Barriers to accessing malaria treatment amongst school-age children in rural Malawi.

BACKGROUND: Over the last two decades, many countries have moved from malaria control toward malaria elimination. However, some sub-Saharan African countries, like Malawi, have recently seen a reversal in malaria control progress with reported increases in confirmed malaria cases. This may be the result of inadequate access to effective malaria control interventions by key population groups that perpetuate transmission. This study aimed to assess the barriers to accessing malaria treatment among school-aged children (SAC) in Malawi. METHODS: A qualitative study was conducted between September and October 2020, where data were gathered in rural Malawi using free-listing interviews, key-informant interviews, semi-structured interviews and focus group discussions. Purposively sampled participants included SAC, parents of SAC, health workers and key stakeholders at community and district levels. Interviews were digitally recorded and transcribed verbatim. Data were organized using NVivo 12 software and analysed using the thematic method. RESULTS: The study recruited 252 participants, with 156 being SAC, equally divided between boys and girls. Health system barriers to malaria treatment included long waiting hours and queues at clinics, frequent stock-outs of medical supplies, and travel time to the facility. Provider barriers included negative attitude and limited service hours. Individual and cultural barriers included fear of malaria tests and beliefs associating witchcraft as the best treatment for malaria. In addition, COVID-19-related barriers included the inability to follow preventive measures, a shift in focus from malaria to COVID-19, and fear of contracting COVID-19 and/or being tested for COVID-19 at the facility. CONCLUSIONS: This study shows most of the barriers to accessing malaria treatment among SAC are similar to those experienced by other population groups. Furthermore, COVID-19 adversely affected SAC's access to treatment. Interventions that support SAC access to prompt diagnosis and treatment are urgently needed to improve the effective control of malaria.

Determinants of pentavalent and measles vaccination dropouts among children aged 12-23 months in The Gambia.

BACKGROUND: Every year, vaccination averts about 3 million deaths from vaccine-preventable diseases (VPDs). However, despite that immunization coverage is increasing globally, many children in developing countries are still dropping out of vaccination. Thus, the present study aimed to identify determinants of vaccination dropouts among children aged 12-23 months in The Gambia. METHODS: The study utilized cross-sectional data obtained from the Gambia Demographic and Health Survey 2019-20 (GDHS). The percentage of children aged 12-23 months who dropped out from pentavalent and measles vaccination were calculated by (1) subtracting the third dose of pentavalent vaccine from the first dose of Pentavalent vaccine, and (2) subtracting the first dose of measles vaccine from the first dose Pentavalent vaccine. Generalized Estimating Equation models (GEE) were constructed to examine the risk factors of pentavalent and measles vaccinations dropout. RESULTS: Approximately 7.0% and 4.0% of the 1,302 children aged 12-23 months had dropped out of measles and pentavalent vaccination respectively. The multivariate analyses showed that when caregivers attended fewer than four antenatal care sessions, when children had no health card or whose card was lost, and resided in urban areas increased the odds of pentavalent dropout. On the other hand, when women gave birth in home and other places, when children had no health card, and being an urban areas dweller increased the odds of measles dropout. CONCLUSION: Tailored public health interventions towards urban residence and health education for all women during ANC are hereby recommended.

Determinants of self-reported correct knowledge about tuberculosis transmission among men and women in Malawi: evidence from a nationwide household survey.

BACKGROUND: Correct knowledge about transmission of tuberculosis (TB) can influence better health-seeking behaviors, and in turn, it can aid TB prevention in society. Therefore, this study aimed to examine the prevalence and predictors of self-reported correct knowledge about TB transmission among adults in Malawi. METHODS: We conducted a secondary analysis of the data obtained from the Malawi Demographic and Health Survey, 2015/16 (MDHS 2015/16). Questions regarding self-reported TB transmission were computed to evaluate the correct knowledge about TB transmission. The factors associated with the correct knowledge about Tb were assessed using univariate and multivariable logistic regression. RESULTS: Overall, the prevalence of correct knowledge about TB transmission in the general population of Malawian adults was 61.5%. Specifically, the prevalence of correct knowledge about TB transmission was 63.6 and 60.8% in men and women, respectively. Those aged 35-44 years, having secondary or high education, belonging to the richest household, being exposed to mass media, being in professional/technical/managerial, having knowledge that "TB can be cured", and those living in urban areas were significantly associated with correct knowledge about TB transmission. CONCLUSIONS: The findings of this study show that if appropriate strategies for TB communication and education to address the rural masses, young individuals, poor individuals, and individuals in the agriculture sector are put it place, can enhance TB prevention in Malawi.

Levels of knowledge regarding malaria causes, symptoms, and prevention measures among Malawian women of reproductive age.

BACKGROUND: Malawi is a malaria-endemic country and approximately 6 million cases are reported annually. Improving knowledge of malaria causes and symptoms, and the overall perception towards malaria and its preventive measures is vital for malaria control. The current study investigated the levels of knowledge of the causes, symptoms and prevention of malaria among Malawian women. METHODS: Data from the 2017 wave of the Malawi Malaria Indicator Survey (MMIS) were analysed. In total, 3422 women of reproductive age (15-49 years) were sampled and analysed. The levels of women's knowledge about: (1) causes of malaria; (2) symptoms of malaria; and, (3) preventive measures were assessed. The tertiles of the composite score were used as the cut-offs to categorize the levels of knowledge as 'low', 'medium' and 'high'. Multinomial logistic regression models were constructed to assess the independent factors while taking into account the complex survey design. RESULTS: Approximately 50% of all respondents had high levels of knowledge of causes, symptoms and preventive measures. The high level of knowledge was 45% for rural women and 55% for urban dwellers. After adjusting for the a wide range of factors, women of age group 15-19 years adjusted odds ratio ((aOR): 2.58; 95% Confidence Interval (CI) 1.69-3.92), women with no formal education (aOR: 3.73; 95% CI 2.20-6.33), women whose household had no television (aOR: 1.50; 95% CI 1.02-2.22), women who had not seen/heard malaria message (aOR: 1.53; 95% CI 1.20-1.95), women of Yao tribe (aOR: 1.95; 95% CI 1.10-3.46), and women from rural areas had low levels of knowledge about the causes of malaria, symptoms of malaria and preventive measures. Additionally, the results also showed that women aged 15-19 years (beta [ß] = - 0.73, standard error [SE] = 0.12); P < .0001, women with no formal education (ß = - 1.17, SE = 0.15); P < .0001, women whose household had no radio (ß = - 0.15, SE = 0.0816); P = 0.0715 and women who had not seen or heard malaria message (ß = - 0.41, SE = 0.07); P < .0001 were likely to have a lower knowledge score. CONCLUSIONS: The levels of malaria knowledge were reported to be unsatisfactory among adult women, underscoring the need to scale up efforts on malaria education. Beside insecticide-treated bed nets (ITNs) and prompt diagnosis, malaria can be best managed in Malawi by increasing knowledge of malaria causes, and symptoms especially for younger women, women with no formal education, women whose households have no media, women from Yao tribes, and rural dwellers.

Submicroscopic malaria infection is not associated with fever in cross-sectional studies in Malawi.

BACKGROUND: Submicroscopic Plasmodium falciparum infections are widespread in many areas. However, the contribution of these infections to symptomatic malaria is not well understood. This study evaluated whether participants with submicroscopic P. falciparum infections have higher prevalence of fever than uninfected participants in southern Malawi. METHODS: A total of 16,650 children and adults were enrolled in the course of six cross-sectional surveys during the dry season (October-November) and after the rainy season (April-May) between 2012 and 2014 in three districts in southern Malawi. Demographic and socioeconomic data were collected in conjunction with data on clinical histories, use of malaria preventive measures, and anti-malarial medication taken within 2 weeks of the survey. Axillary temperatures were measured, and blood samples were collected for P. falciparum detection by microscopy and PCR. Participants without malaria parasites detected on microscopy but with a positive PCR for P. falciparum were defined as having submicroscopic infection. Fever was defined as having any one of: reported fever in the past 2 weeks, reported fever in the past 48 h, or a temperature of ≥ 37.5 °C measured at the time of interview. RESULTS: Submicroscopic P. falciparum infections and fever were both detected in 9% of the study population. In the final analysis adjusted for clustering within household and enumeration area, having submicroscopic P. falciparum infection was associated with reduced odds of fever in the dry season (odds ratio = 0.52; 95% CI 0.33-0.82); the association in the rainy season did not achieve statistical significance (odds ratio = 1.20; 95% CI 0.91-1.59). The association between submicroscopic infection and fever was consistent across all age groups. When the definition of fever was limited to temperature of ≥ 37.5 °C measured at the time of interview, the association was not statistically significant in either the rainy or dry season. CONCLUSIONS: In this series of cross-sectional studies in southern Malawi, submicroscopic P. falciparum infection was not associated with increased risk of fever. Submicroscopic detection of the malaria parasite is important in efforts to decrease transmission but is not essential for the clinical recognition of malaria disease.

Clinical Implications of Asymptomatic Plasmodium falciparum Infections in Malawi.

Background: Asymptomatic Plasmodium falciparum infections are common in Malawi; however, the implications of these infections for the burden of malaria illness are unknown. Whether asymptomatic infections eventually progress to malaria illness, persist without causing symptoms, or clear spontaneously remains undetermined. We identified asymptomatic infections and evaluated the associations between persistent asymptomatic infections and malaria illness. Methods: Children and adults (N = 120) who presented at a health facility with uncomplicated malaria were followed monthly for 2 years. During follow-up visits, participants with malaria symptoms were tested and, if positive, treated. Samples from all visits were tested for parasites using both microscopy and polymerase chain reaction, and all malaria infections underwent genotyping. Cox frailty models were used to estimate the temporal association between asymptomatic infections and malaria illness episodes. Mixed models were used to estimate the odds of clinical symptoms associated with new versus persistent infections. Results: Participants had a median follow-up time of 720 days. Asymptomatic infections were detected during 23% of visits. Persistent asymptomatic infections were associated with decreased risk of malaria illness in all ages (hazard ratio 0.50, P < .001). When asymptomatic infections preceded malaria illness, newly-acquired infections were detected at 92% of subsequent clinical episodes, independent of presence of persistent infections. Malaria illness among children was more likely due to newly-acquired infections (odds ratio, 1.4; 95% confidence interval, 1.3-1.5) than to persistent infections. Conclusions: Asymptomatic P. falciparum infections are associated with decreased incidence of malaria illness, but do not protect against disease when new infection occurs.

Association Between Age and Plasmodium falciparum Infection Dynamics.

Few data exist on the incidence or duration of natural Plasmodium falciparum infections in high-transmission settings. School-aged children (SAC) carry a disproportionate burden of infections, suggesting either increased incidence or increased duration. We estimated the incidence and duration of unique infections according to age groups. The Mfera Cohort Study (2014-2017) in Malawi had 2 years of follow-up, with 120 participants tested monthly and during sick visits. Blood samples were collected to detect P. falciparum by microscopy and polymerase chain reaction. Positive samples underwent genotyping. Simulation was used to account for high rates of nondetection of infection among low-parasitemia infections, which increase in frequency with age. Adults had significantly fewer unique infections per person per year (median, 2.5) compared with SAC and children younger than 5 years of age (6.3 and 6.6, respectively). Over half of all genotypes were persistent. Infections lasted significantly longer in adults (median, 180 days) and SAC (median, 163 days) compared with children younger than 5 years of age (median, 97 days), after accounting for age-dependent nondetection of infection. SAC acquired new infections at the same rate as children younger than 5 years, but they maintained these infections for longer periods of time, similar to adults. This study provides new insights into P. falciparum infection dynamics that should be considered when designing malaria control strategies.

Malawi ICEMR Malaria Research: Interactions and Results Influencing Health Policies and Practices.

Malaria remains a threat to public health in Malawi. It is well acknowledged that malaria research and robust evidence can have an impact on malaria policy and practice, resulting in positive population health gains. We report policy-relevant research contributions that the Malawi International Center of Excellence for Malaria Research (ICEMR) in partnership with local and international collaborators has made. Findings from our ICEMR studies have shown that long-lasting insecticide-treated bed nets (LLINs) impregnated with piperonyl butoxide reduced mosquito blood feeding more compared with conventional LLINs. On the other hand, we showed that few LLINs are maintained up to the end of their 3-year life span, and that older nets are less effective. These results support the policy change decisions by the Malawi National Malaria Control Program to switch from conventional LLINs to piperonyl butoxide LLINs, and to conduct mass LLIN distribution campaigns every 2 years. Our studies on epidemiological patterns of malaria infection showed that school-age children have higher malaria infection rates and lower use of control measures compared with younger children and adults. These findings added to the evidence base that influenced the National Malaria Control Program to endorse school-based malaria interventions as part of its national policy. Research supported by the Malawi ICEMR is contributing to in-country policy decisions and to the implementation of evidence-based interventions. Through our long-term studies we intend to continue providing practical and policy-relevant evidence necessary, ultimately, to eliminate malaria infection in Malawi.

Understanding the Intransigence of Malaria in Malawi.

Despite the scale-up of interventions against malaria over the past decade, this disease remains a leading threat to health in Malawi. To evaluate the epidemiology of both Plasmodium falciparum infection and malaria disease, the Malawi International Center of Excellence for Malaria Research (ICEMR) has developed and implemented diverse and robust surveillance and research projects. Descriptive studies in ICEMR Phase 1 increased our understanding of the declining effectiveness of long-lasting insecticidal nets (LLINs), the role of school-age children in malaria parasite transmission, and the complexity of host-parasite interactions leading to disease. These findings informed the design of ICEMR Phase 2 to test hypotheses about LLIN use and effectiveness, vector resistance to insecticides, demographic targets of malaria control, patterns and causes of asymptomatic to life-threatening disease, and the impacts of RTS,S vaccination plus piperonyl butoxide-treated LLINs on infection and disease in young children. These investigations are helping us to understand mosquito-to-human and human-to-mosquito transmission in the context of Malawi's intransigent malaria problem.

Impact of Multiplicity of Plasmodium falciparum Infection on Clinical Disease in Malawi.

Multiplicity of infection (MOI), the number of unique Plasmodium falciparum parasite genotypes found in one infected individual, may contribute to the development of clinical malaria disease. However, the independent contribution of MOI and parasite density to clinical disease has not been well characterized. We conducted a two-year longitudinal cohort study of adults and children in a high-transmission setting in Malawi to test the hypothesis that increased MOI was independently associated with clinical disease, after accounting for parasite density. Of 1,062 episodes of infection, 477 (44.9%) were associated with symptoms. After controlling for repeated measures within an individual, key demographic factors, and parasite density, there was no association between MOI and clinical disease (OR = 1.02, 95% CI: 0.70-1.51). Although the limited ability to discern MOI in low-density asymptomatic infections may have impacted our results, we conclude that MOI is not an independent risk factor for clinical disease.

Type I Interferon Receptor Variants in Gene Regulatory Regions are Associated with Susceptibility to Cerebral Malaria in Malawi.

Cerebral malaria (CM) remains an important cause of morbidity and mortality. Risk for developing CM partially depends on host genetic factors, including variants encoded in the type I interferon (IFN) receptor 1 (IFNAR1). Type I IFNs bind to IFNAR1 resulting in increased expression of IFN responsive genes, which modulate innate and adaptive immune responses. To comprehensively study IFNAR1 genetic variant associations in Malawians with CM or uncomplicated malaria, we used a tag single nucleotide polymorphism approach, based on the HapMap Yoruba in Ibadan, Nigeria, population database. We identified three novel (rs914142, rs12626750, and rs1041867) and one previously published (Chr21:34696785 [C > G]) IFNAR1 variants to be associated with CM. Some of these variants are in gene regulatory regions. Chr21:34696785 (C > G) is in a region encoding histone modifications and transcription factor-binding sites, which suggests gene regulatory activity. Rs12626750 is predicted to bind embryonic lethal abnormal vision system-like RNA-binding protein 1, a RNA-binding protein which can increase the type I IFN response. Furthermore, we examined these variants in an expression quantitative trait loci database and found that a protective variant, rs914142, is associated with lower expression of IFNAR1, whereas the CM-associated variant rs12626750 was associated with increased IFNAR1 expression, suggesting that activation of the type I IFN pathway may contribute to pathogenesis of CM. Future functional studies of IFNAR1 variants are now needed to clarify the role of this pathway in severe malarial diseases.