A practical guide to cross-cultural and multi-sited data collection in the biological and behavioural sciences.

Researchers in the biological and behavioural sciences are increasingly conducting collaborative, multi-sited projects to address how phenomena vary across ecologies. These types of projects, however, pose additional workflow challenges beyond those typically encountered in single-sited projects. Through specific attention to cross-cultural research projects, we highlight four key aspects of multi-sited projects that must be considered during the design phase to ensure success: (1) project and team management; (2) protocol and instrument development; (3) data management and documentation; and (4) equitable and collaborative practices. Our recommendations are supported by examples from our experiences collaborating on the Evolutionary Demography of Religion project, a mixed-methods project collecting data across five countries in collaboration with research partners in each host country. To existing discourse, we contribute new recommendations around team and project management, introduce practical recommendations for exploring the validity of instruments through qualitative techniques during piloting, highlight the importance of good documentation at all steps of the project, and demonstrate how data management workflows can be strengthened through open science practices. While this project was rooted in cross-cultural human behavioural ecology and evolutionary anthropology, lessons learned from this project are applicable to multi-sited research across the biological and behavioural sciences.

Effect of Acute Illness on Contact Patterns, Malawi, 2017.

The way persons interact when ill could profoundly affect transmission of infectious agents. To obtain data on these patterns in Africa, we recorded self-reported named contacts and opportunities for casual contact in rural northern Malawi. We interviewed 384 patients and 257 caregivers about contacts over three 24-hour periods: day of the clinic visit for acute illness, the next day, and 2 weeks later when well. For participants of all ages, the number of adult contacts and the proportion using public transportation was higher on the day of the clinic visit than later when well. Compared with the day after the clinic visit, well participants (2 weeks later) named a mean of 0.4 extra contacts; the increase was larger for indoor or prolonged contacts. When well, participants were more likely to visit other houses and congregate settings. When ill, they had more visitors at home. These findings could help refine models of infection spread.

"He was no longer listening to me": A qualitative study in six Sub-Saharan African countries exploring next-of-kin perspectives on caring following the death of a relative from AIDS.

In the era of widespread antiretroviral therapy, few studies have explored the perspectives of the relatives involved in caring for people living with HIV (PLHIV) during periods of ill-health leading up to their demise. In this analysis, we explore the process of care for PLHIV as their death approached, from their relatives' perspective. We apply Tronto's care ethics framework that distinguishes between care-receiving among PLHIV on the one hand, and caring about, caring for and care-giving by their relatives on the other. We draw on 44 in-depth interviews conducted with caregivers following the death of their relatives, in seven rural settings in Eastern and Southern Africa. Relatives suggested that prior to the onset of poor health, few of the deceased had disclosed their HIV status and fewer still were relying on anyone for help. This lack of disclosure meant that some caregivers spoke of enduring a long period of worry, and feelings of helplessness as they were unable to translate their concern and "caring about" into "caring for". This transition often occurred when the deceased became in need of physical, emotional or financial care. The responsibility was often culturally prescribed, rarely questioned and usually fell to women. The move to "care-giving" was characterised by physical acts of providing care for their relative, which lasted until death. Tronto's conceptualisation of caring relationships highlights how the burden of caring often intensifies as family members' caring evolves from "caring about", to "caring for", and eventually to "giving care" to their relatives. This progression can lead to caregivers experiencing frustration, provoking tensions with their relatives and highlighting the need for interventions to support family members caring for PLHIV. Interventions should also encourage PLHIV to disclose their HIV status and seek early access to HIV care and treatment services.

'I wanted to safeguard the baby': a qualitative study to understand the experiences of Option B+ for pregnant women and the potential implications for 'test-and-treat' in four sub-Saharan African settings.

OBJECTIVE: To explore what influences on engagement with Option B+ in four sub-Saharan African settings. METHODS: In-depth interviews were conducted in 2015, with 22 HIV-positive women who had been pregnant since Option B+ was available, and 15 healthcare workers (HCWs) involved in HIV service delivery. Participants were purposely selected from four health and demographic surveillance sites in Malawi, Tanzania and Uganda. A thematic content analysis was conducted to investigate what influenced engagement with Option B+. RESULTS: Feeling 'ready' was key to pregnant women accepting antiretroviral treatment (ART) on the same day as diagnosis at antenatal clinic; this was influenced by previous knowledge of HIV-positive status, interactions with HCWs and relationship with their partners. The desire to protect their unborn infant was the main issue that motivated women to initiate treatment, temporarily over-riding barriers to starting ART. Many HCWs recognised that pressurising women into starting ART may lead them to stop treatment following delivery. However, their own responsibility to protect the infant sometimes drove HCWs to use strong persuasive techniques to initiate pregnant women onto ART as early as possible, occasionally causing women to disengage. CONCLUSIONS: Protecting the baby superseded feelings of unpreparedness for lifelong ART and may explain poor retention observed in Option B+ programmes. Women may benefit from more time to accept their status, and counselling on the long-term value of ART beyond the pregnancy and breastfeeding period. Strategies to promote readiness for same-day initiation of lifelong treatment are urgently needed, and may provide important lessons for universal test-and-treat implementation.

Where are we now? A multicountry qualitative study to explore access to pre-antiretroviral care services: a precursor to antiretroviral therapy initiation.

OBJECTIVE: To explore barriers and facilitators to accessing postdiagnosis HIV care in five sub-Saharan African countries. METHODS: In-depth interviews were conducted with 77 people living with HIV (PLHIV) in pre-antiretroviral therapy care or not-yet-in care and 46 healthcare workers. Participants were purposely selected from health and demographic surveillance sites in Karonga (Malawi), Manicaland (Zimbabwe), uMkhanyakude (South Africa), Kisesa (Tanzania) and Rakai and Kyamulibwa (Uganda). Thematic content analysis was conducted, guided by the constructs of affordability, availability and acceptability of care.- RESULTS: Affordability: Transport and treatment costs were a barrier to HIV care, although some participants travelled to distant clinics to avoid being seen by people who knew them or for specific services. Broken equipment and drug stock-outs in local clinics could also necessitate travel to other facilities. Availability: Some facilities did not offer full HIV care, or only offered all services intermittently. PLHIV who frequently travelled complained that care was seldom available to them in places they visited. Acceptability: Severe pain or sickness was a key driver for accessing postdiagnosis care, whereas asymptomatic PLHIV often delayed care-seeking. A belief in witchcraft was a deterrent to accessing clinical care following diagnosis. Changing antiretroviral therapy guidelines generated uncertainty among PLHIV about when to start treatment and delayed postdiagnosis care. PLHIV reported that healthcare workers' knowledge, attitudes and behaviours, and their ability to impart health education, also influenced whether they accessed HIV care. CONCLUSION: Despite efforts to decentralise services over the past decade, many barriers to accessing HIV care persist. There is a need to increase sustained access to care for PLHIV not yet on treatment, with initiatives that encompass biomedical aspects of care alongside considerations for individual and collective challenges they faced. A failure to do so may undermine efforts to achieve universal access to antiretroviral therapy.

'Side effects' are 'central effects' that challenge retention in HIV treatment programmes in six sub-Saharan African countries: a multicountry qualitative study.

OBJECTIVES: To explore the bodily and relational experience of taking antiretroviral therapy (ART) and the subsequent effect on retention in HIV care in six sub-Saharan African countries. METHODS: In-depth interviews were conducted with 130 people living with HIV (PLHIV) who had initiated ART, 38 PLHIV who were lost to follow-up and 53 healthcare workers (HCWs) in Kenya, Uganda, Tanzania, Malawi, Zimbabwe and South Africa. PLHIV were purposely selected to include a range of HIV treatment histories. Deductive and inductive analysis was guided by aspects of practice theory; retention in HIV care following ART initiation was the practice of interest. RESULTS: PLHIV who were engaged in HIV care took ART every day, attended clinic appointments and ate as well as possible. For PLHIV, biomedical markers acted as reassurance for their positive treatment progression. However, many described ART side effects ranging from dizziness to conditions severe enough to prevent them from leaving home or caring for themselves or others. In all settings, the primary concern of HCW was ensuring patients achieved viral suppression, with management of side effects seen as a lower priority. Where PLHIV tolerated side effects, they were deemed the lesser of two evils compared with their pre-ART illnesses. Participants who reported feeling well prior to starting ART were often less able to tolerate side effects, and in many cases these events triggered their disengagement from HIV care. CONCLUSIONS: Retention in ART care is rarely an outcome of rational decision-making, but the consequence of bodily and relational experiences. Initiatives to improve retention should consider how bodily experiences of PLHIV relate to the rest of their lives and how this can be respected and supported by service providers to subsequently improve retention in care.

Traditional healers, faith healers and medical practitioners: the contribution of medical pluralism to bottlenecks along the cascade of care for HIV/AIDS in Eastern and Southern Africa.

OBJECTIVES: There are concerns that medical pluralism may delay patients' progression through the HIV cascade-of-care. However, the pathways of impact through which medical pluralism influence the care of people living with HIV (PLHIV) in African settings remain unclear. We sought to establish the manifestation of medical pluralism among PLHIV, and explore mechanisms through which medical pluralism contributes bottlenecks along the HIV care cascade. METHODS: We conducted a multicountry exploratory qualitative study in seven health and demographic surveillance sites in six eastern and southern African countries: Uganda, Kenya, Tanzania, Malawi, Zimbabwe and South Africa. We interviewed 258 PLHIV at different stages of the HIV cascade-of-care, 48 family members of deceased PLHIV and 53 HIV healthcare workers. Interviews were conducted using shared standardised topic guides, and data managed through NVIVO 8/10/11. We conducted a thematic analysis of healthcare pathways and bottlenecks related to medical pluralism. RESULTS: Medical pluralism, manifesting across traditional, faith-based and biomedical health-worlds, contributed to the care cascade bottlenecks for PLHIV through three pathways of impact. First, access to HIV treatment was delayed through the nature of health-related beliefs, knowledge and patient journeys. Second, HIV treatment was interrupted by availability of alternative options, perceived failed treatment and exploitation of PLHIV by opportunistic traders and healers. Lastly, the mixing of biomedical healthcare providers and treatment with traditional and faith-based options fuelled tensions driven by fear of drug-to-drug interactions and mistrust between providers operating in different health-worlds. CONCLUSION: Medical pluralism contributes to delays and interruptions of care along the HIV cascade, and mistrust between health providers. Region-wide interventions and policies are urgently needed in sub-Saharan Africa to minimise potential harm and consequences of medical pluralism for PLHIV. The role of sociocultural beliefs in mediating bottlenecks necessitate adoption of culture-sensitive approaches intervention designs and policy reforms appropriate to the context of sub-Saharan Africa.

Understanding the relationship between couple dynamics and engagement with HIV care services: insights from a qualitative study in Eastern and Southern Africa.

OBJECTIVE: To explore the interplay between couple dynamics and the engagement of people living with HIV (PLHIV) with HIV care and treatment services in three health and demographic surveillance sites in Tanzania, Malawi and South Africa. METHODS: A qualitative study was conducted involving 107 in-depth interviews with PLHIV with a range of HIV care and treatment histories, including current users of HIV clinics, and people not enrolled in HIV care. Interviews explored experiences of living with HIV and how and why they chose to engage or not with HIV services. Thematic analysis was conducted with the aid of NVivo 10. RESULTS: We found an interplay between couple dynamics and HIV care and treatment-seeking behaviour in Tanzania, Malawi and South Africa. Being in a relationship impacted on the level and type of engagement with HIV services in multiple ways. In some instances, couples living with HIV supported each other which improved their engagement with care and strengthened their relationships. The desire to fulfil societal expectations and attract a new partner, or have a baby with a new partner, or to receive emotional or financial support, strengthened on-going engagement with HIV care and treatment. However, fear of blame, abandonment or abuse resulted in unwillingness to disclose and often led to disputes or discord between couples. There was little evidence of intracouple understanding of each other's lived experiences with HIV, and we found that couples rarely interacted with the formal health system together. CONCLUSIONS: Couple dynamics influenced engagement with HIV testing, care and treatment for both partners through a myriad of pathways. Couple-friendly approaches to HIV care and treatment are needed that move beyond individualised care and which recognise partner roles in HIV care engagement.

Patterns and risk factors for deaths from external causes in rural Malawi over 10 years: a prospective population-based study.

BACKGROUND: Little is known about the pattern or risk factors for deaths from external causes in sub-Saharan Africa: there is a lack of reliable data, and public health priorities have been focussed on other causes. This study assessed the prevalence and risk factor for deaths from external causes in rural Malawi. METHODS: We analysed data from 2002-2012 from the Karonga demographic surveillance site which covers ~35,000 people in rural northern Malawi. Verbal autopsies with clinician coding are used to assign cause of death. Repeated annual surveys capture data on socio-economic factors. Using Poisson regression models we calculated age, sex and cause-specific rates and rate ratios of external deaths. We used a nested case-control study, matched on age, sex and time period, to investigate risk factors for these deaths, using conditional logistic regression. RESULTS: In 315,580 person years at risk (pyar) there were 2673 deaths, including 143 from external causes. The mortality rate from external causes was 47.1/100,000 pyar (95 % CI 32.5-68.2) among under-fives; 20.1/100,000 pyar (95 % CI 13.1-32.2) among 5-14 year olds; 46.3/100,000 pyar (95 % CI 35.8-59.9) among 15-44 year olds; and 98.7/100,000 pyar (95 % CI 71.8-135.7) among those aged ≥45 years. Drowning (including four deaths in people with epilepsy), road injury and suicide were the leading external causes. Adult males had the highest rates (100.7/100,000 pyar), compared to 21.8/100,000pyar in adult females, and the rate continued to increase with increasing age in men. Alcohol contributed to 21 deaths, all in adult males. Children had high rates of drowning (9.2/100,000 pyar, 95 % CI 5.5-15.6) but low rates of road injury (2.6/100,000 pyar, 95 % CI 1.0-7.0). Among 5-14 year olds, attending school was associated with fewer deaths from external causes than among those who had never attended school (adjusted OR 0.15, 95 % CI 0.08-0.81). Fishermen had increased risks of death from drowning and suicide compared to farmers. DISCUSSION: In this population the rate of deaths from external causes was lowest at age 5-14 years. Adult males had the highest rate of death from external causes, 5 times the rate in adult females. Drowning, road injury and suicide were the leading causes of death; alcohol consumption contributed to more than one quarter of the deaths in men CONCLUSIONS: The high proportion of alcohol-related deaths in men, the predominance of drowning, deaths linked to uncontrolled epilepsy, and the possible protective effect of school attendance suggest areas for intervention.

Factors associated with self-reported diagnosed asthma in urban and rural Malawi: Observations from a population-based study of non-communicable diseases.

The growing burden of asthma in low- and middle-income countries has been linked to urbanisation and lifestyle changes. However, this burden has not been well characterised in adults. Therefore, we investigated the prevalence of self-reported diagnosed asthma and associated factors in urban and rural adults in Malawi, Southern Africa. Within a cross-sectional population-based survey to determine the burden and risk factors for non-communicable diseases (NCDs) in the city of Lilongwe and rural Karonga district, we collected information on self-reported previously diagnosed asthma and asthma-related symptoms using an interviewer-led questionnaire. Other data collected included: demographic characteristics, socioeconomic status indicators, NCD comorbidities, environmental exposures, and anthropometric measurements. We used multivariable logistic regression models to explore factors associated with self-reported asthma adjusting for variables associated with the outcome in univariable analysis. Findings were corrected for multiple comparisons using the Bonferroni method. We analysed data from 30,483 adult participants (54.6% urban,45.4% rural and 61.9% female). A prior asthma diagnosis was reported in 5.1% of urban and 4.5% of rural participants. In urban females, being obese (>30 kg/m2) compared to normal weight (18.5-24.9 kg/m2) was associated with greater odds of asthma (OR = 1.59, 95% CI [1.26-2.01], p<0.001), after adjusting for confounders. We observed associations between previously diagnosed heart disease and asthma in female participants which remained significant in rural females after Bonferroni correction (OR = 2.30,95%CI [1.32-4.02], p = 0.003). Among rural males, current smokers had reduced odds of diagnosed asthma (OR = 0.46,95%CI [0.27-0.79], p = 0.004) compared to those who had never smoked. In Malawi the prevalence of self-reported diagnosed asthma was greatest in females and urban dwellers. Notably, our findings indicate relationships between excess body weight as well as comorbidities and diagnosed asthma in females. Future investigations using longitudinally collected data and clinical measurements of asthma are needed to better understand these associations.

Association between physical multimorbidity and common mental health disorders in rural and urban Malawian settings: Preliminary findings from Healthy Lives Malawi long-term conditions survey.

In low-income Africa, the epidemiology of physical multimorbidity and associated mental health conditions is not well described. We investigated the multimorbidity burden, disease combinations, and relationship between physical multimorbidity and common mental health disorders in rural and urban Malawi using early data from 9,849 adults recruited to an on-going large cross-sectional study on long-term conditions, initiated in 2021. Multimorbidity was defined as having two or more measured (diabetes, hypertension) or self-reported (diabetes, hypertension, disability, chronic pain, HIV, asthma, stroke, heart disease, and epilepsy) conditions. Depression and anxiety symptoms were measured using the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item General Anxiety Disorder scale (GAD-7) and defined by the total score (range 0-27 and 0-21, respectively). We determined age-standardized multimorbidity prevalence and condition combinations. Additionally, we used multiple linear regression models to examine the association between physical multimorbidity and depression and anxiety symptom scores. Of participants, 81% were rural dwelling, 56% were female, and the median age was 30 years (Inter Quartile Range 21-43). The age-standardized urban and rural prevalence of multimorbidity was 14.1% (95% CI, 12.5-15.8%) and 12.2% (95% CI, 11.6-12.9%), respectively. In adults with two conditions, hypertension, and disability co-occurred most frequently (18%), and in those with three conditions, hypertension, disability, and chronic pain were the most common combination (23%). Compared to adults without physical conditions, having one (B-Coefficient (B) 0.79; 95% C1 0.63-0.94%), two- (B 1.36; 95% CI 1.14-1.58%), and three- or more- physical conditions (B 2.23; 95% CI 1.86-2.59%) were associated with increasing depression score, p-trend <0.001. A comparable 'dose-response' relationship was observed between physical multimorbidity and anxiety symptom scores. While the direction of observed associations cannot be determined with these cross-sectional data, our findings highlight the burden of multimorbidity and the need to integrate mental and physical health service delivery in Malawi.

Evolutionary dynamics of local pandemic H1N1/2009 influenza virus lineages revealed by whole-genome analysis.

Virus gene sequencing and phylogenetics can be used to study the epidemiological dynamics of rapidly evolving viruses. With complete genome data, it becomes possible to identify and trace individual transmission chains of viruses such as influenza virus during the course of an epidemic. Here we sequenced 153 pandemic influenza H1N1/09 virus genomes from United Kingdom isolates from the first (127 isolates) and second (26 isolates) waves of the 2009 pandemic and used their sequences, dates of isolation, and geographical locations to infer the genetic epidemiology of the epidemic in the United Kingdom. We demonstrate that the epidemic in the United Kingdom was composed of many cocirculating lineages, among which at least 13 were exclusively or predominantly United Kingdom clusters. The estimated divergence times of two of the clusters predate the detection of pandemic H1N1/09 virus in the United Kingdom, suggesting that the pandemic H1N1/09 virus was already circulating in the United Kingdom before the first clinical case. Crucially, three clusters contain isolates from the second wave of infections in the United Kingdom, two of which represent chains of transmission that appear to have persisted within the United Kingdom between the first and second waves. This demonstrates that whole-genome analysis can track in fine detail the behavior of individual influenza virus lineages during the course of a single epidemic or pandemic.

Local and long-distance migration among young people in rural Malawi: importance of age, sex and family.

Background: In sub-Saharan Africa, migration of young people is common and occurs for a variety of reasons. Research focus is often on international or long-distance internal migration; however, shorter moves also affect people's lives and can reveal important information about cultures and societies. In rural sub-Saharan Africa, migration may be influenced by cultural norms and family considerations: these may be changing due to demographic shifts, urbanisation, and increased media access. Methods: We used longitudinal data from a Health and Demographic Surveillance Site in rural northern Malawi to present a detailed investigation of migration in young people between 2004-2017. Our focus is on the cultural effects of gender and family, and separate migrations into short and long distance, and independent and accompanied, as these different move types are likely to represent very different events in a young person's life. We use descriptive analyses multi-level multinomial logistic regression modelling. Results & conclusions: We found two key periods of mobility 1) in very young childhood and 2) in adolescence/young adulthood. In this traditionally patrilocal area, we found that young women move longer distances to live with their spouse, and also were more likely to return home after a marriage ends, rather than remain living independently. Young people living close to relatives tend to have lower chances of moving, and despite the local patrilineal customs, we found evidence of the importance of the maternal family. Female and male children may be treated differently from as young as age 4, with girls more likely to migrate long distances independently, and more likely to accompany their mothers in other moves.

Family network and household composition: a longitudinal dataset derived from the Karonga Health and Demographic Surveillance System, in rural Malawi.

Proximity to family, household composition, and structure are often studied as outcomes and as explanatory factors in a wide range of scientific disciplines. Here, we describe a large longitudinal dataset (currently including data from over 70,000 individuals from 2004 to 2017), including data on household structure, proximity to kin, population density, and other socio-demographic factors derived from data from the Karonga Health and Demographic Surveillance Site (HDSS) in Northern Malawi. We present how the dataset is generated, list some examples of how it can be used, and provide information on the limitations that affect the types of analyses that can be carried out.

Effects of exclusive breastfeeding on educational attainment and longitudinal trajectories of grade progression among children in a 13-year follow-up study in Malawi.

The benefits of exclusive breastfeeding (EBF) for infant health and survival are well documented. However, its impact on educational outcomes has been contested and poorly researched in Africa. It has been hypothesised that positive associations reported in high-income countries can be attributed to residual confounding by socioeconomic status (SES). Our study investigated whether EBF duration in infancy is associated with educational attainment and age-for-grade attainment trajectories at school-age in rural Malawi. Longitudinal data on 1021 children at the Karonga demographic surveillance site in Malawi were analysed. Breastfeeding data were collected 3 months after birth and again at age one. The school grade of each child was recorded each year from age 6 until age 13. We calculated age-for-grade based on whether a child was at, over, or under the official expected age for a grade. Generalised estimating equations estimated the average effect of breastfeeding on age-for-grade. Latent class growth analysis identified age-for-grade trajectories, and multinomial logistic regression examined their associations with EBF. Maternal-child characteristics, SES, and HIV status were controlled. Overall, 35.9% of the children were exclusively breastfed for 6 months. Over-age for grade steadily increased from 9.6% at age 8 to 41.9% at age 13. There was some evidence that EBF for 6 months was associated with lower odds of being over-age for grade than EBF for less than 3 months (aOR = 0.82, 95%CI = 0.64-1.06). In subgroup analyses, children exclusively breastfed for 6 months in infancy were less likely to be over-age for grades between ages 6-9 (aOR = 0.64, 95%CI = 0.43-0.94). Latent class growth analysis also provided some evidence that EBF reduced the odds of falling behind in the early school grades (aOR = 0.66, 95%CI = 0.41-1.08) but not later. Our study adds to the growing evidence that EBF for 6 months has benefits beyond infant health and survival, supporting the WHO's recommendation on EBF.

Characterizing the evolving SARS-CoV-2 seroprevalence in urban and rural Malawi between February 2021 and April 2022: A population-based cohort study.

OBJECTIVES: This study aimed to investigate the changing SARS-CoV-2 seroprevalence and associated health and sociodemographic factors in Malawi between February 2021 and April 2022. METHODS: In total, four 3-monthly serosurveys were conducted within a longitudinal population-based cohort in rural Karonga District and urban Lilongwe, testing for SARS-CoV-2 S1 immunoglobulin (Ig)G antibodies using an enzyme-linked immunosorbent assay. Population seroprevalence was estimated in all and unvaccinated participants. Bayesian mixed-effects logistic models estimated the odds of seropositivity in the first survey, and of seroconversion between surveys, adjusting for age, sex, occupation, location, and assay sensitivity/specificity. RESULTS: Of the 2005 participants (Karonga, n = 1005; Lilongwe, n = 1000), 55.8% were female and median age was 22.7 years. Between Surveys (SVY) 1 and 4, population-weighted SARS-CoV-2 seroprevalence increased from 26.3% to 89.2% and 46.4% to 93.9% in Karonga and Lilongwe, respectively. At SVY4, seroprevalence did not differ by COVID-19 vaccination status in adults, except for those aged 30+ years in Karonga (unvaccinated: 87.4%, 95% credible interval 79.3-93.0%; two doses: 98.1%, 94.8-99.5%). Location and age were associated with seroconversion risk. Individuals with hybrid immunity had higher SARS-CoV-2 seropositivity and antibody titers, than those infected. CONCLUSION: High SARS-CoV-2 seroprevalence combined with low morbidity and mortality indicate that universal vaccination is unnecessary at this stage of the pandemic, supporting change in national policy to target at-risk groups.

A secondary data analysis of a cluster randomized controlled trial: improved cookstoves associated with reduction in incidence of low birthweight in rural Malawi.

BACKGROUND: In northern rural Malawi, the majority of households cook using open fires and there is also a high burden of adverse birth outcomes. The use of open fires or highly polluting cookstoves is associated with low birthweight in babies. There is mixed evidence on whether implementation of cleaner burning cookstoves reduces the number of babies born with low birthweight. METHODS: This is a secondary analysis of a cluster randomized control trial in Malawi, conducted over 2014-17. Households were randomized to receive improved cookstoves or to continue current practices. For this analysis, the primary outcome was low birthweight in households under routine demographic surveillance, among births occurring within the trial time frame (N = 4010). A subset of data with stricter exposure definitions respecting the original randomized allocation was also analysed (N = 1050). A causal, forwards modelling approach was used. RESULTS: The main dataset showed evidence of effect of the intervention on low birthweight [adjusted odds ratio (aOR) 0.69; 95% CI 0.48-0.99, n = 2788). The subset analysis lacked power to provide evidence of association between improved cookstoves and low birthweight in the stricter exposure definition (aOR 0.62; 95% CI 0.35-1.09, n = 932). CONCLUSIONS: This study provides some evidence that an improved cookstove intervention in rural Malawi reduced the number of babies born with low birthweight by 30%. This direction of the effect was also seen in the subset analysis. The analysis suggests that the intervention reduced the number of infants born prematurely or with intra-uterine growth restriction, indicating that improved cookstoves could be a useful maternal health intervention.

Identification and development of a subtype-selective allosteric AKT inhibitor suitable for clinical development.

The serine/threonine protein kinase AKT plays a pivotal role within the PI3K pathway in regulating cellular proliferation and apoptotic cellular functions, and AKT hyper-activation via gene amplification and/or mutation has been implicated in multiple human malignancies. There are 3 AKT isoenzymes (AKT1-3) which mediate critical, non-redundant functions. We present the discovery and development of ALM301, a novel, allosteric, sub-type selective inhibitor of AKT1/2. ALM301 binds in an allosteric pocket created by the combined movement of the PH domain and the catalytic domain, resulting in a DFG out conformation. ALM301 was shown to be highly selective against a panel of over 450 kinases and potently inhibited cellular proliferation. These effects were particularly pronounced in MCF-7 cells containing a PI3KCA mutation. Subsequent cellular downstream pathway analysis in this sensitive cell line revealed potent inhibition of pAKT signalling up to 48 h post dosing. ALM301 treatment was well tolerated in an MCF-7 xenograft model and led to a dose-dependent reduction in tumour growth. Enhanced efficacy was observed in combination with tamoxifen. In summary, ALM301 is a highly specific AKT 1/2 inhibitor with an excellent pharmacological profile suitable for further clinical development.

Use of antiviral drugs to reduce household transmission of pandemic (H1N1) 2009, United Kingdom.

The United Kingdom implemented a containment strategy for pandemic (H1N1) 2009 through administering antiviral agents (AVs) to patients and their close contacts. This observational household cohort study describes the effect of AVs on household transmission. We followed 285 confirmed primary cases in 259 households with 761 contacts. At 2 weeks, the confirmed secondary attack rate (SAR) was 8.1% (62/761) and significantly higher in persons <16 years of age than in those >50 years of age (18.9% vs. 1.2%, p<0.001). Early (<48 hours) treatment of primary case-patients reduced SAR (4.5% vs. 10.6%, p = 0.003). The SAR in child contacts was 33.3% (10/30) when the primary contact was a woman and 2.9% (1/34) when the primary contact was a man (p = 0.010). Of 53 confirmed secondary case-patients, 45 had not received AV prophylaxis. The effectiveness of AV prophylaxis in preventing infection was 92%.

Assessing the implementation of facility-based HIV testing policies in Malawi, South Africa and Tanzania from 2013-2018: Findings from SHAPE-UTT study.

National HIV testing policies aim to increase the proportion of people living with HIV who know their status. National HIV testing policies were reviewed for each country from 2013 to 2018, and compared with WHO guidance. Three rounds of health facility surveys were conducted to assess facility level policy implementation in Karonga (Malawi), uMkhanyakude (South Africa), and Ifakara (Tanzania). A policy 'implementation' score was developed and applied to each facility by site for each round. Most HIV testing policies were explicit and aligned with WHO recommendations. Policies about service coverage, access, and quality of care were implemented in >80% of facilities per site and per round. However, linkage to care and the provision of outreach HIV testing for key populations were poorly implemented. The proportion of facilities reporting HIV test kit stock-outs in the past year reduced over the study period in all sites, but still occurred in ≥17% of facilities per site by 2017. The implementation score improved over time in Karonga and Ifakara and declined slightly in uMkhanyakude. Efforts are needed to address HIV test kit stock-outs and to improve linkage to care among people testing positive in order to reach the 90-90-90 targets.