Two dose levels of once-weekly fosravuconazole versus daily itraconazole in combination with surgery in patients with eumycetoma in Sudan: a randomised, double-blind, phase 2, proof-of-concept superiority trial.

BACKGROUND: Eumycetoma is an implantation mycosis characterised by a large subcutaneous mass in the extremities commonly caused by the fungus Madurella mycetomatis. Despite the long duration of treatment, commonly a minimum of 12 months, treatment failure is frequent and can lead to amputation. We aimed to compare the efficacy of two doses of fosravuconazole, a synthetic antifungal designed for use in onychomycosis and repurposed for mycetoma, with standard-of-care itraconazole, both in combination with surgery. METHODS: This phase 2, randomised, double-blind, active-controlled, superiority trial was conducted in a single centre in Sudan. Patients with eumycetoma caused by M mycetomatis, who were aged 15 years or older, with a set lesion diameter (>2 cm and ≤16 cm) requiring surgery were included. There was a limit of 20 female patients in the initial enrolment, owing to preclinical toxicity concerns. Exclusion criteria included previous surgical or medical treatment for eumycetoma; presence of loco-regional lymphatic extension; osteomyelitis, or other bone involvement; pregnancy or lactation; severe concomitant diseases; a BMI under 16 kg/m2; contraindication to use of the study drugs; pre-existing liver disease; lymphatic extension; osteomyelitis; transaminase levels more than two times the laboratory's upper limit of normal, or elevated levels of alkaline phosphatase or bilirubin; or any history of hypersensitivity to any azole antifungal drug. Patients were randomly allocated in a 1:1:1 ratio to 300 mg fosravuconazole weekly for 12 months (group 1); 200 mg fosravuconazole weekly for 12 months (group 2); or 400 mg itraconazole daily for 12 months (group 3) using a random number list with non-disclosed fixed blocks of size 12, with equal allocation to each of the three arms within a block. To ensure masking between groups, placebo pills were used to disguise the difference in dosing schedules. All groups took pills twice daily with meals. In all groups, surgery was performed at 6 months. The primary outcome was complete cure at end of treatment at the month 12 visit, as evidenced by absence of mycetoma mass, sinuses, and discharge; normal ultrasonography or MRI examination of the eumycetoma site; and, if a mass was present, negative fungal culture from the former mycetoma site. The primary outcome was assessed in the modified intention-to-treat (mITT) population (all patients who received one or more treatment dose with one or more primary efficacy assessment). Safety was assessed in all patients who received one or more doses of the study drug. This study is registered with ClinicalTrials.gov (NCT03086226) and is complete. FINDINGS: Between May 9, 2017, and June 10, 2021, 104 patients were randomly allocated (34 in group 1 and 2, respectively, and 36 in group 3). 86 (83%) of 104 patients were male and 18 (17%) patients were female. After an unplanned second interim analysis, the study was terminated early for futility. Complete cure at 12 months in the mITT population was 17 (50%) of 34 (95% CI 32-68) for group 1, 22 (65%) of 34 (47-80) for group 2, and 27 (75%) of 36 (58-88) in group 3. Neither dose of fosravuconazole was superior to itraconazole (p=0·35 for 200 mg fosravuconazole vs p=0·030 for 300 mg fosravuconazole). 83 patients had a total of 205 treatment-emergent adverse events, and two patients had serious adverse events that led to discontinuation, neither related to treatment. INTERPRETATION: Treatment with either dose of fosravuconazole was not superior to itraconazole, and the two doses had a numerically lower efficacy. However, fosravuconazole presented no new safety signals, and its lower pill burden and reduced risk of drug-drug interactions compared with the relatively expensive and inaccessible itraconazole suggests further research into effective treatments with a shorter duration and higher cure rate, without the need for surgery are warranted. FUNDING: Drugs for Neglected Diseases initiative.

Safety and efficacy of paromomycin/miltefosine/liposomal amphotericin B combinations for the treatment of post-kala-azar dermal leishmaniasis in Sudan: A phase II, open label, randomized, parallel arm study.

BACKGROUND: Treatment for post-kala-azar dermal leishmaniasis (PKDL) in Sudan is currently recommended only for patients with persistent or severe disease, mainly because of the limitations of current therapies, namely toxicity and long hospitalization. We assessed the safety and efficacy of miltefosine combined with paromomycin and liposomal amphotericin B (LAmB) for the treatment of PKDL in Sudan. METHODOLOGY/PRINCIPAL FINDINGS: An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with persistent (stable or progressive disease for ≥ 6 months) or grade 3 PKDL, aged 6 to ≤ 60 years in Sudan. The median age was 9.0 years (IQR 7.0-10.0y) and 87% of patients were ≤12 years old. Patients were randomly assigned to either daily intra-muscular paromomycin (20mg/kg, 14 days) plus oral miltefosine (allometric dose, 42 days)-PM/MF-or LAmB (total dose of 20mg/kg, administered in four injections in week one) and oral miltefosine (allometric dose, 28 days)-LAmB/MF. The primary endpoint was a definitive cure at 12 months after treatment onset, defined as clinical cure (100% lesion resolution) and no additional PKDL treatment between end of therapy and 12-month follow-up assessment. 104/110 patients completed the trial. Definitive cure at 12 months was achieved in 54/55 (98.2%, 95% CI 90.3-100) and 44/55 (80.0%, 95% CI 70.2-91.9) of patients in the PM/MF and AmB/MF arms, respectively, in the mITT set (all randomized patients receiving at least one dose of treatment; in case of error of treatment allocation, the actual treatment received was used in the analysis). No SAEs or deaths were reported, and most AEs were mild or moderate. At least one adverse drug reaction (ADR) was reported in 13/55 (23.6%) patients in PM/MF arm and 28/55 (50.9%) in LAmB/MF arm, the most frequent being miltefosine-related vomiting and nausea, and LAmB-related hypokalaemia; no ocular or auditory ADRs were reported. CONCLUSIONS/SIGNIFICANCE: The PM/MF regimen requires shorter hospitalization than the currently recommended 60-90-day treatment, and is safe and highly efficacious, even for patients with moderate and severe PKDL. It can be administered at primary health care facilities, with LAmB/MF as a good alternative. For future VL elimination, we need new, safe oral therapies for all patients with PKDL. TRIAL REGISTRATION: ClinicalTrials.gov NCT03399955, https://clinicaltrials.gov/study/NCT03399955 ClinicalTrials.gov ClinicalTrials.gov.

Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial.

BACKGROUND: This study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninferior to sodium stibogluconate plus paromomycin (SSG/PM) for treatment of primary visceral leishmaniasis in eastern Africa. METHODS: An open-label, phase 3, randomized, controlled trial was conducted in adult and pediatric patients at 7 sites in eastern Africa. Patients were randomly assigned to either 20 mg/kg paromomycin plus allometric dose of miltefosine (14 days), or 20 mg/kg sodium stibogluconate plus 15 mg/kg paromomycin (17 days). The primary endpoint was definitive cure after 6 months. RESULTS: Of 439 randomized patients, 424 completed the trial. Definitive cure at 6 months was 91.2% (155 of 170) and 91.8% (156 of 170) in the PM/MF and SSG/PM arms in primary efficacy modified intention-to-treat analysis (difference, 0.6%; 97.5% confidence interval [CI], -6.2 to 7.4), narrowly missing the noninferiority margin of 7%. In the per-protocol analysis, efficacy was 92% (149 of 162) and 91.7% (155 of 169) in the PM/MF and SSG/PM arms (difference, -0.3%; 97.5% CI, -7.0 to 6.5), demonstrating noninferiority. Treatments were well tolerated. Four of 18 serious adverse events were study drug-related, and 1 death was SSG-related. Allometric dosing ensured similar MF exposure in children (<12 years) and adults. CONCLUSIONS: PM/MF and SSG/PM efficacies were similar, and adverse drug reactions were as expected given the drugs safety profiles. With 1 less injection each day, reduced treatment duration, and no risk of SSG-associated life-threatening cardiotoxicity, PM/MF is a more patient-friendly alternative for children and adults with primary visceral leishmaniasis in eastern Africa. CLINICAL TRIALS REGISTRATION: NCT03129646.

Randomised controlled trial of fosfomycin in neonatal sepsis: pharmacokinetics and safety in relation to sodium overload.

OBJECTIVE: To assess pharmacokinetics and changes to sodium levels in addition to adverse events (AEs) associated with fosfomycin among neonates with clinical sepsis. DESIGN: A single-centre open-label randomised controlled trial. SETTING: Kilifi County Hospital, Kenya. PATIENTS: 120 neonates aged ≤28 days admitted being treated with standard-of-care (SOC) antibiotics for sepsis: ampicillin and gentamicin between March 2018 and February 2019. INTERVENTION: We randomly assigned half the participants to receive additional intravenous then oral fosfomycin at 100 mg/kg two times per day for up to 7 days (SOC-F) and followed up for 28 days. MAIN OUTCOMES AND MEASURES: Serum sodium, AEs and fosfomycin pharmacokinetics. RESULTS: 61 and 59 infants aged 0-23 days were assigned to SOC-F and SOC, respectively. There was no evidence of impact of fosfomycin on serum sodium or gastrointestinal side effects. We observed 35 AEs among 25 SOC-F participants and 50 AEs among 34 SOC participants during 1560 and 1565 infant-days observation, respectively (2.2 vs 3.2 events/100 infant-days; incidence rate difference -0.95 events/100 infant-days (95% CI -2.1 to 0.20)). Four SOC-F and 3 SOC participants died. From 238 pharmacokinetic samples, modelling suggests an intravenous dose of 150 mg/kg two times per day is required for pharmacodynamic target attainment in most children, reduced to 100 mg/kg two times per day in neonates aged <7 days or weighing <1500 g. CONCLUSION AND RELEVANCE: Fosfomycin offers potential as an affordable regimen with a simple dosing schedule for neonatal sepsis. Further research on its safety is needed in larger cohorts of hospitalised neonates, including very preterm neonates or those critically ill. Resistance suppression would only be achieved for the most sensitive of organisms so fosfomycin is recommended to be used in combination with another antimicrobial. TRIAL REGISTRATION NUMBER: NCT03453177.

Association between traumatic brain injury (TBI) patterns and mortality: a retrospective case-control study.

Background: Low and medium income countries (LMICs) such as Kenya experience nearly three times more cases of traumatic brain injury (TBI) compared to high income countries (HICs). This is primarily exacerbated by weak health systems especially at the pre-hospital care level. Generating local empirical evidence on TBI patterns and its influence on patient mortality outcomes is fundamental in informing the design of trauma-specific emergency medical service (EMS) interventions at the pre-hospital care level. This study determines the influence of TBI patterns and mortality. Methods: This was a case-control study with a sample of 316 TBI patients. Data was abstracted from medical records for the period of January 2017 to March 2019 in three tertiary trauma care facilities in Kenya. Logistic regression was used to assess influence of trauma patterns on TBI mortality, controlling for patient characteristics and other potential confounders. Results: The majority of patients were aged below 40 years (73%) and were male (85%). Road traffic injuries (RTIs) comprised 58% of all forms of trauma. Blunt trauma comprised 71% of the injuries. Trauma mechanism was the only trauma pattern significantly associated with TBI mortality. The risk of dying for patients sustaining RTIs was 2.83 times more likely compared to non-RTI patients [odds ratio (OR) 2.83, 95% confidence interval (CI) 1.62-4.93, p=0.001]. The type of transfer to hospital was also significantly associated with mortality outcome, with a public hospital having a two times higher risk of death compared to a private hospital [OR 2.18 95%CI 1.21-3.94, p<0.009]. Conclusion: Trauma mechanism (RTI vs non-RTI) and type of tertiary facility patients are transferred to (public vs private) are key factors influencing TBI mortality burden. Strengthening local EMS trauma response systems targeting RTIs augmented by adequately resourced and equipped public facilities to provide quality lifesaving interventions can reduce the burden of TBIs.

Health system factors associated with post-trauma mortality at the prehospital care level in Africa: a scoping review.

BACKGROUND: Africa accounts forabout 90% of the global trauma burden. Mapping evidence on health systemfactors associated with post-trauma mortality is essential in definingpre-hospital care research priorities and mitigation of the burden. The studyaimed to map and synthesize existing evidence and research gaps on healthsystem factors associated with post-trauma mortality at the pre-hospital carelevel in Africa. METHODS: A scoping review of published studies and grey literature was conducted. The search strategy utilized electronic databases comprising of Medline, Google Scholar, Pub-Med, Hinari and Cochrane Library. Screening and extraction of eligible studies was done independently and in duplicate. RESULTS: A total of 782 study titles and or abstracts were screened. Of these, 32 underwent full text review. Out of the 32, 17 met the inclusion criteria for final review. The majority of studies were literature reviews (24%) and retrospective studies (23%). Retrospective and qualitative studies comprised 6% of the included studies, systematic reviews (6%), cross-sectional studies (17%), Delphi studies (6%), panel reviews (6%) and qualitative studies (12%), systematic reviews (6%), cross-sectional studies (17%), Delphi studies (6%), panel reviews (6%) and qualitative studies (12%). Reported post-trauma mortality ranged from 13% in Ghana to 40% in Nigeria. Reported preventable mortality is as high as 70% in South Africa, 60% in Ghana and 40% in Nigeria. Transport mode is the most studied health system factor (reported in 76% of the papers). Only two studies (12%) included access to pre-hospital care interventions aspects, nine studies (53%) included care providers aspects and three studies (18%) included aspects of referral pathways. The types of transport mode and referral pathway are the only factors significantly associated with post-trauma mortality, though the findings were mixed. None of the included studies reported significant associations between pre-hospital care interventions, care providers and post-trauma mortality. DISCUSSION: Although research on health system factors and its influence on post-trauma mortality at the pre-hospital care level in Africa are limited, anecdotal evidence suggests that access to pre-hospital care interventions, the level of provider skills and referral pathways are important determinants of mortality outcomes. The strength of their influence will require well designed studies that could incorporate mixed method approaches. Moreover, similar reviews incorporating other LMICs are also warranted. Key Words: Health System Factors, Emergency Medical Services [EMS], Pre-hospital Care, Post-Trauma mortality, Africa.

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac.

Pharmacokinetics, Safety, and Efficacy of an Allometric Miltefosine Regimen for the Treatment of Visceral Leishmaniasis in Eastern African Children: An Open-label, Phase II Clinical Trial.

BACKGROUND: Convenient, safe, and effective treatments for visceral leishmaniasis in Eastern African children are lacking. Miltefosine, the only oral treatment, failed to achieve adequate efficacy, particularly in children, in whom linear dosing (2.5 mg/kg/day for 28 days) resulted in a 59% cure rate, with lower systemic exposure than in adults. METHODS: We conducted a Phase II trial in 30 children with visceral leishmaniasis, aged 4-12 years, to test whether 28 days of allometric miltefosine dosing safely achieves a higher systemic exposure than linear dosing. RESULTS: Miltefosine accumulated during treatment. Median areas under the concentration time curve from days 0-210 and plasma maximum concentration values were slightly higher than those reported previously for children on linear dosing, but not dose-proportionally. Miltefosine exposure at the start of treatment was increased, with higher median plasma concentrations on day 7 (5.88 versus 2.67 µg/mL). Concentration-time curves were less variable, avoiding the low levels of exposure observed with linear dosing. The 210-day cure rate was 90% (95% confidence interval, 73-98%), similar to that previously described in adults. There were 19 treatment-related adverse events (AEs), but none caused treatment discontinuation. There were 2 serious AEs: both were unrelated to treatment and both patients were fully recovered. CONCLUSIONS: Allometric miltefosine dosing achieved increased and less-variable exposure than linear dosing, though not reaching the expected exposure levels. The new dosing regimen safely increased the efficacy of miltefosine for Eastern African children with visceral leishmaniasis. Further development of miltefosine should adopt allometric dosing in pediatric patients. CLINICAL TRIALS REGISTRATION: NCT02431143.

Prevalence of rotavirus infection among children with acute diarrhoea after rotavirus vaccine introduction in Kenya, a hospital cross-sectional study.

BACKGROUND: Rotavirus infection is the most common cause of acute gastroenteritis globally in children under 5 years of age and is responsible for approximately 5% of all child deaths yearly. Rotavirus vaccination is considered an effective public health strategy to prevent infection and reduce the severity of disease. Multi-centre country trials on rotavirus vaccines demonstrated efficacy rates of more than 85% in developed countries but only about 65% in developing nations. Rotavirus vaccination was introduced into the Kenya Expanded Programme on Immunization (KEPI) in 2014. The objective of our study was to determine the prevalence of rotavirus infection, severity of acute diarrhoea and to determine the rotavirus vaccination status among children aged 3-24 months presenting with acute diarrhoea at Kenyatta National Hospital after introduction of rotavirus vaccine in Kenya. METHODS: A total of 365 children aged 3-24 months presenting with acute diarrhoea at KNH were recruited from August 2016 to April 2017. Data on rotavirus vaccination status, nutritional status, feeding practices and sociodemographic characteristics were obtained and a full clinical evaluation of the patients was done. Severity of the gastroenteritis was assessed using the 20 point Vesikari Clinical Severity Scoring System. The children who were admitted were followed up for 7 days using hospital ward registers. Comorbid conditions were established from patient's clinical records and physical examination. Stool specimens from study participants were tested for rotavirus using a commercially available enzyme linked immunosorbent immunoassay kit- ProSpecT Rotavirus Microplate Assay. RESULTS: Majority of the children (96.7%) had received rotavirus vaccinations. The overall rotavirus prevalence was 14.5% and was higher among 17-24 months at 19.5%. The prevalence somewhat differed by gender, nutritional status, exclusive breastfeeding status, age and education level of mother/caregiver. Overall, a half of the children had severe acute diarrhoea and there were some differences in severity by child/mother characteristics. CONCLUSION: There is still burden of rotavirus diarrhoea after introduction of rotavirus vaccine and the prevalence varies by child characteristics.

Estimated Effect of Temperature on Years of Life Lost: A Retrospective Time-Series Study of Low-, Middle-, and High-Income Regions.

BACKGROUND: Numerous studies have reported a strong association between temperature and mortality. Additional insights can be gained from investigating the effects of temperature on years of life lost (YLL), considering the life expectancy at the time of death. OBJECTIVES: The goal of this work was to assess the association between temperature and YLL at seven low-, middle-, and high-income sites. METHODS: We obtained meteorological and population data for at least nine years from four Health and Demographic Surveillance Sites in Kenya (western Kenya, Nairobi), Burkina Faso (Nouna), and India (Vadu), as well as data from cities in the United States (Philadelphia, Phoenix) and Sweden (Stockholm). A distributed lag nonlinear model was used to estimate the association of daily maximum temperature and daily YLL, lagged 0-14 d. The reference value was set for each site at the temperature with the lowest YLL. RESULTS: Generally, YLL increased with higher temperature, starting day 0. In Nouna, the hottest location, with a minimum YLL temperature at the first percentile, YLL increased consistently with higher temperatures. In Vadu, YLL increased in association with heat, whereas in Nairobi, YLL increased in association with both low and high temperatures. Associations with cold and heat were evident for Phoenix (stronger for heat), Stockholm, and Philadelphia (both stronger for cold). Patterns of associations with mortality were generally similar to those with YLL. CONCLUSIONS: Both high and low temperatures are associated with YLL in high-, middle-, and low-income countries. Policy guidance and health adaptation measures might be improved with more comprehensive indicators of the health burden of high and low temperatures such as YLL. https://doi.org/10.1289/EHP1745.

Effectiveness of home-based nutritional counselling and support on exclusive breastfeeding in urban poor settings in Nairobi: a cluster randomized controlled trial.

BACKGROUND: Exclusive breastfeeding (EBF) improves infant health and survival. We tested the effectiveness of a home-based intervention using Community Health Workers (CHWs) on EBF for six months in urban poor settings in Kenya. METHODS: We conducted a cluster-randomized controlled trial in Korogocho and Viwandani slums in Nairobi. We recruited pregnant women and followed them until the infant's first birthday. Fourteen community clusters were randomized to intervention or control arm. The intervention arm received home-based nutritional counselling during scheduled visits by CHWs trained to provide specific maternal infant and young child nutrition (MIYCN) messages and standard care. The control arm was visited by CHWs who were not trained in MIYCN and they provided standard care (which included aspects of ante-natal and post-natal care, family planning, water, sanitation and hygiene, delivery with skilled attendance, immunization and community nutrition). CHWs in both groups distributed similar information materials on MIYCN. Differences in EBF by intervention status were tested using chi square and logistic regression, employing intention-to-treat analysis. RESULTS: A total of 1110 mother-child pairs were involved, about half in each arm. At baseline, demographic and socioeconomic factors were similar between the two arms. The rates of EBF for 6 months increased from 2% pre-intervention to 55.2% (95% CI 50.4-59.9) in the intervention group and 54.6% (95% CI 50.0-59.1) in the control group. The adjusted odds of EBF (after adjusting for baseline characteristics) were slightly higher in the intervention arm compared to the control arm but not significantly different: for 0-2 months (OR 1.27, 95% CI 0.55 to 2.96; p = 0.550); 0-4 months (OR 1.15; 95% CI 0.54 to 2.42; p = 0.696), and 0-6 months (OR 1.11, 95% CI 0.61 to 2.02; p = 0.718). CONCLUSIONS: EBF for six months significantly increased in both arms indicating potential effectiveness of using CHWs to provide home-based counselling to mothers. The lack of any difference in EBF rates in the two groups suggests potential contamination of the control arm by information reserved for the intervention arm. Nevertheless, this study indicates a great potential for use of CHWs when they are incentivized and monitored as an effective model of promotion of EBF, particularly in urban poor settings. Given the equivalence of the results in both arms, the study suggests that the basic nutritional training given to CHWs in the basic primary health care training, and/or provision of information materials may be adequate in improving EBF rates in communities. However, further investigations on this may be needed. One contribution of these findings to implementation science is the difficulty in finding an appropriate counterfactual for community-based educational interventions. TRIAL REGISTRATION: ISRCTN ISRCTN83692672 . Registered 11 November 2012. Retrospectively registered.

Measurement of overweight and obesity an urban slum setting in sub-Saharan Africa: a comparison of four anthropometric indices.

BACKGROUND: As a result of both genetic and environmental factors, the body composition and topography of African populations are presumed to be different from western populations. Accordingly, globally accepted anthropometric markers may perform differently in African populations. In the era of rapid emergence of cardio-vascular diseases in sub-Saharan Africa, evidence about the performance of these markers in African settings is essential. The aim of this study was to investigate the inter-relationships among the four main anthropometric indices in measuring overweight and obesity in an urban poor African setting. METHODS: Data from a cardiovascular disease risk factor assessment study in urban slums of Nairobi were analyzed. In the major study, data were collected from 5190 study participants. We considered four anthropometric markers of overweight and obesity: Body Mass Index, Waist Circumference, Waist to Hip Ratio, and Waist to Height Ratio. Pairwise correlations and kappa statistics were used to assess the relationship and agreement among these markers, respectively. Discordances between the indices were also analyzed. RESULTS: The weighted prevalence of above normal body composition was 21.6 % by body mass index, 28.9 % by waist circumference, 45.5 % by waist to hip ratio, and 38.9 % by waist to height ratio. The overall inter-index correlation was +0.44. Waist to hip ratio generally had lower correlation with the other anthropometric indices. High level of discordance exists between body mass index and waist to hip ratio. Combining the four indices shows that 791 (16.1 %) respondents had above normal body composition in all four indices. Waist circumference better predicted hypertension and hyperglycemia while waist to height ratio better predicted hypercholesterolemia. CONCLUSIONS: There exists a moderate level of correlation and a remarkable level of discordance among the four anthropometric indices with regard to the ascertainment of abnormal body composition in an urban slum setting in Africa. Waist circumference is a better predictor of cardio-metabolic risk.

Outcomes and costs of implementing a community-based intervention for hypertension in an urban slum in Kenya.

OBJECTIVE: To describe the processes, outcomes and costs of implementing a multi-component, community-based intervention for hypertension among adults aged > 35 years in a large slum in Nairobi, Kenya. METHODS: The intervention in 2012-2013 was based on four components: awareness-raising; improved access to screening; standardized clinical management of hypertension; and long-term retention in care. Using multiple sources of data, including administrative records and surveys, we described the inputs and outputs of each intervention activity and estimated the outcomes of each component and the impact of the intervention. We also estimated the costs associated with implementation, using a top-down costing approach. FINDINGS: The intervention reached 60% of the target population (4049/6780 people), at a cost of 17 United States dollars (US$) per person screened and provided access to treatment for 68% (660/976) of people referred, at a cost of US$ 123 per person with hypertension who attended the clinic. Of the 660 people who attended the clinic, 27% (178) were retained in care, at a cost of US$ 194 per person retained; and of those patients, 33% (58/178) achieved blood pressure control. The total intervention cost per patient with blood pressure controlled was US$ 3205. CONCLUSION: With moderate implementation costs, it was possible to achieve hypertension awareness and treatment levels comparable to those in high-income settings. However, retention in care and blood pressure control were challenges in this slum setting. For patients, the costs and lack of time or forgetfulness were barriers to retention in care.

Measuring exposure levels of inhalable airborne particles (PM2.5) in two socially deprived areas of Nairobi, Kenya.

INTRODUCTION: Ambient air pollution is a growing global health concern tightly connected to the rapid global urbanization. Health impacts from outdoor air pollution exposure amounts to high burdens of deaths and disease worldwide. However, the lack of systematic collection of air pollution and health data in many low-and middle-income countries remains a challenge for epidemiological studies in the local environment. This study aimed to provide a description of the particulate matter (PM2.5) concentration in the poorest urban residential areas of Nairobi, Kenya. METHODS: Real-time measurements of (PM2.5) were conducted in two urban informal settlements of Nairobi City, Kenya"s Capital, from February 2013 to October 2013. The measurements were conducted using DustTrak II 8532 hand-held samplers at a height of about 1.5m above ground level with a resolution of 1-min logging. Sampling took place from early morning to evenings according to a fixed route of measurement within areas including fixed geographical checkpoints. RESULTS: The study period average concentration of PM2.5 was 166µg/m(3) in the Korogocho area and 67µg/m(3) in the Viwandani area. The PM2.5 levels in both areas reached bimodal daily peaks in the morning and evening. The average peak value of morning concentration in Korogocho was 214µg/m(3), and 164µg/m(3) in the evening and in Viwandani was 76µg/m(3) and 82µg/m(3) respectively. The daily mid-day average low observed during was 146µg/m(3) in Korogocho and 59µg/m(3) in Viwandani. CONCLUSION: The results show that residents in both slums are continuously exposed to PM2.5 levels exceeding hazardous levels according to World Health Organization guidelines. The study showed a marked disparity between the two slum areas situated only 7km apart indicating the local situation and sources to be very important for exposure to PM2.5.

Impact evaluation of a community-based intervention for prevention of cardiovascular diseases in the slums of Nairobi: the SCALE-UP study.

BACKGROUND: A combination of increasing urbanization, behaviour change, and lack of health services in slums put the urban poor specifically at risk of cardiovascular disease (CVD). This study aimed to evaluate the impact of a community-based CVD prevention intervention on blood pressure (BP) and other CVD risk factors in a slum setting in Nairobi, Kenya. DESIGN: Prospective intervention study includes awareness campaigns, household visits for screening, and referral and treatment of people with hypertension. The primary outcome was overall change in mean systolic blood pressure (SBP), while secondary outcomes were changes in awareness of hypertension and other CVD risk factors. We evaluated the intervention's impact through consecutive cross-sectional surveys at baseline and after 18 months, comparing outcomes of intervention and control group, through a difference-in-difference method. RESULTS: We screened 1,531 and 1,233 participants in the intervention and control sites. We observed a significant reduction in mean SBP when comparing before and after measurements in both intervention and control groups, -2.75 mmHg (95% CI -4.33 to -1.18, p=0.001) and -1.67 mmHg (95% CI -3.17 to -0.17, p=0.029), respectively. Among people with hypertension at baseline, SBP was reduced by -14.82 mmHg (95% CI -18.04 to -11.61, p<0.001) in the intervention and -14.05 (95% CI -17.71 to -10.38, p<0.001) at the control site. However, comparing these two groups, we found no difference in changes in mean SBP or hypertension prevalence. CONCLUSIONS: We found significant declines in SBP over time in both intervention and control groups. However, we found no additional effect of a community-based intervention involving awareness campaigns, screening, referral, and treatment. Possible explanations include the beneficial effect of baseline measurements in the control group on behaviour and related BP levels, and the limited success of treatment and suboptimal adherence in the intervention group.

Analysis of Patterns of Physical Activity and Sedentary Behavior in an Urban Slum Setting in Nairobi, Kenya.

BACKGROUND: Insufficient physical activity and sedentary behavior are key risk factors for the emergence of noncommunicable diseases in the sub-Saharan African setting. Given the limited evidence base, research is required to understand the trends. OBJECTIVES: This study describes the patterns of physical activity and sedentary behavior in a large sample of urban slum residents in Nairobi, Kenya. METHODS: We used data collected from 5190 study participants as part of cardiovascular disease risk assessment. Data were collected about work-, transport-, and recreation-related physical activity as well as sitting and sleeping time. Using time spent on each type of physical activity and respective metabolic equivalents (METs), patterns of physical activity and associated factors were evaluated using descriptive statistics, Pearson correlations, and logistic regression. RESULTS: Nearly 50% of the study population was involved in work-related physical activities, whereas only 6.3% was involved in recreation-related physical activities. Involvement in physical activities decreased with age, and 17.4% had <600 MET-minutes per week. Higher sitting time was associated with insufficient physical activity. There were substantial gender differences in the time spent for physical activity. CONCLUSIONS: Given the positive relationship between insufficient physical activity and sedentary behavior, complementary interventions that improve physical activity and at the same time reduce sitting time are needed.

Interlinkage among cardio-metabolic disease markers in an urban poor setting in Nairobi, Kenya.

INTRODUCTION: The main cardio-metabolic diseases - mostly cardiovascular diseases such as stroke and ischemic heart disease - share common clinical markers such as raised blood pressure and blood glucose. The pathways of development of many of these conditions are also interlinked. In this regard, a higher level of co-occurrence of the main cardio-metabolic disease markers is expected. Evidence about the patterns of occurrence of cardio-metabolic markers and their interlinkage in the sub-Saharan African setting is inadequate. OBJECTIVE: The goal of the study was to describe the interlinkage among common cardio-metabolic disease markers in an African setting. DESIGN: We used data collected in a cross-sectional study from 5,190 study participants as part of cardiovascular disease risk assessment in the urban slums of Nairobi, Kenya. Five commonly used clinical markers of cardio-metabolic conditions were considered in this analysis. These markers were waist circumference, blood pressure, random blood glucose, total blood cholesterol, and triglyceride levels. Patterns of these markers were described using means, standard deviations, and proportions. The associations between the markers were determined using odds ratios. RESULTS: The weighted prevalence of central obesity, hypertension, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia were 12.3%, 7.0%, 2.5%, 10.3%, and 17.3%, respectively. Women had a higher prevalence of central obesity and hypercholesterolemia as compared to men. Blood glucose was strongly associated with central obesity, blood pressure, and triglyceride levels, whereas the association between blood glucose and total blood cholesterol was not statistically significant. CONCLUSIONS: This study shows that most of the common cardio-metabolic markers are interlinked, suggesting a higher probability of comorbidity due to cardio-metabolic conditions and thus the need for integrated approaches.

Household Air Pollution: Sources and Exposure Levels to Fine Particulate Matter in Nairobi Slums.

With 2.8 billion biomass users globally, household air pollution remains a public health threat in many low- and middle-income countries. However, little evidence on pollution levels and health effects exists in low-income settings, especially slums. This study assesses the levels and sources of household air pollution in the urban slums of Nairobi. This cross-sectional study was embedded in a prospective cohort of pregnant women living in two slum areas-Korogocho and Viwandani-in Nairobi. Data on fuel and stove types and ventilation use come from 1058 households, while air quality data based on the particulate matters (PM2.5) level were collected in a sub-sample of 72 households using the DustTrak™ II Model 8532 monitor. We measured PM2.5 levels mainly during daytime and using sources of indoor air pollutions. The majority of the households used kerosene (69.7%) as a cooking fuel. In households where air quality was monitored, the mean PM2.5 levels were high and varied widely, especially during the evenings (124.6 µg/m³ SD: 372.7 in Korogocho and 82.2 µg/m³ SD: 249.9 in Viwandani), and in households using charcoal (126.5 µg/m³ SD: 434.7 in Korogocho and 75.7 µg/m³ SD: 323.0 in Viwandani). Overall, the mean PM2.5 levels measured within homes at both sites (Korogocho = 108.9 µg/m³ SD: 371.2; Viwandani = 59.3 µg/m³ SD: 234.1) were high. Residents of the two slums are exposed to high levels of PM2.5 in their homes. We recommend interventions, especially those focusing on clean cookstoves and lighting fuels to mitigate indoor levels of fine particles.

Results of a hypertension and diabetes treatment program in the slums of Nairobi: a retrospective cohort study.

BACKGROUND: Cardiovascular diseases (CVD) are the world's leading cause of death and their prevalence is rising. Diabetes and hypertension, major risk factors for CVD, are highly prevalent among the urban poor in Africa, but treatment options are often limited in such settings. This study reports on the results of an intervention for the treatment of diabetes and hypertension for adult residents of two slums in Nairobi, Kenya. METHODS: After setting up two clinics in two slums in Nairobi, hypertension and/or diabetes patients were seen by a clinician monthly. Socio-demographic characteristics and clinical data were collected over a 34-month period. Records were analyzed for 726 patients who visited the clinics at least once to determine clinic attendance and compliance patterns using survival analysis. We also examined changes in systolic blood pressure (SBP), diastolic blood pressure (DBP) and random blood glucose (RBG) during the course of the program. RESULTS: There was poor compliance with clinic attendance as only 3.4% of patients attended the clinics on a regular (monthly) basis throughout the 34-month period. 75% of hypertension patients were not compliant after four visits and 27% of patients had only one clinic visit. Significant reduction of mean SBP and DBP (150.4 mmHg to 141.5 mmHg, P = .003, and 89.3 mmHg to 83.2 mmHg, P < .001) was seen for all patients that stayed in care for at least one year. CONCLUSIONS: Establishing a preventative care and treatment system in low resource settings for CVD is challenging due to high dropout rates and non-compliance. Innovative strategies are needed to ensure that benefits of treatment programs are sustained for long-term CVD risk reduction in poor urban populations.

Co-occurrence of behavioral risk factors of common non-communicable diseases among urban slum dwellers in Nairobi, Kenya.

BACKGROUND: The four common non-communicable diseases (NCDs) account for 80% of NCD-related deaths worldwide. The four NCDs share four common risk factors. As most of the existing evidence on the common NCD risk factors is based on analysis of a single factor at a time, there is a need to investigate the co-occurrence of the common NCD risk factors, particularly in an urban slum setting in sub-Saharan Africa. OBJECTIVE: To determine the prevalence of co-occurrence of the four common NCDs risk factors among urban slum dwellers in Nairobi, Kenya. DESIGN: This analysis was based on the data collected as part of a cross-sectional survey to assess linkages among socio-economic status, perceived personal risk, and risk factors for cardiovascular and NCDs in a population of slum dwellers in Nairobi, Kenya, in 2008-2009. A total of 5,190 study subjects were included in the analysis. After selecting relevant variables for common NCD risk factors, we computed the prevalence of all possible combinations of the four common NCD risk factors. The analysis was disaggregated by relevant background variables. RESULTS: The weighted prevalences of unhealthy diet, insufficient physical activity, harmful use of alcohol, and tobacco use were found to be 57.2, 14.4, 10.1, and 12.4%, respectively. Nearly 72% of the study participants had at least one of the four NCD risk factors. About 52% of the study population had any one of the four NCD risk factors. About one-fifth (19.8%) had co-occurrence of NCD risk factors. Close to one in six individuals (17.6%) had two NCD risk factors, while only 2.2% had three or four NCD risk factors. CONCLUSIONS: One out of five of people in the urban slum settings of Nairobi had co-occurrence of NCD risk factors. Both comprehensive and differentiated approaches are needed for effective NCD prevention and control in these settings.