Community based distribution of oral HIV self-testing kits in Zambia: a cluster-randomised trial nested in four HPTN 071 (PopART) intervention communities.

BACKGROUND: The HPTN 071 (PopART) cluster-randomised trial provided door-to-door HIV testing services to a large proportion of individuals residing in 21 intervention communities in Zambia and South Africa from 2014 to 2017 and reached the UNAIDS first 90 target among women in Zambia, yet gaps remained among men and young adults. This cluster-randomised study nested in the HPTN 071 (PopART) trial sought to increase knowledge of HIV status across all groups by offering the choice of oral HIV self-testing in addition to routine door-to-door HIV testing services. METHODS: We nested this cluster-randomised trial in four HTPN 071 (PopART) intervention communities in northern Zambia. 66 zones (clusters) in these communities were randomly allocated (1:1) to either oral HIV self-testing plus routine door-to-door HIV testing services (HIV self-testing group) or the PopART standard of care of door-to-door HIV testing services alone (non- HIV self-testing group) over a 3-month period. All individuals aged 16 years or older were eligible for HIV testing. Randomisation was achieved by randomly selecting one allocation from a list of 10 000 possible allocations during a public ceremony. In HIV self-testing zones, trained lay-counsellors (known as community HIV care providers) visited households and offered eligible individuals the choice of HIV testing using HIV self-testing or routine door-to-door HIV testing services. For individuals aged 18 years or older whose partner was absent during the household visit, an HIV self-test kit could be left for secondary distribution to the absent partner. The primary outcome was knowledge of HIV status (defined as self-reporting HIV positive to the community HIV care providers or accepting an offer of HIV testing services). Outcomes were measured among households that were first visited, and individuals first enumerated as a household member during the HIV self-testing intervention period. We analysed data at the individual level using population-average logistic regression models, accounting for clustering of outcomes by zone, to estimate the effect of the intervention. This trial is registered with ClinicalTrials.gov, number NCT02994329. FINDINGS: Between Feb 1, and April 30, 2017, the community HIV care providers enumerated 13 267 eligible individuals in the HIV self-testing group and 13 706 in the non-HIV self-testing group. After intervention implementation, 9027 (68%) of 13 267 in the HIV self-testing group had knowledge of HIV status compared with 8952 (65%) of 13 706 in the non-HIV self-testing group (adjusted odds ratio 1·30, 95% CI 1·03-1·65; p=0·03). The effect differed by sex (pinteraction=0·01). Among men, knowledge of HIV status was higher in the HIV self-testing group than in the non-HIV self-testing group (3843 [60%] of 6368 vs 3571 [55%] of 6486; adjusted odds ratio 1·31, 95% CI 1·07-1·60; p=0·01). There was no evidence of a between-group difference among female participants. INTERPRETATION: Providing a choice of HIV self-testing during delivery of door-to-door HIV testing services increased knowledge of HIV status, driven by an effect among men. Lay counsellors have a vital role to play in adapting HIV self-testing interventions to local context. FUNDING: The International Initiative for Impact Evaluation (3ie), the Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, National Institute of Mental Health, and the President's Emergency Plan for AIDS Relief

Pathophysiological Mechanisms of Severe Anaemia in Malawian Children

BACKGROUND: Severe anaemia is a major cause of morbidity and mortality in African children. The aetiology is multi-factorial, but interventions have often targeted only one or a few causal factors, with limited success. METHODS AND FINDINGS: We assessed the contribution of different pathophysiological mechanisms (red cell production failure [RCPF], haemolysis and blood loss) to severe anaemia in Malawian children in whom etiological factors have been described previously. More complex associations between etiological factors and the mechanisms were explored using structural equation modelling. In 235 children with severe anaemia (haemoglobin<3.2 mMol/L [5.0 g/dl]) studied, RCPF, haemolysis and blood loss were found in 48.1%, 21.7% and 6.9%, respectively. The RCPF figure increased to 86% when a less stringent definition of RCPF was applied. RCPF was the most common mechanism in each of the major etiological subgroups (39.7-59.7%). Multiple aetiologies were common in children with severe anaemia. In the final model, nutritional and infectious factors, including malaria, were directly or indirectly associated with RCPF, but not with haemolysis. CONCLUSION: RCPF was the most common pathway leading to severe anaemia, from a variety of etiological factors, often found in combination. Unlike haemolysis or blood loss, RCPF is a defect that is likely to persist to a significant degree unless all of its contributing aetiologies are corrected. This provides a further explanation for the limited success of the single factor interventions that have commonly been applied to the prevention or treatment of severe anaemia. Our findings underline the need for a package of measures directed against all of the local aetiologies of this often fatal paediatric syndrome

Association between cervical dysplasia and female genital schistosomiasis diagnosed by genital PCR in Zambian women.

BACKGROUND: Female genital schistosomiasis (FGS) is a neglected tropical gynaecological disease that affects millions of women in sub-Saharan Africa (SSA). FGS is caused by Schistosoma haematobium, a parasitic carcinogen involved in the pathogenesis of squamous cell carcinoma of the bladder. Cervical cancer incidence and mortality are highest in SSA, where pre-cancerous cervical dysplasia is often detected on screening with visual inspection with acetic acid (VIA). There are no studies evaluating the association between VIA positivity and FGS diagnosed by genital PCR. METHODS: Women were recruited from the Bilharzia and HIV (BILHIV) study in Zambia a community-based study comparing genital self-sampling to provider obtained cervicovaginal-lavage for the diagnosis of FGS in women aged 18-31. FGS was defined as positive Schistosoma DNA from any genital PCR. Urogenital schistosomiasis diagnostics included urine circulating anodic antigen, urine microscopy and portable colposcopy. Participants were offered cervical cancer screening using VIA at Livingstone Central Hospital. Associations of PCR confirmed FGS and other diagnostics with VIA positivity were assessed using multivariable logistic regression. RESULTS: VIA results were available from 237 BILHIV participants. A positive Schistosoma PCR in any genital specimen was detected in 14 women (5.9%), 28.6% (4/14) of these women had positive VIA compared to 9.0% without PCR evidence of schistosome infection (20/223). Schistosoma PCR positivity in any genital specimen was strongly associated with VIA positivity (OR: 6.08, 95% CI: 1.58-23.37, P = 0.02). CONCLUSIONS: This is the first study to find an association between FGS and positive VIA, a relationship that may be causal. Further longitudinal studies are needed

The Early Youth Engagement in first episode psychosis (EYE-2) study: pragmatic cluster randomised controlled trial of implementation, effectiveness and cost-effectiveness of a team-based motivational engagement intervention to improve engagement

Background: Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium–long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and the NHS. This study will evaluate the effectiveness, cost-effectiveness and implementation of a team-based motivational Early Youth Engagement (EYE-2) intervention. Method: The study design is a cluster randomised controlled trial (RCT) with economic evaluation, comparing the EYE-2 intervention + standardised EIP service to standardised EIP service alone, with randomisation at the team level. A process evaluation will evaluate the delivery of the intervention qualitatively and quantitatively across contexts. The setting is 20 EIP teams in 5 sites: Manchester, South London, East Anglia, Thames Valley and Hampshire. Participants are young people (14–35 years) with first episode psychosis, and EIP staff. The intervention is the team-based motivational engagement (EYE-2) intervention, delivered alongside standardised EIP services, and supported by additional training, website, booklets and social groups. The comparator is the standardised EIP service. Both interventions are delivered by EIP clinicians. The primary outcome is time to disengagement (time in days from date of allocation to care coordinator to date of last contact following refusal to engage with EIP service, or lack of response to EIP contact for a consecutive 3-month period). Secondary outcomes include mental and physical health, deaths, social and occupational function, recovery, satisfaction and service use at 6, 12, 18 and 24 months. A 12-month within-trial economic evaluation will investigate cost-effectiveness from a societal perspective and from an NHS perspective. Discussion: The trial will provide the first test of an engagement intervention in standardised care, with the potential for significant impact on the mental health and wellbeing of young people and their families, and economic benefits for services. The intervention will be highly scalable, supported by the toolkit including manuals, commissioning guide, training and resources, adapted to meet the needs of the diverse EIP population, and based on an in-depth process evaluation. Trial registration: ISRCTN 51629746 prospectively registered 7th May 2019. Date assigned 10th May 2019

A randomised controlled trial of positive memory training for the treatment of depression within schizophrenia

Abstract Background: Depression is highly prevalent within individuals diagnosed with schizophrenia, and is associated with an increased risk of suicide. There are no current evidence based treatments for low mood within this group. The specific targeting of co-morbid conditions within complex mental health problems lends itself to the development of short-term structured interventions which are relatively easy to disseminate within health services. A brief cognitive intervention based on a competitive memory theory of depression, is being evaluated in terms of its effectiveness in reducing depression within this group. Methods/Design: This is a single blind, intention-to-treat, multi-site, randomized controlled trial comparing Positive Memory Training plus Treatment as Usual with Treatment as Usual alone. Participants will be recruited from two NHS Trusts in Southern England. In order to be eligible, participants must have a DSM-V diagnosis of schizophrenia or schizo-affective disorder and exhibit at least a mild level of depression. Following baseline assessment eligible participants will be randomly allocated to either the Positive Memory Training plus Treatment as Usual group or the Treatment as Usual group. Outcome will be assessed at the end of treatment (3-months) and at 6-month and 9-month post randomization by assessors blind to group allocation. The primary outcome will be levels of depression and secondary outcomes will be severity of psychotic symptoms and cost-effectiveness. Semi-structured interviews will be conducted with all participants who are allocated to the treatment group so as to explore the acceptability of the intervention. Discussion: Cognitive behaviour therapy is recommended for individuals diagnosed with schizophrenia. However, the number of sessions and length of training required to deliver this intervention has caused a limit in availability. The current trial will evaluate a short-term structured protocol which targets a co-morbid condition often considered of primary importance by service users. If successful the intervention will be an important addition to current initiatives aimed at increasing access to psychological therapies for people diagnosed with severe mental health problems. Trial registration: Current Controlled Trials. ISRCTN99485756. Registered 13 March 2014

Real-time PCR Demonstrates Ancylostoma duodenale Is a Key Factor in the Etiology of Severe Anemia and Iron Deficiency in Malawian Pre-school Children

Hookworm infections are a major cause of childhood anemia and iron deficiency. Two hookworm species exist of which Ancylostoma duodenale is the less common, yet causing more blood loss than Necator americanus. Although species differentiation and quantification are both of clinical importance, these are often not performed as the technique is complex and laborious using microscopy. Multiplex real-time PCR is a novel diagnostic tool which allows hookworm species differentiation and infection quantification. We applied this test in 830 stool samples of Malawian children with and without severe anemia. The prevalence of hookworm infections was high. A. duodenale was unexpectedly more prevalent than N. americanus. A. duodenale infections were associated with increased risk for severe anemia and iron deficiency, both of which increased with infection load. The study identifies a need for the quantitative screening of species-specific hookworm infections, which readily can be achieved by real-time-PCR. A. duodenale was independently associated with severe anemia and iron deficiency in our study population

Elevated Plasma Von Willebrand Factor and Propeptide Levels in Malawian Children with Malaria

In children with malaria plasma VWF and propeptide levels are markedly elevated in both cerebral and mild paediatric malaria, with levels matching disease severity, and these normalize upon recovery. High levels of both markers also occur in retinopathy-negative 'cerebral malaria' cases, many of whom are thought to be suffering from diseases other than malaria, indicating that further studies of these markers will be required to determine their sensitivity and specificity

Community based distribution of oral HIV self-testing kits in Zambia: a cluster-randomised trial nested in four HPTN 071 (PopART) intervention communities

Background The HPTN 071 (PopART) cluster-randomised trial provided door-to-door HIV testing services to a large proportion of individuals residing in 21 intervention communities in Zambia and South Africa from 2014 to 2017 and reached the UNAIDS first 90 target among women in Zambia, yet gaps remained among men and young adults. This cluster-randomised study nested in the HPTN 071 (PopART) trial sought to increase knowledge of HIV status across all groups by offering the choice of oral HIV self-testing in addition to routine door-to-door HIV testing services. Methods We nested this cluster-randomised trial in four HTPN 071 (PopART) intervention communities in northern Zambia. 66 zones (clusters) in these communities were randomly allocated (1:1) to either oral HIV self-testing plus routine door-to-door HIV testing services (HIV self-testing group) or the PopART standard of care of door-to-door HIV testing services alone (non- HIV self-testing group) over a 3-month period. All individuals aged 16 years or older were eligible for HIV testing. Randomisation was achieved by randomly selecting one allocation from a list of 10 000 possible allocations during a public ceremony. In HIV self-testing zones, trained lay-counsellors (known as community HIV care providers) visited households and offered eligible individuals the choice of HIV testing using HIV self-testing or routine door-to-door HIV testing services. For individuals aged 18 years or older whose partner was absent during the household visit, an HIV self-test kit could be left for secondary distribution to the absent partner. The primary outcome was knowledge of HIV status (defined as self-reporting HIV positive to the community HIV care providers or accepting an offer of HIV testing services). Outcomes were measured among households that were first visited, and individuals first enumerated as a household member during the HIV self-testing intervention period. We analysed data at the individual level using population-average logistic regression models, accounting for clustering of outcomes by zone, to estimate the effect of the intervention. This trial is registered with ClinicalTrials.gov, number NCT02994329. Findings Between Feb 1, and April 30, 2017, the community HIV care providers enumerated 13 267 eligible individuals in the HIV self-testing group and 13 706 in the non-HIV self-testing group. After intervention implementation, 9027 (68%) of 13 267 in the HIV self-testing group had knowledge of HIV status compared with 8952 (65%) of 13 706 in the non-HIV self-testing group (adjusted odds ratio 1·30, 95% CI 1·03–1·65; p=0·03). The effect differed by sex (pinteraction=0·01). Among men, knowledge of HIV status was higher in the HIV self-testing group than in the non-HIV self-testing group (3843 [60%] of 6368 vs 3571 [55%] of 6486; adjusted odds ratio 1·31, 95% CI 1·07–1·60; p=0·01). There was no evidence of a between-group difference among female participants. Interpretation Providing a choice of HIV self-testing during delivery of door-to-door HIV testing services increased knowledge of HIV status, driven by an effect among men. Lay counsellors have a vital role to play in adapting HIV self-testing interventions to local context

Iron Deficiency and Acute Seizures: Results from Children Living in Rural Kenya and a Meta-Analysis

There are conflicting reports on whether iron deficiency changes susceptibility to seizures. We examined the hypothesis that iron deficiency is associated with an increased risk of acute seizures in children in a malaria endemic area