HIV‐associated Kaposi's sarcoma (KS) is a public health challenge in sub‐Saharan Africa since both the causative agent, Kaposi's sarcoma associated‐herpesvirus (KSHV), and the major risk factor, HIV, ...are prevalent. In a nested case‐control study within a long‐standing clinical cohort in rural Uganda, we used stored sera to examine the evolution of antibody titres against the KSHV antigens K8.1 and latency‐associated nuclear antigen (LANA) among 30 HIV‐infected subjects who subsequently developed HIV‐related KS (cases) and among 108 matched HIV/KSHV coinfected controls who did not develop KS. Throughout the 6 years prior to diagnosis, antibody titres to K8.1 and LANA were significantly higher among cases than controls (p < 0.0001), and titres increased prior to diagnosis in the cases. K8.1 titres differed more between KS cases and controls, compared to LANA titres. These differences in titre between cases and controls suggest a role for lytic viral replication in the pathogenesis of HIV‐related KS in this setting.
What's New?
Infection with Kaposi sarcoma associated‐herpesvirus (KSHV) and HIV, the major risk factor for Kaposi sarcoma, is common in sub‐Saharan Africa. However, little is known about the evolution of KSHV antibody responses in HIV‐infected individuals prior to the clinical onset of KS. This study shows that antibody titres against KSHV antigens K8.1 and latency‐associated nuclear antigen (LANA) increase significantly in the six years leading up to HIV‐associated KS. Titres of K8.1, a lytic antigen, rose more than LANA titres, indicating that the activation of genes in the lytic cycle of viral replication is important in KS development.
•There is a need for a standardized Radiation Therapist (RTT) training and education curriculum in Africa.•An African Community of Practice (CoP) in developing Education Curriculum for RTT has been ...established.•This CoP can advocate the best practice in RTT profession specific education and training.
Supported by the International Atomic Energy Agency (IAEA), the African Regional Cooperative Agreement for Research, Development and Training (AFRA) invited African Member States (MS) with a radiation therapy facility to engage in a 3-day workshop to develop a robust road map for educational standards in radiation therapist (RTT) training. The aim of the paper was to make recommendations of how the African MS could drive forward high educational standards in RTT training and education in Africa.
A pre-workshop survey was developed and sent to the participants to gather background information on each MS’s national RTT training standards. An online survey was sent to all African MS with a radiation therapy facility. Two international RTT education-training experts were tasked by the IAEA to support and facilitate the workshop, which consisted of presentations and discussions around the current RTT training schemes in African MS and aspects of modern training methodology. The agenda of the workshop was structured with the aim to simulate discussions on RTT education and training standards among participants from African MS.
Sixteen African MS completed the pre-workshop survey. The median number of radiotherapy centres within a MS was 3 (range 1––15). All MS provided two-dimensional radiation therapy services as a minimum while 75 % (12/16) MS could offer three-dimensional conformal radiation therapy service. Thirty-eight percent (6/16) reported that they had no radiation therapy machine service maintenance contracts with vendors and 56 % (9/16) MS had no biomedical engineers on site for unplanned and planned machine maintenance. The median number of RTTs at national level among MS was 23 (range 7–73). Fifty-six percent (9/16) MS had a RTT specific national training programme with 75 % (12/16) MS having clinical attachments for 6 months or more. Representatives from 12 African MS attended the AFRA workshop. An African Community of Practice (CoP) in developing Education Curriculum for RTT was established as an outcome of the workshop with the aim to facilitate knowledge exchange and drive quality initiatives among participating African MS. Four work streams were proposed to form the CoP: RTT academic qualifications, core competencies in RTT education and training, RTT education faculty composition and peer review process in RTT education curricula among African MS.
By fostering collaboration, sharing knowledge, and advocating for improved policies, the African COP in developing Education Curriculum for RTT can make significant strides toward developing a RTT education curriculum that not only meets the unique challenges of the African continent but also aligns with global standards.
Objectives
The fungal metabolite aflatoxin is a common contaminant of foodstuffs, especially when stored in damp conditions. In humans, high levels can result in acute hepatic necrosis and death, ...while chronic exposure is carcinogenic. We conducted a pilot study nested within an existing population cohort (the General Population Cohort), to assess exposure to aflatoxin, among people living in rural south‐western Uganda.
Methods
Sera from 100 adults and 96 children under 3 years of age (85 male, 111 female) were tested for aflatoxin–albumin adduct (AF‐alb), using an ELISA assay. Socio‐demographic and dietary data were obtained for all participants; HIV serostatus was available for 90 adults and liver function tests (LFTs) for 99.
Results
Every adult and all but four children had detectable AF‐alb adduct, including five babies reported to be exclusively breastfed. Levels ranged from 0 to 237.7 pg/mg albumin and did not differ significantly between men and women, by age or by HIV serostatus; 25% had levels above 15.1 pg/mg albumin. There was evidence of heterogeneity between villages (P = 0.003); those closest to trading centres had higher levels. Adults who consumed more Matooke (bananas) had lower levels of AF‐alb adduct (P = 0.02) than adults who did not, possibly because their diet contained fewer aflatoxin‐contaminated foods such as posho (made from maize). Children who consumed soya, which is not grown locally, had levels of AF‐alb adduct that were almost twice as high as those who did not eat soya (P = 0.04).
Conclusions
Exposure to aflatoxin is ubiquitous among the rural Ugandans studied, with a significant number of people having relatively high levels. Sources of exposure need to be better understood to instigate practical and sustainable interventions.
Objectifs
Le métabolite fongique aflatoxine est un contaminant commun des denrées alimentaires, surtout lorsqu'elles sont stockées dans des conditions humides. Chez l'homme, des taux élevés peuvent entraîner une nécrose hépatique aiguë et la mort, tandis que l'exposition chronique est cancérigène. Nous avons mené une étude pilote imbriquée dans une cohorte existante de population (la Cohorte de la Population Générale), afin d’évaluer l'exposition à l'aflatoxine, chez les personnes vivant dans les régions rurales du sud‐ouest de l'Ouganda.
Méthodes
Les sérums de 100 adultes et 96 enfants de moins de trois ans (85 hommes, 111 femmes) ont été testés pour le composé aflatoxine‐albumine (AF‐alb), en utilisant un test ELISA. Les données sociodémographiques et alimentaires ont été obtenues pour tous les participants; le statut sérologique VIH était disponible pour 90 adultes et des tests de la fonction hépatique (LFT) pour 99 adultes.
Résultats
Tous les adultes et tous les enfants à l'exception de quatre avaient des composés AF‐alb détectables, y compris cinq bébés signalés comme étant nourris exclusivement au sein. Les taux allaient de 0 à 237,7 pg/mg d'albumine et ne différaient pas significativement entre les hommes et les femmes, l’âge ou la sérologie VIH; 25% avaient des taux étaient > 15,1 pg/mg d'albumine. Il existait une preuve d'hétérogénéité entre les villages (P = 0,003); les plus proches de centres commerciaux avaient des taux plus élevés. Les adultes qui consommaient plus de Matooke (bananes) avaient des taux inférieurs de composés AF‐alb (P = 0,02), peut‐être parce que leur régime alimentaire contient moins d'aliments contaminés par les aflatoxines tels que le posho (à base de maïs). Les enfants qui consommaient du soja non produit localement avaient des taux de composés AF‐alb presque deux fois plus élevés que ceux qui n'en mangeaient pas (P = 0,04).
Conclusions
L'exposition à l'aflatoxine est omniprésente chez les ougandais étudiés en milieu rural, avec un nombre important de personnes ayant des taux relativement élevés. Les sources d'exposition devraient être mieux comprises afin de dynamiser des interventions pratiques et durables.
Objetivos
La aflatoxina, metabolito fúngico, es un contaminante común de la comida, especialmente cuando esta se almacena bajo condiciones de humedad. En humanos, unos altos niveles pueden resultar en una necrosis hepática aguda y muerte, mientras que una exposición crónica es carcinogénica. Hemos realizado un estudio piloto dentro de una cohorte poblacional existente (la General Population Cohort), para evaluar la exposición a aflatoxina de personas viviendo en una zona rural del sudoeste de Uganda.
Métodos
Se realizó un ELISA para aductos de aflatoxina‐albumina (AF‐alb) a muestras de 100 adultos y 96 niños menores de tres años de edad (85 hombres, 111 mujeres). Se obtuvieron datos socio‐demográficos y de dieta de todos los participantes; el estatus de VIH estaba disponible para 90 adultos y las pruebas de función hepática (PFHs) para 99.
Resultados
Cada adulto y todos menos cuatro niños tenían un aducto AF‐alb detectable, incluyendo cinco bebes para los que se había reportados lactancia materna exclusiva. Los niveles estaban en un rango de 0–237.7 pg/mg albúmina y no diferían significativamente entre hombres y mujeres, por edad y seroestatus de VIH; un 25% tenía niveles por encima de 15.1 pg/mg albúmina. Había evidencia de heterogeneidad entre poblados (P = 0.003); aquellos más cercanos a los centros de comercio tenían niveles más altos. Los adultos que consumían más Matooke (bananas) tenían niveles más bajos de aducto AF‐alb (P = 0.02) que los adultos que no las consumían, probablemente porque su dieta contenía menos alimentos contaminados con aflatoxinas tales como el posho (hecho de maiz). Los niños que consumían soja, que no se cultiva localmente, tenían unos niveles de aducto AF‐alb que eran casi el doble de altas que aquellos que no comían soja (P = 0.04).
Conclusiones
La exposición a aflatoxina es ubicua entre los Ugandeses rurales que participaron en el estudio, con un número significativo de personas con unos niveles relativamente altos. Es necesario comprender mejor las fuentes de exposición con el fin de iniciar intervenciones prácticas y sostenibles.
Summary Background Cryptococcal disease remains an important cause of morbidity and mortality in HIV-infected individuals in sub-Saharan Africa, despite the introduction of antiretroviral therapy. We ...studied fluconazole as primary prophylaxis against cryptococcal disease in patients awaiting or starting antiretroviral therapy in Uganda. Methods In this prospective, double-blind randomised controlled trial, we enrolled HIV-positive adults with CD4 counts less than 200 cells per μL, cryptococcal antigen (CrAg)-negative, naive for antiretroviral therapy, and coming from five local AIDS organisations in Masaka district, Uganda. Enrolment took place between Sept 14, 2004, and Feb 1, 2008. Participants were randomly allocated to placebo or 200 mg fluconazole three times per week (1:1) in blocks of 40. Randomisation was done with ralloc procedure in Stata. Participants were reviewed after 4 weeks and referred for antiretroviral therapy, then seen every 8 weeks. Participants discontinued trial treatment when CD4 counts reached 200 cells per μL (median 197 days). Primary endpoints were invasive cryptococcal disease and all-cause mortality. Secondary endpoints were time to first episode and incidence of oesophageal candidosis, time to first episode and incidence of oropharyngeal or vaginal candidosis, and time to first hospital admission or death. The primary safety endpoint was cessation of trial drug because of transaminase concentrations higher than five times the upper limit of normal (ULN), or other major adverse events. Analyses were done by intention to treat and included all participants enrolled in the trial. Participants and researchers were masked to group assignment. This trial is registered with controlled-trials.com , number ISRCTN 76481529. Results Of 1519 individuals enrolled, 760 participants received fluconazole and 759 received placebo. 19 developed cryptococcal disease, one in the fluconazole group and 18 in the placebo group (p=0·0001); adjusted HR (aHR) 18·7 (95% CI 2·5–140·7). One case of cryptococcal disease could be prevented by treating 44·6 patients with baseline CD4 counts lower than 200 cells per μL. Fluconazole was effective against cryptococcal disease both before (aHR=11·0 1·4–85·3) and after start of antiretroviral therapy (no cases in fluconazole vs seven cases on placebo). Seven participants died from cryptococcal disease, none in the fluconazole group. All-cause mortality (n=189) did not differ between the two groups (p=0·46). Fluconazole reduced the time to first episode of oesophageal, and oropharyngeal and vaginal candidosis, as well as the incidence of all candidosis (p<0·0001), but had no effect on hospital admission or death. The frequency of elevated transaminases (>5×ULN) was similar between groups (aHR=0·94 0·65–1·35). Conclusions Fluconazole was safe and effective as primary prophylaxis against cryptococcal disease, both before and during early antiretroviral treatment. Cryptococcal infection was less common than anticipated because of the rapid commencement of antiretroviral therapy and exclusion of those with positive CrAg. In patients with negative CrAg on screening, fluconazole prophylaxis can prevent cryptococcal disease while waiting for and in the early weeks of antiretroviral therapy, particularly in those with CD4 counts of less than 100 cells per μL. Funding Medical Research Council, UK, and Rockefeller Foundation.
Individuals with HIV have a high prevalence of physical and psychological symptoms throughout their disease course. Despite the clinical and public health implications of unresolved pain and ...symptoms, little is known about the effect of anti-retroviral therapy (ART) on these outcomes. This study aimed to assess the impact on symptom burden for the year after ART initiation in individuals with a CD4 count <200 cells/uL in Uganda.
HIV-infected, ART-naıve adults referred from voluntary testing and counseling services in rural Uganda for enrollment into a randomized controlled trial to test fluconazole as primary prophylaxis against cryptococcal disease were invited to complete the Memorial Symptom Assessment Scale-Short Form (MSAS-SF) prior to commencing ART and at two subsequent follow up visits. This tool measures self-reported 7-day period prevalence and associated burden of physical and psychological symptoms. Changes in the total number of symptoms and distress indices with time on ART and trial arm were investigated through fitting Linear Mixed Models for repeated measures.
During the first year of ART initiation the prevalence of most individual symptoms remained constant. The notable exceptions which improved after commencing ART are as follow; prevalence of pain (prevalence changed from 79% to 60%), weight loss (67% to 31%), lack of appetite (46% to 28%), feeling sad (52% to 25%) and difficulty sleeping (35% to 23%). The total number of symptoms and distress indices reduced after treatment commenced. Of concern was that half or more study participants remained with symptoms of pain (60%), itching (57%), skin changes (53%) and numbness in hands and feet (52%) after starting ART. Sixteen symptoms remained with a burden of 25% or more.
Despite the beneficial effect of ART on reducing symptoms, some patients continue to experience a high symptom burden. It is essential that HIV services in sub-Saharan Africa integrate management of symptoms into their programmes.
CRYPTOPRO ISRCTN 76481529 , November 2004.
The epidemiology of anogenital cancers is under going substantial change. Cervical cancer remains a major public health concern, particular in resource-limited settings. Cancers of the anus, penis, ...vagina and vulva are relatively uncommon cancers, but may be increasing in incidence. The change in occurrence of anogenital cancers may be due to increasing HPV transmission secondary to changes in sexual behaviour. Screening programmes and the HPV vaccine offer optimism that anogenital cancers can be prevented. This article reviews the epidemiology of anogenital cancers with a focus on Scottish data.
Introduction:
Anemia is a common problem in HIV in sub-Saharan Africa. We describe the contribution of antiretroviral therapy (ART) regimen to the incidence of anemia and changes in hemoglobin (Hb) ...in HIV-infected patients in Uganda.
Methods:
This study was nested in a prevention of cryptococcal disease trial (CRYPTOPRO; ISCRTN7648152). Patients received 3 different backbones of nucleoside reverse transcriptase inhibitor in a nonrandomized manner.
Results:
Of the 852 patients (161 on zidovudine ZDV, 628 on stavudine d4T, and 63 on tenofovir TDF; all received lamuvidine), the risk of developing grade 4 anemia was higher (adjusted hazard ratio 2.7) for those receiving ZDV than those receiving d4T. Those receivingd4T had a higher average increase in Hb than those receiving ZDV (P = .024) or TDF (P = .014).
Conclusion:
In this observational study, ZDV was associated with severe anemia compared to d4T or TDF; those receiving ZDV and TDF had smaller increases in Hb after ART initiation. We encourage publication of data on cohorts using TDF from Africa.
Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool ...samples using standard methods) and antibodies against Kaposi's sarcoma herpesvirus (KSHV), measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda.
Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01), hookworm (67% vs 56% p = 0.001) and Mansonella perstans (69% vs 59% p = 0.05); seroprevalence increased with increasing intensity of hookworm infection (p < 0.001trend). No associations were found for HIV, five other parasites or active syphilis. These effects were not explained by socioeconomic status or education.
Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.
The UK has a 15% shortfall of clinical oncologists and, by 2027, this shortfall is predicted to increase to 25%.10 For both therapeutic radiographers and medical-physics positions, the shortfall is ...approaching 10%.10 In the UK, about 150 000 radiotherapy treatment courses are delivered each year.10 Throughout the UK, 61 National Health Service (NHS) providers deliver treatment via a multidisciplinary workforce of around 6400 whole-time-equivalent positions.10 Radiotherapy is personalised to each patient, extremely cost-effective (around £3000–4000 per treatment course),10 and technologically advanced. The NHS provides an excellent environment for development of national coordination, data collection, establishment of protocols for implementation of innovations, and value-based assessment of new technologies that could enhance patient outcomes and streamline workforce operations. Radiotherapy research has the potential to attract international collaborations and investments, positively influence economic development, and enhance recruitment and retention of staff.
High-risk human papilloma viruses (HPV) are a causative agent of anogenital and oropharyngeal cancers. Patients treated for a preinvasive or invasive HPV-associated cancer may be at increased risk of ...a second such malignancy.
We performed a systematic review and random effects meta-analysis to estimate the risk of HPV-associated cancer after prior diagnosis. Studies reporting second cancers at anogenital and oropharyngeal sites after prior diagnoses (preinvasive/invasive HPV-associated cancer) were identified. Studies reporting standardised incidence ratios (SIRs) were included in formal meta-analyses of second cancer risk. (PROSPERO ID: CRD42016046974).
Searches returned 5599 titles, including 60 unique, eligible studies. Thirty-two (98 comparisons) presented SIRs for second cervical, anal, vulvo-vaginal, penile, and/or oropharyngeal cancers, included in the meta-analyses. All studies (and 95/98 comparisons) reported increased cancers in the population with previous HPV-associated cancer when compared to controls. Pooled SIRs for second primary cancers ranged from 1.75 (95% CI 0.66-4.67) for cervical cancer after primary anal cancer, to 13.69 (95% CI 8.56-21.89) for anal cancer after primary vulvo-vaginal cancer.
We have quantified the increased risk of second HPV-associated cancer following diagnosis and treatment for initial cancer or preinvasive disease. This has important implications for follow-up, screening, and future therapeutic trials.
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