Proposing the "Value- and Evidence-Based decision making and Practice" (VEDMAP) framework for Priority-Setting and knowledge translation in low and Middle-Income Countries: A novel framework for Decision-Making in Low-and middle income countries like Malawi.

The existence and availability of evidence on its own does not guarantee that the evidence will be demanded and used by decision and policy makers. Decision and policy-makers, especially in low-income settings, often confront ethical dilemmas about determining the best available evidence and its utilization. This dilemma can be in the form of conflict of evidence, scientific and ethical equipoise and competing evidence or interests. Consequently, decisions are made based on convenience, personal preference, donor requirements, and political and social considerations which can result in wastage of resources and inefficiency. To mitigate these challenges, the use of "Value- and Evidence-Based Decision Making and Practice" (VEDMAP) framework is proposed. This framework was developed by Joseph Mfutso-Bengo in 2017 through a desk review. It was pretested through a scoping study under the Thanzi la Onse (TLO) Project which assessed the feasibility and acceptability of using the VEDMAP as a priority setting tool for Health Technology Assessment (HTA) in Malawi. The study used mixed methods whereby it conducted a desk review to map out and benchmark normative values of different countries in Africa and HTA; focus group discussion and key informant interviews to map out the actual (practised) values in Malawi. The results of this review confirmed that the use of VEDMAP framework was feasible and acceptable and can bring efficiency, traceability, transparency and integrity in decision- policy making process and implementation.

COVID-19 vaccine inequity in African low-income countries.

Equitable access and utilization of the COVID-19 vaccine is the main exit strategy from the pandemic. This paper used proceedings from the Second Extraordinary Think-Tank conference, which was held by the Health Economics and Policy Unit at the Kamuzu University of Health Sciences in collaboration with the Malawi Ministry of Health, complemented by a review of literature. We found disparities in COVID-19 vaccine coverage among low-income countries. This is also the case among high income countries. The disparities are driven mainly by insufficient supply, inequitable distribution, limited production of the vaccine in low-income countries, weak health systems, high vaccine hesitancy, and vaccine misconceptions. COVID-19 vaccine inequity continues to affect the entire world with the ongoing risks of emergence of new COVID-19 variants, increased morbidity and mortality and social and economic disruptions. In order to reduce the COVID-19 vaccination inequality in low-income countries, there is need to expand COVAX facility, waive intellectual property rights, transform knowledge and technology acquired into vaccines, and conduct mass COVID-19 vaccination campaigns.

"I do lack peace, and I've run out of answers": primary caregivers' perspectives on social and behaviour problems in cerebral malaria survivors in Blantyre, Malawi.

BACKGROUND: Despite recent advances in treatment and prevention, the prevalence of cerebral malaria (CM) remains high globally, especially in children under 5 years old. As treatment improves, more children will survive episodes of CM with lasting neurodisabilities, such as social and behavioural issues. Behaviour problems in children who survive CM are poorly characterized, and the impact of caring for a child with post-CM behaviour issues has not been well-explored. Caregivers' perceptions of and experiences with their child's post-CM behaviour problems are reported here. METHODS: Semi-structured interviews were conducted with 29 primary caregivers of children who survived CM with reported behaviour issues in Blantyre, Malawi. Interviews were conducted in Chichewa, audio-recorded, transcribed, and translated into English. Data were coded manually, utilizing inductive and deductive approaches. Identified codes were thematically analysed. RESULTS: Post-CM behaviours reported include externalizing, aggressive behaviours and learning difficulties. Variable timescales for behaviour change onset were noted, and most caregivers reported some evolution of their child's behaviour over time. Caregivers experienced a variety of emotions connected to their child's behaviour and to reactions of family and community members. Caregivers who experienced discrimination were more likely to describe negative emotions tied to their child's behaviour changes, compared to caregivers who experienced support. CONCLUSIONS: Caregiver perceptions of behaviour changes in post-CM survivors are variable, and caregiver experience is strongly impacted by family and community member responses. Future educational, rehabilitation, and support-based programmes should focus on the specific types of behaviour problems identified and the difficulties faced by caregivers and their communities.

"We can't handle things we don't know about": perceived neurorehabilitation challenges for Malawian paediatric cerebral malaria survivors.

BACKGROUND: We sought to identify perceptions of neurorehabilitation challenges for paediatric cerebral malaria (CM) survivors post-hospital discharge at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi. METHODS: An exploratory approach was used to qualitatively investigate the perceived neurorehabilitation challenges for paediatric CM survivors. Data were collected through semi-structured in-depth interviews (IDIs) and focus group discussions (FGDs). Eighteen data-gathering sessions were conducted with 38 total participants, including 3 FGDs with 23 primary caregivers, 11 IDIs with healthcare workers at QECH, and 4 IDIs with community-based rehabilitation workers (CRWs). RESULTS: FGDs revealed that caregivers lack important knowledge about CM and fear recurrence of CM in their children. Post-CM children and families experience substantial stigma and sociocultural barriers to integrating into their community and accessing neurorehabilitative care. At a community-level, rehabilitation infrastructure, including trained staff, equipment, and programmes, is extremely limited. Rehabilitation services are inequitably accessible, and community-based rehabilitation remains largely unavailable. CONCLUSIONS: There is an urgent need to establish further training of rehabilitation personnel at all levels and to build accessible rehabilitation infrastructure in Malawi for post-CM patients. Additional work is required to expand this study across multiple regions for a holistic understanding of neurorehabilitation needs.

Neurodevelopmental Impairments 1 Year After Cerebral Malaria.

: media-1vid110.1542/5972295739001PEDS-VA_2018-1026Video Abstract BACKGROUND AND OBJECTIVES: Cerebral malaria (CM) causes significant mortality and morbidity in sub-Saharan African children. Reliable morbidity estimates are scarce because of methodological variability across studies. We describe the incidence, course, and severity of neurodevelopmental impairments in survivors of CM and the associated patient characteristics to inform epidemiologic estimates of malaria morbidity rates and prevention and treatment efforts. METHODS: We conducted an exposure-control study of 85 survivors of CM and 100 age-matched patients in a control group who were enrolled at hospital discharge and assessed after 1, 6, and 12 months using caregiver interviews and standardized developmental, cognitive, and behavioral measures. RESULTS: Developmental or cognitive impairment (<10th percentile of the control distribution) and/or new onset of caregiver-reported behavior problems occurred in 53% of case patients compared with 20% of the patients in the control group (odds ratio 4.5; 95% CI: 2.4 to 8.6; P < .001). In case patients, developmental or cognitive impairment at the 12-month assessment was associated with HIV-positive status and short stature at presentation, more prolonged fever and coma during admission, and severe atrophy or multifocal abnormalities being found on MRI at the 1-month assessment. CONCLUSIONS: One-half of survivors of CM were neurodevelopmentally impaired at the 1-year assessment. With these results, we support prevention trials of acute, neuroprotective interventions and the allocation of resources to evaluation, education, and rehabilitation efforts to reduce the significant long-term burden of CM-associated impairments on families and their communities.

Cognitive Outcomes and Psychiatric Symptoms of Retinopathy-Positive Cerebral Malaria: Cohort Description and Baseline Results.

Cerebral malaria (CM) is a common cause of death and disability among children in sub-Saharan Africa. Many prior studies of neuropsychiatric morbidity have been limited by a cross-sectional design or a short duration of follow-up. Most have included subjects who may have presented with coma due to a disease process other than CM. No studies have assessed the relationship between magnetic resonance imaging (MRI) findings and long-term outcomes. The Cognitive Outcomes and Psychiatric symptoms of retinopathy-positive CM (COPS) cohort is the first large (N = 221) prospectively recruited cohort of stringently defined cases of CM and hospital-based, age-matched, non-CM controls in whom cognitive and psychiatric outcomes are assessed with standardized measures semi-annually for up to 5 years. We report baseline characteristics of the cohort and outcomes at 1 month. At enrollment, CM cases were more likely to come from families with fewer socioeconomic resources and to have health characteristics that increase risk for malaria. In children younger than 5 years, cases were delayed in motor, language, and social development by approximately 6 months, compared with controls. More significant delays occurred in those with MRI abnormalities at the 1-month follow-up visit. There were no differences between cases and controls in inhibitory self-control, nor in cognitive function in children ≥ 5 years of age. The latter finding may be related to the smaller sample size, case-control imbalance in socioeconomic status, or the use of cognitive and behavioral assessments that are less culturally appropriate to this population. Continued follow-up will help determine predictors of long-term outcomes.

Maternal HIV status associated with under-five mortality in rural Northern Malawi: a prospective cohort study.

BACKGROUND: Under-five mortality is decreasing but with little change in neonatal mortality rates. We examined the effect of maternal HIV status on under-five mortality and cause of death since widespread availability of antiretroviral therapy in rural Malawi. METHODS: Children born in 2006-2011 in the Karonga demographic surveillance area were included. Maternal HIV status was available from HIV serosurveys. Age-specific mortality rate ratios for children born to HIV-positive and HIV-negative mothers were obtained by fitting a Poisson model accounting for child clustering by mother and adjusting for potential confounders. Cause of death was ascertained by verbal autopsy. FINDINGS: There were 352 deaths among 6913 under-five singleton children followed for 20,754 person-years (py), giving a mortality rate of 17.0/1000 py overall, 218/1000 py (16.5/1000 live births) in neonates, 20/1000 py (17.4/1000 live births) in postneonatal infants, and 8/1000 py in 1-4 years old. Comparing those born to HIV-positive and HIV-negative mothers, the rate ratio adjusted for child age, sex, maternal age, parity, and drinking water source was 1.5 (95% confidence interval [CI]: 0.6 to 3.7) in neonates, 11.5 (95% CI: 7.2 to 18.5) in postneonatal infants, and 4.6 (95% CI: 2.7 to 7.9) in 1-4 years old. Birth injury/asphyxia, neonatal sepsis, and prematurity contributed >70% of neonatal deaths, whereas acute infections, malaria, diarrhea, and pneumonia accounted for most deaths in older children. CONCLUSIONS: Maternal HIV status had little effect on neonatal mortality but was associated with much higher mortality in the postneonatal period and among older children. Greater attention to HIV care in pregnant women and mothers should help improve child survival, but broader interventions are needed to reduce neonatal mortality.

Measuring causes of adult mortality in rural northern Malawi over a decade of change.

BACKGROUND: Verbal autopsy could be more widely used if interpretation by computer algorithm could be relied on. We assessed how InterVA-4 results compared with clinician review in diagnosing HIV/AIDS-related deaths over the period of antiretroviral (ART) roll-out. DESIGN: In the Karonga Prevention Study demographic surveillance site in northern Malawi, all deaths are followed by verbal autopsy using a semi-structured questionnaire. Cause of death is assigned by two clinicians with a third as a tie-breaker. The clinician review diagnosis was compared with the InterVA diagnosis using the same questionnaire data, including all adult deaths from late 2002 to 2012. For both methods data on HIV status were used. ART was first available in the district from 2005, and within the demographic surveillance area from 2006. RESULTS: There were 1,637 adult deaths, with verbal autopsy data for 1,615. Adult mortality and the proportion of deaths attributable to HIV/AIDS fell dramatically following ART introduction, but for each year the proportion attributed to HIV/AIDS by InterVA was lower than that attributed by clinician review. This was partly explained by the handling of TB cases. Using clinician review as the best available 'gold standard', for those aged 15-59, the sensitivity of InterVA for HIV/AIDS deaths was 59% and specificity 88%. Grouping HIV/AIDS/TB sensitivity was 78% and specificity 83%. Sensitivity was lower after widespread ART use. CONCLUSIONS: InterVA underestimates the proportion of deaths due to HIV/AIDS. Accepting that it is unrealistic to try and differentiate TB and AIDS deaths would improve the estimates. Caution is needed in interpreting trends in causes of death as ART use may affect the performance of the algorithm.

Control of (multi)drug resistance and tuberculosis incidence over 23 years in the context of a well-supported tuberculosis programme in rural Malawi.

BACKGROUND: The rise in tuberculosis (TB) incidence following generalized HIV epidemics can overwhelm TB control programmes in resource-limited settings, sometimes accompanied by rising rates of drug resistance. This has led to claims that DOTS-based TB control has failed in such settings. However, few studies have described the effect of a sustained and well-supported DOTS programme on TB incidence and drug resistance over a long period. We present long-term trends in incidence and drug resistance in rural Malawi. METHODS: Karonga District in northern Malawi has an adult HIV prevalence of ≈ 10%. A research group, the Karonga Prevention Study, collaborates with the National Tuberculosis Programme to support core TB control activities. Bacteriological, demographic and clinical (including HIV status) information from all patients starting TB treatment in the District have been recorded since 1988. During that period isolates from each culture-positive TB patient were exported for drug sensitivity testing. Antiretroviral therapy (ART) has been widely available since 2005. RESULTS: Incidence of new smear-positive adult TB peaked at 124/100,000/year in the mid-90 s, but has since fallen to 87/100,000/year. Drug sensitivity information was available for 95% (3132/3307) of all culture-positive cases. Initial resistance to isoniazid was around 6% with no evidence of an increase. Fewer than 1% of episodes involved a multi-drug resistant strain. DISCUSSION: In this setting with a generalised HIV epidemic and medium TB burden, a well-supported DOTS programme enhanced by routine culture and drug sensitivity testing may well have reduced TB incidence and maintained drug resistance at low levels.

The impact of HIV and ART on recurrent tuberculosis in a sub-Saharan setting.

OBJECTIVE: To estimate the impact of antiretroviral therapy (ART) on the incidence of recurrent tuberculosis (TB) in an African population. DESIGN: A long-term population cohort in Karonga District, northern Malawi. METHODS: Patients who had completed treatment for laboratory-confirmed TB diagnosed since 1996 were visited annually to record vital status, ART use and screen for TB. Survival analysis estimated the effect of HIV/ART status at completion of treatment on mortality and recurrence. Analyses were stratified by time since treatment completion to estimate the effects on relapse (predominates during first year) and reinfection disease (predominates later). RESULTS: Among 1133 index TB cases contributing 4353 person-years of follow-up, there were 307 deaths and 103 laboratory-confirmed recurrences (recurrence rate 4.6 per 100 person-years). Half the recurrences occurred in the first year since completing treatment. HIV infection increased the recurrence rate [rate ratio adjusted for age, sex, period and TB type 2.69, 95% confidence interval (CI) 1.69-4.26], but with less effect in the first year (adjusted rate ratio 1.71, 95% CI 0.87-3.35) than subsequently (adjusted rate ratio 4.2, 95% CI 2.16-8.15). Recurrence rates on ART were intermediate between those of HIV-negative individuals and HIV-positive individuals without ART. Compared with HIV-positive individuals without ART, the adjusted rate ratio was 0.74 (95% CI 0.27-2.06) in the first year, and 0.43 (95% CI 0.11-1.73) later. CONCLUSION: The increased incidence of TB recurrence observed in HIV-positive patients appeared to be reduced by ART. The effects are mostly on later (likely reinfection) disease so the impact of ART on reducing recurrence will be highest in high TB incidence settings.

Profile: the Karonga Health and Demographic Surveillance System.

The Karonga Health and Demographic Surveillance System (Karonga HDSS) in northern Malawi currently has a population of more than 35 000 individuals under continuous demographic surveillance since completion of a baseline census (2002-2004). The surveillance system collects data on vital events and migration for individuals and for households. It also provides data on cause-specific mortality obtained by verbal autopsy for all age groups, and estimates rates of disease for specific presentations via linkage to clinical facility data. The Karonga HDSS provides a structure for surveys of socio-economic status, HIV sero-prevalence and incidence, sexual behaviour, fertility intentions and a sampling frame for other studies, as well as evaluating the impact of interventions, such as antiretroviral therapy and vaccination programmes. Uniquely, it relies on a network of village informants to report vital events and household moves, and furthermore is linked to an archive of biological samples and data from population surveys and other studies dating back three decades.