Effects of an mHealth voice message service (mMitra) on maternal health knowledge and practices of low-income women in India: findings from a pseudo-randomized controlled trial.

BACKGROUND: Mobile Health (mHealth) is becoming an important tool to improve health outcomes in maternal, newborn and child health (MNCH). Studies of mHealth interventions, have demonstrated their effectiveness in improving uptake of recommended maternal services such as antenatal visits. However, evidence of impact on maternal health outcomes is still limited. METHODS: A pseudo-randomized controlled trial (single blind) was conducted to assess the impact of a voice-message based maternal intervention on maternal health knowledge, attitudes, practices and outcomes over time: Pregnancy (baseline/Time 1); Post-partum (Time 2) and when the infant turned one year old (Time 3). Women assigned to the mMitra intervention arm received gestational age- and stage-based educational voice messages via mobile phone in Hindi and Marathi, while those assigned to the control group did not. Both groups received standard care. RESULTS: Two thousand sixteen women were enrolled. Interviews were conducted with 1516 women in the intervention group and 500 women in the control group at baseline and post-partum. The intervention group performed significantly better than controls on four maternal health practice indicators: receiving the tetanus toxoid injection (OR: 1.6, 95% Confidence Interval (CI): 1.05-2.4, p = 0.028), consulting a doctor if spotting or bleeding (OR: 1.72, 95%CI: 1.07-2.75, p = 0.025), saving money for delivery expenses (OR: 1.79, 95%CI: 1.38-2.33, p = 0.0001), and delivering in hospital (OR: 2.5, 95%CI: 1.49-4.35, p = 0.001). The control group performed significantly better than the intervention group on two practice indicators: resting regularly during pregnancy (OR: 0.7, 95%CI: 0.54-0.88, p = 0.002) and having at-home deliveries attended by a skilled birth attendant (OR: 0.46, 95%CI: 0.23-0.91, p = 0.027). Both groups' knowledge improved from Time 1 to Time 2. Only one knowledge indicator, on seeking medical care during pregnancy, was statistically increased in the intervention group compared to controls. Anemia status at or near the time of delivery was unable to be assessed due to missing data from maternal health cards. CONCLUSIONS: This study provides evidence that in low-resource settings, mobile voice messages providing tailored and timed information about pregnancy can positively impact maternal health care practices proven to improve maternal health outcomes. Additional research is needed to assess whether voice messaging can motivate behavior change better than text messaging, particularly in low literacy settings. TRIAL REGISTRATION: The mMitra impact evaluation is registered with ISRCTN under Registration # 88968111, assigned on 6 September 2018 (See https://www.isrctn.com/ISRCTN88968111).

The Impact of an mHealth Voice Message Service (mMitra) on Infant Care Knowledge, and Practices Among Low-Income Women in India: Findings from a Pseudo-Randomized Controlled Trial.

Objectives mHealth interventions for MNCH have been shown to improve uptake of antenatal and neonatal services in low- and middle-income countries (LMICs). However, little systematic analysis is available about their impact on infant health outcomes, such as reducing low birth weight or malnutrition among children under the age of five. The objective of this study is to determine if an age- and stage-based mobile phone voice messaging initiative for women, during pregnancy and up to 1 year after delivery, can reduce low birth weight and child malnutrition and improve women's infant care knowledge and practices. Methods We conducted a pseudo-randomized controlled trial among pregnant women from urban slums and low-income areas in Mumbai, India. Pregnant women, 18 years and older, speaking Hindi or Marathi were enrolled and assigned to receive mMitra messages (intervention group N = 1516) or not (Control group N = 500). Women in the intervention group received mMitra voice messages two times per week throughout their pregnancy and until their infant turned 1 year of age. Infant's birth weight, anthropometric data at 1 year of age, and status of immunization were obtained from Maternal Child Health (MCH) cards to assess impact on primary infant health outcomes. Women's infant health care practices and knowledge were assessed through interviews administered immediately after women enrolled in the study (Time 1), after they delivered their babies (Time 2), and after their babies turned 1 year old (Time 3). 15 infant care practices self-reported by women (Time 3) and knowledge on ten infant care topics (Time 2) were also compared between intervention and control arms. Results We observed a trend for increased odds of a baby being born at or above the ideal birth weight of 2.5 kg in the intervention group compared to controls (odds ratio (OR) 1.334, 95% confidence interval (CI) 0.983-1.839, p = 0.064). The intervention group performed significantly better on two infant care practice indicators: giving the infant supplementary feeding at 6 months of age (OR 1.4, 95% CI 1.08-1.82, p = 0.009) and fully immunizing the infant as prescribed under the Government of India's child immunization program (OR 1.531, 95% CI 1.141-2.055, p = 0.005). Women in the intervention group had increased odds of knowing that the baby should be given solid food by 6 months (OR 1.89, 95% CI 1.371-2.605, p < 0.01), that the baby needs to be given vaccines (OR 1.567, 95% CI 1.047-2.345, p = 0.028), and that the ideal birth weight is > 2.5 kg (OR 2.279, 95% CI 1.617-3.213, p < 0.01). Conclusions for Practice This study provides robust evidence that tailored mobile voice messages can significantly improve infant care practices and maternal knowledge that can positively impact infant child health. Furthermore, this is the first prospective study of a voice-based mHealth intervention to demonstrate a positive impact on infant birth weight, a health outcome of public health importance in many LMICs.

The Elusive Path Toward Measuring Health Outcomes: Lessons Learned From a Pseudo-Randomized Controlled Trial of a Large-Scale Mobile Health Initiative.

Mobile health (mHealth) offers new opportunities to improve access to health services and health information. It also presents new challenges in evaluating its impact, particularly in linking the use of a technology intervention that aims to improve health behaviors with the health outcomes that are impacted by changed behaviors. The availability of data from a multitude of sources (paper-based and electronic) provides the conditions to facilitate making stronger connections between self-reported data and clinical outcomes. This commentary shares lessons and important considerations based on the experience of applying new research frameworks and incorporating maternal and child health records data into a pseudo-randomized controlled trial to evaluate the impact of mMitra, a stage-based voice messaging program to improve maternal, newborn, and child health outcomes in urban slums in India.

Mobile health messaging service and helpdesk for South African mothers (MomConnect): history, successes and challenges.

MomConnect is a flagship programme of the South African National Department of Health that has reached over 1.5 million pregnant women. Using mobile technology, MomConnect provides pregnant and postpartum women with twice-weekly health information text messages as well as access to a helpdesk for patient queries and feedback. In just 3 years, MomConnect has been taken to scale to reach over 95% of public health facilities and has reached 63% of all pregnant women attending their first antenatal appointment. The helpdesk has received over 300 000 queries at an average of 250 per day from 6% of MomConnect users. The service is entirely free to its users. The rapid deployment of MomConnect has been facilitated by strong government leadership, and an ecosystem of mobile health implementers who had experience of much of the content and technology required. An early decision to design MomConnect for universal coverage has required the use of text-based technologies (short messaging service and Unstructured Supplementary Service Data) that are accessible via even the most basic mobile phones, but cumbersome to use and costly at scale. Unlike previous mobile messaging services in South Africa, MomConnect collects the user's identification number and facility code during registration, enabling future linkages with other health and population databases and geolocated feedback. MomConnect has catalysed additional efforts to strengthen South Africa's digital health architecture. The rapid growth in smartphone penetration presents new opportunities to reduce costs, increase real-time data collection and expand the reach and scope of MomConnect to serve health workers and other patient groups.

Concentration-dependent synergy and antagonism within a triple antifungal drug combination against Aspergillus species: analysis by a new response surface model.

Triple antifungal combinations are used against refractory invasive aspergillosis without an adequate understanding of their pharmacodynamic interactions. We initially studied the in vitro triple combination of voriconazole, amphotericin B, and caspofungin against Aspergillus fumigatus, A. flavus, and A. terreus by a spectrophotometric microdilution broth method after 48 h of incubation. We then analyzed these results with a recently described nonlinear mixture response surface E(max)-based model modified to assess pharmacodynamic interactions at various growth levels. The new model allows flexibility in all four parameters of the E(max) model and is able to describe complex pharmacodynamic interactions. Concentration-dependent pharmacodynamic interactions were found within the triple antifungal combination. At the 50% growth level, synergy (median interaction indices of 0.43 to 0.82) was observed at low concentrations of voriconazole (<0.03 mg/liter) and amphotericin B (

Pathogenesis of Aspergillus fumigatus and the kinetics of galactomannan in an in vitro model of early invasive pulmonary aspergillosis: implications for antifungal therapy.

BACKGROUND: Little is known about the pathogenesis of invasive pulmonary aspergillosis and the relationship between the kinetics of diagnostic markers and the outcome of antifungal therapy. METHODS: An in vitro model of the human alveolus, consisting of a bilayer of human alveolar epithelial and endothelial cells, was developed. An Aspergillus fumigatus strain expressing green fluorescent protein was used. Invasion of the cell bilayer was studied using confocal and electron microscopy. The kinetics of culture, polymerase chain reaction, and galactomannan were determined. Galactomannan was used to measure the antifungal effect of macrophages and amphotericin B. A mathematical model was developed, and results were bridged to humans. RESULTS: A. fumigatus penetrated the cellular bilayer 14-16 h after inoculation. Galactomannan levels were inextricably tied to fungal invasion and were a robust measure of the antifungal effect of macrophages and amphotericin B. Neither amphotericin nor macrophages alone was able to suppress the growth of A. fumigatus; rather, the combination was required. Monte Carlo simulations showed that human dosages of amphotericin B of at least 0.6 mg/kg were required to achieve adequate drug exposure. CONCLUSIONS: This model provides a strategy by which relationships among pathogenesis, immunological effectors, and antifungal drug therapy for invasive pulmonary aspergillosis may be further understood.

Use of fluorescent probes to determine MICs of amphotericin B and caspofungin against Candida spp. and Aspergillus spp.

We investigated the utility of mechanism-based fluorescent probes for determination of MICs (FMICs) of amphotericin B and caspofungin against Candida spp. and Aspergillus spp. Amphotericin B was selected as a membrane-active antifungal agent, and caspofungin was selected as a cell wall-active agent. FMICs were also compared to the MIC determined by CLSI (formerly NCCLS) methods. Five isolates per species of Candida albicans, Candida glabrata, Candida parapsilosis, Aspergillus fumigatus, and Aspergillus terreus were studied with either amphotericin B or caspofungin. The fluorescent probes, carboxyfluorescein diacetate (CFDA) for cytoplasmic esterase activity and dihexyloxacarbocyanine iodide (DiOC6) for cell membrane potential, were each added to their respective plates. MICs and FMICs were determined in at least three separate experiments (in duplicate). Fluorescence was measured using a 96-well plate fluorometer. For amphotericin B and caspofungin, the FMIC end point was the lowest concentration of drug at which the percent growth inhibition from treated organisms versus control organisms displayed 80% inhibition for amphotericin B and 50% inhibition for caspofungin as measured by a fluorescent signal. The MIC for amphotericin B was defined as the lowest concentration of antifungal displaying no visible growth for both Aspergillus and Candida spp. The MIC for caspofungin was the lowest concentration of drug that displayed a minimum effective concentration for Aspergillus spp. For Candida spp., the MIC for caspofungin was defined as the concentration at which the antifungal agent significantly inhibits the organism. The FMICs of both antifungals, as measured by the DiOC6 membrane probe, showed good agreement (83% to 100%), within one well dilution, with the MICs against amphotericin B and caspofungin for all species. Also, the FMICs measured by the CFDA cytoplasmic esterase probe reflecting damage due to cell wall or cell membrane showed strong agreement (79 to 100%) with the MICs of both amphotericin B and caspofungin for all species. There was no significant difference in comparisons of MIC and FMIC values (P > or = 0.05). The use of fluorescent probes provides a mechanism-based method of determination of MICs of amphotericin B and caspofungin against Candida spp. and Aspergillus spp. that correlates well with standard methods.

Efficacy, safety, and plasma pharmacokinetics of escalating dosages of intravenously administered ravuconazole lysine phosphoester for treatment of experimental pulmonary aspergillosis in persistently neutropenic rabbits.

Ravuconazole is a new antifungal triazole with broad-spectrum activity and a long half-life in plasma. We studied the antifungal efficacy, safety, and pharmacokinetics of ravuconazole lysine phosphoester in escalating dosages for the treatment of invasive pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits. Treatment groups consisted of rabbits treated with ravuconazole at 2.5 (RVC2.5), 5 (RVC5), and 10 (RVC10) mg/kg of body weight/day, rabbits treated with amphotericin B (AMB) at 1 mg/kg/day, or untreated controls. There was a dose-dependent reduction of pulmonary residual fungal burden (CFU per gram) in RVC5-, RVC10-, and AMB-treated rabbits in comparison to untreated controls (P < 0.01, P < 0.001, and P < 0.01, respectively). These findings correlated with progressive galactomannan antigenemia in untreated controls and the RVC2.5-treated rabbits, a lower galactomannan index (GMI) in RVC5- and RVC10-treated rabbits, and a similarly low GMI in AMB-treated rabbits (P < 0.01). Rabbits treated with RVC5, RVC10, and AMB also showed a reduction of organism-mediated pulmonary injury, as measured by infarct scores and lung weights, in comparison to untreated controls (P < 0.001). These results were supported by decreased pulmonary infiltrates detected by computed tomography in RVC5- and RVC10-treated rabbits in comparison to untreated controls (P < 0.05). Survival throughout the entire study was achieved in 95% of RVC5-treated rabbits (P < 0.001), 85% of RVC10-treated rabbits (P < 0.001), and 50% of AMB-treated rabbits (P < 0.05) in comparison to none of the untreated controls. Ravuconazole showed linear plasma pharmacokinetics and a large volume of distribution while maintaining concentrations in plasma above the MIC throughout the dosing interval. There was no evidence of hepatotoxicity or nephrotoxicity among ravuconazole-treated animals. Intravenously administered ravuconazole lysine phosphoester showed dose-dependent efficacy and an excellent safety profile for the treatment of invasive pulmonary aspergillosis in persistently neutropenic rabbits.

Experimental pulmonary aspergillosis due to Aspergillus terreus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B.

Aspergillus terreus is an uncommon but emerging fungal pathogen, which causes lethal infections that are often refractory to amphotericin B (AmB). In comparison to Aspergillus fumigatus, A. terreus was resistant to the in vitro fungicidal effects of safely achievable concentrations of AmB. These in vitro findings correlated directly with resistance of A. terreus to AmB in experimental invasive pulmonary aspergillosis. Residual fungal pulmonary burden and galactomannan antigenemia demonstrated persistent infection, despite therapy with deoxycholate AmB or liposomal AmB. By comparison, posaconazole and itraconazole resolved GM antigenemia, reduced residual fungal burden, and improved survival. There were no differences in phagocytic host response to A. terreus versus A. fumigatus; however, the rate of conidial germination of A. terreus was slower. The strain of A. terreus with the highest minimum inhibitory and minimum lethal concentration of AmB also had the lowest membrane ergosterol content. The hyphae of A. terreus in vivo displayed distinctive aleurioconidia, which may be a practical microscopic feature for rapid preliminary diagnosis.