Health system assessment for access to care after injury in low- or middle-income countries: A mixed methods study from Northern Malawi.

BACKGROUND: Injuries represent a vast and relatively neglected burden of disease affecting low- and middle-income countries (LMICs). While many health systems underperform in treating injured patients, most assessments have not considered the whole system. We integrated findings from 9 methods using a 3 delays approach (delays in seeking, reaching, or receiving care) to prioritise important trauma care health system barriers in Karonga, Northern Malawi, and exemplify a holistic health system assessment approach applicable in comparable settings. METHODS AND FINDINGS: To provide multiple perspectives on each conceptual delay and include data from community-based and facility-based sources, we used 9 methods to examine the injury care health system. The methods were (1) household survey; (2) verbal autopsy analysis; (3) community focus group discussions (FGDs); (4) community photovoice; (5) facility care-pathway process mapping and elucidation of barriers following injury; (6) facility healthcare worker survey; (7) facility assessment survey; (8) clinical vignettes for care process quality assessment of facility-based healthcare workers; and (9) geographic information system (GIS) analysis. Empirical data collection took place in Karonga, Northern Malawi, between July 2019 and February 2020. We used a convergent parallel study design concurrently conducting all data collection before subsequently integrating results for interpretation. For each delay, a matrix was created to juxtapose method-specific data relevant to each barrier identified as driving delays to injury care. Using a consensus approach, we graded the evidence from each method as to whether an identified barrier was important within the health system. We identified 26 barriers to access timely quality injury care evidenced by at least 3 of the 9 study methods. There were 10 barriers at delay 1, 6 at delay 2, and 10 at delay 3. We found that the barriers "cost," "transport," and "physical resources" had the most methods providing strong evidence they were important health system barriers within delays 1 (seeking care), 2 (reaching care), and 3 (receiving care), respectively. Facility process mapping provided evidence for the greatest number of barriers-25 of 26 within the integrated analysis. There were some barriers with notable divergent findings between the community- and facility-based methods, as well as among different community- and facility-based methods, which are discussed. The main limitation of our study is that the framework for grading evidence strength for important health system barriers across the 9 studies was done by author-derived consensus; other researchers might have created a different framework. CONCLUSIONS: By integrating 9 different methods, including qualitative, quantitative, community-, patient-, and healthcare worker-derived data sources, we gained a rich insight into the functioning of this health system's ability to provide injury care. This approach allowed more holistic appraisal of this health system's issues by establishing convergence of evidence across the diverse methods used that the barriers of cost, transport, and physical resources were the most important health system barriers driving delays to seeking, reaching, and receiving injury care, respectively. This offers direction and confidence, over and above that derived from single methodology studies, for prioritising barriers to address through health service development and policy.

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.

Access to quality care after injury in Northern Malawi: results of a household survey.

BACKGROUND: Most injury care research in low-income contexts such as Malawi is facility centric. Community-derived data is needed to better understand actual injury incidence, health system utilisation and barriers to seeking care following injury. METHODS: We administered a household survey to 2200 households in Karonga, Malawi. The primary outcome was injury incidence, with non-fatal injuries classified as major or minor (> 30 or 1-29 disability days respectively). Those seeking medical treatment were asked about time delays to seeking, reaching and receiving care at a facility, where they sought care, and whether they attended a second facility. We performed analysis for associations between injury severity and whether the patient sought care, stayed overnight in a facility, attended a second facility, or received care within 1 or 2 h. The reason for those not seeking care was asked. RESULTS: Most households (82.7%) completed the survey, with 29.2% reporting an injury. Overall, 611 non-fatal and four fatal injuries were reported from 531 households: an incidence of 6900 per 100,000. Major injuries accounted for 26.6%. Three quarters, 76.1% (465/611), sought medical attention. Almost all, 96.3% (448/465), seeking care attended a primary facility first. Only 29.7% (138/465), attended a second place of care. Only 32.0% (142/444), received care within one hour. A further 19.1% (85/444) received care within 2 h. Major injury was associated with being more likely to have; sought care (94.4% vs 69.8% p < 0.001), stayed overnight at a facility (22.9% vs 15.4% P = 0.047), attended a second place of care (50.3% vs 19.9%, P < 0.001). For those not seeking care the most important reason was the injury not being serious enough for 52.1% (74/142), followed by transport difficulties 13.4% (19/142) and financial costs 5.6% (8/142). CONCLUSION: Injuries in Northern Malawi are substantial. Community-derived details are necessary to fully understand injury burden and barriers to seeking and reaching care.

Post-malnutrition growth and its associations with child survival and non-communicable disease risk: a secondary analysis of the Malawi 'ChroSAM' cohort.

OBJECTIVE: To explore patterns of post-malnutrition growth (PMGr) during and after treatment for severe malnutrition and describe associations with survival and non-communicable disease (NCD) risk 7 years post-treatment. DESIGN: Six indicators of PMGr were derived based on a variety of timepoints, weight, weight-for-age z-score and height-for-age z-score (HAZ). Three categorisation methods included no categorisation, quintiles and latent class analysis (LCA). Associations with mortality risk and seven NCD indicators were analysed. SETTING: Secondary data from Blantyre, Malawi between 2006 and 2014. PARTICIPANTS: A cohort of 1024 children treated for severe malnutrition (weight-for-length z-score < 70 % median and/or MUAC (mid-upper arm circumference) < 110 mm and/or bilateral oedema) at ages 5-168 months. RESULTS: Faster weight gain during treatment (g/d) and after treatment (g/kg/day) was associated with lower risk of death (adjusted OR 0·99, 95 % CI 0·99, 1·00; and adjusted OR 0·91, 95 % CI 0·87, 0·94, respectively). In survivors (mean age 9 years), it was associated with greater hand grip strength (0·02, 95 % CI 0·00, 0·03) and larger HAZ (6·62, 95 % CI 1·31, 11·9), both indicators of better health. However, faster weight gain was also associated with increased waist:hip ratio (0·02, 95 % CI 0·01, 0·03), an indicator of later-life NCD risk. The clearest patterns of association were seen when defining PMGr based on weight gain in g/d during treatment and using the LCA method to describe growth patterns. Weight deficit at admission was a major confounder. CONCLUSIONS: A complex pattern of benefits and risks is associated with faster PMGr. Both initial weight deficit and rate of weight gain have important implications for future health.

Parasites and allergy: Observations from Africa.

Population studies from the African continent have observed a marked increase in the prevalence of allergy-related diseases over the past few decades, but the cause of this rise is not fully understood. The most investigated potential risk factor has been the relationship between exposure to helminths and allergy-related outcomes. Immunologically, parallels exist between responses to helminths and to allergens as both are associated with elevated levels of immunoglobulin E, increased numbers of T helper 2 cells and other immune cells. However, epidemiological studies from the African continent have found inconsistent results. In this review, observations from population studies carried out in Africa over the last decade that focus on the relationship between helminth infections and allergy-related outcomes are examined. How these findings advance our understanding of the complex interactions between helminths and allergies at the population level is also explored as well as some of the underlying immune mechanisms involved. This knowledge is important for better diagnosis, treatment and prevention of allergy-related diseases and has wider global significance.

Aliasing, coherence, and resolution in a lensless holographic microscope.

We have shown that the maximum achievable resolution of an in-line lensless holographic microscope is limited by aliasing and, for collimated illumination, cannot exceed the camera pixel size. This limit can be achieved only when the optimal conditions on the spatial and temporal coherence state of the illumination are satisfied. The expressions defining the configuration, delivering maximum resolution with given spatial and temporal coherence of the illumination, are obtained. The validity of these conditions is confirmed experimentally.

Influence of Parasitic Worm Infections on Allergy Diagnosis in Sub-Saharan Africa.

Epidemiological studies from Sub-Saharan Africa indicate that allergies are on the rise in this region especially in urban compared to rural areas. This increase has been linked to improved hygiene, lifestyle changes, and lower exposure to pathogens in childhood. Reduced exposure to parasitic worm (helminth) infections and allergy outcomes has been the focus of a number of population studies over the years. Paradoxically, there are parallels in the immune responses to helminths and to allergies. Both conditions are associated with elevated levels of immunoglobulin E, high numbers of T helper 2 cells, eosinophils, and mast cells. These immune parallels have meant that the diagnosis of allergies in parts of the world where helminths are endemic can be hampered. The aim of this review is to examine observations from population studies conducted in Sub-Saharan Africa that demonstrate how helminth infections influence the parameters used to diagnose allergy outcomes in this region. We explore specifically how helminth infections hinder the in vitro diagnosis of allergic sensitization, influence the clinical manifestations of allergy, and also the effect of anthelmintic treatment on allergy outcomes. Advancing our understanding of how helminths influence allergy diagnosis is imperative for the development of improved tools to assess, diagnose, and treat allergic disorders in both helminth-endemic and non-endemic countries worldwide.

Helminth-induced IgE and protection against allergic disorders.

The immune response against helminths and allergens is generally characterized by high levels of IgE and increased numbers of Th2 cells, eosinophils, and mast cells, yet the clinical outcome with respect to immediate hypersensitivity and inflammation is clearly not the same. High levels of IgE are seen to allergens during helminth infections; however, these IgE responses do not translate into allergy symptoms. This chapter summarizes the evidence of the association between helminth infections and allergic disorders. It discusses how helminth infection can lead to IgE cross-reactivity with allergens and how this IgE has poor biological activity. This information is important for developing new diagnostic methods and treatments for allergic disorders in low-to-middle-income countries.

Parasitic worms and allergies in childhood: insights from population studies 2008-2013.

The last few decades have seen a marked increase in the global prevalence of allergic diseases particularly among children. Among the factors attributed to this rise has been reduced exposure to pathogens during childhood leading to insufficient maturation of the regulatory arm of developing immune systems. Over the years, a number of epidemiological studies have observed an inverse relationship between parasitic worm (helminth) infections and allergies. The purpose of this review is to highlight insights from population studies conducted among children published between 2008 and 2013 that explore the complex dynamics between helminth infections and allergies. These insights include the effect of anthelmintic treatment on allergic responses, an elucidation of immune mechanisms and an examination of helminth-induced immunoglobulin E cross-reactivity. A better understanding of the relationship between helminths and allergies is imperative as research directions move toward harnessing the therapeutic potential of helminths and their products in the treatment of allergic disorders.

Peanut-specific IgE antibodies in asymptomatic Ghanaian children possibly caused by carbohydrate determinant cross-reactivity.

BACKGROUND: The prevalence of peanut allergy has increased in developed countries, but little is known about developing countries with high peanut consumption and widespread parasitic infections. OBJECTIVE: We sought to investigate peanut allergy in Ghana. METHODS: In a cross-sectional survey among Ghanaian schoolchildren (n = 1604), data were collected on reported adverse reactions to peanut, peanut sensitization (serum specific IgE and skin reactivity), consumption patterns, and parasitic infections. In a subset (n = 43) IgE against Ara h 1, 2, 3, and 9 as well as cross-reactive carbohydrate determinants (CCDs) was measured by using ImmunoCAP. Cross-reactivity and biological activity were investigated by means of ImmunoCAP inhibition and basophil histamine release, respectively. RESULTS: Adverse reactions to peanut were reported in 1.5%, skin prick test reactivity in 2.0%, and IgE sensitization (≥0.35 kU/L) in 17.5% of participants. Moreover, 92.4% of those IgE sensitized to peanut (≥0.35 kU/L) had negative peanut skin prick test responses. Schistosoma haematobium infection was positively associated with IgE sensitization (adjusted odds ratio, 2.29; 95% CI, 1.37-3.86). In the subset IgE titers to Ara h 1, 2, 3, and 9 were low (<1.3 kU/L), except for 6 moderately strong reactions to Ara h 9. IgE against peanut was strongly correlated with IgE against CCDs (r = 0.89, P < .0001) and could be almost completely inhibited by CCDs, as well as S haematobium soluble egg antigen. Moreover, IgE to peanut showed poor biological activity. CONCLUSIONS: Parasite-induced IgE against CCDs might account largely for high IgE levels to peanut in our study population of Ghanaian schoolchildren. No evidence of IgE-mediated peanut allergy was found.

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.

Understanding the health system utilisation and reasons for avoidable mortality after fatal injury within a Three-Delays framework in Karonga, Northern Malawi: a retrospective analysis of verbal autopsy data.

OBJECTIVES: To use verbal autopsy (VA) data to understand health system utilisation and the potential avoidability associated with fatal injury. Then to categorise any evident barriers driving avoidable delays to care within a Three-Delays framework that considers delays to seeking (Delay 1), reaching (Delay 2) or receiving (Delay 3) quality injury care. DESIGN: Retrospective analysis of existing VA data routinely collected by a demographic surveillance site. SETTING: Karonga Health and Demographic Surveillance Site (HDSS) population, Northern Malawi. PARTICIPANTS: Fatally injured members of the HDSS. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of fatal injury deaths that were potentially avoidable. Secondary outcomes were the delay stage and corresponding barriers associated with avoidable deaths and the health system utilisation for fatal injuries within the health system. RESULTS: Of the 252 deaths due to external causes, 185 injury-related deaths were analysed. Deaths were predominantly among young males (median age 30, IQR 11-48), 71.9% (133/185). 35.1% (65/185) were assessed as potentially avoidable. Delay 1 was implicated in 30.8% (20/65) of potentially avoidable deaths, Delay 2 in 61.5% (40/65) and Delay 3 in 75.4% (49/65). Within Delay 1, 'healthcare literacy' was most commonly implicated barrier in 75% (15/20). Within Delay 2, 'communication' and 'prehospital care' were the most commonly implicated in 92.5% (37/40). Within Delay 3, 'physical resources' were most commonly implicated, 85.7% (42/49). CONCLUSIONS: VA is feasible for studying pathways to care and health system responsiveness in avoidable deaths following injury and ascertaining the delays that contribute to deaths. A large proportion of injury deaths were avoidable, and we have identified several barriers as potential targets for intervention. Refining and integrating VA with other health system assessment methods is likely necessary to holistically understand an injury care health system.

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.

Prevalence of Endemic Respiratory Viruses During the COVID-19 Pandemic in Urban and Rural Malawi.

Background: We investigated endemic respiratory virus circulation patterns in Malawi, where no lockdown was imposed, during the COVID-19 pandemic. Methods: Within a prospective household cohort in urban and rural Malawi, adult participants provided upper respiratory tract (URT) samples at 4 time points between February 2021 and April 2022. Polymerase chain reaction (PCR) was performed for SARS-CoV-2, influenza, and other endemic respiratory viruses. Results: 1626 URT samples from 945 participants in 542 households were included. Overall, 7.6% (n = 123) samples were PCR- positive for >1 respiratory virus; SARS-CoV-2 (4.4%) and rhinovirus (2.0%) were most common. No influenza A virus was detected. Influenza B and respiratory syncytial virus (RSV) were rare. Higher virus positivity were detected in the rural setting and at earlier time points. Coinfections were infrequent. Conclusions: Endemic respiratory viruses circulated in the community in Malawi during the pandemic, though influenza and RSV were rarely detected. Distinct differences in virus positivity and demographics were observed between urban and rural cohorts.

Novel application of multi-facility process map analysis for rapid injury care health system assessment in Northern Malawi.

OBJECTIVES: We used the process mapping method and Three Delays framework, to identify and visually represent the relationship between critical actions, decisions and barriers to access to care following injury in the Karonga health system, Northern Malawi. DESIGN: Facilitated group process mapping workshops with summary process mapping synthesis. SETTING: Process mapping workshops took place in 11 identified health system facilities (one per facility) providing injury care for a population in Karonga, Northern Malawi. PARTICIPANTS: Fifty-four healthcare workers from various cadres took part. RESULTS: An overall injury health system summary map was created using those categories of action, decision and barrier that were sometimes or frequently reported. This provided a visual summary of the process following injury within the health system. For Delay 1 (seeking care) four barriers were most commonly described (by 8 of 11 facilities) these were 'cultural norms', 'healthcare literacy', 'traditional healers' and 'police processes'. For Delay 2 (reaching care) the barrier most frequently described was 'transport'-a lack of timely affordable emergency transport (formal or informal) described by all 11 facilities. For Delay 3 (receiving quality care) the most commonly reported barrier was that of 'physical resources' (9 of 11 facilities). CONCLUSIONS: We found our novel approach combining several process mapping exercises to produce a summary map to be highly suited to rapid health system assessment identifying barriers to injury care, within a Three Delays framework. We commend the approach to others wishing to conduct rapid health system assessments in similar contexts.

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.