T cell anergy and activation are associated with suboptimal humoral responses to measles revaccination in HIV-infected children on anti-retroviral therapy in Nairobi, Kenya.

HIV-infected children are less capable of mounting and maintaining protective humoral responses to vaccination against measles compared to HIV-uninfected children. This poses a public health challenge in countries with high HIV burdens. Administration of anti-retroviral therapy (ART) and revaccinating children against measles is one approach to increase measles immunity in HIV-infected children, yet it is not effective in all cases. Immune anergy and activation during HIV infection are factors that could influence responses to measles revaccination. We utilized a flow cytometry-based approach to examine whether T cell anergy and activation were associated with the maintenance of measles-specific immunoglobulin (Ig)G antibodies generated in response to measles revaccination in a cohort of HIV-infected children on ART in Nairobi, Kenya. Children who sustained measles-specific IgG for at least 1 year after revaccination displayed significantly lower programmed cell death 1 (PD-1) surface expression on CD8(+) T cells on a per-cell basis and exhibited less activated CD4(+) T cells compared to those unable to maintain detectable measles-specific antibodies. Children in both groups were similar in age and sex, CD4(+) T cell frequency, duration of ART treatment and HIV viral load at enrolment. These data suggest that aberrant T cell anergy and activation are associated with the impaired ability to sustain an antibody response to measles revaccination in HIV-infected children on ART.

ADHERENCE TO PNEUMONIA GUIDELINES FOR CHILDREN 2 - 59 MONTHS AT GARRISA PROVINCIAL GENERAL HOSPITAL.

BACKGROUND: Clinical Practice Guidelines for childhood illnesses including pneumonia in Kenya are contained in the Ministry of Health Basic Paediatric Protocols. In the presence of a cough and/ or difficulty in breathing and increased respiratory rate for age, pneumonia is diagnosed. In addition to these the presence of lower chest wall indrawing denotes severe pneumonia; The presence of cyanosis, inability to drink/ breastfeed, grunting, level of consciousness using the AVPU scale less than A in addition to the aforementioned is classified as very severe pneumonia. Recommended management is intravascular Crystalline penicillin, gentamycin and oxygen for severe pneumonia, intravascular crystalline penicillin for severe pneumonia and oral amoxyl or cotrimaxole for pneumonia. These guidelines have been disseminated through the Emergency Triage And Treatment Plus (ETAT +) coursesheld since 2007. Implementation of guidelines into care has been shown to reduce case fatality from pneumonia by 36%. OBJECTIVES: To evaluate the level of adherence and factors affecting adherence to the National guidelines on management of pneumonia in children aged two to fifty nine months at Garissa provincial General Hospital, Kenya. DESIGN: Retrospective hospital based cross sectional study. SETTING: Paediatric Department of Garissa Provincial General Hospital (PGH) in Kenya. SUBJECTS: Hospital medical records of children aged two to fifty nine months diagnosed with pneumonia between January and June 2012 were reviewed. Data abstracted from the records included demographic information, recorded clinical signs and symptoms, disease classification and treatment. RESULTS: Records of 91 childrenwere reviewed. Theirmedian age was 12 months (IQR 6 - 18 months). There were more boys than girls with a male to female ratio of 1.25:1. Forty-eight of the participants (52.8%) had severe pneumonia. Guideline adherence was assessed at three levels; assessment of clinical signs and symptoms reflected by their recording, correct disease severity classification and correct treatment prescribed. There were a minimum of two and a maximum of six clinical sign and symptoms recorded. The average level of adherence was 42.9% (SD ± 17.3).Documented correct classification of disease severity was 56.6% and recommended treatment of pneumonia was 27.7%. The presence of a co-morbidity and severe disease was associated with better adherence to the assessment tasks (p = 0.033 and p = 0.021 respectively). Disease severity was associated with better adherence to the disease classification task (p = < 0.001) and treatment task (p = 0.02). CONCLUSION: Adherence to guidelines was low at all assessed levels. Overall, disease severity was associated with better guideline adherence. Presence of co-morbidities improved disease assessment.

ASSOCIATION BETWEEN FINGER CLUBBING AND CHRONIC LUNG DISEASE IN HIV INFECTED CHILDREN AT KENYATTA NATIONAL HOSPITAL.

BACKGROUND: Finger clubbing in HIV infected children is associated with pulmonary diseases. Respiratory diseases cause great morbidity and mortality in HIV infected children. OBJECTIVE: To determine association between finger clubbing and chronic lung diseases in HIV infected children and their clinical correlates (in terms of WHO clinical staging, CD4 counts/percentage, anti-retroviral therapy duration and pulmonary hypertension). DESIGN: Hospital based case control study. SETTING: The Kenyatta National Hospital (KNH) comprehensive care clinic (CCC) for HIV infected children and Paediatric General Wards. SUBJECTS: The study population comprised of HIV infected children and adolescents aged eighteen years and below. RESULTS: Chronic lung disease was more common among finger clubbed (55%) than non finger clubbed patients (16.7%). Finger clubbed patients had higher risk of hypoxemia (46.7%), pulmonary hypertension (46.7%) and advanced disease in WHO stage III/IV (91.7%) compared to non-finger clubbed patients. Finger clubbed patients had lower CD4 cells count and percentage (median 369 cells, 13%) compared to non-clubbed patients (median 861 cells, 28%). Duration of ART use was shorter in finger clubbed patients (median 5.5 months) compared to non-finger clubbed patients (median 40 months). CONCLUSION: Presence of finger clubbing in HIV infected children was associated with chronic lung disease, advanced WHO stage, lower CD4 counts/ percentage, shorter duration of ART use and higher likelihood of developing pulmonary hypertension.

Oral Diseases and Oral Health-Related Quality of Life among Kenyan Children and Adolescents with HIV.

INTRODUCTION: Children and adolescents living with HIV (CALHIV) have a higher risk of hard and soft oral tissue diseases as compared with their healthy peers. It is important to increase awareness regarding the need to integrate oral health within medical care among pediatric HIV populations. Studies on associations of oral diseases with oral health-related quality of life (OHRQoL) in CALHIV are lacking. This study examined the association between oral diseases and OHRQoL in Kenyan CALHIV. METHODS: This cross-sectional analysis was nested in a longitudinal cohort study of CALHIV in Nairobi. CALHIV received oral examinations, and the World Health Organization's Oral Health Surveys and Record Form was administered. OHRQoL was measured with the Parental-Caregiver Perceptions Questionnaire, with the subdomains of global, oral symptoms, function limitations, and emotional and social well-being, with higher scores indicating poorer OHRQoL. Linear regression was used to model associations between OHRQoL and oral diseases, adjusting for age at the time of oral examination, CD4 counts, and caregiver's education. RESULTS: Among 71 CALHIV, the mean age was 12.6 y (SD, 2.9; range, 10 to <21), and the mean composite OHRQoL score was 12.6 (SD, 11.2). Ulcers (not herpes simplex virus or aphthous) were associated with the worst overall OHRQoL (mean, 21.8; SD, 11.1; P = 0.055) and oral symptoms subdomain (mean, 7.0, SD, 2.5; P = 0.003). Children with dry mouth and untreated caries had significantly higher mean global OHRQoL scores than those without disease (P < 0.0001). In the multivariate analysis, the OHRQoL composite score was 6.3 units (95% CI, -0.3 to 12.9) higher for those who had dry mouth and untreated dental caries; dry mouth accounted for the highest percentage of variability of OHRQoL (9.6%) and the global subdomain (31.9%). Ulcers accounted for the highest percentage of variability of the oral symptoms domain (15.4%). CONCLUSIONS: Oral ulcers, dry mouth, and untreated caries were associated with poorer OHRQoL in CALHIV. Integrating oral health into the primary care of CALHIV may improve their OHRQoL. KNOWLEDGE TRANSFER STATEMENT: This study aimed to determine the association of oral diseases with the oral health-related quality of life of children and adolescents living with HIV (CALHIV). The findings will form part of the evidence to incorporate oral health protocols into care programs for CALHIV. Oral health monitoring has the potential to increase the surveillance of HIV clinical status, monitor the effectiveness of antiretroviral therapy, and improve the oral health-related quality of life of CALHIV.

IMPACT OF PARTIAL KANGAROO MOTHER CARE ON GROWTH RATES AND DURATION OF HOSPITAL STAY OF LOW BIRTH WEIGHT INFANTS AT THE KENYATTA NATIONAL HOSPITAL, NAIROBI.

OBJECTIVE: To determine the effect of partial Kangaroo Mother Care (KMC) on growth rates and duration of hospital stay of Low Birth Weight (LBW) infants. DESIGN: Unblinded, randomised clinical controlled trial. SETTING: Kenyatta National Hospital, Nairobi, Kenya. SUBJECTS: Over a nine month period, consecutive recruitment of eligible LBW infants weighing 1000 g to 1750 g was done until a sample of 166 infants was reached. INTERVENTION: Kangaroo mother care was practised over an eight hour period per day for the intervention group while the controls remained in incubators or cots. Weight, head circumference, and mid upper arm circumference were monitored for all infants till discharge at 1800 g. RESULTS: Of the 166 infants recruited 157 were followed up to discharge. Baseline characteristics were similar for the two groups except for mother's age, with the KMC group mothers having a mean age of 26.5 years while the control group mothers had a mean age of 24 years, (p = 0.04). The KMC group had significantly higher growth rates as shown by the higher mean weight gain of 22.5 g/kg/day compared with 16.7g/kg/day for the control group, (p < 0.001); higher mean head circumference gain of 0.91 cm/week compared with 0.54 cm/week for the control group, (p < 0.001) and higher mean mid upper arm circumference gain of 0.76 cm/week compared with 0.48 cm/week for the control group, (p = 0.002). Although overall duration of stay was similar between study arms, when infants were stratified into those above or below 1500 g KMC infants' duration of stay was significantly shorter than those in regular care. Using logistic regression, KMCwas the strongest predictor formeanweight, meanhead circumference and mean MUAC gain while mother's age (older) was the strongest predictor for mean duration of stay with KMC being an independent predictor of duration of stay. CONCLUSION: Low birth weight infants in this cohort achieved rates of growth within the recommended intrauterine growth but babies managed using partial KMC grew faster and were thus discharged earlier than those on standard of care. Since partial KMC was beneficial, it should be fully implemented for all eligible infants.

GLOMERULAR FILTRATION RATE PROFILES IN PAEDIATRIC PATIENTS ON CANCER CHEMOTHERAPY AT THE KENYATTA NATIONAL HOSPITAL, KENYA.

BACKGROUND: An accurate estimation of renal function in children is important in optimising the dose of many drugs used in paediatric oncology for allowing clinical monitoring of the nephrotoxic effects of cytotoxic agents such as cisplatin. The glomerular filtration rate (GFR) is widely accepted as the best index of renal function in patients. Chemotherapy is the mainstay of treatment in the paediatric oncology unit at the Kenyatta National Hospital. OBJECTIVES: To determine the glomerular filtration rate profiles of paediatric oncology patients and to assess changes that had occured over a period of at least six months of continuing cancer chemotherapy. DESIGN: Cross-sectional hospital based survey. SETTING: General Paediatric wards, including Paediatric Oncology and Paediatric Ophthalmology ward. Kenyatta National Hospital, Nairobi, Kenya. Subjects: Paediatric patients who had an established diagnosis of cancer and had been on chemotherapy for at least six months. RESULTS: Out of the 115 children enrolledin the study 43 had abnormal kidney function, This gave a prevalence of 37% (95% CI 28-46).The other 72 children had normal kidney function. Patients aged less than five years and those with solid tumors had a higher likelihood of having an abnormal GFR compared to their older counterparts and thosc with-lymphomas and leukemias. CONCLUSIONS: Monitoring of GFR should be done regularly as decline occurs as one continues on chemotherapy especially for the ones below five years and those witl solid malignancies.

MATERNAL HYPOTENSION AND NEONATAL ACIDAEMIA DURING CAESEREAN DELIVERY UNDER SPINAL ANAESTHESIA.

OBJECTIVES: To determine the incidence of neonatal acidaemia following delivery through caesarean section under spinal anaesthesia and determine the prevalence of maternal hypotension during Caesarean section under spinal anaesthesia and its correlation with neonatal acidaemia. DESIGN: Prospective observational study. SETTING: Kenyatta National Hospital (KNH), Nairobi, Kenya. SUBJECTS: One hundred and seventy-two ASA I and II consecutive term patients undergoing elective Caesarean section under spinal anaesthesia. RESULTS: Forty three babies (27.2%) were born with neonatal acidaemia, defined as umbilical arterial blood pH 7.2. There was, however, no significant difference in the five minute Apgar scores between the acidotic and non-acidotic neonates. Twenty eight patients (17.7%) developed maternal hypotension (systolic Blood Pressure less than 100mmHg). The hypotension was readily corrected within two minutes (mean of 1.43 minutes) of onset using vasopressors and boluses of intravenous fluids. CONCLUSIONS: A short period (< 2 minutes) mean of 1.43 minutes of maternal hypotension has no significant effect on the neonate as assessed by five minute Apgar Scores. Similarly, neonatal acidaemia following Caesarean delivery under spinal anaesthesia does not seem to have any short-term effects on neonatal well-being.

Short term clinical outcome of children with rotavirus infection at Kenyatta National Hospital, Nairobi.

BACKGROUND: Rotavirus infection is the single most common cause of acute gastroenteritis in children under five years of age. Rotavirus gastroenteritis has a high morbidity and mortality in children in Kenya. OBJECTIVES: To determine the short term clinical outcome for children admitted to Kenyatta National Hospital with rotavirus gastroenteritis and the correlates of poor outcome. DESIGN: Short longitudinal survey. SETTING: Kenyatta National Hospital from February to May 2008. SUBJECTS: Five hundred children were screened using a rapid antigen detection kit and ELISA. RESULTS: Of the 191 children who tested positive for rotavirus in stool; 172 children were recruited into the study. Eighty eight per cent of the patients were discharged within one week, 8.1% stayed for more than seven days while 4.1% died. Children who had co-morbidities such as malnutrition, rickets and pneumonia had worse outcomes. CONCLUSION: Rotavirus gastroenteritis has a long hospital stay and a high mortality. Children in shock on admission and those with co-morbid conditions should get priority for they have a poor outcome.

Risk factors for cardiac dysfunction in children on treatment for cancer at Kenyatta National Hospital, Nairobi.

OBJECTIVE: To determine the point prevalence of abnormal cardiac function and to assess the risk factors for cardiac dysfunction in paediatric oncology patients on treatment at Kenyatta National Hospital. DESIGN: Descriptive cross-sectional study with a nested case control. SETTING: Kenyatta National Hospital between February and April 2006. MAIN OUTCOME MEASURES: Left ventricular dysfunction if ejection fraction (EF) <55% or fractional shortening (FS) <29% defined cases. Controls had EF >55% or FS >29%. RESULTS: One hundred and eleven patients were enrolled of whom 32 had abnormal cardiac function and were classified as cases while 79 had normal cardiac function. About a third, point prevalence 29% (95% CI 21.2-37.9), had cardiac dysfunction. Cumulative anthracycline dose was a risk factor for cardiac dysfunction in this population. Above 200 mg/m2 the attributable risk percentage of cardiac dysfunction was 77%. CONCLUSIONS: Serial echocardiography should be performed to identify patients at risk. Alternative treatment protocols should be used when the cumulative anthracycline dose exceeds 200 mg/m2 due to the high attributable risk. Studies to further assess the other associated risk factors and long term effects of anthracycline are recommended.

Predictors of mortality in HIV-1 exposed uninfected post-neonatal infants at the Kenyatta National Hospital, Nairobi.

OBJECTIVES: To identify potential predictors of mortality, to determine mortality rate and to identify prevalent causes of death in a cohort of HIV-1 exposed uninfected infants. DESIGN: Prospective cohort study. SETTING: Kenyatta National Hospital, Nairobi, Kenya. SUBJECTS: Three hundred and fifty one HIV-1 exposed uninfected post-neonatal infants who survived to one year of age. RESULTS: Sixteen infants died (post-neonatal mortality rate of 47/1000 live births), 14 (88%) before six months of age. The most frequently identified medical conditions at death included bronchopneumonia, diarrhoea and failure to thrive. In multivariate analysis, prematurity (RR=10.5, 95%CI 3.8-29.1, p<0.001), teenage motherhood (RR=3.6, Cl 1.0-13.2, p=0.05) and symptomatic maternal HIV-1 disease (RR=2.7, CI 0.9-7.7, p=0.06) were associated with infant mortality. CONCLUSION: Prematurity, teenage motherhood and symptomatic HIV-1 maternal disease were important predictors for post-neonatal mortality in this cohort of HIV-1 exposed uninfected infants. These factors should be considered in monitoring and follow up in prevention of mother-to-child HIV-1 transmission (PMTCT) programs.

Pattern of use of skin care products in children with and without eczematous skin lesions.

OBJECTIVE: To compare the pattern of use of skin care products between children with eczematous skin lesions and those without. DESIGN: Case control study. SETTING: Two well baby clinics at the Kenyatta National Hospital and the Mbagathi District Hospital in Nairobi. SUBJECTS: Eighty nine infants with eczematous skin lesions and 89 age and sex matched controls without skin lesions. MAIN OUTCOME MEASURES: Presence and severity of skin lesions related to the type of skin care products used by the child. RESULTS: Exposure to various products was not significantly different between infants with skin lesions and those without. However, more mothers whose children had a skin rash had made a change in the type of soap and or skin cream used for their child (p<0.0001). The principal reason for changing products was skin rash in the baby and most mothers made changes away from scented baby soap products. CONCLUSION: The study found no significant difference between the cases and controls regarding the type of skin care products used.

Predictive value of interferon-gamma release assays for postpartum active tuberculosis in HIV-1-infected women.

BACKGROUND: Data on the prognostic utility of interferon-gamma release assays (IGRAs) for active tuberculosis (TB) among human immunodeficiency virus 1 (HIV-1) infected individuals are limited. METHODS: Samples from a perinatal cohort of HIV-1-infected women in Kenya, obtained during pregnancy, were tested using T-SPOT®.TB IGRAs to detect Mycobacterium tuberculosis-specific interferon-gamma (IFN-γ) responses. IFN-γ (cut-off values of >0, ≥6 and ≥10 spot-forming cells [SFC]/well) and CD4 cell count (cut-off values of <250 and <350 cells/l) were evaluated to determine sensitivity and specificity using a time-dependent receiver operating characteristic curve and positive predictive value (PPV) using the Kaplan Meier method for future TB within 1 year postpartum. RESULTS: Of 327 women, 9 developed TB within 1 year postpartum (incidence rate 3.5/100 person-years of follow-up, 95%CI 1.66.7). IFN-γ ≥ 6 SFC/well was associated with an optimal trade-off between sensitivity (78%) and specificity (55%) and a PPV of 5.9%. In women with CD4 cell count of <250 cells/µl, the sensitivity and specificity of IFN- 6 SFC/well were respectively 89% and 63%, and the PPV was 19.2%. CONCLUSION: Among HIV-1 infected women, IFN-γ response (≥6 SFC/well) during pregnancy lacked a high PPV for postpartum TB, but had higher sensitivity and PPV among immunosuppressed women (CD4 cell count of <250 cells/µl).

Diagnosis of sexually transmitted infections and bacterial vaginosis among HIV-1-infected pregnant women in Nairobi.

HIV-infected women with sexually transmitted infections (STIs) or bacterial vaginosis (BV) during pregnancy are at increased risk for poor obstetric outcomes. In resource-limited settings, diagnostic testing for STIs and BV is often not available and most pregnant women are managed using syndromic algorithms. As part of a Nairobi perinatal cohort, HIV-1-infected pregnant women were interviewed and samples were collected for STIs and BV testing. Diagnostic accuracy of STIs and BV by syndromic algorithms was evaluated with comparison to the reference standard. Among 441 women, prevalence of BV was 37%, trichomoniasis 16%, chlamydia 4%, syphilis 3% and gonorrhoea 2%. Significantly more women with STIs were aged 21-years-old, had not attended secondary school and had a history of STIs. Syndromic diagnosis of STIs and BV demonstrated a sensitivity of 45% and 57%, and positive predictive value of 30% and 42%, respectively. Among these HIV-infected, pregnant women, STIs and vaginal infections were common and syndromic diagnosis was insensitive, resulting in missed opportunities to intervene and improve infant and maternal health.

Assessment of Inhalation Technique among Asthmatic Children and their Carers at the Kenyatta National Hospital; Kenya

The aim of this study was to evaluate the correctness of use of pressurised metered-dose inhalers and spacer devices and to determine the common errors in the inhalation technique and factors associated with incorrect technique. The descriptive cross-sectional survey took place in the Kenyatta National Hospital; Nairobi; Kenya. Eighty-two asthmatic children aged 6 months to 12 years (median age 45 months; 56males) on inhaler medications and their carers were recruited into the study and assessed for correctness of inhalation technique. Of the 82 subjects; only 37 (45.1) performed all the essential steps of the inhalation technique correctly. The commonest errors were failure to take adequate breaths after actuation of inhaler (45) and not shaking the inhaler before use (18). The characteristics of correct and incorrect users are mainly similar. It was concluded that the majority (55) of asthmatic children and their carers do not perform the inhalation technique correctly

`Keeping Healthy in the Backseat': How Motherhood Interrupted HIV Treatment in Recently Delivered Women in Kenya

Although there is a large body of literature related to the experiences of motherhood and aspects of the change that it brings about; how the experience of motherhood affects the healthcare of women with chronic illness is less documented. This study explores how motherhood in newly delivered HIV-infected mothers in Kenya interrupted their antiretroviral treatment (ART). Qualitative interviews were performed with 26 mothers on ART in a rural or urban area. The data were organised and interpreted using content analysis. The study found that adherence to ART was influenced by contextual differences in socio-cultural expectations and family relationships. Urban life enabled women to make decisions on their own and to negotiate challenges that were often unpredictable. Women in rural areas knew what was expected of them and decisions were normally not for them to make alone. The women in Busia and Kibera had difficulties combining adherence with attaining the socio-cultural definition of good mothering. Lack of support from health providers and weak healthcare systems contributed to inadequate stocks of HIV drugs and inaccessibility of HIV-related care. From the data; we developed the main theme `keeping healthy in the backseat' and the two sub-themes `regaining self-worth through motherhood' and `mother first - patient later.' We suggest that motherhood is context-specific and follows socio-cultural practises; which made it difficult for the women in Kenya to follow ART instructions. There is a need to reassess HIV-related services for mothers on ART in order to give them a better chance to stay on treatment and satisfy their aspiration to be `good mothers.' Contextspecific HIV-treatment policies are necessary for ensuring adherence and successful treatment outcomes