Background For uncomplicated Plasmodium falciparum malaria, highly efficacious single-dose treatments are expected to increase compliance and improve treatment outcomes, and thereby may slow the development of resistance. The efficacy and safety of a single-dose combination of artefenomel (800 mg) plus ferroquine (400/600/900/1200 mg doses) for the treatment of uncomplicated P. falciparum malaria were evaluated in Africa (focusing on children ≤ 5 years) and Asia. Methods The study was a randomized, double-blind, single-dose, multi-arm clinical trial in patients aged > 6 months to < 70 years, from six African countries and Vietnam. Patients were followed up for 63 days to assess treatment efficacy, safety and pharmacokinetics. The primary efficacy endpoint was the polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) at Day 28 in the Per-Protocol [PP] Set comprising only African patients ≤ 5 years. The exposure–response relationship for PCR-adjusted ACPR at Day 28 and prevalence of kelch-13 mutations were explored. Results A total of 373 patients were treated: 289 African patients ≤ 5 years (77.5%), 64 African patients > 5 years and 20 Asian patients. None of the treatment arms met the target efficacy criterion for PCR-adjusted ACPR at Day 28 (lower limit of 95% confidence interval [CI] > 90%). PCR-adjusted ACPR at Day 28 [95% CI] in the PP Set ranged from 78.4% [64.7; 88.7%] to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg ferroquine dose. Efficacy rates were low in Vietnamese patients, ranging from 20 to 40%. A clear relationship was found between drug exposure (artefenomel and ferroquine concentrations at Day 7) and efficacy (primary endpoint), with higher concentrations of both drugs resulting in higher efficacy. Six distinct kelch-13 mutations were detected in parasite isolates from 10/272 African patients (with 2 mutations known to be associated with artemisinin resistance) and 18/20 Asian patients (all C580Y mutation). Vomiting within 6 h of initial artefenomel administration was common (24.6%) and associated with lower drug exposures. Conclusion The efficacy of artefenomel/ferroquine combination was suboptimal in African children aged ≤ 5 years, the population of interest, and vomiting most likely had a negative impact on efficacy. Trial registration ClinicalTrials.gov, NCT02497612. Registered 14 Jul 2015, https://clinicaltrials.gov/ct2/show/NCT02497612?term=NCT02497612&draw=2&rank=1

Background Health worker strikes are a significant threat to universal access to care globally and especially in sub Saharan Africa. Kenya’s health sector has seen an increase in such industrial action. Globally there is limited data that has examined mortality related to such strikes in countries where emergency services were preserved. We sought to assess the mortality impact of an 100 day physician strike which was followed by 151 day nurses’ strike and 20 day clinical officer strike in Kenya. Methods Monthly mortality data was abstracted from four public hospitals, Kenyatta National Referral Hospital, AIC Kijabe Hospital, Mbagathi Hospital and Siaya Hospital between December 2016 and March 2018. Differences in mortality were assessed using t-tests and multiple linear regression adjusting for facility, numbers of patients utilizing the hospital and department. Results There was a significant decline in the numbers of patients seen, comparing the non-strike and strike periods; beta (ß) coefficient − 649 (95% CI -950, − 347) p < 0.0001. The physicians’ strike saw a significant decline in mortality (ß) coefficient − 19.0 (95%CI -29.2, − 8.87) p < 0.0001. Nurses and Clinical Officer strikes’ did not significantly impact mortality. There was no mortality increase in the post-strike period beta (ß) coefficient 7.42 (95%CI -16.7, 1.85) p = 0.12. Conclusion Declines in facility-based mortality during strike months was noted when compared to a non-striking facility, where mortality increased. The decline is possibly associated with the reduced patient volumes, and a possible change in quality of care. Public health facilities are congested and over-utilized by the local population majority of whom cannot afford even low cost private care. Health worker strikes in Kenya where the public health system is the only financially accessible option for 80% of the population pose a significant threat to universal access to care. Judicious investment in the health infrastructure and staffing may decrease congestion and improve quality of care with attendant mortality decline.

The chest radiograph (CXR) is considered a key diagnostic tool for pediatric tuberculosis (TB) in clinical management and endpoint determination in TB vaccine trials. We set out to compare interrater agreement for TB diagnosis in western Kenya. A pediatric pulmonologist and radiologist (experts), a medical officer (M.O), and four clinical officers (C.Os) with basic training in pediatric CXR reading blindly assessed CXRs of infants who were TB suspects in a cohort study. C.Os had access to clinical findings for patient management. Weighted kappa scores summarized interrater agreement on lymphadenopathy and abnormalities consistent with TB. Sensitivity and specificity of raters were determined using microbiologically confirmed TB as the gold standard (n = 8). A total of 691 radiographs were reviewed. Agreement on abnormalities consistent with TB was poor; k = 0.14 (95% CI: 0.10–0.18) and on lymphadenopathy moderate k = 0.26 (95% CI: 0.18–0.36). M.O [75% (95% CI: 34.9%–96.8%)] and C.Os [63% (95% CI: 24.5%–91.5%)] had high sensitivity for culture confirmed TB. TB vaccine trials utilizing expert agreement on CXR as a nonmicrobiologically confirmed endpoint will have reduced specificity and will underestimate vaccine efficacy. C.Os detected many of the bacteriologically confirmed cases; however, this must be interpreted cautiously as they were unblinded to clinical features.

There is inadequate understanding of the epidemiology of Non-Tuberculous Mycobacteria (NTM) among infants in high tuberculosis burden countries. The objective of this study was to document the incidence and diversity of NTM disease or colonisation in sputum specimens from infants with presumptive TB, the risk factors, and clinical characteristics, in a high TB and HIV burden setting in Western Kenya. A cohort of 2900 newborns was followed for 1–2 years to assess TB incidence. TB investigations included collection of induced sputa and gastric aspirates for culture and speciation by HAIN®, Tuberculin Skin Testing (TST), HIV testing, and chest radiography. The American Thoracic Society Criteria (ATS) were applied to identify NTM disease. Among 927 (32% of 2900) with presumptive TB, 742 (80%) were investigated. NTM were isolated from 19/742 (2.6%) infants. M. fortuitum was most frequently speciated (32%). Total person-time was 3330 years. NTM incidence was 5.7/1,000 person-years, 95% CI (3.5, 8.7). Infants diagnosed with TB were more likely to have NTM isolation (odds ratio 11.5; 95% CI 3.25, 41.0). None of the infants with NTM isolated met the criteria for NTM disease. The incidence of NTM isolation was comparable to similar studies in Africa. NTM isolation did not meet ATS criteria for disease and could represent colonisation. TB disease appears to be structural lung disease predisposing to NTM colonisation.