The role of men in promoting women’s reproductive and maternal health in a matrilineal marriage system in Malawi: the case of Ntchisi District

Philosophiae Doctor - PhDThis research explored the role of men in efforts by the Malawi Ministry of Health to promote women’s reproductive and maternal health in accordance with Millennium Development Goal (MDG) number five, i.e. to reduce the maternal mortality ratio by three quarters between 1990 and 2015. The study was conceptualised in 2011 in an effort to contribute to the national strategy to reduce maternal mortality in Malawi, and it was done in the particular cultural context of a matrilineal marriage and kinship system in Ntchisi district, Malawi. At the inception of this study, the highest prevalence of maternal deaths in the country was reported in seven districts, including Ntchisi. A common understanding in public health circles worldwide is that male involvement in reproductive and maternal health activities is an important factor in achieving the above MDG goal. But historically, research on maternal health in Malawi has focused mostly on women and children. Consequently there are only a small number of relevant previous studies or extant literature to draw on for the current investigation. Malawi’s reproductive and maternal health policies largely lack locally-informed research on men and masculinities. My study aimed to explore the relationship between local constructions of masculinity, fatherhood and reproductive health in Malawi among Chichewa speakers who live in Ntchisi. It was guided by the social constructionist theory which recognises the role of the impersonal features of the social world like cultural, personal and group influences in the construction of ideas, knowledge and facts. In this study I adopted an inductive approach to learning in which the participants were the main players in describing and explaining social phenomena as they are constructed and experienced in the research site. I conducted multiple in-depth interviews and focus group discussions with 53 married men, key informant interviews with eight local leaders and traditional birth attendants, as well as focus group discussions with 12 married women who had given birth multiple times. Data analysis involved intensive scrutiny of transcripts to determine prevailing themes. Listening to the tapes and re-reading these transcripts enabled me to detect patterns and categorise different practices and constructions, to find associations between these practices and constructions of concepts. Malawi’s men are considered to be the traditional gatekeepers of maternal and social ideals. Therefore, as elders in a clan or as husbands, their prompt decisions can facilitate the access of their spouses to maternal and reproductive health services. Men as heads of households and decision makers can also support and enable their wives to follow the recommended maternal health counsel. However, men’s “lack of involvement” is not the principal reason why there is increasing maternal challenges among child-bearing women in Ntchisi. Although men are not entirely free of the blame for contributing to the status quo, they already work hard towards ensuring positive pregnancy outcomes for their spouses. The study found that husbands in Ntchisi have long been involved in pregnancy and child care. The study shows that pregnancy is regarded as a liminal state or as a kind of “sickness”. Male involvement in pregnancy means the man should take over the routine household chores of drawing water, fetching firewood and cooking, among other things. However, men construct their involvement in reproductive and maternal health matters in the framework of masculinity and femininity as dictated by the commonly held beliefs of a matrilineal Chewa grouping. The study showed that masculinities are constructed within the context of a matrilineal system, which has nonetheless been changing largely due to the colonial impact of the United Kingdom, the related influences of Christian and westernised social ideals and an education system based on the British model. Men’s gendered practices in reproduction and parenting have foundations in the initiation rites of the secret Nyau societies where the masculine ideals of sexuality and secrecy are inculcated. This research cannot be generally extrapolated to the wider population in Malawi but it is a starting point for understanding the responses of matrilineal Chichewa speaking men to reproductive and maternal health matters. Further and broader research on the construction of fatherhood and masculinity is needed in Malawi to make it possible for public health policy on reproductive and maternal health to be more culturally informed

Risk Factors for High Early Mortality in Patients on Antiretroviral Treatment in a Rural District of Malawi.

OBJECTIVES: Among adults started on antiretroviral treatment (ART) in a rural district hospital (a) to determine the cumulative proportion of deaths that occur within 3 and 6 months of starting ART, and (b) to identify risk factors that may be associated with such mortality. DESIGN AND SETTING: A cross-sectional analytical study set in Thyolo district, Malawi. METHODS: Over a 2-year period (April 2003 to April 2005) mortality within the first 3 and 6 months of starting ART was determined and risk factors were examined. RESULTS: A total of 1507 individuals (517 men and 990 women), whose median age was 35 years were included in the study. There were a total of 190 (12.6%) deaths on ART of which 116 (61%) occurred within the first 3 months (very early mortality) and 150 (79%) during the first 6 months of initiating ART. Significant risk factors associated with such mortality included WHO stage IV disease, a baseline CD4 cell count under 50 cells/mul and increasing grades of malnutrition. A linear trend in mortality was observed with increasing grades of malnutrition (chi for trend = 96.1, P </= 0.001) and decreasing CD4 cell counts (chi for trend = 72.4, P </= 0.001). Individuals who were severely malnourished [body mass index (BMI) < 16.0 kg/m] had a six times higher risk of dying in the first 3 months than those with a normal nutritional status. CONCLUSIONS: Among individuals starting ART, the BMI and clinical staging could be important screening tools for use to identify and target individuals who, despite ART, are still at a high risk of early death

Impact of Dolutegravir-Based Antiretroviral Therapy on Piperaquine Exposure following Dihydroartemisinin-Piperaquine Intermittent Preventive Treatment of Malaria in Pregnant Women Living with HIV

Dihydroartemisinin-piperaquine, an artemisinin-based combination therapy, has been identified as a promising agent for intermittent preventive treatment of malaria in pregnancy. However, in pregnant women living with HIV (PLWH), efavirenz-based antiretroviral therapy (ART) significantly reduces the plasma exposure of piperaquine. In an open-label, nonrandomized, fixed-sequence, pharmacokinetic study, we compared piperaquine plasma concentrations in 13 pregnant women during a 3-day treatment course of dihydroartemisinin-piperaquine when coadministered with efavirenz-based versus dolutegravir-based ART in the second or third trimester of pregnancy. Piperaquine concentrations were measured over a 28-day period, while on efavirenz-based ART and after switching to dolutegravir-based ART. Noncompartmental analysis was performed, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were generated to compare piperaquine pharmacokinetic parameters between these two treatment periods. Compared with efavirenz-based ART, coadministration of dihydroartemisinin-piperaquine and dolutegravir-based ART resulted in a 57% higher overall piperaquine exposure (area under the concentration-time curve from 0 to 672 h [AUC0-672 h]) (GMR, 1.57; 90% CI, 1.28 to 1.93). Piperaquine's day 7 concentrations were also 63% higher (GMR, 1.63; 90% CI, 1.29 to 2.11), while day 28 concentrations were nearly three times higher (GMR, 2.96; 90% CI, 2.25 to 4.07). However, the maximum piperaquine concentration (Cmax) remained similar (GMR, 1.09; 90% CI, 0.79 to 1.49). Dihydroartemisinin-piperaquine was well tolerated, with no medication-related serious adverse events observed in this small study. Compared with efavirenz-based ART, a known inducer of piperaquine metabolism, dolutegravir-based ART resulted in increased overall piperaquine exposure with pharmacokinetic parameter values that were similar to those published previously for pregnant and nonpregnant women. Our findings suggest that the efficacy of dihydroartemisinin-piperaquine will be retained in pregnant women on dolutegravir. (The study was registered on PACTR.samrc.ac.za [PACTR201910580840196].). Erratum: In Fig.2 and Fig. S1, the first value on the y axis should read as “1” instead of “0.

Impact of Dolutegravir-Based Antiretroviral Therapy on Piperaquine Exposure following Dihydroartemisinin-Piperaquine Intermittent Preventive Treatment of Malaria in Pregnant Women Living with HIV.

Dihydroartemisinin-piperaquine, an artemisinin-based combination therapy, has been identified as a promising agent for intermittent preventive treatment of malaria in pregnancy. However, in pregnant women living with HIV (PLWH), efavirenz-based antiretroviral therapy (ART) significantly reduces the plasma exposure of piperaquine. In an open-label, nonrandomized, fixed-sequence, pharmacokinetic study, we compared piperaquine plasma concentrations in 13 pregnant women during a 3-day treatment course of dihydroartemisinin-piperaquine when coadministered with efavirenz-based versus dolutegravir-based ART in the second or third trimester of pregnancy. Piperaquine concentrations were measured over a 28-day period, while on efavirenz-based ART and after switching to dolutegravir-based ART. Noncompartmental analysis was performed, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were generated to compare piperaquine pharmacokinetic parameters between these two treatment periods. Compared with efavirenz-based ART, coadministration of dihydroartemisinin-piperaquine and dolutegravir-based ART resulted in a 57% higher overall piperaquine exposure (area under the concentration-time curve from 0 to 672 h [AUC ]) (GMR, 1.57; 90% CI, 1.28 to 1.93). Piperaquine's day 7 concentrations were also 63% higher (GMR, 1.63; 90% CI, 1.29 to 2.11), while day 28 concentrations were nearly three times higher (GMR, 2.96; 90% CI, 2.25 to 4.07). However, the maximum piperaquine concentration ( ) remained similar (GMR, 1.09; 90% CI, 0.79 to 1.49). Dihydroartemisinin-piperaquine was well tolerated, with no medication-related serious adverse events observed in this small study. Compared with efavirenz-based ART, a known inducer of piperaquine metabolism, dolutegravir-based ART resulted in increased overall piperaquine exposure with pharmacokinetic parameter values that were similar to those published previously for pregnant and nonpregnant women. Our findings suggest that the efficacy of dihydroartemisinin-piperaquine will be retained in pregnant women on dolutegravir

The Malawi National Tuberculosis Programme: an equity analysis

<p>Abstract</p> <p>Background</p> <p>Until 2005, the Malawi National Tuberculosis Control Programme had been implemented as a vertical programme. Working within the Sector Wide Approach (SWAp) provides a new environment and new opportunities for monitoring the equity performance of the programme. This paper synthesizes what is known on equity and TB in Malawi and highlights areas for further action and advocacy.</p> <p>Methods</p> <p>A synthesis of a wide range of published and unpublished reports and studies using a variety of methodological approaches was undertaken and complemented by additional analysis of routine data on access to TB services. The analysis and recommendations were developed, through consultation with key stakeholders in Malawi and a review of the international literature.</p> <p>Results</p> <p>The lack of a prevalence survey severely limits the epidemiological knowledge base on TB and vulnerability. TB cases have increased rapidly from 5,334 in 1985 to 28,000 in 2006. This increase has been attributed to HIV/AIDS; 77% of TB patients are HIV positive. The age/gender breakdown of TB notification cases mirrors the HIV epidemic with higher rates amongst younger women and older men. The WHO estimates that only 48% of TB cases are detected in Malawi. The complexity of TB diagnosis requires repeated visits, long queues, and delays in sending results. This reduces poor women and men's ability to access and adhere to services. The costs of seeking TB care are high for poor women and men – up to 240% of monthly income as compared to 126% of monthly income for the non-poor. The TB Control Programme has attempted to increase access to TB services for vulnerable groups through community outreach activities, decentralising DOT and linking with HIV services.</p> <p>Conclusion</p> <p>The Programme of Work which is being delivered through the SWAp is a good opportunity to enhance equity and pro-poor health services. The major challenge is to increase case detection, especially amongst the poor, where we assume most 'missing cases' are to be found. In addition, the Programme needs a prevalence survey which will enable thorough equity monitoring and the development of responsive interventions to promote service access amongst 'missing' women, men, boys and girls.</p

Impact of dolutegravir-based antiretroviral therapy on piperaquine exposure following dihydroartemisinin-piperaquine intermittent preventive treatment of malaria in pregnant women living with HIV

Dihydroartemisinin-piperaquine, an artemisinin-based combination therapy, has been identified as a promising agent for intermittent preventive treatment of malaria in pregnancy. However, in pregnant women living with HIV (PLWH), efavirenz-based antiretroviral therapy (ART) significantly reduces the plasma exposure of piperaquine. In an open-label, nonrandomized, fixed-sequence, pharmacokinetic study, we compared piperaquine plasma concentrations in 13 pregnant women during a 3-day treatment course of dihydroartemisinin-piperaquine when coadministered with efavirenz-based versus dolutegravir-based ART in the second or third trimester of pregnancy. Piperaquine concentrations were measured over a 28-day period, while on efavirenz-based ART and after switching to dolutegravir-based ART. Noncompartmental analysis was performed, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were generated to compare piperaquine pharmacokinetic parameters between these two treatment periods. Compared with efavirenz-based ART, coadministration of dihydroartemisinin-piperaquine and dolutegravir-based ART resulted in a 57% higher overall piperaquine exposure (area under the concentration-time curve from 0 to 672 h [AUC0–672 h]) (GMR, 1.57; 90% CI, 1.28 to 1.93). Piperaquine’s day 7 concentrations were also 63% higher (GMR, 1.63; 90% CI, 1.29 to 2.11), while day 28 concentrations were nearly three times higher (GMR, 2.96; 90% CI, 2.25 to 4.07). However, the maximum piperaquine concentration (Cmax) remained similar (GMR, 1.09; 90% CI, 0.79 to 1.49). Dihydroartemisinin-piperaquine was well tolerated, with no medication-related serious adverse events observed in this small study. Compared with efavirenz-based ART, a known inducer of piperaquine metabolism, dolutegravir-based ART resulted in increased overall piperaquine exposure with pharmacokinetic parameter values that were similar to those published previously for pregnant and nonpregnant women. Our findings suggest that the efficacy of dihydroartemisinin-piperaquine will be retained in pregnant women on dolutegravir. (The study was registered on PACTR.samrc.ac.za [PACTR201910580840196].

Effect of dihydroartemisinin/piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV.

BACKGROUND: In sub-Saharan Africa, the burdens of malaria and HIV infections overlap. In settings with moderate-to-high malaria transmission intensity, pregnant women living with HIV (PLWH) require both ART and malaria intermittent preventive treatment (IPTp). Dihydroartemisinin/piperaquine has been identified as a promising alternative to sulfadoxine/pyrimethamine for IPTp. However, another antimalarial drug, artesunate/amodiaquine, similar to dihydroartemisinin/piperaquine, was previously shown to reduce dolutegravir exposure in non-pregnant adults. OBJECTIVES: To investigate the effect of dihydroartemisinin/piperaquine on dolutegravir plasma exposure in pregnant women on dolutegravir-based ART. METHODS: We conducted an open-label, non-randomized, fixed-sequence, pharmacokinetic study in PLWH in Malawi. Dolutegravir concentrations were measured over a 24 h period, before and after the recommended 3 day treatment dose of dihydroartemisinin/piperaquine in 12 pregnant women in their second or third trimester. Non-compartmental analysis was performed, and geometric mean ratios (GMRs) and 90% CIs were generated to compare dolutegravir pharmacokinetic parameters between the two treatment periods. RESULTS: Co-administration of dihydroartemisinin/piperaquine and dolutegravir increased dolutegravir's overall exposure (AUC0-24) and Cmax by 30% (GMR 1.30; 90% CI 1.11-1.52) and 31% (GMR 1.31; 90% CI 1.13-1.51), respectively. The dolutegravir trough (C24) concentration increased by 42% (GMR 1.42; 90% CI 1.09-1.85). The combined treatments were well tolerated with no serious adverse events observed. CONCLUSIONS: Dihydroartemisinin/piperaquine may be administered with dolutegravir-based ART in pregnant women as the modest increase in dolutegravir exposure, similar to pharmacokinetic parameter values published previously, ensures its efficacy without any clinically significant adverse events observed in this small study

Protocol for a randomised, multicentre, four-arm, double-blinded, placebo-controlled trial to assess the benefits and safety of iron supplementation with malaria chemoprevention to children in Malawi: IRMA trial

Introduction Approximately 40% of children aged 6–59 months worldwide are anaemic. Iron-containing multiple micronutrient powders (MNPs) and iron supplements (syrup/drops) are used to combat anaemia in children in different parts of the world. However, evidence for functional benefits of iron supplementation in children is scarce, and potential risks remain poorly defined, particularly concerning diarrhoea and malaria. This trial aims to determine if: (1) the efficacy of iron supplements or MNPs (containing iron) given with malaria chemoprevention is superior to malaria chemoprevention alone, or (2) if the efficacy of malaria chemoprevention alone is superior to placebo on child cognitive development.Methods and analysis IRMA is a four-arm, parallel-group, double-blinded, placebo-controlled, triple-dummy, randomised trial in Southern Malawi. The study recruits 2168 infants aged 6 months, with an intervention period of 6 months and a post-intervention period of a further 6 months. Children are randomised into four arms: (1) No intervention (placebo); (2) malaria chemoprevention only; (3) MNPs and malaria chemoprevention; and (4) iron syrup and malaria chemoprevention. The primary outcome, cognitive development (Cognitive Composite Score (CogCS)), is measured at the end of the 6 months intervention. Secondary outcomes include CogCS at a further 6 months post-intervention, motor, language and behavioural development, physical growth and prevalence of anaemia and iron deficiency. Safety outcomes include incidence of malaria and other infections, and prevalence of malaria parasitaemia during and post-intervention period.Ethics and dissemination The trial is approved by the National Health Sciences Research Committee (#19/01/2213) (Malawi) and the Human Research Ethics Committee (WEHI: 19/012) (Australia). Written informed consent in the local language is obtained from each participant before conducting any study-related procedure. Results will be shared with the local community and internationally with academic and policy stakeholders.Trial registration number ACTRN12620000386932

A pharmacokinetic randomised interventional study to optimise dihydroartemisinin-piperaquine dosing for malaria preventive treatment in Malawian infants: A protocol for the OPTIMAL study

Background A newer malaria preventive treatment, dihydroartemisinin-piperaquine (DP), has been identified as an effective alternative to sulfadoxine-pyrimethamine, to which malaria parasites are increasingly becoming resistant. However, how best to dose DP to safely prevent malaria in infants when aligned with routine health facility visits remains unresolved. As infants are usually excluded from participating in early dose optimisation clinical trials, the present study seeks to shift the paradigm and develop optimised DP dosing strategies for malaria preventive treatment in infants. Methods A randomised, single-blind, placebo-controlled, two-arm, interventional study will be conducted in southern Malawi. At 10 weeks (2.5 months) of age, 220 eligible infants will be randomised to receive DP (intervention group, n=110) or placebo (control group, n=110) with routine vaccines. They will be followed until 12 months of age and receive three further DP or placebo treatment courses at 14 weeks, six- and nine months. Infants in the intervention group will contribute capillary samples for piperaquine concentrations pre-dose and at three-, seven-, 14- and 28-days post-DP dosing as well as capillary samples pre-dose and on day 28 post-DP to quantify malaria parasitaemia using microscopy and quantitative PCR. In the control group, infants will contribute capillary blood samples for malaria parasitaemia at the same time points as the intervention group. Malaria incidence and adverse events will be compared between the two groups. Population pharmacokinetic-pharmacodynamic modelling techniques will be applied to derive feasible, optimised, efficacious, and safe DP dosing strategies for malaria preventive treatment in infancy. Conclusions The findings will provide the much-needed evidence to inform DP dosing for malaria preventive treatment in infants when administered with routine health facility visits. Additionally, they will help inform optimal DP dosing for malaria treatment in infants. The trial was registered with the Pan African Clinical Trials Registry; (PACTR202211575727659) on 8 November 2022. Protocol version 3.1, dated 29 September 2022