Achieving HIV Epidemic Control and Improving Maternal Healthcare Services with Community-Based HIV Service Delivery in Zambia: Mixed-Methods Assessment of the SMACHT Project.

Novel community-based approaches are needed to achieve and sustain HIV epidemic control in Zambia. Under the Stop Mother and Child HIV Transmission (SMACHT) project, the Community HIV Epidemic Control (CHEC) differentiated service delivery model used community health workers to support HIV testing, ART linkage, viral suppression, and prevention of mother-to-child transmission (MTCT). A multi-methods assessment included programmatic data analysis from April 2015 to September 2020, and qualitative interviews from February to March 2020. CHEC provided HIV testing services to 1,379,387 clients; 46,138 were newly identified as HIV-positive (3.3% yield), with 41,366 (90%) linked to ART. By 2020, 91% (60,694/66,841) of clients on ART were virally suppressed. Qualitatively, healthcare workers and clients benefitted from CHEC, with provision of confidential services, health facility decongestion, and increased HIV care uptake and retention. Community-based models can increase uptake of HIV testing and linkage to care, and help achieve epidemic control and elimination of MTCT.

Advanced HIV disease management practices within inpatient medicine units at a referral hospital in Zambia: a retrospective chart review.

BACKGROUND: Zambia recently achieved UNAIDS 90-90-90 treatment targets for HIV epidemic control; however, inpatient facilities continue to face a large burden of patients with advanced HIV disease and HIV-related mortality. Management of advanced HIV disease, following guidelines from outpatient settings, may be more difficult within complex inpatient settings. We evaluated adherence to HIV guidelines during hospitalization, including opportunistic infection (OI) screening, treatment, and prophylaxis. METHODS: We reviewed inpatient medical records of people living with HIV (PLHIV) admitted to the University Teaching Hospital in Lusaka, Zambia between December 1, 2018 and April 30, 2019. We collected data on patient demographics, antiretroviral therapy (ART), HIV biomarkers, and OI screening and treatment-including tuberculosis (TB), Cryptococcus, and OI prophylaxis with co-trimoxazole (CTX). Screening and treatment cascades were constructed based on the 2017 WHO Advanced HIV Guidelines. RESULTS: We reviewed files from 200 charts of patients with advanced HIV disease; of these 92% (184/200) had been on ART previously; 58.1% (107/184) for more than 12 months. HIV viral load (VL) testing was uncommon but half of VL results were high. 39% (77/200) of patients had a documented CD4 count result. Of the 172 patients not on anti-TB treatment (ATT) on admission, TB diagnostic tests (either sputum Xpert MTB/RIF MTB/RIF or urine TB-LAM) were requested for 105 (61%) and resulted for 60 of the 105 (57%). Nine of the 14 patients (64%) with a positive lab result for TB died before results were available. Testing for Cryptococcosis was performed predominantly in patients with symptoms of meningitis. Urine TB-LAM testing was rarely performed. CONCLUSIONS: At a referral hospital in Zambia, CD4 testing was inconsistent due to laboratory challenges and this reduced recognition of AHD and implementation of AHD guidelines. HIV programs can potentially reduce mortality and identify PLHIV with retention and adherence issues through strengthening inpatient activities, including reflex VL testing, TB-LAM and serum CrAg during hospitalization.

Examining HPV Vaccination Practices and Differences Among Providers in Virginia.

Virginia has some of the lowest HPV vaccination rates, despite being one of the few states in the USA requiring adolescent girls receive the vaccine. Provider characteristics may be an important factor in HPV vaccination. Thus, the present study assessed provider vaccination, practices, knowledge about the vaccine, and confidence in performing behaviors related to the vaccine. We conducted a cross-sectional electronic survey in a large health care system in Northern Virginia. A total of 53 responses were received. Only respondents who reported seeing adolescent patients were included in analyses (N = 42). Differences in responses were examined by provider age, gender, and type. Respondents reported recommending the vaccine a high percent of the time to eligible patients and had overall high levels of knowledge and confidence. Male providers recommended the vaccine to boys ages 11-12, less frequently than female providers. Providers age 50 and over recommended the vaccine to boys ages 11-12 less frequently than younger providers. This study shows that there are some gaps in HPV vaccine recommendation practices among providers. These gaps may be one reason for the low uptake of the HPV vaccine among adolescents. Thus, educational and training interventions of providers could be considered.

Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of Real-world Experience.

Prophylactic human papillomavirus (HPV) vaccination programs constitute major public health initiatives worldwide. We assessed the global effect of quadrivalent HPV (4vHPV) vaccination on HPV infection and disease. PubMed and Embase were systematically searched for peer-reviewed articles from January 2007 through February 2016 to identify observational studies reporting the impact or effectiveness of 4vHPV vaccination on infection, anogenital warts, and cervical cancer or precancerous lesions. Over the last decade, the impact of HPV vaccination in real-world settings has become increasingly evident, especially among girls vaccinated before HPV exposure in countries with high vaccine uptake. Maximal reductions of approximately 90% for HPV 6/11/16/18 infection, approximately 90% for genital warts, approximately 45% for low-grade cytological cervical abnormalities, and approximately 85% for high-grade histologically proven cervical abnormalities have been reported. The full public health potential of HPV vaccination is not yet realized. HPV-related disease remains a significant source of morbidity and mortality in developing and developed nations, underscoring the need for HPV vaccination programs with high population coverage.

Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in inhabitants from low-income countries and in visitors to these countries. The impact of the human intestinal microbiota on the initiation and progression of ETEC diarrhea is not yet well understood. RESULTS: We used 16S rRNA (ribosomal RNA) gene sequencing to study changes in the fecal microbiota of 12 volunteers during a human challenge study with ETEC (H10407) and subsequent treatment with ciprofloxacin. Five subjects developed severe diarrhea and seven experienced few or no symptoms. Diarrheal symptoms were associated with high concentrations of fecal E. coli as measured by quantitative culture, quantitative PCR, and normalized number of 16S rRNA gene sequences. Large changes in other members of the microbiota varied greatly from individual to individual, whether or not diarrhea occurred. Nonetheless the variation within an individual was small compared to variation between individuals. Ciprofloxacin treatment reorganized microbiota populations; however, the original structure was largely restored at one and three month follow-up visits. CONCLUSION: Symptomatic ETEC infections, but not asymptomatic infections, were associated with high fecal concentrations of E. coli. Both infection and ciprofloxacin treatment caused variable changes in other bacteria that generally reverted to baseline levels after three months.

Microbiota that affect risk for shigellosis in children in low-income countries.

Pathogens in the gastrointestinal tract exist within a vast population of microbes. We examined associations between pathogens and composition of gut microbiota as they relate to Shigella spp./enteroinvasive Escherichia coli infection. We analyzed 3,035 stool specimens (1,735 nondiarrheal and 1,300 moderate-to-severe diarrheal) from the Global Enteric Multicenter Study for 9 enteropathogens. Diarrheal specimens had a higher number of enteropathogens (diarrheal mean 1.4, nondiarrheal mean 0.95; p<0.0001). Rotavirus showed a negative association with Shigella spp. in cases of diarrhea (odds ratio 0.31, 95% CI 0.17-0.55) and had a large combined effect on moderate-to-severe diarrhea (odds ratio 29, 95% CI 3.8-220). In 4 Lactobacillus taxa identified by 16S rRNA gene sequencing, the association between pathogen and disease was decreased, which is consistent with the possibility that Lactobacillus spp. are protective against Shigella spp.-induced diarrhea. Bacterial diversity of gut microbiota was associated with diarrhea status, not high levels of the Shigella spp. ipaH gene.

Comparison of HIV prevalence, incidence, and viral load suppression in Zambia population-based HIV impact assessments from 2016 and 2021.

BACKGROUND: The Zambian government has implemented a public health response to control the HIV epidemic in the country. Zambia conducted a population-based HIV impact assessment (ZAMPHIA) survey in 2021 to assess the status of the HIV epidemic to guide its public health programs. METHODS: ZAMPHIA 2021 was a cross-sectional two-stage cluster sample household survey among persons aged ≥15 years conducted in Zambia across all 10 provinces. Consenting participants were administered a standardized questionnaire and whole blood was tested for HIV according to national guidelines. HIV-1 viral load (VL), recent HIV infection, and antiretroviral medications were tested for in HIV-seropositive samples. Viral load suppression (VLS) was defined as <1000 copies/ml. ZAMPHIA 2021 results were compared to ZAMPHIA 2016 for persons aged 15-59 years (i.e., the overlapping age ranges). All estimates were weighted to account for nonresponse and survey design. RESULTS: During ZAMPHIA 2021, of 25 483 eligible persons aged ≥15 years, 18 804 (73.8%) were interviewed and tested for HIV. HIV prevalence was 11.0% and VLS prevalence was 86.2% overall, but was <80% among people living with HIV aged 15-24 years and in certain provinces. Among persons aged 15-59 years, from 2016 to 2021, HIV incidence declined from 0.6% to 0.3% ( P -value: 0.07) and VLS prevalence increased from 59.2% to 85.7% ( P -value: <0.01). DISCUSSION: Zambia has made substantial progress toward controlling the HIV epidemic from 2016 to 2021. Continued implementation of a test-and-treat strategy, with attention to groups with lower VLS in the ZAMPHIA 2021, could support reductions in HIV incidence and improve overall VLS in Zambia.

Quantitative PCR for detection of Shigella improves ascertainment of Shigella burden in children with moderate-to-severe diarrhea in low-income countries.

Estimates of the prevalence of Shigella spp. are limited by the suboptimal sensitivity of current diagnostic and surveillance methods. We used a quantitative PCR (qPCR) assay to detect Shigella in the stool samples of 3,533 children aged <59 months from the Gambia, Mali, Kenya, and Bangladesh, with or without moderate-to-severe diarrhea (MSD). We compared the results from conventional culture to those from qPCR for the Shigella ipaH gene. Using MSD as the reference standard, we determined the optimal cutpoint to be 2.9 × 10(4) ipaH copies per 100 ng of stool DNA for set 1 (n = 877). One hundred fifty-eight (18%) specimens yielded >2.9 × 10(4) ipaH copies. Ninety (10%) specimens were positive by traditional culture for Shigella. Individuals with ≥ 2.9 × 10(4) ipaH copies have 5.6-times-higher odds of having diarrhea than those with <2.9 × 10(4) ipaH copies (95% confidence interval, 3.7 to 8.5; P < 0.0001). Nearly identical results were found using an independent set of samples. qPCR detected 155 additional MSD cases with high copy numbers of ipaH, a 90% increase from the 172 cases detected by culture in both samples. Among a subset (n = 2,874) comprising MSD cases and their age-, gender-, and location-matched controls, the fraction of MSD cases that were attributable to Shigella infection increased from 9.6% (n = 129) for culture to 17.6% (n = 262) for qPCR when employing our cutpoint. We suggest that qPCR with a cutpoint of approximately 1.4 × 10(4) ipaH copies be the new reference standard for the detection and diagnosis of shigellosis in children in low-income countries. The acceptance of this new standard would substantially increase the fraction of MSD cases that are attributable to Shigella.

Survey of culture, goldengate assay, universal biosensor assay, and 16S rRNA Gene sequencing as alternative methods of bacterial pathogen detection.

Cultivation-based assays combined with PCR or enzyme-linked immunosorbent assay (ELISA)-based methods for finding virulence factors are standard methods for detecting bacterial pathogens in stools; however, with emerging molecular technologies, new methods have become available. The aim of this study was to compare four distinct detection technologies for the identification of pathogens in stools from children under 5 years of age in The Gambia, Mali, Kenya, and Bangladesh. The children were identified, using currently accepted clinical protocols, as either controls or cases with moderate to severe diarrhea. A total of 3,610 stool samples were tested by established clinical culture techniques: 3,179 DNA samples by the Universal Biosensor assay (Ibis Biosciences, Inc.), 1,466 DNA samples by the GoldenGate assay (Illumina), and 1,006 DNA samples by sequencing of 16S rRNA genes. Each method detected different proportions of samples testing positive for each of seven enteric pathogens, enteroaggregative Escherichia coli (EAEC), enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), Shigella spp., Campylobacter jejuni, Salmonella enterica, and Aeromonas spp. The comparisons among detection methods included the frequency of positive stool samples and kappa values for making pairwise comparisons. Overall, the standard culture methods detected Shigella spp., EPEC, ETEC, and EAEC in smaller proportions of the samples than either of the methods based on detection of the virulence genes from DNA in whole stools. The GoldenGate method revealed the greatest agreement with the other methods. The agreement among methods was higher in cases than in controls. The new molecular technologies have a high potential for highly sensitive identification of bacterial diarrheal pathogens.

Addressing the Need for a Preexposure Prophylaxis Monitoring and Evaluation Implementation Guide: Experience From Zambia.

BACKGROUND: The HIV care continuum comprises well-defined steps and indicators. In contrast, indicators along the preexposure prophylaxis (PrEP) cascade are still in the early stages of implementation. Monitoring and evaluation (M&E) of PrEP services is critical to optimizing PrEP uptake and adherence during periods of HIV risk. We provide an overview of global indicators for PrEP, describe the development process and outcomes of Zambia's 2022 National Pre-Exposure Prophylaxis (PrEP) Program Monitoring & Evaluation Implementation Guide, and discuss the guide's implications for other countries in sub-Saharan Africa. NATIONAL M&E GUIDE DEVELOPMENT PROCESS: During the scale-up of PrEP, the Zambia Ministry of Health (MOH) and the National HIV/AIDS/STI/TB Council recognized the need for a national unified monitoring system to guide the effective implementation of PrEP services. Stakeholders from the MOH, civil society, professional organizations, funding agencies, and implementing partners developed the National Pre-Exposure Prophylaxis (PrEP) Program Monitoring & Evaluation Implementation Guide. This guide is aligned with the existing global indicators from the World Health Organization and the U.S. President's Emergency Plan for AIDS Relief and adapted to the country's needs, context, and health information systems. Zambia's experience in developing the guide has highlighted the importance of strengthening client-level monitoring systems for HIV prevention, ensuring flexibility of the PrEP monitoring system to accommodate PrEP delivery modalities and differentiated service delivery models, and training health workers to enhance PrEP services and deliver care PrEP services along the continuum to prevent HIV acquisition effectively. CONCLUSIONS: Using a collaborative and consensus-based approach, Zambia developed its first national PrEP M&E implementation guide to provide standardized guidelines for optimizing the delivery, monitoring, and evaluation of PrEP service delivery. Zambia's experience can inform other countries in sub-Saharan Africa as they develop national M&E implementation approaches for PrEP.

Initial implementation of HIV pre-exposure prophylaxis for people who are incarcerated in Zambia: a cross-sectional observational study.

BACKGROUND: There are over 23 000 incarcerated people in Zambia, a population which has higher HIV prevalence than the general population yet has no access to HIV prevention. To evaluate the feasibility of HIV pre-exposure prophylaxis (PrEP) implementation in Zambian criminal justice facilities, we offered PrEP services to incarcerated people and aimed to describe early implementation outcomes. METHODS: In this cross-sectional observational study, we implemented a PrEP programme between Oct 1, 2020, and March 31, 2021, supporting 16 criminal justice facilities in four Zambian provinces. Before implementation, we held stakeholder engagement meetings with Zambia Correctional Service officials to discuss PrEP benefits, and trained Zambia Correctional Service health-care workers in PrEP management using the national PrEP training package. People who were incarcerated and screened positive for substantial HIV risk by use of a standardised HIV risk assessment tool were offered voluntary HIV testing and counselling. Those who tested positive were linked to antiretroviral therapy, and those who tested negative and met national HIV prevention eligibility criteria were offered PrEP. We assessed PrEP uptake and used descriptive statistics to characterise programme beneficiaries and the cascade of PrEP services. FINDINGS: During the study period, we reached 12 367 people older than 15 years with HIV risk assessment and counselling, including 11 794 (95·4%) men and 573 (4·6%) women. Of these, 2610 people received HIV testing, with 357 (13·7%) testing HIV positive; positivity was significantly higher in women (20·6%) than men (13·2%, p=0·011). 1276 people were identified as HIV negative and PrEP eligible. Of these, 1190 (93·3%) initiated PrEP. The age group with the highest proportion reached and initiated on PrEP was those aged 25-29 years, representing 19·2% (2377 of 12 367) of all people reached and 24·1% (287 of 1190) of those who initiated PrEP. INTERPRETATION: Delivery of PrEP to people who are incarcerated is feasible with adequate resourcing and support to the criminal justice health system, and can result in high uptake among eligible individuals. Further assessment is needed of PrEP persistence and adherence, and the perceptions of people who are incarcerated regarding their HIV risk and preferences for combination HIV prevention services. FUNDING: US President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention.

Fostering Access to PrEP Among Adolescent Girls and Young Women Aged 16 to 24 Years at High Risk of HIV Through the DREAMS Initiative in Four Districts in Zambia.

Adolescent girls and young women (AGYW) in sub-Saharan Africa remain at high risk for HIV, yet limited data exist on implementation of HIV pre-exposure prophylaxis (PrEP) for this group. We examined PrEP uptake among AGYW using a retrospective cohort enrolled in the Determined Resilient Empowered AIDS-free Mentored Safe (DREAMS) initiative in Zambia between October 2020 and March 2022. Consent was obtained from eligible AGYW at substantial risk for HIV, and they voluntarily participated in PrEP. Multivariable logistic regression was used to examine factors associated with PrEP refills following initiation. Of 4,162 HIV-negative AGYW, 3,233 (77%) were at substantial risk and initiated on PrEP. Overall, 68% of AGYW had at least one refill, but this differed significantly by age group and district. DREAMS was successful at reaching AGYW with PrEP services. More evidence is needed to assess reasons for discontinuation and to improve persistence for those with sustained HIV risk.

Treatment-Experienced Patients on Third-Line Therapy: A Retrospective Cohort of Treatment Outcomes at the HIV Advanced Treatment Centre, University Teaching Hospital, Zambia.

Antiretroviral therapy (ART) uptake continues to increase across sub-Saharan Africa and emergence of drug-resistant HIV mutations poses significant challenges to management of treatment-experienced patients with virologic failure. In Zambia, new third-line ART (TLART) guidelines including use of dolutegravir (DTG) were introduced in 2018. We assessed virologic suppression, immunologic response, and HIV drug-resistant mutations (DRMs) among patients on TLART at the University Teaching Hospital (UTH) in Lusaka, Zambia. We conducted a retrospective review of patients enrolled at UTH on TLART for >6 months between January 2010 and June 30, 2021. CD4 and HIV viral load (VL) at TLART initiation and post-initiation were assessed to determine virologic and immunologic outcomes. Regression analysis using bivariate and multivariate methods to describe baseline characteristics, virologic, and immunologic response to TLART was performed. A total of 345 patients met inclusion criteria; women comprised 57.6% (199/345) of the cohort. Median age at HIV diagnosis was 30 (interquartile range: 17.3-36.8). In 255 (73.8%) patients with at least two VLs, VL decreased from mean of 3.45 log10 copies/mL (standard deviation [SD]: 2.02) to 1.68 log10 copies/mL (SD: 1.79). Common ARVs prescribed included DTG (89.9%), tenofovir disoproxil fumarate (68.7%), and darunavir boosted with ritonavir (66.4%); 170 (49.3%) patients had genotypes; mutations consisted of 88.8% nucleoside reverse transcriptase inhibitor, 86.5% non-nucleoside reverse transcriptase inhibitor, and 55.9% protease inhibitor. VL suppression to <1,000 copies/mL was achieved in 225 (78.9%) patients. DRM frequency ranged from 56% to 89% depending on drug class. Treatment-experienced patients receiving TLART in Zambia achieved high rates of suppression despite high proportions of HIV mutations illustrating TLART effectiveness in the DTG era.

Reaching transgender populations in Zambia for HIV prevention and linkage to treatment using community-based service delivery.

INTRODUCTION: Transgender and gender-diverse communities in Zambia are highly vulnerable and experience healthcare differently than cisgender persons. The University of Maryland, Baltimore (UMB) supports projects in Zambia to improve HIV case-finding, linkage and antiretroviral treatment (ART) for Zambia's transgender community. We describe programme strategies and outcomes for HIV prevention, testing and ART linkage among transgender communities. METHODS: UMB utilizes a differentiated service delivery model whereby community health workers (CHWs) recruited from key populations (KPs) reach community members through a peer-to-peer approach, with the support of local transgender civil society organizations (CSOs) and community gatekeepers. Peer CHWs are trained and certified as HIV testers and psychosocial counsellors to offer counselling with HIV testing and prevention services in identified safe spaces. HIV-negative people at risk of HIV infection are offered pre-exposure prophylaxis (PrEP), while those who test positive for HIV are linked to ART services. CHWs collect data using the standardized facility and community tools and a dedicated DHIS2 database system. We conducted a descriptive analysis examining HIV testing and prevention outcomes using proportions and comparisons by time period and geographic strata. RESULTS: From October 2020 to June 2021, across Eastern, Lusaka, Western and Southern Provinces, 1860 transgender persons were reached with HIV prevention messages and services. Of these, 424 (23%) were tested for HIV and 78 (18%) tested positive. Of the 346 HIV-negative persons, 268 (78%) eligible transgender individuals were initiated on PrEP. ART linkage was 97%, with 76 out of the 78 transgender individuals living with HIV initiating treatment. Programme strategies that supported testing and linkage included peer CHWs, social network strategy testing, same-day ART initiation and local KP CSO support. Challenges included non-transgender-friendly environments, stigma and discrimination, the high transiency of the transgender community and the non-availability of transgender-specific health services, such as hormonal therapy. CONCLUSIONS: Peer KP CHWs were able to reach many members of the transgender community, providing safe HIV testing, PrEP services and linkage to care. Focusing on community gatekeepers and CSOs to disburse health messages and employ welcoming strategies supported high linkage to both PrEP and ART for transgender people in Zambia.

Peer community health workers improve HIV testing and ART linkage among key populations in Zambia: retrospective observational results from the Z-CHECK project, 2019-2020.

INTRODUCTION: Zambia has made tremendous progress towards HIV epidemic control; however, gaps remain among key populations (KPs), such as female sex workers (FSWs), men who have sex with men (MSM), people who inject drugs (PWID) and people in prisons and enclosed settings due to cultural, social and legal barriers. The University of Maryland, Baltimore Zambia Community HIV Epidemic Control for Key Populations (Z-CHECK) project aimed to improve HIV case-finding, linkage and treatment adherence at the community level for KPs in Zambia. We describe Z-CHECK strategies and examine HIV positivity yield and antiretroviral therapy (ART) linkage among KPs to inform ongoing programme improvement. METHODS: Z-CHECK recruited, trained and deployed peer community health workers (CHWs) for KP groups, with ongoing mentorship in community engagement. CHWs offered HIV testing in safe spaces and escorted newly HIV-diagnosed clients for same-day ART initiation. Z-CHECK also reached out to KP community leaders and gatekeepers for KP mobilization and trained healthcare workers (HCWs) on KP services and sensitivity. We conducted a retrospective observational review of routinely collected aggregate data for KPs aged ≥15 years at high risk for HIV transmission across five districts in Zambia from January 2019 to December 2020. RESULTS: Z-CHECK provided HIV testing for 9211 KPs, of whom 2227 were HIV positive (positivity yield, 24%). Among these, 1901 (85%) were linked to ART; linkage for MSM, FSW, PWID and people in prisons and enclosed settings was 95%, 89%, 86% and 65%, respectively. Programme strategies that contributed to high positivity yield and linkage included the use of peer KP CHWs, social network testing strategies and opportunities for same-day ART initiation. Challenges to programme implementation included stigma and discrimination among HCWs, as well as KP CHW attrition, which may be explained by high mobility. CONCLUSIONS: Peer CHWs were highly effective at reaching KP communities, identifying persons living with HIV and linking them to care. Engaging KP community gatekeepers resulted in high diffusion of health messages and increased access to health resources. The mobility of CHWs and HCWs is a challenge for programme implementation. Innovative interventions are needed to support PWID and people in prisons and enclosed settings.

Evaluation of the Nigeria national HIV rapid testing algorithm.

Human Immunodeficiency Virus (HIV) diagnosis remains the gateway to HIV care and treatment. However, due to changes in HIV prevalence and testing coverage across different geopolitical zones, it is crucial to evaluate the national HIV testing algorithm as false positivity due to low prevalence could be detrimental to both the client and the service delivery. Therefore, we evaluated the performance of the national HIV rapid testing algorithm using specimens collected from multiple HIV testing services (HTS) sites and compared the results from different HIV prevalence levels across the six geopolitical zones of Nigeria. The evaluation employed a dual approach, retrospective, and prospective. The retrospective evaluation focused on a desktop review of program data (n = 492,880) collated from patients attending routine HTS from six geopolitical zones of Nigeria between January 2017 and December 2019. The prospective component utilized samples (n = 2,895) collected from the field at the HTS and tested using the current national serial HIV rapid testing algorithm. These samples were transported to the National Reference Laboratory (NRL), Abuja, and were re-tested using the national HIV rapid testing algorithm and HIV-1/2 supplementary assays (Geenius to confirm positives and resolve discordance and multiplex assay). The retrospective component of the study revealed that the overall proportion of HIV positives, based on the selected areas, was 5.7% (28,319/492,880) within the study period, and the discordant rate between tests 1 and 2 was 1.1%. The prospective component of the study indicated no significant differences between the test performed at the field using the national HIV rapid testing algorithm and the re-testing performed at the NRL. The comparison between the test performed at the field using the national HIV rapid testing algorithm and Geenius HIV-1/2 supplementary assay showed an agreement rate of 95.2%, while that of the NRL was 99.3%. In addition, the comparison of the field results with HIV multiplex assay indicated a sensitivity of 96.6%, the specificity of 98.2%, PPV of 97.0%, and Kappa Statistic of 0.95, and that of the NRL with HIV multiplex assay was 99.2%, 99.4%, 99.0%, and 0.99, respectively. Results show that the Nigeria national serial HIV rapid testing algorithm performed very well across the target settings. However, the algorithm's performance in the field was lower than the performance outcomes under a controlled environment in the NRL. There is a need to target testers in the field for routine continuous quality improvement implementation, including refresher trainings as necessary.

Diarrheagenic pathogens in polymicrobial infections.

During systematic active surveillance of the causes of diarrhea in patients admitted to the Infectious Diseases and Beliaghata General Hospital in Kolkata, India, we looked for 26 known gastrointestinal pathogens in fecal samples from 2,748 patients. Samples from about one-third (29%) of the patients contained multiple pathogens. Polymicrobial infections frequently contained Vibrio cholerae O1 and rotavirus. When these agents were present, some co-infecting agents were found significantly less often (p = 10 (-5) to 10 (-33), some were detected significantly more often (p = 10 (-5) to 10 (-26), and others were detected equally as often as when V. cholerae O1 or rotavirus was absent. When data were stratified by patient age and season, many nonrandom associations remained statistically significant. The causes and effects of these nonrandom associations remain unknown.

Retrospective Review of Virologic and Immunologic Response in Treatment-Experienced Patients on Third-Line HIV Therapy in Lusaka, Zambia.

Established antiretroviral therapy (ART) programs in sub-Saharan Africa have well-defined first-and second-line therapies but no standard third-line ART regimen. The impact of third-line ART on patients with multiclass-resistant HIV in resource-limited settings has not been well characterized. We conducted a retrospective review of patients on third-line ART at the University Teaching Hospital in Lusaka, Zambia. We assessed virologic and immunologic outcomes following 6 months of third-line therapy and found among those with a documented viral load, viral suppression (≤1000 copies/ml) at 24 weeks was 95% (63/66) with a mean increase in CD4 count of 116 cells/mm3 and viral suppression of 63% (63/100) by imputation of missing data. This study suggests that third-line therapy is clinically and virologically effective among patients with multiclass-resistance in a resource-limited setting in sub-Saharan Africa.

Reporting guidelines for human microbiome research: the STORMS checklist.

The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies. Therefore, a multidisciplinary group of microbiome epidemiology researchers adapted guidelines for observational and genetic studies to culture-independent human microbiome studies, and also developed new reporting elements for laboratory, bioinformatics and statistical analyses tailored to microbiome studies. The resulting tool, called 'Strengthening The Organization and Reporting of Microbiome Studies' (STORMS), is composed of a 17-item checklist organized into six sections that correspond to the typical sections of a scientific publication, presented as an editable table for inclusion in supplementary materials. The STORMS checklist provides guidance for concise and complete reporting of microbiome studies that will facilitate manuscript preparation, peer review, and reader comprehension of publications and comparative analysis of published results.

Natural Infection with Giardia Is Associated with Altered Community Structure of the Human and Canine Gut Microbiome.

Enteric parasitic infections are among the most prevalent infections in lower- and middle-income countries (LMICs) and have a profound impact on global public health. While the microbiome is increasingly recognized as a key determinant of gut health and human development, the impact of naturally acquired parasite infections on microbial community structure in the gut, and the extent to which parasite-induced changes in the microbiome may contribute to gastrointestinal symptoms, is poorly understood. Enteric parasites are routinely identified in companion animals in the United States, presenting a unique opportunity to leverage this animal model to investigate the impact of naturally acquired parasite infections on the microbiome. Clinical, parasitological, and microbiome profiling of a cohort of 258 dogs revealed a significant correlation between parasite infection and composition of the bacterial community in the gut. Relative to other enteric parasites, Giardia was associated with a more pronounced perturbation of the microbiome. To compare our findings to large-scale epidemiological studies of enteric diseases in humans, a database mining approach was employed to integrate clinical and microbiome data. Substantial and consistent alterations to microbiome structure were observed in Giardia-infected children. Importantly, infection was associated with a reduction in the relative abundance of potential pathobionts, including Gammaproteobacteria, and an increase in Prevotella-a profile often associated with gut health. Taken together, these data show that widespread Giardia infection in young animals and humans is associated with significant remodeling of the gut microbiome and provide a possible explanation for the high prevalence of asymptomatic Giardia infections observed across host species.IMPORTANCE While enteric parasitic infections are among the most important infections in lower- and middle-income countries, their impact on gut microbiota is poorly understood. We reasoned that clinical symptoms associated with these infections may be influenced by alterations of the microbiome that occur during infection. To explore this notion, we took a two-pronged approach. First, we studied a cohort of dogs naturally infected with various enteric parasites and found a strong association between parasite infection and altered gut microbiota composition. Giardia, one of the most prevalent parasite infections globally, had a particularly large impact on the microbiome. Second, we took a database-driven strategy to integrate microbiome data with clinical data from large human field studies and found that Giardia infection is also associated with marked alteration of the gut microbiome of children, suggesting a possible explanation for why Giardia has been reported to be associated with protection from moderate to severe diarrhea.