Children with sickle cell anemia (SCA) in areas of Africa with endemic malaria transmission are commonly prescribed malaria chemoprevention. Chemoprevention regimens vary between countries, and the ...comparative efficacy of prevention regimens is largely unknown.
We enrolled Kenyan children aged 1 to 10 years with homozygous hemoglobin S (HbSS) in a randomized, open-label trial conducted between January 23, 2018, and December 15, 2020, in Homa Bay, Kenya. Children were assigned 1:1:1 to daily Proguanil (the standard of care), monthly sulfadoxine/pyrimethamine-amodiaquine (SP-AQ), or monthly dihydroartemisinin-piperaquine (DP) and followed monthly for 12 months. The primary outcome was the cumulative incidence of clinical malaria at 12 months, and the main secondary outcome was the cumulative incidence of painful events by self-report. Secondary outcomes included other parasitologic, hematologic, and general events. Negative binomial models were used to estimate incidence rate ratios (IRRs) per patient-year (PPY) at risk relative to Proguanil. The primary analytic population was the As-Treated population. A total of 246 children were randomized to daily Proguanil (n = 81), monthly SP-AQ (n = 83), or monthly DP (n = 82). Overall, 53.3% (n = 131) were boys and the mean age was 4.6 ± 2.5 years. The clinical malaria incidence was 0.04 episodes/PPY; relative to the daily Proguanil group, incidence rates were not significantly different in the monthly SP-AQ (IRR: 3.05, 95% confidence interval CI: 0.36 to 26.14; p = 0.39) and DP (IRR: 1.36, 95% CI: 0.21 to 8.85; p = 0.90) groups. Among secondary outcomes, relative to the daily Proguanil group, the incidence of painful events was not significantly different in the monthly SP-AQ and DP groups, while monthly DP was associated with a reduced rate of dactylitis (IRR: 0.47; 95% CI: 0.23 to 0.96; p = 0.038). The incidence of Plasmodium falciparum infection relative to daily Proguanil was similar in the monthly SP-AQ group (IRR 0.46; 95% CI: 0.17 to 1.20; p = 0.13) but reduced with monthly DP (IRR 0.21; 95% CI: 0.08 to 0.56; p = 0.002). Serious adverse events were common and distributed between groups, although compared to daily Proguanil (n = 2), more children died receiving monthly SP-AQ (n = 7; hazard ratio HR 5.44; 95% CI: 0.92 to 32.11; p = 0.064) but not DP (n = 1; HR 0.61; 95% CI 0.04 to 9.22; p = 0.89), although differences did not reach statistical significance for either SP-AQ or DP. Study limitations include the unexpectedly limited transmission of P. falciparum in the study setting, the high use of hydroxyurea, and the enhanced supportive care for trial participants, which may limit generalizability to higher-transmission settings where routine sickle cell care is more limited.
In this study with limited malaria transmission, malaria chemoprevention in Kenyan children with SCA with monthly SP-AQ or DP did not reduce clinical malaria, but DP was associated with reduced dactylitis and P. falciparum parasitization. Pragmatic studies of chemoprevention in higher malaria transmission settings are warranted.
clinicaltrials.gov (NCT03178643). Pan-African Clinical Trials Registry: PACTR201707002371165.
Summary At the government, hospital, and health-care provider level, corruption plays a major role in health-care systems in Africa. The returns on health investments of international financial ...institutions, health organisations, and donors might be very low when mismanagement and dysfunctional structures of health-care systems are not addressed. More funding might even aggravate corruption. We discuss corruption and its effects on cancer care within the African health-care system in a sociocultural context. The contribution of high-income countries in stimulating corruption is also described. Corrupt African governments cannot be expected to take the initiative to eradicate corruption. Therefore, international financial institutions, health organisations, and financial donors should use their power to demand policy reforms of health-care systems in Africa troubled by the issue of corruption. These modifications will ameliorate the access and quality of cancer care for patients across the continent, and ultimately improve the outcome of health care to all patients.
Approximately 80 % of children with cancer live in resource-limited settings where prompt access to diagnosis and treatment is challenging. Data regarding delays in diagnosis and treatment and ...outcomes of children with cancer in Kenya are lacking. This study aims to 1) compare the reported and expected number of children with cancer; 2) explore diagnosis, treatment, and total delays; 3) determine patient characteristics that influence delays; and 4) investigate treatment outcomes.
This study combined a retrospective medical records review with a case report. Data on delays and treatment outcomes of children from Bungoma County (Kenya) who were diagnosed with cancer at a large academic hospital between 2010 and 2016 were collected.
Between 2010 and 2016, 92 children, an average of 13 per year, were referred from Bungoma. These 13 children constitute only 9 % of the expected 140 children developing cancer in this region. The most common diagnoses were non-Hodgkin lymphoma (17 %) and acute lymphoblastic leukemia (16 %). The median total delay was 108 (7–1731) days. The median diagnosis delay was 97 days, longer than the median treatment delay (3 days; P < 0.001). A l
onger total delay was associated with referral from another facility (P = 0.008), longer symptom duration (P < 0.001), solid tumors (P = 0.013), stage (P = 0.012), and tribe (P = 0.044). The event-free survival was 21 %. The reasons for treatment failure were abandonment (41 %), progressive/relapsed disease (25 %), or death (13 %). The case study highlights that health beliefs and fear of conventional medicine can delay healthcare seeking.
Underdiagnosis and delays in accessing childhood cancer care are considerable in Bungoma. Increasing awareness among the general public and personnel of primary-care facilities is essential to reducing delays in this county.
IntroductionFebrile neutropenia is an oncological emergency in children with cancer, associated with serious infections and complications. In low-resourced settings, death from infections in children ...with cancer is 20 times higher than in high-resourced treatment settings, thought to be related to delays in antibiotic administration and management. The barriers to effective management of fever episodes in children with cancer have not previously been described. This convergent mixed-methods study will provide the evidence to develop fever treatment guidelines and to inform their effective implementation in children with cancer at Moi Teaching and Referral Hospital (MTRH), a level 6 referral hospital in western Kenya.Methods and analysisProspective data collection of paediatric patients with cancer with new fever episodes admitted to MTRH will be performed during routine treatment. Clinical variables will be collected from 50 fever episodes, including cancer diagnosis and infectious characteristics of the fever episode, and elapsed time from fever onset to various milestones in the management workflow. Semistructured qualitative interviews with healthcare providers (estimated 20 to reach saturation) will explore the barriers to and facilitators of appropriate management of fever episodes in children with cancer. The interview guide was informed by a theoretical framework and Consolidated Framework for Implementation Research. A mixed-methods analysis use of joint display tables and process mapping will link and integrate the two types of data with meta-inferences.Ethics and disseminationInstitutional review board approval was obtained from the MTRH (0004273) and the University of Michigan (HUM0225674), and the study was registered with National Commission for Science Technology and Innovation (P/23/22885). Written consent will be obtained from all participants. Results will be formally shared with local and national policy leadership and local end users, presented at relevant national academic conferences and submitted for publication in a peer-reviewed journal.
Indiana University (IU) initiated fluorescence in situ hybridisation (FISH) methodology for Burkitt Lymphoma (BL) to advance the accuracy and speed of diagnosis in the AMPATH Reference Laboratory at ...Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya. Standard diagnostic testing for BL at MTRH includes morphology of the biopsy specimen or aspirate and limited immunohistochemistry panels.
Tumour specimens from 19 children enrolled from 2016 to 2018 in a prospective study to improve the diagnosis and staging of children with suspected BL were evaluated. Touch preps from biopsy specimens or smears from fine needle aspiration were collected, stained with Giemsa and/or H&E and reviewed by pathologists to render a provisional diagnosis. Unstained slides were stored and later processed for FISH. Duplicate slides were split between two laboratories for analysis. Flow cytometry results were available for all specimens. Results from the newly established FISH laboratory in Eldoret, Kenya were cross-validated in Indianapolis, Indiana.
Concordance studies found 18 of 19 (95%) of specimens studied yielded analysable FISH results for one or both probe sets (
and
) in both locations. There was 94% (17/18) concordance of results between the two FISH laboratories. FISH results were 100% concordant for the 16 specimens with a histopathological diagnosis of BL and two of three non-BL cases (one case no result in IU FISH lab). FISH was similarly concordant with flow cytometry for specimens with positive flow results with the exception of a nasopharyngeal tumour with positive flow results for CD10 and CD20 but was negative by FISH. The modal turn-around time for FISH testing on retrospective study specimens performed in Kenya ranged between 24 and 72 hours.
FISH testing was established, and a pilot study performed, to assess the feasibility of FISH as a diagnostic tool for the determination of BL in a Kenyan paediatric population. This study supports FISH in limited resource settings to improve the accuracy and speed of diagnosis of BL in Africa.
Vincristine-induced peripheral neuropathy (VIPN) is a debilitating side-effect of vincristine. It remains a challenge to predict which patients will suffer from VIPN. Pharmacogenomics may explain an ...individuals' susceptibility to side-effects. In this systematic review and meta-analysis, we describe the influence of pharmacogenomic parameters on the development of VIPN in children with cancer. PubMed, Embase and Web of Science were searched. In total, 1597 records were identified and 21 studies were included. A random-effects meta-analysis was performed for the influence of CYP3A5 expression on the development of VIPN. Single-nucleotide polymorphisms (SNPs) in transporter-, metabolism-, cytoskeleton-, and hereditary neuropathy-associated genes and SNPs in genes previously unrelated to vincristine or neuropathy were associated with VIPN. CYP3A5 expression status was not significantly associated with VIPN. The comparison and interpretation of the results of the included studies was limited due to heterogeneity in the study population, treatment protocol and assessment methods and definitions of VIPN. Independent replication is essential to validate the clinical significance of the reported associations. Future research should aim for prospective VIPN assessment in both a discovery and a replication cohort. Ultimately, the goal would be to screen patients upfront to determine optimal vincristine dosage with regards to efficacy and risk of VIPN.
Background
The COVID‐19 pandemic is of grave concern. As scientific data is being collected about the nature of COVID‐19, government leaders and policy makers are challenged. They might feel ...pressured to take strong measures to stop virus spread. However, decisions could cause more harm than do good. This study maps all existing literature regarding the impact of COVID‐19 containment measures on the health and healthcare of children in East‐Africa.
Methods
This scoping review follows Population Concept Context guidelines of Arksey and O’Malley and PRISMA 2020 checklist. PubMed, Web of Science, and Embase were searched. All peer‐reviewed literature published in English between January 2020 and October 2022 was considered. Initial screening of titles and s was undertaken independently by two reviewers, with a third available in case of doubt. This was followed by full‐text screening involving two independent reviewers.
Results
In total, 70 studies were included. Eight containment measures affecting children's health and healthcare were distinguished: lockdowns, school closures, physical distancing, travel restrictions, business closures, stay‐at‐home orders, curfews, quarantine measures with contact tracing. The consensus in the studies is that containment measures could minimise COVID‐19 spread but have adverse indirect effects on children in East‐Africa. Seven indirect effects were distinguished: economic damage, limited education access, food insecurity, child abuse, limited healthcare access, disrupted health‐programs, and mental health challenges.
Conclusion
Government leaders and policy makers should take adverse indirect effects of COVID‐19 measures into account, particularly in resource‐limited regions such as East‐Africa, apply a holistic approach, and strengthen socioeconomic and health‐systems to protect the most vulnerable.
Highlights
COVID‐19 containment measures have an adverse impact on the health and healthcare of children in East‐Africa.
Not all COVID‐19 containment measures are universally applicable.
Government leaders and policymakers should consider the indirect effects of COVID‐19 containment measures and apply a holistic approach.
Socioeconomic and health‐systems should be strengthened in East‐Africa.
This study aimed to identify the patient characteristics of children with febrile neutropenia, the associated bacterial organisms, and their sensitivity patterns.
A descriptive cross-sectional study ...was conducted at the Moi Teaching and Referral Hospital (MTRH) pediatric oncology ward, from June 2021 to April 2022. A total of 110 children who developed fever and neutropenia during chemotherapy were enrolled. Blood samples for culture were collected aseptically. Patient characteristics were presented in frequency tables. Antimicrobial sensitivity patterns were plotted in tables against the bacterial isolates cultured. Chi-square/Fisher's exact test was used to determine any association between patient characteristics, bacterial growth, and antimicrobial sensitivity.
The majority (n = 66; 60%) were males. The median age was 6.3 years (standard deviation, 3.7). The majority of patients 71 (64.5%) had hematologic malignancies, the most common being AML. There was a significant association between severity of neutropenia and hematologic malignancies (
= .028). In total, 31/110 (28.2%) blood cultures were positive for bacterial growth. Gram-positive bacteria were more frequent (n = 20; 58.1%). The most common organism was
(n = 6; 18.2%), followed by
(n = 5; 15.2%). All the isolates were sensitive to linezolid and vancomycin and also showed good sensitivity toward meropenem (n = 10/11; 90.9%). High resistance to cephalosporins was noted with ceftriaxone (n = 5/6; 83.3%), cefepime (n = 4/7; 57.1%), and ceftazidime (n = 3/4; 75%).
The most common malignancy associated with febrile neutropenia was AML. Gram-positive bacteria were the most common isolates. There was high resistance to cephalosporins.
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