Immunoglobulin heavy variable (IgHV) gene mutation and micro-RNA expression in Burkitt's lymphoma at Moi Teaching and Referral Hospital in Western Kenya.

INTRODUCTION: Burkitt's lymphoma (BL) is a virus associated childhood B-cell cancer common in Eastern Africa. Continued survival of B-cells in germinal centres depend on expression of high affinity immunoglobulins (Ig) to complementary antigens by somatic hypermutation of Ig genes. Cellular microRNAs, non-coding RNAs have been reported to play role in cell cycle regulation. Both viral antigen dependent mutation and micro-RNA expression maybe involved in BL pathogenesis. OBJECTIVE: To describe immunoglobulin heavy variable (IgHV) rearrangement and micro-RNA expressions in BL tumours. METHODS: Genomic DNA were extracted and purified from BL tissue blocks at Moi Teaching and Referral Hospital, before amplification using IgHV consensus primers and sequencing. The sequences were then aligned with germline alleles in IMGT/V-QUEST® database. Total RNA extracted from tissue blocks and cell lines were used to determine relative expression of hsamiR-34a and hsa-miR-127. RESULTS: In all tumours, allele alignment scores and number of mutations range were 89.2-93.2%, 15-24 respectively. The range of IgHV amino acid changes were higher in EBER-1+ (15-25) than EBER-1- (9-15). In MYC+ tumours, the relative expression were: hsa-miR-127(2.09);hsa-miR-34a (2.8) and MYC- hsa-miR-127 (1.2), hsa-miR-34a (1.0). CONCLUSION: B-cell in BL contained somatic mutated IgHV gene and upregulated cellular microRNAs with possible pathogenetic role(s).

A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry.

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.

Global Network for Women's and Children's Health Research: probable causes of stillbirth in low- and middle-income countries using a prospectively defined classification system.

OBJECTIVE: We sought to classify causes of stillbirth for six low-middle-income countries using a prospectively defined algorithm. DESIGN: Prospective, observational study. SETTING: Communities in India, Pakistan, Guatemala, Democratic Republic of Congo, Zambia and Kenya. POPULATION: Pregnant women residing in defined study regions. METHODS: Basic data regarding conditions present during pregnancy and delivery were collected. Using these data, a computer-based hierarchal algorithm assigned cause of stillbirth. Causes included birth trauma, congenital anomaly, infection, asphyxia, and preterm birth, based on existing cause of death classifications and included contributing maternal conditions. MAIN OUTCOME MEASURES: Primary cause of stillbirth. RESULTS: Of 109 911 women who were enrolled and delivered (99% of those screened in pregnancy), 2847 had a stillbirth (a rate of 27.2 per 1000 births). Asphyxia was the cause of 46.6% of the stillbirths, followed by infection (20.8%), congenital anomalies (8.4%) and prematurity (6.6%). Among those caused by asphyxia, 38% had prolonged or obstructed labour, 19% antepartum haemorrhage and 18% pre-eclampsia/eclampsia. About two-thirds (67.4%) of the stillbirths did not have signs of maceration. CONCLUSIONS: Our algorithm determined cause of stillbirth from basic data obtained from lay-health providers. The major cause of stillbirth was fetal asphyxia associated with prolonged or obstructed labour, pre-eclampsia and antepartum haemorrhage. In the African sites, infection also was an important contributor to stillbirth. Using this algorithm, we documented cause of stillbirth and its trends to inform public health programs, using consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. TWEETABLE ABSTRACT: Major causes of stillbirth are asphyxia, pre-eclampsia and haemorrhage. Infections are important in Africa.

Commonly cited incentives in the community implementation of the emergency maternal and newborn care study in western Kenya.

BACKGROUND: Mortality of mothers and newborns is an important public health problem in low-income countries. In the rural setting, implementation of community based education and mobilization are strategies that have sought to reduce these mortalities. Frequently such approaches rely on volunteers within each community. OBJECTIVE: To assess the perceptions of the community volunteers in rural Kenya as they implemented the EmONC program and to identify the incentives that could result in their sustained engagement in the project. METHOD: A community-based cross sectional survey was administered to all volunteers involved in the study. Data were collected using a self-administered supervision tool from all the 881 volunteers. RESULTS: 881 surveys were completed. 769 respondents requested some form of incentive; 200 (26%) were for monetary allowance, 149 (19.4%) were for a bicycle to be used for transportation, 119 (15.5%) were for uniforms for identification, 88 (11.4%) were for provision of training materials, 81(10.5%) were for training in Home based Life Saving Skills (HBLSS), 57(7.4%) were for provision of first AID kits, and 39(5%) were for provision of training more facilitators, 36(4.7%) were for provision of free medication. CONCLUSION: Monetary allowances, improved transportation and some sort of identification are the main incentives cited by the respondents in this context.

NUTRITIONAL STATUS OF CHILDREN ADMITTED FOR DIARRHOEAL DISEASES IN A REFERRAL HOSPITAL IN WESTERN KENYA.

OBJECTIVES: To determine the prevalence of malnutrition among children admitted with acute diarrhoea disease at Moi Teaching and Referral Hospital and to establish the effect of malnutrition on duration of hospital stay. DESIGN: Prospective observational study. SETTING: Paediatric wards of Moi Teaching and Referral Hospital, Eldoret, Kenya. SUBJECTS: A total of 191 children aged 6 and 59 months admitted with acute diarrhoea disease, without chronic co-morbidities or visible severe malnutrition, were systematically enrolled into the study between November 2011 and March 2012. OUTCOME MEASURES: Nutritional status based on WHO WHZ scores taken at admission and duration of hospital stay. RESULTS: The mean age was 13.2 months with a male to female sex ratio of 1.16:1. Of all the children seen with acute diarrhoeal diseases, 43.9% had acute malnutrition (<-2 WHZ score), with 12% being severely malnourished (<-3 Z score). Average duration of hospital stay was 3.36 (SD=1.54) days. Among those with malnutrition the average duration of stay was 3.39 (SD=1.48) days while for those without malnutrition it was 3.21(SD=1.20) days, which was not statistically different. No death was reported. WHO weight for Height Z scores picked 12% of severe form of malnutrition missed out by Welcome Trust classification (weight for age). CONCLUSION: Routine anthrometry including weight for height identifies more children with malnutrition in acute diarrhoeal diseases. Presence of malnutrition did not affect duration of hospital stay.

MANAGEMENT AND OUTCOME OF PATIENTS WITH WILMS' TUMOUR (NEPHROBLASTOMA) AT THE MOI TEACHING AND REFERRAL HOSPITAL, ELDORET, KENYA.

BACKGROUND: Wilms' tumour is a common malignant neoplasm of the kidney and is ranked among the top six solid tumours in children in Kenya. Despite its rapid growth and therefore debilitating effects on its victims, it is one tumour that has shown good response to combined modality approach to its treatmentwith encouraging possibilities of survival even in resource poor settings. OBJECTIVE: To evaluate the management and outcome of patients with Wilms'tumour attended to at Moi Teaching and Referral Hospital (MTRH) during the period between January 2000 and December 2007. DESIGN: Retrospective Study. SETTING: The Paediatric Oncology Service (Oncology unit in the Paediatric Ward, the Paediatric Surgical Ward and the Outpatient Oncology Clinic) at the Moi Teaching and Referral Hospital, Eldoret, Kenya. RESULTS: Information of 45 patients diagnosed with Wilms' tumour was analysed. Forty two (93%) of the patients were referrals from various health facilities in the region. Twenty three (51%) were male and 34 (76%) were aged less than 48 months. Twenty five (56%) had the left kidney affected, 19 (42%) the right kidney and one (2%) bilateral. All the 45 (100%) had an abdominal ultrasound done but none had exhaustive investigations done to stage the disease. Only eight (18%) of the patients had a medical insurance cover. Fourty one (91%) of the patients received specific cancer treatment with 28 (62%) getting combined modality treatment. Nineteen (42%) were lost to follow up. Thirty (67%), 21 (47%), 15 (33%) and 13 (29%) patients were alive six months, one year, two years and three years respectively from the time of diagnosis. 29% survived beyond three years of diagnosis. CONCLUSION: Staging of Wilms tumour fell short of the expected. Neo-adjuvant chemotherapy reduced morbidity and mortality of patients managed for Wilms' tumour. Loss to follow up and cost of treatment had a negative impact on the outcome, a situation that requires to be improved.

Burden and pattern of cancer in Western Kenya.

BACKGROUND: Cancer regisries worldwide have evolved to provide useful information on the burden and diversity of the patterns of cancer, information that is vital for establishing appropriate programmes for disease management. Population based data on cancer in western Kenya as captured in the Eldoret cancer registry established in 1999 is analysed and reported in this paper. OBJECTIVE: To determine the burden and pattern of cancer in Western Kenya by use of data from the Eldoret cancer registry. DESIGN: Retrospective study. SETTING: The cancer registry located in the Department of Haematology at the Moi University, School of Medicine situated at the Moi Teaching and Referral Hospital, Eldoret, Kenya. The hospital has a catchment population of 13 to 15 million people forming about 40% of the Kenyan population. RESULTS: A total of 5,366 patients were diagnosed to have cancer and attended to at the MTRH and other hospitals in Eldoret during the period between January 1999 and December 2006 giving an average of 671 cases per year. Among those treated 2,699 were males and 2,667 were females giving a M: F ratio of 1:1. About 21% of the patients had haematological malignancies with non-Hodgkins lymphoma being the most common. Another 79% of the patients had solid tumours with cancer of the oesophagus being the commonest. Cancer of the cervix and prostrate were the commonest among the females and males respectively. A general increase in the number of patients with Kaposis sarcoma associated with HIV/AIDS pandemic was observed. CONCLUSION: The burden of cancer is a significant health problem in western Kenya and there is need for the development of a comprehensive cancer care programme in the region to address the growing problem.

Characteristics of HIV-infected children seen in Western Kenya.

OBJECTIVES: To describe the characteristics and outcomes of children registered for care in a large HIV care programme in Western Kenya. DESIGN: A retrospective descriptive study. SETTING: USAID-AMPATH HIV clinics in health centres; district and sub-district hospitals; Moi Teaching and Referral Hospital in Western Kenya. SUBJECTS: HIV-infected children below age of 15 years seen in a network of 18 clinics in Western Kenya. INTERVENTIONS: Paediatric HIV diagnosis and care including treatment and prevention of opportunistic infections and provision of combination antiretroviral therapy (CART). MAIN OUTCOME MEASURES: Diagnosis, clinical stage and immune status at enrollment and follow-up; hospitalisation and death. Descriptive statistical analyses and chi square tests were performed. RESULTS: Four thousand and seventeen HIV-infected children seen between June 2002 and April 2008. Median age at enrollment was four years (0-14.2 years), 51% girls, 25% paternal orphans, 10% total orphans and 13% maternal orphans. At enrollment, 25% had weight-for-Age Z scores (WAZ) > or = -1 and 21% had WAZ scores < or = 3. Orphaned children had worse WAZ scores (p=0.0001). Twenty five per cent of children were classified as WHO clinical stage 3 and 4, 56% were WHO clinical stages 1 and 2 with 19% missing clinical staging at enrollment. Cough (25%), gastroenteritis (21%), fever (15%), pneumonia (10%) were the commonest presenting features. Twenty six per cent had been diagnosed with tuberculosis and only 25% started on cotrimoxazole preventive therapy (CPT). Median CD4% at enrollment was 16% (0-64%); latest recorded values were 22% (0-64). Sixty four per cent were on cART (cART+), median age at start was 5.4 (014.4 years). The median initial CD4% among cART+ was 13 (0-62) compared to 24 (0-64) for those not on ART (cART-). Median CD4% for cART+ improved to 22% (0-59); whereas cART- was 23% (0-64) at last appointment. During the period of follow-up, one fifth (19%) of children on cART were lost to follow-up compared to slightly over one third (37%) for those not on cART. Thirty four percent were hospitalised; 41% diagnosed with pneumonia. Six per cent of 4017 were confirmed dead. CONCLUSIONS: HIV-infected children were enrolled in care early in childhood. Orphanhood was prevalent in these children as were gastroenteritis, fever, pneumonia and advanced immuno-suppression. Orphans were more likely to be severely malnourished. Only a quarter of children were put on cotrimoxazole preventive therapy. Children commenced on cART late but responded well to treatment. Loss to follow-up was less prevalent among those on cART.

Patient transfer practices by hospitals in Western Kenya.

BACKGROUND: Patients who are critically ill and those requiring emergency care are transported within and between hospitals on a regular basis seeking diagnostic or therapeutic services not available at the bed side or within the referring institution. The emergency of specialty systems often determines the ultimate destination of patients rather than proximity of facility and this has heightened the need for patient transfer. To achieve a favorable outcome, it is necessary to ensure that any transfer is carried out safely and effectively with minimum disruption of the continuum of care. OBJECTIVES: To determine the gap between existing knowledge of patient transfer principles and the practice by hospitals in Western Kenya referring patients to Moi Teaching and Referral Hospital (MTRH). DESIGN: Cross-sectional descriptive study. SETTING: Accident and emergency department at MTRH. SUBJECTS: Patients transferred in over a period of six months for critical/emergency care. RESULTS: Evaluation was done for 97 transfers during the six months period. Age ranged from four days old to 70 years with a median of 28 years. A wide spectrum of diseases were seen. However in order of frequency the leading five were; trauma and accidents, vascular disorders, infections; anaemia and malignancies. Of the infections, respiratory infections topped the list with pulmonary tuberculosis as the leading disease entity. Majority of patients 43 (44%) were referred within 24 hours of being seen at the primary hospital. Only 56% were transported by ambulance; appropriate escort(nurse) was provided in 60%; documentation was provided in 85%; monitoring enroute was done in 24%; warmth was provided in 62%, 27% were dehydrated requiring resuscitation; respiratory support was inadequate as only 14% (of those who required) had airway and 32% had oxygen provided; intravenous fluids were provided in 34% of those who required; nasogastric intubation was provided in 30% of those who required; urethral catheterisation was provided in 23% of those who required; 50% of those with long bone fractures were splinted and only 3% of those who required cervical spine stabilisation had cervical collar. CONCLUSION: There was significant failure by hospitals in Western Kenya in the application of principles of patient transfer while referring patients to MTRH.

A randomized open label clinical trial to compare the efficacy and safety of intravenous quinine followed by oral malarone vs. intravenous quinine followed by oral quinine in the treatment of severe malaria.

The treatment of patients with severe malaria in sub-Saharan Africa has become a challenge to clinicians due to poor compliance to quinine and the increasing multidrug resistance to antimalarials by the P. falciparum parasite. The aim of this study was to compare the efficacy and safety profile of two truncated antimalarial regimens of intravenous quinine followed by oral Malarone (Malarone arm) with intravenous quinine followed by oral quinine (quinine arm) in the treatment of severe P. falciparum malaria. The outcome measures were parasite clearance time, fever clearance time, efficacy, and adverse events profile. Consecutive patients aged 1-60 years, with a diagnosis of severe malaria with positive blood smears for P. falciparum parasites and admitted to the Moi Teaching and Referral Hospital were randomized into the two study arms. Of the 360 patients studied 167 and 193 cases were randomized into the Malarone and quinine arms, respectively. Of the five (1.4 per cent) patients who died, three came from the quinine arm. The frequency of adverse reactions was higher in the oral quinine group (31.6 per cent) than in the Malarone group (25.7 per cent). The mean parasite clearance time was 120 h and 108 h for the quinine and Malarone arms of the study, respectively, and the mean fever clearance times were 84 h and 72 h for the quinine and Malarone arms, respectively (p=0.1). Truncated therapeutic regimen using malarone after intravenous quinine is safer and as effective as conventional intravenous quinine followed by oral quinine in the treatment of severe malaria. The P. falciparum recrudescence rate was lower with the use of Malarone than for quinine.