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Long-term symptoms often associated with COVID-19 (post-COVID conditions or long COVID) are an emerging public health concern that is not well understood. Prevalence of post-COVID conditions has been reported among persons who have had COVID-19 (range = 5%-80%), with differences possibly related to different study populations, case definitions, and data sources (1). Few studies of post-COVID conditions have comparisons with the general population of adults with negative test results for SARS-CoV-2, the virus that causes COVID-19, limiting ability to assess background symptom prevalence (1). CDC used a nonprobability-based Internet panel established by Porter Novelli Public Services* to administer a survey to a nationwide sample of U.S. adults aged ≥18 years to compare the prevalence of long-term symptoms (those lasting >4 weeks since onset) among persons who self-reported ever receiving a positive SARS-CoV-2 test result with the prevalence of similar symptoms among persons who reported always receiving a negative test result. The weighted prevalence of ever testing positive for SARS-CoV-2 was 22.2% (95% confidence interval [CI] = 20.6%-23.8%). Approximately two thirds of respondents who had received a positive test result experienced long-term symptoms often associated with SARS-CoV-2 infection. Compared with respondents who received a negative test result, those who received a positive test result reported a significantly higher prevalence of any long-term symptom (65.9% versus 42.9%), fatigue (22.5% versus 12.0%), change in sense of smell or taste (17.3% versus 1.7%), shortness of breath (15.5% versus 5.2%), cough (14.5% versus 4.9%), headache (13.8% versus 9.9%), and persistence (>4 weeks) of at least one initially occurring symptom (76.2% versus 69.6%). Compared with respondents who received a negative test result, a larger proportion of those who received a positive test result reported believing that receiving a COVID-19 vaccine made their long-term symptoms better (28.7% versus 15.7%). Efforts to address post-COVID conditions should include helping health care professionals recognize the most common post-COVID conditions and optimize care for patients with persisting symptoms, including messaging on potential benefits of COVID-19 vaccination.

Author(s): Wanga, Valentine; Mackelprang, Romel D; Thomas, Katherine K; Donnell, Deborah; Cohen, Craig R; Mugo, Nelly R; Bukusi, Elizabeth A; de Bruyn, Guy; Irungu, Elizabeth; Celum, Connie; Baeten, Jared M; Lingappa, Jairam R; Partners in Prevention HSV/HIV Transmission Study and the Partners PrEP Study | Abstract: BackgroundWhether bacterial vaginosis (BV) and CD101 immunoglobulin-like (Ig-like) variants independently increase HIV risk through mucosal inflammation is not well understood. We evaluated whether the impact of BV on HIV acquisition in women differs by the presence or absence of candidate CD101 Ig-like variants.MethodsWe used data from 2 studies of HIV serodiscordant couples in east (Kenya, Tanzania, and Uganda) and southern (Botswana, South Africa, and Zambia) Africa, which longitudinally assessed HIV acquisition (by ELISA) and BV (by Nugent score ≥7). We used previously generated CD101 sequence data for each case and control participant to create a binary variable indicating the presence/absence of any of 5 CD101 Ig-like variants.ResultsConfirming previously shown results in this cohort, Ig-like variants increased HIV-infection risk (adjusted hazard ratio [aHR], = 2.63; 95% confidence interval [CI], 1.41 to 4.89). BV was associated with 2.5-fold higher HIV-infection risk only in the absence of Ig-like variants (aHR = 2.47; 95% CI, 0.99 to 6.15; P = 0.052), whereas in the presence of Ig-like variants, BV was not associated with higher HIV-infection risk (aHR = 0.87; 95% CI, 0.35 to 2.15; P = 0.765); however, a test for interaction was nonsignificant (P = 0.116).ConclusionsWe hypothesized that both BV and CD101 Ig-like variants facilitate HIV acquisition by augmenting similar genital inflammation pathways. Our findings indicate that inflammatory mucosal effects of Ig-like variants may influence the impact of BV on HIV risk. Host-defined inflammatory pathways may be useful targets for HIV prevention.

We previously reported a higher incidence of non-albumin proteinuria and a small but significant decline in estimated glomerular filtration rate (eGFR) among HIV-negative adults randomized to emtricitabine/tenofovir disoproxil fumarate preexposure prophylaxis (FTC/TDF PrEP) versus placebo. In a nested case--control study among participants randomized to FTC/TDF PrEP, established kidney injury biomarkers measured at 12 months were not significantly different between participants who subsequently experienced one of these kidney endpoints and randomly selected controls who did not.

As of June 30, 2021, 33.5 million persons in the United States had received a diagnosis of COVID-19 (1). Although most patients infected with SARS-CoV-2, the virus that causes COVID-19, recover within a few weeks, some experience post-COVID-19 conditions. These range from new or returning to ongoing health problems that can continue beyond 4 weeks. Persons who were asymptomatic at the time of infection can also experience post-COVID-19 conditions. Data on post-COVID-19 conditions are emerging and information on rehabilitation needs among persons recovering from COVID-19 is limited. Using data acquired during January 2020-March 2021 from Select Medical* outpatient rehabilitation clinics, CDC compared patient-reported measures of health, physical endurance, and health care use between patients who had recovered from COVID-19 (post-COVID-19 patients) and patients needing rehabilitation because of a current or previous diagnosis of a neoplasm (cancer) who had not experienced COVID-19 (control patients). All patients had been referred to outpatient rehabilitation. Compared with control patients, post-COVID-19 patients had higher age- and sex-adjusted odds of reporting worse physical health (adjusted odds ratio [aOR] = 1.8), pain (aOR = 2.3), and difficulty with physical activities (aOR = 1.6). Post-COVID-19 patients also had worse physical endurance, measured by the 6-minute walk test† (6MWT) (p

Introduction Oral pre-exposure prophylaxis (PrEP) is increasingly being implemented in sub-Saharan Africa. Adolescent girls and young women (AGYW) in Kenya contribute more than half of all new infections among young people aged 15–24 years, highlighting the need for evidence on the cost of PrEP in real-world implementation to inform the budget impact, cost-effectiveness, and financial sustainability of PrEP programs. Methods We estimated the cost of delivering PrEP to AGYW enrolled in a PrEP implementation study in two family planning clinics in Kisumu county, located in western Kenya. We derived total annual costs and the average cost per client-month of PrEP by input type (variable or fixed) and visit type (initiation or follow-up). We estimated all costs as implemented in the study, and under implementation by the Kenyan Ministry of Health (MoH), both at the program volume observed and if the facilities were delivering PrEP at full capacity (scaled-MoH). Results For the costing period between March 2018 and March 2019, 615 HIV-negative women contributed 1,128 (502 initiation and 626 follow-up) visits. The average cost per client-month of PrEP dispensed per study protocol and per the MoH scenario was $28.92 and $14.52, respectively. If the MoH scaled the program so that facilities could see PrEP clients at capacity, the average cost per client-month of PrEP was $10.88. Medication costs accounted for the largest proportion of the total annual costs (48% in MoH scenario and 65% in the scaled-MoH scenario). Conclusions Using data from a PrEP implementation program, we found that the cost per client-month of PrEP dispensed is reduced by 62% if PrEP delivery at the two clinics is scaled up by the MoH. Our findings are valuable for informing local resource allocation and budgetary cost projections for scale-up of PrEP delivery to AGYW. Additionally, previous cost-effectiveness studies have been limited by the use of fixed assumptions of the cost of PrEP per person-month. Our study provides cost estimates from practical data which will better inform cost-effectiveness and budget impact analyses.

HIV risk perception may influence the use of HIV prevention interventions. Using data from HIV-negative adults enrolled in a study of pre-exposure prophylaxis (PrEP) and antiretroviral therapy for HIV-serodiscordant couples in Kenya and Uganda, we examined associations between: (1) condom use and risk perception and (2) risk perception and PrEP adherence. Two-thirds of HIV-negative partners reported condomless sex with their HIV-positive partner or another partner in the month prior to study enrollment. Compared to those who reported no condomless sex, participants who reported condomless sex during the month prior to study visit had fivefold higher odds of reporting “high risk” vs “no risk” perception (36.3 versus 10.9%: aOR 4.9, 95% CI 3.4–6.9). Reporting condomless sex in the most recent sex act was associated with increased odds of perceiving some HIV risk (aOR for high risk = 7.3, 95% CI 4.9–10.8; aOR for moderate risk = 4.8, 95% CI 3.5–6.7; aOR for low risk = 3.5, 95% CI 2.7–4.6). We found no significant association between risk perception and PrEP adherence. Sexual behavior aligned with perceived HIV risk, which can facilitate an HIV-negative individual’s decisions about PrEP use.

Introduction HIV testing is a required part of delivery of pre‐exposure prophylaxis (PrEP) for HIV prevention. However, repeat testing can be challenging in busy, under‐staffed clinical settings, which could negatively impact PrEP uptake and continuation. We prospectively evaluated optional facility‐based HIV self‐testing (HIVST) among young women using PrEP in an implementation programme. Methods Between February and November 2019, we collected data from young women receiving PrEP at two family planning facilities in Kisumu, Kenya. At each PrEP follow‐up visit, women were given the option to choose between provider‐initiated testing and HIVST. We assessed factors associated with HIVST uptake and compared satisfaction with HIV testing and clinic experience between acceptors and decliners of HIVST. Results A total of 172 women were offered HIVST at 202 PrEP follow‐up visits. The median age was 21 years, 27% had multiple partners and 15% reported previously using HIVST. HIVST was accepted at 34.7% (70/202) of visits. Age (adjusted relative risk (aRR) 1.09 per year, 95% CI (confidence interval) 1.01 to 1.18), never being married (aRR 1.81, 95% CI 1.11 to 2.95) and having more PrEP follow‐up visits (aRR 1.13 per visit, 95% CI 1.04 to 1.23) were associated with HIVST uptake. Compared to HIVST decliners, HIVST acceptors were more likely to be very happy with their overall testing experience (73% vs. 47% of visits, p = 0.003) and were more likely to say they would use HIVST in the future (96% vs. 76%, p

Background Pre-exposure prophylaxis (PrEP) with emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) reduces the risk of HIV seroconversion but may promote bone mineral density (BMD) decline. The mechanisms of BMD decline with FTC/TDF remain unclear, and studies in HIV-positive individuals have been confounded by the effects of HIV and concomitant antiretroviral medications. We evaluated the impact of FTC/TDF on biomarkers of bone remodeling and bone mineral metabolism in HIV-negative men and women enrolled in the Partners PrEP Study. Methods In a random sample of HIV-negative participants randomized to FTC/TDF PrEP (n = 50) or placebo (n = 50), serum parathyroid hormone (PTH), bone biomarkers (C-telopeptide, procollagen 1 intact N-terminal propeptide, and sclerostin), and plasma fibroblast growth factor 23 were measured at baseline and month 24, and the percentage change was compared between groups. In a complementary analysis, we compared the change in biomarkers between participants with and without a 25% decline in glomerular filtration rate (GFR) on FTC/TDF. Results Baseline characteristics were similar between the groups (median age, 38 years; 40% women). Vitamin D insufficiency was common, but baseline GFR and PTH were in the normal range. We observed a significantly greater percent increase in serum C-telopeptide in participants randomized to FTC/TDF vs placebo (P = .03), suggesting an increase in bone remodeling. We observed no differences in the other biomarkers, or in a separate analysis comparing participants with and without a decline in GFR. Conclusions Increased bone remodeling may mediate the BMD decline observed with tenofovir-containing PrEP and antiretroviral therapy, independent of a TDF-mediated decrease in kidney function.

Background Few longitudinal studies have examined associations between risk factors during pregnancy and mental health outcomes during the postpartum period. We used a cohort study design to estimate the prevalence, incidence and correlates of significant postpartum depressive symptoms in Kenyan women. Methods We recruited adult women residing in an urban, resource-poor setting and attending maternal and child health clinics in two public hospitals in Nairobi, Kenya. A translated Kiswahili Edinburgh Postpartum Depression Scale was used to screen for depressive symptoms at baseline assessment in the 3rd trimester and follow up assessment at 6–10 weeks postpartum. Information was collected on potential demographic, psychosocial and clinical risk variables. Potential risk factors for postpartum depression were evaluated using multivariate logistic regression analysis. Results Out of the 171 women who were followed up at 6–10 weeks postpartum, 18.7% (95% CI: 13.3–25.5) were found to have postpartum depression using an EPDS cut off of 10. In multivariate analyses, the odds of having postpartum depression was increased more than seven-fold in the presence of conflict with partner (OR = 7.52, 95% CI: 2.65–23.13). The association between antepartum and postpartum depression was quite strong but did not reach statistical significance (OR = 3.37, 95% CI: 0.98–11.64). Conclusions The high prevalence of significant postnatal depressive symptoms among Kenyan women underscores the need for addressing this public health burden. Depression screening and psychosocial support interventions that address partner conflict resolution should be offered as part of maternal health care.

BACKGROUND Tenofovir disoproxil fumarate (TDF) causes kidney toxicity in some patients. We carried out genomewide analyses to identify associations with plasma tenofovir clearance and change in creatinine clearance (CrCl) during the first 6 months after initiating therapy among patients randomized to TDF/emtricitabine-containing regimens in AIDS Clinical Trials Group protocol A5202. METHODS Pharmacokinetic analyses involved 501 patients randomized to the tenofovir arm. CrCl analyses involved 1096 patients, including 548 controls randomized to abacavir-containing regimens. All had been randomized to also receive atazanavir/ritonavir or efavirenz. Multivariable linear regression and generalized least squares models were used to test for associations between polymorphisms and tenofovir clearance and CrCl change, with Bonferroni correction. Planned subanalyses considered candidate genes and polymorphisms. RESULTS Median CrCl at baseline was 116 ml/min (interquartile range 99.8-135.5). The median change in CrCl after 6 months was -0.5 ml/min (-10.7 to +10.8) and 2.2 (interquartile range -9.9 to +13.2) in tenofovir and abacavir arms, respectively. In genomewide analyses SLC17A1 rs12662869 was found to be associated with an increase in tenofovir clearance (P=7.1×10). In candidate gene analysis for tenofovir clearance, most polymorphisms evaluated were in ABCC4. In the ABCC4 region, the lowest P-value was for CLDN10 rs12866697 (P=1.4×10). Among African Americans, SLC22A2 rs3127573 was associated with a greater 6-month CrCl increase in the tenofovir arm after correcting for multiple comparisons (P=3.3×10). CONCLUSION Among patients randomized to receive TDF/emtricitabine in A5202, there were no significant genomewide associations with change in CrCl. This study did not replicate polymorphisms previously implicated in tenofovir-associated renal injury.

The Global Burden of Disease Study (GBD) is a landmark initiative that systematically quantifies the prevalence, morbidity, and mortality for hundreds of diseases, injuries, and risk factors of global health importance. For the neglected tropical diseases (NTDs), the GBD 2010 confirmed a high disease burden for the 17 major NTDs prioritized by the World Health Organization (WHO) as well as for selected conditions also recognized as NTDs by PLOS Neglected Tropical Diseases, including amoebiasis, cholera, cryptosporidiosis, typhoid and paratyphoid fevers, trichomoniasis, venomous animal contact, and scabies (referred to here as “additional NTDs”) [1]. The GBD 2013 is intended to be the first in a series of annual updates for the GBD studies, with its initial results published in 2015 in The Lancet [2–4]. Here, we review information on the NTDs published in the GBD 2013 capstone papers [2–4] and present new NTD data and updated burden estimates from the GBD 2013 study and new country-specific estimates. We show key outputs of GBD 2013 including country-specific estimates of prevalence or incidence and health-gap metrics for the aforementioned NTDs.

Summary Background High-quality epidemiological studies evaluating the burden of cutaneous leishmaniasis worldwide are lacking. We compared the burden of cutaneous leishmaniasis in each country to the overall global burden and assessed the equality of cutaneous leishmaniasis burden across different countries and regions. Methods Data were extracted from scientific literature, hospital sources, country reports, and WHO sources on the prevalence of sequalae of both acute and chronic cutaneous leishmaniasis. Prevalence data were combined with a disability weight to yield years lived with disability. Disability-adjusted life-years (DALYs) are a sum of the years lived with disability and years of life lost (or mortality, assumed to be zero). We compared DALYs due to cutaneous leishmaniasis for 152 countries using standard Z score analysis with Bonferroni correction (p Findings In 2013, the global mean age-standardised DALYs for cutaneous leishmaniasis was 0·58 per 100 000 people. Nine countries had significantly greater DALYs from cutaneous leishmaniasis than the mean: Afghanistan (87·0), Sudan (20·2), Syria (9·2), Yemen (6·2), Iraq (6·0), Burkina Faso (4·8), Bolivia (4·6), Haiti (4·1), and Peru (4·0). The Gini coefficient was 0·89. Andean Latin America, North Africa and Middle East, western sub-Saharan Africa, and south Asia had the highest DALYs from cutaneous leishmaniasis. Among males, Palestine had the highest incidence rates (616·2 cases per 100 000 people) followed by Afghanistan (566·4), Syria (357·1), and Nicaragua (354·8). Among females, Afghanistan had the highest incidence rates (623·9) followed by Syria (406·3), Palestine (222·1), and Nicaragua (180·8). Similar proportions of males and females had cutaneous leishmaniasis in most countries with a high incidence. Interpretation The burden from cutaneous leishmaniasis mainly falls on countries in Africa and the Middle East. Global and national data on the burden of cutaneous leishmaniasis disease are pivotal to promote field studies and initiate behavioural change. Funding Bill & Melinda Gates Foundation.

Background Griffithsin is a broad spectrum antiviral lectin that inhibits viral entry and maturation processes through binding clusters of oligomannose glycans on viral envelope glycoproteins. An efficient, scaleable manufacturing process for griffithsin active pharmaceutical ingredient (API) is essential for particularly cost-sensitive products such as griffithsin -based topical microbicides for HIV-1 prevention in resource poor settings. Our previously published purification method used ceramic filtration followed by two chromatography steps, resulting in a protein recovery of 30%. Our objective was to develop a scalable purification method for griffithsin expressed in Nicotiana benthamiana plants that would increase yield, reduce production costs, and simplify manufacturing techniques. Considering the future need to transfer griffithsin manufacturing technology to resource poor areas, we chose to focus modifying the purification process, paying particular attention to introducing simple, low-cost, and scalable procedures such as use of temperature, pH, ion concentration, and filtration to enhance product recovery. Results We achieved >99% pure griffithsin API by generating the initial green juice extract in pH 4 buffer, heating the extract to 55°C, incubating overnight with a bentonite MgCl2 mixture, and final purification with Capto™ multimodal chromatography. Griffithsin extracted with this protocol maintains activity comparable to griffithsin purified by the previously published method and we are able to recover a substantially higher yield: 88 ± 5% of griffithsin from the initial extract. The method was scaled to produce gram quantities of griffithsin with high yields, low endotoxin levels, and low purification costs maintained. Conclusions The methodology developed to purify griffithsin introduces and develops multiple tools for purification of recombinant proteins from plants at an industrial scale. These tools allow for robust cost-effective production and purification of griffithsin. The methodology can be readily scaled to the bench top or industry and process components can be used for purification of additional proteins based on biophysical characteristics.