Epidemiology and interactions of Human Immunodeficiency Virus - 1 and Schistosoma mansoni in sub-Saharan Africa.

Human Immunodeficiency Virus-1/AIDS and Schistosoma mansoni are widespread in sub-Saharan Africa and co-infection occurs commonly. Since the early 1990s, it has been suggested that the two infections may interact and potentiate the effects of each other within co-infected human hosts. Indeed, S. mansoni infection has been suggested to be a risk factor for HIV transmission and progression in Africa. If so, it would follow that mass deworming could have beneficial effects on HIV-1 transmission dynamics. The epidemiology of HIV in African countries is changing, shifting from urban to rural areas where the prevalence of Schistosoma mansoni is high and public health services are deficient. On the other side, the consequent pathogenesis of HIV-1/S. mansoni co-infection remains unknown. Here we give an account of the epidemiology of HIV-1 and S. mansoni, discuss co-infection and possible biological causal relationships between the two infections, and the potential impact of praziquantel treatment on HIV-1 viral loads, CD4+ counts and CD4+/CD8+ ratio. Our review of the available literature indicates that there is evidence to support the hypothesis that S. mansoni infections can influence the replication of the HIV-1, cell-to-cell transmission, as well as increase HIV progression as measured by reduced CD4+ T lymphocytes counts. If so, then deworming of HIV positive individuals living in endemic areas may impact on HIV-1 viral loads and CD4+ T lymphocyte counts.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Scaled testing for COVID-19 needs community involvement.

With limited vaccine coverage and in the absence of specific therapeutics, the options to curb the COVID-19 pandemic today are mostly infection prevention measures and diagnostic tests to identify infected individuals rapidly, followed by isolation and contact tracing. The past months have seen significant worldwide scale-up of testing through quantitative PCR (qPCR) detecting nucleic acid of SARS-CoV-2. However, with the current resurgence of cases in Europe and elsewhere, qPCR demand far exceeds capacity. Moreover, qPCR is expensive, requires sophisticated laboratories, well-trained staff, and extensive logistics. Capacity deficits are aggravated in LMICs (Lower and Middle-Income Countries) with rampant shortages of tests kits, qualified staff, and laboratories, compromising clinical utility. Africa CDC reports 23 countries with proxy PCR coverage of <5000 tests/million population [1]. Alternative novel molecular diagnostics such as LAMP, DNAnudge and LAMPore remain widely unscalable. Moreover, even qPCR has its limitations in detecting non-infectious traces of viral RNA [2] and false negativity issues [3]. We conclude that molecular testing for COVID-19 is unfit for reaching scale at the community level

Determinants of CD4 counts among HIV-Negative ethiopians: Role of body mass index, gender, cigarette smoking, khat (Catha edulis) chewing, and possibly altitude?

To study the determinants of CD4% and CD4 counts among HIV-negative Ethiopians, and to identify factors susceptible to explain the low CD4 counts observed among Ethiopian subjects. Cohort studies among factory workers in Akaki and Wonji, Ethiopia. Clinical and laboratory examinations, including determination of HIV serological status and T-cell subsets, were performed during follow-up visits every six months. In addition, micronutrients (retinol, carotenoids, tocopherol, transferrin receptor, and selenium) plasma concentrations were determined in a subset of 38 HIV-positive and 121 HIV-negative participants. HIV-negative participants with at least one CD4 count measurement were 157 females in Akaki, 203 males in Akaki, and 712 males in Wonji. CD4 counts were independently and positively associated with body mass index (through an increase in lymphocyte counts), female gender (through an increase in CD4%), cigarette smoking (through an increase in CD4%), khat chewing (through an increase in both lymphocyte counts and CD4%), and Akaki study site (through a large increase in lymphocyte counts compensating a decrease in CD4%). Intestinal parasitic infections were not associated with CD4% or CD4 counts. Retinol, carotenoids, and -tocopherol plasma concentrations decreased with HIV infection and advancing immunosuppression, but were not associated with CD4 counts among HIV-negative subjects. Low body mass index among Ethiopians may have contributed to their overall low CD4 counts. Other factors remain to be elucidate

Anthelmintic resistance and homeostatic plasticity (Brugia malayi)

Homeostatic plasticity refers to the capacity of excitable cells to regulate their activity to make compensatory adjustments to long-lasting stimulation. It is found across the spectrum of vertebrate and invertebrate species and is driven by changes in cytosolic calcium; it has not been explored in parasitic nematodes when treated with therapeutic drugs. Here we have studied the adaptation of Brugia malayi to exposure to the anthelmintic, levamisole that activates muscle AChR ion-channels. We found three phases of the Brugia malayi motility responses as they adapted to levamisole: an initial spastic paralysis; a flaccid paralysis that follows; and finally, a recovery of motility with loss of sensitivity to levamisole at 4 h. Motility, calcium-imaging, patch-clamp and molecular experiments showed the muscle AChRs are dynamic with mechanisms that adjust their subtype composition and sensitivity to levamisole. This homeostatic plasticity allows the parasite to adapt resisting the anthelmintic.This article is published as Kashyap, Sudhanva S., Saurabh Verma, Mark McHugh, Mengisteab Wolday, Paul D. Williams, Alan P. Robertson, and Richard J. Martin. "Anthelmintic resistance and homeostatic plasticity (Brugia malayi)." Scientific reports 11, no. 1 (2021): 14499. doi: https://doi.org/10.1038/s41598-021-93911-4.The authors would like to thank the Filariasis Research Reagent Resource Centre (FR3; College of Veterinary Medicine, University of Georgia, USA) for the supply of live adult B. malayi. The research was funded by: The NIH NIAID Grants R01AI047194 and R01AI155413 to RJM and; The EA Benbrook Endowed Chair of Pathology and Parasitology. The funding agencies had no role in the design, execution or publication of this study

Bacteraemia among severely malnourished children infected and uninfected with the human immunodeficiency virus-1 in Kampala, Uganda

BACKGROUND: To establish the magnitude of bacteraemia in severely malnourished children, and describe the types of bacteria and antimicrobial sensitivity by HIV status. METHOD: Isolates were recovered from 76 blood specimens. Antibiotic susceptibility tests were performed using commercial antibiotic disks and demographic and clinical findings were recorded. RESULTS: Of the 450 children 63% were male; median age 17.0 months (inter quartile range, IQR 12–24) and 57% had oedema. 151 (36.7 %) of 411 tested HIV-positive; 76 (17.1%) of 445 blood specimens grew bacterial isolates; 58% were Gram negative – S. typhimurium (27.6%) and S. enteriditis (11.8%). Staph. aureus (26.3%) and Strep. pneumoniae (13.2%) were the main Gram positive organisms. There was no difference in the risk of bacteraemia by HIV status, age < 24 months, male sex, or oedema, except for oral thrush (OR 2.3 CI 1.0–5.1) and hypoalbuminaemia (OR 3.5 CI 1.0–12.1). Isolates from severely immuno-suppressed children (CD4% <15%) were more likely to grow Salmonella enteriditis (OR 5.4; CI 1.6 – 17.4). The isolates were susceptible (≥ 80%) to ciprofloxacin, ceftriaxone and gentamicin; with low susceptibility to chlorampenicol, ampicillin (< 50%) and co-trimoxazole (<25%). Suspicion of bacteraemia had 95.9% sensitivity and 99.2% specificity. Among bacteraemic children, mortality was higher (43.5% vs 20.5%) in the HIV-positive; OR 3.0 (95%CI 1.0, 8.6). CONCLUSION: Bacteraemia affects 1 in every 6 severely malnourished children and carries high mortality especially among the HIV-positive. Given the high level of resistance to common antibiotics, there is need for clinical trials to determine the best combinations of antibiotics for management of bacteraemia in severely malnourished children

Helminths and HIV infection: epidemiological observations on immunological hypotheses

Parasitic helminths have co-evolved with the mammalian immune system. Current hypotheses suggest that immunological stimulation in the presence of helminths is balanced by immuno-regulation and by the broad spectrum of mechanisms possessed by helminths for countering the host immune response. The degree to which this balance is perfected, and the mechanisms by which this is achieved, vary between helminth species; we suggest that this is reflected not only in the degree of pathology induced by helminths but also in a variety of relationships with HIV infection and HIV disease. Available epidemiological data regarding interactions between helminths and HIV are largely observational; results are variable and generally inconclusive. Well designed, controlled intervention studies are required to provide definitive information on the species-specific nature of these interactions and on the advantages, disadvantages and optimal timing of de-worming in relation to HIV infection

Treatment of Helminth Co-Infection in Individuals with HIV-1: A Systematic Review of the Literature

Many people living in areas of the world most affected by the HIV/AIDS pandemic are also exposed to other common infections. Parasitic infections with helminths (intestinal worms) are common in Africa and affect over half of the population in some areas. There are plausible biological reasons why treating helminth infections in people with HIV may slow down the progression of HIV to AIDS. Thus, treating people with HIV for helminths in areas with a high prevalence of both HIV and helminth infections may be a feasible strategy to help people with HIV delay progression of their disease or initiation of antiretroviral therapy. After a comprehensive review of the available literature, we conclude that there is not enough evidence to determine whether treating helminth infections in people with HIV is beneficial

HIV Incidence in Rural South Africa: Comparison of Estimates from Longitudinal Surveillance and Cross-Sectional cBED Assay Testing

The original publication is available at http:/www.plosone.orgBackground: The BED IgG-Capture Enzyme Immunoassay (cBED assay), a test of recent HIV infection, has been used to estimate HIV incidence in cross-sectional HIV surveys. However, there has been concern that the assay overestimates HIV incidence to an unknown extent because it falsely classifies some individuals with non-recent HIV infections as recently infected. We used data from a longitudinal HIV surveillance in rural South Africa to measure the fraction of people with nonrecent HIV infection who are falsely classified as recently HIV-infected by the cBED assay (the long-term false-positive ratio (FPR)) and compared cBED assay-based HIV incidence estimates to longitudinally measured HIV incidence. Methodology/Principal Findings: We measured the long-term FPR in individuals with two positive HIV tests (in the HIV surveillance, 2003-2006) more than 306 days apart (sample size n = 1,065). We implemented four different formulae to calculate HIV incidence using cBED assay testing (n = 11,755) and obtained confidence intervals (CIs) by directly calculating the central 95th percentile of incidence values. We observed 4,869 individuals over 7,685 person-years for longitudinal HIV incidence estimation. The long-term FPR was 0.0169 (95% CI 0.0100-0.0266). Using this FPR, the cross-sectional cBED-based HIV incidence estimates (per 100 people per year) varied between 3.03 (95% CI 2.44-3.63) and 3.19 (95% CI 2.57-3.82), depending on the incidence formula. Using a long-term FPR of 0.0560 based on previous studies, HIV incidence estimates varied between 0.65 (95% CI 0.00-1.32) and 0.71 (95% CI 0.00-1.43). The longitudinally measured HIV incidence was 3.09 per 100 people per year (95% CI 2.69-3.52), after adjustment to the sex-age distribution of the sample used in cBED assay-based estimation. Conclusions/Significance: In a rural community in South Africa with high HIV prevalence, the long-term FPR of the cBED assay is substantially lower than previous estimates. The cBED assay performs well in HIV incidence estimation if the locally measured long-term FPR is used, but significantly underestimates incidence when a FPR estimate based on previous studies in other settings is used. © 2008 Bärnighausen et al.Publishers' Versio

Correlates of HIV-1 Genital Shedding in Tanzanian Women

BACKGROUND: Understanding the correlates of HIV shedding is important to inform strategies to reduce HIV infectiousness. We examined correlates of genital HIV-1 RNA in women who were seropositive for both herpes simplex virus (HSV)-2 and HIV-1 and who were enrolled in a randomised controlled trial of HSV suppressive therapy (aciclovir 400 mg b.i.d vs. placebo) in Tanzania. METHODOLOGY: Samples, including a cervico-vaginal lavage, were collected and tested for genital HIV-1 and HSV and reproductive tract infections (RTIs) at randomisation and 6, 12 and 24 months follow-up. Data from all women at randomisation and women in the placebo arm during follow-up were analysed using generalised estimating equations to determine the correlates of cervico-vaginal HIV-1 RNA detection and load. PRINCIPAL FINDINGS: Cervico-vaginal HIV-1 RNA was detected at 52.0% of 971 visits among 482 women, and was independently associated with plasma viral load, presence of genital ulcers, pregnancy, bloody cervical or vaginal discharge, abnormal vaginal discharge, cervical ectopy, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, an intermediate bacterial vaginosis score and HSV DNA detection. Similar factors were associated with genital HIV-1 RNA load. CONCLUSIONS: RTIs were associated with increased presence and quantity of genital HIV-1 RNA in this population. These results highlight the importance of integrating effective RTI treatment into HIV care services