Acceptability and feasibility of recruiting women to collect a self-administered vaginal swab at a pharmacy clinic for sexually transmissible infection screening.

Willingness to self-collect vaginal swabs at a pharmacy clinic is of interest as a venue to increase sexually transmissible infections (STIs) screening for chlamydia, gonorrhoea and trichomonas. Women self-collected vaginal swabs at the pharmacy, completed questionnaires and received STI results within 2 h. Women with STIs were offered free treatment. A total of 313 of 777 (40.3%) women consented and prevalence for any STI was 3.9%. Questionnaires demonstrated acceptability for self-collection at the pharmacy, with 63% (95% CI 57.3-68) and 32.3% (95% CI 27.4-37.8) indicating they 'strongly agreed' or 'agreed' that they felt comfortable with pharmacy collection, respectively. Self-collected vaginal swabs for STI testing for women who were at a pharmacy were feasible and acceptable to women.

Performance of the South African triage score among HIV positive individuals presenting to an emergency department.

Introduction: Over a quarter of patients presenting to South African Emergency Centres (EC) have concurrent human immunodeficiency virus (HIV), yet it is unclear how this impacts their presenting complaints, the severity of illness, and overall resource needs in the EC. The primary objective of this study was to compare the performance of the South African Triage Score (SATS) in people living with HIV (PLWH) compared to HIV-negative patients. Secondary objectives included comparing the presentation characteristics and resource utilisation of these populations. Methods: A prospective cross-sectional observational study was conducted in the Livingstone Hospital EC, Gqeberha, South Africa, to compare triage designation and clinical outcomes in PLWH and HIV-negative patients. In this six-week study, all eligible patients received point-of-care HIV testing and extensive data abstraction, including SATS designation and EC clinical course. Descriptive statistical analysis was completed, and a log-binomial model was used to examine the association between HIV status and clinical outcomes using crude (unadjPR) and adjusted prevalence ratios (adjPR). Results: During the study period, 755 adult patients who consented to a POC HIV test were enrolled, of which 193 (25.6%) were HIV positive. HIV-positive patients were significantly more likely to be admitted compared to their HIV-negative counterparts when triaged as low acuity (adjPR 1.48, 95% CI 1.14-1.92, (p=0.003)). HIV-positive patients were also significantly more likely to receive laboratory testing when triaged as low acuity (adjPR 1.31, 95% CI 1.08-1.59 (p=0.006)) and as high acuity (adjPR 1.38, 95% CI 1.08-1.59 (p=0.034)) compared to HIV negative patients of the same triage categories. Conclusion: In our study, PLWH, compared to HIV-negative patients in the same category, were more likely to be admitted and require more EC resources, thus alluding to possible under triage of HIV-positive patients under the current SATS algorithm.

Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy.

Combination therapy for HIV-1 infection can reduce plasma virus to undetectable levels, indicating that prolonged treatment might eradicate the infection. However, HIV-1 can persist in a latent form in resting CD4+ T cells. We measured the decay rate of this latent reservoir in 34 treated adults whose plasma virus levels were undetectable. The mean half-life of the latent reservoir was very long (43.9 months). If the latent reservoir consists of only 1 x 10(5) cells, eradication could take as long as 60 years. Thus, latent infection of resting CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective anti-retroviral therapy.

Determining the prevalence of tuberculosis in emergency departments in the Eastern Cape region of South Africa and the utility of the World Health Organization tuberculosis screening tool.

BACKGROUND: South Africa (SA) faces a significant tuberculosis (TB) burden complicated by high rates of HIV-TB co-infection. In SA, emergency departments (EDs) play an important role in screening for TB. OBJECTIVES: To determine the prevalence of TB in the ED and the effectiveness of the World Health Organization (WHO) TB screening tool. METHODS: This was a cross-sectional observational study, conducted in the ED at Livingstone Hospital, Port Elizabeth, from 4 June to 15 July 2018. All patients aged >18 years and able to consent were administered the WHO TB screening questions and underwent a point-of-care HIV test and demographic data collection. Patients were followed up for 1 year and tracked in the National Health Laboratory Service database to determine TB status using laboratory testing. RESULTS: Over the study period, 790 patients were enrolled. Overall, 121 patients (15.3%) were TB-positive, with 46 (38.0%) diagnosed after presenting to the ED and 75 (62.0%) with a previous TB history determined by self-report or confirmed laboratory testing. A greater proportion of the TB-positive patients were HIV-positive (49.6%) compared with the TB-negative population (24.8%). TB-positive individuals were more likely to present to the ED with a chief complaint of shortness of breath (SoB) (18.2%) compared with the TB-negative population (10.5%). Overall, the WHO TB screening tool had poor sensitivity (46.5%) and specificity (62.5%) for identifying TB-positive patients in the ED. A multiple logistic regression analysis, controlled for age and sex, showed HIV status (odds ratio (OR) 2.81; p<0.001) and SoB (OR 2.19; p<0.05) to be significant predictors of TB positivity. Adding positive HIV status and a presenting complaint of SoB increased sensitivity to 78.3%. CONCLUSIONS: EDs in SA face a high burden of TB. While WHO screening guidelines identify some of these patients, including routine HIV testing in the ED could significantly affect the number of TB diagnoses made.

Comparative clonal analysis of human immunodeficiency virus type 1 (HIV-1)-specific CD4+ and CD8+ cytolytic T lymphocytes isolated from seronegative humans immunized with candidate HIV-1 vaccines.

The lysis of infected host cells by virus-specific cytolytic T lymphocytes (CTL) is an important factor in host resistance to viral infection. An optimal vaccine against human immunodeficiency virus type 1 (HIV-1) would elicit virus-specific CTL as well as neutralizing antibodies. The induction by a vaccine of HIV-1-specific CD8+ CTL in humans has not been previously reported. In this study, CTL responses were evaluated in HIV-1-seronegative human volunteers participating in a phase I acquired immune deficiency syndrome (AIDS) vaccine trial involving a novel vaccine regimen. Volunteers received an initial immunization with a live recombinant vaccinia virus vector carrying the HIV-1 env gene and a subsequent boost with purified env protein. An exceptionally strong env-specific CTL response was detected in one of two vaccine recipients, while modest but significant env-specific CTL activity was present in the second vaccinee. Cloning of the responding CTL gave both CD4+ and CD8+ env-specific CTL clones, permitting a detailed comparison of critical functional properties of these two types of CTL. In particular, the potential antiviral effects of these CTL were evaluated in an in vitro system involving HIV-1 infection of cultures of normal autologous CD4+ lymphoblasts. At extremely low effector-to-target ratios, vaccine-induced CD8+ CTL clones lysed productively infected cells present within these cultures. When tested for lytic activity against target cells expressing the HIV-1 env gene, CD8+ CTL were 3-10-fold more active on a per cell basis than CD4+ CTL. However, when tested against autologous CD4+ lymphoblasts acutely infected with HIV-1, CD4+ clones lysed a much higher fraction of the target cell population than did CD8+ CTL. CD4+ CTL were shown to recognize not only the infected cells within these acutely infected cultures but also noninfected CD4+ T cells that had passively taken up gp120 shed from infected cells and/or free virions. These results were confirmed in studies in which CD4+ lymphoblasts were exposed to recombinant gp120 and used as targets for gp120-specific CD4+ and CD8+ CTL clones. gp120-pulsed, noninfected targets were lysed in an antigen-specific fashion by CD4+ but not CD8+ CTL clones. Taken together, these observations demonstrate that in an in vitro HIV-1 infection, sufficient amounts of gp120 antigen are produced and shed by infected cells to enable uptake by cells that are not yet infected, resulting in the lysis of these noninfected cells by gp120-specific, CD4+ CTL.(ABSTRACT TRUNCATED AT 400 WORDS)

Impact of endemic HIV on emergency care service delivery in South Africa.

BACKGROUND: South Africa (SA) has the highest burden of HIV in the world. This study sought to evaluate the impact of high HIV prevalence on the burden of disease in an emergency department (ED). OBJECTIVES: To determine the burden of comorbidities in HIV-positive emergency care patients, their demographic profiles and severity of illness were compared with the general ED population in order to make recommendations for resource allocation and training in EDs in SA. METHODS: A prospective cross-sectional observational study was conducted from June 2017 to July 2018 in three EDs in Eastern Cape Province. All eligible patients (aged ≥18 years, fully conscious and clinically stable) presenting to the ED during the 6-week study period were approached and asked to give consent for a point-of-care HIV test and collection of demographic information. Simple descriptive statistics were used to analyse data. Log binomial and Poisson models were fitted to estimate prevalence ratios (PRs). RESULTS: Over the total study period, 8 000 patients presented to the ED for care across all sites and 3 537 patients were enrolled. The HIV status of 2 901 individuals (82.0%) was determined. Of those who were screened, 811 (28.0%) were identified as HIV-positive. Medical complaints were more common in HIV-positive patients (n=586, 72.3%) than in trauma patients (n=225, 27.7%). In comparison, HIV-negative patients reported fewer medical complaints (n=1 137, 54.4%) and more trauma (n=953, 45.6%) (p<0.001). HIV-positive patients were more likely to have a life-threatening emergency (n=192, 23.7%) (p=0.004), to be critically ill by triage score (p<0.001) and to be admitted to the hospital (p<0.001) than those who were HIV-negative. Despite high acuity overall, people living with HIV/AIDS were significantly less likely to be deemed critically ill according to vital signs (adjusted PR 0.94; p=0.046). CONCLUSIONS: While EDs in SA provide care to high volumes of patients with trauma-related injuries, in areas where HIV prevalence is highest, patients are more likely to present with acute medical emergencies. Providers of emergency care in SA need to be well versed in the management of HIV and associated complications.

Mycoplasma genitalium compared to chlamydia, gonorrhoea and trichomonas as an aetiological agent of urethritis in men attending STD clinics.

OBJECTIVES: To investigate prevalence of Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis in men, frequency of co-infections, and association of organisms with urethritis in men. METHODS: This was a cross-sectional study of 290 men (age range 19-34 years) attending Baltimore City STD clinics. M genitalium, C trachomatis, N gonorrhoeae and T vaginalis, during 2004 were detected using nucleic acid amplification tests (NAATs) (153 with urethritis and 137 without urethritis). Demographic characteristics and risk factors were ascertained. RESULTS: The overall prevalences of infection with C trachomatis, N gonorrhoeae, T vaginalis and M genitalium were 20.3%, 12.8%, 3.4% and 15.2%, respectively. Prevalences in men with urethritis were 32.7%, 24.2%, 5.2% and 22.2% for C trachomatis, N gonorrhoeae, T vaginalis and M genitalium, respectively. Percentages of co-infections were high. All men with N gonorrhoeae had urethritis. C trachomatis and M genitalium were found to be significantly associated with urethritis in univariate analysis and in multiple logistic regression analysis. CONCLUSION: The association of M genitalium with urethritis in this study provides confirmation of the importance of screening men for M genitalium as a cause of non-gonococcal urethritis and supports treatment considerations for urethritis for agents other than gonococci and chlamydia.

Evaluation of multiplex real-time PCR for detection of Haemophilus ducreyi, Treponema pallidum, herpes simplex virus type 1 and 2 in the diagnosis of genital ulcer disease in the Rakai District, Uganda.

OBJECTIVE: To develop a real-time PCR assay that reliably and accurately detects the predominant sexually transmitted aetiological agents of genital ulcer disease (GUD) (Haemophilus ducreyi, Treponema pallidum and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)) and to assess the use of real-time PCR diagnostic testing in a rural African field site. METHODS: Two multiplex real-time PCR reactions were used to detect H ducreyi/and HSV-1/HSV-2 in ulcer swabs from 100 people with symptomatic genital ulcers in rural Rakai, Uganda. Results were compared with syphilis, HSV-1 and HSV-2 serology. RESULTS: Of 100 GUD samples analysed from 43 HIV positive and 57 HIV negative individuals, 71% were positive for one or more sexually transmitted infection (STI) pathogens by real-time PCR (61% for HSV-2, 5% for T pallidum, 3% for HSV-1, 1% for H ducreyi and 1% for dual H ducreyi/HSV-2). The frequency of HSV in genital ulcers was 56% (32/57) in HIV negative individuals and 77% (33/43) in HIV positive individuals (p = 0.037). Assay reproducibility was evaluated by repeat PCR testing in the USA with 96% agreement (kappa = 0.85). CONCLUSIONS: STI pathogens were detected in the majority of GUD swab samples from symptomatic patients in Rakai, Uganda, by real-time PCR. HSV-2 was the predominant cause of genital ulcers. Real-time PCR technology can provide sensitive, rapid and reproducible evaluation of GUD aetiology in a resource-limited setting.

AIDS in Africa: an epidemiologic paradigm.

Cases of the acquired immune deficiency syndrome (AIDS) have been reported in countries throughout the world. Initial surveillance studies in Central Africa suggest an annual incidence of AIDS of 550 to 1000 cases per million adults. The male to female ratio of cases is 1:1, with age- and sex-specific rates greater in females less than 30 years of age and greater in males over age 40. Clinically, AIDS in Africans is often characterized by a diarrhea-wasting syndrome, opportunistic infections, such as tuberculosis, cryptococcosis, and cryptosporidiosis, or disseminated Kaposi's sarcoma. From 1 to 18% of healthy blood donors and pregnant women and as many as 27 to 88% of female prostitutes have antibodies to human immunodeficiency virus (HIV). The present annual incidence of infection is approximately 0.75% among the general population of Central and East Africa. The disease is transmitted predominantly by heterosexual activity, parenteral exposure to blood transfusions and unsterilized needles, and perinatally from infected mothers to their newborns, and will continue to spread rapidly where economic and cultural factors favor these modes of transmission. Prevention and control of HIV infection through educational programs and blood bank screening should be an immediate public health priority for all African countries.

Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy.

The hypothesis that quiescent CD4+ T lymphocytes carrying proviral DNA provide a reservoir for human immunodeficiency virus-type 1 (HIV-1) in patients on highly active antiretroviral therapy (HAART) was examined. In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus was routinely recovered from resting CD4+ T lymphocytes. The frequency of resting CD4+ T cells harboring latent HIV-1 was low, 0.2 to 16.4 per 10(6) cells, and, in cross-sectional analysis, did not decrease with increasing time on therapy. The recovered viruses generally did not show mutations associated with resistance to the relevant antiretroviral drugs. This reservoir of nonevolving latent virus in resting CD4+ T cells should be considered in deciding whether to terminate treatment in patients who respond to HAART.

Aetiology of genital ulcer disease in female partners of male participants in a circumcision trial in Uganda.

HIV acquisition is associated with herpes simplex virus type 2 (HSV-2) infection and genital ulcer disease (GUD). Three randomized control trials demonstrated that male circumcision significantly decreases HIV, HSV-2, human papillomavirus and self-reported GUD among men. GUD is also decreased among female partners of circumcised men, but it is unknown whether male circumcision status affects GUD pathogens in female partners. For the evaluation of GUD aetiology, two separate multiplex assays were performed to detect Haemophilus ducreyi, Treponema pallidum, HSV-1 and HSV-2. Of all the female GUD swabs evaluated, 67.5% had an aetiology identified, and HSV-2 was the primary pathogen detected (96.3%). However, there was no difference in the proportion of ulcers due to HSV-2 or other pathogens between female partners of circumcised men (11/15, 73.3%) compared with uncircumcised men (15/25, 60.0%, P = 0.39). The seroprevalence of HSV-2 is high in this population and therefore most of the detected HSV-2 infections represent reactivation. Since GUD is associated with HIV acquisition and one-third of GUD in this study did not have an aetiological agent identified, further research is needed to better understand the aetiology of GUD in Africa, and its relationship to circumcision and HIV infection.

Herpes simplex virus type 2 infection among commercial sex workers in Kunming, Yunnan Province, China.

A cross-sectional survey was conducted to determine the sociodemographic correlates of herpes simplex virus type 2 (HSV-2) infection among male and female commercial sex workers in Kunming, Yunnan Province of China. HSV-2 prevalence was 33.0%, human immunodeficiency virus (HIV) infection was 2.4% and hepatitis C virus (HCV) infection was 6.8%. Subjects who were positive for HSV-2 had a significantly higher prevalence of HIV infection (5.5% versus 0.9%, P = 0.002; odds ratio [OR]: 6.4, P = 0.006) and HCV infection (18.7% versus 2.4%, P < 0.001; OR: 7.6, P < 0.001) compared with HSV-2-negative individuals. Risk factors that increased the odds of HSV-2 infection were HIV infection, HCV infection, being female, and having a steady sex partner within the last six months (P < or = 0.01). In a multivariate analysis, being female (OR: 6.6, P < 0.001), having HCV infection (OR: 5.9, P < 0.001) and having a sex partner within the last six months (OR: 2.2, P < 0.05) showed greater odds of being infected with HSV-2. A strong relationship was found between HSV-2, HIV and HCV infections.

Intravascular clearance of parasitized erythrocytes in rodent malaria.

Little is known about host defense mechanisms responsible for protective immunity in malaria. The intravascular location of the infection suggested that removal of parasitized erythrocytes by reticuloendothelial organs might be important. To study this possibility, we examined the clearance of (51)Crlabeled Plasmodium berghei-infected erythrocytes in rats. Infected erythrocytes were removed more rapidly from circulation than homologous uninfected erythrocytes. The rate of clearance of infected cells during the 1st hour after inoculation was approximately three times greater in rats rendered immune by prior infection than in control rats. This accelerated clearance resulted from greater splenic uptake in immune rats and appeared to correlate with spleen size. Since the clearance pattern of infected erythrocytes more closely resembled the clearance of Heinz body-containing uninfected erythrocytes than of antibody-coated (immunoglobulin G) uninfected erythrocytes, rheologic alterations of parasitized erythrocytes might be a more important determinant of clearance than an antibody-dependent process. During the phase of malaria infection in which increasing parasitemia is observed, organ uptake of infected erythrocytes did not increase despite splenic and hepatic enlargement. However during the spontaneous onset of resolution of malaria infection characterized by decreasing parasitemia, a marked enhancement of splenic clearance was noted. These observations suggest that sudden alteration in splenic clearance of parasitized erythrocytes might be important in the resolution of acute malaria.

Relationship of alterations in splenic clearance function and microcirculation to host defense in acute rodent malaria.

During the course of Plasmodium berghei malaria in the rat, splenic clearance of damaged uninfected erythrocytes (heated or Heinz body-containing) underwent changes strikingly similar to those of infected erythrocytes. Splenic trapping of abnormal erythrocytes was impaired during the period of rising parasitemia but became supernormal just before the onset of resolution of the acute infection. These changes could be related to the development of splenomegaly and alterations in splenic cordal microcirculation during infection. The relative distribution of flow through the cords was decreased during rising parasitemia and was restored before the onset of resolution. Together, our observations support the hypothesis that altered rheologic properties of infected erythrocytes are a major determinant of their removal by the spleen. These data suggest that the alterations in splenic microcirculation that occur during malaria may have important implications for host defense.

Demonstration of defective C3-receptor-mediated clearance by the reticuloendothelial system in patients with acquired immunodeficiency syndrome.

The function of macrophage C3 receptors was assessed in vivo by measuring the clearance of C3-sensitized autologous erythrocytes in seven acquired immunodeficiency syndrome (AIDS) patients, eight healthy homosexual men, eight healthy heterosexual men, and four infected controls. Healthy heterosexual men had an initial clearance of 50.1 +/- 2.0% of the inoculum, with a release of a small portion of these cells (10.9 +/- 1.3%) into the circulation. Healthy homosexual men had a greater initial clearance of 66.0 +/- 4.2% (P less than 0.01) followed by a similar release (14.0 +/- 3.3%). AIDS patients had an initial clearance of 60.6 +/- 7.5% but had a relatively large release of cells (25.6 +/- 3.2%) (P less than 0.005 vs. heterosexuals; P less than 0.05 vs. homosexuals), suggesting a failure of macrophage phagocytosis. Infected controls had an initial clearance of 59.4 +/- 4.9%, with a release of 19.6 +/- 3.8% (P = NS vs. AIDS). These data, in addition to Fc-receptor dysfunction, demonstrate a global reticuloendothelial system dysfunction in AIDS patients. This may contribute to their frequent infections with opportunistic pathogens and inappropriate immune responses against these microorganisms.

Studies on phagocytosis in patients with acute bacterial infections.

Polymorphonuclear leukocytes (PMN) and monocytes from 20 patients with acute bacterial infections were examined for phagocytic function. PMN of patients expressed markedly enhanced phagocytosis as measured by the ingestion of erythrocyte (E)IgG and IgG/C3b-coated E. Phagocytosis of E coated with C3b alone was not seen, while low levels of ingestion of iC3b-E by patients' PMNs was noted. Monocytes from patients and controls expressed similar phagocytic activity in a fixed endpoint assay; however, the kinetics of phagocytosis by patients' monocytes was strikingly faster. Superoxide anion (O2.) and myeloperoxidase activities were similar to controls in PMN of four patients studied on day 1 of admission. PMN from two of three patients studied longitudinally showed an initial elevation in EIgG phagocytosis, which fell to normal levels by day 4, concomitantly with increased O2. generation and clinical improvement. Phagocytosis remained elevated in the third patient who did not clear his septicemia. Surface membrane FcRII, FcRIII, CR1, and CR3 were similar on patient and control PMN. In contrast, FcRI was increased on PMN of five of seven patients by monomeric IgG binding, and on two of two patients by monoclonal anti-FcRI binding. Thus, PMN and monocytes of patients with acute bacterial infections are either upregulated with regard to phagocytic function or are less susceptible to downregulation than are normal cells. This presumably would have a beneficial effect on host defenses during infection.

African trypanosomiasis in an American hunter in East Africa.

An American citizen acquired African trypanosomiasis while on a hunting safari in Sudan, East Africa. His travel history and rapid onset of symptoms, including fever, chills, headache, lethargy, and weight loss, were suggestive of Trypanosoma brucei rhodesiense infection, and trypanosomes were demonstrated in routine blood smears and buffy-coat preparations. Despite the presence of headaches, nuchal rigidity, and CSF pleocytosis, he was treated for non-CNS African trypanosomiasis, based on a normal CSF IgM level. This case report, along with a review of previously reported cases of imported African trypanosomiasis, illustrates the importance of clinical consideration of this rare, but often misdiagnosed, tropical illness in febrile patients returning from Africa.