Symptomatic Seroconversion Research Articles

Recent malaria does not substantially impact COVID-19 antibody response or rates of symptomatic illness in communities with high malaria and COVID-19 transmission in Mali, West Africa.

Malaria has been hypothesized as a factor that may have reduced the severity of the COVID-19 pandemic in sub-Saharan Africa. To evaluate the effect of recent malaria on COVID-19 we assessed a subgroup of individuals participating in a longitudinal cohort COVID-19 serosurvey that were also undergoing intensive malaria monitoring as part of antimalarial vaccine trials during the 2020 transmission season in Mali. These communities experienced a high incidence of primarily asymptomatic or mild COVID-19 during 2020 and 2021. In 1314 individuals, 711 were parasitemic during the 2020 malaria transmission season; 442 were symptomatic with clinical malaria and 269 had asymptomatic infection. Presence of parasitemia was not associated with new COVID-19 seroconversion (29.7% (211/711) vs. 30.0% (181/603), p=0.9038) or with rates of reported symptomatic seroconversion during the malaria transmission season. In the subsequent dry season, prior parasitemia was not associated with new COVID-19 seroconversion (30.2% (133/441) vs. 31.2% (108/346), p=0.7499), with symptomatic seroconversion, or with reversion from seropositive to seronegative (prior parasitemia: 36.2% (64/177) vs. no parasitemia: 30.1% (37/119), p=0.3842). After excluding participants with asymptomatic infection, clinical malaria was also not associated with COVID-19 serostatus or symptomatic seroconversion when compared to participants with no parasitemia during the monitoring period. In communities with intense seasonal malaria and a high incidence of asymptomatic or mild COVID-19, we did not demonstrate a relationship between recent malaria and subsequent response to COVID-19. Lifetime exposure, rather than recent infection, may be responsible for any effect of malaria on COVID-19 severity.

Cabotegravir, the Long-Acting Integrase Strand Transfer Inhibitor, Potently Inhibits Human T-Cell Lymphotropic Virus Type 1 Transmission in vitro.

Human T-cell lymphotropic virus type 1 (HTLV-1) is a deltaretrovirus most prevalent in southwestern Japan, sub-Saharan Africa, Australia, South America, and the Caribbean. Latest figures approximate 10 million people worldwide to be infected with HTLV-1. This is likely a significant underestimation due to lack of screening in endemic areas and absence of seroconversion symptoms. The two primary diseases associated with HTLV-1 infection are adult T cell leukaemia-lymphoma, a malignant and, sometimes, aggressive cancer; and HTLV-1 associated myelopathy/tropical spastic paraparesis, a debilitating neurological degenerative disease. Unfortunately, despite the poor prognosis, there is currently no effective treatment for HTLV-1 infection. We previously showed that integrase strand transfer inhibitors (INSTIs) clinically used for human immunodeficiency virus type 1 (HIV-1) prophylaxis and treatment are also effective against HTLV-1 transmission in vitro. In 2021 a new INSTI, cabotegravir, was approved by the FDA for HIV-1 treatment. We thus set out to evaluate its efficacy against HTLV-1 infection in vitro. Strand transfer assays performed using recombinant HTLV-1 integrase treated with increasing concentrations of cabotegravir, effectively inhibited strand transfer activity, displaying an IC50 of 77.8 ± 22.4 nM. Furthermore, cabotegravir blocked HTLV-1 transmission in tissue culture; we determined an EC50 of 0.56 ± 0.26 nM, similar to bictegravir. Alu-PCR confirmed the block in integration. Thus, there are four INSTIs and one reverse transcriptase inhibitor approved by the FDA for HIV-1 treatment, that potently block HTLV-1 infection in vitro. This should strongly encourage the establishment of a new standard of HTLV-1 treatment – particularly for pre-exposure prophylaxis and prevention of mother-to-child transmission.

High anti-SARS-CoV-2 antibody seroconversion rates before the second wave in Manaus, Brazil, and the protective effect of social behaviour measures: results from the prospective DETECTCoV-19 cohort

SummaryBackgroundThe city of Manaus, Brazil, has seen two collapses of the health system due to the COVID-19 pandemic. We report anti-SARS-CoV-2 nucleocapsid IgG antibody seroconversion rates and associated risk factors in Manaus residents before the second wave of the epidemic in Brazil.MethodsA convenience sample of adult (aged ≥18 years) residents of Manaus was recruited through online and university website advertising into the DETECTCoV-19 study cohort. The current analysis of seroconversion included a subgroup of DETECTCoV-19 participants who had at least two serum sample collections separated by at least 4 weeks between Aug 19 and Oct 2, 2020 (visit 1), and Oct 19 and Nov 27, 2020 (visit 2). Those who reported (or had no data on) having a COVID-19 diagnosis before visit 1, and who were positive for anti-SARS-CoV-2 nucleocapsid IgG antibodies at visit 1 were excluded. Using an in-house ELISA, the reactivity index (RI; calculated as the optical density ratio of the sample to the negative control) for serum anti-SARS-CoV-2 nucleocapsid IgG antibodies was measured at both visits. We calculated the incidence of seroconversion (defined as RI values ≤1·5 at visit 1 and ≥1·5 at visit 2, and a ratio >2 between the visit 2 and visit 1 RI values) during the study period, as well as incidence rate ratios (IRRs) through cluster-corrected and adjusted Poisson regression models to analyse associations between seroconversion and variables related to sociodemographic characteristics, health access, comorbidities, COVID-19 exposure, protective behaviours, and symptoms.Findings2496 DETECTCoV-19 cohort participants returned for a follow-up visit between Oct 19 and Nov 27, 2020, of whom 204 reported having COVID-19 before the first visit and 24 had no data regarding previous disease status. 559 participants were seropositive for anti-SARS-CoV-2 nucleocapsid IgG antibodies at baseline. Of the remaining 1709 participants who were seronegative at baseline, 71 did not meet the criteria for seroconversion and were excluded from the analyses. Among the remaining 1638 participants who were seronegative at baseline, 214 showed seroconversion at visit 2. The seroconversion incidence was 13·06% (95% CI 11·52–14·79) overall and 6·78% (5·61–8·10) for symptomatic seroconversion, over a median follow-up period of 57 days (IQR 54–61). 48·1% of seroconversion events were estimated to be asymptomatic. The sample had higher proportions of affluent and higher-educated people than those reported for the Manaus city population. In the fully adjusted and corrected model, risk factors for seroconversion before visit 2 were having a COVID-19 case in the household (IRR 1·49 [95% CI 1·21–1·83]), not wearing a mask during contact with a person with COVID-19 (1·25 [1·09–1·45]), relaxation of physical distancing (1·31 [1·05–1·64]), and having flu-like symptoms (1·79 [1·23–2·59]) or a COVID-19 diagnosis (3·57 [2·27–5·63]) between the first and second visits, whereas working remotely was associated with lower incidence (0·74 [0·56–0·97]).InterpretationAn intense infection transmission period preceded the second wave of COVID-19 in Manaus. Several modifiable behaviours increased the risk of seroconversion, including non-compliance with non-pharmaceutical interventions measures such as not wearing a mask during contact, relaxation of protective measures, and non-remote working. Increased testing in high-transmission areas is needed to provide timely information about ongoing transmission and aid appropriate implementation of transmission mitigation measures.FundingMinistry of Education, Brazil; Fundação de Amparo à Pesquisa do Estado do Amazonas; Pan American Health Organization (PAHO)/WHO.

Pre-Exposure Prophylaxis for HIV Infection and the Role of the Women's Health Care Provider in HIV Prevention.

HIV infection is a major public health problem for women in the United States. Prevention of new HIV infections is essential to the goal of eliminating HIV in the United States. Pre-exposure prophylaxis (PrEP) is an effective and safe HIV prevention method recommended for women at increased risk for HIV infection, including during pregnancy and lactation. The recommended PrEP regimen is a fixed-dose combination of tenofovir disoproxil fumarate and emtricitabine administered as a single daily dose. The initial evaluation for individuals desiring PrEP for HIV prevention includes obtaining a history, laboratory evaluation, and evaluation of the accessibility and acceptability of PrEP. Individuals using PrEP medications are seen every 3 months for follow-up. These follow-up visits include evaluation for signs and symptoms of seroconversion, management of side effects and adverse reactions, and evaluation of adherence to PrEP. Follow-up visits also include testing for HIV, sexually transmitted infections, and renal function and a review of HIV prevention and risk reduction methods. Despite known safety and efficacy of PrEP among women, PrEP use in women in the United States remains low. Gaps exist in HIV prevention that can in part be addressed by women's health care providers through risk screening and provision of HIV prevention methods. All providers of comprehensive sexual health care can and should assess individuals for risk factors for HIV infection and offer HIV prevention methods, including PrEP, to individuals at risk for HIV.

Rare Presentation of Pulmonary Embolism Associated with PCP in a 28-Year-Old Man who was not known to be infected with HIV Before

Introduction Human Immunodeficiency Viruses (HIV) commonly presented with acute seroconversion symptoms or opportunistic infections from immunosuppression, but first presentation of HIV with pulmonary embolism associated with active Pneumocystis pneumonia (PCP) is very rare. Case presentation A 28-year-old man presented with history of fever and cough associated with dyspnoea over 8 weeks and gradually worsen till maximised 2 week prior to admission. he did not improved inspite of antibiotics for suspected pneumonia. Found to be HIV positive with opportunistic infection. Computed Tomography Pulmonary Angiogram (CTPA) confirmed the presence of pulmonary embolism. He was treated successfully with anticoagulants, steroids, and antibiotics . discharged on base of clinical and radiological improvement. Conclusion Pulmonary embolism can be the first presentation of a newly diagnosed with HIV patient. The similar features of both viral pneumonia and subacute pulmonary embolism can lead to delay diagnosis, especially in the era of covid-19 pandemic infection

Short-Duration Pan-Genotypic Therapy With Glecaprevir/Pibrentasvir for 6 Weeks Among People With Recent Hepatitis C Viral Infection.

Among treatment-naive individuals with chronic hepatitis C viral (HCV) infection and without cirrhosis, glecaprevir/pibrentasvir for 8 weeks is recommended. The aim of this analysis was to evaluate the efficacy of glecaprevir/pibrentasvir for 6 weeks in people with acute and recent HCV infection. In this open-label, single-arm, multicenter, international pilot study, adults with recent HCV (duration of infection < 12 months) received glecaprevir/pibrentasvir 300/120 mg daily for 6 weeks. Primary infection was defined by first positive anti-HCV antibody and/or HCV RNA within 6 months of enrollment and either acute clinical hepatitis within the past 12 months (symptomatic seroconversion illness or alanine aminotransferase > 10×upper limit of normal) or anti-HCV antibody seroconversion within 18 months. Reinfection was defined as new positive HCV RNA within 6 months of enrollment and evidence of prior spontaneous or treatment-induced clearance. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12). Thirty men (median age 43 years, 90% men who have sex with men) received treatment, of whom 77% (n=23) were human immunodeficiency virus-positive, 47% (n=14) had ever injected drugs, and 13% (n=4) had HCV reinfection. The majority had HCV genotype 1 (83%, n=25), followed by genotype 4 (10%, n=3) and genotype 3 (7%, n=2). At baseline, median estimated duration of infection was 29 weeks (range 13, 52) and median HCV RNA was 6.2 log10 IU/mL (range 0.9, 7.7). SVR12 in the intention-to-treat and per-protocol populations was achieved in 90% (27/30) and 96% (27/28), respectively. There was one case of relapse, and there were two cases of nonvirological failure (death, n=1; loss to follow-up, n=1). No treatment-related serious adverse events were seen. Glecaprevir/pibrentasvir for 6 weeks was highly effective among people with acute and recent HCV infection, supporting further evaluation of shortened-duration pan-genotypic therapy in this setting.

P195 Diagnosing recent HIV infection in an urban sexual health centre: could more have be done to prevent acquisition?

Background/introduction There are a number of strategies that may be employed by sexual health services to prevent HIV transmission, including motivational interviewing and Pre-Exposure Prophylaxis (PrEP). In order to utilise resources effectively, prevention strategies need to target those at high risk of acquiring HIV such as those having unprotected anal sex or who had known rectal infections. Aim(s)/objectives We aimed to identify individuals in our cohort diagnosed with recently acquired HIV infection, review whether they had previously been accurately identified as high risk and what strategies had been employed to attempt reduce their risk. Methods Electronic records of patients diagnosed HIV positive at an urban sexual health centre over a two year period were reviewed for timing of acquiring infection and previous engagement with sexual health services. Recently acquired infections were determined by: positive avidity, a negative test or a history of seroconversion symptoms in the 6-months prior to positive result. Results 68 patients were diagnosed with HIV; 30 (44.1%) were recently acquired infections. Of these, 13 (43.3%) had attended a sexual health service in the year prior, 12 (92%) of whom had been identified as at risk and had risks discussed by a healthcare professional. Discussion/conclusion Almost half of our patients with recently acquired HIV had had contact with sexual health services in the year before their diagnosis, and the vast majority were identified at high risk. Being able to correctly identify patients at high risk of HIV has implications for using strategies such as PrEP in the future.

Failure of daily tenofovir to prevent HIV transmission or the establishment of a significant viral reservoir despite continued antiretroviral therapy.

IntroductionTruvada is licenced for HIV-1 prevention in the USA and is available in the private sector. Tenofovir performed as well as Truvada in the PARTNERS PrEP study and is used as HIV pre-exposure prophylaxis (PreP) in some settings. The clinical efficacy of Tenofovir for PrEP outside a clinical trial is unknown. Antiretroviral therapy (ART) at acute HIV-1 infection (AHI) limits the size of the reservoir, optimizing the chance of maintaining viral control off therapy. As such ART at acute HIV infection is proposed to offer a functional cure in a minority of subjects. We present two cases where Tenofovir PrEP failed to prevent HIV acquisition and failed to limit viral reservoir.Materials and MethodsTwo individuals receiving tenofovir monotherapy for Hepatitis B monoinfection were diagnosed with AHI as defined by a negative HIV antibody test within three months of a positive HIV test following unsafe sex with casual male partners. In-depth histories were taken. Viral genotypes and Tenofovir drug levels were measured from samples taken as close to HIV seroconversion as possible and subsequent samples were analyzed for proviral Total HIV-1 DNA by qPCR.ResultsPatient A had received tenofovir for the preceding six years and always maintained an undetectable Hepatitis B viral load with no concerns about adherence. Two weeks preceding the positive HIV antibody test, he experienced mild symptoms (fever, pharyngitis) of HIV seroconversion. HIV status was confirmed by a repeat fourth generation HIV antibody test and by Western Blot and an HIV viral load was undetectable. Tenofovir trough level at HIV diagnosis was within normal limits. The regimen was intensified to Eviplera and a total HIV-1 DNA was 1381 copies/million CD4 T cells. Patient B received four regimens for hepatitis B treatment before starting tenofovir monotherapy in 2011 and subsequently maintained an undetectable hepatitis B viral load. After three years of tenofovir monotherapy he developed a severe symptomatic seroconversion illness and tested HIV antibody positive. The baseline HIV viral load was 103,306 copies/mL. The regimen was intensified and total HIV-1 DNA was 2746 copies/million CD4 T cells.ConclusionsFurther investigation into the efficacy of tenofovir for PrEP outside a clinical trial is required. ART at AHI does not always lead to a low viral reservoir. To explore the possibility of replication incompetent virus, viral outgrowth assays are underway.

Missed opportunities for identifying primary HIV within genitourinary medical/HIV services

To assess the ability of three genitourinary medical centres to clinically identify primary HIV infection (PHI). Cases of recently acquired HIV infection, identified using the Health Protection Agency (HPA) avidity assay on all HIV diagnoses from January to August 2009, were investigated by case-note review. Sixty-four individuals were identified as PHI using the HPA avidity assay. Of 64 individuals, 31 (48%) were identified clinically. Imperial College identified 8/26 (31%), Guys and St Thomas' 15/27 (56%) and Brighton 8/11 (73%). Clinical suspicion of PHI was associated with reported unprotected anal intercourse (P = 0.017), seroconversion symptoms (P = 0.0004), a negative HIV test within six months (P = 0.024) and avidity assay result availability (P = 0.0169). Seventy percent of PHI cases missed had a documented risk factor. Thirty-five percent of those clinically identified with PHI were documented as informed of the associated enhanced infectivity. Suspicion of PHI was low despite documented risk factors and recent HIV-negative antibody tests. Counselling to prevent onward transmission was suboptimal.

P172 Transmitted drug resistant HIV presenting as severe encephalitis

BackgroundSelection of the K103N mutation is associated with a small but significant reduction in viral replicative fitness. Therefore it could be hypothesised that transmission of this strain could be associated...

Prevalence of seroconversion symptoms and relationship to set-point viral load

To describe symptoms, physical examination findings, and set-point viral load associated with acute HIV seroconversion in a heterosexual cohort of HIV-discordant couples in Zambia. We followed HIV serodiscordant couples in Lusaka, Zambia from 1995 to 2009 with HIV testing of negative partners and symptom inventories 3 monthly, and physical examinations annually. We compared prevalence of self-reported or treated symptoms (malaria syndrome, chronic diarrhea, asthenia, night sweats, and oral candidiasis) and annual physical examination findings (unilateral or bilateral neck, axillary, or inguinal adenopathy; and dermatosis) in seroconverting vs. HIV-negative or HIV-positive intervals, controlling for repeated observations, age, and sex. A composite score comprised of significant symptoms and physical examination findings predictive of seroconversion vs. HIV-negative intervals was constructed. We modeled the relationship between number of symptoms and physical examination findings at seroconversion and log set-point viral load using linear regression. Two thousand, three hundred and eighty-eight HIV-negative partners were followed for a median of 18 months; 429 seroconversions occurred. Neither symptoms nor physical examination findings were reported for most seroconverters. Seroconversion was significantly associated with malaria syndrome among nondiarrheic patients [adjusted odds ratio (aOR) = 4.0], night sweats (aOR = 1.4), and bilateral axillary (aOR = 1.6), inguinal (aOR = 2.2), and neck (aOR = 2.2) adenopathy relative to HIV-negative intervals. Median number of symptoms and findings was positively associated with set-point viral load (P < 0.001). Although most acute and early infections were asymptomatic, malaria syndrome was more common and more severe during seroconversion. When present, symptoms and physical examination findings were nonspecific and associated with higher set-point viremia.

Increased Rate of CD4+ T-Cell Decline and Faster Time to Antiretroviral Therapy in HIV-1 Subtype CRF01_AE Infected Seroconverters in Singapore

BackgroundIt remains controversial as to whether HIV-1 subtypes influence disease progression. Singapore offers a unique opportunity to address this issue due to the presence of co-circulating subtypes. We compared subtype CRF01_AE and non-CRF01_AE infected patients, with regards to estimated annual rate of CD4+ T-cell loss and time from estimated data of seroconversion (EDS) to antiretroviral therapy (ART).MethodsWe recruited ART-naive patients with known dates of seroconversion between October 2002 and December 2007 at the Singapore Communicable Disease Centre, the national reference treatment centre. Multilevel mixed-effects models were used to analyse the rate of CD4+ T-cell decline. Time from EDS to ART was analyzed with the Kaplan-Meier survival method and compared with Cox proportional hazards models.Results54 patients with previously assigned HIV-1 subtypes (24 CRF01_AE, 17 B, 8 B', 1 CRF33_01B, 3 CRF34_01B and 1 G) were observed for 89 patient-years. Subtype CRF01_AE and non-CRF01_AE infected patients did not differ in age, gender, risk factor, rate of symptomatic seroconversion, baseline CD4+ T-cell count, log10 viral load or haemoglobin concentration. The estimated annual rate of CD4+ T-cell loss was 58 cells/mm3/year (95% CI: 7 to 109; P = 0.027) greater in subtype CRF01_AE infected patients compared to non-CRF01_AE patients, after adjusting for age, baseline CD4+ T-cell count and baseline log10 viral load. The median time from EDS to ART was 1.8 years faster comparing CRF01_AE to non-CRF01_AE infected patient with a 2.5 times (95% CI: 1.2-5.0; P = 0.013) higher hazard for ART initiation, after controlling for age, baseline CD4+ T-cell count and baseline log10 viral load.ConclusionsInfecting subtype significantly impacted the rate of CD4+ T-cell loss and time to treatment in this cohort. Studies to understand the biological basis for this difference could further our understanding of HIV pathogenesis.

Towards targeted screening for acute HIV infections in British Columbia.

BackgroundOur objective was to describe the characteristics of acute and established HIV infections diagnosed in the Canadian province of British Columbia. Province-wide HIV testing and surveillance data were analyzed to inform recommendations for targeted use of screening algorithms to detect acute HIV infections.MethodsAcute HIV infection was defined as a confirmed reactive HIV p24 antigen test (or HIV nucleic acid test), a non-reactive or reactive HIV EIA screening test and a non-reactive or indeterminate Western Blot. Characteristics of unique individuals were identified from the British Columbia HIV/AIDS Surveillance System. Primary drug resistance and HIV subtypes were identified by analyzing HIV pol sequences from residual sera from newly infected individuals.ResultsFrom February 2006 to October 2008, 61 individuals met the acute HIV infection case definition, representing 6.2% of the 987 newly diagnosed HIV infections during the analysis period. Acute HIV infection cases were more likely to be men who have sex with men (crude OR 1.71; 95% CI 1.01-2.89], to have had a documented previous negative HIV test result (crude OR 2.89; 95% CI 1.52-5.51), and to have reported a reason for testing due to suspected seroconversion symptoms (crude OR 5.16; 95% CI 2.88-9.23). HIV subtypes and rates of transmitted drug resistance across all classes of drugs were similar in persons with both acute and established HIV infections.ConclusionsTargeted screening to detect acute HIV infection is a logical public health response to the HIV epidemic. Our findings suggest that acute HIV infection screening strategies, in our setting, are helpful for early diagnosis in men who have sex with men, in persons with seroconversion symptoms and in previously negative repeat testers.

CD4 decline in seroconverter and seroprevalent individuals in the precombination of antiretroviral therapy era

Studies based on seroconverters have increased our understanding of HIV disease. It is not clear, however, whether their disease progression differs from that of the general HIV population, given their reasons for presenting for testing. Using linear mixed models we compared CD4 decline rates for a seroconverter (CASCADE) and seroprevalent group (Concorde trial) with time origin being dates of seroconversion and randomization, respectively. Follow-up was censored at the earlier of last alive date and 1 January 1996. Analyses were adjusted for risk group, age and sex. To explore the role of symptomatic seroconversion we further categorized seroconverters into two groups: with and without an HIV test interval below 30 days as proxy. The 7226 seroconverter and 1746 seroprevalent eligible individuals were mainly men (78 and 85%, respectively) infected through sex between men (52 and 63%) with mean [95% confidence interval (CI)] baseline CD4 cell count of 610 (602, 619) and 492 (479, 505) cells/μl, respectively. There was no evidence that rate of CD4 decline differs between the two groups even after adjusting for potential confounders (P = 0.67). Estimated loss in the year after reaching an arbitrary threshold of 400 cells/μl was 67 (95% CI 65, 69) and 67 (64, 69) cells/μl in the seroconverter and seroprevalent group, respectively. Whereas seroconverters with test interval below 30 days (n = 310) experienced faster decline, there was no difference in rates between other seroconverters and seroprevalent individuals (P = 0.87). These data suggest that estimates of HIV progression derived from seroconverters are likely to hold more generally for the HIV-infected population.

P07-09. Contemporaneous transmission of genetically distinct HIV variants from a single donor to two recipients

Methods We studied two MSM with a history of HIV-1 infection by a third party on 21/7/04 and presenting with symptoms of seroconversion 35 and 42 days later. Samples of plasma from both recipients were taken at presentation and after 24 weeks. No samples were available from the donor. Viral sequences of gag (P24 aa 20–231), RT (aa 32–293) and env were obtained by cloning. To minimise artefactual diversity, env sequences were also amplified by single genome amplification (SGA) and compared with sequences from other acutely infected patients and longitudinal datasets to model the diversity within the donor.

Influence of Host Interleukin-10 Polymorphisms on Development of Traveler's Diarrhea Due to Heat-Labile Enterotoxin-ProducingEscherichia coliin Travelers from the United States Who Are Visiting Mexico

Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenic Escherichia coli (ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to genotype IL-10 SNPs. Stools from subjects who developed diarrhea were also studied for other enteropathogens. One hundred twenty-one of 569 (21.3%) travelers seroconverted to ETEC LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a genotype producing high levels of IL-10; it was seen in 83% of subjects with the GG genotype versus 54% of subjects with the AA genotype at IL-10 gene position -1082 (P, 0.02), in 71% of those with the CC genotype versus 33% of those with the TT genotype at position -819 (P, 0.005), and in 71% of those with the CC genotype versus 38% of those with the AA genotype at position -592 (P, 0.02). Travelers with the GCC haplotype were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% versus 38%; P, 0.002). Travelers genetically predisposed to produce high levels of IL-10 were more likely to experience symptomatic ETEC TD.

Serological testing algorithm shows rising HIV incidence in a UK cohort of men who have sex with men: 10 years application

To investigate whether combining clinical data with the serological testing algorithm for recent HIV seroconversion (STARHS) reliably identifies otherwise unrecognized recent infections and observe their trends. Incorporation of STARHS into routine HIV diagnosis. STARHS was applied to serum collected between 1996 and 2005 at HIV diagnosis and routine clinical/laboratory markers of recent infections were determined. The recent infections were identified by conventional means, by STARHS, and by both combined. Of 1526 infections diagnosed, 812 were new. Of these, 604 were in men who have sex with men (MSM); 208 in heterosexuals; 88% had serum available for STARHS, which identified 88 incident infections that would otherwise have been unrecognized (12% of all new infections, 34% of all recent infections). Of these, 88% reported recent high-risk sex; 47% reported seroconversion symptoms. STARHS confirmed recent infections in 71 of 74 (96%) known to be infected within 6 months by conventional methods. Combining both approaches, recent infections increased over time from 26% (1996) to 45% (2005) [P < 0.001]. STARHS results from 3% new diagnoses and 8% previous diagnoses were deemed false incident (associated with antiretroviral therapy, advanced disease or undetectable viral load). False incident results were only inexplicable in two individuals. Adjunctive use of STARHS with clinical data identified a high and increasing proportion of new HIV diagnoses as recent infections, confirming significant ongoing transmission. Since 2002, 50% of new diagnoses among MSM were recent infections. Identification of additional recent infections by STARHS enables effective intervention that may benefit the individual and reduce onward transmission.

Missed opportunities for diagnosing primary HIV infection

Objective:To investigate the extent to which primary HIV infection (PHI) presents to healthcare providers and the degree to which it is unrecognised.Methods:All individuals diagnosed with having recent HIV infection between...

The relationship between HIV seroconversion illness, HIV test interval and time to AIDS in a seroconverter cohort.

Seroconversion illness is known to be associated with more rapid HIV disease progression. However, symptoms are often subjective and prone to recall bias. We describe symptoms reported as seroconversion illness and examine the relationship between illness, HIV test interval (time between antibody-negative and anibody-positive test dates) and the effect of both on time to AIDS from seroconversion. We used a Cox model, adjusting for age, sex, exposure group and year of estimated seroconversion. Of 1820 individuals, information on seroconversion illness was available for 1244 of whom 423 (34%) reported symptomatic seroconversion. Persons with a short test interval (< or = 2 months) were significantly more likely to report an illness than people with a longer interval (OR 6.76, 95% CI 4.75-9.62). Time to AIDS was significantly faster (P = 0.01) in those with a short test interval. The HIV test interval is a useful replacement for information on seroconversion illness in studies of HIV disease progression.

Pre-exposure anti-Campylobacter jejuni immunoglobulin a levels associated with reduced risk of Campylobacter diarrhea in adults traveling to Thailand.

Diarrhea history questionnaires were administered to 369 U.S. military volunteers before and after deployment to Thailand. Additionally, blood samples obtained from a subset of 221 volunteers 1-3 weeks previously and 3-4 weeks after their deployment were tested by enzyme-linked immunosorbent assay for immunoglobulin A to Campylobacter jejuni. Stool samples from personnel (including volunteers) contracting diarrhea in Thailand were cultured for enteric pathogens. Overall, 35.2% (130 of 369) of questionnaire respondents reported one or more diarrhea episodes during their trip. Volunteers with pretravel anti-C. jejuni reciprocal titers < or = 450 were 1.6 times as likely to have had diarrhea during their stay in Thailand compared with those with pretravel titers > 450 (39.7% versus 25.3%; P = 0.05). The symptomatic seroconversion, or attributable Campylobacter diarrhea attack rate, for the 1-month exercise was 12.7% (28 of 221). The symptomatic seroconversion rate in nonimmune (titer < or = 450) volunteers was 17.1%, whereas that in immune volunteers was only 4.0% (P = 0.002). Campylobacter jejuni or C. coli were recovered from 32.9% (56 of 170) of stool samples cultured and were the most commonly identified enteropathogens. Campylobacter diarrhea was associated with elevated temperatures, fecal red cells, and fecal white blood cells. The results of this study show that Campylobacter continues to represent a significant health threat to Western travelers to Thailand, but many of these travelers have preexisting Campylobacter immunity that protects them from clinically significant Campylobacter enteritis.