High Efficacy of Two Artemisinin-Based Combinations (Artesunate + Amodiaquine and Artemether + Lumefantrine) in Caala, Central Angola.

In April 2004, 137 children 6-59 months of age with uncomplicated Plasmodium falciparum (Pf) malaria (Caala, Central Angola) were randomized to receive either artemether-lumefantrine (Coartem) or artesunate + amodiaquine (ASAQ). After 28 days of follow-up, there were 2/61 (3.2%) recurrent parasitemias in the Coartem group and 4/64 (6.2%) in the ASAQ group (P = 0.72), all classified as re-infections after PCR genotyping (cure rate = 100% [95%CI: 94-100] in both groups). Only one patient (ASAQ group) had gametocytes on day 28 versus five (Coartem) and three (ASAQ) at baseline. Compared with baseline, anemia was significantly improved after 28 days of follow-up in both groups (Coartem: from 54.1% to 13.4%; ASAQ: from 53.1% to 15.9%). Our findings are in favor of a high efficacy of both combinations in Caala. Now that Coartem has been chosen as the new first-line anti-malarial, the challenge is to insure that this drug is available and adequately used

Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.

BACKGROUND: A six-dose antimalarial regimen of artemether-lumefantrine (A/L) may soon become one of the most widely used drug combination in Africa, despite possible constraints with adherence and poor absorption due to inadequate nutrition, and a lack of pharmacokinetic and effectiveness data. METHODS: Within a trial of supervised versus unsupervised A/L treatment in a stable Ugandan Plasmodium falciparum transmission setting, plasma lumefantrine concentrations were measured in a subset of patients on day 3 (C [lum]day3) and day 7 (C [lum]day7) post-inclusion. Predictors of lumefantrine concentrations were analysed to show how both C [lum]day7 and the weight-adjusted lumefantrine dose affect 28-day recrudescence and re-infection risks. The implications of these novel findings are discussed in terms of the emergence of lumefantrine-resistant strains in Africa. RESULTS: C [lum]day3 and C [lum]day7 distributions among 241 supervised and 238 unsupervised patients were positively skewed. Unsupervised treatment and decreasing weight-adjusted lumefantrine dose were negatively associated with C [lum]day3. Unsupervised treatment and decreasing age showed strong negative associations with C [lum]day7. Both models were poorly predictive (R-squared < 0.25). There were no recrudescences in either arm, but decreasing lumefantrine dose per Kg resulted in up to 13-fold higher adjusted risks of re-infection. Re-infections occurred only among patients with C [lum]day7 below 400 ng/mL (p < 0.001). CONCLUSION: Maintaining the present six-dose regimen and ensuring high adherence and intake are essential to maximize the public health benefits of this valuable drug combination

Why do women not use antenatal services in low and middle income countries? A metasynthesis of qualitative studies

Background: Almost 50% of women in low & middle income countries (LMIC’s) don’t receive adequate antenatal care. Women’s views can offer important insights into this problem. Qualitative studies exploring inadequate use of antenatal services have been undertaken in a range of countries, but the findings are not easily transferable. We aimed to inform the development of future antenatal care programmes through a synthesis of findings in all relevant qualitative studies. Methods and Findings: Using a pre-determined search strategy, we identified robust qualitative studies reporting on the views and experiences of women in LMIC’s who received inadequate antenatal care. We used meta-ethnographic techniques to generate themes and a line of argument synthesis. We derived policy relevant hypotheses from the findings. We included 21 papers representing the views of more than 1230 women from 15 countries. Three key themes were identified: ‘Pregnancy as socially risky and physiologically healthy’; ‘Resource use and survival in conditions of extreme poverty’and ‘Not getting it right first time’. The line of argument synthesis describes a dissonance between programme design and cultural contexts that may restrict access and discourage return visits. We hypothesize that centralized, risk-focused antenatal care programmes may be at odds with the resources, beliefs and experiences of pregnant women who underuse antenatal services. Conclusions: Our findings suggest that there may be a mis-alignment between current antenatal provision and the social and cultural context of some women in LMIC’s. Antenatal care provision that is theoretically and contextually at odds with local contextual beliefs and experiences are likely to be underused, especially when attendance generates increased personal risks of lost family resource or physical danger during travel; when the promised care is not delivered due to resource constraints; and when women experience covert or overt abuse in care settings

An assessment of opportunities and challenges for public sector involvement in the maternal health voucher program in Uganda

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Continued inequities in coverage, low quality of care, and high out-of-pocket expenses for health services threaten attainment of Millennium Development Goals 4 and 5 in many sub-Saharan African countries. Existing health systems largely rely on input-based supply mechanisms that have a poor track record meeting the reproductive health needs of low-income and underserved segments of national populations. As a result, there is increased interest in and experimentation with results-based mechanisms like supply-side performance incentives to providers and demand-side vouchers that place purchasing power in the hands of low-income consumers to improve uptake of facility services and reduce the burden of out-of-pocket expenditures. This paper describes a reproductive health voucher program that contracts private facilities in Uganda and explores the policy and implementation issues associated with expansion of the program to include public sector facilities. Methods: Data presented here describes the results of interviews of six district health officers and four health facility managers purposefully selected from seven districts with the voucher program in southwestern Uganda. Interviews were transcribed and organized thematically, barriers to seeking RH care were identified, and how to address the barriers in a context where voucher coverage is incomplete as well as opportunities and challenges for expanding the program by involving public sector facilities were investigated. Results: The findings show that access to sexual and reproductive health services in southwestern Uganda is constrained by both facility and individual level factors which can be addressed by inclusion of the public facilities in the program. This will widen the geographical reach of facilities for potential clients, effectively addressing distance related barriers to access of health care services. Further, intensifying ongoing health education, continuous monitoring and evaluation, and integrating the voucher program with other services is likely to address some of the barriers. The public sector facilities were also seen as being well positioned to provide voucher services because of their countrywide reach, enhanced infrastructure, and referral networks. The voucher program also has the potential to address public sector constraints such as understaffing and supply shortages.Conclusions: Accrediting public facilities has the potential to increase voucher program coverage by reaching a wider pool of poor mothers, shortening distance to service, strengthening linkages between public and private sectors through public-private partnerships and referral systems as well as ensuring the awareness and buy-in of policy makers, which is crucial for mobilization of resources to support the sustainability of the programs. Specifically, identifying policy champions and consulting with key policy sectors is key to the successful inclusion of the public sector into the voucher program

High ANC coverage and low skilled attendance in a rural Tanzanian district: a case for implementing a birth plan intervention

BACKGROUND: In Tanzania, more than 90% of all pregnant women attend antenatal care at least once and approximately 62% four times or more, yet less than five in ten receive skilled delivery care at available health units. We conducted a qualitative study in Ngorongoro district, Northern Tanzania, in order to gain an understanding of the health systems and socio-cultural factors underlying this divergent pattern of high use of antenatal services and low use of skilled delivery care. Specifically, the study examined beliefs and behaviors related to antenatal, labor, delivery and postnatal care among the Maasai and Watemi ethnic groups. The perspectives of health care providers and traditional birth attendants on childbirth and the factors determining where women deliver were also investigated. METHODS: Twelve key informant interviews and fifteen focus group discussions were held with Maasai and Watemi women, traditional birth attendants, health care providers, and community members. Principles of the grounded theory approach were used to elicit and assess the various perspectives of each group of participants interviewed. RESULTS: The Maasai and Watemi women's preferences for a home birth and lack of planning for delivery are reinforced by the failure of health care providers to consistently communicate the importance of skilled delivery and immediate post-partum care for all women during routine antenatal visits. Husbands typically serve as gatekeepers of women's reproductive health in the two groups - including decisions about where they will deliver- yet they are rarely encouraged to attend antenatal sessions. While husbands are encouraged to participate in programs to prevent maternal-to-child transmission of HIV, messages about the importance of skilled delivery care for all women are not given emphasis. CONCLUSIONS: Increasing coverage of skilled delivery care and achieving the full implementation of Tanzania's Focused Antenatal Care Package in Ngorongoro depends upon improved training and monitoring of health care providers, and greater family participation in antenatal care visits

"Workhood"-a useful concept for the analysis of health workers' resources? an evaluation from Tanzania

International debates on improving health system performance and quality of care are strongly coined by systems thinking. There is a surprising lack of attention to the human (worker) elements. Although the central role of health workers within the health system has increasingly been acknowledged, there are hardly studies that analyze performance and quality of care from an individual perspective. Drawing on livelihood studies in health and sociological theory of capitals, this study develops and evaluates the new concept of workhood. As an analytical device the concept aims at understanding health workers' capacities to access resources (human, financial, physical, social, cultural and symbolic capital) and transfer them to the community from an individual perspective. Case studies were conducted in four Reproductive-and-Child-Health (RCH) clinics in the Kilombero Valley, south-eastern Tanzania, using different qualitative methods such as participant observation, informal discussions and in-depth interviews to explore the relevance of the different types of workhood resources for effective health service delivery. Health workers' ability to access these resources were investigated and factors facilitating or constraining access identified. The study showed that lack of physical, human, cultural and financial capital constrained health workers' capacity to act. In particular, weak health infrastructure and health system failures led to the lack of sufficient drug and supply stocks and chronic staff shortages at the health facilities. However, health workers' capacity to mobilize social, cultural and symbolic capital played a significant role in their ability to overcome work related problems. Professional and non-professional social relationships were activated in order to access drug stocks and other supplies, transport and knowledge. By evaluating the workhood concept this study highlights the importance of understanding health worker performance by looking at their resources and capacities. Rather than blaming health workers for health system failures, applying a strength-based approach offers new insights into health workers' capacities and identifies entry points for target actions

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir