decrease of TB transmission rate. The sharp decrease in TB notifications observed in this city from 2008 to 2015 is the combined result of the decrease of TB transmission rate and the decrease of hyper-susceptible individuals in the population. For hyper-susceptible individuals, we propose that the reason for the reduced relapsed active TB risk is HIV treatment delay. According to HIV treatment guidelines issued by Vietnam’s Ministry of Health, hyper-susceptible individuals usually have to wait until their CD4 cell count falls under 350 cells/μl to start ART. Once patients begin ART, they will remain on ART for the rest of their life and thus have greater protection against relapses of TB. We therefore hypothesize that the delay in using ART imposes considerable TB burden on HCMC despite the declining transmission process.</p

Modeling tuberculosis dynamics with the presence of hyper-susceptible individuals for Ho Chi Minh City from 1996 to 2015

Background The depletion of CD4 cell is the underlying reason for TB hyper-susceptibility among people with HIV. Consequently, the trend of TB dynamics is usually hidden by the HIV outbreak. Methods Here, we aim to evaluate the trend of TB dynamics quantitatively by a simple mathematical model using the known prevalence of hyper-susceptible individuals in the population. In order to estimate the parameters governing transmission we fit this model in a maximum likelihood framework to both reported TB cases and data from samples tested with Interferon Gamma Assay from Ho Chi Minh City - a city with high TB transmission and strong synchronization between HIV/AIDS and TB dynamics. Results Our results show that TB transmission in HCMC has been declining among people without HIV; we estimate a 18% (95% CI: 9–25%) decline in the transmission parameter between 1996 and 2015. Furthermore, we show that co-infected patients have limited contribution to the transmission process. For hyper-susceptible individuals, our model suggests that the risk of a new active TB infection occurring is significantly higher than the risk of relapsed active TB, while this is not the case for people without hyper-susceptibility. Conclusions The increase of TB notifications in Ho Chi Minh City from 1996 to 2008 is evitable when, as occurred, the number of hyper-susceptible individuals increased faster than the decrease of TB transmission rate. The sharp decrease in TB notifications observed in this city from 2008 to 2015 is the combined result of the decrease of TB transmission rate and the decrease of hyper-susceptible individuals in the population. For hyper-susceptible individuals, we propose that the reason for the reduced relapsed active TB risk is HIV treatment delay. According to HIV treatment guidelines issued by Vietnam’s Ministry of Health, hyper-susceptible individuals usually have to wait until their CD4 cell count falls under 350 cells/μl to start ART. Once patients begin ART, they will remain on ART for the rest of their life and thus have greater protection against relapses of TB. We therefore hypothesize that the delay in using ART imposes considerable TB burden on HCMC despite the declining transmission process.</p

The influence of Strongyloides stercoralis co-infection on the presentation, pathogenesis and outcome of tuberculous meningitis

Background Helminth infections may modulate the inflammatory response to Mycobacterium tuberculosis and influence disease presentation and outcome. Strongyloides stercoralis is common amongst populations with high tuberculosis prevalence. Our aim was to determine if S. stercoralis co-infection influenced clinical presentation, cerebrospinal fluid (CSF) inflammation, and outcome from tuberculous meningitis (TBM). Methods From June 2017 to December 2019, 668 Vietnamese adults with TBM, enrolled in the ACT HIV or LAST ACT trials (NCT03092817; NCT03100786), underwent pre-treatment S. stercoralis testing by serology, stool microscopy, and/or stool PCR. Comparisons of pre-treatment TBM severity, CSF inflammation (including cytokines), and 3-month clinical endpoints were performed in active S. stercoralis infected and uninfected groups. Results Overall, 9.4% (63/668) participants tested positive for S. stercoralis. Active S. stercoralis infection was significantly associated with reduced pre-treatment CSF neutrophils (3 cells/mm 3[0-25] vs. 14 (cells/mm 3[1-83], p=0.04), and with reduced CSF IFN-ɣ, IL-2, and TNF-α concentrations (11.4 vs. 56.0pg/mL p=0.01; 33.1 vs. 54.5pg/mL p=0.03; 4.5 vs. 11.9pg/mL p=0.02, respectively), compared with uninfected participants. Neurological complications by 3 months were significantly reduced in active S. stercoralis infection vs. uninfected participants (3.8%[1/26] vs. 30.0%[33/110], respectively, p=0.01). Conclusions S. stercoralis co-infection may modulate the intracerebral inflammatory response to M. tuberculosis and improve TBM clinical outcomes

Variations in antimicrobial activities of human monocyte-derived macrophage and their associations with tuberculosis clinical manifestations

Macrophages play a significant role in preventing infection through antimicrobial activities, particularly acidification, and proteolysis. Mycobacterium tuberculosis (Mtb) infection can lead to diverse outcomes, from latent asymptomatic infection to active disease involving multiple organs. Monocyte-derived macrophage is one of the main cell types accumulating in lungs following Mtb infection. The variation of intracellular activities of monocyte-derived macrophages in humans and the influence of these activities on the tuberculosis (TB) spectrum are not well understood. By exploiting ligand-specific bead-based assays, we investigated macrophage antimicrobial activities real-time in healthy volunteers (n = 53) with 35 cases of latent TB (LTB), and those with active TB (ATB), and either pulmonary TB (PTB, n = 70) or TB meningitis (TBM, n = 77). We found wide person-to-person variations in acidification and proteolytic activities in response to both non-immunogenic IgG and pathogenic ligands comprising trehalose 6,6’−dimycolate (TDM) from Mtb or β-glucan from Saccharamyces erevisiase. The variation in the macrophage activities remained similar regardless of stimuli; however, IgG induced stronger acidification activity than immunogenic ligands TDM (P = 10−5, 3 × 10−5 and 0.01 at 30, 60, and 90 min) and β-glucan (P = 10−4 , 3 × 10−4 and 0.04 at 30, 60, and 90 min). Variation in proteolysis activity was slightly higher in LTB than in ATB (CV = 40% in LTB vs. 29% in ATB, P = 0.03). There was no difference in measured antimicrobial activities in response to TDM and bacterial killing in macrophages from LTB and ATB, or from PTB and TBM. Our results indicate that antimicrobial activities of monocyte-derived macrophages vary among individuals and show immunological dependence, but suggest these activities cannot be solely responsible for the control of bacterial replication or dissemination in TB

Development of ligand‐coated beads to measure macrophage antimicrobial activities

Background Information: After macrophage recognises and phagocytoses the microorganism, their phagosome undergoes a maturation process, which creates a hostile environment for the bacterium. The lumen is acidified, and proteolysis occurs to kill and degrade pathogen for further antigen presentation. It is important to understand the association between the macrophage intracellular activities and the outcome of infection. Different methods have been developed to measure the phagosome dynamics of macrophages, but there are still limitations. Results: We used Mycobacterium tuberculosis (Mtb ) antigens, the causative agent of tuberculosis (TB), as a model of infectious disease. Adopting a fluorescent bead‐based assay, we developed beads coated with trehalose 6,6′dimycolate (TDM) from Mtb cell wall and β‐glucan from yeast cell wall to measure the macrophage phagosomal activities using a microplate reader. We examined the consistency of the assay using J774 cells and validated it using human monocyte‐derived macrophages (hMDM) from healthy volunteers and TB patients. There was a decreased pH and increased proteolysis in the lumen of J774 cells after phagocytosing the ligand‐coated beads. J774 macrophage showed no difference in the acidification and proteolysis in response to control IgG beads, TDM and β‐glucan beads. hMDM from healthy volunteers or TB patients showed heterogeneity in the intracellular activities when treated with ligand‐coated beads. Conclusions and Significance: The beads coated with specific ligands from Mtb worked well in both macrophage cell line and human primary macrophages, which can be exploited to further study the phagosomal function of macrophage in TB. Our bead model can be applied to different ligands from other pathogens, which could extend the understanding of the associations between macrophage antimicrobial functions and outcomes of infectious diseases and the possible cellular mechanisms involved.</p

The application of sample pooling for mass screening of SARS-CoV-2 in an outbreak of COVID-19 in Vietnam

We sampled nasal–pharyngeal throat swabs from 96,123 asymptomatic individuals at risk of SARS-CoV-2 infection, and generated 22,290 pools at collection, each containing samples from two to seven individuals. We detected SARS-CoV-2 in 24 pools, and confirmed the infection in 32 individuals after resampling and testing of 104 samples from positive pools. We completed the testing within 14 days. We would have required 64 days to complete the screening for the same number of individuals if we had based our testing strategy on individual testing. There was no difference in cycle threshold (Ct) values of pooled and individual samples. Thus, compared with individual sample testing, our approach did not compromise PCR sensitivity, but saved 77% of the resources. The present strategy might be applicable in settings, where there are shortages of reagents and the disease prevalence is low, but the demand for testing is high

Central nervous system infection diagnosis by next-generation sequencing: a glimpse into the future?

Japanese encephalitis virus was detected by deep sequencing for the first time in urine of a 16-year-old boy with encephalitis. Seroconversion and polymerase chain reaction analysis confirmed the metagenomics finding. Urine is useful for diagnosis of flaviviral encephalitis, whereas deep sequencing can be a panpathogen assay for the diagnosis of life-threatening infectious diseases

Central nervous system infection diagnosis by next-generation sequencing: a glimpse into the future?

Japanese encephalitis virus was detected by deep sequencing for the first time in urine of a 16-year-old boy with encephalitis. Seroconversion and polymerase chain reaction analysis confirmed the metagenomics finding. Urine is useful for diagnosis of flaviviral encephalitis, whereas deep sequencing can be a panpathogen assay for the diagnosis of life-threatening infectious diseases