Dalton Wamalwa

University of Washington Seattle, Seattle, Washington, United States

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Publications (54)155.73 Total impact

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    ABSTRACT: Despite expanded programs for prevention of mother-to-child HIV transmission (PMTCT), HIV-infected infants may not be diagnosed until they are ill. Comparing HIV prevalence and outcomes in infants diagnosed in PMTCT programs to those in hospital settings may improve pediatric HIV diagnosis strategies. HIV-exposed infants <12 months old were recruited from 9 PMTCT sites in public maternal child health (MCH) clinics or from an inpatient setting in Nairobi, Kenya and tested for HIV using HIV DNA assays. A subset of HIV-infected infants <4.5 months of age was enrolled in a research study and followed for 2 years. HIV prevalence, number needed to test, infant age at testing, and turnaround time for tests were compared between PMTCT programs and hospital sites. Among the enrolled cohort, baseline characteristics, survival, and timing of antiretroviral therapy (ART) initiation were compared between infants diagnosed in PMTCT programs versus hospital. Among 1,923 HIV-exposed infants, HIV prevalence was higher among infants tested in hospital than PMTCT early infant diagnosis (EID) sites (41% vs. 11%, p < 0.001); the number of HIV-exposed infants needed to test to diagnose one infection was 2.4 in the hospital vs. 9.1 in PMTCT. Receipt of HIV test results was faster among hospitalized infants (7 vs. 25 days, p < 0.001). Infants diagnosed in hospital were older at the time of testing than PMTCT diagnosed infants (5.0 vs. 1.6 months, respectively, p < 0.001). In the subset of 99 HIV-infected infants <4.5 months old followed longitudinally, hospital-diagnosed infants did not differ from PMTCT-diagnosed infants in time to ART initiation; however, hospital-diagnosed infants were >3 times as likely to die (HR = 3.1, 95% CI = 1.3-7.6). Among HIV-exposed infants, hospital-based testing was more likely to detect an HIV-infected infant than PMTCT testing. Because young symptomatic infants diagnosed with HIV during hospitalization have very high mortality, every effort should be made to diagnose HIV infections before symptom onset. Systems to expedite turnaround time at PMTCT EID sites and to routinize inpatient pediatric HIV testing are necessary to improve pediatric HIV outcomes.
    Full-text · Article · Dec 2015 · BMC Pediatrics
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    ABSTRACT: Background: Human immunodeficiency virus (HIV)-exposed uninfected (HEU) infants are a growing population in sub-Saharan Africa, with higher morbidity and mortality than HIV-unexposed infants. HEU infants may experience increased morbidity due to breastfeeding avoidance. Objectives: We sought to describe the burden and identify predictors of hospitalization among HEU infants in the first year of life. Methods: Using a retrospective cohort of HIV-infected mothers and their HEU infants in Nairobi, Kenya, we identified infants who were HIV-uninfected at birth and were followed monthly until their last negative HIV test, death, loss to follow-up, or study exit at 1 year of age. Incidence, timing, and reason for hospitalization was assessed overall as well as stratified by feeding method. Predictors of first infectious disease hospitalization were identified using competing risk regression, with HIV acquisition and death as competing risks. Results: Among 388 infants, 113 hospitalizations were reported (35/100 infant-years [the combined years of observation contributed by all infants in the study]; 95% confidence interval [CI], 29-42). Ninety hospitalizations were due to 1 or more infectious diseases (26/100 infant-years; 95% CI, 21-32)-primarily pneumonia (n = 40), gastroenteritis (n = 17), and sepsis (n = 14). Breastfeeding was associated with decreased risk of infectious disease hospitalization (subhazard ratio = 0.39; 95% CI, 0.24-0.64), as was time-updated nutrition status (subhazard ratio = 0.73; 95% CI, 0.61-0.89). Incidence of infectious disease hospitalization among formula-fed infants was 51/100 infant-years (95% CI, 37-70) compared to 19/100 infant-years (95% CI, 14-25) among breastfed infants. Conclusion: Among HEU infants, breastfeeding and nutrition status were associated with reduced hospitalization during the first year of life.
    No preview · Article · Oct 2015 · Journal of Human Lactation
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    ABSTRACT: HIV infected children experience a range of hematological complications which show marked improvement within 6 months of initiating anti-retroviral therapy. The Objectives of the study was to describe the changes in hematological indices of HIV-1 infected children following 6 months of treatment with first line antiretroviral drugs (ARVs) regimen. A retrospective study was conducted between September and November 2008. During this period medical records of children attending Comprehensive Care Clinic at Kenyatta National hospital were reviewed daily. HIV infected children aged 5-144 months were enrolled if they had received antiretroviral drugs for at least 6 months with available and complete laboratory results. Medical records of 337 children meeting enrollment criteria were included in the study. The median age was 63 months with equal male to female ratio. Following 6 months of HAART, prevalence of anemia (Hemoglobin (Hb) <10 g/dl) declined significantly from 35.9 to 16.6 % a nearly 50 % reduction in the risk of anemia RR = 0.56 [(95 % CI 0.44, 0.70) p < 0.001]. There was significant increase in Hb, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and platelets above the baseline measurements (p < 0.0001) and a significant decline in total white blood cell counts >11,000 cell/mm(3) but a none significant decrease in red blood cells (RBC). Pre-HAART, World Health Organization (WHO) stage 3 and 4 was associated with a ten-fold increased likelihood of anemia. Chronic malnutrition was associated with anemia but not wasting and immunologic staging of disease. Hematological abnormalities changed significantly within 6 months of antiretroviral therapy with significant increase in hemoglobin level, MCV, MCH and platelet and decrease in WBC and RBC.
    Full-text · Article · Aug 2015 · AIDS Research and Therapy
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    ABSTRACT: Nevirapine (NVP) resistance occurs frequently in infants following NVP use in prevention of mother-to-child transmission (PMTCT) regimens. However, among previously NVP-unexposed infants treated with NVP-ART, the development and impact of NVP resistance has not been well characterized. In a prospective clinical trial providing early ART to HIV-infected infants <5 months of age in Kenya (OPH03 study), we followed NVP-unexposed infants who initiated NVP-ART for 12 months. Viral loads were assessed, and resistance determined using a population-based genotypic resistance assay. Of 99 infants screened, 33 had no prior NVP exposure, 22 of whom were initiated on NVP-ART. Among 19 infants with follow-up, 7 (37%) infants developed resistance: 1 at 3 months, and 6 at 6 months after ART initiation. Cumulative probability of NVP resistance was 5.9% at 3 months, and 43.5% at 6 months. Baseline HIV RNA levels (p=0.7) and other characteristics were not associated with developing resistance. Post-ART, higher virus levels at visits preceding detection of resistance were significantly associated with increased detection of resistance (p=0.004). Virus levels after 6 and 12 months of ART were significantly higher in infants with resistance than those without (p=0.007, p=0.030, respectively). Among infants without previous NVP exposure, development of NVP resistance was frequent and was associated with virologic failure during the first year of ART. Earlier development of NVP-resistance in infants than in adults initiating NVP-ART may be due to longer viremia following ART or inadequate NVP levels resulting from NVP lead-in dosing. Development of NVP resistance may, in part, explain superiority of protease inhibitor-based ART in infants.
    No preview · Article · Mar 2015 · AIDS research and human retroviruses
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    ABSTRACT: 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 antiretroviral 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 IgG 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 one year after revaccination displayed significantly lower Programmed Cell Death 1 (PD1) 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 enrollment. 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. This article is protected by copyright. All rights reserved. © 2015 British Society for Immunology.
    No preview · Article · Mar 2015 · Clinical & Experimental Immunology
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    Full-text · Article · Feb 2015 · Annals of Global Health
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    ABSTRACT: HIV infected children experience a range of hematological complications including anaemia, neutropenia and thrombocytopenia. The objective of the study was to describe the haemoglobin levels, red cell morphology, white blood cells and platelets of Antiretroviral (ARV) naïve HIV-1 infected children. It was a retrospective study done in the period between September and November 2008. During this period medical records of children attending the paediatric HIV comprehensive care clinic (CCC) at Kenyatta National hospital were reviewed daily. HIV infected children were enrolled into the study if they were aged 5-144 months, and results of haematological assessment at baseline were available. Standard tools were used to abstract pre-HAART haematological parameters as well as anthropometric measurements from individual patient medical records. By the end of the study medical records of 337 children meeting enrollment criteria were reviewed. The median age of the children was 63 months with a male to female ratio of 1:1. The prevalence of anemia at baseline was 35.9% with 7% having hemoglobin levels of less than 8gm/dl. Thrombocytopenia was noted in 21% of the study population and leucopenia in 10%. WHO stage 3 and 4 was associated with a tenfold increased likelihood of anaemia OR=10.6 (95% CI 3.6, 36.3). Chronic malnutrition WAZ <-2SD was associated with anaemia (p=0.04) but wasting and immunologic staging were not. The study concluded that haematological abnormalities are common among HIV infected ARV naïve children and anemia was the commonest hematological abnormality with almost half of the study population having microcytic hypochromic picture of anemia.
    Full-text · Article · Dec 2014
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    L. Kebaya · R. Nduati · D. Wamalwa · N. Kariuki · A. Bashir
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    ABSTRACT: Background HIV is a major contributor to infant mortality. A significant gap remains between the uptake of infant and maternal antiretroviral regimens and only a minority of HIV-exposed infants receives prophylaxis and safe infant feeding. Losses to follow-up of HIV-exposed infants are associated with shortcomings of facility-based PMTCT models with weak community support of linkages. Use of mobile phones offers an opportunity to improving care and promoting retention for the mother-baby pairs, which is a major challenge in efforts to achieving an HIV-free generation. Objectives To compare self-reported adherence to infant nevirapine (NVP) prophylaxis and retention in care in HIV exposed infants randomised to 2-weekly mobile phone call versus control (no phone calls). Design Randomised controlled trial. Methods 150 mother infant pairs were drawn from postnatal wards of 3 health facilities in Kisumu, and randomly assigned to receive either phone-based reminders on PMTCT messages or standard health care messages (no calls). The group in the intervention arm received phone calls fortnightly. Data on infant adherence to nevirapine, retention in care, safe infant feeding and early HIV testing among HIV-exposed infants were collected by use of a questionnaire at the scheduled Maternal Child Health (MCH) visits (6 and 10 weeks). All analyses were intention to treat. Results At 6 weeks follow-up, 90.7% (n = 68) of participants receiving phone calls reported adherence to infant NVP prophylaxis, compared with 72% (n = 54) of participants in the control group (p = 0.005). Participants in the intervention arm were also significantly more likely to remain in care than participants in the control group [78.7% (n = 59) vs. 58.7% (n = 44), p = 0.009 at 6 weeks and 69.3% (n = 52) vs. 37.3% (n = 28), p < 0.001 at 10 weeks]. Conclusions These results suggest that phone calls can be an important tool to improve adherence to infant NVP prophylaxis and retention in care for HIV-exposed infants.
    Preview · Article · Oct 2014 · Archives of Disease in Childhood
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    Full-text · Article · Oct 2014 · AIDS Research and Human Retroviruses
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    ABSTRACT: Abstract Optimal pediatric HIV disclosure impacts illness and developmental experiences while improving access to timely treatment. However, disclosure rates in high HIV prevalence countries remain low and there are limited data on best practices. We conducted a qualitative study of disclosure practices and interviewed healthcare providers from five pediatric HIV clinics in Kenya. We identified themes central to disclosure practices, rationale for approaches, barriers to implementing disclosure, and creative strategies to overcome challenges. We used these insights to develop a practice-based framework for disclosure that is sensitive to practical challenges. Overall, providers had limited training but extensive experience in disclosure, endorsed individualized disclosure practices, invested substantial time on disclosure despite clinical burden, and noted adverse outcomes associated with unplanned or abrupt disclosure. Providers advocated for an approach to disclosure that is child-centered but respects caregiver fears and values. Caregiver support was provided to enable caregivers to be the person who ultimately disclosed HIV status to children. Unplanned or abrupt disclosure to children was reported to have severe and persistent adverse impact and was a stimulus to accelerate disclosure in scenarios when providers believed children may be suspecting their diagnosis. Based on these expert insights, the framework we developed incorporates concurrent evaluation of child and caregiver readiness, identifies cues to prompt disclosure discussions, includes caregiver education and support, and utilizes a gradual approach of unveiling HIV diagnosis to the child.
    No preview · Article · Sep 2014 · AIDS PATIENT CARE and STDs
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    ABSTRACT: Background: Infant HIV-1 infection is associated with impaired neurologic and motor development. Antiretroviral therapy (ART) has the potential to improve developmental outcomes but the relative contributions of pre-ART disease status, growth, treatment regimen and ART response during infancy are unknown. Methods: Kenyan ART-naive infants <5-months old initiated ART and had monthly assessment of age of full neck control, unsupported walking and monosyllabic speech during 24 months of follow-up. Pre-ART and post-ART correlates of age at milestone attainment were evaluated using t tests or multivariate linear regression. Results: Among 99 infants, pre-ART correlates of later milestone attainment included: underweight and stunted (neck control, walking and speech, all P values <0.05), missed prevention of mother-to-child transmission (P = 0.04) (neck control), previous hospitalization, World Health Organization (WHO) Stage III/IV, low CD4 count, and wasting (speech and walking, all P values <0.05), and low maternal CD4 (speech, P = 0.04). Infants initiated ART at a median of 14 days following enrollment. Infants receiving lopinavir/ritonavir-based versus nevirapine-based ART attained later speech (18.1 vs. 15.5 months, P = 0.003). Adjusting for pre-ART level, lower 6-month gain in CD4% was associated with later walking (0.18 months earlier per unit increase in CD4%; P = 0.004) and speech (0.12 months earlier per unit increase in CD4%; P = 0.05), and lower 6-month gains in weight-for-age (P = 0.009), height-for-age (P = 0.03) and weight-for-height (P = 0.02) were associated with later walking. Conclusion: In HIV-infected infants, compromised pre-ART immune and growth status, poor post-ART immune and growth responses, and use of lopinavir/ritonavir-based versus nevirapine-based ART were each associated with later milestone attainment. The long-term consequences of these delays are unknown.
    No preview · Article · Aug 2014 · The Pediatric Infectious Disease Journal
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    ABSTRACT: Background There are limited data on the impact of cesarean section delivery on HIV-1 infected women in Sub-Saharan Africa. The purpose of this study was to assess the effect of mode of delivery on HIV-1 disease progression and postpartum mortality in a Kenyan cohort. Methods A prospective cohort study was conducted in Nairobi, Kenya from 2000–2005. We determined changes in CD4+ counts, HIV-1 RNA levels and mortality during the first year postpartum between HIV-1 infected women who underwent vaginal delivery (VD), non-scheduled cesarean section (NSCS) and scheduled cesarean section (SCS) and received short-course zidovudine. Loess curves and multivariate linear mixed effects models were used to compare longitudinal changes in maternal HIV-1 RNA and CD4+ counts by mode of delivery. Kaplan Meier curves, the log rank test, and Cox proportional hazards regression were used to assess difference in mortality. Results Of 501 women, 405 delivered by VD, 74 delivered by NSCS and 22 by SCS. Baseline characteristics were similar between the VD and NSCS groups. Baseline antenatal CD4+ counts were lowest and HIV-1 RNA levels highest in the NSCS group but HIV-1 RNA levels were similar between groups at delivery. The rate of decline in CD4+ cells and rate of increase in HIV-1 RNA did not differ between groups. After adjusting for confounders, women who underwent NSCS had a 3.39-fold (95% CI 1.11, 10.35, P = 0.03) higher risk of mortality in the first year postpartum compared to women with VD. Conclusions Non-scheduled cesarean section was an independent risk factor for postpartum mortality in HIV-1 positive Kenyan women. The cause of death was predominantly due to HIV-1 related infections, and not direct maternal deaths, however, this was not mirrored by differential changes in HIV-1 progression markers between the groups.
    Full-text · Article · Aug 2014 · BMC Pregnancy and Childbirth
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    ABSTRACT: To determine neonatal immunologic factors that correlate with mother-to-child-transmission of HIV-1. This case-control study compared cord blood natural killer (NK) and T-cell populations of HIV-1 exposed infants who subsequently acquired infection by 1 month (cases) to those who remained uninfected by 1 year of life (controls). Control specimens were selected by proportional match on maternal viral load. Cryopreserved cord blood mononuclear cells (CBMCs) were thawed and stained for multiparameter flow cytometry to detect NK and T-cell subsets and activation status. CBMCs were also used in a viral suppression assay to evaluate NK cell inhibition of HIV-1 replication in autologous CD4 T cells. Cord blood from cases contained a skewed NK cell repertoire characterized by an increased proportion of CD16CD56 NK cells. In addition, cases displayed less-activated CD16CD56 NK cells and CD8 T cells, based on HLA-DRCD38 costaining. NK cell suppression of HIV-1 replication ex vivo correlated with the proportion of acutely activated CD68CD16CD56 NK cells. Finally, we detected a higher proportion of CD27CD45RA effector memory CD4 and CD8 T cells in cord blood from cases compared with controls. When controlled for maternal viral load, cord blood from infants who acquired HIV-1 had a higher proportion of CD16CD56 NK cells, lower NK cell activation and higher levels of mature T cells (potential HIV-1 targets) than control infants who remained uninfected. Our data provide evidence that infant HIV-1 acquisition may be influenced by both innate and adaptive immune cell phenotypes and activation status.
    No preview · Article · Apr 2014 · AIDS (London, England)
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    ABSTRACT: Introduction Half of Kenya's high infant and under five mortality rates is due to malnutrition. Proper implementation of World Health Organization's (WHO) Evidence Based Guidelines (EBG) in management of severe acute malnutrition can reduce mortality rates to less than 5%. The objectives were to establish the level of adherence to WHO guideline and the proportion of children appropriately managed for severe acute malnutrition (steps 1-8) as per the WHO protocol in the management of severe acute malnutrition. This was a short longitudinal study of 96 children, aged 6-59 months admitted to the pediatric ward with diagnosis of severe acute malnutrition. Methods Data was extracted from patients’ medical files and recorded into an audit tool to compare care provided in this hospital with WHO guidelines. Results Non-edematous malnutrition was the commonest presentation (93.8%). A higher proportion (63.5%) of patients was male. Most (85.4%) of patients were younger than 2 years. Patients with non-edematous malnutrition were younger (mean age for non-edematous malnutrition was 16 (± 10.6) months versus 25 (± 13.7) months in edematous malnutrition). The commonest co- morbid condition was diarrhea (52.1%). Overall, 13 children died giving an inpatient case fatality rate of 13.5%. Appropriate management was documented in only 14.6% for hypoglycemia (step1), 5.2% for hypothermia (step 2) and 31.3% for dehydration (step 3). Conclusion The level of adherence to MOH guidelines was documented in 5 out of the 8 steps. Appropriate management of children with severe acute malnutrition was inadequate at Garissa hospital.
    Full-text · Article · Mar 2014 · Pan African Medical Journal
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    ABSTRACT: This paper describes results from a cross-sectional study among HIV-infected children 15 months to 12 years of age who were receiving antiretroviral therapy. We found a low prevalence of measles IgG seropositivity (45.7%) and identified CD4% ≥ 25 as a predictor. Most HIV-infected children on ART were not measles seropositive and might benefit from revaccination.
    No preview · Article · Mar 2014 · The Pediatric Infectious Disease Journal
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    ABSTRACT: We compared primary Epstein-Barr virus (EBV) infection and suppression between Kenyan human immunodeficiency virus–infected infants starting nevirapine-based vs lopinavir/ritonavir-based antiretroviral regimens. Although the rate of EBV infection was similar between groups, infants receiving lopinavir/ritonavir suppressed EBV more rapidly. Our findings suggest that specific antiretrovirals may potentially impact the risk of future EBV-associated malignancies.
    Preview · Article · Feb 2014 · Clinical Infectious Diseases
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    ABSTRACT: 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/ breast feed, 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 +) courses held since 2007. Implementation of guidelines into care has been shown to reduce case fatality from pneumonia by 36%. Objectives: 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 children were reviewed. Their median 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.
    Full-text · Article · Jan 2014 · East African medical journal
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    ABSTRACT: Infants born to HIV-1 infected mothers may have increased risk for tuberculosis (TB), but the prevalence of TB infection in this population is undefined. In contrast to tuberculin skin tests that are confounded by recent BCG vaccination, TB interferon gamma release assays (IGRAs) do not cross-react with BCG and enable detection of TB infection in infancy. In a nested observational cohort of HIV-1 infected Kenyan mothers and their infants, we conducted T-SPOT.TB assays on cryopreserved peripheral blood mononuclear cells (PBMCs) from 6-month old infants without prior active TB. Maternal and infant correlates of infant TB infection were assessed. 182 infants were tested with T-SPOT.TB. Of 128 infants with determinate T-SPOT.TB results, the prevalence of a positive T-SPOT.TB was 10.9% (95% confidence interval [CI]: 6.1-17.7%). All infants were BCG-vaccinated and 7.0% were HIV-1 infected. Positive infant T-SPOT.TB was associated with maternal active TB (OR 15.5, [95% CI 1.3-184], p=.04) and prolonged infant fever (>1 month) (OR 18.8 [95% CI 1.6 - 223], p=.03). We observed a high prevalence of TB infection in 6-month old HIV-1 exposed infants. Improved TB detection and prevention is warranted in HIV-1 exposed infants at high risk for active TB disease.
    Full-text · Article · Dec 2013 · The Pediatric Infectious Disease Journal
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    ABSTRACT: 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. 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. 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%. 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).
    No preview · Article · Dec 2013 · The International Journal of Tuberculosis and Lung Disease
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    ABSTRACT: We evaluated the association of single nucleotide polymorphisms (SNPs) in TLRs with infant HIV-1 acquisition and viral control. Infant HIV-1 outcomes were assessed in a Kenyan perinatal HIV-1 cohort. Infants were genotyped for six candidate and 118 haplotype-tagging polymorphisms in TLRs 2, 3, 4, 7, 8, and 9, MYD88 and TIRAP. Cox proportional hazards and linear regression were performed to assess associations with time to HIV-1 acquisition, time to infant mortality, and peak viral load. Among 368 infants, 56 (15%) acquired HIV-1 by month 1 and 17 (4.6%) between 1 and 12 months. Infants with the TLR9 1635A (rs352140) variant were more likely to acquire HIV-1 by 1 month [hazard ratio = 1.81, 95% confidence interval (CI) = 1.05-3.14, P = 0.033] and by 12 months (hazard ratio = 1.62, CI = 1.01-2.60, P = 0.044) in dominant models adjusted for maternal plasma HIV-1 RNA level and genetic ancestry. Among 56 infants infected at 1 month of age or less, at least one copy of the TLR9 1635A allele was associated with a 0.58 log10 copies/ml lower peak viral load (P = 0.002). Female infants with at least one copy of the TLR8 1G (rs3764880) variant had a 0.78 log10 copies/ml higher peak viral load (P = 0.0009) and having at least one copy of the C allele for a haplotype tagging TLR7 variant (rs1634319) was associated with a 0.80 log10 copies/ml higher peak viral load in female infants (P = 0.0003). In this African perinatal cohort, we found several TLR polymorphisms associated with HIV-1 acquisition and progression. Defining mechanisms for these TLR associations may inform HIV-1 prevention strategies that leverage innate responses.
    No preview · Article · Sep 2013 · AIDS (London, England)