Responding to maternal, neonatal and child health equipment needs in Kenya: a model for an innovation ecosystem leveraging on collaborations and partnerships.

BACKGROUND: Up to 70% of medical devices in low-income and middle-income countries are partially or completely non-functional, impairing service provision and patient outcomes. In Sub-Saharan Africa, medical devices not designed for local conditions, lack of well-trained biomedical engineers and diverse donated equipment have led to poor maintenance and non-repair. The Maker Project's aim was to test the effectiveness of an innovative partnership ecosystem network, the 'Maker Hub', in reducing gaps in the supply of essential medical devices for maternal, newborn and child health. This paper describes the first phase of the project, the building of the Maker Hub. METHODS: Key activities in setting up the Maker Hub-a collaborative partnership between the University of Nairobi (UoN) and the Kenyatta National Hospital (KNH), catalysed by Concern Worldwide Kenya-are described using a product development partnership approach. Using a health systems approach, a needs assessment identified a medical equipment shortlist. Design thinking with a capacity building component was used by the UoN (innovators, public health specialists, engineers) working closely and with KNH nurses, physicians and biomedical engineers to develop the prototypes. RESULTS: To date, four medical device prototypes have been developed. Two have been evaluated by the National Bureau of Standards and one has undergone clinical testing. CONCLUSIONS: We have demonstrated an innovative partnership ecosystem that has developed medical devices that have undergone national standards evaluation and clinical testing, a first in Sub-Saharan Africa. Promoting a robust innovation ecosystem for medical equipment requires investment in building trust in the innovation ecosystem.

Placental Structure in Preterm Birth Among HIV-Positive Versus HIV-Negative Women in Kenya.

BACKGROUND: Preterm birth (PTB) is a major cause of infant morbidity and mortality in developing countries. Recent data suggest that in addition to Human Immunodeficiency Virus (HIV) infection, use of antiretroviral therapy (ART) increases the risk of PTB. As the mechanisms remain unexplored, we conducted this study to determine whether HIV and ART were associated with placental changes that could contribute to PTB. SETTING: We collected and evaluated placentas from 38 HIV-positive women on ART and 43 HIV-negative women who had preterm deliveries in Nairobi, Kenya. METHODS: Anatomical features of the placentas were examined at gross and microscopic levels. Cases were matched for gestational age and compared by the investigators who were blinded to maternal HIV serostatus. RESULTS: Among preterm placentas, HIV infection was significantly associated with thrombosis (P = 0.001), infarction (P = 0.032), anomalies in cord insertion (P = 0.02), gross evidence of membrane infection (P = 0.043), and reduced placental thickness (P = 0.010). Overall, preterm placentas in both groups were associated with immature villi, syncytial knotting, villitis, and deciduitis. Features of HIV-positive versus HIV-negative placentas included significant fibrinoid deposition with villus degeneration, syncytiotrophoblast delamination, red blood cell adhesion, hypervascularity, and reduction in both surface area and perimeter of the terminal villi. CONCLUSIONS: These results imply that HIV infection and/or ART are associated with morphological changes in preterm placentas that contribute to delivery before 37 weeks. Hypervascularity suggests that the observed pathologies may be attributable, in part, to hypoxia. Further research to explore potential mechanisms will help elucidate the pathways that are involved perhaps pointing to interventions for decreasing the risk of prematurity among HIV-positive women.

Cluster-Randomized Controlled Study of SMS Text Messages for Prevention of Mother-to-Child Transmission of HIV in Rural Kenya.

Background. Antiretroviral medications are key for prevention of mother-to-child transmission (PMTCT) of HIV, and transmission mitigation is affected by service delivery, adherence, and retention. Methods. We conducted a cluster-randomized controlled study in 26 facilities in Nyanza, Kenya, to determine the efficacy of SMS text messages on PMTCT outcomes. The relative risk and confidence intervals were estimated at the facility level using STATA. Results. 550 women were enrolled, from June 2012 to July 2013. The median age was 25.6 years, and 85.3% received ARVs. Maternal ARV use was similar between the intervention and control arms: 254/261 (97.3%) versus 241/242 (99.6%) at 34-36 weeks of gestation and 234/247 (94.7%) versus 229/229 (100%) at delivery. Among infants, 199/246 (80.9%) and 209/232 (90.1%) received ARVs (RR: 0.91; 95% CI: 0.77-1.14); 88% versus 88.6% were tested for HIV at 6 weeks, with 1/243 (0.4%) and 3/217 (1.4%) positive results in the intervention and control arms, respectively. Communication increased in both the intervention and control arms, with the mean number of 7.5 (SD: 5.70) compared with 6 (SD: 9.96), p < 0.0001. Conclusions. We identified high ARV uptake and infant HIV testing, with very low HIV transmission. Increased communication may influence health-seeking behaviors irrespective of technology. The long-term effectiveness of facilitated communication on PMTCT outcomes needs to be tested. The study has been registered on ClinicalTrials.gov under the identifier NCT01645865.

Linking women who test HIV-positive in pregnancy-related services to HIV care and treatment services in Kenya: a mixed methods prospective cohort study.

INTRODUCTION: There has been insufficient attention to long-term care and treatment for pregnant women diagnosed with HIV. OBJECTIVE AND METHODS: This prospective cohort study of 100 HIV-positive women recruited within pregnancy-related services in a district hospital in Kenya employed quantitative methods to assess attrition between women testing HIV-positive in pregnancy-related services and accessing long-term HIV care and treatment services. Qualitative methods were used to explore barriers and facilitators to navigating these services. Structured questionnaires were administered to cohort participants at enrolment and 90+ days later. Participants' medical records were monitored prospectively. Semi-structured qualitative interviews were carried out with a sub-set of 19 participants. FINDINGS: Only 53/100 (53%) women registered at an HIV clinic within 90 days of HIV diagnosis, of whom 27/53 (51%) had a CD4 count result in their file. 11/27 (41%) women were eligible for immediate antiretroviral therapy (ART); only 6/11 (55%) started ART during study follow-up. In multivariable logistic regression analysis, factors associated with registration at the HIV clinic within 90 days of HIV diagnosis were: having cared for someone with HIV (aOR:3.67(95%CI:1.22, 11.09)), not having to pay for transport to the hospital (aOR:2.73(95%CI:1.09, 6.84)), and having received enough information to decide to have an HIV test (aOR:3.61(95%CI:0.83, 15.71)). Qualitative data revealed multiple factors underlying high patient drop-out related to women's social support networks (e.g. partner's attitude to HIV status), interactions with health workers (e.g. being given unclear/incorrect HIV-related information) and health services characteristics (e.g. restricted opening hours, long waiting times). CONCLUSION: HIV testing within pregnancy-related services is an important entry point to HIV care and treatment services, but few women successfully completed the steps needed for assessment of their treatment needs within three months of diagnosis. Programmatic recommendations include simplified pathways to care, better-tailored counselling, integration of ART into antenatal services, and facilitation of social support.

Exploring the use of mobile phone technology for the enhancement of the prevention of mother-to-child transmission of HIV program in Nyanza, Kenya: a qualitative study.

BACKGROUND: Community-based mobile phone programs can complement gaps in clinical services for prevention of mother-to-child transmission (PMTCT) of HIV in areas with poor infrastructure and personnel shortages. However, community and health worker perceptions on optimal mobile phone communication for PMTCT are underexplored. This study examined what specific content and forms of mobile communication are acceptable to support PMTCT. METHODS: Qualitative methods using focus groups and in-depth interviews were conducted in two district hospitals in Nyanza Province, Kenya. A total of 45 participants were purposefully selected, including HIV-positive women enrolled in PMTCT, their male partners, community health workers, and nurses. Semi-structured discussion guides were used to elicit participants' current mobile phone uses for PMTCT and their perceived benefits and challenges. We also examined participants' views on platform design and gender-tailored short message service (SMS) messages designed to improve PMTCT communication and male involvement. RESULTS: Most participants had access to a mobile phone and prior experience receiving and sending SMS, although phone sharing was common among couples. Mobile phones were used for several health-related purposes, primarily as voice calls rather than texts. The perceived benefits of mobile phones for PMTCT included linking with health workers, protecting confidentiality, and receiving information and reminders. Men and women considered the gender-tailored SMS as a catalyst for improving PMTCT male involvement and couples' communication. However, informative messaging relayed safely to the intended recipient was critical. In addition, health workers emphasized the continual need for in-person counseling coupled with, rather than replaced by, mobile phone reinforcement. For all participants, integrated and neutral text messaging provided antenatally and postnatally was most preferred, although not all topics or text formats were equally acceptable. CONCLUSIONS: Given the ubiquity of mobile phones in Kenya and current health-related uses of mobile phones, a PMTCT mobile communications platform holds considerable potential. This pre-intervention assessment of community and health worker preferences yielded valuable information on the complexities of design and implementation. An effective PMTCT mobile platform engaging men and women will need to address contexts of non-disclosure, phone sharing, and linkages with existing community and facility-based services.

Patient attrition between diagnosis with HIV in pregnancy-related services and long-term HIV care and treatment services in Kenya: a retrospective study.

BACKGROUND: There has been little attention, until recently, to linking women who test HIV positive in pregnancy-related services to long-term HIV care and treatment services. METHODS: A retrospective review of routine hospital data was carried out in 2 hospitals in Kenya. Associations between available demographic information and uptake of HIV-related services within 6 months of HIV diagnosis in pregnancy-related services were assessed using logistic regression. Kaplan-Meier survival analysis was used to assess time between HIV diagnosis and registration at the HIV clinic. Referrals between pregnancy-related and HIV-related services were observed. RESULTS: At Naivasha hospital, the proportion of women registering at the HIV clinic within 6 months was 17.2% (153 of 892); at Gilgil hospital, it was 35.4% (84 of 237). Highly active antiretroviral therapy (HAART) was initiated by 40% and 27% of known eligible women in Naivasha and Gilgil, respectively. Non-systematic registration of clients on first contact at the HIV clinic, and restricted availability of services due to costs and opening hours were observed. In Naivasha, year, attendance at multiple pregnancy-related visits, and attendance at antenatal care in Naivasha hospital were associated with registration at the HIV clinic. In Gilgil, year, attendance at multiple pregnancy-related visits, and women being in their first pregnancy were associated with the outcome. CONCLUSIONS: Only 4% of women estimated to need HAART for their own care initiated HAART within 6 months of HIV diagnosis. Challenges associated with providing longitudinal care are especially evident in the context of high population mobility. Innovation in service delivery is required to improve uptake of services.

Linking women who test HIV-positive in pregnancy-related services to long-term HIV care and treatment services: a systematic review.

OBJECTIVES: To quantify attrition between women testing HIV-positive in pregnancy-related services and accessing long-term HIV care and treatment services in low- or middle-income countries and to explore the reasons underlying client drop-out by synthesising current literature on this topic. METHODS: A systematic search in Medline, EMBASE, Global Health and the International Bibliography of the Social Sciences of literature published 2000-2010. Only studies meeting pre-defined quality criteria were included. RESULTS: Of 2543 articles retrieved, 20 met the inclusion criteria. Sixteen (80%) drew on data from sub-Saharan Africa. The pathway between testing HIV-positive in pregnancy-related services and accessing long-term HIV-related services is complex, and attrition was usually high. There was a failure to initiate highly active antiretroviral therapy (HAART) among 38-88% of known-eligible women. Providing 'family-focused care', and integrating CD4 testing and HAART provision into prevention of mother-to-child HIV transmission services appear promising for increasing women's uptake of HIV-related services. Individual-level factors that need to be addressed include financial constraints and fear of stigma. CONCLUSIONS: Too few women negotiate the many steps between testing HIV-positive in pregnancy-related services and accessing HIV-related services for themselves. Recent efforts to stem patient drop-out, such as the MTCT-Plus Initiative, hold promise. Addressing barriers and enabling factors both within health facilities and at the levels of the individual woman, her family and society will be essential to improve the uptake of services.

Prevention of mother-to-child transmission of HIV: assessing the accuracy of routinely collected data on maternal antiretroviral prophylaxis coverage in Kenya.

OBJECTIVE: To explore the accuracy of routinely collected prevention of mother-to-child transmission of HIV (PMTCT) coverage data in Kenya. METHODS: In case studies at two government hospitals, the authors reviewed national reporting guidelines, interviewed nurses and undertook a retrospective analysis of routine hospital data from antenatal care, maternity and HIV services from January 2009 to June 2010. Each woman attending these services was given a unique study number to enable analysis of her recorded use of PMTCT services across different hospital visits. These data were compared with the hospitals' monthly PMTCT reports to the district. RESULTS: Where a woman made more than one visit, PMTCT drug provision could be reported multiple times for the same woman, and women known to be HIV positive prior to pregnancy were omitted from the denominator of PMTCT coverage calculations. Practices for reporting data on maternal PMTCT prophylaxis provision varied in the two hospitals. According to the study data, using the hospital registers and accounting for multiple visits by the same woman, 642 women were known to have HIV and 412 (64%) were given maternal PMTCT prophylaxis. According to the monthly reports, 430 women were diagnosed as having HIV in pregnancy-related services and 538 (125%) were given maternal PMTCT prophylaxis. CONCLUSIONS: If replicated elsewhere, these reporting practices could lead to overestimation of national PMTCT coverage. Simple yet accurate routine data collection systems are needed to monitor PMTCT coverage accurately and to highlight where changes need to be made so as to ensure that infants are born HIV free.

Hyponatremia, hypochloremia, and hypoalbuminemia predict an increased risk of mortality during the first year of antiretroviral therapy among HIV-infected Zambian and Kenyan women.

Early mortality rates after initiating antiretroviral therapy (ART) are high in sub-Saharan Africa. We examined whether serum chemistries at ART initiation predicted mortality among HIV-infected women. From May 2005 to January 2007, we enrolled women initiating ART in a prospective cohort study in Zambia and Kenya. We used Cox proportional hazards models to identify risk factors associated with mortality. Among 661 HIV-infected women, 53 (8%) died during the first year of ART, and tuberculosis was the most common cause of death (32%). Women were more likely to die if they were both hyponatremic (sodium <135 mmol/liter) and hypochloremic (chloride <95 mmol/liter) (37% vs. 6%) or hypoalbuminemic (albumin <34 g/liter, 13% vs. 4%) when initiating ART. A body mass index <18 kg/m(2) [adjusted hazard ratio (aHR) 5.3, 95% confidence interval (CI) 2.6-10.6] and hyponatremia with hypochloremia (aHR 4.5, 95% CI 2.2-9.4) were associated with 1-year mortality after adjusting for country, CD4 cell count, WHO clinical stage, hemoglobin, and albumin. Among women with a CD4 cell count >50 cells/µl, hypoalbuminemia was also a significant predictor of mortality (aHR=3.7, 95% CI 1.4-9.8). Baseline hyponatremia with hypochloremia and hypoalbuminemia predicted mortality in the first year of initiating ART, and these abnormalities might reflect opportunistic infections (e.g., tuberculosis) or advanced HIV disease. Assessment of serum sodium, chloride, and albumin can identify HIV-infected patients at highest risk for mortality who may benefit from more intensive medical management during the first year of ART.

How late is too late? Timeliness to scheduled visits as an antiretroviral therapy adherence measure in Nairobi, Kenya and Lusaka, Zambia.

Collecting self-reported data on adherence to highly active antiretroviral therapy (HAART) can be complicated by patients' reluctance to report poor adherence. The timeliness with which patients attend visits might be a useful alternative to estimate medication adherence. Among Kenyan and Zambian women receiving twice daily HAART, we examined the relationship between self-reported pill taking and timeliness attending scheduled visits. We analyzed data from 566 Kenyan and Zambian women enrolled in a prospective 48-week HAART-response study. At each scheduled clinic visit, women reported doses missed over the preceding week. Self-reported adherence was calculated by summing the total number of doses reported taken and dividing by the total number of doses asked about at the visit attended. A participant's adherence to scheduled study visits was defined as "on time" if she arrived early or within three days, "moderately late" if she was four-seven days late, and "extremely late/missed" if she was more than eight days late or missed the visit altogether. Self-reported adherence was <95% for 29 (10%) of 288 women who were late for at least one study visit vs. 3 (1%) of 278 who were never late for a study visit (odds ratios [OR] 10.3; 95% confidence intervals [95% CI] 2.9, 42.8). Fifty-one (18%) of 285 women who were ever late for a study visit experienced virologic failure vs. 32 (12%) of 278 women who were never late for a study visit (OR 1.7; 95% CI 1.01, 2.8). A multivariate logistic regression model controlling for self-reported adherence found that being extremely late for a visit was associated with virologic failure (OR 2.0; 95% CI 1.2, 3.4). Timeliness to scheduled visits was associated with self-reported adherence to HAART and with risk for virologic failure. Timeliness to scheduled clinic visits can be used as an objective proxy for self-reported adherence and ultimately for risk of virologic failure.

Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study.

BACKGROUND: Intrapartum and neonatal single-dose nevirapine (NVP) reduces the risk of mother-to-child HIV transmission but also induces viral resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. This drug resistance largely fades over time. We hypothesized that women with a prior single-dose NVP exposure would have no more than a 10% higher cumulative prevalence of failure of their NNRTI-containing antiretroviral therapy (ART) over the first 48 wk of therapy than would women without a prior exposure. METHODS AND FINDINGS: We enrolled 355 NVP-exposed and 523 NVP-unexposed women at two sites in Zambia, one site in Kenya, and two sites in Thailand into a prospective, non-inferiority cohort study and followed them for 48 wk on ART. Those who died, discontinued NNRTI-containing ART, or had a plasma viral load >or=400 copies/ml at either the 24 wk or 48 wk study visits and confirmed on repeat testing were characterized as having failed therapy. Overall, 114 of 355 NVP-exposed women (32.1%) and 132 of 523 NVP-unexposed women (25.2%) met criteria for treatment failure. The difference in failure rates between the exposure groups was 6.9% (95% confidence interval [CI] 0.8%-13.0%). The failure rates of women stratified by our predefined exposure interval categories were as follows: 47 of 116 women in whom less than 6 mo elapsed between exposure and starting ART failed therapy (40%; p<0.001 compared to unexposed women); 25 of 67 women in whom 7-12 mo elapsed between exposure and starting ART failed therapy (37%; p = 0.04 compared to unexposed women); and 42 of 172 women in whom more than 12 mo elapsed between exposure and starting ART failed therapy (24%; p = 0.82 compared to unexposed women). Locally weighted regression analysis also indicated a clear inverse relationship between virologic failure and the exposure interval. CONCLUSIONS: Prior exposure to single-dose NVP was associated with an increased risk of treatment failure; however, this risk seems largely confined to women with a more recent exposure. Women requiring ART within 12 mo of NVP exposure should not be prescribed an NNRTI-containing regimen as first-line therapy.