Effects of Host Genetic Polymorphisms on the Efficacy of the Radical Cure Malaria Drug Primaquine

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.21-1115 ◽

2022 ◽

Author(s):

Minu Nain ◽

Mradul Mohan ◽

Amit Sharma

Keyword(s):

Cytochrome P450 ◽

Genetic Polymorphisms ◽

Low Income ◽

Malaria Elimination ◽

Active Form ◽

Drug Efficacy ◽

Population Based ◽

Low Income Countries ◽

Radical Cure ◽

Host Genes

Malaria is a major cause of death in low-income countries. Malaria relapses are caused by Plasmodium vivax–induced latent liver stage hypnozoites, and relapses contribute significantly to the total disease burden. The goal of malaria elimination is threatened in countries where P. vivax is endemic and relapses remain a key aspect of concern. Targeting of the hypnozoites is crucial for radical cure and this is achieved by primaquine (PQ). In addition to its anti-hypnozoite effects, PQ also possesses gametocidal activity against all malaria causing Plasmodium species and is hence a useful tool to curtail malaria transmission. It is well known that host glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with hemolysis after treatment with PQ. Multiple other host polymorphisms impact on PQ metabolism, potentially affecting drug efficacy. Being a prodrug, PQ requires host factors cytochrome P450 2D6 (CYP2D6), cytochrome P450 NADPH: oxidoreductase (CPR) and monoamine oxidase (MAO) for its metabolism and conversion to active form. The efficacy of PQ in the host is therefore dependent on genetic polymorphisms of these three host genes. The efficacy of PQ is important for clearing reservoirs of P. vivax infection. Here, we have analyzed the known spectrum of genetic polymorphisms for host genes that enable PQ metabolism. It is vital to delineate the polymorphisms that determine the ultimate efficacy of PQ for formulating better malaria elimination strategies in countries with severe malaria burden. Thus population-based studies of these gene variants will provide new insights into the role of host genetics on PQ treatment outcomes.

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Quantifying the under-estimation of cervical Cancer in remote regions of Tanzania

BMC Cancer ◽

10.1186/s12885-020-07439-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Mariah P. Gesink ◽

Robert M. Chamberlain ◽

Julius Mwaiselage ◽

Crispin Kahesa ◽

Kahima Jackson ◽

...

Keyword(s):

Cervical Cancer ◽

Low Income ◽

Population Based ◽

Capital City ◽

Low Income Countries ◽

Treatment Center ◽

Large Country ◽

Number Of Patients ◽

Sub Saharan ◽

Radiotherapy Treatment

Abstract Background Cervical cancer is the most common cancer among women in Sub-Saharan countries, including Tanzania. While early detection and diagnosis are available in some parts of this large country, radiotherapy has been only available at the Ocean Road Cancer Institute (ORCI), in the capital city of Dar es Salaam and is just starting in a few regions. Methods The objective of this study was to compare the observed incidence of cervical cancer for the two remote regions of Mwanza in western Tanzania and Mbeya in southern Tanzania, based on their patients treated at the ORCI from 2011 to 2014. Results: The number patients referred and treated at ORCI were (120 from Mwanza, and 171 from Mbeya, representing 24.6 and 32.8% of the patients histopathologically confirmed in the two sites, respectively. The results showed significant underestimation of cervical cancer in the two regions. The vast majority of patients who were histopathologically-confirmed in their local regions (73.92% from Mwanza and 65.1% from Mbeya), but did not receive the needed radiotherapy treatment at the ORCI. The estimated incidence for the two regions based on the number of patients treated at the ORCI were underestimated by 53.9% for Mwanza and 68.9% for Mbeya. Conclusions Local establishment of radiotherapy treatment facilities in remote regions in Tanzania and similar other low-income countries is essential for providing effective treatment and improving survival of diagnosed cervical cancer patients. Linkage between the records of local remote hospitals and the main cancer treatment center in the capital city can also help support the emerging the population-based cancer registry at ORCI.

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Time trends and sociodemographic determinants of preterm births in pregnancy cohorts in Matlab, Bangladesh, 1990–2014

BMJ Global Health ◽

10.1136/bmjgh-2019-001462 ◽

2019 ◽

Vol 4 (4) ◽

pp. e001462 ◽

Cited By ~ 8

Author(s):

Anisur Rahman ◽

Monjur Rahman ◽

Jesmin Pervin ◽

Abdur Razzaque ◽

Shaki Aktar ◽

...

Keyword(s):

Seasonal Variation ◽

Preterm Birth ◽

Low Income ◽

Time Trends ◽

Maternal Education ◽

Preterm Births ◽

Population Based ◽

Low Income Countries ◽

Sociodemographic Determinants ◽

Gestational Age At Birth

IntroductionPreterm birth is the major cause of under-five mortality. Population-based data on determinants and proportions of children born preterm are limited, especially from low-income countries. This study aimed at assessing time trends and social, reproductive and environmental determinants of preterm births based on a population-based pregnancy cohort over 25 years in rural Bangladesh.MethodsIn this cohort study in Matlab, a rural area in Bangladesh, we used data from the Health and Demographic Surveillance System from 1990 to 2014. Gestational age at birth was based on the reported last menstrual period and verified by ultrasound assessments. Preterm birth proportions were assessed within strata of social and reproductive characteristics, and time series analysis was performed with decomposition for trend and seasonality. We also determined the prevented fractions of preterm birth reduction associated with social and demographic changes during the follow-up period.ResultsAnalyses were based on 63 063 live births. Preterm birth decreased from 29% (95% CI 28.6 to 30.1) in 1990–1994 to 11% (95% CI 10.5 to 11.6) in 2010–2014. Low education, older age and multi-parity were associated with higher proportions of preterm births across the study period. Preterm births had a marked seasonal variation. A rapid increase in women’s educational level and decrease in parity were associated with the decline in preterm births, and 27% of the reduction observed from 1990 to 2014 could be attributed to these educational and reproductive changes.ConclusionThe reduction in preterm birth was to a large extent associated with the sociodemographic transition, especially changes in maternal education and parity. The persistent seasonal variation in the proportion of preterm birth may reflect the environmental stressors for pregnant women across the study period. Continued investments in girls’ education and family planning programmes may contribute to further reduction of preterm births in Bangladesh.

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Improving access to healthcare for women in Tanzania by addressing socioeconomic determinants and health insurance: a population-based cross-sectional survey

BMJ Open ◽

10.1136/bmjopen-2018-023013 ◽

2018 ◽

Vol 8 (9) ◽

pp. e023013 ◽

Cited By ~ 6

Author(s):

Deogratius Bintabara ◽

Keiko Nakamura ◽

Kaoruko Seino

Keyword(s):

Health Insurance ◽

Low Income ◽

Formal Education ◽

Wealth Index ◽

Population Based ◽

Reproductive Age ◽

Low Income Countries ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Low Income Country

ObjectiveThis study was performed to explore the factors associated with accumulation of multiple problems in accessing healthcare among women in Tanzania as an example of a low-income country.DesignPopulation-based cross-sectional survey.SettingNationwide representative data for women of reproductive age obtained from the 2015–2016 Tanzania Demographic and Health Survey were analysed.Primary outcome measuresA composite variable, ‘problems in accessing healthcare’, with five (1-5) categories was created based on the number of problems reported: obtaining permission to go to the doctor, obtaining money to pay for advice or treatment, distance to a health facility and not wanting to go alone. Respondents who reported fewer or more problems placed in lower and higher categories, respectively.ResultsA total of 13 266 women aged 15–49 years, with a median age (IQR) of 27 (20–36) years were interviewed and included in the analysis. About two-thirds (65.53%) of the respondents reported at least one of the four major problems in accessing healthcare. Furthermore, after controlling for other variables included in the final model, women without any type of health insurance, those belonging to the poorest class according to the wealth index, those who had not attended any type of formal education, those who were not employed for cash, each year of increasing age and those who were divorced, separated or widowed were associated with greater problems in accessing healthcare.ConclusionThis study indicated the additive effects of barriers to healthcare in low-income countries such as Tanzania. Based on these results, improving uptake of health insurance and addressing social determinants of health are the first steps towards reducing women’s problems associated with accessing healthcare.

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The burden of serious health-related suffering among cancer decedents: Global projections study to 2060

Palliative Medicine ◽

10.1177/0269216320957561 ◽

2020 ◽

pp. 026921632095756

Author(s):

Katherine E Sleeman ◽

Barbara Gomes ◽

Maja de Brito ◽

Omar Shamieh ◽

Richard Harding

Keyword(s):

Palliative Care ◽

Low Income ◽

Population Based ◽

World Health ◽

Low Income Countries ◽

Cancer Type ◽

Middle Income ◽

Middle Income Countries ◽

Health Related ◽

Health Organization

Background: Palliative care improves outcomes for people with cancer, but in many countries access remains poor. Understanding future needs is essential for effective health system planning in response to global policy. Aim: To project the burden of serious health-related suffering associated with death from cancer to 2060 by age, gender, cancer type and World Bank income region. Design: Population-based projections study. Global projections of palliative care need were derived by combining World Health Organization cancer mortality projections (2016–2060) with estimates of serious health-related suffering among cancer decedents. Results: By 2060, serious health-related suffering will be experienced by 16.3 million people dying with cancer each year (compared to 7.8 million in 2016). Serious health-related suffering among cancer decedents will increase more quickly in low income countries (407% increase 2016–2060) compared to lower-middle, upper-middle and high income countries (168%, 96% and 39% increase 2016-2060, respectively). By 2060, 67% of people who die with cancer and experience serious health-related suffering will be over 70 years old, compared to 47% in 2016. In high and upper-middle income countries, lung cancer will be the single greatest contributor to the burden of serious health-related suffering among cancer decedents. In low and lower-middle income countries, breast cancer will be the single greatest contributor. Conclusions: Many people with cancer will die with unnecessary suffering unless there is expansion of palliative care integration into cancer programmes. Failure to do this will be damaging for the individuals affected and the health systems within which they are treated.

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Curtailing Covid-19 on a Dollar-a-Day in Malawi: Implications for the Ongoing Pandemic

10.1101/2021.03.16.21253632 ◽

2021 ◽

Author(s):

Iliana V. Kohler ◽

Fabrice Kämpfen ◽

Alberto Ciancio ◽

James Mwera ◽

Victor Mwapasa ◽

...

Keyword(s):

Public Health ◽

Low Income ◽

Population Based ◽

Community Leadership ◽

Pivotal Role ◽

Low Income Countries ◽

Effective Response ◽

Trust In Institutions ◽

Primary Prevention Strategy ◽

Sub Saharan

AbstractUtilizing population-based data from the Covid-19 phone survey (N = 2, 262) of the Malawi Longitudinal Study of Families and Health (MLSFH) collected during June 2nd–August 17th, 2020, we investigate behavioral, economic and social responses to Covid-19 and focus on the crucial role that community leadership and trust in institutions play towards shaping these responses. We argue that the effective response of Malawi to limit the spread of the virus was facilitated by the engagement of local leaders to mobilize communities to adapt and adhere to Covid-19 prevention strategies. Village heads (VHs) played pivotal role in shaping individual’s knowledge about the pandemic and the adaption of preventive health behaviors and were crucial for mitigating the negative economic and health consequences of the pandemic. We further show that trust in institutions is of particular importance in shaping individuals’ behavior during the pandemic, and these findings highlight the pivotal role of community leadership in fostering better compliance and adoption of public health measures essential to contain the virus. Overall, our findings point to distinctive patterns of pandemic response in a low-income sub-Saharan African rural population that emphasized local leadership as mediators of public health messages and policies. These lessons from the first pandemic wave remain relevant as in many low-income countries behavioral responses to Covid-19 will remain the primary prevention strategy for a foreseeable future.

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General Healthcare Utilization and Out-of-Pocket Expenditures Associated with Depression in Adults: A Cross-Sectional Analysis in Nepal

10.21203/rs.2.14587/v1 ◽

2019 ◽

Author(s):

Selina Rajan ◽

Sujit D Rathod ◽

Nagendra P Luitel ◽

Adrianna Murphy ◽

Tessa Roberts ◽

...

Keyword(s):

Healthcare Utilization ◽

Low Income ◽

Negative Binomial ◽

Mental Healthcare ◽

Negative Binomial Regression ◽

Population Based ◽

Low Income Countries ◽

Cross Sectional ◽

Universal Healthcare ◽

Probable Depression

Abstract Background: Despite attempts to improve universal healthcare coverage (UHC) in low income countries like Nepal, most healthcare utilization is still financed by out-of-pocket (OOP) payments, with detrimental effects on the poorest and most in need. Evidence from high income countries shows that depression is associated with increased healthcare utilization, which may lead to increased OOP expenditures, placing greater stress on families. To inform policies for integrating mental healthcare into UHC in LMIC, we must understand general healthcare utilization and OOP expenditure patterns in people with depression. Aims: We examined associations between symptoms of depression and frequency and type of general healthcare utilization and OOP expenditure among adults in Chitwan District, Nepal. Methods: We analysed data from a population-based survey of 2040 adults in 2013, who completed the PHQ-9 screening tool for depression and answered questions about general healthcare utilization. We modelled associations between increasing PHQ-9 score and healthcare utilization frequency and OOP expenditure using negative binomial regression. We also compared sector-specific utilization of outpatient healthcare and their related costs among adults with and without probable depression, determined by a PHQ-9 score of 10 or more. Results: We classified 80 (3.6%) participants with probable depression, 70.9% of whom used some form of general healthcare in the past year compared to 43.9% of people without probable depression. Mean annual OOP healthcare expenditures were $118 USD in people with probable depression, compared to $110 USD in people without. With each unit increase in PHQ-9 score, there was a 14% increase in total healthcare visits (95% CI 7%-22%, p<0.0001) and $9 USD increase in OOP expenditures (95% CI $2-$17; p<0.0001). People with depression sought most general healthcare from pharmacists (30.1%) but reported the greatest expenditure on specialist doctors ($36 USD). Conclusions: In this population-based sample from Central Nepal, we identified dose-dependent increases in healthcare utilization and OOP expenditure with increasing PHQ-9 scores. Strengthening UHC to include early detection and treatment for people affected by depression as an integrated component of general healthcare should lead to a reduction in financial pressures on families, which is likely to reduce the incidence of depression in Nepal.

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Healthcare Utilization and Out-of-Pocket Expenditures Associated with Depression in Adults: A Cross-Sectional Analysis in Nepal

10.21203/rs.2.14587/v2 ◽

2019 ◽

Author(s):

Selina Rajan ◽

Sujit D Rathod ◽

Nagendra P Luitel ◽

Adrianna Murphy ◽

Tessa Roberts ◽

...

Keyword(s):

Healthcare Utilization ◽

Low Income ◽

Negative Binomial ◽

Mental Healthcare ◽

Negative Binomial Regression ◽

Population Based ◽

Low Income Countries ◽

Cross Sectional ◽

Universal Healthcare ◽

Probable Depression

Abstract Background: Despite attempts to improve universal healthcare coverage (UHC) in low income countries like Nepal, most healthcare utilization is still financed by out-of-pocket (OOP) payments, with detrimental effects on the poorest and most in need. Evidence from high income countries shows that depression is associated with increased healthcare utilization, which may lead to increased OOP expenditures, placing greater stress on families. To inform policies for integrating mental healthcare into UHC in LMIC, we must understand healthcare utilization and OOP expenditure patterns in people with depression. Aims: We examined associations between symptoms of depression and frequency and type of healthcare utilization and OOP expenditure among adults in Chitwan District, Nepal. Methods: We analysed data from a population-based survey of 2040 adults in 2013, who completed the PHQ-9 screening tool for depression and answered questions about healthcare utilization. We modelled associations between increasing PHQ-9 score and healthcare utilization frequency and OOP expenditure using negative binomial regression. We also compared sector-specific utilization of outpatient healthcare and their related costs among adults with and without probable depression, determined by a PHQ-9 score of 10 or more. Results: We classified 80 (3.6%) participants with probable depression, 70.9% of whom used some form of healthcare in the past year compared to 43.9% of people without probable depression. Mean annual OOP healthcare expenditures were $118 USD in people with probable depression, compared to $110 USD in people without. With each unit increase in PHQ-9 score, there was a 14% increase in total healthcare visits (95% CI 7%-22%, p<0.0001) and $9 USD increase in OOP expenditures (95% CI $2-$17; p<0.0001). People with depression sought most healthcare from pharmacists (30.1%) but reported the greatest expenditure on specialist doctors ($36 USD). Conclusions: In this population-based sample from Central Nepal, we identified dose-dependent increases in healthcare utilization and OOP expenditure with increasing PHQ-9 scores. Strengthening UHC to include early detection and treatment for people affected by depression as an integrated component of healthcare should lead to a reduction in financial pressures on families, which is likely to reduce the incidence of depression in Nepal.

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